CN102816042A - Method for synthesizing beta-amidocarbonyl compounds - Google Patents

Method for synthesizing beta-amidocarbonyl compounds Download PDF

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CN102816042A
CN102816042A CN201210320524XA CN201210320524A CN102816042A CN 102816042 A CN102816042 A CN 102816042A CN 201210320524X A CN201210320524X A CN 201210320524XA CN 201210320524 A CN201210320524 A CN 201210320524A CN 102816042 A CN102816042 A CN 102816042A
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reaction
compound
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amidocarbonylation
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李加荣
杨德利
史大昕
张奇
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Beijing Institute of Technology BIT
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Abstract

The invention provides a method for synthesizing beta-amidocarbonyl compounds. The reaction general formula is disclosed in the specification, wherein R1, R2, R3 and R4 are respectively a substituent group; R1 can be H, F, Cl, Br, NO2, CH3, OCH3 or any other single group, and can also be 2,4-2Cl, 2-Cl-5-F or any other double-substituent group, and the quantity and position of the substituent groups are not defined; R2 can be H, and can also be NO2, CH3, OCH2CH3, aromatic group or any other substituent group; and R3 can be H, and can also be CH3, COOC2H5 or any other substituent group, or hexahydric cycloalkyl group formed by R2, R3 and carbon atom connected with R2 and R3. The reaction is carried out at room temperature in the presence of acetyl chloride by using titanium tetrachloride as a catalyst; and the purification adopts recrystallization, column chromatography or any other separation method. The invention has the advantages of accessible raw materials, simple technique, mild reaction conditions and cheap and nontoxic catalyst; and the applicable substrate range for reaction is wide, and thus, different substrates can be utilized to synthesize a series of beta-amidocarbonyl compounds.

Description

The method of a kind of synthetic β-amidocarbonylation compound
(1) technical field
The present invention relates to a kind of via aromatic aldehyde, the compound method of carbonyl compound and nitrile compounds prepared in reaction β-amidocarbonylation compound (β-acetamide carbonyl compounds).
(2) background technology
β-acid amides ketone is because of extensively having caused chemist and physicians' concern in its structure extensively the is present in a lot of natural drug structure with physiologically active and pharmacologically active in recent years.β-amidocarbonylation compound can be very easy change into 1,3-diamino alcohol, perhaps compound such as beta-amino acids.1, compounds such as 3-diamino alcohol and beta-amino acids all are the more synthetic antibiotic core textures of nucleosides peptide types, for example nikemycin and new polyoxins.The precursor of beta-aromatic isothreonine can be combined into corresponding dipeptides isomer with the amino acid of a part, and it can be that precursor synthesizes with β-amidocarbonylation compound also.Mechanism repressible protein enzyme has also caused chemist and physicians' concern in recent years; For example how research improves and has the peptide class formation and human immunodeficiency virus type1 (HIV 1) disease is had inhibiting repressible protein enzyme; Make it therapeutic action arranged, become a new direction of research treatment AIDS inhibition type proteolytic enzyme acquired immunodeficiency syndrome (AIDS) disease.β-amidocarbonylation compound also has very big use for synthesis mechanism repressible protein enzyme.
Nikkomycin?B
β-amidocarbonylation compound is synthetic with the Dakin-West reaction by Dakin and West in nineteen twenty-eight the earliest, and this reaction is that a-amino acid and acetic anhydride get through azlactone midbody condensation in the presence of alkali.(Dakin, H.D.; West, R.J. Biol.Chem.1928,78,45.) the Iqbal experimental group also synthesized this compounds in 1994 with the one kettle way condensation.（Bhatia.,B.;Reddy，M.M.;Iqbal,J.J.?Chem.Soc.Chem.Comm.1994,6,713.）
This compounds synthetic had bigger development in recent years, and main compound method is following:
(1) Paramasivan of India experiment group is with phenyl aldehyde or substituted phenyl aldehyde, and methyl phenyl ketone or other carbonyl compound are reaction substrate, and nitrile compounds is reaction substrate and solvent, with Ce (SO 4) 2For catalyzer has synthesized this compounds under the condition of reflux, but the employed catalyzer price of this method is comparatively expensive, and the temperature of reaction is higher.(Nagarajan,P.S.;Paramasivan,T.P.Arkivoc,2009,x,265.)
Figure BDA00002085282700021
(2) 2011 years, catalyzer was made with organometallics Metalopthalocyanines by the Bahulayan group of India, in the presence of acyl chlorides, had synthesized this compounds, but the catalyst toxicity that this method is used is bigger.（Shinu,V.S.;Pramitha,P.;Bahulayan,D.Tetrahedron?Lett.2011,52,3110.）
Figure BDA00002085282700022
(3) human Zn (HSO such as Momeni 4) 2And Co (HSO 4) 2Make catalyzer and under the condition of room temperature, close and weighed up this compounds, but this method only relates to CH 3CN makes reactant and solvent, and the nitrile compounds that does not relate to other is made solvent, and the reaction substrate structure is limited bigger.（Momeni,A.R.;Sadeghi,M.;Hadizadeh,M.Turk.J.Chem.2009,33,751.）
Figure BDA00002085282700023
People such as (4) 2007, Khan have reported and have used FeCl 3This type of reaction of catalysis has obtained reasonable result, but having of relating to of these class methods-substituent phenyl aldehyde of NO2 can not be expected product accordingly, and what obtain is the product of brain Tomi Ungerer reaction.（Khan,A.T.;Parvin,T.;Choudhury，L.H.Tetrahedron,2007,63,5593。）
Figure BDA00002085282700024
(5) 2011 years, Gholivand made catalyzer with BPO, had also synthesized this compounds.
In sum, in the compound method of known β-amidocarbonylation compound, or temperature is higher or catalyzer costs an arm and a leg, be difficult to prepare or range of substrate that method is suitable for narrower.These deficiencies have been brought inconvenience to the synthetic especially suitability for industrialized production of this compounds.
(3) summary of the invention
For overcoming above-mentioned existing in prior technology problem, the invention provides the novel method of a kind of β-amidocarbonylation compound, raw material of the present invention is easy to get, and technology is simple, and catalyzer cheaply is easy to get, and reaction conditions is gentle; The reactive applications scope is wide, and available multiple different substrates synthesize multiple β-amidocarbonylation compound.
Technical scheme of the present invention is: under the room temperature, aromatic aldehyde, carbonyl compound and nitrile compounds reaction in the presence of Acetyl Chloride 98Min., are used TiCl 4Make catalyzer and become a series of corresponding β-amidocarbonylation compound, reaction expression is:
Figure BDA00002085282700031
R wherein 1Be the substituting group on the aromatic aldehyde, can be H, F, Cl, Br, NO 2, alkyl, perhaps alkoxyl group also can be 2, the 4-dichloro, 2-Cl-6-F etc. are disubstituted; This substituent quantity and position are not limit.R 2, R 3Can be H, alkyl, aryl or alkoxyl group, perhaps R 1, R 2Form 6 yuan naphthenic base with the carbon atom that is connected.R 4Can be methyl, styroyl or phenmethyl etc.Employed catalyzer is TiCl 4Aromatic aldehyde, methyl phenyl ketone, nitrile compounds, the addition sequence of Acetyl Chloride 98Min. and catalyzer can exchange arbitrarily.
The preparation process is:
(1) reinforced
In reaction vessel, adding mol ratio is the aromatic aldehyde of 1:1 and the mixture of carbonyl compound, and adding consumption is the acyl chlorides of 1 ~ 3 times of aromatic aldehyde, and the adding consumption is that the nitrile solvents of 1 ~ 500 times of aromatic aldehyde is as reaction medium.Aromatic aldehyde does, but is not merely phenyl aldehyde, substituted phenyl aldehyde, and acyl chlorides does, but is not merely Acetyl Chloride 98Min.; Carbonyl compound does, but is not limited to a kind of in the reactants such as methyl phenyl ketone, substituted methyl phenyl ketone, Propiophenone, methyl aceto acetate, methyl ethyl diketone, ethyl malonate, pimelinketone; Nitrile solvents does, but is not limited to a kind of in acetonitrile, benzyl cyanide, the cyanobenzene equal solvent.Add-on is a phenyl aldehyde 1-1.2 catalyzer doubly then.What this method was more excellent is, but is not limited to: the addition sequence of aromatic aldehyde, carbonyl compound, nitrile compounds, acyl chlorides and catalyzer can exchange arbitrarily.
(2) reaction
In the whipping appts of routine, make reactant under the temperature of reaction of room temperature stirring reaction 1-3 hour, with thin-layer chromatography (TLC) monitoring reaction process.The developping agent of thin-layer chromatography is ETHYLE ACETATE, sherwood oil, hexanaphthene, normal hexane, methyl alcohol, chloroform, acetone, THF, perhaps wherein both or three's mixed solution.
(3) reaction solution aftertreatment
Reaction solution after reaction finished is scattered in the reaction solution 1-20 times of dispersion medium below the volume, and dispersion medium does, but is not limited to water, ethanol, methyl alcohol, sherwood oil, perhaps wherein in both mixed solutions.Use ETHYLE ACETATE, or a kind of organic solvent extraction in the methylene dichloride, chloroform, ether 2-5 time, organic phase merged.Filter cake is used methyl alcohol, the perhaps a kind of organic solvent extracting in ethanol, acetone, THF, ETHYLE ACETATE, the acetonitrile, the organic phase after the extracting is mixed with the organic phase that above extraction obtains.Then with mixed liquid with but after being not limited to a kind of drying in SODIUM SULPHATE ANHYDROUS 99PCT, anhydrous calciumsulphate, anhydrous magnesium sulfate, the Calcium Chloride Powder Anhydrous siccative, rotation steams solvent, obtains solid or oily mixture.
(4) product purification
Crude product for step 3 carries out recrystallization or column chromatography purification, and obtaining productive rate is the pure target compound of 1-99%.Recrystallization solvent can be, but be not limited to water, methyl alcohol, ethanol, Virahol, acetone, acetonitrile, THF, dioxane, ETHYLE ACETATE, methylene dichloride, benzene, toluene.Adopt silicagel column or alumina column during column chromatography, developping agent does, but is not limited to ethyl acetate/petroleum ether (1:1 ~ 1:3, volume ratio), methyl alcohol/chloroform (1:5 ~ 1:50, volume ratio), methylene dichloride, acetone.
The invention has the advantages that: raw material is easy to get, and technology is simple, and catalyzer cheaply is easy to get, and the reaction times is short, and reaction conditions is gentle.Have wide range of applications the various β of available multiple different substrate one-step synthesis-amidocarbonylation compound.
(4) embodiment:
Embodiment 1
In the round-bottomed flask of 25ml, add 5ml exsiccant acetonitrile, stir adding 2mmol phenyl aldehyde down, add the 2mmol methyl phenyl ketone, add 1.5ml Acetyl Chloride 98Min. and 2mmol TiCl again 4, with mixed solution stirring reaction 3h, after reaction is accomplished; Reaction solution is poured in the mixture of ice and water of 25ml, separated out oil and solid mixture, use column chromatography product; ETHYLE ACETATE: (1:1 v:v), obtains N-(3-oxo-1 to sherwood oil; The 3-diphenyl propyl) ethanamide (1), yield 90%, Mp103-104 ℃.Phenyl aldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
The spectral data of product (1) is: 1H NMR (400MHz, CDCl 3) δ: 2.00 (3H, s, COCH 3), 3.42 (J 6.0 for 1H, dd, 16.8Hz, CH 2), 3.71 (J 4.8 for 1H, dd, 17.2Hz, CH 2), 5.49-5.54 (1H, m, CH), 6.60 (1H, d, J 8.4Hz, NH), 7.27-7.30 (5H, m, Ph), 7.44 (2H, t, J 8.0Hz, Ph), 7.56 (1H, t, J 7.2Hz, Ph), 7.88 (2H, d, J8.4Hz, Ph); IR (film) ν Max3275,3082,2926,1693,1646,1552,1443,1355,1195,990,752cm -1; MS (ESI): m/z (relative intensity) 290.0 ([M+Na] +, 100).
Embodiment 2
Replace phenyl aldehyde with 4-chloro-benzaldehyde, other is with embodiment 1.Get target compound (2), yield 96%, Mp143-145 ℃.4-chloro-benzaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
The spectral data of product (2) is: 1H NMR (400MHz, CDCl 3) δ: 2.04 (3H, s, COCH 3), 3.42 (J 6.4 for 1H, dd, 17.2Hz, CH 2), 3.74 (J 4.8 for 1H, dd, 17.2Hz, CH 2), 5.52 – 5.59 (1H, m, CH), 6.77 (1H, d, J 8.0Hz, NH), 7.26 – 7.27 (4H, m, Ph), 7.46 (2H, t, J 7.6Hz, Ph), 7.59 (1H, t, J 7.2Hz, Ph), 7.85 (2H, d, J7.6Hz, Ph); IR (film) ν Max3289,3084,2926,1686,1651,1551,1372,1199,987,757cm -1; MS (ESI): m/z (relative intensity) 224.1 ([M+Na] +, 100).
Embodiment 3
Replace phenyl aldehyde with p-Fluorobenzenecarboxaldehyde, other gets target compound (3), yield 93%, Mp108-111 ℃ with embodiment 1.P-Fluorobenzenecarboxaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700052
The spectral data of product (3) is: 1H NMR (400MHz, CDCl 3) δ: 2.04 (3H, s, COCH 3), 3.43 (J 6.0 for 1H, dd, 16.8Hz, CH 2), 3.75 (J 5.2 for 1H, dd, 17.2Hz, CH 2), 5.52 – 5.58 (1H, m, CH), 6.77 (1H, d, J 5.6Hz, NH), 6.97-7.01 (2H, m, Ph), 7.30-7.33 (2H, m, Ph), 7.47 (2H, t, J 7.6Hz, Ph), 7.59 (1H, t, J 7.2Hz, Ph), 7.91 (2H, d, J 8.0Hz, Ph); IR (film) ν Max3286,3082,2956,2844,1687,1648,1550,1508,1371,1226,990,751cm -1; MS (ESI): m/z (relative intensity) 308.0 ([M+Na] +, 100).
Embodiment 4
Replace phenyl aldehyde with the 3-nitrobenzaldehyde, other gets target compound (4), yield 92%, Mp139-142 ℃ with embodiment 1.P-Fluorobenzenecarboxaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700053
The spectral data of product (4) is: 1H NMR (400MHz, CDCl 3) δ: 2.07 (3H, s, COCH 3), 3.51 (J 5.6 for 1H, dd, 17.6Hz, CH 2), 3.61 (J 5.6 for 1H, dd, 17.6Hz, CH 2), 5.65-5.67 (1H, m, CH), 6.99 (1H, d, J 8.0Hz, NH), 7.44-7.70 (5H, m, Ph), 7.88-7.90 (2H, m, Ph), 8.22 (1H, t, J 1.6Hz, Ph), 8.29 (2H, d, J 5.6Hz, Ph); IR (film) ν Max3297,3066,2962,2824,1690,1644,1525,1347,1226,990,751,683cm -1; MS (ESI): m/z (relative intensity) 335.0 ([M+Na] +, 100).
Embodiment 5
Replace phenyl aldehyde with 2-chloro-6-fluorobenzaldehyde, other gets target compound (5), yield 85%, Mp92-93 ℃ with embodiment 1.2-chloro-6-fluorobenzaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
The spectral data of product (5) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.78 (3H, s, COCH 3), 3.40 (1H, dd, J5.2,17.2Hz, CH 2), 3.83 (J 8.8 for 1H, dd, 17.2Hz, CH 2), 5.85 – 5.90 (1H, m, CH), 7.17 (1H, d, J8.0Hz, NH), 7.25-7.34 (2H, m, Ph), 7.53 – 7.65 (3H, m, Ph), 7.96 (2H, t, J 8Hz, Ph), 8.36 (1H, d, J6.8Hz, Ph); IR (film) ν Max3262,3062,2929,1685,1650,1555,1450,1359,1304,1224,990,754,687cm -1; MS (ESI): m/z (relative intensity) 342.1 ([M+Na] +, 100).
Embodiment 6
Replace phenyl aldehyde with 2,4 dichloro benzene formaldehyde, other gets target compound (6), yield 90%, Mp185-187 ℃ with embodiment 1.2,4 dichloro benzene formaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700062
The spectral data of product (6) is: 1H NMR (400MHz, CDCl 3) δ: 2.04 (3H, s, COCH 3), 3.43 (J 5.2 for 1H, dd, 16.8Hz, CH 2), 3.75 (1H, dd, J5.6,16.8Hz, CH 2), 5.74 – 5.77 (1H, m, CH), 7.19 (1H, d, J2.0Hz, NH), 7.43-7.46 (5H, m, Ph), 7.57 (1H, t, J 7.2Hz, Ph), 7.87-7.89 (2H, m, Ph); IR (film) ν Max3283,3082,2970,1689,1652,1549,1471,1353,1298,1232,1000,755,687cm -1; MS (ESI): m/z (relative intensity) 358.0 ([M+Na] +, 100).
Embodiment 7
Replace phenyl aldehyde with p-tolyl aldehyde, other gets target compound (7), yield 89%, Mp87-90 ℃ with embodiment 1.P-tolyl aldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700071
The spectral data of product (7) is: 1H NMR (400MHz, CDCl 3) δ: 2.02 (3H, s, COCH 3), 2.30 (3H, s, CH 3), 3.44 (J 6.4 for 1H, dd, 16.8Hz, CH 2), 3.76 (J 4.8 for 1H, dd, 16.8Hz, CH 2), 5.51 – 5.55 (1H, m, CH), 6.62 (1H, d, J8.0Hz, NH), 7.11-7.23 (4H, m, Ph), 7.45 (2H, t, J7.6Hz, Ph), 7.57 (1H, t, J5.6Hz, Ph), 7.92 (2H, t, J 7.2Hz, Ph) .IR (film) ν Max3288,3084,2950,1686,1653,1553,1447,1365,1296,987,756,688cm -1; MS (ESI): m/z (relative intensity) 304.1 ([M+Na] +, 100).
Embodiment 8
Replace phenyl aldehyde with the 3-methoxybenzaldehyde, other is with embodiment 1.Get target compound (8), yield 91%, Mp125-127 ℃.3-methoxybenzaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
The POP data of product (8) are: 1H NMR (400MHz, CDCl 3) δ: 2.03 (3H, s, COCH 3), 3.43 (J 6.0 for 1H, dd, 16.8Hz, CH 2), 3.73 (J 6.0 for 1H, dd, 17.2Hz, CH 2), 3.77 (3H, s, OCH 3), 5.53 – 5.55 (1H, m, CH), 6.66 (1H, d, J 8.0Hz, NH), 6.76-6.92 (4H, m, Ph), 7.45 (2H, t, J 7.6Hz, Ph), 7.57 (1H, t, J 7.2Hz, Ph), 7.90 (2H, t, J 5.6Hz, Ph) .IR (film) ν Max3258,3079,2950,1689,1642,1558,1450,1291,1149,1223,1049,990,751,703,693cm -1; MS (ESI): m/z (relative intensity) 320.2 ([M+Na] +, 100).
Embodiment 9
Replace phenyl aldehyde with the 4-methoxybenzaldehyde, other obtains target compound (9) with embodiment 1, yield 88%, Mp 113-115 ℃.4-methoxybenzaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700073
The spectral data of product (9) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.77 (3H, s, COCH 3), 3.37 (J 6.0 for 1H, dd, 16.8Hz, CH 2), 3.50 (J 8.0 for 1H, dd, 16.8Hz, CH 2), 3.72 (3H, s, OCH 3), 5.29-5.34 (1H, m, CH), 6.86 (2H, d, J 8.4Hz, CH), 7.26 (2H, d; J 8.4, Ph), 7.52 (2H, t, J 7.6Hz, Ph), 7.64 (1H, t, J7.6Hz; Ph), 7.94 (2H, d, J 8.4Hz, Ph), 8.25 (1H, d, J 8.0Hz, NH) .IR (film) ν Max3304,2833,1649,1625,1240,1031,987,756cm -1; MS (ESI): m/z (relative intensity) 320.2 ([M+Na] +, 100).
Embodiment 10
Replace phenyl aldehyde with the 4-methoxybenzaldehyde, the 3-nitro-acetophenone replaces methyl phenyl ketone, and other obtains target compound (10) with embodiment 1, yield 87%, Mp 186-189 ℃.4-methoxybenzaldehyde and 3-nitro-acetophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700081
The spectral data of product (10) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.77 (3H, s, COCH 3), 3.49 (J 6.0 for 1H, dd, 17.2Hz, CH 2), 3.61 (J 8.8 for 1H, dd, 16.8Hz, CH 2), 3.72 (3H, s, OCH 3), 5.28-5.34 (1H, m, CH), 6.87 (2H, d, J 8.4Hz, Ph), 7.28 (2H, d, J 8.4Hz; Ph), 7.83 (1H, t, J 7.6Hz, Ph), 8.27 (1H, d, J 8.0Hz, Ph), 8.38 (1H; D, J 7.2Hz, Ph), 8.47 (1H, d, J 7.2Hz, Ph), 8.62 (1H, s, NH) .IR (film) ν Max3315,3095,1693,1646,1348,1032,734cm -1; MS (ESI): m/z (relative intensity) 365.1 ([M+Na] +, 100).
Embodiment 11
Replace phenyl aldehyde with 4-chloro-benzaldehyde, the 4-nitro-acetophenone replaces methyl phenyl ketone, and other obtains target compound (11) with embodiment 1, yield 91%, Mp 144-146 ℃.4-chloro-benzaldehyde and 4-nitro-acetophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700082
The spectral data of product (11) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.79 (3H, s, COCH 3), 3.49 (J 5.2 for 1H, dd, 17.2Hz, CH 2), 3.62 (J 8.8 for 1H, dd, 17.6Hz, CH 2), 5.32-5.34 (1H, m, CH), 7.38, (4H, s, Ph), 8.18 (2H, d, J 8.8Hz, Ph), 8.33 (2H, d, J 8.8Hz, Ph), 8.36 (1H, s, NH); 13C NMR (100MHz, DMSO-d 6) δ: 22.6,44.9,48.2,123.8,128.6,129.5,127.4,141.0,141.9,150.0,168.5,186.3.IR (film) ν Max3277,1690,1668,1516,1343,1189,747,690cm -1; MS (ESI): m/z (relative intensity) 369.1 ([M+Na] +, 100).
Embodiment 12
Replace phenyl aldehyde with 2,4 dichloro benzene formaldehyde, the 4-nitro-acetophenone replaces methyl phenyl ketone, and other obtains target compound (12) with embodiment 1, yield 93%, Mp 198-200 ℃.2,4 dichloro benzene formaldehyde and 4-nitro-acetophenone, the reaction formula of acetonitrile is:
The spectral data of product (12) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.80 (3H, s, COCH 3), 3.40 (1H, dd, J4.0,17.6Hz, CH 2), 3.58 (1H, dd, J9.6,17.6Hz, CH 2), 5.61-5.65 (1H, m, CH), 7.44-7.51 (2H, m, Ph), 7.60 (1H, d, J2.0Hz, Ph), 8.20 (2H, d, J 7.2Hz, Ph), 8.34 (2H, d, J 8.8Hz, Ph), 8.42 (1H, d, J 8.0Hz, NH); 13C NMR (100MHz, DMSO-d 6) δ: 22.5,43.5,45.8,123.9,127.6,128.8,129.2,129.6,132.3,139.4,140.8,150.0,168.6,195.8.IR (film) ν Max3296,3077,1695,1654,1532,1228,1101,744,686cm -1; MS (ESI): m/z (relative intensity) 403.1 ([M+Na] +, 100).
Embodiment 13
Replace methyl phenyl ketone with the 4-methoxyacetophenone, other gets target compound (13), yield 90%, Mp127-128 ℃ with embodiment 1.Phenyl aldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
The spectral data of product (13) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.79 (3H, s, COCH 3), 3.20 (J 5.6 for 1H, dd, 16.4Hz, CH 2), 3.46 (J 8.4 for 1H, dd, 16.8Hz, CH 2), 5.32-5.38 (1H, m, CH), 7.03, (2H, d, J12.8Hz, Ph), 7.21 (1H, t, J6.8Hz, Ph), 7.28-7.34 (4H, m, Ph),, 7.93 (2H, d, J 8.8Hz, Ph), 8.29 (1H, d, J8.0Hz, NH); 13C NMR (100MHz, DMSO-d 6) δ: 22.6,40.1,44.2,55.5,113.9,126.6,126.8,128.2,129.5,130.3,143.1,163.1,168.2,195.4.IR (film) ν Max3296,3077,1695,1654,1532,1228,1101,744,686cm -1; MS (ESI): m/z (relative intensity) 320.2 ([M+Na] +, 100).
Embodiment 14
Replace phenyl aldehyde with the 3-nitrobenzaldehyde, the 3-nitro-acetophenone replaces methyl phenyl ketone, and other gets target compound (14), yield 86%, Mp 204-205 ℃ with embodiment 1.3-nitrobenzaldehyde and 3-nitro-acetophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700093
The spectral data of product (14) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.82 (3H, s, COCH 3), 3.62 (J 5.2 for 1H, dd, 18.0Hz, CH 2), 3.77 (J 8.4 for 1H, dd, 17.2Hz, CH 2), 5.45-5.50 (1H, m, CH), 7.64, (2H, t, J8.0Hz, Ph), 7.85 (1H, t; J6.4Hz, Ph), 8.11 (1H, d, J 8.4Hz, Ph), 8.25 (1H, d, J 1.6Hz, Ph); 8.39 (1H, d J 7.2Hz, Ph), 8.46-8.52 (2H, m, Ph), 8.66 (1H, d, J 8.0Hz, NH); 13C NMR (100MHz, DMSO-d 6) δ: 22.6,44.3,48.3,121.4,121.9,122.4,127.5,129.8,130.6,133.7,134.2,137.6,145.3,147.8,148.0,195.3.IR (film) ν Max3296,3077,1695,1654,1532,1228,1101,744,686cm -1; MS (ESI): m/z (relative intensity) 380.1 ([M+Na] +, 100).
Embodiment 15
Replace phenyl aldehyde with the 3-bromobenzaldehyde, the 4-methoxyacetophenone replaces methyl phenyl ketone, and other gets target compound (15), yield 82%, Mp 155-157 ℃ with embodiment 1.3-bromobenzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700101
The spectral data of product (15) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.80 (3H, s, COCH 3), 3.34 (J 6.0 for 1H, dd, 16.4Hz, CH 2), 3.49 (J 8.0 for 1H, dd, 16.4Hz, CH 2), 5.30-5.35 (2H, m, CH), 7.02, (1H, d, J7.6Hz, Ph), 7.28 (1H, t, J 6.8Hz, Ph), 7.35 (1H, d, J 7.2Hz Ph), 7.52 (1H, s, Ph), 7.94 (2H, d, J7.2Hz, Ph), 8.34 (1H, d, J 7.6Hz, NH); 13C NMR (100MHz, DMSO-d 6) δ: 22.6,43.9,48.6,55.5,113.9,125.9,129.4,129.6,130.4,146.1,163.2,168.4,195.1.IR (film) ν Max3296,3077,1695,1654,1532,1228,1101,744,686cm -1; MS (ESI): m/z (relative intensity) 398.1 ([M+Na] +, 100).
Embodiment 16
Replace phenyl aldehyde with the 4-methoxybenzaldehyde, the 4-methoxyacetophenone replaces methyl phenyl ketone, and other gets target compound (16), yield 87%, Mp 134-136 ℃ with embodiment 1.4-methoxybenzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
The spectral data of product (16) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.77 (3H, s, COCH 3), 3.29 (J 6.4 for 1H, dd, 16.4Hz, CH 2), 3.46 (J 7.6 for 1H, dd, 16.4Hz, CH 2), 5.27-5.33 (1H, m, CH), 6.85, (2H, d, J8.8Hz, Ph), 7.02, (2H, d, J 8.8Hz, Ph), 7.24, (2H, d, J 8.8Hz, Ph), 7.92, (2H, d, J 8.8Hz, Ph), 8.24 (1H, d, J 8.0Hz, NH) .IR (film) ν Max3296,3077,1695,1654,1532,1228,1101,744,686cm -1; MS (ESI): m/z (relative intensity) 350.2 ([M+Na] +, 100).
Embodiment 17
Replace phenyl aldehyde with the 3-bromobenzaldehyde, the 4-nitro-acetophenone replaces methyl phenyl ketone, and other gets target compound (17), yield 80%, Mp 155-157 ℃ with embodiment 1.3-bromobenzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
The spectral data of product (17) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.81 (3H, s, COCH 3), 3.52 (J 5.2 for 1H, dd, 18.4Hz, CH 2), 3.64 (J 8.8 for 1H, dd, 17.2Hz, CH 2), 5.31-5.36 (1H, m, CH), 7.30-7.46 (3H, m, Ph), 7.58, (1H, s, Ph), 8.21, (2H, d, J8.4Hz, Ph), 8.34, (2H, d, J8.8Hz, Ph), 8.24 (1H, d, J4.0Hz, NH) .IR (film) ν Max3296,3077,1695,1654,1532,1228,1101,744,686cm -1; MS (ESI): m/z (relative intensity) 415.0 ([M+Na] +, 100).
Embodiment 18
Replace acetonitrile with benzyl cyanide, other gets target compound (18), yield 81%, Mp 98-100 ℃ with embodiment 1.Phenyl aldehyde and methyl phenyl ketone, the reaction formula of benzyl cyanide is:
Figure BDA00002085282700112
The spectral data of product (18) is: 1H NMR (400MHz, DMSO-d 6) δ: 3.43 (1H, dd, J20.4,36.4Hz, CH 2), 3.58 (J 8.8 for 1H, dd, 17.2Hz, CH 2), 3.77 (2H, s, CH 2), 5.37-5.43 (1H, m, CH), 7.20-7.66 (3H, m, Ph), 7.59 (1H, d, J8.0Hz, NH), 13C NMR (100MHz, DMSO-d 6) δ: 42.3,44.6,49.1,126.2,126.5,126.8,128.0,128.1,128.2,128.7,128.9,129.5,133.2,136.3,136.6,142.8,169.2,197.1.IR (film) ν Max3277,3058,3027,1681,1645,1543,1449,1361,1218,1150,982,733,689cm -1; MS (ESI): m/z (relative intensity) 366.2 ([M+Na] +, 100).
Embodiment 19
Replace phenyl aldehyde with 4-chloro-benzaldehyde, Propiophenone replaces methyl phenyl ketone, and other gets target compound (19), yield 94%, Mp 181-183 ℃ with embodiment 1.The cis-trans isomerism ratio is found out cis by methyne H atom in the proton nmr spectra based on the ratio of coupling constant: the trans 15:85 of being.4-chloro-benzaldehyde and Propiophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700121
The spectral data of product (19) is: 1H NMR (400MHz, CDCl 3) δ: 1.19 (3H, d, J6.8Hz, CH 3), 1.97 (3H, s, COCH 3), 4.01 (1H, t, J 7.2Hz, CH), 5.39 (1H, t, J 8.0Hz, CH), 6.11 (1H; D, J 7.6Hz, NH), 7.25 (4H, d, J 5.2Hz, Ph), 7.45 (2H, t; J 7.6Hz, Ph), 7.54-7.58 (1H, m, Ph), 7.87 (2H, d, J 8Hz, Ph) .IR (film) ν Max3267,3064,2979,1682,1651,1554,1491,1372,1290,1089,988,959,781,691cm -1; MS (EI): m/z (relative intensity) 338.0 ([M+Na] +, 100).
Embodiment 20
Replace phenyl aldehyde with 3-methoxyl group formaldehyde, Propiophenone replaces methyl phenyl ketone, and other gets target compound (20), yield 87%, Mp 163-165 ℃ with embodiment 1.The cis-trans isomerism ratio is found out cis by methyne H atom in the proton nmr spectra based on the ratio of coupling constant: the trans 10:90 of being.3-methoxybenzaldehyde and Propiophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700122
The spectral data of product (20) is: 1H NMR (400MHz, CDCl 3) δ: 1.21 (3H, d, J 6.8Hz, CH 3), 1.98 (3H, s, COCH 3), 3.76 (3H, s, OCH 3), 4.04 (1H, t, J 7.2Hz, CH), 5.44 (1H, t, J 8.0Hz, CH); 6.03 (1H, d, J 7.6Hz, NH), 6.75-6.96 (4H, m, Ph), 7.45 (2H, t; J 7.6Hz, Ph), 7.56 (1H, t, J 7.6Hz, Ph), 7.89-7.91 (2H, m, Ph) .IR (film) ν Max3319,3058,2991,1676,1646,1536,1454,1373,1266,1051,970,781,706cm -1; MS (EI): m/z (relative intensity) 334.0 ([M+Na] +, 100).
Embodiment 21
Replace methyl phenyl ketone with Propiophenone, other gets target compound (21), yield 94%, Mp 166-168 ℃ with embodiment 1.The cis-trans isomerism ratio is found out cis by methyne H atom in the proton nmr spectra based on the ratio of coupling constant: the trans 20:80 of being.Phenyl aldehyde and Propiophenone, the reaction formula of acetonitrile is:
Figure BDA00002085282700123
The spectral data of product (21) is: 1H NMR (400MHz, CDCl 3) δ: 1.13 (3H, d, J 6.8Hz, CH 3), 1.85 (3H, s, COCH 3), 4.00-4.14 (1H, m, CH), 5.26 (1H, t, J 11.6Hz, CH), 7.12 (1H; T, J 6.8Hz, Ph), 7.22 (2H, t, J 8.0Hz, Ph), 7.29 (2H, d; J7.6Hz, Ph), 7.47 (2H, t, J 8.0Hz, Ph), 7.58 (1H, t, J6.8Hz; Ph), 7.80 (2H, t, J7.6Hz, Ph), 8.30 (1H, d, J9.2Hz, NH) .IR (film) ν Max3297,3061,2980,1683,1651,1544,1448,1370,1208,1140,970,707,615cm -1.MS (ESI): m/z (relative intensity) 304.2 ([M+Na] +, 100).
Embodiment 22
Replace phenyl aldehyde with the 4-methoxybenzaldehyde, ethyl malonate replaces methyl phenyl ketone, and other gets target compound (22), yield 88%, Mp 112-114 ℃ with embodiment 1.4-methoxybenzaldehyde and ethyl malonate, the reaction formula of acetonitrile is:
Figure BDA00002085282700131
The spectral data of product (22) is: 1H NMR (400MHz, DMSO-d 6) δ: 0.94 (3H, t, J 6.8Hz, CH 3), 1.54 (3H, t, J 7.2Hz, CH 3), 1.76 (3H, s, CH 3), 2.25 (3H, s, COCH 3), 3.89 (4H, m, 2CH 2), 4.42 (1H, t, J7.2Hz, CH), 5.40 (1H, t, J 10.0Hz, CH), 7.09-7.20 (4H, m, Ph), 8.38 (1H, d, J 9.2Hz, NH) .IR (film) ν Max3258,3066,2990,1758,1642,1556,1445,1368,1295,1148,1034,816,727,516cm -1; MS (ESI): m/z (relative intensity) 344.2 ([M+Na] +, 100).
Embodiment 23
Replace phenyl aldehyde with the 3-nitrobenzaldehyde, methyl ethyl diketone replaces methyl phenyl ketone, and other gets target compound (23), yield 83%, Mp 159-161 ℃ with embodiment 1.3-nitrobenzaldehyde and methyl ethyl diketone, the reaction formula of acetonitrile is:
The spectral data of product (23) is: 1H NMR (400MHz, CDCl 3) δ: 1.79 (3H, s, COCH 3), 1.79 (3H, s, COCH 3), 2.03 (3H, s, COCH 3), 2.23 (3H, s, CH 3), 4.64 (J 6.4 for 1H, dd, 10.4Hz, CH), 5.61 (1H, t, J10.4Hz, CH), 7.59-7.78 (2H, m, CH), 8.10-8.23 (2H, m, Ph), 7.11-7.23 (4H, m, Ph), 8.55 (1H, d, J 8.8Hz, Ph) .IR (film) ν Max3283,2930,1723,1699,1530,1350,1277,1208,739,596cm -1; MS (ESI): m/z (relative intensity) 315.2 ([M+Na] +, 100).
Embodiment 24
Replace methyl phenyl ketone with methyl aceto acetate, other gets target compound (24), yield 80%, Mp131-133 ℃ with embodiment 1.The cis-trans isomerism ratio is found out cis by methyne H atom in the proton nmr spectra based on the ratio of coupling constant: the trans 25:75 of being.Phenyl aldehyde and methyl aceto acetate, the reaction formula of acetonitrile is:
Figure BDA00002085282700141
The spectral data of product (24) is: 1H NMR (400MHz, CDCl 3) δ: 2.02 (3H, s, COCH 3), 2.30 (3H, s, CH 3), 3.44 (J 6.4 for 1H, dd, 16.8Hz, CH 2), 3.76 (J 4.8 for 1H, dd, 16.8Hz, CH 2), 5.51 – 5.55 (1H, m, CH), 6.62 (1H, d, J8.0Hz, NH), 7.11-7.23 (4H, m, Ph), 7.45 (2H, t, J7.6Hz, Ph), 7.57 (1H, t, J5.6Hz, Ph), 7.92 (2H, t, J 7.2Hz, Ph), 13C NMR (100MHz, DMSO-d 6) δ: 13.5,13.9,22.6,28.9,29.6,51.1,51.7,61.0,64.0,64.7,127.3,128.2,140.2,166.4,167.0,168.3,200.8.IR (film) ν Max3288,3084,2950,1686,1653,1553,1447,1365,1296,987,756,688cm -1; MS (ESI): m/z (relative intensity) 304.1 ([M+Na] +, 100).
Embodiment 25
Replace methyl phenyl ketone with pimelinketone, other gets target compound (25), yield 82%, Mp 172-174 ℃ with embodiment 1.The cis-trans isomerism ratio is found out cis by methyne H atom in the proton nmr spectra based on the ratio of coupling constant: the trans 30:70 of being.Phenyl aldehyde and pimelinketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700142
The spectral data of product (25) is: 1H NMR (400MHz, CDCl 3) δ: 1.16-1.22 (1H, m, CH 2), 1.49-1.74 (4H, m, CH 2), 1.77 (3H, s, COCH 3), 1.80-1.82 (1H, m, CH 2), 2.73-2.97 (1H, m, CH), 5.17 (1H, t, J 8.8Hz, CH), 7.20-7.25 (1H, m, Ph), 7.29 (4H, d, J4.4Hz, Ph), 8.19 (1H, d, J8.4Hz, NH); 13C NMR (100MHz, DMSO-d 6) δ: 28.3,28.5,33.2,36.1,57.5,60.7,115.1,133.0,133.7,147.1,173.8,216.3.IR (film) ν Max3326,2924,2826,1703,1650,1547,1375,1310,1239,1131,1071,717,699,592cm -1; MS (ESI): m/z (relative intensity) 268.1 ([M+Na] +, 100).
Embodiment 26
Replace phenyl aldehyde with terephthalaldehyde, other gets target compound (26), yield 90%, Mp251-253 ℃ with embodiment 1.Terephthalaldehyde and methyl phenyl ketone, the reaction formula of acetonitrile is:
Figure BDA00002085282700151
The spectral data of product (26) is: 1H NMR (400MHz, DMSO-d 6) δ: 1.77 (6H, s, COCH 3), 3.37 (2H, dd, J4.8,16.8Hz, CH 2), 3.52 (2H, dd, J8,16.4Hz, CH 2), 5.35 (2H, d, J6Hz, NH), 7.29 (4H, s, Ph), 7.52 (4H, s, Ph), 7.63 (2H, s, Ph), 7.95 (4H, d, J 7.6Hz, Ph), 8.28 (2H, d, J 7.6Hz, Ph); IR (film) ν Max3296,3081,2902,1688,1651,1548,1447,1298,991,755,688cm -1; MS (ESI): m/z (relative intensity) 479.2 ([M+Na] +, 100).

Claims (11)

1. the method for synthetic β-amidocarbonylation compound is characterized in that: with aromatic aldehyde and carbonyl compound, nitrile compounds reaction, generate β-amidocarbonylation compound, reaction expression is:
Figure FDA00002085282600011
R wherein 1Be the substituting group on the aromatic aldehyde, can be H, F, Cl, Br, NO 2, alkyl, perhaps alkoxyl group also can be 2, the 4-dichloro, 2-Cl-6-F etc. are disubstituted; This substituent quantity and position are not limit.R 2, R 3Can be H, alkyl, aryl or alkoxyl group, perhaps R 1, R 2Form 6 yuan naphthenic base with the carbon atom that is connected.R 4Can be methyl, styroyl or phenmethyl etc.
2. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound, it is characterized in that: wherein alkyl is selected from the C of straight or branched 1-6Alkyl, alkoxyl group are selected from the C of straight or branched 1-6Alkoxyl group, aryl is selected from C 6-10Aryl, heteroaryl are selected from 5 to 10 yuan of heteroaryls that comprise 1 to 3 Sauerstoffatom or nitrogen-atoms.
3. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound, it is characterized in that: wherein alkyl is selected from methyl, ethyl, propyl group, butyl, amyl group or hexyl; Alkoxyl group is selected from methoxyl group, oxyethyl group, propoxy-, butoxy, pentyloxy or hexyloxy.
4. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound, it is characterized in that: aryl is selected from phenyl, tolyl or ethylbenzene base; Heteroaryl is selected from pyridine, pyrimidine, pyrroles, pyrans.
5. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound; It is characterized in that: reaction medium is acetonitrile, benzyl cyanide, cyanobenzene, propionitrile, cyanic acid ethene, benzene,toluene,xylene, oil of mirbane, chlorobenzene, DMSO 99.8MIN., tetramethylene sulfone, N; Dinethylformamide, N, N-DEF, THF or halogenated hydrocarbon; Be liquid carbonyl compound down for normal temperature, except using aforesaid reaction medium, self also can be used as reaction medium.
6. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound is characterized in that: the reactant aromatic aldehyde is 1:1 ~ 1:99 with the ratio of the amount of substance of carbonyl compound.
7. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound is characterized in that: the catalyst for reaction titanium tetrachloride existence of acyl chlorides is arranged in the reaction system, and the ratio of acyl chlorides and reactant aromatic aldehyde is 1:1 ~ 1:99.
8. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound is characterized in that: catalyst consumption is 1 ~ 1.5 times of amount of substance of reactant aromatic aldehyde.
9. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound is characterized in that: conventional whipping appts is adopted in described reaction, at room temperature reacts 1-3 hour.
10. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound; It is characterized in that: the reaction solution that will react after finishing is scattered in the dispersion medium below the reaction solution 1-20 times volume; Dispersion medium does; But be not limited to water, ethanol, methyl alcohol, sherwood oil, perhaps wherein in both mixed solutions.Filter cake is used methyl alcohol, the perhaps a kind of organic solvent extracting in ethanol, acetone, THF, ETHYLE ACETATE, the acetonitrile, the organic phase after the extracting is mixed with the organic phase that above extraction obtains.Then with mixed liquid with but after being not limited to a kind of drying in SODIUM SULPHATE ANHYDROUS 99PCT, anhydrous calciumsulphate, anhydrous magnesium sulfate, the Calcium Chloride Powder Anhydrous siccative, rotation steams solvent, obtains solid or oily mixture.
11. the method for a kind of synthetic β as claimed in claim 1-amidocarbonylation compound is characterized in that: carry out recrystallization or column chromatography purification for crude product, obtaining productive rate is the pure target compound of 1-99%.Recrystallization solvent can be, but be not limited to water, methyl alcohol, ethanol, Virahol, acetone, acetonitrile, THF, dioxane, ETHYLE ACETATE, methylene dichloride, benzene, toluene.Adopt silicagel column or alumina column during column chromatography, developping agent does, but is not limited to ethyl acetate/petroleum ether (1:1～1:3, volume ratio), methyl alcohol/chloroform (1:5～1:50, volume ratio), methylene dichloride, acetone.
CN201210320524XA 2012-08-31 2012-08-31 Method for synthesizing beta-amidocarbonyl compounds Pending CN102816042A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103086818A (en) * 2013-01-15 2013-05-08 上海药明康德新药开发有限公司 Method for synthesizing alpha-oxyamide with 2-hydroxy propylene cyanide
CN104496837A (en) * 2014-11-24 2015-04-08 苏州乔纳森新材料科技有限公司 Method used for synthesizing beta-ketoamide compounds
CN109232291A (en) * 2017-07-11 2019-01-18 中国科学院福建物质结构研究所 A kind of beta amino acids derivative, its synthetic method and the application in drug

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1381755A (en) * 1971-11-10 1975-01-29 Calgon Corp Substituted n-alkylamino-acrylamides
CN102134176A (en) * 2011-01-18 2011-07-27 北京理工大学 Novel method for preparing aromatic amine through halogenated aromatic hydrocarbon

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1381755A (en) * 1971-11-10 1975-01-29 Calgon Corp Substituted n-alkylamino-acrylamides
CN102134176A (en) * 2011-01-18 2011-07-27 北京理工大学 Novel method for preparing aromatic amine through halogenated aromatic hydrocarbon

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
FARAHNAZ K. BEHBAHANI等: "CuSO4 5H2O: A NOVEL, GREEN, REUSABLE, AND ENVIRONMENTALLY FRIENDLY CATALYST FOR THE ONE-POT, FOUR-COMPONENT SYNTHESIS OF b-ACETAMIDO CARBONYL COMPOUNDS", 《SYNTHETIC COMMUNICATIONS1》 *
NAGARAJAN PANNEER SELVAM等: "Cerium(IV) sulfate catalyzed simple and convenient synthesis of β-acetamidocarbonyl compounds", 《ARKIVOC》 *
杨德利等: "室温下TiCl4 催化简便合成β-氨基酮化合物", 《中国化学会第28届学术年会第6分会场摘要集》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103086818A (en) * 2013-01-15 2013-05-08 上海药明康德新药开发有限公司 Method for synthesizing alpha-oxyamide with 2-hydroxy propylene cyanide
CN103086818B (en) * 2013-01-15 2016-08-10 武汉药明康德新药开发有限公司 Method by 2-hydroxyl the third dicyan synthesis Alpha-hydroxy amide
CN104496837A (en) * 2014-11-24 2015-04-08 苏州乔纳森新材料科技有限公司 Method used for synthesizing beta-ketoamide compounds
CN109232291A (en) * 2017-07-11 2019-01-18 中国科学院福建物质结构研究所 A kind of beta amino acids derivative, its synthetic method and the application in drug

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