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Formation of a vanillic Mannich base — theoretical study

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Abstract

One-pot anti-Mannich reaction of vanillin, aniline and cyclohexanone was successfully catalyzed by ionic liquid triethanolammonium chloroacetate, at room temperature. Yield of the obtained Mannich base was very good and excellent diastereoselectivity was achieved. Mechanism of the reaction was investigated using the density functional theory. The reaction started with a nucleophilic attack of aniline nitrogen at the carbonyl group of vanillin. The intermediate α-amino alcohol formed in this way was further subjected to protonation by the triethanolammonium ion yielding the imminium ion. Theoretically, the obtained imminium ion and the enol form of cyclohexanone can build the protonated Mannich base via the anti and syn pathways. The chloroacetic anion spontaneously abstracts the proton yielding the final product of the reaction anti 2-[1-(N-phenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-H). The syn pathway requires lower activation energy but the anti pathway yields a thermodynamically more stable product, which implies that the examined Mannich reaction is thermodynamically controlled.

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  1. Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, Serbia

    Vladimir P. Petrović, Dušica Simijonović, Zorica D. Petrović & Svetlana Marković

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  1. Vladimir P. Petrović
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  2. Dušica Simijonović
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  3. Zorica D. Petrović
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Petrović, V.P., Simijonović, D., Petrović, Z.D. et al. Formation of a vanillic Mannich base — theoretical study. Chem. Pap. 69, 1244–1252 (2015). https://doi.org/10.1515/chempap-2015-0123

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