CH288889A - Process for preparing a derivative of 1,2,4-triazine. - Google Patents

Description

Process for preparing a derivative of 1,2,4-triazine. Derivatives of 1,2,4-triazine of the general formulas wherein R is a substituted aryl radical, X1 is hydrogen or an alkyl, aralkyl, aryl, heterocyclic or carbacyl radical, and X2 and X3 are hydrogen, alkyl, aralkyl, aryl or heterocyclic remainders have not become known up to now. As found

they can serve as intermediates or as medicines. .

One can synthesize the new compounds by preparing thiosemicarbazones from a-keto acids of the general formulas

or their reactive functional derivatives are treated with ring-closing agents and then optionally treated with alkylating, aralkylating or acylating agents for the subsequent introduction of the radicals Xi and X3. Examples of suitable ring-closing agents are alkalis, such as solutions of sodium carbonate, potassium carbonate or sodium hydroxide; Compounds substituted in the mercapto group are converted into the desired triazine derivatives without further additives on heating in alcohol. Reactive esters of aliphatic and araliphatic alcohols in the presence of alkalis are suitable as alkylating and aralkylating agents. Examples include methyl iodide, dimethyl sulfate, methyl toluenesulfonate, ethyl bromide, diethyl sulfate,

5, Sodium ethylsulphate, propyl chloride, isopropyl bromide, allyl bromide and benzyl chloride called.

Examples of suitable acylating agents are acetyl chloride, acetic anhydride, ketene and benzoyl chloride and their homologues and substitution products, as well as, for example, chloroformic esters and dialkylcarbamic acid chlorides.

The agents mentioned react first with the mercapto group, if this is free, and secondly, the hydrogen atom in the 2-position is substituted.

The thiosemicarbazones of a-keto acids or their reactive functional derivatives required as starting products can, for example, be prepared in the usual way from the a-keto acids or their functional derivatives and thiosemicarbazide or substituted thiosemicarbazides produce. In addition, thiosemicarbazones substituted in position 4 can also be prepared, for example, by first converting the a-keto-s5,urene or their reactive functional derivatives into the hydrazones and reacting these with isothiocyanates, in particular alkyl mustards.

Substituted phenylglyoxylic acids and naphthylglyoxylic acids are generally suitable as a-keto-s5 acids. Substituents which may be mentioned are, for example: alliyl and alkoxy groups, alkylmercapto groups and their oxidation products with tetravalent or hexavalent sulfur, halogens, nitro groups, amino groups and substituted amino groups, where the N atom can also be included in a ring, acylamino, Ureido and thioureido groups, oxy and esterified oxy groups, carbalkoxy, carbamido (carb i amyl) and suhamido groups (siffamyl groups). Particularly suitable are: 2-, 3- and 4-chloro-phenyl-glyoxyl-5-acid, 4-methyl-phenyl-, 4-ethyl-phenyl-, 4-methoxy-phenyl-, 3,4-dimethoxy-phenyl-, 4 -nitro-phenyl-,. 2,4-dinitro-phenyl, 4-amino-phenyl, 4-acetylamino-phenyl, 4-oxy-phenyl, 2,4-dioxy-phenyl, 2-acetoxy-phenyl, 4-carbâthoxy-phenyl -glyoxylic acid.

Substituted thiosemicarbazides which may be mentioned are: 2-methyl, 2-thyl, 2-allyl, 2-butyl, 2-benzyl, 2-phenyl thiosemicarbazide; S-methyl, S-propyl, S-benzyl thiosemicarbazide; 4-methyl, 4-ethyl, 4-isopropyl, 4-allyl, 4-isoamyl, 4-benzyl, 4-phenS,thyl, 4-phenyl, 4-p tolyl, 4-p-anisyl-, 4-pyridyl-(f)methyl-, 4-furfuryl-thiosemicarbazide; 2-methyl-S-methyl-, 2-thyl-S-benzyl-thiosemicarbazide; 4-methyl-S-phenyl-, 4-t-Ilyl-S-ethyl-thiosemicarbazide, 2,4-dimethyl-, 2-benzyl-4-5-ethyl-thiosemicarbazide; S-acetyl-thiosemicarbazide.

Some of the a-keto-s5 acids and thio semicarbazides listed are known; in any case they can be prepared according to the methods described for the preparation of the known compounds in the literature.

The subject matter of the present patent is a process for the production of a derivative of 1,2,4-triazine. The process is characterized in that 6-(4'-amino-phenyl)-3-mercapto-2,5-dihydro-1,2,4-triazin-5-one is acetylated. The new compound obtained, 6-(4'-acetamino-phenyl)-3-mercapto-2,5-dihydro-1,2,4-triazin-5-one, melts at 350 in ter decomposition. It is said to find therapeutic uses.

<I>Example:</I> 22 parts of 6-(4'-amino-phenyl)-3-mercapto-2,5-dihydro-1,2,4-triazin-5-one, which can be prepared from the 4- amino Phenyl-glyoxylic acid -thio-semicarbazone by treatment with ring-closing agents are suspended in 200 parts of glacial acetic acid, 15 parts of acetic anhydride are added at room temperature with stirring and the mixture is heated to 60 to 70 for 2 hours. After cooling, 100 parts of ice water are added and 200 parts of conc. Ammoniali admitted. The precipitate is filtered off and washed with water. After recrystallization from 80% dioxane, 6-(4'-acetaminophenyl)-3-mercapto-2,5-dihydro-1,2,4-triazin-5-one is obtained from the melting point about 350 enter decomposition.

Claims (1)

PATENT CLAIM: Process for the preparation of a derivative of des-1,2,4-triazine, characterized in that 6-(4'-amino-phenyl)-3-mercapto-2,5-dihydro-1,2,4 -triazine-5-one acetylated. The new compound obtained, 6-(4'-acetaminophenyl)-3-mercapto-2,5-dihydro-1,2,4-triazin-5-one, melts at 350 with decomposition.