GB2025967A - Cyclopropane Derivative - Google Patents

Abstract

Novel intermediate in the manufacture of pyrethroid insecticides has the following formula <IMAGE> wherein X is a halogen atom, preferably chlorine or bromine. The compound preferably has the same stereochemical form as the cyclopropane ring in (+)-3-carene. It can be prepared by a process which comprises hydrolysing a compound of formula <IMAGE> wherein R<1> is a methyl group or an acetyl group, and X is a halogen atom. The starting material is preferably derived from (+)-3-carene.

Description

SPECIFICATION Novel Intermediates in the Preparation of Cyclopropanecarboxylate Esters and Process for their Manufacture The invention relates to compounds which are useful intermediates in the preparation of cyclopropaneca rboxylate esters. The invention also relates to a process for the preparation of these intermediates.

The cyclopropanecarboxylate esters are insecticidally-active compounds known as "pyrethroids" and as they combine exceptionally good insecticidal properties with a very low mammalian toxicity, they are of considerable interest to the agrochemical industry and much effort has been expended in finding economic routes to them and to their principal intermediates.

The general formula of one class of these pyrethroid compounds 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. 3phenoxybenzyl or alpha-cyano-3-phenoxybenzyl.

It is known that the stereoisomeric form of the acid portion of the ester of formula I 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 2 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.

Pullman, Nature, 1974,248,710.

It follows, therefore, that if these stereoisomeric esters of formula I 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 stereospecific route which uses a starting material the naturally-occurring substance (+)-3carene whose formula is as follows:-

This compound is an inexpensive readily-available natural terpene and the present application relates to intermediates in a route to the (1 R,cis)acid portion of the pyrethroid ester of formula I starting from (+)-3-carene.

The present invention provides compounds of the formula

wherein X is a halogen atom, preferably chlorine or bromine. This compound may be named 2 (2,2-dihaolvinyl-3,3-dimethylcyclopropyl)ethanal.

Preferably the compound of Forrnula III is in the same stereoisomeric form as that of the cyclopropane ring of (+)-3-carene.

The present invention also provides a process for the preparation of a 2-(2,2-dihalovinyl-3,3dimethylcyclopropyl)ethanal of formula Ill which comprises hydrolysing a compound of formula IV:-

wherein R1 is a methyl group or an acetyl group and X is a halogen atom. The starting material may thus be 2-[2-(2,2-dihalovinyl)-3,3dimethylcyclopropyl]ethanal dimethyl acetal or 2 [2-(2,2-dihalovinyl-3,3dimethylcyclopropyl]ethylidene diacetate. The hydrolysis is preferably carried out in the presence of an acid, for example a weak organic acid such as acetic acid; small quantities of mineral acid, e.g. sulphuric or hydrochloric and are also preferably present.Further examples of suitable hydrolysis media are given in "Methoden der organischen Chemie" (Houben-Weyl), Volume VII, Part 1 (1954) 423-428 and 442-445.

The starting materials may be made by processes known, per se, for example, according to the methods disclosed in UK Patent Specification 1,413,491 which discloses the preparation of dihalovinylcyclopropyl compounds by reacting 2-formyl-3,3-dimethylcyclopropyl compounds with a dihalomethylenephosphorane (which can be prepared by reaction of a triorganophosphine, normally triphenylphosphine, with a carbon tetrahalide).

The starting material is preferably derived from naturally-occurring (+)-3-carene as this enables the process according to the invention to yield a novel intermediate of formula III in a stereoisomeric form which, after conversion to a pyrethroid insecticide, produces the highest level of pyrethroid insecticide activity.

The compound and process according to the invention are of interest as part of a multi-step process to pyrethroid insecticides, e.g. esters based on (1 R,cis)-2(2,2-dichlorovinyl)-3,3- dimethylcyclopropane carboxylic acid, or (1 R,cis) 2-(2,2-dibromovinyl)-3,3-dimethylcyclopropane carboxylic acid.

The following Examples further illustrate the invention.

Example 1 Preparation of 2-(2,2-dichlorovinyl-3,3 dimethylcyclopropyl)ethanal (Compound Ill) Firstly, (1 R,cis)-2-2-(2,2-dichlorovinyl)-3,3- dimethylcyclopropyl ethanal dimethyl acetal was prepared by the following method: Tri(dimethylamino)phosphine (168.3 mmol) was added over a period of 12 minutes to a stirred solution of carbon tetrachloride (167.4 mmol) in pentane (369 ml) kept at O C under nitrogen in a 1-1 flask. Then, the mixture in the flask was stirred for 30 minutes at OOC. This finished the first step.

At 0 C (1 R,cis)-2-(2,)-dimethyoxyethyl)-3,3- dimethylcyclopropanecarbaldehyde (66.4 mmol) was added dropwise to the suspension in the flask over a period of nine minutes. The temperature was increased to 1 20C over a period of 1 5 minutes and stirring was continued at the temperature for a further 15 minutes. This finished the second step. Then, water (75 ml) was added at 120C and-after removal of the aqueous phase-the organic phase was washed with two 35 ml portions of water. The washed organic phase was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried solution to give a residue (17.4 g) containing the dimethyl acetal (100% (1 R,cis), purity 88%, yield 91.1%).

The NMR spectrum of the dimethyl acetal showed the following absorptions: S=1.00 ppm singlet H3C-C-CH3 S=1.13 ppm singletH3C-C-C H3 S=3.33 ppm singlet C-(0-CH3)2 S=4.33 ppm triplet (H3C-0)2-CH- S=5.59 ppm doublet C=CH multipiets for the two H atoms bound to the ring and for HC-CH2-CH.

A 250 ml flask was charged with the residue (17.4 g, containing 60.5 mmol of the (1 R,cis) dimethyl acetal, obtained as above and a 2/1 (v/v) mixture (90 ml) of acetic acid and water to which concentrated aqueous hydrochloric acid (0.02 ml.

sp.gr.1 .19) had been added. The mixture in the flask was heated with stirring under nitrogen for two hours at 600C. Then, most of the acetic acid and water was distilled off from the reaction mixture (600C/1.3 kPa), the residue obtained was taken up in diethyl ether (100 ml), water (25 ml) was added to the ethereal solution and the pH of the liquid was increased to 7 by addition of sodium hydrogen carbonate.The neutralised liquid was washed with two 20 ml portions of water, the washed liquid was dried over anhydrous magnesium sulphate and the diethyl ether was distilled off from the dried liquid to give a residue (13.8 g) containing compound 111(100% 1 R, cis, purity 82.1%, yield 90.4%). The NMR spectrum of compound Ill showed the following absorptions: S=1.02 ppm singlet H3C-C-CH3 S=1.21 ppm singletH3C-C-CH3 S=2.43 ppm double doublet H,C--C(O)H S=5.57 ppm doublet Cl2C=CH b=9.81 ppm triplet --C(O)H multiplets for the two H atoms bound to the ring.

Example 2 Preparation of 2-(2,2-dichlorovinyl-3,3dimethylcyclopropyl)ethanal (Compound Ill) Firstly (1 R,cis)-2-2-(2,2tdichlorovinyl)-3,3- dimethylcyclopropyl ethylidene diacetate was prepared by the following method: The contents of a 50 ml flask charged with 1 [2-(2,2-dichlorovinyl)-3,3-dimethylcyclopropyl]- 3-oxo-2-butyl acetate (11.9 mmol, 100% 1 R,cis, both spatial configurations around C--C(O)CH, being present), chloroform (10 ml) and 3chloroperbenzoic acid (26 mmol) were stirred magnetically for five hours at 200C. Then, another quantity of 3-chloroperbenzoic acid (6 mmol) was added and stirring was continued for 16 hours.

The reaction mixture obtained was mixed with dimethyl sulphide (2 ml), keeping the temperature at 200C, stirring was continued for 15 minutes, dichioromethane (30 ml) was added, the suspended material was filtered off, the filtrate was washed with two 20 ml portions of a saturated aqueous solution of sodium hydrogen carbonate and two 20 ml portions of a 10% w aqueous solution of sodium chloride. The washed organic phase was dried over anhydrous magnesium sulphate and the solvent was evaporated (2 kPa) from the dried liquid to leave a residue (2.3 g) containing the ethylidene diacetate compound (100% 1 R,cis, yield 63%).

The nuclear magnetic resonance spectrum of the compound showed the following absorptions (using a solution of the compound in deuterochloroform and relative to a tetramethysilane standard): S=1.05 ppm singlet H3CCCH3 9=1.15 ppm singletH3C-C-CH3 8=2.12 ppm singlet both H,C--C(O))--O- S=5.62 ppm doublet HC=CCI2 b=6.86 triplet H--CC--O- multiples for each of the H atoms bound to the ring and for HCCH2CH.

The contents of a 25 ml flask charged with the residue (0.85 g, containing 2.8 mmol of the (1 R,cis) ethylidene diacetate compound, obtained as above acetic acid (4 ml), water (4 ml) and concentrated sulphuric acid (s.g.1 .84, containing 1 mmolof H2SO4) were stirred magnetically during eight hours at 700C. After cooling to 200C water (10 ml) was added, the mixture formed was extracted twice with dichloromethane (15 ml), the combined extracts were washed with two 20 ml portions of a saturated aqueous solution of sodium hydrogen carbonate and with an aqueous solution (20 ml) of 10% w sodium chloride. The washed solution was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried solution at 1.3 kPa to leave a residue (0.40 g) containing compound lil (100% 1 R,cis, yield 70%).

Claims (9)

Claims

1. A cyclopropane compound of formula

wherein X is a halogen atom.

2. A compound according to Claim 1 in the same stereoisomeric form as the cyclopropane ring in (+)-3-carene.

3. A process for the preparation of a 2-(2,2dihalovinyl-3,3-dimethylcyclopropyl)ethanal of formula Ill which comprises hydrolyzing a compound of formula IV

where R1 is an acetyl group or a methyl group, and X is a halogen atom.

4. A process according to Claim 3 wherein the hydrolysis is carried out in the presence of an acid.

5. A process according to Claim 4 wherein the acid is a weak organic acid.

6. A process according to Claim 4 or 5 wherein a mineral acid is additionally present.

7. A process according to any one of Claims 3 to 6 wherein the starting material of formula IV is derived from naturally-occuring (+)-3-carene.

8. A process according to Claim 7 substantially as hereinbefore described with reference to the Examples.

9. A 2-(2,2-dihalovinyl-3,3dimethylcyclopropyl)ethanal prepared by a process claimed in any one of claims 3 to 8.