Cu-Catalyzed Expeditious Synthesis of N-Benzylaminoheter-ocycles Using N-Tosylhydrazones and Aminoheteroarenes

Abstract

N‐Tosylhydrazones were successfully coupled in the presence of CuI (10 mol%) with various heterocyclic amines to develop a convenient and high yielding protocol for the preparation of N‐benzylaminoheterocycles under microwave irradiation. This ligand‐free new methodology uses readily available starting materials and a cheaper copper catalyst. A wide range of O, N and S containing heteroarylamines and o‐phenylenediamine were explored to prepare N‐benzylaminoheterocycles and 1,2‐disubstituted benzimidazoles. The protocol was equally effective with N‐tosylhydrazones derived from aldehydes and ketones, especially ferrocene aldehyde to prepare an array of N‐benzylaminoheterocycles in good to excellent yields. Finally, the identified reaction conditions were utilized to prepare drug‐like molecules namely pyrido[1,2‐a]benzimidazole and N‐substituted‐2‐amino‐thiazole derivative as antitubercular agents.

A Borrowing Hydrogen Strategy for Dehydrative Coupling of Aminoisoquinolines with Benzyl Alcohols in Water

“…N ‐Benzylisoquinolin‐5‐amine (3d): Following the general procedure I, 3d was obtained as a pale yellow solid. Yield 202 mg (86 %); m.p.…”

Recent Advances in Transition‐Metal‐Catalyzed Reactions of N‐Tosylhydrazones

“…This reaction provides an efficient access toward CÀ H bond functionalization by a secondary benzyl group which was difficult to perform with other transition-metal-catalyzed direct CÀ H bond functionalization methods up to this point and hence has been employed for several activated azoles, azines and benzene derivatives. [120] Furthermore, Hamze et al and others presented a copper-catalyzed reductive coupling of N-tosylhydrazones with amines to afford α-branched amines (Scheme 93) [121] and adding a novel method for the formation of C(sp 3 )À N bonds. In the presence of Cu(acac) and Cs 2 CO 3 as a base, this protocol provides an alternative to prepare primary and secondary aliphatic amines, aminoalcohols and azole derivatives.…”