CN103922947A - 一种合成n,n-双取代烯胺酮类化合物的新方法 - Google Patents
一种合成n,n-双取代烯胺酮类化合物的新方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 14
- -1 enamine ketone compound Chemical class 0.000 title claims description 7
- 230000002194 synthesizing effect Effects 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- 150000002576 ketones Chemical class 0.000 claims description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000012153 distilled water Substances 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 8
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 claims description 3
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims description 3
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- 239000002994 raw material Substances 0.000 abstract description 6
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- 238000006555 catalytic reaction Methods 0.000 abstract 1
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- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
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Abstract
一种合成N,N-双取代烯胺酮类化合物的新方法，烯胺酮产物特征为氨基上含有两个相同的烃基取代基(图1)。本发明的优点是：1、相比已知的贵金属催化和高温缩合等合成法，本方法所用原料简单、反应条件温和；2、适用范围好，适合不同类型N,N-双取代烯胺酮的合成；3、操作简单、总产率好，适合工业化。
Description
技术领域
本发明涉及一种合成具有不同N,N-双取代烯胺酮的新方法。
背景技术
烯胺酮是一类具有多个不同类型活性反应位点的有机化合物，通过利用其不同反应位点，可以实现大量不同的药物、生物活性分子以及化工中间体等。因此，烯胺酮是非常重要的有机原料。N,N-双取代的烯胺酮是一类较为独特的烯胺酮，其结构中的N,N-双取代的氨基容易在亲和试剂，如伯胺类化合物的存在下快速发交叉氨化得到新的烯胺酮，进而发生各种不同串联反应，实现结构多样性有机化合物的合成。然而，目前较为容易合成的烯胺酮主要是含有NH结构，即，N-单取代的烯胺酮，合成N,N-双取代，特别是甲基以外的其它烃基取代的烯胺酮的方法非常少见。且已知的方法都涉及到实用贵金属催化剂或者空气敏感原料，在成本或操作上难以实现工业化。本发明报道一种原料经济、操作简单的分步合成方法，合成具有不同烃基N,N-双取代的烯胺酮化合物。
发明内容
本发明的目的在于提供一种原料经济、操作简便且容易实现的分步合成方法用于合成具结构多样N,N-双取代的烯胺酮化合物的方法。
本发明是这样来实现的：将苯乙酮4 mmol，甲酸甲酯 4 mmol，甲醇钠4 mmol加入50 ml圆底烧瓶中，加入20 ml乙醚回流1.5 h，反应结束后过滤得到固体，用乙醚冲洗两次，干燥，得固体，将固体置于25 ml圆底烧瓶中，将硫酸二乙酯 3.5 mmol)溶解在10 ml DMF 中，在0 oC 下逐滴加入到圆底烧瓶中，滴加完毕，在常温下继续搅拌反应2 h，反应结束后加入蒸馏水 10 mL，用乙醚萃取，合并有机相，并以蒸馏水洗涤2次，质量分数2% NaOH溶液洗涤两次，再以蒸馏水洗涤两次，加入Na2SO4干燥，过滤，滤液蒸除溶剂后，残余物以硅胶柱层析得到黄色油状物，将黄色油状物 1.0 mmol加入10 ml圆底烧瓶，加入二级胺1.2 mmol，二氯甲烷2 ml，常温下搅拌2h，减压蒸除溶剂，残余物以硅胶柱层析得到N,N-双取代产物，产物结构将核磁共振氢谱测试并比对文献报道结果确定无误。
烯胺酮产物特征为氨基上含有两个相同的烃基取代基。
本发明的技术效果是：本发明所用原料都为稳定化合物，且来源广泛成本低。操作过程简便，适用于多种含不同N,N-取代基的烯胺酮类化合物合成，而且易于工业放大，是一类高效实用的合成烯胺铜这类重要化工中间体的方法。
附图说明
图1为本发明合成流程图。
图2为本发明化合物8a的核磁共振氢谱图。
图3为本发明化合物8b的核磁共振氢谱图。
图4为本发明化合物8c的核磁共振氢谱图。
具体实施方式
本发明是这样来实现的：将苯乙酮 1 (4 mmol)，甲酸甲酯 2 (4 mmol)，甲醇钠 4 (4 mmol) 加入50 ml圆底烧瓶中，加入20 ml乙醚回流1.5 h，反应结束后过滤得到固体，用乙醚冲洗两次，干燥，得固体4。将4置于25 ml圆底烧瓶中，将硫酸二乙酯 5 (3.5 mmol) 溶解在DMF (10 ml)中，在0 oC 下逐滴加入到圆底烧瓶中，滴加完毕，在常温下继续搅拌反应2 h。反应结束后加入蒸馏水 10 mL，用乙醚萃取 (3 × 15 mL)，合并有机相，并以蒸馏水洗涤2次，质量分数2% NaOH溶液洗涤两次，再以蒸馏水洗涤两次，加入Na2SO4干燥，过滤。滤液蒸除溶剂后，残余物以硅胶柱层析得到黄色油状物6。将6 (1.0 mmol)加入10 ml圆底烧瓶，加入二级胺7 (1.2 mmol)，二氯甲烷(2 ml)，常温下搅拌2h，减压蒸除溶剂，残余物以硅胶柱层析得到N,N-双取代产物8，产物结构将核磁共振氢谱测试并比对文献报道结果确定无误。
如图1、2、3、4所示，产物核磁数据分别为：
(8a) 1H NMR (CDCl3, 400 MHz), δ 8.15 (d, 1 H, J = 12.8 Hz), 7.85 (d, 2 H, J = 7.2 Hz), 7.40-7.28 (m, 9 H), 7.18 (t, 4 H, J = 8.0 Hz), 6.00 (d, 1 H, J = 12.8 Hz), 4.36 (brs, 4 H).
(8b) 1H NMR (CDCl3, 400 MHz), δ7.89-7.79 (m, 3 H), 7.43-7.37 (m, 3 H), 5.74 (d, 1 H, J = 12.4 Hz), 3.18 (brs, 4 H), 1.62 (brs, 4 H), 0.91 (t, 6 H, J = 8.0 Hz).
(8c) 1H NMR (CDCl3, 400 MHz), δ7.87 (d, 2 H, J = 8.0 Hz), 7.80 (d, 1 H, J =12.4 Hz), 7.43-7.37 (m, 3 H), 5.76 (d, 1 H, J = 12.4 Hz), 3.28 (q, 4 H, J = 6.8 Hz), 1.19 (t, 6 H, J = 7.2 Hz)。
Claims (2)
1.一种合成N,N-双取代烯胺酮类化合物的新方法，其特征在于：将苯乙酮4 mmol，甲酸甲酯 4 mmol，甲醇钠4 mmol加入50 ml圆底烧瓶中，加入20 ml乙醚回流1.5 h，反应结束后过滤得到固体，用乙醚冲洗两次，干燥，得固体，将固体置于25 ml圆底烧瓶中，将硫酸二乙酯 3.5 mmol)溶解在10 ml DMF 中，在0 oC 下逐滴加入到圆底烧瓶中，滴加完毕，在常温下继续搅拌反应2 h，反应结束后加入蒸馏水 10 mL，用乙醚萃取，合并有机相，并以蒸馏水洗涤2次，质量分数2% NaOH溶液洗涤两次，再以蒸馏水洗涤两次，加入Na2SO4干燥，过滤，滤液蒸除溶剂后，残余物以硅胶柱层析得到黄色油状物，将黄色油状物 1.0 mmol加入10 ml圆底烧瓶，加入二级胺1.2 mmol，二氯甲烷2 ml，常温下搅拌2h，减压蒸除溶剂，残余物以硅胶柱层析得到N,N-双取代产物，产物结构将核磁共振氢谱测试并比对文献报道结果确定无误。
2.根据权利要求1所述的一种合成N,N-双取代烯胺酮类化合物的新方法，其特征在于，烯胺酮产物特征为氨基上含有两个相同的烃基取代基。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105753725A (zh) * | 2016-04-08 | 2016-07-13 | 安顺学院 | 一种烯胺酮类化合物的制备方法 |
| CN113200952A (zh) * | 2021-04-13 | 2021-08-03 | 江西师范大学 | 一种串联环化反应合成2-氨基-3,3-二氯或二溴代色满酮的方法 |
| CN117567912A (zh) * | 2023-11-22 | 2024-02-20 | 江西科技师范大学 | 一种可回收聚丙烯酸酯乳液涂层及其制备方法和应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20040102651A1 (en) * | 2002-11-22 | 2004-05-27 | Board Of Regents, The University Of Texas System | Synthesis of 3-aminomethyl-1-propanol, a fluoxetine precursor |
| CN101591338A (zh) * | 2009-06-30 | 2009-12-02 | 中国人民解放军第三军医大学 | 茚地普隆的合成方法 |
| CN101781222A (zh) * | 2010-01-26 | 2010-07-21 | 广东药学院 | 一种制备烯胺酮类化合物的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040102651A1 (en) * | 2002-11-22 | 2004-05-27 | Board Of Regents, The University Of Texas System | Synthesis of 3-aminomethyl-1-propanol, a fluoxetine precursor |
| CN101591338A (zh) * | 2009-06-30 | 2009-12-02 | 中国人民解放军第三军医大学 | 茚地普隆的合成方法 |
| CN101781222A (zh) * | 2010-01-26 | 2010-07-21 | 广东药学院 | 一种制备烯胺酮类化合物的方法 |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105753725A (zh) * | 2016-04-08 | 2016-07-13 | 安顺学院 | 一种烯胺酮类化合物的制备方法 |
| CN113200952A (zh) * | 2021-04-13 | 2021-08-03 | 江西师范大学 | 一种串联环化反应合成2-氨基-3,3-二氯或二溴代色满酮的方法 |
| CN113200952B (zh) * | 2021-04-13 | 2023-03-10 | 江西师范大学 | 一种串联环化反应合成2-氨基-3,3-二氯代色满酮或2-氨基-3,3-二溴代色满酮的方法 |
| CN117567912A (zh) * | 2023-11-22 | 2024-02-20 | 江西科技师范大学 | 一种可回收聚丙烯酸酯乳液涂层及其制备方法和应用 |
| CN117567912B (zh) * | 2023-11-22 | 2024-05-28 | 江西科技师范大学 | 一种可回收聚丙烯酸酯乳液涂层及其制备方法和应用 |
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