CN107162970B - Method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under catalysis of high-acidity ionic liquid - Google Patents
Method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under catalysis of high-acidity ionic liquid Download PDFInfo
- Publication number
- CN107162970B CN107162970B CN201710521694.7A CN201710521694A CN107162970B CN 107162970 B CN107162970 B CN 107162970B CN 201710521694 A CN201710521694 A CN 201710521694A CN 107162970 B CN107162970 B CN 107162970B
- Authority
- CN
- China
- Prior art keywords
- dihydro
- reaction
- aryl
- ionic liquid
- quinolinone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a method for synthesizing a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of a high-acidity ionic liquid, and belongs to the technical field of chemical material preparation. The invention relates to a method for synthesizing a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of a high-acidity ionic liquid, which takes o-aminoacetophenone and aromatic aldehyde as reaction raw materials to synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of a high-acidity ionic liquid catalyst.
Description
Technical Field
The invention relates to a novel method for synthesizing a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of an acidic ionic liquid, belonging to the technical field of chemical material preparation. The method is suitable for the occasion of synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative by taking aromatic aldehyde with different substituents and o-aminoacetophenone as reaction raw materials.
Background
Quinolinone is a nitrogen-containing heterocyclic compound with good biological activity and pharmacological activity, shows excellent activity in the aspects of sterilization, inflammation diminishing, spasm resisting, pain relieving, cancer resisting and the like, and is a hot point of research of pharmacologists. In recent years, researches on synthesis and biological activity of the compounds are active at home and abroad. On the other hand, 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives, which are one of quinolinones, are aza analogs of flavanones, and also have a spectrum of biological activities, and have attracted considerable attention in medicinal chemistry. Therefore, the synthesis research of the compounds has very important significance.
In the prior art, inorganic or organic acids, e.g. concentrated H, are usually used2SO4P-toluenesulfonic acid, ZnCl2、InCl3And the like as catalysts to catalyze the condensation reaction of different aromatic aldehydes and o-aminoacetophenone to synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative. However, the method has the disadvantages of harsh reaction conditions, low reaction yield, long reaction time, serious environmental pollution, incapability of recycling the catalyst and the like. Therefore, the research of the organic synthesis workers is focused on finding a synthesis method of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative which is green, high in yield, mild in reaction conditions and strong in operability.
The ionic liquid refers to a salt which is liquid at room temperature or near room temperature, and is applied to organic synthesis reaction as a green solvent due to non-volatility, wide liquid phase range and good chemical stability. The anions and cations have acidic functional groups, e.g. -COOH, -SO3The ionic liquid such as H or the like or the ionic liquid with the anion of inorganic acid radical ions is called as Bronsted acidic ionic liquid, not only can be used as a green solvent in the reaction, but also has the function of a green catalyst, and can be applied to the process of catalyzing the reaction of aromatic aldehyde and o-amino acetophenone to synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative.
For example, national Liuchang is synthesized into three kinds of single-SO-carrying products by adopting a two-step method3H, and the catalytic activity and the reusability of the acidic ionic liquids which are respectively used as catalysts to catalyze the synthesis of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives by a one-pot method are considered. The results show that the three acidic ionic liquids have high catalytic activity, the catalyst can be reused for 5 times after vacuum drying treatment, and the catalytic activity of the catalyst is not obviously reduced. The method has the characteristics of mild reaction conditions, high product yield, no use of volatile organic solvent, relative environmental friendliness and the like (Acid ionic liquid catalyzed synthesis of 2-aryl-2, 3-dihydro-4 (1H) -quinolinone [ J]Fine chemical, 2012, 29 (8): 778～782)。
However, when the catalyst is used for catalyzing and synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative, the catalyst is relatively large in usage amount, the purification process of the obtained product is relatively complex, extraction and recrystallization processes are required, and the complex processes also cause large loss of the catalyst and relatively few recycling times. In addition, although the reaction conditions of the method are mild, the reaction time is relatively long, and the yield of the obtained product is still to be further improved.
Disclosure of Invention
1. Technical problem to be solved by the invention
The invention aims to overcome the defects of the existing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative synthesis process and provides a method for synthesizing a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of a high-acidity ionic liquid. The invention selects the specific high-acidity ionic liquid as the catalyst and optimizes the reaction process parameters, thereby effectively overcoming the defects of large catalyst usage amount, relatively poor recycling performance, complex product purification process and further improvement of the yield of the obtained product in the existing synthesis process.
2. Technical scheme
In order to achieve the purpose, the technical scheme provided by the invention is as follows:
the invention relates to a method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives under the catalysis of a high-acidity ionic liquid catalyst, which takes o-aminoacetophenone and aromatic aldehyde as reaction raw materials to synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives under the catalysis of the high-acidity ionic liquid catalyst, wherein the structural formula of the catalyst is as follows:
furthermore, the synthesis device of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative comprises a raw material mixer, an ultrasonic auxiliary reactor, a suction filtration device, a washing device and a drying device, wherein the ultrasonic auxiliary reactor is used for carrying out ultrasonic auxiliary reaction on the mixed materials in the raw material mixer, and the suction filtration device, the washing device and the drying device are respectively used for carrying out suction filtration, washing and drying treatment on the products obtained by the reaction.
Furthermore, the raw material mixer adopts a single-mouth flask with a condensing tube, the drying device adopts a vacuum drying oven, and the temperature is 75 ℃.
Furthermore, the synthesis device also comprises an ice-water bath cooling device, and the ice-water bath cooling device is used for cooling and crystallizing the reaction system obtained by the reaction.
Furthermore, the synthesis process of the invention is specifically as follows: respectively adding reaction raw materials of o-aminoacetophenone, aromatic aldehyde and a catalyst into a raw material mixer, fully and uniformly mixing with a reaction solvent, then carrying out heating reflux reaction under ultrasonic radiation for 1.0-3.5H, cooling to room temperature after the reaction is finished to precipitate a large amount of solids, then placing the raw material mixer into an ice-water bath cooling device for continuous cooling, crushing the precipitated solids when the solid amount is not increased any more, standing, carrying out suction filtration, and washing and vacuum drying the obtained filter residue to obtain the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative.
Further, the mol ratio of o-aminoacetophenone to aromatic aldehyde is 1: 1, wherein the molar amount of the catalyst is 8-12% of the molar amount of the aromatic aldehyde.
Further, the aromatic aldehyde is any one of benzaldehyde, p-chlorobenzaldehyde, p-hydroxybenzaldehyde, p-fluorobenzaldehyde, p-methoxybenzaldehyde, p-methylbenzaldehyde, p-nitrobenzaldehyde, p-cyanobenzaldehyde, m-chlorobenzaldehyde, m-nitrobenzaldehyde, o-bromobenzaldehyde, o-methylbenzaldehyde and o-hydroxybenzaldehyde.
Furthermore, the reaction solvent is ethanol water, and the volume concentration of the ethanol water is 94-97%.
Furthermore, the volume amount of the ethanol aqueous solution serving as the reaction solvent in milliliters is 8-10 times of the amount of the aromatic aldehyde in millimoles.
Furthermore, the washing solution adopts absolute ethyl alcohol.
3. Advantageous effects
Compared with the prior art, the technical scheme provided by the invention has the following remarkable effects:
(1) the method for catalytically synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative by using the high-acidity ionic liquid takes o-aminoacetophenone and aromatic aldehyde as reaction raw materials, and the high-acidity ionic liquid is selected as the catalyst, so that the catalytic activity of the catalyst is relatively high, the yield of the obtained product can be effectively improved, the catalyst is adopted to catalytically synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative, the using amount and the loss amount in the recycling process are small, the recycling performance of the catalyst is good, the recycling frequency is large, the resource loss can be effectively reduced, and the production cost is favorably reduced.
(2) According to the method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid, disclosed by the invention, the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative is synthesized in a microwave-assisted heating reaction mode, so that the catalytic activity of a catalyst can be improved, the reaction rate can be accelerated, the reaction time can be shortened, and the using amount of the catalyst can be reduced.
(3) According to the method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid, the catalytic activity of the catalyst can be brought into full play best by optimally designing the usage amount of the catalyst and reaction process parameters, the highest yield of the obtained product is ensured, the occurrence of side reactions can be effectively reduced, and the purity of the obtained product is further effectively ensured.
(4) According to the method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid, the ethanol aqueous solution with a specific concentration is selected as a reaction solvent, so that the purification treatment of the obtained product is facilitated, the product is easy to separate from the catalyst, the purification operation of the product is simple and convenient, and extraction and recrystallization treatment is not needed.
(5) According to the method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid, the unreacted reaction raw materials in the last reaction can be recycled in the next reaction, the utilization rate of the reaction raw materials is high, and the atom economy is good; meanwhile, the catalyst is simple in pretreatment before being recycled, and energy conservation and emission reduction are facilitated.
Drawings
FIG. 1 is a schematic structural diagram of a device for catalytically synthesizing a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative by using a high-acidity ionic liquid catalyst.
Detailed Description
The invention relates to a method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives under the catalysis of high-acidity ionic liquid, which takes o-aminoacetophenone and aromatic aldehyde as reaction raw materials to synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives under the catalysis of a high-acidity ionic liquid catalyst. As shown in fig. 1, the apparatus for synthesizing a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative in the present invention comprises a raw material mixer, an ultrasonic-assisted reactor, an ice-water bath cooling device, a suction filtration device, a washing device and a drying device, wherein the ultrasonic-assisted reactor is used to perform an ultrasonic-assisted reaction on the mixed material in the raw material mixer, the ice-water bath cooling device is used to perform cooling crystallization treatment on the reaction system obtained by the reaction, and the suction filtration device, the washing device and the drying device are respectively used to perform suction filtration, washing and drying treatment on the product obtained by the reaction. The raw material mixer adopts a single-mouth flask with a condensing tube, and the drying device adopts a vacuum drying oven at the temperature of 75 ℃.
The structural formula of the catalyst used in the invention is as follows:
the preparation method of the catalyst refers to the related information (Synthesis of novel multi-SO)3H functionalized ionic liquid and its catalytic activities for biodieselsynthesis[J]Green Chemistry, 2010, 12: 201-204; preparation method of multi-sulfonic functional ionic liquid [ P]，CN 101348487A)。
The synthesis process of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative is as follows: respectively adding reaction raw materials of o-aminoacetophenone, aromatic aldehyde and a catalyst into a raw material mixer, fully and uniformly mixing with a reaction solvent, then carrying out heating reflux reaction under ultrasonic radiation for 1.0-3.5H, cooling to room temperature after the reaction is finished to precipitate a large amount of solids, then placing the raw material mixer into an ice-water bath cooling device for continuous cooling, crushing the precipitated solids when the solid amount is not increased any more, standing, carrying out suction filtration, and washing and vacuum drying the obtained filter residue to obtain the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative.
The chemical reaction formula of the reaction is as follows:
wherein the aromatic aldehyde is any one of benzaldehyde, p-chlorobenzaldehyde, p-hydroxybenzaldehyde, p-fluorobenzaldehyde, p-methoxybenzaldehyde, p-methylbenzaldehyde, p-nitrobenzaldehyde, p-cyanobenzaldehyde, m-chlorobenzaldehyde, m-nitrobenzaldehyde, o-bromobenzaldehyde, o-methylbenzaldehyde and o-hydroxybenzaldehyde. The molar ratio of o-aminoacetophenone to aromatic aldehyde in the reaction is 1: 1, wherein the molar amount of the catalyst is 8-12% of the molar amount of the aromatic aldehyde. The reaction solvent is ethanol water solution with volume concentration of 94-97%, and the volume of the ethanol water solution in milliliters is 8-10 times of the quantity of the aromatic aldehyde in millimoles. The washing solution adopts absolute ethyl alcohol.
The invention mainly aims at the problems of large catalyst usage amount, relatively few times of recycling of the catalyst, complex synthesis process and product yield to be further improved in the existing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative synthesis process, and through a great amount of experimental research, and combines the characteristics of the synthetic process of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative, finally selects the high-acidity ionic liquid catalyst, the catalyst has relatively high activity and selectivity for catalyzing and synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative, therefore, the catalyst is used in a small amount, the reaction time is short, and the yield of the obtained product is relatively high.
The control of the amount of the catalyst used and the reaction process parameters in the invention is crucial to the yield and purity of the final product. The inventor carries out optimization design on the usage amount of the catalyst and reaction process parameters, thereby effectively ensuring that the catalytic activity of the catalyst is fully exerted, effectively preventing side reaction and further being beneficial to ensuring the yield and the purity of the obtained product. Meanwhile, the invention also carries out reaction in a microwave-assisted heating mode, thereby further improving the catalytic activity of the catalyst, being beneficial to reducing the using amount of the catalyst and shortening the reaction time. The loss of the catalyst in the recycling process is less, so that the catalyst can be recycled for more times, and the catalytic activity of the catalyst is reduced less in recycling, so that the stability of the yield of the obtained product can be ensured.
In addition, the catalyst is adopted to catalyze and synthesize the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative, and ethanol water solution with specific concentration is selected as a reaction solvent, so that the full reaction is ensured, the recycling performance of the catalyst is improved, and the product purification operation is simple. The unreacted reaction raw materials in the last reaction can be recycled in the next reaction, so that the utilization rate of the reaction raw materials is high, and the atom economy is good; meanwhile, the catalyst is simple in pretreatment before being recycled, and energy conservation and emission reduction are facilitated.
The essential features and the remarkable effects of the present invention can be obtained from the following examples, which are not intended to limit the present invention in any way, and those skilled in the art who have the benefit of this disclosure will be able to make numerous insubstantial modifications and adaptations to the present invention without departing from the scope of the present invention. The invention is further illustrated by the following specific embodiments in which infrared spectroscopy of the reaction products of the examples is characterized by the use of an EQUINOX 55 infrared spectrometer (KBr pellet) from Bruker, germany; the nuclear magnetic resonance instrument of AVANCE-II 400MHz of Germany Bruker company is adopted for the characterization of the hydrogen spectrum nuclear magnetic resonance; the melting point of the reaction product was determined by the capillary method.
Example 1
1mmol of benzaldehyde, 1mmol of o-aminoacetophenone and 0.10mmol of high-acidity ionic liquid are respectively added into a 50ml single-neck bottle with a condenser tube and containing 8ml of 94% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 2.1H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to separate out a large amount of solid, placing the solid in an ice-water bath to continuously cool to separate out the solid, crushing the separated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml multiplied by 3), and performing vacuum drying at 75 ℃ to obtain the 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.1% by high performance liquid chromatography, and the calculated yield is 92%. Benzaldehyde and o-amino acetophenone are added directly into the filtrate for reuse.
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example: m.p.150-152 ℃; the performance parameters for IR (KBr) are as follows: 3309, 1692, 1632, 1361, 1259, 1134cm-1；1H NMR(400MHz，CDCl3)：δ＝7.52～7.58(m， 2H)，7.07～7.28(m，6H)，6.88～6.92(m，1H)，5.25(t，1H)，4.73(s，1H)，3.06(dd，1H)，2.72(dd， 1H)。
Example 2
1mmol of p-nitrobenzaldehyde, 1mmol of o-aminoacetophenone and 0.08mmol of high-acidity ionic liquid are respectively added into a 50ml single-mouth bottle with a condenser tube and 9ml of 94% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 1.0H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml multiplied by 3), and performing vacuum drying at 75 ℃ to obtain the 2- (4-nitro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.4% by high performance liquid chromatography, and the calculated yield is 98%. The filtrate is directly added with p-nitrobenzaldehyde and o-aminoacetophenone for reuse.
2- (4-Nitro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example: m.p.169-171 ℃; IR (KBr): 3371, 3169, 1745, 1687, 1602, 1397, 1168cm-1；1H NMR(400MHz，CDCl3) The performance parameters of (a) are as follows: δ is 8.04(d, 2H), 7.51 to 7.60(m, 2H), 7.24 to 7.31(m, 3H), 6.87(d, 1H), 5.27(t, 1H), 4.66(s, 1H), 3.19(dd, 1H), 2.92(dd, 1H).
Example 3
1mmol of p-methoxybenzaldehyde, 1mmol of o-aminoacetophenone and 0.10mmol of high-acidity ionic liquid are respectively added into a 50ml single-mouth bottle with a condenser tube containing 10ml of 97% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 2.3H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml × 3), and performing vacuum drying at 75 ℃ to obtain 2- (4-methoxy) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.2% by high performance liquid chromatography, and the calculated yield is 91%. The filtrate is directly added with p-methoxybenzaldehyde and o-aminoacetophenone for reuse.
The performance parameters of the 2- (4-methoxy) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.196-198 ℃; IR (KBr): 3294, 3056, 1729, 1641, 1593, 1327, 1225, 1140, 1078, 1006cm-1；1H NMR(400MHz，CDCl3)：δ＝7.55～7.64(m，2H)，7.18～7.27(m，3H)，6.80～6.91(m，3H)， 5.17(t，1H)，4.77(s，1H)，3.72(s，3H)，3.04(dd，1H)，2.73(dd，1H)。
Example 4
1mmol of p-fluorobenzaldehyde, 1mmol of o-aminoacetophenone and 0.09mmol of high-acidity ionic liquid are respectively added into a 50ml single-neck flask with a condenser tube and containing 8ml of 95% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 1.6H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml × 3), and performing vacuum drying at 75 ℃ to obtain 2- (4-fluoro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.0% by high performance liquid chromatography, and the calculated yield is 94%. The p-fluorobenzaldehyde and the o-amino acetophenone are directly added into the filtrate for reuse.
The performance parameters of the 2- (4-fluoro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.164-166 ℃; IR (KBr): 3453, 3094, 1705, 1661, 1572, 1315, 1208, 1149, 1012cm-1；1H NMR(400MHz， CDCl3)：δ＝7.52～7.60(m，2H)，7.20～7.29(m，3H)，7.02～7.09(m，2H)，6.88(d，1H)，5.30(t， 1H)，4.78(s，1H)，3.05(dd，1H)，2.71(dd，1H)。
Example 5
1mmol of m-chlorobenzaldehyde, 1mmol of o-aminoacetophenone and 0.09mmol of high-acidity ionic liquid are respectively added into a 50ml single-neck bottle with a condenser tube and containing 8ml of 96% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 1.8H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml multiplied by 3), and performing vacuum drying at 75 ℃ to obtain 2- (3-chloro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.1% by high performance liquid chromatography, and the calculated yield is 92%. The m-chlorobenzaldehyde and o-amino acetophenone are added directly into the filtrate for reuse.
The performance parameters of the 2- (3-chloro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.164-171 ℃; IR (KBr): 3295, 3093, 1718, 1644, 1527, 1312 and 1239cm-1；1H NMR(400MHz，CDCl3)：δ＝7.57～7.65(m，2H)，7.32～7.37(m，2H)，7.20～7.26(m，2H)，7.06(d，1H)，6.91(d，1H)，5.29(t，1H)，4.68(s，1H)，3.19(dd，1H)，2.76(dd，1H)。
Example 6
Adding 1mmol of m-nitrobenzaldehyde, 1mmol of o-aminoacetophenone and 0.08mmol of high-acidity ionic liquid into a 50ml single-neck bottle with a condenser tube containing 9ml of 94% ethanol water solution respectively, and stirring uniformly at room temperature. Heating and refluxing, reacting for 1.2H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml multiplied by 3), and performing vacuum drying at 75 ℃ to obtain the 2- (3-nitro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 98.9% by high performance liquid chromatography, and the calculated yield is 95%. The m-nitrobenzaldehyde and o-aminoacetophenone are directly added into the filtrate for reuse.
The performance parameters of the 2- (3-nitro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.147-149 deg.c; IR (KBr): 3391, 3085, 1737, 1652, 1584, 1239, 1196, 1005cm-1；1H NMR(400MHz， CDCl3)：δ＝8.14～8.21(m，2H)，7.74(d，1H)，7.52～7.60(m，2H)，7.41(t，1H)，7.23(t，1H)， 6.95(d，1H)，5.38(t，1H)，4.77(s，1H)，3.13(dd，1H)，2.78(dd，1H)。
Example 7
1mmol of o-bromobenzaldehyde, 1mmol of o-aminoacetophenone and 0.09mmol of high-acidity ionic liquid are respectively added into a 50ml single-mouth bottle with a condenser tube and containing 8ml of 96% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 1.9H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to separate out a large amount of solid, placing the solid into an ice-water bath to continuously cool to separate out the solid, crushing the separated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml multiplied by 3), and performing vacuum drying at 75 ℃ to obtain the 2- (2-bromo) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.4% by high performance liquid chromatography, and the calculated yield is 90%. The filtrate is directly added with o-bromobenzaldehyde and o-aminoacetophenone for repeated use.
The performance parameters of the 2- (2-bromo) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.225-227 ℃; IR (KBr): 3394, 3248, 3040, 1714, 1609, 1233, 1125, 1006cm-1；1H NMR(400MHz，CDCl3)：δ＝7.54～7.63(m，2H)，7.43～7.47(m，1H)，7.24～7.35(m，3H)，6.95～7.01(m，2H)，5.34(t， 1H)，4.78(s，1H)，3.15(dd，1H)，2.84(dd，1H)。
Example 8
1mmol of o-hydroxybenzaldehyde, 1mmol of o-aminoacetophenone and 0.12mmol of high-acidity ionic liquid are respectively added into a 50ml single-mouth bottle with a condenser tube and 9ml of 97% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 3.5H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml × 3), and performing vacuum drying at 75 ℃ to obtain 2- (2-hydroxy) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.0% by high performance liquid chromatography, and the calculated yield is 84%. The filter liquor is directly added with o-hydroxybenzaldehyde and o-aminoacetophenone for repeated use.
The performance parameters of the 2- (2-hydroxy) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.238-240 ℃; IR (KBr): 3384, 3247, 3052, 1683, 1642, 1594, 1307, 1219, 1102, 1020cm-1；1H NMR(400MHz，CDCl3)：δ＝10.13(s，1H)，7.57～7.64(m，2H)，7.22～7.38(m，3H)，6.87～ 6.94(m，2H)，6.69～6.74(m，2H)，5.21(t，1H)，4.59(s，1H)，3.05(dd，1H)，2.73(dd，1H)。
Example 9
1mmol of o-methyl benzaldehyde, 1mmol of o-amino acetophenone and 0.10mmol of high acidity ionic liquid are respectively added into a 50ml single-mouth bottle with a condenser tube and 10ml of 97% ethanol water solution, and the mixture is stirred uniformly at room temperature. Heating and refluxing, reacting for 2.6H under ultrasonic radiation, detecting by TLC (thin-plate chromatography), removing raw material points, cooling to room temperature after the reaction is finished to precipitate a large amount of solid, placing the solid in an ice-water bath to continuously cool to precipitate the solid, crushing the precipitated solid when the solid amount is not increased, standing, performing suction filtration, washing filter residues with anhydrous ethanol (3ml × 3), and performing vacuum drying at 75 ℃ to obtain 2- (2-methyl) -phenyl-2, 3-dihydro-4 (1H) -quinolinone, wherein the purity is 99.5% by high performance liquid chromatography, and the calculated yield is 87%. The filtrate is directly added with o-methyl benzaldehyde and o-amino acetophenone for reuse.
The performance parameters of the 2- (2-methyl) -phenyl-2, 3-dihydro-4 (1H) -quinolinone obtained in this example are as follows: m.p.133-135 ℃; IR (KBr): 3407, 3240, 1648, 1601, 1302, 1236, 1128, 1014cm-1；1H NMR(400MHz， CDCl3)：δ＝7.52～7.61(m，2H)，7.24(t，1H)，7.00～7.06(m，3H)，6.89～6.91(m，2H)，5.40(t， 1H)，4.77(s，1H)，3.03(dd，1H)，2.74(dd，1H)，2.16(s，3H)。
Example 10
The activity repeatability test of the high-acidity ionic liquid used as a reaction catalyst by using the example 1 as a probe reaction is repeated for 9 times, and the purity and yield of the product 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone are shown in Table 1.
TABLE 1 results of activity repeatability tests of high acidity ionic liquids in catalytic synthesis of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone
Example 11
The activity repeatability test of the high-acidity ionic liquid used as a reaction catalyst by using the example 2 as a probe reaction is repeated for 8 times, and the purity and yield of the product 2- (4-nitro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone are shown in Table 2.
TABLE 2 results of activity repeatability tests of high acidity ionic liquids in catalytic synthesis of 2- (4-nitro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone
| Number of times of use of high acidity ionic liquid | Purity/%) | Calculated yield/% |
| 1 | 99.4 | 98 |
| 2 | 99.2 | 97 |
| 3 | 99.0 | 97 |
| 4 | 98.9 | 96 |
| 5 | 98.7 | 96 |
| 6 | 98.6 | 96 |
| 7 | 98.5 | 94 |
| 8 | 98.4 | 94 |
| 9 | 98.2 | 92 |
Example 12
The activity of the high-acidity ionic liquid used as a reaction catalyst was tested by repeating the reaction using example 5 as a probe for 8 times, and the purity and yield of the product 2- (3-chloro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone are shown in Table 3.
TABLE 3 results of activity reproducibility test of high-acidity ionic liquid in catalytic synthesis of 2- (3-chloro) -phenyl-2, 3-dihydro-4 (1H) -quinolinone
Example 13
The activity of the high-acidity ionic liquid used as a reaction catalyst was tested by repeating the reaction using example 8 as a probe, and the purity and yield of the product 2- (2-hydroxy) -phenyl-2, 3-dihydro-4 (1H) -quinolinone were shown in Table 4.
TABLE 4 Activity repeatability test results of high acidity ionic liquids in catalytic synthesis of 2- (2-hydroxy) -phenyl-2, 3-dihydro-4 (1H) -quinolinone
| Number of times of use of high acidity ionic liquid | Purity/%) | Calculated yield/% |
| 1 | 99.0 | 84 |
| 2 | 98.8 | 83 |
| 3 | 98.7 | 81 |
| 4 | 98.6 | 82 |
| 5 | 98.4 | 80 |
| 6 | 98.3 | 81 |
| 7 | 98.2 | 82 |
| 8 | 98.0 | 80 |
| 9 | 98.0 | 79 |
As can be seen from tables 2 to 4: when the high-acidity ionic liquid catalyzes aromatic aldehyde containing substituents (electron-withdrawing groups or electron-donating groups) with different types and different positions to react with o-aminoacetophenone to synthesize a series of 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives, the calculated yield reduction amplitude of corresponding products after the derivatives are recycled for 8 times is less than 5 percent. In addition, the high performance liquid chromatography purity of the product is reduced with the increase of the number of recycling times, but still more than 98%. Therefore, the high-acidity ionic liquid catalyst can be recycled and can be recycled at least 8 times in the process of catalytically synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative, and the catalytic activity of the high-acidity ionic liquid catalyst is not obviously reduced.
Claims (6)
1. A method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives under the catalysis of high-acidity ionic liquid is characterized in that o-aminoacetophenone and aromatic aldehyde are used as reaction raw materials, and the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivatives are synthesized by heating reflux reaction under the catalysis of high-acidity ionic liquid catalyst under the action of ultrasonic radiation, wherein the structural formula of the catalyst is as follows:
the molar weight of the catalyst is 8-12% of that of the aromatic aldehyde, the reaction solvent is ethanol water solution, the volume concentration of the ethanol water solution is 94-97%, and the volume amount of the reaction solvent ethanol water solution in milliliters is 8-10 times of that of the aromatic aldehyde in millimoles; the aromatic aldehyde is any one of benzaldehyde, p-chlorobenzaldehyde, p-hydroxybenzaldehyde, p-fluorobenzaldehyde, p-methoxybenzaldehyde, p-methylbenzaldehyde, p-nitrobenzaldehyde, p-cyanobenzaldehyde, m-chlorobenzaldehyde, m-nitrobenzaldehyde, o-bromobenzaldehyde, o-methylbenzaldehyde and o-hydroxybenzaldehyde, and the structural formula of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative is as follows:
the synthesis process is as follows: respectively adding reaction raw materials of o-aminoacetophenone, aromatic aldehyde and a catalyst into a raw material mixer, fully and uniformly mixing with a reaction solvent, then carrying out heating reflux reaction under ultrasonic radiation for 1.0-3.5H, cooling to room temperature after the reaction is finished to precipitate a large amount of solids, then placing the raw material mixer into an ice-water bath cooling device for continuous cooling, crushing the precipitated solids when the solid amount is not increased any more, standing, carrying out suction filtration, and washing and vacuum drying the obtained filter residue to obtain the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative.
2. The method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid according to claim 1, wherein the method comprises the following steps: the synthesis device of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative comprises a raw material mixer, an ultrasonic auxiliary reactor, a suction filtration device, a washing device and a drying device, wherein the ultrasonic auxiliary reactor is used for carrying out ultrasonic auxiliary reaction on mixed materials in the raw material mixer, and the suction filtration device, the washing device and the drying device are respectively used for carrying out suction filtration, washing and drying treatment on products obtained by reaction.
3. The method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid according to claim 2, wherein the method comprises the following steps: the raw material mixer adopts a single-mouth flask with a condensing tube, the drying device adopts a vacuum drying oven, and the temperature is 75 ℃.
4. The method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under the catalysis of the high-acidity ionic liquid according to claim 2, wherein the method comprises the following steps: the synthesis device also comprises an ice-water bath cooling device, and the ice-water bath cooling device is used for cooling and crystallizing the reaction system obtained by the reaction.
5. The method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative catalyzed by the high-acidity ionic liquid according to any one of claims 1 to 4, wherein: the mol ratio of o-aminoacetophenone to aromatic aldehyde is 1: 1.
6. the method for synthesizing the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative catalyzed by the high-acidity ionic liquid according to any one of claims 1 to 4, wherein: the washing solution adopts absolute ethyl alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710521694.7A CN107162970B (en) | 2017-06-30 | 2017-06-30 | Method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under catalysis of high-acidity ionic liquid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710521694.7A CN107162970B (en) | 2017-06-30 | 2017-06-30 | Method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under catalysis of high-acidity ionic liquid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107162970A CN107162970A (en) | 2017-09-15 |
| CN107162970B true CN107162970B (en) | 2019-12-20 |
Family
ID=59827270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710521694.7A Active CN107162970B (en) | 2017-06-30 | 2017-06-30 | Method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under catalysis of high-acidity ionic liquid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107162970B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558891A (en) * | 2018-05-11 | 2018-09-21 | 浙江工业大学 | A kind of supported on silica-gel multinuclear sulfonic group acidic ion liquid and application |
| CN113416166B (en) * | 2021-06-23 | 2022-08-05 | 浙江外国语学院 | Method for preparing 4-hydroxyquinoline-2 (1H) -ketone compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101348487A (en) * | 2008-09-04 | 2009-01-21 | 华东师范大学 | Preparation of multi-sulfonic functional ion liquid |
| CN103193607A (en) * | 2013-03-18 | 2013-07-10 | 安徽工业大学 | Method for preparing chalcone and directive through multi-sulfonate ion liquid catalysis |
| CN103193716A (en) * | 2013-03-27 | 2013-07-10 | 安徽工业大学 | Method for preparing 3,4-dihydropyrimidine-2 (1H)-ketone derivative via catalysis of acidic ionic liquid |
-
2017
- 2017-06-30 CN CN201710521694.7A patent/CN107162970B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101348487A (en) * | 2008-09-04 | 2009-01-21 | 华东师范大学 | Preparation of multi-sulfonic functional ion liquid |
| CN103193607A (en) * | 2013-03-18 | 2013-07-10 | 安徽工业大学 | Method for preparing chalcone and directive through multi-sulfonate ion liquid catalysis |
| CN103193716A (en) * | 2013-03-27 | 2013-07-10 | 安徽工业大学 | Method for preparing 3,4-dihydropyrimidine-2 (1H)-ketone derivative via catalysis of acidic ionic liquid |
Non-Patent Citations (2)
| Title |
|---|
| [C8dabco]Br: a mild and convenient catalyst for intramolecular cyclization of 2-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones;Chamseddine Derabli，等;《Chemistry of Heterocyclic Compounds》;20161231;第52卷(第2期);第99-103页 * |
| Bronsted 酸离子液体催化合成2-芳基-2，3-二氢- 4( 1H) - 喹啉酮;刘长春;《精细化工》;20120831;第29卷(第8期);第778-782页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107162970A (en) | 2017-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107162970B (en) | Method for synthesizing 2-aryl-2, 3-dihydro-4 (1H) -quinolinone derivative under catalysis of high-acidity ionic liquid | |
| Seo et al. | Dual Nickel (II)/Mechanoredox Catalysis: Mechanical‐Force‐Driven Aryl‐Amination Reactions Using Ball Milling and Piezoelectric Materials | |
| Hu et al. | Synthesis of a novel sterically hindered chiral cyclic phosphoric acid derived from L-tartaric acid and application to the asymmetric catalytic Biginelli reaction | |
| Zhan et al. | The carbon material functionalized with NH 2+ and SO 3 H groups catalyzed esterification with high activity and selectivity | |
| CN113816973B (en) | Preparation method of medical intermediate benzothiazole [2, 3-b ] quinazolinedione derivative | |
| CN110372611B (en) | Method for selectively synthesizing polysubstituted dihydro quinazolinone or quinazolinone | |
| Wu et al. | Efficient synthesis of sec-butanol from sec-butyl acetate under mild conditions with the basic ionic liquid catalysts | |
| CN112225652B (en) | Preparation and application of tetracarbonyl cyclobutane compound dihydrate | |
| CN106238098B (en) | A kind of preparation method and its catalyst for preparing of 1,2,4,5- tetra- substituted ramification of imidazole | |
| Zong et al. | Ruthenium carbonyl complexes supported by pyridine-alkoxide ligands: synthesis, structure and catalytic oxidation of secondary alcohols | |
| CN110016042B (en) | Method for preparing 1, 4-dihydropyrido [3, 2-c ] [5, 6-c ] dicoumarin derivative through catalysis | |
| CN101481357B (en) | Preparation of quinoxaline derivatives | |
| CN106008265A (en) | Palladium-catalyzed benzyl quaternary ammonium salt C-N bond fission Suzuki coupling method | |
| CN107382961B (en) | Method for preparing 2-thiocarbonyl-2H-thiopyran derivative by chitosan catalysis one-pot method | |
| CN105732518B (en) | A kind of method that trisulfonic acid radical ion liquid catalyst prepares pyrimidone derivatives | |
| CN109824585B (en) | Method for preparing 1-aryl-2-quinolyl ethanol compound under catalysis of acidic ionic liquid | |
| CN111269142B (en) | Method for catalyzing benzylidene malononitrile compound by SBA-15 supported ionic liquid | |
| CN110773223B (en) | g-C 3 N 4 Supported transition metal oxide and application thereof in synthesis of alpha-hydroxy ketone | |
| CN107312008B (en) | A kind of catalysis prepares the catalyst and system and method for benzimidazole simultaneously [2,1-b] quinoline -6- ketone derivatives | |
| CN103896871B (en) | The method of 5-aryl methylene-2,4-thiazolidinedione derivative is prepared in the catalysis of a kind of degradable alkali ionic liquid | |
| CN111635369A (en) | Preparation method of dihydro quinazolinone derivative | |
| CN111100085A (en) | Preparation method of 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound | |
| Dong et al. | Tartaric acid–zinc nitrate as an efficient Brønsted acid-assisted Lewis acid catalyst for the Mannich reaction | |
| CN112979563B (en) | Preparation method of medical intermediate 2, 3-diaryl-2, 3-dihydroquinazoline-4 [1H ] -ketone | |
| CN110862373B (en) | Method for preparing 2-thiocarbonyl-2H-thiopyran derivative through high-efficiency catalysis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221108 Address after: No. 99, Gangcheng Road, Dongying Port Economic Development Zone, Dongying City, Shandong Province 257237 Patentee after: Dongying Ruigang Investment Service Co.,Ltd. Address before: 243000 2, 1669 north section of Huo Li Shan Road, Ma'anshan high tech Zone, Anhui Patentee before: MAANSHAN TAIBO CHEMICAL TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right |