CN116063209A - 可见光促进镍催化苄基c-h键胺化制备苄胺衍生物的方法 - Google Patents
可见光促进镍催化苄基c-h键胺化制备苄胺衍生物的方法 Download PDFInfo
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- CN116063209A CN116063209A CN202310069883.0A CN202310069883A CN116063209A CN 116063209 A CN116063209 A CN 116063209A CN 202310069883 A CN202310069883 A CN 202310069883A CN 116063209 A CN116063209 A CN 116063209A
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- Prior art keywords
- benzyl
- reaction
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- amination
- bond
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- 238000000034 method Methods 0.000 title claims abstract description 41
- 238000005576 amination reaction Methods 0.000 title claims abstract description 38
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- 229910052759 nickel Inorganic materials 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 188
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- 239000000203 mixture Substances 0.000 claims abstract description 36
- 239000003446 ligand Substances 0.000 claims abstract description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
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- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
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- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical group C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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Abstract
本发明公开了可见光促进镍催化苄基C‑H键胺化制备苄胺衍生物的方法,属于可见光催化合成技术领域。该方法为将胺化试剂、钌或铱光敏剂、镍催化剂、路易斯酸、配体按摩尔比分别称取放入反应容器中,在惰性气体氛围下,加入溶剂,搅拌,加入含苄基烷基化物,在可见光光源照射下充分反应后,分离提纯得到苄胺衍生物。本发明使用的原料廉价易得,底物适用性较为广泛。此外,该方法反应条件温和、目标产物的收率高、污染小、反应操作和后处理过程简单,适合于工业化生产。
Description
技术领域
本发明属于可见光催化合成技术领域,具体涉及可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法。
背景技术
含有苄胺类结构的化合物是一类重要的有机化合物,在很多有生物活性的化合物及天然产物中都存在类似结构,特别是在医药方面有广泛应用(Richter,M.F.Nature 545,2017,299–304.)。通过在天然产物或生物活性分子中引入氮原子可以极大地改变分子的物化性质及生物学活性,例如首个具有广谱抗菌的青霉素衍生物氨苄西林(Ampicillin),是在青霉素(Penicillin G)结构中引入了苄胺结构后,抑菌活性显著提高,并可以同时抑制革兰氏阳性菌和革兰氏阴性菌(Acred,P.;Brown,D.M.;Turner,D.H.;Wilson,M.J.Br.J.Pharmacol.1962,18,356–369.)。除此之外,许多市售FDA批准的畅销药物中均含有苄胺基团,例如伊马替尼、氯吡格雷、舍曲林、多奈哌齐等(McGrath,N.A.;Brichacek,M.;Njardarson,J.T.J.Chem.Educ.2010,87,1348-1349)。因此,通过在复杂分子中直接选择性的引入苄胺基团可以加快生物活性分子的发现过程,并可以进一步促进对天然产物衍生候选药物的探索。
传统的苄胺结构的引入主要通过预先构建C-X键(X=氧、卤素等),实现预官能化后进行转化,但该方法不适用于一些复杂分子的后期修饰。另外通过过渡金属催化的氮宾插入反应被发现并可以应用到一系列C-H键的胺化反应中。其中,贵金属Ru是一类常用的催化剂,在配体的调控下可以实现苄位、三级和烯丙位的C-H键胺化反应,但是催化剂价格较为昂贵,且当体系中存在多个活性官能团时,化学选择性和位点选择性较差,产物难以分离。近年来,廉价金属催化的氮宾前体引发的C-H键直接胺化反应也得到了快速发展,钴、铜、铁以及锰等都用来作为催化剂并实现苄胺的合成,但一般需要特定的胺化试剂,或者加入过量氧化剂,不具备普遍适用性,难以广泛应用。
光催化反应是近年来国内外学者研究的热点主题。不仅由于光催化反应可以将光能转化为化学能,进而通过电子、原子或者能量转移来实现化学转变,并且光催化反应可以有效地避免氧化剂、过量的碱的使用并可以减少能源消耗及化学废物的产生,具有反应条件温和、原子经济性好,绿色无污染等优点。包明和于晓强开发了一种光/铁双催化的苄位C-H键胺化方法,但是该方法主要适用于二苯基甲烷类化合物的苄位胺化反应,底物适用范围受到了极大限制(Tang,J.-J.;Yu,X.;Wang,Y.;Yamamoto,Y.;Bao,M.Angew.Chem.Int.Ed.2021,60,16426-16435.)。
综上所述,目前公开的苄胺的合成方法存在诸多不足,如催化剂昂贵、反应选择性差、适用性低等不足,因此开发反应条件温和、使用范围广泛、反应步骤简易、原材料简单的合成方法非常重要。
发明内容
针对现有技术中存在的问题,本发明要解决的一个技术问题在于提供可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,该方法使用的原料廉价易得,底物适用性较为广泛;此外,该方法反应条件温和、目标产物的收率高、污染小、反应操作和后处理过程简单,适合于工业化生产。
为了解决上述问题,本发明所采用的技术方案如下:
可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,将胺化试剂、钌或铱光敏剂、镍催化剂、路易斯酸、配体按摩尔比分别称取放入反应容器中,在惰性气体氛围下,加入溶剂,搅拌混合均匀,加入含苄基烷基化物,在可见光光源照射下充分反应后,分离提纯得到苄胺衍生物;对于判断反应是否完成,可使用TLC(薄层色谱法)、LC(液相色谱)、GC(气相色谱,分子量小于300时)等方式追踪。
苄胺衍生物的结构通知式为:
上述反应式为:
其中,R1选自氢、C1-C4的烷基、烷氧基、芳基、卤素中的任意一种;
R2选自氢、C1-C6的烷基、芳基中的任意一种,其中,R3选自C1-C3的烷基、卤素中任意的一种;R4选自C1-C5的烷基、芳基中的任意一种。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,含苄基烷基化物、胺化试剂、钌或铱光敏剂、镍催化剂、路易斯酸和配体的摩尔比为1∶1-5∶0.05-0.5∶0.05-0.5∶1-3∶0.05-0.25;配体的添加量优选为催化量(即以苄基烷基化物为基准)的15%-25%,进一步优选为20%。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,可见光光源的波长为400-475nm。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,钌或铱光敏剂为Ru(bpy)3Cl2,Ru(bpy)3(PF6)2,Ir(ppy)3,Ir(ppy)2(dtbbpy)PF6,Ir[dF(CF3)ppy)]2(dtbbpy)PF6中的一种;
其化学结构式为:
其中Ru(bpy)3Cl2和Ru(bpy)3(PF6)2金属部分结构相同,仅配阴离子不同。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,路易斯酸为四氟硼酸或者三氟化硼乙醚配合物中的一种。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,镍催化剂为NiX2或者NiX2·dme,其中X为Cl、Br、I中的一种;NiX2·dme优选为溴化镍(II)乙二醇二甲基醚络合物(CAS:28923-39-9)。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,配体为联吡啶类配体或者菲啰啉类配体中的一种;
其化学结构式为:
R5、R7和R8分别独自选自氢、甲基、叔丁基、氟、氯、三氟甲基、氰基、甲酸酯基中的一种。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,所述溶剂为乙腈、二氯甲烷、1,2-二氯乙烷、四氢呋喃或N,N-二甲基甲酰胺中的任一种;惰性气体为氮气或氩气。
所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,采用柱层析、液相色谱提纯产物。
有益效果:与现有的技术相比,本发明的优点包括:
1、本发明使用含烷基化合物为起始物,原料易得、毒性低、成本低廉、种类多;
2、本发明所用胺化试剂,廉价易得、毒性较低、使用方便。
3、本发明反应位点为苄位,胺化试剂为叠氮类的,产物与现有技术不同,该方法不仅适用于苄位磺酰酰胺的合成,对苄位酯基胺同样适用。
4、本发明反应条件温和,反应时间短,目标产物的收率高,反应操作和后处理过程简单,适合于工业化生产。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂,下面结合具体实施例对本发明的具体实施方式做详细的说明。
实施例1
N-苄基对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加入甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率83%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.76(d,J=7.9Hz,2H),7.31(d,J=7.9Hz,2H),7.29–7.24(m,3H),7.26–7.16(m,2H),4.70(brs,1H),4.12(d,J=6.2Hz,2H),2.44(s,3H);13C NMR(101MHz,CDCl3)δ143.69,136.98,136.39,129.89,128.84,128.07,128.01,127.33,47.42,21.68。
实施例2
N-(4-氟苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、对氟甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对氟甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率72%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.74(d,J=8.0Hz,2H),7.31(d,J=8.0Hz,2H),7.17(dd,J=8.4,5.4Hz,2H),6.96(t,J=8.5Hz,2H),4.78(t,J=6.4Hz,1H),4.09(d,J=6.2Hz,2H),2.44(s,3H);13C NMR(101MHz,CDCl3)δ162.52(d,J=246.7Hz),143.79,136.97,132.24(d,J=3.6Hz),129.91,129.76(d,J=8.1Hz),127.29,115.70(d,J=21.7Hz),46.70,21.68。
实施例3
N-(4-氯苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、对氯甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对氯甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率71%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.73(d,J=8.1Hz,2H),7.30(d,J=8.1Hz,2H),7.24(d,J=8.5Hz,2H),7.13(d,J=8.5Hz,2H),4.82(t,J=6.4Hz,1H),4.09(d,J=6.3Hz,2H),2.44(s,3H);13C NMR(101MHz,CDCl3)δ143.84,136.92,134.99,133.90,129.92,129.35,128.95,127.28,46.71,21.68。
实施例4
N-(4-溴苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、对溴甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对溴甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率81%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.72(d,J=8.1Hz,2H),7.38(d,J=8.4Hz,2H),7.29(d,J=8.1Hz,2H),7.07(d,J=8.4Hz,2H),4.88(t,J=6.3Hz,1H),4.07(d,J=6.4Hz,2H),2.44(s,3H);13C NMR(101MHz,CDCl3)δ143.84,136.91,135.52,131.89,129.92,129.67,127.27,121.97,46.74,21.69。
实施例5
N-(2,4-二氟苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、2,4-二氟甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加2,4-二氟甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率76%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.70(d,J=8.1Hz,2H),7.27(d,J=8.1Hz,2H),7.25–7.20(m,1H),6.87–6.52(m,2H),4.84(t,J=6.5Hz,1H),4.17(d,J=6.5Hz,2H),2.42(s,3H);13C NMR(101MHz,CDCl3)δ162.78(dd,J=249.3,11.7Hz),160.84(dd,J=249.3,11.7Hz),143.75,137.00,131.21(dd,J=9.5,5.7Hz),129.82,127.20,119.78(dd,J=14.6,3.7Hz),111.53(dd,J=21.1,3.6Hz),103.96(t,J=25.4Hz),40.89(d,J=3.5Hz),21.63。
实施例6
N-(2-三氟甲基苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、邻甲三氟甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加邻甲基三氟甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率83%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.75(d,J=8.4Hz,2H),7.59(t,J=7.8Hz,2H),7.50(t,J=8.1Hz,1H),7.38(t,J=7.6Hz,1H).7.31(d,J=7.9Hz,2H),4.79(t,J=6.6Hz,1H),4.30(d,J=6.6Hz,2H),2.44(s,3H);13C NMR(101MHz,CDCl3)δ143.85,136.97,135.04,132.50,130.96,129.94,128.19(q,J=30.5Hz),128.16,127.24,127.23,126.13(q,J=5.4Hz),124.33(q,J=273.9Hz),43.89,21.69。
实施例7
N-(2-甲基苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、邻二甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加邻二甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率55%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.77(d,J=7.9Hz,2H),7.32(d,J=7.9Hz,2H),7.23–7.08(m,4H),4.44(t,J=6.0Hz,1H),4.09(d,J=5.9Hz,2H),2.45(s,3H),2.25(s,3H);13C NMR(101MHz,CDCl3)δ143.71,136.89,134.00,130.78,129.89,129.01,128.43,127.36,126.36,45.58,21.70,18.93。
实施例8
N-(4-甲基苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、对二甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对二甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率50%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.76(d,J=7.9Hz,2H),7.31(d,J=7.9Hz,2H),7.10–7.06(m,4H),4.57(t,J=6.1Hz,1H),4.07(d,J=6.0Hz,2H),2.44(s,3H),2.31(s,3H);13C NMR(101MHz,CDCl3)δ143.62,137.85,137.00,133.33,129.86,129.50,128.00,127.34,47.19,21.67,21.22。
实施例9
N-(4-苯基苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、4-甲基联苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加4-甲基联苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率49%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.77(d,J=7.9Hz,2H),7.59(d,J=7.8Hz,1H),7.54(d,J=7.6Hz,2H),7.50(d,J=7.9Hz,2H),7.43(t,J=7.7Hz,2H),7.36(d,J=7.3Hz,1H),7.31(d,J=8.1Hz,2H),7.26(d,J=7.3Hz,1H),4.75(brs,1H),4.17(d,J=5.9Hz,2H),2.43(s,3H);13C NMR(101MHz,CDCl3)δ143.71,141.07,140.64,135.39,129.90,128.95,128.47,127.61,127.55,127.47,127.35,127.23,127.18,47.15,21.68。
实施例10
N-(4-叔丁基苄基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、4-叔丁基甲苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加4-叔丁基甲苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率49%)。产物的分析数据如下:1H NMR(400MHz,CDCl3)δ7.75(d,J=7.9Hz,2H),7.29(d,J=7.9Hz,4H),7.11(d,J=7.9Hz,2H),4.64(t,J=6.6Hz,1H),4.09(d,J=6.0Hz,2H),2.43(s,3H),1.28(s,9H);13C NMR(101MHz,CDCl3)δ151.16,143.56,137.06,133.33,129.84,127.80,127.34,125.74,47.11,34.66,31.42,21.67。
实施例11
N-(1-苯基乙基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、乙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率74%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ1.43(d,3H,J=7.0Hz),2.39(s,3H),4.46(dq,1H,J=6.5,7.0Hz),4.69(d,1H,J=6.5Hz),7.07–7.13(m,2H),7.17–7.23(m,5H),7.61(dd,2H,J=1.6,6.8Hz);13C NMR(68MHz,CDCl3)δ21.5,23.5,53.5,125.9,126.8,127.3,128.3,129.2,137.3,141.7,142.9。
实施例12
N-((4-甲氧基苯基)乙基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、对乙基苯甲醚作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对乙基苯甲醚(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率85%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ1.39(d,3H,J=7.0Hz),2.39(s,3H),3.74(s,3H),4.40(dq,1H,J=7.0Hz),5.06(d,1H,J=7.0Hz),6.70(dd,2H,J=2.2,9.5Hz),7.00(dd,2H,J=2.2,9.5Hz),7.18(d,2H,J=8.4Hz),7.61(d,2H,J=8.4Hz);13C NMR(68MHz,CDCl3)δ21.5,23.5,53.1,55.2,113.7,127.0,127.2,129.3,134.0,137.5,142.8,158.6。
实施例13
N-((4-溴苯基)乙基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、对乙基苯甲醚作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对对溴乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率61%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ1.37(d,3H,J=6.8Hz),2.40(s,3H),4.41(dq,1H,J=7.0,6.8Hz),5.37(d,1H,J=7.0Hz),6.96(d,2H,J=8.6Hz),7.16(d,2H,J=8.1Hz),7.26(d,2H,J=8.1Hz),7.57(d,2H,J=8.6Hz);13C NMR(68MHz,CDCl3)δ21.5,23.4,53.1,121.0,126.9,127.8,129.3,131.3,137.2,140.9,143.2。
实施例14
N-(2-苯基-2-异丙基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、异丙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加对异丙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率70%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ1.61(s,6H),2.37(s,3H),5.38(s,1H),7.12–7.19(m,5H),7.25–7.31(m,2H),7.56(d,2H,J=8.6Hz);13C NMR(68MHz,CDCl3)δ21.5,29.8,58.5,125.4,126.8(2C),127.9,129.1,139.6,142.4,145.0。
实施例15
N-(1-苯基丁基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、异丙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加丁苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率73%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ0.82(t,3H,J=7.3Hz),1.12–1.28(m,2H),1.62–1.77(m,2H),2.34(s,3H),4.27(dt,1H,J=7.3Hz),5.06(d,1H,J=7.3Hz),6.98–7.02(m,2H),7.08–7.15(m,5H),7.53(d,2H,J=8.4Hz);13C NMR(68MHz,CDCl3)δ13.5,19.1,21.4,39.7,58.1,126.5,127.0,127.2,128.3,129.2,137.7,141.0,142.8。
实施例16
N-(1,2,3,4-四氢萘-1-基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、四氢萘作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加四氢萘(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率76%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ1.69–1.86(m,4H),2.46(s,3H),2.57–2.81(m,2H),4.41–4.47(m,1H),4.69(d,1H,J=7.6Hz),6.93(d,1H,J=7.6Hz),7.02–7.16(m,3H),7.34(d,2H,J=8.6Hz),7.82(d,2H,J=8.6Hz);13C NMR(68MHz,CDCl3)δ19.2,21.7,28.9,30.8,51.9,126.2,127.0,127.5,128.7,129.1,129.6,135.4,137.4,137.9,143.2。
实施例17
N-(1,2-二氢茚-1-基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、二氢茚作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加二氢茚(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率88%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ1.71–1.82(m,1H),2.29–2.40(m,1H),2.46(s,3H),2.71–2.80(m,1H),2.85–2.91(m,1H),4.66(d,1H,J=8.6Hz),4.82(dt,1H,J=8.6,7.3Hz),7.06–7.21(m,4H),7.34(d,2H,J=8.6Hz),7.84(d,2H,J=8.6Hz);13C NMR(68MHz,CDCl3)δ21.6,30.0,34.7,58.7,124.0,124.7,126.7,127.0,128.1,129.7,138.0,141.8,142.7,143.3。
实施例18
N-(二苯甲基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、二苯甲烷作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加二苯甲烷(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率96%)。产物的分析数据如下:1H NMR(270MHz,CDCl3)δ2.36(s,3H),5.25(br s,1H),5.56(d,1H,J=7.3Hz),6.81–7.49(m,12H),7.55(d,2H,J=6.5Hz);13C NMR(68MHz,CDCl3)δ21.5,61.4,127.1,127.3,127.4,128.4,129.2,137.3,140.4,143.0。
实施例19
N-(1,3-二氢苯并呋喃-1-基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、1,3-二氢苯并呋喃作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加1,3-二氢苯并呋喃(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率88%)。产物的分析数据如下:1HNMR(270MHz,CDCl3)δ2.45(s,3H),4.91(d,1H,J=12.7Hz),5.00(d,1H,J=12.7Hz),5.21(d,1H,J=10.3Hz),6.54(d,1H,J=10.3Hz),7.19–7.39(m,6H),7.86(d,2H,J=8.4Hz);13C NMR(68MHz,CDCl3)δ21.6,72.0,88.9,121.0,122.9,127.1,128.0,129.4,129.5,136.5,138.5,139.1,143.3。
实施例20
N-(异色满-1-基)对甲苯磺酰胺的合成
以对甲苯磺酰基叠氮、1,3-二氢苯并呋喃作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加1,3-二氢苯并呋喃(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率88%)。产物的分析数据如下:1HNMR(270MHz,CDCl3)δ2.45(s,3H),4.91(d,1H,J=12.7Hz),5.00(d,1H,J=12.7Hz),5.21(d,1H,J=10.3Hz),6.54(d,1H,J=10.3Hz),7.19–7.39(m,6H),7.86(d,2H,J=8.4Hz);13C NMR(68MHz,CDCl3)δ21.6,72.0,88.9,121.0,122.9,127.1,128.0,129.4,129.5,136.5,138.5,139.1,143.3。
实施例21
N-(1-苯基乙基)苯磺酰胺的合成
以苯磺酰基叠氮、乙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加入乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率66%)。产物的分析数据如下:1HNMR(600MHz,CDCl3):δ7.73(d,J=7.6Hz,2H),7.51-7.47(m,1H),7.40-7.36(m,2H),7.21-7.16(m,3H),7.11-7.06(m,2H),5.05(d,J=7.1Hz,1H),4.53-4.47(m,1H),1.44(d,J=6.8Hz,3H);13CNMR(150MHz,CDCl3):δ141.7,140.5,132.3,128.8,128.5,127.5,127.0,S6 126.0,53.7,23.6。
实施例22
N-(1-苯基乙基)对甲氧基苯磺酰胺的合成
以对甲氧基苯磺酰基叠氮、乙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),对甲氧基苯磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加入乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率66%)。产物的分析数据如下:1HNMR(600MHz,CDCl3):δ7.66(d,J=8.8Hz,2H),7.22-7.16(m,3H),7.13-7.09(m,2H),6.84(d,J=8.8Hz,2H),5.24(d,J=7.1Hz,1H),4.49-4.40(m,1H),3.83(s,3H),1.42(d,J=6.8Hz,3H);13CNMR(150MHz,CDCl3):δ162.5,142.0,132.1,129.1,128.4,127.3,126.1,113.9,55.5,53.6,23.6。
实施例23
N-(1-苯基乙基)甲磺酰胺的合成
以对甲磺酰基叠氮、乙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),甲磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加入乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率45%)。产物的分析数据如下:1HNMR(600MHz,CDCl3):δ7.40-7.33(m,4H),7.33-7.29(m,1H),4.98(d,J=6.3Hz,1H),4.69-4.60(m,1H),2.62(s,3H),1.55(d,J=7.1Hz,3H);13C NMR(150MHz,CDCl3):δ142.3,128.9,128.0,126.2,53.7,41.7,24.0。
实施例24
N-(1-苯基乙基)三氯乙氧基甲酰胺的合成
以对三氯乙氧基甲酰基叠氮、乙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),三氯乙氧基甲酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加入乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率45%)。产物的分析数据如下:1H NMR(600MHz,CDCl3):δ7.29(d,J=8.5Hz,2H),6.91(d,J=8.5Hz,2H),4.96(d,J=6.8Hz,1H),4.73-4.67(m,1H),4.46(d,J=10.8Hz,1H),4.43(d,J=10.8Hz,1H),3.81(s,3H),1.62(d,J=6.8Hz,3H);13C NMR(150MHz,CDCl3):δ159.4,133.3,127.5,114.3,93.3,78.0,55.3,54.4,22.6。
实施例25
N-(1-乙基)-1-噻吩磺酰胺的合成
以对三氯乙氧基磺酰基叠氮、乙苯作为原料,其反应步骤如下:
⑴在反应瓶中加入三(2-苯基吡啶)合铱(Ir(ppy)3,0.004mmol),二溴化镍(NiBr2·dme,0.04mmol),2,9-二甲基-1,10-菲啰啉(0.048mmol),噻吩磺酰基叠氮(0.4mmol),抽空换气三次,使反应瓶中处于惰性气体氛围;在惰性气体保护下,加入乙腈(1mL),逐滴加入三氟化硼乙醚配合物(0.2mmol),搅拌5分钟使反应体系混合均匀,加入乙苯(0.2mmol),在475nm蓝色LED灯照射下室温反应24h。
⑵TLC跟踪反应直至完全结束;
⑶反应结束后得到的粗产物经柱层析分离(乙酸乙酯:石油醚=1:20),得到目标产物(产率54%)。产物的分析数据如下:1HNMR(600MHz,CDCl3):δ7.49(d,J=4.9Hz,1H),7.42(d,J=3.7Hz,1H),7.25-7.18(m,3H),7.15(d,J=7.6Hz,2H),6.94(t,J=4.3Hz,1H),5.30(d,J=6.8Hz,1H),4.60-4.52(m,1H),1.48(d,J=6.8Hz,3H);13CNMR(150MHz,CDCl3):δ141.7,141.6,132.2,131.7,128.5,127.5,127.1,126.0,54.0,23.5。
Claims (10)
2.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,含苄基烷基化物、胺化试剂、钌或铱光敏剂、镍催化剂、路易斯酸和配体的摩尔比为1∶1-5∶0.05-0.5∶0.05-0.5∶1-3∶0.05-0.25。
4.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,可见光光源的波长为400-475nm。
5.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,钌或铱光敏剂为Ru(bpy)3Cl2,Ru(bpy)3(PF6)2,Ir(ppy)3,Ir(ppy)2(dtbbpy)PF6,Ir[dF(CF3)ppy)]2(dtbbpy)PF6中的一种。
6.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,路易斯酸为四氟硼酸或者三氟化硼乙醚配合物中的一种。
7.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,镍催化剂为NiX2或者NiX2·dme,其中X为Cl、Br、I中的一种。
8.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,所述配体为联吡啶类配体或者菲啰啉类配体中的一种。
9.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,所述溶剂为乙腈、二氯甲烷、1,2-二氯乙烷、四氢呋喃或N,N-二甲基甲酰胺中的任一种;惰性气体为氮气或氩气。
10.根据权利要求1所述可见光促进镍催化苄基C-H键胺化制备苄胺衍生物的方法,其特征在于,采用柱层析或液相色谱提纯产物。
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