Preparation of a New Chiral Pyridino-Crown Ether-Based Stationary Phase for Enantioseparation of Racemic Primary Organic Ammonium Salts

Abstract

Three novel enantiomerically pure chiral pyridino-18-crown-6 ligands [(S,S)-7, (S,S)-8 and (R,R)-9] containing a linker with a terminal carboxyl function were prepared. One of them [(R,R)-9] containing two tert-butyl groups at the stereogenic centers was covalently attached to silica gel by an amide bond using 3-aminopropyltrimethoxysilane. The resulting chiral stationary phase [(R,R)-11] separated the enantiomers of racemic R-(1-naphthyl)ethylammonium perchlorate and 1-phenylethylammonium perchlorate by high-performance liquid chromatography.

Synthesis of new enantiopure dimethyl- and diisobutyl -substituted pyridino-18-crown-6 ethers containing a halogen atom or a methoxy group at position 4 of the pyridine ring for enantiomeric recognition studies

“…Optical rotations were taken on a Perkin-Elmer 241 polarimeter that was calibrated by measuring the optical rotations of both enantiomers of menthol. NMR spectra were recorded in CDCl3 either on a Bruker DRX-500 Avance spectrometer (at 500 MHz for 1 H and at 125 MHz for 13 C spectra) or on a Bruker 300 Avance spectrometer (at 300 MHz for 1 H and at 75 MHz for 13 C spectra) and it is indicated in each individual case. Mass spectra were recorded on a ZQ 2000 MS instrument (Waters Corp.) using ESI method.…”

“…[4][5][6][7][8][9] Selected enantiopure pyridino-18-crown-6 ethers have been immobilized by covalent bonds on solid supports such as silica gel and Merrifield polymer resin and the chiral stationary phases (CSPs) so obtained have been used successfully for chromatographic enantioseparation of racemic protonated primary amines, amino acids and their derivates. [10][11][12][13][14] In continuation of our studies in this area of research, our attention turned to the preparation of new enantiopure dimethyl-and diisobutyl-substituted pyridino-18-crown-6 ether type macrocycles containing a halogen atom or a methoxy group at position 4 of the pyridine ring [(S,S)-1, (S,S)-2, (S,S)-3, (S,S)-4, (S,S)-5, see Figure 1]. These macrocycles can be transformed to derivatives which are able to function as effective sensor and selector molecule.…”

Application of Flow Chemistry to Macrocyclization of Crown Ethers

“…The best method for this process in analytical and semipreparative scales is the chiral liquid chromatography (CLC), using chiral stationary phases (CSPs) [1]. Among chiral selectors, enantiopure pyridino-18-crown-6 ether derivatives have been used successfully for enantioseparation of racemic protonated amines, amino acids, and their derivatives [2][3][4][5][6][7][8].…”

Synthesis of new enantiopure dimethyl-substituted pyridino-18-crown-6 ethers containing a hydroxymethyl, a formyl, or a carboxyl group at position 4 of the pyridine ring for enantiomeric recognition studies

“…[5][6][7][8][9][10] Among other optically active synthetic macrocycles, enantiopure pyridino-18-crown-6 ethers have received great attention in the last few decades due to their ability to discriminate between the enantiomers of protonated primary organic amines, amino acids and their derivatives. 6,[11][12][13][14][15][16][17][18][19] Selected enantiopure pyridino-18-crown-6 ethers have been immobilized by covalent bonds on solid supports such as silica gel [20][21][22][23][24][25] or Merrifield-type polymer resin. 26 In all these cases the linking units have been attached to the pyridine ring exclusively through an oxygen atom.…”