title: Alkyne-azide cycloadditions with copper powder in a high-pressure continuous-flow reactor: high-temperature conditions versus the role of additives.
abstract: A safe and efficient flow-chemistry-based procedure is presented for 1,3-dipolar cycloaddition reactions between organic azides and acetylenes. This simple and inexpensive technique eliminates the need for costly special apparatus and utilizes Cu powder as a plausible Cu(I) source. To maximize the reaction rates, high-pressure/high-temperature conditions are utilized; alternatively, the harsh reaction conditions can be moderated at room temperature by the joint application of basic and acidic additives. A comparison of the performance of these two approaches in a series of model reactions has resulted in the formation of useful 1,4-disubstituted 1,2,3-triazoles in excellent yields. The risks that are associated with the handling of azides are lowered, thanks to the benefits of flow processing, and gram-scale production has been safely implemented. The synthetic capability of this continuous-flow technique is demonstrated by the efficient syntheses of some highly functionalized derivatives of the antifungal cispentacin.
authors: Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
authors: Sándor B
authors: SB
authors: Ötvös
authors: István M
authors: IM
authors: Mándity
authors: Lóránd
authors: L
authors: Kiss
authors: Ferenc
authors: F
authors: Fülöp
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D061565:Cycloaddition Reaction; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D006358:Hot Temperature; D007536:Isomerism; D011312:Pressure; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000480:Alkynes; D000935:Antifungal Agents; D001386:Azides; D014230:Triazoles; D003515:Cycloleucine; C065594:cispentacin; D003300:Copper