A Multi-Step Continuous Flow Process for the N-Demethylation of Alkaloids

Abstract

Dextromethorphan was N-demethylated using the non-classical Polonovski reaction under continuous flow conditions, in two steps: initial N-oxidation with m-chloroperbenzoic acid followed by iron-catalysed N-demethylation of the resulting N-oxide.

The direct α-C(sp3)–H functionalisation of N-aryl tetrahydroisoquinolines via an iron-catalysed aerobic nitro-Mannich reaction and continuous flow processing

“…9 Efficient iron-catalysed methodologies using O 2 as the oxidant are thus relatively scarce. 10 The relative abundance and low-toxicity of iron has led to our interest in exploring simple iron salts 11 and O 2 as a sustainable catalyst/oxidant combination for the nucleophilic addition of nitroalkanes to imines (nitro-Mannich reaction). 12 The b-nitroamine products are valuable building blocks as they contain a vicinal nitrogen motif that can be selectively manipulated to gain access to 1,2-diamines (by nitro reduction) and a-aminocarbonyls (via the Nef reaction).…”

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

“…The exotherm could be controlled due to the high surface area to volume ratio of the flow reactor. 44 The structural elements of the reactor can also affect chemical transformations. Stainless steel tubing was replaced with commercial copper tubing to catalyze the [3+2] cycloaddition step in the synthesis of Rufinamide (Fig.…”

“…70,104 The combination of multiple, differently functionalized scavenger resins is a common practice for the removal of several different impurities. 44,66,33,102,[105][106][107] In an illustrative example, removal of homogeneous transition metal complexes was possible this way ( Fig. 17), which prevented harmful catalytic activity in downstream heterogeneous nitro group reductions in the flow synthesis of the fungicide Boscalid Ò .…”

One‐Step Synthesis of Spin Crossover Nanoparticles Using Flow Chemistry and Supercritical CO2

“…Flow chemistry hasa lreadyb een successfully applied to differentk inds of materials [16,17] such as luminescent quantum dots, [18][19][20][21][22] metal nanoparticles, [23,24] polymers, [25,26] metal-organic frameworks, [27,28] organometallic species, [29] and molecules. [30][31][32][33] Several advantages of moving from batch to flow modeh ave been recognized, such as facile automation and feedback optimization, increased reproducibility,a nd improved safetya nd process reliability.Indeed, with continuousf low processes, stable reactionp arameters (temperature, time, amount of reagents and solvents, efficient mixing, etc.) can be ensured.…”