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The reactivity of vinyl compounds as alkylating agents

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Abstract

The reactions of 4-(p-nitrobenzyl)pyridine (a trap for alkylating agents with nucleophilicity similar to that of DNA) with the vinyl compounds acrylonitrile, acrylamide, acrylic acid, and acrolein, which can act as alkylating agents of DNA, were investigated. The following conclusions were drawn: (1) vinyl compounds show an alkylating capacity on 4-(p-nitrobenzyl)pyridine. The sequence of the alkylating potential was found to be acrylonitrile > acrylamide > acrylic acid > acrolein (alkylation with acrolein was not observed after 3 weeks). The formation of adducts with acrylonitrile was approximately 10- and 100-fold faster than with acrylamide and acrylic acid, respectively, which is consistent with its highly carcinogenic and mutagenic activity. (2) 4-(p-Nitrobenzyl)pyridine alkylation reactions by vinyl compounds occur through an enthalpy-controlled Michael addition mechanism. The values for the free energy of activation for these reactions with 4-(p-nitrobenzyl)pyridine were: Δ‡ G° (37 °C) acrylonitrile, 98 ± 1 kJ mol−1; acrylamide, 105 ± 2 kJ mol−1; acrylic acid, 109 ± 1 kJ mol−1. (3) Application of Hammett treatment to the kinetic results revealed that these alkylation reactions occur through nucleophilic attack, being moderately accelerated by electron-withdrawing groups.

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Acknowledgments

We thank the Spanish Ministerio de Ciencia e Innovación and the European Regional Development Fund (Project CTQ2010-18999) for supporting the research reported in this article. I·F.C.-C. thanks the Spanish Ministerio de Asuntos Exteriores y de Cooperación (MAEC-AECID) and M.G.-J. thanks the Spanish Ministerio de Educación for PhD grants. Thanks are also given for the valuable comments made by the referees.

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Authors and Affiliations

  1. Departamento de Química física, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008, Salamanca, Spain

    Isaac F. Céspedes-Camacho, José A. Manso, Mario González-Jiménez, Emilio Calle & Julio Casado

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  1. Isaac F. Céspedes-Camacho
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  2. José A. Manso
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  3. Mario González-Jiménez
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  4. Emilio Calle
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  5. Julio Casado
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Corresponding author

Correspondence to Julio Casado.

Additional information

I. F. Céspedes-Camacho and J. A. Manso contributed equally to this work.

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Céspedes-Camacho, I.F., Manso, J.A., González-Jiménez, M. et al. The reactivity of vinyl compounds as alkylating agents. Monatsh Chem 143, 723–727 (2012). https://doi.org/10.1007/s00706-012-0736-2

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  • DOI: https://doi.org/10.1007/s00706-012-0736-2

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