4,6-Dihydroxysalicylic Acid-Catalyzed Oxidative Condensation of Benzylic Amines and Aromatic Ketones for the Preparation of 2,4,6-Trisubstituted Pyridines and Its Application to Metal-Free Synthesis of G-Quadruplex Binding Ligands

Chun-Ping Dong; Shintaro Kodama; Akihiro Nomoto; Michio Ueshima; Akiya Ogawa

doi:10.1021/acsomega.9b00999

4,6-Dihydroxysalicylic Acid-Catalyzed Oxidative Condensation of Benzylic Amines and Aromatic Ketones for the Preparation of 2,4,6-Trisubstituted Pyridines and Its Application to Metal-Free Synthesis of G-Quadruplex Binding Ligands

ACS Omega. 2019 May 23;4(5):9029-9040. doi: 10.1021/acsomega.9b00999. eCollection 2019 May 31.

Authors

Chun-Ping Dong¹, Shintaro Kodama¹, Akihiro Nomoto¹, Michio Ueshima¹, Akiya Ogawa¹

Affiliation

¹ Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan.

Abstract

4,6-Dihydroxysalicylic acid was activated under air to catalyze the one-pot oxidative condensation reaction of benzylamines with acetophenones in the presence of BF₃·Et₂O, affording 2,4,6-trisubstituted pyridines in yields of 59-91%. During this metal-free oxidative condensation reaction, the benzylamines not only provided the aryl moiety at the 4-position of the pyridines but also acted as the nitrogen donor. This method can be applied to the metal-free synthesis of G-quadruplex binding ligands by the sequential addition of 4-chlorobutyryl chloride and pyrrolidine to the reaction system of the 2,4,6-trisubstituted pyridine synthesis.