Nickel-catalyzed electrochemical carboxylation of unactivated aryl and alkyl halides with CO2

Electrochemical catalytic reductive cross couplings are powerful and sustainable methods to construct C−C bonds by using electron as the clean reductant. However, activated substrates are used in most cases. Herein, we report a general and practical electro-reductive Ni-catalytic system, realizing the electrocatalytic carboxylation of unactivated aryl chlorides and alkyl bromides with CO2. A variety of unactivated aryl bromides, iodides and sulfonates can also undergo such a reaction smoothly. Notably, we also realize the catalytic electrochemical carboxylation of aryl (pseudo)halides with CO2 avoiding the use of sacrificial electrodes. Moreover, this sustainable and economic strategy with electron as the clean reductant features mild conditions, inexpensive catalyst, safe and cheap electrodes, good functional group tolerance and broad substrate scope. Mechanistic investigations indicate that the reaction might proceed via oxidative addition of aryl halides to Ni(0) complex, the reduction of aryl-Ni(II) adduct to the Ni(I) species and following carboxylation with CO2.

Esterification of Alginate with Alkyl Bromides of Different Carbon Chain Lengths via the Bimolecular Nucleophilic Substitution Reaction: Synthesis, Characterization, and Controlled Release Performance

To extend the alginate applicability for the sustained release of hydrophobic medicine in drug delivery systems, the alkyl alginate ester derivative (AAD), including hexyl alginate ester derivative (HAD), octyl alginate ester derivative (OAD), decyl alginate ester derivative (DAD), and lauryl alginate ester derivative (LAD), were synthesized using the alkyl bromides with different lengths of carbon chain as the hydrophobic modifiers under homogeneous conditions via the bimolecular nucleophilic substitution (SN2) reaction. Experimental results revealed that the successful grafting of the hydrophobic alkyl groups onto the alginate molecular backbone via the SN2 reaction had weakened and destroyed the intramolecular hydrogen bonds, thus enhancing the molecular flexibility of the alginate, which endowed the AAD with a good amphiphilic property and a critical aggregation concentration (CAC) of 0.48~0.0068 g/L. Therefore, the resultant AAD could form stable spherical self-aggregated micelles with the average hydrodynamic diameter of 285.3~180.5 nm and zeta potential at approximately −44.8~−34.4 mV due to the intra or intermolecular hydrophobic associations. With the increase of the carbon chain length of the hydrophobic side groups, the AAD was more prone to self-aggregation, and therefore was able to achieve the loading and sustained release of hydrophobic ibuprofen. Additionally, the swelling and degradation of AAD microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Meanwhile, the AAD also displayed low cytotoxicity to the murine macrophage RAW264.7 cells. Thanks to the good amphiphilic property, colloidal interface activity, hydrophobic drug-loading performance, and cytocompatibility, the synthesized AAD exhibited a great potential for the development of hydrophobic pharmaceutical formulations.