Synthesis 2024; 56(19): 3001-3008
DOI: 10.1055/a-2356-8297
paper

A Domino One-Pot Approach to Functionalized Benzonitriles from 2-[(3-Hydroxy/acetoxy)propyn-1-yl]benzamides

Sindoori R. Nair
,
Bhavani Shankar Chinta
,
Financial support from the Science and Engineering Research Board, Department of Science and Technology (SERB-DST) (CRG/2023/001303) and the Department of Higher Education, India (MHRD-INDIA) through IoE funding (SB20210792CYMHRD008189) is acknowledged. B.S.C. thanks the Indian Institute of Technology Madras (IIT Madras) for his HTRA doctoral fellowship. S.R.N. thanks the Council of Scientific and Industrial Research, India (CSIR-INDIA) for her SRF fellowship.


Abstract

Functionalized benzonitriles, α,β-epoxyketones and β-hydroxy-α-haloketones are found in numerous medicinally important molecules, whilst benzonitriles in combination with any of these functional groups may be of interest to medicinal chemists. However, the simultaneous incorporation of a nitrile group and these functional groups on the aromatic ring is a challenging task. Herein, we report a strategy for the rapid and simultaneous construction of structurally novel benzonitrile derivatives, possessing either an ortho-α-iodo-β-hydroxyketone, an α,β-epoxyketone or an α,β-enone, from unprotected, 2-[(3-hydroxy/acetoxy)propyn-1-yl]benzamides. This process involves NXS-promoted dehydration–halohydration followed by DIPEA-mediated epoxide formation (from alcohols). We have developed both stepwise and one-pot strategies to improve the synthetic efficiency. No metal catalyst is employed and the method exhibits good substrate scope and yields.

Supporting Information



Publication History

Received: 12 April 2024

Accepted after revision: 13 June 2024

Accepted Manuscript online:
28 June 2024

Article published online:
15 July 2024

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