The use of the Ugi four-component condensation

Abstract

This protocol describes a procedure for the Ugi four-component condensation. It describes the general mechanism as well as the effects of the nature of the components on the Ugi reaction. It also describes the effects of the reaction conditions on the reaction, along with special procedures and workup. The experimental procedure is exemplified by a description of the preparation of N-cyclohexyl 2-[N-(2-chloroacetyl)-N-(4-chlorobenzyl)]amino-2-(4-chlorophenyl)acetamide, a typical Ugi product, that is subsequently used for the synthesis of a 2,5-diketopiperazine, an example of an important type of pharmaceutical compound. The experimental procedure is then extended to the synthesis of a 1,5-disubstituted tetrazole via Ugi four-component condensation. The protocol describes the preparation and characterization of the new 1-cyclohexyl-5-(1-phenylamino-2-methyl)propyltetrazole. The total time for the synthesis and isolation of the two example reactions in parallel is 3 d.

Efficient Multicomponent Reaction Synthesis of the Schistosomiasis Drug Praziquantel

“…This fragment can be advantageously assembled by the classical Ugi multi-component reaction. [10] Therefore, our synthesis strategy uses the Ugi reaction as a key transformation (Scheme 1). Thus, (2-isocyanoethyl)benzene (2) reacts with paraformaldehyde (3), cyclohexylcarboxylic acid (4), and 2,2-dimethoxy ethylamine (5) previously.…”

Experimental and theoretical studies on the effect of the oxo group in 1,4-benzodiazepines

“…Therefore, in the synthesis of benzo[e] [1,4]diazepine-5-ones A, we selected the commercially available 2-nitrobenzoic acid in place of 2-azidobenzoic acid as the carboxylic acid component in the Ugi reaction. Following the most common procedure, 11 the corresponding imine was pre-formed by mixing substituted benzylamine 2a-e (1 equiv.) with a solution of arylglyoxal 1a-b (1 equiv.)…”

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling

“…The Ugi reaction has often been used as a tool in the synthesis of pharmacologically active molecules and we have exploited it to quickly access compounds in the search for new anti-malarial agents (4). It has been observed that Ugi products sometimes precipitate in pure form from the reaction mixture (1,5). This is a very fortunate outcome since the reaction can then be easily scaled up without requiring costly purification procedures such as chromatography.…”

“…The Ugi reaction has proved to be a convenient way to quickly create diverse libraries of compounds (1)(2)(3). It involves the reaction of an amine, an aldehyde, a carboxylic acid and an isonitrile typically in methanol at room temperature.…”