CS268964B1 - Process for preparing enantiomeric pairs of substituted cyclopropanecarboxylic acid cyanobenzyl esters - Google Patents

Abstract

The method for preparing an enantiomeric pair of the configuration e<-S, lRCisj <=Z.-R, lScis oi- -cyano-3-phenoxybenzyl esters of substituted cyclopropanoic acids of the general formula I, where X and Y represent a hydrogen atom or a halogen atom and where Z represents an alkenyl group, each with 1 to 5 carbon atoms and each substituted with 2 to 4 halogen atoms, consists in treating the enantiomeric pair of the configuration <7<-R, lRcisj o<S-S, lScis of the general formula I at a temperature of -10 to 80 °C with ammonium carbonate in an inert solvent and optionally in the presence of seed crystals. The insecticidal activity can be increased by the method described above.

Description

CS 268964 Bl 1 the present invention relates to a method for preparing enantiomeric pairs of -cyanobenzyl esters of substituted cyclopropanecarboxylic acids of the general formula i, where X and Y represent a hydrogen atom or a halogen atom and where z represents an alkenyl group with 1 to 5 carbon atoms, each substituted with 2 to 4 halogen atoms. In particular, the invention relates to a method for preparing enantiomeric pairs of the general formula i in the stereochemical configuration ^Z.~s, IRCis* <Z--r, ISCis by epimerization of an enantiomeric pair of the same formula I in the configuration <Z.-R, IRCisJ «X. -S, ISCis. Epimerization is understood to mean a change in configuration at the benzyl carbon denoted in formula I by the letter oí. . The configuration notation used is based on the proposal of M. Elliott, N. F. Sanes and o. A. Pulmann, presented in the patent document Brit. Pat. 1 604 682 (Int. Cl? , C07C 121/75J filed 30.5.1978). The practical significance of this epimerization lies in the different insecticidal efficacy of the enantiomeric pairs mentioned. It is known (see for example M. Elliot, A. Farnham, N. 0. Jones, o. M. Doderlund: Pestic. Sci. 9, 112, 1978) that enantiomeric pairs of formula I with the configuration oZ.-s, IRCisJ «Z.-R, IScis show in biological tests an order of magnitude higher insecticidal efficacy than the corresponding enantiomeric pairs with the configuration ©Z -r, iRCisJ e>Z-s, IScis.

It is known that the epimerization of the enantiomeric pairs mentioned requires the presence of a catalyst. Basic reagents from the group of ammonia, anions, carbonates, fluorides and hydroxides of alkali metals have so far been used as catalysts (see for example Fr. Pat. 2 481 274, Fr. Pat. 2 481 275, Fr. Pat. 2 470 117). However, the action of these catalysts is not always completely satisfactory. Some catalysts from the mentioned group show low efficiency, allowing work only at high temperatures, when working with other catalysts of the mentioned group, side reactions (hydrolysis, aminolysis, etc.) are often used. Certain difficulties are also encountered with the handling and separation of these catalysts.

The above disadvantages are eliminated by the method of preparing enantiomeric pairs of general formula I in the configuration cZ-S, IRcisJ <?Z-R, IScis according to the invention, the essence of which consists in treating the enantiomeric pair of general formula I in the configuration oZ-r, ircisJ cZ. -S, IScis, or any mixture thereof with the corresponding enantiomeric pair in the configuration oZ. -S, IRCisJ eZ. -R, IScis, at a temperature of -10 °C to 80 °C with ammonium carbonate in an inert organic solvent, for example in alcohols or ethers.

The preparation method according to the invention can be carried out in two different ways. In the first way, the epimerization is carried out in a homogeneous environment, where the products remain dissolved in the reaction medium. In such a case, a mixture is formed containing the enantiomeric pairs ©Z-s, IRclsJ ©Ó-R, IScis'a oZ-r, IRcisJ ©Z.-S, IScis in an equilibrium, thermodynamic ratio. This mixture must be separated into individual enantiomeric pairs by known methods (for example, crystallization) and the unwanted enantiomeric pair (usually -r, IRcisJ řZl-S, IScis) must be returned to the next epimerization cycle. The crystallization of the desired enantiomeric pair can be initiated by the addition of seed crystals.

In the second, more preferred procedure, the epimerization is carried out at temperatures, or in solvents, when the enantiomeric pair ©Z -s, IRclsj oZ-r, IScis is gradually precipitated from the solution, or from the melt in the form of crystals. In this procedure, with a suitable choice of reaction parameters, for example the amount and nature of the solvent and temperature, it is possible to achieve a practically quantitative yield of the desired enantiomeric pair in one or two epimerization cycles,

The epimerization according to the invention can be carried out in an inert solvent from the group of ethers, nitriles and aromatic hydrocarbons or even without a solvent, preferably in a solvent selected from the group of alcohols, optionally in the presence of seed crystals. In this case, it is not necessary to start from a pure enantiomeric pair of CZ. -R, IRcisJ o4 -S, IScis. It is preferable to start from technically available mixtures of enantiomeric pairs X.-R, IRcisJ oC-s, IScis and X.-R, IScisJ ©Z-s, IRcis.

The preparation method according to the invention is further illustrated by the following examples, which, however, do not limit the scope of the invention in any way.

CS 268964 Bl

Example 1

A mixture of -s, IRcis and <Z-R, IScls esters of general formula I, where z » 2,2-dichlorovinyl · X · Y · Η.

g of a roughly equimolar mixture of stereoisomers of the configuration e<.-R, IRcis, -R, IScls, c»ZS, IScls and «Z.-S, IRcis, of the general formula I with the meaning given above, was dissolved in 60 ml of isopropyl alcohol and stirred with 1 g of ammonium carbonate for 24 hours at room temperature, after cooling with ice the solid portion was filtered off with suction and washed with chilled isopropyl alcohol. 7 g of a crystalline product consisting mainly (95%) of the enantiomeric pair of isomers ct4.-r _of IScls and IRcis in a ratio of 1 : 1 was obtained. The mother liquors were used in the next epimerization cycle.

Example 2

The procedure is as in Example 1, except that only half of the catalyst was used. The result after three days of stirring at room temperature and subsequent cooling is practically identical to Example 1.

Example 3 comparison of the catalytic efficiency of ammonium, sodium and potassium carbonate in the epimerization of an equimolar mixture of stereoisomers -R, IRcis, <xú-S, IScis, ^-r, iscis and <yC-S, IRcis of general formula I, where z dichlorovinyl.

1 g of the above mixture of stereoisomers was weighed and dissolved in 6 ml of isopropyl alcohol containing a known amount of internal standard (benzophenone). After addition of catalyst (5% by weight), the mixture was magnetically stirred at 25 °C and samples of the liquid phase (free of crystals forming) were taken at selected time intervals for composition determination (HPLCJ 250 x 4.6 mm Lichrosorb 5 Si 100? mobile phase petroleum ether-0.5% ethyl acetate* flow rate 1 ml/min.). The observed losses of stereoisomeric pairs A (oZL-S, IRcis and «4 -R,1Scis) and 8 (-S, IScis and ©4 -R, IRcis) are summarized in the table.

catalyst concentration of pairs A and 8 in mg/ml in the liquid phase A 0 hours 8 24 A h B A 48 hours B 72 i A h 8 _{NH42CO3 ​} 80 108 26 73 16 29 11 21 ^Na 2 ^C0 3 ' 80 112 31 106 21 38 18 33 to ₂ what ₃ 5 88 and and and and and and

^and Extensive formation of decomposition products.

example 4

Stereoisomeric pair ©4 -S, IRcisJ -R, IScls of the compound of general formula I, where Z = dichlorovinyl, X « 4-F and Y » H . 2 g of a 1 : 1 mixture of stereoisomers of the ester of formula I, where z, X and Y have the meaning given above, in the configuration c^—R, IRcis and cZ-S, IScls are dissolved in 4 ml of isopropyl alcohol, 0.2 g of ammonium carbonate is added and the mixture is stirred at a temperature of 20 °C, then cooled with ice, seed crystals of the isomeric pair °Z--S, IRcis and e£.-R, IScls are added, solid

CS 268964 Bl product ee is filtered off with suction, washed and dried, the product consists predominantly (95%) of the stereoisomeric pair of configurations <Z.-S, IRcis and «Ζ-r, iscis.

Example 5

Stereoisomeric pair —S, IRcis and eZ-R, iScis of compounds of general formula i, where x«Y«Haz= dichlorovinyl

A mixture (2 g) of stereoisomers of formula I, where X, Y and Z are as defined above, consisting of isomers oí. -r, IRcis, oC -s, IScis, .Z-R, IScis and eZ -S, IRcis, in a ratio of approximately 1:1:1:1 was epimerized under the conditions of Example 1, but at a temperature of 0 ° C (two weeks) and then at a temperature of -10 ° (two weeks). 9.2 g of crystalline product consisting mainly of the pair of isomers <Z- -R, iscis and Z.-S, ircis (> 95%) in a ratio of 1:1 was obtained.

Example 6

Establishment of thermodynamic equilibrium between stereoisomeric pairs «< -s, iRcisj ®Z-r, IScis and -S, IScis, σί. -R, iRcis of the ester of general formula I, where X«Y*HaZ« 3,3,3-trifluoro-2-chloro-1-propen-1-yl.

g of a mixture of the above enantiomeric pairs in a ratio of approximately 1:8 was heated with 0.2 g of ammonium carbonate in 10 ml of tetrahydrofuran to boiling, i.e. 55 °C until thermodynamic equilibrium was established (ratio of pairs -S, IRcis^ «Ζ -R, IScis : σΖ -R, IRcisj <?Z-S, IScis approximately 1:1).

Example 7

Establishment of thermodynamic equilibrium between pairs of enantiomers <Z~S, IReisj cZ -R, IScia and ©Z -S, IScisj <Z -R, ircis of the ester of general formula I, X = Y H* Z = dichlorovinyl

A mixture of the above enantiomeric pairs was worked with in a ratio of approximately 1:8 under the conditions of Example 6. The mixture obtained consists of the enantiomeric pairs «Ζ- S, IRcisj σΖ-R, IScis and oZ-r, íRcisj »Z-S, IScis in a ratio of approximately 1:1.

Claims (1)

SUBJECT OF THE INVENTION A method for preparing an enantiomeric pair of cZ-cyanobenzyl esters of substituted cyclopropanecarboxylic acids, of the configuration eZ-S, 1 Rcisj cZ-r, IScis, of the general formula I, where X and Y represent a hydrogen atom or a halogen atom and where z represents an alkenyl group, each with 1 to 5 carbon atoms and each substituted with 2 to 4 halogen atoms, characterized in that the enantiomeric pair of the configuration cZ-r, iRcisj cZ-S, IScis of the general formula I, or a mixture thereof, with the corresponding enantiomeric pair of the configuration oZ-S, IRcisj eZ-R» IScis is treated at a temperature of -10 to 80 °C with ammonium carbonate in the presence of an inert solvent, for example alcohols or ethers and optionally in the presence of seed crystals of the desired enantiomeric pair.