CN113717107B - N-酰基苯并咪唑类化合物的合成方法 - Google Patents

N-酰基苯并咪唑类化合物的合成方法 Download PDF

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CN113717107B
CN113717107B CN202111047506.4A CN202111047506A CN113717107B CN 113717107 B CN113717107 B CN 113717107B CN 202111047506 A CN202111047506 A CN 202111047506A CN 113717107 B CN113717107 B CN 113717107B
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范学森
宋霞
蔡炘原
张新迎
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Abstract

本发明公开了一种N‑酰基苯并咪唑类化合物的合成方法，属于有机合成领域。将N‑芳基脒类化合物1、铑或钴催化剂、银盐添加剂和/或醋酸盐添加剂、二噁唑酮类化合物2和有机溶剂混合，空气氛围下升温反应，得到N‑酰基苯并咪唑类化合物3。本发明与现有技术相比具有以下优点：1)通过N‑芳基脒类化合物和二噁唑酮的一锅串联反应，即可在构建咪唑环的同时引入N‑酰基，直接合成出N‑酰基苯并咪唑类化合物，合成过程简单、高效；2)原料价廉易得，无需氧化剂，操作简便，底物的适用范围广。

Description

N-酰基苯并咪唑类化合物的合成方法
技术领域
本发明属于有机合成技术领域，具体涉及N-酰基苯并咪唑类化合物的合成方法。
背景技术
N-酰基苯并咪唑是一种温和的酰化试剂，在外消旋体的动力学拆分中具有重要且广泛用途。另外，N-酰基苯并咪唑类化合物为CB2大麻素的有效受体，有望用于治疗痴呆、多发性硬化症和阿尔茨海默症等神经炎症性疾病，在合成化学及药物化学等领域具有重要的应用价值。
然而，该类化合物的合成方法仍很有限，而且这些文献方法主要是在预先制备好的苯并咪唑结构单元上进行N-酰基结构修饰，尚存在原料不易得到、反应条件苛刻、官能团耐受性差等问题。
因此，研究并开发从价廉易得的原料出发、在相对温和的反应条件下合成N-酰基苯并咪唑类化合物的新方法，具有重要的研究意义。
发明内容
本发明主要提供了一种N-酰基苯并咪唑类化合物新的合成方法，通过N-芳基脒类化合物和二噁唑酮之间的一锅串联反应，高效合成N-酰基苯并咪唑类化合物。该合成方法具有原料简单易得、操作简便、底物适用范围广等优点。
本发明所合成的N-酰基苯并咪唑类化合物，其结构通式为：
Figure BDA0003251337850000011
其中，R1为氢、C1-6烷基、C1-4烷氧基、苯基、取代苯基、硝基或卤素，R2为苯基、取代苯基、噻吩基、呋喃基、萘基、C1-8烷基、苯基取代C1-3烷基或取代苯基取代C1-3烷基，以上所述取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、甲叉二氧基、三氟甲基、苯基或卤素。
本发明还提供了上述N-酰基苯并咪唑类化合物的合成方法，采用的技术方案为：
N-酰基苯并咪唑类化合物的合成方法，包括如下操作：将N-芳基脒类化合物1、铑或钴催化剂、添加剂、二噁唑酮类化合物2和有机溶剂混合，升温反应得到N-酰基苯并咪唑类化合物3。
反应方程式为：
Figure BDA0003251337850000021
其中，R1为氢、C1-6烷基、C1-4烷氧基、苯基、取代苯基、硝基或卤素，R2为苯基、取代苯基、噻吩基、呋喃基、萘基、C1-8烷基、苯基取代C1-3烷基或取代苯基取代C1-3烷基，以上所述取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、甲叉二氧基、三氟甲基、苯基或卤素。
进一步地，在上述技术方案中，所述有机溶剂为起到溶解原料的作用，优选1,2-二氯乙烷、乙酸乙酯、1,4-二氧六环、四氢呋喃或甲苯。
进一步地，在上述技术方案中，所述铑催化剂为二氯(五甲基环戊二烯基)合铑(III) 二聚体([RhCp*Cl2]2)，钴催化剂为五甲基环戊二烯基羰基二碘化钴(CoCp*(CO)I2)。
进一步地，在上述技术方案中，所述添加剂采用银盐添加剂与醋酸盐添加剂中的一种或两种。该两种添加剂可单独用于反应，也可组合在一起用于反应。优选反应条件下，采用银盐添加剂和醋酸盐添加剂组成的混合添加剂。
进一步地，在上述技术方案中，所述银盐添加剂为六氟锑酸银、三氟甲烷磺酸银、双三氟甲烷磺酰亚胺银或三氟乙酸银。
进一步地，在上述技术方案中，所述醋酸盐添加剂为醋酸钠、醋酸铜、醋酸铯或醋酸锌。
进一步地，在上述技术方案中，所述N-芳基脒类化合物1、二噁唑酮2、铑或钴催化剂、银盐添加剂与醋酸盐添加剂摩尔比为1-1.2:1-1.2:0.02-0.05:0.05-0.2:0.1-0.5。
进一步地，在上述技术方案中，所述反应温度为80-120℃。
进一步地，在上述技术方案中，所述反应在空气氛围下进行。
发明有益效果：
本发明与现有技术相比具有以下优点：1)通过N-芳基脒类化合物和二噁唑酮的一锅串联反应，即可在构建咪唑环的同时引入N-酰基，直接合成出N-酰基苯并咪唑类化合物，合成过程简单、高效；2)原料价廉易得，无需氧化剂，操作简便，底物的适用范围广。
附图说明
图1为实施例3中化合物3o的X-射线单晶衍射图。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
Figure BDA0003251337850000031
向15mL反应管中，依次加入化合物1a、有机溶剂、催化剂、添加剂及化合物2a，在空气条件下将反应管密封，将其置于加热模块中升温搅拌反应。待反应结束后，冷却至室温，加水淬灭反应，乙酸乙酯萃取，有机相干燥后，抽滤，旋干，硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物3a。
通过改变反应的溶剂、催化剂、银盐添加剂、醋酸盐添加剂、反应温度以及物料比等反应条件，结果见表1。
表1不同条件下3a的合成a
Figure BDA0003251337850000032
Figure BDA0003251337850000041
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实施例2
Figure BDA0003251337850000042
向15mL耐压管中，依次加入1a(63.5mg,0.36mmol)、[RhCp*Cl2]2(4.6mg,0.0075mmol)、AgSbF6(10.3mg,0.03mmol)、Zn(OAc)2(16.5mg,0.09mmol)、乙酸乙酯(1.5 mL)和2a(48.9mg,0.3mmol)，将反应管密封并置于110℃反应模块中搅拌反应10h。反应结束后，将反应体系冷却至室温，加水淬灭反应，乙酸乙酯萃取，有机相干燥后，抽滤，旋干，硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物3a(69.3mg,83％)。1H NMR(400MHz,DMSO-d6):1HNMR(CDCl3,400MHz):δ7.82(dd,J1＝8.4Hz,J2＝ 1.2Hz,2H),7.77(d,J＝8.0Hz,1H),7.73-7.69(m,1H),7.52(t,J＝7.6Hz,2H),7.24-7.20 (m,1H),7.05-7.01(m,1H),6.56(d,J＝8.4Hz,1H),1.57(s,9H).13C{1H}NMR(CDCl3, 100MHz):δ170.8,163.3,141.4,135.4,134.9,133.0,130.9,129.3,123.3,123.1,119.7, 112.2,35.4,29.8.HRMS(ESI)m/z:[M+H]+Calcdfor C18H19N2O 279.1492；Found 279. 1509.
实施例3
依照实施例2方法和步骤a,b，通过改变反应物1和反应物2，合成出多种N-酰基苯并咪唑类化合物3a-3mm，具体结果如下：
Figure BDA0003251337850000051
a反应条件:1(0.36mmol),2(0.3mmol),[RhCp*Cl2]2(0.0075mmol),AgSbF6(0.03mmol), Zn(OAc)2(0.09mmol)，乙酸乙酯(1.5mL),110℃,10h,空气氛围；b分离收率。
代表性产物表征数据如下：
(2-(tert-Butyl)-6-methyl-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3b)
1H NMR(CDCl3,600MHz):δ7.82(dd,J1＝8.4Hz,J2＝1.2Hz,2H),7.72-7.69(m,1H),7.63(d,J＝7.8Hz,1H),7.53-7.51(m,2H),7.04(dd,J1＝8.4Hz,J2＝1.2Hz,1H),6.35(s,1H),2.24(s,3H),1.55(s,9H).13C{1H}NMR(CDCl3,100MHz):δ170.9,162.6,139.5, 135.7,134.9,133.3,133.0,130.9,129.3,124.5,119.2,112.1,35.4,29.8,21.7.HRMS(ESI) m/z:[M+H]+Calcd for C19H21N2O 293.1648；Found 293.1649.
(2-(tert-Butyl)-6-methoxy-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3c)
1H NMR(CDCl3,600MHz):δ7.82(dd,J1＝8.4Hz,J2＝1.2Hz,2H),7.72-7.69(m,1H),7.64(d,J＝9.0Hz,1H),7.54-7.51(m,2H),6.84(dd,J1＝9.0Hz,J2＝2.4Hz,1H),6,03(d,J＝2.4Hz,1H),3.56(s,3H),1.55(s,9H).13C{1H}NMR(CDCl3,150MHz):δ170.8,162.3,156.5,136.0,134.9,132.9,130.9,129.3,120.0,111.3,97.0,55.6,35.4,29.8.HRMS(ESI)m/z:[M+H]+Calcd for C19H21N2O2 309.1598；Found 309.1599.
(2-(tert-Butyl)-6-isopropyl-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3d)
1H NMR(CDCl3,600MHz):δ7.83(d,J1＝8.4Hz,J2＝1.2,2H),7.71-7.68(m,1H),7.67(d, J＝8.4Hz,1H),7.52(t,J＝8.4Hz,2H),7.10(dd,J1＝8.4Hz,J2＝1.2,1H),6.35(d,J＝1.2 Hz,1H),2.79-2.75(m,1H),1.56(s,9H),1.05(d,J＝6.6Hz,6H).13C{1H}NMR(CDCl3,150MHz):δ170.9,162.9,144.5,139.8,135.6,134.8,133.2,130.9,129.2,122.1,119.3,109.8,35.4,34.2,29.8,24.2.HRMS(ESI)m/z:[M+H]+Calcd for C21H25N2O 321.1961；Found 321.1967.
(2-(tert-Butyl)-6-fluoro-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3e)
1H NMR(CDCl3,600MHz):δ7.81(dd,J1＝8.4Hz,J2＝1.2Hz,2H),7.75-7.72(m,1H),7.69-7.67(m,1H),7.56-7.53(m,2H),6.98-6.95(m,1H),6.25(dd,J1＝9.0Hz,J2＝2.4Hz,1H),1.56(s,9H).13C{1H}NMR(CDCl3,100MHz):δ170.3,163.8(d,4JC-F＝3.6Hz),159.5 (d,1JC-F＝239.8Hz),137.8,135.4(d,3JC-F＝13.0Hz),135.2,132.4,130.9,129.5,120.4(d,3JC-F＝9.4 Hz),111.3(d,2JC-F＝24.5 Hz),99.3(d,2JC-F＝28.1 Hz),35.5,29.7.19F NMR(CDCl3,565 MHz):δ-117.60--117.64(m).HRMS(ESI)m/z:[M+H]+Calcd for C18H18FN2O297.1398；Found 297.1401.
(2-(tert-Butyl)-6-chloro-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3f)
1H NMR(CDCl3,600 MHz):δ7.82-7.80(m,2H),7.75-7.72(m,1H),7.67(d,J＝8.4Hz, 1H),7.56-7.53(m,2H),7.20(dd,J1＝9.0 Hz,J2＝2.4 Hz,1H),6,57(d,J＝1.8 Hz,1H),1.55 (s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.2,164.0,140.1,135.9,135.4,132.3,130.9, 129.5,128.9,123.8,120.5,112.1,35.5,29.7.HRMS(ESI)m/z:[M+H]+Calcdfor C18H18ClN2O 313.1102；Found 313.1104.
(6-Bromo-2-(tert-butyl)-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3g)
1H NMR(CDCl3,400 MHz):δ7.82-7.80(m,2H),7.74(t,J＝7.6 Hz,1H),7.62(d,J＝8.4 Hz,1H),7.55(t,J＝8.0 Hz,2H),7.34(dd,J1＝8.8 Hz,J2＝2.0 Hz,1H),6.73(d,J＝1.6 Hz, 1H),1.55(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.2,163.8,140.5,136.4,135.4, 132.3,131.0,129.5,126.5,121.0,116.4,114.9,35.5,29.7.HRMS(ESI)m/z:[M+H]+Calcd for C18H18BrN2O 357.0597；Found 357.0585.
(2-(tert-Butyl)-6-iodo-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3h)
1H NMR(CDCl3,600 MHz):δ7.80(dd,J1＝8.4 Hz,J2＝1.2 Hz,2H),7.76-7.73(m,1H), 7.57-7.52(m,4H),6.92(s,1H),1.54(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.2,163.6,141.0,136.8,135.4,132.3,132.2,131.0,129.5,121.4,120.8,86.7,35.4,29.7.HRMS (ESI)m/z:[M+H]+Calcd for C18H18IN2O 405.0458；Found 405.0454.
(2-(tert-Butyl)-6-nitro-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3i)
1H NMR(CDCl3,600 MHz):δ8.18(dd,J1＝9.0 Hz,J2＝2.4 Hz,1H),7.84-7.82(m,3H), 7.79(t,J＝7.8 Hz,1H),7.60-7.56(m,3H),1.57(s,9H).13C{1H}NMR(CDCl3,150MHz):δ 169.6,168.1,145.9,143.8,136.0,134.8,131.8,131.1,129.8,119.8,119.0,108.4,35.9,29.6. HRMS(ESI)m/z:[M+H]+Calcd for C18H18N3O3 324.1343；Found324.1334.
(2-(tert-Butyl)-6-phenyl-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3j)
1H NMR(CDCl3,600 MHz):δ7.87-7.85(m,2H),7.81(d,J＝8.4 Hz,1H),7.72(t,J＝7.8 Hz,1H),7.53(t,J＝8.4 Hz,2H),7.46(dd,J1＝8.4 Hz,J2＝1.8 Hz,1H),7.34-7.30(m,4H), 7.27-7.24(m,1H),6.74(d,J＝1.2 Hz,1H),1.58(s,9H).13C{1H}NMR(CDCl3,150MHz): δ170.7,163.7,141.4,140.9,137.0,136.0,135.1,132.9,131.0,129.4,128.7,127.3,127.0, 123.0,119.8,110.7,35.5,29.8.HRMS(ESI)m/z:[M+H]+Calcd forC24H23N2O:355.1805； Found 355.1797.
(2-(tert-Butyl)-5-methyl-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3k)
1H NMR(CDCl3,400 MHz):δ7.82-7.80(m,2H),7.69(t,J＝7.6 Hz,1H),7.55(s,1H), 7.55-7.49(m,2H),6,84(dd,J1＝8.4 Hz,J2＝0.8 Hz,1H),6.41(d,J＝8.4 Hz,1H),2.40(s, 3H),1.57(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.7,163.3,141.7,134.8,133.5, 133.1,132.8,130.9,129.2,124.5,119.6,111.8,35.4,29.7,21.4.HRMS(ESI)m/z:[M+H]+ Calcd for C19H21N2O 293.1648；Found 293.1635.
(2-(tert-Butyl)-5-chloro-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3l)
1H NMR(CDCl3,600 MHz):δ7.80(dd,J1＝8.4 Hz,J2＝1.2 Hz,2H),7.74-7.73(m,1H), 7.72-7.71(m,1H),7.54-7.52(m,2H),6.99(dd,J1＝9.0 Hz,J2＝2.4 Hz,1H),6.47(d,J＝8.4 Hz,1H),1.56(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.2,164.6,142.4,135.2,134.0, 132.6,130.9,129.4,128.7,123.6,119.6,112.8,35.5,29.6.HRMS(ESI)m/z:[M+H]+Calcd for C18H18ClN2O 313.1102；Found 313.1101.
(2-(tert-Butyl)-4-methyl-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3m)
1H NMR(CDCl3,400 MHz):δ7.86(d,J＝7.6 Hz,2H),7.73(t,J＝7.6 Hz,1H),7.55(t,J＝ 8.0 Hz,2H),7.06(d,J＝7.6 Hz,1H),6.95(t,J＝8.0 Hz,1H),6.41(d,J＝8.4 Hz,1H),2.72 (s,3H),1.62(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ171.0,162.2,140.8,135.2,134.7, 133.2,130.9,129.9,129.2,123.4,123.0,109.6,35.5,29.8,16.7.HRMS(ESI)m/z:[M+H]+ Calcd for C19H21N2O 293.1648；Found 293.1648.
(2-(tert-Butyl)-4-chloro-1H-benzo[d]imidazol-1-yl)(phenyl)methanone(3n)
1H NMR(CDCl3,600 MHz):δ7.80-7.78(m,2H),7.73-7.70(m,1H),7.53-7.51(m,2H), 7.23(dd,J1＝7.8 Hz,J2＝0.6 Hz,1H),6.95(t,J＝8.4 Hz,1H),6.49(dd,J1＝8.4Hz,J2＝1.2 Hz,1H),1.57(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.3,163.7,138.9,136.4, 135.2,132.5,131.0,129.4,124.7,123.7,123.0,110.6,35.6,29.7.HRMS(ESI)m/z:[M+H]+ Calcd for C18H18ClN2O 313.1102；Found 313.1106.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(p-tolyl)methanone(3o)
1H NMR(CDCl3,600 MHz):δ7.76(d,J＝7.8 Hz,1H),7.72(d,J＝7.8 Hz,2H),7.31(d,J＝ 7.8 Hz,2H),7.22(t,J＝7.8 Hz,1H),7.05-7.02(m,1H),6.62(d,J＝8.4 Hz,1H),2.47(s, 3H),1.56(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ170.6.163.1,146.4,141.4,135.5, 131.1,130.2,130.0,123.2,123.0,119.7,112.1,35.4,29.8,21.9.HRMS(ESI)m/z:[M+H]+ Calcd for C19H21N2O 293.1648；Found 293.1643.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(4-methoxyphenyl)methanone(3p)
1H NMR(CDCl3,600 MHz):δ7.80-7.78(m,2H),7.77(d,J＝8.4 Hz,1H),7.23-7.20(m, 1H),7.07-7.04(m,1H),6.98-6.95(m,2H),6.69(d,J＝7.8 Hz,1H),3.90(s,3H),1.55(s, 9H).13C{1H}NMR(CDCl3,150 MHz):δ169.9,165.2,163.0,141.3,135.7,133.6,125.0,123.1,122.9,119.6,114.6,111.9,55.7,35.3,29.8.HRMS(ESI)m/z:[M+H]+Calcd forC19H21N2O2 309.1598；Found 309.1590.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(4-(tert-butyl)phenyl)methanone(3q)
1H NMR(CDCl3,600 MHz):δ7.78-7.74(m,3H),7.52-7.50(m,2H),7.23-7.21(m,1H), 7.06-7.03(m,1H),6.64(d,J＝7.8 Hz,1H),1,56(s,9H),1.37(s,9H).13C{1H}NMR(CDCl3, 100 MHz):δ170.6,163.1,159.3,141.4,135.6,131.0,130.0,126.3,123.2,122.9,119.6, 112.1,35.5,35.4,31.0,29.8.HRMS(ESI)m/z:[M+H]+Calcd for C22H27N2O335.2118； Found 335.2118.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(4-fluorophenyl)methanone(3r)
1H NMR(CDCl3,400 MHz):δ7.88-7.84(m,2H),7.77(d,J＝8.0 Hz,1H),7.25-7.17(m, 3H),7.08-7.03(m,1H),6.59(d,J＝8.0 Hz,1H),1,56(s,9H).13C{1H}NMR(CDCl3,100MHz):δ169.5,166.8(d,1JC-F＝257.1 Hz),163.1,141.5,135.3,133.8(d,3JC-F＝9.3 Hz),129.2(d,4JC-F＝2.8 Hz),123.4,123.2,119.9,116.7(d,2JC-F＝22.4 Hz),111.9,35.4,29.7.19F NMR(CDCl3,565 MHz):δ-101.0--101.1(m).HRMS(ESI)m/z:[M+H]+Calcd forC18H18FN2O 297.1398；Found 297.1398.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(4-chlorophenyl)methanone(3s)
1H NMR(CDCl3,600 MHz):δ7.77-7.75(m,3H),7.51-7.48(m,2H),7.25-7.22(m,1H), 7.07-7.04(m,1H),6.58(d,J＝7.8 Hz,1H),1.56(s,9H).13C{1H}NMR(CDCl3,150MHz): δ169.7,163.2,141.7,141.4,135.2,132.3,131.2,129.8,123.5,123.3,119.9,112.0,35.4, 29.7.HRMS(ESI)m/z:[M+H]+Calcd for C18H18ClN2O 313.1102；Found313.1091.
(4-Bromophenyl)(2-(tert-butyl)-1H-benzo[d]imidazol-1-yl)methanone(3t)
1H NMR(CDCl3,400 MHz):δ7.77(d,J＝8.0 Hz,1H),7.70-7.65(m,4H),7.26-7.22(m, 1H),7.08-7.04(m,1H),6.58(d,J＝8.0 Hz,1H),1.56(s,9H).13C{1H}NMR(CDCl3,150MHz):δ169.9,163.2,141.4,135.2,132.8,132.3,131.7,130.5,123.5,123.3,119.9,112.0, 35.4,29.7.HRMS(ESI)m/z:[M+H]+Calcd for C18H18BrN2O 357.0597；Found357.0592.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(4-iodophenyl)methanone(3u)
1H NMR(CDCl3,400 MHz):δ7.89(d,J＝8.4 Hz,2H),7.77(d,J＝8.0 Hz,1H),7.52(d,J＝ 8.4 Hz,2H),7.24(t,J＝7.6 Hz,1H),7.06(t,J＝7.6 Hz,1H),6.58(d,J＝8.4 Hz,1H),1.55 (s,9H).13C{1H}NMR(CDCl3,100 MHz):δ170.2,163.2,141.4,138.8,135.2,132.3,132.0, 123.5,123.3,119.9,112.0,103.6,35.4,29.7.HRMS(ESI)m/z:[M+H]+Calcdfor C18H18IN2O 405.0458；Found 405.0451.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(4-(trifluoromethyl)phenyl)methanone(3v)
1H NMR(CDCl3,400 MHz):δ7.99(d,J＝8.0 Hz,2H),7.85-7.81(m,3H),7.31-7.27(m, 1H),7.11-7.07(m,1H),6.53(d,J＝8.0 Hz,1H),1.62(s,9H).13C{1H}NMR(CDCl3,150MHz):δ169.6,163.3,141.5,136.08,136.05(q,2JC-F＝32.9 Hz),135.0,131.2,126.4(q,3JC-F＝3.3 Hz),123.6,123.5,123.3(q,1JC-F＝271.2 Hz),120.0,112.1,35.5,29.7.19FNMR (CDCl3,565 MHz):δ-63,27(s).HRMS(ESI)m/z:[M+H]+Calcd for C19H18F3N2O347.1366；Found 347.1368.
[1,1'-Biphenyl]-4-yl(2-(tert-butyl)-1H-benzo[d]imidazol-1-yl)methanone(3w)
1H NMR(CDCl3,600 MHz):δ7.89(dt,J1＝9.0 Hz,J2＝2.4 Hz,2H),7.78(d,J＝8.4Hz, 1H),7.73-7.72(m,2H),7.65-7.64(m,2H),7.49-7.47(m,2H),7.44-7.41(m,1H),7.24-7.22 (m,1H),7.07-7.04(m,1H),6.68(d,J＝7.8 Hz,1H),1.59(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ170.5,163.2,147.8,141.5,139.2,135.5,131.6,131.4,129.2,128.8,127.9,127.4,123.3,123.1,119.7,112.2,35.5,29.8.HRMS(ESI)m/z:[M+H]+Calcd for C24H23N2O355.1805；Found 355.1806.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(m-tolyl)methanone(3x)
1H NMR(CDCl3,400 MHz):δ7.76(d,J＝8.0 Hz,1H),7.68(s,1H),7.55(d,J＝7.6Hz, 1H),7.49(d,J＝8.0 Hz,1H),7.36(t,J＝7.6 Hz,1H),7.22-7.19(m,1H),7.04-7.00(m,1H), 6.58(d,J＝8.4 Hz,1H),2.40(s,3H),1.57(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ170.9,163.3,141.4,139.4,135.8,135.5,133.0,131.2,129.1,128.2,123.2,123.0,119.7, 112.2,35.4,29.8,21.3.HRMS(ESI)m/z:[M+H]+Calcd for C19H21N2O 293.1648；Found 293.1646.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(3-chlorophenyl)methanone(3y)
1H NMR(CDCl3,400 MHz):δ7.87(t,J＝1.6 Hz,1H),7.77(d,J＝8.0 Hz,1H),7.69-7.66 (m,1H),7.65-7.62(m,1H),7.45(t J＝8.0 Hz,1H),7.26-7.22(m,1H),7.08-7.04(m,1H), 6.56(d,J＝8.0 Hz,1H),1.57(s,9H).13C{1H}NMR(CDCl3,100 MHz):δ169.5,163.3,141.5,135.7,135.1,134.9,134.7,130.58,130.57,128.9,123.5,123.4,119.9,112.1,35.5, 29.7.HRMS(ESI)m/z:[M+H]+Calcd for C18H18ClN2O 313.1102；Found 313.1100.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(o-tolyl)methanone(3z)
1H NMR(CDCl3,600 MHz):δ7.73(d,J＝8.4 Hz,1H),7.54-7.51(m,1H),7.41(d,J＝7.8 Hz,1H),7.37(dd,J1＝7.8 Hz,J2＝0.6 Hz,1H),7.24(t,J＝7.8 Hz,1H),7.21-7.18(m,1H), 6.98-6.95(m,1H),6.27(d,J＝8.4 Hz,1H),2.54(s,3H),1.63(s,9H).13C{1H}NMR(CDCl3, 150 MHz):δ170.2,163.5,141.6,140.0,134.8,133.30,133.25,132.2,130.8,126.6,123.5, 123.3,119.8,112.3,35.8,29.7,20.4.HRMS(ESI)m/z:[M+H]+Calcd forC19H21N2O 293.1648；Found 293.1646.
(2-Bromophenyl)(2-(tert-butyl)-1H-benzo[d]imidazol-1-yl)methanone(3aa)
1H NMR(CDCl3,400 MHz):δ7.74-7.71(m,2H),7.57-7.54(m,1H),7.50-7.45(m,2H), 7.24-7.19(m,1H),6.99-6.95(m,1H),6.18(d,J＝8.4 Hz,1H),1.66(s,9H).13C{1H}NMR (CDCl3,100 MHz):δ167.6,163.4,141.8,136.0,134.6,134.3,133.7,131.3,128.2,123.9, 123.8,121.4,120.1,112.4,36.0,29.4.HRMS(ESI)m/z:[M+H]+Calcd forC18H18BrN2O 357.0597；Found 357.0606.
Benzo[d][1,3]dioxol-4-yl(2-(tert-butyl)-1H-benzo[d]imidazol-1-yl)methanone(3bb)
1H NMR(CDCl3,600 MHz):δ7.77(d,J＝8.4 Hz,1H),7.37(dd,J1＝8.4 Hz,J2＝1.8Hz, 1H),7.32(d,J＝1.8 Hz,1H),7.24-7.22(m,1H),7.09-7.07(m,1H),6.86(d,J＝8.4Hz,1H), 6.74(d,J＝8.4 Hz,1H),6.11(s,2H),1.55(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ169.6,162.9,153.7,148.7,141.3,135.6,128.2,126.8,123.2,123.0,119.7,111.9,110.2, 108.7,102.5,35.4,29.7.HRMS(ESI)m/z:[M+H]+Calcd for C19H19N2O3 323.1390；Found 323.1394.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(naphthalen-1-yl)methanone(3cc)
1H NMR(CDCl3,400 MHz):δ8.64(d,J＝8.8 Hz,1H),8.15(d,J＝8.4 Hz,1H),8.00(d,J＝ 7.6 Hz,1H),7.75(d,J＝8.0 Hz,1H),7.70-7.65(m,3H),7.45(t,J＝7.6 Hz,1H),7.19-7.15 (m,1H),6.89-6.85(m,1H),6.27(d,J＝8.0 Hz,1H),1.67(s,9H).13C{1H}NMR(CDCl3, 100 MHz):δ169.9,163.7,141.5,135.2,134.9,134.2,131.2,131.1,130.3,128.99,128.96, 127.2,125.1,124.8,123.4,123.3,119.8,112.6,35.8,29.7.HRMS(ESI)m/z:[M+H]+Calcd for C22H21N2O 329.1648；Found 329.1649.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(thiophen-2-yl)methanone(3dd)
1H NMR(CDCl3,600 MHz):δ7.86(dd,J1＝4.8 Hz,J2＝1.2 Hz,1H),7.77(d,J＝8.4Hz, 1H),7.53(dd,J1＝3.6 Hz,J2＝1.2 Hz,1H),7.24(td,J1＝7.8 Hz,J2＝1.2 Hz,1H),7.15-7.14 (m,1H),7.13-7.10(m,1H),6.93(d,J＝8.4 Hz,1H),1.55(s,9H).13C{1H}NMR(CDCl3, 150 MHz):δ164.2,162.4,141.4,137.7,137.4,137.1,135.8,128.9,123.3,123.1,119.7, 111.6,35.4,29.7.HRMS(ESI)m/z:[M+H]+Calcd for C16H17N2OS 285.1056；Found 285.1046.
(2-(tert-Butyl)-4-methyl-1H-benzo[d]imidazol-1-yl)(furan-2-yl)methanone(3ee)
1H NMR(CDCl3,600 MHz):δ7.71(dd,J1＝1.8 Hz,J2＝0.6 Hz,1H),7.21(dd,J1＝3.6 Hz, J2＝0.6 Hz,1H),7.05-7.00(m,2H),6.66(d,J＝7.8 Hz,1H),6.62(dd,J1＝3.6Hz,J2＝1.8 Hz,1H),2.67(s,3H),1.53(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ161.4,159.6,149.0, 147.6,140.8,135.3,130.0,123.5,123.2,123.1,113.3,108.7,35.4,29.7,16.7.HRMS(ESI) m/z:[M+H]+Calcd for C17H19N2O2 283.1441；Found 283.1441.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)ethan-1-one(3ff)
1H NMR(CDCl3,600 MHz):δ8.02(d,J＝7.8 Hz,1H),7.97(d,J＝8.4 Hz,1H),7.81-7.78 (m,1H),7.54-7.51(m,1H),2.91(s,3H),1.49(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ172.7,167.3,149.8,132.9,129.0,126.3,124.7,122.3,39.4,29.6,21.9.HRMS(ESI)m/z:[M+Na]+Calcd for C13H16N2NaO 239.1155；Found 239.1159.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)hexan-1-one(3gg)
1H NMR(CDCl3,600 MHz):δ8.06(d,J＝8.4 Hz,1H),7.98(d,J＝8.4 Hz,1H),7.80-7.77 (m,1H),7.53-7.50(m,1H),3.24(t,J＝7.8 Hz,2H),1.94-1.89(m,2H),1.51(s,9H),1.46-1.39(m,4H),0.93(t,J＝7.2 Hz,3H).13C{1H}NMR(CDCl3,150 MHz):δ172.7,170.4,150.1,132.6,129.1,126.1,124.3,121.8,39.5,34.2,31.7,29.6,28.0,22.6,14.1.HRMS(ESI) m/z:[M+H]+Calcd for C17H25N2O 273.1961；Found 273.1959.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)-3-cyclohexylpropan-1-one(3hh)
1H NMR(CDCl3,600 MHz):δ8.05(d,J＝8.4 Hz,1H),7.97(d,J＝8.4 Hz,1H),7.79-7.77 (m,1H),7.52(t,J＝7.8 Hz,1H),3.25(t,J＝7.8 Hz,2H),1.85(d,J＝13.2 Hz,2H),1.79-1.71(m,4H),1.67-1.65(m,1H),1.49(s,9H),1.38-1.33(m,1H),1.27-1.20(m,3H),1.02-0.96(m,2H).13C{1H}NMR(CDCl3,150 MHz):δ172.7,170.8,150.1,132.6,129.1,126.2,124.3,121.7,39.5,37.5,36.0,33.3,31.9,29.6,26.7,26.4.HRMS(ESI)m/z:[M+H]+Calcd for C20H29N2O 313.2274；Found 313.2270.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)-4-methylpentan-1-one(3ii)
1H NMR(CDCl3,600 MHz):δ8.05(d,J＝8.4 Hz,1H),7.97(d,J＝8.4 Hz,1H),7.80-7.77 (m,1H),7.52(t,J＝7.2 Hz,1H),3.25(t,J＝7.8 Hz,2H),1.78(q,J＝7.8 Hz,2H),1.73-1.69 (m,1H),1.49(s,9H),1.00(d,J＝6.6 Hz,6H).13C{1H}NMR(CDCl3,150 MHz):δ172.7, 170.7,150.1,132.6,129.1,126.2,124.3,121.7,39.5,37.4,29.7,29.6,28.0,22.5.HRMS (ESI)m/z:[M+H]+Calcd for C17H25N2O 273.1961；Found 273.1960.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)-3-phenylpropan-1-one(3jj)
1H NMR(CDCl3,400 MHz):δ8.03(d,J＝7.6 Hz,1H),7.98(d,J＝8.4 Hz,1H),7.81-7.77 (m,1H),7.53-7.49(m,1H),7.31-7.27(m,4H),7.22-7.18(m,1H),3.58(t,J＝8.4 Hz,2H), 3.28(t,J＝8.4 Hz,2H),1.50(s,9H).13C{1H}NMR(CDCl3,150 MHz):δ172.7,169.0,150.1,141.7,132.7,129.2,128.5,128.4,126.3,126.1,124.1,121.8,39.6,35.8,33.7,29.6. HRMS(ESI)m/z:[M+H]+Calcd for C20H23N2O 307.1805；Found 307.1821.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)-3-(p-tolyl)propan-1-one(3kk)
1H NMR(CDCl3,600 MHz):δ8.01(d,J＝8.4 Hz,1H),7.97(d,J＝8.4 Hz,1H),7.77(t,J＝7.8Hz,1H),7.49(t,J＝7.8Hz,1H),7.17(d,J＝7.2Hz,2H),7.09(d,J＝7.8Hz,2H),3.54 (t,J＝7.8Hz,2H),3.22(t,J＝8.4Hz,2H),2.31(s,3H),1.50(s,9H).13C{1H}NMR(CDCl3, 150MHz):δ172.7,169.2,150.1,138.7,135.5,132.7,129.1,128.4,126.3,124.1,121.8,39.6, 36.1,33.3,29.6,21.0.HRMS(ESI)m/z:[M+H]+Calcd for C21H25N2O321.1961；Found 321.1954.
1-(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)-3-(4-chlorophenyl)propan-1-one(3ll)
1H NMR(CDCl3,600MHz):δ8.00-7.97(m,2H),7.80-7.77(m,1H),7.52-7.50(m,1H),7.23(d,J＝8.4Hz,2H),7.18(d,J＝8.4Hz,2H),3.54(t,J＝8.4Hz,2H),3.25(t,J＝7.8Hz,2H),1.48(s,9H).13C{1H}NMR(CDCl3,150MHz):δ172.6,168.6,150.1,140.1,132.8, 131.8,129.9,129.2,128.5,126.4,123.9,121.7,39.6,35.5,32.8,29.6.HRMS(ESI)m/z: [M+H]+Calcd for C20H22ClN2O 341.1415；Found 341.1410.
(2-(tert-Butyl)-1H-benzo[d]imidazol-1-yl)(cyclohexyl)methanone(3mm)
1H NMR(CDCl3,400MHz):δ7.77-7.75(m,1H),7.39-7.36(m,1H),7.32-7.27(m,2H),3.33-3.25(m,1H),2.07(d,J＝13.6Hz,2H),1.91-1.87(m,2H),1.78-1.62(m,3H),1.54(s,9H),1.41-1.30(m,3H).13C{1H}NMR(CDCl3,100MHz):δ179.1,162.8,141.8,133.7, 123.8,123.5,120.3,111.7,47.3,35.8,29.7,29.6,25.55,25.50.HRMS(ESI)m/z:[M+H]+ Calcdfor C18H25N2O 285.1961；Found 285.1951.
实施例4
本发明所合成产物N-酰基苯并咪唑类化合物3进行一系列反应，从而合成进一步的衍生物。例如：
Figure BDA0003251337850000141
向15mL耐压管中依次加入3a(55.7mg,0.2mmol)和5mL的四氢呋喃，在0℃下加入LiAlH4(15.2mg,0.4mmol)，在空气氛围下将反应管密封，升至室温，并在室温条件下反应2h。反应结束后，加入饱和氯化铵溶液淬灭反应，然后将反应混合物转移至分液漏斗中，乙酸乙酯(10mL×3)萃取。合并有机相，无水硫酸钠干燥，有机相干燥后，抽滤，旋干，硅胶柱分离(石油醚/乙酸乙酯＝3/1)得白色固体产物4(30.7mg, 88％)。1H NMR(DMSO-d6,600MHz):δ12.1(s,1H),7.52-7.41(m,2H),7.11-7.10(m,2H), 1.40(s,9H).13C{1H}NMR(DMSO,150MHz):δ162.6,143.3,135.1,121.9,121.2,118.8, 111.2,33.6,29.7.HRMS(ESI)m/z:[M+H]+Calcd for C11H15N2 175.1230；Found 175.1230.
实施例5
本发明所合成产物N-酰基苯并咪唑类化合物3进行一系列反应，从而合成进一步的衍生物。例如：
Figure BDA0003251337850000151
向15mL耐压管中依次加入3aa(35.7mg,0.1mmol)、DMSO(1mL)、Pd(OAc)2(1.1 mg,0.005mmol)、PPh3(5.2mg,0.02mmol)、K3PO4(25.5mg,0.12mmol)和苯乙炔(16.5μL,0.15mmol)，氩气条件下将反应管密封，放置在80℃的模块中反应24h。反应结束后，加入水稀释，然后将反应混合物转移至分液漏斗中，乙酸乙酯(10mL×3)萃取。合并有机相，无水硫酸钠干燥，有机相干燥后，抽滤，旋干，硅胶柱分离(石油醚/乙酸乙酯＝20/1)得白色固体产物5(32.9mg,87％)。1H NMR(CDCl3,400MHz):δ7.88(d,J ＝7.6Hz,1H),7.78(d,J＝8.0Hz,1H),7.69-7.66(m,2H),7.61-7.56(m,1H),7.33-7.30(m, 3H),7.26-7.22(m,3H),7.05-7.01(m,1H),6.42(d,J＝8.4Hz,1H),1.64(s,9H).13C{1H} NMR(CDCl3,100MHz):δ169.0,163.0,141.8,135.6,134.9,134.3,133.0,131.9,130.8, 128.92,128.89,128.3,123.7,123.54,123.47,121.9,119.8,112.1,95.2,85.6,35.7,29.6. HRMS(ESI)m/z:[M+H]+Calcdfor C26H23N2O 379.1805；Found 379.1800.
实施例6
本发明所合成产物N-酰基苯并咪唑类化合物3进行一系列反应，从而合成进一步的衍生物。例如：
Figure BDA0003251337850000161
向15mL耐压管中依次加入3aa(71.5mg,0.2mmol)、哌啶(1mL)、Pd(PPh3)4(4.6mg,0.004mmol)和CuI(3.8mg,0.02mmol)，在空气条件下将反应管密封，室温条件下反应 15h。反应结束后，加入饱和氯化铵溶液淬灭，然后将反应混合物转移至分液漏斗中，乙酸乙酯(10mL×3)萃取。合并有机相，无水硫酸钠干燥，有机相干燥后，抽滤，旋干，硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物6(23.2mg,32％)。1H NMR (CDCl3,600MHz):δ7.72(d,J＝7.8Hz,1H),7.52(t,J＝7.2Hz,1H),7.47(d,J＝7.2Hz, 1H),7.18(t,J＝7.8Hz,1H),7.09(d,J＝8.4Hz,1H),7.02(t,J＝7.8Hz,1H),6.93(t,J＝ 7.8Hz,1H),6.32(d,J＝9.0Hz,1H),2.97(br s,2H),2.79(br s,2H),1.65(s,9H),1.41-1.37 (m,2H),1.30-1.26(m,4H).13C{1H}NMR(CDCl3,150MHz):δ168.6,163.6,153.7,141.7, 135.0,134.1,132.3,126.6,123.3,123.2,121.6,119.9,119.7,113.0,53.8,36.3,29.3,25.9, 23.8.HRMS(ESI)m/z:[M+H]+Calcd for C23H27N3NaO 384.2046；Found 384.2068.
实施例7
本发明所合成产物N-酰基苯并咪唑类化合物3进行一系列反应，从而合成进一步的衍生物。例如：
Figure BDA0003251337850000162
向15mL耐压管中依次加入3aa(35.7mg,0.1mmol)、1,4-二氧六环(1mL)、Pd(OAc)2(2.2mg,0.01mmol)、PPh3(15.7mg,0.06mmol)、K2CO3(55.3mg,0.4mmol)和苯硼酸 (13.4mg,0.11mmol)，氩气条件下将反应管密封，放置于80℃模块中反应24h。反应结束后，加水稀释，然后将反应混合物转移至分液漏斗中，乙酸乙酯(10mL×3)萃取。合并有机相，无水硫酸钠干燥，有机相干燥后，抽滤，旋干，硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物7(32.6mg,92％)。1H NMR(CDCl3,600MHz):δ7.69- 7.65(m,2H),7.57(dd,J1＝7.8Hz,J2＝1.8Hz,1H),7.50-7.45(m,2H),7.26-7.16(m,6H), 7.00-6.98(m,1H),6.30(d,J＝8.4Hz,1H),1.54(s,9H).13C{1H}NMR(CDCl3,150MHz): δ169.1,163.8,142.9,141.7,139.1,134.5,134.0,132.6,131.7,130.0,128.5,128.3,128.0, 127.8,123.6,123.5,119.9,113.3,36.2,29.3.HRMS(ESI)m/z:[M+H]+Calcd for C24H23N2O 355.1805；Found 355.1804.
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (5)

1.一种N-酰基苯并咪唑类化合物的合成方法，其特征在于，包括如下操作：
Figure FDA0003973072200000011
将N-芳基脒类化合物1、铑或钴催化剂、添加剂、二噁唑酮类化合物2和有机溶剂混合，升温反应得到N-酰基苯并咪唑类化合物3；所述铑催化剂为[RhCp*Cl2]2；钴催化剂为CoCp*(CO)I2；所述添加剂采用银盐添加剂与醋酸盐添加剂中的一种或两种，所述银盐添加剂为六氟锑酸银、三氟甲烷磺酸银、双三氟甲烷磺酰亚胺银或三氟乙酸银，所述醋酸盐添加剂为醋酸钠、醋酸铜、醋酸铯或醋酸锌；R1为氢、C1-6烷基、C1-4烷氧基、苯基、取代苯基、硝基或卤素，R2为苯基、取代苯基、噻吩基、呋喃基、萘基、C1-8烷基、苯基取代C1-3烷基或取代苯基取代C1-3烷基，以上所述取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、甲叉二氧基、三氟甲基、苯基或卤素。
2.根据权利要求1所述N-酰基苯并咪唑类化合物的合成方法，其特征在于：所述有机溶剂选自1,2-二氯乙烷、乙酸乙酯、1,4-二氧六环、四氢呋喃或甲苯。
3.根据权利要求1所述N-酰基苯并咪唑类化合物的合成方法，其特征在于：所述N-芳基脒类化合物1、二噁唑酮2、铑或钴催化剂、银盐添加剂与醋酸盐添加剂摩尔比为1-1.2:1-1.2:0.02-0.05:0.05-0.2:0.1-0.5。
4.根据权利要求1所述N-酰基苯并咪唑类化合物的合成方法，其特征在于：所述反应温度为80-120℃。
5.根据权利要求1-4任意一项所述N-酰基苯并咪唑类化合物的合成方法，其特征在于：所述反应在空气氛围下进行。
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