CN104098577B - 一种唑并吲哚酮稠杂环的高效合成方法 - Google Patents
一种唑并吲哚酮稠杂环的高效合成方法 Download PDFInfo
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Abstract
本发明涉及了11氢-吲哚[1,2-a]苯并咪唑-11-酮、9氢-咪唑[1,2-a]吲哚-9-酮和11氢-吲哚[1,2-a]吲唑-11-酮的高效合成方法,本法采用铁盐为催化剂,取代2-氟代苯甲醛为原料与三类不同的唑杂环为原料,在空气条件下,发生SN2亲核取代/碳氢活化/酰化关环“一锅法”反应合成出相应产物,本发明所述的操作方法简便,原料易得,方法高效新颖,该方法将为含上述三类稠杂环的药物分子或生物活性物质提供新的合成途径。
Description
技术领域
本发明涉及三类稠杂环的合成方法,特别涉及11氢-吲哚[1,2-a]苯并咪唑-11-酮、9氢-咪唑[1,2-a]吲哚-9-酮和11氢-吲哚[1,2-a]吲唑-11-酮的合成方法。
背景技术
过渡金属催化形成碳-碳键的反应是有机合成中重要的反应。过渡金属中,如钯、钌、铑催化剂,能高效催化形成碳-碳键。但是由于他们的价格偏贵而且有毒性,限制了它们的工业应用。因此研究工作者逐渐将目光转向廉价金属催化剂,如铁和铜催化剂。铁盐能催化众多有机反应,如:亲核取代、加成、还原、氧化、加氢、重排、直接碳-氢转化等。铁催化碳-氢活化是近年来有机化学的热点课题。醛基可失去氢,生成酰基自由基,然后发生后续反应。也就是醛基也可以发生碳-氢活化反应。这方面的报道,如Kwong,F.Y.等报道了钯催化下醛和乙酰苯胺的反应,生成了邻酰基乙酰苯胺(Wu,Y.N.;Li,B.Z.;Mao,F.;Li,X.S.;Kwong,F.Y.Org.Lett.2011,13,3258)。Kim,I.S.等报道了铑催化下,苯甲酰胺和醛发生邻位酰化反应(Park,J.;Park,E.;Kim,A.;Lee,Y.;Chi,K.;Kwak,J.H.;Jung,Y.H.;Kim,I,S.Org.Lett.2011,13,4390)。再比如,李志平报道了铁催化下,炔和醛及过氧化物发生的羰基化-过氧化反应(Liu,W.P.;Li,Y.M.;Liu,K.;Li,Z.P.J.Am.Chem.Soc.2011,133,10756)。StuderA.等报道了二茂铁催化下,分别从邻甲酰基联苯和邻甲酰基联苯醚出发,合成了芴和氧杂蒽酮(Wertz,S.;Leifert,D.;Studer,A.Org.Lett.2013,15,928)。但是,据报道过的文献所知,醛基参与的碳氢活化,需要依赖于过氧化物或其他氧化剂作用,但是至今未见报道醛在无氧化剂下,就能直接参与碳氢活化反应。唑并吲哚酮稠杂环是吲哚酮和唑(咪唑、苯并咪唑、吲唑等)结合的稠杂环。1991年,Rosevear,J.等报道了邻氟苯甲醛和唑在碳酸钾/DMSO体系中反应时,除得到了取代产物外,意外发现了副产物唑并吲哚酮,但产率在20-33%(Rosevear,J;Wilshire,J.E.K.Aust.J.Chem,1991,44,1097)。各种底物的扩展也没有得到进一步研究。随着醛基参与的碳氢活化反应发展以及串联反应的发展,唑并吲哚酮的高效合成将得到解决。本专利将解决这方面内容。
发明内容
本发明要解决的问题是提供一种11氢-吲哚[1,2-a]苯并咪唑-11-酮、9氢-咪唑[1,2-a]吲哚-9-酮和11氢-吲哚[1,2-a]吲唑-11-酮的合成方法,该方法简便、高效、原料易得。
为达到发明的目的,本发明采用的技术方案如下:
一种制备11氢-吲哚[1,2-a]苯并咪唑-11-酮、9氢-咪唑[1,2-a]吲哚-9-酮和11氢-吲哚[1,2-a]吲唑-11-酮的高效合成方法,以取代2-氟代苯甲醛为原料与三类不同的唑杂环为原料分别通过铁盐催化,在碱性条件下,在有机溶剂中,一定温度下,“一锅法”反应合成出11氢-吲哚[1,2-a]苯并咪唑-11-酮或9氢-咪唑[1,2-a]吲哚-9-酮或11氢-吲哚[1,2-a]吲唑-11-酮的三类不同的稠杂环化合物,其结构式如下(1)-(3):
本发明所述的三类稠杂环化合物的结构,如式(1)-(3),其中R1=烷基或烷氧基或烷酰基或羧基及酯或卤素或硝基,R2=烷基或芳基或氢。
本发明所述的铁催化剂为二价铁催化剂和三价铁催化剂。
本发明所述的二价铁铁催化剂为FeCl2·4H2O、FeSO4·7H2O;所述的三价铁催化剂FeCl3·6H2O、Fe2(acac)3。
本发明所述的碱性条件,表示反应需要加入相应的碱促进反应的物质。
本发明所述的碱促进反应的物质是碳酸钾或碳酸铯或磷酸钾或乙醇钠或叔丁醇钾。
本发明所述的唑杂环包括苯并咪唑、咪唑和吲唑。
本发明所述的有机溶剂为极性溶剂或非极性溶剂,如:DMF、DMSO、NMP、PhMe等。
本发明所述的控制反应温度为100-140℃。
本发明所述的反应温度为100-140℃。
本发明所述的“一锅法”反应合成结构式为(1)-(3)的化合物。
本发明提供了一种简便、高效的“一锅法”反应方法合成11氢-吲哚[1,2-a]苯并咪唑-11-酮或9氢-咪唑[1,2-a]吲哚-9-酮或11氢-吲哚[1,2-a]吲唑-11-酮化合物,起始原料易得,反应条件温和,反应产率达25-94%。
具体实施方法
下面结合具体实施例对本发明进一步描述,但本发明的保护范围并不仅限于此。
实施例1
在Schlenk反应管中,加入邻氟苯甲醛(0.5mmol)、苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物1,其结构及表征数据如下:
11H-indolo[1,2-a]benzimidazol-11-one(1).anorangesolid(103.4mg,97%),mp:232-234℃;1HNMR(500MHz,CDCl3/TMS):δ7.91(d,J=8.5Hz,1H),7.71(dd,J1=1.0Hz,J2=7.5Hz,1H),7.63-7.60(m,2H),7.62-7.49(m,1H),7.38-7.33(m,2H),7.26-7.21(m,1H)ppm.13CNMR(125MHz,CDCl3/TMS):179.8,149.1,148.9,143.3,136.7,130.0,129.9,127.9,127.5,125.9,124.4,124.0,111.6,111.1ppm。
实施例2
在Schlenk反应管中,加入4-溴-2-氟苯甲醛(0.5mmol)、苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物2,其结构及表征数据如下:
3-bromo-11H-indolo[1,2-a]benzimidazol-11-one(2).anorangesolid(127.1mg,85%),mp:219-221℃;1HNMR(500MHz,CDCl3/TMS):δ7.92(d,J=8.5Hz,1H),7.60-7.51(m,4H),7.40-7.36(m,2H)ppm.13CNMR(125MHz,CDCl3/TMS):178.6,149.0,148.9,143.9,131.3,129.7,129.0,128.3,126.8,126.2,124.8,124.2,115.3,111.1ppm.HRMS(ESI)m/zcalcdforC14H7BrN2O[M+H]+230.1222,Found230.1218。
实施例3
在Schlenk反应管中,加入4-氯-2-氟苯甲醛(0.5mmol)、苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物3,其结构及表征数据如下:
3-chloro-11H-indolo[1,2-a]benzimidazol-11-one(3).anorangesolid(103.2mg,81%),mp:242-244℃;1HNMR(500MHz,CDCl3/TMS):δ7.92(d,J=9.0Hz,1H),7.65(d,J=13.0Hz,1H),7.59(d,J=8.5Hz,1H),7.54-7.51(m,1H),7.39-7.35(m,2H),7.21(dd,J1=2.0Hz,J2=8.0Hz,1H)ppm.13CNMR(125MHz,CDCl3/TMS):178.4,149.1,148.9,144.0,142.9,129.8,128.2,126.8,125.9,125.8,124.8,124.2,112.5,111.0ppm.HRMS(ESI)m/zcalcdforC14H7ClN2O[M+H]+255.6712,Found255.6710。
实施例4
在Schlenk反应管中,加入5-氯-2-氟苯甲醛(0.5mmol)、苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物4,其结构及表征数据如下:
2-chloro-11H-indolo[1,2-a]benzimidazol-11-one(4)anorangesolid(91.5mg,72%),mp:250-252℃;1HNMR(500MHz,CDCl3/TMS):δ7.92(d,J=8.0Hz,1H),7.67(d,J=2.5Hz,1H),7.59-7.56(m,2H),7.64-7.60(m,1H),7.38-7.35(m,1H),7.32(d,J=8.5Hz,1H)ppm.13CNMR(125MHz,CDCl3/TMS):178.5,148.9,148.8,141.5,136.0,131.8,129.9,128.7,128.3,126.2,124.7,124.2,112.6,111.0ppm.HRMS(ESI)m/zcalcdforC14H7ClN2O[M+H]+255.6712,Found255.6715。
实施例5
在Schlenk反应管中,加入5-甲氧基-2-氟苯甲醛(0.5mmol)、苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物5,其结构及表征数据如下:
2-methoxy-11H-indolo[1,2-a]benzimidazol-11-one(5)anorangesolid(75.0mg,60%),mp:202-204℃;1HNMR(500MHz,CDCl3/TMS):δ7.89(d,J=8.0Hz,1H),7.54(d,J=8.0Hz,1H),7.49-7.46(m,1H),7.33-7.30(m,1H),7.27-7.25(m,2H),7.10(dd,J1=2.5Hz,J2=8.0Hz,1H),3.86(s,3H)ppm.13CNMR(125MHz,CDCl3/TMS):179.9,158.0,149.3,148.7,137.0,130.0,128.5,127.8,124.1,124.0,121.7,112.4,111.2,110.8,56.0ppm.HRMS(ESI)m/zcalcdforC14H7N2O2[M+H]+251.2521,Found251.2526。
实施例6
在Schlenk反应管中,加入邻氟苯甲醛(0.5mmol)、5,6-二甲基-苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物6,其结构及表征数据如下:
7,8-dimethyl-11H-indolo[l,2-a]benzimidazol-11-one(6).anorangesolid(49.6mg,40%),mp:279-281℃;1HNMR(500MHz,CDCl3/TMS):δ7.62(d,J=7.5Hz,1H),7.66(s,1H),7.66-7.52(m,1H),7.26(d,J=8.0Hz,1H),7.22(s,1H),7.16-7.13(m,1H),2.83(s,3H),2.32(s,3H)ppm.13CNMR(125MHz,CDCl3/TMS):179.7,148.4,147.6,143.3,138.2,136.3,133.8,128.6,127.7,125.6,125.5,123.5,111.4,111.1,20.9,20.3ppm。
实施例7
在Schlenk反应管中,加入4-溴-2-氟苯甲醛(0.5mmol)、5,6-二甲基-苯并咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物7,其结构及表征数据如下:
3-bromo-7,8-dimethyl-11H-indolo[l,2-a]benzimidazol-11-one(7).anorangesolid(106.3mg,65%),mp:283-285℃;1HNMR(500MHz,CDCl3/TMS):δ7.61(d,J=7.5Hz,1H),7.55-7.51(m,2H),7.26-7.23(m,1H),7.15-7.12(m,1H),2.37(s,3H),2.31(s,3H)ppm.13CNMR(125MHz,CDCl3/TMS):179.7,148.4,147.6,143.2,138.2,136.3,133.8,128.5,127.6,125.6,125.5,123.5,111.4,111.1,20.9,20.3ppm.HRMS(ESI)m/zcalcdforC16H11BrN2O[M+H]+328.1753,Found328.1747。
实施例8
在Schlenk反应管中,加入邻氟苯甲醛(0.5mmol)、咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL)。反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物8,其结构及表征数据如下:
9H-imidazo[l,2-a]indol-9-one(8)anorangesolid(72.3mg,85%),mp:202-204℃;1HNMR(500MHz,CDCl3/TMS):δ7.65(dd,J1=1.0Hz,J2=12.5Hz,1H),7.55-7.51(m,1H),7.40(d,J=1.0Hz,1H),7.27-7.24(m,2H),7.16(d,J=3.0Hz,1H)ppm.13CNMR(125MHz,CDCl3/TMS):170.2,141.5,137.4,135.4,128.4,127.2,125.4,116.3,114.9,111.4ppm。
实施例9
在Schlenk反应管中,加入4-溴-2-氟苯甲醛(0.5mmol)、咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩。利用柱层析分离提纯,得到产物9,其结构及表征数据如下:
6-bromo-9H-imidazo[l,2-a]indol-9-one(9)anorangesolid(102.0mg,82%),mp:229-231℃;1HNMR(500MHz,CDCl3/TMS):δ7.50(d,J=3.0Hz,1H),7.43-7.41(m,2H),7.34(d,J=1.5Hz,1H),7.23(d,J=1.0Hz,1H)ppm.13CNMR(125MHz,CDCl3/TMS):176.4,146.1,142.1,137.8,130.2,129.9,127.1,126.4,115.3,115.0ppm.HRMS(ESI)m/zcalcdforC10H5BrN2O[M+H]+250.0635,Found250.0636。
实施例10
在Schlenk反应管中,加入4-氯-2-氟苯甲醛(0.5mmol)、咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物10,其结构及表征数据如下:
6-chloro-9H-imidazo[l,2-a]indol-9-one(10)anorangesolid(82.0mg,80%),mp:207-209℃;1HNMR(500MHz,CDCl3/TMS):δ7.60(d,J=2.0Hz,1H),7.50(dd,J1=2.0Hz,J2=8.0Hz,1H),7.41(d,J=1.0Hz,1H),7.26-7.24(m,1H),7.11(d,J=8.0Hz,1H)ppm.13CNMR(125MHz,CDCl3/TMS):176.1,146.0,139.6,137.8,134.7,133.1,129.6,125.8,115.2,112.5ppm.HRMS(ESI)m/zcalcdforC10H5ClN2O[M+H]+205.6125,Found205.6126。
实施例11
在Schlenk反应管中,加入5-氯-2-氟苯甲醛(0.5mmol)、咪唑(0.5mmol)、
FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物11,其结构及表征数据如下:
7-chloro-9H-imidazo[l,2-a]indol-9-one(11)anorangesolid(73.5mg,72%),mp:186-188℃;1HNMR(500MHz,CDCl3/TMS):δ7.57(d,J=7.5Hz,1H),7.42(s,1H),7.62-7.23(m,2H),7.18(s,1H)ppm.13CNMR(125MHz,CDCl3/TMS):176.3,146.3,142.3,141.7,137.7,127.2,126.7,126.3,114.9,112.6ppm.HRMS(ESI)m/zcalcdforC10H5ClN2O[M+H]+205.6125,Found205.6120。
实施例12
在Schlenk反应管中,加入5-甲氧基-2-氟苯甲醛(0.5mmol)、咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL)。反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物12,其结构及表征数据如下:
7-methoxy-9H-imidazo[l,2-a]indol-9-one(12)anorangesolid(59.0mg,59%),mp:175-177℃;1HNMR(500MHz,CDCl3/TMS):δ7.35(d,J=0.5Hz,1H),7.26(s,1H),7.18(d,J=2.5Hz,1H),7.05(d,J=8.0Hz,1H),6.97(dd,J1=3.0Hz,J2=10.0Hz,1H),3.83(s,3H)ppm.13CNMR(125MHz,CDCl3/TMS):177.5,159.0,146.2,137.0,134.7,129.6,119.6,115.0,112.3,111.3,55.9ppm.HRMS(ESI)m/zcalcdforC11H8N2O2[M+H]+201.0586,Found205.0588。
实施例13
在Schlenk反应管中,加入邻氟苯甲醛(0.5mmol)、3-甲基咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物13,其结构及表征数据如下:
2-methyl-9H-imidazo[l,2-a]indol-9-one(13)anorangesolid(39.6mg,43%),mp:158-160℃;1HNMR(500MHz,CDCl3/TMS):δ7.58(d,J=7.5Hz,1H),7.48-7.46(m,1H),7.26-7.18(m,1H),7.07-7.04(m,1H),6.97(d,J=0.5Hz,1H),2.33(s,3H)ppm.13CNMR(125MHz,CDCl3/TMS):177.5,147.5,145.1,141.7,135.1,128.1,126.8,125.1,112.1,111.0,14.30ppm.HRMS(ESI)m/zcalcdforC11H8N2O[M+H]+185.1940,Found185.1943。
实施例14
在Schlenk反应管中,加入4-氯-2-氟苯甲醛(0.5mmol)、3-甲基咪唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物14,其结构及表征数据如下:
6-chloro-2-methyl-9H-imidazo[l,2-a]indol-9-one(14)anorangesolid(76.5mg,70%),mp:190-192℃;1HNMR(500MHz,CDCl3/TMS):δ7.54-7.50(m,1H),7.26-7.18(m,1H),7.07(d,J=2.0Hz,1H),6.96(s,1H),2.34(s,3H)ppm.13CNMR(125MHz,CDCl3/TMS):176.2,148.0,145.3,142.5,141.3,126.7,126.4,126.0,112.1,112.1,14.32ppm.HRMS(ESI)m/zcalcdforC11H7ClN2O[M+H]+219.6391,Found219.6386。
实施例15
在Schlenk反应管中,加入邻氟苯甲醛(0.5mmol)、吲唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时。反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物15,其结构及表征数据如下:
11H-indolo[1,2-b]indazol-11-one(15)anorangesolid(58.3mg,53%),mp:193-195℃;1HNMR(500MHz,CDCl3/TMS):δ7.87-7.85(m,1H),7.81-7.79(m,1H),7.67-7.62(m,2H),7.57-7.54(m,1H),7.34-7.26(m,3H)ppm.13CNMR(125MHz,CDCl3/TMS):178.1,154.5,143.5,134.6,129.9,128.4,127.8,127.5,124.6,120.1,119.9,119.6,112.1,99.9ppm。
实施例16
在Schlenk反应管中,加入5-氯-2-氟苯甲醛(0.5mmol)、吲唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物16,其结构及表征数据如下:
2-chloro-11H-indolo[1,2-b]indazol-11-one(16)anorangesolid(63.7mg,50%),mp:179-181℃;1HNMR(500MHz,CDCl3/TMS):δ7.86-7.80(m,2H),7.63(s,1H),7.55(dd,J1=8.0Hz,J2=16.0Hz,2H),7.36(dd,J1=2.8Hz,J2=6.4Hz,2H)ppm.13CNMR(125MHz,CDCl3/TMS):178.4,154.6,141.6,134.4,134.0,132.4,131.3,130.8,128.8,128.2,127.7,125.0,120.0,113.1ppm.HRMS(ESI)m/zcalcdforC14H7ClN2O[M+H]+255.6712,Found255.6710。
实施例17
在Schlenk反应管中,加入5-甲氧基-2-氟苯甲醛(0.5mmol)、吲唑(0.5mmol)、FeCl3·6H2O(8mg,0.05mmol)、磷酸钾(212mg,0.1mmol)和DMF(2mL),反应管密封,在空气氛围下,110℃,反应15小时,反应结束后,二氯甲烷萃取三次,有机层再用饱和食盐水洗涤三次,有机层经无水硫酸钠干燥,减压浓缩,利用柱层析分离提纯,得到产物17,其结构及表征数据如下:
2-methoxy-11H-indolo[1,2-b]indazol-11-one(17)anorangesolid(31.3mg,25%),mp:165-167℃;1HNMR(500MHz,CDCl3/TMS):δ7.87-7.82(m,1H),7.55(d,J=8.4Hz,1H),7.36-7.33(m,2H),7.28(s,2H),7.04-7.01(m,1H)ppm.13CNMR(125MHz,CDCl3/TMS):189.7,156.1,140.8,137.1,132.6,130.3,128.4,128.2,125.7,125.0,122.4,121.6,120.6,117.7,45.2ppm.HRMS(ESI)m/zcalcdforC15H10N2O2[M+H]+251.2521,Found251.2525。
Claims (1)
1.一种11氢-吲哚[1,2-a]苯并咪唑-11-酮、9氢-咪唑[1,2-a]吲哚-9-酮和11氢-吲哚[1,2-a]吲唑-11-酮的高效合成方法;所述三类化合物的结构式如式(1)-(3);它们的合成方法通过FeCl3.6H2O催化,磷酸钾条件下,以取代2-氟代苯甲醛和唑杂环为原料,在DMF中,100-140℃,“一锅法”反应合成相应化合物 ,
其中R1=烷基、烷氧基、卤素、硝基,R2=烷基、氢。
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