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A long-range tautomeric effect on a new Schiff isoniazid analogue, evidenced by NMR study and X-ray crystallography

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Abstract

Long-range tautomerism to a N,O-aminal thereby closing a tetrahydrofuran ring was evidenced for an isoniazid analogue, whose accidental synthesis is presented in the paper. The isoniazid analogue was synthesized by the reaction of isoniazid with 2-hydroxy-tetrahydrofuran which was demonstrated to exist in old THF together with other peroxides, especially 2-HOO-THF. The same compound was efficiently obtained from a THF containing 2-HOO-THF, by reducing this peroxide in the presence of isoniazid. The 2,4-dinitrophenylhydrazone was also synthesized. The oxidation of 1,4-butanediol and the reaction of the resulting mono-aldehyde with isoniazid gave the same compound. The existence of the linear tautomer was evidenced in the NMR spectra in DMSO-d6 and was confirmed by X-ray analysis to be the single tautomer in the crystal. The cyclic N,O-aminal tautomer was found in the NMR spectra in CDCl3, resulting from an intramolecular HCl-catalyzed addition of the hydroxyl group to the double bond CH[double bond, length as m-dash]N of the linear tautomer, thereby closing a tetrahydrofuran ring. This is a favoured cyclization according to Baldwin's rules (5-exo-trig). The same tautomerism was also present for two isoniazid analogues obtained from two lactols, used in prostaglandin synthesis. The compounds 1, 4, 6 and INH had no antibacterial or antifungal activity.

Graphical abstract: A long-range tautomeric effect on a new Schiff isoniazid analogue, evidenced by NMR study and X-ray crystallography

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Publication details

The article was received on 07 Apr 2018, accepted on 19 Jul 2018 and first published on 20 Jul 2018


Article type: Paper
DOI: 10.1039/C8NJ01680A
Citation: New J. Chem., 2018, Advance Article
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    A long-range tautomeric effect on a new Schiff isoniazid analogue, evidenced by NMR study and X-ray crystallography

    C. I. Tănase, C. Drăghici, S. Shova, A. Hanganu, E. Gal and C. V. A. Munteanu, New J. Chem., 2018, Advance Article , DOI: 10.1039/C8NJ01680A

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