CN101279954A - Chiral oxazoline and synthetic method thereof - Google Patents

Chiral oxazoline and synthetic method thereof Download PDF

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CN101279954A
CN101279954A CNA200810096588XA CN200810096588A CN101279954A CN 101279954 A CN101279954 A CN 101279954A CN A200810096588X A CNA200810096588X A CN A200810096588XA CN 200810096588 A CN200810096588 A CN 200810096588A CN 101279954 A CN101279954 A CN 101279954A
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chiral
oxazoline
chiral oxazoline
synthetic method
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罗梅
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Hefei University of Technology
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Hefei University of Technology
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Abstract

4-(1-pyrrolyl)butyronitrile reacts with chiral amino alcohol under the existence of organic solvent and catalyzer under 120-140 DEG C for 20-30h, and the products are separated and purified, obtaining chiral oxazoline(I). The method synthesizes chiral oxazoline(I) through one step, and the organometallic complex of chiral oxazoline(I) is of good catalytic activity and high enantio-selectivity in the asymmetric synthesis of mandelic acid.

Description

A kind of chiral oxazoline and synthetic method 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):
R is selected from isobutyl-(CH in the formula 2CH (CH 3) 2) or phenyl is (ph) or benzyl (CH 2Ph).
Three kinds of chiral oxazolines that are made of above group claim 1a, 1b, 1c successively, its chemical name: 1-[3-(4S)-4-R-4,5-dihydro-oxazolinyls-propyl group] pyrroles.
That the synthetic method of this chiral oxazoline (I) comprises is synthetic, separation and purifying, described synthetic be exactly 4-(1-pyrryl) butyronitrile 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.
Their warps respectively of present method one-step synthesis chiral oxazoline 1a, 1b and 1c 1HNMR, IR, MS characterizes, and its a metal-organic complex shows good catalytic activity and high enantioselectivity in the amygdalic acid asymmetric synthesis.
Four, description of drawings
Fig. 1,3,5 is catalyzer 1a, 1b, 1c successively 1HNMR figure.
Fig. 2,4,6 is catalyzer 1a, 1b, 1c successively 13CNMR figure.
Five, embodiment
1a:1-[3-(4S)-4-isobutyl--4,5-dihydro-oxazolinyls-propyl group] pyrroles's preparation
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, 4-(1-pyrryl) 1.0g (5.6mmol), L-leucinol 2g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove,,, and use CHCl with the residuum water dissolution 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 0.6g productive rate 45%; [a] 5 D=-18.75 ° of (c=0.67, CHCl 3); 1HNMR (300MHz, CDCl 3, 27 ℃), δ (ppm)=4.15-4.20 (m, 1H), 3.97～3.98 (m, 1H), 3.64～3.68 (m, 1H), 2.34～2.40 (m, 6H), 2.19～2.20 (m, 2H), 1.64～1.72 (m, 7H), 1.17～1.17 (m, 1H), 1.44～1.48 (m, 1H), 0.81～0.84 (m, 6H) 13CNMR, 22.63 (x2), 23.32,23.37,25.26,25.38,26.13,45.58,53.88,53.98,55.62,64.38,72.70,166.97.IR:3327,2957,2932,2873,2788,1669,1466,1444,1384,1367,1353,1238,1172,1147,1127,985,922; HRMS (EI): m/z (%): calcd for C 14H 26N 2O:238.2045; Found:238.2048.
1b:1-[3-(4S)-4-phenyl-4,5-dihydro-oxazolinyls-propyl group] pyrroles's preparation
1-[3-(4S)-4-phenyl-4,5-dihydro-oxazol-3-yl-]-preparation of pyrrole
Solvent ethylbenzene, catalyzer trichlorine rare earth, operation is with example 1.
Yellow liquid 0.71g, productive rate 49%; [a] 5 D=-34.27 ° of (c=0.77, CHCl 3); 1HNMR (300MHz, CDCl 3, 27 ℃), δ (ppm)=7.21～7.34 (m, 5H), 5.13 (m, 1H), 4.55～4.59 (m, 1H), 4.03～4.07 (m, 1H), 2.41～2.52 (m, 8H), 1.74～1.92 (m, 6H). 13CNMR, 23.32 (x2), 25.33,26.03,53.87,53.98,55.60,69.36,74.44,126.41 (x2), 127.36,128.55 (x2), 142.38,168.72.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 for C 16H 22N 2O:258.1732; Found:258.1725.
1c:1-[3-(4S)-4-benzyl-4,5-dihydro-oxazolinyls-propyl group] pyrroles's preparation
1-[3-(4S)-4-benzyl-4,5-dihydro-oxazol-3-yl-]-preparation of pyrrole
The solvent ethylene dibromide, catalyst A lCl 3, operation is with example 1.
Yellow liquid 0.72g, productive rate 47%; [a] 5 D=-34.27 ° of (c=0.77, CHCl 3); 1HNMR (300MHz, CDCl 3, 27 ℃), and δ (ppm)=7.28～7.39 (m, 5H), 4.43～4.47 (m, 1H), 4.21～4.27 (t, J=0.3Hz, 1H), 4.00～4.05 (t, J=0Hz, 1H), 3.14～3.19 (dd, J=5.1Hz, 5.1Hz, 1H), 2.70～2.78 (m, 6H), 2.60～2.62 (m, 2H), 1.88 (m, 6H). 13CNMR, 23.45 (x2), 25.19,26.14,41.74,54.11,55.68,67.14 (x2), 71.53,126.50,128.52 (x2), 129.31 (x2), 137.91,167.90.IR:3292,3060,3027,2958,2932,2877,2791,1666,1603,1542,1496,1454,1429,1353,1239,1044,981,928,749,702,505; HRMS (EI): m/z (%): calcd for C 17H 24N 2O:272.1822; Found:272.1889.

Claims (3)

1, a kind of chiral oxazoline is characterized in that: by following chemical formulation, its chemical name is 1-[3-(4S)-4-R-4,5-dihydro-oxazolinyls-propyl group] pyrroles:
Figure A20081009658800021
R is selected from-CH in the formula 2CH (CH 3) 2Or-CH (CH 3) 2Or-ph.
2, by the synthetic method of the described chiral oxazoline of claim 1, comprise synthetic, separation and purifying, it is characterized in that: described synthetic be 4-(1-pyrryl) butyronitrile and chiral amino alcohol reacted 20～30 hours in 120～140 ℃ under the condition that organic solvent and catalyzer exist, catalyst levels is 1～3wt% of material quantity.
3, synthetic method according to claim 2 is characterized in that: catalyst levels is the 2wt% of material quantity.
CNA200810096588XA 2008-05-14 2008-05-14 Chiral oxazoline and synthetic method thereof Pending CN101279954A (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101824031A (en) * 2010-05-17 2010-09-08 合肥工业大学 Chiral oxazoline and use thereof
CN101973951A (en) * 2010-08-30 2011-02-16 罗梅 Chiral D-oxazoline and application thereof
CN101973952A (en) * 2009-09-30 2011-02-16 合肥工业大学 Chiral oxazoline and synthetic method thereof
CN102199149A (en) * 2011-03-22 2011-09-28 罗梅 Preparation and synthesis method for chiral oxazoline
CN102206215A (en) * 2010-11-18 2011-10-05 罗梅 Chiral compound
CN102229604A (en) * 2011-04-22 2011-11-02 罗梅 Preparation and synthetic method for chiral oxazoline

Cited By (8)

* Cited by examiner, † Cited by third party
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
CN101824031A (en) * 2010-05-17 2010-09-08 合肥工业大学 Chiral oxazoline and use thereof
CN101973951A (en) * 2010-08-30 2011-02-16 罗梅 Chiral D-oxazoline and application thereof
CN101973951B (en) * 2010-08-30 2012-10-31 罗梅 Chiral D-oxazoline and application thereof
CN102206215A (en) * 2010-11-18 2011-10-05 罗梅 Chiral compound
CN102206215B (en) * 2010-11-18 2012-08-01 罗梅 Chiral compound
CN102199149A (en) * 2011-03-22 2011-09-28 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

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