CA1123016A - 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

"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 in~ention also relates to a process for the preparation of this intermediate, The cyclopropanecarboxylate esters are insecticidally-active compounds known as "pyre~hroids" and as they combine exceptionally good insecticidal properties with a ~ery low mammalian toxi¢ity9 ~hey are of considerable interest to the a~rochemical industry and much eff`ort has been expended in finding economic routes to them and to their principal inter-mediates, The general formula of one class of these pyrethroid compounds may be represented as follows:

W

CH3 / ~ - ~ \ COOR

where each asterisk denotes an asymmetric carbon atom; each X
is a halogen atom; and R is a member of a group of radicals kno~,~n to impart insecticidal activi~y to the molecule, e.g.

i~
`~

i -: . . .
:: , ~ . : , ..
", -'~ ' 3~

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 maximl1m insecticidal activity, i.e. the absolute configuration at carbon atom 1 is R and the two hydrogen atoms on carbon atoms l 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 for-mula I are to be prepared, either a stereospecific chemical route is re-quired or the desired stereoisomer must be obtained from a racemic form by physical separation techniques. The latter are expensive and laborious andnot readily employed 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~ ~ (II) C113 ~ ~

3 ~1 This compound is an inexpensive readily-available natural terpene and the present 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 gen-eral formula:-/ \ /O-CH3 CH3 / - -\ \ CH2-CH (III) CH3 ~ 2 - H O-CH3 i"-'~' ; ~ :

~ ~3~

The compound may be named 2-(2-hydroxymethyl-3,3-dimethylcyclopropyl)-ethanal dimethyl acetal. Preferably the compound of formula Ill is in the same stereoisomeric form as that of the cyclopropane ring present in naturally-occur-ring (*)-3-carene.
The present invention also provldes a process for the preparation of

2-(2-hydroxymethyl-3,3-dimethylcyclopropyl~ethanal dimethyl acetal of formula III
which comprises hydrolysing under alkaline conditions 1-(2,2-dimethoxyethyl)-3,3-dimethylcyclopropylmethyl acetate of formula /\
/ \ (IV~
/ \ ~ O-C~13 CH / - - _ \ ~ CH2-CH

3 O-CH3 It will be seen that the hydrolysis must be carried out in such a manner that the two methoxy groups remain unchanged; generally speaking, the use of an alka-line-reacting medium enables this to be achieved. Other hydrolysis conditions are described in "Methoden der organischen Chemie" (Houben-~eyl), Volume VIII
(1952) ~18-~23 and 638-639.
The starting material compo~md IV may be prepared by (a) the ozonoly-sis of (+)-3-carene followed by reduction in the presence of methanol and an ace~alising agent of the ozonolysis product; and (b) oxidation of the resulting product with a peracid, e.g. perbenzoic acid. Such a reaction is disclosed in our pending Canadian Application Serial No. 316,588.
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 conver-. ~c ,j , `:
' ~ ~,3~:~ $

sion to a pyrethroid insecticide produces the highest level of pyrethroid in-secti.cide activity.
The compound and process according to the invention are of interest as part o:E a multi-step process to pyret.hroid insecticides, -3a-`~3 , , ' ' ~ :

`
'' ' , ' ' - - \
~ 23'~

e.g. esters based on ~lR, C15) -2-(2,2-dichlorovinyl)-3,3-dimethylcyclopropane carboxylic acid, and their dibromo analogues.
The following Example further illustrates the invention.
E~ample - Preparation of 2-~2-hydroxymet]lyl-3,3-dimethylcyclo-propyl)ethanal dimethyl acetal ~Compound III) A 250 ml flask was charged with water ~75 ml), methanol ~30 ml), sodium hydroxide ~152.2 mmol) and lR,cis-1-~2,2-dimethoxyethyl)-3,3-dimethyl-cyclopropylmethyl acetate ~145 mmol). After stirring for three hours at 20C
methanol was evaporated from the contents of the flask at 40C/2 kPa. The aqueous phase left was saturated with sodium chloride and then extracted with three 70 ml portions of diethyl ether. The combined extract phases were washed with two 10 ml portions of wa-tcr, the washed etherial solution was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried solution to give 120.7 mmol of compound III in 100% lR,cis config-uration ~purity 98%, yield 83%, determined by gas liquid chromatography and nuclear magnetic resonance ~NMR) spectroscopy). The NMR spectrum of compound III showed the following absorptions ~at 90 MHz, using a solution of compound III in deuterochloroform and relative to a tetramethylsilane standard):
~ = 0.97 ppm singlet 113C-C-CH3 20 ~ = 3.00 ppm singlet 113C-O-C-O-CH3 = 4.40 ppm double doublet ~H3CO)2-C11-= 1.06 ppm singlet H3C-C-CH3 ~ = 3.06 ppm singlet H3C-O-C-O-CH3 multiplets for the two H atoms bound to the ring and for CH2OH and ~H3CO)2-CHCH2.

: :
, , , , ~

.

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)

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

3. A process for the preparation of a cyclopropane compound of for-mula III which comprises hydrolysing under alkaline conditions 1-(2,2-dimethoxy-ethyl)-3,3-dimethylcyclopropylmethyl acetate of formula (IV)

4. A process according to Claim 3 wherein the starting material of for-mula IV is derived from naturally-occurring (+)-3-carene.