Synthesis of Heterocycles by Intramolecular Nucleophilic Substitution at an Electron‐Deficient sp² Nitrogen Atom

Abstract

Abstract2‐Aryl(arylsulfonyl)‐6,7‐dihydro‐2H‐imidazo[2,1‐c][1,2,4]triazol‐3(5H)‐ones and 3‐arylimino‐6,7‐dihydroimidazo[2,1‐c][1,2,4]thiadiazoles have been synthesized by intramolecular nucleophilic substitution reactions at the electron‐deficient sp2 nitrogen atom of 2‐(hydroxyimino)imidazolidine O‐sulfonate. The displacement of the sulfate leaving group by both nitrogen and sulfur anionic nucleophiles proceeds exothermically by in‐plane SN2σ nucleophilic substitution.

Reactivity of cyclic alkoxyguanidines – experimental and theoretical studies

“…7 Therefore, the nucleophilic addition products 2a-d were treated with a strong base to form the ambident carboximidate anions D, which, we expected, would undergo intramolecular electrophilic amination [12][13][14] with simultaneous extrusion of methoxide or benzyloxide anion (Scheme 3). However, we found that treatment of 2a-d with bases such as sodium hydroxide, triethylamine or pyrrolidine did not provide the desired imidazo[2,1-c][1,2,4]triazol-3-ones (E), which indicated that the anions D are rather weak nucleophiles, unable to induce the intramolecular electrophilic amination reactions at the sp 2 -hybridized nitrogen atom of the exocyclic alkoxyimino group.…”

Synthesis and reactivity of heterocyclic hydroxylamine-O-sulfonates

“…Thus, at room temperature compound D undergoes a reaction with three molar equivalents of phenyl isothiocyanate that, following desulfurization, affords 3-phenyl-2-phenylimino-2,6,7,8-tetrahydroimidazo[1,2-a] [1,3,5]triazine-4(3H)-thione (20) as the sole product [31]. However, a tandem nucleophilic addition-electrophilic amination reaction takes place when D is treated with aryl isothiocyanates at 40°C; 6,7-dihydro-5H-imidazo[2,1-c] [1,2,4]thiadiazole (21) is formed in case of 4-methylphenyl isothiocyanate, and 7-substituted derivatives 22 and 23 are obtained in the case of more reactive phenyl and p-chlorophenyl isocyanates [35].…”

“…oxaziridine derivatives: rise to the formation of heteroaromatic hydroxylamine-O-sulfonates E, which in solid state and in solution exist in the form of betaines [34,35]. Importantly, the competitive N-amination reaction of a heterocyclic ring has not been perceived.…”

“…As depicted in Scheme 10, treatment of D″ with p-tolylsulfonyl isocyanate at room temperature or heating at 80°C with corresponding arylsulfonyl carbamoylides furnishes 2-(arylsulfonyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ones 28-33 in 23-69% of isolated yield [35]. Apparently, the initially formed sulfonylureas are stronger NH acids than the It is worth noting that the pyridine or isoquinoline formimidates and formamidines react with HOSA in the presence of pyridine to give [1,2,4]triazolo[1,5-a]pyridine or [1,2,4]triazolo[5,1-a]isoquinoline, respectively [55], via the tandem nucleophilic substitution-electrophilic amination reaction.…”

“…As shown in Scheme 9, reaction D with aryl isocyanates carried out in the presence of triethylamine leads to the formation of ureas 24 and 25, that is, the products of nucleophilic addition which can be separated from the reaction mixture in pure form [35]. To induce an intramolecular electrophilic amination reaction, ureas 24 and 25 have to be treated with a strong base, which is able to generate the ambident ureate anion K. Hence, upon treatment with 10% NaOH in aqueous solution, an instantaneous N-N bond-forming reaction takes place furnishing 6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ones 26 and 27 in high yields.…”