GB2085428A

GB2085428A - Process for the preparation of cyclopropane derivatives

Info

Publication number: GB2085428A
Application number: GB8032685A
Authority: GB
Original assignee: Shell Internationale Research Maatschappij BV
Current assignee: Shell Internationale Research Maatschappij BV
Priority date: 1980-10-09
Filing date: 1980-10-09
Publication date: 1982-04-28

Abstract

A process for the preparation of a compound of the general formula: <IMAGE> in which each of Y<1> and Y<2> independently represents a fluorine, chlorine or bromine atom; each of R<1> and R<2> independently represents a hydrogen atom or an alkyl group having up to 10 carbon atoms, or R<1> and R<2> together represent an alkylene group having from 2 to 5 carbon atoms; and X represents a carboxylic acid ester group, a cyano group or a group CO.NR<3>R<4> in which each of R<3> and R<4> independently represents a hydrogen atom or an alkyl group; which comprises reacting a compound of the general formula: <IMAGE> wherein Y<1>, Y<2>, X, R<1> and R<2> have the meanings given for the general formula I, with a compound of the formula: P(NR2<5>)3 (III) or P.OR<5>.(NR2<5>)2 (IV), in which each R<5> independently represents an alkyl group, and a compound of the formula CHal4 (V), in which each Hal independently represents a chlorine or bromine atom. Compounds (I) may be hydrolysed to the corresponding cyclopropanecarboxylic acid compounds.

Description

SPECIFICATION Process for the preparation of cyclopropane derivatives This invention relates to a process for the preparation of cyclopropane derivatives.

German Offenlegungsschrift No. 2639777 disclosed a multistep process for the preparation of certain synthetic pyrethroid insecticides. In this process, an alcohol of the general formula

in which each Hal is a chlorine or bromine atom and X has various manings, is prepared, and converted in a 2-step process into a 2,2dihalovinyl compound of formula

The 2-step process consists of first esterifying the hydroxy group by reaction with a strong acid or derivative thereof, and subsequently inducing elimination of the strong acid by reaction with a base. This elaborate procedure is necessary because the alcohol cannot be dehydrated by the usual dehydrating agents.

The Applicants have now found a method of affecting the desired conversion in a single step.

The present invention provides a process for the preparation of a compound of the general formula

in which each of Y' and Y2 independently represents a fluorine, chlorine or bromine atom; each of R' and R2 independently represents a hydrogen atom or an alkyl group having up to 10 carbon atoms, or R' and R2 together represent an alkylene group having from 2 to 5 carbon atoms; and X represents a carboxylic acid ester group, a cyano group or a group CO.NR3R4 in which each of R3 and R4 independently represents a hydrogen atom or an alkyl group; which comprises reacting a compound of the general formula

wherein Yl, Y2, X, R1 and R2 have the meanings given for the general formula I, with a compound of the formula P(NR25)3 (Ill) or P.OR5.(NR25)2 (IV) in which each R5 independently represents an alkyl group, and a compound of the formula CHal4 (V) in which each Hal independently represents a chlorine or bromine atom.

The compounds of the general formulae I and II exist in the form of optical and geometric isomers, and generally, the configuration present in the starting material II is retained in the product I after the process of the invention has been carried out. Thus, for example, the groups CHY'Y2.CHOH-- and X in the compound of the formula II may be cis or trans to each oher, and in a preferred embodiment of the process according to the invention, a compound of formula II in which said groups are cis to each other is reacted to produce a compound of formula I in which the CYAN2 = CH- and X groups are cis to each other.Similarly, if desired, an optically active starting material may be used to produce an optically active product, for example one having the R configuration at the carbon atom carrying the substituent X.

The substituents Y' and Y2 may be the same or different, but are preferably the same. Preferably Y' and Y2 both represent bromine atoms or, especially, chlorine atoms.

R' and R2 may be the same or different, but are preferably the same. Preferably each of R' and R2 repesents an alkyl group having 1 to 4, especially 1 or 2, carbon atoms. Most preferably, both R' and R2 represent methyl groups.

If X represents a group CO.NR3R4, each of Rr3 and R4 preferably represents an alkyl group having up to 4, especially 1 or 2, carbon atoms. Preferably, however, X represents a carboxylic acid ester group. An ester group preferably has the formula --CO,R6 in which R6 represents an optionally substituted alkyl group, in which the optional substituents are for example selected from halogen atoms, alkoxy groups and phenyl groups, and in which the alkyl moiety preferably has up to 6, especially up to 4, carbon atoms. Preferably R6 represents an unsubstituted alkyl group, especially a methyl or ethyl group.

In a compound of the general formula Ill or IV, any two or more of the alkyl groups R5 may be the same or different. Preferably, each R5 independently represents an alkyl group having up to 4, especially 1 or 2, carbon atoms. An especially preferred compound for use in the process of the invention is tris(dimethylamino)phosphine-i.e. the compound of formula Ill in which each R5 represents a methyl group.

Preferably the compound of formula V is carbon tetrabromide or, especially, carbon tet rachloride.

The process according to the invention is suitably carried out in the presence of an aprotic solvent. If desired, an excess of the compound of formula V may be used as solvent. Alternatively or in addition, an inert solvent may be present, for example dimethylsulphoxide, N-methylpyrrolidone, an alkane such as pentane, an amide such as dimethylformanide, or an ether such as tetrahydrofuran. Mixtures of solvents, for example pentane plus tetrahydrofuran, may often be advantageous. The reaction is preferably carried out at a temperature in the range of from - 20 to 100"C, especially 0 to 50"C. Room temperature is generally most convenient.

The molar ratios of the three reactants are generally not crucial. The reaction proceeds conveniently by reaction of one mole of the compound of the formula Il with one mole of the compound of the formula V and with two moles of the compound of formula Ill or IV.

Generally, however, it is preferred to use a slight excess compared with these figures of the compound of formula Ill or IV over the compound of formula ll, and an overall excess of the compound of formula V.

The three reactants may be admixed in any sequence, but since it is believed that the mechanism of the reaction involves reaction together of the compounds 111 or IV and V and subsequent reaction of this reaction product with the compound of the general formula 11, it may in some circumstances be preferable to mix together the compounds of formula Ill or IV and V, and subsequently to admix the compound of formula 11. Such a procedure may increase the selectivity of the reaction to the desired product.

The starting material of the general formula II may be prepared by any suitable method, for example as described in Offenlegungschrift No. 2639777 by reduction of a ketone of the general formula

where X, R7 and R2 have the meanings given above, using any suitable reducing agent, for example sodium borohydride. The compound of formula VI may also be prepared as described in Offenlegungsschrift No. 2639777, by halogenation of a compound of the general formula

using any suitable halogenating agent.However, in the special case where X represents a carboxylic acid ester group, for example one of formula 402R6 where R6 has the meaning given above, the compound of formula VI is preferably prepared by hydrolysis of a compound of the general formula

in the presence of an alcohol, preferably of formula R60H. Thus, for example, hydrolysis of a compound of the general formula VIII in the pesence of methanol, gives a compound of the general formula VI in which X represents a methylcarbonyl group. Generally, alkaline hydrolysis leads to a trans compound of formula Vl, whereas acid hydrolysis leads to d cis compound. Whichever method of preparation is used, the resulting compound of formula Vl may if desired be isolated before its reduction to the corresponding compound of formula 11, or, with a suitable choice of solvent and reaction conditions, it may be prepared and reduced in situ.

The compound of the general formula VIII may be prepared by the reaction of an anhydride of formula

with a sodium trihaloacetate, or by reaction of a keto acid of formula

here Y3 represents a fluorine, chlorine or bromine atom, or the tautomeric lactone thereof, with zinc and phosphorus trichloride.

A compound of the general formula I prepared by the process according to the invention may be hydrolysed to the corresponding acid of the general formula

or a salt thereof, by any suitable method analogous to known methods for the hydrolysis of an ester, a nitrile or an amide to an acid or a salt.

The following Examples illustrate the invention.

Example 1: Preparation of trans methyl 2 (2, 2-dichlorovinyl)-3, 3-dimethylcyclopropane carboxylate Tris(dimethylamino)phosphine, [P.N(CH3)2]3 (76 mg, 0.46 mmol) and carbon tetrachloride (38 mg, 0.25 mmol) were added to a solution of 56 mg (0.23 mmol) of trans methyl 2-(1 hydroxy-2, 2-dichloroethyl)-3, 3-dimethylcyclopropane carboxylate in dry tetrahydrofuran (0.5 ml) at room temperature. After 5 minutes, the mixture was analysed by NMR and found to contain a yield of 33% of the desired product. A further 38 mg of carbon tetrachloride were added to the reaction mixture, and subsequent NMR analysis showed a yield of 50% of the desired product.

Example 2: Preparation of trans methyl 2 (2,2-d ichiorovinyl)-3, 3-dimethylcyclopropane carboxylate.

Tris(dimethylamino)phosphine ( 1 65 mg, 1 mmol) was added to a solution of methyl 2-(1hydroxy-2, 2-dichloroethyl)-3, 3-dimethylcyclopropane carboxylate (49 mg, 0.2 mmol) in dry dimethylformamide (0.5 ml), and carbon tetrachloride (152 mg, 1 mmol) was then added. The mixture was stirred at room temperature for 1 5 minutes. It was then diluted with water and extracted with deuterochloroform. NMR analysis showed a yield of 60% of the desired product.

Example 3: Comparative Example.

50 mg methyl 2-( 1 -hydroxy-2, 2-dichloroe- thyl)-3,3-dimethylcyclopropane carboxylate was heated for 30 minutes at a temperature of 80"C with 0.1 ml 85% aqueous phosphoric acid. The reaction mixture was then diluted with 0.5 ml water and extracted with 0.5 ml of deuterochloroform, CDCI3. NMR showed that no reaction had taken place.

The procedure was then repeated, with heating being carried out for 5 minutes at 1 40 C. NMR showed that the reaction product was trans 3,3-dimethylcyclopropane-1 2- dicarboxylic acid.

Similar experiments with other common dehydrating agents also failed to produce the desired compound.

Claims

1. A process for the preparation of a compound of the general formula

wherein Y1, Y2, X, R1 and R2 have the meanings given for the general formula I, with a compound of the formula P(NR25) Ill or P.OR5(NR25)2 (IV) in which each R5 independently represents an alkyl group, and a compound of the formula CHal4 (V) in which each Hal independently represents a chlorine or bromine atom.

2. A process as claimed in claim 1, in which Y' and Y2 both represent bromine or chlorine atoms.

3. A process as claimed in either claim 1 or claim 2, in which both R' and R2 represent methyl groups.

4. A process as claimed in any one of claims 1 to 3, in which X represents a carboxylic acid ester group of the ge;1eral formula HO2R6, in which R6 represents an optionally substituted alkyl group.

5. A process as claimed in claim 4, in which 6 represents a methyl or ethyl group.

6. A process as claimed in any one of claims 1 to 5, in which each R5 independently represents a alkyl group having 1 or 2 carbon atoms.

7. A process as claimed in claim 6, in which the compound tris(dimethylamino)phosphine is used.

8. A process as claimed in any one of claims 1 to 7, in which the compound of the general formula V is carbon tetrachloride.

9. A process as claimed in any one of claims 1 to 8, conducted at a temperature in the range of from - 20 to 100"C.

10. A process as claimed in any one of claims 1 to 9, in which the compounds of formula III or IV and V are mixed together and subsequently admixed with the compound of formula II.

11. A process as claimed in claim 1, carried out substantially as described in either Example 1 or Example 2 herein.

1 2. A compound of the general formula I given in claim 1, whenever prepared by a process as claimed in any one of claims 1 to 11.

1 3. A process for the preparation of a compound of the general formula

in which Y1, y2, R' and R2 have the meanings given in claim 1, or a salt thereof, which comprises the hydrolysis of a compound as claimed in claim 12.

14. A compound of the general formula Xl given in claim 1 3 whenever prepared by a process es claimed in claim 1 3.