CN114773136A - 一种合成芳胺的方法 - Google Patents

一种合成芳胺的方法 Download PDF

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CN114773136A
CN114773136A CN202210349635.7A CN202210349635A CN114773136A CN 114773136 A CN114773136 A CN 114773136A CN 202210349635 A CN202210349635 A CN 202210349635A CN 114773136 A CN114773136 A CN 114773136A
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formula
cdcl
nmr
equimolar
product
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CN114773136B (zh
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薛东
宋戈洋
农定展
李琪
李刚
李京晟
李飞
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Shaanxi Normal University
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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了一种合成芳胺的方法，该方法以联吡啶为配体，金属镍络合物为催化剂，以卤代芳烃和不同铵盐为底物，有机碱DBU、MTBD、TMG等作为碱，在氩气氛围中通过光促进镍催化卤代芳烃与铵盐的C‑N偶联反应实现了各种芳胺的合成。本发明反应体系简单、操作简便、反应条件温和，反应后处理简单，收率好、底物范围广，避免了传统的昂贵金属催化剂以及无机碱的使用造成催化体系反应复杂、官能团兼容性差等问题，同时利用铵盐替代了气体胺源，是一种简单、高效合成芳胺的方法，具有很好的应用前景。

Description

一种合成芳胺的方法
技术领域
本发明属于芳胺的合成技术领域，具体涉及一种通过光催化合成芳胺的方法。
背景技术
芳胺是非常重要且有价值的有机中间体，在制药、农业化学、染料、聚合物工业以及化学品等具有广泛的应用。实际上，在过去的几十年中，已经建立了多种芳香伯胺的合成方法，如硝基还原、Buchwald-Hartwig偶联(J.Am.Chem.Soc.,1998,120,9722-9723；J.Am.Chem.Soc.,1999,121,9889–9890；Angew.Chem.Int.Ed.,2002,41,4746–4748)、Ullmann偶联(Chin.J.Chem.,2020,38,879-893)、有机金属试剂(Org.Lett.,2004,6,4619-4621,Nat.Chem.,2017,9,681-688)、C-H键官能团化(J.Am.Chem.Soc.,2014,136,5279-5282)等。然而，硝基化合物的Bechamp还原通常需要使用有较大的安全隐患的还原剂，如金属碱、NaBH4、肼和加压的H2(Chem.Rev.,2019,119,2611-2680；Org.Process Res.Dev.,2018,22,430-445；Org.Process Res.Dev.,2012,16,1156-1153)。由于氨的丰富性和极低的成本，并且可以减少氨废物量，是一种重要的化工产品，在生产和科研中应用广泛。在有机合成中，氨气可以作为非常理想的氮亲核试剂用来参与芳基C-N键交叉偶联反应合成芳胺。然而，许多常见反应并不会与氨发生反应。主要原因是：1)氨气是各种金属的良好配体，并迅速形成稳定的Werner型络合物，从而导致金属催化剂失活(Chem.Soc.Rev.,2010,39,2302–2322)；2)氨气具有很强的N-H键(107kcal/mol)，这使其N-H活化具有挑战性(J.Am.Chem.Soc.,2009,131,11049-11061)；3)氨气的弱碱性和低酸性不利于质子与氨的交换，而且中间体金属-胺络合物的还原消除被认为比较复杂；4)氨气的高压处理需要特殊的设备。随着芳基C-N键偶联反应的不断发展，钯催化(Buchwald-Hartwig)和铜催化(Ullmann)芳基卤化物胺化反应已发展成为最重要的芳香伯胺制备方法。然而在早期，以氨气作为氮源的过渡金属催化芳基C-N键偶联反应中，胺的选择性单芳基化是一个特殊的挑战。因为在碱性条件下，所得的单芳基化产物易于充当亲核试剂与氨气竞争，使反应选择性无法控制，从而形成大量的二芳基和三芳基胺。经过不断的努力，Ma等课题组(J.Org.Chem.,2001,66,3820-3827；J.Am.Chem.Soc.,2008,130,13552–13554；J.Am.Chem.Soc.,2015,137,3085–3092；Angew.Chem.Int.Ed.,2015,54,3768-3772)已开发出多种用于钯、铜催化选择性的芳基卤化物与氨气的交叉偶联反应。金属镍由于天然丰度高，价格便宜，易于商业化的特点，因此镍催化芳基卤化物与氨的芳基C-N键偶联引起了化学家的兴趣。最近，Stradiotto(Nat.Commun.,2016,7,11073)和Hartwig(J.Am.Chem.Soc.,2014,136,1617–1627,Angew.Chem.Int.Ed.,2015,54,3768-3772)等课题组报道了镍催化的芳基亲电试剂与氨气的单芳基化反应。该工作主要是改造相对富电子的Josiphos型配体，主要为二茂铁基富膦配体为主，改善了之前的多芳胺副产物的问题。然而，几乎所有的过渡金属(钯、铜、镍)催化的芳基卤化物与氨的芳基C-N键偶联反应中均需要设计复杂的配体和无机金属醇盐碱，空气敏感的镍催化剂或者已开发出空气稳定的预催化剂，仍然需要复杂富电子膦配体。由于氨气的特殊性，酮、酯以及氰基等官能团很容易发生副反应；无机强碱存在，容易造成溶解性困难以及官能团不兼容，同时受限于氨气的运输以及储存的高要求等问题。因此，开发更温和、廉价的合成芳香胺的制备方法仍然是一个巨大的挑战。
发明内容
本发明的目的是提供一种使用廉价的镍催化与联吡啶体系，同时添加铵盐，实现芳基溴化物或者芳基氯化物胺化反应的方法，该方法不仅解决了铜催化芳基碘化物的位阻问题，同时也避免了过渡金属催化中复杂配体以及无机碱的使用。
针对上述目的，本发明所采用的技术方案是：将式I化合物与铵盐、联吡啶、镍催化剂、有机碱加入有机溶剂中，在氩气氛围中光照反应，反应完后分离纯化产物，得到芳胺；其中，所述铵盐为碳酸铵或溴化铵时，所得芳胺的结构式如式II所示；所述铵盐为甲胺盐酸盐时，所得芳胺的结构式如式III所示；所述铵盐为乙胺盐酸盐时，所得芳胺的结构式如式IV所示；所述铵盐为二甲胺盐酸盐时，所得芳胺的结构式如式V所示；所述铵盐为15N标记氯化铵时，所得芳胺的结构式如式VI所示；所述铵盐为氘代甲胺盐酸盐时，所得芳胺的结构式如式VII所示。
Figure BDA0003579087180000021
式中，Ar代表芳基、取代芳基、杂环芳基、取代杂环芳基中任意一种；X代表Br或Cl。
上述合成方法中，优选铵盐的用量为式I化合物摩尔量的1.1～2.0倍。
上述合成方法中，优选联吡啶的用量为式I化合物摩尔量的5％～10％。
上述合成方法中，优选镍催化剂为醋酸镍、氯化镍等，其用量为式I化合物摩尔量的5％～10％。
上述合成方法中，优选有机碱为1,8-二氮杂二环十一碳-7-烯(DBU)、四甲基胍(TMG)、7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯(MTBD)等，其用量为式I化合物摩尔量的2～3倍。
上述合成方法中，优选有机溶剂为二甲基亚砜、甲苯、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺中任意一种或者它们中任意一种与四氢呋喃的混合溶剂。
上述合成方法中，优选在氩气氛围中，在波长为390～415nm的紫色光照射下80～90℃反24～36小时。
本发明的有益效果如下：
本发明反应体系简单，使用廉价的镍催化与联吡啶体系，同时添加铵盐，在光照条件下实现芳基或杂环芳基卤化物的胺化反应，得到各种不同芳胺，反应经济效益较高、对环境无害，反应后处理简单，不仅解决了铜催化芳基碘化物的位阻问题，同时也避免了过渡金属催化中复杂配体以及无机碱的使用。此外，得到的芳胺具有收率好、选择性好，保持高氘代率等特点。本发明还克服了底物范围有限、原料试剂昂贵、反应体系复杂、经济廉价等缺陷，与目前追求环保、经济、绿色的化学概念相符合，具有非常重要的应用前景。
具体实施方式
下面结合实施例对本发明进一步详细说明，但本发明的保护范围并不仅限于这些实施例。
实施例1
在氩气氛围中，将31.0mg(0.2mmol)溴苯、22.5mg(0.25mmol)碳酸铵、1.9mg(0.01mmol)联吡啶、1.8mg(0.01mmol)醋酸镍、57.6mg(0.5mmol)DBU、2mL二甲基亚砜和磁子加入反应管中，在390～395nm紫色光照下，在85℃反应24小时。反应完后冷却至室温，加入饱和氯化钠水溶液和乙酸乙酯稀释萃取得到有机相，减压蒸馏得到粗产物，以石油醚与乙酸乙酯体积比为10:1至1:1的混合液为淋洗剂，柱层析分离产物，得到淡黄色油状液体苯胺，其产率为70％。
Figure BDA0003579087180000041
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.18(t,J＝7.8Hz,2H),6.79(t,J＝7.4Hz,1H),6.70(d,J＝7.7Hz,2H),3.64(br,2H)；13C NMR(100MHz,CDCl3)δ146.5,129.4,118.6,115.2；GC-MS(ESI)m/z C6H7N[M]:93。
实施例2
本实施例中，用等摩尔4-叔丁基溴苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的淡黄色液体产物，其产率为76％。
Figure BDA0003579087180000042
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.23(d,J＝8.6Hz,2H),6.68(d,J＝8.5Hz,2H),3.50(br,2H),1.32(s,9H)；13C NMR(100MHz,CDCl3)δ143.9,141.5,126.2,115.0,34.0,31.6；HRMS(ESI)m/z C10H16N[M+H]+:理论值150.1277,实测值150.1280。
实施例3
本实施例中，用等摩尔4-溴苯乙腈替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的透明油状液体产物，其产率为78％。
Figure BDA0003579087180000043
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.09(d,J＝8.3Hz,2H),6.67(d,J＝8.4Hz,2H),3.71(br,2H),3.62(s,2H)；13C NMR(100MHz,CDCl3)δ146.4,129.1,119.5,118.6,115.6,22.9；HRMS(ESI)m/z C8H8N2Na[M+Na]+:理论值155.0580,实测值155.0583。
实施例4
本实施例中，用等摩尔4-溴联苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为79％。
Figure BDA0003579087180000051
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.45(d,J＝7.7Hz,2H),7.36–7.29(m,4H),7.19–7.15(m,1H),6.66(d,J＝8.3Hz,2H),3.74(br,2H)；13C NMR(100MHz,CDCl3)δ141.3,128.8,128.5,128.1,126.8,126.5,126.4,115.6；HRMS(ESI)m/zC12H12N[M+H]+:理论值170.0964,实测值170.0962。
实施例5
本实施例中，用等摩尔对溴三氟甲氧基苯替换实施例1中的溴苯，用等摩尔MTBD替换实施例1的DBU，其他步骤与实施例1相同，得到结构式如下的油状液体产物，其产率为85％。
Figure BDA0003579087180000052
所得产物的核磁波谱数据为：1HNMR(400MHz,CDCl3)δ7.45(d,J＝7.7Hz,2H),7.36–7.29(m,4H),7.19–7.15(m,1H),6.66(d,J＝8.3Hz,2H),3.74(br,2H)；13C NMR(100MHz,CDCl3)δ141.3,128.8,128.5,128.1,126.8,126.5,126.4,115.6；HRMS(ESI)m/z C12H12N[M+H]+:理论值170.0964,实测值170.0962。
实施例6
本实施例中，用等摩尔N-(4-溴苯基)-3-苯基丙酰氨替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色固体产物，其产率为81％。
Figure BDA0003579087180000053
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.32–7.24(m,2H),7.24–7.13(m,5H),6.57(d,J＝8.4Hz,2H),3.47(br,2H),3.00(t,J＝7.6Hz,2H),2.58(t,J＝7.6Hz,2H)；13C NMR(100MHz,CDCl3)δ170.4,143.4,140.9,129.2,128.7,128.5,126.4,122.4,115.4,39.3,31.8；HRMS(ESI)m/z C15H16N2Na[M+Na]+:理论值263.1155,实测值263.1159。
实施例7
本实施例中，用等摩尔4'-溴乙酰苯胺替换实施例1中的溴苯，反应时间延长至36小时，其他步骤与实施例1相同，得到结构式如下的黄色固体产物，其产率为71％。
Figure BDA0003579087180000061
所得产物的核磁波谱数据为：1HNMR(400MHz,CD3OD)δ7.22(d,J＝8.8Hz,2H),6.68(d,J＝8.8Hz,2H),2.06(s,3H)；13C NMR(100MHz,CD3OD)δ171.3,145.5,130.7,123.2,116.7,23.5；HRMS(ESI)m/z C8H10N2Na[M+Na]+:理论值173.0685,实测值173.0683。
实施例8
本实施例中，用等摩尔1-(4-溴苯基)吡咯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的淡黄色固体产物，其产率为86％。
Figure BDA0003579087180000062
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.20(d,J＝8.6Hz,2H),7.00(t,J＝2.1Hz,2H),6.73(d,J＝8.6Hz,2H),6.33(t,J＝2.0Hz,2H)；13C NMR(100MHz,CDCl3)δ144.6,133.0,122.5,119.8,115.8,109.6；HRMS(ESI)m/z C10H11N2[M+H]+:理论值159.0917,实测值159.0918。
实施例9
本实施例中，用等摩尔9-(4-溴苯基)咔唑替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为88％。
Figure BDA0003579087180000063
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ8.22(d,J＝7.7Hz,2H),7.47(t,J＝7.4Hz,2H),7.40(d,J＝8.1Hz,2H),7.37–7.31(m,4H),6.85(d,J＝8.4Hz,2H),3.77(br,2H)；13C NMR(100MHz,CDCl3)δ146.0,141.6,128.5,128.2,125.9,123.0,120.3,119.5,116.0,109.9；HRMS(ESI)m/z C18H15N2[M+H]+:理论值259.1230,实测值259.1237。
实施例10
本实施例中，用等摩尔4-溴苯乙烯替换实施例1中的溴苯，用等摩尔TMG替换实施例1的DBU，其他步骤与实施例1相同，得到结构式如下的淡黄色油状产物，其产率为68％。
Figure BDA0003579087180000071
所得产物的核磁波谱数据为：1H NMR(600MHz,CDCl3)δ7.23(d,J＝7.9Hz,2H),6.64(d,J＝7.8Hz,2H),6.63–6.58(m,1H),5.55(d,J＝17.6Hz,1H),5.04(d,J＝10.9Hz,1H),3.73(s,2H)；13C NMR(151MHz,CDCl3)δ146.31,136.67,128.52,127.49,115.14,110.15；HRMS(ESI)m/z C8H10N[M+H]+:理论值120.0808,实测值120.0811。
实施例11
本实施例中，用等摩尔4-溴苯甲酸甲酯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的白色固体产物，其产率为88％。
Figure BDA0003579087180000072
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.7Hz,2H),6.62(d,J＝8.7Hz,2H),4.12(br,2H),3.84(s,3H)；13C NMR(100MHz,CDCl3)δ167.3,151.0,131.6,119.6,113.8,51.7；HRMS(ESI)m/z C8H9NNaO2[M+Na]+:理论值174.0525,实测值174.0526。
实施例12
本实施例中，用等摩尔1-((4-溴苯基)磺酰基)吡咯烷替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的淡黄色固体产物，其产率为89％。
Figure BDA0003579087180000073
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.60(d,J＝8.7Hz,2H),6.69(d,J＝8.7Hz,2H),4.17(br,2H),3.22–3.17(m,4H),1.87–1.62(m,4H)；13C NMR(100MHz,CDCl3)δ150.7,129.8,125.2,114.1,48.0,25.2；HRMS(ESI)m/z C10H14N2NaO2S[M+Na]+:理论值249.0668,实测值249.0673。
实施例13
本实施例中，用等摩尔N-甲基-4-溴苯甲酰胺替换实施例1中的溴苯，用等摩尔MTBD替换实施例1的DBU，反应时间延长至36小时，其他步骤与实施例1相同，得到结构式如下的黄色固体产物，其产率为67％。
Figure BDA0003579087180000081
所得产物的核磁波谱数据为：1H NMR(400MHz,CD3OD)δ7.58(d,J＝8.6Hz,2H),6.66(d,J＝8.6Hz,2H),2.87(s,3H)；13C NMR(100MHz,CD3OD)δ171.0,153.0,129.8,123.3,114.8,26.8；HRMS(ESI)m/z C8H10N2Na[M+Na]+:理论值173.0685,实测值173.0687。
实施例14
本实施例中，用等摩尔3-氟-5-甲氧基溴苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状液体产物，其产率为89％。
Figure BDA0003579087180000082
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.07–5.96(m,3H),3.74(s,3H)；13C NMR(100MHz,CDCl3)δ164.7(d,J＝240.1Hz),161.8(d,J＝13.6Hz),148.7(d,J＝13.5Hz),96.7(d,J＝2.4Hz),95.1(d,J＝24.9Hz),92.0(d,J＝25.5Hz),55.4；19F NMR(376MHz,CDCl3)δ-112.06(s,F)；HRMS(ESI)m/z C7H9FNO[M+H]+:理论值142.0663,实测值142.0663。
实施例15
本实施例中，用等摩尔3-氰基-5-甲基溴苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为82％。
Figure BDA0003579087180000083
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.83(s,1H),6.72(s,1H),6.68(s,1H),3.85(br,2H),2.27(s,3H)；13C NMR(100MHz,CDCl3)δ147.0,140.4,122.8,120.1,119.4,115.0,112.8,21.2；HRMS(ESI)m/z C8H8N2Na[M+Na]+:理论值155.0580,实测值155.0577。
实施例16
本实施例中，用等摩尔3-三氟甲基-4-氯溴苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为93％。
Figure BDA0003579087180000091
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.23(d,J＝8.6Hz,1H),6.98–9.65(m,1H),6.74–6.61(m,1H),3.85(br,2H)；13C NMR(100MHz,CDCl3)δ145.3,132.2,128.9(q,J＝30.8Hz),123.0(q,J＝271.5Hz),120.4,118.8,113.8(q,J＝5.4Hz)；HRMS(APCI)m/z C7H6ClF3N[M+H]+:理论值196.0135,实测值196.0140。
实施例17
本实施例中，用等摩尔6-溴-1,2,3,4-四氢-2-喹啉酮替换实施例1中的溴苯，反应时间延长至36小时，其他步骤与实施例1相同，得到结构式如下的黄色固体产物，其产率为60％。
Figure BDA0003579087180000092
所得产物的核磁波谱数据为：1HNMR(400MHz,CD3OD)δ6.65(d,J＝8.2Hz,1H),6.61–6.52(m,2H),2.86–2.78(m,2H),2.52–2.45(m,2H)；13C NMR(100MHz,CD3OD)δ173.5,144.4,130.4,126.2,117.3,116.4,115.6,31.6,26.4；HRMS(ESI)m/z C9H10N2NaO[M+Na]+:理论值185.0685,实测值185.0684。
实施例18
本实施例中，用等摩尔5-溴苯酞替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色固体产物，其产率为76％。
Figure BDA0003579087180000093
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.23(d,J＝8.2Hz,1H),7.13(d,J＝2.0Hz,1H),6.98(dd,J＝8.1,2.1Hz,1H),5.20(s,2H),4.00(br,2H)；13C NMR(100MHz,CDCl3)δ171.7,147.7,136.5,127.1,122.8,121.8,109.9,69.8；HRMS(ESI)m/zC8H7NNaO2[M+Na]+:理论值172.0369,实测值172.0370。
实施例19
本实施例中，用等摩尔7-溴苯并二氢吡喃替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为84％。
Figure BDA0003579087180000101
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.81(d,J＝8.0Hz,1H),6.22(dd,J＝8.0,2.3Hz,1H),6.15(d,J＝2.3Hz,1H),4.22–4.02(m,2H),3.52(br,2H),2.68(t,J＝6.5Hz,2H),2.03–1.88(m,2H)；13C NMR(100MHz,CDCl3)δ155.6,145.7,130.4,112.7,108.1,103.1,66.6,24.3,22.8；HRMS(ESI)m/z C9H12NO[M+H]+:理论值150.0913,实测值150.0911。
实施例20
本实施例中，用等摩尔2-二氟甲氧基溴苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为84％。
Figure BDA0003579087180000102
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.07–6.98(m,2H),6.80–6.76(m,1H),6.76–6.68(m,1H),6.47(t,J＝74.5Hz,1H),3.86(br,2H)；13C NMR(100MHz,CDCl3)δ138.8,138.7,126.6,120.3,118.7,116.9(t,J＝257.8Hz),116.7；19F NMR(376MHz,CDCl3)δ-79.48(d,J＝75.2Hz,2F)；HRMS(ESI)m/z C7H8F2NO[M+H]+:理论值160.0568,实测值160.0573。
实施例21
本实施例中，用等摩尔2-氧叔丁基溴苯替换实施例1中的溴苯，反应时间延长至36小时，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为78％。
Figure BDA0003579087180000103
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.98–6.94(m,1H),6.91–6.86(m,1H),6.75–6.72(m,1H),6.68–6.63(m,1H),3.79(br,2H),1.41(s,9H)；13C NMR(100MHz,CDCl3)δ143.1,141.2,123.8,123.0,118.1,115.8,79.7,29.1；HRMS(ESI)m/zC10H15NNa[M+Na]+:理论值188.1046,实测值188.1046。
实施例22
本实施例中，用等摩尔1,4-二溴-2,5-二己基苯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为79％。
Figure BDA0003579087180000111
所得产物的核磁波谱数据为：1HNMR(400MHz,CDCl3)δ7.17(s,1H),6.54(s,1H),3.56(br,2H),2.64–2.54(m,2H),2.46–2.37(m,2H),1.66–1.51(m,4H),1.45–1.20(m,12H),0.93–0.88(m,6H)；13C NMR(100MHz,CDCl3)δ143.4,140.2,132.9,126.8,117.2,112.7,35.9,31.8,30.8,30.2,29.4,29.3,28.7,22.8,22.7,14.24,14.22；HRMS(ESI)m/zC18H31BrN[M+H]+:理论值340.1634,实测值340.1638。
实施例23
本实施例中，用等摩尔2-氟-4-溴吡啶替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为89％。
Figure BDA0003579087180000112
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.81(d,J＝5.7Hz,1H),6.39(d,J＝5.7Hz,1H),6.08(d,J＝1.9Hz,1H),4.42(br,2H)；13C NMR(100MHz,CDCl3)δ166.6(d,J＝231.4Hz),157.1(d,J＝11.6Hz),147.8(d,J＝18.5Hz),108.3(d,J＝2.9Hz),93.1(d,J＝41.6Hz)；19F NMR(376MHz,CDCl3)δ-70.06(s,F)；HRMS(ESI)m/z C5H6FN2[M+H]+:理论值113.0510,实测值113.0508。
实施例24
本实施例中，用等摩尔6-溴苯并噻吩替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为75％。
Figure BDA0003579087180000113
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.31(d,J＝6.1Hz,2H),7.23(d,J＝5.6Hz,1H),7.14(t,J＝7.8Hz,1H),6.60(d,J＝7.5Hz,1H),3.92(br,2H)；13C NMR(100MHz,CDCl3)δ141.6,141.2,128.4,125.6,124.5,119.4,113.1,109.0；HRMS(ESI)m/zC8H8NS[M+H]+:理论值150.0372,实测值150.0372。
实施例25
本实施例中，用等摩尔2-甲巯基-5-溴嘧啶替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为62％。
Figure BDA0003579087180000121
所得产物的核磁波谱数据为：1HNMR(400MHz,CDCl3)δ8.09(s,2H),3.55(br,2H),2.53(s,3H)；13C NMR(100MHz,CDCl3)δ161.2,144.6,136.8,14.4；HRMS(APCI)m/z C5H8N3S[M+H]+:理论值142.0433,实测值142.0435。
实施例26
本实施例中，用等摩尔晴菌唑替换实施例1中的溴苯，用等摩尔溴化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色固体产物，其产率为71％。
Figure BDA0003579087180000122
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.90(s,1H),7.75(s,1H),7.07(d,J＝8.3Hz,2H),6.67(d,J＝8.3Hz,2H),4.58(d,J＝14.1Hz,1H),4.45(d,J＝14.1Hz,1H),3.81(br,2H),2.06–1.92(m,2H),1.50–1.39(m,1H),1.38–1.27(m,3H),0.87(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ151.9,147.0,144.1,127.3,124.0,120.9,115.6,58.2,49.0,36.3,27.2,22.6,13.9；HRMS(ESI)m/z C15H19N5Na[M+Na]+:理论值292.1533,实测值292.1531。
实施例27
本实施例中，用等摩尔下述结构的氯化物替换实施例1中的溴苯，用等摩尔溴化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的白色固体胺化产物，其产率为81％。
Figure BDA0003579087180000131
所得产物的核磁波谱数据为：1H NMR(600MHz,CDCl3)δ7.87(d,J＝8.7Hz,2H),6.64(d,J＝8.7Hz,2H),5.10-5.04(m,1H),4.10(br,2H),2.52–2.34(m,1H),2.18–2.07(m,1H),1.78(m,1H),1.71(t,J＝4.5Hz,1H),1.38(m,1H),1.29(m,1H),1.10(m,1H),0.95(s,3H),0.90(s,3H),0.89(s,3H)；13C NMR(150MHz,CDCl3)δ167.0,150.8,131.5,120.5,113.8,79.7,49.1,47.8,45.0,37.0,28.1,27.4,20.0,18.9,13.6；HRMS(ESI)m/z C17H23NNaO2[M+Na]+:理论值296.1621,实测值296.1622。
实施例28
本实施例中，用等摩尔下述结构的氯化物替换实施例1中的溴苯，用等摩尔溴化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的白色固体胺化产物，其产率为84％。
Figure BDA0003579087180000132
所得产物的核磁波谱数据为：1H NMR(600MHz,CDCl3)δ7.85(d,J＝8.7Hz,2H),6.63(d,J＝8.7Hz,2H),5.08–4.92(m,1H),4.07(br,2H),2.14–2.05(m,1H),2.02–1.85(m,1H),1.71(m,2H),1.64–1.42(m,2H),1.20–1.01(m,2H),0.91(m,6H),0.78(d,J＝7.0Hz,3H)；13CNMR(150MHz,CDCl3)δ166.2,150.7,131.6,120.4,113.8,74.0,47.4,41.2,34.4,31.5,26.5,23.7,22.1,20.8,16.6；HRMS(ESI)m/z C17H25NNaO2[M+Na]+:理论值298.1778,实测值298.1780。
实施例29
本实施例中，用等摩尔溴代吉非罗齐甲酯替换实施例1中的溴苯，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为79％。
Figure BDA0003579087180000141
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.55(s,1H),6.50(s,1H),3.86–3.83(m,2H),3.66(s,3H),3.22(br,2H),2.14(s,3H),2.13(s,3H),1.72–1.68(m,4H),1.22(s,6H)；13C NMR(100MHz,CDCl3)δ178.5,150.3,137.8,125.6,120.6,118.2,115.1,69.4,51.8,42.2,37.3,25.5,25.3,17.5,15.8；HRMS(ESI)m/z C16H26NO3[M+H]+:理论值280.1907,实测值280.1912。
实施例30
本实施例中，用等摩尔用下述结构的氯化物替换实施例1中的溴苯，用等摩尔溴化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状胺化产物，其产率为75％。
Figure BDA0003579087180000142
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.45(s,1H),7.07(d,J＝8.3Hz,1H),7.01(s,1H),6.94(s,1H),6.68(s,1H),6.56(d,J＝8.3Hz,1H),5.80–5.71(m,1H),5.20–5.08(m,2H),4.90–4.83(m,1H),4.15–4.10(m,1H),4.03–3.94(m,1H),3.94–3.89(m,1H),3.82(br,2H),3.74–3.68(m,1H)；13C NMR(100MHz,CDCl3)δ147.6,138.0,134.1,133.5,128.8,128.4,124.8,120.1,117.3,115.4,114.2,76.9,70.1,52.1；HRMS(ESI)m/zC14H17ClN3O[M+H]+:理论值278.1055,实测值278.1056。
实施例31
本实施例中，用等摩尔下述结构的氯化物替换实施例1中的溴苯，用等摩尔溴化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状胺化产物，其产率为79％。
Figure BDA0003579087180000151
所得产物的核磁波谱数据为：1H NMR(600MHz,CDCl3)δ7.27(d,J＝7.9Hz,2H),6.69(d,J＝7.8Hz,2H),4.56(s,2H),3.68(br,2H),2.58(t,J＝6.4Hz,2H),2.21(s,3H),2.16(s,3H),2.10(s,3H),1.87–1.71(m,2H),1.60–1.48(m,3H),1.47–1.34(m,4H),1.34–1.19(m,11H),1.20–1.10(m,6H),0.88-0.82(m,12H)；13C NMR(150MHz,CDCl3)δ148.2,147.8,146.3,129.7,128.0,126.1,122.8,117.5,115.0,74.9,74.0,40.1,39.4,37.5,37.4,37.3,32.8,32.7,31.4,28.0,24.8,24.5,23.9,22.8,22.7,21.1,20.7,19.8,19.7,13.0,12.1,11.9；HRMS(ESI)m/z C36H58NO2[M+H]+:理论值536.4462,实测值536.4463。
实施例32
本实施例中，用等摩尔4-溴苯硼酸酯替换实施例1中的溴苯，用等摩尔15N标记氯化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为87％。
Figure BDA0003579087180000152
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.65(d,J＝8.2Hz,2H),6.67(dd,J＝8.3Hz,2H),3.88(d,J＝55.6Hz,2H，15NH2),1.35(s,12H)；13C NMR(100MHz,CDCl3)δ149.40(d,J＝11.7Hz),136.43(d,J＝1.2Hz),114.08(d,J＝2.6Hz),83.3,24.7；HRMS(ESI)m/z C13H19B15N5O2[M+H]+:理论值221.1474,实测值221.1472。
实施例33
本实施例中，用等摩尔3-溴-4-甲基噻吩替换实施例1中的溴苯，用等摩尔15N标记氯化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为78％。
Figure BDA0003579087180000161
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.85–6.75(m,1H),6.16(d,J＝3.3Hz,1H),3.46(br,2H),2.11(s,3H)；13C NMR(100MHz,CDCl3)δ144.0(d,J＝9.8Hz),129.2(d,J＝3.1Hz),120.9(d,J＝1.2Hz),100.1(d,J＝3.0Hz),13.4；HRMS(APCI)m/zC5H8 15NS[M+H]+:理论值115.0342,实测值115.0347。
实施例34
本实施例中，用等摩尔溴代吉非罗齐甲酯替换实施例1中的溴苯，用等摩尔15N标记氯化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为83％。
Figure BDA0003579087180000162
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.55(s,1H),6.50(s,1H),3.89–3.81(m,2H),3.66(s,3H),3.30(br,2H),2.14(s,6H),1.65–1.71(m,4H),1.21(s,6H)；13C NMR(100MHz,CDCl3)δ178.4,150.3,137.78(d,J＝10.0Hz),125.5,120.5(d,J＝2.5Hz),118.2(d,J＝2.6Hz),115.0,69.3,51.8,42.2,37.2,25.5,25.3,17.4,15.8；HRMS(ESI)m/z C16H25 15NNaO3[M+Na]+:理论值303.1697,实测值303.1697。
实施例35
本实施例中，用等摩尔9-(4-溴苯基)咔唑替换实施例1中的溴苯，用等摩尔15N标记氯化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为79％。
Figure BDA0003579087180000163
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ8.12(d,J＝7.7Hz,2H),7.41–7.34(m,2H),7.32–7.28(m,3H),7.27–7.21(m,3H),6.83(d,J＝8.6Hz,2H),3.89(br,1H),3.72(br,1H)；13C NMR(100MHz,CDCl3)δ146.1(d,J＝11.5Hz),141.7,128.6(d,J＝1.3Hz),128.3,125.7,123.1,120.3,119.6,116.0(d,J＝2.9Hz),109.9；HRMS(ESI)m/zC18H15N15N[M+H]+:理论值260.1200,实测值260.1196。
实施例36
本实施例中，用等摩尔2-氯5-甲氧基溴苯替换实施例1中的溴苯，用等摩尔15N标记氯化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为87％。
Figure BDA0003579087180000171
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.12(d,J＝8.7Hz,1H),6.31(t,J＝2.4Hz,1H),6.27(dd,J＝8.7,2.8Hz,1H),4.03(d,J＝52.8Hz,2H,15NH2),3.74(s,3H)；13C NMR(100MHz,CDCl3)δ159.4,143.8(d,J＝13.5Hz),129.9,111.5,105.0,101.5(d,J＝2.9Hz),55.5；HRMS(ESI)m/z C7H9Cl15NO[M+H]+:理论值159.0338,实验值159.0342。
实施例37
本实施例中，用等摩尔氯雷他定替换实施例1中的溴苯，用等摩尔15N标记氯化铵替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为71％。
Figure BDA0003579087180000172
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ8.35(dd,J＝4.8,1.4Hz,1H),7.40(dd,J＝7.6,1.4Hz,1H),7.04(dd,J＝7.6,4.8Hz,1H),6.98–6.87(m,1H),6.48–6.45(m,2H),4.11(q,J＝7.1Hz,2H),3.78(br,2H),3.62(br,2H),3.38–3.23(m,2H),3.21–2.98(m,2H),2.86–2.64(m,2H),2.50–2.32(m,3H),2.31–2.16(m,1H),1.23(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ158.7,155.6,146.4,145.8(d,J＝11.0Hz),138.6,137.1,135.9,135.2,133.8,130.6,129.2,121.9,115.6(d,J＝2.7Hz),112.9(d,J＝2.5Hz),61.3,45.0,32.2,31.6,30.7,14.8；HRMS(ESI)m/z C22H26N2 15NO2[M+H]+:理论值365.1990,实验值365.1992。
实施例38
本实施例中，用等摩尔1-(4-氯苯基)-1-氰基环丁烷替换实施例1中的溴苯，等摩尔甲胺盐酸盐替换实施例1中的碳酸铵，等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为82％。
Figure BDA0003579087180000181
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.22(d,J＝8.6Hz,2H),6.61(d,J＝8.6Hz,2H),3.79(br,1H),2.84(s,3H),2.81–2.71(m,2H),2.62–2.51(m,2H),2.43--2.34(m,1H),2.10–1.97(m,1H)；13C NMR(100MHz,CDCl3)δ148.8,126.5,112.5,39.7,34.8,30.7,17.0；HRMS(ESI)m/z C12H15N2[M+H]+:理论值187.12330,实测值187.1234。
实施例39
本实施例中，用等摩尔4-氯苯乙酮替换实施例1中的溴苯，等摩尔甲胺盐酸盐替换实施例1中的碳酸铵，等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的深黄色油状物产物，其产率为88％。
Figure BDA0003579087180000182
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.82(d,J＝8.7Hz,2H),6.54(d,J＝8.5Hz,2H),4.49(br,1H),2.87(s,3H),2.49(s,3H)；13C NMR(100MHz,CDCl3)δ196.5,153.24,130.8,126.4,111.0,30.0,26.0；HRMS(ESI)m/z C9H12NO[M+H]+:理论值150.0913,实测值150.0915。
实施例40
本实施例中，用等摩尔4-氯苯硫醚替换实施例1中的溴苯，用等摩尔甲胺盐酸盐替换实施例1中的碳酸铵，等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为82％。
Figure BDA0003579087180000191
所得产物的核磁波谱数据为：1HNMR(400MHz,CDCl3)δ7.24(d,J＝8.5Hz,2H),6.56(d,J＝8.5Hz,2H),3.75(br,1H),2.83(s,3H),2.41(s,3H)；13C NMR(100MHz,CDCl3)δ148.4,131.8,124.2,113.1,30.9,19.5；HRMS(ESI)m/z C8H12NS[M+H]+:理论值154.0685,实测值154.0684.
实施例41
本实施例中，用等摩尔氯贝特替换实施例1中的溴苯，用等摩尔甲胺盐酸盐替换实施例1中的碳酸铵，等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为78％。
Figure BDA0003579087180000192
所得产物的核磁波谱数据为：1HNMR(400MHz,CDCl3)δ6.72(d,J＝8.9Hz,2H),6.43(d,J＝8.9Hz,2H),4.16(q,J＝7.1Hz,2H),2.72(s,3H),1.44(s,6H),1.22(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ174.5,146.7,145.3,122.3,112.8,79.7,61.2,31.2,25.3,14.1；HRMS(ESI)m/z C13H20NO3[M+H]+:理论值238.1438,实测值238.1439.
实施例43
本实施例中，用等摩尔4-溴联苯醚替换实施例1中的溴苯，用等摩尔甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为84％。
Figure BDA0003579087180000193
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.27(d,J＝7.9,2H),7.00(t,J＝7.4Hz,1H),6.91(d,J＝7.2,4H),6.65–6.56(m,2H),2.84(s,3H)；13C NMR(100MHz,CDCl3)δ159.2,147.6,146.0,129.5,121.9,121.3,117.1,113.4,31.2；HRMS(ESI)m/zC13H14NO[M+H]+:理论值200.1070,实测值200.1071。
实施例44
本实施例中，用等摩尔4-溴雌酚酮替换实施例1中的溴苯，用等摩尔甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的白色固体产物，其产率为73％。
Figure BDA0003579087180000201
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.10(d,J＝8.4Hz,1H),6.45(d,J＝8.4Hz,1H),6.36(s,1H),3.56(br,1H),2.89-2.80(m,2H),2.80(d,J＝4.1Hz,3H),2.53–2.42(m,1H),2.40-2.30(m,1H),2.26–1.89(m,5H),1.66–1.37(m,6H),0.89(s,3H)；13CNMR(100MHz,CDCl3)δ221.2,147.5,137.3,128.8,126.1,112.5,110.8,50.4,48.1,44.0,38.6,35.9,31.6,31.0,29.8,26.7,26.0,21.6,13.9；HRMS(ESI)m/z C19H26NO[M+H]+:理论值284.2009,实测值284.2009。
实施例45
本实施例中，用等摩尔4-环丙基溴苯替换实施例1中的溴苯，用等摩尔氘代甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的深黄色油状产物，其产率为85％。
Figure BDA0003579087180000202
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.93(d,J＝8.2Hz,1H),6.52(d,J＝8.4Hz,1H),3.38(s,1H),1.90–1.69(m,1H),0.83(dd,J＝5.5,2.9Hz,1H),0.57(d,J＝5.1Hz,1H)；13C NMR(100MHz,CDCl3)δ147.4,132.5,126.9,112.7,14.6,8.2；HRMS(ESI)m/z C17H25D3NO[M+H]+:理论值151.1309,实测值151.1312。
实施例46
本实施例中，用等摩尔6-溴-1,1,4,4-四甲基-1,2,3,4-四氢化萘替换实施例1中的溴苯，用等摩尔氘代甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为86％。
Figure BDA0003579087180000211
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.06(d,J＝8.5Hz,1H),6.46(s,1H),6.38(d,J＝8.4Hz,1H),3.22(br,1H),1.57(s,4H),1.19(s,6H),1.16(s,6H)；13CNMR(100MHz,CDCl3)δ147.0,145.7,134.1,127.4,111.0,110.1,35.5,35.4,34.4,33.6,32.1,31.9,17.4；HRMS(ESI)m/z C18H23D3NO[M+H]+:理论值275.2197,实测值275.2197。
实施例47
本实施例中，用等摩尔3-金刚烷-4-甲氧基溴苯替换实施例1中的溴苯，用等摩尔氘代甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为83％。
Figure BDA0003579087180000212
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.78(d,J＝8.6Hz,1H),6.55(d,J＝2.9Hz,1H),6.44(dd,J＝8.6,2.9Hz,1H),3.76(s,3H),3.12(br,1H),2.07(s,6H),2.05(s,3H),1.76(s,6H)；13C NMR(100MHz,CDCl3)δ151.6,143.4,139.8,113.5,112.8,109.5,55.9,40.7,37.2,37.0,29.2；HRMS(ESI)m/z C18H23D3NO[M+H]+:理论值275.2197,实测值275.2197。
实施例48
本实施例中，用等摩尔2-溴-4-甲基-6-氟吡啶替换实施例1中的溴苯，用等摩尔氘代甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为87％。
Figure BDA0003579087180000213
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.58(s,1H),6.08(s,1H),4.83(br,1H),2.20(s,3H)；13C NMR(100MHz,CDCl3)δ159.9,151.1,140.2,116.8,104.1,20.9；19F NMR(376MHz,CDCl3)δ-72.68(s,F)；HRMS(ESI)m/z C7H7D3FN2[M+H]+:理论值144.1011,实测值144.1015。
实施例49
本实施例中，用等摩尔10-(4-溴苯)-9,9-二甲基-9,10-二氢吖啶替换实施例1中的溴苯，用等摩尔氘代甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为84％。
Figure BDA0003579087180000221
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.41(dd,J＝7.7,1.5Hz,2H),7.12–7.03(m,2H),7.01–6.91(m,2H),6.87(td,J＝7.5,1.2Hz,2H),6.80–6.67(m,2H),6.38(dd,J＝8.2,1.1Hz,2H),3.64(br,1H),1.66(s,6H)；13C NMR(100MHz,CDCl3)δ149.0,141.7,131.8,130.4,130.0,126.4,125.2,120.3,114.3,114.0,36.0,31.4；HRMS(ESI)m/zC22H20D3N2[M+H]+:理论值318.2044,实测值318.2046。
实施例50
本实施例中，用等摩尔溴代吉非罗齐甲酯替换实施例1中的溴苯，用等摩尔氘代甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为84％。
Figure BDA0003579087180000222
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.53(s,1H),6.35(s,1H),3.77(s,2H),3.58(s,3H),2.77(br,1H),2.13(s,3H),2.02(s,3H),1.62(d,J＝2.7Hz,4H),1.13(s,6H)；13C NMR (100MHz,CDCl3)δ177.3,148.0,140.3,124.3,119.2,114.8,111.6,68.7,50.7,41.1,36.2,24.4,24.2,16.3,15.1；HRMS(ESI)m/z C17H25D3NO3[M+H]+:理论值297.2252,实测值297.2259。
实施例51
本实施例中，用等摩尔2-甲基-4-氯硼酸酯替换实施例1中的溴苯，用等摩尔乙胺盐酸盐替换实施例1中的碳酸铵，用等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的淡黄色固体产物，其产率为80％。
Figure BDA0003579087180000231
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.61(d,J＝7.9Hz,1H),6.38(s,2H),3.69(br,1H),3.17(q,J＝7.1Hz,2H),2.47(s,3H),1.30(s,12H)；13C NMR(100MHz,CDCl3)δ150.6,146.8,137.9,113.9,109.0,82.8,378.0,24.9,22.5,14.9；HRMS(ESI)m/zC15H25BNO2[M+H]+:理论值262.1973,实测值262.1975。
实施例52
本实施例中，用等摩尔4-氯苯基甲基砜替换实施例1中的溴苯，用等摩尔乙胺盐酸盐替换实施例1中的碳酸铵，用等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的淡黄色固体产物，其产率为84％。
Figure BDA0003579087180000232
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.66(d,J＝8.8Hz,2H),6.60(d,J＝8.8Hz,2H),4.52(br,1H),3.27–3.14(m,2H),3.00(s,3H),1.26(t,J＝7.2Hz,3H)；13CNMR(100MHz,CDCl3)δ152.5,129.2,126.5,111.6,45.1,37.8,14.4；HRMS(ESI)m/z C9H14NO2S[M+H]+:理论值200.0740,实测值200.0741。
实施例53
本实施例中，用等摩尔4-氯吡啶替换实施例1中的溴苯，用等摩尔二甲胺盐酸盐替换实施例1中的碳酸铵，用等摩尔氯化镍替换实施例1中的醋酸镍，其他步骤与实施例1相同，得到结构式如下的白色固体产物，其产率为80％。
Figure BDA0003579087180000233
所得产物的核磁波谱数据为：1H NMR(400MHz,MeOD)δ7.98(d,J＝3.7Hz,2H),6.66(t,J＝11.8Hz,2H),3.02(s,6H)；13C NMR(100MHz,CDCl3)δ1551,146.7,106.6,39.4；HRMS(ESI)m/z C7H11N2[M+H]+:理论值123.0917,实测值123.0918。
实施例54
本实施例中，用等摩尔4-溴苯并环丁烯替换实施例1中的溴苯，用等摩尔二甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为85％。
Figure BDA0003579087180000241
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.91(d,J＝8.1Hz,1H),6.61(d,J＝8.1Hz,1H),6.56(s,1H),3.09(s,4H),2.88(s,6H)；13C NMR(100MHz,CDCl3)δ151.0,146.3,134.0,123.0,112.4,108.4,41.6,29.2,28.7；HRMS(ESI)m/z C10H14N[M+H]+:理论值148.1121,实测值148.1120。
实施例55
本实施例中，用等摩尔4-溴三甲基苯硅烷替换实施例1中的溴苯，用等摩尔二甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为90％。
Figure BDA0003579087180000242
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ7.40(d,J＝8.7Hz,2H),6.74(d,J＝8.6Hz,2H),2.95(s,6H),0.23(s,9H),13C NMR(100MHz,CDCl3)δ151.8,135.2,126.5,112.9,41.1,0.0；HRMS(ESI)m/z C11H20NSi[M+H]+:理论值194.1360,实测值194.1365。
实施例56
本实施例中，用等摩尔6-溴-1,4-苯并恶烷替换实施例1中的溴苯，用等摩尔二甲胺盐酸盐替换实施例1中的碳酸铵，其他步骤与实施例1相同，得到结构式如下的黄色油状产物，其产率为88％。
Figure BDA0003579087180000251
所得产物的核磁波谱数据为：1H NMR(400MHz,CDCl3)δ6.76(d,J＝9.6Hz,1H),6.38–6.26(m,2H),4.27–4.21(m,2H),4.24–4.14(m,2H),2.84(s,6H)；13C NMR(100MHz,CDCl3)δ146.5,143.78,135.58,117.4,107.1,102.5,64.8,64.3,41.5；HRMS(ESI)m/zC10H14NO2[M+H]+:理论值180.1019,实测值180.1021。

Claims (7)

1.一种合成芳胺的方法，其特征在于：将式I化合物与铵盐、联吡啶、镍催化剂、有机碱加入有机溶剂中，在氩气氛围中光照反应，反应完后分离纯化产物，得到芳胺；其中，所述铵盐为碳酸铵或溴化铵时，所得芳胺的结构式如式II所示；所述铵盐为甲胺盐酸盐时，所得芳胺的结构式如式III所示；所述铵盐为乙胺盐酸盐时，所得芳胺的结构式如式IV所示；所述铵盐为二甲胺盐酸盐时，所得芳胺的结构式如式V所示；所述铵盐为15N标记氯化铵时，所得芳胺的结构式如式VI所示；所述铵盐为氘代甲胺盐酸盐时，所得芳胺的结构式如式VII所示；
Figure FDA0003579087170000011
式中，Ar代表芳基、取代芳基、杂环芳基、取代杂环芳基中任意一种；X代表Br或Cl。
2.根据权利要求1所述的合成芳胺的方法，其特征在于：所述铵盐的用量为式I化合物摩尔量的1.1～2.0倍。
3.根据权利要求1所述的合成芳胺的方法，其特征在于：所述联吡啶的用量为式I化合物摩尔量的5％～10％。
4.根据权利要求1所述的合成芳胺的方法，其特征在于：所述镍催化剂为醋酸镍或氯化镍，其用量为式I化合物摩尔量的5％～10％。
5.根据权利要求1所述的合成芳胺的方法，其特征在于：所述有机碱为1,8-二氮杂二环十一碳-7-烯、四甲基胍、7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯中任意一种，其用量为式I化合物摩尔量的2～3倍。
6.根据权利要求1所述的合成芳胺的方法，其特征在于：所述有机溶剂为二甲基亚砜、甲苯、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺中任意一种或者它们中任意一种与四氢呋喃的混合溶剂。
7.根据权利要求1所述的合成芳胺的方法，其特征在于：在氩气氛围中，在波长为390～415nm的紫色光照射下80～90℃反应24～36小时。
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