Dihydro-1,4-benzothiazines, and related

Brown, C., Davidson, R. M., 1,4-Benzothiazines, Dihydro-1,4-benzothiazines, and Related Compounds, 38, 135. 

Angelini described the preparation of dihydro- 1,4-benzothiazine and related compounds from analogous esters by a two-stage reduction using tin and HC1 or lithium aluminum hydride.129 It is interesting to compare the reaction of 2-nitrophenol with similar reagents to produce benzooxazine derivatives. 2-Nitrophenol reacts with a-bromoethyl acetate, and the adduct is cyclized with zinc and ammonium chloride to the hydroxamic derivative 85.130 The adduct with phenacyl chloride has been similarly cyclized under a variety of conditions.131,132... 

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... 

N-Acyl-2,3-dihydro-l,4-benzothiazines and the related phenothiazines react with both organolithium and organomagnesium reagents to give the / -dicarbonyl derivative 116, indicating that the N-acyl derivatives may have a role to play as useful acylating agents.157 Mechanistic studies have provided novel explanations for this behavior and that of the related 1-oxides and 1,1-dioxides (117).158... 

Benzothiazines find extensive use as ataractic agents, i.e., tranquilizers and central nervous system (CNS) depressants. 4-(Hydroxyalkylcyclicamino)propyl-2-phenyl-3,4-dihydro-l,4-benzothiazines (29) show CNS depressant activity54 without including the anorexia associated with the use of related 1,4-benzothiazine derivatives55,56 such as 30. 

Sianesi and co-workers have alkylated 3,4-dihydro-2H-l,2-ben20thia-zine 1,1-dioxide (77) with ethyl bromoacetate to give ethyl (3,4-dihydro-1,1-dioxo-2H-l,2-benzothiazin-2-yI)acetate (127). The ester functionality in 127 was converted into amides and hydrazides. Zenno and Mizutani have also reported on the N-alkylation of compounds related to 77. Alkylation of... 

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. 

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