DE1263760B - Process for the production of chrysanthemum monocarboxylic acid alkyl esters or the free acid - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07c

German KL: 12 ο - 25

Number: 1 263 760

File number: R 36625IV b / 12 ο

Filing date: November 22, 1963

Open date: March 21, 1968

The present invention relates to a new process for the preparation of chrysanthemum monocarboxylic acid alkyl esters or the free acid.

It is known that certain esters of chrysanthemum monocarboxylic acid, like the pyrethrins, cinerines, allethrins and furethrins, a class \ on very valuable Insecticides because of their great insecticidal effectiveness on the one hand and because of their low level of effectiveness On the other hand, represent toxicity for humans and warm-blooded animals. It is also known that the Chrysanthemum monocarboxylic acid forms two stereoisomeric forms, the cis and trans form, and the ester of the trans acid have an activity which is generally superior to that of the derivatives of the cis form is.

So far, the chrysanthemum monocarboxylic acid was obtained by hydrolysis of rethrins of natural origin or according to the synthesis by Staudinger and co-workers (Helvetica Chimica Acta, Vol. 7 [1924], P. 390), repeated by Campbell and coworkers (J. Chem. Soc. [1945], p. 283). This synthesis based on the reaction of ethyl diazoacetate with 2,5 - dimethylhexadiene - (2,4) to a mixture of the dl-cis- and dl-trans-chrysanthemum monocarboxylic acids leads, but is due to the instability of the diazoacetic acid ethyl ester right difficult to carry out and complicates the technical application.

A similar synthesis, in which the ethyl diazoacetate is replaced by the diazoacetonitrile, leads to the pure dl-trans-chrysanthemum monocarboxylic acid, but it offers even more dangers than before called synthesis.

The German Auslegeschrift 1 149 713 describes a process for the production of dl-trans-chrysanthemum monocarboxylic acid in which 4-methyl-3-isobutenyl - / - valerolactone is produced as an intermediate. This lactone is then opened by treatment with thionyl chloride and then converted into an ester by the action of an ethyl alcoholic solution saturated with hydrogen chloride. It is stated that during this reaction the ethyl 5-methyl-3- (1-chloroisopropyl) hexen (4) acid ester is obtained, which is then cyclized to the chrysanthemum monoarboxylic acid ester by the action of a strongly alkaline agent. In reality, the formation of 3- (1-chloroisopropyl) -5-methyl-5-chlorohexanoic acid ethyl ester also takes place during the opening of the luctone under the specified conditions, as Masanao Matsui and Masaaki Uchiyama (Am ^- . Biol. Chem. Vol. 26 [1962], pp. 532 to 534).

Process for the production of
Chrysanthemum monocarboxylic acid alkyl esters
or the free acid

Applicant: *

Rhone-Poulenc S.A., Paris

Representative:

Dr. F. Zumstein,

Dipl.-Chem. Dr, rer. nat. E. Assmann

and Dipl.-Chem. Dr. R. Koenigsberger,

Patent Attorneys, 8000 Munich 2, Bräuhausstr. 4th

Named as inventor:
Dr. Marc Julia, Paris

Claimed priority:

France of December 21, 1962 (919 497)

These authors have also shown that this dichloro ester by the action of tertiary sodium amylate in benzene medium dl-trans-dihydro- ^ - chlorchrysanthemum monocarboxylic acid ethyl ester ergib ^ der by alcoholic potassium hydroxide then into dl-trans-2,2-dimethyl-3- (2-methylallyl) -cyclopropanecarboxylic acid is converted, which by the action of -p-toluenesulfonic acid to dl-trans-chrysanthemum monocarboxylic acid is isomerizable.

There has now been a new process for the preparation of chrysanthemum monocarboxylic acid alkyl esters or the free acid found. According to this process, methallyl alcohol is used in a manner known per se With an enol ether of an alkyl levulinate in the presence of p-toluenesulfonic acid, converts the allyl ether thus obtained into an alkyl 3-methallyl-levulinate by heating, sets this in a manner known per se with a methyl magnesium halide to 4-methyl-3-methaIlyl -; '- valerolactone, converts this into a known per se Way with thionyl chloride and ethanolic hydrochloric acid into an alkyl 5-methyl-5-chloro-3- (l-chloroisopropyl) hexanoate, treats this with sodium hydride or in a manner known per se with tertiary Sodium amylate in an inert solvent,

preferably in the heat, separates the chrysanthemum monocarboxylic acid alkyl ester formed in the usual way Waste or saponify the mixture obtained after treatment with sodium tertiary amylate Chrysanthemum monocarboxylic acid and cyclopropanecarboxylic acid alkyl esters in a manner known per se alcoholic sodium or potassium hydroxide and isomerizes it after the usual acidification acid mixture obtained from a strong mineral acid in a manner known per se with p-toluenesulfonic acid.

The course of the process according to the invention is described in the following reaction scheme.

CH ₂ OH

+
I.

OR '

COOR p-toluenesulfonic acid

Heat

COOR

, CH, MgHal

IV III

Ethanolic hydrochloric acid | Thionyl chloride

Close

COOR

VI

R and R 'denote alkyl radicals with 1 to 3 carbon atoms, Hal halogen.

The lactone of the general formula IV occurring as an intermediate is made from an enol ether a levulinic acid ester of the general formula I prepared with methallyl alcohol. The reaction includes steps I to IV of the reaction scheme given above. In these formulas, R and R 'mean Alkyl radicals with 1 to 3 carbon atoms. In practice, a levulinic acid derivative is used general formula I, in which R 'and R are identical, for example the enol ethyl ether of levulinic acid ethyl ester, which is obtained according to R. G. Jones (J. Am. Chem. Soc. Vol. 77 [1955]. p. 4069). The roundabout with methallyl alcohol takes place at room temperature. The methallyl ether of the general formula II is then converted into the compound of the general formula III by heating. The conversion of the compound of the general formula III into the lactone of the formula IV takes place by Reaction with a methyl magnesium halide.

This; <- lactone ring is replaced by thionyl chloride and ethanolic hydrochloric acid opened, whereby a 5-methyl - 5 - chloro - 3 - (1 - chloroisopropyl) - hexanoic acid alky 1-ester the general formula V is formed.

The product of the general, formula V is then by the action of sodium hydride or tertiary sodium amylate to form chrysanthemum monocarboxylic acid alkyl esters of the general formula VI or a mixture thereof with alkyl cyclopropanecarboxylates cyclized.

The process is carried out in an organic solvent which is inert under the operating conditions, such as an aromatic hydrocarbon (e.g. benzene-toluene) or an NN-disubstituted amide of a lower saturated fatty acid, preferably dimethylformamide or dimethylacetamide. at a temperature between room temperature (about 15 ^: C) and the boiling point of the medium.

With sodium hydride, the compound of the general formula V gives only or almost only the alkyl chrysanthemum monocarboxylate of the general formula VI. if you have at least 2 moles of sodium hydride per 1 mole of the compound of the general Formula V applies. The chrysanthemum monocarboxylic acid alkyl ester can then with alcoholic Sodium or potassium hydroxide can be saponified to form chrysanthemum monocarboxylic acid. With

The cyclization and the removal of the 5-position chlorine atom proceed with tertiary sodium amylate less easily and therefore a mixture of chrysanthemum monocarboxylic acid is generally obtained and alkyl cyclopropanecarboxylates of the general formulas

and

COOR

COOR

The proportion of these various esters in the mixture obviously depends on the working conditions away. The proportions of these compounds are also of little importance if you want to produce the chrysanthemum monocarboxylic acid, since saponification by customary methods with a suitable amount of sodium or potassium hydroxide a mixture of chrysanthemum monocarboxylic acid and its isomer, 2,2-dimethyl-3-methallylcyclopropanecarboxylic acid, obtained, which is then obtained by heating in the presence of p-toluenesulfonic acid, as Mats'ui has shown, can isomerize.

The following examples illustrate the invention.

example 1

a) 15 g (0.21 mol) of methallyl alcohol and 39 g (0.226 mol) of enol ethyl ether of the levulinic acid ethyl ester are dissolved in 100 ecm of petroleum ether (boiling range 100 to 120 ° C.) and a few milligrams of p-toluenesulfonic acid are added. The mixture is refluxed for 16 hours. After cooling, the organic phase is washed with an aqueous sodium bicarbonate solution and with water and dried over sodium sulfate. The solvent is removed and then rectified. A fraction (7 g) with a boiling point of _-0 J = 55 to 75 ° C. is first obtained, and 32 g of product are then obtained at 75 to 77 ° C. and 0.3 mm Hg, which consists almost exclusively of ethyl 3-methallyl levulinate.

b) A solution of methyl magnesium iodide (0.33 mol) is made from 8 g of magnesium and 50 g of methyl iodide and 200 ecm of anhydrous ether. After the reaction has ended, the magnesium compound is transferred in 62 g (0.31 mol) of ethyl 3-methallyl levulinate. dissolved in 100 ecm of anhydrous ether, keeping the temperature between -2 and -4 C holds. After the addition has ended, the temperature of the mixture is left at room temperature in one hour rise and then hydrolyze with a saturated ammonium chloride solution. The organic is decanted Layer off and carefully extract the mother liquors with ether. The organic fraction will washed with a saturated sodium chloride solution and then dried over sodium sulfate.

After evaporation of the solvent, the distillation gives 45 g of crude 4-methyl-3-methallyl-; -valerolactone with a boiling point of ₀ ^ = 77 to 80 ° C; «! ^: = 1.4578.

To remove traces of the ketoester that are visible in the infrared spectrum, the product is dissolved in 200 ecm of ether and the mixture is stirred for 2 hours with 250 ecm 2 η sodium hydroxide solution. After acidification and extraction with ether, the lactone is obtained, which after renewed distillation _{gives 38 g of pure product with a boiling point of -02} = 77 to 78 ° C, ni ° = 1.4613; the yield is 72%.

c) Dissolve IO g i-methyl-S-methallyl-y-valerolactone in 60 cc of anhydrous benzene and the solution heated with 15 cc of thionyl chloride 4 ^l / ₂ hours under reflux. After cooling, 60 ecm ethanol saturated with HCl is added and the mixture is then left to stand at a temperature of about 20 ° C. overnight. The solvent is evaporated off in vacuo and the residue is distilled. This gives 12.7 g (78%) of product with a boiling point of _-01 = 95 to 100 ° C. which no longer shows the characteristic band of double bonds in the infrared and is characterized as ethyl S-methyl-S-chloro-SO-chloroisopropylJ-hexanoate will.

d) Treat 11.5 g (0.042 mol) of this Dichloresters with 2.3 g (0.095 mol) of sodium hydride in 120 cc of dimethylformamide at 6O ⁰ C until gas evolution ceases (3 '/ ₂ hours). After dissolving in 500 ecm of water, it is extracted three times with 100 ecm of ether each time, then the ethereal solution is washed with water and dried over sodium sulfate. After evaporation of the ethereal solution, 5.5 g of product are obtained, which distills at 0.3 mm Hg at 72 ° C. and has the characteristic infrared spectrum of the ethyl chrysanthemum monocarboxylate. Saponification with methanolic potassium hydroxide and subsequent acidification with hydrochloric acid gives 4.3 g of chrysanthemum monocarboxylic acid from

F. = 47 to 48 ^C C.

The aqueous fraction obtained after the cyclization and extraction with ether is recovered by acidification and extraction with ether, another 0.5 g of chrysanthemum monocarboxylic acid. You get so a total yield of 4.8 g (67% chrysanthemum monocarboxylic acid, based on the dichloro

ester). .

Example 2

a to c) The preparation of the 5-methyl-4c 5 - chloro - 3 - (1 - chloroisopropyl) - hexanoic acid ethyl ester is carried out as in example 1.

d) 12.7 g of the 5 - methyl - 5 - chloro-3- (1-chloroisopropylj-hexanoic acid ethyl ester) obtained then dissolved in 60 ecm anhydrous benzene. One puts 120 ecm of a 1.6 m solution of tertiary Sodium amylate in benzene is added, the mixture is refluxed for 3 hours and then left over Stand overnight at ordinary temperature.

It is diluted with 250 ecm of water, extracted twice with 100 ecm of ether each time, washed with 1N sodium hydroxide solution, with water and with 2N sulfuric acid and dried over sodium sulfate. Distillation gives 7.2 g of product with a boiling point of _{-0 3} = 85 to 90 ° C. which is then saponified with 10 g of potassium hydroxide in 50 ecm of ethanol under reflux within 4 hours. After extraction and distillation, 4 g of crude oily acid are obtained, which are dissolved in 30 ecm of xylene. 10 mg of p-toluenesulfonic acid are added and the mixture is heated under reflux for 1 hour. After the xylene has been distilled off, the residue is distilled. This gives 3.5 g of chrysanthemum monocarboxylic acid, which solidifies.

Claims (1)

Claim: Process for the preparation of chrysanthemum monocarboxylic acid alkyl esters or the free acid, characterized in that one i 263 Methallylalkphol in a manner known per se with an enol ether of an alkyl levulinate in the presence of p-toluene sulfonic acid, the allyl ether thus obtained is converted into an alkyl 3-methallyl levulinate by heating, this in a manner known per se with a methyl magnesium halide to form 4 - methyl-3-methallyl-y-valerolactone converts this in a known manner with thionyl chloride and Ethanolic hydrochloric acid converted into a 5-methyl-5-chloro-3 - (1 - chloroisopropyl) - hexanoic acid alkyl ester, these with sodium hydride or in a known manner with tertiary sodium amylate in an inert solvent, preferably treated with heat, the chrysanthemum monocarboxylic acid alkyl ester formed in usual Way or the mixture obtained after treatment with tertiary sodium amylate of chrysanthemum monocarboxylic acid and cyclopropanecarboxylic acid alkyl esters in themselves known way saponified with alcoholic sodium or potassium hydroxide and that after usual acidification with a strong mineral acid obtained acid mixture in per se known Way isomerized with p-toluenesulfonic acid. Considered publications:
German Auslegeschrift No. 1 149713;
Compt. rend, ed., vol. 250, 1960, p. 4003 to 4005; Vol. 251, 1961, pp. 249-251; Bull. Soc. Chim. France, 1961, pp. 1857-1860; Agr. Biol, Chem., Vol. 26, 1962, pp. 532-534.