CH641139A5 - Process for the preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcyclopropane-2-carbaldehyde - Google Patents

Description

The invention relates to a process for the preparation of compounds which are suitable as intermediates for the preparation of cyclopropanecarboxylate esters.

The cyclopropanecarboxylate esters are insecticidally active compounds known as “pyrethroids”, in which exceptionally good insecticidal properties are associated with low mammalian toxicity. They are of considerable interest for agrochemicals and great efforts have been made to develop economical processes for the production of their intermediates.

One group of these pyrethroid compounds has the following general formula

CH = CX.

COOR

Both hydrogen atoms on carbon atoms 1 and 2 35 are in the cis position to one another. This nomenclature is known as the Elliott nomenclature (M. Elliott, A.W. Farn-ham, N.F. James, P.H. Needham and D.A. Pullman, Nature, 1974, 248, 710).

It follows that if these stereoisomeric esters of formula I are to be prepared, either a stereospecific chemical process must be used or the desired stereoisomer must be obtained from a racemic mixture by physical separation processes. The last-mentioned methods are complex and laborious and cannot be easily applied on an industrial scale.

A stereospecific procedure was developed, in which the naturally occurring (+) - 3-carene, the formula, is used as the starting substance

50

(I)

in which the asterisks each indicate an asymmetric carbon atom, X is a halogen atom and R is selected from the group of residues which are known to confer insecticidal activity on the molecule, e.g. a 3-phenoxybenzyl or a-cyano-3-phenoxybenzyl group. It is known that the acid portion of the ester of formula I should be in (1R, cis) form in order to give the compound maximum insecticidal activity, i.e. the absolute configuration at carbon atom 1 is R and

60

(II)

-H

This compound is an inexpensive, readily available, naturally occurring terpene, and the invention relates to intermediates in a process for the preparation of the (1R, cis) acid portion of the pyrethroid ester of Formula I starting from (+) - 3-carene .

3rd

641 139

The invention relates to a process for the preparation of a cyclopropane compound of the formula

CH

3-7

OH

CHo-CH-C0-CH-

The compound can be referred to as l- (2-hydroxy-3-oxobutyl) -3,3-dimethylcyclopropane-2-carbaldehyde. The compound of the formula III is preferably in the same stereoisomeric form as the cyclopropane ring of the naturally occurring (+) - 3-carene.

This process is characterized in that a 4-acetyl-2-alkoxy-7,7-dimethyl-3-oxabicyclo [4.1.0] heptane of the formula

CO-CKL

(IV)

in which R1 is an alkyl group, hydrolyzed. The alkyl group preferably contains 1 to 6 carbon atoms and is e.g. a methyl, ethyl or propyl group. The preferred starting substance is 4-acetyI-3-methoxy-7,7-dimethyl-3-oxabicyclo [4.1.01heptan. The hydrolysis is preferably carried out in the presence of an aqueous acidic medium, e.g. an organic or inorganic acid such as acetic acid or sulfuric acid. Other examples of suitable hydrolysis media are given in “Methods of Organic Chemistry” (Houben-Weyl), Vol. VII, Part 1 (1954) 423-428.

The starting material, Compound IV, is a new compound which is given in British Patent No. 2 205 966. A process for the preparation of compound IV is also given there. It includes the ozonolysis of 4-hydroxy-3-carene in the presence of an alkanol, preferably methanol, and reduction of the ozonide formed.

The starting compound is preferably derived from naturally occurring (+) - 3-carene and this makes it possible to obtain the new intermediate of formula III in a stereoisomeric form which, after conversion into a pyrethroid insecticide, gives the highest insecticidal activity.

The compound and method of the invention are of particular interest as part of a multi-step process for the preparation of pyrethroid insecticides, e.g. Esters based on (1R, cis) -2- (2,2-dichloro-5 vinyl) -3,3-dimethylcyclopropanecarboxylic acid.

The invention was illustrated by the following examples:

example 1

I- (2-hydroxy-3-oxobutyl) -3,3-dimethylcyclo-lo propane-2-carbaldehyde (compound III)

In a 50 ml flask, 21.7 mmol of 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo [4.1. OJheptan (compound IV) derived from (+) - 3-carene ( 100% IR, ice) and 10 ml of a 1: 1 (vol) mixture of acetic acid and water i5. After the contents of the flask had been stirred for 5 hours at 20 ° C., 30 ml of water were added and the resulting mixture was extracted with 2 × 25 ml of dichloromethane. The combined extracts were washed with 2 x 25 ml of a saturated aqueous sodium bicarbonate solution and then with 25 ml 20 of a 10% sodium chloride solution. The organic phase was dried over anhydrous magnesium sulfate and the solvent was evaporated at 1.3 kPa. 3.5 g of a residue were obtained, containing the compound III (100% 1R, ice, yield 88%). The nuclear magnetic resonance spectrum of compound III showed the following absorptions (solution of compound III in deuterochloroform, based on tetramethylsilane as standard): 8 = 1.24 ppm singlet H3C-C-CH3 8 = 1.33 ppm singlet HjC-C -CH,

30 -

8 = 2.22 ppm singlet H3C-C = 0 8 = 3.5 ppm (variable) wide OH 8 = 4.23 ppm doublet of doublets HC-OH 8 = 9.69 ppm doublet H-C = 0 -

35 multiplets for all H atoms on the ring.

Example 2

l- (2-Hydroxy-3-oxobutyl) -3,3-dimethylcyclopropane-2-carbaldehyde (Compound III)

40 In a 50 ml flask, 10.1 mmol of compound IV (100% 1R, ice), 20 ml of a 1: 1 (vol) mixture of water and acetone and 1.5 mmol of conc. Sulfuric acid (spec. Weight 1.84). Compound IV had been prepared as a derivative of (+) - 3-carene and had the same stereochemical configuration. After stirring the contents of the flask at 20 ° C for 1 hour, the majority of the acetone was distilled off at 1.3 kPa. The residue was extracted with 2 x 10 ml dichloromethane. The combined extracts were washed with 2 x 20 ml of saturated aqueous sodium bicarbonate solution and then with 20 ml of 10% aqueous sodium chloride solution. The organic phase was dried over anhydrous magnesium sulfate and the solvent was evaporated from the organic phase at 1.3 kPa. 1.6 g of a residue were obtained, containing the compound III (100% 1R ice), yield 86%).

Claims (4)

641139 2nd PATENT CLAIMS 1. Process for the preparation of 1- (2-hydroxy-3-oxo-butyl) -3,3-dimethylcyclopropane-2-carbaldehyde of the formula III, CHO CH- OH (III) CH2-CH-CO-CH3 characterized in that a 4-acetyl-2-alkoxy-7,7-dimethyl-3-oxabicyclo [4.1.0] heptane of the formula CO-CHr (IV) 2. The method according to claim 1, characterized in that one starts from 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabi-cyclo [4.1.0] heptane. 5 3. The method according to claim 1 or 2, characterized in that one carries out the hydrolysis in the presence of an aqueous acidic medium. 4. The method according to any one of claims \ to 3, characterized io that one of a compound of the formula IV, which is derived from naturally occurring (+) - 3-carene. 5. The method according to any one of claims 1 to 4, characterized in that a compound of formula III which is in the same stereoisomeric form as the cyclopropane ring of naturally occurring (+) - 3-carene. 20 6. l- (2-Hydroxy-3-oxobutyl) -3,3-dimethylcyclopropane-2-carbaldehyde of the formula III, which has been prepared by a process according to Claims 1 to 5. in which R1 is an alkyl group, hydrolyzed.