Pyrazoles 1,3,4-thiadiazines

Standard methods involving glycosyl halide or ester derivatives in reaction with protected heterocycles have been applied to the synthesis of various glycosyl derivatives of 5-fluoro-uracil and -cytosine, a number of nitro-imidazoles and -pyrazoles, thiadiazines and oxadiazolo-thiadiazines, and 5-methylthio derivatives of -uracil, -4-thiouracil, and -cytosine,/3-D-ribofuranosyl derivatives of 2-thio-6-azauracil, diethyl 4-hydroxypyrazole-3,5-dicarboxylate, 5-acetyl-uraeil, 2,4- and 2,5-thiazolidinediones, 4-thiomethyl-2-azapurine, 2-hydroxypurine, 3-deaza-adenine-8- C, l-deaza-8-azaguanine, imidazo-(l,2- )l,3,5-triazenes, e.g., (5), //n-benzo-guanosine, -inosine, and -xanthosine (6), and a derivative of lV-2-(i3-D-ribopyranosyl)benzotriazoie. Likewise 2-0-... 

The cycloaddition reaction of compound 6 with N-aryl- and N-aralkylazides 23 was also investigated (967(52)7183). Thiadiazabicyclo[3.1.0]hexene derivatives 25 were obtained from the labile triazoline intermediate 24 through nitrogen elimination. This bicyclic system underwent thermal transformation, producing thiadiazine dioxides 26 as the main product together with thiazete dioxides 27 and pyrazoles 28. 

Acyloin 213 with thioamides, thiosemicarbazides, and methyl dithio-carbazate in trifluoroacetic acid give photochromic thiazole-, thiadiazine-, and pyrazole-bridged dihetarylethenes 254,255, and 256-258, respectively (Scheme 72) (OlIZVllS, 06ZOR882). 

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). 

There are several examples of sulfur extrusion from 1,3,4-thiadiazines (144) either under basic conditions via the 877-anion (31) <75AG(E)581, 77S196), or by heating in acetic acid (70LA(741)45, 76JPR971). Both sets of conditions give pyrazoles in good yield. 

Other desulfurization reagents are also effective, and the dithiadiazine (149) gives the thiadiazole (150) on treatment with triphenylphosphine (76JCS(P1)38). Triphenylphosphine also converts thiadiazines (144) into pyrazoles (77S485), and 2,1,4-benzothiadiazines (151) into the corresponding benzimidazoles (74BRP1350277). This latter reaction is in marked contrast to that of the isomeric 1,2,4-benzothiadiazines (145), which lose NH rather than S on treatment with triphenylphosphine. 

The extrusion of SO from some 1,2,6-thiadiazine 1-oxides, such as 198, to give the corresponding pyrazole can be achieved by heating in toluene [79CC891 81JCS(P1)1891 83JCS(P 1)2273]. The reaction of bromine/ dichloromethane with 3-oxo l,2,5-thiadiazine212(R = Me, R2 = Me) in... 

Like the 1,3,4-isomers (see the following section), 1,2,6-thiadiazines 161 afford pyrazoles 162 in desulfurization reactions. As a special feature, a N — N bond is formed in this ring contraction. It is not necessary to isolate the starting 1,2,6-thiadiazines 161 trimethine derivatives 160 as corresponding precursors can also be directly transformed to pyrazoles 162 [81JCS(P1)1891] (Scheme 46). 

Ring-contraction reactions of 6//-l,3,4-thiadiazines 167 (or their tautomeric forms) were widely used for the preparation of pyrazoles 168 (Scheme 47 and Table I) (for reviews, see 69ZC361 70MI1 87MI1 91KGS1443). 

Formation of N-substituted pyrazoles 172 (77ZC173) and 174 [56AK523 62ACS(A)2395] is possible, starting from the corresponding N-substituted 1,3,4-thiadiazines such as 171 or 173 or their precursors (Scheme 48). 

A correlation between C-3 and C-5 of pyrazoles and related 1,2,6-thiadiazine 1,1-dioxides has been established [Eq. (2)](82JOC536). 

In the solid state, compounds (R = phenyl) are in their NH form (88JCR(S)94), which is the tautomer preferred in polar aprotic solvents (DMSO), except for compounds in which R = NHj, which always exist as the CH (B) tautomer (Section II,A,3,b). In nonpolar solvents (CDClj), mixtures of NH (A) and CH (B) tautomers are present. The value of depends on the nature of R. In basic solvents (pyridine), the common anionic form exists (Section II,B,l,a). The OH (C) tautomer, which exists in related pyrazoles in a high percentage (76AHC(Suppl)316), is not present in these thiadiazine derivatives. On the other hand, 6-substituted derivatives, which... 

Zur thermischen Umwandlung von 5-Oxo-2-phenyl-5,6-dihydro-4H-l,3,4-thiadiazin zu 3(5)-Hydroxy-5(3)-phenyl-lH-pyrazol s. Bd. E5, S. 1303 (1985). 

Diimines 1 react with sulfur dichloride or disulfur dichloride to give the 1,2,6-thiadiazines 2aj.23 When compounds 1 are treated with thionyl chloride, the 1,2,6-thiadiazine S-oxides 3a-l are formed.23,24 On heating in toluene to 90°C, compounds 2a-j are converted into the pyrazoles 4 by extrusion of sulfur. The pyrazoles 4 can also be obtained by heating the diimines 1 in pyridine for 8 hours with sulfur dichloride, disulfur dichloride, or thionyl chloride. In contrast, the tetrahydro-l,2,6-thiadiazines23 obtained from 1,3-diamines and sulfur dichloride cannot be converted to pyrazolidine derivatives by extrusion of sulfur. When compounds 2 a j or 3a-l are heated at 60 °C in tetrahydrofuran containing 6M potassium hydroxide, the starting materials 1 are recovered. 

On condensation of 4,4-dialkylthiosemicarbazides with a-halo ketones, ring-closure reactions only at Nl, N2, or S as well as subsequent reactions to pyrazoles are possible on account of the double substitution at the amino group.31,32,44 Thus, A, 7V-dialkyl-6//-1,3,4-thiadiazin-2-amines 4 are the exclusive products of these reactions and undergo interesting ring transformations to afford pyrazoles31,32,44 (see Houben-Weyl, Vol. E8b, p 562). 

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