DD222310A1 - PROCESS FOR THE PREPARATION OF 5-CYAN-1,3-THIAZIN-6-ONEN - Google Patents

Abstract

The invention relates to a process for the preparation of 5-cyano-1,3-thiazine-6-ones which contain as substituents in the 2- and 4-position a substituted or unsubstituted aryl or hetaryl radical. It is the object of the invention, in addition to the already known from the literature 5-cyano-4-methylthio-2-phenyl-1,3-thiazin-6-one other previously unknown representatives of this type in a novel manner. The task is to find a technically feasible synthetic route. The object is achieved by the reaction of 3,5-diaryl (or hetaryl) -1,2,4-dithiazolium salts with cyanoacetic acid aeolides or activated cyanoacetic acid esters. The compounds obtained are of pharmaceutical interest.

Description

Title of the invention · ν.

Process for the preparation of 5-cyano-1,3-thiazine-6-ones

Field of application of the invention

The invention relates to a process for the preparation of 5-cyano-1,3-thiazine-o-ones. Such compounds can gain importance as biologically active preparations.

Characteristic of the known technical solutions

The only 5-cyano-1,3-thiazine-6-one is the 5-cyano-4-methylthio-2-phenyl-1,3-thiazin-6-one known from the literature. This compound was obtained as a by-product of the reaction of 2-cyano-3-mercapto-3-niethylthioacrylamide with benzoic acid in 4% yield (M. Yokoyama, M. Nakamura, H. Ohteki, T. Imamoto, K # Yamaguchi, J. Chem Org Chem 47, 1090 (1982). The process has the disadvantage that only poor yields can be achieved.

There are known from the literature, various methods according to which 5-cyano-1,3-thiazines which have or in the 6-position substituents other than the oxo group 1 ^ thiazine-G-ones other in ¹ 5-position substituents than the Cyano group possess, can be produced. (Cf.'E.IT.Cain,

RN Warrener, Aust. J. Chem. 2 ^ 3, 51 (1970); Ξ..wing, US; Pat. 3062816; J. Goerdeler, H. Horstmann., Chem. Ber. 93,671 (1960); Ε · Steiner, E. Ziegler, Mh. Chem. 9j >> 147, 1550 '(1964) ;. JC Meslin, H. Quiniou, Synthesis 1974 , 298). An analogous representation of the 5-cyano-1,3-thiazine-6-one has not been tried ', because the required starting materials are difficult to access.

Object of the invention . , .

The aim of the invention is to produce 5-cyano-1, '3-thiazine-6-ones in good yields from readily available starting materials.

Explanation of the essence of the invention

The object of the invention is to produce 5-cyano-1,3-thiazine-6-ones in high yields from readily available starting materials in a technically applicable synthesis route in a simple manner.

According to the invention the object is achieved in that 3,5-diaryl-1,2,4-dithiazolium salts of the type II,

S S

R <

II

where R 'is a substituted or unsubstituted aryl or hetaryl radical and X "is an acid radical anion, such as ζζΒI, Br", Cl ", CIOT, PeClT, with cyanoacetic acid azoles or activated cyanoacetic acid esters of type III,

Il

CR ₂ . in

where R is a substituted or unsubstituted imidazolo-, pyrazole-, triazolo-, tetrazolo-, benzimidazole- or benzotriazole radical or a radical substituted or unsubstituted by a ring nitrogen atom in the abovementioned formula with the cyanoacetyl group Represents phenoxy, to the 5-cyano-1,3-thiazine-6-ones of type I,

wherein R has the meaning given above, are reacted.

It is advantageous to carry out the reaction using auxiliary bases, e.g. Alkali salts of weak acids, e.g. IT sodium acetate or sodium carbonate or tertiary amines, e.g. Perform triethylamine. The invention will be explained below nig forth embodiments.

example 1

Compound I with R ¹ = CgH ^ (meaning always parts by weight)

Option A

The mixture of 1 part II (R ¹ = CgH ₅ , X = ClO ₄ ), 0.91 part III (R ² = 3,5-dimethylpyrazol-1-yl), 0.4β parts

Hatriuinacetat and 10 parts of acetonitrile is stirred for 30 min. At room temperature · The precipitate is filtered off with suction and extracted with 100 parts of benzene in the boiling heat. The benzene solution is filtered. After distilling off the benzene, the residue obtained is 0.66 parts (81 %) of the yellow product which has a melting range of 218-223 ° C. (benzene).

Yariante_3,,

Analog variant A, but 0.46 parts III (R = 3,5 · 'Dirnethylpyrazol-1-yl) and 0.23 parts of sodium acetate are used. The yield is 0.48 parts (59 %)

Variant ^ £

Analog variant A, but instead of sodium acetate 0.28 parts of triethylamine are used. The yield is 0.63 parts (78%).

7ariante__D

Analog variant A, but 5 parts of dimethylformamide are used instead of acetonitrile. The yield is 0.53 parts (65%).

The mixture of 1 part II (R ¹ = CgH ₅ , X = GlO ₄ ), 0.91 part III (R ² 's 3,5-dimethylpyrazol-1-yl) and 5 parts of pyridine is stirred for 3Ö min · at room temperature , Workup analogous to Variant A. The yield is 0.33 parts (41 %).

Varia_nte_F

The mixture of 1 part II (R ¹ = CgH ₅ , X = GlO ₄ ), 1.5 parts III (R = o-nitrophenoxy), O, 6o parts of sodium acetate and 5 parts dimethylformamide is stirred at room temperature for 15 min , Workup analogous to variant A. The yield is 0.74 parts (92 %).

Example 2

Compound I with R ¹ = C ₆ H ₄ ( ₃

The mixture of 1 part II (R ¹ = C ₆ H ₄ (P) CH ₃ , X = 010), 0.85 part III (R ² = 3,5 3,5-dimethylpyrazol- ¹ -yl), 0.43 Tiatrium acetate and 10 parts acetonitrile are stirred at room temperature for 30 min. Working up analogously to Example T, variant A · 0.57 parts obtained (69%) of yellow product having a melting range of 221 -. 224 has ⁰ C (benzene).

Example 3

Compound I with R ¹ = C ₆ H ₄ (Bi) CH ₃

1 part II (R ¹ = C ₆ H ₄ (Hi) CH ₃ , X = ClO ₄ ) is analogous to Example

2 implemented. This gives 0.65 parts (78 %) of the yellow product, which has a melting range of 153-155 ⁰ C (benzene).

Example 4

Compound I with R ¹ = CgH

The mixture of 1 part II (R ¹ = C ₆ H ₄ (P) OCH ₃ , X = ClO ₄ ), 0.78 part III (R ² = 3,5-dimethylpyrazol-1-yl), 0.39 Te sodium acetate and 20 parts of acetonitrile become 30 min.

'at room temperature, stirred. Working up analogously to Example 1, variant A. This gives 0.64 parts (76%) of yellow product having a melting range of 204 - 205 ⁰ C has (. Benzene), y '

Example 5

Compound I with R ¹ =

The mixture of 1 part of II (R ¹ = C ₆ H ₄ (P) CIj X = I. _3), 0.46 parts of III (R ² = 3,5-dimethylpyrazole-1-yl), 0.23 parts - Hatriumacetat and 10 parts of acetonitrile is stirred for 30 min · at room temperature · Working up analogously to Example 1, variant A. This gives 0.42 parts (83 %) of the yellow product, which has a melting range of 273 - 275 ⁰ C (benzene) ". ·

Claims (2)

invention claims 1. A process for preparing 5-cyano-1,3-thiazine-6-ones, characterized in that 3, 5-diaryl ~ 1,2 *, 4-dithi "azolium salts of the type II, II where R is a substituted or unsubstituted aryl or hetaryl radical and X is an acid radical anion, such as 1 ^, Br ~, Cl ", CIOT or PeClT, with cyanoacetic acid azoles or activated Type III cyanoacetic acid esters, III where R represents a substituted or unsubstituted imidazolo-, pyrazole-, triazolo-, tetrazolo-, benzimidazole- or benzotriazolo radical linked via a ring nitrogen atom in the above-mentioned manner with the cyanocetyl group or a phenoxy radical which is substituted or unsubstituted on the aromatic to the 5-cyano-1,3-thiazine-6-ones of type I, R " where R has the meaning given above, can be implemented » 2. The method according to item 1, characterized in that the Implementation using auxiliary bales, e.g. Alkali salts of weak acids, ζ · Β. IT sodium acetate or sodium carbonate or tertiary amines, e.g. Triethylamine is performed. , ',. '