The synthesis of some C2-symmetric chiral crown ethers and their applications

Chiral macrocycles have a wide range of applications in enantiomeric recognition, for use in the preparation of chiral stationary phases and in catalysis. As a result, the synthesis of chiral macromolecules has attracted considerable attention of chemists. In particular, C2- symmetric macrocycles have been extensively studied because of their structural architecture, which is suitable for complex formation both with metals and host molecules.In this study, three novel diza-18-crown-6 derivative macrocycles have been synthesized in order to investigate their molecular recognition properties towards ?-amino acid ester salts. Trans-(1R,2R)-1,2-diaminocyclohexane, (S)- propylene oxide and (R)-stiren oxide were used as chiral source. N,N?-Dibenzyl-trans-(1R,2R)-1,2-diamnocyclohexane 1 was prepared by using chiral diaminocyclohexane isolated by classical resolution method. Chiral amino alcohols 2, 3 were synthesized by regioselective ring opening reaction of cyclohexadiamine with (S)-propylene oxide and (R)-stiren oxide in high yields respectively. Diaza-18-crown-6 derivatives 4, 5 were synthesized under high dilution conditions by cylization reaction of chiral amino alcohols 2, 3 and triethylenglycol ditosylate in 31.6, 45.5 % yields respectively. Macrocyclic 6 compund was also obtained by chiral amino alcohols 3 and ditoylate bearing naphto unit as usual manner in a 32,65 % yield. Synthesized chiral amino alcohols precurcars and diaza-18-crown-6 derivative were characterized by their spectral data.Molecular recognition properties of synthesized macrocyclics 4-6 towards alanine, phenylalanine and valine methyl esters hiydrochlorides were investigated by 1H NMR titration method. Host 4 molecule exhibited more stable complexes towards L enantiomers of investigated guests. The highest enetioselectivity was obtained in the case of phenyl alanine guest by a KL/KD = 8.64. However, host molecule 5 exhibited more stable complexes towards D enantiomers of guests, in which high enantiselectivity were obtained towards both alanine and phenylalanine by a KL/KD = 0,24, 0,22 respectively. Additionally, it was also obtained that phenyl alanine enantiomers has the better enantioselectivity by using host 6 by a KD/KL= 6.75. As a result, the obtained high enantioselectivity of hosts toward phenyl alanine is attributed to the more effective ? - ? interaction between aromatic residue of hosts and guest leading favourable diastereomeric complexation.Key Words: 1,2-diaminocyclohexane, chiral crown ethers, molecular recognition, enantioselective complexation, 1H NMR titration.