GB2052479A - Novel bicyclohexane compound useful as an intermediate in the preparation of pyrethroid insecticides - Google Patents

Abstract

A novel bicyclohexane compound, 2-acetoxy-6,6-dimethyl- 4-oxo-3-oxabicyclo[3.1.0]hexane (IV> <IMAGE> is obtained by epoxidation of 3,7,7- trimethyl-5-oxo-4- oxabicyclo[4.1.0]hept-2-ene (I> <IMAGE> to 2,3-epoxy-3,7,7-trimethyl-5-oxo-4- oxabicyclo[4.1.0]heptane (II), <IMAGE> isomerisation of II to form 2-acetyl- 6,6-dimethyl-4-oxo-3- oxabicyclo[3.1.0]hexane (III), <IMAGE> and oxidation of III to IV. Compounds II and III are novel, and compounds II, III and IV are useful intermediates in a stereospecific route to pyrethroid insecticides.

Description

SPECIFICATION A bicyclohexane compound The invention relates to a bicyclohexane compound and to processes for its preparation and to intermediates therefor. This compound is a useful intermediate in the preparation of a group of insecticidally active compounds known as "pyrethroids". As these pyrethroids combine exceptionally good insecticidal properties with a very low mammalian toxicity, they are of great interest to the agrochemical industry and considerable effort has been expended in finding economic routes for their production.

The general formula of one class of these pyrethroids may be represented as follows:-

where each asterisk denotes an asymmetric carbon atom; each X is a halogen atom and R is a member of a group of radicals known to impart insecticidal activity to the molecule, e.g. 3-phenoxybenzyl or alpha-cyano-3-phenoxybenzyl. It is known that the stereoisomeric form of the acid portion of the ester of formula A should be in the (1 R, cis) form for maximum insecticidal activity, i.e. the absolute configuration at carbon atom 1 is R and the two hydrogen atoms on carbon atoms 1 and 3 are in a cis relationship. This nomenclature is known as the Elliott nomenclature and is defined in M. Elliott, A. W.

Farnham, N. F. James, P, H. Needham and D. A, Pillman, Nature, 248(1974) 710.

It follows, therefore, that is these stereoisomeric esters of formula A are to be prepared, either a stereospecific chemical route is required or the desired stereoisomer must be obtained from a racemic form by physical separation techniques. The latter are expensive and laborious and not readily employed on an industrial scale. The Applicant has found a useful stereospecific route to these stereoisomers which proceeds via the bicyclohexane compound according to the invention.

The invention provides the bicyclohexane compound 2-acetoxy-6,6-dimethyl-4-oxo-3 oxabicyclo[3.1 .O]hexane. This compound - also referred to hereinafter as "compound IV" - has the following structural formula.

The invention also provides a process for the preparation of the bicyclohexane compound, compound IV, which comprises epoxidation of 3,7,7-trimethyl-5-oxo-4-oxabicyclo[4.1 .0] hept-2- ene - also referred to hereinafter as "compound I" - with formation of 2,3-epoxy-3,7,7-trimethyl-5 oxo-4-oxabicyclo[4. l.Ol-heptane -- hereinafter also referred as to "compound II" -- isomerisation of the latter compound in the presence of an acid into 2-acetyl-6,6-dimethyl-4-oxo-3-oxabicyclo[3. .0]- hexane -- hereinafter also referred to as "compound III" - and oxidation of the latter compound.

Compounds, I, II and III have the following structural formulae:-

Compounds II and Ill are also novel and the invention provides these two compounds. There are two asymmetric carbon atoms in the cyclopropane ring of compounds 11, III and IV which because of the constraints caused by the other ring give rise to two stereoisomers only (ignoring the presence of other asymmetric carbon atoms in the molecules), one having the 1 R and the other 1 S configuration. The number 1 indicates the carbon atom of the cyclopropane ring bound to the group --OO-C(OO)-. Each compound may consist of either the 1 R or the iS configuration or it may be a mixture of the two configurations.The bicyclohexane compound according to the invention, compound IV, is preferably in the 1 R configuration, because when used as a pyrethroid intermediate it is this configuration which produces the desired ( 1 R, cis) configuration in the acid portion of the insecticidally active ester of formula A. The starting compound in the process according to the invention, compound I, is also preferably in the 1 R configuration as this leads to the 1 R form of compound IV, via the 1 R forms of compounds II and 111.

The epoxidation of compound I may be carried out with any suitable epoxidation agent, for example (a) a peroxy acid or (b) hydrogen peroxide in combination with a catalyst or (c) an alkyl hydroperoxide, for example tert-butyl hydroperoxide, in combination with a catalyst. Peroxy acids are capable of rapidly and quantitatively converting compound I with a high selectivity to compound II.

The selectivity to a certain compound, expressed in a percentage, is defined as: a -x 100 b wherein "a" is the amount of the starting compound converted into that certain compound and "b" is the amount of converted starting compound.

Examples of suitable acids for the isomerisation of compound II are alkanoic acids and traces of ptoluene-sulphonic acid and of mineral acids. Alkanoic acids are usually capable of rapidly and quantitatively isomerising compound II into compound III.

The epoxidation and isomerisation referred to above may suitably be carried out at a temperature in the range 0 to 1 000C; an advantage is that these reactions usually proceed well at a temperature in the range 10 to 400C. The epoxidation is suitably carried out at a molar ratio of peroxy acid to compound I in the range of from 1 1 to 2 1, but molar ratios higher than 2 1 can be employed.

The oxidation may be achieved by the so-called Baeyer-Villiger oxidation, as described in "Methoden der organischen Chemise" (Houben-Weyl) Volume Vll/2b (1976) pp. 1984-1986, and is suitably carried out with a peroxy acid, giving a high yield of compound IV. Suitable temperatures are in the range of from 30 to 900C although temperatures outside this range are also possible; and suitable molar ratios of peroxy acid to compound III are in the range of from 2 1 to 5 1, but molar ratios outisde this range may be used.

The peroxy acids may be inorganic, or aromatic or nonaromatic organic peroxy acids, for example persulphuric acid, peracetic acid, perphthalic acid, persuccinic acid and pernoanoic acid. Very good results have been obtained with optionally substituted perbenzoic acids, for example, with 3chloroperbenzoic acid. The processes described above are suitably carried out in a solvent, for example, chloroform, dichloromethane, carbon tetrachloride, acetone, ethyl acetate or acetic acid. Very good results have been obtained with chloroform.

According to a preferred process according to the present invention the epoxidation of compound I with formation of compound 11, the isomerisation of compound Il into compound Ill and the oxidation of compound Ill to compound IV are carried out with the aid of a peroxy acid in one reaction zone. This has the advantage of requiring only one agent for the epoxidation, isomerisation and subsequent oxidation, and may be effected without isolation of the intermediate compounds II and Ill.

Compound IV can be saponified, for example, in the presence of water, methanol and an alkali metal hydroxide, with formation of an alkali metal salt of 2-formyl-3,3-dimethylcyclopropanecarboxylic acid; the 1 R form of the compound IV yields the ( 1 R, cis) form of the acid. This acid has the following structural formula:

Compound I may be prepared by dehydrating cis 2,2-dimethyl-3-(2oxopropyl)cyclopropanecarboxylic acid with acetic anhydride in the presence of p-toluenesulphonic acid and a solvent, for example, toluene or benzene.

The following Examples further illustrate the invention. Conversions and selectivities were determined by nuclear magnetic resonance (NMR) spectroscopy. The NMR data quoted were recorded at 90MHz; the absorptions given are relative to a tetramethylsilane standard. Compounds I, Il, Ill and IV all had the 1 R configuration. The 3-chloroperbenzoic acid contained about 15% wt of 3-chlorobenzoic acid, calculated on 3-chloroperbenzoic acid.

EXAMPLE 1 Preparation of (1 R) 2-acetoxy-6,6-dimethyl-4-oxo-3-oxabicyclo[3.1.0]hexane (compound IV) (a) Preparation of compound II A 25 ml flask placed in a water bath having a temperature of 200C and provided with a magnetic stirrer was charged with compound 1(6.4 mmol), 3-chloroperbenzoic acid (7.9 mmol) and chloroform (5 ml). After one hour's stirring compound I was quantitatively converted, with a selectivity to compound II of more than 90%. Then, dichloromethane (10 ml) and dimethyl sulphide (1 ml) were added and the resulting solution was washed with a saturated aqueous solution (10 ml) of sodium hydrogen carbonate and with two portions (each of 10 ml) of a 10% wt aqueous solution of sodium chloride.The washed solution was dried over anhydrous magnesium sulphate and the volatile compounds were evaporated from the dried solution at sub-atmospheric pressure to leave an oily residue (1.1 g) of compound li.

The NMR spectrum of compound II showed the following absorptions in deuterochloroform:-- a = 1.30 ppm, singlet, C113-C-CH3 a = 1.33 ppm, singlet, CH3-C-CH a = 1.65 ppm, singlet, CH3-C-0 a = 2.05 ppm, double doublet, H-C-CH(-O-); J =2Hz, 8Hz a = 1.6 ppm, doublet, H--CC-C=O; S = 3.33 ppm, doublet, H-C-O; J = 8Hz J = 2Hz (b) Preparation of compound III An NMR tube placed in a water bath having a temperature of 200C was charged with compound I (0.5 mmol), 3-chloroperbenzoic acid (0.5 mmol) and deuterochloroform (1 ml).After 45 minutes' standing compound I was quantitatively converted; the sum of the selectivities to compounds II and III was 100% and the selectivity to compound II was more than 50%. After three hours' standing the compound II was quantitatively converted into compound Ill. Then, dichloromethane (2 ml) and dimethyl sulphide (0.1 ml) were added and the resulting solution was first washed with a saturated aqueous solution (2 ml) of sodium hydrogen carbonate and then with two 2 ml portions of a 10% wt aqueous solution of sodium chloride. The washed solution was dried over anhydrous magnesium sulphate and the volatile compounds were evaporated from the dried solution at sub-atmospheric pressure to leave a residue of compound Ill.

The NMR spectrum of cqmpound Ill showed the following absorption in deuterchloroform:-- a = 1.10 ppm, singlet, a = 1.19 ppm, singlet, CK3-C-CH3 CH3-C-CH3 a = 1.6 ppm, multiplet, a = 2.3 ppm, multiplet, H-C-C(O)-O- H-C-CH(-O--) a = 2.31 ppm, singlet, a = 4.90 ppm, doublet, CH,-C=O H--C-O; J = 6Hz (c) Preparation of compound IV An NMR tube placed in a water bath having a temperature of 600C was charged with compound lit (0.23 mmol, prepare as described in (b) above), 3-chloroperbenzoic acid (0.35 mmol) and deuterochloroform (1 ml).After 24 hours' standing the conversion of compound III was 50%, with a selectivity to compound IV of more than 90%. Then, dichloromethane (2 ml) and dimethyl sulphide (0.1 ml) were added and the resulting solution was first washed with a saturated aqueous solution (1 ml) of sodium hydrogen carbonate and then with two 1 ml portions of a 10% wt aqueous solution of sodium chloride. The washed solution was dried over anhydrous magnesium sulphate and the volatile compounds were evaporated from the dried solution at sub-atmospheric pressure to leave a residue of compound IV.

The NMR spectrum of compound IV showed the following absorptions in deuterochloroform: a = 1.20 ppm, singlet, S = 1.44 ppm, singlet, CH3-C-CH3 CH3-C-CH3 a = 2.15 ppm, singlet a = 2.2 ppm, multiplet, CH3-C=0 H-C-C-O-C=O multiplet for H--CC-C=O a = 6.63 ppm, doublet, H-C-O-C=O; J = 5Hz EXAMPLE 2 PREPARATION OF COMPOUND IV An NMR tube placed in a water bath having a temperature of 20 C was charged with compound I (0.60 mmol),3-chloroperbenzoic acid (0.75 mmol) and chloroform (2 ml). After one hours standing the tube contained 0.58 mmol of compound II.Then, another quantity of 3-chloroperbenzoic acid (0.84 mmol, dissolved in 1 ml of chloroform) was added and the temperature of the water bath was raised to 600 C. After 1 hour's standing compound il was quantitatively converted into compound Ill.

Subsequently, two solutions of 3-chloroperbenzoic acid (0.50 mmol) in chloroform (1 ml) were added, one after a total of 20 hours and one 6 hours later. After a total of 30 hours' standing the conversion of compound Ill was 80%, with a selectivity to compound IV of 80 to 90%. Then, dichloromethane (2 ml) and dimethyl sulphide (0.3 ml) were added and the resulting solution was washed twice with a saturated aqueous solution (2 ml) of sodium hydrogen carbonate and with two portions (each of 2 ml) of a 10% wt aqueous solution of sodium chloride. The washed solution was dried over anhydrous magnesium sulphate and the volatile compounds were evaporated from the dried solution at subatmospheric pressure to leave a residue containing compounds III and IV.

Claims (15)

1. 2-Acetoxy-6,6-dimethyl-4-oxo-3-oxabicyclo[3. 1 .01-hexane.

2. The compound claimed in claim 1 in the 1 R configuration.

3. A process for the preparation of the compound claimed in claim 1 or claim 2, which comprises epoxidation of 3,f .7-trimethyl-5-oxo-4-oxabicyelo[4. I.0jhept-2-ene with formation of 2,3-epoxy-3,7 ,7- trimethyl-5-oxo-4-oxabicyclo[4.1 .01-heptane, isomerisation of the latter compound in the presence of an acid into 2-acetyl-6,6-dimethyl-4-oxo-3-oxabicyclo[3.1.0]hexane and oxidation of the latter compound.

4. A process according to claim 3 wherein the 3,7,7-trimethyl-5-oxo-4-oxabicyclo[4.1.01hept-2- ene is in the 1 R configuration.

5. A process as claimed in claim 3 or 4, in which the epoxidation, the isomerisation and the subsequent oxidation are carried out using a peroxy acid.

6. A process as claimed in claim 5, in which the peroxy acid is an optionally substituted perbenzoic acid.

7. A process as claimed in claim 6 wherein the optionally substituted perbenzoic acid is 3chloroperbenzoic acid.

8. A process as claimed in any of claims 5 to 7, which is carried out in one reaction zone.

9. A process as claimed in any one of claims 3 to 7 substantially as hereinbefore described with reference to any one of Examples 1 or 2.

10. A process as claimed in claim 8 substantially as hereinbefore described with reference to Example 2.

11.2-Acetoxy-6,6-dimethyl-4-oxo-3-oxabicyclo[3.1.0]hexane whenever prepared by a process as claimed in any one of claims 3 to 10.

12. 2 ,3-Epoxy-3,7 .7-trimethyl-5-oxo-4-oxabicyclo[4. I.Olheptane.

13. The compound claimed in claim 12 in the 1 R configuration.

14. 2-Acetyle-6,6-dimethyl-4-oxo-3xabicyclo[3. 1 .Ojhexane.

15. The compound claimed in claim 14 in the 1 R configuration.