Low Temperature, High Conversion, Liquid‐Phase Benzylic Oxidation with Dioxygen by Metal/NHPI‐Catalyzed Co‐Oxidation with Benzaldehyde

Abstract

A new liquid-phase catalytic oxidation system for the low temperature, high conversion benzylic mono-oxyfunctionalization of 10,11-dihydrocarbamazepine (1) into oxcarbazepine (4) with dioxygen has been developed. The method is based on a co-oxidation of 1 with benzaldehyde in the presence of a four-component catalyst system consisting of Co(-OAc) 2 , Ni(OAc) 2 , Cr(NO 3 ) 3 , and N-hydroxyphthalimide (NHPI). The influence of the catalyst system on the formation and decomposition of the crucial hydroperoxide intermediate

A Structurally Diverse Heterocyclic Library by Decoration of Oxcarbazepine Scaffold

“…The reaction mixture was left cooling to r.t. and added dropwise to stirred ice/water (25 mL), the yellow precipitate was collected by filtration, washed with water and dried under vacuum to afford 27 (64 mg, 49%): the spectroscopic data were in accordance with those reported in the literature [30]. (28). Compound 26 (100 mg, 0.45 mmol) and diaminomalonitrile (49 mg, 0.45 mmol) in AcOH (2 mL) were refluxed for 1 h under stirring.…”

“…The two-fold benzylic oxidation of carbamazepine CBZ in the presence of a metal salt and N-hydroxyphthalimide has been shown by Alsters et al [28] to give the required 25 (in only 8% at best!) and, as far as we are aware, this constitutes the only synthesis of this compound.…”

Cobalt(II)/N-Hydroxyphthalimide-Catalyzed Cross-Dehydrogenative Coupling Reaction at Room Temperature under Aerobic Condition

“…102 mg, 82% yield, R f = 0.5 (mobile phase: petroleum ether/ethyl acetate = 9:1). 1 H NMR (400 MHz, CDCl 3 , δ): 7.38−7.09 (m, 6H), 7.00 (d,J = 8.3 Hz,2H),5.45 (s,1H),3.69 (dd,J = 11.5,5.4 Hz,1H),1H),1H), 2.93 (d,J = 16.3 Hz,1H), 2.31 (s, 3H). 13 C NMR (101 MHz,CDCl 3 ,δ): 146.25,134.5,131.8,130.1,129.6,129.4,128.7,127.1,126.75,118.3,117.7,54.1,44.4,28.6,20.6.…”

Co/NHPI-mediated aerobic oxygenation of benzylic C–H bonds in pharmaceutically relevant molecules

“…10 This methodology has been demonstrated in numerous oxidation reactions, including industrial applications, 8 but the vast majority of studies have focused on simple hydrocarbon substrates. 11 …”