Iodine-mediated one-pot intramolecular decarboxylation domino reaction for accessing functionalised 2-(1,3,4-oxadiazol-2-yl)anilines with carbonic anhydrase inhibitory action

Srinivas Angapelly,P V Sri Ramya,Rohini Sodhi,Andrea Angeli,Krishnan Rangan,Narayana Nagesh,Claudiu T Supuran,Mohammed Arifuddin

doi:10.1080/14756366.2018.1443447

Abstract

A practical and transition metal-free one-pot domino synthesis of diversified (1,3,4-oxadiazol-2-yl)anilines has been developed employing isatins and hydrazides as the starting materials, in the presence of molecular iodine. The prominent feature of this domino process involves consecutive condensation, hydrolytic ring cleavage, and an intramolecular decarboxylation, in a one-pot process that leads to the oxidative formation of a C–O bond. Fluorescence properties of some of the representative molecules obtained in this way were studied. The synthesised 2-(1,3,4-oxadiazolo-2-yl)aniline-benzene sulphonamides (8a–o) were screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity. Most of the compounds exhibited low micromolar to nanomolar activity against human (h) isoforms hCA I, hCA II, hCA IV, and XII, with some compounds displaying selective CA inhibitory activity towards hCA II with KIs of 6.4–17.6 nM.

Highlights

Construction of O–heterocyclic ring systems via intramolecularC–O bond formation has become an emerging tool in drug discovery
We commenced our investigation with a reaction using an equimolar ratio of isatin and 4-methyl benzohydrazide as model substrates using molecular iodine (100 mol%) and Cs2CO3 (1.0 equiv.)
With an attempt to further optimise the yield of the product, we investigated the influence of various iodine reagents

Summary

Introduction

Construction of O–heterocyclic ring systems via intramolecularC–O bond formation has become an emerging tool in drug discovery. The traditional intramolecular Pd-catalysed Hartwig–Buchwald[1] and copper-catalysed[2] Ullmann-type C–O coupling of aryl halides with hydroxyl moieties, and in an alternative approach, the direct dehydrogenative coupling occurs between C–H and O–H bonds[3], leading to various functionalised compounds. In most cases, these elaborative designs implied complex catalytic systems In the perspective of green chemistry, most of the organic chemists have switched to metal-free reactions to reduce the burden of toxicity In this context, iodine and hypervalent iodine reagents have emerged as inexpensive, versatile, and environmentally more friendly reagents[5]. Many efforts have been made to directly functionalise C–H bonds for the construction of C–C and

Methods

Results

Conclusion