2-Chloro-2,3-dihydro-5,6-thiazin-4-ones

The acetamido alkenethiolate (416), generated by the reductive cleavage of 2,3-dihydro-l,4-thiazin-2-one (415) in liquid ammonia (cf. p. 625), reacted with l-chloro-3-bromopropane in a two-stage process to give (417). 

A six-membered nitrogen-sulfur heterocycle, namely, a 2,3-dihydro-2-imino-4//-benzo[e thiazin-4-one, is produced on reaction of methyl 2-chloro-3,5-dinitrobenzoatc with thiourea in basic medium 373 furthermore, a tetrahydrospirobenzothiazine 213 is formed in addition to its hexahydrospiroquinazoline analog on interaction of cyclohexanone with thiourea in hydrochloric acid.329... 

The reaction of 2-chloro-3-(7V-substituted amino)pyrazines (233) with thioglycolates gives 2,3-dihydro-4-substituted-(4//)-pyrazino[2,3-6][ 1,4]thiazin-3-ones (234) <71JAP32670, 74JAP(K)49041397> with analgesic properties (Equation (34)). 

E)-6-chloro-3-[hydroxy(pyridine-2-ylamino)methylene]-2-methyl-2,3-dihydro-4H-thieno [2,3-e] [1,2] thiazin-4-one, 1,1 -dioxide. 

Several synthetic approaches to the l,2-benzothiazin-3-ones have been described. Usually, an ortho-substituted sulfonamide was cyclized to form the thiazine ring. For example, Lombardino and Wiseman14,38 treated /V-methyl-o-toluenesulfonamide (45) with butyllithium the dianion with CO 2 produced o-sulfamoylphenylacetic acid 46 which was cyclodehydrated to 3,4-dihydro-2-alkyl-l,2-benzothiazin-3(2H)-one 1,1-dioxide (47) in good yield (Eq. 10). This same reaction sequence was applied to analogs of 47 such as the 7-methyl, the 7-chloro, and the 2-benzyl derivatives.38... 

Reactions between 3-halogenopropanoyl chlorides (218) (X = C1 or Br) and sodium, or ammonium, dithiocarbamates (219) produce perhydro-3-alkyl-2-thioxo-l,3-thiazin-4-ones (220) (Equation (29)) <85MI 607-0i>. A similar procedure, leading to 3-acyl-2-hydrazono-5,6-dihydro-l,3-thiazin-4(3/f)-ones (221) (R = Et), requires the treatment of hydrazones (222) with 3-chloro-propanoic acid in the presence of propanoic anhydride containing sodium acetate (Scheme 41). If propanoic anhydride is replaced by succinic anhydride then the acid (221) (R = CH2CH2CO2H) is the product, so it is likely that A-acylation occurs after the heterocycles (223) are formed (Scheme 41) <85MI 607-02>. 

C1iHi6CIN3OS, 3,4-Dihydro-7-chloro-6-diethylamino-2H,8H-pyrimido-[2,1-b]thiazine-8-one, 40B, 348... 

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