3- -l,3-thiazine

The thiazin-2,6-diones 49 lose one molecule of COS in boiling dimethylformamide (DMF) to afford l-substituted-6-alkyl uracils 98 (Scheme 2) <2005RJC134,2003TL5279>. The same products are obtained when 5-acyl-4-hydroxy-3,6-dihydro-2//-l,3-thiazine-2,6-diones 61 are heated together with the corresponding primary amine in hoiling DMF. The dimeric compound 99 and the nitrophenyl hydroxylated example 100 are produced by the same route <2005RJC134>. 

The 7-lactam 120, which is very reactive, is obtained from the reaction of methyl 2-(2-methoxycarbonylmethyl-ene)-5-methyl-3,6-dihydro-2//-l,3-thiazine-4-carboxylate 119 with oxalyl chloride and in the presence of triethyl-amine (Scheme 5). Subsequent treatment with methanol affords 3,6-dihydro-2//-l,3-thiazine 121 as a mixture of isomers. Similar treatment of the 4-allyl carboxylate analogue with oxalyl chloride/triethylamine yielded the corresponding 7-lactam <1999J(P1)2449>. 

The Michael attack of the enamine moiety in the 3,6-dihydro-2//-l,3-thiazine 149 on a-phthalimido acrylic acid affords the cyclic product 152, most probably through the intermediate 150. Support for the mechanisms comes from the isolation of the 5,6,7,8-tetrahydro-la//-thiireno[2,3-f]indolizine 151 in 10% yield (Scheme 10) <1999J(P1)3565>. 

Often in the past, 3,6-dihydro-2//-l,3-thiazines were incorrectly named 2,3-dihydro-6//-l,3-thiazines. It is, however, necessary to apply the 1UPAC Rule the atoms bearing the extra hydrogens have numbers as small as possible. 

Cephalosporins have a 3,6-dihydro-2//-l,3-thiazine nucleus, and some of their total syntheses start from 6//-l,3-thiazines. Since the discovery of the cephalosporins by Brotzu in 1943 and the enormous developments occuring in the chemistry of these antibiotics since the 1940s, the 1,3-thiazine nucleus has become one of the most important six-membered heterocycles. Cephalosporins now exceed penicillins in importance and presently account for 31% of the world market of all antibiotics. 

C-Enamino-imines obtained by photolysis of l//-pyrimidin-2-ones have been treated with carbon disulfide, giving 2//-l,3-thiazine-2-thiones (22) and/or l-aryl-l//-pyrimidine-2-thiones (23) (Scheme 13) [82JCS(P1)2149]. 

Phenacylisothiazolium salts were prepared by fusion of isothiazoles with phenacyl bromide (85BSB149). Treatment of the salt with pyridine afforded the 2-benzoyl-2//-l,3-thiazines (44) via intramolecular nucleophilic attack on the sulfur atom (Scheme 25). 

Benzylmercapto-5-methoxycarbonyl-6//-l,3-thiazine (177) slowly hydrates with atmospheric moisture which leads, after elimination of benzyl mercaptan, to the 3,6-dihydro-2//-l,3-thiazine-2-one (178) (Scheme 70)... 

Thermolysis of 4//-l,3-thiazines (271) leads to thioamide vinylogues (272) by ring opening (Scheme 110) (86SC79). At more elevated temperature (toluene reflux), compound 273 is not isolated. A heterocyclic isomer (274) with a 3,4-dihydro-2//-l,3-thiazine structure is obtained (Scheme 111). 

The versatile desulfurization/rearrangement of 1,2-thiazolium salts 117 to pyrroles 119 is believed to proceed via intermediate 2//-l,3-thiazines 118 [93AG797, 93AG(E)712] (Scheme 32). 

Oxazines and 1,3-thiazines have been used quite extensively as substrates in pyrimidine syntheses (B-94MI 602-0l>. 1,3-Thiazines are intermediate structures in several cyclization reactions involving thioxo substrates. Pyrimidine formation from thiazines may involve a Dimroth-like rearrangement of a thiazinamine, an aminolytic displacement of the ring sulfur atom, or a combination of both. Aqueous ethanol in methylamine converts 4-phenyl-5-phenylsulfonyl-2//-l,3-thiazine-2,6(3//)-dithione (589) into the pyrimidine (590) by displacement of the ring sulfur and a nucleophilic substitution of the thioxo sulfur in the 2-position (Scheme 93) (88JHC835). 

Thiazinium salts (78) undergo reductive dimerization on cathodic reduction to afford 6,6 -bithiazinyls (79) (Scheme 10) <81JPC33>. However, 5-acyl-2-phenyl-6//-l,3-thiazines (80) undergo electrochemical reduction under controlled conditions and at 2°C to yield 3,6-dihydro-2//-l,3-thiazines (81) and dihydrodimers (82) coupled through C-2. Further reduction leads to tetrahydro-... 

Benzoyl-2//-l,3-thiazines (144) and diphenylketene enter into [2 + 2] cycloaddition reactions via the imine bond, thereby providing access to thiazolo-)S-lactams (145) <85CS239>. Chloroketenes (from chloroacetyl chlorides and a tertiary amine) react in a similar manner and give chloro derivatives (146) (Scheme 27) <85BSB149>. With 6//-l,3-thiazines (147) the products are the corresponding -lactams (148) (Equation (17)) <86CJC597>. 

Oxidation of diethyl 3-methyl-6-oxo-2//,6//-pyrido[2, -(>][l,3]thiazine-4,9-dicarboxylate and its 7,8-dihydro derivative with CE3CO3H in CH2CI2 at room temperature gave the respective sulfone in 73% and 38% yields, respeetively (99JCS(P1)3569). Sulfoxide 91 or sulfone 92 of... 

Irradiation of 9-substituted 6-oxo-3,4-dihydro-2/f,6/f-pyrido[l,2- >]-[l,3]thiazine-4-carboxylate 93 in benzene afforded tricyclic derivatives 94, sometimes as a diastereomeric mixture (00JCS(P1)4373). 

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