Zilong Cui,Jingling Ye,Liang Yao,Zhi Wang,Ting Wang,Yonghong Hu
In this study, the data on solid–liquid equilibrium of l-prolinamide were studied using the gravimetric method. The solubility of l-prolinamide was measured in ten pure solvents (tetrahydrofuran, n-heptane, n-propanol, acetone, acetonitrile, ethyl acetate, N,N-dimethylformamide, n-hexane, cyclohexane, and isopropanol) and three binary solvent mixtures(ethyl acetate + tetrahydrofuran, n-heptane + ethyl acetate, and n-hexane + acetone) in the temperature range of 278.15–323.15 K at atmospheric pressure. The experimental values showed that the solubility increased with the increase of temperature in all solvents. The solubility data in different pure solvents were fitted using the modified Apelblat model and the Buchowski–Ksiazaczak λh model. For the solubility data of three binary solvent mixtures, the modified Apelblat model, the combined nearly ideal binary solvent/Redlich–Kister (CNIBS/R–K) model, and the Jouyban–Acree model were used to fit. In all four models, the modified Apelblat model had a better correlation with the solubility of l-prolinamide weather in pure solvents or binary solvent mixtures. The experimental results showed that n-heptane and n-hexane could be used as antisolvents, which could be used in the purification process of l-prolinamide and guide the large-scale production of many drugs such as Alpelisib in industries.
The development of single chiral source-derived ligands to fine-switch enantioselectivity has continuously attracted the attention in asymmetric catalysis. Herein, we use the same chiral source L-prolinamide as the starting material, synthesizing chiral bidentate pyridine-type N-oxide ligands (denoted as Py-NO) and chiral monodentate phenyl N-oxide ligands (denoted as Ph-NO); their effectiveness was demonstrated in the switch of enantioselectivity in palladium(II)-catalysed Friedel-Crafts (FC) alkylation of indoles and 2,3-dioxopyrrolidines, and both enantiomers of structurally important indole derivatives can be prepared in good yields (up to 91% yield) and high enantioselectivities (up to 99% ee). Key to the success of switch of enantioselectivity is the existence of two different activation patterns in this palladium(II) catalytic system. Experiments demonstrated that a counteranion would plausibly coordinate to the palladium(II) center in the stereoselectivity-determining step. Preliminary mechanistic studies provide a rational explanation for the above observations. This study was the first example of monodentate ligand in asymmetric catalytic Friedel-Crafts alkylation.
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