RU1817771C - Process for preparing lower -alkyl 2,2-dimethyl-3-(2,2-dichloroethenyl) cyclopropanecarboxylic acid esters - Google Patents

Abstract

SUMMARY OF THE INVENTION: the product is lower C1-C4 alkyl esters of 2,2-dimethyl-3- (2,2-dichloroethenyl) cyclopropanecarboxylic acid. Reagent 1: Ci-C4 alkyl esters of 4,6,6-trichloro-3,3-dimethylhexen-5-one or -4-one acid. Reagent 2: NaOH or KOH. Reaction conditions: in alcohol after After cypermethrin and others). The purpose of the invention is to simplify process technology. According to the invention, the goal is achieved by the method of obtaining lower alkyl esters of 2,2-dimethyldiamic treatment of the reaction mixture HCI to pH 6-7, extraction of the target product, further processing of the resulting aqueous solution containing the sodium or potassium salt of 3,3-dichloroethenyl) -cyclopropanecarboxylic acids of concentrated HCt, followed by the introduction of the resulting mixture of 2,2-dimethyl-3- (2.2-dichloroethenyl) cyclopropanecarboxylic acid and 2- (2,2-dichlorovinyl) -3,2-dichloroethynyl) cyclopropanecarboxylic acid and 2- (2, 2- dichlorovinyl ) -3,3-dimethyl-y-butyrolactone in the reaction with thionyl chloride in the presence of C1-C2 alcohol and further processing of the obtained mixture of CrCa esters of 2,2-dimethyl-3- (2,2-dichloroethenyl) cyclopropanecarboxylic and 4.6.6% trichloro-3,3-dimethylhexen-5-aic acid with a C1-C4 alcohol solution of KOH or NaOH in the presence of a 15-20-fold excess of alcohol to give an additional target product which is isolated. 2 tab. L 3- (2,2-dichloroethenyl) cyclopropanecarboxylic acid by reaction of Ci-C4 alkyl esters of 4,6,6-trichloro-3,3-dimethylhexene-5-oi and 6,6,6-trichloro-3, 3-dimethylhexene-4-hydroxy acid with an alcoholic solution of sodium or potassium hydroxide and subsequent treatment of the reaction mixture with hydrochloric acid, and a distinctive feature is that hydrochloric acid is added to the reaction mass to a pH of 6-7, after which it is immediately recovered the target product, and the resulting aqueous solution containing sodium 00 vj VI VI CO

Description

or the potassium salt of 3,3-dimethyl-4-hydroxy-6,6-dichlorohexen-5-one and 2,2-dimethyl-3- (2.2-dichloroethenyl) cyclopropanecarboxylic acid, treated with concentrated hydrochloric acid, the resulting a mixture of 2,2-dimethyl-3- {2,2-dichloroethenyl) cyclopropanecarboxylic acid and 2- (2,2-dichlorvinyl) -3.3-dimethyl-butyrolactone is reacted with thionyl chloride in the presence of Ci-C2 alcohol, the resulting mixture Ci-Cz esters of 2,2-dimethyl-3- (2.2-dielo-rethenyl) cyclopropanecarbonyl and

4,6,6-trichloro-3,3-dimethylhexene-5-hydroxy acid is treated with an alcoholic solution of potassium or sodium hydroxide in the presence of a 15-20 fold excess of alcohol and the obtained additional amount of the expected product is isolated.

This method avoids distillation using distillation columns, which is a simplification of the process technology.

The reaction proceeds as follows:

01

i

С17С СН-СН-С-СН2СООС2Н5

 slit. AGENT ./

NHS CH3

ill

SOLVENT

: i3c-CH cH-c-CH2cooc2Hs n-jC Hsn3 v

After stripping off the solvent and extra- 75-80%. The recovery of wastewater from the reaction of desired product IV from the reaction — is carried out as follows. The salts of the first VI mixture of salt I and VI are converted into treated concentrated water, from which they are isolated with other acid until they are converted to permethric acid VII 30 are transferred to compounds VII and II with exit

98-100% and are isolated by extraction with organic solvents. The remaining aqueous solution contains only

potassium chloride (sodium). 4R

and 2- (2,2-dichloroethenyl) -3,3-dimethyl-butyrolactone (II). Target product IV is isolated after stripping of the extractant and distillation under reduced pressure with

Н3С СН3

. -. .

+. VI. /

stgs sn-sn-s-sn2coom

OH I

con c. /

H, C CH,

VII

HC1

Lsnz

C1gs sn-chA0

tMC1

Compounds VII and II react with chlorine and undergo a disclosure reaction.

thionyl in the presence of alcohol ROH rings and the formation of the corresponding

(, Et). Permethrinic acid VII of pre-45 esters of y-halo-5-unsaturated is converted to ester IV. y-butyrolactone Oplot.

NSN CH-J SOCI

 Roh

VII CH3, SOC12

C1

/ kA

About ROH C12C CH-CH C-CH2COOR

eleven

bcc cps in

The reaction is carried out in an open system. Koli-55 and upon receipt of the acid chloride, the permethrin content of tisnil chloride should be equivalent to that of the acid itself. For use, within 2–3 mol per 1 molar transfer of the permegrin acid mixture of lactone and permethric acid in IV and III. Prilots and lactone with a high yield require the conversion of pure lactone into III, a 5-excess of 2-3 is needed, which is confirmed by the below-mentioned and more excess (application Yap. 52-57163), given examples.

/

C1jC CH-Cr1-xCH-COOC H 5

X

Н3С СН3 IV

cn

I

C12s sn-sn-s-sn2coom

n, with sn

I

/

H, C CH,

VII

Lsnz

C1gs sn-chA0

tMC1

C1

-CH C-CH2COOR

bcc cps in

As ROH, methanol and ethanol are used in an amount of 2-10 mass, parts as of May 1. including a mixture of II and VIII. The best ratio of 3-5 mass, parts of alcohol per 1 m.h. mixtures. The reaction can be carried out at a temperature of 25-75 ° C; the boiling point of the reaction mixture is optimal.

After completion of the process, the reaction mass is subjected to distillation to remove excess SOCfc and alcohol under reduced pressure. A mixture of products III and IV is obtained with a yield of 97%. Compound III is an intermediate for the synthesis of cyclopropanecarboxylic acid esters. Upon treatment with 111 alkaline agents, permethric acid esters are obtained, and IV are permethric acid salts.

A method has been developed for converting HI and IV without isolating it from the reaction mixture. For this, a mixture of III and IV was used as the starting material.

As the alkaline agent, alkali metal hydroxides are used. The amount of alkaline agent ranges from 1 to 3

ngsch .sn,

xC-CH-CH-C-CH OOR V

etc cH-cH-c-CHtcooR

CE

III

con s n he

Н3С СН3 С12С СН СООСаН5

HjC CH3 vi H3CN xCH3

. ags sn-snn cngsoo

6n 1 |

The spruce product is purified by distillation under reduced pressure. Maybe different, with sn5

C17C CH COOCtH "H3CCH3

ags sn-juice

40

n, cx / sn,

CESC-CH CH-C-CH, COOR V

n, t CHt /

, CfjC C H-CH-c cHjCOOR

lit

kOH

 C, H, Otf

se

-I

C11 CH-CH-C-CH2 COOKJ OH If.

H3cxj: Hj

All the described processes proceed without isolation of pure mixtures using vacuum distillations, and crude technical products are used. Only target product IV is subjected to distillation, which greatly facilitates the isolation and regeneration of by-products.

Example 1. In the flask load 27.4 g, a mixture of III and V () in a ratio of 5: 1 (mol)

mol per mol III in the mixture. The optimal ratio (KOH) 1: 1.5-2 (mol). An increase in the amount of alkaline agent leads to an increase in the yield of products I and VII.

The process is carried out in the presence of solvents - alcohols, THF, benzene and others. The amount of solvent, in particular alcohol, which makes it possible to carry out the reaction in the best way, is 15-20 mass, part as of May 1. part III. Such a large excess of alcohol is necessary to suppress the process of saponification of permethric acid ethyl ester to the corresponding salts and the formation of permethric acid ethyl ester from III.

Treatment of the mixture of III and IV with alkali metal hydroxides allows a significant portion of 111 and IV to be converted. The total yield of permethric acid ester is 96-98%.

The whole process can be represented as follows:

40

adding a mixture of III and IV with a fresh mixture of lit and V. then the scheme will take the form:

HCtU-TcOJ

n, with sn5

VII

sn

NCS ± 1

con s n he

50 ml abs. ethanol, a solution of 8.4 g KOH in 190 ml abs. ethanol. The reaction mixture was stirred at 70 ° C for 30 minutes, cooled, neutralized conc. hydrochloric acid to a pH of 6-7. Ethanol was evaporated, 150 ml of toluene and 100 ml were added to the residue. water, the layers are separated. The organic layer was washed with 50 ml of water and dried over anhydrous MgS04. Toluene was distilled off, and os-TOK was distilled in vacuo. Receive

18.7 g IV (R-F t) (yield 75%, content 95%). Wastewater containing 2.8 g of 1 () and 3.6 g of VI () (yield 10.6 and 14.4%, respectively) is treated with conc. hydrochloric acid until, The resulting organic layer was extracted with diethyl ether, washed with water, dried with anhydrous MgS04. The ether was removed by distillation to obtain 5.1 g of mixture II and VII. HPLC analysis MHc-VII-8.1%, TpaHc-VII-49.3%, ll-42.6, I — traces. The yield of the mixture II + VII relative to I + VI is 85%. The resulting mixture II + VII is treated with 6.0. g of chloride embossed in W ml of EBS, ethanol. The reaction was stirred for 1 hour at boiling point. At the end of the reaction, the excess alcohol and tisnyl chloride were removed by distillation under reduced pressure to obtain 6.1 g of a mixture consisting of 2.9 g (III) and 3.2 g of IV (R to t) yield til and IV quantitative . This mixture is reacted with a cotiric solution of potassium hydroxide (f, 89 g of KOH and 55 ml of abs. Ethanol) at 70 ° C for 3 minutes. The reaction mass is cooled, neut. R-end, hydrochloric acid to pH 6-7. Ethanol was distilled off under reduced pressure, water and diethyl ether were added to the residue, the layers were separated, the organic layer was washed with water and dried with anhydrous MgS04. The ether was distilled off, the residue was distilled in vacuo to give 5.7 g (V (t), content 95%. The obtained permethric acid ethyl ester IV was added to the previously obtained. The total yield of ether IV was 98-%.

PRI me R 2. According to example I, but instead of III and V use 27.3 rill. The total yield of IV-96%.

Example 3. In Example 2, but after receiving 6.1 g of the mixture of III and IV, 209 g of fresh II and V were added to them in a ratio of 5: 1. Further, according to example 1. The total yield of ether IV-96% ..

Example 4. In Example 1, but instead of caustic potassium, 6.0 g of caustic soda is used to prepare the alcohol solution. In the first step of the process, 18.0 g IV (t, yield 76%) are obtained. Wastewater contains sodium salts I and VI in the amount of 2.6 and 3.3 g, respectively. Further, according to example 1, mixtures of II and VII and then III and IV are obtained. At the stage of interaction of III and IV with an alcohol solution of an alkaline agent, a solution prepared from 0.64 g of NaOH and 55 ml of abs. ethanol). Reaction conditions: 70 ° C and 40 min. Further, according to example 1, the yield is 96%.

PRI me R 5. According to example 4, but instead of compounds III and V (R e t) use HI and V

(), an alcoholic solution of caustic soda is prepared using methanol. A 26.0 mixture of III and V () in a 4: 1 ratio and a solution of 6.0 g sodium hydroxide are charged into the flask

and 230 ml of methanol. The process is carried out at 57-60 ° C for 40 minutes. Further by example. 4, IV () is isolated in 76% yield. Wastewater, water contains sodium salts I and VI in the amount of 2.8 and 3.0 g, respectively. At

0 processing of sodium salts of I and VI conc. hydrochloric acid With subsequent extraction of organic products with a solvent, it is isolated: as, for example, 1.5 g of a mixture of II and VII. :: This mixture interacts with 5.8 chloride

5 tyr yna in 13 ml of methanol. The reaction mass is stirred at the boil for 1 hour. Excess alcohol and tisnyl chloride are removed by distillation. 5.8 g of a mixture are obtained (Ni: jy (), quantitative yield,

0 Delaye bshb atyuyut alcohol solution,

r) p r0T10v enmg. from 0.7 g of caustic soda and 57

ml: m: ethanol; gtr 57-60 ° C for 40 mi.

:; chickpeas Train allocation (as in example 1) by,; L.u a rt; 4DtIV (). Methyl obtained; 5; ethe; p;: permethric acid; added: - are / to / previously obtained. Total yield IV () - This is 97%.

Example 6. As in example 5, but instead of caustic: n atra for the preparation of alcohol

0 solution use 8.4 g of caustic feces and 230 m; l of methanol. In the first stage of the process, 17.2 g of lV () are obtained (yield 77%). Wastewater contains potassium salts I and VII in quantities of 2.6 g and 3.3 g, respectively. After 5 treatment steps I and VII () of Example 1, 4.7 g of a mixture of II and VII are recovered. This mixture is reacted with 5.4 g of tisnyl chloride in 12 ml of methanol. Further, in Example 5, 5.4 g of thionyl chloride in 12 ml of methanol are obtained. Further, according to example 5 receive 5.4 g

a mixture of 111 and IV () which is processed

potassium hydroxide solution (0.8 g

KOH and 3.8 ml of methanol). According to example 5 floor. 4.7 g of IV () are taken into account. Total yield IV

5 () is 98%.

PRI me R 7, The conversion of a mixture of II and VII in III and IV. 8.8 g of a mixture of lactone and permethric acid in a ratio of 1: 1.35 and 22 ml of abs. ethanol. 10.0 g of thionyl chloride was added 0 ml. The reaction mixture was stirred at the boil for 1 hour. Excess alcohol and thionyl chloride are removed under reduced pressure. 10.6 g of a mixture of III and IV (R Ј t) are obtained.

5 GLC and HPLC analyzes show: cis-IV - 7.1%, transn-P / -45.5% III - 44.6% (yield for both products 97-98%). Impurities of the starting materials are contained in an amount of not more than 0.2% of each or none at all.

PRI me R 8. In example 7, but using methanol, get 10.5 g of II and IV (yield 96-98%).

PRI me R 9. In example 7, but the temperature is 50 PS, get 10.5 g of a mixture of III and IV (R-t). GLC and HPLC analyzes: cis-IV - 5.3%, trans-IV - 42.7%, III - 42.2%, cis VII - 2.8%, lactone II - 0.3% (yield IV - 88-90%

III -90%).

PRI me R 10. According to example 7, but the temperature is 30 ° C. 10.6 g of a mixture are obtained, (t). GLC and HPLC assays: cis-IV - 2.6%, trans

IV - 26.8%, III - 45.0% cis-VII - 5.0%, trans-VII - 20.6%, I - traces (yield IV - 55%, III - 98%).

EXAMPLE 11 As in Example 7, but 25 g of thionyl chloride were added, 10.2 g of the mixture was obtained. GLC and HPLC analyzes: cis-IV (R Ј t) - 5.2%, trans-IV -45.0%, III (R t) - 45.4%, cis-VII - 1.9%, trans VII - 3.1%, lactone - traces (yield IV 88-91%, III - 95%).

PRI me R 12. In example 7, but add 5 g of thionol chloride in two hours. Obtain 10.0 g of the mixture. GLC and HPLC analyzes: cis-VI -7.2%, trans-U-48%. Ill - 10.6%, cis VII - 0.2%, trans VII - 0.3%, I - 30.0% (yield IV-97%).

PRI me R 13. According to example 7, but added 40 g of thionyl chloride. Obtain 11.0 g of the mixture. GLC and HPLC analyzes: cisM -6.9%, trans IV-38.8%, 111-33.1%, cis VII - 4.0%, trans VII - 1.5%, II - 8.8% (yield II-74 , 0%, IV-88.0%).

PRI me R 14. According to example 7, add 45 ml of abs, ethanol. 10.7 g of a mixture are obtained. GLC and HPLC analyzes: cis-IV - 7.5%, trans IV - 45.0%. Ill - 39.8%, cis VII -, 01%. trans VII - 0.4%, II - 0.5% (yield III - 86%, IV - 98%).

PRI me R 15. In example 7, but add 90 ml of abs. ethanol. Obtain 10.3 g of the mixture. GLC and HPLC analyzes: cis IV-6.8%, trans IV-42.7%, 111-31.0%, cis VII - 1.7%, trans VII - 4.3%, II - 12.8% (yield III - 65%, IV-90%).

Example 16. In Example 7, but 7.5 g of thionyl chloride were added. The process is carried out for 2 hours. 10.7 g of the mixture are obtained. GLC and HPLC analyzes: cis IV-6.3%, trans IV -44.7%. Ill -20.7%. cis VII -0.2%, trans Vll traces, II - 19.2% (yield IV- 95-96%. 111-45%).

PRI me R 17. The conversion of a mixture of III and IV in ether permethric acid IV. 10.6 g of the mixture are charged into the flask; in Example 7, an alcoholic solution of potassium hydroxide is prepared, prepared from 1.45 g of KOH and 90 ml of abs. ethanol. Stirring, the mixture is kept at 70th for; 30 minutes. Reactionary

the mass is cooled, neutralizing conc. hydrochloric acid to pH fi-7. Analyzes of the reaction mixture GLC and HPLC: cis IV 2.9%, trans IV 68.7%, III 2.3%, cis VI 1.4%. 5 trans VI - 9.0%, I - 5.8%, yield IV 60%, VI.- 25%, I - 15% for starting III in the mixture. Ethanol was distilled off under reduced pressure, water was added, the layers were separated, the organic layer was washed with water and dried.

0 atv. MgSO / j. Diethyl ether was distilled off to obtain 11.0 g of a mixture containing 80% IV; 8.8 g of ethyl permethric acid IV was isolated by vacuum distillation of 72-74%, 2 mm Hg. Art.

5 PRI me R 18. According to example 17. but for the preparation of an alcoholic solution of potassium hydroxide, 43 ml of abs. ethanol. Get the reaction mixture containing GLC and HPLC: cis IV-11.2%, trans IV0 49.3%. Ill - 16.4%, cis VI - 3.2%. trans VI - 12.9%, 1-7.0%. (yield IV-37%, VI-34.1%, I -17%). 11 g of product containing 60% IV were isolated. After distillation in vacuo, 6.6 g of IV are obtained.

5 PRI me R 19. According to example 17, but to prepare an alcoholic solution of caustic potassium take 120 ml of abs. ethanol, get the reaction mixture, according to GLC and HPLC: cis-IV - 12.6%, trans-IV - 63.4%.

0 III-2.6%, cis VI-1.7%, trans VI - 10.0%, 1-6.0%, (yield IV-53.3%, VI-26%, 1-16%), 10 8 g of a product containing 76% IV. After vacuum distillation, 8.2 g of IV are obtained.

5- Example 20. According to example 17, but 150 ml were taken to prepare an alcoholic solution of potassium hydroxide. abs. ethanol. GLC and HPLC analyzes: cis IV - 12.3%, trans IV - 49.2%, III - 15.8%. cis VI - 3.3%, trans VI 0 11.7%, 1-6.3% (yield IV-39%, VI -33%, I - 12%). 11.2 g of product are isolated (content IV - 57.3%). After vacuum distillation, 5.7 g of IV are obtained.

Example 21. According to example 17, but for

In the preparation of the alcohol solution, 1.0 g of sodium hydroxide is used, and the reaction is obtained. reaction mixture by GLC and HPLC analysis: cis IV - 13.2%, trans IV - 70%. Ill - 2.3%,. 4HcV (() - 1.3%, TpaHcVI () - 8.0%,

0 I () - 5.3%. (yield IV - 58%, VI () - 260.1 () - 12%, 10.3 g of product are isolated (IV content - 83.2%). After distillation in vacuo - 8.4 g IV.

PRI me R 22. For example 17, in a flask

5 loaded 10.5 g of the mixture obtained in example 8 () and a potassium hydroxide solution prepared from 1.4 g of KOH and 86 ml of methanol. The reaction mixture was stirred at 60 ° C for 30 minutes, then cooled, neutralized conc. salt

acid to a pH of 6-7. Methanol was distilled off under reduced pressure, water was added, the layers were separated, org. the layer is washed and dried anv. MgS04. 8.6 g of product IV () are obtained, and isolated by vacuum distillation at 68-70 / 02 mm Hg. Art.

GLC and HPLC assays mixtures at pH 6-7: dcis IV () - 12.4%, trans IV () - 67.1%, III-2.2%, cis VI - 1.3%. trans IV () - 67.1%, III - 2.2%. cis VI - 1.3%, trans VI -9.2%. I - 6.0% (yield IV - 59%, VI-25%, 1-14%).

Some generalized data for examples 7-22 are given in table .. 1 and 2.

PRI me R 23. In example 1, but instead of ethanol, tert-butanol is used in the synthesis of the permethric acid ester (PC). After carrying out the reaction, neutralizing the reaction mixture, stripping t-butanol (together with ethanol) and extracting the target product, a mixture of ethyl and t-butyl ethers of PC is obtained (yield 70%). PC esters were isolated as in Example 1. Wastewater was treated as in Example 1. In the reaction of mixture III and IV with a highly dilute KOH solution, t-butanol was used. Again get a mixture of esters of PC (R e t and t-Bu). PC esters are isolated by vacuum distillation. The total yield of PC esters is 92%.

Thus, this method greatly simplifies the process technology by eliminating the distillation step using distillation columns.

Table 1

The interaction of a mixture of u-butyrolactone (II) and permethric acid (VII) with thionyl chloride in this zero

Instead of € t, they use MeOH.

Claims (1)

SUMMARY OF THE INVENTION Method for the preparation of lower Ci-C-alkyl esters of 2,2-dimethyl-3- (2,2-dichloroethyl) cyclopropanecarboxylic acid by the interaction of Ci-C4 alkyl esters of 4,6,6-trichloro-3,3-dimethylhexene-5-and 6,6,6-trichloro-3,3-dimethylhexen-4-acids with an alcoholic solution of sodium or potassium hydroxide and subsequent processing of the reaction mixture with hydrochloric acid, characterized in that, in order to simplify the process technology, hydrochloric acid is added to the reaction mass to a pH of 6-7, after which the target is immediately recovered product, and the resulting aqueous solution containing the sodium or potassium salt of 3,3-dimethyl-4-hydroxy-6,6-dichlorohexene-5-and 2,2-dimethyl-3 / 2,2-dichloroethenyl / cyclopropanecarboxylic acid , treated with concentrated hydrochloric acid, the resulting mixture of 2,2-dimethyl-3 / 2,2-dichloroethenyl / cycloprop-necarboxylic acid and 2 / 2,2-dichlorovinyl / 3,3-dimethyl-y-butyrolactone t in reaction with gionyl chloride in the presence of alcohol, the resulting mixture of C1-C2 esters of 2,2-dimethyl-3 / 2,2-dichloro-ethenyl / cyclopropanecarboxylic and 4,6,6-trichloro-3,3-dimethylhexene-5-ova acids treated with a C1-C4 alcohol solution of potassium or sodium hydroxide in the presence of a 15-20-fold excess of alcohol to obtain an additional amount of the desired product, which is isolated. Table 2 Interaction of mixtures III and IV with an alcohol solution of alkali metal hydroxide  Instead of KOH, NAOH is used.  Instead of e. T OH, they use MeOH.