Photochemical N-demethylation of alkaloids

Synthesis of deuterated dextromethorphan derivatives

“…Photochemical N-demethylation is a quite special reaction with moderate yield. 8 The yield of the sodium sulfide or potassium thioacetate method is not high enough and undesired side reactions could be noticed. 9 N-demethylation of the tertiary amine alkaloids e.g.…”

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

“…dissolved in an appropriate anhydride (1 mL) and dioxane (1 mL) was added PdA C H T U N G T R E N N U N G (OAc) 2 (0.01 mmol, 0.1 equiv.). The mixture was heated at 80 8C for 18 h, cooled to room temperature and filtered through a plug of silica with DCM:MeOH:NH 4 OH, 80:20:1 as eluent. The volatiles were removed under vacuum, and the residue was suspended in saturated aqueous NaHCO 3 .…”

“…The mixture was stirred at room temperature for 12 h, then, the reaction was quenched with aqueous 10% Na 2 S 2 O 3 . The organic solvent was removed under reduced pressure, the residue was basified to pH 9 with concentrated aqueous NH 4 OH, then extracted three times with DCM. After combining the organic layers, drying over anhydrous magnesium Table 4.…”

“…Our ongoing investigation [1] of the chemistry of morphine alkaloids and their derivatives, such as hydrocodone (3) and oxycodone (4) (Figure 1), has led to the discovery of conditions for a one-pot sequence of oxidative N-demethylation and subsequent N-acylation reactions. Such a transformation holds immense potential for the production of morphine-derived antagonists such as naloxone (5), naltrexone (6), and other medicinally significant compounds.…”

“…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.…”