SU1468410A3 - Method of producing derivatives of cyclopropanecarboxylic acid - Google Patents

Abstract

The invention relates to all possible isomers and to the isomer mixtures of the compounds of the formula I: <IMAGE> in which the coupling of the cyclopropanoic acid has a 1R cis or 1R trans structure, X represents a halogen atom and R represents a hydrogen atom, a linear, branched or cyclic alkyl radical which is saturated or unsaturated and contained up to 12 carbon atoms, or the radical of an alcohol R-OH used in the synthesis of pyrethroids, where the geometry of the double bond on the carbon in the 3 position can have the E or Z structure. The invention also relates to a process for the preparation of the compounds of formula I. The invention equally relates to the application of the compounds of formula I in the control of parasites.

Description

one

This invention relates to a process for the preparation of novel cyclopropanecarboxylic acid derivatives of the general formula:

NCS CH, C-Ji

-C02R,

where the configuration of the acid can have shsh 1K - trans structure;

X is a halogen, except for iodine, the radical in the double bond with carbon in position 3 can have the structure E or Z |

R is a linear kil or a CH-Ar group in which Z is cyano,

methyl;

Ag radicals. General formula:

SNS

where.8. - hydrogen, fluorine; or r

about

if X is bromine, R is a radical 20

ABOUT

v tjc: t)

and

sh

where E is hydrogen5 fluorine,

then carbon at Z is in the S-configuration "

These compounds have an insectoacaricidal action.

The purpose of the invention is to develop a process for the preparation of new derivatives of lopropancarboxylic acids, which have a higher activity compared with compounds of similar structure for similar purposes.

Example I. 1E is cis 2,2-Dimethyl-3- (E + Z) -2-bromo-2-cyanoethenyl cyclopropanecarboxylic acid.

 In an inert atmosphere, 3s, 5 g of bromo cyanomethylenetriphenylphosphorane, 30 cm of tetrahydrofuran and 4 cm of dimethylformamide are mixed. 5.3 g of lactone 1B of cis-2,2-dimethyldihydroxymethylcyclopropanecarboxylic acid and JO cm tetrahydrofuran are added to the solution obtained. Hold at room temperature for 16 hours, bring to dryness, obtain 5.8 g of an oily residue, which is chromatographed on silica, eluting with a mixture of hexane-ethyl ester of acetic acid (7: 3) containing 1% acetic acid. A mixture of the isomers DE and fiZ is obtained (mp. 132 C).

EXAMPLE 2 (8) og.-Cyano-3-phenoxybenzyl ester 1K-cis-2,2-dimethyl-3 (d, E) -2-bromo-2-cyanoethenyl isyl

ten

15

20

25

35

40

:,

45

50

55

lopropanecarboxylic acid and the corresponding isomer Z.

At 0 - (+) 5 ° C, 30 mg of di- is added;

but

 methylaminopyridine to 10 cm of a solution containing 1.4 g of 1K-cis-2,2-dimethyl 3- (E + Z) -2-bromo-2-cyanoethenyl of cyclopropanecarboxylic acid and 1.4 g of (S) o-cyano -3-phenoxybenzyl alcohol. Then 1.2 gdicycpohexylcarbodiigidea and 5 cm of methylene chloride are added. The temperature of the reaction mixture is allowed to rise to 20 ° C, after which it is stirred for 3 hours. The resulting urea is filtered off, rinsed and the filtrate is brought to dryness. 3.7 g of product are obtained, KOtopbM is chromatographed on silica, eluting with benzene. 1.3 g of isomer E (mp, 60 ° C) and 750 mg of UZ isomer are obtained (t.hr> 64 ° C).

PRI me R 3. Tetrabutyl 1K cis-2,2-dimethyl-3- (DZ) -2-α-ftop-2-dianoethenyl cyclopropanecarboxylic acid and the corresponding isomer &amp;

While stirring for 1 hour, a mixture of 15 g of phenylbromofluorocyanomethylmercury, 180 cm of xylene, 8 g of triphenylphosphine and 5.25 g of 1-Ris c-butyl ether is boiled. -2,2-dimethyl-3-formylcyclopropane-1-carboxylic acid.

The mixture is cooled with ice, filtered and the precipitate formed is dried. 20 g of product are obtained which is chromatographed on silica, eluting with pure benzene.

Get 3 g of isomer & E (, 4); 1.3 g of isomer &amp; Z (, 33).

Preparation of phenylbromofluoro cyano-methylmercury.

a) Bromo-lactoacetamide.

At 5 ° C and with stirring, 86 cm of concentrated ammonium hydroxide is added to 79 g of bromofluoroacetic acid ethyl ester. The mixture is kept at the same temperature with stirring for an additional 30 minutes, then the mixture is evaporated to dryness, the residue is distilled and 53.6 g of the expected product are obtained. TiP.82-84 ° C / 0.1 mmHg

b) Bromofluoroacetonitrile.

92 g of phosphoric anhydride are added to 183 g of bromofluoroacetamide, boosted, heated enough to mix, and then gradually heat the mixture until it is distilled and distilled.

146

between 55 and 80 ° C., 87 g of the crude desired product are obtained.

c) Phenylbromftorgshanometilmertu.

15.65 g of phenylmercury chloride in 100 cm of tetragndrofuran are cooled to -50 ° C, 10.6 g of the obtained fluorobromoacetonitrile are added, and then a suspension containing 7.85 g of tert-butylate is added with stirring at -50 ° C. potassium, 50 cm of tetrahydrofuran and 6.6 cm of t-butyl alcohol.

After 30 min the reaction mixture

drink on ice water containing this

15

6 cm of concentrated hydrochloric acid and extracted with chloroform. The organic layer is dried and concentrated to dryness. The residue is treated with hporoform-hexane (1: 1), the insoluble material is filtered off, cooled with ice, sucked off and 9.3 g of the expected product are obtained (mp. 30-132 C).

PRI me R 4. K-cis-2,2-Dimethyl-25 -3- (LZ) -2-cyano-2-fluorophenyl) -cyclopropanecarboxylic acid.

1.3 g of tert-butyl 1K-cis-2,2-dimethyl- 3- (iZ) -2-cyano-2-fluoropoly ethyl cyclo-30 propancarboxylic acid in 13 cm methylbenzene and 130 are heated to 120-130 C. cm para-toluenesulforate. The reaction mixture is boiled for 15 minutes with stirring. Then the reaction mixture is cooled35

about 20 ° C, washed with water, dried over the toluene solution, filtered off and brought to dryness under reduced pressure. 1 g of the expected product is obtained. 40

Example 5: P cis-2,2-Dimethyl-3- (HE) -2-cyano-2-fluoroethenyl cyclopropanecarboxylic acid.

The method is carried out analogously to example 4, starting from tert-butyl ester 45 1E-cis-2,2-dimethyl-3- (ME) -2-fluoro-2-cyanosis tenyl cyclopropic carboxylic acid, thus obtaining the desired product.

PRI me R 6. (S) oi-Cyano-3-fen-. o-cis-2,2-dimethyl-3-L (&amp; Z) -2-fluorop-2-cyanoethenyl) cyclopropanecarboxylic acid hydroxybenzyl ester.

At 5 C, 30 g of dimetypamine pyridine is added to a solution containing g of 1E cis-2,2-dimethyl-3- (lg) -2-fluoro-2-cnanoethenyl cyclopropanecarboxylic acid, 6 cm of chloride

Yu

15

0

25

0 5

0

five

0

five

106

and 1, 2 g (S) of C.-cyano-3-pheno-sibenzyl ovine ciinp ra. Then, 1.1 g of dicyclohexylcar () O11Lim1c; a and 8 cm of methylene chloride are added. The temperature of the reaction mixture is allowed to rise to 20 ° C and the mixture Eb: core: is sown when peremegaizanii in 2 hours. Then add 0.5 cm of acetic acid and 0.5 cm of ethanol. Dofi 1tro The urea formed at the same time is rinsed with a small amount of chloride (ethyl, and the filtrate is rypartirovat. I get; - 2.8 g of the product that HFH is grafted with silicon dioxide, methylene chloride – hexane (8: 2) is eluted. 8 , 5 g of crude target product. After recrystallization in isopropanol, 3 g of the crude product melting at 90 ° C is obtained.

EXAMPLE 7. 1K-cis-2,2-Dimethyl-3- (E + Z) -2-chloro-2-cyano tenyl) cyclopropancarbon ra-iclota.

The method is carried out as in Example I, but starting from cyanomethyltriphenylphosphine, to obtain the desired product with mp. 50 ° C.

PRI me R 8. (S) fi-Cyano-3-phenoxybenzyl ester of R-cis-2,2-dimethyl-3 {(4E) -2-chloro-2-cyanoethenesh1 cyclopropanecarboxylic acid and with - Corresponding fiZ isomer.

Similarly, 2, but starting from the acid obtained in npiiMepe 7, the isomer b.E. (t.p.66 ° C) and. UZ isomer (mp. -63 C).

PRI me R 9, (S) o -Ciacho-3-phenoxybenzyl ester 1 G -trans-2, 2-dimethyl-3- (DE) -2-cyano-2-f goreti-) cyclopropanecarboxylic acid and the corresponding isomer AZ.

For 2 hours, mixtures containing 10 g of (S) oi-cyano-3-phenoxy-benzyl alcohol P-trans-2,2-dimethyl-3-formylcyclopane and karb it acid, 8 g are boiled. triphenylphosphine, 180 cm of xylene and 15 g of phenylbromo1 dianofluorome-TSH1R1UTI. Chilled with ice, sucked off and the filtrate is brought to dryness. 24 g of oil are obtained, which is chromatographed on silica, eluirou toluo: scrap. After several times: 835 mg of isomer 7., ± 1.5 ° (in SEC1) and 1.8 g of isomer, .2.5 ° (, 52 in SNA 1) are isolated.

Example 10-22. Acting as indicated in example 9, receive the products shown in table. I, corresponding to the formula

X.

12

Vg

w-cis-qb

13

Cr g e

lR-cis

U

 15

sixteen

17

M -6 ° (, 3% toluene)

Jd

C1 gilieE lR-trans-CH-W

B. 0- ci 1 ° (with 1% toluene)

 EraiHZ - --СН-О

1 VIZiC f

B 0t. 94 ° C (E) W.p 71 ± 2 (toluene, Z)

C1 E iai Z lR-cis-

Sh.

And 24 + 2.5 ° (, 5% СНС1,). And + 38 + 2.5 ° (, 5% СНС1,)

 E + Z

 Z Fe

DiSjf +3, 5% СНС1,) Ш-cis-КзС

(S)

Мц +5613, (, 35% СНС1,) +1742.5 (, 5% СНСЦ)

)

 + 8614 °, 2% CHCl,)

Table 1

and -s-SajSilsS (toluene)

- U

 Wj3 +41.512.5 (, 5%

toluene)

Example 23, 1K-cis-2,2-Dimethyl-3-L (Z) -2-6pOM-2-iyiaHO3TeHn.nJ-cyclopropanecarboxylic acid.

Stage A, 1R cis-2,2-dimethyl-3- (Z) -2-bromo-2-cyano-ethenyl) cyclopropicarboxylic acid t-butyl ester and isomer E.

7.5 g of bromo cyanomethylene triphenylphosphorane in 50 cm of tetrahydrofuran and 4 g of tert-butyl 1K-cis-2,2-dimethyl-3-formylcyclopropanecarboxylic acid in 50 cm of tetra schdrofuran are mixed and the mixture is heated for 20 hours at boiling. After cooling, the filtrate is filtered off with suction, the filtrate is concentrated to dryness under reduced pressure, the residue is taken up with 100 cm of isopropyl ether, the insoluble material is filtered off with suction and the resulting filtrate is concentrated to dryness. The residue is chromatographed on silica, eluted with a mixture of hexane and ethyl acetate (95 :: 5 and 1.4 g isomer a E is obtained, m.p.

102-103 ° C, 0.4 g of Z isomer, so pl. 50 C and 0.7 g of isomers.

Stage B. 1K-dis-2,2-Dimethyl-3- (g) -2-bromo-2-dianoethenyl) cyclopropancarboxylic acid.

During 30 minutes, 1.5 g of Z isomer obtained in stage A, 50 cm of anhydrous toluene and 150 mg of para-goluenesulfonic acid are heated at boiling. After cooling to room temperature, the organic layer is washed with water, dried, and the concentrate is rinsed to dryness. Obtain 1.2 g of the target. product, so pl. 1 39-1 40 s.

and idle more} 1 Don't rat

25

30 - 0

five

0

five

And rmimep 24. 1K trans-2 S 2-D .- MO-Tyl-3- (E + Z) -2-bromo 2-C1 gano ete ;; i.yy.p. cyclopropancarbonic jcHCJioTa.

Stage A. 1R-trans-2 J 2-dimethyl-3-j (E + Z) -2-6pOM-2-cyanoethenyl cyclopropanecarboxylic acid tertbugyl ether.

The procedure is as in stage A of Example 23, but starting from 4 g of K-trans-2j2-dimethyl-3-tert-butyl ester tert-butyl ester and floor, and 2.7 g of the desired product, mp.88 C

Stage B. 1 R-TpaHc-2, 2-dimethI-Jr-3- (E + Z) -2-bromo-2-cyanoethenyl) -cyclopropanoic acid.

The method is carried out as in Stage B of Example 23, but starting from 2.7 g of the resulting product, and 2.05 g of the desired product are obtained, mp.136 ° C.

Example 25 (K, 5) -2- (6-Phenoxipirid L) ethyl K-cis-252-dimethyl-3- (Z) -2-chlorop-2-cyanoethenyl) cyclopropanecarboxylic acid ethyl ester and (RjS) - 2- (b-phenoxypyridyl) ethyl ester of P cis-2,2-dnmethyl-3- (G) -2-chloro-2-cyanoethenyl) cyclopropanecarboxylic acid.

Acting anapogically on Example 23, 1H-cis-2, 2-dimesh-1- 3- (Z) -2-chloro-2-cyanoethenyl) cycocyclo- is esterified. pancarboxylic acid (K, 8) -2- (b-phen oxypyridyl) with ethyl alcohol, chromatograph the resulting ester on silica, eluting with a mixture of hexane and ethyl acetate (8: 2), and then a mixture of hexane and ethyl acetate (acetic acid) 7) and get 1.08 g isomer

pa E and 2.65 g of a mixture, which is again purified by chromatography on silica, eluting with a mixture of hexane - ethyl e (| Mr acetic acid (9: 1)) From 1.20 g of isomer Z.

Isomer E: Id + 52.5 ° (; 5% chloroform).

Z isomer: Mo about + 14.5 ° (; 5% chloroform)

EXAMPLE 26. (K, 8) -Ciano 2- (6-phenoxypyridip) methyl 1R-cis-2 52-dimethyl-3- (E) -2-bromo-2-cyanoetenyl isclopropanecarboxylic acid .

Acting as in Example 24, but starting from 1K-cis-2.2 dimesht-3- (Z) -2-6poM 2- cyanoethenyl niclopropanecarboxylic acid and (K, 5) -cyano-2- (6-phenoxy - pyridyl) methyl alcohol, receive the target compound. oi..p +3 (toluene),

Example 27. 1H-trans-2,2-dimethyl-3- (E) -2-bromo 2-cyanoethenip3 cyclopropanecarboxylic acid ((8) o-cyano 3 -phenoxybenzyl ester 1 - trans-2 52-dimethyl-3- (Z) -2-6poM -2 cyanoethenyl cyclopropanecarboxylic acid.

By proceeding analogously to example 25, but starting from the acid described in example 24 and the corresponding alcohol, the desired isomer E with T.rai is obtained. 118 ° C. +20 (to 1% chloroform) and the isomer Z with t.sh1. 115 C,

EXAMPLE 28 (5) -2-Methyl-4-oxy-3-3- (2-propenyl) -2-diclopenten-1-yl ester 1C cis-2,2-dimetsh-1-3- ( Z) -2-Brom 2-cyanoethenyl cyclopropanecarboxylic acid.

1E-cis-5E

lR-cis-, Z

lR-cis-, E

Z

lR-cis-, Z.

lR-cis-, E lR-trans-, E

 five

Sh

15

68410 12

Acting as in Example 25, but starting from the acid described in Example 23 and the corresponding alcohol, the desired product is obtained.

NMR (deuterochloroform): peak at 1.3 ppm of doubled methyl; a peak at 2.0 ppm of hydrogen in 2 upheterolone, a peak at 4.8-5.25 ppm of methylene hydroxide; peaks at 555-6.2 ppm of hydrogen; a peak at 5.7 ppm of hydrogen at the t position of allerotron; peaks at 7., 3-7.5 ppm of ethylene hydrogen double bond carrying CN and Br.

Pr imer 29. Investigation of the effect of the apification of house flies.

The insects under study are domesticated female flies, d. 4 days old. Operate direct pollination in the chamber at a concentration of 0.25 g / l of the test compound 1:. The solvent used is a mixture of acetone and petroleum solvent. The experiment uses 50 insects | x The control is carried out for 10 minutes every minute and KG 50 is determined - the time, 30 required for the destruction of 50% of insects and P - the relative power ratio between the time for the destruction of 50% of the insect; 1x, treated with a known agent, and the time required to kill 50% of insects treated with a compound of this technical solution. KG 50 expressed in minutes

 The results are shown in Table. 2, A well-known comparative compound is 1K-cis-252-dimethyl-3- (2,2-dibromvinp) -cyclopropanone-1-carboxyl aT- (S) oi-cyano-3-phenoxy-benzip alcohol.

table 2

20

25

40

1.843 2.320 2.776 2.324 3.639 4.073 3.212

As can be seen from the table. 2, the compounds obtained according to the inventive method are more active than the known compound 1K-cis-2,2-dimethyl-3- (2J2-dibrophenyl) -cyclo-propano-1-carboxylate-8) in (.cialo- 3-yenoxybenzyl alcohol.

Continuation of table 2

PRI me R 30, the Study of the lethal effect on the cockroach.

Tests are carried out by contact on a glass film, pipetting off acetone solutions of various concentrations to the bottom of a glass Petri dish, the edges of which are preliminarily powdered.

talcum powder. to avoid the flight of insects. Determine the concentration of LCjij in summer, i.e. a dose that allows the killing of half of the cockroaches. . The research results are shown in Table. 3,

Table3

PRI me R PG, and a chain of lethal effect on larvae of the caterpillars of Spodoptera littoralis,

Tests are carried out by topical application of a toxic acetone solution using a micromanipulator to the back of the caterpillars. The product is determined using 15 larvae per dose of the study product. Caterpillars in the hots of the larvae in the fourth larval stage5 i.e. about 10 days old at cultivation on an artificial environment (Poitou's environment) at 24 C and 65% relative humidity. After the treatment, the individuals are monitored t on the nutrient and kyccccased medium. Mortality control is carried out 48 hours after treatment.

The experimental results obtained by dp of the compounds of Examples 2, 6, 8, 21, and 23 are between 0.48 and 4.8 ng per insect.

Example 32. Study of the acaricidal effect.

Bean seedlings are used, containing 2 leaves, on which there are 25 females of Tetranychus Urticae per leaf, and located under the No. 1M ventilation hood under the lighted ceiling under constant illumination.

The seedlings are treated with a Fisher pistol; 4 mp, the studied solution containing a pyrethrinoid, on a sapling, with a mixture of identical volumes of water and acetone. Allow to dry for 12 hours and then provoke infection. Controls-mortality are maintained after 80 hours. LC5o, .T.e is determined.

concentration, dp which receive 50% mortality.

The resulting huge results are presented in Table. four.

Table4

Claims (1)

15 claims The method of obtaining cyclopropane carboxylic acid derivatives of general formula ° X Z.SNz V P .X g Well, n , wherein the cyclopropanoic acid configuration may have an lR-cis or 1R-tr anc structure, X is a halogen, other than iodine, the radical, with a double bond with carbon in position 3, can have the structure E or Z; R - linear C-C-alkyl-ip CH-Ar group, where Z is cyano, Z methyl; Ar - radicals of general formula 40R. where R is hydrogen, fluorine; ipi r SNS Lo however, if X is bromine, R is a radical 171A68410 where P is hydrogen, fluorine, X then carbon when Z is in S-con- (CgHjl P C t factions, CN characterized in that the compound of the general formula where X has the indicated meanings, in xylene, in tetrahydrofuran with HzS CH320 ° C or the boiling point of the reaction of the SOW mixture, the resulting product you. I. - is divided or subjected to etheriLicapin  -II if R is hydrogen, or if R has R - water or R R, then values other than hydrogen, subjected to interaction with the compound, subjected to hydrolysis, and then etterneniem formulation.