The effect of fluorine and trifluoromethyl as substituents in the electrocyclic ring opening of cyclobutenes and the rea...

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Title:
The effect of fluorine and trifluoromethyl as substituents in the electrocyclic ring opening of cyclobutenes and the rearrangement of cyclopropyl carbenes
Physical Description:
ix, 139 leaves : ill. ; 28 cm.
Language:
English
Creator:
Gray, Thomas Anthony, 1961-
Publication Date:

Subjects

Subjects / Keywords:
Cyclobutenes   ( lcsh )
Cyclopropane   ( lcsh )
Fluorine   ( lcsh )
Fluorine compounds   ( lcsh )
Carbenes (Methylene compounds)   ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre:
bibliography   ( marcgt )
non-fiction   ( marcgt )

Notes

Thesis:
Thesis (Ph. D.)--University of Florida, 1989.
Bibliography:
Includes bibliographical references (leaves 135-138).
Statement of Responsibility:
by Thomas Anthony Gray.
General Note:
Typescript.
General Note:
Vita.

Record Information

Source Institution:
University of Florida
Rights Management:
All applicable rights reserved by the source institution and holding location.
Resource Identifier:
aleph - 001514189
oclc - 21887359
notis - AHC7196
System ID:
AA00002122:00001

Full Text











EFFECT


OF FLUORINE


AND


TRIFLUOROMETHYL


SUBSTITUENTS


IN THE


ELECTROCYCLIC


RING


OPENING


OF CYCLOBUTENES


AND


THE


REARRANGEMENT


CYCLOPROPYL


CARBENES


THOMAS


ANTHONY


GRAY


A DISSERTATION
UNIVERSITY OF
REQUIREMENTS


PRESENTED


FLORIDA


FOR


IN PARTIAL


DEGREE


GRADUATE


SCHOOL


FULFILLMENT


OF DOCTOR


OF THE


OF PHILOSOPHY


UNIVERSITY


OF FLORIDA


1989




























Copyright


1989


Thomas


Anthony


Gray
















TO MY LOVING


WIFE


AND


FAMILY















ACKNOWLEDGEMENTS


with


guidance


much


Professor


accomplishment


the


gratitude


William

research


that


acknowledge


Dolbier,


recorded


Jr.,


herein.


the


the


could


a better


advisor


and


friend.


Further


acknowledgements


are


due


to Drs.


Lech


Celewicz


and


Henryk


Koroniak.


Both


these


fine


men


have


provided


excellent


standards


scientists


comrades,


and


their


assistance


are


was


also


vital


to Jeffrey


the


completion


Keaffaber


and


this


Laura


work.


Cooke,


Thanks


whose


research


provided


valuable


information


to help


explain


the


observations


Rocca


recorded


running


some


herein.


Thanks


high


are


field


also


NMR


due


and


to Jim


Larry


Chamusco


obtaining


an FTIR


spectrum


one


the


compounds


mentioned


herein.


Finally,


support


and


encouragement


family


and


friends


during


course


this


work


been


much









appreciated.


A special


acknowledgement


goes to


Sylvia


Tou,


for tolerating me during the


composition


of this work.















TABLE


ACKNOWLEDGEMENTS


OF CONTENTS


S iv
Q*


ABSTRACT


CHAPTERS


INTRODUCTI ON


. . 1


SYNTHESES


AND


EXPERIMENTAL


PROCEDURES


RESULTS


AND


DISCUSSION


APPENDIX


NMR


Spectra


REFERENCES


BIOGRAPHICAL


SKETCH


Page













Abstract
the Ui


Dissertation


university


Presented


of Florida


to the


Partial


Graduate


School


Fulfillment


Requirements


for


Degree


of Doctor


Philosophy


EFFECT


OF FLUORINE


AND


TRIFLUOROMETHYL


SUBSTITUENTS


IN THE


ELECTROCYCLIC


RING


OPENING


OF CYCLOBUTENES


AND


REARRANGEMENT


CYCLOPROPYL


CARBENES


THOMAS


ANTHONY


GRAY


August


1989


Chairman:


William


Dolbier,


Major


Department


Chemi


story


Fluorine


and


trifluoromethyl


substituents


are


useful


probes


the


study


thermal


electrocyclic


ring


opening


cyclobutenes.


Fluorine


expected


serve


as a


strong


donor


substituent


with


little


steric


effect


on the


transition


state,


and


predicted


to rotate


outward.


trifluoromethyl


substituent


a sterically


large


electron


acceptor,


and


should


exhibit


substantial


steric


and







3-Fluorocyclobutene


and


3-trifluoromethylcyclobutene


are


prepared


opening


kinetics


studied.


found


their


that


electrocyclic


ring


ring


opening


fluorocyclobutene


yields


only


1-f luoro-1, 3-butadiene,


accordance


with


prediction.


3-Trifluoromethylcyclobutene


ring


opens


with


an activation


energy


higher


than


that


cyclobutene,


and


gives


a mixture


Z- and


E-5, 5,5-


trifluoro-1, 3-pentadiene.


believed


that


this


result


competition


between


the


unfavorable


electrostatic


effects


outward


rotation


and


the


unfavorable


steric


effects


inward


rotation.


Interest


carbenes


ring


expansion


to cyclobutenes


reaction


use


cyclopropyl


fluorine


and


trifluoromethyl


substituents


as probes


reaction.


predicted


that


fluorine


will


make


cyclopropyl


ring


more


nucleophilic.


Trifluoromethyl


will


withdraw


electrons


from


the


ring,


decreasing


nucleophilicity,


and


should


have


a steric


effect


on the


reaction.


trans


isomers


both


2-fluorocylopropyl-


diazomethane


2-trifluoromethylcyclopropyldiazomethane










are


prepared


and


decomposed


thermally


and


photolytically.


found


that


electrostatic


repulsions


between


fluorine


diazo


fragmentation


substituent


the


increase


reaction.


the


amount


Trifluoromethyl


decreases


both


ring


expansion


and


fragmentation,


principally


giving


intermolecular


products.


believed


that


the


tri fluoromethyl


substituent


decreases


the


energy


carbene














CHAPTER


INTRODUCTION


The

butadiene


electrocyclic


predicted


ring

to be


opening


a concerto


cyclobutene

d process.


substituent


introduced


onto


the


ring


the


3-position,


an element


stereochemistry


added,


that


two


possible


products


can


result


from


either


inward


or outward


rotation


substituent.


inward


outward


Figure


: 3-substituted


cyclobutene.


X


//









Woodward-Hoffman


symmetry


rules


predict


that


thermal


electrocyclic


ring


opening


a cyclobutene,


substituents


on the


4-positions


the


ring


should


move


a conrotatory


fashion.


1 Symmetry


rules


state


whether


inward


or outward


rotation


preferred


particular


substituent.


Frey


and


coworkers


studied


the


effects


methyl


substituents


on the


activation


energy


thermal


electrocyclic


ring


opening


of cyclobutene


' It


was


generally


observed


activation


the


that


ring


alkyl


opening,


groups


and


lowered


that


the


and


energy


alkyl


substituent


effects


on the


energy


activation


were


additive.


was


also


observed


that


the


alkyl


substituents


preferred


to rotate


outward


to give


trans-alkenes.


This


preference


was


attributed


steric


bulk


the


alkyl


groups


which


would


come


into


proximity


with


hydrogen


during


the


transition


state


inward


rotation.


This


explanation


was


commonly


accepted


until


experiments


Curry


Stevens


were


conducted


on the


ring









that


substituent s


that


had


more


steric


bulk


than


methyl


preferred


inward


rotation


over


methyl


when


both


groups


were


on the


3-position


cyclobutene.


Even


though


an extremely


bulky


substituent


like


t-butyl


prefers


outward


rotation,


preference


relatively


low


considering


that


there


no Z-


penta-1, 3-diene


observed


ring


opening


methylcyclobutene


/


R

CHe


Figure


Ring


opening


3,3-disubstituted


cyclobutenes


Such


product


distributions


were


explained


terms


the


electron


donating


ability


the


substituents


the


position


ring


the


frontier


opening.


FMO


molecular


orbitals


analysis


(FMOs)


system


involved


shows


that










transition


HOMO


state.


system


Donor


to similar


substituents


effect,


will


so donor


raise


or acceptor


substituents


should


decrease


energy


activation


ring


opening.


Table


Ring


opening


3-R,3-methylcyclobutenes


Z-isomer


E-isomer


t-Bu


Isopropyl


65.5


n-Propyl

Cyclopropyl


initio


molecular


orbital


calculations


a-electron


flow


substituents


on benzene


show


that


methyl


and


ethyl


are


more


negative


than


hydrogen,


and


that


methyl


negative


relative


to ethyl.


This


would


be consistent


with


ethyl'


experimentally


observed


preference


inward


rotation


relative


to methyl.


T(C)










data


from


Frey,


2 Kirmses


other


sources


They


calculated


substituent


effects


on outward


rotation


from


difference


between


the


energies


activation


the


parent


cyclobutene


effects


and


the


on inward


3-substituted


rotation


were


cyclobutene.


determined


Substituent

comparison of


energies


activation


the


3-substituted


system


cis-3,4-disubstituted


system,


where


one


groups


must


rotate


inward.


Figure


Ring


opening


3-substituted


and


cis-3,4-


disubstituted


cyclobutenes


values


activation


obtained


energies


from


the


these


ring


estimations


opening


predict


cyclobutenes


---~A -.-~--- A -- 4 S A


I'


* a .


a


r


*I 4


tl


1










increase the activation energies


trans-3,4-dichlorocyclobutene


inward rotation.


and trans-3,4-


dialkoxycyclobutenes,


is predicted that


inward rotation


is respectively


and 28


kcal/mol


less


favorable than


outward rotation.


Such large differences


the energies of


activation


for the two possible


transition


states cannot be


solely to


steric effects.


Also,


the A


values and


Taft


values7


for the


systems


studied indicate that


Cl and OR


are relatively


close


in size,


and both are smaller than CH,.


Table 2:
rotation.


Substituent


effects


inward


and


outward


substituent


outward rotation


inward rotation


(kcal/mol)

-1


(kcal/mol)

+3


An additional


case


reported by


Dolbier


and coworkers


- -.1- -2- r


I


n r


P_ Ii-I


___









preferentially


to the


Z,Z-isomer,


with


both


trifluoromethyl


groups


rotating


inward.


transition


state


leading


to the


E, E-product


.2 kcal/mol


higher


energy.


steric


factors


determined


product,


one


would


expect


the


E,E-


isomer


to predominate,


since


near


steric


bulk


t-butyl


= -2


a for


t-Butyl


78'),


while


much


larger


than


Figure


Ring


opening


perfluoro-trans-3,4-


dimethylcyclobutene


Equilibrium


studies


indicate


that


two


possible


products


are


nearly


equal


energy,


so the


large


difference


activation


energy


must


be purely


to a substituent


effect


on the


relative


transition


state


stabilities.


These


= -2










directions


pyramidalization


the


olefinic


carbon


atoms


cyclobutene.


fluorine


substituents


on the


ring


make


olefinic


carbons


pyramidalize


a direction


opposite


what


would


expected


the


substituent


were


methyl.


Assuming


that


pyramidalization


dictates


the


direction


rotation


the


substituent s


at C3


and


one


would


expect


opposite


stereochemistry


the


product.


H3


H3C



Figure


butene


-CH3

CH3


Pyramidalization


and


F CFs


1,2,3, 4-tetramethylcyclo-


perfluoro-3,4-dimethylcyclobutene


Relatively


recent


theoretical


and


experimental


studies


Sby


Rondan


and


Houk


have


done


much


to clarify


stereochemical


observations


' Their


results


indicate


that


A- t~ .~ A-1-~- .8- - t. 2 ---2


A-1^ T^~ltf


__


,L m L A a


-- L __ _


- _










fashion


with


CC,2


orbital.


Given


a donor


substituent


with

the


nonbonding

electrons o


lone


n the


pair


electrons,


substituent


inward


closer


rotation


to the


HOMO


brings

than


outward


rotation.


This


proximity


generates


an unfavorable


four


electron


repulsion.


LUMO


both


transition


states


CC,
3^4


orbital


mixed


with


C1C2


in orbital


antibonding


fashion.


Outward


rotation


donor


substituent


results


overlap


donor


lone


pair


orbitals


with


the


lying


vacant


orbital


through


the


attached

which st


carbon


abilizes


atom,

the


giving


occupied


two


lower


electron i

orbitals.


interactionn

Inward


rotation


brings


the


lone


pairs


into


a node


of the


orbital,


thereby


decreasing


the


interaction


stabilization.


Model


calculations


were


carried


on several


trans-


3, 4-disubstituted


cyclobutenes.


For


heterosubstituted


cyclobutenes


was


found


that


heterosubstituents


prefer


to rotate


outward


outward,


but


rotation


energy


increase


differences


along


order


between


< F


inward


< OH










ability.


use


ionization


potentials


(IPs)


assess


electron


donating


ability


suggested.


the


decreases,


increases.


electron


one


donating


exception


ability


whose


the


substituent


ionization


occurs


from


a 3p


orbital.


Overlap


the


nonbonded


electrons


with


a and


orbitals


poorer


than


that


the


second


row


elements.


correlates


In general,


well


with


increased


increased


donor


preference


ability


outward


rotation.


LUMO(a')


HOMO(a)


Figure


: Donor


orbital


interaction


with


HOMO


and


LUMO


of cyclobutene









was


also


found


that


the


substituent


effects


on the


energy


difference


between


the


two


transition


structures


should


very


nearly


additive.


In going


from


fluorocyclobutene


to cis-3,4-difluorocyclobutene,


the


energy


difference


the


transition


structures


predicted


increase


from


kcal


to 40


kcal.


This


indicates


that


the


activation


energies


are


unlikely


to be


affected


direct


interactions


between


substituents.


A


Figure


: Predicted


ring


opening


of 3-borylcyclobutene


An extreme


example


an acceptor


group


was


also


modeled


using


group


as a substituent.


In the


case


of trans-3,4-diborylcyclobutene


inward


rotation


favored


over


outward


17.8


kcal/mol.


this


case


vacant










orbital


the


ring.


This


overlap


better


on inward


rotation


than


on outward.


This


results


greater


stabilization


inward


HOMO


and


LUMO


than


the


outward


HOMO


and


LUMO.


CHO


CHO


Figure
butene


Ring


opening


3-cyano-


and


3-formylcyclo-


Recently,


3-cyanocyclobutene


and


3-formylcyclobutene


were


theoretically


studied


and


3-formylcyclobutene


was


prepared.


' Ab


initio


calculations


were


used


to determine


transition


structures


inward


and


outward


rotation


two


substituents


the


ring


opening


-. .. I ..


- S


a


a


* 1


r L I









outward


transition


structure,


and


that


activation


energy


outward


transition


structure


kcal/mol


lower


than


that


nonsubstituted


cyclobutene


This


behavior


expected


very


weak


donor.


Evidently


the


filled


--orbitals


cyano


group


have


a greater


influence


on the


transition


structure


than


the


vacant


orbitals.


In contrast,


CHO


3-formylcyclobutene


prefers


inward


rotation


.5 kcal/mol,


and


the


activation


energy


system


expected


to be 6


kcal/mol


below


that


cyclobutene.


preference


inward


rotation


not


to product


stability,


since


the


,4-pentadienal


predicted


to be


kcal/mol


less


stable


than


E isomer.


rotational


preference


purely


to stabilizing


interaction


between


vacant


n" orbitals


the


formyl


bond


and


HOMO


the


transition


state.


3-formylcyclobutene


chlorocyclobutane


was


carboxylate


prepared


reduction


from


methyl


of the


ester


alcohol,


followed


elimination


HC1


from


ring


and


oxidation


the


alcohol


to the


aldehyde


with


pyridinium










open


pentadienal


at 25C


with


a half


life


approximately


hours.


In following


reaction


NMR


spectroscopy


was


found


that


only


the


pentadienal


could


was


observed,


.7 kcal/mol.


formed.


A minimum


so inward


Kinetics


the


rotation


experiments


favored


the


E isomer


at least


temperature


range


on 50-70C


gave


kcal/mol,


equilibrating

completely co


a log


good

with


nverts


= 14.2


agreement


acid


with


or base,


to the


more


.2 and


the

the

stabi


p


= 27.2


reductions


Z-2,4-pentadienal

e E isomer.


summary,


been


found


that


single


substituents


on the


3-position


cyclobutene


decrease


the


energy


activation


relative


to unsubstituted


cyclobutene


whether


they


are


electron


donating


or withdrawing.


It has


also


been


found


that


ring


opening


3-monosubstituted


cyclobutenes


stereospecific,


with


electron


donating


substituents


rotating


outward


and


electron


acceptor


groups


rotating


inward.


This


stereospecificity


is attributed


orbital


interactions


which


serve


to stabilize


transition









substituents,


These


and


interactions


inward


rotation


overwhelm


for acceptor

steric effects


substituents.


cases.


orbital


interaction


theory


advanced


Rondan


Houk


does


address


stereoselectivity


observed


systems


where


the


substituents


possess


orbitals


which


can


interact


with


transition


state


HOMO


and


LUMO,


such


as 3-alkyl


substituted


cyclobutenes.


In order


to obtain


a more


complete


picture


the


substituent


effects


on the


thermal


ring


opening


cyclobutene,


new


3-substituted


systems


were


synthesized


kinetics


their


ring


opening


studied.


Fluorocyclobutene


predicted


to prefer


outward


rotation


over


inward


rotation


kcal/mol


fluorine


substituent


an excellent


example


a nearly


pure


electronic


effect,


since


fluorine


bonded


to carbon


much


larger


than


hydrogen


bonded


to carbon.


interaction


between


fluorine


and


inward


rotating


hydrogen


transition


structure


should


much


larger


than


the


interactions


cyclobutene


itself.


Any


stereospecificity









interaction


nonbonded


electrons


with


the


LUMO


cyclobutenyl


system.


No theoretical


studies


have


been


made


on how


the


trifluoromethyl


substituent


affects


the


ring


opening


cyclobutene,


difficult


to predict


how


t ri fluoromethyl-cyc 1 obutene


will


behave


on ring


opening.


Though


the


trifluoromethyl


substituent


a strong


inductive


electron


withdrawing


group,


there


are


no vacant


orbitals


interact


with


the


HOMO


the


transition


state,


case


of 3-formylcyclobutene.


In addition,


the


substituent


considered


some


measurements


to be


large


as a tert-


butyl


group,


and


should


have


a large


unfavorable


steric


interaction


with


hydrogen


on inward


rotation.


any


diene


effects


product


can


observed,


significant


will


even


indicate


as the


that


absence


electronic


nonbonding


orbitals,


as was


shown


alkyl


substituents


previously


studied.


2 In this


case


however,


the


effect


will


to relative


electron


donor


ability,


but


rather


to acceptor


ability









third


system


to be


studied,


3-fluoro, 3-


trifluoromethylcyclobutene


should


give


a closer


approximation


of the


relative


effect


of the


two


substituents


than


perfluorosystem


previously


studied.


Based


on the


results


from


perfluoro-trans-3,4-dimethylcyclobutene,


expected


that


the


fluorine


will


rotate


outward.


Figure


Ring


opening


3-fluoro-


, 3-trifluoromethyl-


and


3-fluoro-3-trifluoromethylcyclobutenes


interest


in cyclobutenes


bearing


a fluorine


trifluoromethyl


substituent


led


an investigation









cycloalkylcarbenes


ring


size


the


case


which


predominantly


undergoes


rearrangement


to cyclobutene


fragmentation


to ethylene


and


actelylene


Friedman


and


Shechter


reacted


the


tosylhydrazone


cyclopropylcarbox-


aldehyde


with


sodium


methoxide


diethyl


carbitol


(DEC)


or N-methylpyrollidine


(NMP)


1800C


They


obtained


different


product


CHNNHTs


NaOMe


yields


each


LI


solvent.


+ H2C --CH2


+ HC CH


Figure


Products


2 -
decomposition


cyclopropylcarbox-aldehyde


tosylhydrazone


principal


products


were


cyclobutene


(7),


ethylene


and


acetylene


1, 3-butadiene


(10).


No products


were


observed


from


a-H


or B-H


insertion


(i.e.,









Table


Decomposition


cyclopropylcarboxaldehyde


tosyl-hydrazone


presence


strong


base.


Compound

8


Solvent

DEC


Frey


and


Stevens


repeated


the


cyclopropylcarboxaldehyde


tosylhydrazone


work


using


"essentially


the


same


conditions"


while


obtaining


substantially


different


results


response,


a thorough


study


the


reaction


conditions


was


made,


and


varying


starting


solvent,


temperature,


material


amount


As a result


was


base


found


used,


that


reaction


conditions


strongly


affect


the


product


ratios.


results


show


that


decomposition


the


tosylhydrazone


with


an equivalent


or excess


amount


sodium


methoxide


aprotic


or poor


proton


donor


solvent


leads


to cyclobutene


1, 3-butadiene


as the


major


products.


With


less


than


one


equivalent


sodium


methoxide


the


presence


of a good


proton


donor


solvent


such


as ethylene


glycol


(EG),













<1 eq NaOMe


CHNNHTs


eq NaOMe


* H2C=-CH2 + HC0CH


Figure


: Decomposition


tosylhydrazone


under


varying


condition


Table
under


Product


varying


decomposition


tosylhydrazone


conditions


S.M.


NaOCH,


Solvent


Yield


DEC

DEC

DEC

DEC

DEC

Et3COH


results


indicate


that


bicyclo[l


.0]butane


forms


only


environments


where


acidic


protons


are


present.


This


would


indicate


that


forms


through


a cationic









most


likely


mechanism


through


a cyclopropyl


carbonium


cyclopropyl


diazonium


intermediate.


Other


researchers


have


also


found


evidence


that


bicyclobutane


does


arise


from


cyclopropyl


carbene


Cyclopropyl


diazomethane


been


prepared


and


photolyzed


phase


over


a pressure


range


1.38


torr


to 708


torr.


1" Varying


the


pressure


had


little


affect

very


on the


little


product


cyclobutene


distribution


was


and


isolated,


under


the


these


major


condition


products


observed


being


butadiene,


ethylene


and


acetylene.


amount


of ethylene


and


acetylene


observed


indicated


that


starting


fragmentation


material


pathway.


had


The


decomposed


greater


through


amount


the


fragmentation


products


under


more


energetic


conditions


would


indicate


that


fragmentation


expansion.


a higher


That


energy


reaction


pathway


conditions


than


lead


ring


more


energetic


intermediates


consistent


with


the


large


amount


ring


opening


undergone


cyclobutene


to give


butadiene


(Eact


= 32


.5 kcal/mol)


treating










matrix,


other


workers


found


that


the


fragmentation


reaction


was


quite


rapid,


on the


same


time


scale


as energy


transfer


into


the


frozen


matrix.


" It


was


suggested


that


fragmentation


could


occur


concertedly


with


formation


carbene.


Sasaki


and


coworkers


found


that


the


decomposition


tosylhydrazones


cis-


and


trans-2,2-dimethyl-3-


isobutenylcyclopropylcaboxaldehyde


(chrysanthemylaldehyde)


to a large


amount


fragmentation.


S" They


stated


that


the


isobutenyl


group


probably


lowered


the


activation


energy


fragmentation


leading


to the


formation


conjugated


diene


one


fragment action


products.


CHNNHT


HC=CH


Figure


Fragmentation


chysanthemylaldehyde


tosylhydrazones


r .t A------ .' -


_ __A- _- -


- A __ ^ ^ ^ ^ ^ A -? J A_ _


C L~










groups


. Trans-2,3-dimethylcyclopropyl


diazomethane


was


photolytically


decomposed


and


products


were


trapped


and


identified


their


IR spectra


products


were


acetylene


(9),


trans-2-butene


(13),


cis-2-butene


(14),


E,E-


2,4-hexadiene


(15),


and


Z-2,


4-hexadiene


(16).


CHN2


HC CH


+15



15


Figure


Decompo


sition


tran


-2,3-


dimethylcyclopropyl-diazomethane


At lower


stereospecific,


pressures


the


giving


reaction


and


appears


the


major


to be


products.


hexadiene


probably


results


from


the


decomposition


excited


trans-3,4-dimethylcyclobutene.


cyc.l obutene


was


identified,


a single


unidentified


product


occurred


high


yield


the


reactions.


stereospecificity









singlet


carbene


which


undergoes


spin


controlled


decomposition.


Table


decomposition


trans-Dimethylcyclopropyl
t 19


unaer


varying


pressure


diazomethane


P (torr)

11

23


7-13


(+739


torr)


At higher


pressure,


collisional


deactivation


brings


some


the


carbene


lower


lying


triplet


state,


which


can


undergo


ring


cleavage


to form


a biradical


which


possess


a long


enough


lifetime


to undergo


rotation.


Under


these


conditions

biradical


(14)


would


to produce


possible


a mixture


a fragmentation


of cis


pathway,


the

and


and


equilibrating

trans-2-butene


and


trans-3,4-


dimethylcyclobutene,


which


could


then


undergo


ring


opening


to give


hexadienes


15 and













collision


Figure


Colli


sional


deactivation


trans-2,3-


dimethyl-cyclopropyl


carbene


Bird


and


coworkers


decomposed


the


tosylhydrazones


2, 2-dimethylcyclopropane,


cis-2-methylcyclopropane


and


trans-2-methylcyclopropane


methyl


ketones


with


or 4


equivalents


could


sodium


the


methoxide.


or 2-position


ketone


the


methyl


product


group


cyclobutene


ring


Products


were


analyzed


NMR.


In all


three


cases


the


major


product


results


from


migration


less


substituted


cyclopropyl


bond,


giving


1-methylcyclobutenes.


For


2,2-dimethyl


and


the


cis-


2-methyl


specie


selectivity


very


large.


This


selectivity


attributed


to steric


inhibition


caused


methyl


groups


more


substituted


double


bond.












, .CH3


Figure


Methylcyclopropyl


methyl


carbene


rearrangement


Tabl


cyclopropy]


Product
L methyl


cyclobutene


distribution


methyl-


carbene


Starting


methyl


ketone


ylhydrazone


2,2-dimethyl


-2-methyl


In decomposing


the


tosylhydrazones


cis-


and


trans-


c rysanthemyl


that


methyl


principal


ketones,


ring


Sasaki


expansion


and


coworkers


product


both


found


isomers


resulted


from


migration


the


bond


bearing


the


isobutenyl


substituent


They


felt


that


this


result


could


explained


simple


steric


arguments.


\/ ^


.. CH3














(CH3)NNHTs


Figure
methyl


Rearrangement


and


trans


chrysanthemyl


carbenes


stereospecificity


the


decomposition


reaction


cyclopropylcarbenes


was


addressed


Jones


and


Galluci,


believed


that


forming


the


triplet


carbene


they


could


observe


nonstereospecific


rearrangement


and


fragmentation


Separately


irradiating


cis-


and


trans-2, 3-


dimethylcyclopropyldiazoketoesters


benzene


gave


distinct


stereospecific


Irradiation


products


using


mixtures


an excess


each


fluorenone


isomer.


as a triplet


sensitizing


agent


gave


no significant


change


the


product


distribution


or stereochemistry.


That


the


triplet


carbene


was


formed


was


confirmed


the


increased


reactivity


species


with


isobutylene


on irradiation


with


fluorenone,









reaction.


was


suggested


that


this


case


singlet


and


triplet


states


carbene


are


equilibrium,


and


that


singlet


decomposition


faster.


Both


the


preference


ring


expansion


over


fragmentation


and


stereospecificity


the


cyclopropyl


methylene

by Shevlin

indicated


carbene


and

that


reaction


McKee

there


were


Earlier


addressed


theoretical


an important


a recent


studies


interaction


paper


had


between


vacant


p-atomic


orbital


the


carbene


carbon


and


the


occupied


antisymmetric


Walsh


orbital


the


cyclopropane


ring,


resulting


two


energy


minima


conformation


carbene


carbon


relative


the


ring.


23,24


Shevlin


McKee'


calculations


on the


two


conformers


cyclopropyl


carbene

hydrogen


indicated

eclipsing


that

the


conformation


a-hydrogen


on the


with


the


ring,


carbene


the


conformation,


was


stabilized


kcal/mol


relative


to the


anti


conformation,


with


a barrier


to interconversion


conformers


of 14.9 kcal/mol.


high


barrier


loss


stabilizing


interaction


between


the


vacant









ring


during


rotation;


a similar


stabilizing


interaction


exists


the


cyclopropylcarbinyl


cation.


. 14.9 kcal/mol


AH 1.9 kcal/mol


anti conformer


syn conformer


Figure
carbene


Energies


two


conformers


cyclopropyl-


studying


the


two


conformers


separately,


was


found


that


the


activation


barrier


the


rearrangement


the


anti


conformer


to cyclobutene


.4 kcal/mol


higher


energy


than


that


conformer,


since


some


point


along


reaction


coordinate


there


must


rotation


about


bond


between


carbene


carbon


and


the


attached


ring








other


hand,


fragmentation


the


activation


barrier


anti


conformer


kcal/mol


lower


energy


than


the


barrier


conformer,


and


that


the


lowest


energy


pathway


the


conformer


to undergo


fragmentation


rotate


to the


anti


conformer


first.


This


attributed


greater


repulsions


between


the


carbene


electrons


and


developing


ethylene


"-system


the


transition


state


conformer.


Based


on these


calculations,


one


would


expect


the


anti


conformer


cyclopropylcarbene


to rotate


to the


conformer


and


then


rearrange


to cyclobutene,


since


barrier


to rotation


and


the


activation


barrier


rearrangement


the


isomer


are


both


lower


than


the


activation


barrier


No fragmentation


fragmentation


should


observed,


the


which


ant i


not


conformer.


accord


with


experimental


evidence.


Shevlin


and


McKee


suggest


that


both


ring


expansion


fragmentation


proceed


via


a singlet


pathway,


that


fragmentation


proceeds


via


a short


lived


singlet


biradical


which


fragments


before


rotation


and


loss









triplet


biradical


have


similar


energies


and


the


ring


opening


singlet


and


triplet


state


have


nearly


equal


barriers,


possible


that


opening


to the


biradical


could


occur


singlet


state


and


competitive


with


ring


expansion.


Calculations

fragmentation


based


becomes


on these


more


assumptions

important at


indicate


higher


that


temperatures


conformer


and


principal


pathway


anti


conformer.


Both


the


barrier


ring


expansion


of the


conformer


.0 kcal/mol)


and


the


barriers


to formation


1,4-biradical


the


and


anti


conformers


.0 and


kcal/mol,


respectively)


are


substantially


lower


energy


than


the


barrier


to rotation


between


the


two


conformers,


so the


reaction


path


the


carbene


should


dependent


on the


conformation


which


formed.


expected


that


most


carbene


precursors


the


two


conformations


should


nearly


equal


energy,


so in


most


cases


both


conformers


should


present.


summary,


the


two


principal


pathways









expansion


to a cyclobutene,


possibly


followed


ring


opening


to a conjugated


diene,


and


fragmentation


alkene


and


an acetylene.


Experimental


evidence


indicates


that


ring


expansion


the


lower


energy


pathway,


while


fragmentation


quite


possibly


occurs


concert


with


formation


carbene.


When


there


are


substituents


cyclopropyl


ring


an element


stereochemistry


introduced


the


reaction,


with


the


strongest


bond


the


ring


migrating


to the


carbene


center.


Whether


steric


hindrance


substituent s


on the


ring


or electrostatic


interactions


between


the


substituents


and


carbene


carbon


are


more


important


determining


stereochemistry


the


reaction


unclear.


A stabilizing


interaction


between


the


vacant


two


p-atomic


orbital


conformers


the


on the


system


carbene


being


and


energy


ring


minima


results


with


large


barrier


to interconversion.


Theoretical


studies


indicate


that


these


two


conformers


are


important


determining


course


the


reaction


carbene,


and


that


both


conformers


should


be present


under


most









synthesizing


cyclopropylcarboxaldehydes


bearing


trifluoromethyl


and


fluorine


would


possible


to observe


how


these


two


substituents


could


affect


the


intramolecular


reaction.


As a probe,


fluorine


should


have


a large


electrostatic


effect


and


a small


steric


effect


on the


carbene'


attack


on the


ring.


Also,


fluorine


should


affect


hybridization


the


orbitals


the


cyclopropyl


ring,


altering


their


nucleophilicity.


The


trifluoromethyl


substituent


should


serve


as a probe


the


effect


steric


bulk


reaction.


electron


withdrawing


nature


should


also


perturb


framework


the


ring,


and


should


serve


to 'cool'


reaction


providing


additional


vibrational


and


rotational


modes


to dissipate


energy


the


system.


In both


cases,


products


should


observable


NMR.


expected


that


2-fluorocyclopropyldiazomethane


(19)


will


decompose


to give


3-fluorocyclobutene


(20),


fluoro-1,3-butadiene


(21)


and


vinyl


fluoride


(22).


Trifluoromethylcyclopropyldiazomethane


(23)


should


give









pentadiene


(25),


and


3, 3, 3-trifluoropropene


(26).


chemical


shifts


products


are


known


or readily


obtainable.


CF3

+


hv or A


CFs
+ HC CH
n^^-n
1


'CHN2


hv or A


+ HCOCH


'CHN2


Figure


Decomposition


cyclopropyldiazomethanes.


summary,


substituents


effects


on two


fluorine


mechanistically


and


interesting


trifluoromethyl


systems,


cyclobutene


and


cyclopropylcarbene,


are


to be


studied.


believed


that


both


systems


substituents


will


perturb


both


the


reactivities


and


the


product


distributions.


hi ans


tho


flP iiar4 n


mnn


+-r4 if1 r a ,-4t T --- h


e,,1so+ ^ -ian4 a


h Vr hl 1 ^









due to the differences


in electronic and steric effects


the


two


substituents.












CHAPTER


SYNTHESES


AND


EXPERIMENTAL


PROCEDURES


All


IR spectra


were


taken


on a Perkin-Elmer


infrared


spectrometer.


All


and


NMR


spectra


were


taken


on either


a Jeol


FX-100,


a Nicolet


360,


a Nicolet


300,


a Varian


XL-200


or a Varian


VXR-300


spectrometer.


1-Bromo-3-chloro-2-fluoropropane:"


N-Bromosuccinimide


(102


0.574


mol)


was


placed


with


a 500


polyethylene


bottle


equipped


with


a teflon


coated


stirring


bar,


a dry


ice-isopropanol


cooled


polyethylene


reflux


line,


a dry


ice-


isopropanol


cooled


teflon


line


from


an HF


cylinder


a dry


ice-isopropanol


cooling


bath.


Hydrogen


fluoride


(147


.5g,


7.372mol)


was


condensed


into


the


bottle.


this


time


the


contents


the


vessel


were


observed


turn


dark


red.


The


condensing


line


the


was


then


replaced


with


a teflon


addition


funnel


containing










added


solution


with


stirring.


Upon


addition,


the


dark


color


rapidly


faded,


and


manual


agitation


was


necessary


to keep


NBS


from


caking


bottom


the


vessel.


Thirty


minutes


after


addition


was


complete


the


temperature


bath


one


was


hour.


raised


to -10C


reaction


was


and


reaction


quenched


continued


cooling


the


vessel


to -78C


and


pouring


the


contents


onto


ice.


mixture


was


extracted


with


3-100


portions


methylene


water


small


chloride,


dried


amount


the


over


sodium


organic


anhydrous


fluoride.


extracts


washed


magnesium


with


sulfate


Evaporation


and


solvent


and


distillation


gave


.200


mol,


.9%)


material


(b.p.


650-660C,


33mm


which


was


shown


and


NMR


a mixture


desired


product


and


2-bromo-1-chloro-


3-fluoropropane


a ratio


respectively.


The


mixture


could


used


subsequent


step


without


further


purification.


NMR


(CDC13/TMS);


mixture


two


isomers


(dd,


, 1.7 Hz);


Hz);


91 (dd,










= 10


.2 Hz,


Hz) ;


= 46


Hz) .


"C-NMR


(CDC1,) ;


mixture


isomers


6= 29


Hz);


43.2


= 25


.8 Hz);


.3 Hz);


= 20


Hz);


= 177


Hz);


= 181


Hz) .


'F-NMR


(CDC13/CFC,) ;


mixture


two


isomers


.41%,


dtt,


.6 Hz);


(18.59%,


= 46


.5 Hz).


Diethyl


3-fluorocyclobutane-1,1-dicarboxylate:"


Sodium


metal


.272


mol)


was


added


very


dry


diglyme


in a 1000


3 necked


round


bottomed


flask


equipped


with


a pressure


equal


zing


dropping


funnel,


a magnetic


stirring


bar


and


a reflux


condenser


with


a nitrogen


inlet.


Diethyl


malonate


.337


mol)


was


added


to the


mixture


through


the


funnel


and


solution


was


stirred


heated


115-120"C


so that


sodium


was


molten.


mixture


was


then


stirred


until


sodium


was


dissolved,


adding


a small


amount


diethyl


malonate


needed.










suspension


diethyl


malonate


salt.


mixture


bromo-3-chloro-2-fluoropropane


and


2-bromo-l-chloro-3-


fluoropropane


.41g,


80/20


ratio


respectively,


0.2771


desired


1-bromo-3-chloro-2-fluoropropane)


was


then


added


through


the


funnel


to the


mixture.


solution


was


stirred


2 hours


and


then


another


equivalent


sodium


was


added.


A uF


NMR


spectrum


the


crude


reaction


mixture


after


more


hours


showed


that


the


starting


trihalopropane


had


been


attacked


nucleophile


but


had


failed


cyclize.


Only


after


the


consecutive


addition


more


equivalents


sodium


(12.50


two


hour


intervals


did


the

then


uncyclized


cooled


adduct

room t


disappear.


temperature


reaction


and


mixture

water ad


was


ded


dissolve


sodium


salts.


No metallic


sodium


was


observed


this


upper


time


organic


. The r

z phase


resulting


was


mixture


retained


had


while


two

the


phases.

lower aq


The


[ueous


phase


was


extracted


three


times


with


methylene


chloride.


extracts


were


combined


with


the


organic


layer,


washed


with


water


and


dried


over


anhydrous










diglyme


and


subsequent


distillation


under


reduced


pressure


gave


an impure


mixture


the


desired


diester


and


allyl


malonate


-650C,


mm Hg)


The


allyl


malonate


decomposed


on careful


addition


bromine/carbon


tetrachloride


, and


a second


distillation


gave


.4%)


diethyl


3-fluorocyclobutane


-1, 1


-dicarboxylate


which


was


>95%


pure


and


NMR.


MS(70eV)


calculated


CHisFO,4


.0954,


found


.0945


IR: 2980


2355


cm-' (m);


1730


cm-"


1025


cm"-


-NMR


(CDC1,/TMS)


(3H,


Hz) ;


(2H,m);


(2H,m);


(2H,


Hz);


4.23


(2H,


Hz) ;


5.10


(1H, dm,


J2
il-F


= 13


"C-NMR


(CDC13)


= 13


.7 Hz);


= 15


.3 Hz);


Hz) ;


-NMR


(CDC13/CFC3,)


= 171


(dm,


= 55


.7 Hz,


Hz) .


3-Fluorocyclobutene


27.28


Diethyl


-fluorocyclobutane


-1, 1


,b);










hydrochloric


acid,


giving


the


diacid


yield)


diacid


was


thermally


decarboxylated


heating


to 190-


a pressure


mm Hg


. 3-Fluorocyclobutanecarb-


oxylic


acid


distilled


S-95C


over


mixture


of the


two


isomers


(ratio


approximately


and


was


found


to be


>95%


pure


and


NMR.


3-Fluorocyclobutanedicarboxylic


acid:


(70eV


calculated


C,HFO,


found


.0221


1H-NMR


(CDCl,/TMS)


(4H,


5.10


(1H,


= 55


Hz);


(bs) .


"C-NMR


(CDC1,)


= 38


= 23.4


Hz);


= 14


= 208


"F-NMR


(CDC1,/CFC ,)


= 166


(dm,


= 55


.4 Hz)


3-Fluorocyclobutanecarboxylic


acid


calculated


C5HFO,


.0430,


found


.0432


: 3000


cm-1


1700


cm-1


1420


cm-1
cm


1080


cm-


(s,b)


1H-NMR


(CDCl,/TMS)


(8H,


3.16


(2H,


(1H,


= 55


.3 Hz);


5.24


(1H,


= 55


Hz);









-NMR


(CDC1,)


Hz) ;


= 13


= 23


Hz);


= 22


.4 Hz);


= 215


Hz);


= 207


Hz) ;


.6 Hz)


(CDCl,/CFCl3)


(50%,


= 55


Hz);


(50%,


= 55


.5 Hz)


3-Fluorocyclobutanecarboxyli


acid


mol)


as a 1


mixture


the


and


trans


isomers,


was


sso


Lived


with


Cu(OAc)


2 H20


0.290


mmol)


and


pyridine


ml of


very


dry


benzene


a sealed


round


bottomed


ask in


a dry


box


Then


a mixture


Pb(OAc),


.00578


mol)


very


dry


benzene


was


allowed


rubber


to stir


septum


a 50


the


ml round


dark


bottomed


flask


minutes


with


dry


box.


solution


Pb(OAc),


was


then


added


to the


flask


with


the


acid


and


of benzene


used


to wash


undissolved


Pb(OAc)4


into


the


flask.


flask


was


removed


from


dry


box


while


sealed,


equipped


with


a reflux


column,


a distilling


head,


a receiver


cooled


water,









inlet.


flask


was


stirred


the


dark


.5 hours


insure


metathesis


3-fluorocyclobutane


carboxylic


acid


with


Pb(OAc)4.


solution


was


then


gradually


heated


over


minutes


to reflux,


then


heated


at reflux


hours.


Ove r


initial


heating


to reflux


a solid


was


observed


to first


form


then


dissolve


into


the


solution.


Near


end


the


refluxing


period


a large


amount


solid


precipitated


green


the


to blue-green


solution,


A small


which


amount


changed


liquid


color


was


from


observed


receiver


this


time.


The


solution


was


then


distilled


to the


boiling


point


benzene,


resulting


collection


approximately


liquid.


This


mixture


benzene


and


3-fluorocyclobutene


was


separated


GPLC


ft 10%


SE-30


column


T,=60C,


Flow


= 60


ml/min,


retention


time


2 minutes


3-fluorocyclobutene).


Fluorocyclobutene


(0.2676


.7%)


was


analyzed


analytical


GPLC


Triton-X,


=250


and


found


contain


a small


amount


E-1-fluoro-1,3-butadiene


.44%).


3-Fluorocyclobutene


: MS


calculated


C4H,F










3140


cm-'


(w);


cm-1


(w) ;


3060


cm


2940


cm-1


2850


(w);


cm-'


(w)


1H-NMR


(CDC1/ TMS)


6= 2.71


(1H, m);


(1H, m);


(1H,


= 57


(1H,


Hz);


6.14


, s)


"C-NMR


(CDCl,)


= 19


Hz) ;


"F-NMR


= 19


(CDC1,/CFC1,)


.3 Hz);


= 57


= 16


.5 Hz)


1-Chloro-3-trifluooroethylcyclobutane


3-Chlorocyclobutane


carboxyli


acid


was


prepared


literature


procedures,


and


.0743


mol)


acid


were


placed


an autoclave


which


was


cool


to -1979C


and


depressurized.


Then


.223 mol)


sulfur


tetrafluoride


were


then


condensed


into


the


autoclave,


which


was


then


sealed,


allowed


warm


room


temperature,


and


then


heated


a rocker


14 hours


autoclave


was


then


cooled


to -197C


and


excess


sulfur


tetrafluoride


allowed


vent


with


warming


through










fuming


liquid


was


decanted


from


the


autoclave


onto


sodium


fluoride


suspended


.0 ml


pentane


Distillation


gave


.0501


mol,


.4%)


pure


product


. Attempts


to eliminate


directly


to give


3-trifluoromethyl


1H-NMR


cyclobutene


(CDC1,/TMS)


were


(2H,


unsuccessful


(2H,


(1H,


"C-NMR


4.20


(CDC13)


(1H,


= 31


carbon


seen


MHz


spectrum.


- (NMR)


(CDC1,/CFC1,)


Hz) ;


(68%,


Hz) .


3-Trifluoromethylcyclobutene


28.30


Magnesium


metal


.103


g-atoms)


and


THF


were


placed


a 100


round


bottomed


flask


equipped


with


pressure


equali


zing


dropping


funnel


a magnetic


stirrer,


and


reflux


condenser


attached


to a nitrogen


line


. The


-Chloro


-3-trifluoro-


methyl


clobutane


.0504


mol)


was


placed


one


funnel


and


-dibromoethane


placed


the


second.


flask


was


heated


to reflux


and


approximately


; 50


, d,









dibromide.


Alternate


addition


was


continued


until


cyclobutane


was


added,


then


the


reflux


was


continued


more


hours.


the


Grignard


tended


crystalize


from


room


temperature,


the


hot


solution


was


poured


directly


onto


C0, (s)


.5045


mol)


and


vigorously


stirred


until


the


excess


cardice


had


evaporated.


reaction


was


worked


addition


hydrochloric


acid


until


just


acidic,


followed


extraction


with


3-100


portions


diethyl


ether.


ethereal


extracts


were


combined


and


extracted

hydroxide.


with

The


3-50


aqueous


portions

extracts


were


aqueous sodium

acidified with


concentrated


hydrochloric


acid,


extracted


with


ether,


and


dried


over


anhydrous


magnesium


sulfate


Removal


solvent


subsequent


distillation


gave


5.83g


.0347


mol,


.8%)


3-trifluoromethylcyclobutanecarboxylic


acid,


which


distilled


over


isomers.


oxidative


decarboxylation


acid


was


carried


the


same


fashion


as for


the


preparation


3-fluorocyclobutene


above


to give


trifluoromethylcyclobutene


yield.









3-Trifluoromethylcyclobutanecarboxylic


acid


1H-NMR


(CDC1,/TMS)


(4H,


Hz);


(1H,


Hz);


(1H,


(1H,


"IF-NMR


(CDC3,/CFC1,)


74.6


32%,


.5 Hz);


(69%,


.3 Hz)


3-Trifluoromethylcyclobutene


: MS


calculat


ed for


C5HsF3


.0343,


found


.0344


IR: 3148


cm-


(w);


3089


cm- 1


(m);


2980


cm-1
cm


(m);


2942


cm-1


(s);


1365


1150


(s);


1130


cm-1


1H-NMR


(CDCl3/TMS)


(2H,


3.46


(1H,


5.93


(1H,


'3C-NMR


(CDC1,)


Hz);


(1H,


Hz);


= 276


Hz);


INEPT


pulse


sequence


shows


peaks


and


are


'"F-NMR


down.


(CDCl1/CFC13)


1,1,1,2-Tetrafluoro-1,3-pentadiene


1,1,


-Trifluoro-


1,4-


pentadien-3-ol


was


prepared


reaction


trifluorovinyllithium


with


acrylaldehyde


according









purified


to its


instability


A 60


ml polypropylene


bottle


with


a teflon


coated


stirring


bar


charged


with


5.32


ce/isopropanol


bath.


mmol


and


cooled


Anhydrous


a dry


transferred


into


botti


using


a teflon


inlet,


and


mmol


unsaturated


alcohol


was


added


over


5 minutes


reaction


was


then


allowed


warm


room


temperature


with


stirring


over


hour


mixture


poured


onto


water,


extracted


with


CHC13


X 20


ml),


washed


with


water


and


dried


over


MgSO,


product


was


isolated


using


preparative


scale


GPLC


(10'


column).


: calculated


CzH4F,
CH F
544r


.0249,


found


.0258


Z-Isomer


IH-NMR


(CDC1,/TMS)


6= 5.43


(1H,


= 10


Hz) ;


5.77


(1H,


= 17


Hz);


6.13


(1H,


= 11.3


32.1


(1H,


ddd,


= 17


11.3


-NMR


(CDCl,/CFC1,)


(3F,


= 10


Hz);


(IF,


= 10


E-Isomer


"F-NMR


(CDC13/CFC1,


67.8


(3F,


= 12 Hz);


(IF,










Attempts


to photochemically


tetrafluoro-1, 3-pentadiene


to the


cyclize


1,1,1,


cyclobutene


resulted


isomerization


the


substituted


double


bond.


No 3-fluoro-


3-trifluoromethyl-cyclobutene


was


isolated


from


the


reaction.


3-Fluoro-


and


3-trifluoromethylcyclobutene


were


thermolyzed


the


same


fashion.


A small


pressure


cyclobutene


to be


studied


(7-10


mm Hg)


was


condensed


with


mm Hg


pentane


as an


internal


standard


into


an evacuated


bulb


which


had


been


equilibrated


to the


desired


temperature


bath.


Timing


reaction


was


started,


and


aliquots


the


reaction


mixture


were


periodically


transferred


evacuated


sample


tube


to which


argon


as a spacer


was


than


added.


contents


the


bulb


were


analyzed


GPLC


using


a Hewlett


Packard


1095


Chromatograph


with


a flame


ionization


detector.


A20'


, 10%


OV-210


column


was


used


analyze


the


ring


opening


3-fluorocyclobutene.


column


temperature


was


maintained


at 50C,


while


column


flow


rate


was


ml/min.


A 20'


, 10%


OV-210


column


coupled


with










trifluoro


-1,3-pentadiene


column


temperature


was


maintained


at 70C,


column


flow


ml/min.


Rate


constants


were


calculated


from


the


peak


integrals


In each


case


total


values


the


peak


integral


starting


material


and


product


remained


the


same


relative


the


internal


occurring,


standard,


and


indicating


products


no side


were


reactions


accounted


were


In both


systems


the


product


were


equilibrated


CDC13


with


CFC13


an internal


standard


adding


a catalytic


amount


iodine


and


heating


a sealed


NMR


tube


until


no further


changes


NMR


spectra


were


observed


each


temperature.


E-1-Fluoro-l, 3-butadiene


1H-NMR


(CDCl,/TMS)


5.06


(1H,


= 11


.5 Hz,


.7 Hz,


Hz) ;


.4 Hz);


(2H,


5.19


(1H,


= 16


= 16


.5 Hz,


Hz);


(1H,


ddm,


"C-NMR


(CDC1,


= 14.4 Hz);


11.6


= 261


'"F-NMR


(CDC1,/C,F,)


(dd,


= 82


16.5










E-5,5,5


-Trifluoro-1 3-pntadiene:


1H-NMR


(CDCl/ TMS)


5.46


(1H,


= 10


Hz);


(1H,


= 16


Hz);


(1H,


= 15


(1H,


dddm,


= 17


.7 Hz);


, dq,


= 15


6 Hz,


"F-NMR


(CDC1,/CFC13)


.0 Hz)


Z-5,5,5


-Trifluoro-1,3-pentadiene


1"F-NMR


(CDC1,/CFC1,)


.2 Hz)


Tabl


and


Relative


product


GPLC


ring


integral
opening


starting


3-fluoro


material


cyclobutene


temperature


= 67.7"


Time(


sees)


3-fluorocy


clobutene


E-diene


1362


28440
48660
87000









Table


Relative


GPLC


integrals


starting


material


product


ring


opening


3-fluorocyclobutene


temperature


78.10


Time secss)


3-fluorocyclobutene


E-diene


6060


15000


25200


37140


39.0


Table


Relative


GPLC


integrals


starting


material


product


the


ring


opening


3-fluorocyclobutene


temperature


= 84


Time(secs)


3-fluorocyclobutene


E-diene


3600
6720
11160


19380
21900









Table


and


: Relative


product


GPLC
ring


integral
opening


starting


material


3-fluorocyclobutene


temperature


= 92


Time secss)


3-fluorocyclobutene


E-diene


30.1


6360
8160
8760


59.6


Table


and


Relative


product


the


GPLC
ring


integrals


opening


starting


material


3-fluorocyclobutene


temperature


= 97


Time(secs)


3-fluorocyclobutene


E-diene


1500
2100
2700
3300
3960
4500


77.4









Table


and


Relative


product


the


GPLC
ring


integrals


opening


starting


material


3-fluorocyclobutene


temperature


= 103.1"


Time(secs)


3-fluorocyclobutene


E-diene


96.2


23.6
29.5


1080
1560
2280
2640


Table


Relative


GPLC


integrals


starting


material


and


product


cyclobutene at


the


ring


temperature


opening (
= 146.5C


3-trifluoromethyl-


Time(sec)


CF,-cyclobutene


Z and E dienes


3660
7200
9000
14400
19860
25200
30660









Table


14: Relative


GPLC


integral


starting


material


and


product


ring


opening


3-trifluoromethyl


cyclobutene


temperature


= 154


Time (sec)


CF,-cyclobutene


and


E dienes


1200
2460
3600
4800
6000
9000


14.9


12000


Table


and


Relative


GPLC


product


the


integrals


ring


starting
opening


material


trifluoromethylcyclobutene


temperature


= 162


.2C


Time (sec)


-cyclobutene


Z and


E dienes


1080
2160


36.0


5400
7800
10800









Table


Relative


GPLC


product


the


integrals


ring


starting
opening


material


trifluoromethylcyclobutene


temperature


= 169


.8C


Time (sec)


-cyclobutene


Z and


E dienes


900
1800
2760
3600
4500
5400
6300


44.7
54.9


Table


and


: Relative


GPLC


product


the


integral


ring


starting
opening


material


trifluoromethylcyclobutene


temperature


= 177


.2C


Time (sec)


CF,-cyclobutene


Z and


E dienes


22.9
40.0


1800
2400
3000
3900
4500


27.7










Table


Relative


GPLC


product


the


integrals


ring


starting
opening


material


trifluoromethylcyclobutene


temperature


= 186.3C


Time (sec)


-cyclobutene


and


Z-diene


1680
2040
2400
2760


80.1


89.9


1-Fluoro-2-vinylcyclopropane


Fluorodiiodomethane


mmol)


was


placed


an equal


volume


toluene


and


placed


a glass


tube


tube


was


attached


via


a rubber


hose


a vacuum


line,


cooled


to -1970C,


evacuated


and


degassed.


-Butadiene


.mmol)


was


then


condensed


into


the


tube.


A 1


M solution


diethylzinc


toluene


was


then


added


to the


tube


using


a double


ended


syringe


tube


was


then


flame


sealed


and


spun


while


warming


room


temperature


tube


was


then


placed


an oil


bath


and


spun


rapidly


while


the c


bath


, 69


v









hrs.


During


heating


a white


solid


was


observed


to form


inside


tube.


tube


was


then


cooled


to -197C,


opened,


connected


to a nitrogen


line


and


allowed


to vent


with


warming.


A saturated


aqueous


solution


of ammonium


chloride


was


then


slowly


added


until


no more


reaction


was


observed and

mixture was


almost


then


removed


the white

from the


solid

tube,


had


dissolved.


washed


once


with


saturated


ammonium


chloride


solution


ml),


and


dried


over


anhydrous


magnesium


distilled


sulfate.


fraction


solution


collected


at 50


was


-70'C


then


was


observed


NMR


to contain


the


and


trans


product


isomers


a ratio


respectively.


Analytical


GPLC


showed


a product


ratio


45.8


54.2


(10'


carbowax


column,


70C,


flow


ml/min;


retention


time


minutes


trans,


minutes


cis).


products


were


collected


and


purified


preparative


scale


GPLC


using


a 10'


DIDP


column


to give


.5848


the


product


and


0.4455


trans


product


.11%


yield).


calculated


CsH,F


.032;


found


86.053.










cis-1-Fluoro


-2-vinylcyclopropane


(neat)


: 3090


cm-1


(w) ;


3050


(w);


3020


(w) ;


2955


cm-1


(m);


1640


cm-'


1440


cm-'


(m);


1352


cm-1
cm


(w);


1257


1010


cm1
cm


'H-NMR


(CDC1,/TMS)


(2H,


= 13


Hz) ;


(1H,


= 13


6.6 Hz,


6.2 Hz,


.2 Hz)


(1H,


= 64


.7 Hz);


5.11


(1H,


= 10


5.25


(1H,


-= 17


Hz) ;


(1H,


= 17


.5 Hz,


.3 Hz)


-"C-NMR


(CDC13)


= 10


Hz);


.3 Hz);


= 221


(s);


"F-NMR


(CDC1,/CFC1,)


(dddd,


= 64


.5 Hz,


.2 Hz,


.7 Hz).


trans-1-Fluoro-


2-v


inylcyc


lopropane


(neat)


3090


2960


cm"'


(m);


1635


cm-


(m) ;


1259


(s);


cm-1


'H-NMR


(CDC13/TMS)


(1H,


= 10


Hz) ;


(1H,


= 22


.0 Hz,


11.0


Hz) ;


(1H,


= 20


.5 Hz,


4.42


(1H,









Hz);


5.05


(1H,


.9 Hz);


5.54


(1H,


Hz) .


"C-NMR


(CDCl,)


Hz) ;


= 11.1


Hz);


= 225


.9 Hz);


(s).


"F-NMR


(CDC1,/CFC1,)


(dddd,


= 64


.2 Hz,


.7 Hz).


1-Tri fluoromethyl-2-vinylcyclopropane :


2,2,2-Trifluoroethylamine


hydrochloride


.7 mmol)


water


was


slowly


added


via


a pressure


equalizing


dropping


funnel


to a stirred


solution


sodium


nitrite


.9 mmol)


water


at 15C


and


mm Hg


a distillation


apparatus


with


a receiver


cooled


to -78"C.


The


22, 2-trifluorodiazoethane


was


evolved


from


solution


as a gas


which


condenses


as a yellow


liquid


receiver


reaction


was


complete


when


the


hydrochloride


had


been


added


and


yellow


color


had


left


reaction


vessel.


The


diazo


compound


was


quickly


transferred


to a cold


glass


tube


which


was


then


attached









1,3-Butadiene


.327


mol)


was


then


condensed


into


tube,


which


was


sealed


and


placed


an autoclave


with


to increase


the


external


pressure


and


heated


110iC


cooled


8 hours


to -78C,


The


opened


tube


and


was


the


removed


excess


from


butadiene


autoclave,


vented


warming


Distillation


mixture


and


gave


trans


.9 mmol,


isomers,


.1%)


-56C.


Analytical


GPLC

(10'


showed


two


Carbowax


major


products


column,


70"C,


a ratio

flow =


ml/min;


retention


time


minutes


trans,


5.88


minutes


cis)


products


were


collected


and


purified


preparative


scale


GPLC


using


a 10'


DIDP


column


Collected


were


s-product


and


1.01


trans-


product


(yield


.0%,


purity


>98%


GPLC)


calculated


C,HF,


.050;


found


136.050


cis-1


-Trifluoromethyl


-2-vinylcyclopropane


: IR


(neat)


3098cm-'


(s);


3020


cm''


3000


(m) ;


2960


(m) ;


1830


cm-


(m) ;


1645


cm'-


(s);


1470


(s) ;


1410


cm-1


cm1










'H-NMR


(CDC13/TMS)


(1H,


Hz);


(1H,


.5 Hz,


.5 Hz);


(2H,


= 12


Hz);


(1H,


ddd,


= 10


0.5 Hz);


5.29


(1H,


= 16


.9 Hz,


Hz);


5.59


(1H,


= 17


.7 Hz,


-NMR


(CDC13)


6= 117


carbon


seen.


"F-NMR

trans-i


(CDC1,/CFC13


-Trifluoromethyl


.0 Hz)


-2-vinylcyclopropane


(neat)


3100


(w);


2960


cm-


(w);


1475


(m);


1410


(s);


1270


(s);


'H-NMR


(CDC1,/TMS)


(1H,


Hz) ;


(1H,


5.5 Hz,


.5 Hz,


(1H,


.7 Hz,


5.5 Hz,


Hz) ;


(1H,


ddd,


.7 Hz) ;


5.18


(1H,


ddd,


= 17


1.7 Hz,


Hz) ;


5.44


(1H,


= 17


-NMR


(CDC1,)


.7 Hz);


18.6


= 36


Hz) ;


= 270


_ __


m


, m,









"F-NMR


(CDCl1/CFC13)


Hz) .


aldehydes,


tosylhydrazones,


and


sodium


salts


tosylhydrazones


four


isolated


vinylcyclopropanes


were


prepared


an identical


manner,


and


pyrolyses


were


conducted


an identical


manner.


typical


procedure


preparation


the


aldehydes


as follows


cyclopropyl


alkene


.0110


mol)


was


placed


with


CH2C1,


a 100


3-necked


round


bottomed


flask


equipped


with


magnetic


stirring


bar,


a gas


inlet,


a cold


finger


cooled


-78C


and


a water


tower


containing


a saturated


aqueous


solution


potassium


iodide.


flask


was


cooled


to -78C


with


stirring


and


ozone


passed


through


the


solution


until


through


a blue


the


color


solution


persisted.


until


Oxygen


blue


was


color


then


passed


disappeared,


then


nitrogen


ten


minutes.


Then


dimethyl


sulfide


.692


.0111


mol)


was


quickly


added


and


the


solution


allowed


warm


with


stirring


room


temperature


over


three


hours.


Most


solvent


was


removed


and


crude


material


passed


down


a column


with


CH2Cl2/diethyl


ether









(10'


OV-210,


T-=40C,


F= 40


ml/min)


gave


mmol,


.9%)


pure


aldehyde.


cis-2-Fluorocyclopropanecarboxaldehyde


yield)


1H-NMR


(CDCl3/TMS)


6= 1


(1H,


= 12


5.6 Hz);


(2H,


= 12


Hz);


(dm,


= 63


.2 Hz,


Hz);


(dm,


= 5.8


Hz).


13C-NMR


(CDCl,)


= 11


Hz);


= 10


= 22


.3 Hz);


Hz) .


"F-NMR


(CDC1,/CFC1,)


(dm,


= 63


.3 Hz,


.7 Hz,


Hz) .


trans-2-Fluorocyclopropanecarboxaldehyde


yield)


: IR


(neat


: 3396


cm-1


(w);


3107


(w) ;


3061


cm-'


(w);


3020


(w);


2852


(s);


2746


1709


cm-


(vs);


1442


(vs);


1431


cm-


(vs).


1H-NMR


(CDC1,/TMS)


(2H,


= 18


.3 Hz);


(1H,


= 17


.4 Hz,


.5 Hz,


(1H,


dddd,


Hz);


(1H,


= 2.5 Hz,


0.8 Hz).


1"C-NMR


(CDC13)


= 15


Hz);


= 11.2










"F-NMR


(CDC1,/CFC13)


(ddd,


= 64


Hz).


-Trifluoromethylcyclopropanecarboxaldehyde


.02%


yield)


: IR


(neat)


: 3060


(w);


3020


(w);


2825


2630


(m);


1730


1165


(vs)


1H-NMR


(CDCl,/TMS)


(2H,m,


= 5.0


2.22


(1H,


= 3.2


.7 Hz,


.2 Hz);


2.35


(1H,


.7 Hz,


Hz) ;


9.49


(1H,


= 3.2


.7 Hz)


"C-NMR


(CDC1,)


.7 Hz);


= 38


Hz) ;


-NMR


(CDC13/CFCl3)


= 271


.2 Hz);


.7 Hz)


trans-2


-Trifluoromethyl


cyclopropylcarboxaldehyde


.46%


yield)


: IR


(neat)


3010


(w);


2960


cm-


(w) ;


2940


cm"'


2325


(m) ;


1730


1160


cm'-


(vs)


IH-NMR


(CDC3,/TMS)


(1H,


Hz) ;


(1H,


Hz) ;


.3 Hz,


(1H,


(2H,


= 3.4 Hz,


.7 Hz,


.4 Hz).


C-NMR


(CDC13)


Hz);


= 38









"F-NMR


(CDC1,/CFCl3)


tosylhydrazones


were


prepared


an identical


manner


Tosylhydrazine


mmol)


sso


Lived


mixture


methanol,


1.90


ml water,


ml aceti


acid


and


2 drops


concentrated


hydrochloric


acid.


cyclopropylcarbox


-aldehyde


.57 mmol)


then


added


and


mixture


allowed


to stir


3 hours


A white


solid


should


precipitate


solution


filtered


and


the


white


solid


recrystallized


from


methanol


with


a few


drops


of water


give


tosylhydrazone.


-fluorocyclopropylcarboxaldehyde


tosylhydrazone


.0%;


M + H found


at 25


, corresponding


C,,H,,FN20,


trans


-fluorocyclopropylcarboxaldehyde


tosylhydrazone


-2-trifluoromethylcyclopropylcarboxaldehyde


tosylhydrazone


: 84


.3%;


+ H found


at 307,


corresponding


trans


to C12H1,FN20S.


-2-trifluoromethylcyclopropylcarboxaldehyde


tosylhydrazone


: 60


.02%










sodium


salt


the


tosylhydrazone


was


prepared


reacting


tosylhydrazone


mmol)


ml of


mmol)


very


with


sodium


dry


hydride


a dry


box.


There


was


a gradual


evolution


gas


followed


the


precipitation


a white


solid.


solid


salt


was


filtered,


washed


with


very


diethyl


ether


and


dried


under


vacuum.


Pyrolysis


the


Tosylhydrazone


Salt:


salt


was


pyrolyzed


using


a sublimator


whose


cold


finger


was


cooled


-78C.


A small


amount


(-100


of the


salt


was


placed


the

trap


bottom

cooled


the


sublimator,


to -197C.


which


apparatus


was

s was


:hen

then


attached


evacuated


a pressure


0.01


mm Hg


and


the


bottom


part


the


sublimator


heated


to 110C


(70C


the


fluoro


specie)


an oil


bath.


Over


course


of 2 hours


a yellow


liquid


was


observed


to condense


on the


cold


finger.


cold


finger


was


then


allowed


warm


room


temperature,


and


the


cyclopropyldiazomethane


trapped


on the


cold


finger


condensed


the


trap.


diazo


compound


was


identified












CHAPTER


RESULTS


AND


DISCUSSION


synthesis


3-fluorocyclobutene


began


with


the


addition


'BrF'


3-chloropropene


give


1-bromo-3-


chloro-2-fluoropropane


It is


believed


that


the


reaction


Figure


Addition


'BrF'


to 3-chloropropene.


proceeds


formation


the


bromonium


across


the


double


bond,


which


then


displaced


fluorine.


internal


carbon


three


carbon


chain


should


more


able


support


a partial


positive


charge,


so attack


fluorine


should


preferred


there.


- CI













+ NBS


HFITHF
---p


cF

Cl


F

+ Br

CI


+ CH2(CO2C2Hs)2


Diglyme


CO2C2H5
C02C2H5


HCI/HzO


CO2H
CO2H


Pb(OAc)4
Cu(OAc)2


CO2H


-CO2


C6Hg/cat pyr


Figure


Synthesis


3-fluorocyclobutene.


Though


the


product


could


separated


from


2-bromo-


l-chloro-3-fluoropropane,


condensation


with


diethylmalonate


left


the


undesired


isomer


unreacted.


Several


solvent/base


combinations


were


tried


the


condensation,


and


diglyme/sodium


with


careful


monitoring


NMR


was


found


to give


the


least


amount


elimination.


In fact,


the


principal


impurity


formation


diethyl


fluorocyclobutyldicarboxylate


was


allyl


malonate,


which









distillation.


Fortunately,


was


found


that


careful


addition


bromine


to the


mixture


resulted


the


destruction


allyl


malonate,


leaving


the


cyclobutyldicarboxylate


ester


untouched.


Acid


hydrolysis


diester


and


decarboxylation


gave


a 50:50


mixture


trans-3-fluorocyclobutanecarboxylic


acids,


which


were


oxidatively


decarboxylated


with


lead


tetraacetate


to give


fluorocyclobutene


good


yield.


ring


opening


cyclobutene


was


conducted


the


phase


unimolecular


pressures


rate


data.


low


Pentane


enough


was


to insure


added


good


as an internal


standard


insure


that


side


reactions


were


occurring,


kinetics


the


reaction


were


monitored


measuring


GPLC


integral


the


starting


material


against


the


sum


the


integrals


starting


material


and


product.


NMR


had


spectrum


coupling


product


constants


gave


.4 Hz


a signal


and


6.80


.9 Hz,


which


corresponding


to a geminal


coupling


and


a vicinal


trans


H-H


coupling,


establishing


the


product


as E-1-fluoro-1,3-butadiene.


None










NMR.


rate


temperature


and


constants


the


were


activation


calculated


parameters


each


calculated.


- 103.1


Figure


Ring


opening


-fluorocyclobutene


Table


: Rate


constants


and


activation


parameters


ring


opening


3-fluorocyclobutene.


Temperature (OC)


X 10')/secs


3.58


103.

E.a
log


. 7


28.1


.544


kcal/mol
.175


.3 kcal/mol


-3.48


kcal/mol









ring


opening


3-fluorocyclobutene


been


theoretically


studied


Rondan


and


Houk,


and


expected


to have


an activation


energy


substantially


lower


than


that


unsubstituted


cyclobutene,


due


the


favorable


interaction


between


the


nonbonding


filled


p-orbitals


fluorine


substituent


and


the


LUMO


the


transition


structure.


energy


kcal/mol,


activation


as compared


32.5


the


reaction


kcal/mol


the


activation


energy


cyclobutene


energy


activation


3-fluorocyclobutene


also


lower


than


the


value


kcal/mol


determined


3-chlorocyclobutene


This


to be


expected,


to the


better


overlap


between


the


orbitals


fluorine


with


the


LUMO


the


cyclobutenyl


transition


structure.


energy


activation


quite


near


the


value


27.8


kcal/mol


predicted


3-acetoxycyclobutene


Oxygen


a better


electron


donor


than


fluorine,


but


electron


withdrawing


effect


adjacent


carbonyl


should


inhibit


donor


predicted


to have


ability.


an energy


In contrast,


of activation


3-ethoxycyclobutene


23.5









also


incorporating


predicted


inward


that


rotation


transition


the


fluorine


structure

substituent


should


some


kcal/mol


higher


energy


than


the


structure


with


outward


rotation


Though


no Z-1-fluoro-1,3-


butadiene


was


observed


GPLC,


possible


that


a small


amount


could


well


resolved


on the


column


that


was


used,

quite


as authentic

closely. Ho


samples


wever,


no Z-dien


E and

e was


Z isomers

observed


elute


the


NMR


spectra


the


sample


over


the


entire


temperature


range


that


was


studied,


which


places


the


upper


limit


diene


at < 2%.


LUMO(o)


*6


A'.t


HOMO(o)


F
^y


Figure


: Fluorine


interaction


with


HOMO,


LUMO









inward


rotation


fluorine


substituent


destabilizes


transition


state,


would


expected


that


there


would


little


the


Z-diene


observed.


Since


none


Z-1-fluoro-1,3-butadiene


opening


was


3-fluorocyclobutene,


observed


the


difficult


ring


see


how


the


relative


experimental


energies


inward


and


outward


rotation


compare


with


theoretically


determined


values.


However,


Dolbier


and


coworkers


have


recently


studied


the


kinetics


ring


opening


3,3-difluorocyclobutene


energy


activation


ring


opening


3,3-


difluorocyclobutene


kcal/mol


higher


energy


than


3-fluorocyclobutene.


Because


fluorine


a small


substituent,


unlikely


that


a significant


part


increase


between


activation


fluorine


energy


and


due


inward


to steric


rotating


interaction


hydrogen


transition


state.


Part


the


increase


energy


due


a strengthening


substitution.


the


A recent


C3-C,


bond


study


to geminal


Dolbier


and


fluorine


coworkers


rearrangement


1, 1-difluoro-3-









dideuterio-3-methylene


cyclobutane


yielded


information


effect


vicinal


fluorine


substitution


on the


homolytic


cleavage


a a bond.


E-t 45.0 kcal/mol
logA. 152
AH- 43.9 kcaVrmol


-8.1 e.u.


Figure


: Ring


opening


3,3-difluorocyclobutene.


The


parent


dideuteriomethylenecyclobutane


was


studied


Doering


and


Gilbert


and


found


to have


= +48.8


kcal/mol


cyclobutyl


and


e.u


bond


which


This


cleaved


indicates


the


that


rearrangement


stabilized


approximately


5 kcal/mol


the


geminal


fluorines


1,1-difluoro-3-(dideuteriomethylene)cyclobutane


relative


to the


nonfluorinated


hydrocarbon.


Based


on this


information


expected


that


c-bond


which


cleaved









stabilized


5 kcal


more


than


a -bond


fluorocyclobutene.


Adjusting


3,3-difluorocyclobutene


this


activation

difference,


enthalpy


found


that


there


still


a difference


kcal/mol


the


activation


enthalpies


3,3-difluorocyclobutene


and


fluorocyclobutene.


Since


the


transition


states


both


systems


are


stabilized


outward


rotation


one


fluorine,


this


energy


difference


should


serve


as a reasonably


accurate


measure


the


effect


inward


rotation


a fluorine


substituent


the


ring


opening


cyclobutene.


- 53.66 .68 kcal/mol
- 3.30 1.00 e.u.


Figure


Rearrangment


1,1-difluoro-3-


(dideuteriomethylene)


-cyclobutene


E-1-fluoro-1,3-butadiene


was


equilibrated


the









containing


diene,


which


was


then


sealed.


equilibration


was


found


that


a new


peak


appeared


NMR


spectrum


which


was


assigned


to the


diene.


Heating


tube


above


70"C


resulted


decomposition


sample,


so the


equilibration


was


studied


temperature


range


24-60C.


CDC2
24 -60C


4-


Figure


Equilibration


1-fluoro-1,3-butadiene.


Over


almost n

is found


the


o chang

to be


temperature


the


favored


range


observed


equilibrium constants.

at equilibrium by 0.35


that

The


there


Z-diene


kcal/mol.


NMR


with


equilibrium


coupling


constants


mixture


.2 Hz


shows

and


a signal at 6 = 7.15

6.3 Hz, corresponding


"










Table


: Equilibration


1-fluoro-1, 3-butadiene.


System


Temperature (C)


K(Z/E)


1-Fluoro-
1,3-butadiene


The


synthesis


3-trifluoromethylcyclobutene


was


slightly


more


involved.


3-Chlorocyclobutanecarboxylic


acid


was


prepared


according


to a standard


literature


procedure


Treatment


the


acid


with


sulfur


tetrafluoride


yielded


chloro-3-trifluoromethylcyclobutane


good


yield,


and


was


hoped


that


elimination


from


the


ring


would


afford


cyclobutene.


was


found


instead


that


the


proton


geminal


to the


trifluoromethyl


group


was


eliminated


to give


3-chloro(difluoromethylene)cyclobutane


and


decomposition


products.


Instead


the


halocyclobutane


was


reacted


with


magnesium


to give


the


3-trifluoromethylcyclobutyl


Grignard.


30 This


material


had


a tendency


to precipitate


of THF


an off-white


paste


allowed


to cool


room










to give


3-trifliuoromethylcyclobutanecarboxylic


acid.


Oxidative


decarboxylation


acid


with


lead


tetraacetate


gave


the


desired


t rifluoromethylcyclobutene,


which


was


isolated


preparative


GPLC


using


a 10'


SE-30


column.









Br


+ CH2(COC2Hs)2


NaOC2Hs
CH3CH2OH


C02C2H5

C02C2H5


HCIHMO


COgH
CO2H


soCI
(C6HsCO2)2
C6H6


CO2H

CO2H


CO2H


CO2H


Pb(OAc)4


2) CO2


Cu(OAc)2
F3C
CH,6/cat pyr


Figure


: Synthesis


3-trifluoromethylcyclobutene.


kinetics


ring


opening


3-trifluoromethyl-


cyclobutene


was


studied


using


same


procedure


as for


Sinrnrnr' 1 r~nhi'a-nno !acn


f-DT.f


, nr'n~nn1- a


iT


o aT a = I r nr


4---


WS 0!









that


both


isomers


were


present,


and


NMR


exhibited


doublet


quartets


with


coupling


constants


Hz and


corresponding


to trans


H-H


and


vicinal


couplings,


respectively


the


major


isomer.


On this


basis


the


major


product


was


assigned


as the


E-diene.


Table


Ring


opening


products


3-trifluoromethyl-


cyclobutene


at different


temperatures


Temperature (0C)


E-diene


Z-diene


In order


more


accurately


determine


product


ratios,


sealed


NMR


tubes


containing


3-trifluoromethyl-


cyclobutene


CDCl3


with


CFCl3


as an internal


standard


were


heated


over


the


temperature


range


the


kinetics


study


and


products


measured


their


NMR


signals.


There


was


no measurable


decomposition


the


starting


material


products


over


the


temperature


range,


and


was


found


that









little.


were


rate


calculated


constants


should


and


most


activation


influenced


parameters


the


which


reaction


which


leads


to the


E-diene,


since


reaction


to the


Z-diene


proceeds


only


to a small


extent


over


the


time


period


when


reaction


studied.


146.5


186.3


Figure


: Ring


opening


3-trifluoromethylcyclobutene.


Table


Rate


constants


and


activation


parameters


ring


opening


3-trifluoromethylcyclobutene


Temperature (C)


X 10o5) /sec


2.31


10.1


= 36


kcal/mol


= 14


.254


.227


If f3


,L .- 1 /,n.,









3-Trifluoromethylcyclobutene


unique


comparison


with


3-monosubstituted


cyclobutenes


which


have


been


previously


studied.


only


known


example


where


single


substituent


activation


energy


(E,


3-position


cyclobutene


the


ring


32.5


raises


kcal/mol2),


and


only


example


where


both


product


isomers


are


observed.


It is


believed


that


this


unique


behavior


the


result


two


characteristics


the


trifluoromethyl


substituent


ability


as a strong


electron


withdrawing


group,


and


large


size.


work


Curry


and


Stevens3


demonstrated

substituents


that

for


when t

outward


here


rotation


a choice

n, the s


between


strongest


two donor

donor will


rotate


outward


unless


there


are


very


large


steric


repulsions


weaker


donor,


the


case


3-methyl-3-t-


butylcyclobutene


This


argument


could


extended


that electron

would prefer


'donors'


than


accepting

to rotate

hydrogen.


substituents


inward,

What


on the


virtue

observed


cyclobutene


being

the


ring


weaker

ring


opening


3-trifluoromethylcyclobutene


the


result









substituent


would


prefer


inward


rotation.


However,


a strong


steric


interaction


with


the


inward


rotating


hydrogen


4-position


destabilizes


transition


state


for


inward


rotation.


This


results


the


system


opening


the


outward


mode,


which


electronically


destabilized


.8 kcal


relative


to cyclobutene.


steric


and


electronic


effects


must


relatively


close


energy


however,


because


a small


amount


3-trifluoromethylcyclobutene


still


rotates


inward


sterically


destabilized,


but


electronically


favored


transition


state.


outward


inward


Figure


Inward


outward


rotation


trifluoromethyl-cyclobutene.


- t ..


Sr r 4 % -L


*










1, 3-butadiene.


No decomposition


the


two


dienes


was


observed


over


the


temperature


range


study,


and


was


possible


to obtain


standard


parameters


the


equilibrium.


Analysis


the


dat a


gives


a standard


enthalpy


2.49


kcal/mol,


and


a standard


entropy


.349


.233


entropy


units.


Table


Equilibration


5,5, 5-trifluoromethyl-1, 3-


butadiene.


System


Temperature ("C)


K(Z/E)


5,5,5-Trifluoro-
1,3-pentadiene


0.0230
0.0434
0.0495
0.0578


Though


the


synthesis


3-fluoro-3-trifluoromethyl-


cyclobutene


could


completed,


the


synthesis


diene


precursor


proved


to have


wide


applications.


was


found


that


alcohols


formed


the


reaction


alkyl,


vinyl


and


aryl


aldehydes


with


trifluorovinyllithium


reacted


with














EIO..'711


.uTc ,


Figure


Synthesis


1,1, 1, 2-tetrafluoro-2-alkenes.


Careful


study


the


reaction


established


that


HF/THF


ratio


gave


the


best


results.


The


reaction


was


found t

product


o be


stereospecific,


isomer


depending


giving


on the


95-100%


aldehyde


yields


starting


the


material


reaction


was


also


found


to convert


the


alcohols


formed


from


reactions


acetone


and


acetophenone


with


trifluorovinyllithium


into


the


corresponding


1,1,1,


tetrafluoro-2-alkene,


though


the


yield


was


somewhat


lower


and


stereospecificity


the


reaction


was


lost


case


acetophenone.


This


synthetic


technique


sldvanttasn


nuVr


1 *!


s.i mi l R


nrn1rs"i i-s


n2i' n"r


rH alf-hul mil ns


ElpO, *7"E_









that


HF/THF


cheaper


and


safer


on workup


than


DAST.


This


synthetic


method


was


published


1987


Table
alken


Reactions


HF/THF


with


1, 1, 2-trifluoro-1-


-3-ols


Starting


material


Product


Yield(%)


ratio


acrylaldehyde
propionaldehyde
benzaldehyde
acetone
acetophenone


95/5
100/0
100/0


50/50


Known


literature


procedures


were


used


prepare


the


cyclopropyldiazomethanes.


reaction


halodiiodomethanes


with


diethylzinc


provides


an excellent


source


halocarbene


reacting


fluorodiiodomethane


with


diethylzinc


possible


trap


the


the


presence


monofluoromethylene


1, 3-butadiene,


carbene


was


to give


fluoro-2-vinylcyclopropane


(Scheme


Analytical


GPLC


showed


three


major


peaks


after


distillation


the


reaction


mixture.


peaks


were


resolved


and


collected


nronnrrn 4 no


rDT.r


4 fiance Pr P


t-hoi r


anonr- rn


KTMP









order


two


isomers


of 1-fluoro-2-vinylcyclopropane


ethyl


iodide.


In examining


the


NMR


spectra


the


resolved


isomers,


was


found


that


the


isomer


which


eluted


first


from


the


column


had


a chemical


shift


205.59


and


coupling


constants


= 64


.2 Hz,


and


.7 Hz,


which


are


consistent


with


one


geminal,


two


vicinal


and


one


trans


vicinal


proton


fluorine


couplings


on a


cyclopropyl


ring


The


second


isomer


had


an "F


chemical


shift


and


coupling


constants


= 64


.5 Hz,


Hz and


which


are


consistent


with


one


geminal,


one


vicinal


and


two


trans


vicinal


proton


fluorine


couplings


on a cyclopropane


ring.


Also,


expected


that


an alkyl


group


to a fluorine


on a


cyclopropyl


ring


will


shift


fluorine


upfield


frequency.


these


basis,


the


first


isomer


to elute


was


designated


trans-l-fluoro-2-vinylcyclopropane


and


second


isomer


designated


cis-1-fluoro-2-


vinylcyclopropane.









cis-


and


trans-l-fluoro-2-vinylcyclopropanes


were


separately


converted


the


corresponding


aldehydes


ozonolysis


the


double


bond


using


a literature


procedure


GPLC


conditions


allowed


purification


the


aldehydes,


column,


resulted


some


particularly


the


loss


due


case


to decomposition


the


trans-isomer.


was


found


that


the


aldehydes


could


purified


with


less


loss


material


passing


the


crude


reaction


mixture


down


a silica


flash


column


using


mixture


CH2Cl2/Et2O


eluant.


tosylhydrazones


aldehyde s


acid


were


catalyzed


converted


reaction


to the


with


tosylhydrazine


MeOH/H20.


cis-carboxaldehyde


tosylhydrazone


readily


precipitated


the


reaction


mixture


and


was


obtained


50-70%


yield.


trans


isomer


was


much


more


difficult


isolate


from


the


reaction


mixture.


Dissolving


the


tosylhydrazones


very


a dry


box


and


adding


excess


of sodium


hydride


the


formation


the


sodium


salts


tosylhydrazones.


Again


this


case,


the









isolated


near


quantitative


yield,


while


the


trans


species


formed


a suspension


which


slowly


decomposed.


removing


solvent


after


reaction


with


the


sodium


hydride


had


subsided


was


possible


to obtain


tosylhydrazone


salt


trans


isomer.


CHFI,2


+ 40


C5HsCH3


CH2,CI


CHO


+ TsNHNH2


CHO


MeOH/HwO


CHNNHTs


Scheme


Synthesis


2-fluorocyclopropylcarboxaldehyde


tosylhydrazone


sodium


salts


the


tosylhydrazones


were


decomposed


a modified


sublimator


that


allowed


the


diazo


compounds


condense


on a cold


finger


cooled


to -78C


approximately









finger


diazo


warm


compound


after


salt


to condense


into


had


decomposed


a receiver


cooled


allowed


liquid


allowing


diazo


compounds


to become


just


liquid


was


possible


to transfer


them


into


NMR


tubes


study.


Table


decompo


chemical


shifts


sition


and


products
trans


fluorocyclopropyldiazomethanes.


Compound


chemical


shift


-2-fluorocyclopropyl


dia


zomethane


(cis-19)


221.6


trans-2-fluorocyclopropyl


diazomethane


(trans-19)


3-fluorocyclobutene


(20)


-fluoro-1,3-butadiene


(21)


some
some


127.5


Two

spectrum


tubes

of eac


integrated.


Fo


were p

h tube

r each


prepared


was


each


taken


isomer,


isomer.


at -55C,


one


tube


and


was


The

all


then


NMR


peaks


heated


550C foi


J-, u


minutes.


and


one


tube


was


nhotolv zed


unsina


a









and


integration


each


tube


was


then


retaken


at -55C


and


integrals


subtracted.


Taking


an NMR


spectrum


each


tube


room


temperature


showed


little


change


the


peak


distribution,


indicating


that


the


products


are


stable


specie.


Several


peaks


the


region


- 230


were


found


to be


nonvolatile,


and


GC/MS


confirmed


that


they


were


products


cis-


intermolecular


and


reaction.


trans-1-trifluoromethyl-2-vinylcyclo-


propanes


were


prepared


reaction


1,1,l-trifluoro-2-


diazoethane


with


butadiene


(Scheme


II) .


33 Analytical


GPLC


showed


two


major


peaks


the


material


isolated


after


distillation,


which


could


separated


preparative


scale


GPLC.


Analysis


the


and


NMR


spectra


the


two


materials


confirmed


that


they


were


the


two


isomers


trifluoromethyl-2-vinylcyclopropane.


Researchers


who


had


reacted


1,1,1-trifluoro-2-diazoethane


with


propene


to give


1-trifluoro-methyl-2-vinylcyclopropane


were


able


distinguish


two


product


isomers


fine


splitting


NMR


spectrum


isomer


the


case


t