CN106478487B - 吡咯烷类化合物及其合成方法 - Google Patents
吡咯烷类化合物及其合成方法 Download PDFInfo
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- 150000003235 pyrrolidines Chemical class 0.000 title claims abstract description 14
- 238000001308 synthesis method Methods 0.000 title claims 2
- -1 pyrrolidine compound Chemical class 0.000 claims abstract description 21
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- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
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- 238000010992 reflux Methods 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012044 organic layer Substances 0.000 claims description 3
- FGTWRFGVFTTZOI-UHFFFAOYSA-N 2-benzyl-1,3-dihydroisoindole Chemical compound C1C2=CC=CC=C2CN1CC1=CC=CC=C1 FGTWRFGVFTTZOI-UHFFFAOYSA-N 0.000 claims description 2
- AFYZAHZKOFBVLE-UHFFFAOYSA-N 6-benzyl-1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridine Chemical compound C1C2CCCNC2CN1CC1=CC=CC=C1 AFYZAHZKOFBVLE-UHFFFAOYSA-N 0.000 claims description 2
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract 2
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
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- 125000000524 functional group Chemical group 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OXFMJRAOSJKURE-UHFFFAOYSA-N 2-benzyl-1,3,3a,4,5,6,7,7a-octahydroisoindole Chemical compound C1C2CCCCC2CN1CC1=CC=CC=C1 OXFMJRAOSJKURE-UHFFFAOYSA-N 0.000 description 1
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- WITXFYCLPDFRNM-UHFFFAOYSA-N N-Benzylphthalimide Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 WITXFYCLPDFRNM-UHFFFAOYSA-N 0.000 description 1
- GJWAPAVRQYYSTK-UHFFFAOYSA-N [(dimethyl-$l^{3}-silanyl)amino]-dimethylsilicon Chemical compound C[Si](C)N[Si](C)C GJWAPAVRQYYSTK-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
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- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 1
- 229960003702 moxifloxacin Drugs 0.000 description 1
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- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 229920001843 polymethylhydrosiloxane Polymers 0.000 description 1
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- 125000003944 tolyl group Chemical group 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/62—Naphtho [c] pyrroles; Hydrogenated naphtho [c] pyrroles
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/72—4,7-Endo-alkylene-iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
Abstract
一种吡咯烷类化合物及其合成方法，将溶解于有机溶剂中的环状酰亚胺类化合物与作为还原剂的硅氢试剂和作为催化剂的路易斯酸混合，在回流的条件下制备得到芳香环以及脂肪环吡咯烷类化合物。本发明合成路线简洁，高效和经济，条件温和，适用性广，对吡咯烷类化合物的后期工业化生产将起到极大的推动作用。
Description
技术领域
本发明涉及的是一种化工领域的技术，具体是一种路易斯酸催化环状酰亚胺类化合物的硅氢化反应制备吡咯烷类化合物的合成方法。
背景技术
吡咯烷类化合物是杂环化合物中的一种重要类型，普遍存在于一些天然产物、药物中间体、药物分子、功能材料中，因而吡咯烷类化合物的合成在有机合成方面具有重要的意义。
通过还原酰亚胺类化合物来合成吡咯烷类化合物是最直接的方法，目前制备吡咯烷类化合物的经典的还原方法是使用四氢铝锂、硼烷等化合物作为还原剂来实现。由于酰亚胺类化合物的还原存在多个中间体，使用这类还原剂导致副产物的形成，并且这类还原试剂的官能团兼容性差。同时因还原剂的活性较高，对水敏感等缺点，使该反应常常需要在严格控制在无水以及低温的环境下进行，且反应的后处理步骤比较繁琐。
发明内容
本发明针对现有技术存在的上述不足，提出一种吡咯烷类化合物及其合成方法，从酰亚胺类化合物出发，利用简单廉价的硅氢类化合物为还原剂、含硼化合物作为催化剂催化硅氢化还原环状酰亚胺类化合物实现，其合成路线简洁，条件温和，适用于大规模量产。
本发明是通过以下技术方案实现的：
本发明涉及一种吡咯烷类化合物，其结构式为：或其中：
R1为含不同取代基苄基、烷烃、烯烃、炔基、芳基或含有各类官能团(氰基、卤素、羰基、烷氧基、氨基、羟基)烷基链；
R2为卤素、烷氧基、羰基、萘环、氨基或保护氨基；
R3为含不同取代基苄基、烷烃、烯烃、炔基、芳基或含有各类官能团(氰基、卤素、羰基、烷氧基、氨基、羟基)烷基链；
R4为氢、环烷烃、降冰片烷、降冰片烯或六氢吡啶。
本发明涉及上述吡咯烷类化合物的合成方法，将溶解于有机溶剂中的环状酰亚胺类化合物与作为还原剂的硅氢试剂和作为催化剂的路易斯酸混合，在回流的条件下制备得到芳香环以及脂肪环吡咯烷类化合物，其反应式如下：
所述的路易斯酸进一步优选为：三‐(五氟苯基)硼、苯硼酸、取代的苯硼酸或三氟化硼乙醚等。
所述的还原剂进一步优选为芳基三硅氢，烷基三硅氢、二芳基硅氢、二烷基硅氢、1,1,3,3‐四甲基二硅氧烷、PMHS(含氢硅油)或三芳基硅氢等。
所述的有机溶剂为甲苯、1,4‐二氧六环、1,2‐二氯乙烷或氯仿。
所述的环状酰亚胺类化合物和硅氢试剂中氢的量的反应摩尔比为1/6‐1/4，催化剂的用量为环状酰亚胺的0.1‐2.0mol％。
所述的回流是指，在110℃环境下回流反应，反应完成后加入水猝灭剩余的硅氢试剂，萃取有机层后浓缩，直接柱层析得到目标产物。
本发明涉及上述方法制备得到的吡咯烷类化合物的应用，将吡咯烷类化合物中的至少一个化合物用于莫西沙星、米格列奈钙以及普环啶等的重要片段的制造。
技术效果
与现有技术相比，本发明以“高选择性”为背景，利用温和廉价的还原剂硅氢试剂，在路易斯酸催化剂的存在下，优选以常见的甲苯为溶剂，回流的情况下制备各种取代的吡咯烷类化合物。相比现有的制备工艺，本发明所用到的还原剂操作简便，高选择性，底物适用性广，收率高。
具体实施方式
实施例1
本实施例涉及N‐苄基异吲哚啉的合成，其具体步骤如下：
在反应管中加入N‐苄基邻苯二甲酰亚胺(237.3mg,1.0mmol)，B(C6F5)3(10.2mg,2.0mol％)，甲苯(2mL)搅拌溶解后缓慢在体系中加入硅氢试剂TMDS(335.8mg,2.5mmol)，将反应温度升至110℃回流。反应完加入水猝灭剩余的硅氢试剂，萃取有机层后浓缩，直接柱层析得到目标产物，产率：95％。1H NMR(400MHz,CDCl3)δ7.44–7.42(m,2H),7.38–7.34(m,2H),7.31–7.26(m,1H),7.18(s,4H),3.94(s,4H),3.92(s,2H).13C NMR(100MHz,CDCl3)δ140.3,139.2,128.89,128.5,127.2,126.7,122.4,60.4,59.0.
实施例2
本实施例涉及N‐((4‐三氟甲基)苄基)异吲哚啉的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：90％。1H NMR(400MHz,CDCl3)δ7.62–7.60(m,2H),7.55–7.53(m,2H),7.20(s,4H),3.97(s,2H),3.94(s,4H).13C NMR(100MHz,CDCl3)δ143.5,140.1,129.5(q,J＝32.1Hz),129.0,126.9,125.5(q,J＝3.7Hz),124.4(q,J＝270.1Hz),122.5,59.9,59.1.
实施例3
本实施例涉及2,6‐二苄基‐1,2,3,5,6,7‐六氢苯并联吡咯的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：90％。1H NMR(400MHz,CDCl3)δ7.41–7.39(m,4H),7.36–7.32(m,4H),7.29–7.27(m,2H),6.97(s,2H),3.89(s,4H),3.87(s,8H).13C NMR(100MHz,CDCl3)δ139.2,139.0,128.9,128.5,127.2,116.5,60.5,58.9.
实施例4
本实施例涉及N‐苄基‐2,3‐二氢‐苯并异吲哚的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：89％。1H NMR(400MHz,CDCl3)δ7.81–7.79(m,2H),7.63(s,2H),7.49–7.39(m,6H),7.35–7.32(m,1H),4.06(s,4H),3.97(s,2H).13C NMR(100MHz,CDCl3)δ139.4,139.1,133.1,129.0,128.5,127.8,127.3,125.4,120.6,60.6,58.7.
实施例5
本实施例涉及N‐苄基‐4,7‐桥亚甲基‐全氢异吲哚的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：94％。1H NMR(400MHz,CDCl3)δ7.36–7.28(m,4H),7.24–7.21(m,1H),3.52(s,2H),2.76(d,J＝10.0Hz,2H),2.35–2.34(m,2H),2.11(s,2H),2.02–1.98(m,2H),1.77–1.75(m,2H),1.41–1.33(m,2H),1.26–1.24(m,2H).13C NMR(100MHz,CDCl3)δ140.5,128.5,128.2,126.7,60.7,55.4,44.1,42.3,41.4,24.1.
实施例6
本实施例涉及N‐苄基全氢异吲哚的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：90％。1H NMR(400MHz,CDCl3)δ7.38–7.32(m,4H),7.29–7.24(m,1H),3.76(s,2H),2.83–2.79(m,2H),2.57–2.53(m,2H),2.21–2.15(m,2H),1.60–1.46(m,6H),1.38–1.30(m,2H).13C NMR(100MHz,CDCl3)δ139.9,128.8,128.3,126.9,61.4,58.4,37.3,27.0,23.0.
实施例7
本实施例涉及N‐苄基吡咯烷的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：82％。1H NMR(400MHz,CDCl3)δ7.35–7.23(m,5H),3.65(s,2H),2.55–2.53(m,4H),1.82–1.78(m,4H).13C NMR(100MHz,CDCl3)δ139.2,129.0,128.3,127.0,60.8,54.2,23.5.
实施例8
本实施例涉及6‐苄基八氢吡咯并[3,4‐B]吡啶的合成，其具体步骤如下：
按照与实施例1相同的操作，得到目标化合物，产率：85％。1H NMR(400MHz,CDCl3)δ7.34–7.29(m,4H),7.27–7.22(m,1H),3.82–3.69(m,2H),3.28–3.26(m,1H),3.04–3.00(m,1H),2.87–2.84(m,1H),2.80–2.75(m,1H),2.71–2.55(m,3H),2.29–2.21(m,1H),1.69–1.64(m,2H),1.52–1.43(m,2H).13C NMR(100MHz,CDCl3)δ139.0,128.7,128.2,126.9,60.5,59.8,56.1,55.0,43.8,36.2,23.9,21.4.
上述具体实施可由本领域技术人员在不背离本发明原理和宗旨的前提下以不同的方式对其进行局部调整，本发明的保护范围以权利要求书为准且不由上述具体实施所限，在其范围内的各个实现方案均受本发明之约束。
Claims (1)
1.一种吡咯烷类化合物的合成方法，其特征在于，该吡咯烷类化合物的结构式包括：
N-苄基异吲哚啉
N-((4-三氟甲基)苄基)异吲哚啉
2,6-二苄基-1,2,3,5,6,7-六氢苯并联吡咯
N-苄基-2,3-二氢-苯并异吲哚
N-苄基-4,7-桥亚甲基-全氢异吲哚
N-苄基全氢异吲哚
N-苄基吡咯烷或
6-苄基八氢吡咯并[3,4-B]吡啶
所述的合成方法，将溶解于甲苯中的环状酰亚胺类化合物与作为还原剂的1,1,3,3-四甲基二硅氧烷和作为催化剂的B(C6F5)3混合，在回流的条件下制备得到芳香环以及脂肪环吡咯烷类化合物，其反应式为：
所述的环状酰亚胺类化合物和1,1,3,3-四甲基二硅氧烷中氢的量的反应摩尔比为1/6-1/4；
所述的B(C6F5)3的用量为环状酰亚胺的0.1-2.0mol％；
所述的回流是指，在110℃环境下回流反应，反应完成后加入水猝灭剩余的1,1,3,3-四甲基二硅氧烷，萃取有机层后浓缩，直接柱层析得到目标产物。
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Non-Patent Citations (6)
| Title |
|---|
| 1,2:3"",4"";4,5-benzene.《Helvetica Chimica Acta》.1947,第30卷第2035-2045页. |
| 806623-06-3;CAS;《STN-REGISTRY》;20050102 |
| Ruggli,P.et al..Heterocyclic nitrogen compounds. LXI.Dipyrrolino-3",4" |
| Selective Catalytic Monoreduction of Phthalimides and Imidazolidine-2,4-diones;Shoubhik Das,et al.;《Angew. Chem. Int. Ed.》;20110824;第50卷;9180-9184 |
| 莫西沙星的合成;刘明亮等;《中国医药工业杂志》;20041231;第35卷(第3期);第129,131页 |
| 顺式全氢异吲哚的合成;李海波等;《华西药学杂志》;20081231;第23卷(第1期);第20-22页 |
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