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Divergent Synthesis of Quinazolines Using Organocatalytic Domino Strategies under Aerobic Conditions
Author(s) -
Gujjarappa Raghuram,
Maity Suvik K.,
Hazra Chinmoy K.,
Vodnala Nagaraju,
Dhiman Shiv,
Kumar Anil,
Beifuss Uwe,
Malakar Chandi C.
Publication year - 2018
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.201800746
Subject(s) - chemistry , catalysis , organocatalysis , substrate (aquarium) , combinatorial chemistry , cascade reaction , tandem , reaction conditions , domino , organic chemistry , green chemistry , enantioselective synthesis , reaction mechanism , oceanography , materials science , geology , composite material
An easy and efficient organocatalytic approach to the synthesis of 2‐substituted quinazolines is described based on the reaction between 2‐aminobenzylamines and aldehydes or alcohols or amines. Three organocatalytic platforms were investigated, using 3‐nitropyridine, pyridine N ‐oxide, and vitamin B 3 . Having established the new catalytic systems, the tandem transformations of 2‐aminobenzylamines to give substituted quinazolines were achieved in excellent yields and with a broad substrate scope, with no formation of toxic side‐products. The investigated conditions are not restricted to the use of aldehydes; the protocol also works well with alcohols or amines as substrates. These are oxidized in situ to the corresponding aldehydes to achieve the successful transformation. A mechanistic proposal has been drawn up based on control experiments. We found that under aerobic conditions, catalytic amounts of H 2 O 2 can be generated; this plays a key role in the efficacy of the described approach. The green chemistry metrics of the developed method are also presented. The E factor of 8.18 mg/1 mg demonstrates that the reported method is an excellent complement to previous protocols.