CS239447B1 - Process for preparing 3,7-dimethyl-2,7-octadien-1-ol esters - Google Patents

Abstract

The invention relates to a process for preparing esters of 3,7-dimethyl-2,7-octadien-1-ol of the general formula I. The esters prepared by the method according to the invention are useful as sex pheromones of earthworms for monitoring the pest. where R is an alkyl with 1 to 5 carbon atoms, characterized in that 6-methyl-5-hopten-2-one is reacted with trifluoroacetic acid, optionally in an inert organic solvent, such as aromatic hydrocarbons or chlorinated hydrocarbons, preferably in dichloromethane, at a temperature of -30°C to +30°C, preferably at 0°C, after which the isolated trifluoroacetyloxy derivative is pyrolytically cleaved at a temperature of 140°C to 300°C in an inert organic solvent, preferably in pentane or methanol in the presence of salts of acetic acid with alkali metals or alkali metals, preferably sodium acetate, to form 6-methyl-6-hepten-2-one, which is reacted in an inert, organic solvent, preferably in methanol, at laboratory temperature with β triethyl phenylacetate and Baeic catalysis, preferably ethanolate sodium, with the formation of an ester, after which the ethyl 3,7-dimethyl-2,7-octadienoate thus prepared is reduced in an inert organic solvent with complex metal hydrides, preferably lithium aluminum hydride in ether, to an alcohol, which is converted into a compound of general formula I by reaction with a reactive acid derivative of the general formula RCOOH, where R has the above-mentioned meaning.

Description

(54) Process for preparing esters of 3,7-dimethyl-2,7-octadien-1-ol The invention relates to a process for preparing esters of 3,7-dimethyl-2,7-octadien-1-ol of the general formula I

The esters prepared by the method of the invention are useful as sex pheromones of earthworms for monitoring the pest.

where R is an alkyl with 1 to 5 carbon atoms, characterized in that 6-methyl-5-hopten-2-one is reacted with trifluoroacetic acid, optionally in an inert organic solvent, such as aromatic hydrocarbons or chlorinated hydrocarbons, preferably in dichloromethane, at a temperature of -30 °C to +30 °C, preferably at 0 °C, after which the isolated trifluoroacetyloxy derivative is pyrolytically cleaved at a temperature of 140 °C to 300 °C in an inert organic solvent, preferably in pentane or methanol in the presence of salts of acetic acid with alkali metals or alkali metals, preferably sodium acetate, to form 6-methyl-6-hepten-2-one, which is reacted in an inert, organic solvent, preferably in methanol, at laboratory temperature with β triethyl phenoxyacetate and Baeic catalysis, preferably ethanolate sodium, with the formation of an ester, after which the ethyl 3,7-dimethyl-2,7-octadienoate thus prepared is reduced in an inert organic solvent with complex metal hydrides, preferably lithium aluminum hydride in ether, to an alcohol, which is converted into a compound of general formula I by reaction with a reactive acid derivative of the general formula RCOOH, where R has the above-mentioned meaning.

The present invention relates to a process for the preparation of 3,7-dimethyl-2,7-octadien-1-el esters.

The sex pheromones of some economically important pests of the genus of worms are acetates or propionates of alcohols with two amine units. These are mainly mixtures of acetates and propionates of 7-methyl-3-methylene-7-octen-1-ol and (E) and (Z)-isomers of 3,7-dimethyl-2,7-hexadien-1-ol (Andereon R. J. et al., J. Chem. Ecology 7, 4, 695 (S1)). It has also been found that for males of the pernicious beetle (Quadraspidiotus perniciosus, Comsteck) (E)-3,7-dimethyl-2,7-octadien-1-yl propionate is as strong an attractant as the natural pheromone.

At present, several syntheses of these compounds are described, starting from 3-methyl-3-buten-1-ol or 4-methyl-4-pentenyl bromide, which are available by relatively complex synthesis. The complexity lies mainly in the use of complexes of n-butyllithium with N,N,N*,M»tetramethylenediamine, bromide of mixed with dimethyl sulfide and Orignard compounds, which require absolute solvents and relatively complex isolation techniques (Henrick C. A. et al., ACS Symposium Series, No. 190, Insect pheromone technology: Chemistry and Applications). The synthesis according to Author's Certificate S. 228 979, starting from (E)-3,7-dimethyl-2,6-octadion-1-ol, is substantially simpler. However, the disadvantage of this procedure is the relatively poor availability of the pure starting product.

It has now been found that esters of 3,7-dimethyl-2,7-octadien-1-ol can be prepared in good yield from the readily available 6-methyl-5-hepten-2-one.

The subject of the present invention is a process for the preparation of 3,7-dimethyl-2,7-octadion-1-ol esters of the general formula I

O

where R is an alkyl β of 1 to 5 carbon atoms, which is characterized by ao

a) 6-methyl-5-hspten-2-one of formula II

(II) is reacted with trifluoroacetic acid, optionally in an inert organic solvent such as aromatic hydrocarbons or chlorinated hydrocarbons, preferably in dichloromethane, at a temperature of -30 °C to +30 ^° C, preferably at 0 °C, whereupon

b) the isolated trifluoroacetyloxy derivative of formula III ^CF3C ° ² ^A _O ^niI) is pyrolytically cleaved at a temperature of 140 °C to 300 °C in an inert organic solvent, preferably in pentane or methanol in the presence of salts of acetic acid with alkali metals or alkaline earth metals, preferably sodium acetate, to form 6-methyl-6-hepten-2-one of formula IV which is (IV)

c) reacting in an inert organic solvent, preferably methanol, at room temperature with triethylphosphenoacetate under basic catalysis, preferably sodium ethanolate, to form an ester of formula V, whereupon

d) the ethyl 3,7-dimethyl-2,7-octadienoate thus prepared is reduced in an inert organic solvent with complex metal hydrides, preferably lithium aluminum hydride in ether, to the alcohol of formula 71

(VI) which

e) by reaction with a reactive derivative of an acid of the general formula RCOOH, where R has the above meaning, it is converted into a compound of the general formula I.

The key reaction of the process according to the invention is the isomerization of the isopropylidene double bond in 6-methyl-5-hepten-2-one to the methylene double bond of 6-methyl-6-hepten-2-one. The isomerization is carried out by converting 6-methyl-5-hepten-2-one (II) to the corresponding trifluoroacetyl derivative of formula III in a conventional manner and its subsequent pyrolysis. It has been found that pyrolysis by the method described in the literature and used in the author's certificate No. 228 979 does not lead to the desired product. However, it has now been found that by carrying out the pyrolysis reaction in an organic solvent in the presence of salts of acetic acid with alkali metals or alkaline earth metals, the desired 6-methyl-6-hepten-2-one can be prepared in relatively good yield. Pyrolysis can be carried out in a wide range of inert organic solvents, both polar and non-polar, with pyrolysis in per,.tan or methanol providing particularly good yields. The subsequent extension of the thus prepared 6-methyl-6-hepten-2-one by a two-carbon residue is carried out in a commonly known manner, e.g. by the Wittig-Homer reaction with triethylphosphenoacetate, yielding a mixture of E and Z isomers of the ester of the α,-unsaturated acid in a ratio of 6:4.

In case it is necessary to prepare the final product free of the second geometric isomer, the mixture of E and Z isomers is separated at this stage by chromatography, preferably adsorption chromatography on silica gel. The remaining stages, i.e. reduction of the ester functional group in an inert organic solvent with a complex metal hydride and acylation with a suitable reactive derivative of the corresponding acid are carried out - in a commonly known manner. In none of these stages does the isomerization of the methylene double bond occur and the desired product, either in the form of a mixture of E and Z isomers/or in the form of pure E and Z isomers, is thus prepared in a relatively good yield and in sufficient purity to be usable for the biological effect of the sex pheromone.

The course of the reactions can be monitored, for example, by thin layer chromatography, gas or liquid chromatography, and individual intermediates and the final product can be purified by column chromatography and distillation.

The invention is further illustrated in the following examples, which are not intended to limit it in any way.

Example 1

To a stirred solution of 6-methyl-5-hepten-2-one (IX, 0.6 g, 4.76 mmol) in 10 ml of methylene chloride cooled to -20 °C was added dropwise a solution of undistilled trifluoroacetic acid (10 mmol) in 10 ml of methylene chloride over 30 min. The reaction mixture was allowed to warm to room temperature with stirring, while the progress of the reaction was monitored on TLC at five-minute intervals. Once the reaction was complete, neutralization was carried out with a solution of diethylamine in methylene chloride. The reaction mixture was evaporated on a rotary vacuum evaporator at the lowest possible temperature and the residue was chromatographed on silica gel and 25% water. The combined chromatographic fractions were dried for 60 min at 40 °C and a vacuum of 1.6 kPa. The yield was 0.42 g (34%). MÍ 126 (-CF ₃ CO ₂ H);

IR (UR 20 , CC 1 ₄ ): 1783, 1724, 1369, 1271, 1224, 1123 cm'.

Example 2

Trifluoroacetate III, prepared according to Example 1 (0.42 g, 1.7 mmol) is dissolved in 3 ml of pentane and, together with sodium acetate (0.14 g, 1.7 mmol), is heated in a sealed ampoule at 180 °C for 8 hours. After cooling to room temperature, the contents are diluted with 5 ml of water, shaken, the organic layer is separated, the aqueous layer is shaken once more with 5 ml of pentane and the combined organic portions are dried with sodium sulfate. The pentane is evaporated on a rotary vacuum evaporator and the residue is percolated through 10 times silica gel. Product IV is obtained in an amount of 0.16 g (74%). MIC 126; IRt 3,095, 3,075, 1,721, 1,651, 1,359, 892 cm- ¹ . Example 3

To a solution of compound IV (0.16 g, 1.3 mmol), prepared according to Example 2, and triethylphosphonoacetate (0.4 g, 1.8 mmol) in 5 ml of absolute ethanol, a solution of sodium ethanolate, prepared by dissolving metallic sodium (0.041 g,

1.8 mmol) in 3 ml of ethanol and then the reaction mixture was left to stand for 24 hours. The ethanol was carefully evaporated on a rotary evaporator under reduced vacuum, the residue was diluted with water and the aqueous layer was extracted several times with ether and dried over sodium sulfate. After evaporation of the solvent and percolation through 30 times silica gel, 0.24 g of the product was obtained in (95%). M.P. 196;

IR) 3075, 1720, 1714, 1651, 1224, 1150, 892 cm ¹ .

Example

The substance prepared according to Example 3 (0.24 g, 1.22 mmol) was reduced with lithium aluminum hydride (0.075 g, 2.0 mmol) in ether in a conventional manner. The residue from this reduction was subjected to a reaction with acetyl chloride (0.1 g, 1.3 mmol), pyridine (0.12 g, 1.5 mmol) in absolute benzene in a conventional manner. After conventional work-up, 0.19 g of substance X (92%, R = CH ₃ ) was obtained. MIC 196; IR: 3,075, 1,750, 1,650, 1,180, 890 cm'. Example 5

The procedure is as in Example 4, except that propionyl chloride is used instead of acetyl chloride. The yield is 92%. MIC 210; IR: 3075, 1739, 1649, 1180, 890 cm ¹ .

Example 6

Ethyl-(E}Z)-3,7-dimethyl-2,7-octadienoate prepared according to Example 3 is separated into E and Z isomers on 11) 50 parts of silica gel with petroleum ether and ether in a ratio of 10/1 as mobile phase. Further reactions with the individual isomers are carried out in the sequence of reactions described in Examples 4 and 5, respectively. 4 and 6. From ethyl-(E)-3,7-dimethyl-2,7-octadienoate, (E)-3,7-dimethyl-2,7-octadienyl-propionate is obtained in the same yields as those given above. MIC 210; IR: 3,075, 1,739, 1,649, 1,180, 890 cm'.

Claims (3)

BEFORE THE INVENTION 1. Process for the preparation of 3,7-dimethyl-2,7-octadien-1-ol esters of general formula I O where R is alkyl with 1 to 5 carbon atoms, characterized in that a) 6-methyl-5-hepten-2-one of formula II (II) is reacted with trifluoroacetic acid, optionally in an inert organic solvent such as aromatic hydrocarbons or chlorinated hydrocarbons, preferably in dichloromethane, at a temperature of -30 °C to +30 °C, preferably at 0 °C, after which b) the isolated trifluoroacetyloxyderivative of formula III ^CF 3 ^C ° ² >^^% ₀ ^ÍIJI ' is pyrolytically cleaved at a temperature of 140 °C to 300 °C in an inert organic solvent, preferably in pentane or methanol in the presence of salts of acetic acid with alkali metals or alkaline earth metals, preferably sodium acetate, to form 6-methyl-6-hepten-2-one of formula IV (IV) which c) reacting in an inert organic solvent, preferably methanol, at room temperature with triethylphosphonoacetate under basic catalysis, preferably sodium ethanolate, to form an ester of formula V ^(V) whereupon d) the ethyl 3,7-dimethyl-2,7-octadienoate thus prepared is reduced in an inert organic solvent with complex metal hydrides, preferably lithium aluminum hydride in ether, to the alcohol of formula VI OH (VI) which e) by reaction with a reactive derivative of an acid of the general formula RCOOH, where R has the above meaning, it is converted into a compound of the general formula I. 2. The process according to item 1 for the preparation of (E)-3,7-dimethyl-2,7-octadien-1-ol esters, characterized in that the ethyl 3,7-dimethyl-2,7-octadienoate prepared in step c) is chromatographically separated into the £ and Z isomers and the remaining steps d) and e) are carried out with the pure E-isomer. 3. The process according to item 1 for the preparation of (Z)-3,7-dimethyl-2,7-octadien-1-ol esters, characterized in that the ethyl 3,7-dimethyl-2,7-octadienoate prepared in step c) is chromatographically separated into E and Z isomers and the remaining steps d) and e) are carried out with the pure Z-isomer.