6H-l,3-Thiazines

Die durch Natriumethanolat eingeleitete Ringtransformation von 5-Cyan-2,4-diphenyl-6-oxo-6H-l,3-thiazin zu 5-(4-Brom-benzoyl)-2,4-diphenyl-1,3-thiazol (65% Schmp. 151-152 ) mittels co,4-Dibrom-acetophenon verlauft iiber (a-Thiobenzoylamino-benzyliden)-malonsaure-ethylester-nitril, das sich auch isolieren laBt729. 

A significant number of 1,3-thiazine derivatives have been subjected to x-ray crystallographic analysis. Thus, it has been shown that the atoms of the unsaturated chromophore of simple 6H-l,3-thiazines lie in the same plane, with the methylene group at C-6 out of the plane <86CJC597, 87BSF149>, and that in the solid state 4-hydroxy-l,3-thiazin-6-ones (13) are preferred to 4,6-diones (12) <86MI... 

Kappe et al. have reported a microwave-assisted Dimorth rearrangement of a substituted 2-amino-6H-l,3-thiazines 135 to N-3 substituted 136 in sealed vessels (Scheme 50). Thiazines 135 with an ester functionality at C5 (R = COOEt), required higher temperatures for rearrangement than 135 (R = H). 135 (R = H) was transformed into 136 (R = H) in toluene and for the transformation of N-substituted 135 (R = alkyl or aryl) to N-3 substituted 136 (R = alkyl or aryl), N-methyl pyrrolidine was the solvent (06MI13). 

Dimethyl sulfoxide acetic anhydride 2,3-Dihydro-6H-l,3-thiazine ring Oxidative ring closure Protection of alcohol groups as ), ), j -tridilorethyl carbonates Reductive removal of the protective group... 

Substituted 4,5-dihydro-6H-l,3-thiazines (27) are formed in high yields by Michael addition of thioamides, thioureas, or thiocarbamates (25) to the double bond of a 3-unsaturated aldehydes, ketones, or ketols (24) in the presence of boron trifluoride etherate and subsequent spontaneous ring-closure of the resulting intermediate (26). In some instances the products (27) can be converted into the corresponding 6H-l,3-thiazines, c.g. (28), with POCI3 in pyridine or with acid in aprotic solvents. 

Ethyl 9-ethoxycarbonyl- and 9-hydroxymethyl-3-methyl-6-oxo-2/f,6//-pyrido[2,l-Z>][l,3]thiazine-4-carboxylates were isomerized into 4H,6H-pyrido[2,l-b][l,3]thiazine-4-carboxylates by treatment with KOH overnight at room temperature and by treatment with NaOEt at 0 °C for 1 h and room temperature for 3h in EtOH, respectively. In another experiment, when the 9-hydroxymethyl derivative was treated with NaOEt in EtOH at — 10°C for 3h, a 2.5 1 mixture of ethyl 3,4-cw-H-9-ethoxymethyl-3-methyl-6-oxo-3,4-dihydro-2//,6//-pyrido[2,l-Z)][l,3]thiazine-4-carboxylate and the aforementioned 4//,6//-isomer were obtained (00JCS(P1)4373). 

Cyclobnta b qninoxaline 3,8-Dimethyl-l,2-dithiono-l,2,3,8-tetrahydro- E17f, 988 (Oxo,Oxo - Thiono.Thiono) 6H-1,3-Thiazin 5-Cyan-4-methyl-thio-2-phenyl- E5, 1362 (CO-NH2 - CN) 4H-(Thieno 2,3-c -l,2-diazepin) ... 

N-terminus of a peptide, undergoes intramolecular cyclization in acid solution to yield 3-oxo-(2H, 3H, 5H, 6H-l,4-thiazine)-5-carboxylic acid (Bradbury and Smyth 1973), which is ninhydrin-negative. 

Examples of both 2-amino-4 f-1,3-thiazines and 2-amino-6H-1,3-thiazines are known, and in the case of 2-amino-4/f-1,3-thiazines these seem to be favored over their imino tautomers, at least in solution. Thus, 4,4,6-trimethyl-2-(A-methyl-7V-phenylamino)-4H-l,3-thiazine (I), which cannot tautomerize, absorbs at = 264 nm, and 4,4,6-trimethyl-2-(iV-phenylamino)-4H-l,3-thiazine (2), which can, shows = nm. 3,4,4-Trimethyl-2-(7V-phenylimino)-4//-l,3-thiazine (3), which is locked into the imino form, shows a main UV band at = 236 nm with a shoulder at 280 nm. Many 2-amino-6/f-1,3-thiazines are known where there is an unsaturated (acyl) group at C-5. This group serves to extend the delocalization of the chromophore, and 5-ethoxycarbonyl-2-(V-methylamino)-6//-l,3-thiazine (4), for example, exhibits UV bands at A iax = 240 nm, 266 nm, and 330 nm (Figure 1) <90AHC(50)85>. 

The cycloaddition of methyl acrylate with Af -thiobenzoyl-iV,7V-dimethylformamidine (230) under pressure affords the 4-(A, A -dimethylamino)-5,6-dihydro-4/f-l,3-thiazine (231). When this compound is treated with methyl iodide and triethylamine an elimination reaction ensues to give 6H-... 

Reaction of thiazolic 387 and thiazinic 388 diazadienes with a wide variety of ketenes resulted in a [4 4- 2] cyclo-condensation which provided 5H-thiazolo[3,2-(j]pyrimidin-5-ones 389 and 2H,6H-pyrimido[2,l-l)][l,3] thiazin-6-ones 390, respectively, via elimination of dimethylamine (Scheme 119) (2003JOC4912, 1999JCR(S)36). 

More favourable results are obtained in analogous syntheses, which afford the following types of compounds 6H-[l,3,4]thiadiazolo[3,2-b]-[l,2,4]thiadiazol-6-ones (10—53%) (88) 2H-[l,2,4]thiadiazolo[2,3-a]pyridin-2-ones (48%) (89) 2JFf-[I,2,4]thiadiazolo[2,3-b]pyridazin-2-ones (90), and 5,6-dihydro-2H-[l,2,4]thiadiazolo[3,2-b]thiazin-2-one (91). The i.r. spectra... 

C8H6N2OS, 4-Phenyl-1,2,3-thiadiazole 3-oxide, 44B, 355 CbHsN20i,S2 r cis-syri cis-Tetrahydrocyclobuta[ 1,2-e 4,3-e ]bis( 1,3)-thiazine-2,4,5,7-(3H,6H)-tetrone, 37B, 203 C8H7CIN2O2S, 7-Chloro-3-methyl-4H-l,2,4-benzothiadiazine-1,1-dioxide, 43B, 474... 

H-oxathiazines 32, 577 2H-l,3-Thiazete-thioacylimine tautomerism 32, 577 4H-1,4-Thiazine 1,1-dioxides... 

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