Direct high‐performance liquid chromatographic separation of the enantiomers of an aromatic amine and four aminoalcohols using polysaccharide chiral stationary phases and acidic additive

Abstract

The HPLC enantiomeric separation of N-benzyl-alpha-methyl-benzylamine, phenylalaninol, tryptophanol, 2 (diphenylhydroxymethyl)pyrrolidine, and isoproterenol was accomplished in the normal-phase mode using two polysaccharide-derived chiral stationary phases (CSPs) and various n-hexane/2-propanol mobile phases with acidic (TFA) or basic (DEA) additive. The compounds were separated without any derivatization and separation factor range between 2.09 and 1.09 with resolution factor 3.4 and 0.4, respectively. The best separation of the enantiomers of the amine was achieved on amylose tris (3, 5-dimethylphenylcarbamate) CSP with TFA additive in the mobile phase; in acidic conditions, instead, the best enantioseparation of the aminoalcohols was achieved on cellulose tris (3, 5-dimethylphenilcarbamate). A long equilibration time of the CSP when switching from an undoped mobile phase to a doped one is required to obtain reproducible results.

Direct high‐performance liquid chromatographic separation of the enantiomers of venlafaxine and 11 analogs using amylose‐derived chiral stationary phases

“…A similar effect was noted by us for N-benzyl-a-methylbenzylamine and phenylalaninol using the same CSP. 22 This finding is consistent with a dedicated study on the memory effect of the mobile phase additives on a Chiralpak AD column. 29 Chromato- Table 2.…”

“…22 The g-aminoalcohols in Table 1 actually behave as amines. The acidic additive forms an ion pair with the amine group, and this complex has more effective interactions with the helical cavity of the AD column.…”

“…21 We have recently used Chiralpak AD for the enantioseparation of b-aminoalcohols and an aromatic amine, and a comparison of the results obtained under acidic and basic mobile phase was carried out. 22 This was the starting point for the separation of the enantiomers of a series of 12 gaminoalcohols, including venlafaxine, as reported in this article. General formulas of the analytes, obtained as hydrochlorides, are shown in Figure 1.…”

Enantiomer Separations

“…Recently an independent solid-state NMR study confirmed that 2-propanol displaces hexane more efficiently from the polymeric selector, forming more ordered ''solvent-CSP complexes'' [54]. In order to achieve reproducible results, when switching from an additive-free to an additive-containing mobile phase (e.g., 0.1% trifluoroacetic acid or diethylamine), and vice versa, a prolonged equilibration time may be required [55]. In order to achieve reproducible results, when switching from an additive-free to an additive-containing mobile phase (e.g., 0.1% trifluoroacetic acid or diethylamine), and vice versa, a prolonged equilibration time may be required [55].…”

Effect of Mobile Phase Additive on Enantiomer Resolution for Chiral Amines on Polysaccharide-derived Chiral Stationary Phases by High Performance Liquid Chromatography

“…키랄 아민 화합물을 광학분리 하는데 있어서 소량의 아민을 이동상에 첨가하는 이유는 분 석물질인 아민과 고정상의 실리카와의 비특이성 상호작용 을 (non-specific interaction) 최소화하여 분석물질의 머무름 시간을 줄여주거나 또는 피크가 꼬리끌기 (tailing) 되어 용리 되는 것을 막아주는 효과를 가지고 있기 때문이다 [7]. 그런 데 몇 연구그룹에서 키랄 아민을 광학분리할 때 소량의 아민 을 염기 첨가제로 이동상에 가하여 분석하는 일반적인 분석 법대신에 산을 첨가제로 사용한 광학분리 결과를 보고하였 다 [7][8][9][10] …”