Dihydro-1,4-thiazines reactivity

TVA -Disulfonylsulfodiimides 244 react exothermically with butadiene to give 1-sulfo-nylimino-2-sulfonyl-3,6-dihydro-l,2-thiazines 245 (equation 130)121,122. IV-Aryl-AT-sul-fonylsulfodiimides 246 are much less reactive as dienophiles. The addition to butadiene to yield 247 takes place in boiling benzene (equation 131)123. No cycloaddition reactions of dialkyl- or diarylsulfodiimides are known. 

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>. 

Similarly, reaction of 3-chloroacylthio-3-isothiazoline-5-thiones (333) with reactive alkynic compounds proceeds with formation of the 1,3-dithiole derivatives (334) which contain thiazolone or 5,6-dihydro-l,3-thiazin-4-one rings (81H(16)595). 

Although the subject of brief surveys, " the chemistry of mono-cyclic 1,4-thiazines has not previously been discussed in a comprehensive manner. The aim of this review is to consider the synthesis, reactivity, and physicochemical properties of these compounds and their dihydro derivatives. 

X-Ray studies of the system, using dimethyl 4-formyl-2,3-dihydro-1,4-benzothiazine-2,3-dicarboxylate,17 41/-1,4-benzothiazine 1,1-dioxide,18 and the 3-methyl derivative,19 showed these molecules to be essentially planar with only small distortions associated mainly with the heteroatoms in the thiazine ring. The various bond lengths and angles were related to those of indole in an attempt to rationalize their reactivity toward electrophiles, which has been reported20 to be similar to that of indole. Molecular mechanics calculations similarly indicated essentially planar rings for trans-2-dimethyl-4-acetyldihydrobenzo thiazine.21... 

By contrast, the chemistry of dihydro-1,4-thiazines is in a much healthier state. The abundance of syntheses, particularly for the derivation of the 3,4-dihydro tautomers, is in large measure responsible for this situation. It is clear that dihydrothiazines possess some interesting and unusual patterns of reactivity, particularly in their ability to undergo molecular rearrangements, which are of general organic chemical interest. It is also apparent that such compounds are versatile precursors of both known and rare heterocyclic systems. 

Ofloxacin is by far the most representative of the N-l/C-8 tricyclic derivatives only a few other quinobenzothiazine derivatives [41] or pyridobenzothia-zine isosteres of ofloxacin derivatives [40] have been reported. Figure 18 shows the preparation of 7-oxo-2,3-dihydro-7H-pyrido(l,2,3-de) (1,4)benzothiazine-6-carboxylic acids. Interestingly, chlorine substitution of derivative 22 occurred in polar or unpolar solvents only after enhancement of the aromatic nucleus reactivity by oxidation of thiazinic sulfur to sulfoxide or sulfone 23 and 24. Derivative 25 substituted with IV-methylpiperazine (MF-934) was found slightly less active in vitro but more toxic than ofloxacin [40]. 

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