Thiazines and their Fused Derivatives

Sensitized photo-oxidation of 2-aryl-3,5-dimethyl-2//-l,2-thiazine 1,1-dioxides (398) gives 5,6-dioxygenated products (399) these compounds are 

Reagents i, CHCl, at r.t., absence of trap ii, CHCl, at r.t., butadiene 

Reagents i, O2, methylene blue, MeOH, hv ii, Et,N, EtjO, heat 

Kataoka, H. Shimizu, and K. Matsuo, Tetrahedron Lett., 1979, 3969. 

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Oxazines, Thiazines, and their Fused Derivatives 359 Oxazines 359... 

Thiazines and their Fused Derivatives.—A new synthetic route to 3,6-dihydro-1,2-azathiabenzenes has been established thiazyl fluoride (F—S=N) reacts with perfluorobutadiene to give an almost quantitative yield of perfluoro-lA ,2-thiazacyclohexa-1,4-diene (397). It should be noted that alkyl-butadienes react explosively. The C—S bond of this stable, colourless liquid can be cleaved with halogens e.g. see Scheme 153). ... 

In this chapter, consideration is restricted to monocyclic thiazines and their functionalized derivatives. Benzo-fused systems and condensed-fused systems in general are not included. To date there have been few reviews devoted to 1,3-thiazines, probably because of the difficulty dealing with them without including cephalosporins and their derivatives. (Cepha-losporine C is shown here.)... 

In the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) 1,3-thiazines and 1,3-oxazines were reviewed together indeed, much of their chemistry is similar, providing justification for this arrangement. However, there are areas in which this is not so, and in this edition the two types of heterocycle are treated separately. This allows a more focused approach, but as Quiniou and Guilloton <90AHC(50)85> have already pointed out, one feature which complicates any survey of 1,3-thiazines is the interrelationship of these compounds to cephalosporins. The literature dealing with cephems and related systems is vast and requires individual treatment, so here the emphasis is on the synthesis and reactions of simple 1,3-thiazines and their benzo derivatives. Other fused systems are not included unless their chemistry illustrates some important property of the 1,3-thiazine heterocycle itself. 

There is just one group of compounds in this chapter where a number of derivatives have been synthesized, that is, pyrimido[2,l-Z)][l,3]thiazines and their benzo derivatives. Pyrimido[2,l-i][l,3]thiazines, apart from a few genuine and special syntheses (as of (435)), were almost exclusively prepared by the [3 + 3] route, reacting either a pyrimidine-2-thione (2-thiol) or a 2-amino-[l,3]thiazine with bifunctional electrophiles with three carbon atoms. The benzo-fused derivatives were synthesized by analogous routes. 

Oxazines and thiazines were considered together in CHEC(1984) and this meant that the review was restricted. In CHEC-II(1996) <1996CHEC-II(6)383>, the individual heterocycles and their derivatives were reviewed separately, which allowed for a thorough coverage. This trend is continued in this edition where the 1,3-thiazines and their derivatives are discussed, and this includes a review of the chemistry, syntheses, and applications. It does not include the vast literature dealing with cephems and related systems and other fused systems are not included unless their chemistry illustrates some significant property of the 1,3-thiazine heterocycle itself. 

The continuing interest in the chemistry of the 1,3-oxazines and the related thiazines and pyrimidines may arise in part from their versatile synthetic applicability and their pharmacological usefulness. Although six-membered saturated or partially saturated 1,3-heterocycles and their derivatives fused with a benzene ring have been thoroughly studied since the beginning of the twentieth century, much less attention has been paid to their saturated counterparts, the related cycloalkane-fused bicyclic 1,3-heterocycles. 

The systems falling within this group are N-bridgehead pyridazino-, pyrimido- and pyr-azinothiazines and their benzo-fused derivatives. Theoretically, 16 bicyclic systems are possible, but only seven of them are known with 13 benzo-fused derivatives (see Table 5). None of the groups of compounds were considered in CHEC-I and therefore the whole of the literature has been surveyed. The only previous review of this field is that by Mosby <61 Ml 825-01) who lists a few references on pyrimido[2,l-6][l,3]thiazines. That ring system still remains the most extensively studied. 

This group of compounds covers N-bridgehead oxazino-oxazines, thiazino-oxazines, and thia-zino-thiazines, and also their benzo-fused derivatives. Of the theoretically possible 10 oxazino-oxazines, three have ring file numbers, but no reference has been found for [l,4]oxazino[4,3-c][l,3]oxazines. The number of known benzo-fused systems is four. Of the theoretically possible 16 thiazino-oxazines, three are known and one benzo-fused system. Finally, of the 10 theoretically possible thiazino-thiazines two are known and one benzo-fused system (see Table 7). None of the groups of compounds was considered in CHEC-I, nor in previous reviews, therefore the whole of the literature has been surveyed. 

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