Process for preparing cyclopropane carboxylic acids

1-Cyano-3-[2',2'-(dihalogeno and/or trifluoromethyl)vinyl]-2,2-dimethylcyclopropanes are converted into the corresponding 1-amides and 1-carboxylic acids by reaction with sulphuric acid and water, or into the corresponding 1-carboxylic acid esters by reaction with sulphuric acid, water and a lower alkanol. High yields are obtained.

This invention relates to a chemical process and more particularly to a 
process for the preparation of certain cyclopropane carboxylic acids and 
derivatives thereof. 
Esters, such as the m-phenoxybenzyl ester, of 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (I). 
##STR1## 
are valuable insecticides. 
Our cognate copending United Kingdom Application Nos. 48078/76 and 22046/77 
describe and claim a process for the preparation of a compound of the 
formula: 
##STR2## 
wherein R represents a hydrogen atom or a lower alkyl group and X 
represents a chlorine or a bromine atom, which comprises 
(a) the step of alkaline hydrolysis of a cyclopropane carboxylic acid ester 
of the formula: 
##STR3## 
wherein R.sup.1 has the same meaning as R above and may be the same or 
different, and X has the meaning defined above, 
(b) the step of decarboxylation of the compound of formula: 
##STR4## 
obtained in step (a) by heating the compound in a polar aprotic solvent, 
(c) the step of treating the compound of the formula: 
##STR5## 
obtained in step (b) with dry hydrogen chloride in an alcohol R.OH wherein 
R has the meaning defined above, the reaction occurring with concurrent 
alcoholysis or being followed by a hydrolysis step whereby a carboxylic 
acid ester or carboxylic acid of formula (II) above is obtained. 
Compounds of formula (V) exist in cis and trans isomeric forms, according 
to whether the -CN and -CH.dbd.CX.sub.2 groups are on the same side or 
opposite sides respectively of the cyclopropane ring, and the same is true 
of the derived compounds of formula (II) with respect to the -CO.sub.2 R 
and -CH.dbd.CX.sub.2 groups and of the intermediate stage compounds (III) 
and (IV). 
The process described above enables the cis-and trans isomers of the 
compounds of formula (II) to be prepared separately, because at step (c) 
of the process the trans-isomer of the compound of formula (V) can be 
reacted preferentially, leaving the cis-isomer unchanged. The latter can 
then be separated and subjected separately to the reaction of step (c). 
This is a valuable feature of the process, because the cis-isomers of 
insecticidal esters of formula (I) have greater insecticidal potency than 
the corresponding trans-isomers. Consequently, the highly active 
cis-isomers of (I) can be obtained essentially free from the less active 
transisomers. 
The present invention provides an alternative route to certain 
cyclopropanecarboxylic acids and derivatives thereof from the 
corresponding nitriles. 
According to the present invention there is provided a process for the 
preparation of a compound of the general formula: 
##STR6## 
or a compound of the general formula: 
##STR7## 
wherein each X.sup.1 represents a chlorine or bromine atom or a -CF.sub.3 
group, or one X.sup.1 represents a chlorine or bromine atom and the other 
represents a -CF.sub.3 group, and R represents a lower alkyl group, which 
comprises the steps of: 
(i) reacting a compound of the general formula: 
##STR8## 
wherein X.sup.1 has the meaning stated above, with sulphuric acid and 
water to give a compound of formula: 
##STR9## 
and (ii) either (a) further reacting the compound of formula (IX) with 
sulphuric acid and water to give a compound of formula: 
##STR10## 
or (b) reacting the compound of formula (IX) with sulphuric acid, water and 
an alcohol of the formula R.OH, in which R has the meaning stated above, 
to give a compound of formula: 
##STR11## 
The individual steps (i) and (ii) of the above process are also features of 
the invention. 
The reaction conditions for obtaining optimum yields in the first step of 
the above process, i.e. hydrolysis of the nitrile (VIII) to the carboxylic 
acid amide (IX), are somewhat critical. 
The ordinary "concentrated" sulphuric acid of commerce, which contains 
approximately 98% by weight of sulphuric acid and approximately 2% by 
weight of water, can be used in the process without additional water. The 
yield of amide (IX) which is obtained is dependent on the amount of 
sulphuric acid relative to the amount of nitrile (VIII), and on the 
reaction time and temperature. In general, using 98% sulphuric acid the 
reaction temperature should not exceed 50.degree. C. and is preferably 
approximately 30.degree. C., and the amount of sulphuric acid should be 
sufficient to provide at least 1 mol of water per mol of nitrile (VIII). 
Theoretically, approximately 9 moles of 98% sulphuric acid contain 1 mol 
of water, but in practice less than this amount of acid per mol of nitrile 
can be used because concentrated sulphuric acid very quickly absorbs 
moisture from the atmosphere unless strict precautions are taken to 
prevent it. Reaction times from approximately 2 to approximately 24 hours 
may be used. 
It is preferred to use water in the reaction additional to that which is 
contained in "concentrated" sulphuric acid, and up to 30 mols of water per 
mol of nitrile (VIII) may be used, although excessive dilution of the 
sulphuric acid is to be avoided because the rate of reaction is adversely 
affected and the reaction may not go to completion. In general, the use of 
additional water permits higher reaction temperatures, for example, up to 
100.degree. C., to be used. 
Preferred conditions for the conversion of nitrile (VIII) into amide (IX) 
are 4 mols of sulphuric acid and 6 moles of water per mol of nitrile at a 
temperature of 80.degree. C. for 6 hours. The yield of amide under these 
conditions is almost quantitative. The amide may be obtained from the 
reaction mixture by cooling the latter, drowning it into water and 
extracting the amide from the liquor with a water-immiscible organic 
solvent, for example, toluene. The amide may then be isolated by removing 
the organic solvent by conventional means, for example, by evaporation or 
by distillation, optionally under reduced pressure. 
In carrying out step (ii)(a) of the process, i.e. conversion of the amide 
of formula (IX) obtained in step (i) into the carboxylic acid of formula 
(VI), it is not necessary to isolate the amide. Conveniently, more water 
is added to the reaction mixture at the conclusion of step (i) and the 
diluted mixture is then heated in order to hydrolyse the amide (X) to the 
acid (VI). Typically, the reaction mixture may be heated at 100.degree. C. 
for 12 hours but considerable variations in reaction conditions are 
possible without adverse effect on the yield and quality of the product. 
An amount of 4 to 5 mols of water per mol of sulphuric acid is suitable 
for carrying out this stage of the process. If desired, the amide (IX) 
from step (i) may be isolated as described above and then hydrolysed using 
a suitable strength of sulphuric acid to give the carboxylic acid (VI). 
Yields of carboxylic acid of formula (VI) of 90% or even higher are 
readily attainable using the process described above. 
The carboxylic acid may be isolated from the reaction mixture by drowning 
the latter into water, extracting the aqueous liquors with a 
water-immiscible organic solvent, for example, toluene, extracting the 
toluene extract with a dilute aqueous solution of an alkali, for example, 
sodium hydroxide, followed by acidification of the aqueous alkaline 
extract to precipitate the carboxylic acid. 
Step (ii)(b) of the process, i.e. conversion of the amide of formula (IX) 
obtained in step (i) into the carboxylic acid ester (VII) is effected by 
heating the amide in a mixture of sulphuric acid, water and alcohol of 
formula R.OH. The presence of water at this stage is essential, otherwise 
low yields (i.e. 10%) are obtained. The reaction may be carried out 
without isolation of the amide by adding the alcohol R.OH to the reaction 
mixture obtained at the conclusion of step (i), and then heating the 
resulting mixture containing the amide, sulphuric acid, water and alcohol 
in order to convert the amide (IX) into the carboxylic acid ester (VII). 
Reaction conditions for preparation of the ester are similar to those in 
step (ii) (a) for preparation of the carboxylic acid, a reaction 
temperature of 100.degree. C. for 12 hours being suitable. Amounts of 1 to 
2 mols of each of water and the alcohol R.OH per mol of sulphuric acid are 
suitable for carrying out this stage of the process. 
If desired, the amide of formula (IX) may be isolated before being 
converted into the carboxylic acid ester of formula (VII) by reaction with 
sulphuric acid, water and alcohol R.OH as described above. 
Yet again, the nitrile of formula (VIII) may be converted directly into the 
carboxylic acid ester of formula (VII) by reaction with sulphuric acid, 
water and alcohol R.OH without intermediate preparation of the amide of 
formula (IX), and this constitutes a further feature of the invention. 
This single-stage process may be carried out, for example, by mixing 
together the sulphuric acid and water, adding to the cooled mixture a 
mixture of the nitrile of formula (VIII) and the alcohol R.OH, and heating 
the four-component mixture so obtained to effect alcoholysis of the 
nitrile to give the carboxylic acid ester. Conveniently, reaction may be 
carried out at the reflux temperature of the mixture, a reaction time of 
approximately 12 hours being generally suitable. 
The carboxylic acid ester prepared by any of the methods described above 
may be isolated by drowning the reaction mixture, preferably after 
cooling, into water, extracting the aqueous mixture with a 
water-immiscible organic solvent, for example, toluene, and recovering the 
ester from the extract by removal of the organic solvent by evaporation or 
distillation, optionally under reduced pressure. 
Hitherto, the stability of the cyclopropane ring towards strong acids has 
been in doubt. Thus, C. F. H. Allen and R. Boyer (Canadian Journal of 
Research, Volume 9, pages 159-168 (1933)) found that ethyl 1-l 
-cyanocyclopropane-1-carboxylate with 14 mols per mol of sulphuric acid at 
room temperature overnight gave the corresponding ester amide, but the 
yield was low (35%). Surprisingly, it has been found that provided the 
reaction conditions described above are adhered to, cyclopropane nitriles 
of formula (VIII) can be converted in the presence of sulphuric acid into 
the corresponding amide (IX) and also into the corresponding carboxylic 
acid (VI) and carboxylic acid ester (VII) in very good yields, and without 
adverse effect on the cis-trans isomer ratio of the products. 
The invention is illustrated but not limited by the following Examples in 
which parts and percentages are by weight.

EXAMPLE 1 
Preparation of 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid amide 
5.5 Parts of water are added carefully below 30.degree. C. to 19.5 parts of 
concentrated (98% w/w) sulphuric acid. The solution is cooled below 
20.degree. C. and 16.5 parts of 
1-cyano-3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane (57.4% strength; 
cis/trans isomer ratio 67:33) are added dropwise, the temperature being 
maintained below 20.degree. C. by external cooling. The reaction mixture 
is then stirred at 80.degree. C. for 6 hours, cooled to 20.degree. C., 
drowned into 100 parts of water and extracted with toluene (2.times.50 
parts). The toluene extracts are combined and the toluene is evaporated 
off under reduced pressure to give 15.8 parts of 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid amide 
containing 42.8% of the cis-isomer and 20.2% of the trans-isomer. The 
yield is 96%. 
EXAMPLE 2 
Preparation of 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid 
5.5 Parts of water are added carefully below 30.degree. C. to 19.5 parts of 
concentrated (98% w/w) sulphuric acid. The solution is cooled below 
20.degree. C. and 16.5 parts of 
1-cyano-3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane (57.4% strength, 
cis/trans isomer ratio 67:33) are added dropwise, the temperature being 
maintained below 20.degree. C. by external cooling. The reaction mixture 
is then stirred at 80.degree. C. for 6 hours and then cooled below 
30.degree. C. 10 Parts of water are added below 50.degree. C. The mixture 
is then heated at 100.degree. C. for a further 12 hours, cooled to 
20.degree. C. and drowned into 100 parts of water. The aqueous mixture is 
extracted with toluene (2.times.50 parts), the toluene extracts are 
combined and then extracted with 5% aqueous sodium hydroxide solution 
(2.times.50 parts). The aqueous alkaline extracts are separated, combined 
and acidified with dilute sulphuric acid to precipitate the product which 
is filtered off and dried. 9.6 Parts of 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid 
containing 55.6% of the cis-isomer and 32.6% of the trans-isomer are 
obtained. The overall yield is 90%. 
EXAMPLE 3 
Preparation of Ethyl 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate 
The procedure described in Example 2 is repeated up to the point at which 
the mixture of 1-cyano-3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane, 
sulphuric acid and water has been heated and stirred at 80.degree. C. for 
6 hours and then cooled below 30.degree. C. 16 Parts of ethanol are added 
to the reaction mixture below 50.degree. C. The mixture is then heated at 
100.degree. C. for a further 12 hours, cooled to 20.degree. C. and drowned 
into 100 parts of water. The aqueous mixture is extracted with toluene 
(2.times.50 parts), the toluene extracts are combined and the solvent is 
removed by evaporation under reduced pressure. There are obtained 17.6 
parts of ethyl 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate as a brown 
oil containing 40.4% of the cis-isomer and 21.8% of the trans-isomer. The 
overall yield is 92.4%. 
EXAMPLE 4 
Preparation of Ethyl 3-(2',2'-dichlorovinyl)-2,2 
-dimethylcyclopropane-1-carboxylate from the nitrile without intermediate 
preparation of the amide 
16.6 Parts of concentrated (98% w/w) sulphuric acid are stirred and 5 parts 
of water are added, the mixture being maintained below 20.degree. C. by 
external cooling. 8.25 parts of 
1-cyano-3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane (57.4% strength; 
cis/trans isomer ratio 67:33) are dissolved in 25 parts of ethanol and the 
solution is added to the sulphuric acid/water mixture keeping the 
temperature below 30.degree. C. The resulting mixture is then stirred and 
heated at the reflux temperature for 12 hours, cooled to 20.degree. C. and 
drowned into 100 parts of water. The aqueous mixture is extracted with 
toluene (2.times.25 parts), the toluene extracts are combined and the 
solvent is removed by evaporation under reduced pressure. There are 
obtained 9.3 parts of ethyl 
3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate as a brown 
oil containing 36.3% of the cis-isomer and 22.2% of the trans-isomer. The 
yield is 92%.