Synthesis of aza-aromatic hydroxylamine- O-sulfonates and their application to tandem nucleophilic addition–electrophilic 5- endo- trig cyclization

Abstract

Hydroxylamine- O-sulfonic acid (HOSA) was used as an efficient nucleophilic amination reagent for 2-chloropyrimidines, 2-chloroquinolines, and 1-chloroisoquinoline. The newly obtained heteroaromatic hydroxylamine- O-sulfonates subjected to the reaction with acyl isothiocyanates underwent tandem nucleophilic addition–electrophilic 5- endo- trig cyclization. The mechanism of the cyclization was investigated with use of the long-range corrected hybrid density functional ωB97X-D/6-31+G ∗ and SM8 (DMF) solvation model. The structures of the heteroaromatic hydroxylamine- O-sulfonates and N-(5-methoxy-2 H-[1,2,4]thiadiazolo[2,3- a]pyrimidin-2-ylidene)benzamide were confirmed by single crystal X-ray analysis. N-(2 H-[1,2,4]thiadiazolo[3,2- a]isoquinolin-2-ylidene)benzamide exhibited a pronounced in vitro cytostatic activity against human tumor cell lines SISO, LCLC, A-427, DAN-G, and RT-4 (IC 50 in the range 1.47–2.97 μM).