硅胶催化下高效合成Naftopidil及其光学异构体

目的以硅胶作为催化剂,高效合成Naftopidil(Naf)及其光学异构体。方法在室温氮气保护和无溶剂条件下,使用60～100目硅胶催化萘氧基缩水甘油醚与邻甲氧基苯基哌嗪进行反应,得到Naf及其光学异构体。通过筛选催化剂的用量及循环使用次数优化反应。结果用20%的硅胶催化得到Naf,最佳收率为87%;硅胶循环5次,催化活性未见明显降低;对光学异构体的Naf的最佳收率为77%,ee值最高达98.2%。结论所用方法反应条件温和、收率高、产物与催化剂容易分离、催化剂可循环使用、活性未见明显降低,基本符合绿色化学反应的要求,具有良好的工业应用前景。

An efficient synthesis of Naftopidil and its enantiomers under the catalysis of silica gel

OBJECTIVE To optimize an efficient method to synthesize Naftopidil and its chiral enantiomers using silica gel as a catalyst.METHODS 1-naphthyl glycidyl ether and 1-(2-methoxyphenyl)-piperizine were stirring with silica gel(60-100 mesh) at room temperature under nitrogen in solvent-free condition.The reaction conditions were optimized and the chiral enantiomers of Naftopidil were synthesized using these optimum conditions.RESULTS The best result was obtained by using 20% mass percentage of silica gel as the catalyst,with yield up to 87%.Recycling and reusing silica gel for 5 times,we detected no considerable loss of its catalytic ability,with yields all above 70%.When it came to synthesis of chiral Naftopidil enantiomers,the best yield was 77%,the enantiomeric excess of which was as high as 98.2%.CONCLUSION The methods were mild with high yields.Reactants and catalyst were easily separated.Catalyst could be reused for 5 times without apparent degradation.This route suited the basic requirements of green chemistry which had a promising future for industrialization.