CS264272B2 - Process for preparing pyrimidin-5-yl cyclopropancarboxylic acid esters with insecticide and acaricide activity - Google Patents

Abstract

Process for the production of compounds of the general formula of formula I wherein R2 is branched at the carbon C3-6-alkyl and R is a radical of formula A, wherein X is oxygen, sulfur, vinylene or a residue —CR5 = Y—, where Y is nitrogen or a group CR 5, R 4 is hydrogen, methyl, cyano or ethynyl, R5 are independently of one another each hydrogen, halogen or optionally halo-substituted C 1-4 -alkyl and R 6 is hydrogen, halogen, C 1-4 -alkyl, C 1-6 -alkenyl or C 1-6 -alkyl-substituted phenyl, phenoxyl or foenzyl, characterized in that it is a halide acids of formula II wherein Q is halogen, lets react with alcohol formulas R-H in the presence of a base. Produced compounds can be used as insecticides and acaricides.

Description

The present invention relates to a process for the preparation of novel ecyclopropanoic acids and derivatives thereof useful as intermediates, and to insecticidally active esters thereof.

Accordingly, the present invention provides novel cyclopropane derivatives of Formula I

in which

R ² represents a C 3 -C 6 alkyl group branched in the «-position and

R is a radical of formula (A)

in which

X represents oxygen, sulfur, vinylene or a radical of the formula - CR ⁵ = Y; wherein Y represents a nitrogen atom or a CR ⁵ group,

R ⁴ represents a hydrogen atom, a methyl group, a cyano group or an ethynyl group, the individual substituents R ⁵ being selected from the group consisting of hydrogen atom, halogen atoms and alkyl groups containing up to 4 carbon atoms optionally substituted by halogen, and

R ⁶ represents a hydrogen atom, a halogen atom, an alkyl group having up to 4 carbon atoms, an alkenyl group having up to 6 carbon atoms, a phenyl group, a phenoxy group or a benzyl group, or a phenyl, phenoxy or benzyl group substituted with halogen or C 1 -C 4 alkyl .

The object of the invention is a process for the preparation of the insecticidally and acaricidally active pyrimidin-5-ylcyclopropanecarboxylic acid esters of the aforementioned general formula (I), characterized in that the acid halide of the general formula (II)

CH-CH-C-a.

Cl-CH3 (II) in which

R ² is as defined above and Q is halogen, preferably chlorine, is reacted with an alcohol of formula VI

R-H (VI) wherein

R is as defined above, in the presence of a base.

A suitable throw is, for example, an alkali metal pyridine, an alkali metal hydroxide or carbonate or an alkali metal alkoxide.

The reaction according to the invention can optionally be carried out in the presence of a solvent or diluent and can be accelerated by washing at elevated temperature.

Other eseterification methods leading to the formation of insecticidally and acaricidally active esters of the formula I are described in our related Czechoslovak patents Nos. 264,263 and 264,271.

It will be appreciated that the compounds of formula (I) may exist in different isomeric forms and as mixtures of isomers. Thus, the possibility of cis and trans isomers is due to the nature of substitution on the cyclopropane ring, and optical isomerism is based on the presence of two chiral centers in the cyclopropane group, leading to the possibility of (-j -) - cis-, (-) -cis-, (4-) -trans- and (-) -trans-isomers. Further isomerism may occur with the insecticidally active esters of the invention when the alcohol moiety contains an alkenyl group or one or more chiral centers. All such individual isomeric forms, as well as mixtures thereof, including racemates, are within the scope of the invention.

The individual isomers may be prepared in the same manner as above, but using the corresponding individual isomers of the compounds of formula (II) as starting materials. These individual isomers may be obtained from the appropriate mixture of isomers by conventional resolution techniques. Thus, cis- and trans-isomers can be separated by fractional crystallization of the respective carboxylic acids or salts thereof, while various optically active substances can be obtained by fractional crystallization of acid salts with optically active amines, followed by regeneration of optically pure acid.

The optically pure isomeric acid is then reacted with the corresponding alcohol of formula (VI) to give the compound of formula (I) as the individual pure isomer after conversion to the halide.

Particular insecticidally and acaricidally active compounds of the invention include esters derived from the following alcohols:

4-Methyl-2,3,5,6-tetrafluorobenzyl alcohol for use in the preparation of fluorophenol

2B4272

4-allyl-2,3,5,6-tetrafluorobenzyl alcohol

4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol

3-phenoxybenzyl alcohol c-cyano-3-phenoxybenzyl alcohol

6-Phenoxypyrid-2-ylmethanol

1-Cyano-1- (6-phenoxypyrid-2-yl) methanol

3- (4-chlorophenoxybenzyl alcohol) α-ethynyl-3-phenoxybenzyl alcohol

1- (6-phenoxy-pyridin-2-yl) -ethanol

4-fluoro-3-phenoxybenzyl alcohol and 4-fluoro-3-phenoxybenzyl alcohol

5-ibenzyl-3-furylmethanol

2-allyl-3-methyl-4-hydroxycyclopent-2-enone

2-methyl-3-phenylbenzyl alcohol, including, where applicable, their individual isomers and racemates, and from the acid halides of formula II in the form of a racemic mixture of trans isomers or an individual isomer in which R ² represents:

A 2-propyl group,

2-butyl,

2-pentyl group,

3-pentyl group,

2-methylprop-2-yl,

2-methyl-but-2-yl, cyclopropyl or cyclohexyl.

Particularly preferred compounds of the invention include:

4-Methyl-2,3,5,6-tetrafluorobenzyl (+) -trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate

4-allyl-2,3,5,6-tetrafluorobenzyl- (+ J-trans-2,2-dimethyl-3- [2- (2-methylpropyl-2-yl) | pyrimidin-5-yl) cyclopropanecarboxylate

3-Phenoxybenzyl (+) -trans-2,2'-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate (+) -? -Cyano-3-phenoxybenzyl- (+) ^s -trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl j pyrimidiin-5-yl] cyclopropanecarboxylate

6-Phenoxypyrid-2-ylmethyl- (+) - trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate (+} -1-cyano-1 ( 6-Phenoxy-pyridin-2-yl) methyl (+) -trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) -pyrimidin-5-yl] cyclopropanecarboxylate

2-methyl-3-phenylbenzyl (+) - trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate

4-Fluoro-3-phenoxybenzyl (+) -trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecariboxylate (+) -1-cyano 1- (6-Phenoxy-pyridin-2-yl) methyl (+} - trans-2,2-dimethyl-3- (2-prop-2-yl-pyrimidin-5-yl) -cyclopropanecarboxylate (+) -1-cyano-1 (6-Phenoxy-pyridin-2-yl) methyl (+ 1-trans-2,2-dimethyl-3- (2-cyclohexyl-pyrimidin-5-yl) -cyclopropanecarboxylate (+) -1-cyano-1- (6) -f enoxypyrid-2-yl] methyl (+) -trans-2,2-dimethyl-3- ^{(2-cyclopropyl-J-5-yl)} icyklopropankarboxylát (+) -1- (6-f enoxypyrid-2-yl j pentafluorobenzyl (+) -trans-2,2-dimethyl- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate ethyl (+) -trans-2,2-dimethyl- 3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate (±) -? - ethynyl-3-phenoxybenzyl (+) - trans-2,2-dimethyl-3- [2] - (2-Methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate

4-methoxymethyl-2,3,5,6-tetrafluorobenzyl (+) - trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate and

2-methyl-3-phenylbenzyl (+ 1-trans-2,2-dimethyl-3- (2-prop-2-ylpyrimidin-5-yl) cycloipropanecarboxylate).

Intermediates corresponding to the above general formula (I) in which R represents an alkoxy group containing up to 6 carbon atoms which can be used to produce the starting acid halides of the formula (II) can be prepared from the appropriately substituted 5-thymopyrimidine by the following reaction sequence:

(a) 2-alkyl-5-bromopyridine in which the alkyl group is branched in the α-position is converted to the corresponding 5-formyl derivative by conversion to a Grignard compound and subsequent reaction with dimethylformamide. This procedure can be described by the following reaction scheme:

DMF

> R ‘

N- _x 7

CHO

S (Ib) ¹ 5-formylpyrimidine is reacted with 0,0-dialkyl-alkoxykarbonylinethylfosfonátem in the presence of base such natriumhyd6 chloride to give 3- (pyrimidin-5-yl) propemoátu in the following reaction scheme: ..,

A-CHO (EtO ^ PIO) CH _{CO 2} R NZH># - ^<Z ~ N = CH-C0, R ³ (c) This pyrimidinylpropenoát is reacted with isoipropyl-triphenylphosphonium salt in the presence of an organometallic reagent, such as n-butyllithium, to give the cyclopropanoic acid ester. This reaction proceeds according to the following reaction scheme;

According to an alternative process for the preparation of 3-pyrimidin-5-ylpropenoates, 5-bromopyridine can be directly reacted with an alkyl propenoate (especially 1,1-dimethylethyl propenoate) in the presence of a divalent γ-CH ₂ CO ₃ palladium salt (e.g. palladium acetate) , tetramethylethylenediamine and preferably a phosphine derivative (e.g. triphenylphosphine), in the sense of the following reaction scheme:

CH2 = CH — GO2R ⁹ / Pd (000CH3 1 from tetramethylethylenediamine / triphenylphosphine

Some of the 5-bromopyridines used in this process are novel. These compounds can be prepared by reacting a mucobromic acid derivative with an appropriate amidine, followed by decarboxylation of the resulting pyrimidine carboxylic acid, according to the following reaction scheme:

O

II

H — C CO2H \ / c = c / \

Br Br

NH ₂ II

R ² -C-NH 2

---- g>.

284272 &

An alternative process for the preparation of compounds of formula I wherein R represents an alkoxy group containing up to 6 atoms. atoms and R ² is as defined above, consists in the following procedure.

(and Ylide obtained by the reaction of a phosphonium salt of the general formula [R / O-iCH 2 -P '(R ⁸ ) 3] ⁺ Y.

Y. represents any suitable amion, for example chloride or iibromide. the ion, and R ⁷ and R ⁸ represent alkyl or aryl groups, wherein S preferably R ⁷ represents an alkyl group containing up to 6 carbon atoms as methyl or ethyl, and R ⁸ represents a phenyl group with a strong base in and , a protic solvent, preferably a sodium derivative of dimethylsulfoxide in dimethylsulfoxide (prepared by reaction of sodium hydride with dimethylsulfoxide), is reacted with a compound of formula

O

II I!

Ri — C — CH — CH — C — H \ /

C / \

CH 3 i CH 3 for; to form a compound of formula III

O ¹¹

R — C — CH — CH — CHt = CH — OR ⁷ \ /

C / \

CH3. (B) The compound of formula (III) is treated with phosphoryl chloride with dimethylformamide. mamide under Vilsmeier-Haack reaction conditions to form compound; of formula (IV) or / or a compound of formula (V)

O CHO

11 'I

R = C — CH, —CH — C = CH — G / c

/ \

CH3 CHS (IV) ^OR7 G = (V G = N (C'H3) 2 (C Compound IV and / or a compound of formula V is then reacted with an amidine of the formula ·

NH

R ³ - C-NH2 with-preferably in. The presence, of a base such as sodium methoxldu-methanol at. to form a compound of formula I wherein R is as defined above.

The compounds of formulas III, IV and V have not been previously described.

Preferred compounds of formula III include the (+) - cis - and (+) - trans isomers thereof wherein R is methoxy or ethoxy and R ⁷ is an alkyl group containing up to 6 carbon atoms, including the following:

methyl (+ Γ-trans-3 - [(E, Z) -2-methoxy vinyl] -2,2-dimethylcyclopropane carboxylate methyl - (+ 1-cis-3 - [(E, Z) -2- methoxy vinyl] -2 ₇ 2-dimethylcyklopropankarboxylái ethyl (+) -trans-3- [(E, Z) -2-methoxyvinyl] -2,2-dimethylcyclopropanecarboxylate ethyl (+) -cis-3- [(E, Z) -2-methoxy vinyl] -2,2-dimethylcyclopropanecarboxylate.

Corresponding compounds of formula IV and formula V which are also preferred include the following;

methyl (+ 1-trans-3 - [(E, Z) -1-formyl-2-methoxyvinyl] -2,2-dimethylcyclopropanecarboxylate methyl (+) - cis-3 - [(E, Z) - Formyl 2-methoxyvinyl] -2,2-dimethylcyclopropanecarboxylate methyl (+) - trans-3 - [(E, Z) -2-dimethylamino-1-formylvinyl] -2,2-dimethylcyclopropanecarboxylate and methyl (+) - cis 3 - [(E, Z) -2-dimethylamino-1-formylvinyl] -2,27-dimethylcyclopropanecarboxylate as well as the corresponding ethyl esters.

Further details of all these processes are given in the Examples below. The obtained alkyl esters can be saponified to the free acids by hydrolysis, preferably alkaline hydrolysis using, for example, aqueous alcoholic sodium hydroxide solution, and then reacted with a suitable halogenating agent, such as with thtonyl chloride, to convert the desired starting halides of formula II.

The compounds produced by the process of the invention can be used to control harmful insects and other invertebrate pests, such as mites. Among the insect and acarid pests that can be combated using the compounds of the present invention, 264272 are those pests related to agriculture (which includes growing crops for food and fiber production, horticulture and livestock production), forestry, storage of products of plant origin , such as fruit, grain and wood, as well as pests transmitting diseases of humans and animals.

For application to pests, the compounds of the invention are usually formulated to formulations which, in addition to the insecticidally active compound or compounds of formula I, contain suitable inert diluents or carriers and / or surface-active agents. These compositions may also contain other pesticidal active substances, for example other insecticides or acaricides or fungicides, or they may also contain insecticide synergists, such as dodecylimidazole, safroxan or piperoinylbutoxide.

Insecticidal and acaricidal compositions containing as active ingredients compounds produced by the process of the present invention are the subject of our co-pending Czechoslovak patent specification 264,263, where their preparation and composition are also discussed, and the results of their efficacy tests are also discussed.

The invention is illustrated by the following non-limiting examples. In the examples, the products were usually identified and characterized by nuclear magnetic resonance spectroscopy and infrared spectroscopy. In each case where a product is specifically named, its spectral characteristics correspond to the structure.

Example 1

This example illustrates the preparation of pivlamidine hydrochloride

To a mixture of 43 g (0.51 mol) of trimethylacetonitrile and 24 g (0.51 mol) of dry ethanol was added dry hydrogen chloride gas under stirring and cooling in a mixture of ice and sodium chloride until a total of 21 g of hydrogen chloride was consumed. The reaction mixture was diluted with 500 ml of dry diethyl ether to precipitate ethyl trimethylacetimidate hydrochloride, which, after filtering, weighed 34.5 g, was subjected to further reaction by stirring vigorously after stirring at room temperature. A solution of 6 g of dry ammonia gas in 50 ml of dry ethanol is added in portions, the solids are gradually dissolved during the addition, and the resulting solution is left to react at room temperature for 20 hours, then the solvent is evaporated under reduced pressure. pivlamidine hydrochloride.

...... c

Example 1 a d 2

This example illustrates the preparation of 5-bromo-2- (2-methylpro-2-yl) pyrimidine-4-carboxylic acid

To a mixture of 5.18 g pivalamidin hydrochloride and 5 ml of dry ethanol was stirred at 40 ^Q C was carefully added an ethanolic solution of sodium ethoxide (14.5 ml of a solution obtained by dissolving 1.38 g of sodium in 24 mL of dry ethanol). The mucobromic acid solution (5.4 ml of a solution obtained by dissolving 5.16 g of mucobromic acid in 8.0 ml of dry ethanol) was added thereto, and an exothermic reaction occurred during which the temperature rose. to 65 ° C. After the temperature dropped to 50 ° C, the remaining portion of the sodium ethoxide solution and the remaining portion of the mucobromic acid solution were added.

The reaction temperature is maintained by external heating at 50 ° C for 1 hour, then insoluble matter is filtered off at this temperature, washed with ethanol, the filtrate is combined with the washings and the solvent is evaporated off under reduced pressure. The solid residue is washed with 10 ml of 2M hydrochloric acid and water, and dried. 3.8 g of 5-bromo-2- (2-methylprop-2-yl) pyrimidine-4-carboxylic acid are obtained, melting at 142-144 ° C with decomposition. NMR and IC spectra were consistent with the reported product structure.

¹ H-NMR (CDCl 3):

1.45 (singlet, 9H);

05 (singlet, 1 H),

9.44 (broad singlet, 1H).

IR (paraffin suspension):

940, 2 860, 2 500 (wide, 1710,

570, 1 370, 1 305, 1 290, 1 220, 1 190,

175, 750, 680 cm ^-1 .

Example 3

This example illustrates the preparation of 5-bromo-2- (2-methylprop-2-yl) pyrimidine

1.0 g of 5-1-bromo-2- (2-methylprop-2-yl) pyrimidine-4-carboxylic acid is heated with stirring to 145 ° C, after which the decarboxylated product is distilled under a water pump vacuum. The distillate which solidifies upon cooling is 0.6 g of 5-bromo-2- (2-methylprop-2-yl) pyrimidine, m.p. 50 DEG-51 DEG C. NMR and IR spectra are consistent with the structure.

¹ H-NMR (CDCl 3):

1.39 (singlet, 9Hj,

8.71 (singlet, 2H).

6 4 2 7 3

IC (paraffin suspension):

940, 2,860, 1530, 1,480, 1,420, 1,170,

010, 810, 640 ^cm-first

Example 4

This example illustrates the preparation of 2- (2-methylprop-2-yl) pyrimidine-5-carboxaldehyde

To 0.95 g of magnesium shavings for the preparation of Grignard reagents, 7.6 g (0.035 mol) of 5-bromo-2- (2-methylprop-2-yl) pyrimidine dissolved in 50 ml of dry is added in small portions in the presence of several iodine crystals. tetrahydrofuran. The rate of addition depends on the intensity of the exothermic reaction. After the addition was complete, the mixture was warmed to complete the reaction, then cooled to 5 ° C and a solution of 2.58 g of dimethylformamide in 15 ml of tetrahydrofuran was added dropwise. The mixture was allowed to warm to room temperature with stirring over 2 hours and then allowed to stand without stirring for 16 hours.

After addition of 5 ml of water, tetrahydrofuran was evaporated under reduced pressure and the residue was partitioned between 100 ml of dilute aqueous ammonium chloride solution and 150 ml of diethyl ether. The aqueous phase is extracted with 150 ml of ether, the extract is combined with the ether phase, washed with water and dried over anhydrous magnesium sulfate. Evaporation of the ether under reduced pressure yielded a greasy residue (5.8 g) which was purified by silica gel column chromatography (dry-prepared column).

Elution with 100 parts by volume methylene chloride and 2 parts by volume ethyl acetate gave 3.4 g of 2- (2-methylprop-2-yl) pyrimidine-5-carboxaldehyde, m.p. 82-83 ° C.

IR (paraffin suspension):

940, 2,860, 1,700, 1,590, 1,430, 1,230,

150, 860, 650 cm ^-1 .

Example 5

This example illustrates the preparation of ethyl 3- [2- (1,1-dimethylethyl) pyrimidin-5-yl] propenoate

To a suspension of sodium hydride (0.54 g of 50% oil dispersion) in 30 ml of dry diethyl ether stirred at -5 ^Q C, a solution of 3.93 g O, 0-diethyl-ethoxykarbonylmethylfosfonátu in 20 ml of dry diethyl ether, 90 minutes A solution of 2.88 g of 2- (2-methylprop-2-yl) pyrimidine-5-carhoxaldehyde in 40 ml of dry diethyl ether is added dropwise with stirring at 0 ° C, the resulting mixture is left under stirring for 2 hours. The reaction mixture was allowed to warm to room temperature and was allowed to react at this temperature for an additional 16 hours.

The reaction mixture is partitioned between 150 ml of water and 250 ml of diethyl ether, the aqueous phase is extracted with 250 ml of ether and the extracts are combined with the ether phase. After washing with 200 ml of water and drying over anhydrous magnesium sulfate, the solvent is evaporated off under reduced pressure and the oily residue is chromatographed on a dry silica gel column, eluting with dichloromethane with 5% (v / v) ethyl acetate.

3.6 g of ethyl 3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] propenoate are obtained, which solidifies on standing and melts at 43 to 45 ° C. NMR and IR data indicated that the product was the corresponding trans-isomer.

H-NMR (CDCl3):

1.35 (triplet, 3H);

1.42 (singlet, 9H),

4.24 (quartet, 2H),

6.50 (doublet, 1H),

7.60 (doublet, 1H),

8.82 (singlet, 2H) ^; .

IR (paraffin suspension):

960, 1,730, 1,645, 1,590, 1485, 1440,

320, 1185, 1155 ^cm-first

Example 6

This example illustrates the preparation of ethyl trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate

To a solution of 7.1 g of 2-propyl-triphenylphosphonium iodide in 20 ml of dry tetrahydrofuran was added slowly a solution of n-butyllithium (10.6 ml of 1.55 M hexane solution) with stirring at room temperature under nitrogen. The resulting mixture was further stirred for additional 15 minutes, then a ^Q at -5 C was added a solution of 3.2 g of ethyl trans-'3- [2- (2-methylpropionyloxy op-2-yl) -pyrimidin-5-yl of propenoate in 25 ml of dry tetrahydrofuran.

The reaction mixture is allowed to warm to room temperature with stirring over 30 minutes and then allowed to stand at this temperature for 16 hours, then partitioned between 300 ml of water and 200 ml of diethyl ether. The aqueous phase is extracted twice with 200 ml of ether each time and the ether extracts are combined with the ether phase. After washing twice with 100 ml of water each time and drying over anhydrous magnesium sulphate, the ether is evaporated under reduced pressure and the oily residue is chromatographed on a dry silica gel column which is eluted first with dichloromethane (to remove triphenylphosphine) and then eluted with 100 parts by volume of dichloromethane. and 5 parts by volume of ethyl acetate. .

2.8 g of ethyl trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate are obtained, the identity of which is confirmed by IR and NMR spectroscopy.

¹ H-NMR (CDCl s):

1.99 (singlet, 3H);

1.31 (triplet, 3H);

1.40 (singlet, 12 H),

1.96 (doublet, 1H),

2.54 (doublet, 1H),

4.2 (quartet, 2H),

8.5 (singlet, 2 H).

IR (liquid film):

960, 1,730, 1,485, 1,450, 1,420, 1,260,

180, 1165 cm ^-1 .

Mass Spectroscopy: M ⁺ = 276. Example 7

This example illustrates the preparation of trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylic acid

A solution of 2.6 g of ethyl trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate in 50 ml of ethanol is mixed with a solution of 1.0 g of sodium hydroxide. The mixture was acidified to pH 3 with dilute hydrochloric acid and extracted twice with 200 ml of diethyl ether each time, and the combined extracts were washed with water and dried over anhydrous water. After evaporation of the ether under reduced pressure, 2.1 g of trans-2,2-dimethyl-3- (2- (2-methylprop-2-yl) pyrimidin-5-yl) cyclopropanecarboxylic acid of melting point are obtained. 1-8 DEG-169 DEG C. @ ¹ H-NMR (CDCl3):

1.03 (singlet, 3Hj,

1.41 (singlet 9H)

1.48 (singlet, 3Hj,

2.02 (doublet, 1H),

2.6 (doublet, 1H);

8.57 (singlet, 2H).

IR (paraffin suspension):

940, 1,700, 1,485, 1,430, 1,335, 1,250,

230, 1 210 cm ¹ .

Mass Spectroscopy: M ⁺ = 248. Example 8

Preparation of methyl (+) - trans-2,2-dimethyl-3-formylcyclopropanecarboxylate

A mixture of 40.0 g of methyl 2,2-dimethyl-3- (dimethoxymethyl) -clopropanecarboxylate (95 percent (+. Beta.-trans-isomer), 120 ml of glacial acetic acid, 160 ml of acetone and 280 ml of water was stirred at room temperature for 5 hours. The mixture was then diluted with 1500 ml of water and extracted with 1000 ml of diethyl ether, washed twice with 500 ml of ether each time, the washings were combined with the extract and washed with saturated sodium bicarbonate solution until the acidity was lost. magnesium sulfate and the solvent was evaporated to an oily residue which was purified by distillation.

28.5 g of methyl (+) - trans-2,2-dimethyl-3-formylcyclopropanecarboxylate are obtained as a fraction boiling at 46 to 48 ° C / 6.7 Pa.

Example 9

Preparation of (+) - trans-methyl-3 - [(E, Z) -2-methoxy vinyl] -2-dimethylcyclopropanecarboxylate

The sodium hydride obtained by washing 9.6 g of a 50% oil dispersion with n-hexane to remove the oil is suspended in 150 ml of dry dimethylsulphoxide freshly distilled over hydride, calcium and stirred at 38-40 ° C for 5 hours under a dry nitrogen atmosphere. a solution of 68.8 g of methoxymethyl triphenylphosphonium chloride in 200 ml of dry dimethylsulfoxide was added thereto while maintaining the reaction temperature by external cooling to about 20 ^° C over 15 minutes. A solution of the thus-formed ylide is added dropwise with stirring to a solution of 28.5 g of freshly distilled methyl (+ 1-trans-2,2-dimethyl-3-formylcyclopropanecarboxylate in 50 ml of dimethylsulfoxide, maintaining the reaction temperature at about 20 ° for 2 hours. C.

The resulting mixture was stirred for an additional 30 minutes and then allowed to stand at room temperature for 72 hours. After addition of 1500 ml of water, the mixture is extracted once with 1000 ml and twice with 500 ml of diethyl ether, the extracts are combined, washed three times with 300 ml of water each time and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was triturated with petroleum ether (150 ml of b.p. 60-80 ° C). The insoluble material was filtered off and the filtrate was evaporated to a yellow oil (29.0 g) which was distilled under reduced pressure.

There were obtained 21.4 g of methyl (+) -t, trans 3 - [(E, Z) -2-methoxyvinyl] -2,2-dimethylcyklopropanfcarboxylátu b.p. 64 ^Q C / 6.7 mbar. ¹ H-NMR (CDCl 3):

1.13 (singlet)

1.24 (singlet)

1.26 (singlet)

1.4 (multiplet), '1.9 (multiplet),

2.3 (multiplet)

3.5 (singlet)

3.6 (singlet)

3.66 (singlet),

4.1 (two doublets),

4.56 (two doublets),

6.0 (double doublet),

6.4 (doublet).

[According to signal integration, this is a 2: 1 mixture of (Ε) η (Z) isomers.)

IR (liquid film):

960, 1,730, 1,650, 1,440, 1,270, 1,235,

170, 920 cm ^-1 ·

Example 10

This example illustrates the preparation of a mixture of methyl (+) - trans-3 - [(E, Z) -2-dimethylamino-1-formylvinyl] -2,2-dimethylcyclopropanecarboxylate and methyl (+) -trans-3 - [(E Z) -1-formyl-2-methoxy vinyl] -2,2-dimethylcyclopropanecarboxylate

A solution of 12.0 ml of phosphoryl chloride in 10.0 ml of 1,2-dichloroethane was added dropwise with stirring at room temperature to a mixture of 29.5 ml of dimethylformamide and 100 ml of 1,2-dichloroethane. After the addition was complete, the mixture was stirred for 15 minutes, then cooled to 15 ° C and a solution of 10.0 g of methyl (+) - trans-3 - [(E, Z) -2-methoxyvinyl] added in portions. 2,2-dimethylcyclopropanecarboxylate in 80 ml of 1,2-dichloroethane was allowed to stand at room temperature for 16 hours, after which 150 g of anhydrous potassium carbonate and ice were added.

After the exothermic reaction has ceased, the mixture is extracted twice with 300 ml of methylene chloride each time, the extracts are combined, washed with 300 ml of water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. pressure and the residual oil to remove volatile components, heated at 55 ^Q C / 6.7 mbar.

10.3 g of a mixture are obtained containing a small amount of methyl (+) - trans -3- [E, Z) -1-formyl-2-methoxy vinyl] -2,2-dimethylcyclopropanecarboxylate and the predominant amount of methyl (+) - trans-3 - [(E, Z), -1-dimethylamino-1-dimethylamino-1H-vinylvinyl] -2,2-dimethylcyclopropamcarboxylate (A).

¹ H-NMR (CDCl O '): (A)

1.0 (singlet)

1.05 (singlet)

1.27 (singlet)

1.30 (singlet)

2.0 (multiplet)

3.18 (singlet)

3.37 (singlet),

3.68 (singlet),

3.70 (singlet),

6.75 (wide singlet)

8.35 (wide singlet)

8.8 (singlet).

[According to signal integration, this is a 2: 1 mixture of (E) and (Z) isomers.]

IR (paraffin suspension):

960, 720, 1,730, 1,600, 1,450, 1,410,

280, 1 230, 1 175 cm ¹ .

Example 11

This example illustrates the preparation of methyl (+) -trans-3- (2-cyclohexylpyrimidin-5-yl) cyclopropanecarboxylate

To a mixture of 1.0 g of methyl (+) - trans-3 - [(E, Z) -2-dimethylamino-1-formylvinyl] -2,2-dimethylbicyclopropanecarboxylate (as the product of Example 10, containing a small proportion of methyl- (+) - trans-3 - [(E, Z-1-formyl-2-dimethylcyclopropanecarboxylate), 1.08 g of cyclohexanoylamidine and 8 ml of methanol were added dropwise with stirring at room temperature with 3.2 ml of a 2-M solution of sodium methoxide in methanol. The resulting mixture was heated at reflux for 3.5 hours, then cooled to room temperature, poured into 200 ml of water and extracted twice with 200 ml of diethyl ether each time.

The combined extracts were washed with 50 ml of water, dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and the oily residue was purified by silica gel column chromatography using a mixture of 3 volumes of methylene chloride and 1 volume of diethyl ether as eluent.

790 mg of methyl (+) - trans - [(E, Z) -2-dimethylamino-1-formylvinyl] -2,2-dimethylcyclopropanecarboxylate is obtained.

dT-NMR (CDCl3):

1.0 (singlet 3H)

1.4 (singlet, 3 H),

1.2 to 1.8 (broad signal, 10H),

1.95 (doublet, 1H),

2.5 (doublet, 1H);

2.3 (broad signal, 1H),

3.7 (signal, 3H),

8.5 (singlet, 2 H).

IR (liquid film):

940, 2,860, 1,730, 1,600, 1,500, 1,440,

290, 1175 cm ^-1 .

Example 12

In an analogous manner to that. in Example 7, except that methanol is used instead of ethanol, 790 mg of the product of Example 11 is converted to 750 mg of (+) -trans-3- (2-cyclohexylipyrimidin-6-yl) -2,2-dimethylcyclopropanecarboxylic acid m.p. 128-130 ° C.

6 4 2 7 3

IC (paraffin suspension):

500 to 2,200 (wide belt)

710, 1550, 1 340, 1 290, 1 260, 1 190,

120 cm- ¹ .

Mass Spectroscopy: M ⁺ = 274.

Example 13

The following compounds were also prepared from the corresponding amidines using analogous procedures to Example 11:

(i) Methyl (+) -trans-3- (2-β-rop-2-ylpyrimidin-5-yl) -2,2-dimethylcyclopropanecarboxylate.

@ 1 H-NMR (CDCl3, .delta.):

0.98 (singlet, 3H),

1.30 (singlet, 3H);

1.38 (singlet, 3H);

1.40 (singlet, 3H);

1.95 (doublet, 1H),

2.25 (doublet, 1H);

3.2 (multiplet, 1 H),

3.75 (singlet, 1 H),

8.48 (singlet, 2H).

IC (liquid film):

980, 1735, 1,595, 1,550, 1,440, 1,340,

260, 1175, 830 ^cm-first

(ii) Methyl (+) -trans-3- (2-cyclopropylpyrimidin-5-yl) -2,2-dimethylcyclopropanecarboxylate ¹ H-NMR (CDCl 3) δ:

0.96 (singlet, 3H),

1.05 (multiplet, 4H)

1.40 (singlet, 3H);

1.95 (doublet, 1H),

2.2 (multiplet, 1 H),

2.5 (doublet, 2H),

3.75 (singlet, 3H);

8.4 (singlet, 2 H).

IC (liquid film):

010, 2,960, 1,730, 1,600, 1,550.

470, 1445, 1175, 915 ^cm-first

Example 14

This example illustrates the preparation of (1RS, trans) -1-chlorocarbonyl-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropane hydrochloride.

A mixture of 110 mg of (+) -trans-2,2-dimethyl-3- [2- (2-methyliprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylic acid and 2.0 ml of thioinyl chloride was removed under a humid atmosphere. with stirring under reflux for 2 hours. The reaction mixture was cooled to room temperature (ca. 25 ° C), allowed to stand for 16 hours, then excess thionyl chloride was distilled off under reduced pressure. 100 mg of (+) - trans-1-chlorocarbonyl-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropane hydrochloride are obtained. ^X H-NMR (CDCl δj:

1.18 (singlet, 3H);

1.50 (singlet, 3Hj,

1.60 (singlet, 9H);

2.8 (multiplet, 2 H),

7.3 (singlet, 1 H),

9.0 (singlet, 2 H).

IC (liquid paraffin):

400 to 1900, 1 770 cm ¹ (main belt).

This product, which can also be obtained using oxalyl chloride or phosphoryl chloride instead of thionyl chloride, can be directly used without further purification to prepare the insecticidally and acaricidally active esters of the invention, as illustrated in the following example.

Example 15

This example illustrates the preparation of 3-phenoxybenzyl (1RS, trans -2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate

To the blend, not a suspension of 100 mg of (1RS, trans} ^-l-chloro-1 .orkarb3'nyl 2,2-dimethyl-3- [2- (2-methylprop-2-yl j pyrimidin-5-yl] -cyclopropane hydrochloride in 5.0 ml of dry toluene is added dropwise at 0 ° C a solution of 70 mg of dry pyridine in 1.0 ml of dry toluene, and then a solution of 90 mg of 3-phenoxybenzyl alcohol in 1.0 ml of dry toluene is added dropwise. The resulting mixture was warmed to room temperature (ca. 25 degrees Celsius) and stirred for 5 hours. The reaction mixture was heated three times with 10 ml of water each, then the organic phase was dried over anhydrous magnesium sulphate and the solvent was evaporated under reduced pressure. on a silica gel column eluting with dichloromethane / ethyl acetate (100: 2 by volume) to give 108 mg of 3-phenoxybenzyl- (1RS, trans) -2,2-dimethyl-3- [2- (2-methylprop- j 2-yl-pyrimidin-5-yl] cyklopropa.nkarboxylátu as a colorless oil. ¹ H NMR ( deuterochloroform, á values:

0.98 (singlet, 3H),

1.40 (singlet, 12H);

2.02 (doublet, 1H),

2.56 (doublet, 1H),

5.15 (singlet, 2 H),

6.8 to 7.5 (multiplet, 9H).

IC (liquid film):

960, 1,730, 1590, 1,490, 1,260, 1,220,

160 cm ^-1 .

The following esters can also be obtained in an analogous manner to the preceding examples:

(a) 6-Phenoxypyrid-2-ylmethyl trans-2,2-dimethyl-3- [2- (2-methylproip-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate.

¹ H-NMR (CDCl 3):

1.01 (singlet, 3H),

1.41 (singlet, 12H),

2.08 (doublet, 1H),

2.58 (doublet, 1H),

5.18 (siinglet, 2H),

6.7 to 7.8 (multiplet, 8H),

8.50 (singlet, 2 H).

IC (liquid film):

960, 1,730, 1,600, 1,580, 1,490, 1540,

250, 1160 ^cm-first

Mass Spectroscopy: M ⁺ = 431.

(b) 2-methyl-3-phenylbenzyl-trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate.

¹ H-NMR (CDCl 3):

0.99 (singlet, 3H);

1.40 (singlet, 12H);

2.06 (doublet, 1H),

2.25 (singlet, 3H);

2.60 (doublet, 1H),

5.27 (singlet, 2 H),

7.1 to 7.5 (multiplet, 8H)

8.50 (singlet, 2 H).

IC (liquid film):

960, 1,730, 1,485, 1,420, 1,160, 760,

705 cm- ¹ .

Mass Spectroscopy: M ⁺ = 428.

(c)? -cyain-3-phenoxybenzyl-trans-2,2-dimethylmethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5-yl] cyclopropanecarboxylate.

¹ H-NMR (CDCl 3):

0.99 (singlet)

1.04 (singlet)

1.35 (singet),

1.39 (singlet),

1.45 (singlet)

2.05 (multiplet)

2.6 (multiplet)

6.42 (singlet),

6.44 (singlet),

7.26 (multiplet)

8.46 (singlet)

8.50 (singlet).

(Depending on signal integration, this is a 2: 1 mixture of diastereoisomers).

NH

R ² -C-NH /

IC (liquid film):

960, 1,740, 1,590, 1,485, 1,250, 1,140,

695 cm ^1st

Mass Spectroscopy: M ⁺ = 455.

(d) 1-cyano-1- (6-phenoxypyrid-2-yl) methyl-trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-5- yl] cyclopropanecarboxylate.

¹ H-NMR (CDCl) .delta

1.00 (singlet)

1.02 (singlet),

1.35 (singlet),

1.40 (singlet)

2.1 (multiplet)

2.6 (multiplet)

6.4 (three singlets)

6.9 (doublet),

7.2 (multiplet)

7.8 (double doublet),

8.50 (two slnglets).

(According to Signal Integration, this is a 1: 1 mixture of diastereoisomers).

IR (liquid film):

960, 1,745, 1,595, 1,490, 1,450, 1,260,

140, 695 cm ¹ .

Mass Spectroscopy: M ⁺ ~ 456.

(e) 4-methoxymethyl-2,3,5,6-tetrafluorobenzilate - [+] _-trans-2> 2-Dimethyl-3- [2- (2-methylpropionyloxy op-2-yl) pyrrolidin-pyrimidin-5-yl -2,2-dimethylcyclopropanecarboxylate.

¹ H-NMR (CDCl 3, <5):

0.99 (singlet, 3H);

1.40 (two singlets, 12H),

1.95 (doublet, 1H),

2.55 (doublet, 1H),

3.40 (singlet, 3 H),

4.50 (multiplet, 2Ή)

5.30 (multiplet, 2 H),

8.50 (singlet, 2 H).

22ř

IC (paraffin suspension):

735, 1,595, 1,490, 1,295, 1 ISO, 910,

880, 770 ^cm-first

Mass Spectroscopy: M ⁺ - 454.

(f) (+) - 1- (6-Phenoxypyrid-2-yl) ethyl (+) -trans-2,2-dimethyl-3- [2- (2-methylprop-2-yl) pyrimidin-S-yl] cyclopropanecarboxylate.

¹ H-NMR (CDCl 3):

1.0 (singlet)

1.33 (singlet),

1.40 (singlet)

1.5 (singlet)

1.8 (singlet)

2.05 (two doublets),

2.50 (two doublets),

5.85 (quartet)

6.7 (doublet),

7.2 (multiplet)

7.65 (double doublet),

8.50 (two singlets) (According to signal integration, this is a mixture of diastereoisomers in 3: 2 ratio).

IC (liquid film):

980, 1730, 1600, 1580, Γ445, 1 260, '1170, 990, 700 cm' ¹ .

Mass Spectroscopy: M + = 446. (g) 2-Methyl-3-phenylbenzyl (+) - trans -2,2-dimethyl-3- (2-prop-2-ylpyrimidin-5-yl) cyclopropanecarboxylate.

¹ H-NMR (CDCl 3):

0.99 (singlet, 3H);

1.30 (singlet, 3H);

1.38 (singlet 3H),

1.42 (singlet, 3H),

2.1 (doublet, 1H).

2.25 (singlet, 3H);

2.65 (doublet, 1H),

3.2 (multiplet, 1 H),

5.27 (singlet, 2 H),

7.3 (Multiplet, 8H)

8.49 (singlet, 2H).

IC (liquid film):

(h) (+) - 1-cyano-l- (6-phenoxypyrid-2-yl) methyl (+) -trans-2,2-dimethyl-3- (2-prop-2-yl-pyrimidine-5-yl ^J cyclopropanecarboxylate.

@ ¹ H-NMR (CDCl3) .delta.

1.00 (singlet)

1.03 (singlet),

1.31 ‘(singlet),

1.36 (singlet),

1.38 (singlet) _y

1.42 (singlet),

2.05 (multiplet)

2.60 (multiplet)

3.2 (multiplet)

6.35 (wide singlet)

6.9 (doublet),

7.3 (multiplet)

7.8 (double doublet),

8.5 (two singlets).

According to integration, it is a mixture of equal parts of diastereoisomers).

IC (liquid film):

980, 1,745, 1,595, 1,580, 1,450, 14U,

150, 745, 700 cm ¹ .

(i) (+) 6-Cyano-1- (6-phenoxypyrid-4-yl) methyl (+) -trans-2,2-dimethyl-3- (2-cyclopropylpyrimidin-5-yl) cyclopropanecarboxylate.

¹ H-NMR (CDCl 3):

1.06 (singlet), 1.34 (singlet),

1.42 (singlet),

2.0 (two doublets),

2.2 (multiplet)

2.8 (multiplet)

6.4 (singlet),

6.9 (doublet),

7.3 (multiplet)

7.8 (double doublet),

8.35 (two singlets).

'Τ' (Depending on the integration of the signals, these are mixed parts of the diastereoisomers) ¹ .

IR (liquid film):

010, 2 940, 1750, 1 600, 1 450, 1 260,

150, 910, 800, 700 cm ^1. '

980, 1730, 1595, 1550, 1425, 1240, 1165, 740, 710 ^cm-first

2B4272

Claims (1)

Process for the preparation of the insecticidally and acaricidally active pyrimidin-5-ylcyclopropanecarboxylic acid esters of the general formula (I ⁾ . R - C - CH - CH - in which up to 4 carbon atoms optionally substituted by halogen and R ⁸ represents a hydrogen atom, a halogen atom, an alkyl group having up to 4 carbon atoms, an alkenyl group having up to 6 carbon atoms, a phenyl group, a phenoxy group or a benzyl group, or a phenyl, phenoxy or benzyl group substituted with halogen or C 1 -C 4 alkyl characterized in that the acid halide of the general formula II R2 represents a (C 6-C alky ⁾ alkyl group branched on «-carbon and R is a radical of formula (A) N0, II - ^R @ - (y - CH - CH - CS. X CHi (II) in which X is oxygen, sulfur, vinylene or a radical of the formula —CR ⁵ = Y -, wherein Y represents a nitrogen atom or a CR ⁵ group, R ⁸ represents a hydrogen atom, a methyl group, a cyano group or an ethynyl group, the individual substituents R ⁵ being selected from the group consisting of a hydrogen atom, halogen atoms and an alkyl group containing in which: R ² is as defined above and Q is halogen, preferably chlorine, is reacted with an alcohol of the general 'formula VI R - H (Vij in which R is as defined above, in the presence of a base.