Preparation of cyclopropane carboxylic acid esters

Process for the preparation of 3(2,2-dihalovinyl)-2,2-dimethyl cyclopropane carboxylic acids, especially permethrin acid ethyl ester, by reacting a diazoacetic acid ester with a 1,1-dihalo-4-methyl-1,3-pentadiene in the presence of a catalyst comprising a divalent rhodium salt of a carboxylic acid or borofluoric acid. The products have improved yields and better cis/trans isomer ratios than when the more common catalysts, e.g. copper-bronze, are used.

This invention relates to the preparation of cyclopropane carboxylic acid 
esters from alkenes and, especially, halogenated dienes, to form compounds 
useful as insecticides or insecticide intermediates. More particularly it 
relates to the preparation of esters of 
3(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, for example 
the ethyl ester, commonly referred to as permethrin acid ethyl ester 
(PAE). 
PAE exists in four isomeric forms, that is, cis and trans, each of which 
may be in the 1S or 1R optically active form. When PAE is used as an 
insecticide intermediate, both 1S isomers are totally inactive and of the 
1R isomers the cis form is approximately twice as active as the trans. 
Since the thermodynamic equilibrium mixture contains about 20% cis and 
about 80% trans isomers (the proportion of S and R forms being equal), it 
is highly desirable to increase the proportion of cis isomers in the 
product. 
PAE may be prepared by the reaction of 1,1-dihalo-4-methyl-1,3-pentadiene 
with an ester of diazoacetic acid, as described by Farkas et al (Coll. 
Czech Chem. Comm, 1959, 24 pp 2230-2236) and when this reaction is 
catalysed by the catalysts commonly used, e.g. copper bronze, the product 
contains a predominance of the trans isomer. On the other hand, when the 
reaction is catalysed by palladium acetate a predominance of the cis 
isomer is produced; however, the total yield of product is unacceptably 
reduced. 
We have now found that by catalysing the reaction with certain rhodium 
salts one may obtain a good overall yield of products having satisfactory 
cis/trans ratios. 
According to the present invention, a process for the preparation of an 
ester of 3(2,2-dihalovinyl)-2,2-dimethylcyclo-propane carboxylic acid 
comprises reacting a 1,1-dihalo-4-methyl-1,3-pentadiene with an ester of 
diazoacetic acid in the presence of a divalent rhodium salt of a 
carboxylic acid or borofluoric acid, as catalyst. 
By "dihalo" we mean dichloro, dibromo or chlorobromo. 
The reaction is preferably carried out in the presence of an inert solvent 
in which the product is soluble. 
Conveniently the solvent used is immiscible with water to facilitate 
preparation of the diazoacetic ester. More preferably the solvent also has 
a boiling point lower than that of the 1,1-dihalo-4-methyl-1,3-pentadiene 
to facilitate recovery of unreacted diene. 
Suitable solvents include saturated chlorinated hydrocarbon solvents, such 
as ethylene dichloride, dichloromethane, tetrachloroethane, carbon 
tetrachloride and the like. 
A wide variety of divalent rhodium salts of carboxylic acids may be used as 
catalyst, the precise cis/trans ratio of the product being dependent, 
inter alia, upon the actual salt used. Suitable divalent rhodium salts, 
apart from the borofluoride, include the pivalate, octoate, benzoate, 
p-chlorobenzoate, p-methoxy benzoate, m-methoxybenzoate, triphenyl acetate 
and acetyl mandelate. The acetate may also be used; but it tends to give 
lower yields than some of the other salts referred to above. 
It is noted that neither monovalent nor trivalent rhodium salts give rise 
to the desired effect. 
The concentration of catalyst in the reaction mixture is not critical, but 
generally concentrations in the range of 0.00001 to 1 g atoms of Rh(II) 
per liter of reaction mixture, and especially 0.005 to 1 g atoms, are 
suitable. 
The temperature of reaction is generally in the range -10.degree. to 
+130.degree. C., preferably 10.degree. to 90.degree. C. It will be noted 
that these temperature ranges are lower than those usually required when 
other commonly used catalysts e.g. copper-bronze are employed. In fact, 
the reaction may be initiated without external heating, which is not 
possible with, say, copper-bronze catalysts. 
The diazoacetic acid ester may be prepared by reacting a water soluble acid 
addition salt (e.g. the hydrochloride) of an ester of glycine with an 
alkali metal nitrite in an aqueous medium, which is stirred with a 
water-immiscible solvent into which the diazoacetic acid ester is 
dissolved. Alkali metal nitrites which may be used are, for example, the 
potassium or sodium salts, and the reaction with the glycine ester is 
preferably carried out in the presence of an acid catalyst, for example, 
sulphuric acid. 
The solution of diazoacetic acid ester thus formed is then added to a 
solution of the 1,1-dihalo-4-methyl-1,3-pentadiene maintained at the 
desired temperature, and containing the divalent rhodium salt catalyst, 
usually in solution. 
It is usual to use excess diene, the ratio of diene to diazoacetic ester 
being in the range 2/1 to 10/1. 
Progress of the reaction may be monitored by measuring nitrogen evolution, 
which may also be used to determine yield of total products, the 
proportion of the desired product being readily determined by gas liquid 
chromatography (glc). 
Separation of the desired product from the reaction mixture may be achieved 
by any convenient means; but it is generally convenient to first distil 
off the solvent, the diene, then any esters of maleic and fumaric acids 
and finally the required product. Alternatively, the crude product, after 
removal of solvent and unreacted diene, may be used as an intermediate 
without further purification. This latter procedure is particularly 
appropriate when using the process of the present invention, since many of 
our rhodium catalysts give rise to high efficiency in the use of the 
diazoacetic acid ester, with a consequently lower proportion of 
by-products (e.g. esters of maleic and fumaric acid) than are formed using 
the more usual catalysts. 
As has previously been mentioned one would ideally desire to increase not 
only the cis/trans ratio of the product, but also the proportion of the 
insecticidally active optical isomer. This may be achieved by using a 
catalyst comprising a rhodium salt of an appropriate optical isomer of an 
optically active carboxylic acid, e.g. of acetyl mandelic acid. It may 
sometimes be difficult to predict which optical isomer of a particular 
carboxylic acid will give an enhanced proportion of the desired optical 
isomer of the product; but this may be readily determined experimentally 
by testing each optical isomer in turn and determining the product 
distribution e.g. by glc analysis. 
The reaction may also be performed continuously by forming the diazoacetic 
ester in a first vessel and continuously transferring it, in a solvent, to 
a second vessel where it is reacted immediately with the diene, as 
described and claimed in our British Pat. No. 1,459,285. 
Our process may be used to produce a variety of esters of the 
3(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, the 
particular ester produced being dependent upon the particular glycine 
ester used. Thus the process may be used to produce simple alkyl esters, 
which are useful as intermediates in the preparation of insecticides, or 
it may be used to produce the insecticides themselves. In the latter case 
the glycine ester must correspond to the required insecticidal ester. 
Examples of glycine esters of this type include the ester with 
3-phenoxybenzyl alcohol, and with 5-benzyl-3-furyl methanol.

The invention will now be illustrated by the following Examples. 
EXAMPLES 1-14 
General Procedure 
DCMP-1,3 (1,1 dichloro-4-methyl-1,3-pentadiene) (1.81 g, 12 m.mole)) was 
added to a measured quantity of the appropriate catalyst (.ident.0.01 mg 
atoms of metal) under an atmosphere of nitrogen. A solution (0.25 ml) 
containing dodecane (1.76 m.mole per ml) in a chlorinated solvent (1,2 
dichloroethane or 1,1,2,2 tetrachloroethane) was added as a glc internal 
standard. The mixture was then heated to reaction temperature, with 
stirring, under an atmosphere of nitrogen. A solution containing DCMP-1,3 
(12 m.mole) and DAE (diazoacetic acid ethyl ester) (3 m.mole) in a 
chlorinated solvent (2 ml) was then added to the stirred mixture over a 
period of 4 hours. Nitrogen evolution was monitored throughout the 
reaction and small samples of the reaction mixture were withdrawn from 
time to time for glc analysis. Glc product analysis was carried out using 
a 5 ft, 3% silicone O.V.17 on acid washed chromasorb column maintained at 
130.degree. C. The geometric isomer ratio was determined using a 9 ft, 3% 
silicone O.V.17 column at 127.degree. C. 
% yields were determined in terms of moles of PAE per mole of nitrogen 
evolved (i.e. mole of diazoacetic ester decomposed). Results are set out 
in Table 1. 
It will be seen from these, that a wide variety of divalent rhodium 
carboxylates and divalent rhodium borofluoride gave good yields of PAE, 
with enhanced cis/trans ratios. In contrast to this, when the commonly 
used copper bronze was employed, the total yield was lower and cis/trans 
ratio less acceptable. Other metal carboxylates gave very low yields and, 
with the exception of palladium acetate, poor cis/trans ratios. Monovalent 
and trivalent rhodium salt catalysts were also unsatisfactory. When Rh(II) 
Cl.sub.2 [(O-tolyl).sub.3 P].sub.2 was used as catalyst, that is a 
divalent rhodium compound other than a carboxylate or borofluoride, at 
60.degree. C., the evolution of nitrogen was fairly rapid; but the yield 
of PAE was only 1.3%. 
TABLE I 
__________________________________________________________________________ 
Rate of Total Yield 
Ex Divalent Rhodium 
Reaction 
Temp 
DAE Add.sup.n. 
of PAE 
Isomer Ratio 
No Compound Catalyst 
Time (min) 
(.degree.C.) 
(m . mol/min) 
(%) % Cis 
% Trans 
__________________________________________________________________________ 
1 Pivalate 120 20 0.016 53 58 42 
2 Octoate 180 20 0.014 62 54 46 
3 Benzoate 120 20 0.013 48 58 42 
4 Diphenylacetate 
120 20 0.012 50 49 51 
5 Triphenylacetate 
30 80 0.016 90 59 41 
6 Acetylmandelate 
300 80 0.019 30 48 52 
7 p-Methoxybenzoate 
30 20 0.011 99 60 40 
8 p-Chlorobenzoate 
120 20 0.014 46 62 38 
9 Chloroacetate 
120 20 0.013 29 49 51 
10 Borofluoride 
155 20 0.013 66 53 47 
11 Acetate 120 20 0.015 18 50 50 
12 m-Methoxybenzoate 
180 20 0.011 51 61 39 
13 .alpha.-D-methyl camphorate 
105 20 0.019 27 58 42 
CT* 
Cu Bronze 105 80 0.014 25 41 59 
CT Mn(II)Naphthenate 
120 84 0.013 8 38 62 
CT Fe(II)Naphthenate 
180 84 0.015 8 38 62 
CT Pd(II)Acetate 
120 80 0.012 2.5 72 28 
CT Rh(III)Chloride 
120 83 0.012 4.1 36 64 
CT [(C.sub.2 H.sub.4).sub.2 RhCl].sub.2 
90 83 0.018 Nil -- -- 
__________________________________________________________________________ 
*CT = Comparative test 
EXAMPLE 15 
The general procedure of Examples 1-14 was followed, using rhodium(II) D(-) 
acetylmandelate as catalyst. The reaction between DAE and DCMP-1,3 went 
smoothly at 80.degree. C. giving a 30% yield of PAE based on DAE consumed. 
The cis/trans ratio of the PAE produced was 48/52. 
The solvent for the reaction (1,2-dichloroethane) was removed using a 
rotary evaporator and the PAE isolated by column chromatography using an 
alumina (type H) column. Unreacted DCMP-1,3 was washed from the column by 
elution with petroleum ether (40.degree.-60.degree. C.) and the PAE 
subsequently recovered by elution with diethyl ether. Diethyl fumarate and 
diethyl maleate co-products remained on the column. 
The PAE was hydrolysed with ethanolic NaOH to give the free acid which was 
treated with thionyl chloride to give the acid chloride. This was reacted 
with 2-D-octanol to give a mixture of four isomers. These were analysed by 
glc on a 15 ft column of 5% LAC-2R-446 on Embacel at 125.degree. C. Of 
the two diastereoisomers derived from the cis PAE, there was found to be 
an excess of the 2-D-octyl ester having the longer retention time. The 
enantiomeric excess was 4.0% 
EXAMPLE 16 
The procedure of Example 15 was repeated using rhodium(II)L(+) 
acetylmandelate there was an excess of the 2-D-octyl ester having the 
shorter retention time. These last two Examples demonstrate that some 
enhancement of the proportion of one or other optical isomer of PAE is 
possible using the appropriate catalyst compound. 
EXAMPLE 17 
A solution of DAE (30 m.mole) in 1,2-dichloroethane was added to a stirred 
mixture of 1,1'dibromo-4-methylpenta-1,3-diene (28 m.mole) and a weight of 
catalyst equivalent to 0.014 mg atoms of metal. The rate of addition was 
maintained at 0.023 m.mole/min. and reaction was carried out under an 
atmosphere of nitrogen at the temperature stated. The products were 
analysed by glc (using a 15 ft LAC2R446 column at 110.degree. C.); and by 
NMR on a sample isolated by column chromatography (using a neutral alumina 
column eluted with petrol, diethyl ether). The cis/trans ratios obtained 
were the same by each technique. Results are given in Table 2. CT is a 
comparative test. 
TABLE 2 
______________________________________ 
Isomer Ratio 
Catalyst 
Temp (.degree.C.) 
% Cis % Trans 
______________________________________ 
Ex. 17 Rh(II) 50 70 30 
Pivalate 
CT Cu Bronze 84 27 73 
______________________________________ 
EXAMPLE 18 
DCMP-1,3 (28 m.mole) was added to the catalyst under nitrogen. A solution 
(0.25 ml) containing dodecane (1.76 m.mole per ml) dissolved in 
dichloroethane was added as an internal glc standard. The mixture was 
brought to reaction temperature, with continuous stirring maintained under 
an atmosphere of nitrogen. A solution of DAE (30 m.mole) in dichloroethane 
(30 ml) was then added to the mixture over a period of 23 hours. Nitrogen 
evolution was monitored and small samples of the reaction mixture were 
withdrawn periodically for glc analysis. The results are given in Table 3. 
It will be seen that the divalent rhodium pivalate catalyst was as 
effective as the copper containing catalyst with regard to effective use 
of DCMP-1,3; but was much more efficient with regard to utilisation of DAE 
and gave a greatly enhanced cis/trans ratio. 
TABLE 3 
__________________________________________________________________________ 
Products 
DCMP-1,3 
Conversion 
Catalyst Temp 
(m . mole) 
Unreacted 
DAE to 
Yield* PAE(%) 
Cis/Trans 
(m . mole) 
.degree.C. 
PAE 
N.sub.2 
(m . mole) 
PAE (%) 
A B Ratio 
__________________________________________________________________________ 
Rh(II) 
Ex 18 
Pivalate 
20 19.1 
28.8 
2.7 64 76 66 60/40 
(0.005) 
CuSO.sub.4 
CT 5H.sub.2 O 
80 14.0 
30.0 
9.3 47 77 48 44/56 
(0.06) not 
CT None 64 0.7 
4.5 
measured 
2.3 -- 15 44/56 
__________________________________________________________________________ 
*A calculated on DCMP1,3 consumed 
B calculated on N.sub.2 evolved.