Ring-Fused 1,2-Benzothiazine Derivatives

The two preceding sections have discussed replacement of the benzene ring of a 1,2-benzothiazine with other aromatic or heteroaromatic systems. This section details reactions of 1,2-benzothiazines leading to more complex tri- and tetracyclic 1,2-benzothiazine ring systems. 

Rasmussen8132 obtained tricyclic, 1,2-benzothiazines (181) from ethyl 4-hydroxy-2//-l,2-benzothiazine-3-carboxylate 1,1-dioxide (180) and a,a -dihalides (e.g., 1, 3-dibromopropane) (Eq. 38). 

Kubo and co-workers135 reacted 2-cyanomethylbenzenesulfonyl chloride (49) with ethylenediamines to afford l-substituted-2,3-dihydroimidazo-[3,2-b][l,2]benzothiazine 5,5-dioxides (189) (Eq. 40). This is the only sequence in this section that does not use a preformed 1,2-benzothiazine as a starting material. The products are claimed to possess analgesic, antiinflammatory, and antipyretic activities.135 

The versatile ester 180 with N-substituted aziridines (190) affords136137 many 1,2,3,4,-tetrahydro-11 - hydroxypyrazino [ 1,2-b] [ 1,2] benzothiazin-l(2H)-one 6,6-dioxides (191) (Eq. 41). l,2,3,4-Tetrahydro-ll-hydroxy-2-(2-hy droxyethyl)pyrazino [ 1,2-6] [ 1,2] benzothiazin-1 (2H)-one 6,6-dioxide (191 R = CH2CH2OH), after conversion into the methanesulfonate 192, was treated with base to give the tetracyclic system 193 (Eq. 42). Compound 193 can be isolated in the reaction of 192 with various nucleophiles. Thus, reaction of 192 or 193 with secondary amines and mercaptides produces 191 (R = CH2CH2NR1R2) and 191 (R = CH2CH2SR), respectively. Reaction of 192 or 193 with primary amines gave 194 (Eq. 42).136,137 

Similar ring systems were prepared from 3-acety 1-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide (93) and ethylenimine (190 R = H)137,138 (Eq. 43) or ethylene dibromide (forming 95).8,139 The ethylenimine reaction gave only 

Rasmussen obtained tricyclic, 1,2-benzothiazines (181) from ethyl 

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Heterocyclic Ring-fused Thiazines and Ring-fused 2,1-Benzothiazine Derivatives... 

The parent 1,4-thiazine exists exclusively as the 2H tautomer 86, independently of the medium used, as do its pyrimidino-fused derivatives 87 (76AHCS1, p. 80 84MI2). However, the equilibrium could be affected significantly by a substitution pattern in the thiazine ring, as was shown in the example of 1,4-benzothiazine. Thus, 3-phenyl-1,4-benzothiazine 88 (R = H, R = Ph) is present in aqueous hydrochloric acid as a 4 1 mixture of 2H (88a) and AH (88b) isomers... 

Since the publication of CHEC-II(1996), there have been very few examples related to the reactivity of substituents attached to ring carbon atoms. One case involves the reaction of 3-benzylidene-2,3-dihydro-2-methyl-l,2-benzothiazin-4-one 1,1-dioxide 163 with the alkylidenephosphorane derived from salt 164 forming the tricyclic-fused ring compound 165 (Scheme 20) <1996J(P1)2541>. This material 165 was oxidized with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) affording the biphenyl 166. Ring-opened product 167 was produced from 165 upon exposure to />-toluene-sulfonic acid and heat. 

Steiner141 has also prepared heterocyclic derivatives in which a seven- or eight-membered ring is fused to the 3,4-position of the 1,2-benzothiazine molecule. Thus, reaction of ester 199 with 1,2-ethanedithiol, 1,3-propane-dithiol, or ethanolamine gave 215,216, or 217, respectively. Similarly reaction of 199 with 2-mercaptophenol, 1,2-benzenedithiol, or o-aminophenol gave... 

Reductive amination of aldehyde-tethered arylnitro derivatives yielded benzazepines in moderate yields (13EJ05262) while the Lewis acid-catalyzed ring contraction-Friedel-Crafts-type cyclization of a series of methoxy-substituted benzothiazines 37 resulted in thiazolo-fused benzazepines 38 (13EJ06291). 

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