DD290420A5 - PROCESS FOR PREPARING SUBSTITUTED 2-AMINO-5-) 5-OXOPENT-2-EN-1-YLIDENE) -THIAZOLIN-4-ONE - Google Patents

Abstract

The invention relates to a process for the preparation of substituted * thiazolin-4-ones of the formula III in which R1-R3 aryl radicals and R4 and R5 denote identical, different or linked together alkyl radicals. Compounds of this type are useful as intermediates for the synthesis of novel substituted 2-amino-thiazolin-4-ones. The title compounds are prepared according to the invention by reacting pyrylium salts of the formula I (R 1 -R 3 aryl, Xbelieviges anion) with 2-amino-thiazolin-4-ones of the formula II, in which R 4 and R 5 have the abovementioned meaning, in the presence of a buffer component, which may be a dialkylamine or alkali salt of a weak acid, a trialkylamine or an equimolar mixture of trialkylamine and weak acid, in solvents such as lower aliphatic alcohols, halogenated hydrocarbons or dipolar aprotic solvents and thereby applies temperatures up to the boiling point of the reaction mixture. {* Intermediates ; pyrylium; 2-amino-thiazoline-4-one}

Description

Ausführungsbeisplele example 1

Substituted 2-amino-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones III by reaction of pyrylium salts I with aminothiazolinones II in lower aliphatic alcohols or dipolar aprotic solvents (general procedure, Vm iante A, see Table 1)

5 mmol of pyrylium salt I (X = CIO ₄ ), 7.5 mmol of 2-amino-thiazolin-4-one II and 10 mmol of PuVferkomponente in 20 ml of the respective solvent for 0.5 hours under reflux. The crude products which precipitate out of the reaction mixtures-if appropriate with cooling-are filtered off with suction and recrystallized from acetone / ethanol.

Example 2

Substituted 2-amino-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones III by reaction of pyrylium salts I with aminothiazolinones II in halogenated hydrocarbons (general procedure, variant B, see Tab. 1) 5 mmol of pyrylium salt I (X = CIO ₄ ), 7.5 mmol of 2-amino-thiazolin-4-one II and 10 mmol of buffer component are refluxed in 20 ml of halohydrocarbon for 0.5 h. After cooling, the reaction mixture is treated with water, the organic phase separated and the aqueous phase extracted twice with the halogenated hydrocarbon used for the reaction. After washing the organic solutions twice with water, it is dried over sodium sulfate, the solvent i. Vak. and brings the remaining residue by treatment with ethanol for crystallization. The cleaning is carried out analogously to Example 1.>

Tab. 1 yields and melting points of 2-amino-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones prepared according to the Ausf Uhrungsbeispielen III

Verb. Var. R ¹ R ² R ³ Ph NR ⁴ R ⁶ Pu'fer- solution Y. Mp. Ph component medium (%) " ( ⁰ C) purple A Ph Ph Ph Ph morpholino piperidine ethanol 81 195-197 A 4-Me-C ₆ H ₄ Piperidinace- ethanol 90 4-CI-C ₆ H ₄ did ²¹ A 4-Br-C ₆ H ₄ Piperidinpro- ethanol 91 pio.iat ²¹ A Piperidinben- ethanol 89 zoat ²¹ A Dimethylamine ethanol 97 acetate A diethylamine ethanol 98 acetate A Diisobutylamin- ethanol 95 acetate A dicyclohexyl ethanol 96 amine acetate A pyrrolidine ethanol 90 acetate A Morpholinacetat ethanol 85 A triethylamine ethanol 95 purple A Ph Ph Ph morpholino triethylamine / ethanol 97 195-197 acetic acid A sodium ethanol 90 A piperidine methanol 91 A piperidine acetonitrile 73 B piperidine methylene 73 chloride B piperidine chloroform 26 In the B A dimethyl piperidine ethanol 64 178-179 amino IIIc A diethylamino piperidine ethanol 79 164.5 to 165.5 IIId A pyrrolidino piperidine ethanol 64 177-178 IUE A piperidino piperidine ethanol 66 179-180 Ulf A Ph 4-Me-C ₆ H ₄ Ph morpholino piperidine ethanol 89 203-205 IIIg A Ph 4-MeO-C ₆ H ₄ Ph morpholino piperidine ethanol 88 189-190 iiih A Ph 4-ChC ₆ H ₄ Morpholir.o piperidine ethanol 93 185-187 Uli A Ph 4-Br-C ₆ H ₄ morpholino piperidine ethanol 92 196-198 Wed. A Ph 4-O ₂ NC ₆ H ₄ morpholino piperidine ethanol 74 199-201 HIK A 4-Me-C ₆ H ₄ Ph morpholino piperidine ethanol 78 201-203 HII A 4-CI-C ₆ H ₄ Ph morpholino piperidine ethanol 89 - 208-210 Ulm A 4-Br-C ₆ H ₄ Ph morpholino piperidine ethanol 89 209-210

1) Oy yields refer to the crude products;

2) By combining equimolar amounts of AmIn and acid directly generated in the reaction mixture.

R '

Ra

Pirfferkomponente

-HX

V-N

Claims (2)

1. A process for the preparation of substituted 2-amino-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones of the formula III in which R ¹ -R ³ aryl radicals and R ⁴ and R ^{6 are the} same, different or mutually linked alkyl radicals, characterized in that pyrylium salts of the formula I in which R ¹ , R ² and R ^{3 are} aryl radicals and X is an arbitrary anion, with 2-amino-thiazolin-4-ones of the formula II, in which R ⁴ and R ^{5 have} the abovementioned meaning, in the presence of a buffer component in solvents such as lower aliphatic alcohols, for. For example, methanol or ethanol, halogenated hydrocarbons, eg. As methylene chloride or chloroform, or dipolaraprotic Solvenzen, z. As acetonitrile, and while applying temperatures up to the boiling point of the reaction mixture. 2. The method according to item 1, characterized in that as a buffer component dialkylamine weak acid, z. As the acetates, propionates or benzoates of piperidines, dimethylamine, diethylamine, diisobutylamine, dicyclohexylamine, pyrrolidine or morpholine (either used in substance or produced by combining equimolar amounts of dialkylamine and acid in the reaction mixture), tertiary amines, ζ. For example, triethylamine, equimolar mixtures of tertiary amine and weak acid, eg. As the combination triethylamine / acetic acid, or alkali metal salts of weak acids, eg. For example, sodium acetate. For this 1 page formulas Field of application of the invention The invention relates to a process for the preparation of substituted 2-amino-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones of the general formula III in which R ', R ² and R ³ Aryl radicals and R ⁴ and R ⁶ denote identical, different or linked alkyl radicals. Compounds of this type are useful as intermediates for the synthesis of novel substituted 2-aminothiazolin-4-ones. Substituted 2-amino-thiazolin-4-ones are of particular interest as biologically active compounds. Characteristic of the known technical solutions Substituted 2-amino-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones of the general formula III, in which R'-R ^{6 have} the abovementioned meaning, are hitherto unknown , On the potential possibility of compounds of type III by aldocondensation of suitable substituted ketones with 2-dialkylamino-thiazolin-4-ones (cf., eg SU 196855, Chem. Abstr. 68 [1968] 21938) or by aminolysis of 5-Alkylidenrhodaninen (s ARA ROUF, MT OMAR, SMA OMRAN and KE EL-BAYOUMY, Acta Chem. Acad. Sei. Hung 83 (19741359) and 2-alkylmercapto-5-alkylidene-thiazolin-4-ones, respectively (see SM RAMSH, GSANTONOVA , AI GINAK and EC SOCHILIN, Zh. Org. Khim. 11 [1975] 1755), these synthetic variants presuppose the existence of specially substituted starting materials, the preparation of which is usually associated with considerable preparative effort. Object of the invention The aim of the invention is to produce 2-amho-5- (5-oxo-pent-2-en-1-ylidene) -thiazolin-4-ones from available or readily available starting materials in a one-step process, which are described in FIGS. 3- and 5-position of the 5-oxo-pent-2-en-1-ylidene chain carry aryl radicals and on the amine nitrogen alkyl radicals. Explanation of the essence of the invention The invention has for its object to use for preparing the title compounds suitably substituted pyrylium salts. The object is achieved according to the invention by using pyrylium salts of the formula I in which R ', R ² and R ^{3 are} aryl radicals and X is an arbitrary anion, with 2-amino-thiazolin-4-ones of the formula II in which R ⁴ and R ^{8 represent the} same, different or linked together alkyl radicals, in the presence of a buffer component and thereby reacting as a solvent lower aliphatic alcohols, ζ. As methanol or ethanol, halogenated hydrocarbons, such as methylene chloride or chloroform, or dipolaraprotische Solventien, eg acetonitrile, used and applies temperatures up to the boiling point of the crude mixture. Suitable buffer components are dialkylamine salts of weak acids such as the acetates, propionates or benzoates of piperidines, dimethylamine, diethylamine, diisobutylamine, dicyclohexylamine, pyrrolidine and morpholines (used in substance or produced directly in the reaction mixture by combining equimolar amounts of amine and acid), tertiary amines such as triethylamine equimolar mixtures of tertiary amine and weak acid, for example the combination triethylamine / acetic acid, and alkali metal salts of weak acids, eg. For example, sodium acetate. The Reaction products III separate off when working with alcohols or acetonitrile as solvent directly from the reaction mixture in crystalline form, so that their isolation is possible without difficulty (variant A, see Example 1). When using halogenated hydrocarbons as the reaction medium, the resulting reaction mixture is mixed with water and the products are isolated by concentrating the organic phase (variant B, example 2). In solution Thiazolinonu type III exist as a mixture of the E and Z form, between which an equilibrium is established, the position of which depends on the solvent used.
The invention is explained below with reference to two exemplary embodiments in the form of general working instructions.