Hypervalent iodine(V) mediated mild and convenient synthesis of substituted 2-amino-1,3,4-oxadiazoles

Abstract

a b s t r a c tA simple protocol for the synthesis of 2-amino-1,3,4-oxadiazoles starting from the corresponding acylhydrazides by cyclodesulfurization of intermediate acylthiosemicarbazides mediated by o-iodoxybenzoic acid in good yields has been described. The protocol is mild with wide substrate scope, and thus a range of 2-amino-1,3,4-oxadiazoles have been prepared.Ó 2012 Elsevier Ltd. All rights reserved.1,3,4-Oxadiazoles have found extensive use as pharmacophores due to their metabolic profile and ability to engage in hydrogen bonding. 2-Amino-1,3,4-oxadiazoles have a wide range of biological activities such as antimicrobial agents, anti-inflammatory agents, anticancer agents, muscle relaxants, and antimitotics, 1 the 2,5-diaryl-1,3,4-oxadiazoles are known to be platelet aggregation inhibitors.2 Due to myriad of biological applications of 1,3,4-oxadiazole scaffolds, efficient and mild methods to synthesize these moieties have attracted considerable interest. Our research group has recently reported simple access to 2-amino-1,3,4-oxadiazole peptidomimetics using p-TsCl mediated cyclization of amino acid derived thiosemicarbazides. 3 The most commonly followed strategy involves cyclization of the corresponding acyclic semicarbazide 4 (X = O) or thiosemicarbazide derivatives 5 (X = S), (Scheme 1). The reported protocols in the literature involve two steps, wherein semicarbazide/acylthiosemicarbazides were synthesized by reaction of hydrazides with the requisite isocyanate/ isothiocyanate, which is typically isolated and purified. In the following step, cyclization was carried out using an appropriate reagent. Most of these methods have several disadvantages such as handling of harsh and toxic reagents, elevated temperatures, long reaction time etc. Xie et al. has recently described an efficient cyclodeselenization by heating selenosemicarbazides (X = Se) in DMF in one-pot from isoselenocyanates and hydrazides, 6 resulting in high yields of 2-amino-1,3,4-oxadiazoles. This protocol is devoid of the usage of any deselenizing reagent. Also there are a few reports wherein one pot strategy was explored starting from acylhydrazides using p-TsCl/pyridine 5a and PS-carbodiimide 7 and both these methods suffer from harsh conditions which require heating for long hours for the cyclization of the acylthiosemicarbazide intermediate. Thus newer and mild protocols for this privileged class of molecules are continuously sought. In quest of novel methodologies for heterocycles, we have now focused on a simple and efficient protocol for the synthesis of 2-amino-1,3,4-oxadiazoles. Hypervalent iodine reagents have been extensively used in various organic transformations because of their mild oxidizing and environmentally benign nature. The iodine atom in hypervalent iodine(V) reagents has strong electrophilic character and with the leaving ability of the phenyliodino group makes them reagents of choice for various oxidative transformations.8 In addition, their affinity for sulfur has made these reagents attractive alternatives fo...

Molecular‐Iodine‐Mediated, Efficient One‐Pot Synthesis of 2‐Iminohydantoins and 2‐Amino‐1H‐imidazol‐4(5H)‐ones by Cyclodeselenization of Selenourea‐Tethered Amides/Peptides

“…It was observed that the higher temperature and presence of aromatic or electron withdrawing groups were necessary for effective deselenizaton/cyclization and longer reaction time up to 24 h was required for the cyclization at lower temperatures. In continuation of our studies on desulfurization/ deselenization using iodine reagents for the synthesis of 2‐amino‐1,3,4‐oxadiazoles,, we describe a novel I 2 mediated synthesis of 2‐iminohydantoins and 2‐amino‐1H‐imidazol‐4(5H)‐ones from selenourea tethered amides/peptides.…”

Synthesis of Optically Active 2‐Amino‐1,3,4‐oxadiazoles and their Hybrid Peptides

“…2‐Amino‐5‐substituted‐1,3,4‐oxadiazoles can be synthesized by the cyclization of corresponding diacylhydrazines or thiosemicarbazide (Fig. D) . Few amino‐acid‐derived 2‐amino‐1,3,4‐oxadiazoles are reported in the literature by the treatment of CNBr with hydrazide .…”

Study on the synthesis of novel 5-substituted 2-[2-(pyridyl)ethenyl]-1,3,4-oxadiazoles and their acid–base interactions

“…Typically, cyclodehydration of N , N ′-diacylhydrazines is carried out using reagents such as PPA [ 18 ], H 2 SO 4 [ 19 ], SOCl 2 [ 20 , 21 ], POCl 3 [ 22 , 23 ], P 2 O 5 [ 24 ] (CF 3 SO 2 ) 2 O [ 25 ], BF 3 ·OEt 2 [ 26 ] or the Burgess reagent [ 27 ]. 1,3,4-Oxadiazole derivatives may also be prepared by oxidative cyclization of N -acylhydrazones with oxidizing agents such as CAN [ 28 ], KMnO 4 [ 29 ], FeCl 3 [ 30 ], Br 2 [ 31 ], PbO 2 [ 32 ], chloramine T [ 33 ], HgO/I 2 [ 34 ], hypervalent iodine reagents [ 35 – 41 ]. One-pot syntheses of these compounds from acid hydrazides with carboxylic acids [ 42 ] or orthoesters [ 43 – 45 ] in the presence of an acidic catalyst have also been reported.…”