1.2.5- Thiadiazolidine 5,5-dioxides, reaction

Thiadiazoline and thiadiazolidine dioxide rings are easily opened by reaction with nucleophiles. Thus, taking advantage of the known aminoexchange reactions of sulfamides first reported by Paquin (48AG316), compound 101a could be opened by treatment with amines yielding the... 

Reaction of A,A-dimcthylsullamoyl aziridines 323 and 325 with primary amines furnishes substituted 1,2,5-thiadiazolidine 1,1-dioxides 324 and 326, respectively, in a regioselective manner <06SL833>. Aziridine 325 is made from ( I /t,6,S ,Z)-bicyclo[4.2. l]non-3-en-9-one in two steps /V,/V-dimethylsulfamoyl imine formation using dimethylsulfamide and subsequent reaction with trimethylsulfoxonium ylide. The product from the reaction with 4-methoxy-benzyl amine can be subsequently manipulated (debenzylation and derivatization) to give the alternative nitrogen substitution pattern in a controlled manner. 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

Alkyl and aryl A -substituted 1,2,5-thiadiazolidine-1,1-dioxides 316 are synthesized in good yield from the reaction of sulfuryl chloride with 2-chloroethylamine. 2-Chloroethylamine hydrochloride is heated at 80°C with sulfuryl chloride in acetonitrile, and corresponding mono(chloroalkyl)sulfamyl chloride 314 is then extracted with diethyl ether to separate from unreacted amine hydrochloride. This ether solution is added to a solution of primary amine, and the resultant A -aryl (chloroalkyl)sulfamide 315 is treated with potassium carbonate in DMSO to afford A -substituted 1,2,5-thiadiazolidine-l,1-dioxides 316 <03TL5483>. 

The reaction of ethylenediamines with sulfuryl chloride, reported in 1953 (53USP2624729), was the first method employed in the preparation of 1,2,5-thiadiazolidine 1,1-dioxides, and has found little use since then (66MI1 78CB1915). Nevertheless, this procedure (Scheme 47) was used to indirectly prepare the unsubstituted thiadiazolidine 88b, which, as mentioned above, could not be obtained by amino-exchange reactions (78CB1915). 

Preparative Methods the title reagent can be prepared in quantitative yield by addition of DEAD (1 equiv) to a solution of 3,3-dimethyl-l,2,5-thiadiazolidine-l,1-dioxide (1 equiv) and triphenylphosphine(l equiv)inTHEatroomtemperature. 3,3-Dimethyl-l,2,5-thiadiazolidine-l,1-dioxide can be prepared in high 3deldby reaction of sulfamide and l,2-diamino-2-methyl-propane in anhydrous pyridine. 

Mitsunobu-like Processes. Triphenylphosphonium 3,3-dime-thyl-l,2,5-thiadiazolidine 1,1-dioxide (1) can be conveniently utilized as a stable source of [PhsP+J in the promotion of Mitsunobu-like processes. By analogy with the betaine generated by reaction of DEAD and triphenylphosphine, protonation of zwitterionic species 1 by an acidic component HX generates ion pair 2 which on subsequent reaction with an alcohol (ROH) affords oxyphosphonium species (3) and 3,3-dimethyl-1,2,5-thiadiazolidine-1,1-dioxide (4). Finally, Sn2 displacement reaction, occurring with Walden inversion of the alcohol stereochemistry, leads to the coupled product R-X and triphenylphosphine oxide (TPPO) (eq 1). 

The reaction of N-sulphinyltoluene-p-sulphonamide with styrene oxide gives, in addition to the linear products (221) and (222), small yields (6%) of 3-phenyl-2,5-di(toluene-p-sulphonyl)-l, 2,5-thiadiazolidine 1-oxide (223), consistent with the formation of a 2 1 adduct with loss of sulphur dioxide. "... 

---