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Synthesis 2023; 55(13): 2070-2082
DOI: 10.1055/a-2022-2206
paper
Special Issue dedicated to Prof. Alain Krief

Investigating the Mechanism of the Catalytic Intramolecular Aza-Wittig Reaction Involved in the Synthesis of 2-Methylbenzothiazole from the Perspective of Bonding Evolution Theory

Abel Idrice Adjieufack  ∗
a   Laboratory of Theoretical Chemistry (LCT) and Namur Institute of Structured Matter (NISM), University of Namur, Rue de Bruxelles, 61, 5000 Namur, Belgium
b   Physical and Theoretical Chemistry Laboratory, University of Yaoundé 1, Yaoundé, Cameroon
c   Computational Chemistry Laboratory, High Teacher Training College, University of Yaoundé 1, Yaoundé, Cameroon
,
Benoît Champagne  ∗
a   Laboratory of Theoretical Chemistry (LCT) and Namur Institute of Structured Matter (NISM), University of Namur, Rue de Bruxelles, 61, 5000 Namur, Belgium
,
Vincent Liégeois  ∗
a   Laboratory of Theoretical Chemistry (LCT) and Namur Institute of Structured Matter (NISM), University of Namur, Rue de Bruxelles, 61, 5000 Namur, Belgium
› Author AffiliationsA.I.A. thanks the University of Namur (Belgium) for his UNamur-CERUNA Ph.D. Mobility Fellowship. V.L. thanks the FNRS-FRFC for his Research Associate position. The calculations were performed on the computers of the Consortium des Equipements de Calcul Intensif (CECI, http://www.ceci-hpc.be) and particularly those of the Technological Platform of High-Performance Computing, for which the authors gratefully acknowledge the financial support of the F.R.S.-FNRS (GEQ U.G006.15, RW/GEQ2016, U.G018.19, U.G011.22), of the Walloon Region (RW1610468, RW/GEQ2016, and RW2110213), and of the University of Namur.
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This work is dedicated to Prof. Alain Krief at the occasion of his 80th birthday. Prof. Alain Krief has introduced two of us to Organic Chemistry and has trained them to many marvelous facets of Organic Synthesis.

Abstract

Bonding evolution theory has been used at the density functional theory level [ωB97X-D exchange-correlation functional, 6-311G(d,p) basis set, and solvent (toluene) effects with polarizable continuum model] to unravel the reaction mechanism of the intramolecular aza-Wittig reaction of 2-(acetylthio)phenyl isocyanate (1) catalyzed by 3-methyl-1-phenyl-2-phospholene 1-oxide (2) to form 2-methylbenzothiazole (3). The reaction involves four steps (transition states) corresponding to (1) the formation of a cycloadduct (O–C then P–N bonds), (2) a decarboxylation leading to the formation of an iminophosphorane, and (3) an intramolecular [2+2] cycloaddition (N–C then P–O bonds) followed by (4) a retro [2+2] cycloaddition (cleavage of the P–N then O–C bonds) to get the product and regenerate the catalyst. Step 1 is the rate-determining step with an activation Gibbs free enthalpy of 21 kcal mol–1 and it is favored with respect to a competitive pathway leading to the formation of another cycloadduct (P–C then O–N bonds). The whole reaction is exergonic with a Gibbs free energy decrease of 31 kcal mol–1, associated with the liberation of a CO2 molecule and the formation of the aromatic benzothiazole. Following the scale of Domingo, the successive steps of the reaction have a polar nature.

Key words

Wittig reaction - bonding evolution theory - DFT calculations - 2-methylbenzothiazole synthesis - aza-Wittig

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2022-2206.
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Publication History

Received: 15 November 2022

Accepted after revision: 30 January 2023

Accepted Manuscript online:
30 January 2023

Article published online:
08 March 2023

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