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Stereoselective Synthesis of Substituted Thiadiazolidine- and Thiadiazine-1, 1-dioxides and their Conversion to diamines and studies on the catalytic O-Acylation and Nitro-Aldol Reactions

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  • Chemistry
  • Chemistry


Abstract CHAPTER 1 (A) Stereoselective Synthesis of 1,2,5-Thiadiazolidine 1, 1-dioxides and their conversion to diamines: Thiadiazolidine 1,1-dioxides are of interest due to their numerous applications in medicinal and synthetic organic chemistry. Despite their versatility, very few methods are available for their preparation from simple precursors. Practically all of the known methods employ condensation of a vicinal diamine or amino alcohol with sulfamide. This approach is limited by the availability of the precursor diamine or amino alcohol. The objective of our study was to develop a stereoselective synthesis of 1,2,5-thiadiazolidine 1,1-dioxides and examine the possibility of their conversion to vicinal diamines. Initial investigations were conducted on 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide 1a and 3,4-dimethyl thiadiazole 1,1 dioxide 1b. Addition of Grignard reagents (one to two equivalents) to a solution of 1 in THF or benzene rapidly generated the thiadiazoline 1,1-dioxides 2 (85-99%) which were pure by 1H NMR (Scheme 1). Scheme 1. Figure An interesting feature of the above reaction is the relatively slow addition of the second equivalent of the nucleophile. Addition of excess MeMgBr (5 equivalents, 1.5 h, rt.) to 1a generates a 2/1 mixture of bis- and mono-addition products whereas addition of excess iPrMgBr gives only the monoaddition product. This is presumably due to steric factors (quaternary center adjacent to the reaction site). Reduction of 2 (NaBH4/EtOH, rt. 2 h) produced the unsymmetrical 3,4-substituted thiadiazolidine 1,1-dioxide 3 (57-89%) as a mixture of cis/trans isomers. The addition of hydride is governed by the size of the substituent on the adjacent carbon. The ratio of cis/trans isomers was in the range of 1.2:1 to 19:1 (Scheme 2). Scheme 2. Figure Conversion of 3 to unsymmetrical vicinal diamines was studied next. Treatment of 3 with 2N HBr in the presence of phenol generated the diamines 4 in modest yield (33-52%) No cleavage of 3 o

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