Benzo-l,3-thiazines

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 study of the reaction of some 4H-l,3-benzothiazinones, e.g, (29), with Grignard reagents has also appeared. Typically, alkylmagnesium bromides, e.g. EtMgBr, react additively with (29) to give the dihydrobenzothiazinones (30), while in the case of phenylmagnesium bromide, addition takes place preferentially at the carbonyl function, affording the carbinols (31). 

In the area of 4i/-3,l-benzothiazines, a series of 2-substituted 4-formyl-methylene derivatives (33) have been synthesized by allowing various nucleophiles, especially amines, to react with (32), which may be obtained by ringopening of 4,7-dichloroquinoline with thiophosgene and barium carbonate. The benzothiazine-l-thiones (34) have been reported to react readily with tetrachloro- or tetrabromo-o-benzoquinone, giving the hitherto unknown 

The conversion of the 2-thiocyanate (35) into bis(4-thioxo-3,l-benzothiazin-2-yl) sulphide by treatment with triethylamine has been described, and further 

A further example of 1,4-thiazine formation by ring-enlargement of 2-sub-stituted thiazolium salts (see Vol. 3, p. 635) is provided by the reaction of some 2-amidino-derivatives (44) with aqueous sodium carbonate, leading to the 2-iminothiazinones (45) in good yields. 

---

Disubstituted derivatives of 4-mercaptoquinazolines were obtained in good yields by reaction of 5,6-benzo-l,3-thiazine-4-thione with amines (see 7b). 

The solid-state structures of the benzo derivatives (Z)-4-benzylidene-6,8-dichloro-4//-benzo[, ( )-4-(3,4-dichlorobenzylidene)-2-methyl-4//-benzo[< ][l,3]thiazine 20 <2004JOC4545>, and 7-amino-l/7-benzoM[l,3]thiazine-2,4-dithione 21 <2005AXEo387> have been determined. As expected, they possess planar structures, and the thiazine-2,4-dithione 21 molecules pack in the solid state through amino-thione hydrogen bonds <2005AXEo387>. 

The melting points, enthalpies, and associated entropies for a series of A -aryl-4//-benzo[ ][l,3]thiazin-2-amines 71 are presented in Table 3 <2004MI6291>. The melting points of the compounds determined by differential scanning calorimetry (DSC) agreed with the results obtained by hot-stage microscope. 

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). 

Recyclization of benzo-l,3,-thiazine-4-thiones (221) by the action of thiocarbohydrazide yields mesoionic condensed triazole N-amino derivatives (222) (86JHC43). 

Rearrangement of 2-imino-4-oxodihydro-5,6-benzo-l,3-thiazines 269 and 271 took place on heating above the melting point to give 270 and 273, respectively. In case of 269, the direction of rearrangement depended on the electron density on the nitrogen atoms. In the case of 271, 273 is more stable than 272 (67ZC231) (Scheme 88). 

Benzo-l,3-thiazine ring from benzisothiazole ring Reductive ring enlargement... 

In yet another variation of this synthesis, 2,6-dithioxo-2,3-dihydro-4,5-benzo-l,3-thiazine ( trithioisatoic anhydride ) (231) is condensed with hydrazine at room temperature to form the intermediate (232). This is cyclized, by hot formic acid, to l,3,4-thiadiazolo[2,3-Z ]-3,4-dihydro-quinazoline-4>thione (233). The proposed structures are supported by spectral data. ... 

Thion-3.methyl-dihydio-4.6-benzo-l.3-thiazin Oder 2.Hetfaylmereapto-4.S-benzo-1.3-thiadn 27,180 a. 27.109. 

Verbindung C HeNtOsS, vlelleioht 6-Ozo-2-imino-dihydio-4.5-benzo-l, 3-thiazin-1-diozyd 27,187. 

The interaction of l,2-dihydro-4//-benzo[with acid hydrazides provides very satisfactory yields of 5-substituted 3-(o-amino-phenyl)-l,3,4-thiadiazoles (94), undoubtedly by way of the intermediate iV-(2-aminothiobenzoyl)-N -acyl-hydrazines (93). ... 

Benzo-l,3>thiazines.—A direct procedure for preparing 2,3-dehydro-4H-l,3-benzothiazines is afforded by the condensation of 2-mercaptobenzylamine and its derivatives with ketones or aldehydes in alkaline medium. Thus, for example, (46) reacts with acetaldehyde to give (47 R = Me) in excellent yields. A somewhat different course is observed in the condensation of (46) with formaldehyde, which gives the methylene bis-derivative (48), resulting from the fast reaction of the primary product (47 R = H) with more of the aldehyde. 

Recently, interest in the syntheses of polyheterocyclic systems containing fused l,3-thiazin-4-ones has been growing due to the search of new biologically active substances. The synthetic methods used for obtaining these compounds are the same as those used for benzo-TAs. 

Benzo-l,3-thioxin-4-thione (148) reacts with phenylhydrazine to form the dithiole hydrazone (149), which must arise by initial nucleophilic attack at the thione function (80T3309). The l,3-thiazine-2,4-dione (150) possesses a three-carbon unit with an attached sulfur atom. Thionation with phosphorus pentasulfide gives the unsubstituted l,2-dithio e-3-thione (3b) (70AjC5l>. 

---