Continuous-Flow Oxidation of Amines Based on Nitrogen-Rich Heterocycles: A Facile and Sustainable Approach for Promising Nitro Derivatives

Abstract

The oxidation of amines based on nitrogen-rich heterocycles is one of the appealing alternatives for promising nitro derivatives. Herein, we present a continuous-flow process to achieve oxidation of these amines to their nitro derivatives, taking advantage of hydrogen peroxide as an environmentally benign and inexpensive oxidant. Facile and sustainable access to valuable nitro compounds was ensured. The utility of the present continuous-flow oxidation process was demonstrated by synthesizing promising energetic compounds 5-amino-3-nitro-1,2,4-triazole (ANTA) and 1-methyl-3,4,5-trinitropyrazole (MTNP) on a multigram scale.

The Application of Peroxide for Organic Synthesis in Continuous Flow Chemistry

“…12 ). 43 The reliability of the process was confirmed by the successfully obtained 5-amino-3-nitro-1,2,4-triazole and 1-methyl-3,4,5-trinitropyrazole with a high efficiency.…”

Triazene-bridged energetic materials based on nitrotriazole: synthesis, characterization, and laser-ignited combustion performance

“…3-Amino-5-nitro-1,2,4-triazole (ANTA) was prepared according to the previous literature. 37,38 The triazene-bridged 1,2,4-triazole (1) was selected as the first target molecule. The reaction was carried out using ANTA with a solution of half an equivalent of sodium nitrite in diluted nitric acid at 0-5 °C for 24 h, whereby the desired triazene-bridge compound 1 was produced in a yield of 62% as a yellow solid (Scheme 1).…”

Development and Scale-Up of a Fully Continuous Flow Synthesis of 2-Hydroxypyridine-N-oxide

“…Aqueous hydrogen peroxide (H 2 O 2 ) stands out as an ideal oxidant due to its high oxygen content, safety, ease of use, and low production and transportation costs. 7 Compared to other oxidants, such as m-chloroperbenzoic acid (MCPBA), 8 monoperoxyphthalic acid, 9 dioxiranes, 10 and Caro's acid (H 2 SO 5 ), 7 which can generate hazardous waste and byproducts, hydrogen peroxide generates only water as a byproduct. 8 This makes it a more environmentally friendly option for the oxidation processes.…”

“…Continuous synthesis is a more efficient and safer technology compared to batch synthesis. − By taking into account the physical and chemical properties of the reaction materials, the mixed solubility of the materials and solvents, and the heat and mass transfer processes, the targeted design and selection of continuous reactors can improve the controllability, mixing efficiency, and heat and mass transfer characteristics of reactions. ,− In this study, economic considerations led to the selection of 2-chloropyridine as a raw material for synthesizing 2-chloropyridine- N -oxide via catalytic oxidation with hydrogen peroxide, which was then hydrolyzed with sodium hydroxide to produce HOPO (Scheme ). A fixed bed reactor functioned as a continuous catalytic oxidation reactor, and a plug flow reactor was used for continuous hydrolysis.…”

“…However, the exothermic nature of the reaction and potential hydrogen peroxide decomposition issues must be carefully managed during scale-up production. 9 To ensure a stable reaction heat and sufficient safety, the hydrogen peroxide addition rate must be controlled accordingly. Titanium-containing zeolite catalysts, specifically TS-1 molecular sieves, have exhibited excellent performance in many catalytic oxidation reactions, 8,10,11 achieving 99.2% conversion and 95.5% selectivity in pyridine oxidation reactions.…”