CN112239423A - 一种α-芳基化酰胺化合物的合成方法 - Google Patents
一种α-芳基化酰胺化合物的合成方法 Download PDFInfo
- Publication number
- CN112239423A CN112239423A CN202010097726.7A CN202010097726A CN112239423A CN 112239423 A CN112239423 A CN 112239423A CN 202010097726 A CN202010097726 A CN 202010097726A CN 112239423 A CN112239423 A CN 112239423A
- Authority
- CN
- China
- Prior art keywords
- arylated
- reaction
- amide compound
- alpha
- synthesizing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 amide compound Chemical class 0.000 title claims abstract description 37
- 238000010189 synthetic method Methods 0.000 title abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 15
- 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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 claims abstract description 5
- 229910000367 silver sulfate Inorganic materials 0.000 claims abstract description 5
- 150000003936 benzamides Chemical class 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- SJRDNQOIQZOVQD-UHFFFAOYSA-M sodium;2,2-dimethylpropanoate Chemical compound [Na+].CC(C)(C)C([O-])=O SJRDNQOIQZOVQD-UHFFFAOYSA-M 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 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
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 15
- 239000001257 hydrogen Substances 0.000 abstract description 15
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000006880 cross-coupling reaction Methods 0.000 abstract description 2
- 229940078487 nickel acetate tetrahydrate Drugs 0.000 abstract description 2
- 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
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 238000001228 spectrum Methods 0.000 description 22
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 3
- 150000008430 aromatic amides Chemical class 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 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
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 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
- 235000010290 biphenyl Nutrition 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 239000010814 metallic waste Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229940078494 nickel acetate Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- RCCYSVYHULFYHE-UHFFFAOYSA-N pentanediamide Chemical compound NC(=O)CCCC(N)=O RCCYSVYHULFYHE-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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400 MHz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-carb oxade(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)ben zamie(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)be nzade(I-4)
Yield:(54.3 mg,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(CDCl3,100 MHz)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)ben zamide(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)δ 170.2,167.6,148.6,139.4,138.5,136.2,134.5,134.1,133.4,131.7,129.0, 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)benzamid e(I-6)
Yield:(50.6 mg,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)benz amide(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＝5.2 Hz,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)ben zamide(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 (6)
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：将苯甲酰胺化合物、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C1～C5烷基。
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、氟中的一个或者多个；
R2选自甲基或者乙基。
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，同时有作为反应底物参与到反应中。
4.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，所述的镍催化剂为醋酸镍水合物。
5.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，所述的氧化剂为硫酸银。
6.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，反应温度为120℃，反应时间为24小时。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010097726.7A CN112239423B (zh) | 2020-02-17 | 2020-02-17 | 一种α-芳基化酰胺化合物的合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010097726.7A CN112239423B (zh) | 2020-02-17 | 2020-02-17 | 一种α-芳基化酰胺化合物的合成方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112239423A true CN112239423A (zh) | 2021-01-19 |
| CN112239423B CN112239423B (zh) | 2022-03-04 |
Family
ID=74170396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010097726.7A Expired - Fee Related CN112239423B (zh) | 2020-02-17 | 2020-02-17 | 一种α-芳基化酰胺化合物的合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112239423B (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2020
- 2020-02-17 CN CN202010097726.7A patent/CN112239423B/zh not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112239423B (zh) | 2022-03-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lu et al. | Copper-mediated C–H amination of imidazopyridines with N-fluorobenzenesulfonimide | |
| CN109942576B (zh) | Irbinitinib及中间体的制备方法 | |
| CN101189212A (zh) | 合成有机化合物的方法 | |
| Zhang et al. | Advances in silylation and borylation of fluoroarenes and gem-difluoroalkenes via C–F bond cleavage | |
| CN111217736A (zh) | 一种光催化下2-酰基吲哚化合物的合成方法 | |
| CN107033016B (zh) | 一种3-氨基茚酮类化合物的合成方法 | |
| Tang et al. | Rhodium (III)-catalyzed C4-amidation of indole-oximes with dioxazolones via C–H activation | |
| CN108640945B (zh) | 一种酰胺类化合物及其制备方法与应用 | |
| CN112239423B (zh) | 一种α-芳基化酰胺化合物的合成方法 | |
| CN108586372B (zh) | 一种2-芳基噁唑啉酰胺化合物的合成方法 | |
| CN107445894B (zh) | 一种手性环丙基氨基酸的制备方法 | |
| CN113121401B (zh) | 一种n-取代羰基氟磺酰胺化合物、制备方法及其应用 | |
| CN114621218A (zh) | 一种唑吡坦中间体化合物 | |
| JP2021116300A (ja) | イソインドリノン誘導体の製造方法 | |
| Wang et al. | Visible-light induced C (sp 3)–H arylation of glycine derivatives by cerium catalysis | |
| CN112390696A (zh) | 一种制备α-氨基腈的方法及其产品和应用 | |
| CN114160206B (zh) | 一种催化合成光学活性吲哚类化合物的催化剂、应用、合成方法及光学活性吲哚类化合物 | |
| WO2013191287A1 (ja) | アルコール酸化触媒及びそれを用いたアルコール酸化方法 | |
| CN111925325B (zh) | 一种二芳香醚类化合物的合成方法 | |
| CN111704590B (zh) | 一种铁催化的2-芳基苯并噻唑类化合物的合成方法 | |
| CN113636968B (zh) | 一种3-酰基吡咯类化合物的合成方法 | |
| JPH04264074A (ja) | 複素環式化合物の新規合成方法 | |
| CN108440378A (zh) | 一种室温下碘-双氧水促进的3-氨基-2-吲哚酮衍生物的制备方法 | |
| CN115028588B (zh) | 杂环化合物的绿色合成方法 | |
| CN111410656B (zh) | 一种异喹啉酮类衍生物的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Lv Ningning Inventor after: Zhang Yuhong Inventor before: Zhang Yuhong Inventor before: Lv Ningning |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220304 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |