Title: Synthetic and mechanistic studies of 3, 3-dimethoxycyclopropene
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Title: Synthetic and mechanistic studies of 3, 3-dimethoxycyclopropene
Physical Description: x, 138 leaves. : illus. ; 28 cm.
Language: English
Creator: Albert, Rudolph Milton, 1938-
Publication Date: 1973
Copyright Date: 1973
 Subjects
Subject: Dimethoxycyclopropene   ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre: bibliography   ( marcgt )
non-fiction   ( marcgt )
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Thesis: Thesis -- University of Florida.
Bibliography: Bibliography: leaves 134-137.
Additional Physical Form: Also available on World Wide Web
General Note: Typescript.
General Note: Vita.
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Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
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Resource Identifier: alephbibnum - 000580690
oclc - 14074525
notis - ADA8795

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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




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