Synthesis Of Heterocyclic Compounds And Esters Promoted By TBTU

In recent years, peptide-coupling reactions have significantly advanced in parallelwith the development of new peptide-coupling reagents. TBTU which is one of a typeof uronium reagents, is one of the most application as well as best performance-to-costratio among the coupling agents. Peptide coupling agents, starting from uroniumreagents such as2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumtetrafluoroborate (TBTU) are versatile reagents for activation of the carboxylic group.They have enabled the execution of an acid-amine coupling in a single step without therequirement for pre-activation of the acids. Their main advantages include a practicallyconvenient procedure, rapid in situ activation, minimal side reactions, commercialavailability, stability, solubility in a wide range of solvents including water and easyremoval of the byproducts of coupling. Owing to their high practical utility,applications of uronium reagents in a diverse range of conditions is a research focus inin organic and biological chemistry. This paper introduced the basic informations andapplications of TBTU and other peptide-coupling reagents. In view of these advantages,we envisaged employing peptide coupling agents for the first time for the generalsynthesis of carboxylic acid oxime esters, sulphonic acid oxime esters, carboxylic acidN-heterocyclic secondary amines, ureas and carbamates.1. In this paper, we systematicly studied the performance of TBTU promotedesterification of carboxylic acids with oximes. We also researched the influence of thecatalytic reaction conditions (amount, solvent, base) to the catalytic activity. TBTUwas found to be an effective catalyst for the esterification of carboxylic acids withoximes to afford carboxylic acid oxime esters under room temperature. The presentmethod has the advantages of operational simplicity, mild reaction conditions, readyavailability and use of non-toxic materials, fast reaction rates, and simple reactionwork-up.2. A series of sulphonic acid oxime esters were synthesized efficiently bysulphonic acid with oximes under mild conditions promoted by TBTU at50°C inacetonitrile. This itinerary has many advantages, including the process isstraightforward, environmentally benign, simple post-treatment response.3. TBTU was found to be an effective catalyst for the condensation reaction ofcarboxylic acids with heterocyclic secondary amines such as indole or imidazole to afford the object compound under room temperature in acetonitrile. The advantages ofthis reaction include low toxicity of by-products, ease of separation of products andsimple work-up.4. An efficient synthesis of ureas and carbamates promoted by TBTU from thereaction of carboxylic acids, NaN3with amides or ethanol in acetonitrile was alsoreported. This is a one-pot reaction, which is not only operationally simple but alsoconsistently gives the corresponding products in good to excellent yields.