Isothiocyanates 1.3.5- thiadiazine-2-thiones

The 2-oxosulfonamides (e.g., (233)) are versatile reagents and with carbonyl compounds can serve as synthons for a variety of heterocyclic systems including 3,4-dihydro-2//-l,2,4-thiadiazine 1,1-dioxides (234), as exemplified in Scheme 40 <85LA579>. Reaction of the oxosulfonamide with methyl isocyanate produces the 2//-l,2,4-thiadiazin-3(4. -one 1,1-dioxide (235), whereas with phenyl isothiocyanate the 5-hydroxy-5,6-dihydro-2//-l,2,4-thiadiazin-3(4//)-thione 1,1-dioxide (236) is obtained. 

Diphenyl-6-trichloromethyl-27/-l,3,5-oxadiazine-4(37/)-thione (160) is formed as an orange oil in 87% yield by cycloaddition of trichloroacetyl isothiocyanate with benzylideneaniline in DCM at room temperature <84AJC2073). In a like manner, benzoyl isothiocyanate and -phenyl-cyclohexylcarbodiimide yield 3,6-diphenyl-2-cyclohexylimino-277-l,3,4-thiadiazine-4(37/)-thione... 

Alkoxythiocarbonyl isothiocyanates (172 X = S) are also useful 47t components and with imines at room temperature furnish 6-alkoxy-2//-l,3,5-thiadiazine-4(3//)-thiones (173) albeit in variable yields <83CB2044>. In a similar manner ethoxythiocarbonyl isocyanate (172 R = Et, X = O) and benzylideneaniline produce 2,3-diphenyl-6-ethoxy-2/f-l,3,5-thiadiazin-4(3//)-one (174) <82CB1252>. In warm toluene the ethoxythiocarbonyl isocyanate dimerizes to give the 0-ethyl ester (175) of 6-ethoxy-3,4-dihydro-2,4-dioxo-2//-l,3,5-thiadiazine-3-thiocarboxylic acid (Scheme 24). 

Treatment of an A(-(aminothiocarbonyl)benzimidoyl chloride (180) with potassium thiocyanate in methanol, or better, in acetic acid, results in cyclization of the initially formed benzimidoyl isothiocyanate (181) to a 1,3,5-thiadiazine-2-thione (182) (Scheme 26). The isocyanates can be isolated if the reaction is carried out in acetone at room temperature, but ring close to the thiones in boiling methanol <88JPR241,89EGP263768>. 

A(-(Benzimidoyl)imines (191 R = 2,4,6-Me3QH2) undergo cycloaddition with CS2 to yield 3,6-dihydro-6,6-bis(trifluoromethyl)-2/f-l,3,5-thiadiazine-2-thiones (192). Addition to phenyl isothiocyanate, however, is nonregioselective and produces a mixture of the 6-phenylimino-2/f-1,3,5-thiadiazine (193 51%) and the isomeric 3,6-dihydro-2/f-l,3,5-triazine-2(l//)-thione (194 28%) (Scheme 29) <84ZN(B)1442>. 

Sodium hydrogen sulfide Tetrahydro-l,3,5-thiadiazine-2-thiones from isothiocyanates... 

A soln. of p-bromophenyl isothiocyanate in alcohol allowed to react gradually with an equimolar amount of aq. NaHS, 3 moles 37%-formalin soln. and aq. benzylamine sulfate added, stirred 0.5 hr. at room temp. 5-benzyl-3-p-bromophenyltetrahydro-l,3,5-thiadiazine-2-thione. Y 85%. P. Kristidn and J. Bernat, Tetrah. Let. 1968, 679. 

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