CN102627571A - 一种手性铵盐的制备及合成方法 - Google Patents
一种手性铵盐的制备及合成方法 Download PDFInfo
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- CN102627571A CN102627571A CN2012101047222A CN201210104722A CN102627571A CN 102627571 A CN102627571 A CN 102627571A CN 2012101047222 A CN2012101047222 A CN 2012101047222A CN 201210104722 A CN201210104722 A CN 201210104722A CN 102627571 A CN102627571 A CN 102627571A
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- ammonium salt
- phenylethylamine
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- fluorobenzaldehyde
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000003863 ammonium salts Chemical class 0.000 title claims abstract description 7
- 238000001308 synthesis method Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 10
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000004440 column chromatography Methods 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 10
- -1 silicane nitrile Chemical class 0.000 claims description 10
- 239000013078 crystal Substances 0.000 claims description 7
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 claims description 6
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 claims description 6
- 241000545067 Venus Species 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- JNDBWGDXMCXJPM-UHFFFAOYSA-N azane;2-phenylethanamine Chemical compound N.NCCC1=CC=CC=C1 JNDBWGDXMCXJPM-UHFFFAOYSA-N 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- 239000003054 catalyst Substances 0.000 abstract 1
- IZVCCQJOQFBYCY-LSBIWMFESA-L copper;(1r)-1-phenylethanamine;diacetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O.C[C@@H](N)C1=CC=CC=C1 IZVCCQJOQFBYCY-LSBIWMFESA-L 0.000 abstract 1
- 239000003208 petroleum Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005189 flocculation Methods 0.000 description 1
- 230000016615 flocculation Effects 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
一手性铵盐的制备,其化学式如下:
Description
一、技术领域
本发明涉及一种新化合物及其制备方法,特别涉及一种手性化合物及其制备方法,确切地说是一种手性铵盐的制备及合成方法。
二、背景技术
近年来手性含氮化合物相继有许多文献报道,手性含氮化合物及其金属配合物在高分子和有机合成不对称催化领域具有重要意义。成为国内外研究的热点之一。
铵盐是重要的医药化工产品,可用作杀菌剂、絮凝剂,还可用于相转移催化剂。[1-2].
1.Research progress on chitosan quaternary ammonium salt, Li, Rong-chun,
Huaxue Shiji 33(10),
895-898.
2. Quaternary Ammonium
(Hypo)iodite Catalysis for Enantioselective Oxidative Cycloetherification , Uyanik, Muhammet; Okamoto,
Hiroaki; Yasui, Takeshi; Ishihara, Kazuaki , Science
(2010), 328(5984), 1376-1379.
申请人在用配合物α-( R)-苯乙胺乙酸铜配合物不对称催化4-氟苯甲醛腈硅化反应过程中,没有得到手性目标产物(2-三甲基硅氧基)-4-氟-苯基乙腈,但是意外地得到了一种手性化合物。
二、发明内容
本发明旨在提供手性化合物4-氟苯甲酸-(R)-苯乙胺铵盐。所要解决的技术问题是一步合成得到目标产物。
本发明所称的手性化合物是由4-氟苯甲醛与三甲基硅腈制备的由以下化学式所示的化合物:
化学名称:4-氟苯甲酸-(R)-苯乙胺铵盐,简称化合物(I)。
本合成方法包括合成和分离,所述的合成用15mol% α-(R)-苯乙胺乙酸铜做催化剂,4 –氟苯甲醛2mmol,三甲基硅腈6mmol,用5mL无水甲醇做溶剂,室温反应3天后,柱层析分离,用石油醚/二氯甲烷(9/1)洗脱,将收集的第一组份点自然挥发,得单晶4-氟苯甲酸-(R)-苯乙胺铵盐。
合成反应如下:
本合成方法一步得到目标产物,工艺简单,操作方便。
其反应机理可推测如下:
4-氟苯甲醛与三甲基硅腈,在催化剂15mol%α-( R)-苯乙胺乙酸铜的作用下,由于4-氟苯甲醛在空气中不稳定,4-氟苯甲醛首先被氧化成4-氟苯甲酸,而且催化剂α-( S)-苯乙胺乙酸铜,在反应过程中分解,释放出α-( R)-苯乙胺与溶液中4-氟苯甲酸作用,形成4-氟苯甲酸-(S)-苯乙胺铵盐。
其反应过程如下:
四、附图说明
图1是4-氟苯甲酸-(R)-苯乙胺铵盐的X-衍射分析图。
三、具体实施方式
在25mL两口瓶中,无水无氧条件下,加入5mL无水甲醇, 4-氟苯甲醛0.1mL(1mmol), 三甲基硅腈3mmol,催化剂α-(S)-苯乙胺乙酸铜0.132g(0.30mmol),将反应物在室温下搅拌5天,停止反应,柱层析分离,用石油醚/二氯甲烷(9/1)洗脱,将收集的第一组分点自然挥发,得单晶4-氟苯甲酸-(S)-苯乙胺铵盐。产率25%;[a]5 D=
+21.92º (c=0.02, CH2Cl2):
1HNMR (500MHz, CDCl3, 27℃), δ (ppm) = 7.87 (d, 0.6 Hz, 3H), 7.22~7.33 (m, 4H), 7.01(s, 2H),
4.73(s, 1H), 3.67(s, br, 1H), 1.56~1.57 (s, 3H), 13CNMR(125MHz,
CDCl3, 27℃) 190.5, 158.1, 142.9, 132.3, 128.9, 128.8, 127.8, 126.9, 126.2, 116.3,
115.9, 115.7, 56.7, 30.9. IR (KBr) : 2970, 2546, 1607, 1527, 1457, 1394, 1368,
1228, 1149, 858, 785, 766, 698, 611; HRMS(EI):m-C8H11N/z
(%): calcd for C7H5O2F: 140.0274;
found:140.0278.
手性
(R)-
α
-
苯乙胺醋酸铜金属有机配合物催化剂的合成
称取2.000g Cu(CH3COO)2·H2O (0.01mol)加入到100mL圆底烧瓶中,再加入25mL四氢呋喃作溶剂,在搅拌情况下用针筒量取3mL α-(R)-苯乙胺(mol, 稍过量点)加入到烧瓶中,反应完成后,在旋转蒸发仪上抽干后为粘稠状液体,用正己烷重结晶,得淡蓝色晶体,产率=80.1%,[a] 25 D=
+ 14.15º (c 0.4776, THF) Elemental
analysis: found: N:6.45%, C:56.17%, H:6.56%; Calculate: N:6.61%, C:56.65%,
H:6.62%.
腈硅化反应应用
2-苯基-2-(三甲硅氧基)丙腈的制备
0.30mmol 化合物I , 苯甲醛0.2mL, TMSCN 0.6 ml
(3.3mmol) 相继在20~30˚C下加入,3天后, 加入水淬灭经柱层后(石油醚/二氯甲烷:5/1),得无色油状液体, 转化率:65%,1H NMR (300MHz, CDCl3) 7.56–7.59 (m, 0.9 Hz, 2H), 7.31–7.34 (m, 3H), 5.43 (s,
1H), 0.16 (s, 9H). 13C NMR (75 MHz, CDCl3) 136.1, 128.8(x2), 126.2(x2), 119.1,
63.5, -0.39(x3)。
Claims (2)
1.一手性铵盐的制备是由4-氟苯甲醛与三甲基硅腈制备的由以下化学式所示的化合物:
。
2.由权利要求1所述的化合物(I)的合成方法, 包括合成和分离,所述的合成用15mol% α-(R)-苯乙胺乙酸铜做催化剂,4 –氟苯甲醛2mmol,三甲基硅腈6mmol,用5mL无水甲醇做溶剂,室温反应3天后,柱层析分离,用石油醚/二氯甲烷(9/1)洗脱,将收集的第一组份点自然挥发,得单晶4-氟苯甲酸-(R)-苯乙胺铵盐。
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CN103396341A (zh) * | 2013-08-05 | 2013-11-20 | 罗梅 | 一种手性羟基腈的合成方法 |
CN104496835A (zh) * | 2014-12-27 | 2015-04-08 | 罗梅 | 一种手性铵盐晶体的制备及合成方法 |
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CN101973953A (zh) * | 2010-09-14 | 2011-02-16 | 罗梅 | 一种手性噁唑啉的合成方法 |
CN102069014A (zh) * | 2010-09-15 | 2011-05-25 | 罗梅 | 一种手性α-苯乙胺锌、铜配合物的用途 |
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CN101973953A (zh) * | 2010-09-14 | 2011-02-16 | 罗梅 | 一种手性噁唑啉的合成方法 |
CN102069014A (zh) * | 2010-09-15 | 2011-05-25 | 罗梅 | 一种手性α-苯乙胺锌、铜配合物的用途 |
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CN103396341A (zh) * | 2013-08-05 | 2013-11-20 | 罗梅 | 一种手性羟基腈的合成方法 |
CN104496835A (zh) * | 2014-12-27 | 2015-04-08 | 罗梅 | 一种手性铵盐晶体的制备及合成方法 |
CN104496835B (zh) * | 2014-12-27 | 2016-02-03 | 罗梅 | 一种手性铵盐晶体的制备及合成方法 |
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