The m-CPBA–NH₃(g) System: A Safe and Scalable Alternative for the Manufacture of (Substituted) Pyridine and Quinoline N-Oxides

Abstract

An improved, safe, and scalable isolation process for (substituted) pyridine and quinoline N-oxides in quantitative yields along with high purities using the m-CPBA–NH3(g) system is described. The safety was assessed by reaction calorimetry and differential scanning calorimetry studies for possible hazards during the conversion and isolation steps. Careful interpretation of the data substantiated the safety and scalability. The process flow is simplified to meet the industrial requirements of safety, cost-effectiveness, and utility minimization. The reaction was safely demonstrated at a 2.5 kg scale.

Ozone-Mediated Amine Oxidation and Beyond: A Solvent-Free, Flow-Chemistry Approach

“…Pyridine N-oxides are valuable molecules, often formed by the treatment of the corresponding pyridine with m-CPBA. 25 Without reoptimization, our conditions could smoothly oxidize pyridines bearing alcohol (4a), tert-butyl (4b), and oxidizable benzylic C-H bonds (4c) to form the corresponding N-oxides in 65-92% yield (Scheme 3a). We next investigated applications to hydroxylation of tertiary C-H bonds.…”

Nucleophilic Halogenation of HeterocyclicN‐Oxides: Recent Progress and a Practical Guide

“…[2] A convenient alternative is nucleophilic halogenation of heterocyclic N-oxides 1, which are typically accessed by oxidation of the corresponding N-heterocycles (Scheme 1, a). [3] Deoxygenative nucleophilic halogenation strategy requires activation of the N-oxide moiety with a strong electrophile, which enables the addition of the halide anion to the C=N bond in cation A to give adduct B. [4] Subsequent elimination of HOE molecule from B (typically assisted with a base) affords the desired 2halo-substituted heterocycle 2 (Scheme 1, b).…”

“…Unfortunately, C2‐halogenated N ‐heterocycles are often difficult to prepare via direct C−H halogenations routes due to harsh conditions, poor regioselectivity and overhalogenation issues [2] . A convenient alternative is nucleophilic halogenation of heterocyclic N ‐oxides 1 , which are typically accessed by oxidation of the corresponding N ‐heterocycles (Scheme 1, a) [3] …”

Facile Fabrication of Hierarchical MOF–Metal Nanoparticle Tandem Catalysts for the Synthesis of Bioactive Molecules

“…[33][34][35][36] Despite the above mentioned superior properties and vast applications, the synthesis of quinoline N-oxides is considerably underdeveloped. Previously reported methods for the synthesis of quinoline N-oxides include the oxidation of quinolines, 37,38 reductive cyclization reaction of 2nitrochalcones, 39 and others. 40,41 However, both quinolines and 2-nitrochalcones are not readliy available.…”