CN1044807C

CN1044807C - Pyrethroid-high-efficiency cypermethrin

Info

Publication number: CN1044807C
Application number: CN93112374A
Authority: CN
Inventors: 秦裕基; 徐逸楣; 陈娟娟; 王元正; 汪丽君; 邹林立; 黄粤; 曹瑾; 刘鉴松
Original assignee: SHANGHAI PESTICIDE RESEARCH INSTITUTE
Current assignee: SHANGHAI PESTICIDE RESEARCH INSTITUTE
Priority date: 1993-03-23
Filing date: 1993-03-23
Publication date: 1999-08-25
Anticipated expiration: 2013-03-23
Also published as: CN1092762A

Abstract

The present invention relates to a novel pyrethroid whose chemical name is (R, S)-(E)-cyclopropane carboxylic acid-3-(2, 2)-dichloroethenyl-2, 2-dimethyl-(R, S)-(E, Z)-1-cyano-2-methyl-2-pentenyl, and the novel pyrethroid is called trans-form cypermethrin for short. The activity of the pyrethroid is much higher than that of a mixture. Additionally, the present invention has the advantages of simple and feasible synthesizing method and low cost, and finds an outlet for trans-form permethric acid separated from high cis-form cypermethrin.

Description

Pyrethroid-high-effective dichloropentylenetetrazol

The present invention belongs to the field of pesticide.

Since the first pyrethroid allethrin appeared in 1949, the development and research of pyrethroid insecticides has been progressing around the world, with greater production of killing pyrethrins, permethrin, cypermethrin, deltamethrin for agricultural and sanitary spraying control. However, these pyrethroids have a large molecular weight and are not volatile, so that they are not very effective for fumigation of mosquito coil incense. The allethrin with higher vapor pressure has better fumigation effect, but has complex structure and great synthesis difficulty, and although the allethrin is produced in China, the allethrin is only put into production on a small scale due to higher cost.

In recent years, another pyrethroid, permethrin, has begun to be noticed (Japanese patent application No. Sho 54-136821) (tap.J.Sahit.Zool.Vol.34NO.4P263-2681983). The penmen and the like have studied on the pyrethroid and found that the pyrethroid is superior to the other pyrethroids in the aspects of using effect, synthesis difficulty, economic cost and the like, and has further development prospect. (chemical world phase 8P 348-3501986)

The invention aims to further research and develop the pyrethroid so as to obtain excellentcompounds with higher activity, better effect and lower cost, and further realize large-scale industrial production.

The high-efficiency cypermethrin is a novel pyrethroid, and is a trans-isomer of the cypermethrin. The chemical name is (R, S) - (E) -cyclopropane carboxylic acid-3- (2, 2-dichlorovinyl) -2, 2-dimethyl- (R, S) - (E, Z) -1-cyanogen2-methyl-2-pentenyl ester, abbreviated as trans-dichloropenta-thrin. The structural formula is shown asThe following:

the molecular formula is as follows: c₁₅H₁₉Cl₂NO₂Molecular weight: dividing element 316 into sections; calculated% C56.95H6.06N4.43

Determination of% C57.13H6.46N4.23 trait: specific gravity of yellowish transparent liquid: d₂₀Boiling point of 1.08: refractive index of 150-; n is_D ²⁰=1.5000 n_D ¹³=1.5022

Solubility: is easily soluble in organic solvents such as ethanol and is insoluble in water.

Infrared spectrum: (cm)^-1)

2250,1740,1610,1180,890,650

Nuclear magnetic resonance; (CDCl)₃TMS δPPM)

δ0.8-1.4 10H δ1.6-2.4 7H δ5.6 1Hδ5.7 1H

The beta-cypermethrin of the invention can be prepared by the following method.

The invention takes a mixture of cis-trans isomers of DV chrysanthemic acid as a raw material, two isomers of high cis-DV chrysanthemic acid and trans-DV chrysanthemic acid are respectively prepared by separation, then the trans-isomer is subjected to acyl chlorination to prepare trans-dichlorochrysanthemic chloride, and then the trans-dichlorochrysanthemic chloride is condensed with 2-methylpentene-2-aldehyde and sodiumcyanide to finally obtain trans-dichloropentacyanthrin, namely the high-efficiency dichloropentacyanthrin.

The mixture of cis-trans isomers of DV chrysanthemic acid can be prepared by the classical phase-templated-Kurarayi method, whose reaction formula is roughly as follows:

the weight ratio of cis-trans isomers of the resulting mixture of DV chrysanthemic acid is about 4: 6. Separating the mixture in organic solvent such as cyclohexane, petroleum ether and diethyl ether. Most cis-isomers are dissolved in a solvent, the solid part is filtered and recrystallized to obtain the DV chrysanthemic acid of trans-isomers, and the cis-to-trans ratio can reach 2: 98. The obtained high cis-isomer (cis-trans ratio is about 84: 16) can be directly used for the synthesis of the high cis-cypermethrin.

The acyl chlorination of the trans-DV chrysanthemic acid can use thionyl chloride as a chlorinating agent, after heating reflux reaction is carried out in a small amount of toluene solvent, distillate obtained when 130-.

The 2-methylpentene-2-aldehyde as the condensation group may be prepared by dealcoholization and dehydration of propionaldehyde, which may be obtained by oxidation of propanol or by isomerization and rectification of propylene oxide. The chemical reaction formula is as follows:

or

The condensation of trans-dichlorochrysanthemic chloride, 2-methylpentene-2-aldehyde and sodium cyanide is carried out in the presence of hydrocarbon solvent and phase transfer catalyst, the hydrocarbon solvent can be alkane, such as n-hexane, cyclohexane, etc.; but also aromatic hydrocarbons such as benzene, xylene, etc. The phase transfer catalyst can be tetraethylammonium bromide, tetrabutylammonium bromide, triethylbenzylammonium bromide or tetraethylammonium chloride and the like, and the chemical reaction formula is as follows:

dichloropentathrin is a low-toxicity compound, and is used for treating acute LD in mice orally₅₀3205mg/kg, allethrin (LD)₅₀480mg/kg) by approximately one order of magnitude. The trans isomer is tested to have greater activity than the cis isomer. The permethrin and cypermethrin which also take DV chrysanthemic acid as raw materials take cis-isomer as the main active ingredient. The ratio of cis-isomer to trans-isomer in DV chrysanthemic acid is about 3: 7-4: 6, so that by separating DV chrysanthemic acid, its trans-isomer portion can be used for synthesizing trans-dichloropentylenethioate, and its high cis-isomer portion can be used for synthesizing high cis-dichlorophenothrin or cypermethrin, not only can greatly raise biological activity of above-mentioned various products and raise drug effect, but also can be used for making various productsThe method makes the best use of the substances to reduce the generation of products with lower activity, thereby greatly reducing the production cost and enhancing the market competition capability.

Synthesis example 1 preparation of DV chrysanthemic acid

In a 500 ml three-neck flask equipped with a stirrer, a condenser, a thermometer and a water bath, a mixture of methyl DV chrysanthemate with a ratio of 4: 6 of cis-isomer to trans-isomer is added78.1 g (0.35 mol), 1.8 mol of aqueous sodium hydroxide solution was added thereto, and the mixture was hydrolyzed by heating in 50 ml of cyclohexane. After hydrolysis is complete,the organic solvent is recovered by distillation, and the aqueous layer is acidified with a mineral acid such as hydrochloric acid and then washed with water to neutrality. Further, 150 ml of toluene was added for extraction. Discarding the water layer, distilling to remove the solvent, and pouring out and cooling residual liquid in the kettle to obtain a mixture of cis-isomer and trans-isomer of the solid DV chrysanthemic acid with a melting point of 65-68 ℃. By gas chromatography and nuclear magnetic resonance analysis, the cis isomer: the trans isomer ratio was 4: 6, consistent with the ratio before saponification hydrolysis. H NMR: (CDCL)₃TMS δ ppm) cis: 1.2 (S.3H-CH)₃)1.35(S.3H-CH₃)1.83(d.1H-CHCOO-) 2.03(t.

6.09(d.

10.84(b.1H-COOH) trans: 1.21 (S.3H-CH)₃)1.35(S.3H-CH₃)1.61(d.1H-CHCOO-) 2.25(dd.5.61(d.

10.84(b,1H-COOH) Synthesis example 2 separation of cis-and trans-isomers of DV chrysanthemic acid

A mixture of cis and trans isomers of DV chrysanthemic acid (cis isomer: trans isomer = 4: 6 by weight) is added to a 100 ml three-neck flask equipped with a stirrer and a thermometer, and then an appropriate amount of cyclohexane is added, solid DV chrysanthemic acid is dissolved almost half by stirring, cis isomer is mostly dissolved in the solvent, and the residual solid contains more trans isomer. Filtering the residual solid, recrystallizing the filter cake to obtain DV chrysanthemic acid with a main trans isomer and a melting point ofThe temperature is 93-96 ℃, the content is 98.2%, and the cis-form to trans-form = 2: 98 by gas chromatography and nuclear magnetic resonance analysis. Combining the filtrates, recrystallizing the mother liquor, and distilling to remove the solvent to obtain high cis-form DV chrysanthemic acid (cis-form: trans = 84: 16), which can be directly used for the synthesis of high cis-cypermethrin. (H)¹NMR values as in example 1)Synthesis example 3 preparation of trans-dichlorochrysanthemoyl chloride

In a 500 ml three-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a water bath, 29.3 g (0.14 mol) of resolved trans-DV chrysanthemic acid (cis-isomer: trans-isomer = 2: 98) was charged, 60 ml of toluene was added as a solvent, 17.8 g (0.15 mol) of thionyl chloride was added, and the temperature was slowly raised to reflux. After refluxing for 10 hours, distilling off the solvent under normal pressure or reduced pressure, then carrying out reduced pressure distillation, and collecting 130-133 ℃/50mmHg column fractions; obtaining the trans-dichlorochrysanthemic chloride of oily matter. The content is 98 percent, and the yield is more than 96 percent. Synthesis example Synthesis of 42-methylpentene-2-aldehyde

1 ml of 0.06N sodium hydroxide aqueous solution is added into a 100 ml three-neck flask provided with a stirrer, a thermometer, a reflux condenser, a dropping funnel and a water bath, propionaldehyde is dropwise added at room temperature, and after the dropwise addition of the propionaldehyde is finished, the temperature is maintained for 1 hour to ensure that the reaction is completely carried out. And cooling the reaction liquid, pouring the reaction liquid into a separating funnel, standing for layering, washing an organic layer twice with water (25ml multiplied by 2), removing water, adding anhydrous sodium sulfate for drying, filtering out a drying agent, distilling at normal pressure, and collecting distillate at 135-140 ℃, namely the 2-methylpentene-2-aldehyde. The content was 97.7% by gas chromatography, and the yield was 85.9%. Synthesis example 5 Synthesis of trans-Dichloropentylenetrinate

In a 100 ml three-neck flask equipped with a stirrer, a thermometer, a reflux condenser and a water bath, 25 g of solid sodium cyanide, 10 ml of water, 10 ml of toluene and 0.2 g of tetraethylammonium bromide are respectively added, 11.6 g of trans-DV chrysanthemoyl chloride (cis-isomer: trans-isomer = 2: 98) and 5.0 g of 2-methylpentene-2-aldehyde are dropwise added under the cooling of the water bath, the reaction is carried out at room temperature and then the heating is carried out, samples are continuously taken in the reaction process for gas chromatography tracking analysis, and the disappearance of 2-methylpentene-2-aldehyde is taken as the reaction end point. The reaction solution was poured into a separatory funnel，Standing for layering, separating an oil layer and a water layer, washing the oil layer twice with water (25ml multiplied by 2), combining the water layers, extracting twice with toluene, combining the oil layers, washing with 25ml of sodium bicarbonate saturated water solution, separating the water layer, drying, and evaporating under reduced pressure to remove the solvent to obtain the product of the trans-cypermethrin. n is_D ¹³=1.5022, bp = 150-. Cis-isomer: trans-isomer = 2: 98 (determined by nuclear magnetic resonance), the isomer ratio is the same as that of the fed DV chrysanthemic acid, and the cis-isomer and the trans-isomer are not converted in the reaction process. The product is as follows: elemental analysis:

calculated values of% C56, 95H6.06N4.43

Measurement% C57.13H6.46N4.23 Infrared Spectrum: IR (cm)^-1) 2250174016101180890650 nuclear magnetic resonance: h¹NMR(CDCL₃TMS δ ppm) trans: delta 0.8-1.41H delta 1.6-2.47H delta 5.61H delta 5.7 (d).

Tricyclic ring is trans) Synthesis example 6 preparation of high cis-Dichlorochrysanthemoyl chloride

In a 500 ml three-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a water bath, 29.4 g (0.14 g) of high cis DV chrysanthemic acid (cis isomer: trans isomer = 84: 16) in terms of fold was charged, 60 ml of toluene was added, 17.8 g (0.15 g) of thionyl chloride was added, and the temperature was raised to reflux. After ten hours of reflux reaction, the solvent is distilled off under normal pressure, and then 128-fold 133 ℃/50mmH9 column fractions are collected by reduced pressure distillation, so that the oily product, namely the high-cis dichlorochrysanthemoyl chloride, is obtained, the yield is 96 percent, and the content is 98 percent. (cis isomer: trans isomer = 84: 16) Synthesis of example 7 Synthesis of high-cis-deltamethrin

In a 100 ml three-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a water bath, 11.6 g of high cis-dichlorochrysanthemoyl chloride (cis: trans = 84: 16), 2.5 g of solid sodium cyanide, 10 ml of water, 10 ml of toluene, 0.2 g of tetraethylammonium bromide and 5.0 g of 2-methylpentene-2-aldehyde were placed, and other operations of reaction and post-treatment were identical to those of Synthesis example 5, and finally, a water bath was placedObtaining the high cis-dichloropentylenetetrazol. Yield 90%, content 90%, cis/trans isomer = 84: 16 (analyzed by nuclear magnetic resonance). H¹NMR:(CDCL₃TMS δ ppm) cis form: delta 0.8-1.410H delta 1.6-2.47H delta 5.71H delta 6.2 (d).

Tricyclic cis) trans: delta 0.8-1.410H delta 1.6-2.47H delta 5.61H delta 5.7

Tricyclic ring trans) LR (cm)^-1) Cis-form: 2250174016101180820650 trans form: 2250174016101180890650 test of efficacy example 1 mosquito knockdown test of a sample of permethrin containing different cis-trans isomer ratios

Dropping the sample into blank mosquito-repellent incense to make the final concentration be 0.5%, placing 20 female and light culex into standard test cylinder (phi 20cm, h43cm), smoking for one minute, transferring mosquito-repellent incense, observing knock-down time, and calculating KT₅₀The values, using commercial Sanxingxing mosquito incense (original family is imported strong Bina Ming) as a control, are as follows:

1. three-star mosquito-repellent incense K T₅₀4′15″

2. Agro-mosquito No. 1K T₅₀5′02″

3. Agro-mosquito No. 2K T₅₀3′14″

4. No. 3K T agricultural mosquito₅₀3' 11 wherein: agricultural mosquito No. 1 (90% of dichloropentathrin content) (cis: trans = 84: 16)

Agro-mosquito number 2 (90% of permethrin content) (cis: trans = 30: 70)

Pesticide effect test example 2 mosquito knockdown test of beta-cypermethrin with other pyrethroid samples

The sample solution is evenly prepared into 3 percent of sample solution which is dripped into the blank mosquito incense by adopting a closed cylinder test method with the height of 43 centimeters and the diameter of 20 centimeters.

Mosquito seeds: sensitive culex pipiens SENs SEN strain bred in laboratory for long time, 20 female mosquitoes at a timeThe knock-down time is observed to obtain KT₅₀The value is obtained. The test results were as follows:

no. 3 KT of agricultural mosquito₅₀2′33″

No.4 KT of agricultural mosquito₅₀2′48″

5 # KT of agricultural mosquito₅₀4' 49 "-, wherein: agricultural mosquito 3 (90% of cypermethrin content) (cis: trans = 2: 98)

No.4 agricultural mosquito (content 89.8%) (Kingfluthrin sample from Chinese and Western medicine factory)

No. 5 (30% content) of agricultural mosquito (without cyanogen-penta-cypermethrin)

Claims

1. A pyrethroid has chemical name of (R, S) - (E) -cyclopropane carboxylic acid-3- (2, 2-dichlorovinyl) -2, 2-dimethyl- (R, S) - (E, Z) -1-cyano-2-methyl-2-pentene

Structural formula (xvi):

2. a process for the preparation of pyrethroids according to claim 1, characterized in that they are prepared by chlorination of trans isomers obtained by separation of DV chrysanthemic acid mixtures to trans dichlorochrysanthemic chloride, followed by condensation with sodium cyanide and 2-methylpentene-2-al.

3. A process for the preparation of pyrethroids according to claim 2, characterized in that the solvent used for the isolation of the DV chrysanthemic acid mixture is cyclohexane.

4. A process for the preparation of pyrethroids according to claim 2, characterized in that the chlorination of trans isomers of dichlorochrysanthemic acid is performed with thionyl chloride.

5. A process for the preparation of a pyrethroid according to claim 2 in which the condensation of trans-dichlorochrysanthemic chloride with sodium cyanide and 2-methylpentene-2-al is carried out in the presence of a hydrocarbon solvent and a tetraethylammonium bromide catalyst.

6. An insecticide, characterized in that the active ingredient contained is (R, S) - (E) -cyclopropane carboxylic acid-3- (2, 2-dichlorovinyl) -2, 2-dimethyl- (R, S) - (E, Z) -1-cyano-2-methyl-2-pentenoate.