Acetic Acid Accelerated Visible‐Light Photoredox Catalyzed N‐Demethylation of N,N‐Dimethylaminophenyl Derivatives

Abstract

N,N-Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N-demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visiblelight photoredox catalyzed N-demethylation of N,N-dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture.

Continuous Flow Synthesis of Heterocycles: A Recent Update on the Flow Synthesis of Indoles

“…As briefly described in Section 2.5, flow chemistry offers some technological features that arise as extremely useful in view of an intensification of photochemical processes. In the field of indole photochemical derivatization, Chen et al reported a continuous flow preparation of tricyclo-1,4benzoxazines by the intramolecular cyclization of indole derivatives via visible-light photoredox catalysis [99]. For this study, a homemade capillary photoreactor consisting of two quartz glass tubes connected in series, described and named by the authors as "reaction towers", was used.…”

“…For this study, a homemade capillary photoreactor consisting of two quartz glass tubes connected in series, described and named by the authors as "reaction towers", was used. A fluorinated ethylene propylene FEP tube was wrapped around each reaction tower which held a LED corn light bulb (34 W) in the center, thus providing the reaction mixture irradiation [99]. According to the optimized protocol, indole derivative 61, p-toluensulfonic acid (TsOH), a catalytic amount of methylene blue (MB), and the selected alcohol were mixed in a round bottom flask.…”

Flow Synthesis of Biologically-Relevant Compound Libraries

“…Previous studies from the same research group showed that batch reaction suffered from many drawbacks as limited scope, difficulties in scaling up, and low reaction temperature requirement (−70 • C). Optimization of the reaction in flow has been performed using a home-made capillary continuous-flow photoreactor already used in another work from the same authors [22]. It was assembled by connecting in series two reactors towers made of quartz glass tubes (i.d.…”

“…The proposed synthesis employed substituted o-aminophenols 7, that in the presence of a suitable oxidant and catalyst underwent C-H oxidative coupling to yield the desired 2-aminophenoxazin-3-ones 8 (Scheme 3). Optimization of the reaction in flow has been performed using a home-made capillary continuous-flow photoreactor already used in another work from the same authors [22]. It was assembled by connecting in series two reactors towers made of quartz glass tubes (i.d.…”

Synthesis of Mono-N-Methyl Aromatic Amines from Nitroso Compounds and Methylboronic Acid

“…It is a known compound 44 obtained in 72% yield (21.6 mg) from methyl 3-nitrosobenzoate (30.2 mg), methylboronic acid (16.3 mg), and P(OEt) 3 (34 μL). Flash column chromatography eluting with hexane/AcOEt 8:2 yielded the compound as brown oil.…”