Amino-substituted 2,1,3-thiadiazine 1,1-dioxides

Tautomeric equilibrium in amino-substituted 1,2,6-thiadiazine 1,1-dioxides fused with five- or six-membered nitrogen heterocycles has been extensively studied by Goya and colleagues. No amino group participation in tautomeric equilibria in these systems has been observed. 

Diaminothiadiazine dioxide (342) reacts with 1,3-dicarbonyl compounds to deliver pyrido[2,3-c]-l,2,6-thiadiazines, for example (51b) <86CS607>. The pyridothiadiazine 2,2-dioxides (21a,b) and (22a,b) were prepared by reaction of 3-substituted 5-amino-1,2,6-thiadiazine 1,1 -dioxides (343) or (344) with the corresponding /J-keto ester <88AQ89>. 

Azine approach. A number of 2-substituted 4,6-diamino-5-nitropyrimidines have been converted into 7-aminofurazano[3,4-d]pyrimidines (637) upon treatment with LTA in acetic acid. 6-Amino-5-nitrosouracil reacts similarly (71JOC3211). In principle the same reaction can be applied to the preparation of 7-amino-4H-[l,2,5]oxadiazolo[3,4-c][l,2,6]-thiadiazine 5,5-dioxide (638) (76MI42900). 

It has been reported that / -amino- and / -chloro-a/ -unsaturated ketones undergo condensation with sulfamide to yield 2//-l,2,6-thiadiazine 1,1-dioxides in superior yields to those obtained using ) -diketones <91S355>. With unsymmetrically substituted sulfamides enhanced yields and regio-selectivity are noted, particularly with the ) -chloro compounds (see Scheme 32). 

There are several methods available for the synthesis of 1,2,6-thiadiazine 1,1-dioxides. A common method is a two-step procedure condensing a /3-amino ketone or ester with sulfamyl chloride (prepared from chlorosulfonyl isocyanate and water in tetrahydrofuran) followed by cyclization with potassium hydroxide or preferably with sodium methoxide. The synthesis works with substituted sulfamyl chlorides and with CSI (Section 9.07.9.1.1). A solid-phase variant of this reaction was effected. 

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