Benzo-1,2-thiazine, formation

As with five-membered heterocycles, phosphorus pentasulfide may replace a ring oxygen atom by sulfur, or it may effect replacement in an acyclic precursor and then bring about cyclization. Thus isochroman-l-one (99) is converted into thioisochroman-l-thione (100) under the same conditions a 3-arylisocoumarin( 101) produces a 3-ary 1-1-thioisocoumarin (102) only, with no replacement of the ring oxygen atom.122 A typical example of thiation, followed by cyclization, is the formation of 2-alkyl- or 2-aryl-3,l-benzo-thiazine-4-thiones (103) from /V-acylanthranilic acid esters (104) by treatment with phosphorus pentasulfide in boiling xylene.122... 

The activated 4-methylene function of 3,4-dihydro-2-alkyl-l,2-benzo-thiazin-3(2ff )-one 1,1-dioxide (47) permits the formation of an anion. Treatment of the anion in DMSO14,38 or DMF74 with isocyanates yields the corresponding 4-carboxamides (116) (Eq. 28). 

Benzo-l,3-thiazines.—Little work has been reported in this area. A new route to substituted 4/f-l,3-benzothiazines, e.g. (27), has been found in the acid-catalysed condensation of a nitrile with the carbinol (26), arising from the addition of Grignard reagents to 2-mercaptobenzoic esters. In view of the limitations of its applicability, and the low yields obtained, the synthetic value of this reaction is rather circumscribed. Condensation of cyanogen with 2-mercaptobenz-hydrazides results in ring-closure and formation of 3-amino-2-imino-l,3-benzo-thiazin-4-ones, but a similar reaction with 2-mercaptobenzoic acids gives predominantly the bis-l,3-benzothiazinones (28). 

A recent report describes the formation of benzo derivatives of the pyrimido[4,5- ][l,4]thiazine system by cyclization (Scheme 109) <2007BMC2120>. The compounds prepared have some 5-lipoxygenase inhibitory activity, the active inhibitor being the corresponding sulfoxide, which has been prepared by oxidation of the parent (Scheme 109). 

The reaction of benzothiete 41 with 6,7-dimethoxy-27/-benzo[/][l,3]thiazine, which led to the formation of benzothiazino[4,3- ]-6,7-dimethoxy-2/7-benzo[i ][l,3]thiazine 138 revealed that benzothiete had the character of a heterodiene 4T. The tetracyclic compound was obtained in 50% yield <2006M231> (Scheme 23). 

In Chap. 2, the author describes a novel synthesis of 2-(aminomethyl)indole by copper-catalyzed domino three-component coupling and cyclization. Two-step construction of polycyclic indoles by combination with palladium-catalyzed C-H functionalization at the indole C-3 position, scope and limitation of the asymmetric three-component indole formation, and synthesis of benzo[e][l, 2]thiazine derivatives and indene-l,l-dicarboxylate, are also presented in this section. 

Normally, decompositions of azides in hydrogen-rich solvents are avoided in order to minimize the formation of products based on triplet nitrene. Surprising, therefore, is the report that 6i/-dibenzo[c ,e][l,2]thiazine 5,5-dioxide (335) is obtained in optimum yield (80.6%) from the thermolysis of biphenyl-2-sulphonyl azide in cyclohexane at 120 Decomposition of o-(2-thienyl)benzenesul-phonyl azide under similar conditions furnishes the thieno[3,2-c]benzo-l,2-thiazine dioxide (336), in practicable yield (61%). Whereas, in POCla-pyridine... 

Benzo-l,4-thiazines and Related Compounds.— The chemical behaviour of the Vilsmeier product (111), derived from l,4-benzothiazin-3(4H)-one, has been the subject of detailed studies. Hydrolysis under different conditions affords the acid (112), the aldehyde (114), or the chloro-aldehyde (113), depending on the method of hydrolysis. Treatment of the perchlorate of (111) with DMSO leads to the displacement of the chlorine atom to give the dimethylsulphoxonium derivative (115), while reaction with pyridine proceeds with selective attack at the aminomethylene function, yielding the pyridinium salt (116). This latter reacts readily with aniline in acetic acid medium to give, along with 2-formyl-3-anilino-l,4-benzothiazine (117), the anilinomethylene derivative (120), whose formation probably involves an intramolecular rearrangement of the intermediate pyridinium salt (118), as depicted. 

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