Oxidative Cross‐Coupling of Alcohols and Amines Catalyzed by TEMPO under Transition‐Metal‐Free Condition

• Published in: ChemistrySelect (Weinheim) Vol. 5; no. 21; pp. 6285 - 6293
• Main Authors: Chandrasekaran, Revathi, Carlose, Elgin, Muthu, Ajun E., Suresh, Athira, Chinnusamy, Tamilselvi
• Format: Journal Article
• Language: English
• Published: 08.06.2020
• Subjects: Cross-Coupling; Imines; Nitrogen heterocycles; TEMPO; Thiabutazide
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202001417

The transition‐metal‐free catalytic system TEMPO (2,2,6,6‐tetramethylpiperidine‐1‐oxyl)/NaOCl promotes an efficient oxidative cross‐coupling of alcohols and amines to imines 4 as well as 1,2,3,4‐tetrahydroquniazolines 6. A wide variety of alcohols and amines were well tolerated in the catalytic condition. This protocol was operationally very simple, efficiently scaled up to 100 mmol with as low as 0.5 mol% of catalyst loading and applied to the synthesis of biologically important diuretic drug molecule thiabutazide 9 in 98% yield. The recyclable TEMPO catalyst was showed similar reactivity. Moreover, it was reused upto five runs without much drop in the activity. The green chemistry metrics of the estabilished method (E‐factor value 17.80, Atom economy 90.7%, Carbon efficiency 98% and Overall efficiency 97.95%) proved to be efficient to the existing methods. A general and practical one‐pot method for the synthesis of imines and 1,2,3,4‐tetrahydroquinazolines was reported using 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) in combination with eco‐friendly co‐oxidant aq.NaOCl under transition‐metal‐free condition. The oxidative cross‐coupling reaction also carried out using recyclable catalyst, afforded good yields of desired products. This method has successfully utilized to the synthesis of biologically important thiabutazide molecule in gram scale directly from alcohol and amine.