CS239447B1 - Preparation method of esters 3,7-dimethyl-2,7-octadien-1-le - Google Patents

Abstract

The invention relates to a process for preparing esters 3,7-dimethyl-2,7-octadien-1-ol in general of Formula I Esters prepared by the process of the invention they are useful as sex pheromones of Worms for Menitoration of Pests. wherein R is alkyl of 1 to 5 carbon atoms, characterized by the fact that 6-methyl- -5-hopten-2-one reacts with acid trifluoroacetate, optionally in inert organic solvent such as aromatic hydrocarbons or chlorinated hydrocarbons, preferably in dichloromethane at room temperature temperature -30 "C to +30" C, preferably at Then the trifluoroacetyloxy derivative is isolated pyrelytically cleaves at temperature S 140 ° C to 300 ° C in an inert organic a solvent, preferably pentane or methanol in the presence of acid salts acetic acid with alkali metals or metals alkaline salts, preferably sodium acetate the formation of 6-methyl-6-hepten-2-one, which is reacted in an inert, orger solvent, preferably methanol, at room temperature with β-triethylfesphenoacetate with the baesic catalysis, preferably with sodium ethoxide, the formation of an ester whereupon ethyl-3,7-dimethyl-2,7-octadienoate is prepared reduced in inert organic solvent with complex hydrides metals, preferably lithium aluminum hydride in ether, to the alcohol which reacted with a reactive acid derivative the formula RCOOH, wherein R is as defined above, to a compound of formula I.

Description

(54) A process for the preparation of 3,7-dimethyl-2,7-octadien-1-ol esters which relates to a process for the preparation of 3,7-dimethyl-2,7-octadien-1-ol esters of the general formula I

The esters prepared by the process of the invention are useful as sexual pheromones of worms for menitoration of pests.

wherein R is C 1 -C 5 alkyl, 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 pyrlytically cleaves at 140 ° C to 300 ° C in an inert organic solvent, preferably pentane or methanol in the presence of salts of acetic acid with alkali metals or alkali samine metals, preferably sodium acetate, to form 6-methyl-6-hepten-2-one which is reacted in an inert, organic solvent, preferably methanol, at room temperature with β triethylphesphenoacetate where the ethyl-3,7-dimethyl-2,7-octadienoate thus prepared is reduced in an inert organic solvent. Conversely, complex metal hydrides, preferably lithium aluminum hydride in ether, to an alcohol which is converted to a compound of formula I by reaction with a reactive acid derivative of the formula RCOOH, wherein R is as defined above.

The present invention relates to a process for preparing 3,7-dimethyl-2,7-octadiene-1-el esters.

The sex pheromones of some economically important pests of the worms are acetates or prepionates of alcohols with two and ten units. These are in particular mixtures of acetates and propionates of 7-methyl-3-methylene-7-octen-1-ol and (E) and (Z) -isomers of 3,7-dlmethyl-2,7-ectadiene-1-el (Andereon). RJ et al., J. Chem. Ecology 7, 4, 695 (S1)). Further, it has been found that for male Servce weevil (Quadraspidiotus perniciosus, Comsteck), (E) -3,7-dimethyl-2,7-octadien-1-yl is bridged with the same potency 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 through a relatively complex synthesis. Complexity consists mainly in the use of n-butyllithl complexes with N, N, N *, M-tetramethylenediamine, copper bromide and dimethylsulfide and Orignard compounds which require absolute solvents and relatively complex isolation techniques (Henrick CA et al., ACS Symposium Series, No. 190). , Insect pheromone technology: Chomistry and Applications). Substantially simpler is the synthesis according to the Author's Certificate S. 228 979, starting from (E) -3,7-dimethyl-2,6-octadion-1-ol. However, the disadvantage of this process is the relatively poor availability of the pure starting product.

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

The present invention provides a process for preparing the 3,7-dimethyl-2,7-octadion-1-ol esters of formula (I)

O

wherein R is alkyl of 1 to 5 carbon atoms characterized in that α is

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

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

b) the isolated trifluoroacetyloxydorivative of formula III ( ^{CF 3} C ² _{O 4} ^{Al) is} pyrolytically cleaved at 140 ° C to 300 ° C in an inert organic solvent, preferably pentane or methanol, in the presence of alkali or alkaline earth acetic acid salts; 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 ethoxide, to form the ester of formula V, then

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

(VI) which is

e) reacting with a reactive acid derivative of the formula RCOOH, where R is as defined above, to give a compound of the formula I.

A key reaction of the process of the invention is 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 the 6-methyl-5-hepten-2-one (II) to the corresponding trifluoroacetyl derivative of formula III in a manner known per se and following its pyrolysis. It has been found that pyrolysis in the manner described in the literature and also 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 pyrolytic reaction in an organic solvent in the presence of alkali metal or alkaline earth metal acetic acid salts, the desired 6-methyl-6-hepten-2-one can be prepared in a relatively good yield. The pyrolysis can be carried out in a variety of inert organic solvents, both polar and non-polar, with pyrolysis in perane, methanol or methanol giving particularly good yields. The following elongation of the 6-methyl-6-hepten-2-one thus prepared to the bicarbonate residue is carried out in a conventional manner, for example by Wittig-Homer reaction with triethylphosphenoacetate providing a mixture of E and Z isomers of. 4.

If it is desired to prepare a final product free of the second geometric isomer, the mixture of E and Z isomers is separated at this stage by chromatography, preferably by adsorption chromatography on silica gel. The remaining steps, i.e. reduction of the ester function 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 manner known per se. Neither of these steps is methylene double bond isomerized and the desired cell product in the form of a mixture of the E e Z isomers / or pure E and Z isomers is thus prepared in relatively good yield and of sufficient purity usable for the biological effect of sexual pheromone.

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

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

Example 1

To a stirred solution of 6-methyl-5-hepten-2-one (1X, 0.6 g, 4.76 mmol) in 10 mL of -20 ° C methylene chloride was added dropwise a solution of undistilled trifluoroacetic acid (10 mmol) in 10 mL methylene chloride run for 30 min. The reaction mixture was allowed to warm to room temperature with stirring while the reaction was monitored by TLC at five minute intervals. Once the reaction is complete, neutralization is carried out with a solution of diethylamine in methyl chloride. The reaction mixture is concentrated on a rotary evaporator at as low a temperature as possible and the residue is chromatographed on silica gel and 25% water. The combined chromatography fractions were dried at 40 ° C and 60 mm Hg for 60 minutes. Yield: 0.42 g (34%). MI 126 (-CF ₃ CO ₂ H);

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

Example 2

Trifluoroacetate III, prepared according to Example 1 (0.42 g, 1.7 mmol) was dissolved in 3 mL of pentane and heated together with sodium acetate (0.14 g, 1.7 mmol) to 180 ° C in a sealed vial. for 8 hours. After cooling to room temperature, dilute the contents with 5 ml of water, shake, separate the organic layer, shake the aqueous layer once more with 5 ml of pentane and dry the combined organics over sodium sulfate. The pentane was evaporated on a rotary evaporator and the residue was percolated over 10 times silica gel. The product IV was obtained in an amount of 0.16 g (74%). MI 126; IR t 3,095, 3,075, 1,721, 1,651, 1,359, 892 cm ^-1 . Example 3

To a solution of 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 was added dropwise a solution of sodium ethanolate prepared by stirring at room temperature. by dissolving sodium metal (0.041 g,

1.8 mmol) in 3 ml of ethanol and then allowed to stand for 24 hours. Ethanol was carefully evaporated on a rotary evaporator under reduced vacuum, the residue diluted with water and the aqueous layer was shaken 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 product was obtained in (95%). MI 196;

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

Example

The compound prepared in 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 reacted with acetyl chloride (0.1 g, 1.3 mmol), pyridine (0.12 g, 1.5 mmol) in absolute benzene in a manner known per se. After conventional work-up, 0.19 g of compound X (92%, R = CH ₃ ) was obtained. MI 196; IR: 3075, 1750, 1650, 1180, 890 cm -1. Example 5

The procedure of Example 4 was followed except that propionyl chloride was used instead of acetyl chloride. Yield 92%. MI 210; IR: 3,075, 1,739, 1,649, 1,180, 890 cm ^-1 .

Example 6

The ethyl (E) Z) -3,7-dimethyl-2,7-octadienoate prepared according to Example 3 was separated with 11) 50 times silica gel with petroleum ether and ether in a ratio of 10/1 as mobile phase to the E and Z isomers. Further reactions with the individual isomers are carried out in a sequence of reactions as described in Examples 4 and 5, respectively. 4 and 6. From ethyl (E) -3,7-dimathyl-2,7-octadienoate, (E) -3,7-dimethyl-2,7-octadienyl-propxone was obtained in the same yields as above. MI 210; IR: 3,075, 1,739, 1,649, 1,180, 890 cm -1.

Claims (3)

BACKGROUND OF THE INVENTION A process for the preparation of 3,7-dimethyl-2,7-octadien-1-ol esters of the general formula I Wherein R is C 1 -C 5 alkyl; 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, whereupon b) an isolated trifluoroacetyloxyderivát III ^CF 3 ^C ° ^2> ^^ _0% ^{are living} 'pyrolytically cleaved at temperatures of 140 ° C EŽ 300 ° C in an inert organic solvent, preferably pentane, or methanol in the presence of acetic acid, salts with alkali metals or alkaline earth, preferably sodium acetate, to form 6-methyl-6-hepten-2-one of formula IV (IV) which is 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) reducing the ethyl 3,7-dimethyl-2,7-octadienoate thus prepared in an inert organic solvent with complex metal hydrides, preferably lithium aluminum hydride in ether, to an alcohol of formula VI OH (VI) which is e) reacting with a reactive acid derivative of the formula RCOOH, where R is as defined above, to give a compound of the formula I. 2. A process according to claim 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 the step of c) separating the ε and Z isomers chromatographically and carrying out the remaining steps d) and e) with the pure E-isomer. 3. A process according to claim 1 for the preparation of (Z) -3,7-dimethyl-2,7-octadien-1-ol esters, characterized in that ethyl 3,7-dimethyl-2,7-octadienoate prepared in the step of c) separating the E and Z isomers by chromatography and the remaining steps d) and e) are carried out with the pure Z-isomer.