SU740779A1 - Method of preparing alpha-nitroderivatives of thiophene series alpha,beta-unsaturated ketones - Google Patents

Description

The invention relates to a new method for the preparation in the literature of the os-nitro-spore, f-limit ketones of the thiophene series, the general formula B -1c D-CHY-eO-YNz, where R is hydrogen, methyl or ethyl, possessing biological activity B The literature describes the only method for the preparation of oC-nitroderivatives, p-limiting ketones of the thiophene series, namely, the method of producing 3- (thienyl-2) -2-nitro-1-L-propen-2on-1, 2thienyl, consisting in the fact that the ", p -limit thiophene ketones are treated with tetroxide Zot in absolute ether at temperature (-) 30 ° C, followed by aging the reaction mixture for 1-1.5 hours the title product Yield 10-12% 1J.. The disadvantage of this method is an increased fire and explosion hazard, the need to maintain a low temperature process to prevent tarring of the reaction product, as well as a low yield of the target product. There is also known a method for nitrating derivatives of 2,2-bithiophene with concentrated nitric acid in a medium of 1,2-dichloroethane, however, this involves replacing the thiophenic ring 2 with the hydrogen nitro group. The aim of the invention is a new method of preparation. -nitro-derivatives, p-limiting ketones of the thiophene series. The goal is achieved by the described method of producing compounds of the general form. 1, which consists in the fact that 4- (5-K-thienyl-2) -butene-3-one-2 of the general formula: P R L Lyn-eo-en where R - has the indicated values, is treated with concentrated nitric acid (spd weight 1.45-1.50 g / cm) at a molar ratio of 0.65-0.95 in acetonitrile, 1,2-dichloroethane or carbon tetrachloride at a temperature from to the boiling point of the solvent.

In the case of carrying out the process in an acetonitrile medium, preferably the molar ratio of the starting substance: concentrated nitric acid is 0.75-0.95 and the temperature is from 50 ° C to the boiling point of acetonitrile.

When using 1,2-dichloroethane, preferably, the molar ratio is 0.65-0.95 and the temperature is from 45 to the boiling point of 1,2-dichloroethane, and when using carbon tetrachloride, preferably the molar ratio is 0.7-0.9 and the process temperature is from 45 to the boiling point of carbon tetrachloride.

The reaction mass is held at the same temperature for 1.5-2. Yitroproductive is easily added when water is added to the reaction mass, filtered, washed with water from acid traces, dried in air, and recrystallized.

The yield of the target product is 25-40%.

Example 1. Preparation of 4- (tie-nyl-2) -3-nitrobuten-3-one-2, (The ratio of the initial substance: an NCTT agent 0.8).

In a four-necked flask with a capacity of 150 ml, equipped with a mechanical pulverizer, reflux condenser, thermometer and addition funnel, put a solution of 3.04 g {0 |, 02 mol) 4- (thienyl-2) buten-2-one-2 in 15 g acetonitrile and heated to 50 ° C in a water bath. Then, with stirring, a mixture of 1.575 g (0.025 mol) of nitric acid (d l / 45-l, 50 g / cm) is slowly added dropwise, maintaining the temperature at 50 ° C. After the introduction of the total amount of acid, the reaction mixture is kept at 50 ° C for 1.5-2 hours and BEED in 200 ml of water. The precipitate is filtered off, washed with water and dried. The yield of 1.78 g (45.2%). After recrystallization from alcohol, 1.10 g (28%) of 4- (thienyl-2) -3-nitrobutene-3-one-2 is obtained, with a mp. 146, 146 ,,, yellow crystals.

Found,%; C, 48.93; H, 3.24; N, 6.88; S 16.04; None,%: from 48, 3.58; N 7.10; S 16.23.

P p, and I m p 2 (the ratio of the initial substance: nitrousuyu: i agent 0,8)

The experiment was carried out completely according to Example 1 at 81.5 ° C (t, cyp. Acetonitrile)

The yield of crude 4- (thienyl-2) -3-nitro butene-3-one-2 .1.91 g (48.3%), after. recrystallization from alcohol - 1.26 (32%), mp.146-146.5 ° C, yellow lamellar crystals.

Found,%: C 49.01; H 3.03; N 6.91; S 16.45.

Calculated,% J C 48,72; H 3.58; N, 7.104; S: 16.23.

Example 3. (The ratio of the initial substance: nitrous agent 0.9).,

The reaction is carried out completely by priru 1. Take 3.04 g (0.02 mol) of ketone and 1.40 g (0.022 mol) of nitric acid and heat to 71 ° C. The product yield of 1.98 g (50.2%); after recrystallization from alcohol, 1.38 g (35% of 4- (thienyl-2 -) - 3-nitro5uten-3-one-2 with a melting point of 146-146.5 ° C, yellow lamellar crystals) are obtained.

Found,% i C 49, 12; H 3.45; N 7.35; S 16.41.

Calculated,%: C 48.72; H 3.58; N 7, 10 4; S 16,23.

Example 4. Preparation of 4- (5-methylthienyl 2) -3-nitrobuten-3-one 2. {The ratio of the initial substance: the nitrating agent is 0.9).

Analogously to example 1, from 0.5 g (0.003 mol) of 4- (5-methyl-thienyl-2-) butene-3-one-2 and 0.21 g (0.00324 mol of nitric acid in 18 gl of acetonitrile, receive Of 34 : 2 g (53.8%) of the crude product and 0.19 g (30%) after recrystallization from heptane 4- (L-methylthienyl-2} -3-nitrobutene-3-oka-2 with mp 109- 110 ° C, light yellow crystals.

Found,%: C 50, -83; H -5.59; N 6.17; S 14.72

Calculated,%: C 51.17; H 4.30; N 6.63; S 15.2.

Example 5 Preparation of 4- (5ethylthienyl-2) -3-nitrobuten-3-one-2. (The ratio of the source of action: nitrous agent-O, 9).

Similarly, example .1 out of 0.69 g (0.003 mol) of 4- (5-ethylthienyl-2) butene-3-one-2 and 0.24 g (0.00324 mol) of nitric acid in 18 ml of acetonitrile, obtained 0.517 g (61.4%) raw to 0.286 g (34%) after recrystallization from heptane 4- (5ethylthiesL-2) -3-nitrobutene-3-one-2 with mp, 138-139 ° С, yellow needles.

Found,%: C 53.04; H 4.57; N 6.38; S 14.03

Calculated,%; C 53.32; H 4.92; N 6.22; S 14.23.

P p. And m er 6. Getting 4- (tiennl-2) -3-N. nitrobuten-3 she-2,

(The ratio of the original substance: nitrougs agent 0.8).

In a four-necked flask with a capacity of 150 ml, equipped with a mechanical bag, a reflux cooler, a thermometer and an addition funnel, put a solution of 3.04 g (0.02 mol) of 4- (thienyl2) buten-3-one-2 in 15 ml of 1.2 dichloroethna and heated to 45 ° С in a water bath. Then, with stirring, a mixture of 1.57 g (0.025 mol) of nitric acid (1.451, 50 g / sg) is slowly added dropwise, maintaining the temperature. After separation of the total amount of nitric acid, the reaction mixture is kept for 1.5-2 hours at the same temperature. poured into 800 ml of water, the organic layer was separated, thoroughly washed from traces of acid, the solvent was distilled off under vacuum to obtain 1.88 g (47.6%) 4- {thienyl-2) 2-nitrobutene-3-one-2 . After recrystallization from alcohol, 1.05 (26.5%) is obtained with m.p. 146.5 ° C, yellow lamellar crystals.

Found,%: C 48.65; H 3.78; N 7.36; S 16,54,

Calculated,%: C 48.72; H 3.58; N 7,104; S 16.23.

Example 7. (The ratio of the original substance: a nitrating agent of 0.8).

The reaction is carried out at a temperature of 83, (so kip. 1,2-dichloroethane) completely in example 6.

The yield of crude 4- (thienyl-2) -3-nitrobuten-3-one-2 is 2.92 g (74.3%). After recrystallization from alcohol, I get 1.37 g (35%) of the substance with so pl. yellow plate crystals.

Found,%: C 49.2; H 3.20; N7.40; S16.46.

Calculated,%: C 48.72; H 3.58; N 7.104; S 16.23.

Example 8. Obtaining 4- (5-methylthienyl-2) -3-nitrobuten-3-one-2. (The ratio of the original substance: nitric acid is 0.9).

Analogously to example 6 of 0.5 g (0.003 mol) of 4- (5-methylthienyl-2-) butene-Z-one-2 in 8 ml of 1,2-dichloroethane and 0.24 g (0.0034 mol) of concentrated nitric acid, dissolved in 1 ml of dichloroethane, at a temperature of 60 ° C, 0.452 g (71.2%) of 4- (5-methylthienyl-2) -3-nitrobutene-3-one-2 is obtained. After recrystallization from heptane, 0.21 g (33%) of the product is obtained with a mp. 109 ° C, light yellow crystals

Found,%: C 51.35; H 4.70; N 6.89; S 15.80.

Calculated,%: C 51.17; H 4.30; N 6.63; S 15.20.

Example 9. Obtaining 4- (5ethylthienyl-2) -3-nitrobuten-3-ones-2. . (The ratio of the original substance: nitrogen - acid-O, 9).

Analogously to example 6 of 0.5 g (0.0027 mol) of 4- (5-ethylthienyl-2) butene-Z-one-2 in 9 ml of dichloroethane and 0.19 g (0.003 mol) of nitric acid dissolved in 1 ml dichloroethane, at a temperature of 83.7 ° C, 0.54 g (86.3%) of 4- (5-ethylthienyl-2) -3-nitrobuten-3-one-2 is obtained. After recrystallization from alcohol, 0.26 g (42%) of the substance was obtained. .138.5-139 ° С, yellow needles.

Found.%: C 53.45; H 5.20; N 6.37; S 14,51.

Calculated,%: C, 53.32; H 4.92; N 6.22; S 14.23.

Example 10. (The ratio of the original substance: nitric acid-0.85

Analogously to example 6 of 0.5 g (0.0027 mol) of 4- (5-ethylthienyl-2) butene-Z-one-2 in 9 ml of dichloroethane and

0.2 g (O, 0032 mol) of nitric acid in 1 ml of dichloroethane at a temperature of 60 ° C gives 0.462 7 (73.6%) 4- (5 ethylthienyl-2) -3-nitrobutene-3-one-2. After recrystallization from heptane, 0.197 g (30%) of the substance is obtained with a mp. 138-139 ° C.

Found,%: C 53.53; H 4.76; N 6.50; S 14.31.

Calculated,%: C, 53.32; H 4.92; N 6.22; S 14.23.

0

Example 11. Obtaining 4- (thienyl-2-) -3-nitrobuten-3-one-2, (The ratio of the initial substance: nitrous agent -0.7).

In the four-necked flask capacity

5 150 ml, equipped with a mechanical stirrer, reflux condenser, dropping funnel and thermometer, put a solution of 3.04 g (0.02 mol) of 4- (thienyl-2) butene-3-one-2 in 20 ml

0 carbon tetrachloride and heated to a water bath. Then, while stirring, a mixture of 1.8 g (0.0286 mol) of nitric acid specific weight is slowly added dropwise to it.

ca 1.45-1.50 g / cm support

temperature 45 C. After the introduction of the total amount of nitric acid, the reaction mixture is held for 1.5-2 hours at the same temperature, poured

0 in 200 ml of water, the organic layer is separated, carefully washed from traces of acid, the solvent is distilled off under vacuum, and 2.24 g (56.73%) of 4- (thienyl-2) -3-nitrobuten-3-2 are obtained. . After recrystallization

5 from alcohol get 0.925 g of the product (23.50%) with so pl. 146-146 ,.

Found,%: C 48.91; H 3.24; N 7.37; S 16.5.

Calculated,%: C 48.72, H 3.58;

0 N 7.104; 16.23.

Example 12. (The ratio of the original substance: a nitrating agent -0,9).

Analogously to example 11 of 3.04 g

5 0.02 mol) 4- (thienyl-2) butene-3-one-2 in 20 ml of carbon tetrachloride and 1.4 g (0.022 mol) of nitric acid get 2.76 g (69.7%) of the substance. After recrystallization from alcohol

0 yield of 4- (thienyl-2) -3-nitrobutene-Zone-2 1.20 g (30.21%), mp.145 ,.

Example 13. (The ratio of the original substance: nitrating agent -

5 0.8).

Analogously to example 11 of 3.04 g (0.02 mol) of 4- (thienyl-2) buten-3-one2) in 20 ml of carbon tetrachloride and 1.58 g (0.025 mol) of nitric acid at a temperature of 55-60 ° C

0 get 3.03 g (76.4%) of the substance. After recrystallization from alcohol, 1.28 g (36.62%) of 4-thienyl2) -3-nitrobutene-3-one-2 are obtained with mp 146 C,

Claims (2)

5 yellow lamellar crystals. Found,%: C 48.57; N D, 26; N 6.67; Si 16.10. Calculated,%: C 48, -72; H M a 16.23. Example 14. Obtaining 4- (5methylthienyl - 2) -3-nitrobutene-3-one-2 (Ratio of the original substance: nitrating, 8). Similarly to the previous examples, from 0.498 g (0.003 mol) of 4- (5-methylthienyl-2) Uten 3-one-2 in 5 ml of carbon tetrachloride and 0.235 g (0.00375 mol) of nitric acid at a temperature of 75 ° C, 0.458 g are obtained (72.2%) substances. After recrystallization from heptane, 0.232 g (36.5%) of 4- (5-methylthienyl-2) -3-nitro-butene-3-one-2 are obtained. 109.5-110 ° C in the form of light yellow crystals. Found,%: C, 51.40; H 4.58} K 6.85; S 15.43. Calculated,%: C 51.17; H 4.30 N 6.83; S 15.20. Example 15. Obtaining 4- (5ethylthienyl-2) -3-nitrobuten-3-one-2. (The ratio of the initial substance: nitrating agent is 0.9). Analogously to example 11, from 0.675 g (0.003 mol) 4 (5-ethylthienyl-2) buta 3-she-2 in 7 ml of carbon tetrachloride and 0.21 g (0.003 mol) of nitric acid at a temperature of 15 ° С, 0.686 g (81 , 2%) 4- (5: ethylthienyl-2) -3-nitrobuten-3-one-2. After recrystallization from heptane, 0.368 g (43.6%) of the substance is obtained, with a mp. 139 ° C in the form of yellow crystals and needle crystals. Found,%: C 53.47; H 5.21; N 6.54; S 14.60. Calculated,% C 53,32; H 4.92; N 6.22; S 14.23. The claims of the method for producing -nitro derivatives, p-limiting ketones of the thiophene series of the general formula R C-CO-CH H I H0 where R is hydrogen, methyl or ethyl, wherein 4- (5-C-thienyl-2) butene-3-one-2 of the general formula Pn, cn, cn, where R - has the indicated values and is treated with concentrated nitric acid at a molar ratio of 0.65-0.95 in acetonitrile 1,2dichloroethane or carbon tetrachloride at a temperature from boiling solvent. Sources of information taken into account in the examination, 1.Klimenko V.I. et al., Abstracts of the 6th All-Union Conference on the Chemistry of Nitrocompounds, M., 1977, p.118. 2. USSR author's certificate No. 558917, M., class, C 07 D 495/02, 1977.