CN102898342A - Chiral compound - Google Patents
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- CN102898342A CN102898342A CN 201210416588 CN201210416588A CN102898342A CN 102898342 A CN102898342 A CN 102898342A CN 201210416588 CN201210416588 CN 201210416588 CN 201210416588 A CN201210416588 A CN 201210416588A CN 102898342 A CN102898342 A CN 102898342A
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Abstract
The invention relates to a chiral compound, i.e., N-2-hydroxyethyl-1-(R)-benzyl-1-pyrrole propanamide-2-ketone. The structure formula of the chiral compound is shown in the specifications. A method for synthesizing the compound (I) comprises the following steps of: performing a reflux reaction on 2-ketopyrrolidine benzene propane nitrile and D-phenylalaninol in a chlorobenzene solvent under a water-free and oxygen-free condition in the presence of anhydrous ZnCl2 serving as a catalyst for 24 hours, and separating and purifying, i.e., removing chlorobenzene after the reaction is completed, adding water for dissolving, extracting by using methylene dichloride, desolventizing an extract phase, and purifying by using column chromatography; and synthesizing a target product: performing a reflux reaction on a prepared intermediate, i.e., 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl]ethyl]-2-ketopyrrolidine and cupric acetate monohydrate in an ethanol mixed solvent for 48 hours, and recrystallizing by using ethanol and normal hexane to obtain a complex single crystal. The compound shows certain catalytic performance in the nitrile siliconization reaction of 2-tolualdehydes, and the conversion rate of the compound is up to 99 percent.
Description
One, technical field
The present invention relates to a kind of chipal compounds and preparation method thereof, particularly nitrogenous chipal compounds preparation method exactly is a kind of chirality hydroxyl amide compound and synthetic method thereof.
Two, background technology
Chirality hydroxyl amides is widely used in biological medicine and the organic synthesis.Its synthetic method has multiple (1) acids and chiral amino alcohol reaction; (2) oxazolines under an acidic catalyst effect, open loop.【1-3】
Reference:
1. Efficient C-N Bond Formations Catalyzed by a Proton-Exchanged Montmorillonite as a Heterogeneous Bronsted Acid. Motokura, Ken; Nakagiri, Nobuaki; Mori, Kohsuke; Mizugaki, Tomoo; Ebitani, Kohki; Jitsukawa, Koichiro; Kaneda, Kiyotomi. Organic Letters (2006), 8(20), 4617-4620..
2. A randomly branched poly( hydroxyl -β -amino amide ): synthesis and complexation. Wu, Chuan-bao; Hao, Jian-yuan; Deng, Xian-mo. Journal of Polymer Research (2010), 17(6), 869-876.
3. 8,13-Diazaestrones and analogs. I. Pharmacological study and synthesis of heterosteroid analogs to establish structure-analgesic activity relationships.Hocquaux, Michel; Marcot, Bernard; Redeuilh, Gerard; Viel, Claude; Brunaud, Marcel; Navarro, Jenny; Lacour, Colette; Cazaubon, CatherineEuropean Journal of Medicinal Chemistry (1983), 18(4), 319-29。
Three, summary of the invention
The present invention aims to provide a kind of chirality hydroxyl amide compound to be applied to catalytic field, and technical problem to be solved is selected 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-2-Pyrrolidone and synthesizing chiral compound.
The alleged chipal compounds of the present invention is by 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-2-Pyrrolidone and copper acetate dihydrate reaction preparation by the compound shown in the following chemical formula:
Chemical name: N-2-second hydroxyl-1R-benzyl-1-pyrroles's propionic acid amide-2-ketone, be called for short compound (I).
The synthetic method of this chirality hydroxyl amide compound is to prepare first 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-2-Pyrrolidone, comprise reaction, separation and purifying, the reaction that it is characterized in that preparing intermediate by 2-Pyrrolidone phenylpropyl alcohol cyanogen and L-phenylalaninol under the anhydrous and oxygen-free condition and the anhydrous ZnCl of catalyzer
2When existing in chlorobenzene solvent back flow reaction 24 hours, then separate, purifying, i.e. reaction is sloughed chlorobenzene after finishing, the rear dichloromethane extraction of using that is dissolved in water is used column chromatography purification behind the extraction phase precipitation; The reaction of synthetic target product is prepared intermediate 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl-2-pyrrolidone and copper acetate dihydrate feed ratio back flow reaction 48 hours in alcohol mixed solvent of pressing 2:1, then with ethanol and normal hexane recrystallization, get the chirality compound monocrystal.This experiment purpose is to obtain 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] complex monocrystal of ethyl-2-pyrrolidone and copper acetate dihydrate, but, unexpected De is Dao the open-loop products hydroxyl acid amides of oxazoline, venus crystals is not as reactant in this reaction, but as lewis acid catalyst.This compound shows preferably catalytic performance in the nitrile silicification reaction of 2-tolyl aldehyde, its transformation efficiency is up to 99%.
Four, description of drawings
Fig. 1 is the single crystal diffraction figure of chipal compounds (I).
Five, embodiment
(1) preparation of chipal compounds
1,1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-preparation of 2-Pyrrolidone
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl
21.1g (8.08mmol), the 40mL chlorobenzene, 3-(1-hexahydropyridine base)-propionitrile 6.3g, D-phenylalaninol 10g, 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 60% with thick product; [a]
5 D=+40.2o (c=0.298, CH
2Cl
2):
1HNMR (300MHz, CDCl
3, 27 ℃), δ (ppm)=7.24～7.37 (m, 5H), (5.17 t, J=0.3Hz, 1H), 4.59～4.66 (m, 1H), 4.11 (t, 1H), (3.46 t, J=0.9Hz, 2H), (2.65 t, 3H), 2.38 (t, 3H), 1.99～2.04 (m, 6H);
13CNMR, 17.72,26.20,30,65,39.21,47.05,69.38,74.37,126.33,127.31,128.43,141.87,166.07,174.84.IR (KBr compressing tablet): 3436,3029,2932,1733,1682,1494,1454,1385,1425,1378,1288,1226,1172,986,924,849,762,702,655,563,532,494.HRMS(EI): m/z (%): calcd for C
15H
18N
2O
2: 258.1368; found: 258.1373。
2. the preparation of N-2-second hydroxyl-1R-benzyl-1-pyrroles's propionic acid amide-2-ketone
1,1-[2-[(4S)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-2-Pyrrolidone 1g, copper acetate dihydrate 0.6g, alcohol solvent 50mL is put in the 150mL two-mouth bottle, reacts after 48 hours, and mixture is spin-dried for, with ethanol and normal hexane recrystallization, get compound monocrystal.
[ a]
5 D=+10.9o (c=0.045, C
2H
5OH)：
1HNMR (500MHz, CDCl
3, 27℃), δ (ppm) = 7.15～7.26 (m, 5H), 6.91(s, 1H), 4.15(s, 1H), 3.26～3.74(m, 8H), 2.84～2.83(m, 2H), 2.32～2.44 (m, 5H), 1.93～1.97 (m, 3H)。
13C NMR (75 MHz, CDCl3) 73.23, 65.17, 62.99, 57.31, 55.22, 46.05, 43.56, 24.91, 24.13, 22.59, 22.44, 21.74。IR: 3301,2940,2848,1716,1668,1555,149,5,1471,1454,1431,1376,1293,1255,1226,1207,1162,1081,1058,1043,1007,975,753,704,626,535,497. ultimate analyses: C
16H
22N
2O
3, measured value: C:66.43%, N:9.40, H:7.59; Theoretical value: C:66.18%, N:9.65, H:7.64. HRMS (EI): m/z (%): calcd for C
16H
22N
2O
3: 290.1630; Found:290.1636.
(3), the nitrile silicification reaction is used
2-aminomethyl phenyl-2-(three silyloxies) propionitrile
0.2mmol Compound I, 2-tolyl aldehyde 0.1mL, TMSCN 0.3 ml (3.3mmol) adds under 20 ~ 30 C in succession, after 3 days, add shrend go out behind the post layer (sherwood oil/methylene dichloride: 5/1), get colourless oil liquid, transformation efficiency〉99%.
1H NMR (300MHz, CDCl
3) 7.52 – 7.53 (d, 7.5 Hz, 1H), 7.20 – 7.30 (m, 3H), 5.57 (s, 1H), 2.44 (s, 3H), 0.22 (s, 9H).
13C NMR (75 MHz, CDCl
3) 135.8,134.2,131.2,129.5,127.1,126.6,118.9,62.1,18.9 ,-0.2 (X3). and IR (KBr): 3027,2959,2926,1608,1606,1491,1463,1382,1321,1256,1215,1180,1130,1085,950,924,874,847,751,623,460. HRMS (EI): m/z (%): calcd for C
12H
18NOSi:220.1270 found:220.1273.
(4) Henle reaction is used
The preparation of 2-nitro-1 phenylethyl alcohol
The title complex I(catalytic amount of getting 0.20mmol is 20%) in the little flask of 25mL, add 2 milliliters absolute methanol solution, then, add the phenyl aldehyde of 0.1mL and the Nitromethane 99Min. of 0.5mL in mentioned solution, stirring at normal temperature is reacted after 72 hours, carry out nmr analysis, transformation efficiency: 60 %;
1H NMR (300MHz, CDCl
3) 7.28～7.32 (m, 5H, Ar-H), 5.32～5.35 (d, J=9.18Hz, 1H ,-CH), 4.38～4.56 (m, 2H ,-CH
2), 3.89 (br, 1H ,-OH).
Claims (2)
1. chipal compounds, be N-2-second hydroxyl-1 (R)-benzyl-1-pyrroles's propionic acid amide-2-ketone, it is characterized in that 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-preparation of 2-Pyrrolidone and copper acetate dihydrate, by the chipal compounds shown in the following chemical formula:
( I )。
2. by the synthetic method of compound claimed in claim 1 (I), by 2-Pyrrolidone phenylpropyl alcohol cyanogen and D-phenylalaninol under the anhydrous and oxygen-free condition and the anhydrous ZnCl of catalyzer
2When existing in chlorobenzene solvent back flow reaction 24 hours, then separate, purifying, i.e. reaction is sloughed chlorobenzene after finishing, the rear dichloromethane extraction of using that is dissolved in water is used column chromatography purification behind the extraction phase precipitation; The reaction of synthetic target product is prepared intermediate 1-[2-[(4R)-4,5-dihydro-4-benzyl-2-oxazolinyl] ethyl]-2-Pyrrolidone and copper acetate dihydrate be in the alcohol mixed solvent back flow reaction 48 hours, then with ethanol and normal hexane recrystallization, get compound monocrystal.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103274936A (en) * | 2013-06-19 | 2013-09-04 | 罗梅 | Chiral compound |
| CN104557586A (en) * | 2015-01-25 | 2015-04-29 | 罗梅 | Preparation and synthesis method of chiral amide compound |
| CN108558789A (en) * | 2018-04-09 | 2018-09-21 | 合肥工业大学 | A kind of preparation of thiazoline hydrochloride and synthetic method |
-
2012
- 2012-10-28 CN CN 201210416588 patent/CN102898342A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103274936A (en) * | 2013-06-19 | 2013-09-04 | 罗梅 | Chiral compound |
| CN103274936B (en) * | 2013-06-19 | 2014-08-06 | 罗梅 | Chiral compound |
| CN104557586A (en) * | 2015-01-25 | 2015-04-29 | 罗梅 | Preparation and synthesis method of chiral amide compound |
| CN104557586B (en) * | 2015-01-25 | 2017-01-18 | 罗梅 | Preparation and synthesis method of chiral amide compound |
| CN108558789A (en) * | 2018-04-09 | 2018-09-21 | 合肥工业大学 | A kind of preparation of thiazoline hydrochloride and synthetic method |
| CN108558789B (en) * | 2018-04-09 | 2019-07-16 | 合肥工业大学 | A kind of preparation and synthetic method of thiazoline hydrochloride |
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