3- thiazines

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

Takamizawa et al. developed a general ring-expansion reaction of heterocycles that, applied to thiazolium salts, yields 1,4-thiazines (496, 497) thiamine (220) reacts with dialkyl acylphosphonates (221) to give the tricyclic 1,4-thiazine (222) (498), which is easily hydrolyzed to dihydro-1,4-thiazinone (223) (499) (Scheme 106). In the case of thiazolium slats containing no functional groups (224), 1,4-thiazine derivatives (226) were directly obtained in fairly good yields (Scheme 107). 

Other ring-expansion reactions have already been mentioned in regard to addition reactions leading to pyrrolothiazoles (Section III. 3), which sometimes rearrange to 1,4-thiazines (333, 497). 

Thiazine has been formulated as 1 rather than 2 because it does not form a sulfonamide under Hinsberg conditions. Symmetrical azines can form only one classical monocation, e.g., pyrazine forms 3. The nonclassical cation 4 has been postulated for pyridazine, but there is no compelling evidence in its favor. 

The rearrangement of cyclic sulfoxide 130a, which could be obtained from the corresponding thiolsulfinate 163 (Section III.C.l), was studied in different experimental conditions. The ci3-sulfoxide refluxed in toluene for 24 h gave a 1 1 mixture of the pyrrole 131 and the dihydro-1,4-thiazine 132. 

The parent 1,4-thiazine exists exclusively as the 2H tautomer 86, independently of the medium used, as do its pyrimidino-fused derivatives 87 (76AHCS1, p. 80 84MI2). However, the equilibrium could be affected significantly by a substitution pattern in the thiazine ring, as was shown in the example of 1,4-benzothiazine. Thus, 3-phenyl-1,4-benzothiazine 88 (R = H, R = Ph) is present in aqueous hydrochloric acid as a 4 1 mixture of 2H (88a) and AH (88b) isomers... 

Pyrido[2,1 -c][ 1,4] thiazine-8,9-dicarboxylate and pyrido[2,1 -c][ 1,4]ben-zothiazine-7,8-dicarboxylate 329 were obtained by cyclization of tricarboxy-lates 328 (99T7915). 

Much more is known about the sulfur analogues, especially the benz derivatives of 1,4-thiazine. Bromination of AH-1,4-benzothiazine 1,1-dioxide occurred in the 2-position (68TL1041). 

Aus den entsprechenden (2-Nitro-phenyI)-mercapto-essigsaure-Derivaten werden die analogen Benzo-1,4-thiazine erhalten4. 

But when the reaction is carried out in an aqueous solution of sodium hydrogen carbonate, extension of the ring occurs with formation of dihydro-1,4-thiazine derivative (Scheme 19). the structure of which has been established by mean of NMR and infrared spectra (411. 

Ring extension, to dihydro-1,4-thiazine. 35 to djhydro-1,4-thiazine, 36 Ring fusion, of some 2-methylthiazolium,... 

Figure 4 Overview of the known benzologs of pyrido[2,1 -c][1,4]oxazine, pyrido[2,1 -c][1,4]thiazine, and pyrido[1,2-a]pyrazine.

Diaryl-octahydro-pyra/ino[2,1 -c 1,4]thiazines are useful as melanine concentrating hormone receptor ligands <2002W02002/094799>. Pyrazino[2,l-f][l,4]oxazines 245 (Y = 0) and pyrazino[2,1 -c][ 1,4]thiazines 245 (Y = S) exert a tachykinin antagonistic effect <2002W0055518>. 

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