The Zinin Reduction of Nitroarenes

Abstract

The Zinin reduction is a method for the reduction of nitroarenes by negative divalent sulfur. This versatile reaction can be carried out in the laboratory and for plant‐scale manufacture of aromatic amines when other reduction media are destructive to sensitive compounds or result in undesired side reactions. The first reaction, used by Zinin, was to prepare aniline from nitrobenzene. It has been of great importance in the preparation of aromatic amines. Refinements in technique and a better understanding of the reaction mechanism should make this method attractive for the preparation of a variety of amines.

Synthesis, Chemical Characterization, and μ-Opioid Receptor Activity Assessment of the Emerging Group of “Nitazene” 2-Benzylbenzimidazole Synthetic Opioids

“…The nitro group that is ortho to the amino group of intermediate II was then selectively reduced using aqueous ammonium sulfide (or a suitable equivalent) in refluxing ethanol to afford III (Zinin reduction). 51 Condensation of III with an appropriately substituted phenylacetic acid derivative (such as in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) afforded the desired benzimidazoles as free bases. 46 Hydrochloric or citric acid was used to convert some of the resulting benzimidazoles into their corresponding salt forms.…”

HER2 Kinase-Targeted Breast Cancer Therapy: Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Lapatinib Congeners as Selective and Potent HER2 Inhibitors with Favorable Metabolic Stability

“…Reaction of the commercially available 2-chloro-4-nitrophenol ( 1a ) or 2-chloro-1-fluoro-4-nitrobenzene ( 1b ) with 1-(bromomethyl)-3-fluorobenzene ( 2a ) or the appropriate phenol derivative ( 2b–d ) was carried out in dimethylformamide (DMF) or acetonitrile in the presence of potassium carbonate to afford the corresponding nitro derivatives ( 3a–d ) in good yields of 73–89%. , Reduction of the nitro derivatives ( 3a–d ) into their amino analogues ( 4a–d ) were achieved by either heating with Fe/CaCl 2 in aqueous ethanolic solution to prepare ( 4a ) intermediate or via reflux with SnCl 2 for 2.5 h in methanol under nitrogen to afford intermediates ( 4b–d ). The reduction methods gave the desired intermediates in very good yields of 77–82%, in shorter reaction times, and with higher purity than the reported methods using H 2 /Pt–C, , SnCl 2 /EtOAc/reflux/24 h, , Na 2 S/dioxane/70–80 °C/24 h (Zinin reaction), or Fe/NH 4 Cl/EtOH/reflux/2 h . The 1 H NMR spectrum of 4c revealed a broad signal at δ 5.42, exchanged with D 2 O, representing the two protons of the NH 2 group.…”

“…50,51 Reduction of the nitro derivatives (3a−d) into their amino analogues (4a−d) were achieved by either heating with Fe/CaCl 2 in aqueous ethanolic solution to prepare (4a) intermediate or via reflux with SnCl 2 for 2.5 h in methanol under nitrogen to afford intermediates (4b−d). The reduction methods gave the desired intermediates in very good yields of 77−82%, in shorter reaction times, and with higher purity than the reported methods using H 2 /Pt−C, 50,51 SnCl 2 /EtOAc/ reflux/24 h, 52,53 Na 2 S/dioxane/70−80 °C/24 h (Zinin reaction), 54 or Fe/NH 4 Cl/EtOH/reflux/2 h. 44 The 1 H NMR spectrum of 4c revealed a broad signal at δ 5.42, exchanged with D 2 O, representing the two protons of the NH 2 group. The impact of the acetamido linker at position 6 was investigated by applying Scheme 2, and the 3-chloro-4-((3fluorobenzyl)oxy)aniline (4a) was incorporated into position 4 of the quinazoline nucleus through Dimroth rearrangement, as depicted in Scheme 2.…”

Vicarious nucleophilic substitution: a dramatically shortened synthesis of 2‐amino‐6‐nitrobenzoic acid labelled with carbon‐14

“…We next attempted the mono‐reduction of 2,6‐dinitrobenzoic acid to 2‐amino‐6‐nitrobenzoic acid by inorganic sulfide or disulfide (the Zinin reduction11). Reviewing the literature on the Zinin reduction, we found many examples of mono‐reductions of 1,3‐dinitrobenzene derivatives having a hydrogen or an electron donating group on the carbon between the nitro groups.…”