Note: Descriptions are shown in the official language in which they were submitted.
h~759
"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 com-
pounds known as "pyrethroids" and as they combine exceptionally good insec-
ticidal properties with a very low mammalian toxicity, they are of consider-
able interest to the agrochemical industry and much effort has been expend-
ed 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 ~ 3 1 \* COOR
CH3 H
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 impart insecticidal
activity to the molecule, e.g. 3-phenoxybenzyl or alpha-cyano-3-phenoxy-
benzyl. 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 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 nom-
enclature 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.
'~
- .: - .-: .:
i7Si9
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 by
physical separation techniques. The latter are expensive and laborious and
not 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~ ~ ~h (II)
CH3 / ~
CH3 HThis 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 for-
mula:-
H CH0
/ \ , (III)
3 / \ Cll2-cH-co-cH3
CH3 H
This compound may be named 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcycloprop-
ane-2-carbaldehyde. Preferably the compound of formula III is in the same
stereoisomeric form as that of the cyclopropane ring present in naturally-
occurring (+)-3-carene.
The present invention also provides a process for the preparation
-- 2 --
- . , .- : : . , ~
., : , , , . . ~ :
S9
of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethylcyclopropane-2-carbaldehyde of for-
mula III which comprises hydrolysing a 4-acetyl-2-alkoxy-7,7-dimethyl-3-
oxabicyclo[4.1.0]heptane of formula IV
R O ~ ~ CO-CH3
(IV)
3 f ~/
CH3
wherein Rl is an alkyl group. The alkyl group preferably contains 1 to 6
carbon atoms, for example methyl, ethyl and propyl. The preferred starting
material is 4-acetyl-2-methoxy-7,7-dimethyl-3-oxabicyclo[4.1.0]heptane. The
hydrolysis is preferably carried out in the presence of an aqueous acidic
medium, e.g. an aqueous organic or inorganic acid such as acetic acid or
10 sulphuric acid. Other examples of suitable hydrolysis media are given in
"Methoden der organischen Chemie" (Houben-Weyl), Volume VII, Part 1~1954)
423-428.
The starting material, compound IV, is a novel compound and is
claimed in our copending application 331,951 filed July 17, 1979 (K 357~. A
method of preparation of compound IV is also disclosed therein involving
ozonolysis of 4-hydroxy-2-carene in the presence of an alkanol, preferably
methanol, and reduction of the resulting ozonide.
The starting material is preferably derived from naturally-occur-
ring (+)-3-carene as this enables the process according to the invention to
20 yield a novel intermediate of formula III in a stereoisomeric form which,
after conversion to a pyrethroid insecticide produces the highest level of
pyrethroid insecticide-activity.
The compound and process according to the invention are of interest
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
.: .. : ,
. ~ ,, . -
7~
acid.
The following Examples further illustrate the invention.
Example 1 - Preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethyl-
cyclopropane-2-carbaldehyde (Compound III)
A 50 ml flask was charged with 4-acetyl-2-methoxy-7,7-dimethyl-
3-oxabicyclo[4.1.0]heptane (Compound IV) derived from (+)-3-carene ~21.7
mmol, 100% lR,cis) and a 1:1 (v) mixture (10 ml) of acetic acid and water.
After stirring of the contents of the flask for five hours at 20C water
(30 ml) was added and the resulting mixture was extracted with two 25 ml
portions of dichloromethane. The combined extract phases were washed with
two 25 ml portions of a saturated aqueous solution of sodium hydrogen car-
bonate and then with a 10% w aqueous solution (25 ml) of sodium chloride.
The washed organic phase was dried over anhydrous magnesium sul-
phate and the solvent was evaporated from the dried organic phase at 1.3
kPa to leave a residue (3.5 g) containing compound III ~100% lR,cis, yield
88%). The nuclear magnetic resonance spectrum of compound III showed the
following absorptions (using a solution of compound III in deuterochloro-
form and relative to a tetramethylsilane standard):
~ = 1.24 ppm singlet H3C-C-CH3 ~ = 1.33 ppm singlet H3C-C-CH3
~ = 2 22 ppm singlet H3C-C=O ~ = 3.6 ppm (variable) broad-OH
~ = 4.23 ppm doublet of doublets HC-OH ~ = 9.69 ppm doublet H-C=O
multiplets for each of the H atoms bound to the ring.
Example 2 - Preparation of 1-(2-hydroxy-3-oxobutyl)-3,3-dimethyl-
cyclopropane-2-carbaldehyde (Compound III)
A 50 ml flask was charged with Compound IV (10.1 mmol, 100%
lR,cis), a 1:1 (v) mixture (20 ml) of water and acetone and concentrated sul-
phuric acid (1.5 mmol), sp. gr. 1.84. Compound IV had been prepared as a
derivative of (+)-3-carene and had the same stereochemical configuration.
-- 4 --
. .
~: . . .
.- ' ~
fi~
After stirring of the contents of the flask for one hour at 20C the major-
ity of acetone was distilled off at 1.3 kPa. The residue was extracted
with two 10 ml portions of dichloromethane. The combined extract phases
were washed with two 20 ml portions of a saturated aqueous solution o~ so-
dium hydrogen carbonate and then with a 10% w aqueous solution (20 ml) of
sodium chloride. The washed organic phase was dried over anhydrous magnes-
ium sulphate and the solvent was evaporated from the dried organic phase at
1.3 kPa to leave a residue (1.6 g) containing compound III (100% lR,cis,
yield 86%).
~r,,
, :: : :: .,~, , :
