Structural assessment of novel spiro-naphthalene-1.2'- [1,3,4] oxadiazol-4-ones prepared under batch and flow chemistry with a concise antifungal and anti(myco)bacterial activity

The reaction of hydrazonyl chlorides with 2,3-dichloro-1,4-naphthoquinone yielded pharmaceutically important spiro-naphthalene-1,2'-[1,3,4]oxadiazol-4-ones under batch and flow synthesis methods. The regioselective cycloaddition protocol operates under mild conditions, tolerates a wide range of structural moieties and delivers versatile spiro-oxadiazole motif with high efficiency. The obtained products were elucidated by IR, 1H NMR, 13C NMR, HRMS and compound 6h was characterized by single crystal X-ray diffraction technique. The synthesized molecules have been subjected to theoretical analysis by quantum chemical calculations at DFT/B3LYP/def2-TVZP level, which provided supporting data for the experi-mental findings. In addition, a concise biological evaluation of some selected novel spirocyclic molecules is reported.(c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

The reaction of hydrazonyl chlorides with 2,3-dichloro-1,4-naphthoquinone afforded spiro-naphthalene-1,2'-[1,3,4]oxadiazol-4-ones of pharmaceutical importance using batch and flow synthesis methods. The regioselective cycloaddition protocol showed excellent tolerance towards various structural moieties and delivered versatile spiro-oxadiazole motif with high efficiency. The synthesized molecules were characterized by various analytical techniques and their biological activities were evaluated.