Congshan Zhou

Enantiomeric separation of oxybutynin by recycling high-speed counter-current chromatography with hydroxypropyl-β-cyclodextrin as chiral selector.

Recycling high-speed counter-current chromatography was successfully applied to the preparative separation of oxybutynin enantiomers. The two-phase solvent system consisted of n-hexane, methyl tert-butyl ether, and 0.1 mol/L phosphate buffer solution (pH = 5.0) with the volume ratio of 6:4:10. Hydroxypropyl-β-cyclodextrin was employed as the chiral selector. The influence of factors on the chiral separation process, including the concentration of chiral selector, the equilibrium temperature, the pH value of the aqueous phase were investigated. Under optimum separation conditions, 15 mg of oxybutynin racemate was separated with the purities of both the enantiomers over 96.5% determined by high-performance liquid chromatography. Recovery for the target compounds reached 80-82% yielding 6.00 mg of (R)-oxybutynin and 6.15 mg of (S)-oxybutynin. Technical details for recycling elution mode were discussed.

Studies on Enantioselective Liquid–Liquid Extraction of Amino-(4-nitro-phenyl)-acetic Acid Enantiomers: Modeling and Optimization

BINAP-metal complexes were prepared as extractant for enantioselective liquid-liquid extraction (ELLE) of amino-(4-nitro-phenyl)-acetic acid (NPA) enantiomers. The influence of process variables, including types of organic solvents and metal precursor, concentration of ligand, pH, and temperature on the efficiency of the extraction, were investigated experimentally. An interfacial reaction model was established for insightful understanding of the chiral extraction process. Important parameters required for the model were determined. The experimental data were compared with model predictions to verify the model prediction, It was found that the interfacial reaction model predicted the experimental results accurately. By modeling and experiment, an optimal extraction condition with pH of 7 and host (extractant) concentration of 1 mmol/L was obtained and high enantioselectivity (αop ) of 3.86 and performance factor (pf) of 0.1949 were achieved.

Enantioselective extraction of hydrophilic 2-chloromandelic acid enantiomers by hydroxypropyl-β-cyclodextrin: experiments and modeling

Enantioselective extraction of hydrophilic 2-chloromandelic acid (CMA) enantiomers from organic to aqueous phase with hydroxypropyl-β-cyclodextrin (HP-β-CD) as the selector was investigated. Equilibrium of the extraction system was modeled using a reactive extraction model with a homogeneous aqueous phase reaction. The influence of important process variables on the extraction efficiency, such as the type of the organic solvent and β-cyclodextrin derivatives (β-CDs), concentration of the selector, pH and temperature, was investigated by experiment and modeling. Important parameters of this model were determined experimentally. Results showed that the experimental data agree with the model prediction perfectly and the model was further applied to accurately predict the extraction efficiency influenced simultaneously by pH and the concentration of HP-β-CD. Combining the experiment and the model data, the best extraction conditions were: pH of 2.5, HP-β-CD concentration of 0.05 mol L−1, and temperature of 5°C, providing the enantioselectivity of 1.285 and the performance factor (pf) of 0.011.

Metal-Free Oxidative C–C Bond Functionalization of Methylenecyclopropanes with Ethers Leading to 2-Substituted 3,4-Dihydronaphthalenes

A novel metal-free oxidative ring-opening/cyclization of methylenecyclopropanes with ethers was established for the synthesis of diverse 2-substituted 3,4-dihydronaphthalenes with high selectivity and efficiency. This oxidative cyclization is achieved by C(sp3)-H functionalization, ring-opening, and cyclization, and this method represents a new example of methylenecyclopropane oxidative cyclization with an aromatic carbon and a C(sp3)-H bond by simultaneously forming two new carbon-carbon bonds.

Iodine-mediated sulfenylation of 4-hydroxycoumarins with sulfonyl hydrazides under aqueous conditions

An efficient, metal-free approach to the synthesis of sulfenylated coumarins based on the iodine catalyzed regioselective sulfenylation of 4-hydroxycoumarins with arylsulfonyl hydrazides was developed under mild conditions in water. Various sulfenylated coumarin derivatives were obtained in good to excellent yields with good functional group tolerance.

Visible-Light-Mediated Ipso-Carboacylation of Alkynes: Synthesis of 3-Acylspiro[4,5]trienones from N-(p-methoxyaryl)propiolamides and Acyl Chlorides

A novel visible-light-mediated ipso-carboacylation of N-(p-methoxyaryl)propiolamides with acyl chloride has been established for the synthesis of diverse 3-acylspiro[4,5]trienones with high selectivity and efficiency. This method represents a new difunctionalization of alkynes through cross coupling of the acyl chloride C-Cl bonds with an ipso-aromatic carbon by simultaneously forming two new carbon-carbon bonds and one carbon-oxygen double bond.

DCC-assisted direct esterification of phosphinic and phosphoric acids with O-nucleophiles

GRAPHICAL ABSTRACT ABSTRACT A novel and efficient dicyclohexylcarbodiimide-promoted protocol for the selective and controllable esterification of P(O)OH compounds using O-nucleophiles (alcohols and phenols) as efficient esterification reagents is described. This method features a high efficiency and good functional-group tolerance, meaning a simple way to synthesize a broad spectrum of phosphinic and phosphoric acid esters from basic starting materials with moderate to excellent yields.

Copper-catalyzed α-C–H acyloxylation of carbonyl compounds with terminal alkynes

Herein, a copper/TBHP catalyst system for the α-C–H acyloxylation of carbonyl compounds is developed using terminal alkynes as the acyloxy source. A variety of carbonyl compounds and terminal alkynes are tolerated in this reaction. In addition, its possible mechanism is proposed.

Bu4NI-Catalyzed Dehydrogenative Coupling of Diaryl Phosphinic Acids with C(sp3)–H Bonds of Arenes

An efficient phosphorylation of C(sp3)-H bonds of arenes with diaryl phosphinic acids via Bu4NI-catalyzed dehydrogenative coupling has been developed. This transformation proceeds efficiently under transition-metal-free reaction conditions and represents a straightforward method to prepare valuable organophosphorus compounds from readily available arenes and diaryl phosphinic acids.

Oxidative C–C Bond Functionalization of Methylenecyclopropanes with Aldehydes for the Formation of 2-Acyl-3,4-dihydronaphthalenes

A new FeCl2- and DTBP (di- tert-butyl peroxide)-promoted oxidative ring-opening and cyclization of methylenecyclopropanes with aldehydes for the synthesis of 2-acyl-3,4-dihydronaphthalenes is presented. This oxidative cyclization reaction proceeds via a radical addition, ring-opening, and cyclization sequence facilitated by a Lewis acid, and it offers a practical and straightforward route for the oxidative cyclization of methylenecyclopropanes with an aromatic carbon and a C(sp2)-H bond by simultaneously forming two new carbon-carbon bonds.