Synthetic Protocols for Aromatic Nitration: A Review

Abstract

Nitration of aromatic compounds represents a powerful and widely used transformation that allows introducing nitro group into aromatic systems. New synthetic strategies for aromatic nitration are deeply needed, including highly efficient and selective nitration methods. Aromatic nitration plays an important part in the industry, as the main use of nitration is to produce important products such as dyes & intermediate compounds, drugs, and Agrochemicals. The electrophilic aromatic nitration is most studied and important transformation in industrial process. This review will describe different possible methodologies that apply to this fundamental transformation with special attention to the most recent development that lasted from 2017–2020. The main pros and cons of recent nitration methods are briefly described with their specific reaction mechanism and highlighting the most important feature of the present aromatic nitration method.

Electrochemical Nitration with Nitrite

“… [2] Interestingly, nitroarenes rarely occur in nature. [1b] However, there are numerous nitro‐containing approved drugs (Scheme 1 ), such as Niclosamide ( 1 ), which treats tapeworm infections. [3] The calcium channel blocker Nifedipine ( 2 ) is mainly used to medicate high blood pressure[ 3c , 4 ] and Flutamide ( 3 ) is utilized against prostate cancer.…”

“…Furthermore, vast amounts of waste are generated due to the excess of mineral acids used. [ 1a , 1b , 1d , 1f , 14 ] It is worth mentioning that the process of electrophilic aromatic nitration is hazardous and has led to a number of accidents in the past. [15] In future, nitric acid in higher concentration will be limited available in order to fulfil the homeland security aspects.…”

Site-selective and metal-free C–H nitration of biologically relevant N-heterocycles

“…Since the landmark discovery by Mitscherlich and Laurent in 1834 (Patel et al 2021 ), nitro compounds are important and versatile building blocks in organic chemistry (Ono 2001 ), and their derivatives are widely utilized in various pharmaceuticals, agrochemicals, pigments, and dyes as well as a variety of fine chemicals such as solvents, perfumes, explosives, and polymers, as shown in Fig. 1 (Fan et al 2004 ; McNamara et al 2011 ; Nepali et al 2019 ).…”

Electrochemical Reductive N-Methylation with CO2 Enabled by a Molecular Catalyst

“…Although electrochemical reductive N-methylation of amines, hydroxylamines, and hydrazine with CO 2 are novel reactions with potential in the sustainable synthesis of fine chemicals, it would be desirable to utilize cheaper and synthetically more accessible nitrogen sources such as nitro-compounds, which are prepared commercially using robust nitration methods. − Nitro-compounds are used as precursors in the synthesis of common amines such as aniline, which is produced industrially by the hydrogenation of nitrobenzene at high temperature over a metal catalyst . The reduction of nitro-compounds in tandem with reductive amination using aldehydes or ketones to yield secondary and tertiary amines is a well-known reaction that has been bolstered in the past decade by the development of efficient and selective non-noble metal catalysts, including recent examples using iron oxide and cobalt oxide nanocatalysts. , Inspired by these reports, we hypothesized that our reductive N-methylation reaction with CO 2 could be made compatible with nitro-compounds as the nitrogen source by reducing them in situ to provide the coupling nucleophile.…”