Protocol abstract
Nature Protocols 2, - 1713 - 1721 (2007)
Published online: 5 July 2007 | doi:10.1038/nprot.2007.224
Subject Category: Synthetic chemistry
Automated generation of a dihydropyrimidine compound library using microwave-assisted processing
Doris Dallinger1 & C Oliver Kappe1
Abstract
Here we report the generation of a small focused library of 12 diversely functionalized dihydropyrimidine (DHPM) derivatives via one-pot three-component Biginelli cyclocondensation of 
-ketoesters, aldehydes and (thio)ureas. By applying controlled microwave heating under sealed vessel conditions using a fully automated microwave instrument including a gripper and liquid handler, the sequential synthesis of DHPMs can be performed in a shorter reaction time (10–20 min per one DHPM derivative) compared to conventional heating methods, which normally require several hours of reflux heating. The solid products either crystallize directly upon cooling or can be precipitated upon addition of water, requiring only filtration for isolation. In this way, the DHPM derivatives are obtained in high purity and no further purification by recrystallization or chromatography is necessary. This can be ascribed to the microwave heating technology where less side-product formation is often seen. The preparation of this 12-membered DHPM library can be carried out within 
9 h.
- Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Correspondence to: C Oliver Kappe1 e-mail: oliver.kappe@uni-graz.at
nature-products
A-Z product listing
- 2,3-Dichlorobenzaldehyde(Aldrich)
- 2-Chlorobenzaldehyde(Aldrich)
- 2-Thiophenecarboxaldehyde(Aldrich)
- 3-Hydroxybenzaldehyde(Aldrich)
- 3-Nitrobenzaldehyde(Aldrich)
- 4-Fluorobenzaldehyde(Aldrich)
