2- Amino-1,3-benzothiazin-4-ones

Piperazine NH group of 9-fluoro-10-(l-piperazinyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7e]-l,4-benzothiazine-6-carboxylate was reacted with 4-nitrophenylsulfonyl chloride, 2,6-dichloropyrazine, 2,6-dichloropyridine in DMF in the presence of pyridine, and with 4-nitrophenyl isothiocyanate in aqueous acetone in the presence of KOH (01MIP13). A side chain amino group on a 2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazin-7-one skeleton was acylated (OOMIPIO). 

Isoxicam Isoxicam, 1,1-dioxide 4-hydroxy-2-methyl-A-(5-methyl-3-isoxazolyl)-2/7-l,2-benzothiazine-3-carboxamide (3.2.80), is synthesized analogous to piroxicam, using ami-dation of 1,1-dioxide 3-methoxycarbonyl-3,4-dihydro-2-//-l,2-benzothiazine-4-one (3.2.78) in the last stage with 3-amino-5-methylisoxazole, instead of 2-aminopyridine [127-130]. 

Synthesis The reaction of benzothiazolo-3(2H)-one-1,1-dioxide with methyl chloroacetate gives the methyl 2(3H) acetate derivative, which is isomerized with sodium methoxide in toluene/terf-butanol yielding methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1 -dioxide. The subsequent methylation with methyl iodide in methanol yields the 2-methyl compound. Finally this compound is treated with 2-amino-5-methylthiazole in xylene (Trummlitz et al. (Thomae GmbH), 1979 Trummlitz et al., 1989 Kleemann et al., 1999). 

Reaction of 9-(carboxymethylene)tetrahydropyridopyrimidin-4-one 546 (R = COOH) and 2-aminothiophenol gave 9-(benzothiazin-2-yl)tetrahy-dropyridopyrimidin-4-one 550 as a mixture of erythro and threo isomers (90JHC247). The addition was accompanied by spontaneous cyclization between the amino and carboxyl group of intermediate 549 to the yield 9-(benzothiazin-2-yl) moiety. 

From 2-Amino-3,l-benzoxazin-4-ones and 2-Amino-3,l-benzothiazin-4-ones... 

Amino-3,l-benzoxazin-4-one (1, X = O) and 2-amino-3,l-benzothiazin-4-one (1, X = S) undergo a facile rearrangement to furnish quinazolin-2,4(li/,3i/)-diones and 2-thioxo-2,3-dihy-droquinazolin-4(]7T)-ones 2. respectively, under relatively mild conditions on heating in acidic solution or on standing for a longer time in dilute alkali (cf. p 142). ... 

Dimroth rearrangement involving migration of an alkyl or aryl substituent from N3 to the amino or imino group at position 4 or 2 is the main type of rearrangement with retention of ring size in the quinazoline series. Although transformations of 2-amino-3,l-benzoxazin-4-ones and 2-amino-3,l-benzothiazin-4-ones to quinazolines also represent, from the mechanistic viewpoint, a Dimroth-type reaction, they are treated in Section 6.3.1.1.2.3. 

The 2-bromo lactams were treated with a solution of gaseous ammonia in tetrahydrofuran to afford 2-amino-2//-I,4-benzoxazin-3(4//)-one and 2-amino-2//-1,4-benzothiazin-3(4F/)-one, respectively. 

Conversion of l,2-benzothiazin-4-one 102 to the corresponding oxime 103 followed by high-pressure catalytic hydrogenation produced the cyclized amide 104 (Eq. 24).66 Hydrolysis of compound 104 in aqueous acid yielded the amino acid 105. By an analogous procedure, 4-amino-3,4-dihydro-2-... 

Sianesi and co-workers39 have nitrated the 3-amino- 1,2-benzothiazine 122 to the 7-nitro derivative 123 in good yield. Reduction and hydrolysis of 123 gave 7-amino-3,4-dihydro-3(2H)-one 1,1-dioxide (124). 

In addition to the 2-amino and 2-nitro derivatives, various other substituted benzenethiols have been used as precursors for the benzothia-zine system. 6,7-Dimethoxy-l,4-benzothiazin-3-one (88) has been prepared... 

The formation of the l,4-benzothiazin-3-one (104) has been observed in the course of sequential analysis of proteins, using 2-methyl-N-benzenesulfonyl-AT-bromoacetylquinone diimide.146 The protein chain is cleaved at the cysteine amino acid unit, with cysteine forming a benzothiazinone with the diimide reagent. 

Amino-2,3-dihydro-l,4-benzothiazin-3-one (134) is a useful source of a wide variety of 6-substituted derivatives via diazotization. The amino group has been replaced by halogens and pseudohalogens, by NO, and by N02, as well as by HgCl, H2As03, and H2Sb03.61... 

Amino-3,l-benzothiazin-4-one (296) is obtained from A-(2-cyanophenyl)-A -benzoylthiourea (297) in contact with concentrated sulfuric acid over 2 d. In this reaction the nitrile group of the starting material is slowly hydrolyzed, affording the amide (298), which then undergoes acid-catalyzed cyclization and amide hydrolysis to give the benzothiazinone (Scheme 58) <90ZC440>. 

In an attempt to make octahydroquinazoline-2-thione, ds-2-bromometh-ylcyclohexylamine was fused with thiourea at 155°C for 3 hr, but only ds-2-amino-4a,5,6,7,8,8a-hexahydro-4//-1,3-benzothiazine (79) could be isolated (good yield). Aqueous thiocyanic acid gave the same product (low yield). Aqueous cyanic acid furnished the corresponding aminobenzoxazine (excellent yield), whereas fusion with guanidine carbonate at 120°C furnished cis-4a,5,6,7,8,8a-hexahydrobenzoxazin-2-one (good yield).61... 

Amino-2-imino-3,4-dihydro-2H-l,3-benzothiazin-4-ones from o-mercaptocarboxylic acid hydrazides... 

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). 

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