PL236887B1 - Derivative of thiophene and method for obtaining it - Google Patents

Abstract

The subject of the application is a new thiophene derivative, 4-(3-methylthiophen-2-yl)-butan-2-ol acetate of formula 1. The application also includes a method for obtaining a thiophene derivative, 4-(3-methylthiophen-2-yl)-acetate butan-2-ol of the formula 1, which consists in the fact that 4-(3-methylthiophen-2-yl)-butan-2-one is subjected to a reduction reaction with sodium borohydride in methanol, and the 4-( 3-Methylthiophen-2-yl)-butan-2-ol, after being isolated from the reaction medium, is subjected to esterification with acetic anhydride in the presence of pyridine in dichloromethane, and the esterification product, after being isolated from the reaction medium, is purified by chromatography.

Description

Description of the invention

The subject of the invention is a new compound, a thiophene derivative and the method of its preparation.

Thiophene is a structural fragment of numerous sensory active compounds, both of natural and synthetic origin (Safety evolution of substituted thiophene used as flavoring ingredients., Food and Chemical Toxicology, 99, pp. 40-59, 2016).

The thiophene derivative 2-acetyl-5-methylthiophene of formula A is known

About pattern A

This derivative is obtained in a two-stage process - by methylation of thiophene with methyl iodide and then arylation of the 2-methylthiophene resulting from the methylation reaction with acetyl chloride in the presence of anhydrous aluminum chloride.

The subject of the invention is a new thiophene derivative, which is racemic 4- (3-methylthiophen-2-yl) -butan-2-ol acetate of the formula 1

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About formula 1

The new thiophene derivative of formula 1, which is a mixture of two enantiomers, is a light straw-colored liquid characterized by a very pleasant, fruity aroma reminiscent of the aroma of pigwood with a hint of lime. The spectral data of the new compound, 4- (3-methylthiophen-2-yl) -butan-2-ol acetate are as follows:

H ¹ -NMR (CDCl 3), 7.00 ppm (d 1 H-1), 6.77 ppm (d 1 H-2), 4.93 ppm (m 1 H-8), 2.76 ppm (m 2 H-6), 2.15 ppm (s 3 H-5), 2.05 ppm (s 3 H-11), 1.94 -1.78 ppm (m 2 H-7), 1.25 ppm (d 3 H-9);

C ¹³ -NMR (CDCl), 170.55 ppm (s C-10), 137.10 ppm (s C-4), 132.67 ppm (s C-3), 129.87 ppm (s C-2), 121.09 ppm (s C- 1), 70.21 ppm (s C-8), 37.41 ppm (s C-7), 23.79 ppm (s C-6), 21.25 ppm (C-11), 19.94 ppm (s C-9), 13.44 ppm ( s C-5);

IR (cm ¹ ), 2974.80, 2935.52, 1733.40, 1371.32, 1237.07;

GC-MS (m / z), 43 (18), 45 (6), 77 (9), 110 (11), 111 (60), 125 (10), 137 (100), 152 (63), 153 (7), 212 (M ⁺ 6).

The new compound, due to its valuable aromatic qualities, fragrance stability and ease of preparation, is a potential component of fragrances for various purposes.

The method of obtaining a new thiophene derivative, 4- (3-methylthiophen-2-yl) -butan-2-ol acetate of the formula 1, using the ketone reduction reaction with a hydride in an alcohol environment and the esterification of alcohol with acetic anhydride in an alkaline environment, according to the invention is in that 4- (3-methylthiophen-2-yl) -butan-2-one is reduced with sodium borohydride in methanol at 0-5 ° C for 2 hours using 0.13 g of borohydride and 5 ml of methanol per 1 g of 4- (3-methylthiophen-2-yl) -butan-2-one, and the 4- (3-methylthiophen-2-yl) -butan-2-ol obtained in this reaction, after separation from the medium reaction, subjected to esterification with acetic anhydride in the presence of pyridine in a medium of dichloromethane at the temperature of 40 ° C for 1.5 hours, using 1.24 g of acetic anhydride, 1.2 ml of pyridine, 3 ml of dichloromethane per 1 g of 4- (3 -methylthiophen-2-yl) butan-2-ol.

PL 236 887 Β1

The esterification product, after isolation from the reaction medium, is purified by chromatography.

The following example illustrates the subject of the invention.

Example

A solution of 11.02 g (0.066 mol) of 4- (3-methylthiophen-2-yl) -butan-2-one in 50 ml of methyl alcohol was prepared in a beaker, then this solution was placed in an ice bath and 1 was added with stirring. , 46 g (0.038 mol) of sodium borohydride. Then the methyl alcohol was evaporated on a rotary evaporator, the residue was acidified with hydrochloric acid to a pH of about 2 and extracted with hexane (2 portions x 50 ml), and then washed with water until neutral. After evaporating the solvent in a vacuum evaporator, 9.0 g of 4- (3-methylthiophen-2-yl) -butan-2-ol were obtained with a chromatographic purity of 99%, which was 81% of theory. The structure of the compound was confirmed by the spectra: H ¹ -NMR (CDCb), 7.04 - 6.82 ppm (dd 2 H-1.2), 3.86 ppm (m 1 H-8), 2.85 ppm (m 2 CH ₂ -chain), 2.21 ppm (s 3 H-5), 1.82 ppm (m 2 CH 2 -chain), 1.28 ppm (dd 3 H-9);

C ¹³ -NMR (CDCb), 137.70 ppm (s C-4), 132.40 ppm (s C-3), 129.77 ppm (s C-2), 120.77 ppm (s C-1), 66.99 ppm (s C- 8), 40.39 ppm (s C-7), 23.98 ppm (s C-6), 23.32 ppm (s C-9), 13.37 ppm (s C-5);

IR (cm ¹ ), 3349.26, 2965.86, 2925.02, 2859.43, 1450.65, 1374.05, 1328.02;

GC-MS (m / z), 45 (19), 77 (12), 97 (26), 111 (100), 112 (31), 137 (81), 152 (14), 170 (M ⁺ 29) .

2 g (0.012 mol) of 4- (3-methylthiophen-2-yl) -butan-2-ol, 2.45 g (0.024 mol) acetic anhydride, 2.4 ml of pyridine, 5 ml of dichloromethane were placed in the flask and the mixture was heated. to boil for 1.5 hours. After this time, 10 ml of water was added and the mixture was heated for 30 minutes at 70 ° C and then the product was extracted with dichloromethane (3 portions of 15 ml). The combined organic layers were washed with hydrochloric acid until the pyridine odor disappeared completely. After washing with water, drying and evaporating the solvent, 2.12 g of 4- (3-methylthiophen-2-yl) -butan-2-ol acetate were obtained with a chromatographic purity of 99% in a yield of 83%. The structure of the compound was confirmed by its spectral data.

Claims (2)

1. Thiophene derivative, 4- (3-methylthiophen-2-yl) -butan-2-ol acetate of formula 1. formula 1 2. The method for the preparation of the thiophene derivative, 4- (3-methylthiophen-2-yl) -butan-2-ol acetate of formula 1, as defined in claim 1 1, using the reaction of ketone reduction with a hydride in an alcohol medium and an esterification reaction of the alcohol with acetic anhydride in an alkaline medium, characterized in that 4- (3-methylthiophen-2-yl) -butan-2-one is subjected to reduction reaction with sodium borohydride in a medium methanol at 0-5 ° C for 2 hours, using 0.13 borohydride and 5 ml of methanol per 1 g of 4- (3-methylthiophen-2-yl) -butan-2-one, and the 4- (3-methylthiophen-2-yl) -butan-2-ol, after isolation from the reaction medium, is subjected to esterification with acetic anhydride in the presence of pyridine in dichloromethane at 40 ° C for 1.5 hours using 1.24 g of acetic anhydride, 1.2 ml of pyridine, 3 ml of dichloromethane per 1 g of 4- (3-methylthiophen-2-yl) -butan-2-ol, and the esterification product, after isolation from the reaction medium, is purified by chromatography.