NL8102596A - TRIHALOGENETHYL HYDROXYLACTONES AND METHOD FOR PREPARING THESE. - Google Patents

Description

K k2 “1 NET

SBIHALOGYL METHYL HYDROXYLACTORILE M METHOD FOR PREPARING THEREOF

The present invention relates "to trihalo-methylhydroxylactones and to a process for their preparation. These compounds can be used as an intermediate in the preparation of insecticides known as pyrethrolides.

These pyrethroids exhibit a marked activity against various insects and furthermore a very low mammalian toxicity; this combination of properties makes them suitable as pesticides for crop protection. One of the most useful groups of pyrethrolides includes esters of 2- (2,2-di-10-halovinyl) -3 # 3-dimethylcyclopropanecarboxylic acid and esters based on the cis form of this acid have been found to have even better insecticidal activity . This cis-dihalo-vinyl acid can be represented as follows:

OH

.CH è = 0 ^ f \ f U)

Hal / \ 8102596 -: 2 in which Hal represents a halogen atom. Such great efficacy is an incentive for research into new and economical methods for the preparation of cis-dichlorovinyl acid and the present invention relates to new intermediates which can be used in their preparation. the present invention relates to trihalomethylhydroxylactones of the following general formula:

OH

x2 ~ 7 \ 7 (I)

A A

0 = 30¾ and the cis-tautomeric keto acids, esters and salts thereof, wherein X., X-, X- may or may not have the same meaning and each r2, 3, 10 individually represents a fluorine, chlorine or bromine atom; X.j, Xg and X ^ preferably represent chlorine atoms.

The trihadogenmethylhydroxylactones of the invention may exist in cis-tautomeric ketoacid form, the tautomerism being represented by the following equation:

'OH o 2? H

X V -> \ 1 \ 0 / \ r 7_ N / f_J (II) / X / X7

\ x λ x * i X

X3 CB3 ÖH3 3 OH3 Cl3 The cis-keto acid of the general formula II can be easily esterified or converted into salts by conventional techniques and can be used as a useful intermediate in the preparation of pyrethroids; therefore, these salts and esters are also included in the present invention. Special examples of esters and salts are alkyl esters, especially esters and alkali metal, alkaline earth metal-1 ammonium and substituted ammonium salts.

The lactones, cis-keto acids and derivatives thereof according to the invention can for instance be converted into a compound having the following structure by means of sodium boron hydride in an aqueous medium:

H OH OH

V l X, c c = o

<A

J CH3 CH3 which can be converted back into the corresponding cis-dihalo-vinyl vinyl acid (A), as stated in Dutch patent application 78069151, wherein the cis-dihalo-vinyl acid (A) is the main intermediate in the preparation of the pyrethroxide insecticide.

It has been found that pyrethroxide insecticides based on this cis-dihalovinyl acid1 have much greater insecticidal activity than the trans-dihalovinyl vinyl acids and consequently are the compounds of the invention, all of which can be used for the preparation of cis-dihalovinyl vinyl. acids, of considerable economic and agronomic significance.

The compounds of the invention can be prepared by known methods, such as those described in Journal of Organic Chemistry, Vol. 32 (1967), biz. 2166-21J1. According to a preferred method of preparation, cis-caronic anhydride is reacted under anhydrous or substantially anhydrous conditions with a trihaloacetate of the general formula:

X - C-C00M

^ t 8102596 3

<C V

k in which X 2, X 2 and X 2 may or may not have the same meaning, and each may represent a fluorine, chlorine or bromine atom and M represents an alkaline metal atom, for example sodium or potassium, and the claim keto acid is optionally converted to the corresponding ester or salt, preferably X ^ = X ^ = X ^ =? chlorine and M = Na. The process can be carried out at ambient temperature, but generally a temperature of -60 to 60 ° C can be used.

Inert solvents, such as dimethoxyethane, can be used, but the reaction is preferably carried out in a high polar aprotic inert solvent. Examples of such a solvent are Ν, Ν-dimethylformamide, N, H-dimethyl-acetamide, N-methyl-2-pyrrolidone and acetonitrile, of which acetonitrile is preferred. The term "high polar" as used herein indicates the presence of a dielectric constant of at least 25 measured at 25 ° C. The term "aprotic" as used herein denotes a solvent that does not contain hydrogen atoms that can form hydrogen bonds with anions. These definitions are consistent with "Physical Chemistry of Organic Solvent Systems", by A.K. Corrington and T. Dickinson, Plenum Press (1973), pages 332 and 333.

Cis-caronic anhydride can be prepared by any suitable method, for example, by isomerization and dehydration of trans-caronic acid or an alkali metal salt thereof. This isomerization can be carried out, for example, by converting at least one of the carboxyl groups into an alkyl halide group or into an anhydride, and then thermally inducing isomersation, for example by heating the functional derivative to a temperature of at least 130 ° C, at preferably at least 160 ° C, 30 in the presence of a high boiling solvent, eg, 1-methylpyrrolidone.

Therefore, transcaronic acid can be treated, for example. with acetic anhydride or acetyl chloride and the resulting mixed anhydride, a reflux condenser can be boiled in the presence of a suitable solvent, thereby obtaining cis-earonic arihydride. This anhydride can be separated from the reaction mixture by known methods or it can be reacted in situ. with an alkali metal trihalogen-5 acetate to give the desired compound of general formula I.

The present invention also relates to all isomeric forms of the trihalomethylhydroxylactones and their tautomeric cis-keto acids, esters and salts including their individual optical and geometric isomers, and, optionally, isomer combinations.

The invention will now be further described by means of the following Examples.

EXAMPLE I - The preparation of U-hydroxy-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyelo [3.1.0] hexane and the 15-tautomeric cis-keto acid_

A solution of 0.5 g of earonic anhydride (3.6 mmol.) And 0.67 g of CCl 4 COOITa (3.6 mmol.) In 10.8 ml of dimethoxyethane was stirred at 20 ° C for 2 h. Ba acidification with concentrated hydrochloric acid, 75 nil water was added and the aqueous layer was extracted with C 1 Cl 2 (3 x 20 ml). The resulting CH 2 Clg extracts were washed with water (10ml), dried over MgSO 2, filtered and the solvent was removed under reduced pressure to leave 0.8g of an oil.

BMR analysis showed: conversion 66%; selectivity: cis-25 earonic acid: $ 50; U-hydroxy-1-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo [3.1.0] hexane: 6 $ (hydroxylactone), cis-2,2-dimethyl-3- (trichloroacetyl) - cyclopr opanecarboxylic acid: 27 $ cis-keto acid.

EXAMPLE II - The preparation of U-hydroxy-U-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo [3.1.0] hexane and the tautomeric cis-ketoacid

A solution of 0.5 g of earonic anhydride (3> 6 mmole) and 0.67 g of CCl 2 COOBa (3.6 mmole) in 10.8 ml of dimethoxyethane was stirred at 80 ° G for 8 hours for 8 hours. After the reaction mixture was cooled to 200C and was taken up with concentrated hydrochloric acid, it was diluted with 50 ml of water and extracted with CSgGlg (3 x 15 ml). The CHgClg extracts obtained. were washed with water (3 x 10 ml), dried over MgSO 4, filtered and the solvent was removed under reduced pressure, leaving 0.57 g of a colorless oil.

NMR analysis showed: conversion: $ 75; Selectivity: cis-caronic acid: 28 #; -hydroxy-U-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo [3.1.0] hexane :. 7 # (hydroxylactone); cis-2,2-dimethyl-3- (trichloroacetyl) cyclopropanecarboxylic acid: 21 # (cis-keto acid).

EXAMPLE III - The preparation of U-hydrosyl-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo [3.1. Ohehexane and the tautomeric cis-keto acid]

This Example demonstrates the use of dimethylformamide (DMF) as the reaction medium and its effect on higher selectivity to the hydroxy lactone and the cis-keto acid and the absence of unwanted caronic acid. A solution of 0.5 g of caronic anhydride (3.6 mmol.) And 0.67 g of CCl2 COONa (3.6 mmol.) In 10.8 ml of DMF was stirred at 0 ° C for 3 hours, after which the reaction mixture was acidified with concentrated HCl, diluted with 75 ml of water and extracted with CHgClg (3 x 10 ml). The resulting CHgCl 2 extracts were washed with water (3 x 10 ml), dried over MgSO 2, filtered and the solvent was removed under reduced pressure, leaving 0.9 g of an oil.

HMR analysis showed: conversion: 59 #; Selectivity: U-hydroxy-U-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo [3.1.0] hexane: 1 ^ # (hydroxylactone); cis-2,2-dimethyl-3- (trichloroacetyl) cycloprano-carbonic acid: (cis-ketoacid).

8102596 EXAMPLE IV - The "Preparation of H-Hydroxy-Trichloromethyl-6,6-Dimethyl-2-oxo-3-oxabicyclo [3.1-Hexhexane and Tautomeric Cis-Ketoic Acid"

This Example demonstrates the use of acetonitrile as a reaction medium and the higher yields of hydroxylactone and cis-5-keto acid obtained therewith.

A suspension of 0.7 ^ g CCl ^ COONa (h, 0 mmol) in 10 ml acetonitrile and 0.5 g caronic anhydride was stirred at room temperature for 20 hours, after which the reaction mixture was acidified with 0.5 ml concentrated HCl, diluted with 70 ml of water and extracted with CHgClg (3 x 10 ml). The combined CHgClg extracts were washed with water (3 x 10ml), dried over MgSO4, filtered and the solvent was removed under reduced pressure to leave a white solid (0.8g).

HMR analysis showed: conversion: 95 #; selectivity: cis-2,2-dimethyl-3- (trichloroacetyl) cyclopropanecarboxylic acid: 5%, k-hydroxy-h-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyelo [3.1.0] -hexane: 33 £.

HMR: Varian EM-390 90 MHz HMR spectrometer; solvent: CDC1

J

temperature: -30 ° C.

1H HMR

~0 ~ ci3cy \ __ j '

K B

hydrogen dum from TMS

25 A and B 1.30 (s, 3H) and 1.53 (s, 3H) C 2.1H (d, 1H) = 6.0 Hz B 2.55 (a, 1H) JDC = 6.0 Hz E 7.88 (tr, s) 8102596 'u ^ 8 ch3 ch3

A B

A and B 1.1 * 0 (s, 3H) and 1.1 * 2 (s, 3H) C 2.1 * 3 (d, 1H) JCD = 9.0 Hz D 2.78 (d, 1H) JDC = 9.0 Hz E 7.78 (tr, s) EXAMPLE V - The preparation of U-hydroxy-1 * -trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo [3.1 .0] hexane and the _____________ tautomeric cis-keto acid

A mixture of 3.3 mmol, earonic anhydride, 1 *, 1 * mmol. sodium trichloroacetate and 0.1 mmol. methyltricaprylammonium chloride in 5 ml of acetonitrile (gearooga over molecular sieves) vera 6 hours at 18-21 ° C geroera. After acidification with 0.1 * ml concentrated HCl, the precipitated NaCl was filtered off and washed with acetone, the CH3CH solution and the acetone-washed material were collected and the solvent was removed under reduced pressure, after which 1.05 g of a mixture of caronic anhydriae, caronic acid and the desired cis-keto acid-hydroxylactone mixture.

The largest amount of the resulting caronic acid could be removed by adding 25 ml of toluene (in which the diacid dissolves poorly) and filtration. After toluene was removed under reduced pressure, 0.8 g of a white solid was obtained. NMR analysis showed that the product obtained was 90 wt.% Pure cis-keto acid + hydroxy lactone.

EXAMPLE VI - Preparation of the sodium salt of cis-2,2-dimethyl-3- (trichloroacetyl) cyclouropanecarboxylic acid_

The cis-keto acid / hydroxylactone-20 mixture prepared according to Example V was dissolved in a small molar excess of sodium bicarbonate to obtain the sodium salt of the cis-keto acid, the structure of which was confirmed by NMR analysis.

Si 0 2 5 9 6 9 EXAMPLE VII - The preparation of the methyl ester of cis-2,2-dimethyl-3- (trichloroacetyl) cyclopropane-carbononic acid

A mixture of 3.0g (21.6mmol) earonic anhydride and 5g sodium trichloroacetate (2kmmol) was stirred at 20 ° C for 2 hours. Then 2k mmol. dimethyl sulfate was added and after stirring at 20 ° C for 65 hours, the solvent was removed under reduced pressure. The residue was diluted with water and extracted with dichloromethane. The organic phase was washed with an aqueous HaHCO 2 solution, dried over MgSO 2, filtered and the solvent was removed under reduced pressure to give 3.6 g of 50% pure cis ketoic acid methyl ester, the structure of which was confirmed by MR analysis.

EXAMPLE VIII - The preparation of cis-2,2-dimethyl-3- (tribromo-acetyl) cyclourouanecarboxylic acid_

This compound was prepared according to the procedure described in Example IV

15, but now sodium tribromoacetate was used instead of sodium trichloroacetate. KMR showed that the product dissolved in CDCl2 was mainly in the form of cis-keto acid.

/

Br, C-CCOH

* f jr

W.

0¾ <* 3 MR (A) (B) 20 A and B 1.30 (s, 3H) and 1.33 (z, 3H) C 2.33 (d, 1H) = 8 Hz D 2.98 (d 1H) 8102596

Claims (5)

1. Trihalomethylhydroxylactones of the general formula: OH Σ2 CD CH3 CH3 and the cis tautomeric keto acids, esters and salts thereof, wherein Xj and X3 may or may not have the same "meaning and each individually represents a fluorine, chlorine or chromium atom . Compounds according to claim 1, characterized in that X.j, Xg and X3 represent chlorine atoms. Process for the preparation of a trihalomethylhydroxy-lactone and / or its cis-tautomeric keto acid according to claim 1 or 2, characterized in that cis-caronic anhydride is reacted under anhydrous or substantially anhydrous conditions with a trihaloacetate with the general formula: x -C-C00M ^ I * 3 in which X ^, Xg and X3 may or may not have the same meaning and each individually represents a fluorine, chlorine or bromine atom and M represents an alkali metal atom, and the cis-keto acid optionally is converted to the corresponding ester or salt. Process according to claim 3, characterized in that the reaction is carried out in a high-polar aprotic inert solvent. 5. Process according to claim k, characterized in that the solvent is acetonitrile. 8102596