CN101723771A - Novel method for preparing beta-aminoketone, ester, nitrile and amide derivatives through catalysis of functional ionic liquid - Google Patents
Novel method for preparing beta-aminoketone, ester, nitrile and amide derivatives through catalysis of functional ionic liquid Download PDFInfo
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- CN101723771A CN101723771A CN 200810167605 CN200810167605A CN101723771A CN 101723771 A CN101723771 A CN 101723771A CN 200810167605 CN200810167605 CN 200810167605 CN 200810167605 A CN200810167605 A CN 200810167605A CN 101723771 A CN101723771 A CN 101723771A
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- amide derivatives
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- 239000002608 ionic liquid Substances 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 22
- 150000002148 esters Chemical class 0.000 title claims abstract description 19
- 150000001408 amides Chemical class 0.000 title claims abstract description 14
- 150000002825 nitriles Chemical class 0.000 title claims abstract description 14
- 238000006555 catalytic reaction Methods 0.000 title abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- 150000001412 amines Chemical class 0.000 claims abstract description 16
- 150000001336 alkenes Chemical class 0.000 claims abstract description 15
- 239000000126 substance Substances 0.000 claims abstract description 14
- 238000005966 aza-Michael addition reaction Methods 0.000 claims abstract description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 60
- 239000012074 organic phase Substances 0.000 claims description 19
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical group COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 18
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 17
- 230000007812 deficiency Effects 0.000 claims description 13
- 150000002460 imidazoles Chemical class 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 6
- 239000012071 phase Substances 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 claims description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 3
- FUOZJYASZOSONT-UHFFFAOYSA-N 2-propan-2-yl-1h-imidazole Chemical compound CC(C)C1=NC=CN1 FUOZJYASZOSONT-UHFFFAOYSA-N 0.000 claims description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical class NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 3
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 3
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 3
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 claims description 3
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 3
- 150000003233 pyrroles Chemical class 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 238000004440 column chromatography Methods 0.000 claims 1
- 230000002950 deficient Effects 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract 2
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- 238000013375 chromatographic separation Methods 0.000 description 18
- 238000004809 thin layer chromatography Methods 0.000 description 18
- 239000002994 raw material Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 125000002757 morpholinyl group Chemical group 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 11
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 9
- 235000014655 lactic acid Nutrition 0.000 description 9
- 239000004310 lactic acid Substances 0.000 description 9
- -1 lactic acid ion Chemical class 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- 238000006845 Michael addition reaction Methods 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- WRFUXAYDZDQDKY-UHFFFAOYSA-N 1-hexylpiperazine Chemical compound CCCCCCN1CCNCC1 WRFUXAYDZDQDKY-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- WTLNOANVTIKPEE-UHFFFAOYSA-N 2-acetyloxypropanoic acid Chemical compound OC(=O)C(C)OC(C)=O WTLNOANVTIKPEE-UHFFFAOYSA-N 0.000 description 1
- 229910021617 Indium monochloride Inorganic materials 0.000 description 1
- 229910013684 LiClO 4 Inorganic materials 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- APHGZSBLRQFRCA-UHFFFAOYSA-M indium(1+);chloride Chemical compound [In]Cl APHGZSBLRQFRCA-UHFFFAOYSA-M 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for generating beta-aminoketone, ester, nitrile and amide derivatives by performing aza-Michael addition on amine substances and electron-deficient alkenes through an efficient environment-friendly catalyst under solvent-free mild (room temperature) reaction conditions. The method comprises the steps of taking ionic liquid as the catalyst, subjecting amine substances and electron-deficient alkenes to aza-Michael addition at room temperature under normal pressure and obtaining corresponding beta-aminoketone, ester, nitrile and amide derivatives. The ionic liquid is repeatedly used five times, and reaction yield does not obviously drop. The method has the advantages of simple operation, high yield, good using repeatability of the catalytic reaction system, mild reaction conditions and good prospects for industrialization.
Description
Technical field
The present invention relates under a kind of efficient, green, condition of no solvent, is the method that the Michael addition of catalyzer prepares beta-amino ketones, ester, nitrile and amide derivatives with the new function ionic liquid.
Technical background
Beta-amino ketones, ester, nitrile and amide derivatives are widely used in fine chemistry industry and microbiotic field of medicaments as intermediate.General synthetic method comprises Mannich reaction and aza-Michael addition.By contrast, the Michael addition is more suitable in preparation beta-amino ketones, ester, nitrile and amide derivatives.For many years, emerged in large numbers a lot of catalyzer, as: SnCl
4/ FeCl
3, InCl
3, CeCl
37H
2O-NaI, Yb (OTf)
3, CAN, Bi (NO
3) and LiClO
4Deng, though these methods have all obtained certain success,, wherein there are some defectives in they, as: need excessive greatly reagent, long reaction times, the reaction conditions of harshness and the use of some noxious solvents such as methylene dichloride and acetonitrile.Therefore, develop efficient, green amine and grip altogether and add to electron deficiency olefin production beta-amino ketones, ester, nitrile and amide derivatives method and not only have important economic benefit, and also have good environment and social benefit.
In recent years, functional ion liquid had pointed out to explore the important directions of eco-friendly catalystic converter system for people.Ionic liquid itself has characteristics such as special physicochemical characteristic and thermodynamic stability, dissolving power are strong, low volatility, molecular structure adjustability, make it be successfully applied to catalyzed reaction (as solvent or catalyzer), aftertreatment is simple, ionic liquid can be repeatedly used, and shows very excellent characteristics.Therefore, it is necessary utilizing catalysis of functional ionic liquid carbonnitrogen bond Michael addition newly developed.
Summary of the invention
The objective of the invention is to replace the method for traditional catalysis aza-Michael addition amine and electron deficiency olefin production beta-amino ketones, ester, nitrile and amide derivatives, a kind of efficient, eco-friendly catalyzer is provided, and solvent-free gentleness (room temperature) reaction conditions is realized the aza-Michael addition down.
According to the present invention, the method that described aza-Michael addition by amine substance and electron deficiency alkene prepares beta-amino ketones, ester, nitrile and amide derivatives comprises: be catalyzer with the ionic liquid, under room temperature, the normal pressure, need not any solvent, amine substance and electron deficiency alkene carried out the aza-Michael addition reaction 1～24 hour, obtained corresponding beta-amino ketones, ester, nitrile and amide derivatives; Wherein, described ionic liquid is:
Wherein, the mol ratio of described amine substance and electron deficiency alkene is 1: 1～1: 2.
Wherein, described ion liquid molar weight is 0.01～1 times of amine substance.
Wherein, described amine substance is morpholine, Tri N-Propyl Amine, pyrroles, N methyl piperazine, N-ethyl piperazidine, imidazoles, 2 isopropyl imidazole, piperidines, diethylamine, hexahydroaniline or para-totuidine.
Wherein, it is characterized in that described electron deficiency alkene is methyl acrylate, ethyl propenoate, n-butyl acrylate, Methyl Methacrylate, vinyl cyanide, methylene acetone, α, β-unsaturated cyclonene or acrylic acid amides.
Wherein, after reaction finishes, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation obtain product (after substrate surpasses 1 mole, direct rectifying separation reaction solution, obtain high purity product), extracting phase (raffinate in the rectifying tower still) 60 ℃ of vacuum-dryings of ionic liquid are used for the next batch reaction after 5 hours, ionic liquid is reused 5 times, does not find that reaction yield obviously descends.
Provided by the inventionly utilize novel ion liquid catalysis to grip the addition amine substance altogether, generate the method for beta-amino ketones, ester, nitrile and amide derivatives, realize by following approach to electron deficiency alkene:
The ion liquid preparation process of new function used in the present invention (applying for a patent separately):
Carboxylic acid (lactic acid, acetate, n Propanoic acid and butanic acid) is added drop-wise among the DBU of equimolar amount, temperature of reaction is controlled at below 10 ℃ during dropping, drips off in 0.5-2 hour, and room temperature mechanical stirred 24 hours, 60-80 ℃ vacuum-drying 5-10 hour, obtain light yellow transparent liquid.The ionic liquid of preparation is used
1H NMR,
13C NMR structural confirmation.Four kinds of ionic liquids are respectively described ionic liquid and are:
Abbreviate [DBU] [Ac] as,
Aza-Michael adduct preparation process is:
In the there-necked flask of magnetic stirring apparatus is housed, add Ammonia material, electron deficiency alkene and ionic liquid successively.Wherein the mol ratio of Ammonia material and electron deficiency alkene is 1: 1-1: 2, and the mol ratio of ionic liquid and Ammonia material is 0.01: 1-1: 1, need not any solvent compartment normal temperature and pressure reaction 1-24 hour, thin-layer chromatography (TLC) is followed the tracks of extent of reaction.After reaction finishes, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product (after substrate surpasses 1 mole, directly the rectifying separation reaction solution obtains high purity product), 60 ℃ of vacuum-dryings of extracting phase (bottom product) ionic liquid are used for the next batch reaction after 5 hours, ionic liquid is reused 5 times, does not find that reaction yield obviously descends.
Embodiment
The present invention will be further described below with reference to embodiment, and embodiments of the invention only are used to technical scheme of the present invention is described, and non-limiting the present invention.
Embodiment 1
Morpholine (5mmol), methyl acrylate (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 95%, content 98%.3-(1-Morpholinyl)-propionic?acid?methylester：
1H?NMR(400MHz，CDCl
3)(ppm)：3.66(s，3H，OCH
3)，3.67-3.65(m，4H，morpholinyl)，2.65(t，2H，J＝6Hz，CH
2)，2.48(t，2H，J＝6Hz，CH
2)，2.43-2.41(m，4H，morpholinyl)；
13C?NMR(100MHz，CDCl
3)(ppm)：172.8，66.8，53.8，53.3，51.6，31.7.
Embodiment 2
Tri N-Propyl Amine (5mmol), methyl acrylate (5.5mmol), 1mmol n Propanoic acid ionic liquid [DBU] [Pr] are joined in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 86%, content 95%.3-(1-Propylamine)-propionic?acidmethyl?ester：
1H?NMR(400MHz，CDCl
3)(ppm)：3.63(s，3H，OCH
3)，2.62(t，2H，J＝6.4Hz，CH
2)，2.45(t，2H，J＝6.4Hz，CH
2)，2.58(m，2H，CH
2)，1.41(m，2H，CH
2)，0.90(m，3H，CH
3)；
13C?NMR(100MHz，CDCl
3)(ppm)：170.5，66.8，52.8，52.1，44.9，28.1，12.3.
Embodiment 3
Piperidines (5mmol), methyl acrylate (5.5mmol), 1mmol acetato-liquid [DBU] [Ac] are joined in the 50mL single port bottle successively, stirring at room 1.5 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 96%, content 98%.3-(1-Piperidinyl)-propionic?acidmethyl?ester：
1H?NMR(400MHz，CDCl
3)(ppm)：3.86(s，3H，OCH
3)，2.86(t，2H，J＝6Hz，CH
2)，2.68(t，2H，J＝6Hz，CH
2)，1.80-1.75(m，4H，piperidinyl)，1.61-1.44(m，4H，piperidiny)，1.42-1.26(m，2H，piperidinyl)；
13C?NMR(100MHz，CDCl
3)(ppm)：173.8，54.2，53.8，52.9，31.8，29.3，25.8，24.6，23.1.
Embodiment 4
2 isopropyl imidazole (5mmol), methyl acrylate (5.5mmol), 1mmol butanic acid ionic liquid [DBU] [n-Bu] are joined in the 50mL single port bottle successively, stirring at room 10 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 87%, content 98%.3-(2-Isopropyl-1-imidazole)-propionic?acid?methyl?ester：
1H?NMR(400MHz，CDCl
3)(ppm)：6.94(d，1H，J＝1.2Hz，imidazole)，6.81(d，1H，J＝1.2Hz，imidazole)，4.20(t，2H，J＝7.2Hz，CH
2)，3.71(s，3H，OCH
3)，3.03(q，1H，J＝7.2Hz，CH)2.76(t，2H，J＝7.2Hz，CH
2)，1.33(d，6H，2CH
3)；
13C?NMR(100MHz，CDCl
3)(ppm)：170.9，152.4，127.4，118.3，52.0，40.6，35.6，25.7，21.8.
Embodiment 5
Morpholine (5mmol), ethyl propenoate (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 3 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 90%, content 96%.3-(1-Morpholinyl)-propionic?acid?ethylester：
1H?NMR(400MHz，CDCl
3)(ppm)：4.15(q，2H，J＝7.2Hz，OCH
2)，3.7(m，4H，J＝4.4Hz，morpholinyl)，2.69(t，2H，J＝7.6Hz，CH
2)，2.50(t，2H，J＝7.6Hz，CH
2)，2.47(q，4H，J＝4.4Hz，morpholinyl)，1.27(t，3H，J＝7.2Hz，CH
3)；
13C?NMR(100MHz，CDCl
3)(ppm)：175.4，66.9，60.4，53.9，53.4，32.1，14.2.
Embodiment 6
Morpholine (5mmol), n-butyl acrylate (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 4 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 90%, content 96%.3-(1-Morpholinyl)-propionic?acid?butylester：
1H?NMR(400MHz，CDCl
3)(ppm)：4.09(t，2H，J＝8.4Hz，OCH
2)，3.69(t，4H，J＝4.4Hz，morpholinyl)，2.68(t，2H，J＝7.6Hz，CH
2)，2.49(t，2H，J＝7.6Hz，CH
2)，1.65-1.58(m，2H，CH
2)，0.94(t，3H，J＝7.2Hz，CH
3)；
13C?NMR(100MHz，CDCl
3)(ppm)：172.5，66.9，64.3，53.9，53.3，32.1，30.6，19.1，13.7.
Embodiment 7
Morpholine (5mmol), Methyl Methacrylate (5.5mmol), 1mmol acetato-liquid [DBU] [Ac] are joined in the 50mL single port bottle successively, stirring at room 4 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 90%, content 96%.2-Methyl-3-(1-morpholinyl)-propionic?acid?methyl?ester：
1H?NMR(400MHz，CDCl
3)(ppm)：3.69(s，3H，OCH
3)，3.68-3.64(m，4H，morpholinyl)，2.74-2.62(m，2H，morpholinyl)，2.50-2.41(m，2H，morpholinyl)，2.41-2.36(m，2H，CH
2)，2.33-2.28(m，1H，CH)，1.15(d，3H，J＝6.8Hz，CH
3)；
13C?NMR(100MHz，CDCl
3)(ppm)：176.4，67.0，62.0，53.7，51.6，37.5，15.5.
Embodiment 8
Morpholine (5mmol), vinyl cyanide (5.5mmol), 1mmol n Propanoic acid ionic liquid [DBU] [Pr] are joined in the 50mL single port bottle successively, stirring at room 3 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 92%, content 98%.3-(1-Morpholinyl)-propionitrile：
1H?NMR(400MHz，CDCl
3)(ppm)：3.72(t，4H，J＝4.4Hz，morpholinyl)，2.68(t，2H，J＝7.2Hz，CH
2)，2.53(t，2H，J＝7.2Hz，CH
2)，2.51(t，4H，J＝4.4Hz，morpholinyl)；
13C?NMR(100MHz，CDCl
3)(ppm)：118.5，66.5，53.4，52.9，15.6.
Embodiment 9
Morpholine (5mmol), acrylic acid amides (5.5mmol), 1mmol butanic acid ionic liquid [DBU] [n-Bu] are joined in the 50mL single port bottle successively, stirring at room 3 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 93%, content 98%.3-(1-Morpholinyl)-propanamide：
1HNMR(400MHz，CDCl
3)(ppm)：7.84(br，1H，NH)，6.06(br，1H，NH)，3.73(s，4H，morpholinyl)，2.64(t，2H，J＝6Hz，CH
2)，2.51(s，4H，morpholinyl)，2.41(t，2H，J＝6Hz，CH
2)；
13C?NMR(100MHz，CDCl
3)(ppm)：175.0，66.7，54.1，52.9，31.6.
Embodiment 10
Imidazoles (5mmol), methyl acrylate (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 92%, content 96%.3-Imidazol-1-yl-propionic?acid?methylester：
1H?NMR(400MHz，CDCl
3)(ppm)：7.54(s，1H，imidazole)，7.05(s，1H，imidazole)，6.93(s，1H，imidazole)，4.27(t，2H，J＝6.6Hz，CH
2)，3.70(s，3H，OCH
3)，2.78(t，2H，J＝6.6Hz，CH
2)；
13C?NMR(100MHz，CDCl
3)(ppm)：172.8，66.8，53.8，53.3，51.6，31.7.
Embodiment 11
Diethylamine (5mmol), methylene acetone (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 88%, content 96%.4-Diethyamino-1-yl-butan-2-one：
1H?NMR(400MHz，CDCl
3)(ppm)：2.76(m，4H，2CH
2)，2.52(q，4H，J＝7.2Hz，2CH
2)，2.14(s，3H，CH
3)，1.03(t，6H，J＝7.2Hz，2CH
3)；
13C?NMR(100MHz，CDCl
3)(ppm)：207.3，52.4，47.1，40.0，30.3，12.2.
Embodiment 12
With miaow N methyl piperazine (5mmol), α, β-unsaturated cyclonene (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] join in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, and raw material disappears, and uses the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 95%, content 98%.3-(1-Methylpiperazine)-6-yl-cyclohexan-1-one：
1H?NMR(400MHz，CDCl
3)(ppm)：2.88(m，4H)，2.70(m，1H，CH)，2.27(s，3H，CH
3)，2.13(m，2H，CH
2)，1.72(m，2H，CH
2)，1.55(m，2H，CH
2)，1.42(m，2H，CH
2)；
13C?NMR(100MHz，CDCl
3)(ppm)：207.0，55.9，49.1，47.9，45.8，40.8，32.8，27.8，22.2.
Embodiment 13
With miaow N-hexyl piperazine (5mmol), α, β-unsaturated cyclonene (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] join in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, and raw material disappears, and uses the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 96%, content 98%.3-(1-ethylpiperazine)-6-yl-cyclohexan-1-one：
1H?NMR(400MHz，CDCl
3)(ppm)：3.25(q，2H，J＝7.2Hz，CH
2)，2.85(m，4H)，2.65(m，1H，CH)，2.35(m，2H，CH
2)，2.15(q，3H，J＝7.2Hz，CH
3)，2.08(m，2H，CH
2)，1.69(m，2H，CH
2)，1.52(m，2H，CH
2)，1.40(m，2H，CH
2)；
13C?NMR(100MHz，CDCl
3)(ppm)：206.8，56.7，50.2，48.7，40.3，32.5，21.8，11.5.
Embodiment 14
Hexahydroaniline (5mmol), methylene acetone (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 2 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 85%, content 96%.4-Cyclohexylamine-1-yl-butan-2-one：
1HNMR(400MHz，CDCl
3)(ppm)：2.73(m，4H，2CH
2)，2.30(m，1H)，2.12(s，3H，CH
3)，1.90(m，1H)，2.30(m，1H)，1.73(m，1H)，1.62(m，1H)，1.14(m，1H)，1.02(m，1H)，；
13C?NMR(100MHz，CDCl
3)(ppm)：207.5，53.1，51.1，41.2，37.5，30.9，27.2，25.4.
Embodiment 15
4-monomethylaniline (5mmol), methyl acrylate (5.5mmol), 1mmol lactic acid ion liquid [DBU] [Lac] are joined in the 50mL single port bottle successively, stirring at room 3 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 94%, content 98%.3-(4-Methlphenyl)-propionic?acidmethyl?ester：
1H?NMR(400MHz，CDCl
3)(ppm)：6.79-6.73(m，2H，ArH)，6.59-6.56(m，2H，ArH)，1.73(s，3H，CH
3)，3.73(s，3H，OCH
3)，3.37(t，2H，J＝6.4Hz，CH
2)，2.58(t，2H，J＝6.4Hz，CH
2)；
13C?NMR(100MHz，CDCl
3)(ppm)：168.9，149.4，139.5，112.9，112.4，53.6，49.7，38.8，32.1.
Embodiment 16
Extracting phase among morpholine (5mmol), methyl acrylate (5.5mmol), the embodiment 1 is joined in the 50mL single port bottle successively through the ionic liquid of 60 ℃ of vacuum-dryings after 5 hours, stirring at room 2 hours, TLC detects, raw material disappears, use the extracted with diethyl ether reaction solution, merge organic phase, lean on chromatographic separation and obtain product, yield 93%, content 98%.Ionic liquid is reused 5 times, does not find that yield obviously descends, and specifically sees Table 1.NMR data embodiment 1.
Table 1
Need to prove that foregoing invention content and embodiment are intended to prove the practical application of technical scheme provided by the present invention, should not be construed as qualification protection domain of the present invention.Those skilled in the art are in spirit of the present invention and principle, when doing various modifications, being equal to and replacing or improve.Protection scope of the present invention is as the criterion with appended claims.
Claims (10)
1. the aza-Michael addition by amine substance and electron deficiency alkene prepares the method for beta-amino ketones, ester, nitrile and amide derivatives, it is characterized in that, described method comprises with the ionic liquid being catalyzer, amine substance and electron deficiency alkene carry out the aza-Michael addition reaction under room temperature, the normal pressure, obtain corresponding beta-amino ketones, ester, nitrile and amide derivatives; Wherein, described ionic liquid is:
2. the method for claim 1 is characterized in that, the mol ratio of described amine substance and electron deficiency alkene is 1: 1～1: 2.
3. the method for claim 1 is characterized in that, described ion liquid molar weight is 0.01～1 times of amine substance.
4. as claim 1,2 or 3 described methods, it is characterized in that described amine substance is morpholine, Tri N-Propyl Amine, pyrroles, N methyl piperazine, N-ethyl piperazidine, imidazoles, 2 isopropyl imidazole, piperidines, diethylamine, hexahydroaniline or para-totuidine.
5. method as claimed in claim 1 or 2, it is characterized in that, described electron deficiency alkene is methyl acrylate, ethyl propenoate, n-butyl acrylate, Methyl Methacrylate, vinyl cyanide, methylene acetone, α, β-unsaturated cyclonene or acrylic acid amides.
6. the method for claim 1 is characterized in that, reaction process need not any solvent.
7. as claim 1 or 6 described methods, it is characterized in that the reaction times is 1～24 hour.
8. method as claimed in claim 7 is characterized in that, reaction is used the extracted with diethyl ether reaction solution after finishing, and merges organic phase, and column chromatography for separation obtains product.
9. method as claimed in claim 8 is characterized in that, after reaction finished, behind the extracted with diethyl ether reaction solution, extracting phase repeated repeatedly to use through 60 ℃ of vacuum-dryings in 5 hours, and wherein, extracting phase is an ionic liquid.
10. method as claimed in claim 7 is characterized in that, after reaction finished, if when described amine substance surpasses 1 mole, directly rectifying, separating reaction liquid obtained high purity product.
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