CN103467321B - Method for preparing beta-amino-carbonyl compound - Google Patents

Method for preparing beta-amino-carbonyl compound Download PDF

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CN103467321B
CN103467321B CN201310422079.2A CN201310422079A CN103467321B CN 103467321 B CN103467321 B CN 103467321B CN 201310422079 A CN201310422079 A CN 201310422079A CN 103467321 B CN103467321 B CN 103467321B
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beta
carbonyl compound
phenyl
preparation
aldehyde
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CN103467321A (en
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高子伟
吴亚
张伟强
孙华明
陈纯
朱序阳
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Shaanxi Normal University
Xian Shiyou University
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Shaanxi Normal University
Xian Shiyou University
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Abstract

The invention provides a method for preparing a beta-amino-carbonyl compound. Aldehydes, ketones and amines are directly mixed under the condition of synergetic catalysis of titanocene dichloride and a ligand, and react at room temperature to obtain the beta-amino-carbonyl compound, wherein the ligand is salicylic acid or salicylic acid derivatives or structural analogues thereof. According to the method, the catalyst used in the method is low in cost, nontoxic and stable and effective to air and water, the reaction condition is mild, a solvent is not needed, the operation is simple, and the atom economy is high.

Description

The preparation method of beta-amino carbonyl compound
Technical field
The present invention relates to the preparation method of beta-amino carbonyl compound.
Background technology
Beta-amino carbonyl compound is the important structure unit of a lot of natural products, medicine, synthetic intermediate.For example, containing 1 of beta-amino carbonyl structure unit, the two Mannich bases of 2-cyclopentanone etc. have stronger anti-inflammatory, antitumour activity.Mannich reaction is the most basic most important reaction method of reaction that builds beta-amino carbonyl compound always.Three component Mannich reaction of atomic economy are high, simple to operate, and environmental protection is the first-selected approach of preparing beta-amino carbonyl compound.A lot of Bronsted acid or Lewis acid catalyst are all used for catalysis and prepare this compounds, for example sulfonic acid of sulfonic compound, Polymer-supported, heteropolyacid, proline(Pro), FeCl 3, InCl 3, BiCl 3, Bi (OTf) 3, CeCl 3, CAN, Yb (OPf) 3, ZrOCl 2, Salen-Zn title complex etc.Kobayashi(Kobayashi in numerous Bronsted acid, Org.Lett., 1999,1:1965 – 1967) use Witco 1298 Soft Acid Surfactant-Catalyzed aldehyde, ketone, amine three component reaction to prepare beta-amino carbonyl compound and obtain good productive rate, but, tensio-active agent and reaction product separation difficulty.Afterwards, for catalyzer is easily separated, sulfonic acid catalyst is carried out to load, as the sulfonic acid catalyst of Polymer-supported (S.Iimura, Chem.Commun.2003,1644), but its preparation process is loaded down with trivial details, condition harshness, and application is difficulty relatively.Heteropolyacid (Azizi N, Org Lett, 2006,8:2079-2082) is also used to catalysis and prepares this compounds, for the substrate of aryl or chain alkyl replacement, and its compatible variation, catalyzed reaction efficiency obviously declines.The common reaction conditions gentleness of Lewis acid catalyst, productive rate is higher, but, the water that produces equivalent due to ketone, aldehyde and the amine direct polycondensation of unmodified reduces catalyst activity or dosage increase, conventionally choose the ketone of modification or use imines to carry out for raw material at the substrate of preparing beta-amino carbonyl compound, the preparation of its raw material is complicated, and imines has certain toxicity, and these all make three component Mannich reactions of Lewis acid catalysis Atom economy have huge challenge.For example InCl 3(T-P Loh, Tetrahedron, 2000,56,3227) catalysis silyl enol ether and aldehyde, amine carry out three components, and productive rate reaches 80%.The method not only needs organic solvent but also can not break away from the shortcomings such as raw material preparation is complicated, Atom economy is poor.Japanese Patent (JP2002275140A) is at supercritical CO 2middle use silyl enol ether and imine reaction, at Yb (OTf) 3within 3 hours, prepare beta-amino carbonyl compound with lower 50 DEG C of polyvinyl alcohol catalysis, 15MPa reaction.Although the method is used green solvent, reaction efficiency improves greatly, and the complex substrate of its operating process, harsh reaction conditions and expensive catalyzer have restricted its application equally.FeCl 3the catalyzer of a class cheap and simple, but, the FeCl that dosage is 20% 3only has 58% productive rate in 18h reaction.Recently, phenylo boric acid (S.V.Goswami, Mol.Diversity, 2013,17,33) be found to be the effective Lewis acid catalyst of a class effectively catalysis aldehyde, ketone, amine three component reaction prepare beta-amino carbonyl compound, but reaction needed organic solvent, and the reaction times reach 8 hours.
Summary of the invention
Technical problem to be solved by this invention is to overcome the shortcoming that existing beta-amino carbonyl compound preparation method exists, a kind of preparation method of beta-amino carbonyl compound is provided, the method is used cyclopentadienyl titanium dichloride and Whitfield's ointment and derivative thereof as catalyzer, under room temperature solvent-free condition, the ketone of catalysis unmodified, aldehyde and amine direct polycondensation react in the short period of time and obtain the very product of high yield.Catalyzer used is inexpensive, nontoxic, stable, efficient to empty G&W, and reaction conditions gentleness, need not add solvent, and simple to operate, Atom economy is high.
Solving the problems of the technologies described above adopted technical scheme is: aldehyde is mixed for 1:1～4:1～2 in molar ratio with ketone, amine, add cyclopentadienyl titanium dichloride, part, the add-on of cyclopentadienyl titanium dichloride is 1%～5% of aldehyde molar weight, the add-on of part is 1～4 times of cyclopentadienyl titanium dichloride molar weight, room temperature reaction 1～12 hour, obtains beta-amino carbonyl compound.
Preferred 1:1～2:1～1.5 of mol ratio of above-mentioned aldehyde and ketone, amine, the best is 1:2:1.1, add-on the best of cyclopentadienyl titanium dichloride is 5% of aldehyde molar weight, 1～2 times of the preferred cyclopentadienyl titanium dichloride molar weight of add-on of part, the preferred room temperature reaction of reaction conditions 1～5 hour.
Part of the present invention is any one in Whitfield's ointment, 5-chloro-salicylic acid, 4-chloro-salicylic acid, 3-chloro-salicylic acid, 5-methoxyl group Whitfield's ointment, 5-aminosalicylic acid, 5-NITROSALICYLIC ACID, thiosalicylic acid, 2-hydroxyl-3-naphthoic acid, 2-hydroxyl-1-naphthoic acid, preferably any one in Whitfield's ointment, 5-chloro-salicylic acid, 5-methoxyl group Whitfield's ointment, 5-aminosalicylic acid, 2-hydroxyl-3-naphthoic acid, 2-hydroxyl-1-naphthoic acid.
Ketone of the present invention is preferred or in formula, X, Y, Z independently represent H, CH separately 3, CH 3o, F, CF 3, Cl, Br, NO 2in any one, the value of n is 1 or 2, R 1, R 2independently represent separately C 1～C 3any one in alkyl.
Aldehyde of the present invention is preferred or in formula, A, B, C independently represent H, CH separately 3, CH 3o, F, CF 3, Cl, Br, NO 2in any one, M represents N, O or S.
Amine of the present invention is preferred or naphthylamines, in formula, D, E, F independently represent H, CH separately 3, CH 3o, F, Cl, Br, NO 2in any one.
The present invention, under cyclopentadienyl titanium dichloride and part concerted catalysis condition, directly mixes ketone, aldehyde and amine, and room temperature reaction obtains beta-amino carbonyl compound, and wherein part is Whitfield's ointment or salicylic derivative or its analog.The present invention's catalyzer used is inexpensive, nontoxic, stable, efficient to empty G&W, reaction conditions gentleness, need not add solvent, simple to operate, Atom economy is high, and the beta-amino carbonyl compound preparing has very large application potential in the preparation of medicine, natural product and organic synthesis intermediate.
Embodiment
Below in conjunction with embodiment, the present invention is described in more detail, but invention which is intended to be protected is not limited to these embodiment.
Embodiment 1
To prepare following formula: compound 1,3-phenylbenzene-3-(phenylamino)-1-acetone is example, raw materials used and preparation method thereof as follows:
By 203uL(2.0mmol) phenyl aldehyde, 201uL(2.2mmol) aniline, 467uL(4.0mmol) methyl phenyl ketone, 24.9mg(0.1mmol) cyclopentadienyl titanium dichloride, 13.8mg(0.1mmol) Whitfield's ointment is placed in reaction flask, room temperature reaction 1 hour, stopped reaction adds 2mL saturated sodium bicarbonate aqueous solution in system, with 10mL ethyl acetate extraction three times, merge organic phase, with anhydrous sodium sulfate drying, column chromatography for separation, obtain white solid product, its productive rate is 97%.Products therefrom characterizes with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is as follows: 1h NMR (400MHz, CDCl 3) δ ppm:7.89 (m, 2H), 7.55 (m, 1H), 7.43 (m, 4H), 7.32 (dd, J=10.3,4.7Hz, 2H), 7.23 (m, 1H), 7.09 (m, 2H), 6.66 (t, J=7.3Hz, 1H), 6.57 (m, 2H), 5.00 (m, 1H), 3.47 (qd, J=16.1,6.4Hz, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:197.25,145.99,141.98,135.76,132.37,128.09,127.80,127.67,127.19,126.33,125.36,116.79,112.84,53.84,45.29.
Embodiment 2
To prepare following formula: compound 1-phenyl-3-(2-chloro-phenyl-)-3-(4-anisole amino)-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar o-chlorobenzaldehyde, aniline is replaced with equimolar P-nethoxyaniline, other steps are identical with embodiment 1, be prepared into white solid 1-phenyl-3-(2-chloro-phenyl-)-3-(4-anisole amino)-1-acetone, its productive rate is 79%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.95 (d, 2H), 7.68-7.72 (m, 1H), 7.53-7.60 (m, 2H), 7.40-7.47 (m, 2H), 7.22-7.30 (m, 1H), 7.07-7.14 (m, 1H), 6.58-6.72 (m, 4H), 5.28-5.34 (m, 1H), 3.74-3.85 (m, 1H), 3.69 (s, 3H), 3.42-3.54 (m, 1H); 13c NMR (101MHz, CDCl 3) δ ppm:198.32,152.46,141.33,140.56,136.63,133.31,133.02,128.69,128.48,128.44,128.24,127.90,122.62,114.96,114.68,55.51,54.89,43.92.
Embodiment 3
To prepare following formula: compound 2-methyl isophthalic acid-(4-chloro-phenyl-)-1-anilino-propione as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar 4-chloro-benzaldehyde, methyl phenyl ketone is replaced with equimolar propione, other steps are identical with embodiment 1, be prepared into faint yellow solid 2-methyl isophthalic acid-(4-chloro-phenyl-)-1-anilino-propione, its productive rate is 81%, is 74:26 along inverse ratio, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.17 (t, J=8.2Hz, 4H), 6.99 (t, J=7.5Hz, 2H), 6.57 (d, J=7.1Hz, 1H), 6.38 (d, J=7.5Hz, 2H), 4.56 (d, J=5.3Hz, 1H), 2.89 (m, 1H), 2.27 (m, 2H), 1.10 (d, J=6.9Hz, 1H), 1.02 (d, J=6.9Hz, 3H), 0.87 (t, J=7.1Hz, 3H); 13c NMR (101MHz, CDCl 3) δ ppm:213.88,211.97,145.69,139.36,138.85,131.99,131.93,128.13,128.09,127.82,127.76,127.27,126.96,116.92,116.51,112.66,112.29,76.33,76.02,75.70,59.02,57.63,50.98,50.90,35.31,34.55,14.57,10.56,6.48,6.21.
Embodiment 4
To prepare following formula: compound 2-methyl isophthalic acid-(4-p-methoxy-phenyl)-1-(4-chloroanilino)-propione as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced methoxyl group formaldehyde with equimolar, aniline is replaced with equimolar p-Chlorobenzoic acid amide, methyl phenyl ketone is replaced with equimolar propione, other steps are identical with embodiment 1, are prepared into white solid 2-methyl isophthalic acid-(4-p-methoxy-phenyl)-1-(4-chloroanilino)-propione, and its productive rate is 83%, be 78:22 along inverse ratio, characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.09 (t, J=10.7Hz, 2H), (6.93 d, J=8.9Hz, 2H), 6.76 (dd, J=8.5,4.9Hz, 2H), (6.34 t, J=6.0Hz, 2H), 4.47 (s, 1H), 4.31 (s, 1H), 3.70 (d, J=3.5Hz, 3H), 2.98-2.82 (m, 1H), 2.36-2.12 (m, 2H), 1.03 (d, J=7.0Hz, 3H), 0.86 (t, J=7.2Hz, 3H); 13c NMR (101MHz, CDCl 3) δ ppm:212.46,157.71,146.08,132.13,128.01,126.87,116.54,112.95,112.63,57.73,54.18,51.38,34.58,10.79,6.48.
Embodiment 5
To prepare following formula: compound 4-phenyl-4-phenylamino-2-butanone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, methyl phenyl ketone used is replaced with equimolar acetone, and other steps are identical with embodiment 1, is prepared into white solid 4-phenyl-4-phenylamino-2-butanone, and its productive rate is 49%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.21-7.37 (m, 5H), 7.09 (t, J=7.7Hz, 2H), 6.68 (t, J=7.3Hz, 1H), 6.56 (d, J=8.2Hz, 2H), 4.84 (t, J=6.4Hz, 1H), 2.94 (d, J=6.4Hz, 2H), 2.09 (s, 3H); 13c NMR (101MHz, CDCl 3) δ ppm:207.34,146.71,142.45,129.40,129.01,127.58,126.49,118.27,114.21,54.78,51.26,31.03.
Embodiment 6
To prepare following formula: compound 2-[(phenyl) (anilino) methyl]-cyclopentanone is as example, raw materials used and preparation method thereof as follows:
In embodiment 1, methyl phenyl ketone used is replaced with equimolar cyclopentanone, and other steps are identical with embodiment 1, is prepared into yellow solid 2-[(phenyl) (anilino) methyl]-cyclopentanone, its productive rate is 75%, characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.19-7.40 (m, 5H), 7.05-7.10 (m, 2H), 6.57-6.73 (m, 3H), 4.75 (d, J=4.3Hz, syn, 1H), 4.52 (anti, J=7.4Hz, 1H), 2.63-2.73 (m, 1H), 2.24-2.38 (m, 1H), 2.07-2.15 (m, 1H), 1.66-1.94 (m, 4H); 13c NMR (101MHz, CDCl 3) δ ppm:220.8,219.6,147.8,147.0,141.9,141.1,129.3,129.2,128.9,128.8,127.7,127.6,127.4,118.1,117.7,114.4,113.9,59.3,57.9,54.3,53.6,40.0,39.5,26.9,26.1,20.9,20.7.
Embodiment 7
To prepare following formula: compound 2-[(phenyl) (anilino) methyl]-pimelinketone is as example, raw materials used and preparation method thereof as follows:
In embodiment 1, methyl phenyl ketone used is replaced with equimolar pimelinketone, and other steps are identical with embodiment 1, is prepared into white solid 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 78%, characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.18-7.38 (m, 5H), 7.03-7.09 (m, 2H), 6.59-6.66 (m, 1H), 6.51-6.56 (m, 2H), 4.80 (anti, d, J=4.5Hz, 1H), 4.62 (d, J=7.0Hz, syn, 1H), 4.59 (brs, 1H), 2.73-2.81 (m, 1H), 2.25-2.44 (m, 2H), 1.52-2.08 (m, 6H); 13cNMR (101MHz, CDCl 3) δ ppm:213.2,211.6,147.7,147.2,141.74,141.71,129.3,129.2,128.7,128.6,127.7,127.5,127.4,127.2,117.9,114.3,114.0,58.4,57.6,57.5,56.8,42.6,42.0,31.5,28.9,28.1,27.3,25.1,23.9.
Embodiment 8
To prepare following formula: compound 1-phenyl-3-(2-furans)-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar furtural, and other steps are identical with embodiment 1, is prepared into white solid 1-phenyl-3-(2-furans)-3-phenylamino-1-acetone, and its productive rate is 76%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.92 (d, J=7.6Hz, 2H), 7.56 (t, J=7.3Hz, 1H), 7.44 (t, J=7.6Hz, 2H), 7.30 (s, 1H), 7.16 (t, J=7.8Hz, 2H), 6.70-6.76 (m, 3H), 6.20-6.27 (m, 2H), 5.22 (t, J=6.1Hz, 1H), 3.59 (d, J=6.1Hz, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:198.1,155.0,146.6,141.9,137.0,133.6,129.5,128.9,128.4,118.7,114.3,110.6,106.8,49.0,42.5.
Embodiment 9
To prepare following formula: compound 1-phenyl-3-(4-trifluoromethyl)-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar p-trifluoromethyl benzaldehyde, and other steps are identical with embodiment 1, is prepared into white solid 1-phenyl-3-(4-trifluoromethyl)-3-phenylamino-1-acetone, its productive rate is 85%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.89 (d, J=7.4Hz, 2H), 7.55-7.59 (m, 5H), 7.44 (t, J=7.7Hz, 2H), 7.11 (t, J=7.9Hz, 2H), 6.71 (t, J=7.3Hz, 1H), 6.56 (d, J=7.8Hz, 2H), 5.06 (t, J=6.3Hz, 1H), 3.52 (d, J=2.5Hz, 1H), 3.50 (d, J=3.7Hz, 1H); 13c NMR (101MHz, CDCl 3) δ ppm:197.9,147.3,146.7,136.7,133.9,129.8,129.5,129.0,128.6,128.4,127.1,126.0,124.3,118.5,114.2,54.6,46.2.
Embodiment 10
To prepare following formula: compound 1-(4-fluorophenyl)-3-phenyl-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, methyl phenyl ketone used is replaced fluoro acetophenone with equimolar, and other steps are identical with embodiment 1, are prepared into white solid 1-(4-fluorophenyl)-3-phenyl-3-phenylamino-1-acetone, and its productive rate is 45%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.88-7.95 (m, 2H), 7.44 (d, J=7.0Hz, 2H), 7.23-7.35 (m, 3H), 7.05-7.19 (m, 4H), 6.59-6.74 (m, 3H), 5.00 (t, J=6.4Hz, 1H), 3.49 (d, J=6.4Hz, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:196.52,168.31,163.31,146.84,142.73,133.18,130.87,130.71,129.09,128.67,127.40,126.33,117.91,115.94,115.53,113.89,54.90,46.01.
Embodiment 11
To prepare following formula: compound 1,3-phenylbenzene-3-(2-methoxyl group-4-oil of mirbane amino)-1-acetone is example, raw materials used and preparation method thereof as follows:
In embodiment 1, aniline used is replaced with equimolar 2-methoxyl group-4-N-methyl-p-nitroaniline, and other steps are identical with embodiment 1, be prepared into yellow solid 1,3-phenylbenzene-3-(2-methoxyl group-4-oil of mirbane amino)-1-acetone, its productive rate is 81%, characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.90-7.92 (m, 2H), 7.74 (dd, J=8.9,2.4Hz, 1H), 7.61 (d, J=2.3Hz, 1H), (7.58 t, J=7.5Hz, 1H), (7.46 t, J=7.7Hz, 2H), 7.32-7.40 (m, 4H), 7.25-7.28 (m, 1H), 6.37 (d, J=9.0Hz, 1H), 5.17 (t, J=6.3Hz, 1H), 3.95 (s, 3H), (3.57 d, J=3.3Hz, 1H), (3.55 d, J=2.0Hz, 1H); 13c NMR (101MHz, CDCl 3) δ ppm:197.5,145.7,143.1,141.6,137.8,136.7,133.9,129.3,129.0,128.4,128.1,126.4,119.7,108.5,104.9,56.2,53.9,46.2.
Embodiment 12
To prepare following formula: compound 1-phenyl-3-(4-p-methoxy-phenyl)-3-(4-methylbenzene amino)-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar aubepine, aniline is replaced with equimolar para-totuidine, other steps are identical with embodiment 1, be prepared into white solid 1-phenyl-3-(4-p-methoxy-phenyl)-3-(4-methylbenzene amino)-1-acetone, its productive rate is 90%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.90 (d, J=7.4Hz, 2H), 7.53 (d, J=6.8Hz, 1H), 7.43 (t, J=6.9Hz, 2H), 7.34 (d, J=8.3Hz, 2H), 6.87 (dd, J=21.7,8.1Hz, 4H), 6.48 (d, J=8.1Hz, 2H), 4.92 (d, J=6.0Hz, 1H), 4.35 (s, 1H), 3.76 (s, 3H), 3.42 (dd, J=17.8,6.3Hz, 1H), 2.17 (s, 3H); 13c NMR (101MHz, CDCl 3) δ ppm:198.48,158.77,144.76,136.84,135.15,133.31,129.60,128.66,128.19,127.48,126.95,114.17,114.04,55.24,54.52,46.39,20.35.
Embodiment 13
To prepare following formula: compound 1-(4-nitrophenyl)-3-phenyl-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, methyl phenyl ketone used is replaced with equimolar p-nitroacetophenone, the Whitfield's ointment of 0.1mmol is replaced with the thiosalicylic acid of 0.15mmol, reaction times extends to 12 hours, other steps are identical with embodiment 1, obtain white solid 1-(4-nitrophenyl)-3-phenyl-3-phenylamino-1-acetone, its productive rate is 77%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:8.26 (d, J=8.6Hz, 2H), 8.00 (d, J=8.6Hz, 2H), 7.45 (t, J=8.7Hz, 2H), 7.30-7.22 (3H), 7.11 (t, J=7.7Hz, 2H), 6.78 (t, J=7.2Hz, 1H), 6.59 (t, J=7.6Hz, 2H), 5.04 (t, J=6.3Hz, 1H), 3.55 (d, J=5.7Hz, 1H); 13c NMR (101MHz, CDCl 3) δ ppm:196.83,150.42,146.45,142.03,141.12,129.24,129.16,128.96,127.73,126.41,123.88,118.49,114.13,54.90,46.47.
Embodiment 14
To prepare following formula: compound 1-(3-p-methoxy-phenyl)-3-phenyl-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, methyl phenyl ketone used is replaced with equimolar meta-methoxy methyl phenyl ketone, the Whitfield's ointment of 0.1mmol is replaced with 2-hydroxyl-1-naphthoic acid of 0.2mmol, room temperature reaction 5 hours, other steps are identical with embodiment 1, obtain white solid 1-(3-p-methoxy-phenyl)-3-phenyl-3-phenylamino-1-acetone, its productive rate is 98%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.36 (m, 4H), 7.23 (td, J=7.9,5.9Hz, 3H), 7.14 (dd, J=5.4,1.8Hz, 1H), 6.99 (m, 3H), 6.56 (t, J=7.3Hz, 1H), 6.47 (m, 2H), 4.91 (dd, J=7.5,5.3Hz, 1H), 3.72 (s, 3H), 3.35 (qd, J=16.1,6.4Hz, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:197.04,158.87,145.97,141.95,137.07,128.61,128.07,127.78,126.31,125.34,119.80,118.97,116.75,112.79,111.33,54.39,53.81,45.38.
Embodiment 15
To prepare following formula: compound 1-(2-p-methoxy-phenyl)-3-phenyl-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, the Whitfield's ointment of 0.1mmol is replaced with the 5-chloro-salicylic acid of 0.2mmol, room temperature reaction 3 hours, other steps are identical with embodiment 1, obtain white solid 1-(2-p-methoxy-phenyl)-3-phenyl-3-phenylamino-1-acetone, its productive rate is 90%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.63 (dd, J=7.9,2.0Hz, 1H), 7.43-7.52 (m, 3H), 7.19-7.35 (m, 3H), 7.06-7.13 (m, 2H), 6.94-7.01 (m, 2H), 6.61-6.75 (m, 3H), 4.93-5.00 (m, 1H), 3.91 (s, 3H), 3.57-3.66 (m, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:200.50,158.42,147.14,143.33,133.67,130.51,129.02,128.56,128.29,126.98,126.43,120.90,117.62,113.78,111.58,55.48,55.22,51.29.
Embodiment 16
To prepare following formula: compound 1,3-phenylbenzene-3-(3-methylbenzene amino)-1-acetone is example, raw materials used and preparation method thereof as follows:
In embodiment 1,2.2mmol aniline replace with the p-Nitroaniline of 2.0mmol, 4.0mmol methyl phenyl ketone replace with the p-methoxy-acetophenone of 2.4mmol, Whitfield's ointment is replaced with equimolar 5-methoxyl group Whitfield's ointment, other steps are identical with embodiment 1, obtain white solid 1,3-phenylbenzene-3-(3-methylbenzene amino)-1-acetone, its productive rate is 93%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:7.90 (m, 2H), 7.55 (m, 1H), 7.44 (dt, J=7.4,3.8Hz, 4H), 7.32 (dd, J=10.3,4.7Hz, 2H), 7.24 (m, 1H), (6.96 t, J=7.8Hz, 1H), (6.48 d, J=7.5Hz, 1H), 6.41 (s, 1H), 6.34 (m, 1H), 5.00 (dd, J=7.4,5.5Hz, 1H), 3.45 (ddd, J=23.6,16.1,6.4Hz, 2H), 2.20 (s, 3H); 13c NMR (101MHz, CDCl 3) δ ppm:197.25,146.01,142.08,137.80,135.74,132.33,127.96,127.76,127.64,127.17,126.27,125.34,117.74,113.69,109.78,53.74,45.24,20.53.
Embodiment 17
To prepare following formula: compound 1-(4-chloro-phenyl-)-3-(4-nitrophenyl)-3-phenylamino-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar paranitrobenzaldehyde, methyl phenyl ketone is replaced with equimolar parachloroacetophenone, the Whitfield's ointment of 0.1mmol is replaced with the 5-aminosalicylic acid of 0.15mmol, room temperature reaction time lengthening to 5 hour, other steps are identical with embodiment 1, obtain white solid 1-(4-chloro-phenyl-)-3-(4-nitrophenyl)-3-phenylamino-1-acetone, its productive rate is 87%, and characterization data is: 1h NMR (400MHz, CDCl 3) δ ppm:8.18 (d, J=8.7Hz, 2H), 7.80-7.84 (m, 2H), 7.61 (d, J=8.7Hz, 2H), 7.41-7.45 (m, 2H), 7.06 (d, J=8.7Hz, 2H), 6.48 (d, J=8.7Hz, 2H), 5.05 (t, J=6.2Hz, 1H), 3.51 (m, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:195.8,149.7,147.4,144.5,140.4,134.6,129.5,129.2,127.5,124.1,123.7,115.3,54.5,45.3.
Embodiment 18
To prepare following formula: compound 1-(4-p-methoxy-phenyl)-3-phenyl-3-(4-oil of mirbane amino)-1-acetone as example, raw materials used and preparation method thereof as follows:
In embodiment 1, the aniline of 2.2mmol is replaced with 2.0mmol p-Nitroaniline, 4.0mmol methyl phenyl ketone replace with the p-methoxy-acetophenone of 3.0mmol, the Whitfield's ointment of 0.1mmol is replaced with the 5-NITROSALICYLIC ACID of 0.2mmol, room temperature reaction time lengthening to 5 hour, other steps are identical with embodiment 1, obtain white solid 1-(4-p-methoxy-phenyl)-3-phenyl-3-(4-oil of mirbane amino)-1-acetone, its productive rate is 37%, and characterization data is: 1hNMR (400MHz, CDCl 3) δ ppm:8.07 (d, J=9.0Hz, 1H), 7.99 (d, J=9.1Hz, 2H), 7.86 (d, J=8.9Hz, 2H), 7.44-7.30 (m, 4H), 7.27 (d, J=7.0Hz, 2H), 6.91 (d, J=8.8Hz, 2H), 6.62 (d, J=9.0Hz, 1H), 6.50 (d, J=9.1Hz, 2H), 5.10-5.00 (m, 1H), 3.86 (s, 3H), 3.51-3.39 (m, 2H); 13c NMR (101MHz, CDCl 3) δ ppm:196.34,164.04,152.21,141.23,130.56,129.45,129.06,127.82,126.29,126.10,113.93,113.33,112.16,55.49,54.57,45.04.

Claims (5)

1. the preparation method of a beta-amino carbonyl compound, it is characterized in that: aldehyde is mixed for 1:1～4:1～2 in molar ratio with ketone, amine, add cyclopentadienyl titanium dichloride, part, the add-on of cyclopentadienyl titanium dichloride is 1%～5% of aldehyde molar weight, the add-on of part is 1～4 times of cyclopentadienyl titanium dichloride molar weight, room temperature reaction 1～12 hour, obtains beta-amino carbonyl compound;
Described part is any one in Whitfield's ointment, 5-chloro-salicylic acid, 4-chloro-salicylic acid, 3-chloro-salicylic acid, 5-methoxyl group Whitfield's ointment, 5-aminosalicylic acid, 5-NITROSALICYLIC ACID, thiosalicylic acid, 2-hydroxyl-1-naphthoic acid;
Described ketone is or or in formula, X, Y, Z independently represent H, CH separately 3, CH 3o, F, CF 3, Cl, Br, NO 2in any one, the value of n is 1 or 2, R 1, R 2independently represent separately C 1～C 3any one in alkyl;
Described aldehyde is or in formula, A, B, C independently represent H, CH separately 3, CH 3o, F, CF 3, Cl, Br, NO 2in any one, M represents N, O or S;
Described amine is or naphthylamines, in formula, D, E, F independently represent H, CH separately 3, CH 3o, F, Cl, Br, NO 2in any one.
2. according to the preparation method of the beta-amino carbonyl compound described in claim 1, it is characterized in that: the mol ratio of described aldehyde and ketone, amine is 1:1～2:1～1.5.
3. the preparation method of beta-amino carbonyl compound according to claim 2, is characterized in that: the mol ratio of described aldehyde and ketone, amine is 1:2:1.1.
4. the preparation method of beta-amino carbonyl compound according to claim 3, is characterized in that: the add-on of described cyclopentadienyl titanium dichloride is 5% of aldehyde molar weight, and the add-on of part is 1～2 times of cyclopentadienyl titanium dichloride molar weight.
5. according to the preparation method of the beta-amino carbonyl compound described in claim 4, it is characterized in that: described reaction conditions is room temperature reaction 1～5 hour.
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