ElectrochemicalN-demethylation of tropane alkaloids

A practical, efficient, and selective electrochemicalN-demethylation method of tropane alkaloids to their nortropane derivatives is described. Nortropanes, such as noratropine and norscopolamine, are important intermediates for the semi-synthesis of the medicines ipratropium or oxitropium bromide, respectively. Synthesis was performed in a simple home-made electrochemical batch cell using a porous glassy carbon electrode. The reaction proceeds at room temperature in one step in a mixture of ethanol or methanol and water. The method avoids hazardous oxidizing agents such as H(2)O(2)orm-chloroperbenzoic acid (m-CPBA), toxic solvents such as chloroform, as well as metal-based catalysts. Various key parameters were investigated in electrochemical batch or flow cells, and the optimized conditions were used in batch and flow-cells at gram scale to synthesize noratropine in high yield and purity using a convenient liquid-liquid extraction method without any need for chromatographic purification. Mechanistic studies showed that the electrochemicalN-demethylation proceeds by the formation of an iminium intermediate which is converted by water as the nucleophile. The optimized method was further applied to scopolamine, cocaine, benzatropine, homatropine and tropacocaine, showing that this is a generic way ofN-demethylating tropane alkaloids to synthesize valuable precursors for pharmaceutical products

Tacticity Influence on the Electrochemical Reactivity of Group Transfer Polymerization-Synthesized PTMA

Spectroscopic, thermal, and electrochemical characterization results are presented for the redox active polymer poly­(2,2,6,6-tetramethyl-1-piperinidyloxy-4-yl methacrylate) or PTMA, synthesized by group transfer polymerization (GTP), and its precursors 4-hydroxy-tetramethylpiperidine-<i>N</i>-oxyl (HO-TEMPO) and 4-methacryloyloxy-tetramethylpiperidine-<i>N</i>-oxyl (MO-TEMPO). DSC analysis of synthesized PTMA showed that the glass transition temperature (<i>T</i>_g) of the polymer structure occurs at 155 °C, corroborated by dynamic mechanical analysis (DMA), which is higher when compared with <i>T</i>_g data for PTMA synthesized by other methods. Also, the amount of radical species present in PTMA synthesized by GTP reactions (100%) is higher than the values typically upon synthesizing PTMA by radical polymerization. Electrochemical and spectroelectrochemical-electron spin resonance studies in acetonitrile revealed two redox events in the PTMA polymer, one of which is reversible, accounting for ca. 80% of the spins in the polymer and giving rise to the battery behavior. The other redox event is irreversible, accounting for the remaining ca. 20% of spins, which has not previously been reported. These two redox events are linked to a structural property associated with the tacticity of the polymer, where the reversible feature (responsible for cathode behavior) is the dominant species. This corresponds to a number of isotactic domains of the polymer (determined by high temperature ¹H NMR). The second feature accounts for the three-line impurity observed in the ESR, which has been reported previously but poorly explained, associated to the number of heterotactic/syndiotactic triads

Access to carbonyl compounds via the electroreduction of N-benzyloxyphthalimides: Mechanism confirmation and preparative applications

A method to access carbonyl compounds using reductive conditions was evaluated via electrochemical reduction of their corresponding N-benzyloxyphthalimide derivatives (NBOPIs). The mechanism of this originally reported electrochemical reaction was proposed based on DFT calculation and is experimentally confirmed herein, contrasting simulated and experimental cyclic voltammetry data. The reaction scope studied in a preparative scale and using redox sensitive functional groups showed good selectivity and tolerance toward oxidation under the reaction conditions with a moderate to good yield (50–71%). Nevertheless, some restrictions with reducible functional groups, like benzyl-brominated and nitro-aromatic derivatives, were observed. The present approach can be considered a self-sustainable electrochemical catalysis for the synthesis of aromatic carbonylic compounds passing through anion radical intermediates produced by a cathodic reaction

Competition between Hydrogen Bonding and Proton Transfer during Specific Anion Recognition by Dihomooxacalix[4]arene Bidentate Ureas

Competition between hydrogen bonding and proton transfer reactions was studied for systems composed of electrogenerated dianionic species from dinitrobenzene isomers and substituted dihomooxacalix[4]­arene bidentate urea derivatives. To analyze this competition, a second-order E_rC_rC_i mechanism was considered where the binding process is succeeded by proton transfer and the voltammetric responses depend on two dimensionless parameters: the first related to hydrogen bonding reactions, and the second one to proton transfer processes. Experimental results indicated that, upon an increase in the concentration of phenyl-substituted dihomooxacalix[4]­arene bidentate urea, voltammetric responses evolve from diffusion-controlled waves (where the binding process is at chemical equilibrium) into irreversible kinetic responses associated with proton transfer. In particular, the 1,3-dinitrobenzene isomer showed a higher proton transfer rate constant (∼25 M^–1 s^–1) compared to that of the 1,2-dinitrobenzene (∼5 M^–1 s^–1), whereas the 1,4-dinitrobenzene did not show any proton transfer effect in the experimental conditions employed