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Preparation and evaluation of chiral stationary phases based on N,N‐2,4‐(or 4,6)‐disubstituted 4,5‐(or 2,5)‐dichloro‐1,3‐dicyanobenzene
Author(s) -
Kontrec Darko,
Vinković Vladimir,
Šunjić Vitomir
Publication year - 2000
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(2000)12:2<63::aid-chir2>3.0.co;2-w
Subject(s) - chemistry , regioselectivity , amide , steric effects , dipeptide , stereochemistry , isopropyl , hydrogen bond , structural isomer , nucleophilic substitution , silica gel , nucleophile , amino acid , medicinal chemistry , organic chemistry , molecule , catalysis , biochemistry
Regioselective functionalization of 2,4,5,6‐tetrachloro‐1,3‐dicyanobenzene (TCDCB) by nucleophilic substitution of the chlorine at C(4) with l ‐Ala, l ‐Phe or l ‐Pro, followed by amide‐bond formation to lipophilic amines containing strong π‐donor group, and by final introduction of the spacer 3‐aminopropyltriethoxysilyl (APTES), provided a number of new brush‐type chiral selectors in the form of 1–2:1 mixture of 2,4 and 4,6‐di(alkyl)amino regioisomers ( 8/9 , 10/11 , 12/13 , 14/15 , 20/21 , 23/24 ). Linking these to silica gel (Nucleosil 100‐5) gave new chiral stationary phases for HPLC columns ( CSP I‐CSP VI ). Being strong π‐basic selectors, most of these columns exhibited good resolution properties for π‐acid test racemates ( TR 1‐TR 9 ), specifically rac 3,5‐dinitrobenzoyl‐α‐amino acid isopropyl‐esters (DNB‐AA). CSP V [1,3‐dicyano‐2,5(5,6)‐dichloro‐6(2)‐(γ′‐silica bound propylamino)‐4‐N‐{[N‐butyl]‐N′‐[ (1R)‐ cyclohexylethyl]‐N′‐[naphthylmethyl]acetamido}‐aminobenzene] and particularly the dipeptide‐containing CSP VI [2,5(5,6)‐dichloro‐6(2)‐(γ′‐silica bound propylamino)‐4‐N‐(3′,5′‐dimethylanilido)‐ l ‐alanyl‐ l ‐prolyl‐aminobenzene] proved to have the highest efficiency, comparable with the best commercial brush‐type columns with π‐donor properties. Further evidence revealed that multiple hydrogen bonding via the amide group in the chiral environment and π–π interaction play a major role in chiral recognition, whereas steric perturbations via nonbonding VDW interactions contribute substantially only to the resolution of CSP III [2,5(5,6)‐dichloro‐6(2)‐(γ′‐silica bound propylamino)‐4‐N‐(cyclohexylamido)‐L‐alanyl‐aminobenzene]. This contribution is minor for the other CSPs. Chirality 12:63–70, 2000. © 2000 Wiley‐Liss, Inc.