CA1147347A - Intermediate in the preparation of cyclopropanecarboxylate esters and process for its manufacture - Google Patents

Abstract

ABSTRACT
Novel intermediate in the manufacture of pyrethroid insecticides has the following formula:-

Description

73D~7 "Novel intermediate in the preparation of cyclopropanecarboxylate esters and process for its manufacture"
_ _ .
The invention relates to a compound which is a useful intermediate in the preparation of cyclopropanecarboxylate esters. The invention also relates to a process for the preparation of this intermediate.
The cyclopropanecarboxylate esters are insecticidally-active compounds known as "pyrethroids" and as they com~ine exceptionally good insecticidal prop-erties 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:-H CH=CX2 CH3 7/~ - ~COOR (I) ./ :

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 lmpart 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 I
should be in the (lR,c ) form for maximum insecticidal activity, i.e. the ab-solute configuration at carbon atom 1 ls R and two hydrogen atoms on carbon atoms 1 and 2 are in a cis relationship. This nomenclature is known as the Flliott 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 4~

`~

desired stereoisomer must be obtained from a racemic form by physical separa-tion techniques. The latter are expensive and laborious and not readily em-ployed on an industrial scale. The Applicant has found a stereospecific route which uses as starting material the naturally-occurring substance ~+)-3-carene whose formula is as follows: -H
CH3 ~

3 ~l This compound is an inexpensive readily-available natural terpene and the pres-ent application relates to an intermediate which can be used in a route to the ~lR,c )-acid portion of the pyrethroid ester of formula I starting from ~+)-3-carene.
The present invention provides a cyclopropane compound of the for-mula: -H CHO

/ \ O-CO-CH
3 ~ CH2 -CH-CO-CH3 ~III) in the ~lR,cis)-stereoisomeric form. This compound may be named ~lR,cis)-1-~2-formyl-3,3-dimethylcyclopropyl)-3-oxo-2-butyl acetata.
The present invention also provides a process for the preparation of (lR,cis)-1-~2-formyl-3J3-dimethylcyclopropyl)-3-oxo-2-butyl acetate of formula III which comprises reacting ~lR,cis)-1-~2-hydroxy-3-oxobutyl)-3,3-dimethyl-cyclopropane-2-carbaldehyde of formula: -~73~7 \

H CHO

/~\ OH
CH3 __~ \ CH2-CH-CO-CH3 (IV) with an acetylating agent, for example an acetyl halide such as acetyl chloride or bromide, or acetic anhydride. If an acid halide is employed a hydrogen hal-ide acceptor, for example an organic base such as an amine is preferably pres-ent; pyridine has been used with advantage. This process may be carried out according to conditions described in "Methoden der organischen Chemie" ~Houben-Weyl), Volume VIII (1952) 516-526, 543-550.
The starting material, compound IV, is a novel compound and is claimed in our copending application ~K 365). A method of preparing com-10 pound IV is also disclosed therein involving the hydrolysis, preferably using anaqueous acidic medium, 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo[4.1.03hep-tane.
The starting material is conveniently derived from naturally occurring )-3-carene and this produces compound I~ in the~ (lR,cis)-form.
The compound and process accordmg to the invention are of interest as part of a multi-step process to pyrethroid insecticides, e.g. esters based on (lR,cls)-2-(2,2-dichlorovinyl)-3,3-dlmethylcyclopropane carboxylic acid, and the corresponding dibromo analogue.
The following Example further illustrates the invention: -20 Example - Preparation of ~lR?cis)-1-~2-formyl-3,3-dimethylcyclo-propyl)-3-oxo-2-butyl acetate ~Compound III) Acetyl chloride ~30 mmol) was added with stirring over a period of 30 minutes and at a temperature between 5 and 10C to a 50 ml flask charged with (lR,cis)-1-~2-hydroxy-3-oxobutyl)-3,3-dimethylcyclopropane-2-carbaldehyde.

~19.0 mmol, 100% (lR,cis) both spatial configurations around the C~OH being present), pyridine ~60 mmol) and dichloromethane (20 ml). The starting material had been derived from ~ 3-carene. Then, consecutively, stirring was continued for 15 minutes, the temperature was allowed to rise to 20C, water ~20 ml) was added, the resulting mixture was acidified with concentrated aqueous hydrochlor-ic acid ~s.g.l.19) to pH of 2, the acidified mixture was allowed to settle into an aqueous and an organic phase and after separating off the aqueous phase, the organic phase was washed with two 30 ml portions of a 10% w aqueous solution of sodium chloride and a saturated aqueous solution (30 ml) of sodium hydrogen car-bonate. The washed organic liquid was dried over anhydrous magnesium sulphateand the solvent was evaporated from the dried liquid at 1.3 kPa to leave a res-idue ~3.3 g) containing compound III ~100% (lR,cis) yield 77%). The nuclear magnetic resonance spectrum of compound III showed the following absorptions ~using a solution of compo~md III in deuterochloroform and relative to a tetra-methylsilane standard):
= 1.23 ppm singlet H3C-C-CH3 ~ = 1.33 ppm singlet H3C-C-C~13 = 2.16 ppm singlet _3C-C~O)-O- ~ = 2.19 ppm singlet H3C-C~O)-C
~ = 5.07 ppm doublet of doublets H2C-CH-O- ~ = 9.63 ppm doublet H-C=O
~multiplets for each of the H atoms bound to the ring and for HC CH2 CH.

:

~i ~

, .
.

.

Claims (4)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A cyclopropane compound of the formula (III) (III) in the (1R, cis)-stereoisomeric form.

2. A process for the preparation of (1R, cis)-1-(2-formyl-3,3-dimethyl-cyclopropyl)-3-oxo-2-butyl acetate which comprises reacting (lR, cis)-1-(2-hy-droxy-3-oxobutyl)-3,3-dimethylcyclopropane-2-carbaldehyde of formula (IV):- (IV) with an acetylating agent.

3. A process according to claim 2 wherein the acetylating agent is an acetyl halide.

4. A process according to claim 2 or 3 which is carried out in the presence of a hydrogen halide acceptor.