Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi 13, 56124 Pisa, Italy.
J Org Chem. 2020 Apr 17;85(8):5342-5350. doi: 10.1021/acs.joc.0c00027. Epub 2020 Mar 30.
Thiourea derivatives of 2-[(1)-1-aminoethyl]phenol, (1,2)-1-amino-2,3-dihydro-1-inden-2-ol, (1,2)-(1,2)-1-amino-2,3-dihydro-1-inden-2-ol, and ()-1-phenylethanamine have been compared as chiral solvating agents (CSAs) for the enantiodiscrimination of derivatized amino acids using nuclear magnetic resonance (NMR) spectroscopy. Thiourea derivative, prepared by reacting 2-[(1)-1-aminoethyl]phenol with benzoyl isothiocyanate, constitutes an effective CSA for the enantiodiscrimination of 3,5-dinitrobenzoyl (DNB) derivatives of amino acids with free or derivatized carboxyl functions. A base additive 1,4-diazabicyclo[2.2.2]octane(DABCO)/,-dimethylpyridin-4-amine (DMAP)/NBuOH) is required both to solubilize amino acid derivatives with free carboxyl groups in CDCl and to mediate their interaction with the chiral auxiliary to attain efficient differentiation of the NMR signals of enantiomeric substrates. For ternary systems CSA/substrate/DABCO, the chiral discrimination mechanism has been ascertained through the NMR determination of complexation stoichiometry, association constants, and stereochemical features of the diastereomeric solvates.
2-[(1)-1-氨基乙基]苯酚、(1,2)-1-氨基-2,3-二氢-1-茚醇、(1,2)-(1,2)-1-氨基-2,3-二氢-1-茚醇和()-1-苯乙胺的硫脲衍生物已被用作手性溶剂（CSA），通过核磁共振（NMR）光谱法对衍生氨基酸进行对映体选择性识别。通过将 2-[(1)-1-氨基乙基]苯酚与苯甲酰异硫氰酸酯反应制备的硫脲衍生物，对于具有游离或衍生羧基官能团的 3,5-二硝基苯甲酰（DNB）衍生物的氨基酸对映体选择性识别是有效的 CSA。碱性添加剂 1,4-二氮杂二环[2.2.2]辛烷（DABCO）/，-二甲吡啶-4-胺（DMAP）/NBuOH）既需要溶解具有游离羧基的氨基酸衍生物在 CDCl 中，又需要介导它们与手性辅助物的相互作用，以实现对映体底物 NMR 信号的有效区分。对于三元体系 CSA/底物/DABCO，通过 NMR 测定配合物化学计量、缔合常数和非对映异构体溶剂化物的立体化学特征，确定了手性识别机制。
