Studies On Synthesis Of New Axially Chiral Compounds And Their Applications In Chiral Recognition

Abstract:The enantiomers of chiral drugs tend to have different biological activities, therefore, analyze the absolute configuration and enantiomeric purity of chiral drugs has great significance.Chirality recognition is an easy and fast method to measure the purity of enantiomer of the chirality guest compound.1,1’-binaphthalene-2,2’-diamine (BINAM) is a typical case of the axial chirality compounds. BINAM and its derivatives posses a C2-symmetry characteristic, the use of BINAM and its derivatives as chiral soluting agent to recognize the purity of chirality carboxylic acid compounds was merely reported by far, So in this work, three new optical activity BINAM derivatives were synthesized, and their recognition abilities as chiral soluting agent hosts towards carboxylic acid compounds guests were studied, the methods and results are described below:Firstly,2-Acetonaphthone Oxime was synthesized by2-acetonap hthone and hydroxylamine hydrochloride in sodium acetate solvent, then2-acetyl aminonaphthalene was synthesized by the rearrangement of2-Acetonaphthone Oxime, and2-aminonaphthalene was got by the hydrolization of2-acetyl aminonaphthalene in EtOH/HCl(Conc.), then BINAM was got by oxidation and coupling reaction of2-aminonaph thalene. Finally, optical activity of BINAM was got by racemates resulotion with the help of d-(+)-Camphora-10-sulfonic acid.Then, the reaction of optical BINAM with5-trifluoromethy1-2-(di methylamino)benzaldehyde,5-bromine-2-(dimethylamino) benzaldehyde and4-benzoyl-[2,2]paracyclophane got the schiff base intermediates, then the reduction of the intermediates got the target molecules:2-trifluorome thyl-5-(Dimethylamino)subunit-[1,1’-binaphthalene]-2,2’-diamine80,2-bromo-5-(Dimethylamino)subunit-1,1’-binaphthalene-2,2’-diamine81and [2,2]paracyclophane phenyl-1,1’-binaphthalene-2,2’-diamine82。Finally, the target compounds80,81and82were used as chiral soluting agent to recognize the racemate chirality carboxylic acid compounds83and84. The recognition abilities of the three host compounds were distinguished by the different△△δ1HNMR value when they were used as probes to induce guest compounds.The experiment results show that the new axial chiral compound81has good recognition ability toward ibuprofen and chiral racemate carboxylic acid compounds. The△△δ value of a methyl proton of ibuprofen is8Hz, and both of the△△δvalues of the carboxylic acid a methyl proton and4-methyl proton of the phenyl group are16Hz on the enantiomer2-(4-methylphenylsulfonyl amido)propanoic acids that induced by the new axial chiral compound81.