JPS6337783B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a highly active α-cyano-3-phenoxybenzyl 2,2-dimethyl-3-(2,
The present invention relates to a method for producing a stereoisomer mixture of 2-dichlorovinyl)-cyclopropanecarboxylate (hereinafter abbreviated as cypermethrin). Cypermethrin is a new pyrethroid compound discovered by M. Elliott et al.
In recent years, along with new pyrethroids that have a similar structure, their high insecticidal and acaricidal efficacy, appropriate residual efficacy, and safety for mammals have been recognized, and they are gaining an important position not only for epidemic prevention purposes but also for agricultural purposes. be. Cypermethrin is a compound with the structure shown in formula (), It has two asymmetric carbon atoms on the acid side and one asymmetric carbon on the alcohol side, and the "racemic form" synthesized by normal methods is actually a mixture of eight isomers. (Table 1 below
(abbreviated as shown)

[Table] In addition, acid side dl-cis ester (hereinafter simply referred to as cis-form), dl-trans-form ester (hereinafter simply referred to as trans-form)
When these two peaks are separated using a chromatographic means (for example, liquid chromatography conditions described below) that are suitable for separation, each peak is separated into two peaks. The order to elute this component is cisX, cisY, transX and
Call it transY. Here, cisX consists of cisAβ and cisBα, cisY consists of cisAα and cisBβ, and transX
Consists of transAβ and transBα, transY is transAα
and transBβ. cis unless otherwise noted
cisX, cisY, trans, transX, transY are themselves racemic. In addition, cisX and transX and cisY and transY are collectively referred to as X-form and Y-form, respectively.
It's called a body. The relationship between the configuration and insecticidal power of Cypermethrin is already known, and among these eight isomers,
The substances that have practical efficacy are cisAα and transAα (JP-A-52-131559, Akeda et al., Agr.
Biol.Chem., 42 , 895-896 (1978) and M.
Elliott et al., Pestic.Sci., 9, 112-116 (1978)).
The efficacy ratio of cis and trans forms differs depending on the target insect; for example, the above-mentioned Pestic.Sci., 9, 114 (1978).
As shown in (the cis form is more effective for house flies, and the trans form is more effective against mustard beetles), it changes depending on the target pest. However, as mentioned above, the "racemate" synthesized by the usual method contains eight isomers, and therefore the method of producing cypermethrin with as much Aα content as possible is extremely difficult in practical terms. It is meaningful. A possible means for this is that the acid side is d-
(i.e., a mixture of Aα and Aβ), ester with S-form on the alcohol side (i.e., Aα
and Bα) or Aα itself may be obtained. The optical resolution of 2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropanecarboxylic acid (hereinafter referred to as DV acid), which constitutes the acid side of Cypermethrin, has been shown, for example, by PEBurt et al. (Pestic. Sci., 5, 791-799 (1974))
However, it requires a very complicated operation and also produces by-products.
Regarding the racemization of -form DV acids, only the photoracemization method (Japanese Unexamined Patent Application Publication No. 52-5738) is known, and this method cannot be said to be industrially superior. Method for deriving optically active DV acids from optically active chrysanthemum acids (M. Elliott et al., Nature , 244 , 456-457
(1973)), but this also requires a large number of steps. On the other hand, from cisA in Japanese Patent Application Laid-open No. 52-148040,
A method leading to cisAα has been shown, and as long as cisA is obtained, it can be said to be an excellent method for achieving high activity, but as mentioned above, obtaining d-cisDV acid requires an extremely large number of steps. . As a method for obtaining an optically active substance on the alcohol side, in addition to the method described in JP-A-52-148040, there is also a method of separating cisA or transA by chromatography (M.Elliott et al., Pestic.Sci., 9, 105-111). 1978))
Alternatively, there are methods using optically active mandelic acid derivatives as starting materials (Japanese Patent Application Laid-open Nos. 153930/1982 and 98938/1982), but these are hardly industrial methods. By the way, the combinations of Aα and Bβ and Aβ and Bα each have a pair of enantiomers, so if the racemic Y form could be obtained by some means, it would nearly double the activity of Cypermethrin since it would contain 50% Aα. can be raised. As a result of intensive study on the method for obtaining the Y form under these circumstances, the present inventors surprisingly found that in Cypermethrin, both the cis and trans forms are not the Y form, but the X form is extremely easy to crystallize. We discovered a new finding and arrived at a method for obtaining Y-enriched cypermethrin by removing the crystallized X-isomer, and have filed a separate patent application for this. On the other hand, various studies have been conducted on more industrial methods to directly obtain the Y-isomer as crystals, but as mentioned above, the X-isomer of cypermethrin is extremely easy to precipitate, and the technology for obtaining appropriate Y-isomer seed crystals has been studied. Its development remained undeveloped for several reasons, including that it had not yet been completed. The present inventors conducted further detailed studies and found that under conditions where cisX and/or transX seed crystals are substantially absent, cisY and/or
cisY and/or transY can be selectively precipitated by inoculating transY seed crystals;
In particular, by having a basic catalyst in the system,
We have found that the yield can be increased and that cypermethrin rich in cisY and/or transY can be produced by precipitating cisY and/or transY in the presence of a basic catalyst and recovering cypermethrin in the system. The fact that cisY and/or transY could be precipitated as crystals is surprising, even though cisX and transX tend to precipitate preferentially in cypermethrin as described above. According to the method of the present invention, cypermethrin rich in cisY, transY, or a mixture of both can be produced, and a more highly active stereoisomer mixture of cypermethrin can be produced without using means such as so-called optical resolution or asymmetric synthesis. As a result, the activity as an insecticide and acaricide can be almost doubled, and the economic effect is extremely large. The present invention is racemic in the presence of a basic catalyst.
Inoculating cisY and/or transY crystals into a solution of cis and/or trans Cypermethrin to precipitate cisY and/or transY,
A method for obtaining cisY and/or transY (hereinafter referred to as method A) is provided. In method A, cisY
and/or in the mother liquor separated from transY.
Cypermethrin, which is rich in cisX and/or transX, is brought into contact with a basic substance to partially release cisX.
By converting transX to cisY and transY, it is possible to return to the cis and/or trans forms (the ratio of each X and Y form is an equilibrium composition), which is used again as a raw material for Method A. be able to. In this case, a poorly soluble basic substance, such as a basic ion exchange resin, is suitable because it can be easily separated. The present invention also provides a method for obtaining cypermethrin rich in cisY and/or transY (hereinafter referred to as method B) by recovering the entire amount of cypermethrin from the reaction solution of method A without separating cisY and/or transY. In Methods A and B, the raw material Cypermethrin may have any cis/trans ratio, but it is more preferably 80% or more of the cis form or 80% or more of the trans form. Also, cisX/
The ratio of cisY and transX/transY may be any value. Desirable solvents are lower alcohols such as methanol and ethanol, aliphatic hydrocarbons such as pentane, hexane, heptane, and octane, or mixed solvents containing these, particularly methanol and mixed solvents of methanol and aliphatic hydrocarbons such as hexane and heptane. is desirable. The amount of solvent varies depending on its type and temperature, but is usually used in an amount of 0.1 to 10 times (by weight), preferably 0.4 to 5 times, the amount of Cypermethrin used as the raw material. In methods A and B, the seed crystals are cis
Cypermethrin has cisY crystals, trans Cypermethrin has crystals of transY, and
Cis/trans cypermethrin is inoculated with both. Furthermore, cisAα or cisBβ crystals may be used instead of cisY crystals. The amount of seed crystals may be any amount, but it is usually used in an amount of 0.001% by weight or more based on the raw material Cypermethrin. When the amount of seed crystals is increased, precipitation tends to be faster. Of course, in the method of the present invention, supply of raw materials and precipitation of crystals can be carried out continuously or semi-continuously, and seed crystals do not necessarily need to be inoculated at this time. In addition, care must be taken to avoid the presence of cisX or transX crystals as much as possible, especially
In the trans form, transX tends to precipitate, so care must be taken. In Methods A and B, the precipitation temperature is preferably below room temperature (20-30°C), more preferably in the range of 0°C to -30°C. In addition, the basic catalysts used include nitrogen bases, phosphorus bases, quaternary ammonium, hydroxides, hydroxides, oxides, alcoholates, hydrides, carbonates, and cyanates of alkali metals or alkaline earth metals. , metal-containing bases such as amides, and the like. Among these, nitrogen bases are preferred, and ammonia and triethylamine are particularly preferred. The amount of catalyst is preferably such that it does not significantly cause decomposition at the reaction temperature, and is usually used in an amount of 1 to 50 mol % based on cypermethrin. cisY and/or precipitated in method A
When separating transY from the mother liquor, the remaining catalyst may cause conversion of cisY to cisX, transY to transX, or significant decomposition, so it is preferable to remove the used catalyst from the system. It is preferable to use a method such as removing it directly or neutralizing it with an acid. This also applies to method B. Examples will be described below. In this example, the ratio of each isomer was analyzed by high performance liquid chromatography. Conditions Column: μPolasil (Waters Limited brand name) Inner diameter 4 mm, length 0.3 m Mobile phase: Hexane/ethyl acetate 500/7 (volume ratio) Detector: Ultraviolet absorption spectrometer (254 nm) Flow rate: 1 ml/mm Injection volume: Add 2μ of a 10mg/ml chloroform solution.The development time for each isomer is as follows. cisX: 16 minutes cisY: 19 minutes transX: 21 minutes transY: 24.5 minutes In the examples, the ratios of these isomers are expressed as percentages. Example 1 cis body (cisX: 49.7, cisY: 49.2, transX: 0.5,
transY:0.6) Dissolve 5g in 10g of methanol,
Cooled to -10°C. 10 mg of cisAα seed crystals were added, and further 0.4 cc of 12.6% ammonia/methanol solution was added, followed by stirring at the same temperature for 1 day. 1% hydrochloric acid 20 days later
cc and 20 c.c. of toluene were added, and the temperature was raised to 20°C. After separating the aqueous layer and washing the oil layer twice with water, the oil layer was concentrated to obtain 4.92 g of cisY-rich cypermethrin. Analysis value cisX: 8.0, cisY: 90.9, transX: 0.4,
transY: 0.7 Also, 1.18g of cypermethrin, which is rich in cisY
Dissolve it in 2.43g of methanol and store it in the refrigerator (approximately 0.0
℃) overnight, filter the precipitated crystals, and cool to approximately 0℃.
of hexane to obtain 0.74 g of crystalline cisY. Melting point 54-56℃ Analysis value cisX: 0.6 cisY: 98.5
transX: 0.3 transY: 0.6 Example 2 trans body (cisX: 0.9, cisY: 0.6, transX:
60.9, transY: 37.6) was dissolved in 10.72 g of methanol, cooled to -10°C, and transY seed crystals (cisX:
0.0, cisY: 2.9, transX: 0.2, transY: 96.9)
10mg and 0.65cc of 8.4% ammonia/methanol solution
was added, and the mixture was stirred as it was. 50 hours later 2% hydrochloric acid 10
cc and 10 c.c. of toluene were added, and the same procedure as in Example 1 was carried out. 5.03 g of Cypermethrin rich in transY was obtained. Analysis value cisX: 1.5, cisY: 1.0, transX: 30.0,
transY: 68.4 Example 3 cis form 10.04 with the same composition as that used in Example 1
g was dissolved in 20.08 g of isopropanol, cooled to -10°C, and 1.63 cc of 28% ammonia water and 10 mg of cisY seed crystals (containing cisX: 0.6%, transX: 0.3%, transY: 0.6%) were added. A cream-like semi-solid was precipitated in the system, but the mixture was stirred as it was at -10°C for 140 hours. Even after 140 hours, the state of the system did not change at all, and 3
% hydrochloric acid and 20 c.c. of toluene were added, and 10.02 g of Cypermethrin was recovered in the same manner as in Example 1. Analysis value cisX: 44.7, cisY: 53.9, transX: 0.2
transY: 1.2 Example 4 5 g of cis-cypermethrin recovered in Example 3 was dissolved in a mixed solvent of 2.5 g of methanol and 7.5 g of heptane, and cooled to -10°C. Add 10 mg of cisY seed crystals (same as those used in Example 3) and 0.59 cc of 8.4% ammonia-methanol solution, and incubate at -10 °C for 20 min.
Stir for hours. Then 2% hydrochloric acid 10 c.c. and toluene 10
cc was added, and 5.96 g of cisY-rich cypermethrin was recovered in the same manner as in Example 1. Analysis value cisX: 9.2, cisY: 90.6, transX: 0.2
transY: 1.0 Comparative Example 1 Trans body with the same composition as that used in Example 2
Dissolve 5.04g in 10.08g of methanol, cool to -10℃, and make 0.41cc of 12.6% ammonia/methanol solution.
was added and stirred for 72 hours, then 20 c.c. of 1% hydrochloric acid and 20 c.c. of toluene were added and treated in the same manner as in Example 1. The obtained trans body (5.01 g) was rich in transX. Analysis value cisX: 1.3, cisY: 1.8, transX: 61.1,
transY: 35.8 Comparative Example 2 The reaction was carried out in exactly the same manner as in Example 1 except that 10 mg each of cisX crystal and cisY crystal were added as seed crystals. The obtained 4.84 g of cis isomer was a mixture of equal amounts of cisX and cisY. Analysis value cisX: 48.1, cisY: 49.4, transX: 0.6
transY: 0.9

Claims (1)

[Claims] 1. In the presence of a basic catalyst, racemic cis
- and/or trans-2,2-dimethyl-3
-(2,2-dichlorovinyl)cyclopropanecarboxylic acid α-cyano-3-phenoxybenzyl ester (hereinafter referred to as cis- and/or trans-cypermethrin) was added with the acid side d-cis,
Ester of alcohol side S (hereinafter referred to as cisAα)
, a crystal of its enantiomer (hereinafter referred to as cisBβ), a crystal of a mixture thereof (hereinafter referred to as cisY), and/or a mixture consisting of an ester with d-trans on the acid side and S on the alcohol side and its enantiomer ( below
inoculated with crystals of cisY and /
Alternatively, a method for producing cisY and/or transY of cypermethrin, which comprises precipitating transY in the solution and separating the precipitate from the mother liquor. 2. The method according to claim 1, wherein the basic catalyst is a nitrogen base. 3. Claim 1, in which cisY is produced by inoculating cisY crystals into a solution of cis-cypermethrin.
The method described in Section 1 or Section 2. 4. The method according to claim 1 or 2, wherein transY is produced by inoculating transY crystals into a solution of trans-cypermethrin. 5. The method according to claim 1, 2, 3, or 4, wherein the precipitation of cisY and/or transY is performed continuously or semi-continuously. 6. The method according to claim 1, 2, 3, 4, or 5, wherein the solvent to be precipitated is a lower alcohol, an aliphatic hydrocarbon, or a mixed solvent containing these. 7 Claim 6 in which the solvent is methanol
The method described in section. 8. The method according to claim 6, wherein the solvent is a mixed solvent of methanol and an aliphatic hydrocarbon. 9. Claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein the precipitation temperature is -30°C to 0°C. the method of. 10 In the presence of a basic catalyst, it is racemic
A solution of cis- and/or trans-cypermethrin is inoculated with crystals of cisAα, cisBβ, or cisY and/or crystals of transY to precipitate cisY and/or transY into the solution, and then the precipitate is added to the mother liquor. A method for producing cypermethrin rich in cisY and/or transY, comprising recovering cypermethrin together with cisY and/or transY. 11. The method according to claim 10, wherein the basic catalyst is a nitrogen base. 12. The method according to claim 10 or 11, wherein cisY crystals are inoculated into a solution of cis-cypermethrin to produce cisY-rich cypermethrin. 13 TransY in a solution of trans-cypermethrin
Claim 10 or 1 for producing transY-enriched cypermethrin by inoculating crystals.
The method described in Section 1. 14 Claim 10: Precipitating cisY and/or transY continuously or semi-continuously
11, 12 or 13. 15 Claims 10, 11, 12, 1, wherein the solvent for precipitation is a lower alcohol, an aliphatic hydrocarbon, or a mixed solvent containing these.
The method according to item 3 or item 14. 16. The method according to claim 15, wherein the solvent is methanol. 17. The method according to claim 15, wherein the solvent is a mixed solvent of methanol and an aliphatic hydrocarbon. 18. Claim 10, 11, 12, 13, 14, 15, 16 or 17, wherein the precipitation temperature is -30°C to 0°C. the method of.