DE2248175A1 - 3-AMINO-4,5,6-TRICHLORO-7-NITRILOINDAZOLE - Google Patents

Description

Troisdorf, September 29, 1972

DYNAMIT NOBEL AKTIENGESELLSCHAFT Troisdorf, District Cologne

"3-Amino-4,5, ö-trichloro-y-nitrilo-indazole"

The present invention relates to 3-amino-4,5,6-trichloro-7-nitrilo-indazoles and a method for producing these compounds.

There are already 3-aminoindazoles and their N derivatives known, those in the 4- or 5-position by chlorine, bromine or the trifluoromethyl group are substituted. These compounds can, inter alia, by reacting an o-halobenzonitrile with hydrazine or a Hydrazine derivative produced v / earth with the reaction temperature is preferably above 45 ° C and hydrochloric acid is necessary as a catalyst for the cyclization reaction. These connections are used as pharmaceuticals directly or in the form of their salts.

The present compounds are those of the general formula

k 0 9 8 H / 1 1 7.8

where R is hydrogen or a C, C alkyl or chloroalkyl radical or represents an optionally alkyl-substituted phenyl radical.

The compounds can also occur in the isomeric form, which is characterized by the following formula, their formation but for reasons of reaction kinetics it is less favored:

in which R has the meaning given above.

These compounds are prepared in a manner known per se by reacting tetrachloroisophthalic acid dinitrile with hydrazine or derivatives of hydrazine of the general formula HpN-NHR, in which R has the abovementioned meaning. In principle the reaction also succeeds if R also stands for other radicals, such as polynuclear phenols or longer alkyl chains, the given

4098 U / 1 1 78

can optionally be halogen-substituted. However, you can Side reactions occur to a greater extent, especially if the radical R contains reactive groups that are analogous competing reaction how the hydrazine group can enter into and if the reaction rate this eventual Side reaction of such a group is greater than that of hydrazine.

Because of the presence of two nitrile groups in the second starting compound, it is necessary that the reaction is carried out at the lowest possible temperature so that only one of the two nitrile groups reacts with the hydrazine. Surprisingly, the reaction succeeds even at temperatures between 10 and 50 ^° C. with yields of over 90 % without the use of a catalyst, if it is carried out in a suitable solvent.

Suitable solvents are those compounds in which the starting compounds are readily soluble and in which the resulting compounds End products are sparingly soluble at room temperature. In general, dioxane is particularly suitable, either as a pure one Isomer or as a mixture of isomers. In special cases, the reaction can also take place in lower alcohols, acetone or acetonitrile be carried out as a solvent.

The hydrogen chloride released in the reaction is preferred intercepted with excess hydrazine. But it can also be achieved by adding other bases, such as soda or

Triethylamine, neutralize.

4098 U / 1 1 78

The end product crystallizes out of the reaction mixture and is already very pure after washing with water. When using dioxane as the solvent, the yields are over 90 % and are thus considerably higher than in analogous processes for the preparation of halogen-substituted aminoindazoles, which use dimethylformamide as the solvent at temperatures of 150.degree.

The new 4,5,6-trichloro-7-nitrilo-aminoindazoles and their salts have effects on the central nervous system and can can be used specifically as muscle relaxants, analgesics, antipyretics or as mild sedatives. As a result of being responsive Nitrile groups, which can be saponified or hydrogenated, for example, can be used as starting materials for the new compounds can be used for other complex pharmaceuticals that have the effects mentioned in greater or greater strength show in a weaker way.

The new compounds are mostly yellow in color and have melting points above 200 ^° C., and they often begin to sublime. They form salts with inorganic and organic acids, for example the corresponding hydrochlorides or acetates.

The structure of the new compounds was determined by IR analysis and Nuclear magnetic resonance spectra elucidated; their masses were mass spectrographed certainly.

4098 14/1178

example 1

In a three-necked flask equipped with stirrer, condenser and dropping funnel, 13 * 29 g Tetrachlorisophthalsäuredinitril (0.05 mol) dissolved in 170 ml of dioxane while heating to about 60 ⁰ C. A solution of 5.5 g of hydrazine hydrate (100%, 0.11 mol) is added dropwise to the solution, which has cooled to room temperature. The reaction is slightly exothermic. The mixture was stirred for about 22 hours at room temperature and then the yellow precipitate which had separated out was filtered off, washed with dioxane and water and dried. 12.37 g (= 94.5 % of theory) were obtained.

The crude product was recrystallized from about 9 liters of methanol; 9.41 g (= 72.0 % of theory) of a very pure product with a melting point of 339 to 344 ^° C. (determined in a sealed capillary) were then obtained. Slight decomposition occurred at the melting point.

Gross formula C ₈ H ₃ Cl ₃ N ^, molecular weight 261.50.

Elemental analysis

Calculated: C 36.74 H 1.16 Cl 40.67 N 21.43. Found: C 36.35 H 1.20 Cl ¹ 39.67 N 21.35.

The molecular peak determined by mass spectrometry is 261.

The compound is in the cold, among other things in sulfuric acid, 'trifluoroacetic acid, Tetrahydrofuran, dimethyl sulfoxide, dimethylformamide,

4098 U / 1 1 78

Dimethylacetamide and N-methylpyrrolidine soluble and insoluble, e.g. in dioxane, lower aliphatic alcohols and ethers. In the warmth it is partially soluble in methyl and ethyl alcohol, Dioxane, o-dichlorobenzene, glacial acetic acid.

Example 2

As described in Example 1, 13t29 g of tetrachloroisophthalic acid dinitrile were obtained (0.05 mol) brought to conversion with 11.9 g of phenylhydrazine (0.11 mol) in a dioxane solution. After 22 hours Reaction time, the yellow precipitate was filtered off, washed with dioxane and water and dried.

Crude yield 16.07 g (95.20 % of theory )

It was recrystallized from tetrahydrofuran, dioxane or acetonitrile. Melting point 290 to 296 ° C (determined in a sealed capillary).

Gross formula C ₁₄ H ₇ Cl ₃ N ₄ , molecular weight 337.59.

Elemental analysis

calcd: C 49.81 H 2.09 Cl 31.51 N 16.60 found: C 49.87 H 2.00 Cl 31.15 N 16.62

By differential thermal analysis, this compound had a melting point of 294 ⁰ C and the following weight losses (heating rate 8 ° / min.).:

1% i 3O4 ° C, 5%: 331 ⁰ C, 10% '. 345 ⁰ C, 20 %: 378 ⁰ C.

4098 U / 1 1 78

The product is soluble in the cold, e.g. in dimethylformamide, dimethylacetamide, tetrahydrofuran. In the warmth she is in almost Soluble in all common solvents. Acetonitrile, dioxane, methanol and toluene are suitable for crystallization and recrystallization.

Example 3

As described in Example 1, 13.29 g of tetrachloroisophthalic acid dinitrile were obtained (0.05 mol) brought to conversion with 5.1 g of methylhydrazine (0.11 ml) in dioxane solution .. The precipitated yellow Crystal slurry was filtered off after a reaction time of about 20 hours, washed with dioxane and water and dried.

Yield 12.77 g (92.8 % of theory)

It was recrystallized from acetonitrile or acetone. Melting point 275 to 281 ⁰ C.

Gross formula CQH ₅ Cl ₃ N ^, molecular weight 275.53

Elemental analysis

Calculated: C 39.23 H 1.83 Cl 38.60 N 20.33 Found: C 39.59 H 2.16 Cl 37.66 N 20.20

By differential thermal analysis (. Heating rate 8 ° / min) the substance has a transition point at 256 ⁰ C, a melting point of 281 ⁰ C and the following Gev / layer loss: 1%: 256 ⁰ C, 5%: 304 ⁰ C, 10% : 328 ⁰ C, 20%: 35O ⁰ C.

409814/1178

The connection is in the heat among others in dimethylformamide, Dime thylacetamide, acetone, acetonitrile, chloroform soluble, while they are sparingly soluble in these solvents at room temperature is. Acetone and acetonitrile are suitable for recrystallization.

40981 4/1178

Claims (5)

Claims 1. 3-Amino-4,5,6-trichloro-7-nitrilo-indazole of the general formula in which R is hydrogen, a C ^ -Cg alkyl or chloroalkyl radical, Denotes phenyl or an alkyl-substituted phenyl radical. 2. 3-Amino-4,5, e-trichloro-T-nitrilo-indazole. 1 3. 3-Amino-4,5 »6-trichloro-7-nitrilo-N -methylindazole. 4. 3-Amino-4,5, ö-trichloro-T-nitrilo-N -phenylindazole. 5. Process for the production of ^ - trilo-indazoles according to claim 1, characterized in that tetrachloroisopithalic acid dinitrile with hydrazine or a substituted hydrazine HpN-NHR, in which R has the abovementioned meaning, is reacted in a dioxane solution at 10 to 50 ⁰ C, preferably room temperature, and the precipitated product is isolated in a manner known per se, A098U / 1178
Dr.Sk/Ko