Group Title: effect of a single fluorine substituent on the 1,5 homodienyl hydrogen shift, the solvolytic ring-opening of bromocyclopropane, and the 1,3 carbon shift of 6-methylenebicyclo3.2.0hept-2-ene
Title: The effect of a single fluorine substituent on the 1,5 homodienyl hydrogen shift, the solvolytic ring-opening of bromocyclopropane, and the 1,3 carbon shift of 6-methylenebicyclo3.2.0hept-2-ene
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Title: The effect of a single fluorine substituent on the 1,5 homodienyl hydrogen shift, the solvolytic ring-opening of bromocyclopropane, and the 1,3 carbon shift of 6-methylenebicyclo3.2.0hept-2-ene
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Language: English
Creator: Phanstiel, Otto, 1963-
Copyright Date: 1988
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THE EFFECT OF A SINGLE FLUORINE SUBSTITUENT ON THE [1,5]
HOMODIENYL HYDROGEN SHIFT, THE SOLVOLYTIC RING-OPENING OF
BROMOCYCLOPROPANE, AND THE [1,3] CARBON SHIFT OF
6-METHYLENEBICYCLO[3.2.0]HEPT-2-ENE












BY

OT'O PHANSTIEL IV


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

UNIVERSITY OF FLORIDA

1988


W! Yr OF FLORIDA UMAX$














TO MOM, DAD, AND SUSAN













ACKNOWLEDGEMENTS

It is with much gratitude that I acknowledge the guidance of Professor William R.

Dolbier, Jr., in attaining this dream. His friendship and dedication to chemistry has been

an inspiration throughout my career as a graduate student.

The diligent training of Dr. Adam Alty, an English post-doc, was crucial to the

rapid completion of my first project and served as a springboard for the remainder of my

studies. He is indeed, greatly appreciated. I also valued the assistance of my Korean

co-worker, Dr. Suk-Kyu Lee, in the synthesis of the 7-fluoro-6-methylenebicyclo[3.2.0]-

hept-2-ene systems in Chapter 3. It is also a pleasure to thank Tom Gray, Jeff Keaffaber,

Dr. Henryk Koroniak, Dr. Lech Celewicz, and Sarah Weaver for their helpful discussions

and comraderie throughout my graduate studies.

Finally, the support from my mother and father has been invaluable throughout

my life and this scholastic accomplishment is attributed to them. The special support of

my fiance, Susan, has been undying, and indeed, vital to the completion of this work.













TABLE OF CONTENTS

Page

ACKNOWLEDGEMENTS ------------------------------------------ iii

ABSTRACT----------------------------------------- --------------------- v

CHAPTER

1 THE [1,5] HYDROGEN SHIFT -------------------------------------- 1

Introduction ---------------------------------------- ---------------- 1
Syntheses ---------------------------------------------------------- 8
Results and Discussion ------------------------------------- ----------- 8
Conclusion --------------------------------------------------------- 12

2 THE NON-STERIC ORIGIN OF SPECIFIC DISROTATORY
RING-OPENINGS IN SOLVOLYSES OF CYCLOPROPYL
DERIVATIVES. THE 2-FLUOROCYCLOPROPYL
BROMIDE SYSTEM -------------------------------------- ---------- 14

Introduction ---------------------------------------------------------- 14
Syntheses ------------------------------------ ------- 16
Results and Discussion -------------------------------------- ---------- 18
Conclusion -------------------------------------------------------- 23

3 [1,3] SIGMATROPIC MIGRATIONS OF CARBON --------------- 25

Introduction -------------------------------------- ------------------ 25
Syntheses ---------------------------------------- ---------------- 29
Results and Discussion ------------------------------------------------- 30
Conclusion -------------------------------------- ------------------- 39
Summary -------------------------------------- --------------------- 40

4 EXPERIMENTAL SECTION ------------------------------------------- 41

General Methods -------------------------------------------------- 41
Experimental Procedures -------------------------------------- --------- 42

APPENDIX

SELECTED SPECTRA ----------------------------------------------- 65

REFERENCES -------------------------------------- -------------------- 107

BIOGRAPHICAL SKETCH ----------------------------------------- 112












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


THE EFFECT OF A SINGLE FLUORINE SUBSTITUENT ON THE [1,5]
HOMODIENYL HYDROGEN SHIFT, THE SOLVOLYTIC RING-OPENING OF
BROMOCYCLOPROPANE, AND THE [1,3] CARBON SHIFT OF
6-METHYLENEBICYCLO[3.2.0]HEPT-2-ENE

By

Otto Phanstiel IV

August 1988

Chairman: William R. Dolbier, Jr.
Major Department: Chemistry

Investigations into the effect of fluorine substituents on pericyclic reactions have

yielded keen insights into the mechanistic and geometric requirements for several impor-

tant electrocyclic rearrangements. This study probed the effect of a single fluorine

substituent on the homodienyl [1,5] Hydrogen shift of cis 1-fluoromethyl-2-vinylcyclo-

propane, the solvolysis of cis and trans 1-bromo-2-fluorocyclopropane, and the [1,3]

carbon shift of endo and exo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene.

The rearrangement of cis 1-fluoromethyl-2-vinylcyclopropane is a well behaved,

irreversible, first order process, which forms competitively the (Z,Z) (Ea = 34.1 + 0.2

kcal/mole, log A = 11.2 +0.1) and (E,Z)-l-fluoro-1,4 hexadienes (Ea = 34.7 + 0.4

kcal/ mole, log A = 11.2 + 0.2). The kinetic ratio favored the formation of the (Z,Z)-

1-fluoro-l,4-hexadiene (1.9 : 1) over the (E,Z) isomer and was attributed to the

thermodynamic preference for the Z diene. Comparison of the observed Ea of 34.1 kcal/

mole (log A = 11.2) of the fluoro system with that for the parent system (31.2 kcal/mol,

log A = 11.0) indicated a strengthening effect upon the C-H bond of 2.9 kcal/mole by the

a fluorine substituent.









The acetolyses of cis and trans 2-fluorocyclopropyl bromides were examined in

detail and it was found that, in a system where steric effects should be negligible, the

trans isomer (Ea = 30.2 + 1.1 kcal/mole, log A = 10.0 + 0.5) solvolyzes at a rate 10.7

times faster than its cis isomer (Ea = 32.4 + 1.1 kcal/mole, log A = 10.0 + 0.5) at 1870C.

The trans / cis ratio was found to be greater for the fluorine substituent than for the methyl

substituent, in spite of the negligible steric requirements of the fluorine substituent in

undergoing inward rotation. Thus, the enhanced rates of solvolyses for trans versus cis

2-substituted cyclopropyl derivatives were attributed to substituent electronic effects

rather than steric factors.

The thermal isomerization of exo and endo 7-fluoro-6-methylenebicyclo-

[3.2.0]hept-2-ene was investigated. The exo fluoro compound gave 93% inversion of

configuration at C-7 in the formation of 6-fluoro-5-methylenebicyclo[2.2.1]hept-2-ene;

whereas the endo fluoro starting material gave only 36% inversion of configuration at C-7.

The entropy of activation of the endo isomer (AS' = 4.9 e.u.) along with its greater Ea

(41.3 + 1.2 kcal/mole) supports the premise that more C1-C7 bond breaking occurs in its

transition state. This is in direct contrast to the more concerted process reflected in the

essentially zero change in entropy (AS+ = 0.7 e.u.) and lower activation energy (Ea = 38.4

+ 0.2 kcal/mole) of the exo isomer.















CHAPTER 1
THE [1,5] HYDROGEN SHIFT

Introduction

Since the discovery in 1961 of the [1,5] hydrogen shift rearrangement by Mironov

and coworkers,1 the isomeric transformations of dienyl and homodienyl systems have

been intensely studied. In the series of sigmatropic rearrangements the [1,5] Hydrogen

shift is perhaps the best understood and the most thoroughly investigated reaction. Studies

in this field as well as in other types of thermal intramolecular rearrangements are im-

portant in elucidating the general problem of valence isomerization and valence tauto-

merization.

A sigmatropic rearrangement is defined as migration, in an uncatalyzed intra-

molecular process of a o bond, adjacent to one or more 7T systems, to a new position in a

molecule, with the t systems becoming reorganized in the process.2 The order of a

sigmatropic rearrangement is expressed by two numbers set in brackets [i, j], with i and j

determined by counting the number of atoms over which each end of the o bond has

moved. The original termini are given the number 1.

In the following example (Figure 1-1) the carbon terminus has moved from C-1 to

C-5 but the hydrogen has not moved at all, so the order is [1,5].

There are several examples of thermal or photochemical rearrangements involving

H migration across i systems.3'4'5 It was found that geometrical conditions were very

important. Furthermore, pericyclic mechanisms are involved and the hydrogen must in the

transition state be in contact with both ends of the chain at the same time. This means for

rearrangements greater than or equal to the [1,5], the molecule must adopt a cisoid









2

conformation. There exist two possible pathways by which the hydrogen can migrate:

a) across the n system from bottom to top or top to bottom (known as an "antarafacial

migration") or b) along the top or bottom face of the 7r system (known as a "suprafacial

migration").


3 3

2 4 2 4
[1,5]

R 1 H 5 Hydrogen R 1 5
1 Shift
1 1 2

Figure 1-1. The [1,5] Hydrogen Shift


Woodward and Hoffmann used a modified frontier orbital approach2 to evaluate

which of these two pathways was allowed or forbidden. In order to treat this migration it

was assumed that as the C-H bond breaks from the rest of the system it can be treated as a








S. R H
R H R H


Figure 1-2. W-H Treatment of n system and migrating atom









3

free radical and the 7 system can be envisioned as a 1,3 pentadienyl radical (Figure 1-2).

The n system contains five 7c orbitals but since a thermal process is taking place, the

HOMO (highest occupied molecular orbital) is the one of concern. For the hydrogen atom

only the spherically symmetric Is orbital is involved. The rule controlling the mode of

migration of the H atom is that the H atom must move to an orbital of the same phase sign

(Figure 1-3).






4





H
Figure 1-3. The Orbital Interpretation of the [1,5] H Shift


Therefore the allowed mode of migration for the thermal [1,5] sigmatropic shift

must be suprafacial. Suprafacial migrations are allowed thermally for the general case of

[ij] where i = 1 andj is of the form 4n + 1 and photochemically ifj has the form 4n 1;

the opposite is true for antarafacial migrations.



[1,5] H


Homodienyl

shift H


Figure 1-4. The homodienyl [1,5] Hydrogen Shift









4

A direct analog of the [1,5] H shift rearrangement is one in which a cyclopropane

ring replaces one of the double bonds. These homodienyl systems were first investigated

in 1964 by Ellis and Frey in their study of l-methyl-2-vinyl cyclopropane (Figure 1-4). 6,7

Therein, they reported that the process of transferring the hydrogen atom and the breaking

of the cyclopropane ring was concerted. In addition, they postulated the existence of a

seven-membered transition state corresponding to the considerable loss of entropy ob-

served in the transition state complex (AS+ = -11.6 e.u.) and the observed low activation

energy. In 1966, Winstein and coworkers reported the apparent similarity between [1,5]

H shifts in cyclic dienes and a shift across a homodiene. 8 They also suggested a transition

state similar to the [1,5] transition state. Furthermore, Frey and Solly extended this model

of the transition state to allow for conformational preferences. 9






A +




7 8 9


H H /

R i.R R R
R R
2 3
1 3 1 2

A B


Figure 1-5. Pyrolysis of 1,1 diethyl-2-vinyl-cyclopropane via transition states A and B









5

In the thermolysis of 1,1 diethyl-2-vinylcyclopropane (7), they found a 1:1 product

ratio of trans, cis-3-ethyl-2,5-heptadiene (8) and cis, cis-3-ethyl-2,5-heptadiene (). The

product distribution indicates the apparent similarity in the two possible transition states

(A and B) and that the substituents R2 and R3 (where R2 = CH3 and R3 = H) occupy posi-

tions that are intermediate between ation in the transition state). (See Figure 1-5.)

These results are in direct contrast to those found in the thermolysis of cis 1,3-hex-

adiene, which showed a 40 : 1 preference in the formation of cis, trans- over the cis, cis-

2,4-hexadiene (Figure 1-6). Presumably, the reaction proceeded via a transition state,

which favored the placement of the methyl substituent in a pseudo-equatorial position. 10

CH3 A


H 1,5 H Shift cis, trans cis, cis
40:1
1,3 hexadiene
H .... .. --- H
...... ..... H ...... H





favored t.s. '
H CH3 CH3 H

equatorial methyl axial methyl

Figure 1-6. Thermolysis of cis 1,3 -hexadiene

As a direct consequence of these findings, Frey and Solly also proposed that an

exo or "boat" like conformation (14)11 (Figure 1-7) may be competing with the endo or

"chair" conformations (A and B) depicted in Figure 1-5. However, in the pyrolysis of 1,1

dimethyl 2-vinyl cyclopropane (10) only cis-2-methyl-1,4-hexadiene (11) is formed

(Figure 1-7). Therefore, these workers concluded that the "chair" or endo transition state

(13) is at least 4.5 kcal/mole lower in energy than the "boat" or exo form (14).
























H --......... .
R I./


12 trans not
observed




"boat" or exo
gives trans


Figure 1-7. Pyrolysis of 1,1 dimethyl-2-vinyl-cyclopropane via transition state 13


53-87
H
53-870C


F

F


(95%)


A



200.650


C
D


Figure 1-8. Pyrolysis of 2,2 difluoro-3-methyl-l-vinyl- cyclopropane


2600C
No


11 cis


"chair" or endo
gives cis


F + 17



1.9: 1









7

Recently in 1982 Dolbier and Sellers reported 12 the synthesis and pyrolysis of

both cis (15) and trans (16) 2,2 difluoro-3-methyl-l-vinylcyclopropane (Figure 1-8).

These fluorinated systems were shown to be very similar to the thermal rearrangement of

their respective hydrocarbon systems. Both the cis-isomer (15) (log A = 10.3, Ea = 23.4

in undergoing its concerted [1,5] H shift process and the trans isomer (16), in rearranging

via homolytic cleavage to a diradical, exhibited an incremental 8-9 kcal/mol lower activa-

tion energy than their respective hydrocarbon parent systems. This lowering was expected

for reactions involving cleavage of the cyclopropyl carbon-carbon bond opposite the gem-

difluoro substituents. Such weakening of carbon-carbon bonds by -CF2 groups has been

observed in geometrical isomerizations 13.14 and in vinylcyclopropane rearrange-

ments. 14,15,16

W.R. Dolbier and coworkers reported in 1984 the dramatic kinetic effect of fluor-

ine substituents, upon electrocyclic cyclobutene-butadiene interconversions. 17,18 These

studies along with their subsequent theoretical explanation 18,19 demonstrated a very sig-

nificant propensity for outward vs. inward rotation for 3-fluoro substituents 17,20 (Figure

1-9). These findings coupled with the aforementioned studies on 1-alkyl-2-vinylcyclo-

propanes induced us to look for similar stereochemical preferences in the [1,5] Hydrogen

Shift.

Recently the synthesis and thermal isomerization of another fluorinated 1-methyl

2-vinyl cyclopropyl system was investigated; 21 one in which the effect of a single

fluorine substituent on the stereochemical and energetic processes involved in the [1,5]

Hydrogen shift of the 1-alkyl-2-vinyl cyclopropyl systems could be further elucidated; i.e.

cis 1-fluoromethyl 2-vinyl-cyclopropane (19). 21 This rearrangement of cis-1-(fluoro-

methyl)-2-vinyl-cyclopropane to (E,Z)- and (Z,Z)- -fluoro-1,4-pentadiene (23 and 24) was

chosen as an ideal model system to demonstrate the effect of fluoro substituents in reac-

tions of these types.













F'
A, 910C CF3

F F3 kF out F CF3
F --


F F F CF3
A 2570C F
F3 I F
kF-in

F3C F

Figure 1-9. Propensity for Outward Rotation of F- Substituent


Syntheses

Cis-1-(fluoromethyl)-2-vinylcyclopropane (9) was synthesized from 1-carbo-

ethoxy-2-vinylcyclopropane 22 with the key step being displacement by fluoride (using

"anhydrous TBAF") 23,24 on the tosylate (20) formed in situ from alcohol 21 25 (Scheme

1-1). In this synthesis a mixture of cis and trans isomers (trans : cis = 60:40) was car-

ried through until the final stage at which 19 was separated by GC from its trans isomer

(22). Treatment of alcohol 21 directly with DAST unfortunately led to no 19 but only

products where the cyclopropane ring was not intact. Tosylate 20 could be prepared

separately and then treated by anhydrous TBAF, but the overall yields for the two-step

procedure were inferior to the in situ method.

Results and Discussion

Homodienyl 1,5-Hydrogen Shift. The rearrangement of cis 1-(fluoromethyl)-2-

vinylcyclopropane (19) is a well behaved, irreversible, first-order process, which forms

competitively the (E,Z)- and (Z,Z)-1-fluoro-l,4-hexadienes (23 and 24). (See Figure 1-10.)












CO Et CH2HH '20["s
LiAIH4 TBAF


(87%) (24%)
21
CH22
CH F CH2

+

19 22 _--


Scheme 1-1. Synthesis of 1-fluoromethyl-2-vinyl cyclopropane



These isomers were readily distinguished by their 19F NMR, where (Z,Z)-1-fluoro-1,4
hexadiene (24) exhibits a J3ta HF of 42.6 Hz and (E,Z)-1 -fluoro- 1,4-hexadiene (23)

exhibits a J3cis HF of 18.8 Hz.

CH2F



<- + F

193-2280C F



19 23 24


Figure 1-10. Pyrolysis of cis 1-fluoromethyl-2-vinyl- cyclopropane (19)













The kinetic data for the thermal rearrangement of (19) were derived from the raw

data tabulated in Chapter 4, Table 4-1. The calculated rate constants are found in Table

1-1, while the activation parameters for the two competitive processes are in Table 1-2.



Table 1-1. Rate Constants for the Rearrangement of cis-1-fluoromethyl- 2-vinylcyclo-
propane ab



Temp, OC 24 /23 overall kz kE


193.25 1.90 2.83 1.85 0.98

201.25 1.94 5.24 3.46 1.78

209.75 1.90 10.0 6.55 3.45

219.25 1.89 19.4 12.7 6.72

227.25 1.82 35.4 22.8 12.6


a x 10-5 s -1; b for raw data at each temperature see Table 4-1


It can be seen that the Z isomer, 24, is formed preferentially. The thermodynamic

preference of 24 over 23 was found to be consistent with earlier work wherein Z-1-fluoro-

propene was found to be similarly more stable than E-1-fluoropropene. 26 These results

are also consistent with those found in the study of the Cope rearrangement of Z and E

1-fluoro-1,5 hexadienes to 3-fluoro-1,5 hexadiene 21 (Scheme 1-2). Indeed, the kinetic

ratio for the formation of the Z over the E 1-fluoro-1,5 hexadienes was found to be 1.82 at

256.90C, while the thermodynamic Z to E ratio was 1.98. 21 One can see that the same

rationale which was applied to explain the thermodynamic preference of the










Table 1-2. Activation Parameters for the Rearrangement of cis 1-fluoromethyl-2-vinyl-
cyclopropane (19)


k log A Eaa AH+ ac AS+ b', AG+ a,c


kz 11.2 + 0.1 34.1 + 0.2 33.1 -10.0 38.0

kE 11.2 + 0.2 34.7 + 0.4 33.7 -10.1 38.6


a kcal/mol b cal/deg c At 210.0C
fluoropropenes and the Cope rearrangement can be applied also to this homodienyl [1,5]
hydrogen shift system. Therefore, the kinetic ratio is simply reflective of the thermo-
dynamic preference for the Z diene.


3-fluoro-1,5 hexadiene


F


Z-l-fluoro-1,5 hexadiene E-l-fluoro-1,5 hexadiene

Scheme 1-2. Cope Rearrangement of 3-fluoro-1,5 hexadiene


/J









12

The only related results in the literature are those for the rearrangement of

cis-1,1-diethyl-2-vinylcyclopropane (7), where as discussed earlier, little preference was

exhibited for the disposition of the methyl substituent in the E or the Z geometry of

products 8 and 9. 9

Kinetically the presence of the a-fluorine substituent had a significant effect upon

the activation energy for the hydrogen transfer. Comparison of the observed Ea of 34.1 +

0.2 kcal/mol (log A = 11.2 + 0.1) with that for the parent system (31.2 kcal/mol, log A =

11.0) 27 indicates an inhibition of 2.9 kcal/mol in the rearrangement of 19. There are little

data on the effect of a-fluorine substituents on C-H bond strengths and what there are

indicate an irregular but generally strengthening effect of a-fluorination upon C-H bond

strength. 28

Conclusion

The lack of significant transition-state derived kinetic effect or stereochemical

preference in this study provides considerable insight into those factors which give rise to

such effects.






A

.. ......, H
F H

CH3

19 23 or 24

Figure 1-11. Transition State Rigidity in the Rearrangement of cis-
1-fluoromethyl-2-vinyl-cyclopropane









13

An examination of the transition state for the [1,5] rearrangements (Figure 1-11)

shows that little rotation or torsional movement is required at the site of substitution in the

creation of the new sp2 site in these reactions, in contrast to the very significant torsional,

twisting motion required in the transition state for cyclobutene ring opening (Figure 1-12):



CF3


F F_ / F F ........... ,: F F F

A.F F

CFCF CF3
CF3





Figure 1-12. Torsional Motion in Cyclobutene-Butadiene Rearrangement



It is expected that if dramatic effects such as those observed in the cyclobutene

system are to be observed in any other pericyclic reactions, it will be for those which the

substituent must undergo considerable torsional motion in reaching the transition state.

In Chapter 2 this torsional criterion was further investigated in the solvolysis of the

1-fluoro-2-bromocyclopropanes.















CHAPTER 2
THE NON-STERIC ORIGIN OF SPECIFIC DISROTATORY
RING-OPENINGS IN SOLVOLYSES OF CYCLOPROPYL DERIVATIVES.
THE 2-FLUOROCYCLOPROPYL BROMIDE SYSTEM.

Introduction

The solvolysis of cyclopropyl derivatives has been a subject of considerable

interest among physical organic chemists, since Roberts and Chambers first discovered

that cyclopropyl tosylate underwent acetolysis at a rate 105 slower than cyclohexyl

tosylate and yielded only ring-opened allyl acetate as a product. 29 In a classic series of

studies by de Puy et al. 30 and von Schleyer et al., 31 the solvolyses were demonstrated to

be stereospecific, two-electron electrocyclic processes involving synchronous ionization

and disrotatory C2-C3 cyclopropane bond fragmentation. It was, moreover, found that

only one of the two possible disrotatory modes was operative, namely that where the

groups trans to the leaving group rotate outward and those cis rotate inward. Theoretical

work supported these conclusions. 30,32

The wealth of data from which such mechanistic insights have been obtained de-

rives from numerous experimental studies wherein carbonium ion stabilizing substituents

produce abnormally small rate enhancements when at C-1, 33 but substantial rate accel-

erations result from attachment at C-2 or C-3. 30a,34 Moreover, trans-2-substituted

monocyclic cyclopropyl halides or tosylates have without exception been found to react

faster than their respective cis isomers. 35 For example, trans-2-methyl-cyclopropyl

bromide (25) undergoes acetolysis at a rate 13.7 times faster than its respective cis-isomer

(26) at 1000C. 36 (See Figure 2-1.) It should be noted that the allyl cations formed

(E and ) arise from the single disrotatory pathway predicted by de Puy et al. 30 and

Woodward and Hoffmann. 32









15



CH HOAc +:
-- PRODUCTS
1000C
25 Br 10 E
CH3


HOAc

\+ > PRODUCTS
Br lOOC
CH3 26 H3C-. F

k trans k cis = 13.7

Figure 2-1. Acetolysis of cis and trans 2-methyl cyclopropyl bromide


These initial findings were later confirmed by Sch61kopf et al. 37 and others in

their study of the acetolysis of endo and exo bicyclo[3.1.0]hexyl-6-tosylate (Figure 2-2),

where the endo isomer (27) was found to solvolyze at a rate 2.6 x 106 times faster than

its exo isomer (28).

In these systems the cis or endo species were shown to be kinetically more labile

than their trans or exo counterparts. This was due to the geometric constraints of the bi-

cyclic system, wherein the trans or exo isomer in undergoing synchronous halide loss and

ring opening would have been forced to react via an endocyclic trans double bond (H) or

some other high energy cation. Such problems are not, however, present in the mono-

cyclic systems studied.

From the beginning, the greater rate of solvolysis for trans versus cis isomers of

monocyclic systems has been rationalized in terms of a steric origin, with this conclusion

deriving from an expected greater steric inhibition for bulky groups to rotate inwards than

outwards. With the recent revelations 38,39 regarding cyclobutene butadiene









16

interconversions, wherein the observed specific conrotatory electrocyclic processes were

shown not to be steric in origin but due to substituent electronic effects, it was considered

possible that the effects observed in the mechanistically similar cyclopropyl solvolyses

might also be non-steric in origin. An indication that this might indeed be the case is the

observation that cis-2-tert-butylcyclopropyl bromide actually undergoes acetolysis at a

rate two times faster than its methyl analog 26. 36b




H H HOAc
\^]/ ___-----

OTs .. +

endo 27 G
OAc


OTs

HH
SX- H

exo 28
k k
endo / exo = 2.5 x 106

Figure 2-2. Acetolysis of endo and exo bicyclo[3.1.0]hexyl-6-tosylate


Syntheses

The synthesis of trans and cis 1-bromo-2-fluorocyclopropane (29 and 30) was

accomplished first by the preparation of phenyl tribromomethyl mercury 40 followed by

treatment of vinyl fluoride with this dibromocarbene precursor. 41,42 This reaction was

done in an autoclave at 800C and gave a 21% yield of 1,1 dibromo-2-fluorocyclopropane

(28a) (Figure 2-3). Reduction of this 1,1 dibromocyclopropane derivative was









17

accomplished by tributyl tin hydride 43 at room temperature and resulted in a 68% yield

of trans and cis 1-bromo-2-fluorocyclopropane (60:40 = trans : cis) (Figure 2-3). These

isomers were separated by gas chromatography and the solvolysis of each isomer was

studied.

800C Br Br
PhHgCBr3 + CH2=CHF
benzene
21% -
28a
Tributyl tin
hydride (68%)
Br Br


F + H
H H


30 H 29 F

Figure 2-3. Synthesis of trans (29) and cis (30) 1-bromo-2-fluorocyclopropane


In order to better elucidate the reaction pathway, all six possible intermediates and

products were synthesized independently and their solvolytic behavior examined. The

synthesis of the bromofluoropropenes was successfully accomplished by a route previ-

ously used in the synthesis of monofluoroallene. 44 The reaction of dibromofluoro-

methane with ethylene in an autoclave at 1200C gave a 46% yield of 1,3 dibromo,

1-fluoropropane (Figure 2-4). The ensuing dehydrobromination with solid potassium

hydroxide at 1100C afforded a 46% yield of the desired bromofluoropropene mixture

(Figure 2-4). The cis and trans isomers of 1-fluoro-3-bromo-l-propene (trans: cis =

20:20) and 1-bromo-l-fluoro-2-propene (60%) were separated by gas chromatography

(GC).











autoclave
CHBr2F + CH2=CH2 autoclave CHBrF-CH2-CH2-Br
1200C
46 %

SKOH at 110C

46%


F H F CH2Br
\ / \ /
C=C + C=C + FCHBr-CH=CH2

H 37 CH2Br H H
37 38 35


20% 20% 60%

Figure 2-4. Synthesis of Bromo-fluoro propenes 35, 37, 38.

Likewise, the corresponding acetates were synthesized from their bromide deriv-

atives by treatment with buffered acetic acid and typically gave yields > 93%. However,

1-acetoxy-l-fluoro-2-propene (36) was found to be very unstable and was synthesized

from the mixture of bromofluoropropenes by treatment with silver nitrate and buffered

acetic acid at 600C followed by GC isolation.

Results and Discussion

The acetolyses of trans- and cis-2-fluorocyclopropyl bromides, 29 and 30, 45

were examined in detail and it was found that, in a system where steric effects should be

negligible, the trans isomer remains significantly more reactive than the cis isomer. As

indicated in Figure 2-5 the trans isomer 29 solvolyzes at a rate 10.7 times faster than the

cis isomer 30 at 1870C. The raw kinetic data can be found in Chapter 4, Tables 4-2

and 4-3. The rate data for the acetolysis of 29 and 30 are found in Table 2-1, whereas

the activation parameters are listed in Table 2-2.













F


Br


HOAc, 1870C
--------
(74 % )

k = 4.94 x 10-"


22 %


78 %

OAc


HOAc, 1870C F


F 30 Br (76%) 29%
k = 4.60 x 10-6
Figure 2-5. Acetolysis of trans and cis 2-fluorocyclopropyl bromides


Table 2-1. Solvolytic

isomer


cis (30)





trans (29)


Rate Constants For the Acetolysis of 29 and 30.

tempoC Rate Constant (x 10-5 s-1)


187.0

210.0

218.0


187.0

210.0

218.0


0.46 ( 0.03)

2.34 (+ 0.06)

4.38 ( 0.11)


4.94 (+ 0.24)

22.54 ( 0.36)

40.75 ( 3.54)


While the observed product ratios might be considered indicative of a lack of

stereospecificity in the ring opening, this is not likely the case. As demonstrated in

Figure 2-6, it is probable that the formation of non-stereochemistry-retained products

derives from the kinetic quenching by Br or -OAc at both ends of the respective


OAc


71%












Table 2-2. Activation Parameters for the Acetolysis of 29 and 30


isomer temp (oC) log A Ea AH+ AS+ AG+

trans 206.7 10.0 + 0.5 30.2 + 1.1 29.3 -15.5 36.7

(29)


cis 206.7 10.0 + 0.5 32.4 + 1.1 31.5 -15.4 38.9

(30)

stereospecifically- formed trans- and cis-1-fluoroallyl cations (33 and 34), with the pre-

sumed a-fluoro bromide or acetate intermediates 35 and 36 having lost their stereochem-

ical identity and the former being kinetically unstable relative to isolated acetates 31 and

32.


Br OAc

HOAc 37 + 31
29 + / + / -
29
F F
F

33

+ -F
AF AcO

HOAc 35 Br 36 F
30 \
+.' S Br OAc


S38 + 32
34 F


Figure 2-6. Kinetic Scenario for the Acetolysis of 29 and 30









21

As mentioned previously all potential bromide and acetate intermediate products

(35, 36, 37 and 38) have been prepared by alternative routes 44 and subjected to solvo-

lytic conditions. At 1270C, a fluoroacetate 36 is diverted non-productively to acrolein.

The rate data and product distributions of 35, 37, 38 are given in Table 2-3. Table 4-4

in Chapter 4 provides the raw kinetic data for these bromofluoropropenes. It can be seen

that the likely intermediacy of 35 provides a reasonable pathway for the partial scrambling

of stereochemistry in the products. It is probable that the solvolyses proceed with total

stereospecificity of ring-opening.



Table 2-3. Rates and Acetolysis Product Distributions for Bromofluoro-
propenes 35, 37, and 38 at 1270C.


Starting % Products Observed
bromide 31 32 37 38 35 k(x105) time (min) yield

35 (a) 36 23 17 24 -- 22.6 130 71

37 (tr) 93 5 -- 2 -- 17.0 267 91

38 (cis) 6 88 3 3 6.9 267 74



Further experiments using silver acetate as a bromide quenching agent demon-

strated that the ring opening was indeed highly stereospecific (>99.0%) in trifluoroacetic

acid. The trifluoroacetolysis of trans 1-bromo-2-fluorocyclopropane in the presence of a

1.6 molar excess silver acetate yielded (57% yield after 41% conversion) the trifluoro-

acetate derivatives of the a-fluoroacetate 36a (52%) and trans fluoroacetate 31a

(47.9%); where kt, was found to be 5.91 x 105 s-1 at 25.50C (see Figure 2-7). It

should be noted that less than 1% of the trifluoroacetate derivative of the cis fluoroacetate

32a was formed. As depicted in Figure 2-7, the trifluoroacetolysis of cis 1-bromo-









22

2-fluorocyclopropane in the presence of a 1.4 molar excess of silver acetate at 980C gave

a mixture of cis and trans trifluoroacetates. This apparent lack of stereospecificity was

attributed to the further solvolysis of the cis trifluoroacetate 32a at 980C, where kis was

found to be 8.8 x 10-5 s-1. The ratio of ktr/kcis was 86 at 25.50C.




F OCOCF3

\ I +OF*
25.5C // F
+ + F

29 25.5 OCOCF3
S Br k = 5.91 x 10 -5s -
F 31a F 48: 52 36a


Ag OCOCF3 OCOCF3

98.00C + 31a
F 30 Br
k k=8.8 x 10-s1 3 F
32a F



Figure 2-7. Trifluoroacetolysis in the Prescence of Silver Acetate of 29 and 30.


Comparisons of the acetolysis rates for the 2-fluoro system with those of the par-

ent46 and the 2-methyl system 36 are instructive. Table 2-4 provides the relative rate data,

all extrapolated to 1000C, and activation parameters for these five species. It can be seen

that (1) the fluorine substituent, when it can rotate outward, is a rate-enhancing

substituent, although not nearly so much as is methyl, a fact consistent with substantial

allylic cation character in the solvolysis transition state, and (2) the trans/cis ratio is

greater for the fluorine than it is for the methyl substituent, this in spite of the fact that a

fluorine substituent could be expected to exert virtually no steric effect upon inward

rotation (the A value for fluorine is 0.24 versus a value of 1.8 kcal/mole for methyl). 47











Table 2-4. Comparison of Rate Data a for Cyclopropyl Bromides at 1000C.


Cyclopropyl Bromide k (x 10 9) kre, trans/ cis AH+b AS+c Reference

parent 1.6 1 33.0 -10.8 36, 45

trans-2-fluoro 22.8 14.25 19 29.3 -15.5 this work

cis-2-fluoro 1.2 0.75 31.5 -15.4 this work

trans -2-methyl 987.0 616.9 13.8 30.9 -3.6 36

cis-2-methyl 71.7 44.8 31.4 -7.7 36


a extrapolated from activation parameters; b kcal/ mole; c cal/ mole-deg



The kinetic results in this case thus would not seem to be derived from a steric ef-

fect and are actually contrary to thermodynamic considerations. In contrast to the methyl

system where the kinetic effects seem to correlate with steric effects in that trans products

are more stable thermodynamically than cis products, it is likely that cis acetate [32] is

more stable thermodynamically than trans acetate [311. 48,49

Conclusions

A logical conclusion derived from these results is that the generally observed en-

hanced rates of solvolyses for trans versus cis 2-substituted cyclopropyl derivatives

likely do not derive from steric factors but most likely from substituent electronic effects

related to those observed in the cyclobutene ring-opening. The diminished effect of a

fluorine substituent in the present system when compared to the cyclobutene system

(where kre1 was 10 4) 38 may derive from the fact that, in contrast to the cyclobutene

system, much of the activation barrier in cyclopropyl bromide solvolyses derives from

ionization of the C-Br bond, with the fluorine only able to assist with the concomitant









24

C2-C3 bond cleavage. Even though these cyclopropyl systems meet the significant tor-

sional requirements outlined in Chapter 1, the dramatic effect of the fluorine substituent

seems to be subdued by the ability of the bromine to dissociate. It has been postulated by

Fleming 50a and Wallace 50b that most of the twisting of the 2-substituents is complete

before reaching the transition state, which gives the transition state more allylic cation

character. Therefore, the product-like cation-forming transition state, wherein rotation of

the fluoro-substituent is almost complete, may be the cause of the diminished kinetic ef-

fect. In addition, the largest kinetic effect would be expected for a symmetrical transition

state in which the 2-substituent is involved in its rotation. Furthermore, it is expected that

if dramatic kinetic effects are to be observed in other pericyclic processes besides the

cyclobutene system, it will be for those with which the fluoro-substituent must undergo

considerable torsional motion in reaching a symmetrical transition state and those with

which the rate determining step is influenced largely by the cleavage of the bond alpha to

the fluoro substituent. Preliminary theoretical examinations of this system have provided

support to these conclusions. 50C

Chapter 3 explores this premise in detail by the investigation of the 1,3 Carbon

Shift in the 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene system, where the rate

determining step is directly influenced by the fluorine substituent.















CHAPTER 3
[1,3] SIGMATROPIC MIGRATIONS OF CARBON

Introduction

In the middle 1960s Woodward and Hoffman published a series of preliminary

communications 51- 53 which constructed some fundamental bases for the theoretical

treatment of all concerted reactions. The basic premise enunciated was the conservation

of orbital symmetry. In other words, they proposed that reactions which obtain a

"congruence" between reactant and product orbitals will occur more readily that those

which do not. This ideology of conservation of orbital symmetry was then formulated into

a series of orbital symmetry rules which had certain predictive powers. These rules were

then investigated by a multitude of scientists. 54

One classification of reactions addressed by the orbital symmetry rules was the

sigmatropic migrations of alkyl or aryl groups. 55- 57 However, it was found that these

migrations are less common than their corresponding hydrogen migrations and in fact the

migratory aptitudes of methyl and phenyl were shown to be lower than hydrogen. 58,59

Moreover, there is a major difference that occurs when carbon migrates instead of hydro-

gen. Unlike hydrogen whose electron is in a Is orbital that has only one lobe, the carbon

free radical has its odd electron in a p orbital that has two lobes of opposite sign.

Therefore, looking at the frontier orbitals involved in a thermal [1,3] alkyl shift (Figure

3-1), it is apparent that an inversion of configuration must occur (i.e. the migrating

carbon switches lobes.)

The Woodward and Hoffmann orbital symmetry rules predict that suprafacial [i, j]

migrations of carbon in systems, where j = 4n 1, proceed with inversion thermally and














DCCD


C C

0 0

Figure 3-1. Orbital Interpretation of the [1,3] Alkyl Shift

retention photochemically, while systems where j = 4n + 1 show opposite behavior. The
first experimental corroboration of this prediction was the pyrolysis of deuterated endo
bicyclo[3.2.0]hept-2-en-6-yl acetate (39), 60 which gave the exo-deuterio-exo-norboryl
acetate (40). 61 (See Figure 3-2.) This elegant study by Berson verfied that the thermal
[1,3] alkyl sigmatropic rearrangement, indeed, took place with complete inversion at
C-7, as predicted by the orbital symmetry rules.
H
[1,3] shift
H >with
OAc
inversion

S Ac-O H 3000C--


Figure 3-2. The Pyrolysis of Deuterated endo bicyclo[3.2.0]hept-2-en-6-yl acetate








27
However, it was found that rotation of the C-7 carbon in the bicyclo[3.2.0]-

hept-2-ene system was required to be clockwise. Moreover, the pathway leading to inver-

sion can be blocked by the introduction of an endo methyl group at C-7, in which case the
reaction takes place with predominant retention. 62- 65 It has been suggested that an
orbital-symmetry-forbidden concerted reaction takes place in these cases. 62,66 These
initial studies gave way to a host of investigations of the thermal [1,3] carbon shift. 67- 72



OD slow

D

41 42
[3,31 D D D

S[1,3]] 3 D

H H via
HD HCH2
slow

D -.,- ;


43 44 D
Figure 3-3. The Thermal Isomerization of 6-(dideuterio-methylene) bicyclo[3.2.0]hept-2-ene.

Thermal isomerizations of the 6-methylene-bicyclo[3.2.0]hept-2-ene system have
been examined by Hasselmann. 73-75 In his elegant study of 6-(dideuteriomethylene)-
bicyclo[3.2.0]hept-2-ene (41), it was shown (Figure 3-3) that a relatively slow auto-
merization process of 41 to 42 proceeded at a rate factor of 8-10 slower than that to the
bicyclo[2.2.1] system, but also gave a 60: 40 preference for the formation of the [1,3]
alkyl shift product 43 over the 44. He attributed this result to the reluctance, due to

steric repulsions of the allyl radical I to rotate through the methylene group at C-4.









28

Since 42 was also preferentially converted to 44 over 43, a significant corollary of these

systems was that the [1,3] shift of C-7 from C-1 to C-3 was an innately preferred

process and that the reaction did not proceed via an equilibrated diradical.

Hasselmann further illustrated this argument in his comprehensive study of the

methylated-6-methylenebicyclo[3.2.0]hept-2-enes. 74 In this study he proposed that "non-

equilibrating diradicals" offered an explanation for the experimental findings. These rad-

icals appeared to behave as individual transition states in the sense of the "continuous

diradicals" proposed by Doering and Sachdev. 76 Later work done by W.R. Dolbier et al.

shown in Figure 3-4 investigated the thermal isomerization of the 6-difluoromethylene-

bicyclo[3.2.0]hept-2-ene 77 system (45). It was concluded with a logic similar to that

proposed by Hasselmann that the rearrangement occurred exclusively via two competing

[1,3] sigmatropic processes. This exclusivity was attributed to the significantly greater

barrier for passage of the -CF2 end of the allyl radical in J through the -CH2 group at

C-4 than for the comparable rotation of I. The product distribution was thereby

explained by a least rotation argument in which the diradical J, collapsed to the products

46 and 47 after a minimized rotational movement around C5 C6 (Figure 3-4).


H H H H

F H F 2520
F
H F F

H V i 1800 0% F
45 720
45 rotation

F

FFF
F F
46 84% 47 16%

Figure 3-4. The Thermal Isomerization of 6-(difluoromethylene)bicyclo[3.2.0]hept-2-ene








29
The synthesis and thermal isomerization of another fluorinated 6-methylene-
bicyclo[3.2.0]hept-2-ene system were investigated, one in which the stereochemical
aspects of the sigmatropic shifts were further elucidated, i.e. the endo (48) and exo
(49) isomers of 7-fluoro-6-methylene-bicyclo[3.2.0]hept-2-ene.

Syntheses
The 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-enes were synthesized by Wittig
olefination of the corresponding 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-en-6-ones (50
and 51). 78 These in turn were synthesized from the reaction of monofluoroketene and
cyclopentadiene 79 (Scheme 3-1). The isomers (48 and 49) were readily distinguished
due to the characteristic syn hydrogen-fluorine coupling present in the exo fluoro com-
pound (0 = -163.7, dd, J2H-F = 58 Hz, J3H-F = 16.7 Hz) and absent in the endo isomer
( = -178.8, d, J2HF = 57 Hz).




FCH2 COCI Ph3 P=CH2

NEt 3 O O Et2
-780C--0 C +reflux
(28%) 50 H51 2 hours
90: 10 (23%)


r^ .r^)


F 'H


Scheme 3-1. Synthesis of endo and exo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-enes


H' 'F









30

Results and Discussion

The endo (48) and exo (49) isomers of 7-fluoro-6-methylene-bicyclo-

[3.2.0]hept-2-ene underwent thermal rearrangement in the gas phase giving the rate

constants found in Table 3-1 and Table 3-2, respectively. The product distributions are

given in Figures 3-5 and 3-6. The activation parameters for isomerization of the two

isomers are found in Table 3-3. (It should be noted that the keo/kend at 2000C was

3.1.)



Table 3-1. Rate Constants for the rearrangement of endo 7-fluoro-6-methylene
bicyclo[3.2.0]hept-2-ene.

Temp, OC Rate (x 10 -5 sec) Std. Dev. Corr. Coeff.
179.75 0.36 0.01 0.9996
199.75 2.28 0.06 0.9985
205.25 3.84 0.08 0.9984
213.50 9.54 0.21 0.9988
223.00 18.30 0.75 0.9966



Table 3-2. Rate Constants for the rearrangement of exo 7-fluoro-6-methylene-
bicyclo[3.2.0]hept-2-ene.

Temp, oC Rate (x 10-5 sec) Std. Dev. Corr Coeff
172.25 0.56 0.02 0.9976
187.25 2.35 0.08 0.9969
194.00 4.30 0.11 0.9972
205.50 11.30 0.20 0.9994
213.50 22.20 0.80 0.9961



Table 3-3. Arrhenius Parameters for endo and exo 7-fluoro-6-methylenebicyclo-
[3.2.0]hept-2-ene

k log A Eaa + a,b AS+ c AG+ab

kendo 14.5 (+0.5) 41.3 (1.2) 40.4 4.9 38.1
kexo 13.6 (0.1) 38.4 (+0.2) 37.4 0.7 37.1

a kcal/mole; b the mean temperatures for the endo and exo isomers
were 204.050C and 194.30C, respectively; c cal/deg.












H H

+ +
F H F

SA 72.5% 13.6%


F H H


endo (48) H


F H
5.0% 8.9%


Figure 3-5. Product Distribution for endo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene 8)



The pyrolysis of the endo 7-fluoro-6-methylene-bicyclo[3.2.0]hept-2-ene (48) af-

forded four products. The kinetically formed (at 8% conversion) product ratios were the

E isomer of 5-fluoromethylene bicyclo[2.2.1]hept-2-ene (52) (72.5%), exo 6-fluoro-

5-methylenebicyclo[2.2.1]hept-2-ene (53) (8.9%), endo 6-fluoro-5-methylenebicyclo-

[2.2.1]hept-2-ene (54) (5.0%) and exo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene

(49) (13.6%). The observed yield for the overall rearrangement after one half-life was

93% and after 98% conversion, 88%.

These pyrolysis products were separated by GC and fully characterized by 1H

NMR, 19F NMR, and low resolution mass spectroscopy. The E (52) (19F NMR: 0 =

-138.8, d, J2H-F = 87.0 Hz) and Z (55) (4 = -136.8, dd, J2HF = 87.0 Hz, H-F =

3.5 Hz) isomers of 5-fluoromethylenebicyclo[2.2.1]hept-2-ene were synthesized pre-

viously from cyclopentadiene and monofluoroallene. 80 The exo (53) ('H NMR: 8 4.82,









32
d, 1H, J2H-F = 58.4 Hz, -CHF; 19F NMR: = -171.8, d, J2H-F = 58.3 Hz) and endo (54)

(6 5.41, d, 1H, J2HTF = 57.8 Hz, -CHF; ( = -177.4, d, J2HTF = 58.0 Hz) isomers of

6-fluoro-5-methylene-bicyclo[2.2.1]hept-2-ene were assigned according to the well-docu-

mented evidence for the shielding of endo substituents at C-6 in norbornene. 81



H H


F + +
F F H

A 19.0% 9.2%


H F H H H H
F H H


exo (49)


F H
5.4% 66.4%


Figure 3-6. Product Distribution for exo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene (49)


Likewise, the exo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene (49) was

pyrolyzed and also yielded four products as seen in Figure 3-6. The kinetically formed

(at 15% conversion) product ratios (see Chapter 4) were E-5-fluoromethylenebicyclo-

[2.2.1]hept-2-ene (52)(19%), exo 6-fluoro-5-methylenebicyclo[2.2.1]hept-2-ene (53)

(66.4 %), endo 6-fluoro-5-methylene bicyclo[2.2.1]hept-2-ene (54) (5.4%), and endo

7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene (48) amount of Z-5-fluoromethylene-

bicyclo[2.2.1]hept-2-ene (55) formed in both the pyrolyses of the endo and exo

isomers was less than 1% (none actually observed).








33
All of the products were kinetically stable under the reaction conditions except the

endo 6-fluoro-5-methylenebicyclo[2.2.1]hept-2-ene which decomposed slowly. The

amount of the endo or exo 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene formed during

the pyrolysis of each of the (>98%) pure starting materials was taken into account by

extrapolation to zero time (see Chapter 4). This allowed for facile assignment of the

kinetically formed product ratios. A comparison with the 7-methyl-6-methylenebicyclo-

[3.2.0]hept-2-enes studied by Hasselmann 74 is tabulated in Table 3-4.


Table 3-4. Comparison of the exo and endo 7-fluoro isomers with the 7-methyl
system


H H
Ix

Ar 1 H


H H




52


49 48


a methyl product distributions after 1 half-life. b The amounts of E- and Z-
6-ethylidenebicyclo[3.2.0]hept-2-ene were (3.0% and 0.1% respectively for the exo
starting material) and (5.4% and 0.2% respectively for the endo starting material). These
products are not listed since they were not observed in the pyrolyses of the fluoro systems.
The amount of Z-5-substituted-methylenebicyclo[2.2.1]hept-2-ene formed in the pyrolysis
of both the methyl and fluoro systems was less than 1%.


H


54 X


exo

X=Me


X=F

endo

X=Me

X=F


8.3% 62.4% 22.4% 50.0% a,b 3.4%



5.4% 66.4% 19.0% S.M. 9.2%


5.9% 8.9% 70.4% 8.7% 50.0% a,b


5.0% 8.9% 72.5% 13.6% S.M.









34

Most significant is the 93% inversion of configuration at C-7 in the formation of

exo 6-fluoro-5-methylenebicyclo[2.2.1]hept-2-ene (53) from the exo 7-fluoro-6-methyl-

enebicyclo[3.2.0]hept-2-ene (49). However, the endo 7-fluoro-6-methylenebicyclo-

[3.2.0]hept-2-ene (48) gave 64% retention of configuration at C-7. These results are very

similar to those of Hasselmann's study of the 7-methyl-6methylene-bicyclo[3.2.0]hept-

2-ene systems 74 and Berson and Nelson's related work on the rearrangement of endo and

exo 7-methylbicyclo[3.2.0]hept-2-enes to the bicyclo[2.2.1]heptenes. 82 In all three cases

there was a substantial preference for a suprafacial inversion [1,3] shift in the exo starting

materials but little specificity with the endo isomers.

Gajewski has proposed that the ring opening of the exo 7-methyl-6-methylenebi-

cyclo[3.2.0]hept-2-enes can occur via stereospecific conrotatory-bevel motions as in the

parent methylenecyclobutane system. 56 Furthermore, work by Baldwin and Fleming de-

monstrated that cis and trans 2,4 dimethyl- methylenecyclobutane (56) rearrange

preferentially to the (E)-2-methylethylidenecyclobutane (57) by a factor of ten over the Z

isomer (58). 83 This result illustrated in Figure 3-7 demonstrates the propensity for sub-

stituents in C-2 position to rotate away from C-3 during the initial ring opening.

CH3
iCH3
H H
fast H2 C
H3C
CH3CH K
2 3 CH2 K .


(...H
3 --------
".4 CH3
-4


CH3


H3C


E isomer 57


H3C


6 H3 C
56 slow


L
CHI


H3C


Z isomer 58

Figure 3-7. Rearrangement of cis and trans 2,4 dimethyl-methylene cyclobutane












CH3


CH3 slow
H CH2 H. M H
.H H
CH3 CH2 fast CH3 fast H2C CH3
CH3
60
59 J

H CH3
H NH3
fast CH
fast N
H CH3 fast C H
59a C H 61

Figure 3-8. Rearrangement of trans 3,4 dimethyl- 1,2 dimethylene- cyclobutane


In a similar system optically active trans 3,4 dimethyl 1,2 dimethylenecyclo-

butane (59) also racemizes (i.e. formed 59a) 2.2 times faster than it rearranges to

1-methylene-anti-2-ethylidene-4-methylcyclobutane (60), so there is a precedence for

reclosure of these types of biradicals at the more substituted carbon. 84 Also as revealed in

Figure 3-8 is the tendency for outward rotation of the methyl substituents. It should be

noted that central bond rotation around C1-C2 in the 2,2' bis-allyl ( and N) is fast com-

pared with ring closure; whereas C1-C4 rotation in the biradical (K and L) derived from

methylene-cyclobutane is competitive with ring closure. This reflects the higher Eact for

reclosure of two stabilized allylic radicals versus an allylic radical plus an alkyl radical.

Necessarily, rotation around C-3 in the bis-allyl species does not occur, no doubt due the

substantial 10.5 kcal/mol energy barrier imposed by the allyl radical resonance energy. 85

Moreover, Gajewski found this conrotatory bevel motion to occur in all thermal cyclobutane









36
ring openings by the same pathway involving conrotatory motions and a third rotation

whose axis is orthogonal to the conrotatory rotation axis. This conrotatory-bevel pathway

was found to "minimize steric repulsions and maximize overlap between the originally

bonded carbons" (p. 5254). 86

This information along with the previously discussed work by Dolbier on per-

fluorocyclobutene-butadiene interconversions 87 which displayed a remarkable tendency

of a fluorine substituent to rotate outwards led to the following proposed mechanistic

scheme (Scheme 3-2). In the case of the exo isomer (49) the product distribution can

explained by the conrotatory-like bevel motions proposed by Gajewski. 86 The rotation of

the fluorine substituent outward coupled with the bevel motion clockwise around C5-C6

brings C-7 and C-3 into close proximity and also points the back lobe of the newly formed

p- orbital at C-7 towards the p- orbital on C-3. Thus, a proposal involving the initial

outward rotation of the substituent at C-7 coupled with the bevel motion around C5-C6

can easily rationalize the formation of inverted exo 6-fluoro-5-methylene bicyclo[2.2.1]-

hept-2-ene as the major product formed. (See Scheme 3-2.)

X = F, CH3


<=> H H2 H2
H O
H X) conrotatory H
-4 like 4 bevel motion C5-C6
49
opening
H H
X
CH2
closure CH2

4 53 with H
major H inversion


Scheme 3-2. Rotational Preference of exo isomer.









37

In the case of the endo isomer (48), the ring cleavage may occur with a disrota-

tory-like motion followed by a rotation (or bevel) counter-clockwise around C5-C6

(Scheme 3-3). These bevel motions have been postulated by Gajewski 86 to be funda-

mental to the motions involved in cyclobutane ring openings. It is important to realize

that the terms dis and con refer only to rotational pathways and not to concertedness in the

Woodward and Hoffmann sense. Moreover, the terms "disrotatory-like" and "conrotatory-

like" simply refer to the motion of the orbitals involved in the cleavage of the a bond of

the cyclobutane ring. It is recognized that the substituent rotations that occur are not the

complete con- or disrotatory motions involved in the classical monocyclic cases. In fact,

it is more probable that a simple outward monorotation of the substituent at C-7 occurs

in conjunction with rehybridization at C-1. However, the terms are utilized to simplify

any conceptual difficulties involving the rotational pathways followed.





Q X CH2 CH2


H H H x
H disrotatory -
Sdisr y counter clockwise
48 like bevel around C5-C6
opening
2
H H
H
closure I H


major X X scrambled I X
H
in minor prods. R
52 H


Scheme 3-3. Rotational Preference of the endo isomer.









38

As seen in Scheme 3-3 the proposed opening would rotate the X- substituent

outward. In addition, the twisting or beveling motion in a counter-clockwise motion

around C5-C6 would place the stereochemical marker (X = F or CH3) at a large distance

from C-3 and cause the -CH2 end of the X-labelled-allyl radical to pass through the

-CH2 group at C-4 (R), hence contributing to the higher activation energy observed for

cleavage. This process appears to have an incremental barrier of -1.9 kcal/mole. 73

With the stereochemical marker (X) at a large distance from the bicyclo[2.2.1]

reclosure site at C-3, it would lose much of its stereochemical integrity in rotating back

towards closure. This distance effect may be responsible for the somewhat scrambled

stereochemical result (approx. 60% retention) observed in both the endo 7-methyl and

7-fluoro-6-methylene-bicyclo[3.2.0]hept-2-ene systems.

It should also be noted that the proposed pathway (Scheme 3-2) for the exo iso-

mer does not involve the passage of the -CH2 end of the X-labelled allyl radical (Q)

through the -CH2 group at C-4. Therefore, the ease of conrotatory-like ring opening

coupled with the lack of any induced steric crowding at C-4 explains the 2.9 kcal/mole

difference in activation energy for the [ endo (48) and exo (49)] systems and presumably

the faster rate (greater than 3 fold) of exo C7- substituted systems over their endo

counterparts. Steric arguments would favor the opposite result, in which the endo

isomers might be expected to exhibit a steric acceleration of ring cleavage. However, this

is not the observed experimental findings in either the methyl 74 or the fluorine-substituted

systems, wherein 2- to 3- fold rate acceleration of the exo substituted systems over their

corresponding endo isomers has been observed.

The rotation of the methyl substituent outward was rationalized by Hasselmann as

deriving from a substantial steric retardation for the inward rotation, which may still be

the case in these systems. However, the fluorine substituent is much smaller ( A value =

0.25 kcal/mol) 88 and its preferred rotation outward may be attributed to electronic

arguments. 87









39

Conclusions
The lack of a dramatic stereochemical preference or kinetic effect in the 7-fluoro-

6-methylenebicyclo[3.2.0]hept-2-ene pyrolyses provides considerable insight into those

factors which give rise to such effects. An examination of the product distributions and

activation parameters supports a non-concerted diradical process. The stability of the

bis-allylic system warrants one to believe that it must lie in a potential well where some

rotation around C5-C6 can occur. As a result of the three systems studied including the

7-dideuterio, 74 7-methyl, 74 and 7-fluoro systems, it is possible that substituents in the

C-7 position compete for their preferred rotational pathways, leading to the ring opening

of the cyclobutane ring by either a specific conrotatory-like or disrotatory-like motion.

These pathways then yield non-equilibrating diradicals which close to products via a least

motion process.

The entropy of activation of the endo isomer (8) (AS+ = 4.9 e.u.) along with its

greater activation energy ( Ea = 41.3 kcal/mole ) supports the premise that more C1-C7

bond breaking occurs in its transition state. This seems reasonable since the molecule is

forced to rotate the methylene group at C-6 through the hydrogens at C-4, which is of

higher energy than the more concerted process reflected in the essentially zero change in

entropy (AS+ = 0.7 e.u.) and lower activation energy (Ea = 38.4 kcal/mole) of the exo

isomer (49).

Moreover, the direction of the beveling or rotational motion around C5-C6, which

apparently occurs in concert with C1-C7 homolysis, would appear to determine the major

product of the reaction, since it moves two radical centers into closer proximity. The

significantly preferred inversion process observed in the rearrangement of the exo isomer

can be explained by the specific conrotatory-like ring opening of 49, which combined

with the beveling motion around C5-C6 rotates the stereochemical marker at C-7 into

close proximity with C-3. The endo isomer's specific disrotatory-like ring opening









40
coupled with the concurrent specific beveling motion around C5-C6 (Q) places the stereo-

chemical marker at a large distance from the bicyclo[2.2.1] reclosure site at C-3, thereby

largely losing its stereochemical integrity, as it rotates back towards closure.

It is expected that these postulates will be substantiated by the placement of two

different substituents on the C-7 position causing a competition for outward rotation and

therefore skewing the product distribution. Experiments with substrates such as these are

in progress and should further elucidate the intricate mechanisms present.

Summary
In the aforementioned chapters the effect of a single fluorine substituent on several

pericyclic and homolytic processes was investigated. This effort, as mentioned previ-

ously, was initiated by the dramatic kinetic effects observed in perfluorocyclobutene-

butadiene interconversions. 17,18 As a result of this investigation certain criteria can be

postulated. It is expected that if dramatic kinetic effects are to be observed in other

pericyclic reactions it will be for those in which a) the fluoro-substituent must undergo a

considerable torsional motion in reaching the transition state, b) those with which the rate

determining step is influenced largely by the cleavage of the bond alpha to the fluoro-

substituent, and c) those in which a high degree of concertedness is present. Continued

study into these criteria should be quite informative and this field of study quite

productive for future research.














CHAPTER 4
EXPERIMENTAL SECTION

General Methods

Nuclear magnetic resonance (NMR) chemical shifts are reported in parts per

million (ppm) downfield (8) from internal TMS for 1H and 13C spectra, and as (,

ppm upfield from CFC13 in the case of 19F spectra. All spectra were taken in CDC13

unless otherwise indicated. The 13C assignments were determined with the aid of APT

(attached proton test) spectra. All NMR spectra were acquired on either a Varian

VXR-300, Varian XL-200, Jeol FX-100, or a Nicolet NT-300.

Infrared (IR) spectra were determined as films between KBr plates. The IR

spectra were taken on a Perkin-Elmer 283B spectrophotometer in the absorbance range

from 240 to 500 nm and are reported in cm'-. Mass spectra and exact masses were

determined on a Kraytos/AEI-MS 30 spectrometer at 70 eV.

Chromatographic separations were performed by gas-liquid chromatography

(GLC). Unless otherwise indicated, preparative GC was done on a Varian Aerograph

A90-P3 gas chromatograph with a thermal conductivity detector. The kinetic runs in

Chapters 1 and 3 were performed on a Hewlett-Packard 5710A gas chromatograph

equipped with a flame ionization detector and an attached HP 3380S Integrator.

The product ratios and yields were determined either by 1H NMR, 19F NMR, or

by the average of at least three injections on a HP 5710A gas chromatograph. The

internal standards used to determine yields are listed where necessary.









42

Experimental Procedures
1-(Hydroxymethyl)-2-vinylcyclopropane (21). 25

Into a clean three-necked 500-mL round-bottomed flash equipped with a 125-mL

pressure-equilized addition funnel with nitrogen inlet, a mechanical stirrer, and a vertical

water condenser that was attached to a drying tube of calcium chloride was placed under a

positive nitrogen pressure LiA1H4 (3.53 g: 0.093 mol) in 150 mL of THF (dried by

CaH2 then distilled from LiAlH4 onto activated 4A sieves). This solution was stirred

mechanically for 20 min. Ethyl (2-vinylcyclopropane) carboxylate 22 (13.0g: 0.093 mol)

was added dropwise via the addition funnel. This mixture was monitored by GC and

additional hydride (1.03 g : 0.03 mol) was added after 2.5 h.

After 2 hours of additional stirring the dark grey reaction mixture was then cooled

to 0C and the excess hydride quenched by the very slow addition of water. A 20%

HCI solution was added until all the white precipitate was dissolved. This clear solution

was then extracted with 3 x 100 mL of diethyl ether, dried by MgSO4, and filtered and

the ether was removed. The crude product, a yellow oil, was vacuum distilled at 640C

(12 mm Hg, bath temperature 1050C) to give 7.96g (87%) of (21).

1-(hydroxymethyl)-2-vinylcyclopropane (21): 1H NMR 5 5.55 4.78 (m, 3H,

olefinic), 3.87 (s, 1H, -OH), 3.62- 3.42 (m, 2H, CH2-O), 1.33 0.40 (m, 4H, cyclo-

propyl H); IR (neat) 890, 1040, mass spectrum gave M+ 98.0744 + 0.0014, calculated

for C6H0oO 98.0731 + 0.0013.

1-(Fluoromethyl)-2-vinylcyclopropane (19 and 22).

Into a preweighed three-necked 100-mL round-bottomed flask equipped with two

stoppers, vacuum adapter, and stirring bar was placed 13.0g of tetrabutyl-ammonium

fluoride trihydrate (TBAF x 3H20, Aldrich). This flask was attached to a vacuum line (<2

mm Hg) and heated at 450C for 48 h. 23 To the dry TBAF (calculated 16% H20 loss)

was added a mixture of tosyl fluoride (3.56g: 0.0204 mol) and 1-(Hydroxymethyl)-2-vinyl-










43
cyclopropane (21) (1.Og: 0.0102 mol) in 30 mL of diethyl ether (dried from LiA1H4 onto

activated 4A sieves). The TBAF/ TsF/alcohol mixture formed two layers upon com-

bination. The TBAF formed an orange gelatinous solid which could be stirred freely upon

use of ultrasonics (E/MC Model 250, RAI Research) and slight heating (not >400C). This

mixture was stirred for 61 h. At this time the product mixture (2 layers) was poured into

a 200 mL separatory funnel and 20 mL of deionized H2O was added. The ether layer was

separated and the aqueous layer extracted with 2 x 20 mL diethyl ether. The ether layers

were combined, dried with MgSO4, and filtered. The ether was removed at atmospheric

pressure pot temperature <480C). The yellow oil was vacuum transferred twice. The cis

(19) and trans (22) isomers of 1-(fluoromethyl)-2-vinylcyclopropane (24%) were

separated by GC using a 10 ft x 1/4 in., 20% SE 30 on Chrom P 60/80 column.

The cis-l-(fluoromethyl)-2-vinylcyclopropane (19) was further GC purified on a

10 ft x 1/4 in., 10% ODPN column (98% GC pure). The kinetic studies were done on

this purified sample.

trans- -(Fluoromethyl)-2-vinylcyclopropane (22): 1H NMR (300 MHz), 5 5.42

(ddd, 1 H, C-CH=C), 5.10 (dd, 1H, t-C=CH), 4.92 (dd, 1H, C-C=CH), 4.28 (ddd,

2H, CH2F) 1.5 0.7 (complex m, 4H, cyclopropyl H); 19F NMR, 0 = -210.46 (td,

J2HF = 48.9 Hz, J3HF = 7.3 Hz); mass spectrum, m/z (relative intensity) 101 (M + 1,

1.36), 100 (M+, 30.07).

cis-l-(Fluoromethyl)-2-vinylcyclopropane (9): 'H NMR (200 MHz), 5 5.7 (m

(ddd?), 1H, C-CH=C), 5.2 (m (dd?), 1H, t-C=CH, 5.1 (m (dd?), 1H, C-C=CH), 4.4-

4.0 (ddm, 2H, CH2F), 1.8 0.5 (complex m, 4H, cyclopropyl H); 19F NMR, =

-211.3 (t, J2HF = 48.9 Hz); 13C NMR, 5 135.8 (s, HC=), 115.9 (s, =CH2), 84.0 (d,

JC-F = 166 Hz, CH2F), 19.7 (d, JC-F = 5 Hz, H2C cyclopropyl), 17.8 (d, JC-F = 25 Hz,
HC-CH2F cyclopropyl), 9.6 (d, JC-F = 5 Hz, HC-C cyclopropyl); mass spectrum, m/z

(relative intensity ) 101 (M+ + 1, 1.50), 100 (M+, 27.46).









44

Thermal Rearrangement of cis- 1-(Fluoromethyl)-2-vinvlcyclopropane (19).

cis-1-(Fluoromethyl)-2-vinylcyclopropane (80.0 mm) was expanded into a

well-conditioned pyrolysis bulb and pyrolyzed at five temperatures between 193.25 and

227.250C. The reaction was followed by GC with a 16 ft. x 1/8 in., 10% ODPN on

Chrom P 60/80 column at 550C. The raw kinetic data is listed in Table 4-1, whereas the

rate constants are given in Table 1-1. The pyrolysis afforded only two products:

(Z,Z)-1-fluoro-1,4-hexadiene (24) and (E,Z)-1-fluoro-1,4-hexadiene (23) in the ratio of

65 : 35, respectively. These isomers were readily distinguished by their 19F NMR.

(Z,Z)-1-Fluoro-l,4-hexadiene (24): 19F NMR, ( = -131.64 (ddt, JZHF = 85.4 Hz,

trans HF = 42.6 Hz, JHF = 1.7 Hz, =CHF).

(E,Z)-l-Fluoro-l,4-hexadiene (23): 19F NMR, ( = -131.87 (ddt, J2HF= 85.5 Hz,

3cis HF = 18.8 Hz, J5HF = 2.6 Hz, =CHF).
Kinetics Procedure for the Acetolysis of trans and cis 1-bromo-2-fluorocyclopropane (29)
and (30).

The kinetic vessels were sealed 507 NMR tubes. Each tube contained approxi-

mately 0.05g of either (> 99% pure) cis or trans l-bromo-2-fluorocyclopropane, along

with 0.5 ml of buffered acetic acid (Buffer #1). This buffered solution (#1) was prepared

by combining freshly distilled acetic acid (5.0 ml), sodium acetate (0.265 g: .0025

moles), freshly distilled acetic anhydride (0.306 g: 0.003 moles), hexafluorobenzene

(0.22 g) as an internal standard and deuteriochloroform (1.25 ml). New samples were

prepared for each temperature. A Statim type isothermal heater was used to pyrolyze

these tubes at 187.0, 210.0, and 218.00C. At designated intervals, the tubes were

cooled to 0C and reaction rates determined by 9F NMR integration versus the internal

standard. The raw kinetic data are listed in Tables 4-2 and 4-3, whereas the rate constants

and activation parameters are given in Tables 2-1 and 2-2. The pyrolysis of each isomer

afforded a mixture of cis and trans 1-fluoro-3-acetoxy- 1-propene (32 and 31), which

were shown to be thermally stable by extended pyrolysis at 199.00C.












Table 4-1. Raw Kinetic Data for the Thermolysis of (19).

Temperature: 193.25 C
time (min) (19) (24) (23)

0 100.00 0.00 0.00
50 79.75 6.07 2.96
121 70.75 11.34 5.68
181 62.25 15.87 8.50
240 55.84 19.82 10.13
307 47.72 22.20 11.75
360 35.25 20.91 10.14
457 37.75 27.58 14.50
545 32.38 28.68 15.35
628 21.66 30.62 15.95


Temperature: 201.25 C
0 96.68 1.24 0.49

154 58.66 26.72 13.92
212 49.28 32.71 17.19
255 43.02 37.03 19.28
444 23.66 49.45 25.81
507 19.68 52.34 24.65
568 16.19 53.62 27.24













Table 4-1. --continued

Temperature: 209.75 C

time (min) (19)

0 100.00
28 78.45

45 69.74
75 58.89

93 49.87
114 45.07
136 38.56
182 29.25
229 20.66


Temperature: 219.25 C

0 100.00


74.38

58.55

43.65

39.53
34.51

32.54
29.70

29.06

22.78


(24)

0.00
12.22

17.04
24.04

28.30

31.17
34.43
38.95
41.97


0.00

14.20

25.06

34.38

36.62
39.12

40.65
41.05

42.22

44.96


(23)

0.00
6.26

8.84
12.73

14.68

16.58
18.19

20.45
22.38


0.00

7.52

13.19

18.51

19.78
20.92

21.80
21.92

22.97

22.99











Table 4-1. --continued

Temperature: 227.25 C
time (min) (19) (24) (23)

0 100.00 0.00 0.00
6 85.99 8.43 4.44
11 72.03 14.21 7.48
17 63.33 19.40 10.26

23 56.10 24.01 12.87
29 47.79 26.55 14.46
34 41.95 29.16 15.69
40 39.33 31.63 17.17
46 30.67 35.02 18.34

52 24.72 33.86 17.99





Kinetics Procedure for the Acetolvsis of cis and trans 3-bromo- -fluoro- 1-propene and
1 -bromo-1 -fluoro-2-propene:

The kinetic procedure was identical to that of the bromofluorocyclopropanes. The

rates were determined at 127.00C by 19F integration of the starting propene vs. the

hexafluorobenzene internal standard. The raw kinetic data is listed in Table 4-4, while

the rate constants are tabulated in Table 2-3.

1,1 dibromo-2-fluorocyclopropane (28a) 42

Into a clean, dry 330 ml stainless steel bomb was placed freshly recrystallized phenyl

tribromomethyl mercury 40,41 (78.0 g: 0.147 moles) and freshly distilled benzene (300

ml). The solution was stirred for 10 minutes to dissolve the mercurial. The bomb was

then sealed and degassed twice, and vinyl fluoride (27.16 g : 0.59 moles) was













Table 4-2. The Acetolysis of trans 1-bromo-2-fluorocyclopropane (29).

Temperature = 187.00C
Time (min) Int. Standard Trans (29) cis acet. (32) trans acet. (31)

0 53.83 46.17 0.00 0.00
153 59.59 27.83 2.58 10.01
236 59.97 22.51 3.80 13.72

286 60.87 20.18 4.10 14.85

552 66.85 11.17 5.96 8.50
624 71.65 9.51 5.29 4.80

Temperature = 210.00C
0 54.08 45.92 0.00 0.00

16 52.90 39.79 1.11 6.21
41 54.88 28.91 2.45 13.76
61 55.27 22.03 4.02 18.68

81 55.53 16.68 5.47 22.32
101 56.10 13.45 6.25 24.19
122 56.67 10.11 7.11 26.11

Temperature = 218.00C

0 46.13 53.87 -
70 52.09 17.46
75 54.86 15.15
84 59.80 14.00
93 74.44 13.84











Table 4-3. The Acetolysis of cis 1-bromo-2-fluoro cyclopropane (30).

Temperature = 187.0C
Time (min) Int. Standard Cis (29) cis acet. (32) trans acet. (31)

0 63.11 36.89 0.00 0.00
153 62.29 35.74 1.04 0.93

303 64.03 34.82 0.72 0.42

569 64.54 32.42 1.72 1.32

648 65.19 32.28 1.56 0.97


Temperature = 210.0C

0 64.41

60 64.49
126 64.60

441 66.23

565 78.48

626 82.13


Temperature

0
121

198

334
409

470


= 218.0OC

60.78

56.19

56.42

57.73
59.44

70.68


32.29

29.99
27.61

18.57

18.21

17.08


39.22

34.78

28.67

20.76
17.75

17.19


1.76

3.13
4.41

8.73
3.82

0.51


0.00

5.42

8.92

13.08
14.44

9.63


1.54

2.39
3.38

6.47

1.41

0.27


0.00
3.60

5.98

8.43
8.37

2.51













Table 4-4. Acetolysis of The Bromo-Fluoro Propenes 35, 37, and 38.
Temperature = 127.00C
Time (min) Int. Standard a fluoro bromo 2-propene (35)


67.15

65.37

69.97

70.10

70.40

71.09


30.85

11.53

9.41

7.18

4.94


3.38


Time (min)


Int. Standard trans 1-fluoro 3-bromo 1-propene (37)


0 72.05 27.29
67 73.12 6.19
138 72.91 3.23
200 72.80 1.71
267 73.47 0.81

Time (min) Int. Standard cis 1-fluoro 3-bromo 1-propene (38)

0 62.79 28.88
67 60.95 13.25
138 65.49 10.91
200 64.70 8.48
267 64.48 6.11










51
condensed into the bomb. The bomb was then warmed to room temperature and placed

into a preheated shaker at 800C for 18 hours. At this time, the bomb was cooled,

vented and opened. The yellow solution was filtered through a sinted glass funnel, con-

centrated by rotary evaporator and vacuum transferred to provide a clear liquid, which

was then separated by GC on a 10 ft. x 1/4 in., 20% SE-30 on Chrom P 60/80 column at

1000C to provide 6.69 g (21% yield) of 1,1 dibromo-2-fluorocyclopropane.

1,1 dibromo-2-fluorocyclopropane (28a) : H NMR 5 4.77 (d, J2H-F = 64.2 Hz,

dd? (second order), 1H), 2.03 1.87 (m, 2H); 19F NMR 0 = -195.76 (ddd, J2HF =

64.2 Hz, J3HF = 19.7 Hz, J3HF = 12.4 Hz); 13C NMR 74.5 (d, J C-F = 244.5 Hz, C-F),

29.4 (d, J2C-F = 11.9 Hz, CH), 21.3 (d, J2C-F = 12.5 Hz, CBr2); MASS SPECTRUM,

m/z (relative intensity) 220 (M + 4, 2.26), 218 (M + 2, 4.940), 216 (M+, 2.24), 139

(96.5), 137 (100.0), 113 (32.9), 111 (33.4), 57 (52.2); high resolution mass spectrum

gave M+= 215.8600 + 0.0024 (+ 11.1 ppm), calculated for C3H3FBr2: 215.8584 +

0.0015 (+ 7.0 ppm).

Cis and trans 1-bromo-2-fluorocyclopropane (29) and (30) 43

1,1 dibromo-2-fluorocyclopropane (6.69 g: 0.031 moles) was placed in a

3-necked, 25 ml round-bottomed flask equipped with a magnetic stirrer, a nitrogen inlet,

and a septum. The contents were cooled to 0C in an ice bath and tributyl tin hydride

(9.01 g: 8.33 ml: 0.031 moles) was added under an atmosphere of nitrogen via a long

needle syringe, dropwise, over a period of one hour. The reaction mixture was then

warmed to room temperature and monitored by GC. After 2 hours, additional hydride

(2.2 ml: 2.38 g) was added and the reaction was left stirring for an additional hour. The

contents were then vacuum transferred to provide a clear liquid. Cis and trans 1-bromo-

2-fluorocyclopropane (cis/trans = 40 : 60) were then isolated by preparative GC on a 10

ft. x 1/4 in., 20% SE-30 on Chrom P 60/80 column at 750C to provide 1.78 g of the

trans isomer and 1.14 g of the cis isomer for a 68% yield.









52
Cis 1-bromo-2-fluorocvclopropane (30): H NMR (300 MHz) 5 4.51 (dddd, J2H-F

= 64.98 Hz, J3H-H = 6.44 Hz, J3H_ = 5.27 Hz, J3H-H = 3.50 Hz, 1H), 2.83 (m, 1H),

1.46 1.16 (complex m, 2H); 19F NMR (300 MHz) ( = -216.88 (dddd, J2H-F = 64.94

Hz, J3H-F = 21.00 Hz, J3H-F = 12.86 Hz, J3H-F = 2.65 Hz); 13C NMR 68.2 (d, J1C-F =

226.9 Hz, C-F), 16.4 (d, J2C-F = 10.2 Hz, CHBr), 15.5 (d, J2C-F = 10.9 Hz, CH2); mass

spectrum, m/z (relative intensity) 140 (M+2, 1.76), 138 (M+, 1.84), 59 (100.0), 57

(7.01), 39 (14.88), 37 (1.66); high resolution mass spectrum gave M+2 139.9471 +

0.0011 (+ 8.1 ppm) calculated for C3H4F 81Br 139.9459 + 0.0011 (+ 8.1 ppm), M+

137.9492 + 0.0008 (+ 5.8 ppm) calculated for C3H4F 79Br 137.9480 + 0.0012 ( 9.1

ppm).
Trans 1-bromo-2-fluorocyclopropane (29): H NMR (300 MHz) 5 4.73 (dddd,
2H-F = 63.20 Hz, J3H-H = 6.93 Hz, J3HH = 3.33 Hz, J3H-H = 1.25 Hz, 1H), 3.17 (dddd,

J3HH = 16.76 Hz, J3H-H = 9.86 Hz, J3H.H = 5.64 Hz, J3H.H = 1.24 Hz, 1H), 1.61 (dddd,

J3H-H = 22.70 Hz, J3H-H = 8.94 Hz, J3H-H = 9.86 Hz, J3H-H = 3.32 Hz, 1H) 1.25 1.14
(dddd?, 1H); 19F NMR 0 = -204.2 (dddd, J2HF = 63.3 Hz, J3H-F = 22.73 Hz, J3HF =

16.78 Hz, J3HF = 10.25 Hz); 13C NMR 73.8 (d, JIc-F = 232.9 Hz, C-F), 17.3 (d, J2C-F

= 12.4 Hz, CH2), 15.3 (d, J2C-F = 12.1 Hz, CBrH); mass spectrum, m/z (relative

intensity) 140 (M+2, 2.15), 138 (M+, 2.31), 59 (100.0), 57 (6.84), 39 (17.93),

37 (2.76); high resolution mass spectrum gave M+2 139.9474 + .0009 ( 6.5 ppm), calc-

ulated for C3H4F 81Br: 139.9459 + 0.0014 (+ 10.3 ppm), M+ 137.9491 + 0.0009 (+ 6.8

ppm), calculated for C3H4F 79Br: 137.9480 + 0.0010 (+ 7.7 ppm).
Cis (38) and trans (37) 1-fluoro-3-bromo-l-propene and l-bromo-1-fluoro-2-propene (35).

These were made by a previously reported procedure for monofluoroallene
synthesis from the dehydrobromination of 1-bromo-1-fluoro-3-bromopropane.44 This

reaction provided a mixture of cis and trans 1-fluoro-3-bromo-l-propene (cis/trans = 20%

:20%) and l-bromo-l-fluoro-2-propene (60%). These were separated by preparative GC









53
on a 20 ft. x 1/4in., 20% diisodecylpthalate (DIDP) on Chrom P 60/80 at 250C.

This preparation provided samples >87% pure of each isomer for use in the kinetic study

of their solvolysis.

cis 1-fluoro-3-bromo-l-propene (38) : H NMR 6 6.55 (dd, J2H-F = 84 Hz,

J3H-H= 6 Hz, 1H), 5.25 (complex m, 1H), 4.05 (dd?, 2H); '9F NMR ( =-125.1 (dd,

J2H-F = 82.4, J3H-F = 38.1 Hz).

trans 1-fluoro-3-bromo-1-propene (37) : 1H NMR 6 6.79 (ddt, J2H-F = 81.38 Hz,

J3H-H = 11.09 Hz, J4H-H = 0.66 Hz, 1H), 5.70 (m, 1H), 3.88 (ddd?, 2H); 19F NMR (188
MHz) ( = -123.8 (dd, J2H-F = 81.1 Hz, J3H-F = 15.1 Hz).

1-bromo-l-fluoro-2-propene (35) : H NMR 6 6.90 (dd, J2HF= 50 Hz, J3H-H

6Hz, 1H), 6.20 (m, 1H), 5.80 5.20 (m, 2H); 9F NMR (188 MHz) ( = -135.0 (dd,

J2H-F = 50.3 Hz, J3H-F = 13.7 Hz).

Cis (32) and trans (31) 1-fluoro-3-acetoxy-1-propene.

Each isomer was prepared from its corresponding 3-bromo-l-fluoro-1-propene

derivative by heating in buffered acetic acid (Buffer #1). After 500 minutes at 127.0C,

the cis and trans bromofluoropropenes were completely converted to their corresponding

cis (32) or trans (31) 1-fluoro- 3-acetoxy-l-propene derivatives. These were then

isolated by preparative GC on a 10 ft. x 1/4 in. 20% OV-210 column at 500C, to

provide a greater than 93% yield of each isomer.

cis 1-fluoro-3-acetoxy-1-propene (32) : 'H NMR 5 6.56 (ddt, J2HF = 83.0 Hz,

3HH = 4.8 Hz, J4H-H = 0.9 Hz, 1H), 5.05 (m, 1H), 4.72 (ddd?, 2H), 2.07 (s, 3H); 19F
NMR 0 = -124.7 (dd, J2H-F = 83.3 Hz, J3H-F = 40.4 Hz); 13C NMR 170.8 (s, C--O),

150.5 (d, J'C-F = 264.8 Hz, =C-F), 106.1 (d, J2C-F = 2.9 Hz, =C-H), 56.2 (d, J3CF =

8.5 Hz, -CH2-O), 20.9 (s, -CH3).

trans 1-fluoro-3-acetoxy-l-propene (31) : H NMR 8 6.77 (ddt, J2HF = 82.3 Hz,

J3H-H = 11.17 Hz, J4HH = 1.14 Hz, 1H), 5.55 (m, 1H), 4.50 (ddd?, 2H), 2.06 (s, 3H);









54
'9F NMR ( = -123.0 (dd, J2H-F = 82.4 Hz, J3H-F = 16.4 Hz); 13C NMR 6 170.7

(s, C-O), 153.3 (d, J2C-F = 263 Hz, =C-F), 106.8 (d, J2CF = 12.4 Hz, =C-H), 59.0 (d,

J3C-F = 15.7 Hz, -CH2-O), 20.9 (s, -CH3); mass spectrum, m/z (relative intensity ) 118
(M, 0.87), 75 (10.20), 59 (27.35), 46 (0.74), 43 (100.0).

1-acetoxy- -fluoro-2-propene (36)

This unstable isomer was prepared by the acetolysis of a mixture of cis and

trans 3-bromo-l-fluoro- -propenes and 1-bromo-1-fluoro-2-propene. Into a 100 ml

3-necked round- bottomed flask equipped with two stoppers and a pressure equilized

addition funnel [containing the mixture of bromofluoropropenes (5.0g : 0.036 moles) ]

was placed silver nitrate (6.79g : 0.040 moles), 30 ml of freshly distilled acetic acid and

sodium acetate (5.44g : 0.663 moles). The bromofluoropropenes were added dropwise at

room temperature then heated by an oil bath to 600C for 2 hours. A yellow grey precip-

itate formed. The reaction mixture was then cooled to room temperature and 20 ml of

CH2Cl2 was added, the mixture was then filtered to provide a filtrate, which was washed

with deionized water, dried with MgSO4 and concentrated. The resulting residue was

vacuum transferred and the 1-acetoxy-1-fluoro derivative was isolated (greater than 99%

pure) by GC on a 10' x 1/4 in., 20% OV-210 on Chrom P 60/80 column at 600C. The

yield was approximately 50 % (determined by the above column).

1-acetoxy-1-fluoro-2-propene (36): 'H NMR 5 6.63 (ddd?, J2H-F = 54.9 Hz,

J3H-H = 5.3 Hz, J4HH = 0.7 Hz), 1H), 5.95 (m, 1H), 5.66 5.44 (m, 2H), 2.16 (s, 3H);

19F NMR 0 = -126.3 (dd, J2H-F = 54.8 Hz, J3H-F = 6.4 Hz); mass spectrum, m/z

(relative intensity) 118 (M+, 0.12), 62 (54.69), 59(20.68), 56 (40.81), 47 (44.76), 43

(100.0).

Kinetic Procedure for the Trifluoroacetolysis of trans 1-bromo-2-fluorocyclopropane (29).

Into a preweighed 5 ml round-bottomed flask equipped with a magnetic stir bar

was placed silver acetate (0.0789g : 0.4727 mmoles), benzene (0.0124g : 0.1590 mmoles),









55

hexafluorobenzene (0.0364g : 0.1957 mmoles), and trifluoroacetic acid (1.2420g:

0.0109 moles). This mixture was stirred until homogeneous. At this time trans

1-bromo-2-fluorocyclopropane (0.041 1g : 0.2957 mmoles) was added quickly and the

stopwatch started. This mixture was then pipeted into a 2 ml ampuole, which was

equipped with a tiny magnetic stir bar, and flame sealed. Aliquots were taken by

cracking the ampuole, pipeting approximately 0.5 ml of the mixture through a glass wool

plug to remove the silver bromide precipitate, and washing the filtrate through with

d6 acetone into a 507 NMR tube. This tube was then frozen in liquid nitrogen until 'H

NMR and 19F NMR were run. Aliquots were taken at 25.50C and at 103, 209 and 304

minutes. The rate constant is listed in Chapter 2.

Kinetic Procedure for the Trifluoroacetolysis of cis 1-bromo-2-fluorocyclopropane (30)

Into a preweighed 5 ml round-bottomed flask equipped with a magnetic stir bar

was placed silver acetate (0.0820g : 0.4913 mmoles), bibenzyl (0.0171g : 0.09396

mmoles), hexafluorobenzene (0.0394g: 0.21183 mmoles), and trifluoroacetic acid

(1.0580g : 0.0093 moles). This mixture was stirred until homogeneous. At this time cis

1-bromo-2-fluorocyclopropane (0.0488g: 0.35118 moles) was added and the mixture

stirred until homogeneous. This solution was then separated into 3 x 0.20 ml aliquots

each of which was placed in a 1 ml ampuole, flame sealed, and placed in the

aforementioned Statim isothermal oil bath at 98.00C. Aliquots were taken by cooling the

ampuole to 0C then cracking it open and washing the contents through a glass wool

plug with d6 benzene into a 507 NMR tube. 1H NMR and 19F NMR were then taken at

132, 280, and 436 minutes. The rate constant is found in Chapter 2.

trans 1-fluoro-3-trifluoroacetoxy-1-propene (31a): 19F NMR 0 = -73.8 (s, -CF3,

3F), -118.1 (dd, J2tr H-F= 81.1 Hz, J3HF = 15.5 Hz).

cis l-fluoro-3-trifluoroacetoxy-l-propene (32a): 19F NMR 0 = -120.5 (dd, J2HF

= 83.3 Hz, J3ci H-F = 42.8 Hz). [ Note -CF3 group buried under trifluoroacetic acid peak.]








56
1-fluoro-1-trifluoroacetoxy-2-propene (36a): 19F NMR C = -125.9 (dd, J2HF =

53.1 Hz, J3H-F = 9.3 Hz). [ Note -CF3 group buried under trifluoroacetic acid peak.]

endo (50) and exo (51) 7-fluorobicyclo[3.2.0]hept-2-en-6-one:

Into a 3 necked 250 ml round bottom flask equipped with a stirring bar, addition

funnel and a nitrogen inlet was placed a solution of triethylamine (11.0g : 0.1089 moles),

freshly distilled cyclopentadiene (26.0g : 0.3939 moles) and 150 ml of dry diethyl ether.

This solution was cooled to -780C and fluoro-acetyl chloride (8.60g : 0.0878 moles ) in

50 ml of dry diethyl ether was added dropwise over 30 minutes. After the addition was

complete the flask was warmed to 0C and stirred for 48 hours. The white precipitate

was filtered off and vacuum distillation gave 3.70g of a crude mixture. The endo and

exo isomers were separated on a 20 ft. x 1/8 in. OV-210 column at 700C to yield 3.15g

(28%). The endo: exo ratio was 90: 10.

endo 7-fluorobicyclo[3.2.0]hept-2-en-6-one (50):

'HNMR 5.95 (m, 1H, olefinic), 5.71 (m, 1H, olefinic), 5.60 (dddd, 1H, J2HF

= 53.4 Hz (from 19 F NMR ), J3HH = 8.3 Hz, J4H-H = 0.8 Hz, -CHF), 3.90 (broad m,

1 H, CH-CF), 3.51 (m, 1H, CH-C-O), 2.85- 2.45 (complex m, 2H, -CH2); 9F

NMR = -185.8 (d, J2 H-F = 53.4 Hz); 13C NMR 6 180.8 (s, C=O), 136.2

(s, =CH-CH2), 126.4 (d, J3C-F = 3.6 Hz, =CH-CH), 96.8 (d, JC-_F = 239.5 Hz, CHF),

53.1 (d, 3C-F = 12.2 Hz, CH C=O), 46.2 (d, 2C-F = 18.9 Hz, CH-CHF), 35.4

(s, -CH2).

exo 7-fluorobicyclo[3.2.0]hept-2-en-6-one (51):

1H NMR 6 5.90 (m, 2H, olefinic), 4.96 (ddd, 1H, J2HF = 54.1 Hz, J3H-H = 2.85 Hz,

J4HH = 2.22 Hz, CHF), 4.05 (complex m, 1H, CH-C-O), 3.63 (complex m, 1H,
CH-CF), 2.65 (m, 2H, -CH2); 19F NMR 0 = -178.5 (dd, J2HF = 54.6 Hz, J3H-F = 15.3

Hz); 13C NMR 5 180.8 (s, C--O), 134.8 (d, J = 2.2 Hz, =CH-CH2), 127.9 (d, J= 5.9

Hz, =CH CH), 102.6 (d, J1cF = 223.5 Hz, C-F), 59.8 (d, J = 4.9 Hz, CH-C--O),








57
47.1 (d, J = 20.9 Hz, CH-CF), 35.5 (s, -CH2); mass spectrum, m/z (% relative

intensity) 127 (M' + 1, 0.16), 126 (M+, 0.89), 125 (M+-1, 7.96), 98 (50.47), 97(100.0),

79 (45.36), 78 (17.21), 77 (27.67).

endo and exo 6-methylene-7-fluorobicyclo[3.2.01hept-2-ene (48) and (49).

A solution of 1.6 ml of n-butyl lithium in hexane (2.5M) and 12 ml of dry ether is

stirred under nitrogen and 1.42g of methyltriphenylphosphonium bromide is added over 5

minutes using a solid addition funnel. Upon stirring at room temperature for four hours a

small amount of the Wittig reagent precipitates. 7-fluorobicyclo[3.2.0]hept-2-en-6-one

(0.500g) in 5 ml of ether was added dropwise to this mixture and refluxed for 2 hours then

allowed to stir at room temperature overnight. After filtration the ether solution was

washed with water, dried with MgSO4, filtered, concentrated and purified by GC on a

20 ft. x 1/4 in. DNP Column at 1000C (Yield = 23%). The endo and exo isomers were

separated by the above column each > 98% pure. The kinetics were done on these

purified samples.

endo 6-methvlene-7-fluorobicyclo[3.2.01hept-2-ene (48):

1H NMR 6 5.85 (m, 2H, CH=CH), 5.45 (ddt, 1H, J2H-F = 56.2 Hz, J3H-H = 7.4 Hz,

4H-H =2.1 Hz, -CHF), 5.20 (m, 2H, =CH2), 3.70 (broad m, 1H, CH-CH), 3.05 (dd?,
1H, CH-CF), 2.72 2.38 (complex m, 2H, -CH); 19F NMR 0 = -178.8 (d, J2H-F

56.5 Hz); 13C NMR 5 154.3 (d, J2CF = 14.7 Hz, quarternary olefinic), 134.8 (s,

=CH-CH2), 127.5 (d, J3C-F = 5.3 Hz, =CH-CH), 109.4 (s, =CH2), 89.6 (d, J'lcF = 220.4

Hz, CHF), 52.0 (d, JC-F = 18.7 Hz, CH-CF), 39.8 (d, J4CF = 1.9 Hz, -CH2 ), 38.1 (d,

J3C-F = 11.1 Hz, CH- CH2). high resolution mass spectrum: mean of 10 scans was
124.0675 + .00077 (6.3 ppm), calculated for C9H9F1 was 124.0688, deviation =

-0.00127 (-10.3 ppm).

exo 6-methylene-7-fluoro bicyclo[3.2.01hept-2-ene (49):

1H NMR 6 5.78 (m, 2H, CH=CH), 5.27 (complex m, 2H, =CH2), 4.92 (ddt, 1H,








58

J2H-F = 57.9 Hz, J3H-H = 3.2 Hz, J4H-H = 1.3 Hz, -CHF), 3.68 (broad m, 1H, CH-CH,),
3.45 (complex m, 1H, CH-CF), 2.71 2.32 (complex m, 2H, -CH2); '9F NMR 0 =

-163.7 (dd, J2H-F = 57.9 Hz, J3H-F = 16.7 Hz); "'C NMR quarternary olefinic not vis-
ible, 5 134.0 (d, J4-F = 2.2 Hz, =CH -CH2), 128.2 (d, J3CF = 7.2 Hz, =CH-CH), 114.4

(s, =CH2), 94.0 (d, J1-F = 205 Hz, CHF), 52.0 (d, J2CF = 22.8 Hz, CH-CF), 42.1 (d,

J3C-F = 3.6 Hz, CH-CH2), 39.2 (s, -CH2); mass spectrum: m/z (% relative intensity)

125 (M+ + 1, 0.76), 124 (M, 8.88), 123 (M+ 1, 17.51), 109 (96.31), 103 (20.38), 91

(46.78), 78 (63.20), 77 (23.35), 66 (100.00).

endo and exo 6-fluoro-5-methvlenebicyclo[2.2.1 1hept-2-enes (54) and (53).

These products were separated by GC after pyrolyses of the 7-fluoro-6-methylene-
bicyclo[3.2.0]hept-2-enes (48) and (49).

exo 6-fluoro-5-methylenebicyclor2.2.llhept-2-ene (53):

H NMR 66.30 (m, 1H, olefinic), 6.01 (m, 1H, olefinic), 5.13 (m, 2H, =CH2),

4.82 (d, 1H, J2HTF = 58.4 Hz, -CHF), 3.20 (s, 1H, bridgehead), 3.06 (s, 1H, bridge-

head), 1.93 (m, 2H, -CH2); 19F NMR 4 = -171.8 (d, J2HF = 58.3 Hz); 13C NMR 6
141.2 (s, olefinic), 133.0 (d, JC-F = 8.7 Hz, olefinic), 123.1 (s, olefinic), 108.1 (d, JC-F

= 4.7 Hz, olefinic), 93.3 (d, J1CF = 189.4 Hz, CHF), 48.2 (s, bridgehead), 47.8 (d,

JCF = 19.0 Hz, bridgehead), 47.1 (d, JC-F = 3.1 Hz, -CH2); mass spectrum: m/z (%
relative intensity) 125 (M + 1, 1.75), 124 (M+, 22.23), 123 (M 1, 15.60), 109 (82.61),

91(32.81), 78 (63.83), 77 (20.22), 66 (100.00).

endo 6-fluoro-5-methylenebicyclor2.2.1 hept-2-ene (54):
(obtained as a 6% impurity in the E isomer of 5-fluoromethylenebicyclo[2.2.1]hept-2-ene

(52).) 'H NMR 6 6.40 (m, 1H, olefinic), 6.10 (m, 1H, olefinic), 5.41 (d, 1H, JH-F =
58.0 Hz, CHF), 5.12 (m, 2H, olefinic), (bridgehead resonances buried at 3.2 (s, 1H) and

3.06 (s, 1H)), 1.61 (m, 2H, -CH2); 9F NMR 0 = -177.4 (d, JH-F = 58.0 Hz); mass

spectrum: m/z (% relative intensity) 125 (M+ + 1, 0.57), 124 (M+, 17.40), 123 (M+- 1,









59
16.81), 109 (100.00), 103 (19.97), 91 (39.66), 78 (75.27), 77 (27.13), 66(99.59), 65

(22.70).

E and Z 5-fluoromethylenebicyclo[2.2.11hept-2-ene (52) and (55).

The E (52) and Z (55) isomers of 5-fluoromethylenebicyclo[2.2.1]hept-2-ene

were synthesized by reacting monofluoroallene and cyclopentadiene at 0C. In the 19F

NMR the E isomer had 0 = -138.8 (d, J2H-F = 87.0 Hz) and the Z isomer had p =

-136.8 (dd, J2H-F = 87.0 Hz, J4HF = 3.5 Hz).

Thermal Rearrangement of 6-methylene-7-fluorobicyclof3.2.0]hept-2-ene.

Endo 6-methylene-7-fluorobicyclo[3.2.0]hept-2-ene (48) (80 mm) was expanded

into a well-conditioned pyrolysis bulb and pyrolyzed at five temperatures between 179.75

and 223.000C. The reaction was followed by GC with a J&W Scientific MEGABORETM

column at 250C. The rate constants and activation parameters are given in Tables 3-1,

3-2, and 3-3. The pyrolysis afforded four products one of which was unstable. The

kinetically formed (15% conversion) product ratios were determined by 19F NMR

integration and found to be (these values are uncorrected for products produced from

other isomer present at time = 0) the E isomer of 5-fluoromethylene bicyclo[2.2.1]

hept-2-ene (70.0%), exo 2-methylene 3-fluoro bicyclo[2.2.1] hept-5-ene (10.7%), endo

2-methylene 3-fluoro bicyclo[2.2.1] hept-5-ene (4.8%) and exo 6-methylene 7-fluoro

bicyclo[3.2.0]hept-2-ene (14.5%). The corrected values are found in the text in Chapter

3. This endo product then decomposed slowly. The yield after one half-life was 93%;

however, after 98% conversion the yield was 88%.

Exo 6-methylene-7-fluorobicyclo[3.2.0]hept-2-ene (49) (80 mm) was likewise

expanded into the same vessel as above and pyrolyzed at five temperatures between

172.25 and 213.500C. The reaction was followed by the same column and the rate

constants and activation parameters are in Tables 3-2 and 3-3. The kinetically formed

(20% conversion) product ratios were determined by 19F NMR integration and found to









60

be (these values are uncorrected for products produced from other isomer present at

time = 0) exo 2-methylene-3-fluorobicyclo[2.2.1]hept-5-ene (51.8%), endo

2-methylene-3-fluorobicyclo[2.2.1]hept-5-ene (3.5%), E-5-fluoromethylenebicyclo-

[2.2.1]hept-2-ene (23.5%), and endo 6-methylene-7-fluorobicyclo[3.2.0]hept-2-ene

(21.2%). The corrected values are found in the text in Chapter 3. The yield at 89%

conversion was 90%. The amount of Z-5-fluoromethylenebicyclo[2.2.1]hept-2-ene

formed in both the pyrolyses of the endo and exo isomers was less than 1%.

The raw kinetic data for the pyrolysis of the endo and exo 7-fluoro-6-methylene-

bicyclo[3.2.0]hept-2-enes are listed in Tables 4-5 and 4-6, respectively.











Table 4-5. Raw Kinetic Data for the Gas Phase Pyrolysis of endo 7-fluoro-
6-methylene bicyclo[3.2.0]hept-2-ene (48).


Temperature = 179.750C
Time (min) Int. Std. endo (48)


E (52) exo (53) endo (54)


0 99.58 -- -- --
52 98.21 0.90 0.15 0.59
130 96.01 2.30 0.42 0.87
372 91.93 5.43 1.06 1.45
1077 78.61 15.34 3.17 2.66
1468 72.81 19.56 4.28 3.18

Temperature = 199.750C
0 98.49 -- --
90 86.26 9.53 1.89 2.15
160 75.64 17.09 3.81 3.13
230 70.43 21.34 4.63 3.43
489 48.72 37.45 9.64 4.02
656 40.01 44.18 11.73 3.94

Temperature = 205.250C

0 49.15 48.71 -- -- -
62 50.75 36.27 3.81 1.07 2.10
125 51.59 32.69 9.49 2.25 1.63
185 46.07 31.75 13.81 3.40 2.10
246 59.22 16.96 12.93 3.66 1.29
309 54.22 18.09 16.95 4.70 1.78
445 47.12 15.59 23.83 6.82 1.86
513 49.66 11.98 24.03 7.34 1.74











Table 4-5. -- continued.

Temperature = 213.500C


Int. Std. endo (48) E (52)


0
24
46
62
75
124
171


99.89
85.43
73.39
66.53
63.52
49.03
34.75


10.09
18.53
23.50
25.44
38.05
45.19


exo (53) endo (54)


2.03
4.28
5.74
6.22
10.51
14.75


2.28
3.40
3.94
4.49
2.74
1.73


Temperature = 223.000C

0 50.60
13 41.92
23 48.19
33 57.89
69 36.56
96 48.06


Time (min)


47.96
48.38
37.61
25.39
29.18
15.83


5.30
8.37
8.76
22.67
22.41


1.08
1.90
2.54
5.61
6.18


1.39
1.68
1.97
2.75
2.34











Table 4-6. Raw Kinetic Data for the Gas Phase Pyrolysis of exo 7-fluoro-
6-methylene bicyclo[3.2.0]hept-2-ene (49).

Temperature = 172.250C
Time (min) Int. Std. exo (49) endo (48) exo (53) E (52)

17 45.05 44.31 2.70 5.63 1.57
153 39.87 46.18 3.18 7.77 2.34
363 38.85 42.59 3.59 10.79 3.31
597 40.12 38.12 3.46 13.53 3.89
1057 38.65 32.70 3.86 18.46 5.67
1297 42.41 27.23 2.60 20.25 6.20
1522 33.66 31.52 4.91 22.01 7.15
1816 33.69 28.50 4.98 24.30 7.83

Temperature = 187.250C
0 43.35 48.82 2.71 3.30 0.62
64 38.81 47.32 3.65 7.01 2.16
129 37.68 44.48 3.95 10.01 3.22
198 47.79 32.79 2.78 12.52 3.43
263 34.98 38.19 4.19 16.29 5.64
327 39.48 32.14 3.54 18.55 5.69
429 33.48 31.37 5.02 21.95 7.43
518 37.65 25.18 3.97 24.56 7.91

Temperature = 194.000C
0 97.39 2.43
40 87.76 1.84 7.94 2.33
80 78.35 3.17 13.95 4.48
120 69.01 2.20 23.03 6.50
160 63.85 2.53 25.58 7.97
215 54.96 2.29 32.55 10.13


34.24 11.67


49.65 4.37












Table 4-6. -- continued.

Temperature = 205.500C
Time (min) Int. Std.


0
61
107
130
152
175
267


exo (49) endo (48) exo (53) E (52)


93.53
63.32
46.18
38.03
33.00
28.74
15.97


Temperature = 213.500C
0 97.10
13 83.92
25 69.79
47 52.30
58 46.62
68 40.56
85 34.40
95 26.50


2.49
3.55
4.42
2.96
3.93
3.75
3.47


2.14
1.22
2.93
1.68
2.07
2.33
1.74
1.04


24.38
35.67
43.41
46.19
50.33
60.28


11.08
20.33
34.23
37.52
44.39
48.17
55.85


7.96
12.14
14.22
15.32
16.61
20.28


3.69
6.74
11.51
13.38
13.50
16.85
15.87















APPENDIX
SELECTED SPECTRA

The 1H, 19F, and 13C NMR spectra of all new compounds are depicted graphic-

ally in this appendix. The spectral data have been transcribed and are presented in numer-

ical form in Chapter 4. The cis and trans 1-fluoromethyl-2-vinylcyclopropanes are

listed in Figures A-1 through A-5. The cis and trans isomers of 1-bromo-2-fluoro-

cyclopropane are given in Figures A-11 through A-16. The endo and exo 7-fluorobi-

cyclo[3.2.0]hept-2-en-6-ones are given in Figures A-31 through A-36. The endo and

exo isomers of 7-fluoro-6-methylenebicyclo[3.2.0]hept-2-ene are listed in Figures A-25

through A-30. The endo 6-fluoro-5-methylenebicyclo[2.2.1]hept-2-ene (54) could not

be separated from E-5-fluoromethylenebicyclo[2.2.1]hept-2-ene (52) and its spectra are

depicted as those of the mixture in Figures A-40 and A-41.










REGION SfTART (F'F'M) END IINTEb:AI
01 5.869 5.412 10.4
02 5.361 4.815 21.6
03 4.752 3.800 25.4
04 1.935 1.135 22. 0
05 :L .072 0.145 22. 1


7U 4.LO 4.50 4.40 4.30 4.20 4.1(


PPMiI


Figure A-i. 200 MHz 'II NMR Spectrum of 19.

































INDEX FRED PPM INTENSITY
('I 36.8 0.196 362.003
02 -39724.9 -211.056 95.886
03 -39773.8 -211.315 194.086
"4 -39805.5 -211.484 19.270
S5 -39822.9 -211.577 109.311


rmnTTr1mTIVT TTpTrr'lTprr Tr p nlrn
3.8 -211. -211.2 -211.4 -211.6 PPM


I I I,


I r-T--T I I r 1 1 l1 I 1 I1 I I - I I I I I | '
0 -20o -40 -60


-0 100 -eo 0 -140


-1BO


Figure A-2. 188 Mllz 19F NMR Spectrum of 19.


-200


-220


-0 4 . .j-] - 1 . ... ... .. .. .. .... .,..... .. .r r-r-r il- -r -l i i i i i -I i i i



























\r00







20.0 19.5 19.0 18.5 18.0 17 ;5 PP1




ri N


140 120 100 80 60 40 20 u'PM 0

Figure A-3. 50 Milz 3C NMR Spectrum of 19.










TABLE 4. UREASE AND TRYPSIN INHIBITOR ACTIVITIES
SOYBEAN PRODUCTS


OF THE DIFFERENT


Product Trypsin Inhibitor Urease Activity
mg/gm defatted sample pH change


Unheated soybeans 53.95a 1.97
Roasted 110 C; 0% water 40.00 1.82
Roasted 110 C; 10% water 24.00 1.30
Roasted 125 C; 0% water 22.88 0.55
Roasted 125 C; 10% water 9.18 0.25
Soybean meal (48%) 3.11 0.10


a Larger values are indicative of less heat processing.








70

in similar reductions in TI. The inclusion of 10% water prior to

roasting at 125 C resulted in the largest reductions in TI and UA

(83.0 and 87.3%, respectively) yet the product still contained between

two- and three-fold the TI and UA of soybean meal. Pig performance

data reflect the difference in heat processing and indicate that

soybean products having a UA of .25 or higher are not adequate protein

supplements for weanling pigs. These results concur with the work of

Albrecht et al. (1966), McNaughton and Reece (1980), and Waldroup

(1985) which suggest that increasing the moisture content of soybeans

prior to heating increased the inactivation of TI and UA. These data

also agree with the findings of Campbell et al. (1984) in that

soybeans roasted at 125 C had a higher nutritional value when compared

to soybeans roasted at 110 C. In addition, the depressed performance

of weanling pigs fed soybeans having a UA higher than .2 is in

agreement with the optimum range of UA used by the American Feed

Manufacturer Association to indicate soybean products that have

received adequate heat processing (Smith, 1977).

The Bragg variety of soybeans roasted in this study had remained

in the field for a longer period of time (1-2 months) than normal

before being harvested. The moisture content of these soybeans was

10.33% and with the addition of 10% water was analyzed to be 20.45%

prior to roasting. Roasting the soybeans at 110 C with and without

added water reduced the moisture content to 13.1 and 9.0%,

respectively. Further evaluation of the soybeans noted lower protein

(32.7%) and higher fat (23.9%) contents than that published by the NRC

(1979; 37.0 and 18.0%, respectively). However, the actual values and







































~ ri, 7 ?14 1IJB
e 1., -2 '. 227
- '''610.t] -:21 449
'/I.4. -21 471
- ;' -21'. 71 1
9 '6 -21'.. 7-


- j .


S I
rTr7-'r FTr T7-i'r rr Tr FTTrrFT T TT-ri Trr-rTrrTfI
0 -20 -40 -GO


-140


7-T rlT-rT-T--TinTTrTTT TT I T1 -r1 [ rrT T 1i 1 iT
-160 IUO 200 -;20 P;'H


Figure A-5. 188 MHz F9I NMR Spectrum of 22.


17 '1
7/.411
144.662
14 6.4.UO
75. S04





CI ,F


-210.2 -210.4 -21 6 PPM-210 .8













I ROMi .,' IU 1.37 rrn
INTEGRAL= 1.01
FROM 4.82 10 4.74 PPM
INTEGRAL= 1.01
IROM 4.57 10 4.48 PPM
INTEGRAL= 2.19
FROM 4.41 TO 4.12 PPH
IHNEGRAL= 2.18













I 23


I I I I I I i I I i -,-I r
4.8 4 .7 4.6 4.5 1 ,4 PPM

Figure A-6. 300 MHz II NMR Spectrum of 23 and 24.





























'F


23
-132.1PP















11I I-I r
132. 1 PPr


-131.q -131.5 -131.6 -131.7 -131.8 -131.9 -132.0

Figure A-7. 282 Mllz 19F NMR Spectrum of 23 and 24.
































S.90 .85 '1.80 4.75 4.70 4.65 PPM


I I I 5 I
,D. 0 4. i n.


3.5 3.0 2.5 2.0 1.5 1 .
Figure A-8. 300 MHz 'H NMR Spectrum of 28a.


19 Q lc


'' ~'"
' ' -~`



























Br B




28a


LINEN HEI6HT HEIGHT(L) FREO(HZ) PPm
I 799.78 848.95 -55212.78 -195.599
2 745.96 952.42 -55225.15 -195.633
3 649.74 651.95 -55232.49 -195.659
4 733.32 871.43 -55244.91 -195.783
5 753.86 972.65 -55277.12 -195.817
6 755.77 900.59 -55289.78 -195.862
7 748.45 1138.51 -55296.35 -195.886
8 819.71 972.61 -55319.11 -195.931


S F 1 .
195.6


II I' I 1 ----- -1 I-
-195.7 -195.8 -195.9


I I I
-100


-150


S -200 PPM
-200 P P M


Figure A-9. 282 MHz 19F NMR Spectrum of 28a.


0---
0


-50
-50


PPF


-c-- -- -I--- ---`1 ------. ~-~ -- -











































r 28 r






28a


LINE HE II H l HEllHII ItlI II H I n
I 6a8.89 6 2.56 .842. 9 ,''.4
2 671. 5 6,1.11 51 I .J I ?3 .JI
3 652.15 653.59 517 8 ;. .', l
4 531.73 533.97 5742.39 76.1
5 519.67 527.34 54( .92 2.t .
6 798.97 /11 .01 2227.33 .2.'I
7 697.89 704.9' 2215. 4 .' .3 '0
0 258.83 259.42 1612.54 .'1.3 O0
9 253.47 253,.4 l 10 . 1I.
1 123.01 1:3.12 -.-' '


U Pp t


Figure A-10. 75 MHz 3C NMR Spectrum of 28a.


7n rn 50 40 '30 20 1 U


















' i ' I '- ' I ' I ' '-- 1i 7- o
S.8 .6 3.2 3.0 1.6 1. 1.2

F

29
29 Br


I Il I I I L
6 L 2 0 PPM1
Figure A-11. 300 MHz 'H NMR Spectrum of 29.


-J"--






































I I .0 -I 0 I I I -I I
S20'I 0. 1 -201'4 .2


-50


-100


I I I I

-150


29 r


FREnHZ '
.080

-57603.01
-57609.98
-57616.01
-57626.85
-57650.53
-576656.77
-57664.45
-57671.45'


FPn



-20 4. 0
-2j 4 .0 f
-204.0.2

-20 4.1 2
-2041. .2 '
-204.226
-2'1 ..' 5 i
-:!20.2 '8


I I I I F


Figure A-12. 282 MHz 19F NMR Spectrum of-29.


S -20 I .3 -20' '
-20'T .3 I -rri


-4'


I 1 I I I I i I I I I















r- I






~i~ynfr~v4fv vvA4ZJ:pN



18 17 16 15
to



inhn
N






- ,- [ -- l -- -- i -- ,I ,I ,----,----,-- 1 "- ---
L I I I


29 Br


60


40


I I I
20


I I

t '1 *J I


Figure A-13. 75 MHz 13C NMR Spectrum of 29.


Si0


80
-T
C-)c















































-i


5 4 3 2 1 0 PPM


Figure A-14. 300 MHz II1 NMR Spectrum of 30.


w





















































216.7 -216.8 -216.9


HE IGillt ) f (EO(HZ) f-


473.84 -61168.65
5Y3.72 -61171.30
511.82 -61181.50
621.33 -61184.16
532.62 -5118 .62
631.81 -61192.2?
521.32 -61202.51
616.?4 -61205.14
522.30 -61233.58
615.75 -61236.21
541.86 -61246.43
628.03 -61249.10
538.49 -612M4.53
614.43 -61257.20
512.33 -61267.41
5?7.24 -6127e.06


-216.6'3
-216..'il
-216. 73'
-21I .'lit
-216.', I
- 2 16 ..'Vi.'
-216..'??
-216.81.e
-215.822
-216.923
-216.'32
-216.'96

-216.9.'11
-216.'117
-217.e ,'
-217.041
-217.';2


U F 30 Br






-217.0 -217.1 PPM


-1- I I 1 1 I I I I I I I

-50 -100 -150 -200


I I


PPM


Figure A-15. 282 Milz 19F NMR Spectrum of 30.


__










































HEIGHI(L) FkEO (HZ)
616.78 5842.28
54.52 5830.68
57.72 5825.61
626.78 5818.34
613.93 5778.39
98.45 5258.27
111.28 5031.33
74.97 1245.54
84.55 1235.38
114.62 1174.27
111.34 1163.33
1'4 h* -I Ill


PPM
77.423
,?.261
77.202
77.101)1
76.576
69.683
66.676
16.371

15.416
~ ij


16.6 16.I 16.2 16.0 15.8 15. 15
16.6 16.4 16.2 16.0 15.8 15.6 15.-


I I I 1 2 0I I I r 1- I I

jO 70 G30 50 40 30 20 10 0 PPM


Figure A-16. 75 MHz 13C NMR Spectrum of 30.


F 30


LINE HEIGHT
I 614.75
2 54.52
3 57.41
4 611.95
5 .612.34
6 97.12
7 111.27
8 74.92
9 82.88
16 111.16
11 189.14
1 1 19 21



















OAc


F31

F


Figure A-17. 200 MHz 'H NMR Spectrum of 31.































OAc


1 31

F


Figure A-18. 188 MHz 19F NMR Spectrum of 31.


! 'U I "



















1o .o010


IJv1!ulrlInj I mllUr Ii llD LI' l ri irll 'UiJ lllII 1 i \ In III'Lli$ T ll riI r..l 'lIlFl IaIn rQ J -IU A E. .Ill.. 11 l4 it l


pi m 7''


'I:.'-


I f Ii .


ou r 0


OAc


/


40 20 PPM


Figure A-19. 50 MHz 13C NMR Spectrum of 31.


I


~ku~i~kr~


rnriiiin II


i 0


I~h~YI1


fl


S A i it
i





Figure A-20. 200 MHz 'H NMR Spectrum of 32.


?-iri
;i


--7

CIS 1-FLUORO 3-ACE10YL I-FFOPEII
REGION START(PPM) END IrNTEGRA,L
01 6.823 6.724 6.1 51-
02 6.394 6. 138 5.U26
03 5.220 4.872 12.2:,0>
04 4.778 4.601 28.250? 1
05 2.0 2.8 2.021 4/.644) 3












OAc



S32
F
















i i .1"E


Si I I 'I
I I




ji r * *. [ _ .H o- |
OAc I 1L





1ii: ,. '
: ^I--I- T.



Figure A-21. 188 MHz 19F NMR Spectrum of 32
Figure A-21. 188 MHz 19F NMR Spectrum of 32.













;-
i : ii 'f i'i I

IIR











-i~
I . ,! :i


Fiiir Al2lll liqM z 3 : NMRl ,Tm 3
j J' h I i ,





' -: 32



r 1, i,,
, - I- *-.IIII









...... .


I I I 1 03















Figure A-22 50 MHz 13C NMR Spectrum of 32.























i AcO 0o
MF
I i I ,
I I







36 F














Figure A-23. 200 MHz IH NMR Spectrum of 36.
























/ - . ..,*
00





1 I I I I i I II" I I II p i- tI
Sti .2 60 1 1 6.

1, o 18 ..00 71o

Figure A-24. 188 Milz 19F NMR Spectrum of 36.



























(, n ; 1" fl III I '( I 1 i I l )
Itl 1 ,L .,ri.F 10 1 1 11) st 1i LF AL
1 6., 9 :. L,.I .1-,192
,. 17 '.171,7 .579

| n,. "* 1 1 I4 2. | |12 | |
i"






























6.0 5.5 5.0 4.5 4.0 3.5 3 0 2.5 PPM


Figure A-25. 300 MlHz I' NMR Spectrum of 48.



















IN UC FIh o IM Irirl, I
O( -3:619.2 -1/LiU.I ,
02 -3 1675.7 -171i. |














I I


-180.0 PPM


-r r r- i i
0 -20


Si Ir t I 1 -TT I-MT-" T-T T TT F 'T rl7-r r TT T- r- -TT
-120 -140 -IbO -180 PPM


Figure A-26. 282 MHz 19F NMR Spectrum of 48.


-17 .0


-176.5


-17b.o


I I


I


I '- o'


-i'"'|"



























olr FiEP 13 WITTIS PRODUCT ENDO
StELI(.NL LINES FOR TH" 24.62
RFL. 100.5 RFPF 0

INDI x FREO PPM INIrNSITV
01 7770.2 154.4,: 0 49.826
02 7755.5 134.157 29.122
o2 6779.0 134.747 162.742
03 6415.7 127.526 99.025
04 6410.4 127.422 103. 24
.5 23,3.9 109.4-3 132.7b.
b6 5501. 4 109.353 39.407
07 4616.1 91.796 81.566
08 4397.7 87.413 82.200
01 2624.1 52.161 87.876
02 2605.4 51.789 91.4:4
03 2002.1 39.797 97.692
04 2000.2 39.758 101.054
05 1925.4 38.272 94.7B6
06 1914.3 3B0.01 75.370


I1 4


17 I Il T1~- }F1 1- I jI


Figure A-27. 75 MHz 13C NMR Spectrum of 48.


T rr () l


---


-------


I I


. . .
































T, TTT -l II I II 4 i9 I r |7-4 T5 4 4 rrT
5.10 5.05 5.00 4.95 4.90 4.65 4.80 4.75 PPM


Figure A-28. 300 Mlz 1H NMR Spectrum of 49.




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