Thiazines rearrangement

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). 

Indolo[2,3-d][l,3]thiazine-2,4-dithione formation, 4, 299 Indolothiazines synthesis, 4, 519 Indoloyl azides Curtius rearrangement, 4, 288 Indolyl anions acylation, 4, 232 alkylation, 4, 235 Michael-type additions, 4, 236 Indomethacin... 

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. 

Among the heterocyclic systems that have been used to provide a backbone for acidic, nonsteroidal antiinflammatory agents are benzo-1,2-thiazine dioxides, such as 193-195. Entry to the ring system is gained by an interesting ringenlarging rearrangement. 

Rearrangement reactions involving 1,3-thiazines are often very facile. For example, reaction of 2-imino-4-phenyl-2/7-1,3-thiazinium perchlorate 957 with NaOH at room temperature gave 4-phenylpyrimidine-2(l//)-thione 958 <2004CHE1595>, while treatment of 6-amino-2,3-dihydro-l,3-thiazin-4(l// )-ones 959 with KOH readily gave the potassium salt of the dihydropyrimidinone 960 <2005HAC426>. 

One notable advance in this chemistry since the publication of CHEC-II(1996) is the use of enantiomerically enriched 3,6-dihydro-l,2-thiazine 1-oxides in the rearrangement sequence. For instance, iV-Cbz-protected bicyclic 1,2-dihydrothiazine 44 undergoes ring opening upon treatment with phenylmagnesium bromide (Scheme 16). The synthesis of allylic amino alcohol 129 is completed in excellent yield upon exposure of the intermediate sulfoxide 130 to trimethyl phosphite and methanol at 80 °C <2002TA2407, 2000TL3743>. 

Intramolecular thermal rearrangement of /ra r-4//-5,6-dihydro-l,3-thiazines 93 affords /ra r-4,5-dihydro-l,3-thiazoles 94 (Equation 2) <1997JPP09136881>. 5-Halotetrahydro-l,3-thiazine-2-thiones 95 undergo facile rearrangement when heated with methanol, ethanol, or isopropanol, probably via intermediate 96, to give 5-(halomethyl)thiazoli-dine-2-thiones 97 (Scheme 1). No solvolysis products are observed <2002CHE1533>. 

Synthesis of a new dipyrido-l,4-thiazine 328 has been described involving a Smiles rearrangement, and A -alkylation, arylation and heteroarylation of 328 have been repotted as well as its promising anti-tumor activity <2007H(71)1347>. Phenothiazine derivatives such as 329 and 330 have been developed for use in dye-sensitized solar cells <2007CC3741>. 

Treatment of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione with ethyl diazoacetate gives, among other products, ethyl 1,3-thiazine carboxylate (179) (99). The formation of 179 has been rationalized by an acid-catalyzed addition of ethyl diazoacetate to the thiocarbonyl ylide 177 to first give intermediate 178, which undergoes a subsequent ring enlargement reaction via a Tiffeneau-Demjanov rearrangement. 

An interesting rearrangement of thioureas leading to tetrahydro-1,3-thiazines has been reported by Tisler,297,298 who found that 1-trimethylene-3-aryl-2-thioureas undergo facile conversion to 150 in concentrated HC1. The same products (150) could also be prepared by treating the appropriately substituted thiourea with 1,3-dibromo-propane.298... 

H- 1,2-Oxazines are stabilized as 4,4-disubstituted derivatives but 4H- and 6if-l,2-thiazines are almost unknown. Possibly the paucity of these compounds simply reflects a lack of interest, for 6if-l,2-oxazines are comparatively common, and 3,5-diphenyl-6if- 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). 

These and other venerable synthetic routes to the tricyclic oxazines and thiazines have been reviewed in detail (B-78MI22701). 2-Hydroxy(or mercapto)-2, 4 -dinitrodiphenylamines readily cyclize to phenoxazines (or phenothiazines) in basic media through elimination of nitrous acid. This is the so-called Turpin reaction, which is complicated by the fact that the intermediate Meisenheimer complexes (251) may undergo a Smiles-type rearrangement so that mixtures of isomeric products are obtained (Scheme 112). 

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