CN103044346A - Chiral oxazoline and synthesis method thereof - Google Patents
Chiral oxazoline and synthesis method thereof Download PDFInfo
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- CN103044346A CN103044346A CN2013100106590A CN201310010659A CN103044346A CN 103044346 A CN103044346 A CN 103044346A CN 2013100106590 A CN2013100106590 A CN 2013100106590A CN 201310010659 A CN201310010659 A CN 201310010659A CN 103044346 A CN103044346 A CN 103044346A
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- chiral
- chiral oxazoline
- catalyst
- metal chloride
- oxazoline
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- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 238000001308 synthesis method Methods 0.000 title abstract 2
- -1 alkoxy metal compound Chemical class 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 229910052761 rare earth metal Inorganic materials 0.000 claims abstract description 5
- 150000002910 rare earth metals Chemical group 0.000 claims abstract description 5
- 230000003197 catalytic effect Effects 0.000 claims abstract description 4
- 229910021381 transition metal chloride Inorganic materials 0.000 claims abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract description 3
- 238000010189 synthetic method Methods 0.000 claims description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 3
- QMXOFBXZEKTJIK-UHFFFAOYSA-N Glycinol Natural products C1=C(O)C=C2OCC3(O)C4=CC=C(O)C=C4OC3C2=C1 QMXOFBXZEKTJIK-UHFFFAOYSA-N 0.000 claims description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- QVTPWONEVZJCCS-UHFFFAOYSA-N 2-formylbenzonitrile Chemical compound O=CC1=CC=CC=C1C#N QVTPWONEVZJCCS-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 abstract 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 abstract 2
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 abstract 1
- HGZJJKZPPMFIBU-UHFFFAOYSA-N 3-formylbenzonitrile Chemical compound O=CC1=CC=CC(C#N)=C1 HGZJJKZPPMFIBU-UHFFFAOYSA-N 0.000 abstract 1
- 230000002349 favourable effect Effects 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
- 238000000746 purification Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-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
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 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
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- PKKGKUDPKRTKLJ-UHFFFAOYSA-L dichloro(dimethyl)stannane Chemical compound C[Sn](C)(Cl)Cl PKKGKUDPKRTKLJ-UHFFFAOYSA-L 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 238000004090 dissolution 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
- 238000000605 extraction Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention relates to a chiral oxazoline which has a chemical formula shown in the specification. A synthesis method of the chiral oxazoline comprises synthesis, separation and purification. The invention is characterized in that the synthesis refers to reacting m-cyanobenzaldehyde and chiral D-phenylglycinol at 110-145 DEG C in the presence of a catalyst in organic solvent for 20-30 hours, wherein the catalyst accounts for 120-122 wt% of the raw materials; and the catalyst is rare-earth metal chloride or transition metal chloride or AlCl3 or alkoxy metal compound. The chiral oxazoline serving as a catalyst exhibits favorable catalytic activity in the cyanosilylation reaction of benzaldehyde.
Description
One, technical field
The present invention relates to a kind of new compound and preparation method thereof, particularly a kind of chipal compounds and preparation method thereof exactly is a kind of chiral oxazoline and synthetic method thereof.
Two, background technology
The title complex of chiral oxazoline and metal at asymmetric catalysis field such as Diels-Alder(Di Le-Ai and the spy) diene cycloaddition reaction, Michael(Mi Xieer) condensation reaction, Fu Friedel-Crafts(Rui De-carat Buddhist hereby) condensation reaction, Aldol(alcohol aldehyde) show good catalytic activity and high enantioselectivity in many reactions such as condensation reaction, thereby paid close attention to widely.
Three, summary of the invention
The present invention is intended to provide a kind of efficient chiral catalyst for the asymmetric synthesis field particularly prepares chiral drug, and technical problem to be solved is to select corresponding raw material and set up corresponding method synthesis of chiral catalyzer.
(1) the alleged chiral oxazoline of the present invention is the compound shown in the following chemical formula:
Its chemical name: 3-(4-phenyl-4,5-dihydro-2-oxazolinyl) phenyl aldehyde
That the synthetic method of this chiral oxazoline comprises is synthetic, separation and purifying, described synthetic be exactly between cyanobenzaldehyde and chiral D-benzene glycinol in organic solvent, have catalyzer to exist condition under reacted 20 ~ 30 hours in 110 ~ 145 ℃, catalyst levels is 121 wt%(per-cents of material quantity, and is lower same).
Preferred 120 ~ 140 ℃ of reactions 22 ~ 28 hours, catalyst levels is 121 wt%. of material quantity
Its chemical equation is as follows:
Described organic solvent is selected organic solvent inertia, that its boiling point and temperature of reaction adapt, such as picoline or chlorobenzene or dichlorobenzene or ethylbenzene or dimethylbenzene or propyl benzene or alkane or halogenated alkane etc.At this moment synthesize and under refluxad to carry out.
Described catalyzer is selected from rare-earth metal chloride (trichlorine rare earth) or transition metal chloride (ZnCl
2, CuCl
2, NiCl
2, CoCl
2, FeCl
3, MnCl
2Deng) or AlCl
3Or alkoxide compound (tetraisopropoxy titanium, dimethyl dichloro stannane etc.).Preferred trichlorine rare earth or transition metal chloride.
Present method one-step synthesis chiral oxazoline, their warps respectively
1HNMR, IR, MS characterizes, and it shows good catalytic activity as catalyzer in the nitrile silicification reaction of phenyl aldehyde.
Four, description of drawings
Fig. 1 is compound I
1HNMR figure;
Fig. 2 is compound I
13CNMR figure.
Five, embodiment
(1) 3-(4-phenyl-4, the 5-dihydro-2-oxazolinyl) preparation of phenyl aldehyde (compound I)
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl
21.2649g (9.30mmol), 40mL chlorobenzene, 3-itrile group aniline 1.0437g(7.97mmol), D-benzene glycinol 10.0g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is with desolventizing,, with the residuum water dissolution, and use CHCl
3(20mLx2) extraction, the organic phase anhydrous sodium sulfate drying, the rotation desolventizing with sherwood oil/methylene dichloride (4:1) column chromatography, gets colourless oil liquid, productive rate 65 % with thick product; [a]
5 D=+27.7o (c=0.1624, CH
2Cl
2):
1HNMR (500MHz, CDCl
3, 27 ℃), δ (ppm)=10.05(s, 1H), 8.53 (s, 1H), 8.30 (d, J=0.66Hz, 1H), 8.03 (d, J=0.72Hz, 1H), 7.59～7.61 (m, 1H), 7.25～7.37 (m, 1H), 5.42 (t,, 1H), 4.84 (t, J=0.4Hz, 1H), (4.32 t, J=0.6Hz, 1H)
13CNMR (150MHz, CDCl
3, 27 ℃) and 191.6,163.6,141.9,136.5,134.1 (x2), 131.6,130.6,129.3 (x2), 128.9,127.8,126.7(x2), 75.2,70.2. IR (KBr): 3063,3030,2963,2900,2849,2731,1702,1648,1604,1582,1494,1453,1382,1359,1,316 1273,1182,1162,1066,1029,1002,977,916,844,807,760,700,679,648,607,541; HRMS (EI): m/z (%): calcd for C
16H
13NO
2: 251.0946; Found:251.0943.
(2) the 2-phenyl-2-(three silyloxies) preparation of acetonitrile
0.20mmol compound I, phenyl aldehyde 0.1mL, TMSCN 0.3 ml (3.3mmol) adds under 20 ~ 30 C in succession, behind the 6h, add shrend go out behind the post layer (sherwood oil/methylene dichloride: 5/1), get colourless oil liquid, transformation efficiency: 84.2 %,
1HNMR (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, CDCl
3) 136.1,128.8 (x2), 126.2 (x2), 119.1,63.5 ,-0.39 (x3).
Claims (3)
1. chiral oxazoline is characterized in that: by following chemical formulation, its chemical name is: 3-(4-phenyl-4,5-dihydro-2-oxazolinyl) phenyl aldehyde
。
2. the synthetic method of this chiral oxazoline, comprise synthetic, separation and purifying, it is characterized in that: described synthetic be a cyanobenzaldehyde with chiral D-benzene glycinol under the condition that catalyzer exists in organic solvent, 110～145 ℃ of lower reactions 20～30 hours, catalyst levels is 120～122wt% of material quantity, and described catalyzer is selected from rare-earth metal chloride or transition metal chloride or AlCl
3Or alkoxide compound.
3. it shows good catalytic activity as catalyzer in the nitrile silicification reaction of phenyl aldehyde.
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| CN103044346B CN103044346B (en) | 2014-05-07 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319428A (en) * | 2013-07-07 | 2013-09-25 | 罗梅 | Chiral oxazoline and synthesis method thereof |
| CN103342685A (en) * | 2013-07-10 | 2013-10-09 | 罗梅 | Chiral oxazoline and synthetic method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101973952A (en) * | 2009-09-30 | 2011-02-16 | 合肥工业大学 | Chiral oxazoline and synthetic method thereof |
| CN101973951A (en) * | 2010-08-30 | 2011-02-16 | 罗梅 | Chiral D-oxazoline and application thereof |
| CN102659706A (en) * | 2012-05-10 | 2012-09-12 | 罗梅 | Preparation and synthetic methodof chiral oxazoline |
| CN102702124A (en) * | 2012-07-08 | 2012-10-03 | 罗梅 | Preparation and synthesis method of chiral oxazoline |
-
2013
- 2013-01-12 CN CN201310010659.0A patent/CN103044346B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101973952A (en) * | 2009-09-30 | 2011-02-16 | 合肥工业大学 | Chiral oxazoline and synthetic method thereof |
| CN101973951A (en) * | 2010-08-30 | 2011-02-16 | 罗梅 | Chiral D-oxazoline and application thereof |
| CN102659706A (en) * | 2012-05-10 | 2012-09-12 | 罗梅 | Preparation and synthetic methodof chiral oxazoline |
| CN102702124A (en) * | 2012-07-08 | 2012-10-03 | 罗梅 | Preparation and synthesis method of chiral oxazoline |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319428A (en) * | 2013-07-07 | 2013-09-25 | 罗梅 | Chiral oxazoline and synthesis method thereof |
| CN103319428B (en) * | 2013-07-07 | 2015-01-07 | 罗梅 | Chiral oxazoline and synthesis method thereof |
| CN103342685A (en) * | 2013-07-10 | 2013-10-09 | 罗梅 | Chiral oxazoline and synthetic method thereof |
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| CN103044346B (en) | 2014-05-07 |
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