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Soluble Polymer‐Supported Flow Synthesis: A Green Process for the Preparation of Heterocycles
Author(s) -
Prosa Nicolò,
Turgis Raphaël,
Piccardi Riccardo,
Scherrmann MarieChristine
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101726
Subject(s) - chemistry , aldehyde , oxazines , nitroalkene , organic chemistry , combinatorial chemistry , green chemistry , aqueous solution , peg ratio , flow chemistry , enantioselective synthesis , catalysis , ionic liquid , finance , economics
PEG‐supported aqueous flow synthesis coupled with ultrafiltration as the separation technique has been investigated for the first time. This strategy was applied to the preparation of new 3,4‐dihydropyrimidin‐2(1 H )‐ones, tetrazoles and tetrahydro‐1,3‐oxazines from the same PEG‐linked aldehyde as case studies. Dihydropyrimidinones were prepared by a copper(II)‐catalysed Biginelli reaction whereas a new tetrazole‐containing compound was obtained by Baylis–Hillman reaction followed by reduction and 1,3‐dipolar cycloaddition. Finally, various new tetrahydro‐1,3‐oxazines were prepared by a four‐step synthesis, that is, Baylis–Hillman reaction, Michael addition of amines, cyclization with formaldehyde and hydrolysis of the linkage to PEG. The use of water during the synthesis and most of the purification steps, as well as the benefits of the flow process in terms of improved safety and heat transfer agree with the principles of green chemistry.