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Synthesis 2005(19): 3412-3422  
DOI: 10.1055/s-2005-918473
PAPER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Synthesis of 2,5-Piperazinediones under Solvent-Free Conditions

Alberto López-Cobeñas, Pilar Cledera, J. Domingo Sánchez, Pilar López-Alvarado, M. Teresa Ramos, Carmen Avendaño, J. Carlos Menéndez*
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Fax: +34(91)3941822; e-Mail: josecm@farm.ucm.es;
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Publication History

Received 14 September 2005
Publication Date:
14 November 2005 (online)

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Abstract

A general, efficient and environmentally friendly procedure for the synthesis of 2,5-piperazinediones is described, involving the microwave irradiation of N-Boc dipeptide esters.

Key words

microwave irradiation - diketopiperazines - dipeptides - cyclizations - heterocycles

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21

Attempts to use a silica gel bath as the heat sink were unsuccessful.

22

Working at these scales, it is advisable to preheat the alumina in the heat sink before introducing the vial or flask containing the dipeptide. For instance, the preparation of compound 5g starting from 1 g of the dipeptide was carried out in 97% yield after preheating the alumina bath for 5 min followed by a single 5 min pulse, while a reaction in the same scale without preheating required 18 min (in 3-min pulses) and gave 87% yield.

35

In order to facilitate the comparison of NMR assignments, the numbering employed for C6-unsubstituted systems has been retained in these compounds, even though it does not assign the lowest locant to the first named substituents, all other factors being equal.