Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
11~85~5
~ 3~9 c~
"Novel intermediates in the preparation of cyclopropane-
carboxylate esters and process for their manufacture"
~he invention relates to compounds which are u6eful
intermediatee in the preparation of cyclopropanecarboxylate
esters. ~he invention also relates to a proces~ for the
preparation of these intermediates.
~he cyclopropanecarboxylate e~ters are inse¢ticidally-
active compounds known as "pyrethroids" and as they combine
exoeptionally good insecticidal properties with a ~ery 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.
~ he general formula of one class of these pyrethroid
compounds may be represented as follow~s-
~ C~CX2
/~\
C~ ~ 2 1 ~ COOR ~I)
C~2
where each asteri~k denotes an asymme~tric carbon atom eachX is a halogen atom~ and R i8 a member of a group of
radicals known to impart insecticidal acti~ity to the
molecule, e.g. 3-phenoxybenzyl or al~ha-cyano-3-phenoxy-
benzyl. It is known that the stereoi~omeric form of the
acid portion of the ester of formula I should be ln the
(lR,c~) form for maximum lnseoticidal acti~lty, i.e. the
absolute oonfi~uration at carbon atom 1 i~ R and the two
hydrogen atoms on carbon atoms 1 and 3 are in a ci~
relationship. This nomenclature is known as the Elliott
nomenclature and is defined in M. ~lliott, A.W. Farnham,
N.F. James, P.~. ~eedham and D.A. Pullman, ~ature, 1974,
248, 710.
~1485~5
It follows, therefore, that if these stereoisomeric
esters of formula I are to be prepared, either a stereo-
specific chemical route i8 required or the de3ired stereo-
isomer must be obtained from a racemic form by physical
separation techniques. The latter are expensi~e and labo~ous
and not readily e~ployed on an industrial scale. The
Appli¢ant has found a stereospecific route which uses as
startin~ material the naturally-occurring substance (+)-3-
carene whose formula is a~ follows:-
CH3
~`
C~3 ~
C~3 ``This compound is an inexpensive readily-available natural
terpene and the present application relates to intermediates
in a route to the (lR,cis)-acid portion of the pyrethroid
ester of formula I starting from (+)-3-carene.
The present invention provides compounds of the
general formula:-
~I C~-CRal2
\/
~ C0-C~3 (III)
CH3 ~ / \ \ C~2 ~
CEr3 H 0-CO-CR3
wherein each ~al represents a halogen atom, espe¢ially
chlorine or bromine.
Preferably the compounds of formula III are in the
same stereoisomeric form as that of the cyclopropane ring
of (+)-3-carene.
~ preferred compound of the general formula III is
1-~2-(2,2-dichlorovinyl)-3,3-dimethylcyclopropyl]-3-oxo-2-
butyl acetate.
1~48565
Particularly preferred compounds are those having the same stereoisomer-
ic form as that of the cyclopropane ring of (+)-3-carene, e.g. the compound pre-
pared in the Examples
The compounds and their preferred sterèoisomeric form according to the
invention may be prepared by processes known per se, for example, according to
the methods disclosed in United Kingdom Patent Specification 1,413,491 which
discloses the preparation of dihalovinylcyclopropyl compounds by reacting 3-
formyl-2,2-dimethylcyclopropane-carboxylate with a dihalomethylenephosphorane
~which can be prepared by reaction of a triorganophosphine, normally triphenyl-
phosphine, with a carbon tetrahalide).
The compounds and their isomers according to the invention are prefer-
ably prepared by a proces6 characterised in that (a) a tri(dialkylamino)phosphine
or an alkyl ester of an orthophosphorous acid bis(dialkylamide) is reacted with
a tetrahalomethane or a trihalomethane and (b) the product resulting from the
first step is reacted with an aldehyde of the general formula:-
HVCHO
A ~CO-CH3
CH / - \ CH2-CH (IV)
CH3 H 0-C0-CH3
both steps being carried out in the presence of a substantially inert solvent.
Preferably step (a) is allowed to proceed to substantial completion.
The alkyl groups present in the tri(dialkylamino)phosphine or the
alkyl ester of an ortho-phosphorous acid bis(dialkylamide) may be the same or
different and linear or branched. The alkyl groups are suitably the same, have
preferably less than six carbon atoms and more preferably less than three. The
use of tri(dialkylamino)phosphines is
--3--
~,~
856S
preferred, because they usually afford the compounds of
formula III in a higher yield than the alkyl ester~ of
ortho-phosphorous acid bis(dialkylamines) (the latter
compounds are obtained by replacing one of the dialkyl-
amino groups in a tri(dialkylamino)phosphine by an alkoxygroup). ~ri(diethylamino)phosphine and tri(dimethylamino)
phosphlne are most preferred.
~ rl(dialkylamino)phosphlnes may be prepared by reaction
of a dlalkylamine with a phosphorous trihalide, as desaribed
in "Organlc Synthesis", Coll.Vol.~ (1973) 602-603. This
reactlon results in the formation of a solution of the tri
(dialkylamino)-phosphine which also contains precipitated
dialkylammonium halide. According to a feature of the
present invention a tri(dialkylamino)-phosphine may be
prepared by reacting a dialkylamine with a phosphorous
trihallde in the presence of a substantlally-inert solvent.
~he rasulting rea¢tion mixture can then be washed with
water to remove unwanted by-products (whether or not after
prior separation of the precipitated dialkylammonium halide)
and the tri(dialkylamino)phosphine dissolved in the washed
solution reacted with the halomethane. It is not necessary
to ~eparate the precipitated dialkylammonlum halide prior
to washing, because this salt i~ water-soluble. ~he yleld
of the compound of formula III can be further enhanced by
drying the washed liquid, for example, over a solid drying
agent such as anhydrous sodium sulphate or anhydrous
magnesium sulphate.
~ nother attracti~e feature of the process according
to the present invention is that it may be carried out in
the presence of an alkane solvent, for example, alkane
solvents with a boiling point or boilin~ range up to 200C.
This also appliea to the said reaction between a dialkyl-
amine and a phosphorous trihalide. Examples of alkane
solvents are pentane, hexane, heptane, octane and nonane.
Mixtures of alkanes are ~ery suitable, for example,
85~5
gasolines having a boiling range from 62C to 82C or from
80C to 110C. If desired, the proces~ may be csrried out
in substantially-inert solvents other than alkanes, for
e~ample, in tetrahydrofuran.
Examples of tetrahalomethanes or trihalomethanes which
are compounds capable of generating a dihalocarbene under
the conditions of the process according to the present
invention are carbon tetrahalides, chloroform, bromoform
and iodoform. Very good results have been obtained with
carbon tetrahalides. Examples of carbon tetrahalides are
carbon tetrachloride, carbon tetrabromide, carbon tetra-
iodide, bromotrichloromethane (forming dichlorocarbene) and
dibromodifluoromethane (forming difluorocarbene). Very good
re~ults have been obtained with carbon tetrachloride. These
halomethanes may also act as solvent or ¢o-~olvent for the
proces~ according to the invention.
Both steps of the process according to the present
invention are preferably carried out at a temperature in
theran~e of from -50C to +50C, particularly at tempera-
ture3 of from -20C to +35C.
~he compounds and process a¢¢ording to the invention
are of interest as part of a multi-step pro¢es~ to
pyrethroid inse¢ticides, e.g. esters based on (lR,¢is)-3-
(2,2-dlchlorovinyl)-2,2-dimethyl¢yclopropane carboxylic
acid.
~ he following Examples further illustrate the inventio~
Yields and purities were determi~e d by means of gas-liquid
chromatography and nuclear magnetic resonance (NMR)
spectro~copy. The ~M~ data quoted were recorded at 90 M~z
using solutions of the compounds in deuterochloroform~ the
absorption3 given are relative to a tetramethyl~ilane
standard.
1~4~565
Exam~le I - Pre~aration in two ~te~a of (l~,cis~ 2-
(2,2-dichlorovinyl)-~ dimethylcyclo~ro~yl~-~-oxo-2-but~l
acetate
Tri(dimethylamino)phosphine (40 mmol) was added at
-20C and with stirring under nitrogen to a 250 ml flaak
charged with carbon tetrachloride (40 mmol) and diethyl
ether (160 ml). Then, the temperature was allowed to rise
to +10C. This finished the first step. ~he resulting
suspension was cooled to -20C and a solution in diethyl
ether (5 ml) of the lR, as isomer of 1-(2-for~yl-3,3-
dimethylcyclopropyl)-3-oxo-2-butyl acetate was added. Then,
the temperature of the mixture was allowed to rise to 20C.
~his finished the second step. Water (50 ml) waa added, the
mixture was stirred for 5 minutes and, after ~ettling, the
organic phase was isolated and washed with two 50 ml
portions of water. The wa8hed organic liquid Was dried over
anhydrous magnesium sulphate and the solvent was evaporated
from the dried liquid at 1.3 kPa to leave a residue (3.5 g)
containing the title compound (100% (lR,cia), yield 84%).
~he ~MR spectrum of the title compound showed the
following absorptions:
6~ 1.04 ppm singlet R3C-C-CH3 ~ = 1.16 ppm singlet ~3C-C-CH~
5~ 2.19 ppm singlet H3C-C(0)-C and ~3C-C(0)-0-
6- 5.05 ppm doublet of doublets H2C-C~-0- 1. 5.59 ppm
doublet HC=CC12
multiplets for each of the H atoms bound to the ring and
for HC-CH2-CH.
Exam~le II - Pre~aration in one stén of (lR.cis)-1-r2-(2.2-
dichloro~inY~ -dimeth~lc~cloPro~ -oxo-2-butYl acet~te
~0 ~ri(dimethylamino)phosphine (40 mmol) was added with
stirring at -20C to a solution Or 1-(2-formyl)-3,3-dimeth
cyclopropyl-3-oxo-2-butyl acetate (14.2 mmol) and carbon
tetrachloride (40 mmol) in diethyl ether (160 ml) kept under
nitrogen. Then, the temperature of the mixture was allowed
to rise to 20C. Water (50 ml) was added, the mixture was
114856S
stirred for 5 minutes and, after settling, the organic
phase was isolated. ~he organic phase was washed with two
50 ml portions of water. ~he washed organic phase was
dried over anhydrous maenesium sulphate and the solvent
wa~ evaporated from the dried solution to leave a residue
(2.2 g) containine the title compound (100% (lR,cis),
yield 54%).
