Continuous Flow Oxidation of Alcohols Using TEMPO/NaOCl for the Selective and Scalable Synthesis of Aldehydes

Abstract

A simple and benign continuous flow oxidation protocol for the selective conversion of primary and secondary alcohols into their respective aldehyde and ketone products is reported. This approach makes use of catalytic amounts of TEMPO in combination with sodium bromide and sodium hypochlorite in a biphasic solvent system. A variety of substrates are tolerated including those containing heterocycles based on potentially sensitive nitrogen and sulfur moieties. The flow approach can be coupled with inline reactive extraction by formation of the carbonyl-bisulfite adduct which aids in separation of remaining substrate or other impurities. Process robustness is evaluated for the preparation of phenylpropanal at decagram scale, a trifluoromethylated oxazole building block as well as a late-stage intermediate for the anti-HIV drug maraviroc which demonstrates the potential value of this continuous oxidation method.

TEMPO-Grafted Polystyrene/Polymethacrylate Organosiloxane Janus Nanohybrids as Efficient Pickering Interfacial Catalyst for Selective Aerobic Oxidation of Cinnamyl Alcohol

“…To eliminate the above obstacles, several strategies have been applied, particularly the functionalization of TEMPO on solid materials, which makes the system heterogeneous and simplifies the recovery process. Therefore, effective separation and recovery of TEMPO for practical applications is highly desirable to make the Anelli–Montanari alcohol oxidation process more sustainable in industries. − …”

Continuous Flow Synthesis of N,O-Dimethyl-N′-nitroisourea Monitored by Inline Fourier Transform Infrared Spectroscopy: Bayesian Optimization and Kinetic Modeling

“…N , O -dimethyl- N ′-nitroisourea ( 3 ) and 1-methyl-3-nitroguanidine ( 4 ) are crucial intermediates in neonicotinoid insecticides, produced through the nucleophilic substitution of O -methyl- N -nitroisourea ( 1 ) with methylamine ( 2 ). − Traditional batch synthesis of these intermediates often struggles with inconsistent reaction conditions, potential safety risks, and long reaction times . In contrast, continuous flow microreactors have been recognized for their superior mixing efficiency, , precise control over reaction parameters, and safety benefits, − showing potential for improving reaction selectivity. − However, their application in synthesizing these specific intermediates remains unexplored.…”