Vinylcyclopropanes at standard room temperature and atmospheric force per unit area were expeditiously synthesised utilizing the Wittig reaction. The reaction involved the usage of a strong base ( benzyltriphenylphosphonium chloride ) dissolved in ethyl alcohol and cyclo-propylphenyl ketone reacted with Na ethoxide solution. A comparatively pure merchandise was obtained at a output of 4.54g ( 73.2 % ) . A runing point of 145-148oC was obtained and infra-red of the merchandise was taken.
Vinylcyclopropane were foremost synthesised by Gustavson in 1896.1 Vinylcyclopropane in 1922 was so prepared by thorough methylation of aminoalkane acquired from the oxime of methyl cyclopropyl ketone. Demjanov and Dojarenko supposed these hydrocarbons could n’t be synthesised by the desiccation of methylcyclopropylcarbinol.1 In recent research vinylcyclopropane was successfully synthesised via the desiccation of methylcyclopropylcarbinol.
Vinylcyclopropanes are made from a 3 C propane ring and a vinyl group attached.
Vinyl is an organic compound which has a chemical expression of -CH=CH2 which is a derivative of ethylene.
Primary olefines contain a vinyl group and on a skeletal construction sp2 hybridised Cs are called vinylic.
The synthesis of vinylcyclopropane in a pure signifier is rather hard due to the inclination of the hydrocarbon to organize azeotropic mixtures with some solvents.2
The purpose of this research undertaking is to synthesize assorted vinylcyclopropanes utilizing efficient paths of synthesis.
To synthesize compound A the reaction would be carried out in a 3 measure procedure:
First I?-chorobutyryl chloride will be prepared following the readying of ‘Close’13 so reacted with phenyl in AlCl3 reaction conditions to bring forth the intermediate merchandise.
The 2nd measure is to respond the intermediate with methyl Mg iodide and bring forth the 2nd intermediate in diethyl ether reaction conditions.
In the 3rd measure the 2nd intermediate was heated in Ac2O conditions to fix the concluding merchandise.
The reaction mechanism below shows the reaction stairss which will be carried out:
The mechanism above illustrates the planned reaction strategy which was proposed but the procedure could non be completed. Step 1 was successfully carried out, but due to the deficiency of clip the needed compound was non obtained and the other stairss could non be accomplished.
Compound B will be synthesised from methyltriphenylphosphonium bromide which will be reacted with the Na ethoxide solution and so the cyclopropyl phenyl ketone will be added. The Wittig reaction is used to change over the aldehydes/ketone to an olefine by replacing the O atom with CH2. The strategy below shows briefly an illustration of a Wittig procedure.
The synthesis of compound C would affect the same synthesis as compound B but the Wittig reagent used would be benzyltriphosphonium chloride as this is a stronger base and would be more efficient to deprotonate the phosphonium ion.
The Wittig reaction is by and large one of the most prima reactions which convert ketones/ aldehydes to olefines utilizing P ylides which are the Wittig reagents.
The strategy shown below is a general Wittig reaction to synthesize alkenes.5
The P ylide attacks the carbonyl compound due to its electrophillic nature and two smaller C atoms join together to do the olefine dual bond.
The dissolvers normally used in Wittig reactions are the undermentioned:
Dimethyl sulfoxide ( DMSO )
Tetrahydrofuran ( THF )
Phosphorus ylides can besides be prepared utilizing a two measure procedure. Alkyl halides are used to fix the reagents, the undermentioned stairss are carried out to fix the Wittig reagent:
Triphenylphosphine is reacted with alkyl halide to bring forth the alkyltriphenylphosphonium halide.
This salt is ionic and crystallises from non-polar dissolvers, so when extracted the salt is reacted with a strong base, it is deprotonated, to organize the coveted triphenylphosphonium ylide.
Common strong bases used to deprotonate the phosphonium ions are butyl Li. This base requires a wet free environment. Other bases which could be used as an option are sodium hydrated oxide.
An ylide is known to be a impersonal molecule which has a negative C adjacent to a positive heteroatom.
The two resonance constructions shown below are phosphoric ylides which can be characterised as loanblend.
The Wittig reaction is a regioselective reaction where the E-isomer is favoured so it ‘s obtained in a larger measure than the Z-isomer.
Disadvantages of utilizing the Wittig reagents are that simple ylides can be really reactive in air or wet therefore a volatile merchandise may be formed. The byproduct triphenylphosphine has to be separated from the alkene merchandise as it is an organic soluble compound
Compound C would be synthesised utilizing the Wittig reaction. Cyclopropyl phenyl ketone would be reacted with benzyltriphenyl phosphonium chloride in the presence of Na ethoxide solution. This procedure would change over the ketone to an olefine as shown in the diagram below.
Articles researched for undertaking thoughts
Near and colleagues studied13 compounds incorporating cyclopropyl groups and the methods of synthesis to bring forth their derived functions. This study gives a thorough method to synthesize I?-butyrolactone and besides the intermediate I?-chlorobutyryl chloride can be used to synthesize many different cyclopropyl aromatic ketones. The common processs used have developed a I?-halogenated butyronitrile which is the common intermediate. I?-chlorobutyryl chloride is successfully produced by handling butyrolactone with hydrochloric acid and thionyl chloride in an 88 % output. The merchandise can be farther condensed with benzine to give the chloro ketone which thenceforth is cyclised with methanolic K hydrated oxide to organize the cyclopropyl phenyl ketone in about 77 % output.
Friedel-Craft reactions were carried out with the I?-halogenated acid chlorides where the acyl halide from the I±-halogenated acid chlorides merely entered in to the reaction.
They found it hard to wholly extinguish the replacing of I?-chloro groups but when the reaction was carried out at low temperatures of less than 20oC the byproduct formed was in a really low output.
The Friedel-Crafts permutation reactions affecting aromatic compounds such as chlorobenzene, methylbenzene, phenetole and naphthalene were treated with I?-chlorobutyryl chloride to bring forth the needed merchandises.
Sarel and colleagues reported in 1963, 12 the methods of synthesis for some parity substituted cyclopropylstyrenes. “ The survey investigated the effects of permutations in the aromatic karyon and the capableness of vinycyclopropane mediety to come in in to the conjugative add-on reactions. ” Many aryl cyclopropyl ketones were reacted with methyl Mg iodide which resulted in other possible methods to be found to synthesize cyclopropylstyrenes. The proposed Grignard reaction methods were suited to fix third carbinols and 3 catalytic methods were found for the desiccation of methylcyclopropylcarbinol. The most acidic dissolvers gave a low output and in some instances none of the needed merchandise was formed but utilizing acetic anhydride as the least acidic a 55 % output was obtained.
C. Larock and Kgun Yum reported in 1996,14 high outputs of heterocyclic compounds and carbocycles can be prepared when aryl iodide is substituted in the ortho place by the polymers OH, CH2OH, NH2, NHT and CH ( CO2Et ) 2 groups. These substituted aryl iodides react with the vinylic cyclopropanes and cyclobutanes with a accelerator nowadays in the reaction such as Pd. Besides a suited base was required to carry through the demands of the reaction. The merchandises were formed by the add-on of Pd in to the C iodide bond. A ring was formed by the interpolation of the accelerator and a Pd intermediate is formed, other lending factors to the ring formation were:
The arypalladium add-on across the C to carbon dual bond of the olefine.
Carbon-palladium beta riddance caused the gap of the ring of cyclopropane or the cyclobutane.
Rearrangement of the unsaturated alkylpalladium to a Iˆ-allypalladium compound by a sequence of reversible Pd hydride beta riddance and re-addition stairss.
The arene contains a functional group from where the proton was removed to organize an anion.
The caboannulation procedure was carried out ensuing in high outputs of 80-82 % obtained for the NaOAc, KOAc in the absence of PPH3.
The constructions of olefines were varied analyzing the consequence on the output of the carbocycle. This resulted in low outputs and longer reaction times were required.
The heteroannulation of the cyclopropanes and cyclobutanes was examined and the best consequences achieved were of 70 % output utilizing KOAc as the base with other iodophenols and olefines but PPH3 was non used.
H. Yamaoka, Y. Yamada, S. Ono and T. Hanafusa reported in 1979 their process for the synthesis of vinylcyclopropane. 15 Besides the derived functions of vinylcyclopropane are used in farther cycloaddition reactions with negatron rich olefins via the Zwitterionic intermediates.
The research showed the vinylcyuclopropane can be synthesised from I± , I?-unsaturated thione derived functions and dimethyloxosulfonium methylide. The add-on of tetracyanoethylene with 4-methylene-4H-homochromenes formed dihydrobenzoxazepine derived functions.
The report15 above will non be used for this research undertaking due to the fact that diazo compounds are used in this method and have explosive belongingss. Therefore for wellness and safety issues in a university research lab and in the presence of other pupils these compounds are non safe to utilize.
From reading the assorted diaries and research articles it was decided to utilize the method proposed by W. J. Close, 13 which requires the usage of methoxy-benzene which would give the best consequences due to a solid merchandise being formed.
Consequences and Discussion
A general Friedal-Crafts reaction was carried out in the synthesis of the cyclopropyl p-tolyl ketone. The I?-chlorobutyryl chloride was purchased from Sigma-Aldrich and the aryl cyclopropyl ketone was produced by distilling I?-chlorobutyryl chloride with methylbenzene in the presence of AlCl3. A proton and C NMR was taken to further analyze the ketone intermediate acquired. A extremum at 200ppm shows the carbonyl ( C=O ) is present in the merchandise. At about 130ppm the ( C=C ) bonds from the phenyl ring are besides present. The ( C-C ) bonds from the cyclopropyl ring can be seen at 11.3ppm and 16.8ppm. The methyl extremum is present at 21.5ppm. The proton NMR shows the H extremums from the cyclopropyl ring at 1.02ppm and 1.20ppm. The individual H from the ring is shown at 2.65ppm. The protons on the methyl group can be seen at 2.40ppm. The H atoms from the phenyl pealing closest to the carbonyl are present at 7.24ppm and the H atoms closest to the methyl group are shown at about 7.92ppm. This indicates the intermediate merchandise was obtained. This ketone would hold been farther reacted with methyl Mg iodide in the 2nd measure but due to miss of clip available the reaction could non be completed. Figure shows the two isomers which could be the merchandise.
The following Wittig reaction to synthesize I±-phenylvinylcyclopropane was analysed and during the reaction there was merely a little cloud cover in the solution whereas the coloring material of the solution should hold changed to demo the reaction was successful. An infrared of the merchandise was taken which showed the ketone nowadays at a wave figure of 1725cm-1. This proved the reaction was non successful as the ketone should hold been converted to an olefine and the O would hold been removed. The reaction possibily was n’t successful because the base methyltriphenylphosphonium bromide might hold non been strong plenty to de-protonate the acid. A topographic point t.l.c was carried out and an Rf value of 0.456 was obtained. This was used to bespeak if the reaction did work but showed no alteration in the musca volitanss observed under ultraviolet visible radiation. Figure shows the expected merchandise from this reaction.
In the following Wittig reaction to synthesize Ph ( cyclo-C3H5 ) C=CH ( CH2Ph ) carried out a stronger base was used. This clip the stronger base used was benzyltriphenylphosphonium chloride and a color alteration was observed. When the Na ethoxide solution was added the coloring material of the ylid was a xanthous which was present for a short period of clip. A solid merchandise was obtained after rotary vaporization and the Infra-red spectrum taken showed the vinyl ( C=CH ) peak present at a wave figure of 3057cm-1. The olefine ( C=C ) at 1676cm-1 was present and an aromatic ( C=C ) stretch at 1598cm-1. The monosubstituted benzine was besides shown at a extremum of 747cm-1 and the C-H crook was seeable at 993cm-1. The infra-red spectrum indicated the reaction was successful hence this method was the most efficient path to synthesize a Vinylcyclopropane.
Synthesis of I±-Cyclopropyl-4-methyl-styrol
Cyclopropyl p-tolyl ketone was prepared utilizing the undermentioned method:
In a 500ml 3-necked unit of ammunition bottomed flask anhydrous aluminum chloride ( 20g, 3.17mol )
was suspended in methylbenzene ( 100ml, 1.09 mol ) an orangish solution was observed. The mixture
was stirred whilst chilling the temperature of the solution to 10-15oC. A solution of methylbenzene
( 20ml, 1.09 mol ) with I?-chlorobutyryl chloride ( 16ml ) was placed in a dropping funnel to be
added to the mixture. The mixture was added to the aluminum chloride solution whilst the
temperature was maintained at 15-20oC, a dark brown solution was observed. 20 proceedingss
were required for the add-on and heat was produced from the solution whilst the add-on
was carried out. Removing the ice bath stirring was continued at room temperature for a
farther 20 proceedingss. The mixture was poured in to frost H2O ( 200ml ) to divide the methylbenzene
bed. The organic bed was separated and dried over Mg sulfate. Solution was
decanted and dissolver was removed utilizing rotary movie evaporator. An oil was obtained with
some precipitate formed. The ketone was treated with Potassium hydrated oxide pellets ( 14.14g,
4.5 mol ) were dissolved in methyl alcohol ( 57ml, 1.09 mol ) . A gas evolved and a cloudy pick
colored precipitate was observed. The mixture was left to stand for 30 proceedingss whilst
on a regular basis agitating the flask. The mixture was cooled in ice and filtered to take the
methyl alcohol. The residue was washed in quintessence and H2O so the quintessence bed was separated utilizing
a separating funnel. The organic bed was once more washed with H2O and dried over
Mg sulfate to take the H2O from the merchandise. Dissolved in methylene chloride the
residue was so vacuum distilled to give a blue coloured solid which altered to a yellow
coloured solid whilst chilling in ice. Solid was recrystallised to take any staying drosss and yielded 9.07g ( 50.6 % ) of merchandise.
Note: Further synthesis would be carried out to complete synthesis of first Vinylcyclopropane if more clip would be available.
The reaction of methylbenzene can bring forth the methyl group to be in the ortho or para place. This molecule can be farther reacted and so dehydrated with acetic anhydride to derive the needed Vinylcyclopropane.
Preparation of I±-phenylvinylcyclopropane utilizing the Wittig reaction
In a dry conelike flask Na metal ( 0.76g ) was added to ethanol ( 100ml ) to fix Na
ethoxide solution. In another dry flask methyltriphenylphosphonium bromide ( 9.65g,
0.0270mol ) was dissolved in ethyl alcohol ( 150ml ) and cyclo-propyl-phenyl ketone ( 3.87g,
0.0265mol ) was added. The solution was stirred at a changeless gait and easy the Na
ethoxide solution was added at intervals. The mixture turned cloudy after the add-on was
complete. The mixture was left to stand for 30 proceedingss minimal at room temperature to
allow the reaction to finish.
T.l.c of the merchandise was taken to corroborate if the reaction had worked.
The dissolvers used were less polar to more polar dissolvers.
Light crude oil quintessence ( 60-80 ) used as dissolver
70 % crude oil quintessence ( 60-80 ) and 30 % dicloromethane
50 % crude oil quintessence ( 60-80 ) and 50 % methylene chloride
30 % crude oil quintessence ( 60-80 ) and 70 % methylene chloride
The t.l.c indicated that the reaction was non successful hence the following stairss to sublimate and derive a solid merchandise were non carried out.
An infrared of the merchandise was besides taken to see if the ketone was still present in the merchandise.
Wavenumber ( Cm-1 )
Chemical bond quiver
Weak set C=O stretch
Preparation of Ph ( cyclo-C3H5 ) C=CH ( CH2Ph )
In a dry 3-necked unit of ammunition underside flask Na metal ( 0.75g ) was added to ethanol ( 100ml ) to
prepare Na ethoxide solution. In another dry flask Benzyltriphenylphosphonium chloride
( 10.50g, 0.0270mol ) was dissolved in ethyl alcohol ( 150ml ) and cyclo-propyl-phenyl ketone
( 3.87g, 0.0265mol ) was added. The solution was stirred at a changeless gait and easy the
Na ethoxide solution was added at intervals. The mixture turned xanthous for a short period
and turned to a white solution after the add-on was complete. The mixture was left to stand
for 30 proceedingss minimal at room temperature to let the reaction to finish.
A t.l.c was taken with 30 % crude oil quintessence ( 60-80 ) and 70 % methylene chloride as the dissolver
for an indicant to see if reaction had worked. The dissolver was extracted via rotary movie
evaporator and an oil was obtained. The oil was filtered over silica gel in a fritted funnel and
washed with parts of methylene chloride. The dissolver was extracted once more and a solid
merchandise was gained in a output of 9.54g.
Infrared was taken of the ketone used.
Cyclopropyl phenyl ketone
Wavenumber ( Cm-1 )
Chemical bond quiver
Aromatic ( mono-substituted )
Infrared of merchandise in nujol
Wavenumber ( Cm-1 )
Chemical bond quiver
A C, proton NMR and infrared of the merchandise were submitted. *
*NMR non received for farther analysis.
The merchandises shown above are the two possible merchandises which can be formed from the reaction to find the right merchandise the consequences have to be farther analysed.
The purpose of the experiment was to synthesize assorted vinylcyclopropanes and utilize alternate paths to synthesize the molecule in a university research lab. This was partially accomplished as from the three synthesis carried out the 3rd reaction was successful. The synthesis was the reaction affecting the Na ethoxide solution responding with benzyltriphenylphoshonium chloride and cyclo-propy phenyl ketone. The vinyl extremum was present on the infrared spectra besides the olefine extremum turn outing the synthesis was successful.
The infra-red was taken and allowed the finding of the Vinylcyclopropane. The purpose of the undertaking was fulfilled and if given more clip the desiccation of methylcyclopropylcarbinol over aluminum oxide would be carried out as it is a safe synthesis to be carried out and gives a sensible output.
If farther research was carried out or there was more clip available so from the many other articles and diaries researched, the methods of synthesis for vinylcyclopropanes can be improved or more efficient methods could be used to derive high outputs and in some instances a concluding merchandise.
Vernon A. Slabey in 1952 reported a method of synthesis. This method could be tried to retroflex which involves the desiccation of methylcyclopropylcarbinol over aluminum oxide. A output of 54 % was obtained which shows a good output could be obtained but the temperatures used are rather high at 270oC of warming required.
Another method proposed by Toshio Tsumoda and Tomas Hudlicky synthesised a 62.9 % output of the vinylcyclopropane. The merchandise distilled at suited temperatures and it besides involves the Wittig reaction.