The use of the Ugi four-component condensation.
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.
Marcaccini
Stefano
S
Dipartimento di Chimica Organica Ugo Schiff, Università di Firenze, Via della Lastruccia, 13, I-50019 Sesto Fiorentino, Italy.
Torroba
Tomás
T
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003486:Cyanides / Q000737:chemistry; D054659:Diketopiperazines; D007659:Ketones / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000081:Acetamides; D000447:Aldehydes; D000588:Amines; D002264:Carboxylic Acids; D003486:Cyanides; D054659:Diketopiperazines; D007659:Ketones; D010879:Piperazines; D013777:Tetrazoles