DD152937A1 - PROCESS FOR PREPARING SUBSTITUTED 6-AMINO-2H-THIAZOLO [4,5-C] ISOTHIAZOLENE - Google Patents

Abstract

Substituted in 3-position 3-amino-2-thioxo and 6-amino-2-arylimino-2H-thiazolo & 4,5-c! Isothiazole, which can be used as novel intermediates especially for dyes use, according to the invention by cyclo-oxidation of 4-amino-2-thioxo and 4-amino-2-arylimino-thiazoline-5-thiocarbonsaeure-amides, which are obtained by addition of hydrogen sulfide to the corresponding nitriles, the thioxo compounds are also available in one stage from isothiocyanates, sulfur and Cyanacetthioacetamid available.

Description

223797

Process for the preparation of substituted 6-amino-2H-thiazolo [4, 5-o] isothiazoles

Field of application of the invention

The invention relates to a process for preparing 3-substituted-6-amino-2-thLo: xo- and 6-amino-2-aryliminothiazolo [4,5-c ·] isothiazoles Such compounds can be used as intermediates, in particular for the synthesis of IParbstof - / fen, be used. /

Characteristic of the known technical solutions

It is known that substituted 6-aminothiazolo [4,5-c] isothiazoles can be prepared by oxidative cyclization of 4-aminothiazole-5-thiocarboxylic acid aeid, namely according to Liebigs Ann. Chem. 1979 »1271 so 3 compounds of this system have been synthesized, the preparation of the precursors is sometimes relatively expensive. 3-substituted 2H-6-aminothiazolo [4 *, 5-c] isothiazoles as well as other, related thiazolo [4,5-c] isothiazoles have not previously been described in the literature.

Object of the invention

The aim of the invention is to prepare 6-amino-2H-thiazolo [4,5-c] isothiazoles in a simple manner.

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Explanation of the invention of the invention

It is an object of the invention to make available novel 2,3-disubstituted 6-amino-2H-thiazolo [ ^z , 5 "-c] isothiazoles by a simple process the title compounds of the formula I in which R is a

NH ₁ '

Represents an alkyl or C 1 -aryl radical and X represents a sulfur atom or an arylimino group, by cyclooxidation of substituted C 3 -aminothiazoline-C 1 -thiocarboxamides of the formula II,

NH

^ττ

preferably with hydroperoxide. The thioamides II are in turn obtainable by addition of hydrogen sulfide to the 4 ~ amino-5-cyanthiasolines of the formula III, where

in the formulas II and III, R and X have the abovementioned meaning. Optionally, the 4-amino-2-thioxo-thiazoline-5-thiocarboxamides of formula II in which X represents a sulfur atom may also be prepared from gyantioacetamide, sulfur and isothiocyanates in one step. The nitriles of the formula III are according to J. Pralct. Chem. [4] ^, 26 (1966) easily representable. ,

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embodiments

Example 1: 6-Amino-3-methyl-2-thioxo-2H-thiazolo [4-, 5-c] iso-thiazole

a) In a mixture of 0.05 mol of methyl isothiocyanate, 0.05 g atom of sulfur, 0.05 mol of malononitrile and 12 ml of dimethylformamide 6 ml of triethylamine are added dropwise with stirring so that the temperature does not exceed 50 ⁰ O. After 1.5 hours, it is stirred into 200 ml of water, filtered off with suction and recrystallized from DIvIP / »Yasser. 10 mmol of the thus obtained 4-amino-3-methyl-2-thioxo-thiazoline-5-thiocarbonsäureamides (Yield 58 % m.p. 25O-252 ⁰ O) are dissolved in a mixture of 25 ml of dimethylformamide and 8 ml of triethylamine. At 4-0 ⁰ G is added dropwise 6 g 3Oproz. Hydroperoxide too. After standing at room temperature for one hour, it is stirred into water and filtered with suction. Y. 80%, m.p. «258-260 ⁰ C ⁽¹ DME / water).

b) A solution of 10 mmol of 4-amino-5-oyan-3-ethylthiazoline-2-thione and 3 ml of triethylamine in 14 ml of iyridine is saturated with .H ^ S. After standing for 10 hours in a closed vessel at room temperature, about 150 ml of water are stirred in and filtered off with suction. Y. 75%, mp 249-251 ⁰ C (from formamide). The resulting crude 4-amino-3-methyl-2-thioxo-thiazoline-5-thiocarbonsäureamid is further processed according to a)

Example 2: 6-Amino-3-phenyl-2-thioxo-2H-thiazolo [4-, 5-c] isothiazole

a) A solution of 10 mmol of 4-amino-5-cyano-3-phenylthiazolin-2-thione in 14 ml of pyridine is saturated after addition of 3 ml of triethylamine with hydrogen sulfide and allowed to stand in a closed vessel for 10 hours. Thereafter, it is stirred into water and filtered with suction. 10 mmol of the thus obtained crude 4-amino-5-phenyl-2-thioxo-thiazoline-5-thiocarbonsäureamids (yield 87 % \ mp 239-24-1 ⁰ G, carefully recrystallized from glacial acetic acid) are dissolved in 20 ml of dimethylformamide. After addition of 3 liters of triethylamine is added dropwise at 4-0 ⁰ G 6 30proz. Hydroperoxide slowly too. After 1 hr. Standing at

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Room temperature is stirred into 250 ml of water and filtered with suction. Y. 72%, mp 209-211 ⁰ C (from N-propyl alcohol).

b) 6 ml of triethylamine are slowly added dropwise at about 20 ° with stirring to a mixture of 0.05% phenyl isothiocyanate, 0.05% sulfur, 0.05% cyanogen acetamide and 10 ml dimethylformamide. After stirring for a further 2 hours, it is stirred into 150 ml of water and filtered with suction. The dry, crude or from DLIP / water recrystallized 4-amino-3-phenyl-2-thioxo-thiazoline-5-thiocarbonsäureamid is further processed as indicated above under a),

Example 3: 6-Amino-3-benzyl-2-thioxo-2H-thiazolo [4,5-c] isothiazole

10 mmol 4-amino-3-benzyl-2-thioxo-thiazoline-5-thiocarboxamide (mp. 249-252 ⁰ C of n-propanol, prepared analogously to Example 1a with 80% yield or analogously to Example 1b with 73% yield) are dissolved in a mixture of 30 ml of dimethylformamide and 8 ml of triethylamine. Is added dropwise at 40 ⁰ C slowly with stirring 6 g 3Oproz «hydroperoxide. After standing for one hour at room temperature, about 200 ml of water are stirred in and filtered with suction. Y. 52 %, mp. I68-I70 ⁰ C (from ethanol).

Example 4: ö-Amino-ethoxycarbonylmethyl-thioxo-H-thiazolo [4,5-c] isothiazole

To one solution of 10 mmol 4-amino - ^ - ethoxycarbonylmethyl ^ - thioxo-thiazoline-5-thiocarbonsäureamid (mp 204-206 ⁰ C from n-propanol, prepared analogously to the procedure given in Example 1a or 1b rule) is added dropwise after addition of 2 ml of triethylamine slowly 6 g 30proz. Hydroperoxide at 40 ⁰ C to. After 0.5 hours standing at room temperature, it is stirred into water and filtered off with suction. Y. 60%, mp 181-183 ⁰ C from ethanol.

Example 5: 6-Amino-2-anisylimino-3-phenyl-2H-thiazolo [4,5-c] isothiazole

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A solution of 10 mmol 4-amino-cyanothiazolin-1-one-anisylimin (mp 196-198 ⁰ C) in 15 ml of iyridine is saturated after addition of 3 ml of triethylamine with IL) S and 2.5 hr. left in a closed container. Thereafter, the mixture is stirred in 150 ml of water and filtered with suction. Y. 76 %, m.p. 14-5-147 ⁰ C (from dil. Glacial acetic acid). 10 mmol of this crude product are dissolved in a mixture of 10 ml DIIF and 3 al triethylamine and slowly with stirring at 40 ⁰ C 6 g 30proz. Hydroperoxide added dropwise. After one hour of stirring at room temperature, about 1 50 ml of water is stirred in and filtered off with suction. The crude product is dissolved in a little hot methanol and triturated until incipient crystallization. After I5 min. Sucked off. Y. 60% _t mp. 162-165 ⁰ O.

Example 6: 6-Amino-2-anisylimino-3-methyl-2H-thiazolo [4,5-c] isothiazole

10 mmol 4-amino-5-C3 ^ -an-3-methylthiazolin-2-one-anisylimin (mp 169-17Ί ⁰ C) are as described in Example 5 to 6-amino-2-anisylimino-3-methylthiazolin-5 -thiocarbaraid reacted (yield 90%, mp 185-187 ⁰ O from ethanol) and this then oxidized according to the procedure given in Example 5 and worked up. The crude product is recrystallized from ethanol. Yield _68%% Schnp. 161-163 ⁰ G.

Example 7J 6-Amino-p-aminophenylimino-3-phenyl-2H-thiazolo [4,5-c] isothiazole

After the Torschrift given in Example 5, 10 mmol of 4-amino-5-cyano-3-phenylthiazolin-2-one (p-aminophenyl) imine (mp. 96-100 ⁰ C) to ^ Aniino ^ -p-phenylimino ^ -phenyltüiazolin-5-thiocarbanid (yield 72 %, mp 165-169 ⁰ G from n-propyl alcohol), which is oxidized as described in Example 5. The dark colored crude product is recrystallized from ethanol with the addition of a little dithionite. Dark colored crystals of mp. 171-173 ° C, Ausb. 48 %.

Claims (2)

-6- 2 2 3 7 9 7- Claim 1 _β Process for the preparation of substituted 6-amino-2H-thiazolo [4-, 5-c] isothiazoles of the formula I, wherein R is a Lr or aryl radical and X represents a sulfur atom or an arylimino group, characterized in that 4-aminothiazoline ~ 5 "- fckiocarbonsäureamide of formula II, which by NH, Addition of hydrogen sulfide to 4-aminothiazoline-5-carbonitriles of the formula III are prepared in solution III be treated with an oxidizing agent, preferably hydroperoxide, wherein in the formulas II and III E and X have the meaning given above. 2 · ^ Experienced according to item 1, characterized in that the amino-2-thioxo-thiazolin-'4-thiocarbonsäureamide of the formula II, wherein X is a sulfur atom, optionally also from Cyanthioacetamid (NG-CH ₂ -CSITHp), sulfur and isothiocyanates of the formula 17 where R is an alkyl or aryl group. RN = C = S 17
suggests being made in one step.