SU407905A1 - METHOD OF OBTAINING 4-AMINOMETHYLTIAZOL-2-TAL - Google Patents

Description

one

A method of producing 4-aminomethyl-2alkyl- or arylthiazoles is known, which consists in reacting the corresponding 4-chloromethyl-2-alkyl- or arylthiazole with the corresponding amine.

Using the known method, the authors obtained a series of new 4-aminomethylthiazol-2-ols derivatives having biological activity different from those of the known compounds.

A method for the preparation of 4-aminomethylthiazol-2-ols of the general formula is provided.

BUT

 - {

Oh

where A is the residue of polymethylenimine with the number of methylene groups 4-6, the residue of morpholine or dialkylamine with the number of carbon atoms in alkyl up to 2,

in that 4-chloromethylthiazol-2-OL is reacted with an appropriate amine in an organic solvent medium, followed by isolation of the target product in a known manner. Typically, 4-chloromethylthiazol-2-ol is dissolved in an organic solvent, preferably in dioxia, and the resulting solution is mixed with a solution of the corresponding amine (two equivalents) in that solvent. If volatile amines are used, it is preferable to introduce them directly into the gaseous form of 4-chloromethylthiazol-2-ol.

The process is usually carried out at 15-70 ° C. To accelerate the reaction when using low volatile amines, it is recommended to heat the reaction mixture to 60-70 ° C for 5-20 minutes.

Example 1. 5.98 g (0.04 mol) of 4-chloromethylthiazol-2-ol is dissolved in 50 ml of dioxane and at 20-60 ° C (with a gradual warming of the reaction mass on a water bath) is passed through a solution of dry dimethylamine in for 20 minutes in an amount of 0.1 mol. Crystals of hydrochloric dimethylamine are gradually released. 30 ml of benzene are added, cooled to 10 ° C and filtered. The solution is evaporated in vacuo and the residue is crystallized from heptane. After several repeated recrystallizations from heptane, 1.6 g (25%) of colorless crystals of 4-dimethylaminothiazol-2-ol, m.p. 124-126 ° C.

Found,%: C 45.95; H 6.65; N 17.92. CeHioNaOS.

Calculated,%: C 45,55; H 6.37; N 17.71. Example 2. 7.48 g (0.05 mol) of 4-chloromethylthiazol-2-ol is dissolved in a mixture of 100 ml of benzene and 50 ml of dioxane. 7.8 g (0.1 mol) of diethylamine was added to the solution and heated at 60-70 ° C for 15 minutes. Crystals of hydrochloric acid diethylamine are isolated. The mass is cooled to 10–15 ° C, the precipitate is separated, the solution is evaporated to a volume of 30 ml, cooled to 10–15 ° C, as a result the precipitate of diethylamine hydrochloride is separated and the filtrate is evaporated to dryness in vacuum. A few milliliters of ether are added and the mixture is triturated with a glass rod while cooling until crystallization. The product is separated and crystallized from ethanol. Obtain 4 g (43%) of colorless crystals of 4-diethylaminomethylthiazol-2-ol, so pl. 88-89 ° C.

Found,%: C 51.16; Pi 7.69; N 15.05.

CgHuNaOS.

Calculated,%: C, 51.58; H 7.45; N 15.04.

Example 3. 5.98 g (0.04 mol) of 4-chloromethylthiazol-2-ol is dissolved in 50 ml of dioxane and 6.8 g (0.08 mol) of piperidine is added to the solution.

The mixture is heated at 60-70 ° C for 15 minutes, the piperidine hydrochloride crystals are separated and the solution is evaporated to dryness in vacuo. The residue is extracted with boiling benzene (a small amount of piperidine hydrochloride remains), and the solution is evaporated. The product is crystallized from a mixture of benzene and hexane (1: 1). Obtain 3.2 g (40%) of colorless crystals of 4-piperidinomethylthiazole 2-ol, so pl. 153-154C.

Found,%: C 54.10; H 7.17; N 13.77.

CgHnNaOS.

Calculated,%: C 54.54; H 7.12; N 14.14.

Example 4. 2.99 g (0.02 mol) of 4-chloromethylthiazol-2-ol are dissolved in 20 ml of dioxane. 3.48 g (0.04 mol) of morpholine is added to the mixture and heated at 60-70 ° C for 20 minutes, cooled until the hydrochloric acid morpholine is separated and the filtrate is evaporated in vacuo. After recrystallization from benzene, 2.82 g (70%) of colorless crystals of 4-morpholinomethylthiazol-2-ol, m.p. 189-190 ° C.

Found,%: C 47.81; H 6.20; N 14.06.

C8Hi2N2O2S.

Calculated,%: C 48.00; H 6.05; N 14.00.

Prev Invention of Invention

1. The method of obtaining 4-aminomethylthiazole-2oloB of the general formula

where A is the residue of polymethylenimine with the number of methylene groups 4-6, the residue of morpholine or dialkylamine with the number of carbon atoms in the alkyl up to 2,

characterized in that 4-chloromethylthiazol-2-ol is reacted with an appropriate amine in an organic solvent medium, for example dioxane, followed by isolation of the target product by a known method.

2. A method according to claim 1, wherein the process is carried out at 15-70 ° C.