Synthesis of Naphthoxazoles by Photocyclization of 4‐/5‐(Phenylethenyl)oxazoles

Abstract

Promising test results on the biological activity of our previously described naphtho[1,2‐d]oxazoles and heterobenz[1,2‐d]oxazoles, obtained by the photochemical cyclization of 5‐phenylethenyl‐ and 5‐heteroarylethenyloxazoles, prompted us to continue with the photochemical synthesis of substituted naphtho[1,2‐d]oxazoles, and to extend the photochemical cyclization to the synthesis of naphtho/heterobenz[2,1‐d]oxazoles from 4‐(aryl/heteroarylethenyl)oxazoles. The required p‐ and o‐phenyl‐substituted 5‐arylethenyloxazoles were prepared from the corresponding α,β‐unsaturated aldehydes and the TosMIC reagent (tosylmethyl isocyanide) by the Van Leusen reaction. The substituted 4‐(aryl/heteroarylethenyl)oxazoles were prepared by the Wittig reaction starting from various phosphonium salts and 2‐H/methyl‐4‐oxazolecarbaldehydes.

Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

“…Using the reaction of N-alkylation on the previously synthesised trans-chloro-arylethenyloxazole 1 20 , new trans-amino-5-arylethenyl-oxazole derivatives trans-2-18 were synthesised (Scheme 1) with an aim to add a new functional group at the end of the oxazole derivative that resembles acetylcholine, the substrate of cholinesterase. The Buchwald-Hartwig reaction 21 was utilised with two catalysts and the reaction was optimised for best conditions to enhance the yield.…”

“…Four of the polycyclic naphtho[1,2-d]oxazoles compounds (19,20,21,23) and two isolated cis-isomers of amino-5-arylethenyloxazole derivatives (cis-18, cis-22) were also tested as potential inhibitors of cholinesterases. All compounds, except 23, inhibited both enzymes more than 50% with concentrations in mM range and the evaluated IC 50 values are given in Table 1.…”

“…Styryl-oxazole that has chlorine as a substituent was then N-alkylated by Buchwald-Hartwig type reaction to give oxazole benzylamines which were tested as cholinesterase inhibitors. All of the styryl-oxazole amines were also photochemically cyclized to give naphthoxazole benzylamines 20 . Naphthoxazoles synthesised by this manner were also tested.…”

Recent Advances in the Synthesis of Oxazole-Based Molecules via van Leusen Oxazole Synthesis

“…To further broaden the substrate scope of naphtho [1-d]oxazoles, other 5-(arylethenyl)oxazoles 55 were prepared from the corresponding aryl-substituted α-unsaturated aldehydes 54 and TosMIC 25. This process took place as depicted above, treating with TosMIC in one-step synthesis through the van Leusen reaction (Scheme 10, method C) [51].…”

“…To further broaden the substrate scope of naphtho [1d]oxazoles, other 5-(arylethenyl)oxazoles 55 were prepared from the corresponding aryl-substituted α-unsaturated aldehydes 54 and TosMIC 25. This process took place as depicted above, treating with TosMIC in one-step synthesis through the van Leusen reaction (Scheme 10, method C) [51]. In 2011, Hamon and co-workers adopted a convergent process based on the cross-coupling of 2,6-bis(oxazol-5-yl) pyridine 57 and 2-bromopyridine 58 derivatives through the double C-H activation of the oxazole rings, to perform the synthesis of oligo-heteroaryles.…”