CN107141235B - 一种蓝光激发下合成苄基叠氮的方法及其药物 - Google Patents
一种蓝光激发下合成苄基叠氮的方法及其药物 Download PDFInfo
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Abstract
本发明属于医药学技术领域,公开了一种蓝光激发下合成苄基叠氮的方法及其药物,蓝光激发下合成苄基叠氮的方法采用3W~10W的蓝光灯照射,在钌吡啶配合物的催化下,甲苯和叠氮乙酰氧基碘苯反应合成苄基叠氮;同时公开一种抗癫痫药物卢非酰胺。本发明的原料简单易得;反应条件温和,且反应收率高,达到95%以上;反应用3W~10W的蓝光灯照射即可促进反应发生,不需要加热。
Description
技术领域
本发明属于医药学技术领域,尤其涉及一种蓝光激发下合成苄基叠氮的方法及其药物。
背景技术
含氮有机化合物在自然界中普遍存在,天然的和合成的含氮有机化合物在许多商业领域有重要和广泛的应用,该类化合物在医药化学领域中的作用特别令人感兴趣。苄基叠氮是一种重要的医药、农药中间体,在医药、农药领域中有着广泛的应用前景,许多由苄基叠氮合成的化合物具有显著的杀菌、消炎及抗肿瘤等生理活性,开展苄基叠氮的合成方法的研究具有非常重要的意义。传统的苄基叠氮合成方法是:苄基卤化物和叠氮化钠的亲核取代反应。然而,基于可见光促进的反应合成苄基叠氮却鲜有文献报道,最近,2016年Greaney报到了30W的白光照射下,铜催化甲苯合成苄基叠氮的方法。
综上所述,现有技术存在的问题是:第一,大多数合成方法使用无机叠氮化钠和苄基卤化物反应,反应需要用到有爆炸性、剧毒的无机叠氮盐;第二,在铜催化甲苯合成苄基叠氮的方法中,反应需要用有毒的乙腈做反应溶剂。
现有技术中,原料的获得比较困难;反应中需要加热,浪费能源,且反应收率低,没有结合的蓝光灯照射促进反应。
发明内容
针对现有技术存在的问题,本发明提供了一种蓝光激发下合成苄基叠氮的方法及其药物。
本发明是这样实现的,一种蓝光激发下合成苄基叠氮的方法,所述蓝光激发下合成苄基叠氮的方法采用3W~10W的蓝光灯照射,在钌吡啶配合物的催化下,甲苯和叠氮乙酰氧基碘苯反应合成苄基叠氮。
进一步,所述蓝光激发下合成苄基叠氮的方法包括:
在100mL的三口瓶中加入5mL甲苯,2mol的叠氮乙酰氧基碘苯,50mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2,用3W~10W的蓝光灯照射,室温下反应10小时,减压蒸去溶剂,残余物柱层析纯化得苄基叠氮;
进一步,得苄基叠氮的化学反应式为:
进一步,所述蓝光激发下合成苄基叠氮的方法还包括:
在100mL的三口瓶中加入5mL对甲基甲苯,2mol的叠氮乙酰氧基碘苯,60mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2,用3W-10W的蓝光灯照射,室温下反应8小时,减压蒸去溶剂,残余物柱层析纯化得对甲基苄基叠氮。
进一步,得对甲基苄基叠氮的方法化学反应式为:
本发明的另一目的在于提供一种抗癫痫药物卢非酰胺(rufinamide)。
所述抗癫痫药物卢非酰胺的制备化学反应式为:
本发明的优点及积极效果为:
用3W-10W的蓝光灯照射,在Ru(bpy)3Cl2的催化下,苄基叠氮的收率可以达到98%;反应不需要用到有毒的无机叠氮盐及有毒的溶剂;和现有合成苄基叠氮技术对比,本发明合成1000克苄基叠氮可节约成本2万元(RMB)。
附图说明
图1是本发明实施例提供的蓝光激发下合成苄基叠氮的方法流程图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
现有技术中,原料的获得比较困难;反应中需要加热,浪费能源,且反应收率低,没有结合的蓝光灯照射促进反应。
下面结合附图对本发明的应用原理作详细描述。
本发明实施例提供的蓝光激发下合成苄基叠氮的方法,包括:
采用10W的蓝光灯照射,在钌吡啶配合物的催化下,甲苯和叠氮乙酰氧基碘苯反应合成苄基叠氮。
如图1所示,蓝光激发下合成苄基叠氮的方法包括:
S101:在100mL的三口瓶中加入5mL甲苯,2mol的叠氮乙酰氧基碘苯,50mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2。
S102:用3W~10W的蓝光灯照射,室温下反应10小时,减压蒸去溶剂,残余物柱层析纯化得苄基叠氮。
下面结合具体实施例对本发明的应用原理作进一步描述。
实例一:
在100mL的三口瓶中加入5mL甲苯,2mol的叠氮乙酰氧基碘苯2,50mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2,用10W的蓝光灯照射,室温下反应10小时,减压蒸去溶剂,残余物柱层析纯化得苄基叠氮3,收率95.5%。
1H NMR(CDCl3,400MHz),(ppm):7.50-7.46(m,2H),7.41-7.39(m,3H),4.39(s,2H).13C NMR(CDCl3,100MHz),(ppm):54.6,128.1,128.4,129.0,135.6。
方程式为:
实例二:
在100mL的三口瓶中加入5mL对甲基甲苯,2mol的叠氮乙酰氧基碘苯2,60mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2,用10W的蓝光灯照射,室温下反应8小时,减压蒸去溶剂,残余物柱层析纯化得对甲基苄基叠氮5,收率98%。
1H NMR(CDCl3,400MHz),(ppm):7.44(d,J=6.4Hz,2H),7.13(d,J=6.4Hz,2H),4.31(s,2H),2.33(s,3H).13C NMR(CDCl3,100MHz),(ppm):21.6,55.3,125.9,128.4,128.6,138.1。
方程式为:
本发明实施例提供一种抗癫痫药物卢非酰胺(rufinamide)。
所述抗癫痫药物卢非酰胺化学反应式为:
本发明提供的蓝光激发下,钌吡啶配合物催化甲苯合成苄基叠氮的方法具有如下优点:第一:原料简单易得;第二:反应条件温和,且反应收率高,达到95%以上;第三:反应用10W的蓝光灯照射即可促进反应发生,不需要加热。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (6)
1.一种蓝光激发下合成苄基叠氮的方法,其特征在于,所述蓝光激发下合成苄基叠氮的方法采用3W~10W的蓝光灯照射,在钌吡啶配合物Ru(bpy)3Cl2的催化下,甲苯和叠氮乙酰氧基碘苯反应合成苄基叠氮。
2.如权利要求1所述的蓝光激发下合成苄基叠氮的方法,其特征在于,所述蓝光激发下合成苄基叠氮的方法包括:
在100mL的三口瓶中加入5mL甲苯,2mol的叠氮乙酰氧基碘苯,50mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2,用3W~10W的蓝光灯照射,室温下反应10小时,减压蒸去溶剂,残余物柱层析纯化得苄基叠氮。
3.如权利要求2所述的蓝光激发下合成苄基叠氮的方法,其特征在于,得苄基叠氮的化学反应式为:
4.一种得对甲基苄基叠氮的方法,其特征在于,得对甲基苄基叠氮的方法包括:
在100mL的三口瓶中加入5mL对甲基甲苯,2mol的叠氮乙酰氧基碘苯,60mL六氟异丙醇,0.02mol的Ru(bpy)3Cl2,用10W的蓝光灯照射,室温下反应8小时,减压蒸去溶剂,残余物柱层析纯化得对甲基苄基叠氮。
5.如权利要求4所述的得对甲基苄基叠氮的方法,其特征在于,得对甲基苄基叠氮的方法化学反应式为:
6.一种利用蓝光激发下合成苄基叠氮的方法在制备抗癫痫药物卢非酰胺的应用,其特征在于,抗癫痫药物卢非酰胺的制备化学反应式为:
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