MXPA97003663A - Halogenated eteres useful as intermediaries for insecticide - Google Patents

Abstract

The present invention relates to novel compounds of the formula (I): CF3-CXCl-CH (OH) CH2-C (CH3) 2 -CH2-CO2R, in which X represents chlorine or bromine and R represents hydrogen or alkyl up to 4 carbon atoms, processes to prepare them and their use as intermediaries in the preparation of cyclopropane insecticide derivatives. New compounds of the formula (IV) are also provided: BrCH2-CH2-C (CH3) 2-CH2-CO2R, in which R represents alkyl of up to 4 carbon atoms, useful as intermediates in the preparation of the compounds of the formula (

Description

USEFUL HALOGEN ESTERS AS INTERMEDIARIES FOR INSECTICIDES * DESCRIPTION OF THE INVENTION "This invention relates to halogenated esters useful as intermediaries for insecticides, to processes for preparing them and to processes for preparing insecticides therefrom." Patent No. 2000,764 describes valuable insecticidal esters, including 3- (2-Chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylic acid a-cyano-3-phenoxybenzyl ester, which in the racemate form * formed by its isomers (Z) -IR, cis-aS and (Z) -lS-cis-aR is a widely used commercial insecticide having the common name ISO of lambda-cyhalothrin. The present invention relates to novel halogenated esters, which can be used as intermediates in the preparation of cis-3- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2 acid. , 2-dimethylcyclopropanecarboxylic acid (cyhalothrin acid) from which lambdacyhalothrin is manufactured. According to the present invention, a compound of the formula is provided: 5 CF3-CXCl-CH (OH) CH2-C (CH3) 2-CH2-C02R (I) where X represents chlorine or bromine and R represents hydrogen or alkyl of up to 4 carbon atoms. Particular examples of the compounds of the formula I include methyl 6-bromo-6-chloro-3, 3-dimethyl-5-hydroxy-7,7-7-trifluoroheptanoate, 6-bromo-6-chloro-3, 3 ethyl -dimethyl-5-hydroxy-7, 7, 7-trifluoroheptanoate, 6,6-dichloro-3, 3-dimethyl-5-hydroxy-7,7,7-trifluoroheptanoate and 6,6-dichloro-3 , Ethyl 3-dimethyl-5-hydroxy-7,7-, 7-trifluoroheptanoate and the corresponding carboxylic acids. The present invention also provides a process for preparing a compound of the formula I, wherein X represents chlorine or bromine and R represents alkyl of up to 4 carbon atoms, which comprises reacting a compound of the formula: CF3-CHXCI (II) with a compound of the formula: 0 = CH-CH2-C (CH3) 2CH2-C02R (III) in the presence of a strong base and an inert solvent.

The process is carried out in the presence of a strong base, which is believed to act by generating a perhaloalkyl ion, which then reacts with the aldehyde. Suitable strong bases include lower alkali metal alkoxides, such as sodium or potassium alkoxides containing up to 6 carbon atoms, for example sodium isopropoxide, potassium isopropoxide, sodium t-butoxide or potassium t-butoxide, but other bases such as alkali metal hydrides, for example sodium hydride and amides of alkali metal, for example sodium amides can also be used. The preference process is carried out at lower temperatures to avoid the production of undesirable byproducts. A preferred temperature is within the range of -80 ° C to 0 ° C, especially where a polar aprotic solvent is used. Particular examples of polar aprotic solvents, which may be useful in the process include amides such as dimethylformamide, dimethylacetamide and di-n-butylacetamide, cyclic ethers such as tetrahydrofuran, tetrahydropyran and dioxane, glycol ethers such as ethylene glycol dimethyl ether and ethylene glycol diethyl ether and sulfoxides such as dimethyl sulfoxide. However, other inert solvents such as aromatic hydrocarbons, for example toluene can also be used.

The compounds of formula III can be obtained by reacting a compound of the formula: BrCH2-CH2-C (CH3) 2-CH2-C02R (IV) with an oxygen donor and a base. The pyridine N-oxide is a suitable oxygen donor and the base is conveniently an alkali metal carbonate, such as sodium or potassium carbonate. The compounds of formula IV are believed to have not been previously described and accordingly in another aspect of the present invention there is provided a compound of formula IV, wherein R is alkyl of up to 4 carbon atoms, preferably methyl and ethyl. - The compounds of the formula IV can be obtained by reacting a compound of the formula: CH2 = CH-C (CH3) 2-CH2-C02R (V) with hydrogen bromide in the presence of a free radical catalyst, such as an organic peroxide. The compounds of formula I can be converted to cyhalothrin acid (as their alkyl ester) by a simple two-step process. Accordingly, in yet another aspect of the present invention, a tf process is provided for preparing an alkyl ester of 3- (2-chloro-3,3,3-trifluoroprop-1-en-yl) -2,2-dimethylcyclopropanecarboxylic acid , which comprises a) treating the compound of the formula I with a dehydrating agent to obtain a compound of the formula: CF3-CXC1-CH = CH-C (CH3) 2-CH2-C02R (VI) j "and (b) treating the compound of formula VI with at least a molar equivalent of a base in an inert solvent and recover the alkyl ester of 3- (2-chloro-3,3,3-trifluoroprop-1-en-yl) -2,2-dimethylcyclopropanecarboxylic acid from the reaction mixture. A preferred dehydration agent for used in step (a) is phosphorus oxychloride and the process of preference is carried out in a suitable solvent such as a pyridine base, for example lutidine. The base used in step (b) is preferably an alkali metal alkoxide and the process can be carried out in a Suitable solvent or diluent such as, for example, a polar aprotic solvent such as dimethylformamide or an excess of the alcohol corresponding to the alkali metal alkoxide. Sodium or potassium t-butoxide are preferred bases and the reaction is preferably carried out in dimethylformamide.

Other bases such as alkali metal amides, for example sodium amide or alkali metal disililazides, for example sodium disilyllazide, can also be used, preferably in the presence of a catalytic amount of an alkanol such as t-butanol. A particularly useful technique to be used in step (b) is to carry out the reaction in the presence of an aromatic hydrocarbon solvent, such as toluene or xylene under conditions which remove t-butanol by distillation. Other details of the process involved in preparing and using the compounds of formula I are set forth in the following Examples, which are illustrative of the various aspects of the invention.

EXAMPLE 1 This Example illustrates the preparation of methyl 5-bromo-3, 3-pent-4-enoate. The methyl 3, 3-dimethylpentenoate (50.0 g) is dissolved in carbon tetrachloride (500 cm3) and heated to 60 ° C under a nitrogen atmosphere. Benzoyl peroxide (2.44 g) is added in one portion and the mixture is stirred for 10 minutes, after which a stream of gaseous hydrogen bromide is introduced through a sintered glass for a period of 45 minutes. The reaction mixture is purged with nitrogen and kept at room temperature for 72 hours. The mixture is then heated to 50 ° C, another quantity (2.44 g) of benzoyl peroxide is added and the gaseous hydrogen bromide is introduced over a period of 15 minutes to complete the reaction. After removal of the residual hydrogen bromide by sparging with nitrogen, the reaction mixture is concentrated by removal of the solvent by evaporation under reduced pressure. The residual liquid is purified by distillation to obtain methyl 5-bromo-3, 3-dimethylpentanoate as a colorless liquid, e.g. 80 ° C / 2 mmHg, 80% yield) H1 NMR (ppm): 3.70 (3H, s, OMe); 3.40 (2H, m, CH2Br); 2.25 (2H, s, CH2C02ME); 1.95 (2H, m, CH2); 1.05 (6H, s, CMe2) EXAMPLE 2 This Example illustrates the preparation of methyl 3,3-dimethyl-5-oxopentanoate. A mixture of methyl 5-bromo-3, 3-dimethylpentanoate (5.0 g), pyridine N-oxide (4.49 g), sodium bicarbonate (3.77 g) and toluene (30 cm3) is heated to reflux temperature with vigorous agitation for a period of 14 hours. After cooling the mixture to room temperature, water (20 cm3), saturated ammonium carbonate solution (20 cm3) and toluene (50 cm3) are added and the aqueous phase is separated and extracted with toluene (3x75 cm3). The toluene extracts are added to the main organic phase and dried completely over anhydrous magnesium sulfate., concentrated by evaporation of the most volatile components 5 under reduced pressure. The residual liquid was purified by Kugelrohr distillation (130 ° C / pressure of a water pump) to give the methyl 3, 3-dimethyl-5-oxopentanoate in 63% yield. ,) H1 NMR (ppm): 9.85 (1H, m, CHO); 3.65 (3H, s, OMe); 2.50 (2H, m, CH2CHO); 2.40 (2H, s, CH2C02Me); 1.15 (6H, s, CMe2) EXAMPLE 3 This Example illustrates the preparation of methyl 6,6-dichloro-3,3-dimethyl-5-hydroxy-7,7-7-trifluoroheptanoate. To a stirring mixture of methyl 3, 3-dimethyl-5-oxopentanoate (1.0 g), 1,1-dichloro-2,2,2-trifluoroethane (1.06 g) and dry tetrahydrofuran (10 cm 3) maintained at - 78 ° C, sodium t-butoxide (1.66 cm3 of a 42% w / w solution in dimethylformamide) is added over a period of 5 minutes after which the mixture continues to be stirred at -78 ° C for another 60 minutes. minutes The reaction is stopped with saturated ammonium chloride at low temperature and the mixture is allowed to warm to room temperature. After addition of water (20 cm3) and separation of the organic phase, the aqueous phase is extracted with di-isopropyl ether (3x30 cm3) and the extracts combined with the organic phase, which is washed with brine (2x10 cm3) and dried over anhydrous magnesium sulfate. After removal of the volatile components by evaporation under reduced pressure, the residual oil is purified by column chromatography (column of silica gel eluted with a 9: 1 mixture (by volume) of hexane and ethyl acetate) to give the Methyl 6,6-dichloro-3, 3-dimethyl-5-hydroxy-7,7,7-trifluoroheptanoate as a colorless oil (yield 56%). H1 NMR (ppm): 4.50 (1H, d, OH); 4.28 (1H, m, CHOH); 3.73 (3H, s, OMe); 2.48 (2H, d [ab], CH2C02Me); 1.95 (2H, m, CH3); 1.15 (3H, s, CMe2); 1.09 (s, 3H, CMe2). MS: 279 (M-OMe); 257 (M- [Cl + H20]. Infrared: 1710, 3400 cm "1 (broad) EXAMPLE 4 This Example illustrates the preparation of methyl 6,6-dichloro-3, 3-dimethyl-7,7,7-trifluorohept-4-enoate. Phosphorus oxychloride (10 cm3) is added dropwise to a stirred solution of methyl 6,6-dichloro-3, 3-dimethyl-5-hydroxy-7,7,7-trifluoroheptanoate (5.49 g) in 3.5 - lutidine (50 cm3) maintained at 0 ° C. The resulting mixture is heated at 100 ° C for 30 minutes and then cooled to room temperature under a nitrogen atmosphere and empty in a stirred mixture of water and ice (300 cm3). The mixture is extracted with ethyl acetate (2 × 150 cm 3), diethyl ether (3 × 150 cm 3) and finally with ethyl acetate. (150 cm3). The volume of the combined extracts is reduced to * \ approximately 400 cm3 by evaporation of some of the solvents under reduced pressure and then washed with dilute hydrochloric acid (3.5M). The aqueous washings are extracted with diethyl ether (3x50 cm 3) and the extracts are combined with the organic phase. After washing the combined organic phase with brine and drying over anhydrous magnesium sulfate, the Solvents are removed by evaporation under reduced pressure and the residual oil purified by Kugelrohr distillation (128 ° C / 1 mmHg) to give 6,6-dichloro-3, 3-dimethyl-7,7,7-trifluorohept-4- methyl enoate as a pale yellow oil (2.86 g, 52% yield), together with an amount of the amically rearranged isomer 4,6-dichloro-3,3-dimethyl-7,7,7-trifluorohept-5-enoate methyl. H1 NMR (ppm): 6.50 (1H, d, = CH); 5.70 (1H, d, = CH); 3.65 (3H, s, OMe); 2.40 (2H, s, CH2C02Me); 1.25 (6H, s, CMe2). 25 MS: 257 (M-Cl); 219 (M-CH2C02Me).

Infrared: 1750 cm "1.

EXAMPLE 5 This Example illustrates the preparation of ethyl 3- (2-chloro-3,3,3-trifluoroprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate. A stirring solution of ethyl 6,6-dichloro-3, 3-dimethyl-7,7-7-trichlorohept-4-enoate (0.1 g) in dimethylformamide (10 ml) is cooled to -25 ° C under one atmosphere of nitrogen and sodium t-butoxide (0.1 ml of a 42% solution in dimethylformamide) is added in drops. After 30 minutes, an additional five drops of the sodium t-butoxide solution are added and the mixture is stirred for another 15 minutes, before the reaction is stopped with saturated ammonium chloride solution (2 ml) for a period of time. 10 minutes. Water (40 mL) is added and the mixture is extracted with hexane (3x40 mL) the combined extracts are washed with brine (20 mL) and dried over anhydrous sodium sulfate. The dried solution is filtered and concentrated by evaporation under reduced pressure to give ethyl 3- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate as a mixture of isomers EXAMPLE 6 This Example illustrates the preparation of 3- (2-chloro-3,3,3-trifluoroprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate. By the use of a procedure similar to that described in the previous Example, the desired product is obtained by treating a solution of methyl 6,6-dichloro-3, 3-dimethyl-7,7-7-trichlorohept-4-enoate ( 0.217 g) in dry dimethylformamide (10 ml) at 0 ° C under a nitrogen atmosphere with sodium t-butoxide (0.2 ml of a 40% solution in dimethylformamide). The identity of the product was confirmed by gas chromatographic mass spectroscopy which consisted mainly of cis-3- (Z-2-chloro-3,3,3-trifluoroprop-1-en-1-yl) -2,2-dimethylcyclopropanecarboxylate of methyl.

EXAMPLE 7 This Example illustrates the preparation of methyl 3- (2-chloro-3,3,3-trifluoroprop-l-en-2-yl) -2,2-dimethylcyclopropane-carboxylate under conditions where t-butanol is removed by azeotropic distillation with toluene. Sodium t-butoxide (2.5 g) is added rapidly to a mixture of methyl 6,6-dichloro-3, 3-dimethyl-7,7,7-trichlorohept-4-enoate (5.55 g, 91% strength) and toluene (50 cm3) maintained under atmospheric pressure at 40 ° C. The resulting mixture is stirred as the pressure is reduced to 40 mm Hg and held at that value for 2 hours, after which pressure is restored to atmospheric and the mixture is stopped with acetic acid (4.0 cm3). Sampling of the mixture by quantitative gas chromatographic analysis showed that the desired product (as cis-Z isomer) was present in a 75% yield. X 10 EXAMPLE 8 This Example illustrates the preparation of methyl 3- (2-chloro-3,3,3-trifluoroprop-l-en-2-yl) -2,2-dimethylcyclopropanecarboxylate under conditions where t-butanol is removed by azeotropic distillation with xylene. The procedure of the previous Example r is used except that the xylene (50 cm 3) is used in place of toluene and the reduced pressure was 20 mm Hg and is maintained for 2.5 hours. During this period additional xylene is added to maintain a constant volume. Sampling the reaction mixture shows that the desired product (such as cis-Z isomers) is obtained in 75% yield.

Claims (14)

1. A compound of the formula: CF3-CXCl-CH (OH) CH2-C (CH3) 2-CH2-C02R (I) characterized in that X represents chlorine or bromine and R represents hydrogen or alkyl of up to 4 carbon atoms.

2. The compound according to claim 1, characterized in that X represents chlorine and R represents methyl.

3. A process for preparing a compound of the formula I, wherein X represents chlorine or bromine and R represents alkyl of up to 4 carbon atoms, characterized in that it comprises reacting a compound of the formula CF3-CHXCI (II) with a compound of the formula: 0 = CH-CH2-C (CH3) 2CH2-C02R (III) in the presence of a strong base and an inert solvent.

4. The process in accordance with the claim 3, characterized in that the strong base is an alkali metal alkoxide.

5. The process in accordance with the claim 4, characterized in that the alkali metal alkoxide is sodium or potassium t-butoxide.

6. The process according to claim 3, characterized in that it is carried out within the temperature range of -80 to 0 ° C.

7. The process according to claim 3, characterized in that the compound of the formula III is obtained by the additional step of reacting a compound of the formula: BrCH2-CH2-C (CH3) 2-CH2-C02R (IV) with an oxygen donor and a base.

8. The process according to claim 7, characterized in that the oxygen donor is pyridine N-oxide and the base is an alkali metal carbonate.

9. The process according to claim 7, characterized in that the compound of the formula IV is obtained by the additional step of reacting a compound of the formula: CH2 = CH-C (CH3) 2-CH2-C02R (V) with hydrogen bromide in the presence of a free radical catalyst.

10. The process according to claim 9, characterized in that the free radical catalyst is an organic peroxide.

11. A process for preparing an alkyl ester of 3- (2-chloro-3,3,3-trifluoroprop-1-en-yl) -2,2-dimethyl-cyclopropanecarboxylic acid, characterized in that it comprises (a) treating the compound of the formula I with a dehydrating agent to obtain a compound of the formula: CF3-CXC1-CH = CH-C (CH3) 2-CH2-C02R (VI) and (b) treating the compound of the formula VI with at least one molar equivalent of a base in an inert solvent and recovering the alkyl ester of 3- (2-chloro-3,3,3-trifluoroprop-1-en- il) -2,2-dimethylcyclopropanecarboxylic acid from the reaction mixture.

12. The process according to claim 11, characterized in that the dehydrating agent is phosphorus oxychloride.

13. The process according to claim 11, characterized in that the base used in step (b) is an alkali metal alkoxide.

14. The process according to claim 12, characterized in that the alkali metal alkoxide is sodium or potassium t-butoxide.