CN112239423B - 一种α-芳基化酰胺化合物的合成方法 - Google Patents
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- 238000000034 method Methods 0.000 claims abstract description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000000758 substrate Substances 0.000 claims abstract description 8
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- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 150000003936 benzamides Chemical class 0.000 claims abstract description 5
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- 229910000367 silver sulfate Inorganic materials 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
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- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- HIIGGQNLPWIVAG-UHFFFAOYSA-L nickel(2+);diacetate;hydrate Chemical group O.[Ni+2].CC([O-])=O.CC([O-])=O HIIGGQNLPWIVAG-UHFFFAOYSA-L 0.000 claims description 2
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- OINIXPNQKAZCRL-UHFFFAOYSA-L nickel(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Ni+2].CC([O-])=O.CC([O-])=O OINIXPNQKAZCRL-UHFFFAOYSA-L 0.000 abstract description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
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- 239000002184 metal Substances 0.000 description 3
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- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
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- 125000004429 atom Chemical group 0.000 description 2
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- 238000002156 mixing Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
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- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical compound C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
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- VQTOKXHLOLTVRS-UHFFFAOYSA-N benzamide quinolin-8-amine Chemical compound NC(=O)C1=CC=CC=C1.C1=CN=C2C(N)=CC=CC2=C1 VQTOKXHLOLTVRS-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
- NHFVAONVLCETEV-UHFFFAOYSA-N tert-butyl 4-isoquinolin-5-ylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC2=CN=CC=C12 NHFVAONVLCETEV-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
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Abstract
本发明公开了一种α‑芳基化酰胺化合物的合成方法，包括如下步骤：将苯甲酰胺衍生物、四水合醋酸镍、硫酸银、特务酸钠加入到有机溶剂N,N‑二甲基乙酰胺中，氮气条件下加热进行反应，反应完全后，后处理得到所述的α‑芳基化酰胺化合物。该方法通过简单易得的原料通过碳氢键直接的交叉偶联一步合成α‑芳基化酰胺化合物，转化效率高，原子经济性好；同时合成方法操作简单，反应条件温和，同时底物适应性广。
Description
技术领域
本发明属于有机合成领域，具体涉及一种α-芳基化酰胺化合物的合成方法。
背景技术
α-芳基化酰胺化合物是一类十分重要的结构分子，其广泛存在于药物分子、天然产物以及功能性材料中。目前，能够有效合成α-芳基化酰胺化合物的方法主要集中在以下几种。使反应条件控制在强碱条件下，拔除酰胺化合物α-羰基的氢，再与芳基卤代烃发生偶联反应得到目标产物。由于该反应不仅需要对芳烃进行官能团化得到活性比较高的芳基卤代烃并且反应条件苛刻，难于控制和操作，所以大大限制该反应的应用。另外一种方法就是将酰胺化合物直接进行α位的卤化，再进一步与金属试剂发生反应也能够生成目标产物。同样，该方法也难以避免需要对底物进行官能团转化，从而才能进行反应。冗长的反应步骤以及苛刻的反应条件都会使得反应体系产生大量的废碱，废酸以及金属废料。寻求发展新型高效的合成方法是非常必要的。
近年来，过渡金属催化的导向基团辅助的C-H键活化的策略，经过几十年的发展提供了一种原子经济型、步骤经济型方法来构筑碳碳以及碳杂键，同时在导向基团的辅助下，反应活性以及化学选择性得到大大的提升。我们课题组一直致力于利用双齿导向基团的辅助策略，来实现一些新颖的化学转化以及一些难于实现的化学转化。我们利用8-氨基喹啉苯甲酰胺的底物作为导向基团，在廉价易得无毒的金属镍的催化下，首次发展了一种以硫酸银作为反应的氧化剂，特戊酸钠作为添加剂在氮气的反应氛围下能够顺利合成α-芳基化酰胺化合物，该方法条件温和，反应化学选择性高，而作为导向基团的8-氨基喹啉基在反应结束之后，可以通过酸性条件或者碱性条件进行脱除(1、Da Liu等，European Journal ofOrganic Chemistry，2019年，第41期第6930-6934页，Nickel-Catalyzed Ortho C–HMethylation of Aromatic Amides with Di-tert-butyl Peroxide as MethylationReagent；2、J.Org.Chem.2018,83,7860-7866，Palladium-Catalyzed H/D ExchangeReaction with 8-Aminoquinoline as the Directing Group:Access to ortho-Selective Deuterated Aromatic Acids andβ-Selective Deuterated AliphaticAcids)，为合成对称以及不对称的α-芳基化酰胺化合物提供了一种行之有效的方法。
发明内容
本发明提供了一种α-芳基化酰胺化合物的合成方法，该合成方法底物适用性广，化学选择性好，反应活性高。
一种α-芳基化酰胺化合物的合成方法，包括如下步骤：将苯甲酰胺衍生物、醋酸镍水合物、硫酸银以及特戊酸钠加入到有机溶剂N,N-二甲基乙酰胺中，氮气条件下加热到120℃进行反应24h，反应完全后，后处理得到所述的α-芳基化酰胺化合物；
所述的苯甲酰胺衍生物的结构如式(II)所示：
所述的α-芳基化酰胺化合物的结构如式(I)所示：
式(I)～(II)中，R1选自甲基、苯基、甲氧基、苯基、三氟甲基、卤素、萘基以及脂肪烷基；
本发明的合成方法不需要在苛刻的反应条件下，以及不需要对底物进行预官能团化得到活化物种进而发生经典的偶联反应即可实现目标产物的合成，可直接由芳香烃以及小分子酰胺化合物通过碳氢键之间的直接偶联得到目标α-芳基化酰胺产物，值得注意的是酰胺化合物在反应过程中不仅仅作为反应底物同时也作为反应溶剂参与到反应过程中来。
R2选自C1～C5烷基。
作为优选，R1选自甲基、苯基、三氟甲基、甲氧基、溴、氟中的一个或者多个；
R2选自甲基或者乙基。
作为优选，所述的有机溶剂为N,N-二甲基乙酰胺(DMAc)。
作为优选，反应催化剂为水合醋酸镍，反应氧化剂为硫酸银，反应最优的碱为特戊酸钠。
作为优选，反应温度为120℃，反应时间为24小时。
同现有技术相比，本发明的有益效果体现在：
(1)本发明通过简单易得的原料直接通过导向基团辅助的策略，可以在温和的反应条件下，通过碳氢键的直接交叉偶联一步合成α-芳基化酰胺化合物，转化效率高，原子经济性好；
(2)本发明的合成方法操作简单，反应收率高，同时底物适应性广。
附图说明
图1为实施例1得到的化合物的氢谱和碳谱谱图；
图2为实施例2得到的化合物的氢谱和碳谱谱图；
图3为实施例3得到的化合物的氢谱和碳谱谱图；
图4为实施例4得到的化合物的氢谱和碳谱谱图；
图5为实施例5得到的化合物的氢谱和碳谱谱图；
图6为实施例6得到的化合物的氢谱和碳谱谱图；
图7为实施例7得到的化合物的氢谱和碳谱谱图；
图8为实施例8得到的化合物的氢谱和碳谱谱图；
图9为实施例9得到的化合物的氢谱和碳谱谱图；
图10为实施例10得到的化合物的氢谱和碳谱谱图；其中，氢谱在400MHz核磁仪器上进行测试。碳谱在100MHz核磁仪器上进行测试。测试条件均为室温下使用四甲基硅烷作内标，样品用氘代氯仿溶解。
具体实施方式
下面结合具体实施例对本发明做进一步的描述，以下具体实施例都是本发明的最优实施方式。
实施例1～10
按照表1的原料配比在试管中加入苯甲酰胺(0.2mmol)、四水合醋酸镍(0.06mmol)、硫酸银(0.4mmol)、特戊酸钠(0.4mmol)和有机溶剂DMAc(2ml)，混合搅拌均匀，充氮气在氮气氛围下反应24h。按照表2的反应条件反应完成后，冷却，用硅藻土抽滤，用饱和食盐萃取，收集有机相用硫酸钠干燥，硅胶拌样，经过柱层析纯化得到相应的α-芳基化酰胺化合物(Ⅰ)，反应过程如下式所示：
表1实施例1～10的原料配比
表2实施例1～10的反应条件和反应结果
表1和表2中，T为反应温度，t为反应时间，Me为甲基，CF3为三氟甲基，Ph为苯基，1-naphthyl为1-萘基。
实施例1～10制备得到部分化合物的结构确认数据：
2-(2-(dimethylamino)-2-oxoethyl)-6-methyl-N-(quinolin-8-yl)benzamide(I-1)
Yield:(45.0mg,65％,18:1)；White solid；mp:125.3-126.5℃.1H NMR(CDCl3,400MHz)δ10.05(s,1H),8.96(dd,J1＝7.2Hz,J2＝2.4Hz,1H),8.76(dd,J1＝4.0Hz,J2＝1.6Hz,1H),8.17(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.62-7.56(m,2H),7.44(dd,J1＝8.0Hz,J2＝4.0Hz,1H),7.32(t,J＝7.6Hz,1H),7.19(d,J＝7.6Hz,2H),4.72(d,J＝21.6Hz,0.12H)3.82(s,1.87H),2.89(s,3H),2.77(s,3H),2.45(s,3H).13C NMR(CDCl3,100MHz)δ168.6,148.5,138.6,137.8,136.2,134.8,134.4,132.3,129.4,129.0,128.0,127.3,127.2,122.2,121.8,116.8,37.9,37.6,35.5,19.6.HRMS(EI-TOF)calcd for C21H21N3O2[M]+:347.1634,found:347.1634.
3-(2-(dimethylamino)-2-oxoethyl)-N-(quinolin-8-yl)-[1,1'-biphenyl]-2-carboxade(I-2)
Yield:(54.0mg,66％,18:1)；White solid；mp:208.4-209.5℃.1H NMR(CDCl3,400MHz)δ9.71(s,1H),8.71(dd,J1＝7.2Hz,J2＝1.6Hz,1H),8.59(dd,J1＝4.0Hz,J2＝1.6Hz,1H),8.04(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.52-7.42(m,5H),7.39(t,J＝6.4Hz,2H),7.33(dd,J1＝8.0Hz,J2＝4.0Hz,1H),7.19(t,J＝7.6Hz,2H),7.06(t,J＝7.6Hz,1H),4.84(d,J＝12.8Hz,0.11H),3.96(s,1.9H),2.97(s,3H),2.79(s,3H).13C NMR(CDCl3,100MHz)δ170.8,168.1,148.1,140.3,139.9,138.4,136.6,135.9,134.4,133.7,129.6,129.3,128.9,128.7,128.2,127.7,127.3,127.1,121.8,121.5,116.3,37.8,37.7,35.6.HRMS(EI-TOF)calcd for C26H23N3O2[M]+:409.1790,found:409.1792.
2-(2-(dimethylamino)-2-oxoethyl)-N-(quinolin-8-yl)-6-(trifluoromethyl)benzamie(I-3)
Yield:(28.9mg,36％)；White solid；mp:144.5-146.3℃.1H NMR(CDCl3,400MHz)δ10.12(s,1H),8.92(dd,J1＝5.6Hz,J2＝3.6Hz,1H),8.77(dd,J1＝4.4Hz,J2＝1.6Hz,1H),8.17(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.68(d,J＝7.6Hz,1H),7.62-7.59(m,3H),7.55(t,J＝7.6Hz,1H),7.44(dd,J1＝8.0Hz,J2＝4.4Hz,1H),3.84(br,2H),2.86(s,3H),2.68(s,3H).13C NMR(CDCl3,100MHz)δ169.9,165.7,148.6,138.5,136.2,135.4(q,J＝1.8Hz),134.5,134.4,134.2,129.5,127.9,127.5(q,J＝31.6Hz),127.2,124.9,(q,J＝4.5Hz),122.5,121.8,116.9,37.5,37.3,35.5.HRMS(EI-TOF)calcd for C21H18F3N3O2[M]+:401.1351,found:401.1353.
6-(2-(dimethylamino)-2-oxoethyl)-3-methoxy-2-methyl-N-(quinolin-8-yl)benzade(I-4)
Yield:(54.3mg,72％)；White solid；mp:143.2-145.6℃.1H NMR(CDCl3,400MHz)δ10.02(s,1H),8.95(dd,J1＝7.2Hz,J2＝2.0Hz,1H),8.75(dd,J1＝4.0Hz,J2＝1.6Hz,1H),8.16(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.61-7.55(m,2H),7.43(dd,J1＝8.4Hz,J2＝4.4Hz,1H),7.18(d,J＝8.8Hz,1H),6.89(d,J＝8.4Hz,1H),3.86(s,3H),3.75(s,2H),2.88(s,3H),2.74(s,3H),2.29(s,3H).13C NMR(CDCl3,100MHz)δ171.1,168.4,156.7,148.5,138.8,138.6,136.2,134.3,128.0,127.9,127.2,123.8,123.5,122.2,121.8,116.7,111.1,55.7,37.6,37.3,35.5,13.1.HRMS(EI-TOF)calcd for C22H23N3O3[M]+:377.1739,found:377.1737.
3-bromo-6-(2-(dimethylamino)-2-oxoethyl)-2-methyl-N-(quinolin-8-yl)benzamide(I-5)
Yield:(21.3mg,50％)；White solid；mp:123.5-125.2℃.1H NMR(CDCl3,400MHz)δ10.06(s,1H),8.93(dd,J1＝5.6Hz,J2＝3.2Hz,1H),8.78(dd,J1＝4.0Hz,J2＝1.6Hz,1H),8.18(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.61-7.59(m,3H),7.45(dd,J1＝8.4Hz,J2＝4.4Hz,1H),7.08(d,J＝8.4Hz,1H),3.74(s,2H),2.87(s,3H),2.71(s,3H),2.48(s,3H).13C NMR(CDCl3,100MHz)δ170.2,167.6,148.6,139.4,138.5,136.2,134.5,134.1,133.4,131.7,129.0,128.0,127.2,124.5,122.5,121.9,66.9,37.6,37.5,35.5,20.4.HRMS(EI-TOF)calcd for C21H20BrN3O2[M]+:425.0739,found:425.0738.
2-(2-(dimethylamino)-2-oxoethyl)-4,6-dimethyl-N-(quinolin-8-yl)benzamide(I-6)
Yield:(50.6mg,70％,39:1)；White solid；mp:128.3-129.6℃.1H NMR(CDCl3,400MHz)δ10.03(s,1H),8.95(dd,J1＝6.8Hz,J2＝1.6Hz,1H),8.75(dd,J1＝4.4Hz,J2＝1.6Hz,1H),8.16(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.61-7.54(m,2H),7.43(dd,J1＝8.4Hz,J2＝4.0Hz,1H),7.01(s,2H),4.69(d,J＝19.6Hz,0.06H)3.79(s,1.93H),2.89(s,3H),2.77(s,3H),2.41(s,3H),2.34(s,3H).13C NMR(CDCl3,100MHz)δ170.9,168.9,148.4,139.2,138.6,136.2,135.1,134.7,134.4,132.2,129.8,128.0,127.8,127.3,122.1,121.7,116.7,37.9,37.6,35.5,21.3,19.6.HRMS(EI-TOF)calcd for C22H23N3O2[M]+:361.1790,found:361.1791.
2-(2-(dimethylamino)-2-oxoethyl)-3-fluoro-6-methyl-N-(quinolin-8-yl)benzamide(I-7)
Yield:(38.0mg,52％)；White solid；mp:155.2-157.9℃.1H NMR(CDCl3,400MHz)δ10.22(s,1H),8.94(dd,J1＝6.0Hz,J2＝2.4Hz,1H),8.80(dd,J1＝4.4Hz,J2＝1.6Hz,1H),8.16(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.61-7.56(m,2H),7.44(dd,J1＝8.4Hz,J2＝4.0Hz,1H),7.16(dd,J1＝8.4Hz,J2＝5.2Hz,1H),7.05(t,J＝9.2Hz,1H),3.79(d,J＝1.2Hz,2H),2.93(s,3H),2.69(s,3H),2.40(s,3H).13C NMR(CDCl3,100MHz)δ169.5,167.5(d,JC-F＝2.7Hz),159.5(d,JC-F＝242.9Hz),148.6,139.6(d,JC-F＝3.6Hz),138.8,136.1,134.4,130.5(d,JC-F＝8.1Hz),130.4(d,JC-F＝3.6Hz),128.0,127.2,122.3,121.7,120.4(d,JC-F＝18.1Hz),117.0,115.8(d,JC-F＝22.5Hz),37.3,35.5,31.1(d,JC-F＝2.7Hz),19.1.HRMS(EI-TOF)calcd for C21H20FN3O2[M]+:365.1540,found:365.1538.
2-(2-(dimethylamino)-2-oxoethyl)-N-(quinolin-8-yl)-1-naphthamide(I-8)Yield:(30.0mg,39％)；White solid；mp:168.2-169.5℃.1H NMR(CDCl3,400MHz)δ10.25(s,1H),9.10(dd,J1＝7.2Hz,J2＝1.2Hz,1H),8.68(dd,J1＝4.4Hz,J2＝1.6Hz,1H),8.17(dd,J1＝8.4Hz,J2＝1.6Hz,1H),8.02-8.00(m,1H),7.92(d,J＝8.4Hz,1H),7.89-7.87(m,1H),7.67-7.59(m,2H),7.53-7.47(m,3H),7.42(dd,J1＝8.0Hz,J2＝4.0Hz,1H),4.01(s,2H),2.93(s,3H),2.82(s,3H).13C NMR(CDCl3,100MHz)δ170.5,168.2,148.5,138.6,136.2,134.6,134.4,132.4,130.2,130.1,129.7,128.1,128.0,127.3,127.2,127.1,126.2,125.0,122.4,121.8,117.0,38.4,37.6,35.6.HRMS(EI-TOF)calcd for C24H21N3O2[M]+:383.1634,found:383.1635.
6-(2-(diethylamino)-2-oxoethyl)-3-methoxy-2-methyl-N-(quinolin-8-yl)benzamide(I-9)
Yield:(41.3mg,51％)；White solid；mp:138.2-139.6℃.1H NMR(CDCl3,400MHz)δ10.04(s,1H),8.95(dd,J1＝6.8Hz,J2＝1.6Hz,1H),8.75(dd,J1＝4.0Hz,J2＝1.6Hz,1H),8.16(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.61-7.54(m,2H),7.43(dd,J1＝8.0Hz,J2＝4.0Hz,1H),7.18(d,J＝8.4Hz,1H),6.89(d,J＝8.4Hz,1H),3.86(s,3H),3.79(s,2H),3.24-3.15(m,4H),2.29(s,3H),0.94(t,J＝7.2Hz,3H),0.85(t,J＝7.2Hz,3H).13C NMR(CDCl3,100MHz)δ170.2,168.5,156.7,148.4,138.9,138.6,136.2,134.4,128.1,127.9,127.2,124.0,123.5,122.1,121.7,116.7,111.0,55.6,42.2,40.2,37.3,14.0,13.1,12.7.HRMS(EI-TOF)calcd for C24H27N3O3[M]+:405.2052,found:405.2055.
N5,N5,2,2-tetramethyl-N1-(quinolin-8-yl)pentanediamide(I-10)
Yield:(21.9mg,35％)；Organe liquid.1H NMR(CDCl3,400MHz)δ10.27(s,1H),8.82(dd,J1＝4.0Hz,J2＝1.6Hz,1H),8.77(dd,J1＝6.8Hz,J2＝1.6Hz,1H),8.16(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.56-7.49(m,2H),7.46(dd,J1＝8.4Hz,J2＝4.0Hz,1H),2.97(s,3H),2.91(s,3H),2.41-2.38(m,2H),2.10-2.06(m,2H),1.45(s,6H).13C NMR(CDCl3,100MHz)δ176.0,172.7,148.4,138.7,136.3,134.5,127.9,127.4,121.7,121.4,116.2,43.3,37.3,36.5,35.4,29.3,25.7.HRMS(EI-TOF)calcd for C18H23N3O2[M]+:313.1790,found:313.1792。
Claims (3)
1.一种α-芳基化酰胺化合物合成方法，其特征在于，包括如下步骤：将苯甲酰胺衍生物、镍催化剂、氧化剂、特戊酸钠和N，N-二烷基酰胺加入到有机溶剂中，控制反应在氮气条件下进行，加热进行反应，反应完全后，后处理得到所述的α-芳基化酰胺化合物；
所述的苯甲酰胺衍生物的结构如式(II)所示：
所述的α-芳基化酰胺化合物的结构如式(I)所示：
式(I)～(II)中，R1选自甲基、苯基、甲氧基、三氟甲基、卤素、萘基或脂肪烷基；
R2选自甲基或者乙基；
所述的镍催化剂为醋酸镍水合物；
所述的氧化剂为硫酸银；
反应温度为120℃，反应时间为24小时。
2.根据权利要求1所述的α-芳基化酰胺化合物合成方法，其特征在于，R1选自甲基、苯基、三氟甲基、甲氧基、溴、氟中的一个。
3.根据权利要求1所述的α-芳基化酰胺化合物的合成方法，其特征在于，所述的有机溶剂为N,N-二甲基乙酰胺，同时又作为 反应底物参与到反应中。
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| CN105669542A (zh) * | 2016-03-08 | 2016-06-15 | 南京师范大学 | 一种直接催化氧化法合成吡啶伯酰胺化合物的方法 |
| CN107417614A (zh) * | 2017-05-18 | 2017-12-01 | 湖北工业大学 | N‑苯基‑n‑[8]喹啉基‑4‑氟‑苯甲酰胺的制备方法 |
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| WO2002026713A1 (en) * | 2000-09-29 | 2002-04-04 | King's College London | Antiparasitic compounds |
| CN105669542A (zh) * | 2016-03-08 | 2016-06-15 | 南京师范大学 | 一种直接催化氧化法合成吡啶伯酰胺化合物的方法 |
| CN107417614A (zh) * | 2017-05-18 | 2017-12-01 | 湖北工业大学 | N‑苯基‑n‑[8]喹啉基‑4‑氟‑苯甲酰胺的制备方法 |
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