A Multicomponent Synthetic Strategy for 2‐Pyrazolines and Pyrimidines Through Activation of Renewable Alcohols by a Versatile Fe(III) Catalyst and Friedländer Quinoline Synthesis

In this study, a multicomponent synthesis of pyrazolines, pyrimidines, and quinoline synthesis via activation of greener primary alcohols catalyzed by a well-defined bimetallic Fe(III) catalyst is reported. A broad range of substrates of pyrazoline, pyrimidines, and quinolines was explored via the current protocol. Several controlled experiments were also performed for a mechanistic investigation.

Abstract

In this study, we have reported the first Fe(III) catalyzed eco-friendly, practical, and less expensive multicomponent synthesis (MCS) of pyrazolines and pyrimidines by dehydrogenation of greener benzyl alcohols. A well-defined bimetallic μ-oxo iron(III) was synthesized and characterized by a number of spectroscopic techniques. The molecular structure of the complex was determined by single-crystal X-ray diffraction. The iron(III) complex (C1) has been utilized as a catalyst for the MCS of pyrazolines from sustainable benzyl alcohols, aromatic ketones, and phenylhydrazine. The catalyst was further utilized for the MCS of pyrimidines from phenylacetylene, amidine derivatives via activation of alcohols. The efficiency of this catalyst was also scrutinized for quinoline synthesis from acceptorless dehydrogenative (AD) coupling of 2-aminobenzyl alcohol with aromatic ketones. A wide range of substrates with diverse functionality was explored, and a total of 44 derivatives of 1,3,5-trisubstituted pyrazolines, 38 derivatives of 2,4,6-trisubstituted pyrimidines, and 35 derivatives of quinolines were explored and characterized, having an isolated yield up to 95%. The current methodology is also utilized for gram-scale synthesis for large-scale applicability. Various controlled experiments and DFT optimized study were performed to reveal the possible intermediates and explain the plausible reaction mechanism.