CN101824031A - Chiral oxazoline and use thereof - Google Patents

Chiral oxazoline and use thereof Download PDF

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CN101824031A
CN101824031A CN 201010179411 CN201010179411A CN101824031A CN 101824031 A CN101824031 A CN 101824031A CN 201010179411 CN201010179411 CN 201010179411 CN 201010179411 A CN201010179411 A CN 201010179411A CN 101824031 A CN101824031 A CN 101824031A
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chiral
chiral oxazoline
oxazoline
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罗梅
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Hefei University of Technology
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Abstract

A chiral oxazoline is characterized in that the chiral oxazoline is represented by the following chemical formula with the chemical name of 1-[3-(4S)-4-R-4, 5-dihydro-oxazolyl-ethyl]-pyrrole-2-one, wherein R in the chemical formula is selected from -CH2CH(CH3)2, -CH(CH3)2, -ph or -CH2Ph. The compound has the application in the silicification reaction of nitrile as catalyst.

Description

A kind of chiral oxazoline and uses thereof
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 shows the active and high enantioselectivity of good asymmetry catalysis in many reactions such as Diels-Alder (Di Le-Ai and spy) diene cycloaddition reaction, Michael (Mi Xieer) condensation reaction, Friedel-Crafts (Fu Ruide-carat Buddhist now) condensation reaction, Aldol (alcohol aldehyde) condensation reaction, thereby is subjected to paying close attention to widely.
The applicant is engaged in the development of asymmetric compound for a long time, once developing with hexahydropyridine propionitrile and chiral amino alcohol is the synthetic chiral oxazoline 1-[2-(4S) of raw material-R base-4,5-dihydro-2-oxazoline-ethyl] piperidines, and applied for patent of invention CN1939911A.Also having developed with dinitrile benzene and chiral amino alcohol is that raw material has synthesized chiral oxazoline, has also applied for patent of invention 200810020198.4.
Three, summary of the invention
The present invention is intended to provide a kind of chiral catalyst efficiently 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.
The alleged chiral oxazoline of the present invention is the compound shown in the following chemical formula I:
Figure GSA00000130837900011
R is selected from isobutyl-(CH in the formula 2CH (CH 3) 2) or sec.-propyl (CH (CH 3) 2) or phenyl is (ph) or benzyl (CH 2Ph).
Four kinds of chiral oxazolines that are made of above group claim 1a, 1b, 1c and 1d successively, its chemical name: 1-[3-(4S)-4-R-4,5-dihydro-oxazolinyls-ethyl] pyrroles-2 ketone.
That the synthetic method of this chiral oxazoline (I) comprises is synthetic, separation and purifying, described synthetic be exactly 2-carbonyl-1-pyrryl propionitrile and chiral amino alcohol in organic solvent, have catalyzer to exist condition under reacted 20～30 hours in 120～140 ℃, catalyst levels is the 1～3wt% (weight percent, down together) of material quantity.
The preferred catalyst consumption is the 2wt% of material quantity.
The organic solvent that described organic solvent selects inert, its boiling point and temperature of reaction to adapt is such as chlorobenzene or ethylbenzene or alkane or halohydrocarbon etc.At this moment synthetic can under refluxad carrying 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 2) or AlCl 3Deng.Preferred transition metal chloride.
Chemical equation is as follows:
Figure GSA00000130837900021
Described L-amino alcohol is selected from L-leucinol or L-valerian ammonia alcohol or L-benzene glycinol or L-phenylalaninol.Closed-loop shaped oxazoline base when above-mentioned each L-amino alcohol reacts with 2-carbonyl-1-pyrryl propionitrile respectively, the R base that it carries is followed successively by-CH 2CH (CH 3) 2,-CH (CH 3) 2,-Ph and-CH 2Ph.
Present method one-step synthesis chiral oxazoline 1a, 1b, 1c and 1d they respectively through 1HNMR, IR, MS characterize, it shows good catalytic activity as catalyzer in the nitrile silicification reaction.
Four, description of drawings
Fig. 1,3,5,7 is catalyzer 1a, 1b, 1c, 1d successively 1HNMR figure.
Fig. 2,4,6,8 is catalyzer 1a, 1b, 1c, 1d successively 13CNMR figure.
Five, embodiment
(the preparation of a) chiral oxazoline
1a:1-[3-(4S)-4-isobutyl--4,5-dihydro-oxazolinyls-propyl group] preparation of pyrroles-2-ketone
1-[3-(4S)-4-isobutyl-4,5-dihydro-oxazol-3-yl-propyl]-preparation of pyrrole
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl 260mg (0.37mmol), the 40ml chlorobenzene, 2-carbonyl-1-pyrryl propionitrile 6.0g (5.6mmol), L-leucinol 10g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove, and with the residuum water dissolution, and uses CHCl 3(20mLx2) extraction, the organic phase anhydrous sodium sulfate drying, rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got yellow liquid, productive rate 85%; [a] 5D=-86.2 ° (c=0.0232, CHCl3); 1HNMR (300MHz, CDCl 3, 27 ℃), and δ (ppm)=4.28 (t, J=0.5H exists, 1H), 4.04～4.07 (m, 1H), 3.75 (t, 1H), 3.37～3.61 (m, 4H), 2.46 (t, 1H), 2.33 (t, 2H), 1.97～2.00 (m, 2H), 1.69～1.72 (m, 1H), 1.50～1.53 (m, 1H), 0.89 (t, J=0.5Hz, 6H) 13CNMR, 17.60,22.24,22.34,24.96,26.20,29.29,30.48,38.99,45.10,46.87,64.12,72.65,164.37,174.61.IR:2955,2924,2869,1690,1494,1463,1425,1384,1367,1287,1225,1174,984,942,847,721,654,563,493; HRMS (EI): m/z (%): calcd for C13H22N2O2:238.1681; Found:238.1678.
1b:1-[3-(4S)-4-sec.-propyl-4,5-dihydro-oxazolinyls-propyl group] preparation of pyrroles-2-ketone
2-carbonyl-1-pyrryl propionitrile 6.0g (5.6mmol), L-valerian ammonia alcohol 10g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove, and with the residuum water dissolution, and uses CHCl 3(20mLx2) extraction, the organic phase anhydrous sodium sulfate drying, rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got yellow liquid, productive rate 80%; [a] 5 D=-69.33 ° (c=0.09, CHCl3); 1HNMR (300MHz, CDCl 3, 27 ℃), δ (ppm)=4.17 (t, J=0.5Hz, 1H), 3.86 (t, 1H), 3.78～3.80 (m, 1H), 3.35～3.52 (m, 4H), 2.46 (t, J=0.5Hz, 2H), 2.30 (t, 1H), 1.92～1.98 (m, 2H), 1.63～1.65 (m, 1H), 0.80 (d, 3H), 0.90 (d, 2H) 13CNMR, 17.56,17.78,18.42,26.13,30.48,32.18,39.02,46.85,69.79,71.79,164.48,174.58.IR:3454,3060,3026,2925,2899,1686,1603,1495,1462,1454,1424,1378,1355,1288,1225,1176,1081,1029,983,944,923,852,754,735,703,655,565; HRMS (EI): m/z (%): calcd for C 12H 20N 2O 2: 225.1603; Found:225.1583.
1c:1-[3-(4S)-4-phenyl-4,5-dihydro-oxazolinyls-propyl group] preparation of pyrroles-2-ketone
1-[3-(4S)-4-phenyl-4,5-dihydro-oxazol-3-yl-]-preparation of pyrrole
Solvent ethylbenzene, catalyzer trichlorine rare earth is operated with example 1 2-carbonyl-1-pyrryl propionitrile 6.0g (5.6mmol), L-benzene glycinol 10g, productive rate 75%; [a] 5D=-63.55 ° of (c=0.346, CHCl 3); 1HNMR (300MHz, CDCl 3, 27 ℃), and δ (ppm)=7.26～7.39 (m, 5H), 5.18 (t, 1H), 4.64 (t, J=1.5Hz, 1H), 4.12 (t, J=0.5Hz, 1H), 3.69～3.70 (m, 2H), 3.47～3.48 (m, 2H), 2.64～2.67 (m, 2H), 2.38～2.41 (m, 2H), 2.01～2.04 (m, 2H); 13CNMR, 17.51,25.99,30.47,38.97,46.84,69.18,74.19,126.14 (x2), 128.24 (x2), 141.63,165.84,174.66.IR:3307,3062,3029,2963,2906,2877,2793,1665,1604,1493,1475,1454,1429,1353,1292,1237,1170,1146,1124,1077,1029,986,916,759,700,530; HRMS (EI): m/z (%): calcd forC 15H 18N 2O 2: 258.1368; Found:258.1370.
1d:1-[3-(4S)-4-benzyl-4,5-dihydro-oxazolinyls-propyl group] preparation of pyrroles-2 ketone
1-[3-(4S)-4-benzyl-4,5-dihydro-oxazol-3-yl-]-preparation of pyrrole
The solvent ethylene dibromide, catalyst A lCl 3, 2-carbonyl-1-pyrryl propionitrile 6.0g (5.6mmol), L-phenylalaninol 10g, operation is with example 1.
Productive rate 72%; [a] 5 D=-122.59 ° of (c=0.42, CHCl 3); 1HNMR (300MHz, CDCl 3, 27 ℃), and δ (ppm)=7.16～7.26 (m, 5H), 4.13～4.31 (m, 1H), 3.90 (t, 1H), 3.53～3.55 (m, 2H), 3.36～3.38 (m, 2H), 3.02～3.06 (m, 1H), 2.57～2.61 (m, 1H), 2.44～2.47 (m, 2H), 2.33 (t, 2H), 1.96～1.99 (m, 2H). 13CNMR, 17.58,26.08,30.47,38.94,41.20,46.87,66.86,71.34,126.06,128.07 (x2), 128.74 (x2), 137.40,165.13,174.59.IR:3455,2959,2874,1671,1465,1425,1384,1366,1310,1289,1227,1172,1115,1081,1021,985,945,920,894,738,656,566,497,470; HRMS (EI): m/z (%): calcd forC16H20N2O2:272.1525; Found:272.1521.
(2) 2-phenyl-2-(three silyloxies) propionitrile
The preparation of 2-(4-phenyl)-2-(trimethylsilyloxy) acetonitrile
0.3mmol catalyzer 1a, 1b, 1c and 1 add down at 10～20 ℃ in succession with phenyl aldehyde 1mmol and trimethyl silicane nitrile 0.3ml (3.3mmol) respectively, behind the 19h, add shrend go out behind the post layer (sherwood oil/methylene dichloride: 5/1), colourless oil liquid. 1HNMR(300MHz，CDCl 3)7.56-7.59(m，0.9Hz，2H)，7.31-7.34(m，3H)，5.43(s，1H)，0.16(s，9H). 13CNMR(75MHz，CDCl 3)136.1，128.8(x2)，126.2(x2)，119.1，63.5，-0.39(x3).
Figure GSA00000130837900041
Catalyzer Solvent Temperature (℃) Reaction times (h) Productive rate %
??1a ??THF ??10-20 ?19 ??99
??1b ??THF ??10-20 ?19 ??99
??1c ??THF ??10-20 ?19 ??84
??1d ??THF ??10-20 ?19 ??83

Claims (2)

1. chiral oxazoline is characterized in that: by following chemical formulation, its chemical name is 1-[3-(4S)-4-R-4,5-dihydro-oxazolinyl-ethyl] pyrroles-2-ketone:
Figure FSA00000130837800011
R is selected from-CH in the formula 2CH (CH 3) 2Or-CH (CH 3) 2Or-ph or-CH 2Ph.
2. the purposes of chiral oxazoline as claimed in claim 1, it is characterized in that the: chiral oxazoline in the nitrile silicification reaction as Application of Catalyst.
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102174006A (en) * 2011-03-02 2011-09-07 罗梅 Chiral compound
CN102199149A (en) * 2011-03-22 2011-09-28 罗梅 Preparation and synthesis method for chiral oxazoline
CN102206211A (en) * 2011-04-06 2011-10-05 罗梅 Method for preparing and synthesizing chiral oxazoline
CN102206212A (en) * 2011-04-06 2011-10-05 罗梅 Preparation and synthesis method for chiral oxazoline
CN102229604A (en) * 2011-04-22 2011-11-02 罗梅 Preparation and synthetic method for chiral oxazoline
CN102295540A (en) * 2011-05-18 2011-12-28 罗梅 Preparation method of acetal
CN102336776A (en) * 2011-06-07 2012-02-01 罗梅 Chiral zinc nitrogen complex

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1939911A (en) * 2006-09-09 2007-04-04 合肥工业大学 Chiral oxazoline and its production
CN101099936A (en) * 2007-07-31 2008-01-09 合肥工业大学 Use of chiral oxazoline
CN101279954A (en) * 2008-05-14 2008-10-08 合肥工业大学 Chiral oxazoline and synthetic method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1939911A (en) * 2006-09-09 2007-04-04 合肥工业大学 Chiral oxazoline and its production
CN101099936A (en) * 2007-07-31 2008-01-09 合肥工业大学 Use of chiral oxazoline
CN101279954A (en) * 2008-05-14 2008-10-08 合肥工业大学 Chiral oxazoline and synthetic method thereof

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* Cited by examiner, † Cited by third party
Title
《Heteroatom Chemistry》 20070914 Luo Mei等 Synthesis of Novel Oxazolines and Application in Cyanosilylation of Prochiral Ketones 第679-683页 1-2 第18卷, 第6期 2 *
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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102174006A (en) * 2011-03-02 2011-09-07 罗梅 Chiral compound
CN102199149A (en) * 2011-03-22 2011-09-28 罗梅 Preparation and synthesis method for chiral oxazoline
CN102206211A (en) * 2011-04-06 2011-10-05 罗梅 Method for preparing and synthesizing chiral oxazoline
CN102206212A (en) * 2011-04-06 2011-10-05 罗梅 Preparation and synthesis method for chiral oxazoline
CN102206212B (en) * 2011-04-06 2013-07-03 罗梅 Preparation and synthesis method for chiral oxazoline
CN102206211B (en) * 2011-04-06 2013-09-11 罗梅 Method for preparing and synthesizing chiral oxazoline
CN102229604A (en) * 2011-04-22 2011-11-02 罗梅 Preparation and synthetic method for chiral oxazoline
CN102229604B (en) * 2011-04-22 2014-03-26 罗梅 Preparation and synthetic method for chiral oxazoline
CN102295540A (en) * 2011-05-18 2011-12-28 罗梅 Preparation method of acetal
CN102336776A (en) * 2011-06-07 2012-02-01 罗梅 Chiral zinc nitrogen complex

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