2H-1,4-Benzothiazin

H-1,4-Benzothiazines can be obtained from 2-aminothiophenols, by their reactions with either a-bromocarbonyl compounds (70AC(R)383) or active methylene compounds (Scheme 34) (76JCS(P1)1146). 

Phenylsulfonyl)furo[2,3- ]quinoline and its parent unsubstituted heterocycle were found to have very similar absorption maxima hence, the sulfone group does not provide an additional conjugative effect <83JOC774>. In addition, furo[2,3-/ quinoline and its isomeric furo[3,2-< ] counterpart were found to exhibit UV absorption maxima that are almost identical. An absorption maximum at 435 nm consistent with the presence of a 2H-1,4-benzothiazine chromophore was one of the key pieces of data that enabled the structure determination of compounds based upon the new 1,2-dihydro-3//,8//-pyrrolo[2,3-/z][l,4]benzothiazine skeleton <87T5357>. The UV spectrum of l,4-benzodioxano[6,7-c]furoxan was found to exhibit four characteristic band maxima in the 350-480 nm region <88JHC803>. 

Equation (48) <87T5357>. A mechanism similar to that commonly accepted for the formation of 2H-1,4-benzothiazines via condensation of /1-aminothiols with simple o- and p-benzoquinones was suggested. It was noted that the products (87 R3 = H) rapidly decompose to oligomeric materials whereas the others are much more stable to this presumed oxidative lability. 

The first synthesis of a derivative was reported by Unger,11 who claimed that reaction of phenacyl bromide with 2-aminobenzenethiol gave 3-phenyl-2H- 1,4-benzothiazine (10a). Nearly 70 years later Friedrich et al. proposed the 4H structure (10b).12... 

Trichochromes E and F are based on the 2H-1,4-benzothiazine ring, while trichochromes B and C are mixed systems, with both 1,4-benzothiazine and l,4-benzothiazin-3-one fragments. These may be extracted from red hair and feathers under alkaline conditions.31,32 Apparently33 only trichochromes B and C occur in red feathers, and trichochromes E and F, reportedly isolated from this source, arise as artifacts. The chromophore in the trichochrome... 

Prota and co-workers34 prepared 18 by oxidative coupling of 3-aryl-2H-1,4-benzothiazines, and established the structures of the cis and trans isomers of the 3-p-bromophenyl derivatives by X-ray crystallography. The cis and trans isomers are readily interconverted in solution at room temperature, with the red, cis isomer predominating over the yellow, trans isomer, both isomers being stable in the solid state. 

Prota s method cannot be employed in the synthesis of the trichochrome E and F skeleton because it would require the unstable 2H-1,4-benzothiazine 8 as starting material. However, the Italian group observed the spontaneous formation of compound 20 while attempting to prepare 2H- 1,4-benzothiazine... 

Preparation by ring expansion can be contrasted with that of ring contraction recently reported, whereby 1,6-benzothiazocine derivatives (79) undergo ring contraction in the presence of lead tetraacetate to give the 2H-1,4-benzothiazine derivatives 80 and 81. The proposed mechanism for the reaction involves a transannular sulfur migration. The structure of 81 was confirmed by X-ray crystallography.123... 

All of the synthetic routes reviewed so far have primarily involved the use of sulfur as a nucleophile. Sulfur can also act as an electrophile in the formation of precursors of the benzothiazine ring system. Reaction of sulfenyl chloride with ketones gives / -keto sulfides. The acetophenone adduct 90 has been cyclized with stannous chloride and hydrogen chloride in acetic acid to give 3-phenyl-6-chloro-2H-1,4-benzothiazine (91).135... 

N-Alkylation of the 4//-l,4-benzothiazine 95 has been reported.138 Kiprianov et al. described the quaternary salts of some 2H- 1,4-benzothiazines which are less conveniently prepared by direct N-alkylation than by synthesis... 

Ring contraction has also been observed in hydrogenation reactions of benzothiazines. Catalytic hydrogenation of 3-phenyl-2H-1,4-benzothiazine (141) gave 2-methyl-2-phenylbenzothiazoline (142), and not the dihydro-1,4-benzothiazine as might have been expected.14... 

Acctyl-3-methyl-l,3-benzothiazolium-trifluormethansulfonat laBt sich mit 0,1 N Salzsaure in 2,4-Dime-thyl-2-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzothiazin uberfiihren1073 (73%) ... 

The 2-amino and 2-mercapto derivatives of the 2H-1,4-benzoxazin-3(4/f)-one and 2H-1,4-benzothiazin-3 (4//)-one skeletons have not yet been described. We prepared them from the starting 2-bromo-2//-l,4-benzoxazin-3(4//)-one and 2-bromo-2//-l,4-benzothiazin-3(4//)-one, respectively [126] (Fig. (16)). 

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