CN102675150B - Preparation method and synthesis method of chiral compound - Google Patents
Preparation method and synthesis method of chiral compound Download PDFInfo
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- CN102675150B CN102675150B CN 201210130713 CN201210130713A CN102675150B CN 102675150 B CN102675150 B CN 102675150B CN 201210130713 CN201210130713 CN 201210130713 CN 201210130713 A CN201210130713 A CN 201210130713A CN 102675150 B CN102675150 B CN 102675150B
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- chiral compound
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- phenylethylamine
- phenyl
- methylene dichloride
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title abstract description 6
- 238000001308 synthesis method Methods 0.000 title abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- -1 trimethyl silicon nitrile Chemical class 0.000 claims abstract description 10
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical class BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000004440 column chromatography Methods 0.000 claims abstract description 4
- 238000000926 separation method Methods 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 238000010189 synthetic method Methods 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 5
- 241000545067 Venus Species 0.000 claims description 5
- 239000013078 crystal Substances 0.000 claims description 5
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 claims description 3
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 abstract description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 8
- 229910052794 bromium Inorganic materials 0.000 abstract description 8
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 abstract 2
- 229940076286 cupric acetate Drugs 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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- MFHFWRBXPQDZSA-UHFFFAOYSA-N 2-(4-bromophenyl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=C1 MFHFWRBXPQDZSA-UHFFFAOYSA-N 0.000 description 1
- FEOXGIVWOKWUIT-UHFFFAOYSA-N 2-(ethylamino)-2,2-diphenylacetonitrile Chemical compound C(C)NC(C#N)(C1=CC=CC=C1)C1=CC=CC=C1 FEOXGIVWOKWUIT-UHFFFAOYSA-N 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical group C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- AAPLIUHOKVUFCC-UHFFFAOYSA-N trimethylsilanol Chemical compound C[Si](C)(C)O AAPLIUHOKVUFCC-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 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
The invention discloses a preparation method of chiral compound, wherein the chiral compound has the following chemical formula (I). A synthesis method of the chiral compound comprises the following steps of: taking 15mol% (S) alpha-phenylethylamine cupric acetate as catalyst, taking 2mmol of 4-bromobenzaldehydes, 6mmol of trimethyl silicon nitrile and 4mL of absolute methanol as solvent, reacting for 3days in a stirring way under room temperature, carrying out column chromatography separation, eluting by that the ratio of petroleum ether to methylene dichloride being 1:1, and naturally volatilizing a collected third component point, to obtain single crystal-ethylamino group phenyl-(4-bromine) phenyl acetonitrile.
Description
One, technical field
The present invention relates to a kind of preparation and synthetic method of chipal compounds, exactly is a kind of preparation and synthetic method of nitrogenous nitrile compounds.
Two, background technology
Ethylamino phenyl-phenylacetonitrile is important medicine intermediate, can be used to synthesizing heterocyclic class medicine arylpyrazines [1]
Reference:
1. Novel Asymmetric Synthesis of Atropisomeric 6-Aryl Pyrazinones via an Unusual Chirality Transfer Process, Tulinsky, John; Cheney, B. Vernon; Mizsak, Stephen A.; Watt, William; Han, Fusan; Dolak, Lester A.; Judge, Thomas; Gammill, Ronald B. Journal of Organic Chemistry (1999), 64(1), 93-100.
The applicant has obtained a kind of chipal compounds (S, S)-1-ethylamino phenyl-(4-bromine) phenylacetonitrile with in title complex (S)-α-phenylethylamine venus crystals title complex asymmetry catalysis 4-bromobenzaldehyde nitrile silicification reaction process.
Three, summary of the invention
The present invention aims to provide chipal compounds (S, S)-1-ethylamino phenyl-(4-bromine) phenylacetonitrile.Technical problem to be solved is that one-step synthesis obtains target product.
The alleged chipal compounds of the present invention be by the preparation of 4-bromobenzaldehyde and trimethyl silicane nitrile by the compound shown in the following chemical formula:
( I ) 。
Chemical name: (S, S)-1-ethylamino phenyl-(4-bromine) phenylacetonitrile, be called for short compound (I).
This synthetic method comprises synthesizes and separates, the described synthetic 15mol%(S of using)-the α-phenylethylamine venus crystals makees catalyzer, 4-bromobenzaldehyde 2mmol, trimethyl silicane nitrile 6 mmol make solvent with the 2mL anhydrous methanol, behind the room temperature reaction 3 days, column chromatography for separation is with sherwood oil/methylene dichloride (1/1) wash-out, with the 3rd component point nature volatilization of collecting, get monocrystalline (S, S)-1-ethylamino phenyl-(2-bromine) phenylacetonitrile.
Building-up reactions is as follows:
One step of this synthetic method obtains target product, and technique is simple, and is easy to operate.
This compound has shown certain catalytic effect in the nitrile silicification reaction of phenyl aldehyde, its transformation efficiency reaches 62%
Its reaction mechanism can be presumed as follows:
4-bromobenzaldehyde and trimethyl silicane nitrile, at catalyzer 15mol%(S)-effect of α-phenylethylamine venus crystals under, at first generate product S-(-)-(α-trimethylsiloxy group) 4-bromobenzylcyanide, product again with catalyst action, hydrogen proton in the phenylethylamine and trimethylsilyl ethers form trimethyl silanol and slough, right chipal compounds (S, S)-1-ethylamino phenyl-(4-bromine) phenylacetonitrile that forms.
Four, description of drawings
Fig. 1 is the X-diffraction analysis figure of (S, S)-1-ethylamino phenyl-(4-bromine) phenylacetonitrile.
Five, embodiment
In the 25mL two-mouth bottle, under the anhydrous and oxygen-free condition, add the 4mL anhydrous methanol, 4-bromobenzaldehyde 2mmol, trimethyl silicane nitrile 6 mmol, catalyzer (S)-α-phenylethylamine venus crystals 0.134g(0.30 mmol), reactant was at room temperature stirred 3 days, stopped reaction, column chromatography for separation is with sherwood oil/methylene dichloride (1/1) wash-out, with the 3rd component point nature volatilization of collecting, get monocrystalline (S, S)-1-ethylamino phenyl-(4-bromine) phenylacetonitrile.Productive rate 30 %; [a]
5 D=-16.44o (c=0.0304 CH
2Cl
2):
1HNMR (300MHz, CDCl
3, 27 ℃), δ (ppm)=7.55～7.59 (m, 2H), 7.32～7.53 (m, 9H), (4.34 s, 1H), 4.23 (d, 5Hz, 1H), 1.56 (s, 1H), 1.44 (d, J=5 Hz, 1H)
13CNMR (100MHz, CDCl
3, 27 ℃) and 132.0,129.0,128.9,128.0,126.9,119.9,56.9,58.19,51.8,24.8. IR (KBr): 3245,2970,2546,1607,1527,1457,1368,1228,1149,1090,856,785,766,716,698,611; HRMS:m-CH
3/ z (%): calcd for C
15H
12N
2Br, 301.0163; Found:301.0185.
The nitrile silicification reaction is used
2-phenyl-2-(three silyloxies) acetonitrile
0.2 the mmol Compound I, phenyl aldehyde 0.1mL, TMSCN 0.3 ml (3.3mmol), the 2mL methylene dichloride adds under 20 ~ 30 C in succession, after 5 days, adds the shrend (sherwood oil/methylene dichloride: 5/1) behind the post layer that goes out, get colourless oil liquid, transformation efficiency rate: 62 %;
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. chipal compounds, its chemical formula is as follows:
(I)。
2. the synthetic method of compound claimed in claim 1 (I), comprise and synthesize and separate, it is characterized in that the described synthetic 15mol%(S of using) the α-phenylethylamine venus crystals makees catalyzer, 4-bromobenzaldehyde 2mmol, trimethyl silicane nitrile 6mmol, make solvent with the 4mL anhydrous methanol, the stirring at room reaction is after 3 days, and column chromatography for separation is with sherwood oil/methylene dichloride=1/1 wash-out, the 3rd component point nature volatilization with collecting gets the monocrystalline target product.
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| CN 201210130713 CN102675150B (en) | 2012-05-23 | 2012-05-23 | Preparation method and synthesis method of chiral compound |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102069014A (en) * | 2010-09-15 | 2011-05-25 | 罗梅 | Chiral zinc complex and copper complexes of alpha-phenylethylamine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102069014A (en) * | 2010-09-15 | 2011-05-25 | 罗梅 | Chiral zinc complex and copper complexes of alpha-phenylethylamine |
Non-Patent Citations (2)
| Title |
|---|
| John Tulinsky, et al.Novel Asymmetric Synthesis of Atropisomeric 6-Aryl Pyrazinones via an Unusual Chirality Transfer Process.《J. Org. Chem.》.1998,第64卷(第1期),93-100. |
| Novel Asymmetric Synthesis of Atropisomeric 6-Aryl Pyrazinones via an Unusual Chirality Transfer Process;John Tulinsky, et al;《J. Org. Chem.》;19981215;第64卷(第1期);93-100 * |
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Effective date of registration: 20191211 Address after: Room 207, main office building, No.118 Longxing Road, Haining Economic Development Zone, Haining City, Jiaxing City, Zhejiang Province Patentee after: Haining Economic Development Industrial Park Development and Construction Co., Ltd Address before: 230009 Tunxi Road, Anhui, China, No. 193, No. Patentee before: Luo Mei |