CS231983B2 - Manufacturing process of the 3,7.11-trimethyl-2,4-dodecadiene acid derivative - Google Patents

Abstract

3,7,11-trimethyl-2,4-dodecadienoates of the general formula /I/ <IMAGE> wherein R<1> represents hydrogen or an alkoxy group, Z<1> represents hydrogen, or R<1> and Z<1> together form a double bond, Z<2> and Z<3> each represent hydrogen or together form an ethylene group, R<2> and R<3> each denote an alkyl group, provided that when Z<2> and Z<3> form an ethylene group, R<1> is hydrogen, R<2> is methyl and R<3> is ethyl, are prepared by reacting a compound of the general formula /II/ <IMAGE> wherein R<1>, Z<1>, Z<2>, Z<3> and R<3> have the above specified meanings, and Q represents a group of the general formula /IIIB/ -COR /IIIB/ wherein R stands for an alkyl, phenyl or phenyl-/lower alkyl/ group, and with a compound of the general formula /VI/ Li-Cu/R<2>/2 /VI/ wherein R<2> has the above defined meaning. The advantage of the process is that it consists of less reaction steps than the known methods and can be used also on an industrial scale. The compounds of formula /I/ are insect growth regulators and can be used to advantage in plant protection. The intermediates of formula /II/ are new.

Description

The present invention relates to a novel process for the preparation of 3,7-triethyl-2,4-di-decadiene-P-acid derivatives. The compounds which can be prepared according to the invention correspond to the general formula I

COOR ⁵ (!) Where they mean

R ¹ is hydrogen or alkoxy having one to three carbon atoms;

Z ^{1 is} hydrogen or

R 1 and Z ¹ together represent a double bond and

Z ² and Z ³ represent hydrogen or together form an ethylene group

R @ 1 and R @ 3 are the same or different C1 -C4 alkyl groups, with the proviso that when Z @ - and Z @ 3 = ethylene, R @ 1 is hydrogen, R @ 3 is methyl and R @ 3 is ethyl.

Some of the compounds of formula I, for example, isopropyl-1-methoxy-5'-trimethyl-2 (E), 4 (E) -dodecadienoate ⁽ hereinafter Methoprene) and ethyl (3-, 7,11-trimethyl) -2 (E), 4 (E) -dcdecadienolat (hereinafter Hydropren) can be purchased from the market and can be used in the field of plant protection and veterinary medicine against animal pests. Methopren has produced good results, for example in combating the following pests: mosquitoes. for example, mosquitoes causing malaria (Aedes A ^ yp-i) [WL Jakob, Mosq. News 32, 592 (1972); WL Jakob: J. Ecou. Entomol. 66, 819 (1973); CA Henrick et al: J. Agric. Food Chem., 24, 207 (1976)), flies, for example house flies (Musea Domestica) [WL Jakob: J. Ecou. Entomol. 66, 819 (1973); WF

Plapp and S.R.V. Biochem. Physiol. 3, 131 (1973); Henrick et al., J. Agric. Food Chem. 24, 207, (1976)], the flour worms (Tenebrio molitor) [C. A. Henrick .et. al., J. Agric. Food Chem. 24, 207 (1976)], aphids such as green aphids parasitizing on bro (Acyrthosipon pisumi) [C. A. Henrick et al., J. Agric. Food Chem. 24, 207 (1976)] and cockroaches (e.g., Nanphoeta. Cinerea) [W. Radwan. And F. Sehnal. Experimente 30, 615 (1974)].

Hydropren has been successfully used against aphids parasitizing on potato leaves [J. Benskin and J. M. Porron: Oan Entomol. 105, 619 (19713)], flour worms [R. A. Hamlen, J. Econ. Entomol. 68, 223 (1975): C.A. Henrick et al., Bioorganic Chemistry 7,235 (1978)]. and other animal pests [R. G. Strong and J. Dlekrnan: J. Econ. Entomol. 66, 1167 (1973)].

A compound of formula I (R ¹ = H, Z ¹ = H, Z ² + Z 3 = ethyl, ^R2 = CH3, R3 = C2H5 (containing cyklopeutadienovou group), decreases significantly the development of the flies, causing mud fever (Aedes aegypti) and moth (Heliothris virescens) [CA Henrick et al., Bioorganic Chemistry 7, 235 (1978)].

For the production of ethyl-3,7,11-trimethyl-2 [E], 4 (E) -dodecadienoates, C.A. Henrick et al. [J. Org. Chem. 40, 8 (1975)]. According to. In one of these methods, the 6,7-dihydrocitronellal is reacted with an apoptosis formed from diethyl-2-oxopolyl phosphonate and the resulting 2-oxo-6,10-dimethyl-11-undecene is reacted with an acetic acid salt. The resulting 3-hydroxy-3,7,11-trimethyl-4-uidecenoic acid is reacted with phosphoryl chloride and N-ethyldiisoyropylaryl to give the acid chloride from which it is treated by treatment with quaternary fracture. yields the 2 (Z) -stereoisomer of hydroprene and, as a result of the double bond rearrangement, the corresponding 3,5-dodecayneic acid derivative (10%).

A drawback of the process is that the esterification can only be carried out with the wrong one. yield (50%) and a significant amount of by-products is formed.

According to an improved variant of this process (CA Henrick et al.), 3,3-dimethylacrylic acid is used as starting material. From this compound, a dianion is formed by reaction with a lithium compound of diisopropylamine which is reacted with 6,1-dihydrocitpopellal. The resulting 3-hydroxy-2 rcxy - sopropenol-5,9-di-methyldecanoic acid is converted to thermal conversion to 5-ltydrcxy 3 _J 7 · lllΐΓl methyll- (Z) -4o4eeenovou acid from which in the acidic environment created six lactone. The lactone is reacted with sodium methylate to form the * 2 (Z) -stereoisomer of Hydroprene.

Treatment with thiophenol gives a mixture containing Hydropren and its 2 (Z) -stereoisomer in a ratio of 6.5: 3.5. The process is disadvantageous due to the high cost of the starting compound and the low yields of the individual steps.

According to the latest method also developed by CA Henkel et al. (J. Org. Chem. 48, 8 (1975): J. Agric. Food Chem. 23, 396 (19715)), 6,7-dihydrocitronellail is reacted with lithium compound of 1-propyne.

The resulting 4-hydroxy-6,10-dimethyl-2-piperidine is reacted with ethyl ortho-acetic acid ester and the resulting ethyl (3,7,11-trimethyl-3,4-4,4-ocadiadienoate) is converted into a mixture using the base. , consisting of hydroprene and its 2 (Z) -stereoisomer. Treatment with Μ-phenophenol gave an equilibrium ratio (6.5: 3.5) in the mixture. The practical value of this method is greatly influenced by poor yields of the individual process steps (yield of the first edition stage is .29%).

Recently. a new process for the production of hydroprene methyl analogs has been published by G. Cardill et al. (J.C. Perkin I, 1979, 1729)

S (R 1 = z ¹ = Z ² = Z 3 = H, R 2 = R ³ = CH 3). From the 3-methyl-3-buten-1-ol used as the starting material, a dianiop is formed with twice the stoichiometric amount of butyllithic, which, when reacted with 6,7-dihydrocitronellel, yields 1,5-dihydroxy-3- [3-] -yloxy-3- methylene-η 7,11-dimethyldodecane. This compound is acylated to the obtained dia.cyl (the derivative is partially hydrolyzed. The obtained 5-acetoxy-3-methylene-7,11-dimethyldodecan-1-ol is oxidized with Jones reagent, the obtained carboxylic acid is esterified with diazomethane and from the ester sc '. by reaction with sodium hydrides in the presence of ether (crown ether) forms a mixture of isomers 2 (E], 4 (E), -2 (Z), 4 (E) .The process is disadvantageous with respect to the use of expensive starting materials and reagents.

In the known method [C. A. Henrick et al., J. Org. Chem. 40, 1 (1975)] For the production of methoprene, the acetic acid ester is dimerized in an acidic medium, and the dimer is treated with 3-methylglutaconester by treatment with sodium alcoholate which is condensed in an alcoholic potassium hydroxide solution with 7-methoxy-6,7-dihydrocitro.nellal. and the obtained 11-methnyl-4-carboxy-3,7J-trimethyl-2 (Z), 4 (E) -dodicadienic acid is decarboxylated by heating in the presence of 2,4-dimethylpyridine.

The Z-reaction mixture is isolated as the main product 11-methoxy-3,7,11-trimethyl-2 (Z), 4 (E) -dodecadienoic acid, the unreacted starting material, lactone 10-methoxy-2,6, 10- trimethyl-1,3- (Z) -undecadiene resulting from sodium decarboxylation Dodecadienic acid isomerized is thiophenol, a mixture of stereoisomers 2 (E), 4 (E], 2 (Z) and

Ammonium salts 2 (E] and 4 (E) are separated from each other by - crystallization. The acid released from the ammonium salt is - converted - by a mixture consisting of thionyl chloride and dimethylformamide in acid chloride and this is converted into methoprene with isopropanol.

The economy and applicability of the process are adversely affected by the fact that at least two moles of acetic acid ester are necessary for the production of 1 mole of methopremi, furthermore, the separation of by-products after decarboxylation is tedious, the formation of acid chloride eliminates some of the methoxy groups and the product is contaminated with i-propyl-3,7,11-trin] ethyl-2 (E), 4 (E) -10-dodecatriencate and i-propyl-β 1 -trimethyl-11-chloro-2 (E), 4 (E) -decoddienoate.

For the preparation of ethyl 3- (3,7-dimethyl-octylidene) -2-methyl-2-cyclopentenecarboxylate, a method is known [CA Henrick et al., Bioorgamc Chemistry 7, 235 (1978)], which is produced from 1- ethoxyicarbonylcyclopropyltriflylphosphonium η 5 (η 6 - (η 1 - (N - (-) - and diethyl 2-oxopropyltosphonate ethyl 3-diethylphosphoryl-2-methyl-1-cyclliopenteine carboxylate) and this is reacted with 6 The disadvantage of this process is that the starting compound phosphonium fluoroboroborate is expensive and the yields of the individual process steps are very low (10-20%).

It is an object of the present invention to provide a process for the preparation of compounds of the formula I which has a smaller number of steps and is more economical than the known processes, and is easy to carry out on an industrial scale.

Claims (9)

A process for the preparation of 3,7,11-trimethyl-2,4-dodecadenoic acid derivatives of the general formula: COOR (lil R ¹ is hydrogen or alkoxy having one to three carbon atoms; Z ^{1 is} hydrogen or R ¹ and Z ¹ together represent a double bond and ^; Z ² and Z ³ represent hydrogen or together form an ethylene group and R ² and R ³ are the same or different C 1 -C 4 alkyl groups, with the restriction that when Z ² and Z ³ are ethylene, R ^{1 is} hydrogen, R ^{2 is} methyl and R ^{3 is} ethyl characterized in that the compounds of formula (II) wherein the meaning of R ¹ , Z ¹ , Z ² , Z ³ and R ³ is the same as above and κ represents a group of formula (IIIA) or (IIIB) a ^and _x R ^ O ^ P-> O (HlAl or —COR in which (IIIB), R is C 1 -C 5 alkyl, phenyl or C 1 -C 3 phenylalkyl; R ⁴ represents a C 1 -C 4 alkyl group, linear or branched, reacted with compounds of formula VI LiCu (R ²⁾ ₂ (VI) wherein the meaning of R ² is the same as above. 2. A method - for preparing derivatives of 3,7,11-trimethyl-2,4-dodecadienoic acid of formula I, wherein the meaning of R1, Z1, Z2, Z3 is the 'same as above and R 2 and R ³ are independently alkyl groups The compound of formula (II d) wherein the meaning of R 1, Z ¹ , Z ² , Z 3 and R 3 is the same as above. -a K represents a group of the general formula IIIA, wherein - R 4 represents a C 1 -C 4 alkyl group having a linear or branched chain, reacted with a compound of the general formula VI LiCu (R ²⁾ ₂ (VI) wherein the meaning of R2 is the same as-above. 3. A process for the preparation of 3,7,11-trimethyl-2,4-dodeca dioic acid derivatives of the general formula I, wherein the meaning of the substituents is the same as above, except for the meanings of Z2 and Z3, which here can mean only hydrogen, characterized by: wherein the compound of formula II wherein R ¹ , Z ¹ , Z 2, Z 3 -and R 3 is the same as above -a K is a group of the general formula IIIB -COR (IIIB) wherein R is an alkyl group of 1 to 2 5-carbon atoms, a phenyl group or a phenylalkyl group having 1 to 3 carbon atoms in the -alkyl moiety, is reacted with the compound. - formula VI L1Cu (R2) _² (VI) wherein the meaning of R2 is the same as above. 4. The process of claim 2, wherein the reaction is carried out in an inert gas atmosphere. The process according to claim 2, characterized in that the reaction is carried out at temperatures between - 100 ° C to -10 ° C, preferably -50 to -80 ° C. Process according to one of Claims 2, 4, and 5, characterized in that the reaction is carried out in an aprotic organic solvent, preferably in diethyl ether or tetrahydrofuran. 7. The process of claim 3 wherein the reaction is conducted under an inert gas atmosphere. Process according to Claim 3, characterized in that the reaction is carried out at temperatures between -100 to -10 ° C, preferably -50 to -80 ° C. 9. A process according to claim 3, wherein the reaction is carried out in an aprotic solvent, preferably diethyl ether or tetrahydrofuran.