The ring opening of 3,4-dichloro-1,2,5-thiadiazole with metal amides. A new synthesis of 3,4-disubstituted-1,2,5-thiadiazoles

Thiadiazole Carbamates: Potent Inhibitors of Lysosomal Acid Lipase and Potential Niemann−Pick Type C Disease Therapeutics

“…When 4 was treated with 1.0 equiv of LiHMDS in THF at 22 °C, the starting material was consumed within minutes (Scheme ). 13 C NMR analysis of the product 29 (isolated by column chromatography) revealed a distinct shift in the carbon atoms of the thiadiazole ring which matched those of an identical compound reported by Merschaert . When 29 was treated with the Li enolate of tert -butyl acetate, the desired substitution product 18 was isolated in good yield, albeit in lower yield than in the one-pot protocol.…”

“…However, Merschaert recently reported that 1 cleanly reacts with LiHMDS at the sulfur atom to give a stabilized ring-opened product. 21 The resulting intermediate was then able to undergo substitution reactions with various nucleophiles, including enolates. Given the similarities between our optimal conditions and those reported for the ring-opening, we investigated the possibility of the reaction proceeding through an analogous ring opened intermediate.…”

“…13 C NMR analysis of the product 29 (isolated by column chromatography) revealed a distinct shift in the carbon atoms of the thiadiazole ring which matched those of an identical compound reported by Merschaert. 21 When 29 was treated with the Li enolate of tert-butyl acetate, the desired substitution product 18 was isolated in good yield, albeit in lower yield than in the one-pot protocol. On the basis of the above data, it is not likely that a direct nucleophilic substitution occurs at C(3) of the thiadiazole ring.…”

“…We had assumed that the enolate substitution was occurring through a direct nucleophilic attack at C(3) to displace the chloride via a S N Ar mechanism. However, Merschaert recently reported that 1 cleanly reacts with LiHMDS at the sulfur atom to give a stabilized ring-opened product . The resulting intermediate was then able to undergo substitution reactions with various nucleophiles, including enolates.…”

Dissociation pathways for the molecular cation of 3,4‐dichloro‐1,2,5‐thiadiazole: A time‐of‐flight mass spectrometry and computational study

“…Various properties of these 1,2,5‐thiadiazoles have been utilized in the drugs industry for many years. The ring opening of readily available 3,4‐dichloro‐1,2,5‐thiadiazole has been utilized for the synthesis of various 3,4‐disubstituted‐1,2,5‐thiadiazoles which are the precursors of different drugs . From the viewpoint of organic conductors, a small HOMO–LUMO gap is required and tuning the band gap by an appropriate substituent on both the donor and acceptor building units is a crucial question.…”