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Synthetic and mechanistic studies of 3, 3-dimethoxycyclopropene

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Title:
Synthetic and mechanistic studies of 3, 3-dimethoxycyclopropene
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Albert, Rudolph Milton, 1938-
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1973
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English
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x, 138 leaves. : illus. ; 28 cm.

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Adducts ( jstor )
Chlorides ( jstor )
Esters ( jstor )
Ethers ( jstor )
Flasks ( jstor )
Infrared spectrum ( jstor )
Nitrogen ( jstor )
Protons ( jstor )
Room temperature ( jstor )
Solvents ( jstor )
Chemistry thesis Ph. D
Dimethoxycyclopropene ( lcsh )
Dissertations, Academic -- Chemistry -- UF
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Thesis -- University of Florida.
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Bibliography: leaves 134-137.
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SYNTHETIC AlND MECHANISTIC STUDIES OF
3,3-DI !HETHO::'.'CYCLOPROPEN;E












By

RUDOLPH MILTON ALBERT, JR.


A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF
THE UNIVERSITY OF FLORIDA
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
DEGREE OF DOCTOR OF PHILOSOPHY






UNIVERSITY OF FLORIDA
1973





















This Dissertation is Dedicated to

Carol

and

Elizabeth, Laura, Robert,

Pebecca and Daniel















AC K':O'..LE DGE E TS


I wish to express my deep appreciation to Dr. G.B. Butler

for his friendship and guidance as my research director. The advice

and suggestions of the other members of my supervisory committee

are also acknowledged with gratitude.

I:y colleagues in the laboratory made working more pleasant

and for this I am grateful. A special note of thanks is extended

to Dr. Richard L. Veazey for many valuable discussions and helpful

suggestions.

I wish also to thank the management of the Organic Chemicals

Group, Glidden-Durkee Division of the SCt; Corporation and especially

Mr. R.P.T. Young for a very generous leave of absence which made

it possible to come here at all.

The patience and skill of my typist, Mrs. Jimmie McLeod, was

of inestimable value in the preparation of this manuscript and I

would like to give special recognition to her.

Finally, I wish to give a special expression of gratitude

to my family. All have sacrificed much to make the completion of

this program possible and their abiding love has been a source of

strength and determination.


iii
















TABLE OF CONTENTS


Page


ACKNIOWLEDGEMENTS . . . . . . . . .


LIST OF TABLES . . .

LIST OF FIGURES . .


ABSTRACT . . . . . . . . . .


CHAPTER


I. INTRODUCTION . . . . . . .


II. STUDIES RELATED TO THE PREPARATION OF
3,3-DItMETHOXYCYCLOPROPENE . . . . . . 7

A. Reaction Ey-Products . . . . . . 10
B. Extension to Other Systems . . .. . . 14
C. Preparation of Other Ketals . . . ... 16
D. Cyclization of the Ethylene Ketal ...... 19
E. Improved Procedure for Preparation of
Dimethoxvcvclopropene . . . . . ... 23
F. Other Cyclization Processes . . . ... 25

III. CHARGE TRANSFER COMPLEXATION . . . ... 26

IV. 4+2 CYCLOADDITIOI. THE DIELS ALDER REACTION . 33

A. Reaction with Butadiene Derivatives . . .. 36
B. Reaction with Cyclic Dienes . . . ... 47


V. 2+2 CYCLOADDITION REACTIONS . . . . .

A. Reaction with Hexafluoroacetone . . .
B. Reaction with Enamines . . . .
C. Reaction with Triazolinediones ..


S. 57

S. 58
S. 63
S. 65


D. Reaction with Dimethylacetylenedicarbo::ylate

VI. REACTIONS WITH AMINES . . . . . . . .


. . . vi


viii


1












VII. SU:-::-IARY AND CONCLUSIONS

VIII. EXPERIMENTAL . . .

A. Equipment and Data
B. Synthesis . . .
C. Procedures and Data
Couple:: Studies .

REFERENCES CITED . . . .

BIOGRAPHICAL SKETCH . . .


Page

88

92

92
94

130

134

138


for Charge Transfer
. . . . . . . .

. . . . . . . .

. . . . . . . .















LIST OF TABLES


Table Page

I. Mass Spectral Fragments from 3,3-Eth'lenedioxv-
cyclopropane . . . . . . . .... . 20

II. Variation of the Chemical Shift of the Ring Protons
of 3,3-Dimethoxycyclopropene with Solvent . . .. 27

III. IIMR Determination of the Equilibrium Constants of
Charge Transfer Complexes . . . . . .... 32

IV. Relative Abundances of Mass Spectrumr Peaks from
Diels Alder Adduct . . . . . . . . 42

V. Data for Dimethox:,'cy,'clopropene-Styrene Complex Study 132

VI. Data for Dimethox:ycyclopropene-Divinyl Ether Complex
Stud, . . . . . . . . .... . . .. 133















LIST OF FIGURES


Figure Page

1 NMR Spectrum of C3H BrC13 .............. 12

2 Ultraviolet Spectrum of 3,3-Dimethoxycyclopropene 28

3 iNR Study of the Complex Between Dimethoxycyclopropene
and Styrene . . . . . . . . ... .. 30

4 M.? Study of the Complex Between Dimethoxycyclopropene
and Divinyl Ether . . . . . . . ... 31

5 -iR Spectrum of the Dimethoxycyclopropene-Dimethyl-
butadiene Adduct . . . . . . . . ... .37

6 !.MR Spectrum of Dimethoxycyclopropene-Isoprene Adduct 38

7 M1IR Spectrum of the Adduct Formed Between Dimethoxy-
cyclopropene and Tetracyclone . . . . ... 51

8 U.R Spectrum of Dinethoxycyclopropene-Hexafluoro-
acetone Adduct . . . ... . . . .. . .60

9 NIR Spectrum of l,l-Dimethoxy-2-diethylaminocyclo-
propane . . . . . . . . ... .. . .75

J0 UfIR Spectrum of N,N-dipropyl-B-alanine . . ... 77

11 I-:R Spectrum of N,N-diphenyl-B-alanine . . ... 81

12 NRP. Spectrum of the Intermediate Leading to N,NI-diphenyl-
B-alanine . . ... . ... . . . .83









Abstract of Dissertation Presented to the
Graduate Council of the University of Florida in Partial
Fulfillment of the Requirements for the Degree of Doctor of Philosophy


SYNTHETIC AND MECHANISTIC STUDIES OF
3,3-DIIMETHO'XYCYCLOPROPENE


By

Rudolph Milton Albert, Jr.

August, 1973


Chairman: Dr. George B. Butler
Major Department: Chemistry


The preparation of 3,3-dimetho:-:ycyclopropene in pure form was

first reported in 1970. It was synthesized by treating l-bromo-3-

chloro-2,2-dimetho:x:ypropane with potassium amide in liquid ammonia.

The precursor was obtained by the acid-catalyzed reaction of 2,3-

dichloropropene with N-bromosuccinimide and methanol.

This research program has been directed toward expanding and

improving the reactions leading to dimetho::ycyclopropene as well

as toward defining the reactivity of this unusual intermediate.

Direct synthesis of different ketals was attempted by substituting

other alcohols for methanol. Bromine addition was a major competing

reaction. Likewise, 2,3-dibromopropene gave only 1,2,2,3-tetra-

bromopropane when reacted with 11-bromosuccinimide and methanol.

Successful preparation of the ethylene ketal of l-bromo-3-

chloro-2-propanone was realized by acid-catalyzed exchange of ethylene

glycol on the dimethyl ketal. Cyclization of this intermediate was

also attempted since the resulting cyclopropene might be more reactive

than dimethoxycyclopropene in situations where steric crowding is

v iii









critical. Two products were obtained from its reaction with potassium

amide, however. One was the expected cyclopropene which could not

be purified. The second product was obtained in pure form and was

identified as the cyclopropane derivative L ,7-dioxaspiro[2.u]heptane.

Significant improvement in both yield and operational convenience

was realized by modifications in the reaction procedures. Instead

of adding the ketal intermediate to the aide solution, potassium

amide was prepared in one flask and then transferred by means of

nitrogen pressure to a second flask containing the intermediate in

additional ammonia.

Dimethoxycyclopropene was found to be an electron-deficient

olefin that forms weak charge transfer complexes with styrene and

with divinyl ether.

In Diels-Alder reactions, dimethoxycyclopropene reacted quanti-

tatively with derivatives of butadiene to give the expected 7,7-

dimethoxy-3-norcarenes. With cyclic dier.es, such as cyclopentadiene

and furan, reaction was inhibited by steric interaction. In both

these cases only dimerization of dimethoxycyclopropene was observed.

Its reaction with tetracyclone gave the ket.al of a 2t5H)-furanone

by addition of the opened cyclopropene system to the carbonyl function

of the diene.

Cycloaddition reactions with olefins to give cyclobutane

products were unsuccessful with simple carbon-carbon double bonds.

Eoth electron-rich (enamines) and electron-poor (acetylene dicarboxvlate)

oltfins were completely unreactive. Species containing a hetero atom

did react, however. Hexafluoroacetone gave a bicyclic adduct by








formal 2t2 cycloaddition of the olefin and the carbonyl group. With

4-phenyl-1,2,4-triazoline-3,5-dione and the corresponding 4-methyl

derivative the products were copolymers which did not retain the

cyclopropyl system.

Reaction of dimethoxycyclopropene with diethylamrine gave only

1,l-dimethoxy-2-diethylaminocyclopropane. With dipropylamine,

however, II,11-dipropy'l-B-alanine methyl ester was obtained along with

the expected cyclopropylamine. 'When diphenylamine was used there

was no c,,clopropylamrrine observed and only the methyl ester of

tN.,l-diphenyl-B-alanine was recovered. An intermediate was detected

but could not be purified due to the ease with which it was converted

to the alanine derivative. A mechanism involving a ketene acetal

as the intermediate is consistent with the data available.















CHAPTER I

Introduction


Although cyclopropene and many of its derivatives have been

available for many years, cyclopropene chemistry has been the object

of considerable interest only in the past two decades. The upsurge

of activity which took place in the mid-fifties was due to three

main factors. These factors were (1) the developments in carbene

chemistry which aided synthesis of cyclopropene systems, (2) the

applications of molecular orbital theory which made attack on theo-

retical problems a desirable goal, and (3) the discovery of the

cyclopropene system in natural products.

Many systems were designed and studied, but cyclopropene deriv-

atives unsubstituted in the double bond positions are relatively

uncommon. The parent hydrocarbon was first synthesized in 19222

but it was not until the facile preparation by Closs3 in 1966

that it was used for extensive studies. Geminal dimethyl cyclopropene

was prepared by Closs4 in 1961 by base catalyzed thermal decomposition

of 3-methyl-2-butenal tosylhydrazone. This procedure also yielded

the very unstable 3-methylcyclopropene5 although in poor yield.

Studies of the chemistry of these derivatives is limited and deal

mainly with isomerization reactions. A kinetic study of the thermal

isomerization of 3-methyl-, 3,3-dimethyl-, 1,3,3-trimethyl-, and

1,2,3,3-tetrainethylcyclopropene showed that increased substitution

caused an increase in thermal stability.6

1








Synthesis of 3,3-diphcnylcyclroropene was observed upon irrad-

iation of 3,3-diphenyl-3H-pyrazole7 but rearrangement to 3-phenyl-

indene occurred on gas chromatography.




-Ph

Ph Ph


A mixture of the halogenated derivatives, 3-chloro-, 3,3-dichloro-

and 1,3-dichlorocyclopropene is produced by reduction of tetrachloro-
0
cyclopropene with tri-n-butyltin hydride. Breslow used 3-chloro-

cyclopropene in the preparation of unsubstituted cyclopropenyl cation

and 3,3-dichlorocyclopropene was hydrolyzed to cyclopropenone.

The mixture of reduction products was used as a probe into the
10
mechanism of Diels-Alder adduction of perhalocyclopropenes0 but

no adducts with 3,3-dichlorocyclopropene were observed.

Bertrand and Monti devised the following scheme for the

preparation of cyclopropenyl ketones:

IH3 HCBr, C 3 Zn 3
R-CH=C-C-CH > R-CH-L-CH R-CH-C-CECH
tBuOK H, HAc \C

Br Br Br H




CH CH
Ht+ It 1. tEu. L 3 CH
HE > R-CH---C- CH > -
glycol 3 2. H 0
Er H H









They studied the thermal rearrangement of this ketone to 3-acetyl-
12 13
1-methylcyclopropene2 and also the Diels-Alder adducts which it3

and its ethylene ketall form with cyclopentadiene. These adducts

are to be described in Chapter IV.

In the course of studies directed toward the synthesis of

cyclopropenone, Pratt prepared 3,3-dimethoxycyclopropene and

presumably cyclopropenone itself for the first time. His plan

was to e::trude the cyclopropene derivative from the Diels-Alder

adduct formed between tropone dimethylketal and dimethyl

acetylenedicarboxylatc. Purification of the adduct was a major

problem in this procedure and it was, in fact, during an attempted

distillation that the formation of dimethoxycyclopropene was first

suggested. Subsequent experiments indicated that this "batch

pyrolysis" was the preferred process for the extrusion reaction.


COACH CH0
OC 2C 3 302
OH3 OCH
+: ). .. 3,
OCH I OCH3
CO CH 3 CH








02 CH








Although he was never able to isolate dimethoxycyclopropene in

pure form, he did report MIR and I. spectra which support its presence

among his reaction products. Attempts were made to determine the

molecular weight by mass spectrometry and by a gas density method

but neither gave satisfactory results. Reaction with cyclopentadiene

was attempted and the lack of reactivity was attributed to inadvertent

hydrolysis to cyclopropenone. The evidence presented fcr cyclo-

propenone formation was by inference only and a later evaluation of

this worki6 did not claim its preparation.

In the course of attempting to synthesize compounds potentially

capable of charge-transfer complexation prior to polymerization,

Eaucom discovered an easy and relatively simple procedure for the

preparation of l-bromo-3-chloro-2,2-dimetho::ypropane.17 Subsequent

investigation of this reagent led to the successful isolation of

pure 3,3-dimethoxycyclopropene. (Scheme I)

The reactivity of this ketal was investigated in a preliminary

series of experiments.8 Baucom found that it gave a Diels-Alder

adduct with 1,3-diphenylisobenzofuran but not with tetracyclone.

In the latter case, a product was isolated which was the result of

p17
solvent carbon tetrachloride addition to the dimertho.:ycyclopropene.


CH i OCH OCH3
3 -s- 3 CH O C4 OCH3
3 CC1 3
--. CHC1=CH-C" + *CC1

OCH3

OCH
I 3
ChC1=CH-C-OCHJ
CC1
3









0

CH2= -CH2C1 I-Br t Cil OH H2 4 BrCH2--C-CH2Cl
C11 3 H SO BC


CH 30 OCH

H2CCM CH2Br


YKIH2
KNH3
K 1 1 H 2


CHO CH3

H C CH Br
O-1 2


-Br
>


CH 0 OCH3

HC--CH
2
Li--%H


CH 30\ OCH 3
C H
2
-C1H


KIH
NH3
3


-Cl
---->


CH3O 0 CH3

HC= CH
I


Scheme 1. Synthesis of 3,3-Dimethoxycycloopropene7


When a pure sample of dimethoxycyclopropene was added to

deuterium oxide, it was hydrolyzed immediately to cyclopropenone.

No attempt was made, however, to isolate the pure ketone.

In an attempt to prepare a Diels-Alder adduct with a-pyrone,

the major product isolated was a dimer of dimethoxycyclopropone.

Preliminary evidence was also obtained for the formation of the

Diels-Alder adduct but this was not confirmed.


CH OC.3 CH 0 OCHI 3


0 0


CH3(








Treatment of l-bromo-3-chloro-2,2-dimerhoxypropane with potassium

tert-butoxide gave only 1,l-dimethoxy-2-t-butoxycyclopropane, even

in experiments designed to trap the cyclopropene as it was formed.

This suggested that dimethoxycyclopropene experiences facile attack

by nucleophilic reagents. The addition of other nucleophiles was,

therefore, of interest and Baucom reacted the ketal with excess

dimethvlamine and did, indeed, obtain the expected dimethylamino

derivative.

The results of these experiments indicate that 3,3-dimethoxy-

cyclopropene is a highly reactive reagent possessing a somewhat

electron-deficient double bond. Its ready availability in relatively

large quantity suggests its use as a source of cyclopropenone and

also as a means of incorporating a cyclopropanone moiety into

previously inaccessible systems by preliminary adduct formation and

subsequent hydrolysis to the free carbonyl function.

The present research program was undertaken to investigate this

system on several fronts. First, the reactions leading to 3,3-di-

methoxycyclopropene are unique and their generality was to be esta-

blished. Second, only MINR and I. properties of dimethoxycyclopropene

were reported by Baucom and other characteristics of this reagent

were desired. The third and most general objective was to establish

the chemical reactivity of this compound toward a variety of systems

and consequently to suggest the most efficient use of 3,3-dimethoxy-

cyclopropene as a synthetic reagent and as a possible monomer in

copolymer preparations.
















CHAPTER II

Studies Related to the Preparation of 3,3-Dimethoxvcvclopropene


The series of reactions leading to 3,3-dimethoxycyclopropene

which Baucom discovered involves rather unique procedures and one

objective of this research program was to evaluate the scope of

these reactions. Also, while the chemical processes involved are

the same as those of the original work, significant improvements

in yield and operational convenience have resulted from modifications

in procedures.

When Baucom added Jl-bromosuccinimide to 2,3-dichloropropene

in refluxing methanol containing a catalytic amount of sulfuric

acid, l-bromo-3-chloro-2,2-dimethoxypropane was obtained in up to

40 percent yield as a pure crystalline material.17 A Second major

reaction product was proposed to be l-bromo-2,2,3-trichloropropane.

The proposed sequence of reactions is shown in scheme 2. Because

of the complexity of side reactions possible, the 33-40 percent

yield of the desired ketal was thought to be quite good and incapable

of significant improvement without resorting to very expensive or

complex procedures.

One possibility which was investigated, however, was blowing

air through the reacting mixture. This would serve to remove some

of the by-product HCI and to possibly air-oxidize Br and promote

further reaction. A definite increase in yield was noted when this













-Er i H+


>


Cl1
Er + CH=C-CH C1 >


ErCH2-C-CH2C1






Cl
ErCH -C-CH Cl
2 + 2
OCH3



Cl
ErCH -C-CH2C 1
2 2
t1


Cl
BrCH 2-CH2Cl
+


cl
MleH E BrC.- -T-CH2Cl
3,


+ H+


OCH

UCH3
+ CH H ErCH -2CHC1 + C1
2 Ii1 H 2"


+ Cl


+ H+


-> ErCH2CCl 2CH2C1
2 V


Scheme 2. Reaction of 2,3-Dichloropropene with iE.S.'/Methanoll7




was done but a subsequent series of reactions revealed that the

effect was due to a decrease in reaction temperature and not to

any action of the air itself. Thus, modification of Eaucom's

procedure resulted in routine yields of around 65 percent by slow

addition of il5S at 25-30' without the use of air-blowing. Slight

increases could be realized to 5-10 but the time required for each

portion of IBS to react increased and made the overall process too


+ Er









lengthy. One experiment using perchloric acid as catalyst gave

a slightly higher yield but the added hazard of the reagent out-

weighed this advantage.

One explanation for the effect of lower temperature is that

solvolysis of l-bromo-2-methoxy-2,3-dichloropropane (reaction 4

of scheme 2) is slower. This would decrease the rate of formation

of by-product HC1 and favor production of the intermediate (reaction

3) over the formation of l-bromo-2,2,3-trichloropropane (reaction 5).

If this were the case, then very rapid addition of NBS with subsequent

rapid formation of the intermediate would further favor the desired

reaction. It had been felt that rapid addition of the reagent would

have an adverse effect on the yield by favoring Br2 addition and

at the same time make control of the reaction e::otherm difficult.

However, experience with the process began to indicate that if

the initial temperature were low, an adequate ice bath should control

the temperature and allow an evaluation of the yield.

Thus, N-bromosuccininide was added as rapidly as possible to

2,3-dichloropropene in cold methanol containing a catalytic amount

of sulfuric acid. The temperature, originally at -100, rose to -30

but quickly fell to -100 again. This temperature was held for

three hours and then gradually warmed to room temperature overnight

as the ice/acetone bath melted and equilibrated. The yield of

l-bromo-3-chloro-2,2-dimethoxypropane was 71 percent of theory.

Wiile the increase in yield may be moderate, the added operational

convenience is significant. Typically, the apparatus can be assembled

and the reagents charged in the last half-hour of the day. After









stirring overnight, the product is isolated and purified by standard

procedures. The older procedure required addition times of two to

five hours and then storage overnight before work-up.


A. Reaction By-Products

An evaluation of the by-products was also attempted in an

effort to better understand the reactions taking place. Analysis

by Ill-IM of the by-product mixture revealed that very little direct

bromination takes place. A sample of the oil was fractionally

distilled under reduced pressure and 85 percent of it was collected

as a single fraction (b.p. 103-1040/58 mm. Hg). Chromatography on

silica gel removed the last traces of impurity and gave what was

apparently pure compound.

The mass spectrum gave a molecular ion peal: at m/e 224 with

the proper isotopic distribution ratio for C3H BrCl3. The base

peak at m/e 145 corresponds to the expected loss of a bromine radical

and further fragmentation by loss of HC1 gives an abundant peak

at m/e 109 (55 percent of base peak). These observations are consistent

with the structure proposed in scheme 2 but do not allow any con-

clusions about the structure. The major inconsistency in correlating

the spectrum with the proposed structure is an abundant (53 percent)

peak at m/e 83 with isotopic distribution ratio for CHC1 Rearrange-

ment pathways leading to this ion are difficult to rationalize.

The only fragments retaining bromine are relatively small (12 percent)

and appear at m/e 189 and 175 corresponding to loss of -Cl and -CH2Ci

respectively. The loss of these radicals is most easily visualized










as a-cleavage of a molecular ion bearing bromine on the central

carbon atom.


Brt
11
CICH -C-C1
1. --CHC
Br
Ir^2 ej- 2
CICH -C-'C
CH Cl Br+
2 2. -Cl. II
2. -Cl CICH2-C-CH2Cl



The NtIR spectrum of this sample is also inconsistent with the

suggested l-bromo-2,2,3-trichloropropane as seen in Figure 1.

The three singlets appear to have a ratio of 2:1:1 and 1-bromo-

1,2,3-trichloropropane was considered a possibility. This structure,

however, should have a more complex: spectrum and greater differences

in the chemical shifts of the methylene and the methine protons.

The observed spectrum could arise if the rotation about one of the

C-C bonds were sufficiently hindered to place the two protons affected

in different environments. There is no indication of such hindrance

in either the product ketal or the dibromodichloropropane which was

prepared by addition of bromine in carbon tetrachloride to 2,3-dichloro-

propene, however.


CH 2=CC1-CH Cl t Br2/CC1 ---> BrCH -CClBr-CH Cl


It appears likely, therefore, that two by-products are produced

that differ only in the positions of the bromine atom and one of

the chlorines. This condition could arise by attack of Cl with

equal facility on either end of a bromonium ion intermediate.




































_i__--------_____ 5 -cps


, 7I0 *60-- I 5.0
7.0 6.0


Figure 1. NMR Spectrum of C3H PrC13


4.0














Cl
C11-CH1 ,C1
Cl Br C1
+


Cl
SCICH -C-CH2Cl

2Br



BrCH2-C-CH2 C
1


It is interesting to note that there is very little, if any, of the

corresponding attack at C-1 by CH30H to give l-methoxy-2-bromo-

2,3-dichloropropane.









B. Extension to Other Systems

Extension of these reactions to other systems could serve three

purposes. First, their scope could be evaluated to determine whether

they are general or specific processes. Second, a comparison of

the reactivity of various derivatives would be a probe of the

mechanism of the cyclization reaction (viz., 1,3-dibromo- and

1,3-dichloro- vs. l-bromo-3-chloro-2,2-dimethoxypropane). Third,

the reactivity of other ketals (especially the ethylene ketal)

might be favored over the dimethyl derivative for steric reasons.

Application of the IJBS/methanol reaction to 2,3-dibromopropene

would yield 1,3-dibromo-2,2-dimethoxypropane if the same sequence

as scheme 2 were followed. Such was not to be, however, as the

dichloro and dibromo olefins were found to react differently in

our system. When 2,3-dibromoropene was reacted in methanol with

NES, the major product had only a sharp singlet at 4.266 in the in.R

spectrum. This is very near to the chemical shift of the -CHBEr

protons of the starting clefin which indicates that the major reaction

involved is probably direct bromination:

Br
CH,Br-C=CH + 1IES + CH3OH H BrCH -C-CH,Br
S2 ---- 2
Br Er

Similarly, substitution of ethylene glycol for methanol failed

to yield the ethylene ketal directly. Analysis of the crude reaction

mixture indicated that some ketal formation did occur but that

direct bromination was again the major reaction pathway. Similar

results h2ve been observed using anhydrous ethanol as solvent.

These results point to a high degree of specificity in this





15




reaction which requires chlorine on the starting olefin (although

probably only on C-2) and only methanol for efficient solvolysis

of the intermediates. These factors as well as elucidation of

the reaction mechanism require a separate program of study.









C. Preparation of Other Ketals

Successful preparation of l-bromo-3-chloro-2,2-ethylenedioxy-

propane was achieved in essentially quantitative yield by acid-

catalyzed exchange of ethylene glycol on the dimethoxy derivative.


CH3 CH 6 0
\V 3 H
BrCH -C-CH C1 + HOCH2CH,.OH 0 BrCH2-C-CHCl + 2 CH OH



The new ketal is a colorless liquid (m.p. 100) boiling at 70 under

1.2 mm. Hg pressure. In the InIR spectrum there are two 2-proton

singlets at 3.626 and 3.476 and one 4-proton singlet at 4.056.

The infrared spectrum and elemental analysis are consistent with

the proposed structure. The mass spectrum shows no parent peak.

The base peak at m/e 121 shows an unusual isotopic abundance ratio

of 1.65 to 1 since it can arise from two sources, one with bromine

and one with chlorine (scheme 3). The ions are at m/e 49 and 93 and

correspond to CH2Cl and CH2Br+ respectively, but the expected

metastable peaks are not observed to confirm that they. arise from

the oxonium ion species as indicated in the scheme.

Furthe-r extension of this process to the sulfur analog was

next attempted. When ethane dithiol was substituted for ethylene

glycol and the mixture was heated on the steam bath, a very vigorous

exothermic reaction initiated which erupted from the flask. Due

to the extremely disagreeable conditions which resulted, this reaction

was not repeated, but there seems to be little doubt that l-bromo-

3-chloro-2,2-ethylenedithiopropane could be prepared by this route














-CH2M


C-Cl2 Cl
m/e 121


-C2H0O



+0C-CH Cl
2
m/e 77

-CO


+CH2Cl

m/e 49


H2CL-



BrCH -C
m/e 165



-C2H40



BrCH -CHO+
m/e 121

-CO

ErCH2
m/e 93


Scheme 3. Mass Spectral Fragmentation Pattern for 1-Bromo-
3-chloro-2,2-ethylenedioxypropane




if its production were required and the proper precautions were

taken to control the vigor of the reaction.

Three other ketals were prepared by more conventional routes

from the appropriate ketones. These were


CH.i OCH
\ClCH / 3
C1CH2-C-CH2C1l


0 [
C \/P
CICH -C-CO Cl
2- 2 1


C1{30\ /CH3
BrCH2 -C -C12 Br









A fourth, 1,3-dibromo-2,2-ethvlenedioxypropane, would complete the

series but was not prepared.

The dimethyl ketals were prepared by refluxing the ketone with

methanol containing a trace of acid catalyst. Water of reaction was

removed by passing the condensed solvent through a bed of molecular

sieve before returning it to the reaction flask. In the case of

the glycol reaction, a benzene azectrope was adequate for removing

the water. Because these ketals were difficult to obtain and are

available in very limited quantity, the comparison of their reactivity

in producing cyclopropene derivatives was not attempted. This study

should be revived when an acceptable material balance on the cyclization

process is realized or when a dependable method of derivitizing all

cyclopropene products becomes available.









D. Cyclization of the Ethylene Ketal

Since l-brono-3-chloro-2,2-ethylenedioxypropane was readily

available in large quantity, its cyclization was attempted using

the procedures available. The reaction was conducted as described

by Baucom for the dimethoxy derivative and a yield of distilled

product of 13 percent was obtained. Analysis of the material by

NMR showed three singlets at 7.72, '.01, and 0.906 with integration

intensities of 15, 140, and 110 respectively. The absorbance at

7.726 was assigned to the cyclopropene ring protons of the expected

product and the signal at 4.01 is very near that of the methylene
H H
HMH
0 0

HH



protons of the ketal moiety in the starting material (4.056). The

intensity of this absorbance, however, should only be twice that

of the 7.726 absorbance or thirty units. Since the excess was exactly

equal to the intensity of the absorbance at 0.906, the presence of
20
a cyclopropane derivative20 was suggested although none had ever

H H
H^H


H4
H H

been detected in the dimethoxy reactions and its preparation would

be difficult to rationalize. Relative area ratios indicated that

the product mixture was 20 percent cyclopropene and 80 percent

cyclopropane.








Treatment of the mixture with water removed all of the cyclo-

propene but left the cyclopropane unaffected. A pure sample of the

colorless liquid was obtained by preparative gas chromatography.

In the NMR there were two singlets of equal intensity at 4.016 and

at 0.916. The mass spectrum showed an abundant molecular ion at

m/e 100 which had 74 percent the intensity of the base peak at m/e 99.

Each of these ions, then, apparently experiences a similar frag-

mentation pattern as indicated by the following table.


Table I. Mass Spectral Fragments from 3,3-Ethylenedioxycyclopropane

m/e relative intensity molecular formula fragment lost

100 74 C H 0 +molecular ion

56 62 C3H40 C2H

44 48 C2H O C3H0

99 100 C5H702 H

55 92 C3H30 C2H4O
33 24
43 90 C2H30O+ H C
3 C3H4
40 42 C3H C2HO02



The appearance of ions at m/e 44 and 43 by loss of C H 0 from

the molecular ion and the base peak ion respectively suggests

rupture of the dioxolane ring and extrusion of the elements of

cyclopropanone. Such involvement of the dioxolane ring is unusual

and reflects the structural peculiarity of this spiro ketal.21

Support for this process is found in the metastable peaks produced.

The transition m/e 99 to 55 by loss of C2H 0 is a common reaction of

ethylene ketals and gives an observable metastable peak at 30.6.









A metastable peak at 18.7 is only slightly less intense and cor-

responds to the transition m/e 99 to 43 by loss of C H 0.

A characteristic feature of the infrared spectra of dioxolane

derivatives is a group of four or five peaks between 1000 and
-I
1200 cm. This pattern is prominent in the spectrum of 1-bromo-

3-chloro-2,2-ethylonedio:ypropane with peaks at 1030, 1095, 1130,
-1
and 1140 cm. The spectrum of the cyclization product, however,

does not have this characteristic pattern. In the region of interest

there are only two strong peaks at 1030 and 1185 cm.- Apparently

the molecular vibrations responsible for absorptions at these

frequencies are constrained by the small ring attached as a spiro

derivative to the dioxolane ring.




SKINH2I 0 0
BrCH -C-CH 2Cl IIH > 2
H H H. H
H. H


Formation of this product, 4,7-dio:aspiro[2,4]heptane, is

difficult to rationalize. The preparation of the potassium amide

was carefully conducted to insure that no unreacted metal remained.

Thus, when the bromochloroketal was added, the reaction medium

should not have been a reducing system and it is unlikely that

the cyclopropene derivative is being hydrogenated. Likewise, a

dehalogenation reaction involving the free metal is not possible.

Baucom obtained a similarly unexpected product retaining all four

methylene protons from the reaction of l-bromo-3-chloro-2,2-dimetho:.:y-








propane with lithium hydride in the presence of tetracyclone.
The reaction scheme postulated to account for his product could
apply in this case although the amjide displacement on bromine does
not have compelling precedence.


K
BrCH -C-CH C1
KIJH
1


-I

0X


F--:

H., -C -H -C1









E. Improved Procedure for Preparation of Dinethoxvcyclopropene

Cyclization of l-bromo-3-chloro-2,2-dimethoxypropane with

potassium amide in liquid arnmonia yields 3,3-dimetho:-:ycyclopropene
17
as shown in scheme 1. The procedure developed by Baucom7 is

essentially the same as that described earlier for the ethylene

ketal. Yields were reported to be 30 to 50 percent but in the

current program this process yielded 0 to 50 percent with 10 to

15 percent being the most frequent result.

Significant improvement was realized by reversing the order

of addition of reactants in the cyclization process. The yield

was 58 percent for the first run and has been consistently above

40 percent in later runs. In addition to higher yield and fairly

consistent results, this procedure is more convenient and is a

safer process which has allowed scaling up to three times the

usual run. In the case of the first reaction using this procedure,

the starting material was completely consumed and there was little

residue after distillation of the product. Nevertheless, a total

material balance was still not achieved. Only about 75 percent of

the starting material was accounted for. This has been a persistent

problem that makes comparison of reagents and mechanism probes

unreliable and is one reason none have been attempted.

The apparatus used was similar to that of Schlatter.22

Essentially, it consisted of two flasks arranged side by side with

appropriate connecting tubes and provision for pressurizing one of

them. The potassium amide was prepared in the usual fashion in





24



one of them and then transferred by means of nitrogen pressure to

the other flask which contained the intermediate in excess ammonia.

A relatively short reaction time at the temperature of refluxing

ammonia was required to complete the cyclization and excess amide

was destroyed with ammonium chloride. Isolation of the product

then followed the established process.










F. Other Cyclization Processes

Several other systems were evaluated in an effort to find an

alternate method for the preparation of dimethoxycyclopropene.

Hexamethylphosphoramide (HMPA) has been used to effect dchydro-
23
halogenation23 and the following reaction can be visualized.



CH 0 OCH3 CH30 OCH
+ 2 HMPA )
BrCH2-C-CH2CI HMPA 2 H3)2




2((CH3)2) 2P=O


It should be possible to distill the product from the mixture as

it is formed. When a sample of the bromochloroketal was added to

HMPA and slowly heated to 2200 an exothermic reaction seemed to

take place and the mixture became very dark. A few milliliters

of a clear liquid distilled from the reactor but it rapidly boiled

away when warmed to room temperature. Apparently the ketal was

reactive toward HMPA and produced decomposition of the solvent to

give dimethylamine which was the liquid collected. The conditions

employed here were too severe for practical use, however.

When the bromochloroketal was heated for two hours at 750 with

sodium hydride in HMPA it was recovered unchanged in quantitative

y field.















CHAPTER III

Charge Transfer Complexation


The use of 3,3-dimethoxycyclopropene in copol.ymerization

processes affords the interesting possibility of incorporating

cyclopropanone units in polymer chains by subsequent hydrolysis

of the ketal moiety. Modification of polymer properties by further

reaction at these sites could lead to materials of considerable

interest.

A good deal of evidence has accumulated for the participation

of charge transfer complexes in many copolymerization reactions.2a

The ease with which 3,3-dimethoxycyclopropene experiences nucleo-
18
philic addition (eg. tert-butoxide and dimethylamine) suggests

that it is a rather electron-deficient olefin. Therefore, the

formation of charge transfer complexes between this reagent and

two electron-rich monomers was investigated. These monomers were

s-yrene and divinyl ether.

Of the two methods commonly used to study charge transfer

complexation, namely ultraviolet spectroscopy and nuclear magnetic

resonance, the latter is clearly preferred in this case for two

reasons. First, it is extremely difficult to obtain 3,3-dimethoxy-

cyclopropene of spectroscopically pure form in sufficient quantity

for use in UV studies and secondly, the IMRP, singlet of the ring

protons appears to be sensitive to changes in the electronic nature









of various solvents (Table II). Also, the UV spectrum of dimethoxy-

cyclopropene (rig. 2) shows no absorption above 210 mu.


Table II. Variation in the chemical shift of the ring protons
of 3,3-dimethoxycyclopropene with solvent.

Solvent 6 Value for Cyclopropene Protons

hexane 7.62

cyclohexane 7.65

carbon tetrachloride 7.75

chloroform 7.83

dioxane 7.90

acetone-d6 7.98

benzene-d6 7.33


A study of charge transfer complexation between maleic anhydride

and both styrene and divinyl ether by the INMR method was reported

24c
by Butler and Campus in 1970. Thus, a semi-quantitative measure

of the electron affinity of 3,3-dimetho:xycyclopropene relative to

maleic anhydride should be available from a comparison of the

equilibrium constants of the two systems.

The NMR studies were done on a Varian Associates analytical l.IMR

spectrometer. The shift of acceptor protons (singlet of 3,3-dimethoxy-

cyclopropene) was observed. The concentration of acceptor was kept

constant while the donor concentration (always in large excess) was

increased. Solutions were prepared at room temperature and the

spectra were obtained at the normal operating temperature of the

spectrometer. Peagents and solvents were all purified by distillation

just prior to use.


























































I I I I I I
180 190 200 210 220 230

Wa lengthgt, mw
Figure 2. Ultraviolet Spectrum of 3,3-Dimethox:ycyclopropene









The I;:R technique utilizes the linear relationships derived by

Hanna and Ashbaugh:25

1 1 1 1
A = A CD + A
SQA D AAD
obs AD AD

where:
A A A
A = 6 -6 is the difference between the shift of the
obs obs 0'
acceptor protons in completing media and the shift

of the acceptor in uncomplexed form.


D A A
A = 6 -6 is the difference in the shift of the acceptor
AD AD 0
protons in pure complex.


CD is the concentration of the donor (which must always be

much greater than the acceptor concentration in order

that the quotient YAD/yA yD remains constant over the

range of solutions studied and thus 0 = K, the equi-

librium constant of comple:.ation).


In these experiments the acceptor concentration was kept constant
-i
at 0.05 mole liter while the donor concentration was increased
from 0.4 to 8.8 moles liter- A
from 0.4 to 8.8 mols liter By plotting 1/A as a function of
obs

1/CD a straight line was obtained in both cases. (Figures 3 and 4).

The slope of the line and its intersection with the ordinate permit

a first approximation of the equilibrium constant of co.plexation and

of th- shift of acceptor protons in the pure complex. For a more
A
exact determination of K and A the method of least squares was
AD'
applied to equation 1, and the results obtained are shown in Table Ill.

The corresponding values for maleic anhydride complexes are shown for

comDarison.




30













0.5






0.4 -




C,-
a.
S0.3

< 0
,-o



0.2







0.1






I I I I I
0.2 0.4 0.6 0.8 1.0

)n 1 -1-1
Lstyr]

Figure 3. J11R Study of the Complex Between Dimerhoxycyclopropene
and Styi'ene





31









1.0






0.8






0.6-


,-


O. 4

<0





0.2-








0.2 0.4 0.6 0.8 1.0
1) -1


Figure 4. :MIIR Study of the Complex Between Dimetho:-:ycyclopropene
and Divinyl Ether








lWhile the values of K are quite low, they appear to be real

and of the same approximate order of magnitude as other weak complexes.

(Butler and Campus report K = 0.008 and AD = 127.5 for the complex
AE
24b
between divinyl ether and fumaronitrile.) As expected, the

electron affinity of 3,3-dimethoxycyclopropene is considerably

less than that of maleic anhydride.


Table III. IMRE Determination of the Equilibrium Constants of Charge
Transfer Complexes.
A
Complex Solvent Temp., OC AD' cps K, 1 M-

DVE:DMCP hexane 38 125.0 0.005
24b
DVE:MA CDC13 24 33.5 0.036

St:DMCP CC14 38 37.0 0.093
t 24b
St:.A CC1 38 125.0 0.216















CHAPTER IV

1 + 2 Cycloadditions. The Diels-Alder Reaction


The use of cyclopropene derivatives ad dienophiles in Diels-

Alder reactions is a process of synthetic utility as well as

mechanistic interest. The parent hydrocarbon reacts rapidly and

quantitatively with cyclopentadiene at 00 to form the tricyclic

adduct (I). The reaction is stereospecific and only the endo isomer





+ OOC
H H o HH

H H
(I)

is formed.26 Substitution at the double bond positions of cyclo-

propene affects the stability and reactivity of the olefin but does

little to alter the course of the Diels-Alder reaction. A single

substituent in the 3-position directs the geometry of the product

but as long as C-3 carries only one substituent the reaction proceeds

smoothly and the adducts have the endo configuration. Thus,

3-methylcyclopropene adds to cyclopentadiene to give only the endo-

anti isomer -nd none of the other three possibilities, while 3,3-

dimethylcyclopropene does not add even at 100. Battiste investigated

the reactivity of a number of derivatives and found that geminally

substituted cyclopropens ae unreactive ard any diene.27
substituted cyclopropenes are unreactive toward any diene.








In 1968 Tobey demonstrated that all tetrahalocyclopropenes

undergo facile 1,4 addition to cyclopentadiene, furan, and 1,3-
28
butadiene.28 His experiments indicate that electronic rather than

steric effects would account for the observed results. Again the

products were all of endo configuration. The adducts from the

cyclic dienes, however, were rearranged bicyclic derivatives (II).




C1 + 1 - 1 >
C+ Cl C

\ Z Lc i C l -Cl C


Cl Cl_
/"L





0 Cl

Cl

C1l

II

Sprouse reacted cyclopropene and some of its derivatives with

1,3-diphenylisobenzofuran (III) and obtained adducts with exo-

stereochemistry.29 Sargent also obtained an exo adduct when he

reacted 1,2-bis(trifluoromethyl)-3,3-difluorocyclopropene with
30 29
cyclopentadiene. Sprouse found that reaction of tetrachloro-

cyclopropene with CIII) gave a stable tricyclic adduct (IV) which

could be rearranged to a structure like (II) upon heating. Adduct

IV also had the exo stereochemistry like the other adducts from

diphenylisobenzofuran.








Ph



Ph


Cl 0
CC1

c Ci Ci
Cl Cl


0



Cl Cl


The only example of a geminally disubstituted cyclopropene

derivative giving rise to the exclusive formation of an exo adduct

with any diene other than III is the report of Monti and Bertrand
14
in 1970.1 They reacted cyclopentadiene with the ethylene ketal of

3-acetyl-3-methylcyclopropene at 1400 in a sealed tube and obtained

exo-3-methyl-3-acetyltricyclo[3.2.1.0 2' -6-octene ethylene ketal.


0


CH3

C-CH
+o 3
U-


CH 3


The observation by Baucom and Butler8 that the reaction of

3,3-dimethoxycyclopropene with III yielded the exo adduct was

consistent with the work of Sprouse. Baucom also obtained evidence

for adduct formation between dimethoxycyclopropenc and a-pyronel

but this was not confirmed.


If3CO OCH 3

A,1


/0CH

OCH3


+ III







A. Reaction with Butadiene Derivatives

When dimetho:.xycyclopropene was mixed with an excess of butadiene,

isoprene, or 2,3-dimethyl butadiene and the solution allowed to

react at room temperature for several days, the expected adducts

were formed in high yield. Because of the symmetry of the system,

only one isomer was possible in each case. After evaporating excess

diene, the products were analyzed by gas chromatography and the

adduct peak was greater than 90 percent of the crude reaction mixture.

Pure samples were obtained by preparative GC while none of the by-

products could be isolated in sufficient quantity for identification.



CH 30 OCH3 R R R ICH3
CO OCX P ^________ ^l DCH3

1 FF:2 CH 3
Re

V R=R2=H

VI PR=R2=CH3

VII R1=H; R2 CH3



Figure 5 shows the IMR spectrum of the dimethylbutadiene adduct.

The two methoxy groups are different at 3.3 and 3.46. The ring

protons are centered at 2.16. The singlet at 1.66 is due to the

methyl groups in positions 3 and 4, while the bridgehead protons

give a multiple at 1.36. If the methyl groups are replaced by

hydrogen as in the butadiene adduct, the vinyl protons give a broad

singlet at 5.56 and the peak due to the methylene protons is shifted

just slightly downfield. (Note shaded areas in Fig. 5.)





























































I I






-0





rn mrn
I I
u u


C,


















O
a
















E-
c










oo
cs













U











O
o















oJ
u


0 )









rQ.
0)






o 0
0.
I)





S a)
o n
1C t-









Q.





















































I I







0 0
u- -r


a)





a
0i
0u

4::
Eu
0
I. C
0~
E

0U
a)
a









In the spectrum of the adduct with isoprene (Fig. 6) both of

these groups are present on the double bond and the resulting increase

in coupling produces much broader peaks. Upon expanding the scale,

the two different sets of protons at positions 2 and 5 can be

separated.

The mass spectra of these adducts indicated that analogous

fragmentation pathways were followed as would be expected. The

usual procedure for interpreting mass spectra involves localizing

the charge on the hetero atom and then considering logical reorgan-

ization of the resulting ion-radical. The spectra of these adducts

showed an abundant molecular ion which would be predicted by this

procedure of analysis. Clearly the weakest bond in every case is

the 1,7 bond and initial 0-cleavage of this bond in A leads to the

very stable ion-radical B.



I OCH3 1

> ~,CH3
R2 OCH3 R %CH3

A B
molecular ion

From here, however, it is difficult to rationalize the remainder of

the spectrum. The base peak in every case corresponded to the loss

of a dimethoxymethyl radical. There was also a fairly abundant

peak corresponding to the loss of a methyl radical and fragments

attributable to consecutive reactions of the resulting ester ion

were detected.








These processes were more readily accommodated by considering

an alternate representation of the ion-radical, C, which is actually

a resonance form of B.



CH DCH <
R
P2 'CH 2 \CH3
B C

Using these two structures, then, the major features of the spectra

follow very logical rearrangement pathways. The base peak is

adequately rationalized from C as involving a 1,3 hydrogen migration

to give an allylic radical, D, and then a homolytic cleavage of the

6,7 bond to lose the requisite radical and give an ion with extended

conjugation, E. The metastable peak for the transition C (or D) ->

+ 1 .+ H
OCHL -> *3- 3
JCH 2 3
H OCH3 H JCH3
C D E


was just detectable, but it was present. The loss of a methyl

radical from C is also a very logical process and many features

of the spectrum arise from further reaction of the ester ion (scheme

4)--including alternate pathways to the base-peak ion. Further,

the metastable peaks (indicated by in scheme 4) observed for the

proposed transitions are prominent and offer further evidence for

the proposed sequence of reactions. The relative abundances of the

ions resulting from the proposed transitions are given for each adduct

in Table IV.













-CH "1+ R1
OCH 3 3- -CH OH

P CH3 3
c 3 F


-HCO2CH3 CO

R2



+ -OCH3
J R2
m/e 59 E


C/: -CH4


// ,


R

H I



Scheme 4. Mass Spectral Fragmentation Pattern for Diels-Alder
Adducts Between Dimethoxycyclopropene and Butadienes









Table IV Relative Abundances of Mass Spectrum Peaks from
Adducts Between Dimethoxycyclopropene and Butadiene
2,3-Dimethylbutadiene (VI), and Isoprene (VII).

Relative Abundance

Transition Ion V VI

molecular ion B or C 66 63

loss of methyl radical F 15 32

loss of CH3 then CH30H G 27 30

loss of C3H 02 E 100 100

loss of H2 from base peak H 60 20

loss of CH4 from base peak I 7 43

loss of cyclohexadiene J 67 33


Diels-Alder
(V) ,




VII

49

29

25

100

37

41

33


The reactivity of these adducts was partially evaluated in

a preliminary series of experiments. One interesting reaction

would be hydrolysis of the acetal to give 7-norcarenone derivatives

which would be a unique series of cyclopropanones. This was attempted

by refluxing the 2,3-dimethylbutadiene adduct with aqueous dioxane

containing a drop of sulfuric acid. After eight hours under these

conditions, the adduct was recovered unchanged.

Hydrogenation of the butadiene adduct over palladium on carbon

led to cleavage of one of the exocyclic bonds of the cyclopropane

ring as well as saturation of the olefin. The major product identified

from this reaction was the methyl ester of cyclohexane carboxylic acid.

Likewise attempted bromination of the double bond with bromine

in carbon tetrachloride ruptured the cyclopropane ring as evidenced

by the loss of the signal at 1.36 in the UIMP and the evolution of










hydrogen bromide gas frcm the reaction mixture. The isoprene adduct

was used for this reaction and none of the products were identified.

When the reaction of dimethoxycyclopropene with l-methoxy-

butadiene (50 percent excess) was attempted in THF, there was no

indication of adduct formation. However, mixing the two liquid

reactants (threefold excess of diene) without solvent resulted

in high conversion to the adduct. Analysis of the product fraction

after distillation (by gas chromatography) showed two components

in the approximate ratio of 30:70. Isolation of the major component

by preparative GC gave a product whose I.1R, IR, and elemental analysis

were completely consistent with the expected adduct. In the NMR,


CH3 O CH3 >

+ OCH3

OCH3 OCH3


the methoxy group at position 2 gave a peak which coincided with the

low-field methoxy of the ketal function. The corresponding methine

proton in position 2 appeared as a poorly resolved multiple at

3.9 to 4.06. All of the other absorptions were shifted downfield

by one to two parts per million from their counterparts in the

adducts obtained from the butadiene hydrocarbons.

The mass spectrum, while not inconsistent with the proposed

structure, was difficult to rationalize. No molecular ion was

evident, but this was not unexpected. The species corresponding

to the molecular ion of the hydrocarbon derivatives should readily

lose a methoxy radical. Further loss of molecular hydrogen to









give the ion M could account for the highest m/e value exceeding

20 percent of the base peak. The base peak appeared at m/e 105

and the second most abundant peak (89 percent of base) was at

m/e 77. Since m/e 77 corresponds to C6H the base peak is likely

OCH3


-OCH -H
3 3


OCH3 ICH 3 CH3
K L 3 1.1


to be the oxonium ion 1, although its formation from M is difficult

to rationalize. There was an abundant metastable peak at 56.5

which arises from the transition -- -CJH + CO. The remaining
b 5
features of the spectrum indicated that a variety of competing

reactions were occurring and that no single fragmentation pathway

was followed.


m =5 6.6 I +
+ I + CO


m/e 105 m/e 77
base peak

Another possible e::planation for the difficulty in interpreting

the mass spectrum is that the adduct is not thermally stable.

Operating techniques for the mass spectrometer involve storage of

the sample in a reservoir at about 2000 before injection into the

ionization chamber. Thermal stability of samples must therefore

be considered and additional samples of the adduct were required

in order to investigate this possibility.










When another analysis of the distilled product was made on the

gas chromatograph, a lower rate of flow was used for the carrier

gas. Four components were observed this time which were sufficiently

well separated to allow isolation. Peak four was the major component

(66 percent) and was determined to be 2,7,7-trimethoxy-3-norcarene.

Peaks one and two were suspected decomposition products while

peak three might possibly be an isomer of the adduct.

All of the mixture available was subjected to preparative gas

chromatography and these four components were collected. There was

not enough of peak one to permit its identification. Peak two was

identified as methyl benzoate by its NMR and IR spectra. Peak three

was not obtained in pure form and could not be identified. Its

infrared spectrum gave a carbonyl absorbance but comparison with

that of peak two indicated that this was due to methyl benzoate

as an impurity. Instead of the characteristic three or four bands
-i
for a ketal between 1000 and 1200 cm. there was only a single
-i
broad absorption centered at 1100 cm. In the NMR there were the

expected absorbances due to methyl benzoate. In addition there were

the following:

6-value Protons Description

5.93 1 multiple

3.33 2 singlet

2.68-1.30 3 broad multiple

1.18-0.96 2 singlet









These results proved that peak three is not an isomer of the

adduct but assignment of a structure cannot be made without further

information.

The thermal stability of 2,7,7-trimethoxy-3-norcarene was checked

by reinjection of a sample of peak four into the gas chromatograph.

In addition to unchanged adduct there were "lights" and peaks

corresponding to one and two. There was none of the compound giving

peak three, however.

Thus, thermal decomposition of 2,7,7-trimethoxy-3-norcarene

produced methyl benzoate as a major product. The main features

of the mass spectrum were then easily explained by considering

this ester to be the species actually being analyzed.








B. Reaction With Cyclic Dienes

Diels-Alder reactions with cyclic dienes could conceivably lead

to derivatives of cyclopropyl norbornene, possibly with exo- stereo-

chemistry if the analogy to the diphenylisobenzofuran study were

followed. Such adduction seemed feasible since the reactivity of


CH30 OCH3
3^3


to


room
temp.


700


No Reaction


CH 30
3


OCH

and


CH30 OCH3
3 3


OCH
I 3


0


)CH3


Scheme I'. Diels-Alder Reactions of Dimethoxycyclopropene with
Cyclic Dienes


(dark)








32
cyclopentadiene (toward maleic anhydride) is much greater than any

of the other dienes used in our work and in the light of recent

reports of successful adduct formation using other geminally substi-

tuted cyclopropenes. However, when dimethoxycyclopropene and cyclo-

pentadiene were allowed to stand together at room temperature no

reaction occurred at all. At 700 the two appeared to react indepen-

dently as the IIR showed a change in the diene pattern, presumably

due to formation of dicyclopentadiene, and the characteristic peaks

of the dimethox:ycyclopropene dimer appeared. There was no indication

of adduct formation. Apparently steric factors inhibit this reaction

as proposed for other systems.

Because of the very facile reaction observed by Eaucom with

diphenylisobenzofuran, it seemed reasonable to expect dimethoxycyclo-

propene to react with furan as well. Eut when a solution of the

cyclopropene in furan was stored in the dark for several days at

room temperature, there was again no evidence for adduct formation.

Instead, there was almost quantitative dimerization of the dimethoxy-

cyclopropene.

Diels-Alder reaction of dimethoxycyclopropene with tetracyclone

would be expected to give first the bridged carbonyl adduct VIII.

This structure should be readily decarbonylated to give the norcara-

diene IX or possibly its valence isomer X. Compounds with structures

VIII or IX should show two different U-IF. signals for the methoxy

groups and a singlet for the ring protons. The tropone ketal should

show two equivalent protons in the vinyl region but possibly a

















Ph =o






H


Ph 4


OCH

SOCH3










3 Ph


Scheme 5. Diels-Alder Reaction of Dimethoxycyclopropene with Tetra-
cyclone


VIII








singlet for the methoxy groups. The actual spectrum (Fig. 7) of

the product isolated showed a six-proton singlet at 36 for the

nethoxy groups and an AB quartet between 6.0 and 6.36 as well as

a 20-proton multiple in the aromatic region. This was clearly

inconsistent with any of the expected structures. Further, elemental

analysis corresponded to a 1:1 adduct without the loss of carbon

monoxide while the infrared spectrum was free of carbonyl absorption.

Treating a sample of this adduct with aqueous acetone and a trace

of acid resulted in the loss of methoxy signals in the 11l1F, and the
-1
appearance of an intense carbonyl peak at 1780 cm. in the infrared

spectrum. The IMIR spectrum also showed a widely separated AB

quartet with a coupling constant, JAB, of 5.5 cps. One doublet

of this system was centered at 7.456 and the other at 6.106.

These observations are consistent with a structure in which

an opened cyclopropene has added across the carbonyl of the tetra-

cyclone. Two modes of addition appear possible, giving either XI

or XII.

SH OCH3

CH3 OCH3
CH30 H

Ph4 Ph4

XI XII


Acid catalyzed hydrolysis of these compounds would give derivatives

of a 3(2H)-furanone (XIa) and a 2(5H)-furanone (XIIa) respectively.



















Ci
0


SC-,


4-'



C J
-U

Cl
a
I o C

0





C-,







C)
4-',
Cl
s 3,~
cl


E

-~L.





C)





Ci

-,







0r.











L.














H h Phe4


XIa XIIa




Spectral data for the unsubstituted furanones, available from

the literature, are tabulated below and compared with the data obtained

for the hydrolysis product.
Chemical Shift, 6
Compound IR absorbance A-protons B-protons AB' cps

3(2H)-furanone, XIa33 1706 5.70 8.23 2.5
34 35
2(5H)-furanone, XIIa 1775, 17453 7.6335 6.15 5.2

H/drolyzed adduct 1780 7.45 6.10 5.5


On the basis of these comparisons, structure XII can be assigned to

the adduct. A similar structure was proposed by Breslow36 in the

reaction of cycloheptenocyclopropene with tetracyclone, but no mechanism

was suggested for its formation. The only spectral data relevant

to the present situation were the infrared absorbances which included
-i
a strong band at 1765 cm.-

Unsubstituted cyclopropenone reacted with tetracyclone in

methylene chloride in the normal Diels-Alder fashion to give tropone
37
after decarbonylation of the initial adduct. Thus, it appears

that the steric effect imposed by geminal substitution in dimethoxy-

cyclopropene is sufficient to inhibit its reaction with tetracyclone

while the carbonyl group of this dine is sufficiently reactive to

allow an alternate reaction pathway to become operative.








37
The dimerization of cyclopropenone as well as its reaction

with diphenylcyclopropenone gave 2(5H)-furanone derivatives. The

mechanism suggested for this process was nucleophilic attack on the

carbonyl carbon of cyclopropenone, followed by 1,2 cleavage and
Ph Ph
S^ -0 Ph- 0
pY \ / /10 --"

Ph /--
.Ph Ph xC=-C-H Ph H
H

cyclization. Operation of a similar mechanism in the tetracyclone

reaction with dimethoxycyclopropene would involve nucleophilic

attack on the ketal carbon accompanied by 1,3 cleavage and then

cyclization.



CH30 0 OCH3 OCH 3

-C +-OCH > OCH
/I' 1 HC=CH
Ph Ph/ H
P4Ph
4 H

Alternatively, since tetracyclone has an electron-deficient

carbonyl group, the mechanism could be viewed as nucleophilic attack

by the olefin on that carbonyl carbon, followed by 1,3 bond cleavage

and cyclization.

OCH

3 C 3

t D OCH 3 C
\ / >- >


Ph4


















CH 0 OCH3


R


+ I


R


(OCH3


Scheme 7. Diels-Alder Reaction of Dimethox',c,clopropene with
Tetrazine


0'H 3


XIII



j2


,C H 3
SH3

OCH.









A third possibility is that the 1,3 bond of dinethoxycyclopropene

is cleaved first to give either a dipolar of a diradical species

which is then trapped by the tetracyclone carbonyl system. It is

not possible to distinguish the actual mechanism from the data

available from these experiments.

Another interesting possibility for using dimethoxycyclopropene

as a synthetic intermediate is its reaction with tetrazines. The

initial adduct (XIII) should readily lose nitrogen to give the

diazanorcaradiene XIV or possibly the diazatropone ketal XV.

Hydrolysis of this ketal would then give a route to diazatropone.
38
Sauer and Hinrichs found that cyclopropene and 1,2,3-tri-

phenylcyclopropene both added readily to tetrazines to give the

diazanorcaradiene products. Rearrangement to the diazacyclohepta-

triene system was observed for the triphenyl cyclopropene adduct.

Reaction of dimethoxycyclopropene was attempted with two

tetrazines. Preliminary 1MR evidence indicated that for the case

of 3,6-dicarbomethoxy-s-tetrazine, the diazanorcaradiene was present

in the reaction mixture but the complexity of the mixture and the

paucity of material available did not permit its isolation. There

is no indication of adduct formation at all when 3,6-diphenyltetrazine

and dimetho:,xycyclopropene were reacted for 18 hours in refluxing

methylene chloride.

Tetrachlorocyclopentadiene affords the interesting possibility

of reacting with dimethoxycyclopropene in two ways. Diels-Alder

reaction could lead to the adduct XVI.












CH30 OCH3
3^v3


+ .1


OCH3
OCH 3


In addition, if the methylene protons of the diene were sufficiently

active, a very unusual fulvene derivative could result from reaction

CH+ 3i -- > + 14CI + H 2 CH OH




at the ketal function. The formrjation of fulvenes has been observed

for reactions of tetrachlorocyclopentadiene with aromatic aldehydes.


C1l4--


+ ArCHO


Cl -- --=Ar
C y1A


However, when the two reagents were allowed to stand for several

days at room temperature in'just enough benzene-d6 to effect solution,

the tetrachlorocyclopentadiene was recovered unchanged while the

dimethoxycyclopropene decomposed.















CHAPTER V

2+2 Cycloaddition Reactions


A few reactions are known where cyclopropenes undergo cyclo-

additions with formation of a four-membered ring. The initial

adducts often rearrange, however, and only secondary products are

actually isolated. 1 When 1,3,3-trimethylcyclopropene was irradiated

with ultraviolet light in acetone solution containing benzophenone

as sensitizer, the two isomeric tricyclic dimers were isolated in

15 percent yield.40


H C HC3 H3 C CH
3 3 HG CH

HHhv 3 t 3
HC (C 6H5) 2CO H 3C-
H365-2 3 H3

H3C CH3 H3C CH3



Baucom found, however, that contrary to the reaction of 1,3,3-

trimethylcyclopropene, the dimerization of 3,3-dimethoxycyclopropene

was not a photolvtic process but was a thermal reaction probably

proceeding by a two-step mechanism.7

Since the dimerization appears to be a very facile process

undr mild conditions, and in the light of recent observations in

the condensed phase, other cycloaddition reactions of dimethoxycyclo-

propene were studied. A number of interesting and novel systems








could be approached in this manner by the proper choice of olefin.

The charge transfer studies discussed earlier indicate that

dimethoxycyclopropene is an electron-deficient olefin. Its facile

reaction with electron-rich dienes in the Diels-Alder reaction

supports this conclusion. However, the formation of a dimer via

2+2 cycloaddition requires that it react as an electron-rich species

also. In addition, the unusual reaction of dimethoxycyclopropene

with tetracyclone suggests that the presence of a hetero atom in

the reacting system is important. Therefore, 2+2 cycloaddition

reactions were investigated using an electron-deficient carbonyl

species (hexafluoroacetone), electron-rich olefins Cenamines) and

electron-poor olefins (triazolinediones and methyl acetylenedicarbox-

ylate. The results indicate that dimethoxycyclopropene does not

undergo 2+2 cycloaddition reactions with carbon-carbon double bonds

regardless of their electronic character, but that appropriately

activated hetero-olefins react readily.


A. Reaction with Hexafluoroacetone

This reagent is electrophilic in nature and two modes of addition

to dimethox:ycyclopropene could be predicted. The first is analogous

to the tetracyclone reaction, involving opening of the cyclopropene

ring.


CH30 OCH3
CH 30 OCH 0 CH 0 OCH
3 3 Lp 3H
A + CF -C-C 3--> E > 0
N P ----
+ C-CF3 H F
C3 CF_
^ --- ^" r^ .on









With the tetracyclone adduct in mind, the I;MR spectrum of a compound

with such a structure would be predicted to show an AB quartet for

the vinyl protons and a singlet for the methoxy groups. The tri-

fluoromethyl groups are also equivalent and should appear as a

singlet in the F19 1-,R spectrum. Hydrolysis of such a compound

should proceed readily to give 5-bis(trifluoromethyl)-2(5H)-furanone.

Alternatively, the reaction could retain the three -mebered

ring and terminate by closure at C-2 to give a bicyclic system.


CHO /OCH3
CHCH 3 -
SCH3 0

CH30 3 CH30 C-F3 H2 CF3
C 3 CF3




A compound of this structure should have an IM.R spectrum indicative

of non-equivalent methoxy groups and also non-equivalent trifluoro-

methyl groups. The ring protons are also different and coupling

would be expected. Hydrolysis of the ketal would produce a cyclo-

propanone and therefore should be difficult to achieve.

%hen dimetho:ycyclopropene and excess he::afluoroacetone were

mixed and allowed to react for three days at room temperature

there was smooth and complete conversion to a single compound.

The small amount of impurity present was easily removed by treatment

with silica gel.

The NMP. spectrum (Fig. 8) gave the following data:



































0
o
r- U





'0
C


0
o 0)
r- U



-4

X



0
I





0
a,




U-
0



o
0



0
o 0)


i I


~tL -
-- --- ` .-- I-. ~ -- -- .

---~---------



--7









6 Protons Description

5.66 1 multiple

'1.86 1 broad singlet

3.81 3 singlet

3.50 3 singlet


These absorbances are consistent with the bicyclic structure and the

multiplet at 5.666 was assigned to the ring proton at C-4 because

it is possible to realize long-range coupling with the trifluoro-

methyl groups. The broad singlet at 4.866 was assigned to the other

ring proton and the other singlets were attributed to non-equivalent

methoxy groups.
19
The F 19 IR spectrum indicated two non-equivalent trifluoromethyl

groups which experience coupling with each other and with something

else, probably one or more protons. No other features of the structure

could be determined.
-i
In the infrared, there were absorbances between 1300 and 1500 cm.-
-i
characteristic of trifluoromethyl groups and between 1000 and 1200 cm.

for the ketal chromophore. There was also an intense absorbance at
-i
1670 cm.1 which could be in the carbonyl range. An aldehyde could

result from rearrangement of the bicyclic product:


IOCH3 c Cr H3OCH3

CrF 43 OCH C> CH H
JT 3 CF 0









However, no aldehyde proton was observed in the IHP. and if this were

the structure, the methox:y groups would be equivalent.

The mass spectrum was very clean, showing only two fragments

with an intensity greater than 20 percent of the base peak. A

very small molecular ion peak was detected at m/e 266. The base peak

occurred at m/e 197 corresponding to the loss of a trifluoromethyl

radical. Other fragments were due to loss of a metho:-:y radical

(m/e 235) and to the trifluoromethyl ion (m/e 69).

Hydrolysis of a sample of the adduct was also attempted in

order to provide additional structural information. After 17 hours

in refluxing aqueous dio:-:ane containing a trace of acid, the adduct

was recovered unchanged.

Thus, the second mode of addition appears to be operative and

the adduct produced was 3,3-bis(trifluoromethyl)-5,5-dimethoxy-2-

oxabicyclo[2.1.0] pentane:


CH30, 5OCH3



u



H q 3/CF3
CF3









B. Reaction with Enamines

Enamines are electron-rich olefins and should be ideal for reaction

with an electron-deficient system such as dimetho::ycyclopropene. A

number of cyclopropenone derivatives have been reacted with a variety

of enemies to give both "C-C" and "C-N" insertion.1-4 The

former, observed only in low yield, results from 2+2 cycloaddition

and then reopening of the four-membered ring. The latter involves

cleavage of the 1,2 bond of the cyclopropenone and insertion into

the C-1i bond of the enamine. Eicher and Bohm obtained stable

ketaines from the reaction of phenyl-methyl-cyclopropenone and

diphenylcyclopropenone with acyclic enamines. '5,6 These last

reactions require the participation of the carbonyl oxygen of the

cyclopropenone and would be impossible for dimethoxycyclopropene.

However, reactions analogous to the studies of Dreiding would provide

interesting results regardless of the mode of insertion and the effect

of the ketal instead of a ketone could be valuable from a theoretical

point of view.

Two enamines were selected for reaction with dimethoxycyclroropene.

They were N,IN-diethylstyrylamine and l-(2-methyl-l-propenyl)-pyrrolidine.


Ph\ CHI H
H C =C CH "1 /

C2H15 C113 I


The reactions were conducted neat, at 530, under nitrogen. In the case

of the styrylamine, decomposition of the dimethoxycyclopropene occurred




6L4



but the enamine was unaffected. Both the pyrrolidine enamine and

the dimethoxycyclopropene remained after 16 hours of reaction time

in the second case.

These results indicate that dimethoxycyclopropene does not

add to electron-rich olefins.








C. Reaction with Triazolinediones

4-Phenyl-A -1,2, '-triazoline-3,5-dione (XVII) is a cis-locked

azodicarbonyl compound and a very electrophilic cyclophile.7

Cycloaddition of XVII with simple nonoolefins is limited to 1,2-
"7
addition leading to diazetidines. For example,7 the diazetidine

XVIII was obtained from PhTD and indene.


+ o -
I
Ph
XV II


,0



0 J -Ph
0


0


)> J-Ph

0
XVIII

The proposed dipolar intermediate was trapped with water.

Reaction of XVII with alkenylidenecyclopropanes (e.g., XIX)

gave two 1:1 adducts in stereochemically pure form. A concerted

cycloaddition across carbon atoms 2 and 4 was implicated.


H ,C6H5
3 C 6 5 ,C3
l> C=C 4-+
2 3 "H3
H H


.0O

I -Ph

0


HC CH







133C Ci3 0
H2C I- Ph





0
C CH
65^
^"s


03








The same products could arise from a dipolar intermediate such as

XX by two different modes of isomerizing the cyclopropyl cation

portion, but their data argue against its intervention.

Ph

=C


R =-- 0

Ph

XX


Dimetho>ycyclopropene, reacting as a simple olefin in a 2+2

cycloaddition,would give the very unusual diazetidine XXI. The steric


CH3 OCH


+ :'. I---


CH 3:

CH 3


requirements for this adduct should be no more severe than those of

the dimer. Participation of a dipolar intermediate such as XXII

would very likely lead to rearranged products resulting from opening

of the cyclopropyl ring (XXIII).


H 30 OCH3






0
I

Ph

:XX I


CH3O OCH,
3\ 3
HC=CH-C
|I +
-- > 1-- _h
n- P


Ph


OC H


CH3




Fh


XX I II








The alternate ring closure at the oxygen atom would produce a cyclo-

heptadiene with one trans double bond--a prohibitively strained system.

When XVII was reacted with dimethoxycyclopropene, however,

neither of these adducts was formed. Instead, a spontaneous copoly-

merization reaction occurred giving a product with a number average

molecular weight of 12L'4 as determined by vapor phase osmometry.

Elemental analysis was inconsistent with either a 1:1 or a 2:1

copolymer composition. Wagener has obtained evidence for incor-

poration of additional triazolinedione into the copolymer, presumably

by nucleophilic attack of the dipolar intermediate on the monomer.

Postulating a product consisting of four units of 1:1 copolymer and

one extra phenyltriazolinedione molecule results in a molecular

weight of 1275 and elemental analysis is consistent with this composition.

Assignment of the structure of the copolymer rests mainly on
-l
the infrared spectrum. Carbonyl peaks at 1720 and 1780 cm.- indicated

that reaction had occurred through both the nitrogen and the oxygen

of the triazolinedione moiety. In unreacted XVII the carbonyl
50 -1
double appears at 1780 and 1760 cm. Reaction through the oxygen

atom leads to the formation of a C-N double bond in the product and

an absorbance at 1620 cm.- can be assigned to this chromophore.51

Also observed are bands at 1655 cm.-1 (C-C double bond, cis disub-

stituted) and the characteristic bands for a ketal between 1000 and

1200.

The !IMR spectrum provides much less information. There is a

broad absorption around 7.56 and a very broad doublet centered at 3.56.

The relative areas of these two regions is 8:6.








Thus, the most likely structure for the major portion of the

product is C OCH
3 \/ 3
CH=CH-C
N-lJ
0< i--- -


Ph

with some units going through both nitrogen atoms and with about one

extra XVII unit for each four units of the copolymer.

The dipolar intermediate in the copolymerization of XVII and

ethyl vinyl ether has been trapped with acetone and with cyclo-.
51
hexanone. No evidence for a similar termolecular adduct could

be detected when XVII and dimethoxycyclopropene were reacted in acetone.

OCH



H-CH 3 / C3
produced. CH









O JN--0 C 330
CL3 3s

I I
















I II 3 -3 CHIV
Ph Ph
XXI I

Trapping of the 1,5 dipole (XXIII) leading to a seven-membered ring

in the product was also considered possible but only polymer was

produced. C

S OCOCH3 N=J




X CH3 XXIV
Ph









It was felt that the less reactive N-nethyltriazolinedione (XXIV)

night be a more effective substrate for interception of a dipolar

intermediate and this possibility was investigated. To provide a

basis for comparison with the PhTD e::periments, this reaction was

also run in methylene chloride. The results in both solvents were

the same. There was no evidence for monomeric species in either

case, although the yield of purified polymer product was lower than

in the XVII study. Molecular weights were determined by VPO and

found to be about 990 when methylene chloride was solvent and 760

when the reaction was run in acetone. Elemental analyses suggested

the monomer ratio in the produce was 1.3:1 (XXIV:dimethoxycyclopropene)

in both instances and spectroscopic analyses were consistent with

the ring-opened structure proposed earlier.








D. Reaction with Dimethylacetylenedicarboxylate

The cycloaddition of dimethoxycyclopropene in dimethylacetylene-

dicarboxylate was attempted as both a thermal and a photolytic

process. Because of the interesting possibility for a 2:1 adduct,

excess acetylenedicarboxylate was used and the reactions were run

without solvent. Two different routes can be visualized, depending

upon whether or not the initial 1:1 adduct forms a four-merrbered ring.

S. CH CH CH

R-C-C-R + 3 3 R --

OCH3 R R
CH O OCH
C3 O3 R-C-C-R

R = -CO CH3 R
23 /


R-C-C-R +


CH 3 OCH
3 A


OCH
CH30 OCH3 HCCH-d 3
UCH3
-\- 3
R-C=C-R
P-C=C-R








OC H3
S P.-C-C-iR ,n
-;;:~^ / \np


The thermal reaction was patterned after the room temperature dimer-

izations in which the reagents are allowed to stand together for

several days under ordinary laboratory conditions. The photolytic




71




process was attempted by exposing the mixture to the sunlight in

a quartz UV cell. In both cases the course of the reaction was

followed by periodic sampling for !;I-R analysis and in both experiments

decomposition of the dimethoxycyclopropene was observed with no

indication at all of adduct formation. It is likely that traces

of free acid catalyzed the decomposition.













CHAPTER VI

Reactions With Amines


The observation by Baucom that nucleophiles apparently add

very readily to dimetho::ycyclopropene led him to the preparation

of 1 ,-dimethoxy-2-dimethylaminocyclopropane.


CH30 O'CH3

s3i


+ (CH3)2JH >


CH OCH3
3 \ N(CH3

1I(CH3 2


If a similar reaction could be effected using diallylamine

as the nucleophile, the very unusual 1,6 diene produced would afford

the possibility of producing a polymer with pendant cyclopropane groups.


CH3 OCH3


+ (CH2CHCH-CH2 2H


'OCH3
3









Modification of polymer properties might then be expected to arise

by cross-linking through or chemical reactions of the very reactive

cyclopropyl system.

However, exposure of these reagents to conditions that led

to quantitative production of the dinethylaminocyclopropane failed

to give any indication at all of the addition compound. Diallyl-

aminocyclopropane would be expected to show a multiple near 1.36

as well as a methoxy doublett". Neither of these features was

observed in the spectrum of the crude reaction mixture while typical

decomposition patterns dominated. Distillation of this material

failed to produce any fractions indicative of the anticipated

course of reaction.

This result raised the question of why the two amines should

react so differently and suggested that reaction with a variety

of amines might reveal something of the electronic character of

dimethoxycyclopropene.

When dimetho::ycyclopropene was added to excess diethylamine

and the mixture stored at room temperature for several days, the

major product formed (60 percent) and the only one isolated was 1,1-

dimethoxy-2-diethylarriinocyclopropane. The pure product was isolated

by preparative gas chromatography but there was not enough sample

available to allow collection of the two observed minor components.


CH30^ ___CH3 CHOOCH
CH30 CH3 + (C2115)2rH CH3 CH


N(C2H5 2










The NMR spectrum (Figure 9) gave the following data:


6-value Protons Description

3.42 3 singlet

3.32 3 singlet

2.89-2.51 4 quadruplet

2.14-1.90 1 multiple

1.18-0.94 6 triplet

1.05-0.75 2 multiple


The two singlets at 3.42 and 3.326 were assigned to the nonequiv-

alent methoxy protons. The quadruplet at 2.706 and the triplet

at 1.066 were assigned to the diethylamino protons. The absorbances

at 2.12 and 0.906 were assigned to the cyclopropyl ring protons.

The mass spectral analysis was completely consistent with the

proposed structure and produced a fragmentation pattern analogous

to that observed by Baucom for the dimethylamino derivative.

Continuation of the series to di-n-propylamine was next attempted

and the course of the reaction was found to be considerably more

complex. As in the case of diallylamine, the crude reaction mixture

did not appear to contain any of the addition product. However, this

time one fraction from the product distillation showed INMR absorption

which could be assigned to the nonequivalent methoxy groups.

Analysis of this fraction by gas chromatography indicated two major

components comprised about 85 percent of the mixture and that these

components were present in a ratio of 40:60. Pure samples of each

one were then obtained by preparative gas chromatography.

































a'


0
0

-1
u

0

c

E


-4

a'


CrI


X
0


ul




o
- '





0



u



0,












L.









The first component gave absorptions in the NMR at 3.45 and 3.356

for the non-equivalent methoxy groups and a one-proton multiple at

2.08 characteristic of the lone proton at C-2 of the cyclopropane

ring. The absorbance of the geminal protons on the ring overlapped

with the characteristic multiplets for ths propyl groups and could

be detected only by analysis of the integration areas. The infrared

spectrum of this component was almost superimposable on that of the

diethl,,laminocyclopropane which confirmed that it was 1,1-dimethoxy:

2-di-n-propylaminocyclopropene.


CH30 3 CH 3 OCHa new

+ (CH3-CH2-CH22 H + compound
N(C3H7 )2



The NtTR spectrum (Figure 10) of the second component gave the

following data:


6-value Protons Description

3.65 3 singlet

2.97-2.62 2 multiple

2.56-2.17 6 multiple

1.78-1.17 4 multiple

1.07-0.66 6 multiple


In the infrared spectrum there was an intense carbonyl absorption

at 5.72u which was interpreted with the corroboration of the C-0

stretching at 8.30p as being indicative of an ester. Elemental

analysis gave an empirical formula of C 1H2 102 and in the mass

















































r-
C:





fn


Cl






0

*.





a
Q.




. O



o 0
















L*



L.









spectral analysis there was a molecular ion at m/e 187 (13 percent

of the base peak). The base peak was at m/e 158 and another fragment

appeared at in/e 114 which was 65 percent of the base. These data

indicated that the second component of the mixture was n1,iI-di-n-propyl-

amino-f-alanine methyl ester (X:XV).


(e) (d) (c)
CH 3-CH -CH
3X2 -CH -CH -OCH

CH3-CH2-CH2 (c) (b) (a)
(e) (d) (c)

xxv


Assignments of the UMR absorbances of Figure 10 to the protons of

this structure can be made as follows:


6-value Protons Assignment

3.62 3 a

2.97-2.62 2 b

2.59-2.17 6 c

1.67-1.17 4 d

1.07-0.66 6 e


The mass spectral fragmentation pattern arises from the expected

two modes of cleaving a C-C bond next to the nitrogen which is

directing the fragmentation to the virtual exclusion of all other

possibilities because of its greater electronegativity.

The change in reactivity through this series of amines cannot

be attributed to differences in basicity since all are of nearly

equal value. Aromatic amines are considerably less basic than











2 1
CH- CII -CH "'C-'C CH C-OCH
3 2 2 2 2 3

3H7
m/e 187
-C HO i
-C3H502 1 2 -CH
25

C3} I7 +
i=CH2 CH -=I-CH -CH -C-OCH
/32 C12 2 3
C3 7 3
m/e 114 m/e 158
(base)


aliphatic amines so a study of their reactivity could provide additional

information about the chemistry of dimethoxycyclopropene.

Diphenylamine was selected for first evaluation since examination

of the products should be less complicated due to the presence of

only aromatic protons in the IJ.R. Because this amine is a solid,

a solvent (CH Cl ) was required. The amine was used in only 10 percent

molar excess due to its low bulk density and the resulting high

volume of material required.

Analysis of the crude reaction product by NMR did not reveal

the presence of cyclopropyl protons, but some adduct formation was

indicated by the characteristic absorbances of two non-equivalent

methoxy groups. A large new singlet at 3.186 was also observed

along with several smaller peaks.

Separation of this ni:-:ture by silica gel chromatography was

attempted but when the sample was placed on the column it immediately

experienced a vigorous exothermic reaction. Development of the

column yielded a weight recovery of approximately 65 percent which










appeared to be mostly a single component plus some free diphenylamine.

A second chromatography yielded pure samples of this component.

The NMR spectrum (Figure 11) gave the following data:


6-value Protons Description

7.32-6.65 10 multiple

4.15-3.80 2 multiple

3.51 3 singlet

2.75-2.38 2 multiple


This appeared to also be an amino acid ester--the methyl ester of

N,N-diphenyl-B-alanine. The low-field absorbances were assigned

to the aromatic protons and the singlet at 3.56 to the methyl group

of the ester. The two 2-proton multiplets form an A 2B pattern

which would be expected for the four methylene protons of structure

XXIV.




N-CH2-CH 2--OCH3
C6H5
65
:,::: IV

The infrared spectrum showed carbonyl absorption at 5.721 and strong
0
asymmetrical C-C-0 stretching at 8.50U indicating an ester. Elemental

analysis gave an empirical formula of C16 H17NO and the mass spectral

analysis was consistent with the proposed structure. The molecular

ion at m/e 255 was 40 percent of the base peak which appeared

at m/e 182. The next largest fragment was 16 percent of the base

at m/e 77 (C6.H ) and all others were less than 10 percent.
b 5











































C)
C,



r-i
'-









0
C



o C















C)
>.

















ro









e-I



o 3


L-4


I
-o









C 6H5 +. 0 C3H50 C6H5, t
R "0 -CH 6 =CH2
-CH2- CH2-C-OCH > /UCH
/ 2 3 / 2
C6H5 C6H5
m/e 255 m/e 182


Identification of the intermediate which was isomerized on

silica gel was next attempted using the second half of the same

mixture. The first procedure tried was to cool a pentane solution

of the material to -780. The oil which separated confirmed that

the non-equivalent methoxy groups were present without cyclopropyl

protons but no purification of components was realized. After a

few days, these samples were blended back together and the NIHR

spectrum was taken. Very little of the absorbances assigned to

the methoxy groups remained and the singlet at 3.186 dominated

the spectrum.

This material was dissolved in methanol and then divided into

two portions. The first portion was allowed to stand at room temper-

ature in an open flask to slowly evaporate solvent in an effort to

effect crystallization. No crystals ever formed and when all of

the solvent had evaporated the resulting oil was again analyzed

by NMR. The result was a pure sample of !I,N-diphenyl-6-alanine

methyl ester with no sign of free diphenylamine.

The second portion of the methanol solution was treated with

a few drops of water and an oil separated. It was dried under

vacuum and analyzed by IM'iR (Figure 12). Absorbances due to the

alanine ester were obvious. An absorbance at 2.30-1.936 appeared

to be one portion of a second A2 2 pattern. The second portion




















































2.0


Figure 12. NMR Spectrum of the Intermediate Leading to
1J,NJ-diphenyl-6-alanine









would be expected in the range of 4.10 to 3.406 but absorbances due

to the alanine ester also appear in this range. However, if that

portion of the integration attributable to the known compound was

subtracted from the total integration in this area, the difference

was exactly equal to the integration of the 2.30-1.936 multiple.

Thus, another A2B2 system seemed likely. If the singlet at 3.185

was due only to a compound containing this A2B2 system, then this

singlet was equivalent to nine protons. In the aromatic region the

absorbance was due to the S-alanine derivative and some free diphenyl-

amine as well as the unknown intermediate. Subtracting the known

compounds from the total left thirteen aromatic protons for the

intermediate which implied that it contained only one diphenylamiino

group. When this IMIR sample was poured onto silica gel and then

extracted with ether the next day, N,II-diphenyl-3-alanine methyl

ester was again obtained with some contamination by the free amine.

In the infrared spectrum of the sample rich in the intermediate there

were few absorbances not present in the alanine derivative although

some intensities were different. Weak absorbances at 8.90, 10.55,

and 10.95p and a strong absorbance at 13.30p with a shoulder at 13.55p

appeared to be unique with the unknown intermediate. The carbonyl

absorption was considerably less intense as would be expected if

the intermediate lacked this chromophore. The absorbances due to

the aromatic system were only slightly less intense.

No further purification of this sample could be effected and

continued manipulation saw it all be slowly converted to the -

alanine ester. Thus, no positive identification of the intermediate










was possible. One structure which could satisfy the observed phenomena

is the ortho ester XXVI although its formation would be difficult

to rationalize.


C6 5 OCH
N-CH -CH -OCH
2 22 3
C6H5 OCH3
XXVI

Baucom observed the formation of methyl orthoacrylatel7 under

certain conditions during the preparation of dimethoxycyclopropene

and found that the orthoester moiety gave a nine-proton singlet

at 3.226. In the present case the predominant single occurs at

3.186.

Although structure XXVI is consistent with the main features

of the spectra, its formation would require a very unlikely series

of reactions. First, a portion of the dimethoxycyclopropene would

have to react with diphenylamine in an exchange reaction of some

sort at the ketal center to produce methanol. Then all of the

methanol would have to react with additional dimethoxycyclopropene

to give methylorthoacrylate. This reaction has been observed

but a number of other products are also obtained. Addition of di-

phenylamine to the methyl orthoacrylate52 would then lead to compound

XXVI. The probability of such a sequence occurring is very low and

there was also no evidence for any of the by-products to be expected

from them.

A more likely mechanism for the formation of the alanine ester

involves a ketene acetal as the intermediate. The simple addition











H3CO OCH3 H3CO OCH3 H CO CH
R "H + 7 >

2H 2 H




reaction is nucleophilic attack at C-i by the electron pair on

nitrogen with production of negative charge at C-2 where protonation

completes the addition. Alternatively, 1,3 cleavage could occur

followed by reorganization of the electron system and protonation

at C-I to give the ketene acetal.


CH 0 OCH CH 0
3 3 3 H Uj CH 3C- C H-
-r I' ?, 2r-CH a2-a Hsr
2 F. 2 1 --U 2Cr H
S2>\H H OCH3



Hydrolysis of the ketene acetal would then give the alanine esters

observed. One possible reason for the difference in reactivity in

the series of aliphatic amines is the increasing bulk of the

substituents which could hinder the approach to C-2 to complete

the simple addition process.

Corey53 reported that the lJMR spectrum of l,l-dimetho::yethylene

consisted of two singlets at 3.08 and 3.466 in the ratio of 3:1.

These absorbances are in the general region of the spectrum observed

for the intermediate but more detailed comparison is not possible

without a purer sample of the compound.

The possibility of further reaction of the cyclopropyl amines

was also considered. At the same time it was possible to investigate

the case of adding amines to methyl orthoacrylate. A sample of










dimethoxycyclopropene containing eighteen mole percent methyl

orthoacrylate was treated with excess dimethylamine for four days

at room temperature. Following evaporation of the amine, the crude

reaction product was analyzed by NMR. The only absorbances observed

were those for l,l-dimethoxy-2-dimethylaminocyclopropane and eighteen

mole percent methyl orthoacrylate.

Diphenylamine was then added to the U11R tube to attempt a

ring opening reaction. No change at all was observed after 3 hours

at 40-450 and after eighteen hours at 60-650 there was only partial

reaction of the orthoacrylate. Thus, the cyclopropyl amines appear

to be stable once formed and it seems unlikely that methyl ortho-

acrylate would add amines under the conditions where formation of

the alanine esters was observed.
















CHAPTER VII

Summary and Conclusions


The objectives of this research program were (1) to improve

and expand the reactions leading to 3,3-dimethoxycyclopropene,

(2) to further evaluate its physical and spectral properties, and

(3) to establish its chemical reactivity toward a variety of systems.

Significant improvement was realized in both yield and operational

convenience by modifications in the reported procedures. Attempts

to expand the scope of the reactions involved indicated that they

are very specific for the reagents used and that other materials

behave quite differently in the same system.

The ultraviolet spectrum of dimethoxycyclopropene shows no

absorbance above 210 mp. The observed spectrum was a triplet

centered at 187 with = 1670. The NMR absorbance for the
max
cyclopropene protons was found to be sensitive to the electronic

nature of the solvent and charge transfer studies were conducted

using the technique of Hanna and Ashbaugh. The results of these

studies indicated that dimethoxycyclopropene is an electron-deficient

olefin in that weak complexes were formed with electron-rich species.

The donors in this case were sty,'rene and divir.,rl ether. The use

of more powerful donors such as enamines would be a logical extension

of this work. It would be especially interesting to see if stronger

charge transfer complexation followed the use of this particular










type of donor since enamines failed to give chemical reactions with

dimetlhoycyclopropene.

As a dienophile, dimethoxycyclopropene is only moderately

reactive. Adduct formation was realized in excellent yield with

acyclic diencs, but an extended reaction time of a week or more

was required. No reaction at all could be effected using cyclic

dienes, presumably due to the steric interference of the geminal

substitution. The unusual adduct observed to form between tetra-

cyclone and dimethoxycyclopropene indicates that the olefin is also

an electron source since the most likely mechanism for its formation

involves nucleophilic attack on the carbonyl carbon of the diene.

Formation of a normal Diels-Alder adduct was indicated but not

proved in the reaction of dimethoxycyclopropene with 3,6-dicarbo-

methoxy-s-tetrazine. The tricyclic adduct in this case is [3.2.2.0]

instead of [3.2.1.0] which should ease the steric requirements,

but it is also interesting to note that the diene system includes

hetero atoms. The importance of this feature would be an interesting

program of study.

Dimerization of dimetho::ycyclopropene, observed early in the

program, is still the only successful 2+2 cycloaddition reaction

with a carbon-carbon double bond. The product of the reaction with

hexafluoroacetone is a four-membered ring from what is formally a

2+2 cycloaddition reaction, but the most likely mechanism is not

an electrocyclic process. As in the case of tetracyclone, the

mechanism probably involves nucleophilic attack on the carbonyl

group. In the hexafluoroacetone reaction, however, the cyclopropane










ring is preserved since ring closure at C-2 occurs instead of

bond cleavage.

Cycloaddition with electron-rich olefins should be a facile

process for dimethoxycyclopropene if the conclusions about its

electron-deficient character are correct. The lack of reactivity

toward enamines was therefore unexpected. The reason for this

result is probably steric rather than electronic, however, since

no adduction was observed with electron-poor species either.

Dimethylacetylenedicarboxylate gave no indication of reaction at

all. With phenyl triazolinedione, a very electrophilic cyclophile,

none of the diazetidine which would result from cycloaddition was

observed. Instead a copolymer was formed, presumably by nucleophilic

attack of the olefin on the triazolinedione and coupling of the

resulting dipolar intermediate. It is interesting to note also

that again the reactive center contains a hetero atom. Other

reactive species involving oxygen, nitrogen, or sulfur should

provide an enlightening area of investigation. Possibly effective

reagents include isocyanates, thioketones, diazoalkanes, isothio-

cyanates, and diimides.

Nucleophilic addition of secondary amines to dimethoxycyclc-

propene supports the conclusion that it is an electron--deficient

olefin. Simple addition was observed for lower aliphatic amines

to give 1,l-dimethoxy-2-dialkylaminocyclopropanes. As the size of

the substituents on the amine increased, however, a second process

became increasingly important. This process involved destruction

of the three-membered ring and formation of 1N,1-dialkylalanine




Full Text

PAGE 1

SYNTHETIC AND MECHANISTIC STUDIES OF 3 , 3-DIMETHOXYCYCLOPROPENE By RUDOLPH MILTON ALBERT, JR. A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 1973

PAGE 2

This Dissertation is Dedicated to Carol and Elizabeth , Laura , Robert , Rebecca and Daniel

PAGE 3

ACKNOWLEDGEMENTS I wish to express my deep appreciation to Dr. G.B. Butler for his friendship and guidance as my research director. The advice and suggestions of the other members of my supervisory committee are also acknowledged with gratitude. Hy colleagues in the laboratory made working more pleasant and for this I am grateful. A special note of thanks is extended to Dr. Richard L. Veazey for many valuable discussions and helpful suggestions. I wish also to thank the management of the Organic Chemicals Group, Glidden-Durkee Division of the SCM Corporation and especially Mr. R.P.T. Young for a very generous leave of absence which made it possible to come here at all. The patience and skill of my typist, Mrs. Jimmie McLeod, was of inestimable value in the preparation of this manuscript and I would like to give special recognition to her. Finally, I wish to give a special expression of gratitude to my family. All have sacrificed much to make the completion of this program possible and their abiding love has been a source of strength and determination. Ill

PAGE 4

TABLE OF CONTENTS Page ACKNOWLEDGEMENTS iii LIST OF TABLES vi LIST OF FIGURES vii ABSTRACT viii CHAPTER I. INTRODUCTION 1 II. STUDIES RELATED TO THE PREPARATION OF 3,3-DIMETHOXYCYCLOPROPENE 7 A. Reaction By-Products 10 B. Extension to Other Systems 14 C. Preparation of Other Ketals 16 D. Cyclization of the Ethylene Ketal 19 E. Improved Procedure for Preparation of Dimethoxycyclopropene 23 F. Other Cyclization Processes 25 III. CHARGE TRANSFER COMPLEXATION 26 IV. 4+2 CYCLOADDITION. THE DIELS ALDER REACTION ... 33 A. Reaction with Butadiene Derivatives 36 B. Reaction with Cyclic Dienes 47 V. 2+2 CYCLOADDITION REACTIONS 57 A. Reaction with Hexafluoroacetone 53 B. Reaction v,'ith Enamines 53 C. Reaction with Triazolinediones 65 D. Reaction with Dimethylacetylenedicarboxylate . 70 VI. REACTIONS WITH AMINES 72 IV

PAGE 5

Page VII. SUMMARY AND CONCLUSIONS 88 VIII. EXPERIMENTAL 92 A. Equipment and Data 92 B. Synthesis 9U C. Procedures and Data for Charge Transfer Complex Studies 130 REFERENCES CITED 13*+ BIOGRAPHICAL SKETCH 138

PAGE 6

LIST OF TABLES Table Page I. Mass Spectral Fragments from 3 ,3-Ethylenedioxycyclopropane 20 II. Variation of the Chemical Shift of the Ring Protons of 3,3-Dimethoxycyclopropene with Solvent 27 III. MR Determination of the Equilibrium Constants of Charge Transfer Complexes 32 IV. Relative Abundances of Mass Spectrum Peaks from Diels Alder Adduct 42 V. Data for Dimethoxycyclopropene-Styrene Complex Study 132 VI. Data for Dimethoxycyclopropene-Divinyl Ether Complex Study 133 vi

PAGE 7

LIST OF FIGURES figure Page 1 NMR Spectrum of C H BrCl 12 2 Ultraviolet Spectrum of 3,3-Dimethoxycyclopropene . . 28 3 NMR Study of the Complex Between Dimethoxycyclopropene and Styrene 30 4 NMR Study of the Complex Between Dimethoxycyclopropene and Divinyl Ether 31 5 NMR Spectrum of the Dimethoxycyclopropene-Dimethylbutadiene Adduct 37 6 NMR Spectrum of Dimethoxycyclopropene-Isoprene Adduct 38 7 W-IR Spectrum of the Adduct Formed Between Dimethoxycyclopropene and Tetracyclone 51 8 NMR Spectrum of Dimethoxycyclopropene-Hexafluoroacetone Adduct 60 9 NMR Spectrum of l,l-Dimethoxy-2-diethylaminocyclQpropane 75 10 NMR Spectrum of N,N-dipropyl-B-alanine 77 11 NMR Spectrum of N,N-diphenyl-B-alanine 81 12 NMR Spectrum of the Intermediate Leading to N,N-diphenylB-alanine 83 VI 1

PAGE 8

Abstract of Dissertation Presented to the Graduate Council of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy SYNTHETIC AND MECHANISTIC STUDIES OF 3 ,3-DIMETHOXYCYCLOPROPENE By Rudolph Milton Albert, Jr. August, 1973 Chairm.an: Dr. George B. Butler Major Department: Chemistry The preparation of 3 ,3-dimethoxycyclopropene in pure form vras first reported in 1970. It was synthesized by treating l-bromo-3chloro-2,2-dimethoxypropane with potassium amide in liquid ammonia. The precursor was obtained by the acid-catalyzed reaction of 2,3dichloropropene with N-bromosuccinimide and methanol. This research program has been directed toward expanding and improving the reactions leading to dimethoxycyclopropene as well as toward defining the reactivity of this unusual intermediate. Direct synthesis of different ketals was attem.pted by substituting other alcohols for methanol. Bromine addition was a major competing reaction. Likewise, 2,3-dibromopropene gave only 1,2 ,2,3-tetrabromopropane when reacted with N-bromosuccinimide and methanol. Successful preparation of the ethylene ketal of l-bromo-3chloro-2-propanone was realized by acid-catalyzed exchange of ethylene glycol on the dimethyl ketal. Cyclization of this intermediate was also attempted since the resulting cyclopropene might be more reactive than dimethoxycyclopropene in situations where steric crowding is viii

PAGE 9

critical. Two products were obtained from its reaction with potassium amide, however. One was the expected cyclopropene which could not be purified. The second product was obtained in pure form and was identified as the cyclopropane derivative 4,7-dioxaspiro[2 .U]heptane. Significant improvement in both yield and operational convenience was realized by modifications in the reaction procedures. Instead of adding the ketal intermediate to the amide solution, potassium amide was prepared in one flask and then transferred by means of nitrogen pressure to a second flask containing the intermediate in additional ammonia. Dimethoxycyclopropene was found to be an electrondeficient olefin that forms weak charge transfer complexes with styrene and with divinyl ether. In Diels-Alder reactions, dimethoxycyclopropene reacted quantitatively with derivatives of butadiene to give the expected 7,7dimethoxy-3-norcarenes. With cyclic dienes, such as cyclopentadiene and furan, reaction was inhibited by steric interaction. In both these cases only dimerization of dimethoxycyclopropene was observed. Its reaction with tetracyclone gave the ketal of a 2C5H)-furanone by addition of the opened cyclopropene system to the carbonyl function of the diene. Cycloaddition reactions with olefins to give cyclobutane products were unsuccessful with simple carbon-carbon double bonds. Both electron-rich (enamines) and electron-poor (acetylene dicarboxylate) olefins were completely unreactive. Species containing a hetero atom did react, however. Hexafluoroacetone gave a bicyclic adduct by IX

PAGE 10

formal 2+2 cycloaddition of the olefin and the carbonyl group. With 4-phenyl-l,2,4-triazoline-3,5-dione and the corresponding 4-niethyl derivative the products were copolymers which did not retain the cyclopropyl system. Reaction of dimethoxycyclopropene with diethylamine gave only l,l-dimethoxy-2-diethylaminocyclopropane . With dipropylamine , however, N,N-dipropyl-3-alanine methyl ester was obtained along with the expected cyclopropylamine . When diphenylamine was used there was no cyclopropylamine observed and only the methyl ester of N,N-diphenyl-B-alanine was recovered. An intermediate was detected but could not be purified due to the ease with which it was converted to the alanine derivative. A m.echanism involving a ketene acetal as the intermediate is consistent with the data available .

PAGE 11

CHAPTER I Introduction Although cyclopropene and many of its derivatives have been available for many years, cyclopropene chemistry has been the object of considerable interest only in the past two decades. The upsurge of activity which took place in the mid-fifties was due to three main factors. These factors were (1) the developments in carbene chemistry which aided synthesis of cyclopropene systems, (2) the applications of molecular orbital theory which made attack on theoretical problems a desirable goal, and (3) the discovery of the cyclopropene system in natural products. Many systems were designed and studied, but cyclopropene derivatives unsubstituted in the double bond positions are relatively 2 uncommon. The parent hydrocarbon was first synthesized in 1922 3 but It was not until the facile preparation by Closs in 1966 that it was used for extensive studies. Geminal dimethyl cyclopropene was prepared by Closs in 1961 by base catalyzed thermal decomposition of 3-methyl-2-butenal tosylhydrazone . This procedure also yielded the very unstable 3-methylcyclopropene although in poor yield. Studies of the chemistry of these derivatives is limited and deal mainly with isomerization reactions. A kinetic study of the thermal isomerization of 3-methyl-, 3,3-dimethyl, 1,3,3-triraethyl, and 1,2,3,3-tetramethylcyclopropene showed that increased substitution caused an increase in thermal stability.

PAGE 12

Synthesis of 3,3-diphenylcyclopropene was observed upon irrad7 iation of 3 ,3-diphenyl-3H-pyrazole but rearrangement to 3-phenylindene occui'red on gas chromatography. ^\ Ph ^ -Ph Ph Ph A mixture of the halogenated derivatives, 3-chloro-, 3 ,3-dichloroand 1 ,3-dichlorocyclopropene is produced by reduction of tetrachlorog cyclopropene with tri-n-butyltin hydride. Breslow used 3-chloro9 cyclopropene in the preparation of unsubstituted cyclopropenyl cation 8 and 3 ,3-dichloroc3''clopropene was hydrolyzed to cyclopropenone . The mixture of reduction products was used as a probe into the mechanism of Diels -Alder adduction of perhalocyclopropenes but no adducts with 3 ,3-dichlorocyclopropene were observed. Bertrand and Monti devised the following scheme for the preparation of cyclopropenyl ketones: f^3 HCBr R-CH=C-C^CH Zn ^ J^ > R-CH-C-CECH j:'' > R-CH-C-C=CH tBuOK < y HOAc < \ Br Br Br H He ++ > glycol f3 Br "^H 1. tBuOK DMSO 2. H^O -> CH, -i-C"3

PAGE 13

They studied the thermal rearrangement of this ketone to 3-acetyl12 13 1-methylcyclopropene and also the Diels-Alder adducts which it 14 and its ethylene ketal form with cyclopentadiene. These adducts are to be described in Chapter IV. In the course of studies directed toward the synthesis of cyclopropenone , Pratt prepared 3,3-dimethoxycyclopropene and presumably cyclopropenone itself for the first time. His plan was to extrude the cyclopropene derivative from the Diels-Alder adduct formed between tropone dimethylketal and dimethyl acetylenedicarboxylate. Purification of the adduct was a major problem in this procedure and it was , in fact , during an attempted distillation that the formation of dimethoxycyclopropene was first suggested. Subsequent experiments indicated that this "batch pyrolysis" was the preferred process for the extrusion reaction. OCH, OCH„ I 9°2^"3 CO2CH3 ^"3°2 CH3O2C OCH, OCH, A OjCHg CH3(\^OCH3 °2C"3

PAGE 14

Although he was never able to isolate dimethoxycyclopropene in pure form, he did report NMR and IR spectra which support its presence among his reaction products. Attempts were made to determine the molecular weight by mass spectrometry and by a gas density method but neither gave satisfactory results. Reaction with cyclopentadiene was attempted and the lack of reactivity was attributed to inadvertent hydrolysis to cyclopropenone. The evidence presented for cyclopropenone formation was by inference only and a later evaluation of 1 R this work did not claim its preparation. In the course of attempting to synthesize compounds potentially capable of charge -transfer coraplexation prior to polymerization, Baucom discovered an easy and relatively simple procedure for the 17 preparation of l-bromo-3-chloro-2,2-dimethoxypropane. Subsequent investigation of this reagent led to the successful isolation of pure 3,3-dimethoxycyclopropene. (Scheme I) The reactivity of this ketal was investigated in a preliminary 18 series of experiments. Baucom found that it gave a Diels-Alder adduct with 1,3-diphenylisobenzofuran but not with t etracy clone . In the latter case, a product was isolated which was the result of 17 solvent carbon tetrachloride addition to the dimethoxycyclopropene. CH 0. .OCH_ _ ^ /CH 3 >r 3 CH — / ^ OCH ^ ' 7 cci Ps / . > CHC1=CH-C+ -CCl^ ^ I 3 OCH3 NK OCH. I 3 CHC1=CH-C-0CH^ I 3 CCI3

PAGE 15

.i'-c CH2=C-CH2C1 + I -Br + CH^OH CHgOH V°7 BrCHj— C-CHjCl CH3O ^OCH, ?S. HjCCl ^CH^Br KNH, KH, CH3O f)CH3 0_^ 2 CH3O OCH3 KNH, NH, HC^CH -CI CH3O ncH3 HC=CH Scheme 1. Synthesis of 3,3-Dimethoxycyclopropene 17 When a pure sample of dimethoxycyclopropene was added to • 19 deuterium oxide, it was hydrolyzed immediately to cyclopropenone . No attempt was made, however, to isolate the pure ketone. In an attempt to prepare a Diels-Alder adduct with a-pyrone, the major product isolated was a dimer of dimethoxycyclopropene. Preliminary evidence was also obtained for the formation of the Diels-Alder adduct but this was not confirmed. CH^O^ ^OCHg /^^ ^o-^^o CH3O ^OCHg CH^Cr ^CH3

PAGE 16

Treatment of l-bromo-3-chloro-2 ,2-dimethoxypropane with potassium tert-butoxide gave only l,l-dimethoxy-2-t-butoxycyclopropane, even in experiments designed to trap the cyclopropene as it was formed. This suggested that dimethoxycyclopropene experiences facile attack by nucleophilic reagents. The addition of other nucleophiles was, therefore , of interest and Baucom reacted the ketal with excess dimethylamine and did, indeed, obtain the expected dimethylamino derivative. The results of these experiments indicate that 3, 3 -dimethoxycyclopropene is a highly reactive reagent possessing a somewhat electron-deficient double bond. Its ready availability in relatively large quantity suggests its use as a source of cyclopropenone and also as a means of incorporating a cyclopropanone moiety into previously inaccessible systems by preliminary adduct formation and subsequent hydrolysis to the free carbonyl function. The present research program was undertaken to investigate this system on several fronts. First, the reactions leading to 3,3-dimethoxycyclopropene are unique and their generality was to be established. Second, only NMR and IR properties of dimethoxycyclopropene were reported by Baucom and other characteristics of this reagent were desired. The third and most general objective was to establish the chemical reactivity of this compound toward a variety of systems and consequently to suggest the most efficient use of 3 ,3-dimethoxycyclopropene as a synthetic reagent and as a possible monomer in copolymer preparations.

PAGE 17

CHAPTER II Studies Related to the Preparation of 3 ,3-Diinethoxycyclopropene The series of reactions leading to 3,3-dimethoxycyclopropene which Baucom discovered involves rather unique procedures and one objective of this research program was to evaluate the scope of these reactions. Also, while the chemical processes involved cire the same as those of the original work, significant improvements in yield and operational convenience have resulted from modifications in procedures. When Baucom added N-bromosuccinimide to 2,3-dichloropropene in refluxing methanol containing a catalytic amount of sulfuric acid, l-bromo-3-chloro-2,2-dimethoxypropane was obtained in up to 17 40 percent yield as a pure crystalline material. A Second major reaction product was proposed to be l-bromo-2,2,3-trichloropropane. The proposed sequence of reactions is shown in scheme 2. Because of the complexity of side reactions possible, the SS-UO percent yield of the desired ketal was thought to be quite good and incapable of significant improvement without resorting to very expensive or complex procedures. One possibility which was investigated, however, was blowing air through the reacting mixture. This would serve to remove some of the by-product HCl and to possibly air-oxidize Br~ and promote further reaction. A definite increase in yield k<^s noted when this

PAGE 18

i -Br + H \v. J NH + Br "\ ?1 Br + CH =C-CH CI -C-( -> BrCH2-C-CH2Cl + CI BrCH2-(!:-CH2Cl + MeOH 91 BrCH -C-CH CI OCH3 + H CI BrCH -C-CH CI 6CH3 + CH OH o OCH. I 3 -> BrCH„-C-CH^Cl + CI 2 4CH, 2 + H CI BrCH -C-CH CI + Cl" > BrCH^CCl^CH^Cl Scheme 2. Reaction of 2 ,3-Dichloropropene with NBS/Methanol 17 was done but a subsequent series of reactions revealed that the effect was due to a decrease in reaction temperature and not to any action of the air itself. Thus, modification of Baucom's procedure resulted in routine yields of around 65 percent by slow addition of NBS at 25-30° without the use of air-blowing. Slight increases could be realized to 5-10° but the time required for each portion of NBS to react increased and made the overall process too

PAGE 19

lengthy. One experiment using perchloric acid as catalyst gave a slightly higher yield but the added hazard of the reagent outweighed this advantage. One explanation for the effect of lower temperature is that solvolysis of l-bromo-2-methoxy-2,3-dichloropropane (reaction 4 of scheme 2) is slower. This would decrease the rate of formation of by-product HCl and favor production of the intermediate (reaction 3) over the formation of l-brorao-2,2,3-trichloropropane (reaction 5). If this were the case, then very rapid addition of NBS with subsequent rapid formation of the intermediate would fxirther favor the desired reaction. It had been felt that rapid addition of the reagent would have an adverse effect on the yield by favoring Br addition and at the same time make control of the reaction exotherra difficult. However, experience with the process began to indicate that if the initial temperature were low, an adequate ice bath should control the temperature and allow an evaluation of the yield. Thus, N-bromosuccinimide was added as rapidly as possible to 2,3-dichloropropene in cold methanol containing a catalytic amount of sulfuric acid. The temperature, originally at -10°, rose to -3° but quickly fell to -10° again. This temperature was held for three hours and then gradually warmed to room temperature overnight as the ice/acetone bath melted and equilibrated. The yield of l-bromo-3-chloro-2,2-dimethoxypropane was 71 percent of theory. Wliile the increase in yield may be moderate, the added operational convenience is significant. Typically, the apparatus can be assembled and the reagents charged in the last half-hour of the day. After

PAGE 20

10 stirring overnight , the product is isolated and purified by standard procedures. The older procedure required addition times of two to five hours and then storage overnight before work-up. A. Reaction By-Products An evaluation of the by-products was also attempted in an effort to better understand the reactions taking place. Analysis by MR of the by-product mixture revealed that very little direct bromination takes place. A sample of the oil was fractionally distilled under reduced pressure and 85 percent of it was collected as a single fraction (b.p. 103-104°/58 mm. Hg). Chromatography on silica gel removed the last traces of impurity and gave what was apparently pure compound. The mass spectrum gave a molecular ion peak at m/e 224with the proper isotopic distribution ratio for C H BrCl„. The base peak at m/e 145 corresponds to the expected loss of a bromine radical and further fragmentation by loss of HCl gives an abundant peak at m/e 109 (55 percent of base peak). These observations are consistent with the structure proposed in scheme 2 but do not allow any conclusions about the structure. The major inconsistency in correlating the spectrum with the proposed structure is an abundant (53 percent) peak at m/e 83 with isotopic distribution ratio for CHCl . Rearrangement pathways leading to this ion are difficult to rationalize. The only fragments retaining bromine are relatively small (12 percent) and appear at m/e 189 and 175 corresponding to loss of -CI and -CH^Cl respectively. The loss of these radicals is most easily visualized

PAGE 21

11 as a-cleavage of a molecular ion bearing bromine on the central carbon atom. Br" II CICH^-C-Cl Br* ClCHj-C-Cl ((H2CI CICH2-C-CH CI The NMR spectrum of this sample is also inconsistent with the suggested l-brorao-2,2,3-trichloropropane as seen in Figure 1. The three singlets appear to have a ratio of 2:1:1 and l-brorao1,2,3-trichloropropane v/as considered a possibility. This structure, however, should have a more complex spectrum and greater differences in the chemical shifts of the methylene and the methine protons. The observed spectrum could arise if the rotation about one of the C-C bonds were sufficiently hindered to place the two protons affected in different environments. There is no indication of such hindrance in either the product ketal or the dibromodichloropropane which was prepared by addition of bromine in carbon tetrachloride to 2,3-dichloropropene , however. CH2=CC1-CH2C1 .+ Br2/CCl^ -> BrCH^-CClBr-CH CI It appears likely, therefore, that two by-products are produced that differ only in the positions of the bromine atom and one of the chlorines. This condition could arise by attack of Cl~ with equal facility on either end of a bromonium ion intermediate.

PAGE 22

12 J I — ^ — — •-— — I — '—' — ' — ^ _« i—i ' ' — ; 7.0 6.0 5.0 PPM ((5) 4.0 Figure 1. NMR Spectrum of C H BrCl

PAGE 23

13 CI CI K'^^^^-2 CI Br CI CI I ClCHj-C-CHjCl Br ? BrCH„-C-CH^Cl It is interesting to note that there is very little, if any, of the corresponding attack at C-1 by CH.OH to give l-methoxy-2-brorao~ 2 , 3 -d i ch loropropane .

PAGE 24

14 B. Extension to Other Systems Extension of these reactions to other systems could serve three purposes. First, their scope could be evaluated to determine whether they are general or specific processes. Second, a comparison of the reactivity of various derivatives would be a probe of the mechanism of the cyclization reaction (viz., 1,3-dibromoand 1 ,3-dichlorovs. l-bromo-3-chloro-2,2-dimethoxypropane) . Third, the reactivity of other ketals (especially the ethylene ketal) might be favored over the dimethyl derivative for steric reasons. Application of the NBS/methanol reaction to 2,3-dibromopropene would yield l,3-dibromo-2 ,2-dimethoxypropane if the same sequence as scheme 2 were followed. Such was not to be, however, as the dichloro and dibromo olefins were found to react differently in our system. When 2,3-dibromopropene was reacted in methanol with NBS, the major product had only a sharp singlet at U.265 in the NMR spectrum. This is very near to the chemical shift of the -CH Br protons of the starting olefin which indicates that the major reaction involved is probably direct bromination: Br CH^Br-C=CH_ + NBS + CK OH h"^ ^ BrCH -C-CH Br Br Br Similarly, substitution of ethylene glycol for methanol failed to yield the ethylene ketal directly. Analysis of the crude reaction mixture indicated that some ketal formation did occur but that direct bromination was again the major reaction pathway. Similar results have been observed using anhydrous ethanol as solvent. These results point to a high degree of specificity in this

PAGE 25

15 reaction which requires chlorine on the starting olefin (although probably only on C-2) and only methanol for efficient solvolysis of the intermediates. These factors as well as elucidation of the reaction mechanism require a separate program of study.

PAGE 26

16 C. Preparation of Other Ketals Successful preparation of l-bromo-3-chloro-2,2-ethylenedioxy~ propane was achieved in essentially quantitative yield by acidcatalyzed exchange of ethylene glycol on the dimethoxy derivative. CH Q OCH„ 6 \/ H-^ \/ BrCH -C-CH CI + HOCH CH^OH ^^^^ > BrCH -C-CH CI + 2 CH^OH The new ketal is a colorless liquid (in. p. 10°) boiling at 70° under 1.2 mm. Hg pressure. In the NMR spectrum there are two 2-proton singlets at 3.525 and 3.476 and one ^--proton singlet at 4.056. The infrared spectrum and elemental analysis are consistent with the proposed structure. The mass spectrum shows no parent peak. The base peak at m/e 121 shows an unusual isotopic abundance ratio of 1.65 to 1 since it can arise from two sources, one with bromine and one with chlorine (scheme 3). The ions are at m/e 49 and 93 and correspond to CH CI and CH Br respectively, but the expected metastable peaks are not observed to confirm that they arise from the oxonium ion species as indicated in the scheme. Further extension of this process to the sulfur analog was next attempted. When ethane dithiol was substituted for ethylene glycol and the mixture was heated on the steam bath, a very vigorous exothermic reaction initiated which erupted from the flask. Due to the extremely disagreeable conditions which resulted, this reaction was not repeated, but there seems to be little doubt that 1-bromo3-chloro-2,2-ethylenedithiopropane could be prepared by this route

PAGE 27

17 -CH^Br>o C-CH^Cl m/e 121 \> -sv "^0=C-CH CI m/e 77 -CO + CH^Cl m/e 49 «-c-ci BrCH^-C-CHjCl m/e 165 sv BrCH2-C=0'*' m/e 121 -CO t BrCHj"^ m/e 93 Scheme 3. Mass Spectral Fragmentation Pattern for 1-Bromo3-chloro-2,2-ethylenedioxypropane if its production were required and the proper precautions were taken to control the vigor of the reaction. Three other ketals were prepcur>ed by more conventional routes from the appropriate ketones. These were CH.O^ OCH, o\ / 3 ClCHj-C-CHjCl SI. CH30. CH, ClCHj-C-CH^Cl BrCH^-C-CH^Br

PAGE 28

18 A fourth, l,3-dibromo-2,2-ethylenedioxypropane, would complete the series but was not prepared. The dimethyl ketals were prepared by refluxing the ketone with methanol containing a trace of acid catalyst . Water of reaction was removed by passing the condensed solvent through a bed of molecularsieve before returning it to the reaction flask. In the case of the glycol reaction, a benzene azeotrope was adequate for removing the water. Because these ketals were difficult to obtain and are available in very limited quantity, the comparison of their reactivity in producing cyclopropene derivatives was not attempted. This study should be revived when an acceptable material balance on the cyclization process is realized or when a dependable method of derivitizing all cyclopropene products becomes available .

PAGE 29

19 D. Cyclization of the Ethylene Ketal Since l-bromo-3-chloro-2,2-ethylenedioxypropane was readily available in large quantity, its cyclization was attempted using the procedures available. The reaction was conducted as described by Baucom for the diraethoxy derivative and a yield of distilled product of 13 percent was obtained. Analysis of the material by NMR showed three singlets at 7.72, H.Ol, and 0.905 with integration intensities of 15, mO, and 110 respectively. The absorbance at 7.726 was assigned to the cyclopropene ring protons of the expected product and the signal at 4.01 is very near that of the methylene H^ ^H protons of the ketal moiety in the starting material C+.OSfi), The intensity of this absorbance, however, should only be twice that of the 7.726 absorbance or thirty units. Since the excess was exactly equal to the intensity of the absorbance at 0.906, the presence of 20 a cyclopropane derivative was suggested although none had ever H H been detected in the dimethoxy reactions cind its preparation would be difficult to rationalize. Relative area ratios indicated that the product mixtiire was 20 percent cyclopropene and 80 percent cyclopropane .

PAGE 30

20 Treatment of the mixture with water removed all of the cyclopropene but left the cyclopropane unaffected. A pure sample of the colorless liquid was obtained by preparative gas chromatography. In the NMR there were two singlets of equal intensity at 4-. 016 and at 0.915. The mass spectrum showed an abundant molecular ion at m/e 100 which had 74 percent the intensity of the base peak at m/e 99, Each of these ions, then, apparently experiences a similar fragmentation pattern as indicated by the following table. Table I. Mass Spectral Fragments from 3,3-Ethylenedioxycyclopropane m/e

PAGE 31

21 A metastable peak at 18.7 is only slightly less intense and corresponds to the transition m/e 99 to 43 by loss of C H 0. A characteristic feature of the infrared spectra of dioxolane derivatives is a group of four or five peaks between 1000 and 1200 cm. . This pattern is prominent in the spectrum of l-brorao~ 3-chloro-2,2-ethylenedioxypropane with peaks at 1030, 1095, 1130, and IIUO cm. . The spectrum of the cyclization product, however, does not have this characteristic pattern. In the region of interest there are only two strong peaks at 1030 and 1185 era." . Apparently the molecular vibrations responsible for absorptions at these frequencies are constrained by the small ring attached as a spiro derivative to the dioxolane ring. n BrCH^-C-CH^Cl KNH^

PAGE 32

22 17 propane with lithium hydride in the presence of tetracyclone . The reaction scheme postulated to account for his product could apply in this case although the amide displacement on bromine does not have compelling precedence. n r^ 0^ BrCH^-C-CH^Cl CH2-C-CH2^C1 KNHX^

PAGE 33

23 E. Improved Procedure for Preparation of Dimethoxycyclopropene Cyclization of l-bromo-3-chloro-2,2-diinethoxypropane with potassium amide in liquid ammonia yields 3,3-dimethoxycyclopropene 17 as shown in scheme 1. The procedure developed by Baucom is essentially the same as that described earlier for the ethylene ketal. Yields were reported to be 30 to 50 percent but in the current program this process yielded to 50 percent with 10 to 15 percent being the most frequent result. Significant improvement was realized by reversing the order of addition of reactants in the cyclization process. The yield was 58 percent for the first run and has been consistently above HO percent in later runs. In addition to higher yield and fairly consistent results, this procedure is more convenient and is a safer process which has allowed scaling up to three times the usual run. In the case of the first reaction using this procedure, the starting material was completely consumed and there was little residue after distillation of the product . Nevertheless , a total material balance was still not achieved. Only about 75 percent of the starting material was accounted for. This has been a persistent problem that makes comparison of reagents and mechanism probes unreliable and is one reason none have been attempted. 22 The apparatus used was similar to that of Schlatter. Essentially, it consisted of two flasks arranged side by side with appropriate connecting tubes and provision for pressurizing one of them. The potassium amide was prepeired in the usual fashion in

PAGE 34

24 one of thera and then transferred by means of nitrogen pressure to the other flask which contained the intermediate in excess ammonia. A relatively short reaction time at the temperature of refluxing ammonia was required to complete the cyclization and excess amide was destroyed with ammonium chloride. Isolation of the product then followed the established process.

PAGE 35

25 F« Other Cyclization Processes Several other systems were evaluated in an effort to find an alternate method for the preparation of dimethoxycyclopropene. Hexamethylphosphoramide (HMPA) has been used to effect dehydro23 halogenation and the following reaction can be visualized. CHgO OCHg CHgOv^^OCHg \/ " +2 HMPA BrCHj-C-CH^Cl HMPA ' /-\ ^ 2^(^3)2 2((CH3)2N)2P=0 It should be possible to distill the product from the mixture as it is formed. When a sample of the bromochloroketal was added to HMPA and slowly heated to 220° an exothermic reaction seemed to take place and the mixture became very dark. A few milliliters of a clear liquid distilled from the reactor but it rapidly boiled away when warmed to room temperature. Apparently the ketal was reactive toward HMPA and produced decomposition of the solvent to give dimethylamine which was the liquid collected. The conditions employed here were too severe for practical use, however. When the bromochloroketal was heated for two hours at 75° with sodium hydride in Ht-lPA it was recovered unchanged in quantitative yield.

PAGE 36

CHAPTER III Charge Transfer Complexation The use of 3,3-dimethoxycyclopropene in copolymerization processes affords the interesting possibility of incorporating cyclopropanone units in polymer chains by subsequent hydrolysis of the ketal moiety. Modification of polymer properties by further reaction at these sites could lead to materials of considerable interest. A good deal of evidence has accumulated for the participation of charge transfer complexes in many copolymerization reactions. The ease with which 3,3-dimethoxycyclopropene experiences nucleo18 philic addition (eg. tert-butoxide and dimethylamine ) suggests that it is a rather electron-deficient olefin. Therefore, the formation of charge transfer complexes between this reagent and two electron-rich monomers was investigated. These monomers were styrene and divinyl ether. Of the two methods commonly used to study charge transfer complexation, namely ultraviolet spectroscopy and nuclear magnetic resonance, the latter is clearly preferred in this case for two reasons. First, it is extremely difficult to obtain 3,3-dimethoxycyclopropene of spectroscopically pure form in sufficient quantity for use in UV studies and secondly, the NMR singlet of the ring protons appears to be sensitive to changes in the electronic nature 26

PAGE 37

27 of various solvents (Table II). Also, the UV spectrum of dimethoxycyclopropene (Fig. 2) shows no absorption above 210 ray. Table II. Variation in the chemical shift of the ring protons of 3,3-dimethoxycyclopropene with solvent. Solvent 6 Value for Cyclopropene Protons hexane 7.62 cyclohexane 7.65 carbon tetrachloride 7.75 chloroform 7.83 dioxane 7.90 acetone-d7 qr b benzene-d7 33 b A study of charge transfer complexation between maleic anhydride and both styrene and divinyl ether by the NMR method was reported by Butler and Campus in 1970. ^ Thus, a semi -quantitative measure of the electron affinity of 3,3-dimethoxycyclopropene relative to maleic anhydride should be available from a comparison of the equilibrium constants of the two systems. The NMR studies were done on a Varian Associates analytical NMR spectrometer. The shift of acceptor protons (singlet of 3,3-dimethoxycyclopropene) was observed. The concentration of acceptor was kept constant while the donor concentration (always in large excess) was increased. Solutions were prepared at room temperature and the spectra were obtained at the normal operating temperature of the spectrometer. Reagents and solvents were all purified by distillation just prior to use.

PAGE 38

28 200 210 220 V/avelength , my "igure 2. Ultraviolet Spectrum of 3 ,3-Dimethoxycyclopropene

PAGE 39

29 The NMR technique utilizes the linear relationships derived by Hanna and Ashbaugh: 1 111 where ; obs AD AD A A A A , = 6 , -5^, is the difference between the shift of the obs obs ' acceptor protons in complexing media and the shift of the acceptor in uncomplexed form. D A A A.,, = 6.^-6^, is the difference in the shift of the acceptor AD AD 0' protons in pure complex. C is the concentration of the donor (which must always be much greater than the acceptor concentration in order that the quotient YAn/^A Y^ remains constant over the range of solutions studied and thus Q = K, the equilibrium constant of complexation). In these experiments the acceptor concentration was kept constant at 0.05 mole liter , while the donor concentration was increased -1 A from O.U to 8.8 moles liter . By plotting 1/A as a function of 1/C a straight line was obtained in both cases. (Figures 3 and 4). The slope of the line and its intersection with the ordinate permit a first approximation of the equilibrium constant of complexation and of the shift of acceptor protons in the pure complex. For a more exact determination of K and A.^^, the method of least squares was applied to equation 1, and the results obtained are shown in Table III, The corresponding values for maleic anhydride complexes are shown for comoarison.

PAGE 40

30 ( r / . ) 1 M"^ LstyrJ Figure 3. NMR Study of the Complex Between Dimethoxycyclopropene and Styrene

PAGE 41

31 l.Oi Figure U. NMR Study of the Complex Between Dimethoxycyclopropene and Divinyl Ether

PAGE 42

32 While the values of K are quite low, they appear to be real and of the same approximate order of magnitude as other weak complexes, (Butler and Campus report K = 0.008 and A = 127.5 for the complex AU 24b between divinyl ether and f umaronitrile . ) As expected, the electron affinity of 3 ,3-dimethoxycyclopropene is considerably less than that of maleic anhydride. Table III, Complex DVE:DMCP 24b DVE:MA St:DMCP StrMA^^^ NMR Determination of the Equilibrium Constants of Charge Transfer Complexes . Solvent hexane CDClg CCl^ CCl.. Temp. , °C 38 24 38 38 AD' cps K, 1 M -1 125.0

PAGE 43

CHAPTER IV 1 -h 2 Cycloadditions. The Diels-Alder Reaction The use of cyclopropene derivatives ad dienophiles in DielsAlder reactions is a process of synthetic utility as well as mechanistic interest. The parent hydrocarbon reacts rapidly and quantitatively with cyclopentadiene at 0° to form the tricyclic adduct (I). The reaction is stereospecif ic and only the endo isomer 26 is formed. Substitution at the double bond positions of cyclopropene affects the stability and reactivity of the olefin but does little to alter the course of the Diels-Alder reaction. A single substituent in the 3-position directs the geometry of the product but as long as C-3 carries only one substituent the reaction proceeds smoothly and the adducts have the endo configuration. Thus, 3-methylcyclopropene adds to cyclopentadiene to give only the endo~ anti isomer and none of the other three possibilities, while 3,3dimethylcyclopropene does not add even at 100°. Battiste investigated the reactivity of a number of derivatives and found that gerainally 27 substituted cyclopropenes are unreactive toward any diene. 33

PAGE 44

3U In 1958 Tobey demonstrated that all tetrahalocyclopropenes undergo facile 1,4 addition to cyclopentadiene , furan, and 1,328 butadiene . His experiments indicate that electronic rather than steric effects would account for the observed results. Again the products were all of endo configuration. The adducts from the cyclic dienes, however, were rearranged bicyclic derivatives (.11). II Sprouse reacted cyclopropene and some of its derivatives with 1,3-diphenylisobenzofuran (III) and obtained adducts with exoStereochemistry. Sargent also obtained an exo adduct when he reacted l,2-bis(trifluoromethyl)-3 ,3-difluorocyclopropene with 30 29 cyclopentadiene. Sprouse found that reaction of tetrachlorocyclopropene with ClII) gave a stable tricyclic adduct (IV) which could be rearranged to a structure like (II) upon heating. Adduct IV also had the exo stereochemistry like the other adducts from diphenylisobenzof uran .

PAGE 45

35 III IV The only example of a geminally disubstituted cyclopropene derivative giving rise to the exclusive formation of an exo adduct with any diene other than III is the report of Monti and Bertrand 11 in 1970. They reacted cyclopentadiene with the ethylene ketal of 3-acetyl-3-methylcyclopropene at 140° in a sealed tube and obtained 2 4 exo-3-methyl-3-acetyltricyclo[ 3.2.1.0 ' ]-6-octene ethylene ketal. -CH, 18 The observation by Baucom and Butler that the reaction of 3,3-dimethoxycyclopropene with III yielded the exo adduct was consistent with the work of Sprouse. Baucom also obtained evidence 17 for adduct formation between dimethoxycyclopropene and a-pyrone but this was not confirmed. OCH, + III

PAGE 46

36 A. Reaction with Butadiene Derivatives When dimethoxycyclopropene was mixed with an excess of butadiene, isoprene, or 2,3-dimethyl butadiene and the solution allowed to react at room temperature for several days , the expected adducts were formed in high yield. Because of the symmetry of the system, only one isomer was possible in each case. After evaporating excess diene, the products were analyzed by gas chromatography and the adduct peak was greater than 90 percent of the crude reaction mixture. Pure samples were obtained by preparative GC while none of the byproducts could be isolated in sufficient quantity for identification. CHgO OCHg R + 1 V^ ^iV^^ /o R^^ )CH3 DCHg V R^=R2=H VI R^=R2=CH3 VII R^=H; R2=CH2 Figure 5 shows the NMR spectrum of the dimethylbutadiene adduct, The two methoxy groups are different at 3.3 and 3.M-5. The ring protons are centered at 2.16. The singlet at 1.66 is due to the methyl groups in positions 3 and 4 , while the bridgehead protons give a multiplet at 1.36. If the methyl groups are replaced by hydrogen as in the butadiene adduct , the vinyl protons give a broad singlet at 5.56 and the peak due to the methylene protons is shifted just slightly do'rfnfield. (Note shaded areas in Fig. 5.)

PAGE 47

37 ^ -8 m X u >

PAGE 48

38 -8 \y •P o < c u o M M I Q) C OJ o f^ o rH O >1 o X o +-> 0) e •H O Uh O u p o (1) a, in Pi to U

PAGE 49

39 In the spectrum of the adduct with isoprene (Fig. 6) both of these groups are present on the double bond and the resulting increase in coupling produces much broader peaks. Upon expanding the scale, the two different sets of protons at positions 2 and 5 can be separated. The mass spectra of these adducts indicated that analogous fragmentation pathways were followed as would be expected. The usual procedure for interpreting mass spectra involves localizing the charge on the hetero atom and then considering logical reorganization of the resulting ion-radical. The spectra of these adducts showed an abundant molecular ion which would be predicted by this procedure of analysis. Clearly the weakest bond in every case is the 1,7 bond and initial a-cleavage of this bond in A leads to the very stable ion-radical B. molecular ion From here, however, it is difficult to rationalize the remainder of the spectrum. The base peak in every case corresponded to the loss of a dimethoxymethyl radical. There was also a fairly abundant peak corresponding to the loss of a methyl radical and fragments attributeible to consecutive reactions of the resulting ester ion were detected.

PAGE 50

no These processes were more readily accommodated by considering an alternate representation of the ion-radical, C, which is actually a resonance form of B. Using these tvjo structures, then, the major features of the spectra follow very logical rearrangement pathways. The base peak is adequately rationalized from C as involving a 1,3 hydrogen migration to give an allylic radical, D, and then a hemolytic cleavage of the 5,7 bond to lose the requisite radical and give an ion with extended conjugation, E, The metastable peak for the transition C (or D) -^E H + CH^O-C-OCH^ o • o R " tAi c was just detectable, but it was present. The loss of a methyl 31 radical from C is also a very logical process and many features of the spectrum arise from further reaction of the ester ion (scheme 4) — including alternate pathways to the base-peak ion. Further, the metastable peaks (indicated by " in scheme 4) observed for the proposed transitions are prominent and offer further evidence for the proposed sequence of reactions. The relative abundances of the ions resulting from the proposed transitions are given for each adduct in Table IV.

PAGE 51

Ul Scheme U. Mass Spectral Fragmentation Pattern for Diels-Alder Adducts Between Dimethoxycyclopropene and Butadienes

PAGE 52

42 Table IV Relative Abundances of Mass Spectrum Peaks from Diels-Alder Adducts Between Dimethoxycyclopropene and Butadiene (V), 2,3-Dimethylbutadiene (VI), and Isoprene (VII). Relative Abundance Ion

PAGE 53

U3 CH3(X.0CH3 hydrogen bromide gas from the reaction mixture. The isoprene adduct was used for this reaction and none of the products were identified. When the reaction of diraethoxycyclopropene with 1-methoxybutadiene (50 percent excess) was attempted in THF, there was no indication of adduct formation. However, mixing the two liquid reactants (threefold excess of diene) without solvent resulted in high conversion to the adduct. Analysis of the product fraction after distillation (by gas chromatography) showed two components in the approximate ratio of 30:70. Isolation of the major component by preparative GC gave a product whose NMR, IR, and elemental analysis were completely consistent with the expected adduct. In the NMR, > "X L J^ OCHdCHg OCHg the methoxy group at position 2 gave a peak which coincided with the low-field methoxy of the ketal function. The corresponding methine proton in position 2 appeared as a poorly resolved roultiplet at 3.9 to 4.06. All of the other absorptions were shifted downfield by one to two parts per million from their counterparts in the adducts obtained from the butadiene hydrocarbons. The mass spectrum, while not inconsistent with the proposed structure, was difficult to rationalize. No molecular ion was evident, but this was not unexpected. The species corresponding to the molecular ion of the hydrocarbon derivatives should readily lose a methoxy radical. Further loss of molecular hydrogen to

PAGE 54

44 give the ion M could account for the highest m/e value exceeding 20 percent of the base peak. The base peak appeared at m/e 105 and the second most abundant peak (89 percent of base) was at m/e 77. Since m/e 77 corresponds to C H , the base peak is likely OCH, :v K -OCH, -H, ^ ^^*===^ to be the oxonium ion N, although its formation from M is difficult to rationalize. There was an abundant metastable peak at 56.5 which arises from the transition N C.H^ + CO. The remaining b b feat\ires of the spectrum indicated that a variety of competing reactions were occurring and that no single fragmentation pathway was followed . m" = 56 .6 -^ + CO N m/e 105 base peak m/e 77 Another possible explanation for the difficulty in interpreting the mass spectrum is that the adduct is not thermally stable. Operating techniques for the mass spectrometer involve storage of the sample in a reservoir at about 200° before injection into the ionization chamber. Thermal stability of samples must therefore be considered and additional samples of the adduct were required in order to investigate this possibility.

PAGE 55

^5 When another analysis of the distilled product was made on the gas chromatograph , a lower rate of flow was used for the carrier gas. Four components were observed this time which were sufficiently well separated to allow isolation. Peak four was the major component (66 percent) and was determined to be 2 ,7 ,7-trimethoxy-3-norcarene. Peaks one and two were suspected decomposition products while peak three might possibly be an isomer of the adduct. All of the mixture available was subjected to preparative gas chromatography and these four components were collected. There was not enough of peak one to permit its identification. Peak two was identified as methyl benzoate by its NMR and IR spectra. Peak three was not obtained in pure form and could not be identified. Its infrared spectrum gave a carbonyl absorbance but comparison with that of peak two indicated that this was due to methyl benzoate as an impxirity. Instead of the characteristic three or four bands for a ketal between 1000 and 1200 cm. there was only a single broad absorption centered at 1100 cm. . In the NMR there were the expected absorbances due to methyl benzoate. In addition there were the following: 6-value

PAGE 56

46 These results proved that peak three is not an isomer of the adduct but assignment of a structure cannot be made without further information. The thermal stability of 2 ,7,7-trimethoxy-3-norcarene was checked by reinjection of a sample of peak four into the gas chromatograph . In addition to unchanged adduct there were "lights" and peaks corresponding to one and two. There was none of the compound giving peak three, however. Thus, thermal decomposition of 2 ,7 ,7-trimethoxy-3-norcarene produced methyl benzoate as a major product. The main features of the mass spectrum were then easily explained by considering this ester to be the species actually being analyzed.

PAGE 57

U7 B. Reaction With Cyclic Dienes Diels-Alder reactions with cyclic dienes could conceivably lead to derivatives of cyclopropyl norbornene, possibly with exostereochemistry if the analogy to the di phenyl isobenzofuran study were followed. Such adduction seemed feasible since the reactivity of CH3O OCH, room temp. No Reaction OCH VII OCH, and CH, OCH, R.T. (dark) ^ OCH OCH, Scheme "4. Diels-Alder Reactions of Dimethoxycyclopropene with Cyclic Dienes

PAGE 58

48 32 cyclopentadiene (toward maleic anhydride) is much greater than any of the other dienes used in our work and in the light of recent reports of successful adduct formation using other geminally substi14 tuted cyclopropenes. However, when dimethoxycyclopropene and cyclopentadiene were allowed to stand together at room temperature no reaction occurred at all. At 70° the two appeared to react independently as the NMR showed a change in the diene pattern, presumably due to formation of dicyclopentadiene , and the characteristic peaks of the dimethoxycyclopropene dimer appeared. There was no indication of adduct formation. Apparently steric factors inhibit this reaction as proposed for other systems. Because of the very facile reaction observed by Baucom with diphenylisobenzofuran, it seemed reasonable to expect dimethoxycyclopropene to react with furan as well. But when a solution of the cyclopropene in furan was stored in the dark for several days at room temperature, there was again no evidence for adduct formation. Instead, there was almost quantitative dimerization of the dimethoxycyclopropene. Diels-Alder reaction of dimethoxj'-cyclopropene with tetracyclone would be expected to give first the bridged carbonyl adduct VIII. This structure should be readily decarbonylated to give the norcaradiene IX or possibly its valence isomer X. Compounds with structures VIII or IX should show two different NMR signals for the methoxy groups and a singlet for the ring protons. The tropone ketal should show two equivalent protons in the vinyl region but possibly a

PAGE 59

U9 II^och; ^ Ph VIII Scheme 5. Diels-Alder Reaction of Dimethoxycyclopropene with Tetracyclone

PAGE 60

50 singlet for the methoxy groups. The actual spectrum (Fig. 7) of the product isolated showed a six-proton singlet at 36 for the methoxy groups and an AB quartet between 5.0 and 6.36 as well as a 20-proton multiplet in the aromatic region. This was clearly inconsistent with any of the expected structures. Further, elemental analysis corresponded to a 1:1 adduct without the loss of carbon monoxide while the infrared spectrum was free of carbonyl absorption. Treating a sample of this adduct with aqueous acetone and a trace of acid resulted in the loss of methoxy signals in the NMR and the appearance of an intense carbonyl peak at 1780 cm. in the infrared spectrum. The NMR spectrum also showed a widely separated AB quartet with a coupling constant, J.^,, of 5.5 cps . One doublet AB of this system was centered at 7.45 6 and the other at 6.106. These observations are consistent with a structure in which an opened cyclopropene has added across the carbonyl of the tetracyclone . Two modes of addition appear possible, giving either XI or XII. P XI XII Acid catalyzed hydrolysis of these compounds would give derivatives of a 3(2H)-furanone (XIa) and a 2(5H)-furanone (Xlla) respectively.

PAGE 61

51 0) c o r-l U >^ o OJ u i-> > O >, X o +-» 0) a •H Q C a>
PAGE 62

52 IR absorbance

PAGE 63

53 37 The dimerization of cyclopropenone as well as its reaction with diphenylcyclopropenone gave 2(5H)-furanone derivatives. The mechanism suggested for this process was nucleophilic attack on the carbonyl carbon of cyclopropenone, followed by 1,2 cleavage and Ph cyclization. Operation of a similar mechanism in the tetracyclone reaction with dimethoxycyclopropene would involve nucleophilic attack on the ketal carbon accompanied by 1,3 cleavage and then cyclization. CHgO^^OCH^ OCH, Ph, ^0. ?<^"3 -OCH HC=CH ^ °h ^^ H Alternatively, since tetracyclone has an electron-deficient carbonyl group, the mechanism could be viewed as nucleophilic attack by the olefin on that carbonyl carbon, followed by 1,3 bond cleavage and cyclization. /^h + C ^ ,OCH11

PAGE 64

54 CH^O OCH^ R N, R R OCH3 N CH, OCH, R Scheme 7. Diels-Alder Reaction of Dimethoxycyclopropene with Tetrazine

PAGE 65

55 A third possibility is that the 1,3 bond of dimethoxycyclopropene is cleaved first to give either a dipolar of a diradical species which is then trapped by the tetracyclone carbonyl system. It is not possible to distinguish the actual mechanism from the data available from these experiments. Another interesting possibility for using dimethoxycyclopropene as a synthetic intermediate is its reaction with tetrazines. The initial adduct (XIII) should readily lose nitrogen to give the diazanorcaradiene XIV or possibly the diazatropone ketal XV. Hydrolysis of this ketal would then give a route to diazatropone. 38 Sauer and Heinrichs found that cyclopropene and 1,2,3-triphenylcyclopropene both added readily to tetrazines to give the diazanorcaradiene products. Rearrangement to the diazacycloheptatriene system was observed for the triphenyl cyclopropene adduct. Reaction of dimethoxycyclopropene was attempted with two tetrazines. Preliminary NMR evidence indicated that for the case of 3,6-dicarbomethoxy-s-tetrazine, the diazanorcaradiene was present in the reaction mixture but the complexity of the mixture and the paucity of material available did not permit its isolation. There is no indication of adduct formation at all when 3,6-diphenyltetrazine and dimethoxycyclopropene were reacted for 18 hours in refluxing methylene chloride. Tetrachlorocyclopentadiene affords the interesting possibility of reacting with dimethoxycyclopropene in two ways. Diels-Alder reaction could lead to the adduct XVI.

PAGE 66

CHgO^^/OCHg •<:i, 56 OCH. OCH, XVI In addition, if the methylene protons of the diene were sufficiently active, a very unusual fulvene derivative could result from reaction CH„0 OCH^ -CI, -> CI, + 2 CH-OH at the ketal function. The formation of fulvenes has been observed for reactions of tetrachlorocyclopentadiene with aromatic aldehydes. 39 CI, + ArCHO CIH 'Ar Hov/ever, when the two reagents were allowed to stand for several days at room temperature in just enough benzene-d^ to effect solution, the tetrachlorocyclopentadiene was recovered unchanged while the dimethoxycyclopropene decomposed .

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CHAPTER V 2+2 Cycloaddition Reactions A few reactions are knovm where cyclopropenes undergo cycloadditions with formation of a four-membered ring. The initial adducts often rearrange, however, and only secondary products are actually isolated. \ifhen 1,3,3-trimethylcyclopropene was irradiated with ultraviolet light in acetone solution containing benzophenone as sensitizer, the two isomeric tricyclic dimers were isolated in 15 percent yield. "3^ H3C^CH3 H3C hv "3^ "3^ -CH, CH, "3^\^^"3 -CH, -CH, H3C CH3 Baucom found, however, that contrary to the reaction of 1,3,3^ trimethylcyclopropene , the dimerization of 3,3-dimethoxycyclopropene was not a photolytic process but was a thermal reaction probably 17 proceeding by a two-step mechanism. Since the dimerization appears to be a very facile process under mild conditions, and in the light of recent observations in the condensed phase, other cycloaddition reactions of dimethoxycyclopropene were studied. A number of interesting and novel systems 57

PAGE 68

58 could be approached in this manner by the proper choice of olefin. The charge transfer studies discussed earlier indicate that dimethoxycyclopropene is an electron-deficient olefin. Its facile reaction with electron-rich dienes in the Diels-Alder reaction supports this conclusion. However, the formation of a dimer via 2+2 cycloaddition requires that it react as an electron-rich species also. In addition, the unusual reaction of dimethoxycyclopropene with tetracyclone suggests that the presence of a hetero atom in the reacting system is important. Therefore, 2+2 cycloaddition reactions were investigated using an electron-deficient carbonyl species (hexafluoroacetone) , electron-rich olefins Cenaraines) and electron-poor olefins (triazolinediones and methyl acetylenedicarboxylate. The results indicate that dimethoxycyclopropene does not undergo 2+2 cycloaddition reactions with carbon-carbon double bonds regardless of their electronic character, but that appropriately activated hetero-olefins react readily. A. Reaction v/ith Hexafluoroacetone This reagent is electrophilic in nature and two modes of addition to dimethoxycyclopropene could be predicted . The first is analogous to the tetracyclone reaction, involving opening of the cyclopropene ring. CHgO OCH CHgO OCHg

PAGE 69

59 With the tetracyclone adduct in mind, the NMR spectrum of a compound with such a structure would be predicted to show an AB quartet for the vinyl protons and a singlet for the methoxy groups. The trifluoromethyl groups are also equivalent and should appear as a 19 singlet in the F NMR spectrum. Hydrolysis of such a compound should proceed readily to give 5-bis(trifluoromethyl)-2(5H)-furanone, Alternatively, the reaction could retain the three -membered ring and terminate by closure at C-2 to give a bicyclic system. A compound of this structure should have an NMR spectrum indicative of non-equivalent methoxy groups and also non-equivalent trifluoromethyl groups. The ring protons are also different and coupling would be expected. Hydrolysis of the ketal would produce a cyclopropanone and therefore should be difficult to achieve. When dimethoxycyclopropene and excess hexafluoroacetone were mixed and allowed to react for three days at room temperature there was smooth and complete conversion to a single compound. The small amount of impurity present was easily removed by treatment with silica gel. The NMR spectrum (Fig. 8) gave the following data:

PAGE 70

50 -8 1 ~\ o < C o 0) o O fj O 3 H LM (fl X
PAGE 71

Protons

PAGE 72

62 However, no aldehyde proton was observed in the NMR and if this were the structxire, the methoxy groups would be equivalent. The mass spectrum was very clean, showing only two fragments with an intensity greater than 20 percent of the base peak. A very small molecular ion peak was detected at m/e 266 . The base peak occurred at m/e 197 corresponding to the loss of a trifluoromethyl radical. Other fragments were due to loss of a methoxy radical (m/e 235) and to the trifluoromethyl ion (jn/e 69). Hydrolysis of a sample of the adduct was also attempted in order to provide additional structural information. After 17 hours in refluxing aqueous dioxane containing a trace of acid, the adduct was recovered unchanged. Thus, the second mode of addition appears to be operative and the adduct produced was 3,3-bisCtrifluoromethyl)-5 ,5-diraethoxy-2oxabicyclo[2.1.0] pentane: CH^O 5 OCHg

PAGE 73

03 B. Reaction with Enamines Enamines are electron-rich olefins and should be ideal for reaction with an electron-deficient system such as dimethoxycyclopropene. A number of cyclopivDpenone derivatives have been reacted with a variety 111 _iiii of enemines to give both "C-C" and "C-N" insertion. The former, observed only in low yield, results from 2+2 cycloaddition and then reopening of the four-membered ring. The latter involves cleavage of the 1,2 bond of the cyclopropenone and insertion into the C-N bond of the enamine. Eicher and Bohm obtained stable ketaines from the reaction of phenyl-methyl-cyclopropenone and diphenylcyclopropenone with acyclic enamines. ' These last reactions require the participation of the carbonyl oxygen of the cyclopropenone and would be impossible for dimethoxycyclopropene. However, reactions analogous to the studies of Dreiding would provide interesting results regardless of the mode of insertion and the effect of the ketal instead of a ketone could be valuable froiji a theoretical point of view. Two enamines were selected for reaction with dimethoxycyclopropene. They were N,N-diethylstyrylamine and 1( 2 -methyl-l-propenyl) -pyrrolidine. P\ ;^ CH_ H C=C C H K / h" ^N^2"5 ^C=Q^ S"5 C"3 ' The reactions were conducted neat, at 53°, under nitrogen. In the case of the styrylamine, decomposition of the dimethoxycyclopropene occurred

PAGE 74

64 but the enamine was unaffected. Both the pyrrolidine enamine and the dimethoxycyclopropene remained after 16 hours of reaction time in the second case. These results indicate that dimethoxycyclopropene does not add to electron-rich olefins.

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65 C. Reaction with Triazolinediones U-Phenyl-A -l,2,U-triazoline-3,5-dione (XVII) is a cis-locked azodicarbonyl compound and a very electrophilic cyclophile. Cycloaddition of XVII with simple monoolefins is limited to 1,2addition leading to diazetidines. For example, the diazetidine XVIII was obtained from PhTD and indene. ©U N=N f Ph XVII o €oi V N-Ph OCnd Ph XVIII The proposed dipolar intermediate was trapped with water. no Reaction of XVII with alkenylidenecyclopropanes Ce.g., XIX) gave two 1:1 adducts in stereochemically pure form. A concerted cycloaddition across carbon atoms 2 and 4 was implicated. |>=C=C + I N-Ph — H H y H^C + =0"5

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66 The same products could arise from a dipolar intermediate such as XX by two different modes of isomerizing the cyclopropyl cation portion, but their data argue against its intervention. Ph. XX Dimethoxycyclopropene , reacting as a simple olefin in a 2+2 cycloaddition, would give the very unusual diazetidine XXI. The steric CH3O OCH, + XVII CH, CH, N-Ph -N. XXI I requirements for this adduct should be no more severe than those of the dimer. Participation of a dipolar intermediate such as XXII would very likely lead to rearranged products resulting from opening of the cyclopropyl ring CXXIII). CHgO^^^OCHg CH30^CH3 HC=CH-C ^ I * ' > I Ph 0=^ -> OCH, CH, o-C X. Ph XXII XXIII

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67 The alternate ring closure at the oxygen atom would produce a cycloheptadiene with one trans double bond — a prohibitively strained system. When XVII was reacted with dimethoxycyclopropene, however, neither of these adducts was formed. Instead, a spontaneous copolymerization reaction occurred giving a product with a number average molecular weight of 1244 as determined by vapor phase osmometry. Elemental analysis was inconsistent with either a 1:1 or a 2:1 copolymer composition. Wagener has obtained evidence for incorporation of additional triazolinedione into the copolymer, presumably by nucleophilic attack of the dipolar intermediate on the monomer. Postulating a product consisting of four units of 1:1 copolymer and one extra phenyltriazolinedione molecule results in a molecular weight of 1275 and elemental analysis is consistent with this composition. Assignment of the structure of the copolymer rests mainly on the infrared spectrum. Carbonyl peaks at 1720 and 1780 cm. indicated that reaction had occurred through both the nitrogen and the oxygen of the triazolinedione moiety. In unreacted XVII the carbonyl doublet appears at 1780 and 1760 cm." . Reaction through the oxygen atom leads to the formation of a C-N double bond in the product and an absorbance at 1620 cm. can be assigned to this chromophore. Also observed are bands at 1655 cm." (C-C double bond, cis disxibstituted) and the characteristic bands for a ketal between 1000 and 1200. The hfMR spectrum provides much less information. There is a broad absorption around 7.56 and a very broad doublet centered at 3.56. The relative areas of these two regions is 8:6.

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68 Thus, the roost likely structure for the major portion of the C„30 <,C„3 CH=CH-C I— N I Ph with some units going through both nitrogen atoms and with about one extra XVII unit for each four units of the copolymer. The dipolar intermediate in the copolymerization of XVII and ethyl vinyl ether has been trapped with acetone and with cyclo51 hexanone. No evidence for a similar termolecular adduct could be detected when XVII and dimethoxycyclopropene were reacted in acetone, OCH, CH3O OCHg XXII Trapping of the 1,5 dipole (XXIII ) leading to a seven-membered ring in the product was also considered possible but only polymer was produced. ^ 3 XXIV

PAGE 79

b
PAGE 80

70 D. Reaction with Dimethylacetylenedicarboxylate The cycloaddition of dimethoxycyclopropene in dimethylacetylenedicarboxylate was attempted as both a thermal and a photolytic process. Because of the interesting possibility for a 2:1 adduct , excess acetylenedicarboxylate was used and the reactions were run without solvent. Two different routes can be visualized, depending upon whether or not the initial 1:1 adduct forms a four-membered ring CH3O OCHg R-C=C-R R = -CO^CHg

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71 process was attempted by exposing the mixture to the sunlight in a quartz UV cell. In both cases the course of the reaction was followed by periodic sampling for NMR analysis and in both experiments decomposition of the dimethoxycyclopropene was observed with no indication at all of adduct formation. It is likely that traces of free acid catalyzed the decomposition.

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72 CHAPTER VI Reactions With Amines The observation by Baucom that nucleophiles apparently add very readily to dimethoxycyclopropene led him to the preparation of l,l-dimethoxy-2-dimethylaminocyclopropane. CHgO OCHg CH, + (CH2)2NH OCH, ^NCCHg)^ If a similar reaction could be effected using diallylamine as the nucleophile, the very unusual 1,6 diene produced would afford the possibility of producing a polymer with pendant cyclopropane groups. CHgQ^OCHg + (CH2=CH-CH2)2NH CHgO OCH3 % % CHjCf -OCH3

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73 Modification of polymer properties might then be expected to arise by cross-linking through or chemical reactions of the very reactive cyclopropyl system. However, exposure of these reagents to conditions that led to quantitative production of the dimethylaminocyclopropane failed to give any indication at all of the addition compound. Diallylaminocyclopropane would be expected to show a multiplet near 1.36 as well as a methoxy "doublet". Neither of these features was observed in the spectrum of the crude reaction mixture while typical decomposition patterns dominated. Distillation of this material failed to produce any fractions indicative of the anticipated course of reaction. This result raised the question of why the two amines should react so differently and suggested that reaction with a variety of amines might reveal something of the electronic character of dimethoxycyclopropene . When dimethoxycyclopropene was added to excess diethylamine and the mixture stored at room temperature for several days, the major product formed (60 percent) and the only one isolated was 1,1dimethoxy-2-diethylaminocyclopropane . The pure product was isolated by preparative gas chromatography but there was not enough sajnple available to allow collection of the two observed minor components. CHgO^CHg + (C2H5)2NH NCC^H^)^

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74 The NMR spectrum (Figure 9 ) gave the following data : 6-value Protons Description 3.42 3 singlet 3.32 3 singlet 2.89-2.51 4 quadruplet 2.14-1.90 1 multiplet 1.18-0.94 6 triplet 1.05-0.75 2 multiplet The two singlets at 3.42 and 3.326 were assigned to the nonequivalent methoxy protons. The quadruplet at 2.706 and the triplet at 1.066 were assigned to the diethylamino protons. The absorbances at 2.12 and 0.906 were assigned to the cyclopropyl ring protons. The mass spectral analysis was completely consistent with the proposed structure and produced a fragmentation pattern analogous to that observed by Baucom for the dimethylamino derivative. Continuation of the series to di-n_-propylamine was next attempted and the course of the reaction was found to be considerably more complex. As in the case of diallylamine, the crude reaction mixture did not appear to contain any of the addition product. However, this time one fraction from the product distillation showed NMR absorptions which could be assigned to the nonequivalent methoxy groups. Analysis of this fraction by gas chromatography indicated two major components comprised about 85 percent of the mixture and that these components were present in a ratio of 40:60. Pure samples of each one were then obtained by preparative gas chromatography.

PAGE 85

75 c (0 cu o u o. o o >> CJ o c •H E (0 >^ JZ X! I i X o x: *-•
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76 The first component gave absorptions in the NMR at 3.45 and 3.356 for the non-equivalent methoxy groups and a one-proton multiplet at 2.08 characteristic of the lone proton at C-2 of the cyclopropane ring. The absorbance of the geminal protons on the ring overlapped with the characteristic multiplets for ths propyl groups and could be detected only by analysis of the integration areas . The infrared spectriim of this component was almost superimposable on that of the diethylaminocyclopropane which confirmed that it was 1,1-dimethoxy2-di-n-propylaminocyclopropene . CHgOs^OCHg CHgO OCHg + (cu^-c}i^-cii^)^m NCCgH^)^ a new compound The NMR spectrum (Figure 10) of the second component gave the following data: 6-value 3.65 2.97-2.62 2.56-2.17 1.78-1.17 1.07-0.66 Protons 3 2 6 4 6 Description singlet multiplet multiplet multiplet multiplet In the infrared spectrum there was an intense carbonyl absorption at 5.72y which was interpreted with the corroboration of the C-0 stretching at 8.30y as being indicative of an ester. Elemental analysis gave an empirical formula of C H NO and in the mass

PAGE 87

77

PAGE 88

78 spectral analysis there was a molecular ion at m/e 187 (.13 percent of the base peak). The base peak was at m/e 158 and another fragment appeared at m/e 114 which was 65 percent of the base. These data indicated that the second component of the mixture was N,N-di-n_-propylainino-3-alanine methyl ester (XXV). (e) (d) (c) CH3-CH2-CH2 ^N-CH^-CH^-C-OCHg CHg-CH^-CH^ (c) (b) (a) (e) (d) (c) XXV Assignments of the NMR absorbances of Figure 10 to the protons of this structure can be made as follows: 6-value Protons Assignment 3.62 3 a 2.97-2.62 2 b 2.59-2.17 6 c 1.67-1.17 4 d 1.07-0.66 6 e The mass spectral fragmentation pattern arises from the expected two modes of cleaving a C-C bond next to the nitrogen which is directing the fragmentation to the virtual exclusion of all other possibilities because of its greater electronegativity. The change in reactivity through this series of amines cannot be attributed to differences in basicity since all are of nearly equal value. Aromatic amines are considerably less basic than

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79 CH CH^-^^H^Ff-'^ir^CH^-C-OCH, SVt :CH, = 3"7 7 m/e 114 3 2 2 2 2 S"7 -SV2 /I m/e 187 .1 CH =N-CH -CH -C-OCH S"7 m/e 158 (base) aliphatic amines so a study of their reactivity could provide additional information about the chemistry of dimethoxycyclopropene. Diphenylamine was selected for first evaluation since examination of the products should be less complicated due to the presence of only aromatic protons in the NMR. Because this ciraine is a solid, a solvent (CH CI ) was required. The amine was used in only 10 percent molar excess due to its low bulk density and the resulting high volume of material required. Analysis of the crude reaction product by NMR did not reveal the presence of cyclopropyl protons, but some adduct formation was indicated by the characteristic absorbances of two non-equivalent methoxy groups. A large new singlet at 3.186 was also observed along with several smaller peaks. Separation of this mixture by silica gel chromatography was attempted but when the sample was placed on the column it immediately experienced a vigorous exothermic reaction. Development of the column yielded a weight recovery of approximately 65 percent which

PAGE 90

80 appeared to be mostly a single component plus some free diphenylamine , A second chromatography yielded pure samples of this component. The NMR spectrum (Figure 11) gave the following data: 6-value Protons Description 7.32-6.65 10 raultiplet 4.15-3.80 2 multiplet 3.51 3 singlet 2.75-2.38 2 multiplet This appeared to also be an amino acid ester — the methyl ester of N,N-diphenyl-3-alanine . The low-field absorbances were assigned to the aromatic protons and the singlet at 3.55 to the methyl group of the ester. The two 2-proton multiplets form an A B pattern which would be expected for the four methylene protons of structure XXIV . ^6^5, y^-CH^-CH^-C-OCHg ^6^5 XXIV The infrared spectrum showed carbonyl absorption at 5.72;) and strong II asymmetrical C-C-0 stretching at 8.50y indicating an ester. Elemental analysis gave an empirical formula of C -H^„NO_ and the mass spectral analysis was consistent with the proposed structure. The molecular ion at m/e 255 was 40 percent of the base peak which appeared at m/e 182 . The next largest fragment was 16 percent of the base at m/e 77 (C.H^ ) and all others were less than 10 percent. D D

PAGE 91

81 c •H C (0 r-i (0 I OQ I C 0) tx •o I » o e 3 . 5 O 0) cc -i <0 u bO . -I

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82 ^6"5^.+^^ -CHO ^6"5,+ m/e 255 m/e 182 Identification of the intermediate which was isomerized on silica gel was next attempted using the second half of the same mixture. The first procedure tried was to cool a pentane solution of the material to -78° . The oil which separated confirmed that the non-equivalent methoxy groups were present without cyclopropyl protons but no purification of components was realized. After a few days, these samples were blended back together and the NMR spectrum was taken. Very little of the absorbances assigned to the methoxy groups remained and the singlet at 3.186 dominated the spectrum. This material was dissolved in methanol and then divided into two portions. The first portion was allowed to stand at room temperature in an open flask to slowly evaporate solvent in an effort to effect crystallization. No crystals ever formed and when all of the solvent had evaporated the resulting oil was again analyzed by NMR. The result was a pure sample of N,N-diphenyl-3-alanine methyl ester with no sign of free diphenylamine . The second portion of the methanol solution was treated with a few drops of water and an oil separated. It was dried under vacuum and analyzed by Nt-IR (Figure 12). Absorbances due to the alanine ester were obvious. An absorbance at 2.30-1.936 appeared to be one portion of a second A B pattern. The second portion

PAGE 93

83 200 100 ''l*''^'''''^*'^* 4.0 3.0 PPM ((5) 2.0 Figure 12. NMR Spectrum of the Intermediate Leading to N,N-diphenyl-6-alanine

PAGE 94

84 would be expected in the range of 4.10 to 3.406 but absorbances due to the alanine ester also appear in this range. However, if that portion of the integration attributable to the known compound was subtracted from the total integration in this area, the difference was exactly equal to the integration of the 2.30-1.936 multiplet. Thus, another A^B system seemed likely. If the singlet at 3.186 was due only to a compound containing this A B^ system, then this singlet was equivalent to nine protons . In the aromatic region the absorbance was due to the 3-alanine derivative and some free diphenylamine as well as the unknown intermediate. Subtracting the known compounds from the total left thirteen aromatic protons for the intermediate which implied that it contained only one diphenylamino group. When this NMR sample was poiired onto silica gel and then extracted with ether the next day, N,N-diphenyl-S-alanine methyl ester was again obtained with some contamination by the free amine. In the infrared spectrum of the sample rich in the intermediate there were few absorbances not present in the alanine derivative although some intensities were different. Weak absorbances at 8.90, 10.55, and 10.95y and a strong absorbance at 13.30y with a shoulder at 13.55y appeared to be unique with the unknown intermediate. The carbonyl absorption was considerably less intense as would be expected if the intermediate lacked this chromophore. The absorbances due to the aromatic system were only slightly less intense. No further purification of this sample could be effected and continued manipulation saw it all be slowly converred to the Balanine ester. Thus, no positive identification of the intermediate

PAGE 95

85 was possible. One structure which could satisfy the observed phenomena is the ortho ester XXVI although its formation would be difficult to rationalize. C H OCH6 5^ Y 3 ^-CH^-CHj-ci-OCHg hh °C"3 XXVI 17 Baucom observed the formation of methyl orthoacrylate under certain conditions during the preparation of dimethoxycyclopropene and found that the orthoester moiety gave a nine-proton singlet at 3.226. In the present case the predominant singlet occurs at 3.186. Although structure XXVI is consistent with the main features of the spectra, its formation would require a very unlikely series of reactions. First, a portion of the dimethoxycyclopropene would have to react with diphenylamine in an exchange reaction of some sort at the ketal center to produce methanol. Then all of the methanol would have to react with additional dimethoxycyclopropene to give methylorthoacrylate. This reaction has been observed but a number of other products are also obtained. Addition of diphenylamine to the methyl orthoacrylate^^ would then lead to compound XXVI. The probability of such a sequence occurring is very low and there was also no evidence for any of the by-products to be expected from them. A more likely mechanism for the formation of the alanine ester involves a ketene acetal as the intermediate. The simple addition

PAGE 96

86 HXOv /OCH^ H^CO. /OCH^ H CO, O ^y^ O 3 \f^ d -J R2NH + /v, — > /\ > ^2^H reaction is nucleophilic attack at C-1 by the electron pair on nitrogen with production of negative charge at C-2 where protonation completes the addition. Alternatively, 1,3 cleavage could occur followed by reorganization of the electron system and protonation at C-1 to give the ketene acetal. 3"^X^ 3 ^ „ 3' OCH^ nCH fl ^^=^ 2it>H*^ H °^"3 Hydrolysis of the ketene acetal would then give the alanine esters observed. One possible reason for the difference in reactivity in the series of aliphatic amines is the increasing bulk, of the substituents which could hinder the approach to C-2 to complete the simple addition process. 53 Corey reported that the NMR spectrum of 1,1-dimethoxyethylene consisted of two singlets at 3.08 and 3.466 in the ratio of 3:1. These absorbances are in the general region of the spectrum observed for the intermediate but more detailed comparison is not possible without a purer sample of the compound. The possibility of further reaction of the cyclopropyl amines was also considered. At the same time it was possible to investigate the case of adding amines to methyl orthoacrylate . A sample of

PAGE 97

87 dimethoxycyclopropene containing eighteen mole percent methyl orthoacrylate was treated with excess dimethylamine for four days at room temperature. Following evaporation of the amine, the crude reaction product was analyzed by NMR. The only absorbances observed were those for l,l-dimethoxy-2-dimethylaminocyclopropane and eighteen mole percent methyl orthoacrylate . Diphenylamine was then added to the NMR tube to attempt a ring opening reaction. No change at all was observed after 3 hours at 40-45° and after eighteen hours at 50-65° there was only partial reaction of the orthoacrylate. Thus, the cyclopropyl cunines appear to be stable once formed and it seems unlikely that methyl orthoacrylate would add amines under the conditions where formation of the alanine esters was observed.

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CHAPTER VII Summary and Conclusions The objectives of this research program were (1) to improve and expand the reactions leading to 3,3-dimethoxycyclopropene, (2) to further evaluate its physical and spectral properties, and (3) to establish its chemical reactivity toward a variety of systems. Significant improvement was realized in both yield and operational convenience by modifications in the reported procedures. Attempts to expand the scope of the reactions involved indicated that they are very specific for the reagents used and that other materials behave quite differently in the same system. The ultraviolet spectrum of dimethoxycyclopropene shows no absorbance above 210 my. The observed spectrum was a triplet centered at X 187 with e = 1670. The NMR absorbance for the rna.x cyclopropene protons v;as found to be sensitive to the electronic nature of the solvent and charge transfer studies were conducted using the technique of Hanna and Ashbaugh. The results of these studies indicated that dimethoxycyclopropene is an electron-deficient olefin in that weak complexes were formed with electron-rich species. The donors in this case were styrene and divinyl ether. The use of more powerful donors such as enamines would be a logical extension of this work. It would be especially interesting to see if stronger charge transfer complexation followed the use of this particular 88

PAGE 99

89 type of donor since enamines failed to give chemical reactions with dimethoxycyclopropene . As a dienophile, dimethoxycyclopropene is only moderately reactive. Adduct formation was realized in excellent yield with acyclic dienes, but an extended reaction time of a week or more was required. No reaction at all could be effected using cyclic dienes , presumably due to the steric interference of the geminal substitution. The unusual adduct observed to form between tetracyclone and dimethoxycyclopropene indicates that the olefin is also an electron source since the most likely mechanism for its formation involves nucleophilic attack on the carbonyl carbon of the diene. Formation of a normal Diels-Alder adduct was indicated but not proved in the reaction of dimethoxycyclopropene with 3,6-dicarbomethoxy-s-tetrazine. The tricyclic adduct in this case is [3.2.2.0] instead of [3.2.1.0] which should ease the steric requirements, but it is also interesting to note that the diene system includes hetero atoms. The importance of this feature would be an interesting program of study. Dimerization of dimethoxycyclopropene, observed early in the program, is still the only successful 2+2 cycloaddition reaction with a carbon-carbon double bond. The product of the reaction with hexafluoroacetone is a four-membered ring from what is formally a 2+2 cycloaddition reaction, but the most likely mechanism is not an electrocyclic process. As in the case of tetracyclone, the mechanism probably involves nucleophilic attack on the carbonyl group. In the hexafluoroacetone reaction, however, the cyclopropane

PAGE 100

90 ring is preserved since ring closure at C-2 occurs instead of bond cleavage. Cycloaddition with electron-rich olefins should be a facile process for dimethoxycyclopropene if the conclusions about its electron-deficient character are correct . The lack of reactivity toward enamines was therefore unexpected. The reason for this result is probably steric rather than electronic, however, since no adduction was observed with electron-poor species either. Dimethylacetylenedicarboxylate gave no indication of reaction at all. With phenyl triazolinedione , a very electrophilic cyclophile, none of the diazetidine which would result from cycloaddition was observed. Instead a copolymer was formed, pres\jmably by nucleophilic attack of the olefin on the triazolinedione and coupling of the resulting dipolar intermediate. It is interesting to note also that again the reactive center contains a hetero atom. Other reactive species involving oxygen, nitrogen, or sulfur should provide an enlightening area of investigation. Possibly effective reagents include isocyanates, thioketones , diazoalkanes , isothiocyanates, and diimides. Nucleophilic addition of secondary amines to dimethoxycyclopropene supports the conclusion that it is an electron — deficient olefin. Simple addition was observed for lower aliphatic amines to give l,l-dimethoxy-2-dialkylaminocyclopropanes . As the size of the substituents on the amine increased, however, a second process became increasingly important. This process involved destruction of the three-membered ring and formation of N,N-dialkylalanine

PAGE 101

91 methyl esters, presumably going through a ketene acetal as intermediate. Only the latter reaction was observed for the addition of diphenylamine so it is unlikely that base-strength causes the ring opening reaction. It is possible that steric effects cause the different modes of reaction in that it could become more difficult for the larger amines to approach C-2 for proton transfer to terminate the reaction. Consequently, the alternate process has opportunity to become operative. Stabilization of the ammonium ion intermediate could also be influential, and a series of reactions designed to probe these effects would be informative.

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CHAPTER VIII Experimental A. Equipment and Data All temperatures are reported uncorrected in degrees centigrade. Melting points were determined in open capillary tubes using a ThomasHoover melting point apparatus. All pressures are expressed in millimeters of mercury. Elemental analyses were performed by Atlantic Microlab, Inc., Atlanta, Georgia or PCR, Inc., Gainesville, Florida. Proton nuclear magnetic resonance (NMR) spectra were obtained on a Varian A-60 spectrometer. The chemical shift data are reported relative to the internal reference tetramethylsilane (TMS) using the parameter 6. Unless noted otherwise the solvent was deuteriochloroform. Mass spectral data were obtained from a Hitachi Perkin-Elmer RMU mass spectrometer using an ionization voltage of 70 ev. Infrared spectra were recorded with either a Beckman IRS Infrared Spectrophotometer or a Perkin-Elmer 137 Sodium Chloride Spectrophotometer. The IRS scan is linear with respect to wavenumber and the data are reported in units of reciprocal centimeters (cm. ). The Perkin-Elmer 137 is linear in wavelength so the data obtained on this instrument are reported in microns (y). Gas chromatography was conducted on a Hewlett-Packard 700 Laboratory Chromatograph or on an Aerograph Hy-Fi Model 600-D.

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93 Refractive indices were measured on a Bausch and Lomb ABBE-3L Refractometer. Number average molecular weights of polymers were obtained using a Mechrolab Model 302 Vapor Pressure Osmometer. The ultraviolet spectrum was obtained with a nitrogen purged Beckman Model DK-2A Ratio Recording Spectrophotometer. A nitrogen purge of 1.5 ft. /min. was used. The solution spectrum was determined _3 on a U X 10 molar solution in a 0.1 cm. far ultraviolet cell. Samples of 3,6-dicarbomethoxy-s-tetrazine and 3,6-diphenyl-stetrazine were obtained from Mr. Rudi Moerck and the N,N-diethyl-. styrylamine was provided by Mr. Robert Posey. All other chemicals used as reactants were commercial reagent grade and were used as received unless otherwise noted. Wherever possible the reactions were carried out in a hood or with other adequate precautions to prevent the escape of harmful or unpleasant fumes .

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94 B. Synthesis Preparation of l-bromo-3-chloro-2 ,2-diTnethoxypropane To a one-liter three-necked flask equipped with a magnetic stirrer and thermometer was charged 450 ml. anhydrous methanol and 3 drops of concentrated sulfuric acid. The flask was then cooled in an ice/acetone bath. When the temperature was about -5°, 50 ml. (0.54 mole) of freshly filtered 2 ,3-dichloropropene was added and the temperature rose to -3°, but it quickly fell back to -10°. This temperature was held for three hours and then gradually warmed to room tem.perature as the bath melted. Stirring was continued overnight . Saturated sodium bicarbonate solution (300 ml.) was carefully added to neutralize the acid catalyst and by-product HCl. The pale yellow color of the initial solution was discharged toward the end of the addition and large white crystals precipitated. This mixture was then transferred to a two-liter separatory funnel using a total of 500 ml. of pentane to dissolve the solids and to rinse the equipment. Additional water was added to the maximum capacity of the funnel and the two phases were vigorously mixed. The aqueous phase was separated and extracted three times with 50 ml. portions of pentane which were combined with the original organic phase. The pentane solution v/as washed once with 50 ml. of water and dried by filtering through anhydrous sodium sulfate into a one-liter Erlenmeyer flask. This flask was tightly stoppered and cooled for one hour in a dry ice/isopropanol bath. The white solid product formed a hard cake against the walls of the flask

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95 from which the supernatant liquid was easily decanted. Evaporation of the pentane gave 31.5 g. of by-product oils in which there was very little, if any, of the desired ketal according to NMR analysis. The solid product was redissolved in 500 ml. of fresh pentane and again precipitated at -78° for one hour. Following removal of the liquid phase, the product was allowed to warm under a stream of dry nitrogen to prevent condensation of moisture and to remove any remaining solvent. The yield of pure white crystalline product was 83.0 g. (71%). In some cases, infrared analysis of the product showed contamination with traces of a carbonyl compound which was undetectable by NMR. In these instances, the l-bromo-3-chloro-2,2-dimethoxypropane was purified by dissolving in pentane, passing it through a column of silica gel and then freezing out as before . One experiment was conducted in this manner except that the temperature was -78° when the N-bromosuccinimide was added. The yield of 85 g. was only a very slight increase that does not justify the more severe conditions. Identification of reaction by-products The oils obtained by evaporating the pentane from crystallization mother liquors at the purification step of l-bromo-3-chloro2,2-dimethoxypropane were combined from a number of runs. Distillation of this material gave an 85% yield of fractions boiling at 103-10U° under 58 mm. pressure. Analysis of one center fraction indicated mostly the compound(s) giving NMR signals near U.l6. Thin layer chromatography on silica gel indicated one major component

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96 which eluted v/ith pentane and one minor one which remained at the origin. ^ Column chromatography then afforded material which gave three signals in the NMR at 4.18, 4.15 and 4.076 in the approximate ratio of 2:1:1. The mass spectrum showed a small parent peak at m/e 224 with the correct isotopic distribution for CI Br. Subtraction of the halogen leaves 40 mass units for the remainder of the molecule which can be realized as C H . Elemental analysis corroborated this conclusion: Calc. for CgH^^BrCl^: C, 15.92; H, 1.78; Br, 35.31; CI, 46.99. Found: C, 15.12; H, 1.82; Br, 35.22; CI, 46.89. Other fragments of the mass spectrum occurred at m/e 189, 175, 145 (base peak), 109, 96, 83, 61, and 49. The infrared spectrum showed absorbances at 3045 (m), 2985 (m), 2850 (w), 1420 (s), 1290 (m), 1250 (m), 1220 (m), 1200 (m), 1118 (m), 980 (m), 918 (s), 870 (w), 758 (s), 742 (s), 708 (s), 670 (s), 650 (s), and 620 (s) cm. R eaction of 2 ,3-dibromopropene with NBS/methanol To a 250 ml. three-necked flask equipped with magnetic stirrer, thermometer, and straight condenser was added 20 g. (0.1 mole) of freshly distilled 2 ,3-dibromopropene , 100 ml. of nethanol and 5 drops of 70% perchloric acid. A total of 18 g. (0.1 mole) of N-bromosucciniraide was added in small portions over one hour at about 30°. After stirring overnight, the reaction mixture was worked up as described earlier except that no solid products were obtained. Analysis of the crude mixture by NMR indicated that the maximum possible content of the desired ketal was only 20l. Chromatography

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97 on alumina with pentane as eluant showed that the major reaction product gave only one signal in the NMR — a singlet at 4.26 6 (compare to 4.155 for the CH -Br protons of the starting olefin). The infrared spectrum (neat) gave absorptions at 3050 (w), 2990 (w), 2950 (w), 1U15 (s), 1250 (m), 1230 (m), 1180 (m), 1110 (m), 950 (m), 880 (s), 710 (w), 680 (m), and 650 (s) cm." . These results indicate that direct bromination was the main reaction pathway and that the product obtained was 1,2,2,3-tetrabromopropane. Reaction of 2,3-dichloropropene with NBS/ethylene glycol A 500 ml. three-necked flask was charged with 300 ml. of ethylene glycol, 47 ml. (0.5 mole) of 2,3-dichloropropene, two drops of concentrated H SO and 50 ml. of 1,4-dioxane to homogenize the mixture. The addition of 75.1 g. (0.5 mole) of N-bromosuccinimide and treatment of the reaction products followed established procedures. The NMR spectrum of the crude reaction mixture showed peaks at 4.20, 4.15, 4.08, 3.63, and 3.486 and all appeared to be singlets. The last three correspond in shift and intensity to the desired ketal obtained later. When a sample of 2,3-dichloropropene was treated with bromine in carbon tetrachloride, the NMR of the product showed singlets at 4.20 and 4.156. Preparation of l-bromo-3-chloro-2,2-ethylenedioxypropane A mixture of 21.7 g. (0.1 mole) of l-bromo-3-chloro-2 ,2-dimethoxypropane and 7.6 g. (0.12 mole) of ethyleneglycol was placed in a 100 ml. round bottomed flask along with two drops of concentrated H^SO and heated on the steam bath for six hours. Analysis of an aliquot indicated quantitative conversion to the ethylene ketal.

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98 The crude product was dissolved in pentane and washed with water. After drying with Na^SO^, the solvent was stripped on a rotary evaporator to yield 17.0 g. (79%) of ketal. Distillation under reduced pressure (b.p. 70°/1.2 mm.) gave analytically pure material which had a melting point of 10° and a refractive index of 1.5020 at 26°. In the NMR spectrum there was a 4proton singlet at 4-.056, and two 2-proton singlets at 3.62 and 3.476. Infrared absorbances were observed at 2980 (s), 2905 (s), 1477 (s), 1422 (s), 1200-1020 (group of 4 strong bands), 1000 (s), 950 (s), 805 (m), 750 (s), and 660 (m) cm. The mass spectral analysis showed no parent peak. Fragments were observed at m/e 155 (1:1), 121 (1.65:1) (base peak), 93 (1:1), 77 (3:1), and 49 (3:1). [The numbers in parentheses are the ratios of the indicated peak to the P+2 peak]. Analysis: Calc. for C^H_0„BrCl: C, 27.87; H, 3.74; Br, 37.09; CI, 16.45. Found: C, 28.01; H, 3.71; Br, 36.80; CI, 16.32. Preparation of l,3-dichloro-2 ,2-ethylenedioxypropane The method of preparing this compound was essentially that of Pfeiffer and Bauer. A 250 ml. round bottomed flask was charged with 32 g. (0.25 mole) of l,3-dichloro-2-propanone , 19 g, (0.3 mole) ethylene-glycol, 0.2 g. p-toluenesulfonic acid and 125 ml. of benzene, The mixture was stirred and refluxed under a Barrett water trap. After two hours less than 0.5 ml. of water had collected and there was no moisture in the refluxing solvent. Addition of three drops of concentrated H SO and 18 hours of additional refluxing produced 4-5 ml. of water in the trap.

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99 Sodium carbonate (5 g.) was added to neutralize the acid catalyst and the benzene solution was washed well with water. After drying through Na-SO , the solvent was removed on a rotary evaporator and the product purified by distillation. The yield of pure material (b.p. 90° /7 mm.) was 38.5 g. (90%). The reported boiling point was 105-6°/12 mm. The NHR spectrum showed two singlets of equal intensity at U.02 and 3.576. Absorbances in the infrared were observed at 2980 (s), 2905 (s), 1U71 (m), 1425 (s), 1315 (m), 1290 (m), 1250 (m, doublet), 1215 (s), 1143-1020 (group of four strong bands), 950 (s), 830 (m), 760 (s), and 715 (w) cm."-"-. Mass spectral analysis gave no parent peak , but fragments were observed at m/e 121 (base peak), 77, and 49, having the isotopic distribution ratio indicative of one chlorine atom. Anal. Calc. for C^HgCl^O^: C, 35.11; H, 4.71; CI, 41.46. Found: C, 35.31; H, 4.89; CI, 41.24. The refractive index, measured at 23°, was 1.4766. Preparation of l,3-dichloro-2,2-dimethoxypropane To a 500 ml. round bottomed flask was added 60.4 g. (0.48 mole), l,3-dichloro-2-propanone, 250 ml. anhydrous methanol and five drops of concentrated H2S0j^. A soxhlet extractor filled with 3A molecular sieves was placed between the flask and a reflux condenser so that the condensed solvent passed through the bed of sieves before returning to the reaction flask. After refluxing overnight, the infrared spectrum of an aliquot

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100 showed a small absorbance at 1720 cm. . Fresh molecular sieves were added and refluxing was continued for four hours. At the end of this time there was no carbonyl absorbance in the infrared. The mixture was then diluted with water and the product was extracted into pentane , washed and dried. Freezing to -78° failed to separate the product from colored impurities so the solvent was evaporated and methanol was added. Crystallization from this solvent gave 18 g. (22%) of colorless crystals, m.p. 82.5-83.5°. The 55 reported melting point was 81.5°. The NI^R spectrum consisted of two singlets at 3.55 and 3.226 in the ratio of 2:3 respectively. The infrared spectrum (KBr) showed absorbances at 3055 (m) , 3020 (s), 2985 (s), 2950 (m), 2850 (s), 1450 (s), 1445 (s), 1430 (s), 1305 (s), 1255 (m) , 1220 (s), 1190 (s), 1100 (s), 1050 (s), 990 (m), 825 (s), and 755 (s) cm." . Mass spectral analysis showed no parent peak. Fragments were observed at m/e 141, 123, 105, 91, 79, 74, and 63. Anal. Calcd. for C H CI 0^: C, 34.70; H, 5.83; CI, 40.98. Found: C, 34.98; H, 5.99; CI, 40.73. Preparation of l,3-dibromo-2 ,2-dimethoxypropane A mixture of 15 g. (0.07 mole) of l,3-dibromo-2-propanone , 50 ml. of anhydrous methanol, and one drop of concentrated H SO^ was placed in a 100 ml. round bottomed flask which was then topped with a soxhlet extractor containing 20 g. of 3A molecular sieves. Refluxing overnight failed to remove all carbonyl absorbance from the IR, so it was continued for ten hours longer. Isolation of the product as described for l-bromo-3-chloro-2 ,2-dimethoxypropane gave 5.3 g. (27%)

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101 of crystals for which NMR analysis showed only a 2-proton singlet at 3.50 6 and a 3-proton singlet at 3.256. The melting range, however, was 58-66°. Two recrystallizations from pentane gave material melting at 65.5-66.5°. The reported^^ melting point of the dibromoketal is 62.5°. Cyclization of l-bromo-3-chloro-2 ,2-ethylenedioxvpropane A 500 ml. three-necked flask was equipped with a large dry ice/ isopropanol cooled condenser and an all-glass, single-unit fitting for the center hole which had a U mm. inlet tube reaching as near as possible to the bottom of the flask. A glass stopper was placed in the third opening and the vent from the condenser was protected from the atmosphere by a drying tube filled with potassium hydroxide pellets. Before charging the condenser, the entire assembly was flamed dry while purging with nitrogen. Commercial anhydrous ammonia was purified by passing it through a tower of barium oxide and approximately 1150 ml. was collected in the flask. Nitrogen through the inlet tube was then adjusted to a steady rate to provide agitation for the reaction and a small piece of potassium metal was added. The initial blue color of dissolved metal was discharged a few minutes after the addition of feric chloride catalyst. Two other small portions of potassium were allowed to react completely in order to insure initiation of the electron transfer reaction and the remainder of the potassium was added as rapidly as the vigor of the reaction would allow. After all the potassium had reacted, the glass stopper was

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102 removed and replaced with a dropping funnel containing 21.5 g. (0.1 mole) of l-bromo-3-chloro-2,2-ethylenedioxypropane. This ketal was added dropwise over one hour. The entire assembly was then transferred to a cold box and stored overnight at -48° . Nitrogen bubbling continued to provide agitation during this time. Following return of the reaction to the hood, any unreacted amide was destroyed by adding 10.7 g. (0.2 mole) of anhydrous ammonium chloride. Evaporation of ammonia in a slow stream of nitrogen was accompanied by periodic additions of ethyl ether so that a fairly constant volume of solution was maintained . When the temperature had risen to -20° , most of the ammonia was off and the ether solution was filtered from the solid by-products, The ether was then removed at reduced pressure and the product was recovered by distillation. The yield was 1.3 g. (13%) as an 80% solution in ether. Residue remaining in the flask weighed 4,0 g. The NMR spectrum showed three singlets at 7.72, 4.01, and 0.906. When a sample was treated with DO, the signal at 7.726 disappeared and left the other two in equal intensities. Hydrolysis of the entire reaction mixture was then effected by stirring for three hours with 17 ml. of HO. Preparative gas chromatography on a twelve-foot column of Carbowax-30 at 150° gave a pure sample of 4,7-dioxaspiro[2.4]heptane. The infrared spectrum gave absorbances at 3110 (w), 3030 (m), 2990 (m), 2910 (s), 1490 (m), 1460 (s), 1405 (w), 1335 (s), 1185 (s), 1030 (s), 1000 (s), 930 (w), 945 (w), 850 (m) , 765 (w), and 755 (w) -1 cm.

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103 Mass spectral analysis showed a molecular ion at m/e 100, which was 74% as intense as the base peak which occurred at m/e 99. Other fragments were observed at m/e 56, 55, UU, 43, and UO. Anal. Calc. for C^H„0-: C, 59.98; H, 8.05. Found: C, 59.85; H, 8.13. b o
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104 line to the "left" flask, opening the line between the two flasks and partially blocking the vent from the "right" flask with a finger. The stirring of the reaction mixture caused the flask to be filled when the addition was only two-thirds complete, so some ammonia was allowed to evaporate. As a result, the total addition time was 1.5 hours. The color of the reaction was bright yellow until near the end when it became dark green. Stirring was continued for four hours longer and then excess amide was destroyed by adding ammonium chloride . A marked color change from green to brown occurred when 4.5 g. (0.08 mole) had been added. Ammonia was then allowed to evaporate under vigorous stirring and ethyl ether was added as replacement solvent . After 400 ml. had been added, the mixture was stirred until the temperature rose to -25°. The solution was then filtered and the equipment and solid by-products were rinsed well with ether. The solids weighed 25.0 g. (theory should be about 26) and gave an aqueous solution of pH 7 or 3 in which very little organic material was apparent. Following overnight storage in the dry ice chest , the ether was distilled from the filtered solution under 80 mm. pressure until the temperature of the flask rose to 0° . Receivers were then changed and the pressure was slowly reduced to 0.5 mm. Product was distilled until the pot temperature rose to 25°. The yield v;as 12.5 g. of a 38 mole per cent solution of dimethoxycyclopropene in ether. This represents a weight yield of 4.9 g. (49%) of pure product. Redistillation of the ether solvent at atmospheric pressure yielded an additional 0.9 g.^.for a total recovery of 58%. Residue

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105 from the main product distillation weighed only 1.6 g. and did not contain any unreacted starting material. When scaled up to five times this size, the amide was prepared in a two-liter flask and the reaction was conducted in a three-liter flask. The yield from 108.5 g. (0.5 mole) of bronochloroketal was 32.1 g. (65%) of pure dimethoxycyclopropene-. Reaction of l-bromo-3-chloro-2,2-dirnethoxypropane with hexamethylphosphoramide (HI'iPA) The solvent was dried by distillation under nitrogen over Linde 13X molecular sieve (calcined under nitrogen at 350° for four hours ).^^ A solution was prepared from 2.2 g. (0.01 mole) of l-bromo-3-chloro2,2-dimethoxypropane and an equal weight of HMPA. This solution was then diluted with an additional 10 ml. of solvent and slowly heated to 220°. The mixture became very dark in color and about 2 ml. of liquid collected in an ice-cooled receiver. This liquid was probably dimethylamine since it boiled away when the bath was removed. No products were recovered from the reaction flask. Reaction of the bromochloroketal with NaH in HMPA To a 250 ml. three-necked flask was added 4.8 g. (0.022 mole) of the ketal and 100 ml. of HMPA. The mixture was cooled to 0° and 2.0 g. (0.044 mole) of NaH (50% dispersion in mineral oil) was added in small portions. The reaction was mildly exothermic and foaming indicated hydrogen evolution. Warm'ihg to room temperature and stirring overnight failed to effect any reaction at all. An additional gram of NaH was added and the mixture was heated at 75° for two hours. Dilution with water and extraction into methylene chloride resulted in a quantitative recovery of unreacted starting material.

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106 Preparation of 3 ,U-dimethyl-7 ,7-dimethoxy-3-norcarene A mixture of 0.8 g. (8 mmole) of dimethoxycyclopropene and 1.0 g. (12 mmole) of 2 ,3-dimethylbutadiene was charged to a 5 ml. round bottomed flask and stored at room temperature for four weeks. At the end of this time the excess diene was evaporated in a stream of nitrogen and NMR analysis of the residue indicated almost quantitative conversion to the expected adduct . Analysis by gas chromatography on a tv/elve-foot column of Carbowax 30 at 150° indicated that the major component was 90-95% of the mixture. A pure sample was obtained by preparative GC under the same conditions. In the NMR spectrum there was a singlet at 3.385, a singlet at 3. 286, a broad singlet at 2.106, a singlet at 1.586, and a multiplet centered at 1.306 v?ith area ratios of 3: 3:4:6:2, respectively. The infrared spectrum (neat) gave absorbances at 3.45 (s), 6.92 (s), 7.08 (m), 7.23 (w) , 7.55 (m), 7.88 (s), 8.12 (m), 8.30 (m) , 8.88 (s), 9.54 (s), 9.80 (w) , 10.20 (w), 10.70 (m) , 1120 (w), and 1228 (w) y. it Mass spectral analysis gave an abundant molecular ion at m/e 182 (63% of base peak) and other fragments at m/e 167, 135, 108, 107 (base peak), 105, 94, 93, 91, and 59. Anal. Calcd, for C,,H : C, 72.49; H, 9.95. Found: C, 72.54; H, 9.72. Preparation of 7 ,7-dimethoxy-3-norcarene Approximately 10 ml. of butadiene was condensed into a pressure bottle by cooling with dry ice. To this was added 1.0 g. (10 mmole) of dimethoxycyclopropene. The bottle was then sealed and the mixture

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107 stored at room temperature for four days. Analysis of an aliquot at the end of this time revealed some unreacted cyclopropene so the reaction was continued for nine days. . Removal of excess butadiene gave a mixture which gas chromatography indicated was 90% product. A pure sample was isolated by preparative gas chromatography on a twelve-foot column of Carbowax 30 at 160° . Analysis by MMR revealed a broad singlet at 5.626, sharp singlets at 3.47 and 3.356, and two other broad singlets at 2.24 and 1.346. The eirea ratios were 2:3:3:4:2, respectively. In the infrared spectrum there were absorbances at 3.32 (s), 3.40 (s), 3.46 (s), 3.53 (s), 5.73 (m), 5.90 (m), 5.98 (w), 6.12 (m), 6.92 (s), 7.08 (s), 7.49 (m), 7.88 (s), 8.24 (s), 8.90 (s), 9.03 (s), 9.54 (s), 9.78 (m), 10.03 (w), 10.30 (m), 10.88 (m), 11.22 (m), and 14.00 (m) y. The mass spectrum showed a parent peak at m/e 154 which was 66% of the base peak. Other fragments were observed at m/e 139, 123, 107, 88, 79 (base peak), 77, and 59. Anal. Calcd. for C^H-,,0^: D 14 2. C, 70.10; H, 9.15. Found: C, 69.85; H, 9.11. Preparation of 3-methyl-7 ,7-dimethoxy-3-norcarene To a 10 ml. round bottomed flask was added 1.4 g. (14 minole) of dimethoxycyclopropene and 3.7 g. (55 mmole) of isoprene. The flask was stoppered and stored at room temperature for thirteen days. A sample was analyzed and no cyclopropene was left. Excess isoprene was then removed by evaporation in a stream of nitrogen. The residue was analyzed by GC (8' x 1/4" column of 10% Carbowax at 175°) and the major component (93%) eluted last.

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108 Pure product was then obtained by collecting this fraction as it eluted from the column. Signals in the MR were observed at 5.296 (broad singlet) for one proton, 3.42 and 3.325 (singlets) for three protons , each, 2.38 to 1.986 (multiplet) for four protons, 1.676 (singlet) for three protons and at 1.45 and 1.256 (multiplet) for two protons. The infrared spectrum showed absorbances at 3.45 (s), 5.72 (m), 5.90 (w), 5.93 (s), 7.08 (s), 7.28 (m), 7.45 (w), 7.56 (m), 7.70 (m), 7.90 (s), 8.18 (m), 8.30 (m), 8.65 (w), 8.90 (s), 9.55 (s), 9.85 (m), 10.15 (m), 10.35 (m), 10.90 (s), 11.42 (w), 12.25 (m) , and 12.72 (s) u Mass spectral analysis gave a molecular ion at m/e 158 whose intensity was 49% of the base peak which occurred at m/e 93. Other fragments were observed at m/e 153, 121, 91, 88, 79, 77, and 59. Anal. Calcd. for C^.H^.O.: C, 71.39; H, 9.59. Found: C, 71.50; H, 9.55. Hydrogenation of the butadiene adduct Approximately 0.3 g. of the adduct, 15 ml. of petroleum ether, and 0.5 g. of 5% palladium on carbon were charged to a pressure bottle and shaken for forty minutes under 50 psi of hydrogen on a Parr hydrogenation apparatus. The catalyst was then removed by filtration through Celite and the solvent was evaporated. Gas chromatography (12', 30% Carbowax at 150°) showed three components which were poorly separated. In order of elution they were approximately 20%, 15%, and 65% of the mixture. When preparative scale chromatographs were attempted, the first two were not separated and when collected

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109 together did not provide sufficient material for identification. The major component was isolated and it showed a sharp NMR singlet at 3.76 and a poorly resolved multiplet between 2.0 and 1.06 in the ratio of 3:11. Mass spectral analysis gave a molecular ion at m/e 1U2 which corresponds to C^H^^^O^. Infrared analysis confirmed that this compound was the methyl ester of cyclohexane carboxylic acid. Attempted hydrolysis of the 2 ,3-dimethylbutadiene adduct A small sample of the adduct was treated overnight at room temperature with aqueous acetone containing a drop of hydrochloric acid. When no reaction was noted, the mixture was refluxed for two hours with no effect . Another sample was placed in 50% aqueous dioxane containing a trace of sulfuric acid and refluxed for eight hours; again the adduct was recovered unchanged . Attempted bromination of the isoprene adduct A sample of the adduct formed with isoprene was dissolved in CClj^ in an NHR tube and treated with Br^ in CCl . Since the concentration of the latter solution was unknown, the stoichiometry could not be determined. However, when the solution was analyzed by NMR after partial reaction, there was no change in the ratio of vinyl protons to bridgehead protons as would be expected if the cyclopropane ring remained intact while the olefin was brominated. Exhaustive bromination resulted in the loss of all cyclopropyl protons in the NHR and the production of a very dark colored solution along with the evolution of hydrogen bromide gas. No attempts were made to identify any of the products.

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110 Preparation of 2 ,7 ,7-trimethoxy-3-norcarene A mixture of 1.0 g. (10 mmole) of dimethoxycyclopropene and 2.5 g. (30 mmole) of 1-methoxybutadiene was stored at room temperature for nine days. Analysis by NMR of a sample did not show any unreacted cyclopropene . Distillation under reduced pressure gave one fraction of 0.76 g. (41%) which NMR indicated was fairly pure adduct. Additional product was present in the residue but was not recovered. Gas chromatography of the product fraction (8' x 1/4" column of 10% Carbowax 30 at 190°) showed four significant peaks eluting after the solvents and low-boiling material. These peaks were isolated by preparative gas chromatography using the same conditions of operation. Peak Elution Time, Hin. Relative Abundance 1

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Ill Mass spectral analysis failed to show a molecular ion. The base peak was observed at m/e 105 and another major fragment (89% of base) was recorded at m/e 77 accompanied by a metastable peak at 56.5. Other fragments were noted at m/e 152, 151, 136, 121, 117, 106, 93, 91, 78, 79, 59, 57, and 51. Anal. Calcd. for Cj^QH^gO^: C, 65.19; H, 8.70. Found: C, 65.25; H, 8.70. These data are consistent with the structui-'e expected for the title compound. When a sample of peak four was injected into the gas chromatograph, several components eluted instead of the expected single pure compound. There were "lights" and compounds with retention times corresponding to peaks one and two of the preparative work as well as peak four. There was none of the compound giving peak three, however. The ratio P2:PH was 1:3. Peak two was shown to be methyl benzoate . The NMR spectrum gave absorbances at 7.38-7.0U6 (multiplet), 6.80-5.346 (multiplet), and 3.096 feinglet) with relative area ratios of 2:3:3. The infrared spectrum was identical to the spectrum of methyl benzoate. Peak three was not obtained in pure form. Its hflW and IR spectra showed absorbances due to methyl benzoate. In addition, the NMR spectrum showed peaks at 5.936 (multiplet), 3.336 (singlet), 2.68-1.306 (broad multiplet), and 1.18-0.966 (doublet) with area ratios of 1:2:3:2 respectively. The intensity of the carbonyl aibsorbance in the infrared indicated that it was only due to the ester impurity. In the region between 1000 and 1200 cm. there was a single broad absorption centered at 1100 cm. . No other features of the pure compound were discernible.

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112 These data do not give enough information for a structure to be proposed, but they do rule out the possibility of peak three being a geometrical isomer of 2 ,7 ,7-trimethoxy-3-norcarene. Peak one was not obtained in sufficient quantity to permit its identification. Attempted reaction of dimethoxycyclopropene with cyclopentadiene The cyclopentadiene was prepared by thermal cracking of commercial dicyclopentadiene and distillation at atmospheric pressure through a '2 2—' X 1" column filled with stainless steel protruded packing. A mixture of 1.0 g. (15 mmole) of cyclopentadiene and 1.0 g. (10 mmole) of dimethoxycyclopropene was dissolved in 25 ml. of methylene chloride which had been passed through a column of alumina. This solution was refluxed for 7— hours . Following evaporation of solvent and diene, an aliquot indicated no change in the dimethoxycyclopropene. Solvent was then removed to give about 2 ml. of a concentrated solution and fresh diene was added. No reaction was indicated after standing overnight at room temperature nor after the addition of 2 ml. of vapor from a bottle of BF„ etherate and an additional 22 hours of reaction time. The solution was next transferred to a pressure bottle with a little dimethoxyethane and heated at 70° for 3^ hours. All cyclopropene was gone from the NMR spectrum and some reaction of the cyclopentadiene was indicated.Dimethoxycyclopropene dimer was observed but there was no indication of adduct formation as a major reaction pathway .

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113 Reaction of dimethoxycyclopropene with tetracyclone To a solution of 0.5 g. (5 mmoles) of dimethoxycyclopropene in 25 ml. of freshly distilled tetrahydrofuran was added a solution of 1.9 g. (5 mmoles) of tetracyclone in the same solvent. This mixture was heated to reflux and held for eight hours with no observed color change. Analysis of a sample indicated decomposition of the olefin and no reaction of the diene. Additional dimethoxycyclopropene (0.6 g. ) was added and the mixture was stored at room temperature. After two weeks the color had faded from the solution. Solvent was evaporated from the reaction mixture and methanol was added to the tan residue. A white solid separated which was recrystallized from acetone to yield 0.3 g. (12.5%) of pure material. Additional material was present in the methanolic liquors, but it was not recovered. The melting point of the purified material was 213.5-215.0°. The NMR spectrum showed absorbances at T.UU to 6.686 (multiplet), 6.35 to 5.966 (AB quartet) and 2.955 (singlet) with area ratios of 10:1:3, respectively. In the infrared spectrum there were weak absorbances at 3100, 3070, 3050, 2990, 2960, and 2860 cm."""". Other peaks were observed at 1630 (w), 1600 (w), lUQS (m), 1UU7 (m), 1345 (m), 1265 (m), 1240 (m), 1190 (m), 1160 (m), 1130 (s), 1105 (w), 1070 (s), 1045 (s)', 1000 (s), 870 (m), 820 (m), 780 (m), 765 (m), 735 (m), and 700 (s) cm."-"-. Mass spectral analysis gave a molecular ion at m/e 484 which was also the base peak. Other major fragments were observed for P-15 and P-28. Anal. Calcd. for C-j^H : C, 84.27; H, 5.82. Found: C, 84.11; H, 5.79.

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114 The following structure was proposed for the compound: OCH, Hydroly sis of the tetracyclone adduct A very small sample of the adduct was treated with aqueous acetone at room temperature and extracted into CCl . The NMR spectrum showed only aromatic protons and an AB quartet with the A proton doublet centered at 7.456 and the E at 6.16. The coupling constant, J.r,5 "^s 5.5 cps. In the infrared spectrum there was a prominent carbonyl absorption at .1780 cm. ; . These data are consistent with the following proposed structure: Ph; ^=^y^H Reaction of dimethoxycyclopropene with 3 ,6-dicarbomethoxy-s-tetrazine Methylene chloride for solvent in this reaction was purified by passing it through a column of alumina. A solution of 48 mg . (0.48 mmole) of dimethoxycyclopropene in 10 ml. of this solvent was placed in a 50 ml. Erlenmeyer flask and sealed with a rubber septum.

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115 The atmosphere inside the flask was purged with dry nitrogen by the use of hypodermic needles. A solution of 97 mg. (0.U8 iranole) of 3,6-dicarbomethoxy-s-tetrazine in 15 ml. of methylene chloride was added with a syringe which was rinsed with about 5 ml. of additional solvent. The initial red color of the tetrazine slowly faded and nitrogen was evolved for about three hours. After standing overnight all traces of red were gone leaving a clear yellow solution. Solvent was evaporated from an aliquot and an NMR spectrum was obtained on the residue. Main features of the spectrum were singlets at 3.88, 3.72, and 3.336 and a multiplet at 1.30 to 0.856. The intensity was too low for reliable integration of the relative areas. When solvent was next evaporated from the bulk of the reaction mixture, a yellow oil was produced which was insoluble in hexane. It was redissolved in methylene chloride and non-solvent hexane v/as added in an effort to effect crystallization. The oil which separated was isolated by decanting and dissolved in carbon tetrachloride. The NMR spectrum of this solution did not have any of the features described for the aliquot above. Carbon tetrachloride was removed and the oil was dissolved in methylene chloride. Dropwise addition of this solution to hexane gave material for which the NMR spectrum (acetone-d^.) showed absorbances at 5.986 (multiplet), 4.566 (doublet), 4.086 (multiplet), 3.86, 3.79, 3.705 (all singlets), 3.406 (multiplet), and 2.876 (broad). The three singlets were the dominant features of the spectrum, but integration

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116 was not possible. Column chromatography and solvent separation techniques were unsuccessful in producing a pure compound. Attempted reaction of dimethoxycyclopropene with 3 ,6-diphenyl-stetrazine A solution of 7.1 mg. (.71 mmole) of dimethoxycyclopropene in 10 ml. of methylene chloride (treated with alumina) was charged to a 50 ml. Erlenmeyer flask which was stoppered with a rubber septum and purged with dry nitrogen. When a solution of 155 mg. (0.71 ramole) of the tetrazine in 10 ml. of methylene chloride was added, there was no apparent color change or evolution of nitrogen to indicate reaction. After eight days, the mixture was transferred to a 100 ml. round bottomed flask and refluxed under nitrogen for three days with no color change . Most of the solvent was then evaporated and then just enough methylene chloride was added to effect solution. When ethyl ether was added a red solid separated which gave NMR absorb ances only in the aromatic region. The ether phase was cooled until all red color precipitated and the yellow solution was separated. Evaporation of the solvent left an oil which did not show any aromatic absorbance in the NMR. Attempted reaction of dimethoxycyclopropene with 1,2 ,3,U-tetrachlorocyclopentadiene The diene for this reaction was purified by sublimation at 70° under 1-2 mm. pressure. Only a few crystals of colorless material were collected, and they were rinsed into an NMR tube with 1.0 to 1.5 ml. of benzene-d-. The NMR spectrum of this solution showed a sharp singlet at 2.256. Two drops of dimethoxycyclopropene were

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117 added and the mixture was stored in the dark at room temperature for three days. Analysis of the solution by NMR showed no remaining cyclopropene but no change in the signal at 2.256. Preparation of 3,3-bis(trifluoromethyl)-5 ,5-dimethoxy-2-oxabicyclo[?.1.0] pentane Approximately 5 ml. of hexafluoroacetone was condensed into a Fisher-Porter pressure bottle by cooling the bottle in a dry iceisopropanol bath and also using a dry ice cooled condenser over it. To this was added 1 ml. of dimethoxycyclopropene . The pressure bottle was then sealed and allowed to warm to room temperature . After three days, the excess hexafluoroacetone was allowed to evaporate and the residue was analyzed by NMR. The spectrum was very simple and showed a poorly resolved multiplet at 5.666 (one proton), a broad singlet at 4.866 (one proton), and sharp singlets at 3.81 and 3.506 (three protons each). There was also evidence for a small cimount of impurity near 3.356, but this was easily removed by dissolving the sample in pentane and passing it through a column of silica gel. 19 The r NMR spectrum could only reveal that the compound had two different trifluoromethyl groups which were coupled to each other. Additional coupling, probably to one or more protons, was indicated but no information about the structure was forthcoming. In the infrared spectrum there were absorbances at 3150 (w), 2970 (m), 2865 (w), 2855 (w), 1725 (w), 1670 (s), 1U65 (m), 1410 (m), 1358 (m), 1325 (s), 1290 (s), 1225 (s), 1115 (s), 1055 (s), 1008 (m), 962 (s), 945 (s), 828 (m), 775 (m), 746 (w), 736 (w), and 715 (s) cm."-"-.

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118 The mass spectrum showed a small peak at m/e 265 for the molecular ion. The base peak occurred at m/e 197, corresponding to loss of a trifluoromethyl radical. Other abundant fragments (greater than 20% of base peak) were observed at m/e 235 (loss of methoxy radical) and 69 (CF^"^ ion). Anal . Calcd. for CgHgF^O^: C, 36.10; H, 3.03; F, U2.83. Found: C, 36.13; H, 3.02. Preparation of l-(2-methyl-l-propenyl)-pyrrolidine The procedure for this reaction was a modification of the method 57 described by Heyl and Herr. To a 1-liter round bottomed flask equipped with a thermometer well was added 145 g. (2 moles) of pyrrolidine, 250 ml. of benzene and a magnetic stirrer. A nitrogen atmosphere was maintained throughout the reaction. A solution of 72 g. (1 mole) of isobutyraldehyde in 100 ml. of benzene was then added dropwise over 1.5 hours while stirring the mixture. The addition was mildly exothermic, raising the temperature to about 45°. A Barrett type water trap was assembled between the flask and a watercooled reflux condenser and heating was applied by means of an electric heating mantle. A temperature of 130° was required xo reflux the benzene and remove the water of reaction as an azeotrope . Approximately 23 ml. of an aqueous phase collected and the reaction was discontinued when the volume remained constant for 1 hour. Most of the benzene was removed on a rotary evaporator and the remainder was distilled at reduced pressure as was the excess pyrrolidine. The yield of crude enamine was 110 g. (88%). From this was distilled 39 g. of pure material boiling at 75° under 47 mm. pressure. (Reported

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119 boiling point is 70-71° at 38 mm.). A strong infrared absorbance -1 59 was observed at 1G72 cm. which is characteristic of this compound. Reaction of dimethoxycyclopropene with l-(2-methyl-l-propenyl)pyrrolidine To a 10 ml. round bottomed flask was added 2.5 g. (20 mmole) of the enamine and 2.0 g. (20 mmole) of dimethoxycyclopropene. The flask was purged with nitrogen and sealed with a rubber septum. The mixture was placed in a 45° oil bath for 2 hours and then a sample was removed for NMR analysis. The spectrum showed only absorbances due to the two reagents and low intensity peaks indicative of decomposition. Continued heating overnight at 53° failed to produce any significant change in the NMR spectrum. Reaction of dimethoxycyclopropene with N,N-diethylstyrylamine A 10 ml. round bottomed flask was sealed with a rubber septum and then purged with nitrogen. Approximately 2 ml. (1.9 g., 10.9 mmole) of the enamine was introduced with a hypodermic syringe and then approximately 1 ml. (1.1 g., 11 mmole) of dimethoxycyclopropene was added by the same method. The reagents were mixed well and stored in the dark at room temperature for three days. Analysis of a sample by NMR indicated little or no reaction had occurred. The flask was then placed in a 45° oil bath for 3 hours and again sampled. There was some indication of decomposition but nothing to suggest any type of adduct formation. Further heating of the mixture at 53° overnight resulted in the disappearance of alnost all of the cyclopropene absorbance in the NMR. The characteristic peaks of the

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120 enamine were still present but there was no change in the vinyl region of the spectrum to indicate adduction. Peaks typicallyobserved for decomposition of dimethoxycyclopropene were also seen. Reaction of dimethoxycyclopropene with phenyltriazolinedione This reaction was run in a heavy-walled polymer tube. To 0.9 g. (5 mmoles) of phenyltriazolinedione in this tube was added 15 ml. of methylene chloride. The tube was then purged with dry nitrogen and sealed with a rubber septum. It was cooled to -78° in a dry ice/ isopropanol bath. Dimethoxycyclopropene (0.5 g., 5 mmole) was added with a hypodermic syringe using methylene chloride to rinse it all in. One milliliter of a solution containing 0.11 g. of AIBN in 10 ml. of methylene chloride was added and the walls of the tube were rinsed down with additional solvent. After degassing through two freezethaw cycles on the vacuum rack, the tube was evacuated and sealed. The red color was gone after three hours at room temperature. The tube was then opened and the solution was added dropwise through a coarse glass filter to hexane which precipitated the polymer formed. It was collected by filtration and dried overnight under vacuum at 78°. The yield of crude product was 0.95 g. (58%) with an additional 0.2 g. being recovered from the equipment used. Evaporation of the hexane filtrate gave 0.3 g. of a yellow solid which was polymeric in nature and was not investigated further. Purification of the product was effected by precipitating three times from methylene chloride into hot hexane. The yield of white solid product (m.p. 168-178°) was 0.5 g. The NMR spectrum (DMSO-dg)

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121 showed a broad singlet at 7.U8(5 and a broad doublet centered at 3.U86 with a relative area ratio of 8:6. The infrared spectrum (KBr) showed broadened peaks at all frequencies. Absorbances were observed at 3085 (w), 29G0 (m), 2875 (w), 1780 (shoulder), 1730 (s), 1620 (m), 1600 (m), 1500 Cs), lUlO (s), 1260 to 1070 (two very broad peaks), 1020 (w), 750 Cs), 688 Cm), and 6U0 (w) cm.""'". The number average molecular weight was determined by vapor pressure osmometry with acetone as solvent and was found to be 1244. Anal. Calcd. for C^qH^^N^^O^q : C, 56.46j H, 4.50; N, 16.47. Found: C, 55.86; H, 4.40; N, 16.99. Reaction of dimethoxycyclopropene with phenyltriazolinedione in aceton e An NMR tube was charged with 13.4 ng. (0.076 mmole) of phenyltriazolinedione, 23.0 mg. (0.23 mmole) of dimethoxycyclopropene and approximately 1.5 ml. of acetone-d^. When the color was discharged, the mixture was analyzed by NMR and excess olefin and polymer were observed, but there was no indication of any other monomeric adduct . Reaction of dimethoxycyclopropene with methyl triazolinedione This reaction was run twice in different solvents using the same experimental technique. The two solvents were acetone and methylene chloride. To a 50 ml. Erlenmeyer flask containing a magnetic stirring bar was added 0.5 g. (4.4 mmole) of methyltriazolinedione . The flask was sealed with a rubber septum and then purged witn nitrogen. Solvent (15 ml.) was added to give a red solution of the diene. To

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122 this was added a solution of 0.U4 g. (4.4 mole) of dimethoxycyclopropene in 10 ml. of the same solvent. The solution was stirred and warmed with a magnetic stirrer for 24-28 hours. After this time all of the red color was discharged. The volume of solution was next reduced to about 15 ml. and then added dropwise to 300 ml. of hexane. The crude polymer (0.7 g.,(75%) from acetone and 0.6 g. (64%) from methylene chloride) was purified by precipitating three times from methylene chloride into hot hexane and then drying overnight under vacuum at 78° . Evaporation of the solvent from the hexane filtrate in the acetone run gave only 0.1 g, of material for v/hich the NMR spectrum was very complex, but no indication of acetone incorporation was evident. Spectral properties of the two polymers were identical. Their NMR spectra showed only three broad peaks between 4.2 and 3.86. The infrared spectra (KBr) showed broad absorbances at 3000 Cshoulder), 2950-(m), 2855 (w), 1775 (s), 1720 (s), 1455 (s), 1395 (m) , 1275 (m), 1220 (s), 1075 (s), and 755 Cs) cm.""*". Number average molecular weights were found to be 745 (acetone run) and 985 (CH CI run) by vapor pressure osmometry in acetone. Anal . Calcd. for 1:1 copolymer: C, 45.07; H, 5.20; N, 19.71. Calcd. for 2:1 (triazolinedione:cyclopropene) copolymer: C, 40.49; H, 4.32; N, 25.76. Found for product of acetone reaction: C, 41.25; H, 5.10; N, 22.08. Found for product of CH CI reaction: C, 42.23; H, 4.85 2 2 5 N, 22.36,

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123 Thermal reaction of dimethoxycyclopropene with dimethylacetylenedicarboxylate A mixture of 0.5 g. (5 mmole) of dimethoxycyclopropene and l.U g. (10 mmole) of dimethylacetylenedicarboxylate was allowed to react at room temperature for ten days. The NMR spectrum of the resulting material showed complete reaction of the cyclopropane but no indication of adduct formation. Photolytic reaction of dimethoxycyclopropene with dimethylacetylenedicarboxylate To a standard 1 cm. quartz cell for ultraviolet spectroscopy was added 0.5 g. (5 mmole) of the cyclopropene and 1.4 g. ClO mmole) of the acetylene . The cell was then capped and exposed for three days to sunlight. Results of the product analysis were the same as those in the preceding reaction. Attempted reaction of dimethoxycyclopropene with diallylamine Dimethoxycyclopropene for this reaction was obtained as a 30% solution in ether containing 1.3 g. (13 mmole) of the reagent. To this solution was added 20 ml. of freshly distilled diallylamine and the mixture was stored for one week at room temperature. Distillation gave a product which was almost exclusively diallylamine. There was another compound present which gave a singlet at 3.106, but the area ratio indicated it was in low concentration. Preparation of l,l-dimethoxy-2-diethylaminocyclopropane A mixture of 1.5 g. (15 mmole) of dimethoxycyclopropene and 25 ml. of diethylamine was stored at room temperature for three weeks.

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124 Excess amine was evaporated in a stream of nitrogen and the residue was distilled bulb to bulb at 1 mm. pressure. Analysis by gas chromatography indicated one major and two minor components. The major component constituted about 60% of the mixture and was isolated by preparative GC (8' column of 10% Carbowax at 160°). The minor components were obtained in insufficient quantity for identification. The NMR spectrum gave absorbances at 3.42 and 3.326 (singlets), 2.89 to 2.516 (quadruplet), 2.14 to 1.906 (multiplet), 1.18 to 0.946 (triplet), and 1.05 to 0.756 Cmultiplet) with relative area ratios of 3:3:4:o:6:2, respectively. In the infrared spectrum Cneat) there were peaks at 3.38 (s), 3,52 (m), 4.54 (w), 5.71 (w), 5.15 Cw), 6.90 (s), 7.20 (m), 7.30 (m), 7.80 (s), 8.20 (s), 8.53 (s), 9.12 Cs), 9.40 (s), 9.55 (_s), 9.85 (m), 10.08 (m), 10.85 (m), 11.20 (jn), 11.43 Cm), and 13.10 Cs) p. Mass spectral analysis showed a trace of the parent peak and a peak at P-1 for loss of hydrogen. The base peak occurred at m/e 158 corresponding to the loss of methyl radical. Other fragments were observed at 142, 126, 116, 101, 98, 84, and 56. The peak at m/e 56 is prominent (64% of base peak) but it is difficult to rationalize . Anal . Calcd. for C H NO^ : C, 52.39; H, 11.05; N, 8.09. Found: C, 62.15; H, 11.00; N, 7.89. Preparation o f l,l-dimethoxy-2-dipropylaminocyclopropane and N,N-dipropyl-B-alaninem.ethylester Freshly distilled di-n-propylamine (22 ml.) and 1.0 g. (10 mraole) of dimethoxycyclopropene were mixed and the solution was stored at

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125 room temperature for three weeks. Distillation under reduced pressure gave one fraction (b.p. 50° /0. 5 mm., 1.5 g.) whose hfMR spectrum indicated some of the expected cyclopropylamine . Gas chromatography (8' Carbowax, 190°) showed two major components in the approximate ratio of 40:60 in the order of elution time. These two components were isolated by preparative gas chromatography. The first component (40% of the mixtxare) gave an infrared spectrvim almost superimposable on that of the diethylaminocyclopropane. The NMR spectrum showed absorbances at 3.45 and 3.356 (singlets, 2.85 to 2.406 (multiplet), 2.22 to 1.906 (doublet of doublets), 1.80 to 1.196 (multiplet), and 1.10 to 0.656 (multiplet) with relative area ratios of 3:3:4:1:4:8, respectively. This compound was assigned the structure of the expected cyclopropylamine . The second component (60% of the mixture) gave an NMR spectrum showing a singlet at 3.656 and multiplets at 2.97 to 2.626, 2.56 to 2.176, 1.78 to 1.176, and 1.07 to 0.666 with relative area ratios of 3:2:6:4:5, respectively. The infrared spectrum gave absorbances at 3.40 (s), 3.48 (w), 3.57 (m), 5.72 (s), 6.85 (m), 6.95 (m), 8.00 (m), 8.30 (s), 9.25 (w), and 9.45 (w) y. Mass spectral analysis showed a molecular ion at m/e 187 which was 13% of the base peak which was observed at m/e 158 (loss of ethyl radical). Another abundant fragment was recorded at m/e 114 (65% of base peak) and arises from the loss of a methyl acetate radical. Anal. Calcd. for C^qH^.NO^: C, 64.13; H, 11.30; N, 7.48. Found: C, 64.25; H, 11.37; N, 7.39. The following structure was proposed for

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126 this compound. N-CH^-CH^-C-OCHg S«7 Preparation of N,N-diphenyl-B-alanine methyl ester To a 25 ml. round bottomed flask was added 1.0 g. ClO mmole) of dimethoxycyclopropene , 1.8 g. Cll mmole) of diphenylamine Crecrystallized from pentane) and 10 ml. of methylene chloride which had been passed through a column of alumina. The solution was stored at room temperature for four weeks and then added dropwise to pentane to precipitate any unreacted diphenylamine . When all material was found to be soluble at 0° , the solvents were removed and the residue was analyzed by NMR. Adduct formation was indicated by two nonequivalent methoxy groups. A new compound giving a sharp singlet at 3.185 was also noted. About half of this sample was placed on a silica gel column with pentane to attempt chromatographic separation of the mixture. It immediately experienced a vigorous exothermic reaction. Development of the column gave 1.0 g. of material which appeared to be largely a single compound. A second chromatography on silica gel gave this material in pure form. The NMR analysis gave absorbances at 7.32 to 6.656 (lO-proton multiplet), t+.15 to 3.806 (2-proton multiplet), 3.515 (3-proton singlet), and 2.75 to 2.386 (2-proton multiplet). In the infrared there were absorbances at 3.29 (m), 3.38 (m) ,

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127 5.72 (s), 6.25 (s), 6.66 (s), 6.83 (m), 6.95 (m), 7.33 (s), 7.60 Cs), 7.80 to 8.60 (3 or 4 broad bands), 9.10 (m), 9. 40 (s), 9.68 On), 10.05 (m), 11.15 (w), and m.35 (s) y. The mass spectrum showed only two major peaks — an abundant (M0% of base peak) molecular ion at m/e 255 and the base peak at m/e 182. The next most abundant fragment was m/e 77 and that was only 16% of the base peak. Anal . Calcd. for C^^U^^HO^: C, 75.26j H, 6.71; N, 5.49. Found: C, 75.33; H, 6.76; N, 5. 42. The following structure was suggested by these results . ^6" ^6"5 'N-CH^-CH^-C-CH^-CIU-C-OCHg Solvent separation techniques were applied to that portion of the original reaction mixture which was not chromatographed . First, it was dissolved in pentane and cooled in dry ice. No selective precipitation could be achieved, however. The solvent was then evaporated and the material was dissolved in methanol. This solution was divided into two portions. One portion was allowed to slowly evaporate but no crystallization occurred. The oil which remained after all the methanol was gone was found to be the product from the chromatography experiment (N,N-diphenyl-0-alanine methyl ester). The second half of the methanolic solution was treated with a few drops of water which caused an oil to separate. This oil was separated and dried under vacuum at room temperature . The NMR spectrum of this material showed some of the expected absorptions for the 6-alanine ester. In addition there was a multiplet at 8.30

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128 to 1.935. Another multiplet was observed in the same region as absorptions assigned to the 3-alanine ester. If these known areas are subtracted from the total integration, the remainder is equal in intensity to the multiplet around 2.15. A singlet at 3.186 had an area ratio of about 4.5 to 1 compared to the 2.16 multiplet. Aromatic protons were also observed which were due to the B-alanine ester, some free diphenylamine , and the new intermediate. Subtraction of the areas representing the known compounds from the total integration left an £Lrea representing about thirteen protons for the intermediate . The infrared spectrum (neat) of this sample gave absorbances at 2.95 (w), 3.30 (w), 3.40 (m), 5.75 (m), 6.00 (w), 6.28 (s), 6.70 (s), 6.85 (w), 6.95 (w), 7.35 (m), 7.65 (m), 7.90 (w), 8.15 (s), 8.40 (w), 8.68 (m), 8.90 (w), 9.22 (ra), 9.45 (s), 10.08 (w), 10.18 (w), 10.55 (w), 10.95 (w), 11.48 (w), 13.30 (s), 13.55 (shoulder), and 14.35 (s) y. Further attempts to produce a pure compound were unsuccessful as manipulations resulted in conversion of all the material to N,N-diphenyl-B-alanine methyl ester. Reaction of l,l-dimethoxy-2-dimethylaminocyclopropane with diphenyl amine Approximately 10 ml. of dimethylamine was condensed into a pressure bottle by cooling in an ice/acetone bath. To this was added 1.5 g. of dimethoxycyclopropene containing eighteen mole percent methyl orthoacrylate. The bottle was sealed and warmed to room temperature . After four days , the mixture was again cooled and

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129 an aliquot was removed for analysis. The HMR spectrum of the material remaining after evaporation of the excess amine showed only absorptions for the cyclopropylamine and methyl orthoacrylate . Diphenylamine was then added to the NMR tube which was stored at U0-45° for three hours. Analysis of the mixture indicated no reaction and that the amine was present in slightly less than an equimolar amount . More diphenylamine was added and the mixture was transferred to a 10 ml. round bottomed flask, using a little more CDClto rinse the NMR tube. The flask was then placed in a 65° oil bath and the solution was gently refluxed for about eighteen hours. The NMR absorbances due to the cyclopropylamine were tinchanged. The intensity of the singlet at 3.226 was unchanged, but the multiplet at 5.556 due to the vinyl protons of the orthoacrylate were either gone or hidden under the N-H absorbance of diphenylamine. The NMR sample was then passed through a short column of silica gel and eluted with acetone. Solvent was evaporated from the eluate and the residue was analyzed by NMR. The singlet at 3.226 was not observed. There were absorbances near *+.0 and 2.556 as multiplets and a singlet at 3.516 which correspond to N,N-diphenyl-B-alanine methyl ester. The main product, l,l-dimethoxy-2-dimethylaminocyclopropane, was unaffected.

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130 C . Pro cedures and Data for Charge Transfer Complex Studies Ptirified dimethoxycyclopropene was obtained by redistillation under reduced pressure (b.p. 36° /33 mm.). The donor reagents, styrene and divinyl ether, as well as the solvents, were all distilled just prior to use. In each study, a stock solution of dimethoxycyclopropene was prepared in approximately 0.25 molar concentration. Tetramethylsilane was added before dilution to volume. One milliliter of this stock solution was then transferred by pipet to a series of labeled 5 ml. volumetric flasks. The concentration of acceptor was thus held constant for each series of solutions. A varying quantity of donor was added to each flask from a buret and then each solution was diluted to volume with the solvent being used for that study. After dilution, each solution was mixed thoroughly and an aliquot was transferred to the appropriately labeled NMR tube. The NMR spectra for each series were obtained without the intervention of other samples which might affect the instrument response. No special precautions v/ere taken to maintain a constant temperat\ire , but five minutes were allowed for each solution to equilibrate at the ambient operating temperature of the spectrometer (about 38°). Because of the large concentration difference between donor and acceptor, only the NMR signals for TMS and the cyclopropene protons were recorded. The chemical shift of the acceptor protons C6^j^^) was measured as cycles per second downfield from TMS. Data and observations for the study using styrene as donor are shown in Table V and those for the divinyl ether case are given in Table VI.

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131 The equilibrium constant for complex formation and the shift of acceptor protons in the pure complex were calculated by use of 25 the Hanna-Ashbaugh equation. Application of the method of least squares to this equation was made in order to evaluate the data more precisely than graphical methods would allow. The data from Table VI for the divinyl ether study were submitted to a computer program for evaluation by the least squares method. The results corroborated those obtained with a simple calculation, and further, a correlation coefficient of 0.9995 was indicated. Deviation of this coefficient from unity is a measxire of the deviation from linearity of a graphical representation of the data.

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132 Table V. Data for Dimethoxycyclopropene Styrene Complex Study Sample Styrenet obs obs obs Styrenet 1 2 3 5 6 7 8 9 0.421 0.972 1.362 1.745 2.643 3.459 4.326 5.357 462.9

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133 Table VI. Data for Dimethoxycyclopropene Divinyl Ether Complex Study 1 Sample

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REFERENCES CITED 1. G.L. Closs in Advances in Alicyclic Chemistry , Vol. I, H. Hart and G.J. Karabatsos, Ed., Academic Press, New York, N.Y., 1966, page 53. 2. N.Y. Dem'yanov and M.N. Doyarenko, Bull. Akad . Sci. Russ. 16_, 297 (1922). See in Chem. Abstr. 20_, 2988 (1926). 3. G.L. Closs and K.D. Krantz, J. Org. Chem. 3]^, 538 (1966). 4. G.L. Closs and L.E. Closs, J. Amer. Chem. Soc. 83_, 2015 (1961). 5. G.L. Closs, L.E. Closs and W.A. Boll, J. Amer. Chem. Soc. 85_, 3796 (1963). 6. R. Srinivasan, J. Chem. Soc. D 1971 , 1041. 7. G. Snatzke and H. Langen, Chem. Ber. 102 , 1865 (1959). 8. R. Breslow and J.T. Groves, J. Amer. Chem. Soc. 92_, 988 (1970). 9. R. Breslow and J.T. Groves, J. Amer. Chem. Soc. 92_, 984 (1970). 10. R.M. Magid and S.E. Wilson, J. Org. Chem. 36_, 1775 (1971). 11. M. Bertrand and H. Monti, C. R. Acad. Sci., Paris, 264 , Ser. C, 998 (1967). 12. H. Monti and M. Bertrand, Tetrahedron Letters 1969 , 1235. 13. H. Monti and M. Bertrand, Tetrahedron Letters, 1970 , 2591. 14. H. Monti and M, Bertrand, ibid., p. 2587. 15. T.J. Pratt, Ph.D. Dissertation, University of Washington, 1964. Dissertation Abstr. 25_, 4962 (1965). 16. T.J. Pratt and Hyp J. Dauben, Jr., U.S. Clearinghouse Fed. Sci. Tech. Inform. AD 1969 , A9-684293. Avail. CFSTI from U.S. Go^^t . Res. Develop. Rep. 69_, 68 (1969). 17. K.B. Baucom, Ph.D. Dissertation, University of Florida, 1971. 134

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135 18. K.B. Baucom and G.B. Butler, J. Crg. Chem. 37^, 1730 (1972). 19. R. Breslow and H. Oda, J. Amer. Chem. Soc. 9U, 4787 (1972). 20. N.J. Turro and W.B. Hammond, Tetrahedron 2U_, 6017 (1968). 21. H. Budzikiewicz, C. Djerassi, and D.H. Williams, Mass Spectrometry of Organic Compounds , Holden-Day, Inc., San Francisco, Calif., 1967, p. 265. 22. M.J. Schlatter, Organic Synthesis, Coll. Vol. 3, p. 223. 23. R.S. Monson, Chem. Communications, 1971 , 113. 2M. (a) G.B. Butler and K.C. Joyce, J. Polym. Sci. (C), No. 22, U5 (1968). (b) G.B. Butler and A.F. Campus, J. Polym. Sci. A-1 £, 545 (1970). (c) G.B. Butler and A.F. Campus, ibid., p. 523. (d) G.B. Butler, J.T. Badgett and M. Sharabash, J. Macromol. Sci.Chem..Ai»_, 51 (1970). 25. M.W. Hanna and A.L. Ashbaugh, J. Phys. Chem. 6£, 811 (1964). 26. K.B. Wiberg and W.J. Bartley, J. Amer. Chem. Soc. 82_, 6375 C1950). 27. M.A. Battiste, Tetrahedron Letters, 3795 (1964). 28. D.C.F. Law and S.W. Tobey, J. Amer. Chem. Soc. 90, 2376 (1968). 29. C.T. Sprouse, Jr., Ph.D. Dissertation, University of Florida, 1969. 30. P.B. Sargent, J. Amer. Chem. Soc. 9]^, 3061 (1969). 31. D.H. Williams and Ian Howe, Principles of Organic Mass Spectrome try, McGraw-Hill Book Co., London, 1972, p. 111. 32. L.F. Fieser and M. Fieser, Reagents for Organic Synthesis , John Wiley and Sons, Inc., New York, N.Y., 1968, pp. 181-182. 33. A. Hofman, W. Philipsborn, and C.H. Eugster, Helv. Chim. Acta 48, 1322 (1965). — 34. R.J.D. Smith and R.M. Jones, Can. J. Chem. 37_, 2092 (1959). 35. Varian Associates NMR Spectra Catalog compiled by N.S. Ghacca, L.F. Johnson, and J.N. Shoolery, National Press, 1962, Spectrum No. 51. 36. R. Breslow, L.J. Altman, A. Krebs, E. Mohacsi, I. Murata, R.A. Peterson, and J. Posner, J. Amer. Chem. Soc. 87, 1326 (1965).

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136 37. M. Oda, R. Breslow, and J. Pecorano, Tetrahedron Letters 1972 , 4419. 38. J. Sauer and G. Heinrichs, Tetrahedron Letters 1966 , 4979. 39. E.T. McBee, R.K. Meyers, and C.F. Baranauckas , J. Araer. Chem. Soc. 77, 85 (1955). 40. H.H. Stechl, Angew. Chem. 75_, 1176 (1963). 41. M.A. Steinfels and A.S. Dreiding, Helv. Chim. Acta. 55_, 702 (1972). 42. V. Bilinski, M.A. Steinfels and A.S, Dreiding, ibid., p. 1075. 43. V. Bilinski and A.S. Dreiding, ibid., p. 1271. 44. M.A. Steinfels, H.W. Krapf, P. Riedh, J. Sauer, and A.S. Dreiding, ibid. , p. 1759. 45. T. Eicher and S. Bohm, Tetrahedron Letters 1972 , 2603. 46. T. Eicher and S. Bohm, Tetrahedron Letters 1972 , 3965. 47. E.K. von Gustorf, D.V. White, B. Kim, K. Hess, and J. Leitich, J. Org. Chem. 35_, 115 5 (.1970). 48. N. Ahmed, N.S. Bhacca, J. Silbin, and J.D. Wander, J. Amer. Chem. Soc. 93_, 2562. 49. K.B. Wagener, Ph.D. Dissertation, University of Florida, 1973. 50. R.C. Cookson, S.S.H. Gilani, and I.D.R. Stevens, Tetrahedron Letters 1962 , 615. 51. S.R. Turner, Ph.D. Dissertation, University of Florida, 1971, p. 15 and references cited therein. 52. D. Edwards, D. Hamer, and W.H. Stewart, J. Pharm. Pharmacol. 16 , 618 (1964). 53. E.J. Corey, J.D. Bass, R. LeMahieu, and R.B. Mitra, J. Amer. Chem. Soc. ,86_, 5570 (1964). 54. P. Pfeiffer and K. Bauer, Chem. Ber. 80_, 7 (1947). 55. N.D. Pryanishsikov and V.A. Leontovich, Chem. Ber. 68B , 1866 (1935) 56. T.J. Wallace and A. Schriesheim, Tetrahedron 21, 2271 (1965). 57. F.W. Heyl and M.E. Herr, J. Amer. Chem. Soc. 75_, 1918 (1953).

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137 58. E. Benzing, Angew. Chem. 71, 521 (1959). 59. G. Opitz, H. Hellmann, and H.W. Schubert, Ann. der Chem. 623 , 112 (1959).

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BIOGRAPHICAL SKETCH Rudolph Milton Albert, Jr. was born September 20 » 1938 in Pulaski, Virginia. He attended the public schools of that city and graduated from Pulaski High School in June, 1956. He received his Bachelor of Arts degree, cum laude , from King College, Bristol, Tennessee in Hay of 1960 with a major in chemistry and mathematics. In June of that year he enrolled in the Graduate Program of the Virginia Polytechnic Institute at Blacksburg, Virginia. He received his Master of Science degree from V.P.I, in June, 1962 v;ith a major in Organic Chemistry. During the summer of 1961 he was employed by Eastman Chemical Products, Inc., Kingsport , Tennessee. From June, 1962 through August, 1968 he was employed as a research chemist by the Organic Chemicals Group, Glidden-Durkee Division of the SCM Corporation in Jacksonville, Fla. At that time he was granted a leave of absence in order to enter the Graduate School of the University of Florida to pursue the degree of Doctor of Philosophy. On September 6, 1960 he was married to the former Miss Carol Elaine Goedert of Jacksonville, Florida. They have five children: Mary Elizabeth (age 12), Laura Elaine (age 11), Robert Milton (age 9), Rebecca Lynn (age 7), and Daniel Lawrence (age 2). 138

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I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. George B. Butler, Chairman Professor of Chemistry I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Merle A. Battiste Professor of Chemistry I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. '{d^n.,A'-S/t>lC'
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I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Frank 1'. May T\ Professor of Chemical Engineering This dissertation was submitted to the Department of Chemistry in the College of Arts and Sciences and to the Graduate Council, and was accepted as partial fulfillment of the requirements for the degree of Doctor of Philosophy. August, 1973 Dean, Graduate School


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