1.2.5- Thiadiazolidine 1,1-dioxides

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. 

Diamination of a variety of conjugated terminal olefins yields a series of 1,2,5-thiadiazolidine 1,1-dioxide 2T8, using CuCl as the catalyst and di-fert-butylthiadiaziridine... 

The direct formation of disubstituted l,2,5-thiadiazole-l,l-dioxides (57) by condensation of a-diketones with sulfamide was reported by Wright and by Vorreither and Ziegler. The 1,2,5-thiadiazoline-1,1-dioxides (58) were prepared by a similar method employing a-hydroxy ketones. Hydrogenation of both 57 and 58 over Adams catalyst provided the corresponding disubstituted 1,2,5-thiadiazolidine-1,1 -dioxides (60). 2-Alkyl-l, 2,5-thiadiazoline-l, 1-... 

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). 

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). 

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... 

Several examples of 1,2,4-thiadiazolidin-3-one 5,5-dioxides 191-194 were isolated as by-products in the synthesis of sulfonopeptides. These are formed by refluxing in benzene or toluene the corresponding acylazides. These sulfonyl-hydantoins are extremely labile in protic solvents (96T(52)5303). 

Chiral l,2,5-thiadiazolidin-3-one 5,5-dioxides 250 were synthesized by way of conventional methods, with the intention of introducing them in new pseudonucleosides as aglicone (96T(52)993). The synthetic methodology, in accord with previous reports, gave the l,2,5-thiadiazolidin-3-ones in good overall yield (35-55%). The glycosilation was performed on the protected heterocycles to prevent the condensation involving the N-2 atom, the most acidic reactive site. As expected only one anomer was obtained that is the p-one. 

Alkylation of mesoionic 132 (R = H) with 2-chloromethyl-4-(3-methyl-butyl)-5-methyl-l,2,5-thiadiazolidin-3-one 1,1-dioxide gave a mixture of C-3 and 2-6>-alkylated products 141 and 142 (96USP5512576). 

The thiobenzyl-substituted thiadiazolidine 1,1-dioxide 31 can undergo nucleophilic displacement when treated with ammonia gas to give the 3-amino derivative 32 (Equation 8) <1997AJC1027>. 

Stereoselective hydride reduction of 1,2,5-thiadiazoline 1,1-dioxides 60 generates unsymmetrical 1,2,5-thiadiazol-idine 1,1-dioxides 61 <1998SL623> that can be readily converted to unsymmetrical vicinal diamines 62 with HBr in the presence of phenol (Scheme 5) <1996TL2859, 1998SL623>. The unsymmetrical thiadiazolidine 1,1-dioxides 63 can also be converted into 1,2-diketones 64 on treatment with selenium dioxide followed by alkaline hydrolysis (Equation 7) <1997SL671>. 

Treatment of enantiomerically pure (R,R)- and (A,A)-l,2-bis(pentafluorophenyl)ethane-l,2-diamines with thionyl chloride gave the corresponding thiadiazolidine 1-oxides in high yield <2004BCJ1001>. A series of Aralkyl-substituted thiadiazolidine 1,1-dioxides 171 were also prepared from the starting 1,2-diamine 170 by treatment with sulfamide followed by a regioselective monoalkylation (Scheme 26) <2005BML4212>. 

Treatment of a-amino esters with sulfonamide in the presence of DBLJ at 160°C also affords 2-unsubstituted-l,2,5-thiadiazolidin-3-one 1,1-dioxides 199 in moderate yield <2005SL834>. 

MeNHCHjCHjNHMe S02C12 2,5-Dimethyl-l, 2,5-thiadiazolidine 1,1-dioxide 78CB1915... 

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). 

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