CN114805172A - 一种合成非对称杂环二芳基甲烷类化合物的方法 - Google Patents
一种合成非对称杂环二芳基甲烷类化合物的方法 Download PDFInfo
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- UCYRAEIHXSVXPV-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)indiganyl trifluoromethanesulfonate Chemical compound [In+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F UCYRAEIHXSVXPV-UHFFFAOYSA-K 0.000 description 1
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- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
-
- 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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- Indole Compounds (AREA)
Abstract
本发明提供了一种合成非对称杂环二芳基甲烷类化合物的方法,是以吲哚乙酸(IAA)及衍生物和芳腈衍生物为原料,在碱、光敏剂及可见光条件下反应1‑10小时,反应结束后减压蒸馏除去溶剂,柱层析分离,即得目标产物。本发明反应试剂价格低廉,条件温和,操作简便,环境污染小,反应速率快,后处理简单,产物收率高,纯度好,适合用于工业化生产。
Description
技术领域
本发明涉及一种合成杂环二芳基甲烷类化合物的方法,尤其涉及一种合成非对称杂环二芳基甲烷类化合物的方法,属于化学合成技术领域。
背景技术
杂环二芳基甲烷衍生物是很多生物碱天然产物以及药物活性分子的重要组成结构。具有广泛的生物学活性和药理活性,例如,抗菌性、抗真菌药物性、抗癌性等。此外,含二芳基甲烷骨架的一些分子对COVID-19有一定抑制作用。同时,杂环二芳基甲烷衍生物也是有机合成中重要的中间体,因此,杂环二芳基甲烷衍生物的合成研究已经获得了广泛的关注。
目前常用的杂环二芳基甲烷类衍生物的合成方法主要有傅克烷基化反应、交叉偶联反应、还原反应及其他方法,常见的催化剂有路易斯酸(三氟甲磺酸的镧系元素盐、InCl3、三氟甲磺酸铟、CuBr2、硝酸铈铵、Eu(NTf2)3、三氯化铝、三氯化铈、SbCl3、NbCl5、)、质子酸、离子液体、固载催化剂、过渡金属等。但是非对称杂环二芳基甲烷类化合物报道较少,国内外文献报道的合成非对称杂环二芳基甲烷类化合物的具体实例如下:(1)Suzuki-Miyaura偶联反应( Jiang, S.; Dong, X.; Gu, Q.; Ye, L.; Li, Z.; Liu, X. J. Am. Chem. Soc. 2020,142, 19652-19659.)。(2)其他偶联反应(Poremba, K.; Kadunce, N.;Suzuki, N.; Cherney, A.; Reisman, S. J. Am. Chem. Soc.2017,139, 5684-5687.)。(3)活性酯与吲哚的反应(Guo, G.; Yuan, Y.; Bao, X.; Cao, X.; Sang, T.; Wang,J.; Huo, C.Org. Lett. 2021,23 (17), 6936-6940)。以上合成非杂环二芳基甲烷的工艺中,有些方法使用了贵金属催化剂,难以用简单方法合成或获取的反应底物;或使用了一些反应后难处理的溶剂,不仅增加了合成的成本,而且一些难处理的金属催化剂对环境造成很大的负面影响;最后一种方案虽然合成方法比较环保,但是使用的原料为活性酯,这个原料需要合成,市场直接买不到,因此原料不易得,此外,反应产率低,该反应产率如果以羧酸作为标准计算的话,产率大多为50%以下。这些缺点使得以上合成方法应用推广到工业生产中受到了很大的阻碍。
发明内容
本发明的目的是针对现有技术的不足,提供一种原料易得、低成本、时间简短、操作方便、环境友好并且适用于工业化生产的合成非对称杂环二芳基甲烷类化合物的方法。
本发明合成非对称杂环二芳基甲烷类化合物的方法,是以吲哚乙酸(IAA)和芳腈衍生物为原料,在碱、光敏剂及可见光条件下反应1-10小时,反应结束后减压蒸馏除去溶剂,柱层析分离,即得目标产物。
所述吲哚乙酸(IAA)的结构式为:
其中,R1为氢或烃氧基。
原料芳腈衍生物的结构式为:
其中,R2为烃基或卤素,X为C或N。
所述吲哚乙酸(IAA)衍生物和芳腈衍生物的摩尔比为3:1-1:1。
所述碱为K2CO3、K3PO4、Na2CO3、NaOAc、CsF或DMAP;碱的用量为吲哚乙酸(IAA)衍生物摩尔量的0.5-2倍。
所述光敏剂为fac-Ir(ppy)3、[Ir(dtbbpy)(ppy)2][PF6]、Ru(bpy)2(PF6)2、Ru(bpy)2Cl2·2H2O、曙红或孟加拉玫瑰红;光敏剂的用量为吲哚乙酸(IAA)衍生物摩尔量的1%-3%。
所述反应是在有机溶剂中进行,且有机溶剂为乙腈、二氯甲烷、1,2-二氯乙烷、丙酮、1,4-二氧六环、四氢呋喃或N,N-二甲基甲酰胺。所述可见光光源为蓝光。
合成路线为:
反应是以廉价的芳基乙酸和芳腈衍生物为原料,在碱、光敏剂及可见光条件下发生脱羧偶联反应,成功得到了非对称杂环二芳基甲烷类化合物。
本发明相对现有技术具有以下优点:
1. 反应所需原料简单,直接可从市场购买,试剂价格低廉,生产成本低;
2. 反应收率高,反应速率较快,所需时间短;
3. 反应条件温和,步骤简便,后处理简单,环境污染小。
具体实施方式
下面结合具体实例对本发明合成非对称杂环二芳基甲烷类化合物的方法进一步说明。
实施例1:化合物1的合成
向干燥的10 ml史莱克管中加入3-吲哚乙酸(0.2 mmol)、对苯二腈(0.1 mmol)、K2CO3(1.0equiv)、和fac-Ir(ppy)3(2 mol%),然后抽真空,充入氩气,来回置换3次,加入乙腈,将反应置于6W蓝光下照射3小时,反应完成后,减压浓缩反应混合物,柱层析(硅胶:200-300目,洗脱剂为乙酸乙酯/正己烷),可以得到75%的白色固体产物。
该化合物核磁数据如下:1H NMR (600 MHz, CDCl3) δ 7.98 (s, 1H), 7.54 (d,J = 8.2 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.8 Hz, 1H), 6.93 (d,J = 0.9 Hz, 1H), 6.89 - 6.85 (m, 1H), 6.84 (d, J = 2.3 Hz, 1H), 4.13 (s, 2H),3.79 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 154.1, 146.9, 132.2, 131.6, 129.3,127.5, 123.4, 119.1, 113.6, 112.3, 112.0, 109.7, 100.9, 55.9, 31.8. HRMS(ESI) exact mass calcd for C17H15N2O [M+H] + m/z 263.1184, found 263.1185.
实施例2:化合物2的合成
合成路线和分离方法同实施例1,其中仅将原料对苯二腈换成2-甲基对苯二腈。得到白色固体产物,产率为80%(rr = 4:5)。
该化合物核磁数据如下:1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.53 -7.39 (m, 2H), 7.36 (d, J = 3.6 Hz, 1H), 7.26 - 7.11 (m, 3H), 7.11 - 7.02 (m,1H), 6.94 (s, 0.4H), 6.75 (s, 0.5H), 4.10 (d, J = 6.7 Hz, 2H), 2.46 (s,1.3H), 2.35 (s, 1.7H). 13C NMR (151 MHz, CDCl3) δ 146.9, 145.1, 141.9, 137.9,136.5, 133.4, 132.5, 130.5, 129.9, 129.8, 127.2, 127.2, 126.6, 122.6, 122.3,122.3, 119.6, 119.4, 118.9, 118.8, 118.5, 114.0, 113.2, 111.3, 111.3, 110.1,109.8, 31.7, 29.5, 20.5, 19.4. HRMS (ESI) exact mass calcd for C17H15N2 [M+H] +m/z 247.1235, found 247.1240.
实施例3:化合物3的合成
合成路线和分离方法同实施例1,其中仅将原料对苯二腈换成4-氰基-2-氟吡啶。得到白色固体产物,产率为71%。
该化合物核磁数据如下:1H NMR (400 MHz, CDCl3) δ 1H NMR (400 MHz, CDCl3)δ 8.18 (s, 1H), 8.08 (d, J = 5.1 Hz, 1H), 7.46 - 7.31 (m, 2H), 7.24 - 7.19(m, 1H), 7.14 - 7.06 (m, 2H), 7.02 (s, 1H), 6.80 (s, 1H), 4.14 (s, 2H). 13CNMR (151 MHz, CDCl3) δ 164.2 (d, J = 238.2 Hz), 156.6 (d, J = 7.6 Hz), 147.2(d, J = 15.1 Hz), 136.4, 127.0, 122.7, 122.5, 121.7 (d, J = 3.9 Hz), 119.8,118.7, 112.6, 111.3, 109.2 (d, J = 37.0 Hz), 30.9, 30.9. HRMS (ESI) exactmass calcd for C14H12FN2 [M+H] + m/z 227.0985, found 227.0989.
实施例4:化合物4的合成
合成路线和分离方法同实施例1,其中仅将原料对苯二腈换成4-氰基-2-氯吡啶。得到白色固体产物,产率为74%。
该化合物核磁数据如下:1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 8.24 (d,J = 5.1 Hz, 1H), 7.47 - 7.36 (m, 2H), 7.22 (t, J = 7.5 Hz, 2H), 7.15 - 7.06(m, 2H), 7.00 (s, 1H), 4.09 (s, 2H). 13C NMR (151 MHz, CDCl3) δ 154.0, 151.6,149.4, 136.4, 126.9, 124.2, 122.8, 122.8, 122. 5, 119.8, 118.7, 112.5, 111.3,30.8. HRMS (ESI) exact mass calcd for C14H12ClN2 [M+H] + m/z 243.0689, found243.0683.
实施例5:化合物5的合成
合成路线和分离方法同实施例1,其中仅将原料对苯二腈换成4-氰基-3-氯吡啶。得到白色固体产物,产率为79%。
该化合物核磁数据如下:1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.55 (d,J = 2.3 Hz, 1H), 8.30 (d, J = 5.0 Hz, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.39 (d,J = 8.1 Hz, 1H), 7.22 (d, J = 7.2 Hz, 1H), 7.16 - 7.10 (m, 1H), 7.08 (d, J =5.0 Hz, 1H), 7.03 (d, J = 2.1 Hz, 1H), 4.23 (s, 2H). 13C NMR (151 MHz, CDCl3)δ 148.9, 148.0, 147.5, 136.4, 132.1, 127.1, 125.0, 123.2, 122.4, 119.7,118.8, 111.4, 111.4, 28.5.HRMS (ESI) exact mass calcd for C14H12ClN2 [M+H] + m/z 243.0689, found 243.0692。
Claims (8)
2.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:所述吲哚乙酸衍生物和芳腈衍生物的摩尔比为3:1-1:1。
3.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:碱为K2CO3、K3PO4、Na2CO3、NaOAc、CsF或DMAP。
4.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:碱的用量为吲哚乙酸衍生物摩尔量的0.5-2倍。
5.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:光敏剂为fac-Ir(ppy)3、[Ir(dtbbpy)(ppy)2][PF6]、Ru(bpy)2(PF6)2、Ru(bpy)2Cl2·2H2O、曙红或孟加拉玫瑰红。
6.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:光敏剂的用量为吲哚乙酸衍生物摩尔量的1%-3%。
7.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:所述反应是在有机溶剂中进行,有机溶剂为乙腈、二氯甲烷、1,2-二氯乙烷、丙酮、1,4-二氧六环、四氢呋喃或N,N-二甲基甲酰胺。
8.如权利要求1所述合成非对称杂环二芳基甲烷类化合物的方法,其特征在于:所述可见光光源为蓝光。
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CN113582915A (zh) * | 2021-07-25 | 2021-11-02 | 河南师范大学 | 一种4-取代吡啶类化合物的合成方法 |
Non-Patent Citations (2)
Title |
---|
SHAOKE ZHANG ET AL: "Cobalt-Catalyzed Hydrogenative Transformation of Nitriles", ACS CATAL., vol. 11, pages 13761 - 13767 * |
ZHIWEI ZUO ET AL: "Decarboxylative Arylation of α‑Amino Acids via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug Pharmacophore", J. AM. CHEM. SOC., vol. 136, pages 5257 - 5260, XP055241878, DOI: 10.1021/ja501621q * |
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