DD220309A1 - PROCESS FOR THE PREPARATION OF N, N-DISUBSTITUTED 5-AMINO-4-ARYLPYRAZOLENE - Google Patents

Abstract

Such compounds have significance as potential biologically active substances, the invention of which is to achieve the previously unknown N, N-substituted 5-amino-4-arylpyrrazole in a simple manner. THIS HAPPENS IN THE MANNER THAT 3-HYDRAZINOTHIOACRYLIC ACID AMIDE IN A SOLVENT AT TEMPERATURES BETWEEN 20 AND 200 DEGREES, IF ANY, IS CARRIED OUT IN THE PRESENCE OF AN ALKYLATION AGENT TO THE N, N-DISUBSTITUTED 5-AMINO-4-ARYLPYRAZOLES OF GENERAL FORMULA I. THE INVENTION CAN BE USED IN THE CHEMICAL AND PHARMACEUTICAL INDUSTRY.

Description

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Process for the preparation of Μ, Ν-disubstituted 5-amino-4-arylpyrazoles

Field of application of the invention

The invention relates to a process for the preparation of N, 1-disubstituted 5-amino-4-arylpyrazoles. Such compounds are important as potential biological agents,

Characteristic of the known technical solutions

It is known that 5-dimethylamino-4 ~ be arylpyrazoles by UmsBfczung of 2-Cnlorcarbonylverbindungen produced with thiosemicarbazides [H.Beyer, H.Honek, I.Reichelt: Liebigs Ann, 741/45 (Τ978) ^] ₀ The known process has the disadvantage that only 5-amino-4-arylpyrazoles can be synthesized which are unsubstituted on the ring nitrogen and which always carry a substituent in the 3-position *,

Object of the invention

The aim of the invention is to make available N, N-disubstituted 5-amino-4-arylpyrazoles which have a free 3-position and may be substituted on the ring nitrogen »

Explanation of the essence of the invention

The object of the invention is a simple process for the preparation of N, W-disubstituted 5-amino-4-arylpyrazoles

which makes it possible to synthesize representatives which have a free 3-position and may also be substituted on the ring nitrogen.

According to the invention, this object is achieved in that a 3-Hydrazinothioäcrylsäureamid the general formula I.

BM-NH-CH-CC-NR ² R ³

in "a" solvent such as glacial acetic acid, acetonitrile, dioxane, methanol, ethanol, propanol, ethylene glycol or dimethylformamide at temperatures between 20 ° and 200 ° and optionally in the presence of an alkylating agent such as methyl iodide or dimethyl sulfate N, N-disubstituted 5-amino-4-arylpyrazole of the general formula II,

II

J ^ ¹ NR ² R ³ N "^ N- ^

i -. : ·. ,

where in the general formulas R is the hydrogen atom, an alkyl radical or a substituted or unsubstituted phenyl radical, R is a substituted or unsubstituted phenyl radical and R and R · are identical or different

'': '' · "-."'''''' O ^ ''

Alkyl radicals or RR together a tetramethylene, .Pentarnethylen- or 3 ^ 0xapentamethylenbrUcke mean, is reacted, l

The process according to the invention makes it possible to synthesize in a surprisingly simple manner N, N-disubstituted 5-amino-4-arylpyrazoles which have a free 3-position and may also be substituted on the ring nitrogen. Thus, it is possible to make novel compounds accessible by the method according to the invention, which can expect interesting biological properties. The 3-hydrazinothiacrylacrylamides used can be conveniently prepared, for example, from 3-amino or 3-hydroxythioacrylic acid amides and hydrazines.

embodiments

The Ν, Ν-disubstituted 5-amino-4-arylpyrazoles of general formula II prepared according to the various variants are compiled in Table 1.

option A

A mixture of 0.0 mol of 3-hydrazinothioacrylamide of the general formula I and 20 ml of glacial acetic acid is refluxed for 5 hours. Each dem, Ν-disubstituted 5-amino-4-arylpyrazole of the general formula II is filtered off with suction and recrystallized.

Variant B

A mixture of 0.01 mol of 3-hydrazinothioacrylamide of the general formula I and 10 ml of methanol is mixed with 1.3 g of dimethylsulfate and then refluxed for one hour. The final product of the general formula II which precipitates on cooling is filtered off with suction and recrystallized.

Variant C

Analog variant B, but 2 g of methyl iodide are used instead of the dimethyl sulfate ·

Variant D

A mixture of 0.011 mol of 3-hydrazinothioacrylamide of the general formula I and 15 ml of ethanol is refluxed for 15 minutes. The final product of the general formula II, which may be obtained from the cooled reaction mixture only when diluted with water, is filtered off with suction and recrystallized.

Variant E ^

Analog variant D, but 15 ml of acetonitrile are used instead of the ethanol.

    ,. ·. -4-. , , , ..-

Table 1t The N _t N-disubstituted 5-amino-4-arylpyrazoles of the general formula II prepared by the various variants

R R ¹ R ² p3 Xl Xv Aueb./Var. / * ' Schmp./°C C ₆ H ₅ ° 6 ^H 5 (CH ₂ > ₂ O (CH ₂ ) 2 35 / B 78 / A 206 ^v (methanol) P-NO ₂ C ₆ I I ₄ -C ₆ Hj. \ CHp / oO ν CHp / ρ 57 / B 537C 219 (glacial acetic acid) H P-ClC ₆ H ₄ CH ₃ CH ₃ 4Ti / D 58-6T (gasoline) H P-CH ₃ C ₆ H ₄ (CHg) ₂ O (CH ₂₎ 2 97 / E 136-1138 (petroleum ether)

Claims (3)

invention claim 1. Process for the preparation of N, N-disubstituted 5-amino-4-arylpyrazoles of the general formula II » R ² R ³ ET II in the R, the hydrogen atom, an alkyl radical or a substituted or unsubstituted phenyl radical, R is a substituted or unsubstituted phenyl radical and R and R ^ are identical or different alkyl radicals or Rr together form a tetramethylene », pentamethylene or 3-oxapentarnethylene bridge, characterized '^; in that a 3-hydrazinothioacrylamide of the general formula I RNH-NH-CH = OC-NR ² R ³ I is reacted with the meaning explained for R, R ¹ , R ² and R ³ or R ² R ³ in a solvent at temperatures between 20 and 200 ° and optionally in the presence of an alkylating agent 2. The method according to item 1, characterized in that the solvent used is, for example, glacial acetic acid, acetonitrile, dioxane, methanol, ethanol, propanol, ethylene glycol or dimethylformamide. 3. The method according to item 1, characterized in that is used as the alkylating agent, for example, dimethyl sulfate or methyl iodide ·