6H-1,3-Thiazines

An alternative approach to 6H-1,3-thiazines requires the thermally promoted addition of a,/3-unsaturated carbonyl derivatives to thionoimines. Dihydrothiazines are the initial products but they readily decompose by elimination of the 4-substituent (Scheme 66) <79BSF(2)347>. 

Simple 6H- 1,3-oxazines and -thiazines are commonly encountered as intermediates in the reactions of oxazinium and thiazinium salts with nucleophiles (see Section 2.27.2.2.3). Additionally there is a considerable interest in 6H-1,3-thiazines as intermediates in the synthesis of cephem antibiotics (see Section 2.27.3.24) and many approaches have been... 

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) ... 

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>. 

BF3 OEt2 is an effective reagent for debenzyloxycarbonyla-tions of methionine-containing peptides. Substituted 6H-1,3-thiazines can be prepared in high yields from BF3-OEt2-catalyzed... 

Ethyl 9-ethoxycarbonyl- and 9-hydroxymethyl-3-methyl-6-oxo-2, 6i/-pyrido[2,1-Z ][1,3]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-m-H-9-ethoxymethyl-3-methyl-6-oxo-3,4-dihydro-2, 6/f-pyrido[2,1 -Z ][ 1,3]thiazine-4-carboxylate and the aforementioned 47/,6 -isomer were obtained (00JCS(P1)4373). 

AH- 1,2-Oxazines are stabilized as 4,4-disubstituted derivatives but AH- and 6H-1,2-thiazines are almost unknown. Possibly the paucity of these compounds simply reflects a lack of interest, for 6H-1,2-oxazines are comparatively common, and 3,5-diphenyl-6//- 1,2-oxazine, for example, is a stable crystalline solid. Similarly, cyano-1,2-oxazines (6 R=alkyl) are formed by the photolysis of azidopyridine oxides (5). However in the case where R3 = H, these products rearrange to pyrroles (7) (81CC36). 

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... 

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... 

Propyl-3- ethyl - 6- ethoxy -1H- pyri-mido [5,4 - b] [1,4] thiazine -2,4,7 (3H,-6H,8H)-trione 5-oxide mixed with coned, aq. NHg and allowed to stand overnight 6-ethyl-4,5,6,7-tetra-... 

Cl sHi 6CI6N2O2Si,Te CaHaOj, Bis[2,3-dihydro-3-hydroxy-thiazolo[2,3-blbenzothiazolium] hexachlorotellurate(lV) dioxane, 46B, 412 C1bH16N2OS, 2,3,4,5-Tetrahydro-6,6-diphenylimidazo[2,1-b]thiazine-7(6H)-one, 46B, 413... 

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

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