1,2,3-Thiadiazine 1-oxides

The oxidation of 2-benzenesulfonylisothiazol-2-imines 7T, 130 and their perchlorates 73,132 with hydrogen peroxide gave 1,2,3-thiadiazine 1-oxides 402 and 403 in 26-52% yield they were then converted into the corresponding 1,2,3-thiadiazine 1,1-dioxides 406 and 407 in 24-90% yield using m-chloroperoxybenzoic acid. 

The oxidation of isothiazolium chlorides 135 with hydrogen peroxide in acetic acid at room temperature gave the 1,2,3-thiadiazine 1-oxides 408a,b in 15-51% yield. They were also converted into 1,2,3-thiadiazine 1,1-dioxides 409a-c in 16-43% yield. The structure 408b was confirmed by X-ray diffraction (00SUL109, Scheme 137). 

Several 1,2,3-thiadiazine 1-oxides were prepared in moderate yields by oxidation of 2-benzenesulfonylaminothia-zolium salts and the corresponding imines with hydrogen peroxide at 0° C (Scheme 4) <1999JHC1081>. The X-ray crystal structure of the 1,2,3-thiadiazine 1-oxide 27e, where R = R = CH3 and R = 4-Br, has also been reported. The structures of the products were confirmed by IR and H and NMR spectroscopy. Conversion of the 1,2,3-thiadiazine 1-oxides to the more common 1,2,3-thiadiazine 1,1-dioxides was achieved by treatment with meta-chloroperbenzoic acid (Scheme 4). 

Phenothiazines, benzo-l,2,4-thiadiazine 1,1-oxides, fluoroquinolones, nicotinic acid, and nitrofuran derivative as potentially dangerous photosensitizers 98MI11. 

Although 2H- and 4//-thiadiazines with divalent sulfur are virtually unknown, both isomers have been prepared as the 1-oxides and, more commonly, as the 1,1-dioxides 109 (X = SO2) and 110 (X = SO2). 

CuHj8N208S 2,3 -Didehydro-[5-methyl-2H-l,2,6-thiadiazin-3-yl 4,6-di-0-acetyl-2,3-dideoxy-a-D-riho-hexopyranoside) 1,1-di-S-oxide... 

Investigation of transformations of the zwitterion 207 led to the elaboration of a new synthetic route to imidazo[ 1,2-t]-thiadiazines <2003JOC4791>. Treatment of this compound 207 with carbon disulfide in the presence of sodium hydroxide resulted in elimination of carbon oxide sulfide and in formation of the cyclized product 208. 

Oxidation of pyrido[23-c][l,2,4]thiadiazines 94 with sodium hypochlorite and, separately, iR-chloroperbenzoic add affords the 1,1-dioxide derivatives 95 and the 5-oxide derivatives 97, respectively. Oxidation of 1,1-dioxide derivatives yields the novel 1,13-trioxides 96 <98T13645>. 

Similar methodology to that employed above gave dialkylated dihydropyrido[3,2- ]thiadiazines 207a-c (Scheme 29), while alkylation of the oxidized form 208 gave the A -monoalkyl derivatives 209a-c <1998JME2946>. 

The pyrido[2,3- ]-l,2,4-thiadiazine 1,1-oxides 267 are readily prepared by the reaction of 2-aminopyridine-3-sulfonamides 266 with sources of C-1 units such as orthoesters (Equation 28 Table 20), <1998T13645, 2003S1603> and anhydrides (Equation 29 Table 21) <1995T3221, 2000JME1456>. 

Table 20 Pyrido[2,3-e]-1,2,4-thiadiazine 1,1 -oxides 267 from the reaotion of 2-aminopyridine-3-sulfonamides 266 with orthoesters...

H-1,2,6-Thiadiazine 1-oxides on heating in toluene extrude sulfur monoxide to give pyrazole derivatives in high yields (Scheme 55) (83JCS(P1)2273). 

Less useful preparations of 1,3,5-thiadiazines in which they are formed as components of mixtures include that of Chase and Walker.262 They isolated a thiadiazine as a product of the reaction of thiourea, bromine, and p-chlorophenylacetonitrile in acetone. The function of the nitrile, which was not incorporated into the product, is not apparent. The product of a similar reaction, without the nitrile, was assigned a dithiazine structure by Baumann.304 Oliver and Stokes202 also reported that a 1,3,5-thiadiazine is formed among the myriad of identified products of the 15-month air oxidation of l,l,5,5-tetramethyl-2,4-dithiobiuret. 

Electrophilic sulfur species such as thionyl chloride are frequently used in the synthesis of sulfur-containing heterocycles and, for example, reaction with N-N 1,5-dinucleophiles is a direct route to 1,2,6-thiadiazine 1-oxides. Thus the thiadiazines (138 n-1) are readily prepared by treatment of (231) with thionyl chloride in pyridine (81JCS(Pl)l89l), and the benzothiadiazine (232) is similarly made from (233) (64JOC2717). Reaction of (234) with thionyl chloride gives the dithiatriazine (235) (74ZOR488). 

An equimolar ratio of a substrate and oxidizing agent gives oxides 23 and 24 in yields of 71% and 4%, respectively, whereas triple the amount of oxidizing agent leads only to dioxide 24 in 93% yield. The intermediate naphtho[nitrogen elimination even at room temperature. Dioxide 24 may be obtained only on oxidation of monoxide 23, and not via the formation of... 

IJOC4570). Photolysis or thermolysis of naphtho[ c]thiete 20 and naph-tho[carbon disulphide, also occurs by a free-radical mechanism which leads to naphtho[other products of these conversions [79JA7684 81JCS(P1)413]. 

The reaction of 9-amino- 1-phenaleneimine 453 with thiony(aniline results in the corresponding thiadiazine 5-oxide 454, which is protonated in sulfuric acid and then dehydrated to give phenaleno[c[Pg.77]

In El mass spectrometers, 1-phenyl-substituted 1,2,4-thiadiazine 1-oxides can undergo migration of the phenyl group from the sulfur atom to nitrogen, a common feature in the mass spectra of aryl alkyl sulfoximes (77JOC952). 

In cyclic sulfoximides such as 3-ethoxy-4,5-dihydro-3-oxo-l-phenyl-and 3,4,5,6-tetrahydro-3,5-dioxo-1 -phenyl-1H-1 A6,2,4-thiadiazine 1 -oxides (46), the C6 proton signals appear at much higher fields [4.35 and 4.9 ppm (2H)] than for aromatic systems [benzene, 7.27 ppm thiophene, 7.2 (C2-H) and 6.95 ppm (C3-H)]. Similarly, the, 3C-NMR signals of the C6 atom appear at higher fields. These facts suggest a degree of ylidic character (77JOC952), which can be demonstrated by the reactivity of such compounds towards electrophiles (see Section III, C,3,f). 

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