ChemInform Abstract: Catalytic N‐Dealkylation of Tertiary Amines. A Biomimetic Oxygenation Reaction.

Palladium‐Catalyzed N‐Demethylation/N‐Acylation of Some Morphine and Tropane Alkaloids

“…The standard procedures for N-demethylation of alkaloids, including morphine derivatives, involve the use of cyanogen bromide (the von Braun reaction), [2] the reaction of a tertiary amine with chloroformates followed by hydrolysis, [3] photochemical demethylation, [4] Polonovski-type reactions, [5,6] and other methods. The case of Pd-catalyzed oxidative demethylation with stoichiometric amounts of Pd/C appears in a single report by Chaudhuri, [7] however, our repetition of this procedure with hydrocodone (3) resulted in the isolation of only N-formylnorhydrocodone in low yield.…”

The Power of Visual Imagery in Drug Design. Isopavines as a New Class of Morphinomimetics and Their Human Opioid Receptor Binding Activity

“…(5 S ,6 R ,12 R )-6-Methylisopavine (20). To a solution of 7a (410 mg, 1.6 mmol) in MeOH (10 mL) was added Pd/C (1.0 g, 10%) at 0 °C, and the reaction mixture was stirred at room temperature in open-air atmosphere for 24 h . The mixture was filtered through Celite and washed with 30% MeOH in EtOAc.…”

“…The p -bromoarylisopavines were transformed to the corresponding bis- N- alkyl and bis -N- phenyl analogues 13 − 19 by versatile Pd-catalyzed insertion reactions of appropriate substituted amines . Scheme shows the oxidative demethylation of 7a to yield the corresponding des- N- methyl analogue 20 . Allylation, benzylation, and acetylation afforded the respective N -substituted compounds 21 − 23 .…”

“…By use of the above procedure, 7b (41 mg) was subjected to amination to give 19 (30 mg, 61%) as a yellow viscous oil: [R]D +7.2°(c 1.0, CHCl3); TLC Rf ) 0.58 (10% MeOH in CHCl3); 1 H NMR (300 MHz, CDCl3) δ 7.29-6.68 (m, 6H), 4.41 (bs, 1H), 3.52 (dd, 1H, J ) 3.0, 18.0 Hz), 3.49 (s, 1H), 3.23 (q, 1H, J ) 6.5 Hz), 3.12 (bs,-8H), 2.71 (dd, 1H, J ) 3.0, 18.0 Hz), 2.68 (m, 2H), 2.49 (bs, 8H), 2.36 (s, 6H), 1.14 (d, 3H, J ) 6.0 Hz), 0.99 (m, 1H), 0.59 (m, 2H), 0.17 (m, 2H); 13 (5S,6R,12R)-6-Methylisopavine (20). To a solution of 7a (410 mg, 1.6 mmol) in MeOH (10 mL) was added Pd/C (1.0 g, 10%) at 0 °C, and the reaction mixture was stirred at room temperature in open-air atmosphere for 24 h. 63 The mixture was filtered through Celite and washed with 30% MeOH in EtOAc. The combined filtrates were dried over Na2SO4 and concentrated in vacuo.…”

Methods for the Cleavage of Allylic and Propargylic C–N Bonds in Amines and Amides – Selected Alternative Applications of the 1,3‐Hydrogen Shift

“…The catalytic dealkylation of tertiary amines has been performed with palladium on charcoal in the presence of air, in methanol at 0 °C 67. Under these oxidative conditions methyl and ethyl groups are cleaved, and no dealkylation occurs for saturated alkyl groups containing more than two carbons.…”