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CN104193667B - 一种发散型导向的氮杂环的合成方法 - Google Patents

一种发散型导向的氮杂环的合成方法 Download PDF

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CN104193667B
CN104193667B CN201410378274.4A CN201410378274A CN104193667B CN 104193667 B CN104193667 B CN 104193667B CN 201410378274 A CN201410378274 A CN 201410378274A CN 104193667 B CN104193667 B CN 104193667B
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CN104193667A (zh
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徐华栋
徐科
贾志宏
周皓
沈美华
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Shandong Xuedi Aluminum Technology Co ltd
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Changzhou University
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered

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Abstract

本发明一种发散型导向的氮杂环的合成方法，属于化学制药和精细化工制备技术领域。实现了多取代N‑烯丙基‑3‑吲哚醛和3‑氮杂二环[3,1,0]己醛的一步合成，使用了金属催化的磺酰三氮唑分解成金属卡宾，随后金属卡宾环化高效的得到两种结构截然不同的氮杂环，即N‑烯丙基‑3‑吲哚醛和3‑氮杂二环[3,1,0]己醛。本发明为高效制备官能化N‑烯丙基‑3‑吲哚醛和3‑氮杂二环[3,1,0]己醛衍生物提供了一条新的技术路线，在化学制药和精细化工领域有广阔的应用。

Description

一种发散型导向的氮杂环的合成方法
技术领域
本发明属于化学制药和精细化工制备技术领域，即发散合成导向的N-烯丙基-3-吲哚醛和3-氮杂二环[3,1,0]己醛，尤其涉金属催化的卡宾环化反应，高效的生成两种多取代的氮杂环，并且可以有效的控制产物的相对比例。本发明为高效制备官能化的氮杂环衍生物提供了一条新的技术路线和设计策略，在化学制药和精细化工领域有广阔的应用。
背景技术
氮杂环是一大类重要的有机化合物，很多氮杂环具有特别的化学与生物活性，存在于许多天然产物和药物分子中，也被应用于功能材料中。而含醛基的氮杂环类化合物更是高附加值的有机分子，因为醛基可以非常方便的进一步衍生化得到很多其它结构的氮杂环。N-烯丙基-3-吲哚醛和3-氮杂二环[3,1,0]己醛因其结构中含有多种官能团和药效团是两类非常有价值的氮杂环化合物，目前这两类化合物的制备方法有限，文献报道的方法基本可以概括为以下几个方程式：
(1)从吲哚1出发，经过Vilsmeier甲酰化得到3-吲哚醛2(式1)。
(2)从烯炔3出发，金催化剂催化氧化得到4(式2)。
(3)从烯炔5出发，金属催化剂催化氧化得到6(式3)。
这些方法都有一定的局限性，比如底物复杂不易制备，以及底物范围窄等缺点。考虑到以上缺点，本发明将要阐述一种便捷通用的同时制备两种结构截然不同的氮杂环的新方法。
发明内容
本发明的目的是阐述一种发散型氮杂环制备方法，具体来说就是发明了一种高效一步制备两种氮杂环N-烯丙基-3-吲哚醛和3-氮杂二环[3,1,0]己醛。
为实现上述合成目的，本发明采用如下技术方案，概括为所示的反应方程式：(式4)。在适当溶剂中，各种1-磺酰基三氮唑7在适当金属催化剂催化下环化，经过适当水解处理后得到N-烯丙基-3-吲哚醛8和3-氮杂二环[3,1,0]己醛9。
分子结构通式7、8、9中的R1为各种取代的芳基(具体为苯基、对甲基苯基、对硝基苯基等)、各种取代的烷基等(具体为甲基、三甲基硅基乙基等)；R2为各种取代的芳基(具体为苯基、对甲基苯基等)、各种取代的烷基(具体为甲基、乙基、苄基等)、各种脂基(具体为甲酯、乙酯等)、各种卤素(具体为氯、溴氟)等；R3为各种取代的芳基(具体为苯基)、各种取代的烷基(具体为甲基)、各种取代的烷氧基(具体为对甲氧基、3、5-二甲氧基苯基)、各种取代的芳基氧基(具体为苯氧基)、硝基(具体为对硝基、间硝基)、脂基(具体为甲酯、乙酯)、腈基(具体为甲腈)、卤素(具体为氯、溴、碘、氟等)等。
一种发散导向的氮杂环的合成，按照下述步骤进行：
按一定比例1-磺酰基三氮唑7、金属催化剂混合在一种有机溶剂中搅拌，根据底物和试剂特性，温度控制在一定温度之间，一定时间后，停止反应，加入适量甲醇，碳酸钾和少量水，搅拌过夜。用有机溶剂乙酸乙酯或二氯甲烷萃取三遍，有机相合并后用饱和食盐水洗，再用无水硫酸钠干燥，减压蒸除溶剂，残留物用乙酸乙酯和石油醚为洗脱剂，硅胶柱色谱分离纯化，得到相应氮杂环醛8和9。或者反应完成后减压蒸除有机溶剂，残渣直接硅胶色谱柱分离。
其中所述1-磺酰基三氮唑7的结构式为其中R1为各种取代的芳基(具体为苯基、对甲基苯基、对硝基苯基等)、各种取代的烷基等(具体为甲基、三甲基硅基乙基等)；R2为各种取代的芳基(具体为苯基、对甲基苯基等)、各种取代的烷基(具体为甲基、乙基、苄基等)、各种脂基(具体为甲酯、乙酯等)、各种卤素(具体为氯、溴氟)等；R3为各种取代的芳基(具体为苯基)、各种取代的烷基(具体为甲基)、各种取代的烷氧基(具体为对甲氧基、3、5-二甲氧基苯基)、各种取代的芳基氧基(具体为苯氧基)、硝基(具体为对硝基、间硝基)、脂基(具体为甲酯、乙酯)、腈基(具体为甲腈)、卤素(具体为氯、溴、碘、氟等)等。
其中所述溶剂为四氢呋喃、甲苯、二氯甲烷、三氯甲烷、1,2-二氯甲烷等非极性溶剂。
其中所述的1-磺酰基三氮唑7、催化剂摩尔比为1.0：0.005到1.0：0.05之间。
其中所述的催化剂为醋酸铑、辛酸铑、间苯二酸铑等铑化合物和三氟甲磺酸，三氟醋酸铜等铜化合物和三氟甲磺酸银等银盐。
其中所述反应温度在50-120度之间。
其中所述反应时间为10分钟到5小时之间。
本发明的优点
1、该反应操作简便，只需一步反应就可以高效的制备两种氮杂环。
2、该反应的产品结构新颖，用其他方法不易制备。
3、该方法可以实现产物比例调控。
4、该反应的产品是高附加值的化合物。
具体实施方式
下面通过实例对本发明给予做进一步说明：
下述非限制性实施例1-3#或对比实施例1-2#用来解释说明本发明，而不是对本发明进行限制，在本发明的精神和权力要求的保护范围内，对本发明作出的任何修改和改变，都属于本发明的保护范围。
本发明所使用的原料、试剂及催化剂是通过参考相关文献制备，溶剂经过纯化和精制。
实施例1
将2毫摩尔1-对甲苯磺基三氮唑7a、0.01毫摩尔醋酸铑混合在10毫升甲苯中搅拌，温度控制120度，2小时后，停止加热，加入2毫升甲醇，5毫摩尔碳酸钾和一滴水，室温搅拌12小时。用有机溶剂乙酸乙酯萃取三遍，有机相合并后用饱和食盐水洗，再用无水硫酸钠干燥，减压蒸除溶剂，残留物用乙酸乙酯和石油醚为洗脱剂，硅胶柱色谱分离纯化，得到相应氮杂环醛8a和9a(见表1)。或者反应完成后减压蒸除有机溶剂，残渣直接硅胶色谱柱分离。
实施例2
将2毫摩尔1-对甲苯磺基三氮唑7b、0.1毫摩尔醋酸铑混合在10毫升二氯乙烷中搅拌，温度控制50度，5小时后，停止加热，加入2毫升甲醇，5毫摩尔碳酸钾和一滴水，室温搅拌8小时。用有机溶剂乙酸乙酯萃取三遍，有机相合并后用饱和食盐水洗，再用无水硫酸钠干燥，减压蒸除溶剂，残留物用乙酸乙酯和石油醚为洗脱剂，硅胶柱色谱分离纯化，得到相应氮杂环醛8b和9b(见表1)。或者反应完成后减压蒸除有机溶剂，残渣直接硅胶色谱柱分离。
实施例3
将2毫摩尔1-对甲苯磺基三氮唑7c、0.04毫摩尔醋酸铑混合在10毫升甲苯中搅拌，温度控制120度，10分钟后，停止加热，加入2毫升甲醇，5毫摩尔碳酸钾和一滴水，室温搅拌12小时。用有机溶剂乙酸乙酯萃取三遍，有机相合并后用饱和食盐水洗，再用无水硫酸钠干燥，减压蒸除溶剂，残留物用乙酸乙酯和石油醚为洗脱剂，硅胶柱色谱分离纯化，得到相应氮杂环醛8c和9c(见表1)。或者反应完成后减压蒸除有机溶剂，残渣直接硅胶色谱柱分离。
表1.发散型N-烯丙基-3-吲哚醛和3-氮杂二环[3,1,0]己醛的制备
8a:79％；The spectral data matched that reported by Black and co-workers2.1H NMR(400MHz,CDCl3)δ10.36(s,1H),7.73(s,1H),6.41(d,J＝1.8Hz,1H),6.39(d,J＝1.8Hz,1H),5.98(ddd,J＝22.5,10.6,5.5Hz,1H),5.29(dd,J＝10.3,0.8Hz,1H),5.14(dd,J＝17.1,0.7Hz,1H),4.68(d,J＝5.4Hz,2H),3.95(s,3H),3.85(s,3H).
8b:17％；1H NMR(400MHz,CDCl3)δ10.44(s,1H),7.85(s,1H),7.22(t,J＝8.1Hz,1H),7.00(d,J＝8.2Hz,1H),6.73(d,J＝7.9Hz,1H),5.99(ddd,J＝22.6,10.6,5.5Hz,1H),5.29(dd,J＝10.2,0.8Hz,1H),5.16(dd,J＝17.1,0.7Hz,1H),4.74(d,J＝5.5Hz,2H),4.00(s,3H)；13C NMR(125MHz,CDCl3)δ188.0,154.7,138.2,131.8,131.2,123.9,119.0,118.5,117.0,103.9,102.59,55.49,49.98；HRMS(ESI)m/z理论值C13H14NO2 +[M+H]+216.1019,实测值216.1015.
8b’:48％；1H NMR(400MHz,CDCl3)δ9.89(s,1H),8.16(d,J＝8.7Hz,1H),7.60(s,1H),6.94(dd,J＝8.7,2.2Hz,1H),6.77(d,J＝2.2Hz,1H),5.99(ddt,J＝17.0,10.6,5.5Hz,1H),5.30(dd,J＝10.3,0.9Hz,1H),5.16(dd,J＝17.1,0.8Hz,1H),4.70(dt,J＝5.4,1.5Hz,2H),3.84(s,3H)；13C NMR(100MHz,CDCl3)δ184.5,157.7,138.3,138.1,131.7,122.8,119.3,119.0,118.4,112.1,94.2,55.7,49.5；HRMS(ESI)m/z理论值C13H14NO2 +[M+H]+216.1019,实测值216.1016.
8c:53％；The spectral data matched that reported by Wilson and co-workers3.1H NMR(400MHz,CDCl3)δ9.92(s,1H),7.79(s,1H),7.65(s,1H),7.23(m,2H),6.94(d,J＝8.9Hz,1H),6.06–5.87(m,1H),5.30(d,J＝10.2Hz,1H),5.17(d,J＝17.1Hz,1H),4.72(d,J＝5.4Hz,2H),3.87(s,3H).
8d:41％；1H NMR(400MHz,CDCl3)δ9.96(s,1H),8.12(s,1H),7.67(s,1H),7.29–7.20(m,1H),7.15(d,J＝8.4Hz,1H),6.00(ddd,J＝22.4,10.6,5.5Hz,1H),5.30(d,J＝10.3Hz,1H),5.17(d,J＝17.1Hz,1H),4.74(d,J＝5.5Hz,2H),2.48(s,3H)；13C NMR(100MHz,CDCl3)δ184.6,138.5,135.7,132.8,131.8,125.7,125.6,121.9,119.0,118.0,110.0,49.6,21.5；HRMS(ESI)m/z理论值C13H14NO+[M+H]+200.1070,实测值200.1064.
8e:33％；The spectral data matched that reported by Chen and co-workers4.1H NMR(400MHz,CDCl3)δ9.99(s,1H),8.36–8.25(m,1H),7.74(s,1H),7.43–7.27(m,3H),6.02(ddd,J＝22.3,10.6,5.5Hz,1H),5.33(d,J＝10.2Hz,1H),5.20(d,J＝17.1Hz,1H),4.79(d,J＝5.4Hz,2H).
8f:29％；1H NMR(400MHz,CDCl3)δ9.92(s,1H),8.27(s,1H),7.71(s,1H),7.25(m,2H),6.07–5.91(m,1H),5.33(d,J＝10.2Hz,1H),5.17(d,J＝17.1Hz,1H),4.75(d,J＝4.9Hz,2H)；13C NMR(101MHz,CDCl3)δ184.4,139.1,135.6,131.4,129.0,126.3,124.4,121.7,119.4,117.8,111.4,49.8；HRMS(ESI)m/z理论值C12H11ClNO+[M+H]+220.0524,实测值220.0520.
8g:13％；1H NMR(400MHz,CDCl3)δ10.07(s,1H),9.21(d,J＝2.0Hz,1H),8.23(dd,J＝9.0,2.0Hz,1H),7.90(s,1H),7.43(d,J＝9.1Hz,1H),6.05(ddd,J＝22.2,10.5,5.4Hz,1H),5.40(d,J＝10.2Hz,1H),5.22(d,J＝17.0Hz,1H),4.86(d,J＝5.3Hz,2H)；13C NMR(125MHz,CDCl3)δ184.2,144.2,140.4,140.0,131.0,125.0,120.0,119.7,119.1,110.6,100.1,50.1；HRMS(ESI)m/z理论值C12H11N2O3 +[M+H]+231.0764,实测值231.0766.
8i:12％；1H NMR(400MHz,CDCl3)δ7.77(d,J＝8.2Hz,2H),7.39(d,J＝7.9Hz,1H),7.29-7.27(m,3H),7.20(t,J＝7.2Hz,1H),7.06(t,J＝7.4Hz,1H),6.90(s,1H),4.69(t,J＝5.4Hz,1H),4.28(d,J＝5.4Hz,2H),4.12-4.06(m,4H),2.44(s,3H),2.23(t,J＝7.1Hz,2H),2.07(p,J＝7.0Hz,2H),1.23(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ172.7,143.4,136.9,136.4,129.7,127.3,127.0,126.8,126.4,122.2,119.6,118.9,109.7,109.6,60.7,45.2,38.9,31.1,25.4,21.6,14.2.
9a:9％；1H NMR(400MHz,CDCl3)δ9.06(s,1H),5.93(s,1H),5.77(d,J＝1.6Hz,2H),3.80-3.74(m,7H),3.61(d,J＝9.3Hz,1H),3.58(d,J＝9.4Hz,1H),3.35(dd,J＝9.3,4.4Hz,1H),2.36-2.31(m,1H),1.66(dd,J＝8.5,5.1Hz,1H),1.33(t,J＝5.3Hz,1H)；13CNMR(125MHz,CDCl3)δ198.0,161.7,149.8,91.7,89.6,55.3,49.4,47.9,40.6,26.8,18.7；HRMS(ESI)m/z理论值C14H18NO3 +[M+H]+248.1281,实测值248.1270.
9b:23％；1H NMR(400MHz,CDCl3)δ9.07(s,1H),7.14(t,J＝8.2Hz,1H),6.32(dd,J＝8.1,2.1Hz,1H),6.22(dd,J＝8.2,2.0Hz,1H),6.15(t,J＝2.3Hz,1H),3.79(s,3H),3.75(d,J＝9.5Hz,1H),3.64(d,J＝9.3Hz,1H),3.60(d,J＝9.5Hz,1H),3.34(dd,J＝9.3,4.4Hz,1H),2.34(dt,J＝8.8,5.0Hz,1H),1.66(dd,J＝8.5,5.1Hz,1H),1.35(t,J＝5.2Hz,1H)；13CNMR(100MHz,CDCl3)δ198.0,160.7,149.2,130.0,105.6,102.4,99.0,55.2,49.3,47.9,40.6,26.8,18.7；HRMS(ESI)m/z理论值C13H16NO2 +[M+H]+218.1176,实测值218.1167.
9c:31％；1H NMR(400MHz,CDCl3)δ9.06(s,1H),6.84(d,J＝8.8Hz,2H),6.59(d,J＝8.2Hz,2H),3.75(s,3H),3.62(dd,J＝19.5,9.2Hz,3H),3.25(dd,J＝9.0,4.1Hz,1H),2.38–2.26(m,1H),1.63(dd,J＝8.3,5.1Hz,1H),1.47(s,1H)；13C NMR(100MHz,CDCl3)δ198.1,152.1,142.4,115.0,113.8,55.9,50.0,48.5,40.8,26.9,18.2；HRMS(ESI)m/z理论值C13H16NO2 +[M+H]+218.1176,实测值218.1160.
9d:46％；1H NMR(400MHz,CDCl3)δ9.07(s,1H),7.06(d,J＝8.2Hz,2H),6.57(d,J＝8.3Hz,2H),3.74–3.56(m,3H),3.30(dd,J＝9.2,4.3Hz,1H),2.37–2.31(m,1H),2.26(s,3H),1.65(dd,J＝8.4,5.1Hz,1H),1.46(t,J＝5.0Hz,1H)；13C NMR(100MHz,CDCl3)δ198.0,145.6,129.9,112.9,49.8,48.3,40.7,26.9,20.4,18.4；HRMS(ESI)m/z理论值C13H16NO+[M+H]+202.1226,实测值202.1214.
9e:53％；1H NMR(300MHz,CDCl3)δ9.05(s,1H),7.30–7.13(m,2H),6.73(t,J＝7.3Hz,1H),6.62–6.52(m,2H),3.65(dt,J＝14.1,9.5Hz,3H),3.31(dd,J＝9.2,4.4Hz,1H),2.38–2.23(m,1H),1.64(dd,J＝8.5,5.1Hz,1H),1.34(t,J＝5.2Hz,1H)；13C NMR(100MHz,CDCl3)δ198.0,147.9,129.3,117.2,112.4,49.2,47.7,40.6,26.9,18.6；HRMS(ESI)m/z理论值C12H14NO+[M+H]+188.1070,实测值188.1061.
9f:54％；1H NMR(400MHz,CDCl3)δ9.04(s,1H),7.15(d,J＝8.5Hz,2H),6.49(d,J＝8.5Hz,2H),3.70(d,J＝9.4Hz,1H),3.57(dd,J＝20.3,9.3Hz,2H),3.30(dd,J＝9.2,4.3Hz,1H),2.40–2.28(m,1H),1.66(dd,J＝8.1,5.4Hz,1H),1.34(t,J＝5.2Hz,1H)；13C NMR(100MHz,CDCl3)δ197.7,146.4,129.0,122.0,113.6,49.4,48.0,40.6,26.7,18.6；HRMS(ESI)m/z理论值C12H13ClNO+[M+H]+222.0680,实测值222.0669.
9g:72％；1H NMR(400MHz,CDCl3)δ9.05(s,1H),8.08(d,J＝9.2Hz,2H),6.49(d,J＝9.2Hz,2H),3.98(d,J＝10.2Hz,1H),3.71(d,J＝10.0Hz,1H),3.66–3.55(m,2H),2.49–2.42(m,1H),1.79(dd,J＝8.3,5.6Hz,1H),1.27(t,J＝5.5Hz,1H)；13C NMR(100MHz,CDCl3)δ197.1,129.7,126.4,126.1,111.1,49.6,48.1,40.5,26.4,19.4；HRMS(ESI)m/z理论值C12H13N2O3 +[M+H]+233.0921,实测值233.0908.
9h:87％；1H NMR(400MHz,CDCl3)δ9.07(s,1H),7.50(dd,J＝8.0,1.9Hz,1H),7.33-7.29(m,2H),6.83(dd,J＝8.2,2.4Hz,1H),3.83(d,J＝9.5Hz,1H),3.68(d,J＝9.4Hz,1H),3.61(d,J＝9.5Hz,1H),3.45(dd,J＝9.3,4.5Hz,1H),2.46-2.42(m,1H),1.76(dd,J＝8.5,5.3Hz,1H),1.33(t,J＝5.4Hz,1H)；13C NMR(100MHz,CDCl3)δ197.3,149.0,148.3,129.7,118.0,111.4,106.3,49.4,47.9,40.4,26.4,18.8；HRMS(ESI)m/z理论值C12H13N2O3 +[M+H]+233.0921,实测值233.0917.
9i:65％；1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.0Hz,2H),7.29-7.25(m,3H),7.20(d,J＝8.0Hz,2H),6.94(d,J＝8.4Hz,2H),5.88(d,J＝6.1Hz,1H),4.53(s,1H),4.12(q,J＝7.1Hz,2H),3.30(dd,J＝12.8,6.2Hz,1H),3.12(td,J＝12.4,4.5Hz,1H),2.89(dd,J＝9.1,4.9Hz,1H),2.62(dt,J＝13.4,5.5Hz,1H),2.43(d,J＝8.5Hz,1H),2.38(s,3H),2.14(dd,J＝13.7,9.3Hz,1H),2.01(d,J＝9.4Hz,1H),1.47(d,J＝13.6Hz,1H),1.22(t,J＝7.0Hz,3H)；13C NMR(100MHz,CDCl3)δ172.5,148.1,143.4,138.1,129.4,129.4,127.8,120.5,116.9,75.1,61.4,59.1,46.7,40.9,31.7,28.4,21.6,14.2.

Claims (1)

1.一种发散型导向的氮杂环的合成，其特征在于按照下述步骤进行：
按一定比例1-磺酰基三氮唑、金属催化剂混合在一种有机溶剂中搅拌，根据底物和试剂特性，温度控制在一定温度之间，一定时间后，停止反应，加入适量甲醇，碳酸钾和少量水，搅拌过夜，用有机溶剂乙酸乙酯或二氯甲烷萃取三遍，有机相合并后用饱和食盐水洗，再用无水硫酸钠干燥，减压蒸除溶剂，残留物用乙酸乙酯和石油醚为洗脱剂，硅胶柱色谱分离纯化，得到N-烯丙基-3-吲哚醛8和3-氮杂二环[3,1,0]己醛9；或者反应完成后减压蒸除有机溶剂，残渣直接硅胶色谱柱分离；
其中所述溶剂为四氢呋喃、甲苯、二氯甲烷、三氯甲烷、1,2-二氯甲烷；
其中所述的1-磺酰基三氮唑、催化剂摩尔比为1.0：0.005到1.0：0.05之间；
其中所述的催化剂为醋酸铑、辛酸铑、间苯二酸铑、三氟甲磺酸，三氟醋酸铜、三氟甲磺酸银；
第一步反应温度在50-120度之间，第二步为室温；第一步反应时间为10分钟到5小时之间，第二步反应时间为8-12小时；
其中所述1-磺酰基三氮唑的结构式为 ，
其中所述的N-烯丙基-3-吲哚醛8 结构式为 ；
其中所述的3-氮杂二环[3,1,0]己醛9 结构式为 ；
其中R 为甲基、甲氧基、硝基、氯、H；R1为甲基；R2为H；R3 为甲基、甲氧基、硝基、氯、H。
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