JPH0224266B2 - - Google Patents

Description

[Detailed description of the invention]

The subject matter of the present invention relates to a method for the synthesis of α-cyanoalcohol esters. In particular, the invention relates to the following general formula _B in all stereoisomeric forms or in the form of a mixture of stereoisomers: [Here, (a) R ₁ is the following group R′ ₁ {Here, Y ₁ represents a hydrogen atom, and Y ₂ represents the following group Y′ ₂ or Y ₁ represents a hydrogen atom and Y ₂ represents the following group (Y ₃ and Y ₄ are the same and represent a fluorine, chlorine or bromine atom, or Y ₃ and Y ₄ each represent a methyl group). And this R′ ₁
, Y ₂ is the following group When it represents, it corresponds to a racemic or optically active acid residue with a cis or trans structure, or a mixture of a cis-structure acid and a trans-structure acid residue}
or (b) R ₁ is the following group R′ ₁ (Here, Z represents a hydrogen atom or a chlorine atom.
and this R″ ₁ group corresponds to a racemic or optically active acid residue), and R ₂ is the following formula when Y ₂ is different from the group Y′ ₂ or the residue of or R ₂ represents a group Y′ ₂ , _the following formula furthermore, the presence of an asymmetric carbon atom with a group CN is
For esters obtained from acids of well-defined stereoisomers, resulting in the existence of two diastereomers (referred to as isomer A and isomer B), are the compounds present in all stereoisomeric forms? or the following formula _A in the form of a mixture of stereoisomers: (Here, R ₁ and R ₂ have the same meaning as in formula _B ,
Furthermore, the presence of an asymmetric carbon atom bearing the group X results in the existence of two diastereomers (termed isomer A and isomer B) for esters obtained with well-defined stereoisomeric acids. . ). The method for producing the α-cyano alcohol ester of formula _B , which is the subject of the present invention, consists of reacting a compound that generates CN ^- ions with a compound of general _{formula A.}
(which exists in a stereoisomeric form corresponding to the stereoisomeric form of the compound of formula _A used). More specifically, the questions of the present invention include the following general formula in all forms of stereoisomers: [Here R ₂ and X are defined as above,
And R is the following group R′ (Here, Y ₁ represents a hydrogen atom, and Y ₂ represents the following group. (Y ₃ and Y ₄ are the same and represent a fluorine, chlorine or bromine atom, or Y ₃ and Y ₄ each represent a methyl group). and this
The R′ group is such that Y ₂ is represents a racemic or optically active acid residue in cis or trans structure, or a mixture of acid residues in cis structure and acid residue in trans structure}, or R represents the above. represents the group R″ ₁ as described in the following general formula _C (wherein R and R ₂ are as described above). The method of the present invention is based on the general formula _A or in
This is particularly useful when represents a fluorine or chlorine atom. The condensation of a compound of general formula _A or with an agent generating a CN ^- ion is conveniently carried out in an anhydrous organic solvent selected from the group consisting of acetonitrile and dimethylformamide. CN ^- reacted with a compound of formula _A or
The ion generating agent is preferably an alkali cyanide such as sodium or potassium cyanide. Furthermore, as the cyanating agent, tetraethylammonium cyanide, 1-methyl-1-ethylethanonitrile or cuprous cyanide can also be advantageously used. In particular, compounds of the general formula _B or _C , which are obtained as mixtures of isomers at the carbon atom bearing the -CN group, can be separated into their separate components in a known manner. More particularly, the subject of the invention provides that 1R,cis-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
-Carboxylic acid RS-α-cyano-3-phenoxybenzyl is produced, and the raw material compound used is 1R,cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl; 1R,cis-2,2-dimethyl-3-(2′,2 ′-
dibromvinyl) cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl, and the raw material compound used is
1R,cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid
A method characterized in that RS-α-fluoro-3-phenoxybenzyl; 1R, cis-2,2-dimethyl-3-(2′,2′-
dichlorovinyl) cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl is produced, and the raw material compound used is
1R,cis-2,2-dimethyl-3-(2',2'-dichlorovinyl)cyclopropane-1-carboxylic acid
RS-α-chloro-3-phenoxybenzyl; A method for producing RS-α-cyano-3-phenoxybenzyl 2-p-chlorophenyl-2-isopropylacetate, The raw material compounds used are 2
-p-chlorophenyl-2-isopropylacetic acid
RS-α-chloro-3-phenoxybenzyl; and 1R, trans-2,2-dimethyl-3-(1′,
2'-dibromo-2',2'-dichloroethyl)cyclopropane-1-carboxylic acid (R,S)-α-cyano-3-phenoxybenzyl is produced, and the raw material compounds used are 1R, trans-2,2
-dimethyl-3-(1',2'-dibrome-2',2'-
dichloroethyl) cyclopropane-1-carboxylic acid (R,S) α-chloro-3-phenoxybenzyl or 1R,trans-2,2dimethyl-3-(1′,
2'-Dibrom2',2'-dichloroethyl)cyclopropane-1-carboxylic acid (R,S) α-fluoro-3-phenoxybenzyl. Compounds _A and _B exist in many stereoisomeric forms. In the group R′ ₁ , Y ₁ represents a hydrogen atom and Y ₂ represents a group When represented, the group R ₁ has two asymmetric carbon atoms at the 1 and 3 positions of its cyclopropane ring.
The corresponding cyclopropanecarboxylic acid may be in a racemic or optically active form with a cis or trans structure, or may be a mixture of an acid with a cis structure and an acid with a trans structure. Furthermore, when Y ₃ is different from Y ₄ , isomerism (E) and (Z) exist at the double bond. The group _R''1 is derived from a substituted 2-aryl-2-isopropylacetic acid, but the carbon atom at the 2-position of this compound is an asymmetric carbon atom, which gives this group two enantiomers and one racemic form. Further, in the compounds of formulas _A and _B , the carbon atom bearing the substituent CN is an asymmetric carbon atom. According to the method for preparing the compounds of formulas _A and _B , the group R ₁
If it contains one or more asymmetric carbon atoms with a well-defined absolute configuration, it could be assumed that there would be an asymmetric-sensing effect at the carbon atom bearing X or CN. However, the induced effect obtained in this way is generally not perfect;
Therefore, chiral centers (with X or CN) are generally not of the fully (R) or fully (S) configuration. As a result of this, the compound _B obtained in this case is a mixture of two diastereomers (which can be separated)
It turns out that. These diastereomers are referred to below as isomer A and isomer B. By convention, isomer A is the more mobile of the two in thin layer chromatography. According to a certain theoretical consideration, although of course we do not wish to be bound by the accuracy of what chirality inferred from that consideration is attributed to, the absolute configuration (S) for a carbon atom with a substituent It seems possible to attribute it to field A. In formulas _A and _B , R ₁ is the group R′ ₁ (where Y ₁ represents a hydrogen atom and Y ₂ is the group The asymmetric carbon atom of the ethyl side chain of the compound (representing ) results in the existence of two diastereomers for some of them, which can be separated, for example, by chromatography. The compounds of general formulas _A and _B of the present invention, for the given definitions of the substituents X, R _{1 and} R ₂ , have optical activity (or racemic) isomer and the following formula It includes all compounds derived from the alcohol moiety in combination with the corresponding optically active (or racemic) isomer. Further, the compound of general formula _A used in the method of the present invention can be prepared by the following general formula in the presence of an acid catalyst. (where X and R ₁ have the meanings given above)
The acid halide has the following general formula: (where R ₂ has the meaning given above) with an aldehyde. Particularly preferably as starting materials the general formula
_A (where X and R are as described above) are used. The preparation of acid chlorides or bromides of general formula or _A is carried out by standard methods. The preparation of acid fluorides of the formula is advantageously carried out by the method described by Mukaiyama in Chem. Letters p. 303-306 (1976). The acid catalyst present in carrying out the condensation of an acid halide of the formula with an aldehyde of the formula can be a Lewis acid such as zinc chloride, aluminum chloride or ferric chloride or a Lewis acid such as p-toluenesulfonic acid or oleum. It is a protonic acid. The condensation of acid halides of the formula with aldehydes of the formula is conveniently carried out by simply mixing these agents and the acid catalyst without the addition of a solvent. Moreover, this condensation can also be carried out in the presence of an organic solvent. Furthermore, X used in the method of the present invention represents a fluorine atom, and R ₂ is the following residue.

【formula】 or the next residue

The compound of general formula _A , which represents [formula], is prepared by combining quaternary ammonium fluoride deposited on a resin with the following formula: Or the following formula

[Formula] is reacted with chloride Z ₁ , and the resulting corresponding fluoride Z ₂ is reacted with N-bromsuccinimide in the presence of azoisobutyronitrile to form the following formula: Or the following formula

A mixed brominated fluorinated derivative Z ₃ of the formula is obtained, and this compound is then converted to the following general formula (wherein R has the meaning given above and M represents an ion derived from an alkali metal). For the production of fluoride Z ₂ , a resin of the type Amberlite A26, sold by Rohm and Haas, is advantageously used, which is first washed by percolation with an aqueous sodium hydroxide solution; It is then washed with water until it becomes neutral. The wet resin is then dehydrated by stirring in an aqueous hydrofluoric acid solution, washing with water, and then washing with an organic solvent. Fluorination of the chloride Z ₁ with the resin so prepared is advantageously carried out in an organic solvent such as toluene. Fused in the presence of azoisobutyronitrile
The preparation of the hybrid brominated fluorinated derivative Z ₃ by condensation of Z ₂ with N-bromsuccinimide is conveniently carried out in carbon tetrachloride under reflux. The condensation of the hybrid brominated fluorinated derivative Z ₃ with the sodium salt of the acid of formula is advantageously carried out in an organic solvent such as dimethylformamide. Many of the compounds of formula _B are well known for their particularly strong insecticidal properties (in particular French patent no.
No. 2185612 and French Patent Application Publication No. 2364884
(see issue). In this regard, 1R, cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl, 1R, cis-2 ,2-dimethyl-
3-(2′,2′-dichlorovinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl or 1R,trans-2,2-dimethyl-3-(1′,2′- Dibromo-2',2'-dichloroethyl)cyclopropane-1-carboxylic acid RS-α
-Cyano-3-phenoxybenzyl is mentioned. The process for making compounds of formula _A and their use in making compounds of formula _B represents a new economical approach to compound _B. This has the advantage of using readily available drugs and leading to high yields of compound _B. Additionally, this approach is difficult to use for α-cyano-3-, a compound that is unstable and requires careful handling.
This avoids the use of phenoxybenzyl alcohol. The compounds of formula used at the beginning of the process are known compounds. Among these, the following general formula The acid chloride of is described in French Patent Application No. 2364884, which also includes the preparation of the corresponding acid. Other acid halides are obtained by standard methods starting from the acids described in French Patent Application No. 2,364,884. The examples below are illustrative of the invention and do not limit it in any way. Example 1: 1R, cis-2,2-dimethyl-3-(2',
2′-Dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl 6.4 g of 1R,cis-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
- Add 10 mg of molten zinc chloride (powdered) to a mixture of carboxylic acid chloride and 4 g of m-phenoxybenzaldehyde. An increase in temperature and thickening of the medium is observed. Leave in contact for a further 1 hour at 20° C. under strictly anhydrous conditions. Crude 1R,cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl is obtained. Infrared spectrum (chloroform) Characteristic absorption NMR spectrum of C=O at 1749 cm ^-1 (deuterochloroform) gem - 1.26, which is the characteristic of hydrogen in methyl
The peak at 1.33ppm is 1.85-, which is characteristic of cyclopropyl hydrogen.
The peak at 2.10ppm, the peak at 6.76-6.90ppm which is characteristic of ethylenic hydrogen, and the characteristic of aromatic and benzylic hydrogen.
Peaks at 7.0ppm and 7.66ppm. 1R, cis-2,2-dimethyl-3-(2′,2′-
Dibromvinyl) cyclopropane-1-carboxylic acid chloride is an example of French Patent No. 2185612.
It can be obtained by a method similar to that described in 16 and 17. Example 2: 1R, cis-2,2-dimethyl-3-(2′,
2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl Produced in an analogous manner to Example 1, adding 10 mg of zinc chloride.
The crude 1R,cis-2,2-
Dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-
3-Phenoxybenzyl is obtained. Example 3: 1R, cis-2,2-dimethyl-3-(2′,
2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl Produced in an analogous manner to Example 1, adding 10 mg of zinc chloride.
Replaced with 60 mg of p-toluenesulfonic acid hydrate,
After stirring for 20 hours, the crude 1R, cis-2,
2-dimethyl-3-(2',2'-dibromvinyl)
Cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl is obtained. Example 4: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl Produced in a similar manner to Example 1, replacing 10 mg of zinc chloride with 1 drop of 65% oleum, and After stirring for 1 hour, the crude 1R,cis-2,2-dimethyl-
3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl is obtained. Example 5: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromovinyl)cyclopropane-1-carboxylic acid RS-α-bromo-3-phenoxybenzyl 5.66 g of 1R,cis-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
- Add 5 mg of zinc chloride to a mixture of carboxylic acid bromide and 3.11 g of m-phenoxybenzaldehyde. An increase in temperature and thickening of the reaction mixture is observed.
Leave again for 1 hour under fully anhydrous conditions at 20°C.
1R,cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid
RS-α-bromo-3-phenoxybenzyl is obtained. Infrared spectrum (chloroform) Characteristic absorption NMR spectrum of carboxyl at 1750 cm ^-1 (deuterochloroform) gem - 1.26, which is the characteristic of hydrogen in methyl
The peak at 1.33ppm is 1.75- which is the characteristic of hydrogen in cyclopropyl.
2.16ppm peak, 6.76-6.88ppm peak characteristic of ethylenic hydrogen, 7.0 characteristic of phenyl and benzyl hydrogen.
-7.75ppm peak 1R,cis-2,2-dimethyl-3-(2',2'-
Dibromvinyl)cyclopropane-1-carboxylic acid bromide can be obtained by the following method. 60 c.c. of toluene was dissolved in 18 g of 1R, cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid, 0.2 cc of pyridine, then 6 c.c. Gradually add phosphorus tribromide of .
After stirring for 6 days at 20°C, the viscous oil formed at the bottom of the reaction mixture was separated by decantation, the solvent was removed by vacuum distillation, and the residue was rectified to give 14 g of 1R, cis-2,2-dimethyl-
3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid bromide is obtained. BP=110℃/
0.2mmHg. Infrared spectrum (chloroform) Characteristic absorption NMR spectrum of carboxyl at 1792 cm ^-1 (deuterochloroform) gem - 1.32, which is the characteristic of hydrogen in methyl
The peak at 1.36ppm is characteristic of hydrogen at the 1-position of cyclopropyl.
The peak at 2.12-2.26-2.40ppm is characteristic of hydrogen at the 3-position of cyclopropyl.
Peak at 2.66-2.80ppm, peak at 6.53-6.66ppm which is characteristic of ethylenic hydrogen Example 6: 1R,trans-2,2-dimethyl-3-(2',
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl 6.4 g of 1R,trans-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
- Add 10 mg of zinc chloride to a mixture of carboxylic acid chloride and 4 g of m-phenoxybenzaldehyde and stir for 1 hour to form 1R, trans-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclo Propane-1-carboxylic acid RS-α-chloro-3-
Obtain a solution of phenoxybenzyl. Example 7: 1R, cis-2,2-dimethyl-3-(2′,
2′-dichlorovinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl 4.6 g of 1R,cis-2,2-dimethyl-3-
(2′,2′-dichlorovinyl)cyclopropane-1
- Add 10 mg of zinc chloride to a mixture of carboxylic acid chloride and 4 g of m-phenoxybenzaldehyde, stir for 1 hour, and prepare 1R,cis-2,2-dimethyl-3-(2',2'-dichlorovinyl)cyclo A solution of propane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl is obtained. Example 8: 2,2-dimethyl-3R-(2'-methyl-
1'-propenyl)cyclopropane-1R-carboxylic acid RS-α-chloro-3-phenoxybenzyl 1.89 g of 2,2-dimethyl-3R-(2'-methyl-1'-propenyl)cyclopropane-1R - Add 10 mg of zinc chloride to a mixture of carboxylic acid chloride and 2 g of m-phenoxybenzaldehyde,
Stir for 30 minutes to obtain 3.89 g of crude 2,2-dimethyl-3R-(2'-methyl-1'-propenyl)cyclopropane-1R-carboxylic acid RS-α-chloro-3-phenoxybenzyl. . Example 9: 2-(p-chlorophenyl)-2-isopropylacetic acid RS-α-chloro-3-phenoxybenzyl 4.7 g of 2-(p-chlorophenyl)-2-isopropylacetic acid chloride and 4 g of m-phenoxybenzyl Add 10 mg of zinc chloride to the mixture with cibenzaldehyde and stir at 20°C for 3 hours to obtain a solution of RS-α-chloro-3-phenoxybenzyl 2-(p-chlorophenyl)-2-isopropylacetate. Example 10: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chlorcinnamyl 4.84 g of 1R,cis-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
- Add 10 mg of zinc chloride to a mixture of carboxylic acid chloride and 2.22 g of cinnamaldehyde, and add 10 mg of zinc chloride to the mixture at 20°C.
Stir for an hour, 7.06g of crude 1R, cis-2,2
-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-chlorcinnamyl is obtained. MP = approximately 82℃. Example 11: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-fluoro-3-phenoxybenzyl
It can be obtained by reacting 2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid fluoride and m-phenoxybenzaldehyde. This can also be obtained in the following way. Step A: Production of fluorinated m-phenoxybenzyl a resin According to the method reported by Messrs. G. Cainelli and F. Manescalchi (Synthesis 1976 , 472). 220g Rohm and Haas
The Amberlite A26 resin is washed by percolation with 1.5 of a 1N aqueous sodium hydroxide solution and then washed with water until neutral. OH―
The wet resin containing the groups is stirred in an approximately 1N aqueous solution of hydrofluoric acid at 20° C. for 20 hours, then filtered under vacuum, washed thoroughly with water, and then with acetone and ether. Finally, the resin is dried under reduced pressure at 50° C. for 10 hours. b Production of m-phenoxybenzyl chloride 10.5g m-phenoxybenzyl chloride, 150c.c.
of toluene and 40 g of the resin obtained in step b above are heated to 100° C. for 20 hours with stirring. Separate the resin, wash with methylene chloride, remove the solvent by vacuum distillation, and rectify the residue.
g of m-phenoxybenzyl fluoride is obtained. B.P.
=93℃/0.05mmHg. NMR spectrum (deuterochloroform) - Peak at 4.91-5.71 ppm, which is characteristic of hydrogen in CH ₂ F, peak at 6.91-7.6 ppm, which is characteristic of hydrogen in aromatic nucleus Step B: 1-bromofluoromethyl-3 - Phenoxybenzene 2 g of m-phenoxybenzyl fluoride, 2 g of N-bromsuccinimide and 50 mg of azoisobutyronitrile are added to 20 c.c. of carbon tetrachloride, and the reaction mixture is refluxed. It continued for 1 hour, was cooled, the succinimide was separated off, concentrated to dryness by vacuum distillation, and the residue was dissolved in petroleum ether (BP=35-75
1.8 g of 1-bromofluoromethyl-3-phenoxybenzene are obtained. Analysis: Calculation: C%55.54 H%3.58 Br%28.42 F%6.75 Actual measurement: 56.1 3.7 28.0 6.4 NMR spectrum (deuterochloroform)

A peak at 6.43-7.75ppm, which is characteristic of hydrogen in [Formula], a peak at 6.91-7.5ppm, which is characteristic of hydrogen in aromatic nuclei, Step C: 1R, cis-2,2-dimethyl-3-(2' ，
2′-dibromovinyl)cyclopropane-1-carboxylic acid RS-α-fluoro-3-phenoxybenzyl 1.19 g of 1-bromofluoromethyl-3-phenoxybenzene in 10 c.c. of dimethylformamide.
1.5 g of 1R,cis-2,2-dimethyl-3-(2′,
2'-Dibromvinyl)cyclopropane-1-carboxylic acid sodium salt was added, stirred at 20°C for 17 hours, the reaction mixture was poured into ice-cold water, extracted with benzene, and after the usual work-up concentrated to dryness by vacuum distillation. harden Crude 1R,cis-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
-A residue corresponding to the carboxylic acid RS-α-fluoro-3-phenoxybenzyl is formed, but the two diastereomers are separated from petroleum ether (BP).
= 35~75℃) and ethyl ether (95/
5) is separated by chromatography using silica gel as an eluent. 0.530 g of the more mobile diastereomer A (MP = 80°C), 0.700 g of the less mobile diastereomer (MP = 50°C) and 0.420 g of a mixture of both isomers, i.e. A total of 1.65 g of 1R,cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-fluoro-
3-Phenoxybenzyl is obtained. The more mobile isomer (MP=80°C), isomer A, has the following properties: NMR spectrum (deuterochloroform) gem - 1.32, which is the characteristic of hydrogen in methyl
A peak at 1.35ppm, a peak at 6.8-7.71ppm which is characteristic of hydrogen bonded to the same carbon atom as fluorine, and a peak at 1.85- which is characteristic of hydrogen in cyclopropyl.
Peak at 2.1ppm, 6.66ppm which is characteristic of hydrogen in aromatic nucleus.
7.83 ppm peak circular dichroism (dioxane) Δε = +0.30, 284 nm (max) Δε = +0.25, 278 nm (max) Δε = +10.8, 215 nm (max) Less mobile isomer ( MP=50℃),
That is, isomer B has the following properties. NMR spectrum (deuterochloroform) A peak at 1.28 ppm, which is characteristic of hydrogen in gem-methyl, a peak at 6.8-7.7 ppm, which is characteristic of hydrogen bonded to the same carbon atom as fluorine, and a characteristic of hydrogen in cyclopropyl. 1.86―
Peak at 2.25ppm, peak at 6.8-7.6ppm which is characteristic of hydrogen in aromatic nuclei Circular dichroism (dioxane) Δε=-0.77, 277nm (maximum) Δε=-12.5, 227nm (maximum) Δε=+7. 23, 207nm (maximum) Example 12: 1R,trans-2,2-dimethyl-3-(1',
2'-dibromo-2',2'-dichloroethyl)cyclopropane-1-carboxylic acid R,S-α-chloro-3-phenoxybenzyl 8 g of 3-phenoxybenzaldehyde and 11.5
1R, trans-2,2-dimethyl-3-(1',
Mix with 2′-dibromo-2′,2′-dichloroethyl)cyclopropane-1-carboxylic acid chloride, heat to obtain a homogeneous liquid, cool to 20°C, add 0.150 g of anhydrous zinc chloride, and stir. The crude 1R,trans-2,2-dimethyl-3-(1',2'-dibromo-2',2'-dichloroethyl)cyclopropane-1-carboxylic acid R,S ―
α-chloro-3-phenoxybenzyl is obtained. The infrared spectrum of this compound has a characteristic absorption (carbonyl) at 1750 cm ^-1 . The NMR spectrum confirms the absence of aldehyde protons. Example 13: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl In 50 c.c. of anhydrous acetonitrile, 5.5 g of the crude α-chlorinated derivative obtained in Example 1 and 0.8 g of anhydrous potassium cyanide, stirred at 20°C for 17 hours, added water and extracted with benzene, after normal treatment, 5.6 g of crude product was recovered, which was dissolved in petroleum ether (BP=35-75 It was purified by chromatography on silica gel using a mixture (9/1) of
1R,cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid
RS-α-cyano-3-phenoxybenzyl is obtained. Example 14: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl α- obtained in Example 5 by a method analogous to Example 13
Starting from the brominated derivative, 1R, cis-2,2-
Dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-
3-Phenoxybenzyl is obtained. Example 15: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl 1.17 g of the crude α-fluorinated derivative obtained in Example 11 was dissolved in 15 c.c. of acetonitrile. , stirred for 17 h at 20°C, and the residue was chromatographed on silica gel with a mixture of petroleum ether and ether (9/1) as eluent to obtain 1 g of 1R, cis-
2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1R-carboxylic acid RS-α-
Cyano-3-phenoxybenzyl is obtained. Example 16: 1R,trans-2,2-dimethyl-3-(2',
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl 1R,trans-2,2-dimethyl-3-(2′,2′-dibromvinyl) obtained in Example 6 ) 90 c.c. of acetonitrile and a solution of cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl
Add 1.5 g of potassium cyanide, stir for 16 hours, add water, extract with benzene and then, after conventional treatment, concentrate to dryness by distillation under reduced pressure. The residue was chromatographed on silica gel eluting with a mixture of benzene and cyclohexane (6/4) and 7.5 g of 1R,trans-2,2-
Dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyano-
3-Phenoxybenzyl is obtained. Example 17: 1R, cis-2,2-dimethyl-3-(2′,
2'-dichlorovinyl)cyclopropane-1-carboxylic acid RS-α-cyano-3-phenoxybenzyl 1R,cis-2,2-dimethyl- obtained in Example 7
A solution of 3-(2',2'-dichlorovinyl)cyclopropane-1-carboxylic acid RS-α-chloro-3-phenoxybenzyl with 80 c.c. of acetonitrile
Add 1.5 g of potassium cyanide, stir for 17 hours, add water, extract with benzene, after standard work-up, concentrate to dryness by vacuum distillation, and dissolve the residue in a mixture of benzene and cyclohexane (6/4). Chromatographed on silica gel as eluent, 6.4 g of 1R,cis-2,2-dimethyl-3-
(2′,2′-dichlorovinyl)cyclopropane-1
-Carboxylic acid RS-α-cyano-3-phenoxybenzyl is obtained. Example 18: 2,2-dimethyl-3R-(2'-methyl-
1′-propenyl)cyclopropane-1R-carboxylic acid RS-α-cyano-3-phenoxybenzyl 3.09 g of the crude 2,2-dimethyl-3R- obtained in Example 8 in 50 c.c. of acetonitrile. Dissolve (2′-methyl-1′-propenyl)cyclopropane-1R-carboxylic acid RS-α-chloro-3-phenoxybenzyl, add 1.1 g of potassium cyanide,
Stir for 48 hours, add ice, extract with benzene,
Dehydrate over magnesium sulfate, filter, and concentrate to dryness by vacuum distillation. The residue (3.96 g) was chromatographed on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9/1) and 0.48 g of 2,2-dimethyl-3R-(2'-methyl-1' -propenyl)cyclopropane-1R-carboxylic acid RS-α-cyano-3-phenoxybenzyl is obtained. Infrared spectrum (chloroform) Characteristic absorption of carbonyl at 1733 cm ^-1 , characteristic absorption of aromatic nucleus at 1487-1587 cm ^-1 Example 19: 2-(p-chlorophenyl)-2-isopropylacetic acid RS-α-cyano-3-phenyl Enoxybenzyl 2-(p-chlorophenyl)- obtained in Example 9
Add 80 c.c. of acetonitrile and 1.5 g of potassium cyanide to a solution of RS-α-chloro-3-phenoxybenzyl 2-isopropylacetate, stir at 20°C for 72 hours, add ether, and separate the resulting insoluble matter. The liquid was concentrated to dryness by distillation under reduced pressure, and the residue was chromatographed on silica gel using a mixture of cyclohexane and acetone (95/5) as an eluent to obtain 6.5 g of 2-(p-chlorophenyl)-. 2-Isopropylacetic acid RS-α-cyano-
3-Phenoxybenzyl is obtained. Example 20: 1R, cis-2,2-dimethyl-3-(2′,
2′-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-cyanocinnamyl 4.76 g of the crude 1R, cis-2, obtained in Example 10,
2-dimethyl-3-(2',2'-dibromvinyl)
1.5 g of potassium cyanide was added to a solution of cyclopropane-1-carboxylic acid RS-α-chlorcinnamyl dissolved in 75 c.c. of acetonitrile.
Stir for a while, add ice, extract with benzene, wash with water, dehydrate over magnesium sulfate, filter, and concentrate to dryness by distillation under reduced pressure. 5.3 g of the residue was chromatographed on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9/1) to give 1.76 g of 1R,cis-2,2-dimethyl-3-
(2′,2′-dibromvinyl)cyclopropane-1
-Carboxylic acid RS-α-cyanocinnamyl. Analysis: C ₁₈ H ₁₇ Br ₂ NO ₂ (439.16) Calculation: C%49.2 H%3.9 Br%36.4 N%3.2 Actual measurement: 49.5 4.1 34.2 2.8 Example 21: 1R,trans-2,2-dimethyl-3-(1 ′、
2'-dibrome-2',2'-dichloroethyl)cyclopropane-1-carboxylic acid R-α-cyano-3-phenoxybenzyl and 1R, trans-
2,2-dimethyl-3-(1',2'-dibromo-
2′,2′-dichloroethyl)cyclopropane-1
-Carboxylic acid S-α-cyano-3-phenoxybenzyl 17.8 g of the crude 1R,trans-2, obtained in Example 12,
2-dimethyl-3-(1′,2′-dibrome-2′,
2′-dichloroethyl)cyclopropane-1-carboxylic acid R,S-α-chloro-3-phenoxybenzyl dissolved in 200 c.c. of benzene.
Add 20 g of potassium cyanide and stir while stirring.
℃ for 50 hours, diluted with water, extracted with benzene, concentrated to dryness, and the residue was chromatographed on silica gel using a mixture of ether and petroleum ether (1/9) as eluent. 1R,
trans-2,2-dimethyl-3-(1',2'-dibromo-2',2'-dichloroethyl)cyclopropane-
R-α-cyano-3-phenoxybenzyl 1-carboxylate (Compound A), then 1.13 g of 1R, trans
-2,2-dimethyl-3-(1',2'-dibrome-
2′,2′-dichloroethyl)cyclopropane-1-
S-α-cyano-3-phenoxybenzyl carboxylate (Compound B) is isolated. The NMR spectrum of compound A (deuterochloroform) shows the following characteristics. Peaks characteristic of the methyl hydrogen at the 2-position of cyclopropyl at 1.32-1.35 ppm, peaks characteristic of the hydrogen at the 1' position of the ethyl side chain at 4.18 and 4.35 ppm and 4.35 and 4.53 ppm, and the nitrile group at 6.37 ppm. The NMR spectrum of compound B (deuterochloroform) shows the following characteristics: Peaks corresponding to the methyl hydrogen at the 2-position of cyclopropyl at 1.2-1.25-1.32 ppm, peaks attributable to the proton at the 1' position of the ethyl side chain at 4.21-4.38-4.37-4.53 ppm, and the benzyl proton at 6.46 ppm. peak attributed to.

Claims (1)

[Claims] 1. The following general formula _B in all forms of stereoisomers or in the form of mixtures of stereoisomers: [Here, (a) R ₁ is the following group R′ ₁ {Here, Y ₁ represents a hydrogen atom, and Y ₂ represents the following group Y′ ₂ or Y ₁ represents a hydrogen atom and Y ₂ represents the following group (Y ₃ and Y ₄ are the same and represent a fluorine, chlorine or bromine atom, or Y ₃ and Y ₄ each represent a methyl group). and this
R′ ₁ group is Y ₂ is the following group represents a racemic or optically active acid residue with cis or trans structure, or a mixture of cis-structure acid and trans-structure acid residue}, or ( b) R ₁ is the following group R″ ₁ (Here, Z represents a hydrogen atom or a chlorine atom.
and this R″ ₁ group corresponds to a racemic or optically active acid residue), and R ₂ is the following formula when Y ₂ is different from the group Y′ ₂ or the residue of or when R ₂ represents the group Y′ ₂ , _the following formula furthermore, the presence of an asymmetric carbon atom with a group CN is
For esters obtained from acids of well-defined stereoisomerism, resulting in the existence of two diastereomers (referred to as isomer A and isomer B) ^. The resulting compound in all forms of stereoisomers or in the form of a mixture of stereoisomers has the following general formula: (where R ₁ and R ₂ are as described above,
X represents a fluorine, chlorine or bromine atom. Furthermore, the presence of an asymmetric carbon atom bearing the group X results in the existence of two diastereomers (termed isomer A and isomer B) for esters obtained with well-defined stereoisomeric acids. . ₎ to obtain a compound of formula _B , which compound is in a stereoisomeric form corresponding to the stereoisomeric form of the compound of formula _A used. 2 The following general formula in all forms of stereoisomers or in the form of mixtures of stereoisomers: [Here, R ₂ is as described in claim 1, and X represents a fluorine, chlorine or bromine atom, and R represents the following group R' (Here, Y ₁ represents a hydrogen atom, and Y ₂ represents the following group. (Y ₃ and Y ₄ are the same and represent a fluorine, chlorine or bromine atom, or Y ₃ and Y ₄ each represent a methyl group). and this
R′ is the group where Y ₂ is , it corresponds to a racemic or optically active acid residue with a cis or trans structure, or a mixture of a cis-structure acid and a trans-structure acid residue)
or R is a group R″ ₁ as defined in claim 1
The following general formula _C in the form of the corresponding stereoisomer is obtained using a compound with the structure of 2. A process according to claim 1, characterized in that a compound of: (wherein R and R ₂ are as defined above) is obtained. 3. The method according to claim 1 or 2, wherein in general formula _A or X, X represents a fluorine or chlorine atom. 3. A method according to claim 1 or 2, characterized in that the condensation with the agent generating 4 CN ^- ions is carried out in an anhydrous organic solvent selected from the group consisting of acetonitrile and dimethylformamide. 5. Claim 1, wherein the agent that generates CN ^- ions is an alkali cyanide.
Or the method described in Section 2. 6 The compound of general formula _A used is 1R, cis-
2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-
chlor-3-phenoxybenzyl, and
1R,cis-2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid
The method according to claim 1, characterized in that RS-α-cyano-3-phenoxybenzyl is obtained. 7 The compound of general formula _A used is 1R, cis-
2,2-dimethyl-3-(2',2'-dibromvinyl)cyclopropane-1-carboxylic acid RS-α-
fluoro-3-phenoxybenzyl, and 1R, cis-2,2-dimethyl-3-(2′,2′-
The process according to claim 1, characterized in that RS-α-cyano-3-phenoxybenzyl dibromvinyl)cyclopropane-1-carboxylic acid is obtained. 8 The compound of general formula _A used is 1R, cis-
2,2-dimethyl-3-(2',2'-dichlorovinyl)cyclopropane-1-carboxylic acid RS-α-
chlor-3-phenoxybenzyl, and
1R,cis-2,2-dimethyl-3-(2',2'-dichlorovinyl)cyclopropane-1-carboxylic acid
The method according to claim 1, characterized in that RS-α-cyano-3-phenoxybenzyl is obtained. 9 The compound of general formula _A used is 2-p-chlorophenyl-2-isopropylacetic acid RS-α-
chloro-3-phenoxybenzyl, and 2-p-chlorophenyl-2-isopropylacetic acid
The method according to claim 1, characterized in that RS-α-cyano-3-phenoxybenzyl is obtained. 10 The compound of general formula _A used is 1R,
trans-2,2-dimethyl-3-(1',2'-dibrome-2',2'-dichloroethyl)cyclopropane-1
-Carboxylic acid RS-α-chloro-3-phenoxybenzyl or 1R,trans-2,2-dimethyl-3
-(1′,2′-dibrome-2′,2′-dichloroethyl)
cyclopropane-1-carboxylic acid RS-α-fluoro-3-phenoxybenzyl, and
1R, trans-2,2-dimethyl-3-(1',2'-
The process according to claim 1, characterized in that RS-α-cyano-3-phenoxybenzyl dibromo-2',2'-dichloroethyl)cyclopropane-1-carboxylate is obtained.