Synthesis Of Bridging Chiral Calix[4]arenes With A Morpholinocarbonyl Bridge-substituent And Determination Of Acetaldehyde By Gas Chromatography

Objective:（1）At present,a series of bridging chiral calix[4]arenes with formamidyl bridge-substituent have been synthesized through ortho-Fries rearrangement.In order to enrich the categories of bridged chiral calix[4]arenes and lay a foundation for their property study,our first research is to prepare bridging chiral calix[4]arene with a morpholinocarbonyl bridge-substituent through ortho-Fries rearrangement,and to optically resolved it with（1S）-（+）-camphor-10-sulfonyl chloride as chiral auxiliary.（2）Acetaldehyde is a small volatile compound,which is thought to be the carcinogen of class 2B.Developing an efficient method to detect residue of acetaldehyde is one of the key issues still awaiting be solved in the process of quality control of drug intermediates.Acetaldehyde can’t be detected by HPLC for the low absorption in ultraviolet region.The limitation of chemical derivatization method is its complicated procedure and toxic reagent.The reaction between acetaldehyde and sample leads to low recovery by headspace gas chromatography.Thus,the second research content of this paper is to determine acetaldehyde by liquid injection in the gas chromatography.Methods:（1）First,p-tert-butycalix[4]arene was dipropylated with bromopropane and monoesterificated with 4-morpholinecarbonyl chloride.Then,bridging chiral calix[4]arene with a morpholinocarbonyl bridge-substituent was synthesized through ortho-Fries rearrangement and finally optically resolved with chiral auxiliary.（2）GC direct injection was performed on Aglilent DB-624（75 m×530μm×3μm）with FID detector.The column temperature was controlled on 50℃,maintained for5.5 min with the flow rate of N₂ of 6 mL·min^-1.The postrun temperature was controlled on 240℃,maintained for 10.5 min with the flow rate of N₂ of 8 mL·min^-1.Results:（1）Bridging chiral calix[4]arene with a morpholinocarbonyl bridge-substituent was successfully prepared after the etherification,esterification and ortho-Fries rearrangement of p-tert-butycalix[4]arene.The optically pure bridging chiral calix[4]arenes W-3-a and W-3-b were prepared through conjugation of bridging chiral calix[4]arene racemates with chiral auxiliary（1S）-（+）-camphor-10-sulfonyl chloride,separation of the resulted diastereoisomers W-3-Ca and W-3-Cb on conventional column chromatography,and subsequent removal of chiral auxiliary.（2）The calibrated linear curve of acetaldehyde was in the rang of 1.36μm·mL^-1188.96μm·m L^-1 with R²=0.9999.The average recovery of acetaldehyde was between 99.74%and 102.87%with RSD（n=9）=1.19%,0.55μm·mL^-1 was limit of detection of this method.Conclusions:（1）A pair of bridging chiral calix[4]arenes with a morpholinocarbonyl bridge-substituent had been synthesized through ortho-Fries rearrangement of the p-tert-butylcalix[4]arene o-carbamate and optical resolution of their racemate,which lays a foundation for their property study.（2）The determination of acetaldehyde was conveniently solved by GC indirect injection which showed the characteristics of good specificity,nice reproduction,high sensitivity.