Enantiomeric recognition and separation of chiral organic ammonium salts by chiral pyridino-18-crown-6 ligands

Synthesis and determination of pKa values of new enantiopure pyridino- and piperidino-18-crown-6 ethers

“…The macrocyclization reaction was carried out with pyridino-2,6-dicarbonyl dichlorides (14)(15)(16) [prepared in situ from the corresponding dicarboxylic acids (17 23,24 , 18 25,26 and 19 [25][26][27][28] )] and chiral diamines [(S,S)-9, (S,S)-10] and resulted in new amide type pyridino-crown ethers [(S,S)-1-(S,S)-6, see Scheme 2]. These reactions used the high dilution technique.…”

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

“…Dimethyl chelidamate 21 was prepared from chelidamic acid as reported. 6 Diester 21 was treated with thionyl chloride and a catalytic amount of DMF for 2 days at reflux temperature in CHCl3 to obtain dimethyl 4-chloro-pyridine-2,6-dicarboxylate 15 (see Scheme 4). This method gave 15 with a higher yield (91%) than applying the reported 22 one (69%), where Markees and Kidder used the more expensive and more dangerous PCl5 for this transformation.…”

“…2,3 In the past quarter of the century, optically active pyridino-18-crown-6 ether type macrocycles have received a great deal of attention due to their ability of enantiomeric discrimination toward protonated chiral primary amines, amino acids and their derivates. [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].…”

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].…”