Dihydrothiazines reduction

Thiazolidine-2,4-dione, 2-dialkylamino-bisimide synthesis, 5, 129 Thiazolidine-2,4-diones IR spectroscopy, 6, 242 tautomerism, 6, 270 Thiazolidine-2,5-diones synthesis, 5, 138 Thiazolidine-4,5-diones synthesis, 5, 129 6, 316-317 Thiazolidine-2,4-dithiones tautomerism, 6, 270 Thiazolidines "C NMR, 6, 243 conformation, 6, 242, 247 dihydrothiazines from, 2, 93 hydrolysis, 6, 273 IR spectra, 6, 242 ring fission, 5, 80 synthesis, 5, 118 6, 316-321 Thiazolidines, imino-tautomerism, 6, 273 Thiazolidines, methyl-conformation, 6, 242 Thiazolidine-2-thione, 3-acyl-reduction, 1, 469 Thiazolidine-2-thione, 4-alkyl-synthesis, 6, 318... 

Recently, a series of substituted dihydrothiazines such as (93) was reported by workers at Merrell Dow to display potent inhibition of partially purified rat neutrophil 5-LO (0.2-2.0 //M) [243], Substitution on the phenyl group or variation of the benzyl to other alkaryl had little effect on activity, but replacement of the benzyl by alkyl or hydroxyalkyl reduced potency about 10-fold. Replacement of the phenyl substituent by benzoyl reduced potency, while reduction of the trisubstituted double bond completely destroyed activity. No anti-inflammatory activity was reported for this series. 

Successful double-bond reductions are shown in Scheme 36. Formic acid can be used <1970LA(739)32>, although N-formylation may occur <1970M1295>. With the right conditions, sodium cyanoborohydride is also a suitable reagent for dihydrothiazines <1994ACS517> and dihydrothiazin-2-ones <2006SL3259>. 

Tetrahydrothiazin-3-ones are lactams that have been reduced to tetrahydrothiazines with borane <1980JHC449>, sodium borohydride <1992JOC4215>, or LAH <1987H(26)1503>, without cleavage of carbon-sulfur bond. In one case, incomplete reduction occured with LAH the intermediate lactol was dehydrated to give a dihydrothiazine as main product <1989JPS937>. 

There are many reactions that result in the conversion of dihydrothiazines into other heterocycles. They may be divided into three categories those that involve a nonoxidative and nonreductive cleavage, those that require an oxidative cleavage, and those that proceed by a reductive cleavage of the dihydrothiazine ring. 

With hydrogen sulhde in the presence of a base, dihydrothiazines undergo reductive ring contraction to give thiazolidines, usually in good yield for example, 2,2-diethyIthiazolidine was formed from the compound 60a. S-Labeling experiments are consistent with the pathway outlined in Scheme... 

The only example of an oxidative ring opening of the dihydrothiazine ring involves the ozonolysis of the derivative 172 to give compound 193. The 1—2 bond of dihydrothiazinones can be reductively cleaved in the presence of sodium in liquid ammonia. Thus compound 80a was converted into the salt 119 (Section V,B,4,a) although a stable isolable material, 119 readily underwent S-alkylation when treated with alkyl halides. Although Raney nickel is expected to effect the reductive desulfurization of dihydrothiazines, only one example of this reaction has been reported thus the compound 80b afforded N-acetylalanine ethyl ester. The 3—4 bond of dihydrothiazinones can be reductively cleaved under certain circum-... 

However, dihydrothiazine oxides that have a strong electron-withdrawing group on nitrogen reportedly do not undergo this reduction. 

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