CA1148565A - Intermediates in the preparation of cycolpropane-carboxylate esters and process for their manufacture - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Compounds of the general formula:-

Description

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:-~`
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) 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 ~,~

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 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%).

Claims (9)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. Compounds of the general formula:- (III) wherein each Hal is a halogen atom.

2. Compounds according to claim l wherein the compounds are in the same stereoisomeric form as that of the cyclopropane ring of (+)-3-carene.

3. A process for the preparation of compounds of formula III wherein (a) a tri(dialkylamino)phosphine or an alkyl ester of an ortho-phosphorous 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:

(IV) both steps being carried out in the presence of a substantially inert solvent.

4. A process according to claim 3 wherein the tri(dialkylamino) phosphine is tri(diethylamino)phosphine or tri(dimethylamino)phosphine.

5. A process according to claim 3 or 4 wherein the substantially-inert solvent is an alkane or tetrahydrofuran.

6. A process according to claim 3 or 4 wherein the tetrahalo- or trihalo-methane is a carbon tetrahalide, chloroform, bromoform or iodoform.

7. A process according to claim 3 or 4 wherein the tetrahalomethane is employed as the substantially-inert solvent.

8. A process according to claim 3 or 4 wherein the process is carried out at a temperature in the range -50°C to +50°C.

9. A process according to claim 3 or 4 wherein the aldehyde of general formula IV is in the same stereoisomeric form as the cyclopropane ring of (+)-3-carene.