CN105985256B - 一种合成α‑烷基芳乙酰胺的方法 - Google Patents

一种合成α‑烷基芳乙酰胺的方法 Download PDF

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CN105985256B
CN105985256B CN201510061148.0A CN201510061148A CN105985256B CN 105985256 B CN105985256 B CN 105985256B CN 201510061148 A CN201510061148 A CN 201510061148A CN 105985256 B CN105985256 B CN 105985256B
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acetamide
nmr
nitrile
alkyl virtue
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CN105985256A (zh
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李峰
陆磊
王娜娜
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Nanjing University of Science and Technology
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Abstract

本发明公开了一种合成α‑烷基芳乙酰胺的方法。在反应容器中，加入芳乙腈、化合物醇、过渡金属催化剂金属铑络合物、碱、膦配体和有机溶剂；反应混合物在微波反应器或者磁力搅拌下，130℃下反应后，冷却到室温，然后通过柱分离，得到目标化合物。本发明从腈和醇作为起始原料，在过渡金属催化剂,膦配体和碱的参与下，直接合成α‑烷基苯乙酰胺，反应展现出三个显著的优点：1)使用商品化或容易制备的腈和近于无毒的醇为起始原料；2)反应原子经济性高；因此，该反应符合绿色化学的要求，具有广阔的发展前景。

Description

一种合成α-烷基芳乙酰胺的方法
技术领域
本发明属有机合成化学技术领域，具体涉及一种合成α-烷基芳乙酰胺的方法。
背景技术
α-烷基芳乙酰胺是一类独特的结构单元,它广泛地出现在天然产物和药物活性分子中(a)A.M.Aronov.M.A.Murcko,J.Med.Chem.2004,47,5616-5619；b)P.Pevarello,M.G.Brasca,P.Orsini,G.Traquandi,A.Longo,M.Nesi,F.Orzi,C.Piutti,P.Sansonna,M.Varasi,A.Cameron,A.Vulpetti,F.Roletto,R.Alzani,M.Ciomei,C.Albanese,W.Pastori,A.Marsiglio,E.Pesenti,F.Fiorentini,J.R.Bischoff,C.Mercurio,J.Med.Chem.2005,48,2944-2956；c)J.B.Thomas,L.Zhang,H.A.Navarro,F.I.Carroll,J.Med.Chem.2006,49,5597-5609；d)N.Mahindroo,M.C.Connelly,C.Punchihewa,H.Kimura,M.P.Smeltzer,S.Wu,N.Fujii,J.Med.Chem.2009,52,4277-4287；d)Y.Cheung,H.Yu,K.Xu,B.Zou,M.Wu,O.B.McManus,M.Li,C.W.Lindsley,C.R.Hopkins,J.Med.Chem.2012,55,6975-6979；e)J.A.Pfefferkorn,A.Guzman-Perez,J.Litchfield,R.Aiello,J.L.Treadway,J.Pettersen,M.L.Minich,K.J.Filipski,C.S.Jones,M.Tu,G.Aspnes,H.Risley,J.Bian,B.D.Stevens,P.Bourassa,T.D’Aquila,L.Baker,N.Barucci,A.S.Robertson,F.Bourbonais,D.R.Derksen,M.MacDougall,O.Cabrera,J.Chen,A.L.Lapworth,J.A.Landro,W.J.Zavadoski,K.Atkinson,N.Haddish-Berhane,B.Tan,L.Yao,R.E.Kosa,M.V.Varma,B.Feng,D.B.Duignan,A.El-Kattan,S.Murdande,S.Liu,M.Ammirati,J.Knafels,P.DaSilva-Jardine,L.Sweet,S.Liras,T.P.Rolph,J.Med.Chem.2012,55,1318-1333；f)R.Sarabu,F.T.Bizzarro,W.L.Corbett,M.T.Dvorozniak,W.Geng,J.F.Grippo,N.Haynes,S.Hutchings,L.Garofalo,K.R.Guertin,D.W.Hilliard,M.Kabat,R.F.Kester,W.Ka,Z.Liang,P.E.Mahaney,L.Marcus,F.M.Matschinsky,D.Moore,J.Racha,R.Radinov,Y.Ren,L.Qi,M.Pignatello,C.L.Spence,T.Steele,J.Tengi,J.Med.Chem.2012,55,7021-7036)
这类化合物也是构建生物活性分子的关键性中间体.(a)P.L.Ornstein,D.M.Zimmerman,M.B.Arnold,T.J.Bleisch,B.Cantrell,R.Simon,H.Zarrinmayeh,S.R.Baker,M.Gates,J.P.Tizzano,D.Bleakman,J.Med.Chem.2000,43,4354-4358；b)N.Haynes,W.L.Corbett,F.T.Bizzarro,K.R.Guertin,D.W.Hilliard,G.W.Holland,R.F.Kester,P.E. Mahaney,L.Qi,C.L.Spence,J.Tengi,M.T.Dvorozniak,A.Railkar,F.M.Matschinsky,J.F.Grippo,J.Grimsby,R.Sarabu,J.Med.Chem.2010,53,3618-3625)
传统的合成方法需要从芳乙酸或芳乙酸酯作为起始原料,经过多步反应才能合成,在这个过程中要使用大量有毒的试剂和产生大量有害的副产物(见上面的参考文献).因此,从有机合成和环境的角度,发展一种环境友好的新合成方法具有重要的意义。
发明内容
本发明的目的在于提供一种合成α-烷基芳乙酰胺的新方法。
本发明通过下述技术方案实现：一种合成α-烷基芳乙酰胺(式Ⅰ)的方法，
通过芳乙腈(式Ⅱ)
与化合物醇(式IV)反应
反应是在过渡金属催化剂、膦配体和碱的参与下发生，其反应通式为
其中，Ar选自芳基、单或多取代芳基，单或多取代芳基优选甲基苯基、甲氧基苯基、三氟甲基苯基、三氟甲氧基苯基、卤代苯基或萘基；
R代表一个取代基，选自芳基、单或多取代芳基，单或多取代芳基优选甲基苯基、异丙基苯基、甲氧基苯基、三氟甲氧基苯基、卤代苯基或萘基。
本发明合成α-烷基苯乙酰胺的新方法通过下述具体步骤实现：
在反应容器中，加入芳乙腈、化合物醇、过渡金属催化剂金属铑络合物、碱、膦配体和有机溶剂；反应混合物在微波反应器或者磁力搅拌下，130℃下反应后，冷却到室温，然后通过柱分离，得到目标化合物。
步骤中所述的金属铑络合物为[Rh(cod)Cl]2，其用量为腈的1mol％；膦配体为三苯基膦，其用量为腈的10mol％；碱为氢氧化钾，其用量为腈的40mol％；化合物醇的用量为腈的1.1-2equiv.
同现有技术相比，本发明从腈和醇作为起始原料，在过渡金属催化剂,膦配体和碱的参与下，直接合成α-烷基苯乙酰胺，反应展现出三个显著的优点：1)使用商品化或容易制备的腈和近于无毒的醇为起始原料；2)反应原子经济性高；因此，该反应符合绿色化学的要求，具有广阔的发展前景。
具体实施方式
展示一下实例来说明本发明的某些实施例，且不应解释为限制本发明的范围。对本发明公开的内容可以同时从材料，方法和反应条件上进行许多改进，变化和改变。所有这些改进，变化和改变均确定地落入本发明的精神和范围之内。
实施例1:2,3-二苯基丙酰胺
2,3-diphenylpropanamide
将氰化苄(117mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：90％。
1H NMR(500MHz,CDCl3)δ7.33-7.24(m,5H,ArH),7.21(t,J＝7.3Hz,2H,ArH),7.15(t,J＝7.3Hz,1H,ArH),7.10(d,J＝7.8Hz,2H,ArH),5.37(br s,1H,NH),5.30(br s,1H,NH),3.64(t,J＝7.5Hz,1H,CH),3.54(dd,J＝13.6Hz and 7.6Hz,1H,CH),2.99(dd,J＝13.7Hz and 7.9Hz,1H,CH)；13C NMR(125MHz,CDCl3)δ175.4,139.4,139.3,128.9,128.6,128.2,127.9,127.3,126.1,54.5,39.2.
实施例2:2-苯基-3-(4-甲基苯基)丙酰胺
2-phenyl-3-p-tolylpropanamide
将氰化苄(117mg,1mmol),4-甲基苯甲醇(134mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22.mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：85％。
1H NMR(500MHz,CDCl3)δ7.33-7.24(m,5H,ArH),7.03-6.99(m,4H,ArH),5.33(brs,1H,NH),5.29(br s,1H,NH),3.62(t,J＝7.6Hz,1H,CH),3.49(dd,J＝13.6Hz and 7.5Hz,1H,CH),2.96(dd,J＝13.6Hz and 7.2Hz,1H,CH),2.28(s,3H,CH3)；13C NMR(125MHz,CDCl3)δ175.4,139.4,136.3,135.6,128.9,128.8,128.7,128.0,127.3,54.8,38.9,21.0.
实施例3:2-苯基-3-(2-甲基苯基)丙酰胺
2-phenyl-3-o-tolylpropanamide
将氰化苄(117mg,1mmol),2-甲基苯甲醇(134mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：82％。
1H NMR(500MHz,CDCl3)δ7.32-7.26(m,5H,ArH),7.11-7.00(m,4H,ArH),5.37(brs,1H,NH),5.29(br s,1H,NH),3.62(t,J＝7.2Hz,1H,CH),3.54(dd,J＝13.9Hz and 7.5Hz,1H,CH),2.99(dd,J＝13.9Hz and 7.2Hz,1H,CH),2.25(s,3H,CH3)；13C NMR(125MHz,CDCl3)δ175.2,139.6,137.6,136.2,130.2,129.6,128.7,128.0,127.4,126.3,125.8,53.4,36.5,19.4；HRMS-EI(70eV)m/z calcd for C16H17NONa[M+Na]+262.1208,found162.1204.
实施例4:2-苯基-3-(4-异丙基苯基)丙酰胺
3-(4-isopropylphenyl)-2-phenylpropanamide
将氰化苄(117mg,1mmol),4-异丙基苯甲醇(165mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10mL微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：80％。
1H NMR(500MHz,CDCl3)δ7.34-7.25(m,5H,ArH),7.09-7.04(m,4H,ArH),5.29(brs,2H,NH2),3.63(t,J＝7.5Hz,1H,CH),3.42(dd,J＝13.8Hz and 8.1Hz,1H,CH),2.96(dd,J＝13.9Hz and 6.9Hz,1H,CH),2.84(sept,J＝6.9Hz,1H,CH),1.21(d,J＝6.9Hz,6H,2xCH3)；13C NMR(125MHz,CDCl3)δ175.2,146.7,139.6,136.8,128.8,128.8,128.0,127.4,126.3,54.8,38.9,33.6,24.0；HRMS-EI(70eV)m/z calcd for C18H21NONa[M+Na]+290.1521,found 290.1529.
实施例5:2-苯基-3-(4-甲氧基苯基)丙酰胺
3-(4-methoxyphenyl)-2-phenylpropanamide
将氰化苄(117mg,1mmol),4-甲氧基苯甲醇(152mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：83％。
1H NMR(500MHz,DMSO-d6)δ7.41(br s,1H,NH),7.35(d,J＝7.6Hz,1H,ArH),7.28(t,J＝7.4Hz,2H,ArH),7.20(t,J＝7.1Hz,1H,ArH),7.08(d,J＝8.1Hz,2H,ArH),6.79-6.77(m,3H,2xArH and NH),3.70-3.67(m,4H,CH and CH3),3.22(dd,J＝13.4Hz and 9.8Hz,1H,CH2),2.77(dd,J＝13.6Hz and 5.9Hz,1H,CH2)；13C NMR(125MHz,DMSO-d6)δ174.0,157.5,140.8,131.8,129.8,128.1,127.7,126.6,113.5,54.9,53.1,37.8；HRMS-EI(70eV)m/z calcd for C16H17NO2Na[M+Na]+278.1157,found 278.1170.
实施例6:2-苯基-3-(4-氟苯基)丙酰胺
3-(4-fluorophenyl)-2-phenylpropanamide
将氰化苄(117mg,1mmol),4-氟苯甲醇(139mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26.2mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合 物，产率：88％。
1H NMR(500MHz,CDCl3)δ7.33-7.25(m,5H,ArH),7.03(t,J＝6.7Hz,2H,ArH),6.89(t,J＝8.5Hz,2H,ArH),5.39(br s,1H,NH),5.30(br s,1H,NH),3.59(t,J＝7.4Hz,1H,CH),3.50(dd,J＝13.7Hz and 7.5Hz,1H,CH),2.96(dd,J＝13.6Hz and 7.6Hz,1H,CH)；13C NMR(125MHz,CDCl3)δ175.0,161.4(d,JC-F＝243.2Hz),139.1,135.1,130.4(d,JC-F＝7.7Hz),128.8,128.0,127.5,115.0(d,JC-F＝20.8Hz),54.9,38.5.
实施例7:2-苯基-3-(4-氯苯基)丙酰胺
3-(4-chlorophenyl)-2-phenylpropanamide
将氰化苄(117mg,1mmol),4-氯苯甲醇(157mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：81％。
1H NMR(500MHz,DMSO-d6)δ7.43(br s,1H,NH),7.35(d,J＝7.6Hz,2H,ArH),7.30-7.27(m,4H,ArH),7.22-7.18(m,3H,ArH),6.81(br s,1H,NH),3.71(dd,J＝9.1Hz and6.3Hz,1H,CH),3.26(dd,J＝13.6Hz and 9.3Hz,1H,CH2),2.85(dd,J＝13.6Hz and6.2Hz,1H,CH2)；13C NMR(125MHz,DMSO-d6)δ173.7,140.5,139.0,130.7,130.6,128.2,128.0,127.7,126.7,52.6,37.9.HRMS-EI(70eV)m/z calcd for C15H14NOClNa[M+Na]+282.0662,found 282.0658.
实施例8:2-苯基-3-(2-氯苯基)丙酰胺
3-(2-chlorophenyl)-2-phenylpropanamide
将氰化苄(117mg,1mmol),2-氯苯甲醇(157mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：88％。
1H NMR(500MHz,DMSO-d6)δ7.47(br s,1H,NH),7.40(d,J＝7.1Hz,1H,ArH),7.35(d,J＝7.4Hz,2H,ArH),7.29(t,J＝7.33Hz,2H,ArH),7.23-7.20(m,4H,ArH),6.84(br s,1H,NH),3.82(t,J＝7.3Hz,1H,CH),3.35(m,1H,CH),2.96(dd,J＝13.6Hz and 5.4Hz,1H,CH)；13C NMR(125MHz,DMSO-d6)δ173.5,140.7,137.2,133.3,131.3,129.2,128.3,128.1,127.6,126.9,126.8,50.6,36.4；HRMS-EI(70eV)m/z calcd for C15H14NONaCl[M+Na]+282.0662,found 282.0664.
实施例9:2-苯基-3-(4-三氟甲基苯基)丙酰胺
2-phenyl-3-(4-(trifluoromethoxy)phenyl)propanamide
将氰化苄(117mg,1mmol),4-三氟甲氧基苯甲醇(211mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22.44mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：91％。
1H NMR(500MHz,CDCl3)δ7.34-7.25(m,5H,ArH),7.10(d,J＝8.7Hz,2H,ArH),7.05(d, J＝8.2Hz,2H,ArH),5.36(br s,1H,NH),5.30(br s,1H,NH),3.60(t,J＝7.3Hz,1H,CH),3.54(dd,J＝13.4Hz and 7.4Hz,1H,CH),2.98(dd,J＝13.5Hz and 7.3Hz,1H,CH)；13CNMR(125MHz,CDCl3)δ174.6,147.7,139.0,138.2,130.3,128.9,128.0,127.7,120.8,120.4(q,JC-F＝255.5Hz),54.7,38.6；HRMS-EI(70eV)m/z calcd for C16H14NO2F3Na[M+Na]+332.0874,found 332.0878.
实施例10:2-苯基-3-(1-萘基)丙酰胺
3-(naphthalen-1-yl)-2-phenylpropanamide
将氰化苄(117mg,1mmol),1-萘甲醇(174mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：87％。
1H NMR(500MHz,CDCl3)δ8.06(d,J＝8.1Hz,1H,ArH),7.86(d,J＝7.6Hz,1H,ArH),7.69(d,J＝8.1Hz,1H,ArH),7.51(m,2H,ArH),7.32-7.26(m,6H,ArH),7.17(d,J＝6.7Hz,1H,ArH),5.27(br s,1H,NH),5.21(br s,1H,NH),4.06(dd,J＝13.8Hz and 7.5Hz,1H,CH2),3.82(t,J＝7.0Hz,1H,CH),3.42(dd,J＝14.0Hz and 6.7Hz,1H,CH2)；13C NMR(125MHz,CDCl3)δ175.0,139.7,135.3,133.9,131.6,128.9,128.8,127.9,127.5,127.4,127.1,126.0,125.4,123.4,53.5,36.5；HRMS-EI(70eV)m/z calcd for C19H17NONa[M+Na]+298.1208,found 298.1201.
实施例11:2-苯基-3-(2-二茂铁基)丙酰胺
2-phenyl-3(Ferrocenemethyl-2-yl)propanmide
将氰化苄(117mg,1mmol),二茂铁甲醇(238mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：79％。
1H NMR(500MHz,CDCl3)δ7.32(t,J＝7.3Hz,2H,ArH),7.27-7.25(m,3H,ArH),5.26(br s,2H,NH),4.10(br s,1H,ferrocene H),4.08(s,5H,ferrocene H),4.01(br s,1H,ferrocene H),3.95(br s,1H,ferrocene H),3.78(br s,1H,ferrocene H),3.43(t,J＝7.17Hz,1H,CH),3.28(dd,J＝7.25Hz and 7.3Hz,1H,CH2),2.77(dd,J＝7.3Hz and7.45Hz,1H,CH2)；13C NMR(125MHz,CDCl3)δ175.28,139.69,128.74,127.75,127.35,85.89,68.85,68.78,68.55,67.43,67.29,55.28,33.93.
实施例12:2-苯基己酰胺
2-phenylhexanamide
将氰化苄(117mg,1mmol),正丁醇(148mg,2mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：74％。
1H NMR(500MHz,CDCl3)δ7.36-7.26(m,5H,ArH),5.41(br s,1H,NH),5.34(br s,1H,NH),3.37(t,J＝7.3Hz,1H,CH),2.19-2.11(m,1H,CH),1.82-1.75(m,1H,CH),1.38-1.13(m,4H,2×CH2),0.86(t,J＝7.1Hz,3H,CH3)；13C NMR(125MHz,CDCl3)δ176.4,140.0,128.8,127.9,127.2,52.8,32.6,29.8,22.5,13.9.
实施例13:2-苯基辛酰胺
2-phenyloctanamide
将氰化苄(117mg,1mmol),正辛醇(204mg,2mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：76％。
1H NMR(500MHz,CDCl3)δ7.36-7.27(m,5H,ArH),5.40(br s,1H,NH),5.34(br s,1H,NH),3.37(t,J＝7.6Hz,1H,CH),2.18-2.11(m,1H,CH2),1.81-1.74(m,1H,CH2),1.35-1.14(m,8H,4×CH2),0.85(t,J＝7.0Hz,3H,CH3)；13C NMR(125MHz,CDCl3)δ176.3,140.0,128.8,127.9,127.2,52.8,32.9,31.6,29.1,27.6,22.5,14.0；HRMS-EI(70eV)m/z calcdfor C14H21NONa[M+Na]+242.1521,found 242.1527.
实施例14:3-苯基-2-(4-甲基苯基)丙酰胺
3-phenyl-2-(p-tolyl)propanamide
将4-甲基苯乙腈(131mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标 化合物，产率：83％。
1H NMR(500MHz,CDCl3)δ7.21(t,J＝7.32Hz,2H,ArH),7.17-7.14(m,3H,ArH),7.11(t,J＝6.90Hz,4H,ArH),5.26(br s,2H,NH2),3.91(t,J＝7.32Hz,1H,CH),3.53(dd,J＝7.35Hz and 7.30Hz,1H,CH),2.98(dd,J＝7.30Hz and 7.90Hz,1H,CH),2.32(s,3H,CH3)；13C NMR(125MHz,CDCl3)δ175.41,139.59,137.06,136.33,129.44,128.93,128.20,127.83,126.12,54.31,39.23,21.01.
实施例15:3-苯基-2-(2-甲基苯基)丙酰胺
3-phenyl-2-o-tolylpropanamide
将2-甲基苯乙腈(131mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：84％。
1H NMR(500MHz,CDCl3)δ7.39(d,J＝7.5Hz,1H,ArH),7.26-7.11(m,6H,ArH),7.07(d,J＝7.1Hz,2H,ArH),5.34(br s,1H,NH),5.20(br s,1H,NH),3.91(t,J＝7.3Hz,1H,CH),3.57(dd,J＝13.7Hz and 6.7Hz,1H,CH),2.96(dd,J＝13.6Hz and 7.9Hz,1H,CH),2.16(s,3H,CH3)；13C NMR(125MHz,CDCl3)δ175.4,139.6,137.6,136.1,130.6,128.9,128.2,127.5,127.3,126.6,126.2,50.4,38.8,19.6.HRMS-EI(70eV)m/z calcd for C16H17NONa[M+Na]+262.1208,found 262.1206.
实施例16:3-苯基-2-(4-甲氧基苯基)丙酰胺
2-(4-methoxyphenyl)-3-phenylpropanamide
将4-甲氧基苯乙腈(147mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：80％。
1H NMR(500MHz,CDCl3)δ7.22-7.08(m,5H,ArH),7.09(d,J＝7.8Hz,2H,ArH),6.84(d,J＝8.5Hz,2H,ArH),5.38(br s,1H,NH),5.30(br s,1H,NH),3.79(s,3H,OCH3),3.59(t,J＝7.4Hz,1H,CH),3.51(dd,J＝13.6Hz and 7.4Hz,1H,CH),2.96(dd,J＝13.6Hz and7.7Hz,1H,CH)；13C NMR(125MHz,CDCl3)δ175.6,158.8,139.6,131.4,129.1,129.0,128.2,126.1,114.1,55.2,53.9,39.4.
实施例17:3-苯基-2-(3,4-二甲氧基甲基)丙酰胺
2-(3,4-dimethoxyphenyl)-3-phenylpropanamide
将3,4-二甲氧基苯乙腈(177mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：91％。
1H NMR(500MHz,CDCl3)δ7.22(t,J＝7.3Hz,2H,ArH),7.16(t,J＝7.3Hz,1H,ArH),7.09(d,J＝7.0Hz,2H,ArH),6.79-6.78(m,3H,ArH),5.31(br s,2H,NH2),3.86(s,3H,OCH3),3.84(s,3H,OCH3),3.58(t,J＝7.4Hz,1H,CH),3.50(dd,J＝13.8Hz and 7.3Hz, 1H,CH),2.98(dd,J＝13.6Hz and 7.6Hz,1H,CH)；13C NMR(125MHz,CDCl3)δ175.4,149.0,148.3,139.5,131.8,129.0,128.2,126.2,120.3,111.1,110.9,55.83,55.80,54.3,39.4；HRMS-EI(70eV)m/z calcd for C17H19NO3Na[M+Na]+308.1263,found 308.1269.
实施例18:3-苯基-2-(4-氟苯基)丙酰胺
2-(4-fluorophenyl)-3-phenylpropanamide
将4-氟苯乙腈(135mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：92％。
1H NMR(500MHz,CDCl3)δ7.26-7.21(m,4H,ArH),7.17(t,J＝7.2Hz,1H,ArH),7.08(d,J＝7.1Hz,2H,ArH),7.00(t,J＝8.6Hz,2H,ArH),5.39(br s,1H,NH),5.29(br s,1H,NH),3.61(t,J＝7.6Hz,1H,CH),3.49(dd,J＝13.7Hz and 7.6Hz,1H,CH),2.96(dd,J＝13.6Hz and 7.6Hz,1H,CH)；13C NMR(125MHz,CDCl3)δ174.9,162.1(d,JC-F＝244.7Hz),139.1,135.0,129.6(d,JC-F＝8.1Hz),128.9,128.3,126.4,115.6(d,JC-F＝21.2Hz),54.0,39.6；HRMS-EI(70eV)m/z calcd for C15H14NOFNa[M+Na]+266.0957,found 266.0956.
实施例19:3-苯基-2-(3-氟苯基)丙酰胺
2-(3-fluorophenyl)-3-phenylpropanamide
将3-氟苯乙腈(135mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：89％。
1H NMR(500MHz,DMSO-d6)δ7.47(br s,1H,NH),7.35-7.15(m,8H,ArH),7.04(t,J＝7.9Hz,1H,ArH),6.86(br s,1H,NH),3.79(t,J＝7.1Hz,1H,CH),3.27(dd,J＝13.5Hzand9.8Hz,1H,CH),2.86(dd,J＝13.3Hz and 5.9Hz,1H,CH)；13C NMR(125MHz,DMSO-d6)δ173.5,162.0(d,JC-F＝241.6Hz),143.5(d,JC-F＝7.2Hz),139.6,130.0(d,JC-F＝8.2Hz),128.8,128.1,126.0,124.0,114.5(d,JC-F＝20.8Hz),113.4(d,JC-F＝20.8Hz),52.4,38.5；HRMS-EI(70eV)m/z calcd for C15H14NOFNa[M+Na]+266.0957,found 266.0952.
实施例20:3-苯基-2-(4-氯苯基)丙酰胺
2-(4-chlorophenyl)-3-phenylpropanamide
将4-氯苯乙腈(152mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：83％。
1H NMR(500MHz,DMSO-d6)δ7.47-7.16(m,10H,9xArH and NH),6.86(br s,1H,NH),3.76(br s,1H,CH),3.27(br s,1H,CH),2.85(br s,1H,CH)；13C NMR(125MHz,DMSO-d6)δ173.6,139.6,131.3,129.6,128.8,128.1,127.7,126.6,126.0,52.0,38.5；HRMS-EI(70eV)m/z calcd for C15H14NOClNa[M+Na]+282.0662,found 282.0652.
实施例21:3-苯基-2-(3-三氟甲基苯基)丙酰胺
3-phenyl-2-(3-(trifluoromethyl)phenyl)propanamide
将3-三氟甲基苯乙腈(185mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：84％。
1H NMR(500MHz,DMSO-d6)δ7.68-7.54(m,5H,4xArH and NH),7.22-7.18(m,5H,ArH),6.91(br s,1H,NH),3.89(br s,1H,CH),3.35(br s,1H,CH),2.89(br s,1H,CH)；13CNMR(125MHz,DMSO-d6)δ173.3,142.0,139.5,131.9,129.2,128.9(q,JC-F＝30.8Hz),128.8,128.1,126.1,124.3(q,JC-F＝271.0Hz),124.2,123.4,52.4,38.5；HRMS-EI(70eV)m/zcalcd for C16H14NOF3Na[M+Na]+316.0925,found 316.0929.
实施例22:3-苯基-2-(4-三氟甲氧基苯基)丙酰胺
3-phenyl-2-(4-(trifluoromethoxy)phenyl)propanamide
将4-三氟甲氧基苯乙腈(201mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26.2mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：90％。
1H NMR(500MHz,DMSO-d6)δ7.49-7.17(m,10H,9xArH and NH),6.87(br s,1H,NH),3.82(br s,1H,CH),3.30(br s,1H,CH),2.85(d,J＝7.9Hz,1H,CH)；13C NMR(125MHz, DMSO-d6)δ173.6,147.1,140.1,139.7,129.5,128.8,128.1,126.0,120.8,120.1(q,JC-F＝254.4Hz),52.0,38.6；HRMS-EI(70eV)m/z calcd for C16H14NO2F3Na[M+Na]+332.0874,found 332.0867.
实施例23:3-苯基-2-(1-萘基)丙酰胺
2-(naphthalen-1-yl)-3-phenylpropanamide
将1-萘乙腈(167mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26.2mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：82％。
1H NMR(500MHz,CDCl3)δ8.07(d,J＝5.2Hz,1H,ArH),7.89-7.78(m,2H,ArH),7.53-7.43(m,4H,ArH),7.26-7.13(m,5H,ArH),5.27(m,2H,NH2),4.40(br s,1H,CH),3.74(br s,1H,CH),3.18(br s,1H,CH)；13C NMR(125MHz,CDCl3)δ175.2,139.9,135.2,134.1,131.2,129.2,128.9,128.3,128.2,126.6,126.2,126.1,125.8,125.6,123.0,51.0,38.4；HRMS-EI(70eV)m/z calcd for C19H17NONa[M+Na]+298.1208,found 298.1207.
实施例24:3-苯基-2-(2-萘基)丙酰胺
2-(naphthalen-2-yl)-3-phenylpropanamide
将2-萘乙腈(167mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到10ml微波反应管中。混合物在130℃下反应2小时后，冷却到室温。 旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：88％。
1H NMR(500MHz,CDCl3)δ7.82-7.70(m,4H,ArH),7.48-7.44(m,3H,ArH),7.26-7.12(m,5H,ArH),5.41(br s,1H,NH),5.34(br s,1H,NH),3.81(t,J＝7.0Hz,1H,CH),3.63(dd,J＝13.5Hz and 7.5Hz,1H,CH),3.10(dd,J＝13.4Hz and 7.5Hz,1H,CH)；13C NMR(125MHz,CDCl3)δ175.0,139.4,136.8,133.4,132.6,129.0,128.6,128.3,127.7,127.6,127.0,126.3,126.2,126.0,125.8,54.9,39.2；HRMS-EI(70eV)m/z calcd for C19H17NONa[M+Na]+298.1208,found 298.1210.
实施例25:
将氰化苄(117mg,1mmol),苄醇(119mg,1.1mmol),[Rh(cod)Cl]2(4.9mg,0.01mmol,1mol％),三苯基膦(26mg,0.1mmol,10mol％),氢氧化钾(22mg,0.4mmol,40mol％)依次加到25ml Schlenk反应管中。混合物在130℃下反应17小时后，冷却到室温。旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：95％。

Claims (6)

1.一种合成α-烷基芳乙酰胺的方法，其特征在于，所述的α-烷基芳乙酰胺Ⅰ
通过芳乙腈Ⅱ
与化合物醇IV反应，
反应是在过渡金属催化剂金属铑络合物[Rh(cod)Cl]2、膦配体三苯基膦和碱氢氧化钾的参与下发生，
其中，Ar选自甲基苯基、甲氧基苯基、三氟甲基苯基、三氟甲氧基苯基、卤代苯基或萘基；
R代表一个取代基，选自甲基苯基、异丙基苯基、甲氧基苯基、三氟甲氧基苯基、卤代苯基或萘基。
2.如权利要求1所述的合成α-烷基芳乙酰胺的方法，其特征在于，包括如下步骤：
在反应容器中，加入芳乙腈、化合物醇、过渡金属催化剂金属铑络合物、碱、膦配体和有机溶剂；反应混合物在微波反应器或者磁力搅拌下，130℃下反应后，冷却到室温，然后通过柱分离，得到目标化合物。
3.如权利要求1或2所述的合成α-烷基芳乙酰胺的方法，其特征在于，所述的金属铑络合物用量为腈的1mol％。
4.如权利要求1或2所述的合成α-烷基芳乙酰胺的方法，其特征在于，所述的膦配体用量为腈的10mol％。
5.如权利要求1或2所述的合成α-烷基芳乙酰胺的方法，其特征在于，所述的碱用量为腈的40mol％。
6.如权利要求1或2所述的合成α-烷基芳乙酰胺的方法，其特征在于，化合物醇的用量为腈的1.1-2equiv。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3751465A (en) * 1967-08-15 1973-08-07 Asahi Chemical Ind Preparations of n,n-dialkyl-substituted fatty amides from nitriles and alcohols and n,n-dialkylformamides from hydrogen cyanide and alcohols
CN1749240A (zh) * 2004-09-16 2006-03-22 弗门尼舍有限公司 作为加香成分的腈衍生物
CN103113176A (zh) * 2013-02-02 2013-05-22 南京理工大学 一种合成n-烷基酰胺的方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3751465A (en) * 1967-08-15 1973-08-07 Asahi Chemical Ind Preparations of n,n-dialkyl-substituted fatty amides from nitriles and alcohols and n,n-dialkylformamides from hydrogen cyanide and alcohols
CN1749240A (zh) * 2004-09-16 2006-03-22 弗门尼舍有限公司 作为加香成分的腈衍生物
CN103113176A (zh) * 2013-02-02 2013-05-22 南京理工大学 一种合成n-烷基酰胺的方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Dialkylamino cyclopentadienyl ruthenium(II) complex-catalyzed α-alkylation of arylacetonitriles with primary alcohols;Hung Wai Cheung等;《Dalton Transactions》;20091123;第39卷;第265-274页 *
Direct Coupling of Arylacetonitriles and Primary Alcohols to α-Alkylated Arylacetamides with Complete Atom Economy Catalyzed by a Rhodium Complex–Triphenylphosphine-Potassium Hydroxide System;Feng Li等;《Advanced Synthesis& Catalysis》;20150325;第357卷;第1405-1415页 *
Efficient Solvent-Free Selective Monoalkylation of Arylacetonitriles with Mono-, Bis-, and Tris-primary Alcohols Catalyzed by a Cp*Ir Complex;Christian Lofberg等;《J. Org. Chem.》;20060606;第71卷;第8023-8027页 *

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