DE1173097B - Process for the preparation of 5-nitro-thiazole derivatives - Google Patents

Description

Process for the production of 5-nitrothiazole derivatives. Here, R1 is a mono- or polynuclear aromatic or heterocyclic radical optionally substituted by alkoxy, hydroxy, methylenedioxy, nitro or acylated amino groups or halogen atoms, and R2 is a hydrogen atom or an alkyl or aralkyl radical or a cycloaliphatic, aromatic or heterocyclic group or an optionally etherified hydroxy or mercapto group or an alkyl, aralkyl or aryl sulfone group or an acylated amino group. The process described in the main patent consists in condensing a 4-methyl-5-nitrothiazole substituted in the 2-position by the substituent R2 with an aldehyde of the general formula R1CHO.

In the further processing of the process described in the main patent, it was found that 5-nitrothiazole derivatives of the general formula in the same way in which X has the meaning given above for R2 and Y is represented by alkyl radicals, dialkylamino groups, nitrile groups, carboxy groups, sulfonic acid groups or functional derivatives of carboxy or sulfonic acid groups (e.g. esterified carboxy groups, carbonamide or sulfonamide groups) and optionally also by alkoxy groups , Hydroxy, nitro or acylated amino groups or halogen atoms means substituted mono- or polynuclear aromatic or heterocyclic radicals, can be obtained. The compounds of the formula I and, if appropriate, their salts with inorganic or organic bases are prepared by adding a 4-methyl-5-nitrothiazole derivative of the general formula with an aldehyde of the general formula optionally in the presence of a solvent and preferably in the presence of ammonia or amines or their salts with carbonic acid or carboxylic acids or of alkali alcoholates or amides at elevated temperature and the resulting compounds of the formula 1 optionally converted into their salts with inorganic or organic bases. Particularly suitable solvents are those with a boiling point above 50 ° C.

It is surprising that in compounds of the general formula II under the process conditions the methyl group in the 4-position of the thiazole ring can be easily condensed with aldehydes. Namely, it is known that 2-acetamino-4-methylthiazole when treated with formaldehyde and dimethylamine in the presence of acetic acid supplies the 5-dimethylaminomethyl derivative ("Journal of the American Chemical Society", Vol. 70, 1948, pp. 669 and 670) and that in 2,4-dimethylthiazole and in 2,4-dimethyl-5-phenylthiazole the methyl group in the 2-position of the thiazole ring reacts with benzaldehyde ("Chemical Abstracts", Vol. 32, 1938, So. 16997 or "Helvetica Chimica Acta", Vol. 31, 1948, pp. 1142 to 1158).

All melting points in the following examples are uncorrected.

Example 1 4 g of 2-acetamido4-methyl-5-nitrothiazole are 25 cm3 n-propanol, 3 g of p-cyanobenzaldehyde and 0.5 cm3 of piperidine under reflux for 1 hour cooked.

After cooling, it is neutralized with glacial acetic acid. The crystals formed are suctioned off and boiled with methanol. One obtains in a yield of 560 / o of theory, 2-acetamido-4- (p-cyanstyryl) -5-nitrothiazole which melts at 299 to 300 "C with decomposition.

Example 2 1.8 g of terephthalaldehyde acid are dissolved in 60 cm3 of n-propanol dissolved with warming. Then 2 g of 2-acetamido-4-methyl-5-nitrothiazole and 1 cm3 of piperidine are added, the reaction mixture is refluxed for 1 hour and concentrated it is then reduced to about 25 cm3 in a vacuum. After neutralization with acetic acid, it is filtered off with suction and the residue is boiled with methanol. That which melts above 300 ° C. is obtained in this way 2-Acetamido-4- (p-carboxystyryl) -5-nitrothiazole in a yield of 39 ° 1o of theory.

Example 3 1.8 g of terephthalaldehyde acid are mixed with a solution of 1.5 g of diethanolamine in 20 cm3 of n-propanol and then with 2 g of 2-acetamido-4-methyl-5-nitrothiazole offset. The reaction mixture is refluxed for 2 hours and then evaporated in vacuo. The residue is dissolved in water and acidified with acetic acid. The precipitate is filtered off, dissolved in a little pyridine and filtered. The filtrate is poured into water, acidified with acetic acid, and then the precipitate becomes suctioned off and boiled with methanol. The same product is obtained as in the example 2, but in a yield of 630io of theory.

Example 4 2 g of 2-acetamido-4-methyl-5-nitrothiazole are with 4.5 g of the piperidine salt of benzaldehyde-3-sulfonic acid (obtained from the free acid by neutralizing with piperidine), 20 cm3 n-propanol and 0.5 cm3 piperidine for 1 hour refluxed.

The resulting solution is evaporated to dryness in vacuo and the The residue was dissolved in water with the addition of a little sodium hydroxide solution. After filtering it becomes the filtrate is acidified with hydrochloric acid and the resulting precipitate is filtered off with suction. The residue is treated with sodium bicarbonate solution and after filtering obtained solution acidified with hydrochloric acid. The resulting precipitate is 3- {fl- [2'Acetamido-5'-nitrothiazolyl- (4 ') J-vinyl} -phenylsulfonic acid. yield 27 ° lt, the theory.

Melting point above 300 "C.

Claims (1)

Claim: Process for the preparation of 5-nitrothiazole derivatives of the general formula in which X denotes a hydrogen atom or an alkyl or aryl group or a cycloaliphatic, aromatic or heterocyclic group or an optionally etherified hydroxy or mercapto group or an alkyl, aralkyl or arylsulfone group or an acylated amino group and Y denotes an alkyl group, dialkylamino group, nitrile group , Carboxy groups, sulfonic acid groups or functional derivatives of carboxy or sulfonic acid groups and optionally also mono- or polynuclear aromatic or heterocyclic radicals substituted by alkoxy, hydroxy, nitro or acylated amino groups or halogen atoms, and optionally their salts with inorganic or organic bases, according to the method according to patent 1159450, characterized in that a 4-methyl-5-nitrothiazole derivative of the general formula with an aldehyde of the general formula optionally in the presence of a solvent and preferably in the presence of ammonia or amines or their salts with carbonic acid or carboxylic acids, or of alkali metal alcoholates or amides at elevated temperature and the resulting compounds of the formula 1 optionally converted into their salts with inorganic or organic bases.