CN112939839A - 一种2-芳香酰吡咯类化合物的合成方法 - Google Patents
一种2-芳香酰吡咯类化合物的合成方法 Download PDFInfo
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 8
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 13
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
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- MXJGZAMERDEUKM-UHFFFAOYSA-N N[Li].C[Si](N[Si](C)(C)C)(C)C Chemical compound N[Li].C[Si](N[Si](C)(C)C)(C)C MXJGZAMERDEUKM-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
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- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229910052783 alkali metal Inorganic materials 0.000 abstract description 2
- 150000001340 alkali metals Chemical class 0.000 abstract description 2
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- 239000002994 raw material Substances 0.000 abstract description 2
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- 150000003624 transition metals Chemical class 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 description 42
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 238000012512 characterization method Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- -1 nitrile salts Chemical class 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 2
- JAFHHNYLLHRTIT-UHFFFAOYSA-N N-Benzoyl-Pyrrole Natural products C1=CC=CN1C(=O)C1=CC=CC=C1 JAFHHNYLLHRTIT-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 description 2
- 150000001491 aromatic compounds Chemical group 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
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- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 2
- 229960004752 ketorolac Drugs 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
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- 239000000843 powder Substances 0.000 description 2
- JPGWTZORMBTNMF-UHFFFAOYSA-N pyoluteorin Chemical compound OC1=CC=CC(O)=C1C(=O)C1=CC(Cl)=C(Cl)N1 JPGWTZORMBTNMF-UHFFFAOYSA-N 0.000 description 2
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- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 2
- 229960001017 tolmetin Drugs 0.000 description 2
- VPAMZQVPJOAFJG-UHFFFAOYSA-N (3-chloro-5-hexyl-2,6-dihydroxyphenyl)-(4,5-dichloro-1h-pyrrol-2-yl)methanone Chemical compound CCCCCCC1=CC(Cl)=C(O)C(C(=O)C=2NC(Cl)=C(Cl)C=2)=C1O VPAMZQVPJOAFJG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 150000007927 N-acylbenzotriazoles Chemical class 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- ZJBMQVPEJHVSQA-OCYVVMCSSA-N Pyrromycin Chemical class O([C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)[C@H]1C[C@H](N(C)C)[C@H](O)[C@H](C)O1 ZJBMQVPEJHVSQA-OCYVVMCSSA-N 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
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- 230000000844 anti-bacterial effect Effects 0.000 description 1
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- 230000009286 beneficial effect Effects 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
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- 239000006227 byproduct Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
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- 230000008020 evaporation Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract
本发明涉及有机合成领域，公开了一种2‑芳香酰吡咯类化合物的合成方法，该方法用N‑芳香酰吡咯类化合物为原料，在碱金属催化下通过全新的重排反应，得到的一系列2‑芳香酰吡咯衍生物。本发明的合成方法工艺简单、无需过渡金属催化剂、高效环保，从而扩大其在药物中间体合成反应及有机合成反应中的应用范畴。
Description
技术领域
本发明涉及有机合成领域，具体涉及一种2-芳香酰吡咯类化合物的合成方法。
背景技术
吡咯是一类非常重要的五元氮杂环结构。具有吡咯结构的衍生物广泛应用于新药研发、光电材料、化学催化、功能材料等诸多领域。其中2-芳香酰吡咯类化合物在制药领域发挥的作用不可忽视，它是常见的药物中间体，也是很多重要生物活性分子的母核结构，像托美汀(Tolmetin)、佐美酸(Zomepirac)、酮咯酸(Ketorolac)等非甾体抗炎药，均为2-芳香酰吡咯类衍生物；此外从假单胞菌中分离得到的吡咯霉素生物碱Pyoluteorin，对多重耐药菌和分枝杆菌有较高的抑制作用；而从链霉菌中分离得到的Celastramycin A则是具有多种抗菌活性的免疫抑制剂。
2-芳香酰吡咯类化合物的传统合成方法包括傅克酰化反应和Vilsmeier-Haack芳酰化反应。此外，还有基于使用硒代酯或硫代酯、N-酰基苯并三唑、腈盐、羧酸、苯甲醛和芳基乙醛酸作为替代酰基源的合成方法。具体如下：
傅克酰化反应合成2-芳香酰吡咯的反应式如下：
Vilsmeier-Haack芳酰化反应合成2-芳香酰吡咯的反应式如下：
金属钯催化的2-芳香酰吡咯的反应式如下：
但是上述方法都具有明显的局限性，包括需要化学计量甚至过量的路易斯酸以及强酸性条件、操作繁琐和化学选择性差等缺点。近年来，基于钯金属催化的吡咯与醛、腈和烯丙基酯的酰化反应，尽管取得了重要进展，但仍有改进的余地，存在使用昂贵的配体，产生金属盐副产物，反应普适性低等缺点。因此针对该类化合物发展更加绿色、高效的制备方法不仅具有非常重要的应用价值，同时基于此开发新的合成方法学的建立在理论上也具有非常重要的科学意义。
发明内容
本发明提供了一种合成2-芳香酰吡咯类化合物的方法，该合成方法以N-芳香酰吡咯类化合物为原料，在碱金属催化下通过全新的重排反应，得到的一系列2-芳香酰吡咯衍生物。其结构如下：
上述的2-芳香酰吡咯类化合物的制备方法如下：(ⅰ)在非质子溶剂中，将如通式(Ⅰ)所示的化合物和碱(例如六甲基二硅基胺基锂)混合，加热反应，然后从反应产物中收集式(Ⅱ)化合物。
其中，Ar选自苯基、取代苯基、萘基、吡啶、喹啉等芳香化合物；
式(Ⅰ)化合物和碱的摩尔比为1:3，反应温度为100～120℃，反应时间为3小时以上。
本发明的有益效果如下：本发明的2-芳香酰吡咯类化合物新的制备方法，工艺简单，无需过渡金属催化剂，对环境友好，所制备的2-芳香酰吡咯类化合物具有重要的药用价值，为此类重要化合物的合成提供了一条简洁高效的方法。
具体实施方式
下面根据优选实施例详细描述本发明，本发明的目的和效果将变得更加明白。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
本发明实施例提供的2-芳香酰吡咯类化合物的合成方法如下：
在惰性气体保护下，将式(Ⅰ)所示的化合物溶于甲苯中，在搅拌下加入六甲基二硅基胺基锂的四氢呋喃溶剂(1mol/L)，100℃加热条件下反应3个小时，然后加入3滴水萃灭反应，加入少量硅胶粉滤过，用乙酸乙酯洗涤后减压蒸干，混合物柱用层析柱分离(PE:EA＝20:1～10:1)得到产物(Ⅱ)。
其中，Ar选自苯基、取代苯基、萘基、吡啶、喹啉等芳香化合物；式(Ⅰ)化合物和碱的摩尔比为1:3。
以下通过实例来进一步说明。
实施例1
化合物Ⅱ-1的制备与表征：
在氮气保护下，将N-苯甲酰吡咯(17.1mg，0.1mmol)溶于1mL甲苯中，在搅拌下逐滴加入六甲基二硅基胺基锂的四氢呋喃溶剂(1.0mol/L，0.3mL，0.3mmol)，100℃加热条件下反应3个小时，然后加入3滴水萃灭反应，加入少量硅胶粉滤过，用乙酸乙酯洗涤后减压蒸干，混合物柱层析分离(PE:EA＝20:1～10:1)得到目标化合物Ⅱ-1，白色固体，产率81％；1HNMR(500MHz,CDCl3):δ9.84(s,1H),7.92–7.90(m,2H),7.59–7.55(m,1H),7.51–7.47(m,2H),7.17–7.15(m,1H),6.91–6.89(m,1H),6.36–6.34(m,1H).
实施例2
化合物Ⅱ-2的制备与表征：
制备条件同实施例1，白色固体，产率68％；1H NMR(500MHz,CDCl3):δ9.73(s,1H),7.84–7.82(m,2H),7.30–7.28(m,2H),7.14–7.13(m,1H),6.90–6.89(m,1H),6.35–6.33(m,1H),2.44(s,3H).
实施例3
化合物Ⅱ-3的制备与表征：
制备条件同实施例1，白色固体，产率76％；1H NMR(500MHz,CDCl3):δ10.17(s,1H),7.89–7.87(m,2H),7.52–7.50(m,2H),7.16–7.15(m,1H),6.94–6.92(m,1H),6.35–6.33(m,1H),1.37(s,9H).
实施例4
化合物Ⅱ-4的制备与表征：
制备条件同实施例1，白色固体，产率81％；1H NMR(500MHz,CDCl3):δ9.87(s,1H),8.02–7.99(m,2H),7.73–7.71(m,2H),7.67–7.65(m,2H),7.51–7.47(m,2H),7.42–7.39(m,1H),7.18–7.17(m,1H),6.97–6.96(m,1H),6.38–6.36(m,1H).
实施例5
化合物Ⅱ-5的制备与表征：
制备条件同实施例1，浅黄色固体，产率72％；1H NMR(500MHz,CDCl3):δ10.18(s,1H),7.97–7.93(m,2H),7.19–7.14(m,3H),6.88–6.87(m,1H),6.36–6.34(m,1H).
实施例6
化合物Ⅱ-6的制备与表征：
制备条件同实施例1，白色固体，产率78％；1H NMR(500MHz,CDCl3):δ10.05(s,1H),7.87–7.84(m,2H),7.48–7.45(m,2H),7.18–7.17(m,1H),6.88–6.86(m,1H),6.36–6.34(m,1H).
实施例7
化合物Ⅱ-7的制备与表征：
制备条件同实施例1，白色固体，产率74％；1H NMR(500MHz,CDCl3):δ10.42(s,1H),7.80–7.77(m,2H),7.64–7.61(m,2H),7.20–7.18(m,1H),6.88–6.86(m,1H),6.35–6.33(m,1H).
实施例8
化合物Ⅱ-8的制备与表征：
制备条件同实施例1，白色固体，产率70％；1H NMR(500MHz,CDCl3):δ9.85(s,1H),8.00–7.98(m,2H),7.77–7.75(m,2H),7.21–7.20(m,1H),6.88–6.86(m,1H),6.38–6.36(m,1H).
实施例9
化合物Ⅱ-9的制备与表征：
制备条件同实施例1，白色固体，产率75％；1H NMR(500MHz,DMSO-d):δ12.22(s,1H),8.01–7.98(m,2H),7.94–7.91(m,2H),7.30–7.28(m,1H),6.79–6.78(m,1H),6.30–6.28(m,1H).
实施例10
化合物Ⅱ-10的制备与表征：
制备条件同实施例1，白色固体，产率72％；1H NMR(500MHz,DMSO-d6):δ12.15(s,1H),7.95–7.92(m,2H),7.51–7.48(m,2H),7.26–7.24(m,1H),6.81–6.80(m,1H),6.29–6.27(m,1H).
实施例11
化合物Ⅱ-11的制备与表征：
制备条件同实施例1，黄色固体，产率84％；1H NMR(500MHz,CDCl3):δ9.99(s,1H),7.97–7.94(m,2H),7.10–7.08(m,1H),6.92–6.90(m,1H),6.73–6.70(m,2H),6.33–6.32(m,1H),3.06(s,6H).
实施例12
化合物Ⅱ-12的制备与表征：
制备条件同实施例1，白色固体，产率72％；1H NMR(500MHz,CDCl3):δ9.83(s,1H),7.96–7.93(m,2H),7.13–7.12(m,1H),7.00–6.97(m,2H),6.90–6.89(m,1H),6.35–6.33(m,1H),3.89(s,3H).
实施例13
化合物Ⅱ-13的制备与表征：
制备条件同实施例1，反应温度为120℃，反应时间为10小时，白色固体，产率84％；1H NMR(500MHz,CDCl3):δ9.74(s,1H),7.46–7.42(m,2H),7.12–7.10(m,1H),7.02–6.99(m,2H),6.65–6.63(m,1H),6.28–6.26(m,1H),3.83(s,3H).
实施例14
化合物Ⅱ-14的制备与表征：
制备条件同实施例1，白色固体，产率70％；1H NMR(500MHz,CDCl3):δ10.35(s,1H),7.50–7.47(m,2H),7.43–7.39(m,1H),7.36–7.32(m,1H),7.21–7.20(m,1H),6.62–6.60(m,1H),6.30–6.28(m,1H).
实施例15
化合物Ⅱ-15的制备与表征：
制备条件同实施例1，反应温度为120℃，反应时间为10小时，白色固体，产率71％；1H NMR(500MHz,DMSO-d6):δ11.92(s,1H),7.60–7.57(m,1H),7.50–7.45(m,3H),7.32–7.22(m,5H),7.11–7.09(m,1H),6.39–6.38(m,1H),6.12–6.11(m,1H).
实施例16
化合物Ⅱ-16的制备与表征：
制备条件同实施例1，反应温度为120℃，反应时间为10小时，浅黄色固体，产率85％；1H NMR(500MHz,CDCl3):δ10.48(s,1H),8.31–8.27(m,1H),8.01–7.99(m,1H),7.94–7.91(m,1H),7.80(dd,J＝7.0,1.2Hz,1H),7.56–7.52(m,3H),7.20–7.19(m,1H),6.71–6.69(m,1H),6.31–6.29(m,1H).
实施例17
化合物Ⅱ-17的制备与表征：
制备条件同实施例1，浅黄色固体，产率77％；1H NMR(500MHz,CDCl3):δ10.20(s,1H),8.46(s,1H),8.01–7.91(m,4H),7.62–7.55(m,2H),7.21–7.20(m,1H),7.01–6.99(m,1H),6.39–6.38(m,1H).
实施例18
化合物Ⅱ-18的制备与表征：
制备条件同实施例1，浅粉色固体，产率61％；1H NMR(500MHz,DMSO-d6):δ12.23(s,1H),8.96–8.95(m,1H),8.77(dd,J＝4.8,1.7Hz,1H),8.17–8.15(m,1H),7.55–7.53(m,1H),7.29–7.27(m,1H),6.83–6.81(m,1H),6.29–6.28(m,1H).
实施例19
化合物Ⅱ-19的制备与表征：
制备条件同实施例1，白色固体，产率73％；1H NMR(500MHz,DMSO-d6):δ12.19(s,1H),9.01(dd,J＝4.2,1.8Hz,1H),8.58(dd,J＝8.3,1.8Hz,1H),8.53(d,J＝1.6Hz,1H),8.14–8.10(m,2H),7.63(dd,J＝8.3,4.2Hz,1H),7.29–7.28(m,1H),6.94–6.93(m,1H),6.32–6.31(m,1H).
实施例20
化合物Ⅱ-20的制备与表征：
制备条件同实施例1，浅黄色固体，产率68％；1H NMR(500MHz,DMSO-d6):δ12.28(s,1H),9.22(d,J＝2.1Hz,1H),8.85(d,J＝2.1Hz,1H),8.19(dd,J＝8.2,1.3Hz,1H),8.10(d,J＝8.4Hz,1H),7.89–7.86(m,1H),7.71–7.67(m,1H),7.32–7.31(m,1H),6.98–6.96(m,1H),6.33–6.32(m,1H).
本领域普通技术人员可以理解，以上所述仅为发明的优选实例而已，并不用于限制发明，尽管参照前述实例对发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实例记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。凡在发明的精神和原则之内，所做的修改、等同替换等均应包含在发明的保护范围之内。
Claims (4)
1.一种2-芳香酰吡咯类化合物的合成方法，其特征在于，在惰性气体保护下，将式(Ⅰ)所示的化合物溶于甲苯中，在搅拌下加入1mol/L的六甲基二硅基胺基锂的四氢呋喃溶剂，加热条件下进行反应，然后从反应产物中收集式(Ⅱ)化合物
其中，Ar选自苯基、取代苯基、萘基、吡啶、喹啉中的任意一种。
2.根据权利要求1所述的2-芳香酰吡咯类化合物的合成方法，其特征在于，所述加热反应的温度为100～120℃。反应时间为3小时以上。
3.根据权利要求1所述的2-芳香酰吡咯类化合物的合成方法，其特征在于，所述式(Ⅰ)化合物和碱的摩尔比为1:3。
4.根据权利要求1所述的2-芳香酰吡咯类化合物的合成方法，其特征在于，所述加热反应通过加入3滴水萃灭反应，并经乙酸乙酯洗涤后减压蒸干，混合物柱用层析柱分离得到产物(Ⅱ)。
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| WO2013127768A1 (en) * | 2012-03-01 | 2013-09-06 | Syngenta Participations Ag | Pyridine carboxamide pesticides |
| CN104529686A (zh) * | 2014-12-22 | 2015-04-22 | 内蒙古师范大学 | 一种利用芳基酯与酰胺或内酰胺反应制备非对称酰亚胺 |
| CN110041220A (zh) * | 2019-04-30 | 2019-07-23 | 浙江大学城市学院 | 一种对称酰亚胺类化合物及其合成方法 |
| CN110483323A (zh) * | 2019-08-27 | 2019-11-22 | 浙江大学城市学院 | 一种不对称酰亚胺类化合物的制备方法 |
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| WO2013127768A1 (en) * | 2012-03-01 | 2013-09-06 | Syngenta Participations Ag | Pyridine carboxamide pesticides |
| CN104529686A (zh) * | 2014-12-22 | 2015-04-22 | 内蒙古师范大学 | 一种利用芳基酯与酰胺或内酰胺反应制备非对称酰亚胺 |
| CN110041220A (zh) * | 2019-04-30 | 2019-07-23 | 浙江大学城市学院 | 一种对称酰亚胺类化合物及其合成方法 |
| CN110483323A (zh) * | 2019-08-27 | 2019-11-22 | 浙江大学城市学院 | 一种不对称酰亚胺类化合物的制备方法 |
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