INTERMEDIATE IN THE PREPARATION OF CYCLOPROPANECARBOXYLATE ESTERS AND PROCESS FOR ITS MANUFACTURE

PRODUIT INTERMEDIAIRE DANS LA PREPARATION DES CYCLOPROPANECARBOXYLATES, ET PROCEDE POUR SA FABRICATION

English Abstract

ABSTRACT
Novel intermediate in the manufacture of pyrethroid insecticides
has the following formula
<IMG>
The compound preferably has the same stereoisomeric form as the cyclopropane
ring in (+)-3-carene. The novel intermediate can be prepared by a process
which comprises oxidising 2-(2-hydroxymethyl-3,3-dimethylcyclopropyl)ethanal
dimethyl acetal, for example by means of a chromium trioxide-pyridine complex
of a pyridinium chlorochromate. The starting material is preferably derived
from (+)-3-carene.

Claims

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:
<IMG> (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 1-(2,2-dimethoxyethyl)-3,3-dimethyl-
cyclopropane-2-carbaldehyde of formula III, as defined in claim 1, which
comprises oxidising 2-(2-hydroxymethyl-3,3-dimethylcyclopropyl) ethanal dimethyl
acetal of formula
<IMG> (IV)
with a reagent capable of oxidising the hydroxymethyl group into a formyl group.
4. A process according to Claim 3 wherein the oxidation is effected by
employing a chromium trioxide-pyridine complex or a pyridinium chlorochromate.

5. A process according to Claims 3 or 4 wherein the starting material of
formula IV as defined in Claim 3 is in the same stereoisomeric form as that of
the cyclopropane ring present in naturally-occurring (+)-3-carene.

Description

~1238S7
"Novel intermediate in the preparation of
cyclopropanecarboxylate esters and process
for its manufacture"
The inven-tion 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 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 rou-tes to them and to their principal inter-
mediates.
The general formula of one class of these pyrethroid
compounds may be represented as follows:-
H CH=CX2
C~3 ~ ~ \ COOR (I)
cl3 H
where each asterisk denotes an asymmetric carbon atom; each Xis a halogen atom; and R is a member of a group of radicals
known to impart insecticidal activity to the molecule, e.g.
- 1 --

~3~3~7
3-pheno~yben~yl or alpha-cyano-3-~heno~ybenzyl. It is known that the
stereoisomeric form oE the acid portion oE the ester of formulcl I should be
in the ~lR,c ) form for ma~imum 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 re-
quired or the desired stereoisomer must be obtained from a racemic form byphysical separation techniques. The latter are e~pensive and laborious and
not readily employed on an industrial scale. The ~pplicant has found a
stereospecific route which uses as starting material the naturally-occurring
substance (~)-3-carene whose formula is as follows:-
CH3
h (II)
CH3
CH3
This compound is an ine~pensive readily-available natural terpene and the
present application relates to an intermediate which can be used in a route
to the (IR,c )-acid portion of the pyrethroid ester of formula I starting
from ~I)-3-carene.
The present invention provides a cyclopropane compound of the gen-
eral formula:-
H CHO
O-CH3 (III)
\
C~3 ~ \ 2
H3 H O-CH3
-- 2 --

~38~
This compound may be named 1-(2,2-dimethoxyethyl)-3,3-dimethylcyclopropane-2-
carbaldehyde. Preferably the Compound of formula III is in the same sterois-
meric fonn as that of the cyclopropane ring present in naturally-occurrlng
(+)-3-carene.
The present invention also provides a process Eor the preparation of
1-(2,2-dimethoxyethyl ~-3,3-dimethylcyclopropane-2-carbaldehyde of formula III
which comprises oxidising 2-(2-hydroxymethyl-3,3-dimethylcyclopropyl) ethanal
dimethyl acetal of formula
2H
~ /O-C~13
CH3 2 \ (IV)
CH3 H O-CH3
~ith a reagent capable of oxidising the hydroxymethyl group into a formyl group.
The oxidation may conveniently be carried out by employing a chromium trioxide-
pyridine complex or a pyridinium chlorochromate, for example as described in
J. Org. Chem. 35 (1970) No. 11,4000-4002 and Tetrahedron Letters 31 (1975
2647-2650. Another method of oxidising the hydroxymethyl group involves
catalytic dehydrogenation, Eor example in the presence of a copper chromite
catalyst. Other methods for conversion oE n hyclroxymethyl group into a Eormyl
group can be Eouncl in "~lethoden der organischen Chemie" ~llouben-~eyl), Volume
VII, Part 1, (1945) 159-192.
The starting material, compound IV, is a novel compound and is claimed
in our copending Canadian application No. 331,953. A method of preparation of
compound IV is also disclosed therein involving hydrolysis of 1-(2,2-dimethoxy-
ethyl)-3,3-dimethylcyclopropylmethyl acetate, for example, by employing an
alkaline-reacting medium.
The starting material is preferably derived from naturally-occurring
-- 3 --
~3.

385~
(+)-3-carene as this enables the process accordlng to the invention to yield
a novel intermediate of form~lla III in a stereoisomeric Eorm which, a:Eter
conversion to a pyrethroid

~23~7
insecticide produces the highest level of pyrethroid insccticide activity.
The compound and process according to the invention are of intercst
as part of a multi-step process to pyrethroid insecticides, e.g. esters
based on (lR,c )-2-~2,2-dichlorovinyl)-3,3-dimethylcyclopropane carboxylic
acid and the dibromo analogues.
The following Example further illustrates the invention.
Example - Preparation of l_~2,2_dimethoxyethyl)-3,3-dimethylcyclopropane-
2-carbaldehyde ~Compound III)
A solution of ~lR,cis)-2-~2-hydroxymethyl-3,3-dimethylcyclopropyl)-
ethanal dimethyl acetal ~84.8 mmol) in dichloromethane ~80 ml) was added at
once to a stirred solution of pyridinium chlorochromate ~132 mmol) in di-
chloromethane ~160 ml) in a 500 ml flask. After stirring for three hours at
20C the black precipitate present in the reaction mixture was filtered off
and the precipitate was washed with three 50 ml portions of diethyl ether.
The solvent was evaporated from the combined filtrates to give 100 ml of a
residual liquid. This liquid was filtered and the diethyl ether was evapor-
ated from the filtrate ~40C/2 kPa) to give a residue ~14.2 g) containing
compound III in 100% lR,cis configuration purity 87%, yield ~0.5%, determined
by gas-liquid chromatography and nuclear magnetic resonance ~NhlR) spectro-
scopy. The NMR spectrum of compound III showed the followin~ absorptions
(at 90 h~lz, using a solution of compound III in deuterochloroform and rel-
ative to a tetramethylsilane standard):
= 1.22 ppm singlet H3C-C-C}13
= 2.03 ppm double doublet HC-CH3-CH
= 4.32 ppm triplet (}13C-O)2C}I-
- l.33 ppm singlet H3C-C-CH3
~ = 3.34 ppm singlet H3C-O-C-O-CH3
multiplets for the two H atoms bound to the ring.
-- 4 --