PL192465B1 - Novel lactones with a limonen system and method of obtaining them - Google Patents

Abstract

1. New lactones with the limonene system, with the general formula 1, where the configuration of centers chiral is defined as 1R, 4R, 6R or 1S, 4S, 6S.

Description

Description of the invention

The subject of the invention is new lactones with the limonene system and a method for the production of new lactones with the limonene system.

There are no known compounds with the activity of food deterers (antifidants), which are obtained by chemical synthesis.

The essence of the invention are new lactones with the limonene system of the general formula I, where the configuration of the chiral centers is defined as 1R, 4R, 6R or 1S, 4S, 6S.

The process according to the invention consists in that the corresponding R or S isomer of peryllium alcohol is subjected to Claisen rearrangement by the orthoacetate method and the formed alkyl esters are hydrolyzed under basic conditions to acids which are iodolactonized with iodine in potassium iodide solution. Then, the obtained iodolactones are reduced with tri-n-butyltin hydride to form lactones.

Preferably, the Claisen rearrangement reaction is carried out with ethyl orthoacetate, and ethanolic potassium hydroxide is used for the hydrolysis of the esters.

The obtained lactones show the activity of food detectors in relation to pests of grain storage facilities: trout (Tribolium confusum), grain peel (Trogoderma granarium) and grain weevil (Sitophilus granarius). The 1S, 4S, 6S isomer also showed detecting activity against the peach-potato aphid (Myzus persicae).

The results of biological tests carried out according to the method described by J. Nawrot, E. Błoszyk, J. Harmeth, L. Novotny and B. Drożdż (Acta Entomol. Bohemoslov. Vol. 83, pp. 327335, 1986) are presented in the table.

Table

Isomer Deterential activity (sum factor) Grain peel (larvae) Troika succumb to (larvae) Trojszyk to fall (beetles) Grain weevil (beetles) Isomer 1R, 4R, 6R 130.4 153.8 173.4 195.4 Isomer 1S, 4S, 6S 159.4 123.0 143.8 70.1

The subject of the invention is explained in more detail in the examples of embodiments.

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Example 1. To 3.1 g (0.02 mol) of S (-) peryllium alcohol, 25 cm ³ (0.14 mol) of ethyl orthoacetate and 2 drops of propionic acid are added and the mixture is heated at 138 ° C for 2 hours, while distilling off the ethanol formed in the reaction. Then the excess orthoacetate is distilled off under reduced pressure and the crude product (4.0 g, 90% yield) consisting of 88% of trans- (4S) -1-methylene-4- (1-methylethenyl) cyclohexa acid ethyl ester The -2-ylacetic acid and 12% of the cis-isomer of this ester are subjected to basic hydrolysis with 50 ml of a ⁴ % solution of potassium hydroxide in ethyl alcohol. The resulting reaction mixture was heated to reflux for 2 hours. The ethanol is then distilled off and the residue is dissolved in water and washed with diethyl ether to remove non-acid organic impurities. The aqueous solution is acidified with 0.1 M hydrochloric acid and the resulting product is extracted with diethyl ether. The ether extracts are dried with anhydrous magnesium sulfate.

3.0 g (85% yield) of a mixture of the isomers: trans (88%) and cis (12%) of (4S) -1-methylene-4- (1-methylethenyl) cyclohex-2-ylacetic acid are obtained. The thus prepared acid is dissolved in 50 cm ³ of diethyl ether and added to 50 cm ³ of 0.5 M sodium bicarbonate solution. The mixture is stirred for 0.5 hours at room temperature and then heated to reflux. To the refluxing solution was added 50 cm ^{3 of} aqueous solution containing 6 g of iodine and 12 g of potassium iodide. The reaction mixture is further heated for 5 hours and then stirred for 12 hours at room temperature. After this time the reaction mixture is added 100 cm ^{3 of} ethyl ether, shaken and separated the aqueous layer from the organic. The organic layer is washed successively with sodium thiosulfate solution and water. After drying the ether solution with anhydrous magnesium sulfate and distilling off the solvent, 4.1 g (84% yield) of the crude product were obtained as a mixture of trans (88%) and cis (12%) (1S, 4S, 6S) -1-iodomethyl-4. - (1-methylethenyl) -9-oxabicyclo [4.3.0] nonan-8-one.

PL 192 465B1

This mixture was separated by column chromatography on silica gel using a 9: 1 mixture of hexane and ethyl acetate as eluent. 3.5 g of pure trans iodolactone isomer are recovered. The physical and spectroscopic properties of the obtained compound are as follows:

top temp. 76-78 ° C; [α] D ²³ = + 44.4 ° (C 1.09, acetone) ¹ H NMR (d); 1.73 (S, 3H, -C (CH2) CH3); 2.61 and 2.68 (AB system two dd, J = 17.1 and 9.9 Hz, 1H and J = 17.1 and 10.7 Hz, 1H, -CH2-C (O) -); 2.82 (m, 1H,> CHCH2C (O) -); 3.57 (m, 2H, -CH2I); 4.75 (m, 2H, -C (CH2) CH3);

IR (cm- ¹ ): 1776 (s), 1220 (s), 1152 (s).

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To the thus obtained iodolactone (0.011 mol) dissolved in 50 cm ^{3 of} dry benzene, 12.7 g (0.04 mol) of tri-n-butyltin hydride are added and the mixture is stirred at room temperature under nitrogen for 48 hours. After this time, benzene was distilled off from the mixture, and the residue was separated by column chromatography (silica gel, eluent: hexane: ethyl acetate, 9: 1).

1.6 g (75% yield) of pure trans (1S, 4S, 6S) 1-methyl-4- (1-methylethenyl) -9-oxabicyclo [4.3.0] nonan-8-one. The yield of the four-step synthesis is 42% based on (S) - (-) peryllium alcohol. The physical and spectroscopic properties of the lactone so obtained are as follows:

top temp. 63-65 ° C; [α] D ¹⁶ = + 38.03 ° (C 108, acetone);

¹ H NMR (d): 1.49 (S, 3H, -CH3), 1.76 (S, 3H, -C (CH2) CH3); 2.48 and 2.61 (two dd, J = 18.6 and 7.5 Hz, 1H and J = 18.6 and 14.7 Hz, 1H, -CH2 (O) -); 2.47 (m, 1H,> CHCH2C (O) -); 4.74 (m, 2H, = CH2);

IR (cm ^-1 ): 1787 (s), 1212 (s), 1096 (s).

Example 2 The procedure is analogous to that of Example 1, except that from 1.5 g (0.01 mol) of R (+) peryllium alcohol in the reaction with ethyl orthoacetate 1.9 g (yield 85%) are obtained. crude (4S) -1-methylene-4- (1-methylethenyl) cyclohex-2-ylacetic acid ethyl ester as a mixture of trans (87%) and cis (13%) isomers. The crude ester is hydrolyzed with ethanolic potassium hydroxide to 1.5 g (95% yield) of a mixture of trans (87%) and cis (13%) (4S) -1-methylene-4- (1-methylethenyl) acid. ) -cyclohex-2-ylacetic acid which, without separation and purification, is iodolactonized to a trans and cis mixture of 1-iodomethyl-4- (1-methylethenyl) -9-oxa-bicyclo [4.3.0] nonan-8-one. The pure trans isomer (1.9 g, 75% yield) is isolated from the crude product mixture by column chromatography (silica gel, hexane: ethyl acetate, 9: 1). Its physical properties are as follows:

top temp. 75-80 ° C, [α] D ²² = -74.5 ° (C, 1.26, acetone).

The iodolactone thus obtained is reduced with tri-n-butyltin hydride to (1R, 4R, 6R) -1-methyl-4- (1-methylethenyl) -9-oxabicyclo [4.3.0] nonan-8-one. 0.9 g (75% yield) of pure compound is obtained, mp. 62-64 ° C and [a] D ²⁶ = - 32.8 ° (C, 0.84, acetone). The yield of the four-step synthesis is 45%.

Claims (4)

Patent claims 1. New lactones with the limonene system of the general formula I, where the configuration of the chiral centers is defined as 1R, 4R, 6R or 1S, 4S, 6S. Method for the production of new lactones with the limonene system of the general formula I, where the configuration of chiral centers is defined as 1R, 4R, 6R or 1S, 4S, 6S, characterized in that the appropriate R or S isomer of peryllium alcohol is subjected to Claisen rearrangement using the orthoacetate method and the formed esters are hydrolyzed under basic conditions to acids, which are subjected to iodolactonization with iodine in potassium iodide solution, and then the obtained iodolactones are reduced with tri-n-butyltin hydride. 3. The method according to p. The method of claim 2, wherein the Claisen rearrangement is ethyl orthoacetate. 4. The method according to p. The method of claim 2, wherein the ester hydrolysis is carried out with an ethanolic solution of potassium hydroxide.