SU1133268A1 - Process for preparing beta-alkylthiobutanones - Google Patents

Abstract

METHOD OF OBTAINING / E-ALKYL-THIOBUTANONES of the general formula RSCHnCHgCCH,,; "O where R, H-C3H2, H-C4H9, n-C5H, 1, ..., H-C5H, H-C7H, 5, C-CdH 7 J based on ketone, methyl bromide and sulfur-containing compound in the presence of water, characterized by that, in order to increase the yield and expand the range of target products, thiourea is reacted with alkyl bromide in an aqueous-alcoholic medium in the presence of sodium hydroxide and pyridine at boiling, followed by sequential treatment of the resulting reaction mixture with formaldehyde at room temperature and acetone in the presence of sodium bicarbonate at 50-55 ° C and mo Flax ratio of thiomogane: alkyl bromide: caustic soda:: formaldehyde: acetone; sodium bicarbonate equal to 1: 1: 2.2-2.5: 1.2-1.4: 10-12, 5: 1.4 -1.8.

Description

with so to

Od 00 The invention relates to an improved method for the production of p-alkylthiobutanoic in total fornula RS-CH CHgCOCH,, I where R is a normal alkl of 2-8 carbon atoms that can be used as starting materials for the synthesis of biologically active compounds, in particular 2 -methyl-2- (2-E-thio) ethyl-1,3-dioxolanes with anticonvulsant and hypnotic effects. A known method for the preparation of representatives of B-alkylthiobutanones of formula (1), and of genetically -button thiobutanone, is that methylvinyl ketone is reacted with butschercaptan under irradiation. The disadvantage of this method is the use of expensive and poisonous mercaptan in it. The closest to the invention is a method for producing ft -buttibutanone, in which methyl vinyl ketone is reacted with butyl bromide and sodium sulfide, taken in a molar ratio of 1: 1-2: 1-3, in an aqueous medium at 45 -70 С, Впсод 37% 2. The disadvantages of this method are the low yield, as well as the limited amount of target products obtained. The purpose of the invention is to increase the input and the expansion of the range of target products. This goal is achieved by the fact that, according to the method of producing (3-kiltiobutanones) of the general form (I), thiourea is reacted with alkyl bromide in an aqueous-alcoholic medium in the presence of sodium hydroxide and pyridium while boiling followed by sequential processing of the resulting reaction mixture at room temperature and with acetone in the presence of sodium bicarbonate at 50-55 ° C and a molar ratio of thiourea: alkyl bromide: sodium cesium: formaldehyde: acetone: sodium bicarbon, equal to 1: 1: 2.2-2.5: 1, 2-1, 4: 10-12,5: 1,4-1,8. With the indicated molar ratio of the reactants, the highest yields of the target products are achieved. The use of a ratio of reactants smaller than the indicated limits causes a decrease in the yield (experiments 2, 3, 12, and 13, Table 1); exceeding these limits does not lead to an increase in yield (experiments 6 and 16, Table 1). Carrying out the process at a temperature of less than 50 ° C leads to a decrease in yield (experiments 7, 8, 17, and 18, Table 1). The upper limit of the reaction temperature is limited by the boiling point of the starting acetone. The advantages of the proposed method are an increased yield (with R C4H9 and obtaining new compounds the form in (1), where R H-CjHj,, HC | Hjj, H-CgH, which expands the range of target products. Example 1, 1-amylthio -3-butanone. To the mixture obtained after 4-5 hours of boiling 38 g (0.5 M) of thiourea, 75.5 g (0.5 M) of amyl bromide, 100 ml of ethanol and 2 ml of pyridine, 44 g (1.1 M) sodium hydroxide and 75 ml of water, mix and boil the resulting solution for 1-1.5 hours. After cooling, 45 ml (0.5 M + 20% g) 35% g are added to it. solution of formalin and 25 ml of water. After a vigorous stirring, 365 ml (5 M) of acetone and 60 g (0.71 M) of sodium bicarbonate are added to the suspension heated to 50-55 0 C. The reaction mixture is stirred at a given temperature for another JO minutes. the mixtures are separated from the water-salt organic layer. The latter is washed with ether (50 ml-3). The ether extracts are combined with the organic layer and washed successively with a saturated solution of sodium chloride (100 ml 3), 5% HCl (50 ml 3 ) and again with a solution of sodium chloride to a neutral environment. The ether extract is dried over anhydrous magnesium sulfate. After removal of the solvents, the reaction product is fractionated in vacuo. The product yield was 53.24 g (61.2%), bp. 103-104 ° C (4 mmHg), p 1.4780, d 0 ,. R found 52.3. MR calculated 51.95. ol.ves. 174. Found,%: C 62.02; H 10.48; S 18.12. C, H ,, OS

Calculated,%: C 62.017 -, H 10.408; S 18,395.

Example 2. 1-heptylthio-3-buta non. Analogously to Example 1 and 39 ml (0.25 M) of heptyl bromide, 19 g (0.25 M) of thiourea, 50 ml of ethanol, 1 ml of pyrvdine, 22 g of NaOH (0.55 M), 22.5 ml of 35% - Formalin, 160 ml (2.5 M) of acetone, 30 g (0.355 M) of sodium bicarbonate, 39.4 g (78%) of 1-heptylthio-3-butanone are obtained.

The product has t, kip. 119-120C (2 mmHg), p 1.4680, 9090. MR found 61.80. MR calculated 61.24 Mol. 202.

Found,%: C 65.31; H 11.08; S 15.53.

C, H, jOS

Calculated,%: C 65.29, H 10.54; S 15.84.

Analogously to example 1 and 2, other p-alkylthio-butanones were obtained, the constants and outputs of which are listed in Table 2. Thus, the proposed method for the production of A-alkylthio-3-butanones makes it possible to increase, by comparison with known yield, of the target products and to expand the range of compounds that are starting materials in the synthesis of biologically active 2-methyl-2- (2-E-thio) ethyl -1,3-dioxolanes.

Table 2

Cj, H -s-eH2-eH2-co-CHj

C H -S-CH-CH -CO-CHj, OS

 -S-CH -CH -CO-CHg CgH, gOS

SbH, -8-CH2-CH2-CO-CH

CgH, y-S-CH -CHg-CO-CHg,

Substance C Hj-S-CHjj-CHjf-ObCHg 0.9589 30

1.4750

1.4752

1.4774

1.4679

1,4692

Continuation of table 2 38,6838,006

Claims (1)

METHOD FOR PRODUCING / 3-ALKILTIO- BUTANONES of the general formula Y5CH ₂ CH ₂ CCH ₃ , where R = C _? Н ₅ , Н-С ₃ Н _g , Н-С ^ Н ₁₃ , н-Cj Н ₁₅ , Н-J based on ketone, alkyl bromide and sulfur-containing compound in the presence of water, which is characterized by the fact that, in order to produce a yield and expanding the assortment of target products, thiourea is reacted with bromine alkyl in an aqueous-alcoholic medium in the presence of sodium hydroxide and pyridine during boiling, followed by sequential treatment of the reaction mixture with formaldehyde at room temperature and acetone in the presence of sodium bicarbonate at 50-55 C and molar thiomach ratio wine: alkyl bromide: sodium hydroxide:: formaldehyde: acetone: sodium bicarbonate, equal to 1: 1: 2.2-2.5: 1.2-1.4: 10-12.5: 1.4-1.8 .