NOUVEAU PRODUIT INTERMEDIAIRE DANS LA PREPARATION D'ESTERS CYCLOPROPANECARBOXYLATES ET PROCEDE POUR LEUR FABRICATION

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

Abrégé anglais

K 361
ABSTRACT
Novel intermediate in the manufacture of pyrethroid
insecticides has the following formula
<IMG>
The compound preferably has the same stereochemical form as the
cyclopropane ring in (+)-3-carene, The novel intermediate can
be prepared by a process which comprises hydrolysing under
alkaline conditions 1-(2,2-dimethoxyethyl)-3,3-dimethylcyclo-
propylmethyl acetate, the latter compound being preferably
derived from (+)-3-carene.

Revendications

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

Description

K 361
"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
CH3
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:-
CH3
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:-
1 X H2 OH
/ \ /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
H CH2-O-CO-CH3
/\
/ \ (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-
-3-
. ~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.
: :
,
, , , ~
.