Design,Synthesis And Evaluation Of Amine R-BINOL Chiral Stationary Phase

In this paper,three series and six amines(R)-1,1’-Binaphthol((R)-BINOL)chiral stationary phases(CSPs)were designed and prepared using(R)-BI-NOL as raw material.The CSPs were packed into the corresponding high performance liquid chromatography columns.The chiral resolution performance of(R)-CSP-SA-1 chiral column in normal phase mobile phase was evaluated.Objective:To explore the method of designing,synthesizing and preparing amines(R)-BINOL CSPs efficiently with(R)-BINOL as raw material.2.To evaluate the chiral resolution performance of chiral solutes in high performance liquid chromatography.Methods:1.Study on synthesis and preparation of CSPs of amines(R)-BINOL:①The CSPs of amines R-BINOL were synthesized from(R)-BINOL by protection of chloromethyl ether,electrophilic substitution,oxidation,hydrolysis and condensation.②In order to bond small amine molecules with silica gel efficiently,two methods of carboxylation and toluene reflux were investigated.Carboxylation method:with(R)-BINOL as raw material,monocarboxyl or bicarboxyl groups were introduced into(R)-BINOL at 3 or 3,3’positions to obtain(R)-BINOL carboxylic acid,and then carboxylic acid was carboxylated with aminopropyl silica gel to obtain carboxylation CSPs.Toluene reflux method:amine functional small molecules were obtained by carboxylation of(R)-BINOL carboxylic acid with aminopropylsilane.These functional small molecules were bonded to the surface of acidified silica gel under toluene reflux condition to obtain CSPs by toluene reflux method.③The related compounds and CSPs were characterized by NMR,elemental analysis,infrared spectroscopy and scanning electron microscopy;④Amine chiral stationary phases were packed into corresponding high performance liquid chromatography columns by high pressure homogenization.2.Evaluation of(R)-CSP-SA-1:using n-hexane as mobile phase,adding different kinds of alcohol modifiers and trifluoroacetic acid,four conjugated chiral solutes 1,1’-BINOL(solute(1)),N-(3,5-dinitrobenzoyl)-1-phenylethylamine(solute(2)),2’-hydroxyflavanone(solute(3)),3-hydroxymethyl-2,2’-bis(methoxymethoxy)-1,1’-binaphthalene(solute(4))were selected to evaluate the chiral resolution performance of(R)-CSP-SA-1.Results:1.Study on Synthesis and preparation of CSPs of amines(R)-BINOL:six amines(R)-BINOL CSPs were synthesized and prepared:(R)-CSP-SA-1,(R)-CSP-SA-2,(R)-CSP-SA-3,(R)-CSP-SI-1,(R)-CSP-SI-2 and CSP-DA-1.These CSPs were characterized by NMR,elemental analysis,infrared spectroscopy and scanning electron microscopy.2.Evaluation of(R)-CSP-SA-1:in the normal phase,the chiral resolution of(R)-CSP-SA-1 column was evaluated by using four chiral solutes.The types of alcohol modifiers,the amount of alcohol modifiers and the concentration of TFA all affected the retention and separation of solutes:Solute(1)obtained the best separation when n-hexane-n-butanol-trifluoroacetic acid(99:1:0.4,v/v/v)was used as mobile phase,the separation factor was 1.135,and the separation degree was 2.200;Solute(2)obtained the best separation when n-hexane-n-propanol(95:5,v/v)was used as mobile phase,the separation factor was 1.157,the separation degree was 2.730;Solute(3)was n-hexane-n-n-butanol-trifluoroacetic acid(99:1:0.1,v/v).The best separation was obtained when the mobile phase was n-hexane-n-butanol(95:5,v/v),the separation factor was 1.075 and the separation degree was 0.680.The best separation was obtained when the solute(4)was n-hexane-n-butanol(95:5,v/v),the separation factor was 1.041 and the separation degree was 0.810.Conclusion:In the preparation of CSPs of amines(R)-BINOL,toluene reflux method was superior to carboxylic method.In the normal mobile phase.The(R)-CSP-SA-1 HPLC column showed enantiomeric separation ability for four chiral solutes,indicating that this type of CSP has good potential in chiral separation.