Q-Tube®-Assisted Alkylation and Arylation of Xanthines and Other N-H-Containing Heterocycles in Water
Cecilia Scimmi,
Margherita Cardinali,
Laura Abenante,
Marina Amatista,
Francesca Giulia Nacca,
Eder J. Lenardao,
Luca Sancineto,
Claudio Santi
Affiliations
Cecilia Scimmi
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
Margherita Cardinali
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
Laura Abenante
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
Marina Amatista
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
Francesca Giulia Nacca
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
Eder J. Lenardao
Laboratorio de Sintese Organica Limpa—LASOL, CCQFA, Universidade Federal de Pelotas—UFPel, P.O. Box 354, Pelotas 96010-900, Brazil
Luca Sancineto
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
Claudio Santi
Group of Catalysis, Synthesis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy
In this paper, a simple and clean process for the alkylation and arylation of nitrogen-containing heterocycles is reported. The reactions were conducted using the Q-tube® as a non-conventional technology, in water as a green solvent, at overboiling temperature. The developed strategy was used to improve two steps in the total synthesis of caffeine, as reported by Narayan, and then extended to the preparation of N-decorated xanthines. Finally, piperidine, methyl piperazine, and isatine were proven to be suitable substrates for the protocol proposed herein.
