DE3229537A1 - Process for the preparation of (1R,3R)-trans-caronaldehyde esters - Google Patents

Abstract

Process for the preparation of (1R,3R)-trans-caronaldehyde esters, in which R-glyceraldehyde acetonide is reacted with (carbalkoxymethylene)triphenylphosphorane in the presence of, preferably, acetic acid to give trans-3-(2,2-dimethyl-1,3-dioxolan-4-yl) acrylate and this ester is reacted with (dimethylmethylene)triphenylphosphorane to give (1R)-trans-2,2-dimethyl-3(2,2-dimethyl-1,3-dioxolan-4-yl) cyclopropanecarboxylate, and the latter is cleaved oxidatively in a manner known per se.

Description

Process for the preparation of (1R, 3R) -trans-caronaldehyde-

ester It is known that the insecticidally active natural pyrethrins have the 1R configuration on the C1 atom of the cyclopropane ring: (Pyrethrin I) The 1-R configuration is also most effective in the case of synthetic modified pyrethroid active ingredients (Wegler, Chemistry of Plant Protection and Pest Control Agents, Volume 7, Springer Verlag Berlin, Heidelberg, New York 1981).

The synthesis of 1R-configured precursors of pyrethroids, namely the cyclopropanecarboxylic acids or their esters (2) is possible in different ways; E.g. by racemate separation of corresponding mixtures, e.g. RS-dimethyl-dimethyl-vinylcyclopropanecarboxylic acid with optically active amines (DE-OS 2 348 930) or the racemate resolution of the pure trans-RS form of the same acid, e.g. with optically active -naphthylethylamine ( JA 49 109 344), one can produce sterically uniformly structured cyclopropanecarboxylic acid esters (2) by reacting tetramethylene butadiene with optically active diazoacetic esters in the presence of optically active Cu complexes (BE 810 959).

Various processes are based on natural substances, such as -Caren (Indian. J. Chem. 3 14, 776 (1976) or α-pinene (Synth. Commun. 7,245 (1977).

The processes leading to the 1R-configured cyclopropanecarboxylic acids (2) are all cumbersome and time-consuming.

The object of the invention arose from the fact that the caronaldehyde esters (1) are suitable as optically active intermediates for the synthesis of the IR-trans form of the vinyl cyclopropanecarboxylic acid esters.

According to DE-OS 2,326,066, they can easily be converted into the desired cyclopropanecarboxylic acid esters (4) by a Horner-Wittig or a Wittig reaction, for example after It has now been found that (1R, 3R) -trans-caronic acid aldehyde ester can be prepared in high yields from the easily accessible R-glyceraldehyde acetonide by an enantioselective synthesis.

The process according to the invention reproduced in the claim can be described by the following reaction scheme: The starting material, D-glyceraldehyde acetonide, can, for example, according to J.Biolog.Chem. 12a, 463 (1939) by cleaving diacetonmannitol with lead tetraacetate. In the further reaction with carbomethylene triphenylphosphorane in solvents such as methylene chloride, it has been shown that a solution obtained after filtering off the lead salts, which still contains acetic acid, is formed almost exclusively of the trans-ester (2), while with isolated and purified D-glyaerinaldehyde acetonide a mixture of cis and trans compounds is formed.

The invention is thus based on the observation that the implementation with the carbethylene triphenylphosphorane in the presence of a carboxylic acid in the desired Meaning expires, in the following reaction step one expediently uses an in "situ" Dimethylmethylene triphenylphospho made from isopropyl triphenylphosphonium bromide and n-butyllithium deal with the trans-ester (2) in a known manner. (1R, 3R) -trans-2,2-dimethyl-3 (2,2-dimethyl-1,3-dioxolan-4-yl) -cyclopropanecarboxylic acid ester is obtained selectively. This ester can then e.g. with sodium periodate in the presence of an acid (e.g. sulfuric acid) and a solvent (e.g. THF) oxidatively to the (1R, 3R) -trans-caronic acid aldehyde ester (1) split, which is favorable for the technical design that the Periodate can be regenerated electrochemically and is therefore continuous or quasi-continuous Implementation permitted.

The practice of the sequence of reactions according to the invention is not difficult; the conditions given in the example below e.g. with regard to concentration and temperature range and conversion time are only to be regarded as a reference. When carrying out on a technical scale are also economic considerations, e.g. with regard to vessel size, occupancy time, costs of auxiliary materials etc., which may require a deviation from the practical information.

Example a) Preparation of trans-3- (2,2-dimethyl-1,2-dioxan-4-yl ) -acrylic acid methyl ester That from the cleavage of 31.2 g (119 mmol) 1,2,5,6-diacetonmannitol The resulting crude D-glyceraldehyde acetonide filtrate was after removal of the solvent Dissolved in 100 ml of absolute methylene chloride in a rotary evaporator (3000/17 mbar).

In a 250 ml Schlenk flask with an attached bubble counter In the solution cooled to OOC in a stream of nitrogen, 51.48 g (154 mmol) carbomethoxymethylene-triphenyl-phosphorane added, whereby it becomes a slight Warming the solution came. After stirring at room temperature for 12 hours, the solvent became Stripped off in a rotary evaporator and the oily residue three times with 100 ml of pentane extracted. After drying the extracts over magnesium sulfate and removing the solvent could 22.1 g of the unsaturated ester by distillation (bp 62 ° C / 5.10-3 mbar) can be obtained.

[α] 22 D = + 52.8 ° (c = 10.0%; CHCl3) to [α] 22 D = + 54.53 ° (c = 11.66%; CHCl3).

b) Preparation of 1R-trans-2,2-dimethyl-3 (2,2-dimethyl-1,3-dioxolan-4-yl) -cyclopropanecarboxylic acid methyl ester 1.1 Schlenk flasks equipped with bubble counters are placed in a dropping funnel 94.35 g (244.9 mmol) isopropyltriphenylphosphonium bromide in 200 ml of absolute THF submitted. After cooling to OOC, 140.25 ml (224.4 mmol) of n-butyllithium (solution Pn hexane) within 15 min. dripped, being the characteristic deep red color of Elijah appeared.

After stirring for 15 min at room temperature, the mixture was cooled to -78 ° C. and within 20 min a solution of 38.0 g (204.0: nmol) of the prepared according to a) Compound, dissolved in 100 ml of absolute THF, was added dropwise. With increasing precipitation the color of the ylid disappeared; the mixture was stirred at -78 ° C. for a further 1 hour. Afterward let it come to room temperature. After two hours the reaction was over Addition of water (100 ml) canceled. In the clear orange solution settled a yellow precipitate.

It was suctioned off and the clear filtrates on a rotary evaporator concentrated (5000/17 mbar).

It was taken up with 300 ml of ether, the aqueous phase was separated off, the ethereal solution dried over MgSO4 and the solvent removed. In the end was distilled in a high vacuum. Oil bath temperature: 80-90 ° C / 5.10-3 mbar), whereby the Target compound passed over as a colorless, slightly viscous liquid.

Yield: 25> 1 g (53.9%), [α] D22 = 8.820 (c = 10.5%, CHCl3) c) Production of (1R, 3R) -trans-Caronaldehydsäuremethylester in a with bubble counter equipped 250 ml round bottom flask was a mixture of 50 ml THF, 6.0 g (26.28 mmol) the compound obtained according to b), 5.9 g (27.58 mmol) of sodium metapertodate and 30 ml of 2N sulfuric acid was stirred for 24 hours at room temperature. After that, the Sucked off precipitated sodium iodate, the filtrates concentrated, with Ether taken up and extracted with dilute thiosulphate solution. After separation and drying the ethereal solution over magnesium sulfate became the solvent stripped off on a rotary evaporator and 3.9 g of methyl caronaldehyde ester (95% yield) isolated in the form of a colorless liquid.

[α] D22 = + 9.15 (c = 12.5% CHCl3) D = +9.15 (c = 12.5%, CHCl3, Application example Production of d-trans-Chrysanthemum carboxylic acid methyl ester (lR, 3R) In a 25C ml Schlenk flask fitted with a dropping funnel and bubble counter 11.22 g (29.13 mmol) isopropyltriphenylphosphonium bromide in 50 ml of absolute THF submitted. After cooling to OOC, with rapid stirring (magnetic stirrer), 15.4 ml (24.65 mmol) of n-butyllithium were added dropwise over the course of 10 min. After stirring for 15 min at room temperature the mixture was cooled to -78 ° C. and a solution was obtained within 10 min of 3.5 g (22.41 mmol) (1) in 10 ml of absolute THF was added dropwise and the mixture was stirred for 10 min, then allowed to come to room temperature and, after 2 hours, the reaction was stopped Add water (5C ml). It was concentrated, extracted several times with pentane (100 ml), dried over magnesium sulfate, the solvent removed and the product (2.5 g, 61.2%) isolated by distillation (boiling point 36 ° C./1 mbar).

[α] 22D = + 19.7 ° (c = 11.0 CHCl3) [α] 22D = + 15.2 ° (C = 1.4 ethanol)

Claims (1)

p Patent claim Process for the preparation of (1R, 3R) -trans-caronaldehyde ester of the formula 1 in the alk denotes the remainder of an aliphatic or arallphatic alcohol, characterized in that R-glyceraldehyde acetonide is converted with carboalkoxymethylene triphenylphosphorane in the presence of preferably acetic acid to give trans-3- (2,2-dimethyl-1,3-dioxolan-4-yl) - acrylic acid ester of the formula 3 converts this with dimethylmethylene triphenylphosphorane to 1R-trans-2,2-dimethyl-3- (2,2-dimethyl-1,3-dioxolan-4-yl) - cyclopropanecarboxylic acid ester (4) and (4) cleaves oxidatively in a manner known per se to the trans - (1R, 3R) -caronaldehyde ester.