A parallel Ugi reaction at students laboratories in the Ural and Moscow

Abstract

Abstract-A four-component Ugi reaction was adapted for students education. To this end, a series of almost odorless aromatic isonitriles with donor substituents was reacted with a specific carboxylic acid, phthaloyl glycine, to obtain poorly soluble (although nicely crystallized) products. The process was performed and compared in two versions by using (1) a standard centrifuge for parallel separation of precipitates and (2) parallel filtration with SynCore apparatus. It is shown for a broad series of aliphatic ketones and benzyl amines that the yields are satisfactory and the products require no further purification.In 2000-2001, at the Ural State Technical University, Yekaterinburg, there was developed a "Combinatorial Chemistry" laboratory training course for third year students specializing in biotechnology. The aim of this laboratory course was to develop practical skills in the field of parallel synthesis and consolidate the lecture material on combinatorial chemistry. Taking into account the basic student' training level, we had to find a simple and illustrative example of the parallel organic synthesis technology. The Ugi reaction is an ideal decision, since it allows compound libraries to be obtained without a complex equipment and hardly accessible reagents. The reagents were chosen so that to obtain precipitates which could be separated in parallel by centrifuging. It should be mentioned that the Ugi reaction is also used at students laboratories at some foreign universities (for example, at the Munich Technical University).The practical work at the USTU was envisioned for four lessons: an introductory workshop and three practical lessons. For fourth year students, an extended program comprising five practical lessons requiring a higher level basic training was suggested. In the first part of this paper we present a series of procedures and instructions which can help one to include the Ugi reaction in any laboratory training in combinatorial chemistry.Almost simultaneously, special laboratory training in combinatorial chemistry for fifth year students was initiated at the Lomonosov MSU. The Moscow group first experimented with training tasks on solid-phase synthesis [1,2], and the task in parallel liquid-phase synthesis involved reductive amination [3]. After the MSU had acquired instrumentation for parallel filtration, a necessity arose to find an illustrative training task. After the heads of these training courses (the authors of the present paper) had met face-to-face and exchanged experience, the Moscow group attempted to adapt the procedure developed at the USTU for use for the Syncore reactor (I. Dlinnykh, E. Belykh, and V. Alifanov were involved in this work in different times). In the second part of this paper we present the results of this experiment. In our opinion, the experience in such collaboration may be of interest for other universities. Basic Information on the Ugi ReactionWe consider it useful, to start with a workshop on the methodology of parallel synthesis and application of mu...