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Alkyne–Azide Cycloadditions with Copper Powder in a High‐Pressure Continuous‐Flow Reactor: High‐Temperature Conditions versus the Role of Additives
Author(s) -
Ötvös Sándor B.,
Mándity István M.,
Kiss Lóránd,
Fülöp Ferenc
Publication year - 2013
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201201125
Subject(s) - cycloaddition , chemistry , alkyne , continuous flow , copper , high pressure , azide , combinatorial chemistry , antifungal , reaction conditions , chemical engineering , organic chemistry , catalysis , thermodynamics , biochemical engineering , medicine , physics , dermatology , engineering
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.