CN102617499B - 一种手性锌配合物 - Google Patents
一种手性锌配合物 Download PDFInfo
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- 239000011701 zinc Substances 0.000 title abstract description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title abstract 2
- 229910052725 zinc Inorganic materials 0.000 title abstract 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000004440 column chromatography Methods 0.000 claims abstract description 7
- VPSSPAXIFBTOHY-LURJTMIESA-N (2s)-2-amino-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 claims abstract description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000000605 extraction Methods 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 6
- NLDYACGHTUPAQU-UHFFFAOYSA-N tetracyanoethylene Chemical group N#CC(C#N)=C(C#N)C#N NLDYACGHTUPAQU-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000000926 separation method Methods 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000000746 purification Methods 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 6
- UHIJLWIHCPPKOP-UHFFFAOYSA-N [N].[Zn] Chemical compound [N].[Zn] UHIJLWIHCPPKOP-UHFFFAOYSA-N 0.000 claims description 5
- 238000010189 synthetic method Methods 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 abstract description 5
- 239000013078 crystal Substances 0.000 abstract description 3
- 235000005074 zinc chloride Nutrition 0.000 abstract description 3
- 239000011592 zinc chloride Substances 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
- 238000010992 reflux Methods 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 abstract 2
- 238000006842 Henry reaction Methods 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 238000004807 desolvation Methods 0.000 abstract 1
- 238000002386 leaching Methods 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 abstract 1
- 239000003208 petroleum Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 4
- -1 67.46% Inorganic materials 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- JTNVCJCSECAMLD-QZTJIDSGSA-N (4s)-4-phenyl-2-[2-[(4s)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]propan-2-yl]-4,5-dihydro-1,3-oxazole Chemical compound C1([C@@H]2N=C(OC2)C(C)(C)C=2OC[C@@H](N=2)C=2C=CC=CC=2)=CC=CC=C1 JTNVCJCSECAMLD-QZTJIDSGSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-Phenylethanol Natural products OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 1
- 0 CC**COC([C@](C)C#N)=I Chemical compound CC**COC([C@](C)C#N)=I 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- BUKJRQHSQSNQKA-UHFFFAOYSA-N O1C(=NCC1)C=1C(=C(C=CC=1)[Ru+])C=1OCCN=1 Chemical class O1C(=NCC1)C=1C(=C(C=CC=1)[Ru+])C=1OCCN=1 BUKJRQHSQSNQKA-UHFFFAOYSA-N 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
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- HFWIMJHBCIGYFH-UHFFFAOYSA-N cyanoform Chemical compound N#CC(C#N)C#N HFWIMJHBCIGYFH-UHFFFAOYSA-N 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development 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
- 239000011982 enantioselective catalyst Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000005623 oxindoles Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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Abstract
Description
一、技术领域
本发明涉及一种金属有机配位化合物(配合物)及其制备方法,特别涉及含氮的手性金属有机配合物及其制备方法,确切地说是一种手性锌氮配合物及其合成方法。
二、背景技术
随着有机化学的发展,金属有机化合物在有机合成中的应用愈来愈广,是现在有机化学中极为活跃的领域之一,已经广泛应用于有机合成反应中。20世纪60年代后期出现的使用手性配体与过渡金属络合物催化的不对称合成反应大大加速了手性药物的研究。化学催化不对称合成法的重要内容便是手性配体及含金属催化剂的设计,从而使反应具有高效和高对映选择性。通常不对称催化剂所用的配体是噁唑啉,近年来噁唑啉锌配合物被广泛合成并取得较好的催化效果。
参考文献:
1. Synthesis of highly modular bis(oxazoline) ligands by Suzuki cross-coupling and evaluation as catalytic
ligands,Cattoen, Xavier; Pericas, Miquel A. Tetrahedron,65(39),8199-8205。
2.The synthesis of new oxazoline-containing bifunctional catalysts and their application in the addition of
diethylzinc to aldehydes, Coeffard, Vincent; Mueller-Bunz, Helge; Guiry, Patrick J, Organic &
Biomolecular Chemistry, 7(8), 1723-1734.
3. New Bis(oxazolinyl)phenyl-Ruthenium(II) Complexes and Their Catalytic Activity for Enantioselective
Hydrogenation and Transfer Hydrogenation of Ketones, Ito, Jun-ichi; Ujiie, Satoshi; Nishiyama, Hisao,
Organometallics, 28(2),630-638.
4.Lewis Acid-Catalyzed Enantioselective Hydroxylation Reactions of Oxindoles and β-Keto Esters
Using DBFOX Ligand,Ishimaru, Takehisa; Shibata, Norio; Nagai, Jun; Nakamura, Shuichi; Toru, Takeshi;
Kanemasa, Shuji, Journal of the American Chemical Society,128(51),6488-16489
三、发明内容
本发明旨在提供一种Zn-N金属有机配合物以应用于催化领域,所要解决的技术问题遴选噁唑啉作为配体并合成手性锌氮配合物。
本发明所称的手性锌配合物是双-(4-异丁基-4,5-二氢化-2-噁唑啉基)-乙腈锌配合物由四腈乙烯制备的由以下化学式所示的配合物:
化学名称:双-(4-异丁基-4,5-二氢化-2-噁唑啉基)-乙腈锌配合物,简称配合物(I)。
本手性化合物的合成方法包括反应、分离和纯化,其特征是制备中间体的反应由四氰乙烯和L-亮氨醇在无水无氧条件下和催化剂无水ZnCl2 (42%)时于氯苯溶剂中回流反应72小时离、纯化,即反应结束后脱去氯苯,加水溶解后用氯仿萃取,萃取相脱溶后用柱层析纯化;
本配合物(I)的合成方法是四氰乙烯与L-亮氨醇在氯溶剂中回流反应72小时。
配合物(I)用石油醚及二氯甲烷淋洗,柱层析分离,自然挥发得配合物单晶。
该配合物的反应机理可推测为四氰乙烯在空气中及氯化锌作用下,不稳定,分解成三氰基甲烷,与2分子的L-亮氨醇作用形成双噁唑啉再与氯化锌按照2:1配位,并脱去两分子盐酸。
四、附图说明
图1是配合物 (I) 的单晶衍射图。
五、具体实施方式
(一)手性配合物的制备
1、双-(4-异丁基-4,5-二氢化-2-噁唑啉基)-乙腈锌配合物的制备
在100mL两口瓶中,无水无氧条件下,加入无水ZnCl2 0.45g (3.30mmol), 40mL氯苯, 四氰乙烯1.0g(7.81mmol), L-亮氨醇 4g, 将混合物在高温下回流24h,停止反应,减压以除去溶剂, ,将剩余物用水溶解,并用CHCl3(20mLx2)萃取,有机相用无水硫酸钠干燥,旋转除去溶剂,将粗产品用石油醚/ 二氯甲烷(4:1)柱层析,得白色晶体,产率32%;[a]5 D=+166.33o (c=0.30, CH2Cl2):1HNMR (500MHz, CDCl3, 27℃), δ (ppm) = 4.60(t, J=0.5Hz, 4H), 3.94~4.05 (m, 8H), 1.29~1.72(m, 12H), 0.89~0.93(m, 24H); 13C NMR (75 MHz, CDCl3) 170.1, 118.3, 73.0, 61.7, 45.6, 24.9, 22.3, 21.8。IR :3439, 2955, 2927, 2871, 2201, 1611, 1530, 1430, 1386, 1368, 1342, 1281, 1260, 1239 1218, 1133, 1068, 1048, 951, 746 元素分析:C:59.32%, H, 67.46%, N, 13.77%.
(三)、亨利反应应用
2-硝基-1苯基乙醇的制备
取0.20mmol的配合物I(催化用量为20%)于25mL的小烧瓶中,加入2毫升的无水甲醇溶液,然后,向上述溶液中加入0.1mL的苯甲醛与0.5mL的硝基甲烷,常温搅拌,反应小120小时后,进行核磁分析,转化率:29%;1H NMR (300MHz, CDCl3) 7.28~7.32 (m, 5H, Ar-H), 5.32~5.35(d, J=9.18Hz, 1H, -CH), 4.38~4.56 (m, 2H, -CH2), 3.89(br, 1H, -OH)。
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