CN101580499B - Reaction system and method for generating flavanone by cyclization of 2'-hydroxy chalcone - Google Patents

Abstract

The invention discloses a reaction system for generating flavanones by cyclization of 2'-hydroxychalcone, which is mainly composed of pyridine and water, and can be reacted by heating or lighting. This reaction system has a high yield and the solvent is easy to recover.

Description

Reaction system and method for cyclization of 2'-hydroxychalcones to generate flavanones

technical field

The present invention relates to preparation of flavanones by cyclization of 2'-hydroxychalcones, and in particular to a reaction system and a method for cyclization under the reaction system.

Background technique

Flavanones are one of the active ingredients of various medicinal plants. Due to its remarkable biological and pharmacological activities and unique plastic structure, it has attracted strong research interest of chemists for nearly a hundred years. According to relevant literature reports, many flavanone compounds have many biological activities such as antibacterial, anti-inflammatory, anti-HIV virus, anti-tumor, anti-mutagenesis, and anti-oxidation. They are a class of compounds with high research value and broad application prospects. Flavanone derivatives are mostly extracted from natural plants, and the substituents are mostly hydroxyl, methoxy, benzyloxy, isopentenyl, geranyl, etc. Although flavanone compounds widely exist in the plant kingdom, the content of such compounds in plants is less, or the drug effect is not ideal, so they need to be obtained by chemical synthesis or chemical modification; at the same time, the flavanone parent There are a total of 10 substitutable positions on it, which has great potential for structural modification, so it is also an intermediate for the synthesis of various flavonoid compounds. Therefore, it is a very meaningful work to study its synthesis.

There are various methods for artificially synthesizing flavanones, and one of the important synthetic methods is to obtain them through cyclization of 2'-hydroxychalcone. In the method for synthesizing flavanones from chalcones, one step of ring closure is relatively difficult, so people have done a lot of exploration work on the improvement of its cyclization conditions, and proposed many cyclization reagents, such as acid-base catalyst cyclization , Silica gel catalytic cyclization, NiCl ₂ /Zn/KI system catalytic cyclization, photocyclization, heating cyclization, electrochemical transformation method cyclization, organic amine cyclization, macroporous resin A-21 cyclization, solid basic catalyst Cyclization etc. Because the above-mentioned various cyclization methods either have poor target product selectivity, long reaction time, low yield, product separation needs to consume a large amount of organic solvent, or are only effective for special structural compounds, or use expensive catalysts, or produce a large number of by-products or Disadvantages such as great harm to the environment have affected their popularization and application in industry.

Contents of the invention

Aiming at the disadvantages of poor selectivity, low yield and high cost of generating flavanones by cyclization of 2'-hydroxychalcones, the first object of the present invention is to provide a method for synthesizing flavanones from 2'-hydroxychalcones Ketone reaction system, this reaction system can effectively convert 2'-hydroxychalcone into flavanone, and the solvent is easy to obtain, the product is easily separated from the reaction system, and the yield is high.

The second object of the present invention is also to provide a method for cyclization of 2'-hydroxychalcones to generate flavanones.

In order to realize the first object of the present invention, the following scheme is adopted: a reaction system for generating flavanones by cyclization of 2'-hydroxychalcones is a reaction system mainly composed of pyridine and water.

The volume ratio of the pyridine to water may be 1:0.67-2.5, preferably 1:1.5.

In order to realize the second purpose of the present invention, adopt following technical scheme:

(1) Add 2'-hydroxychalcone, pyridine and water into the reaction kettle, stir, heat to 80-90°C, and the reaction time is 0.5-1.5h;

(2) The reacted mixture is concentrated under reduced pressure, separated by chromatography in a chromatographic column, and evaporated under reduced pressure to remove the solvent to obtain flavanones with a yield of 82.8-91.1%.

The volume ratio of the pyridine to water is 1:0.67-2.5, preferably 1:1.5.

The present invention can also be prepared by the visible light illumination method, adopting the following technical scheme:

(1) In the reaction system composed of pyridine and water, add 2'-hydroxychalcone, stir, illuminate with a 500W xenon lamp, and the reaction time is 1 to 4 hours;

(2) The reacted mixture was concentrated under reduced pressure, separated by chromatography on a silica gel column, and the eluate was collected, concentrated under reduced pressure to obtain flavanones with a yield of 84.5-99.6%.

The volume ratio of the pyridine to water is 1:0.67-2.5, preferably 1:1.5.

The present invention can also be prepared by adopting the method of natural light illumination, adopting the following technical scheme:

(1) In the reaction system composed of pyridine and water, add 2'-hydroxychalcone, stir, and adopt indoor natural light for illumination, and the reaction time is 1 to 4 hours;

(2) The reacted mixture was concentrated under reduced pressure, separated by chromatography on a silica gel column, and the eluate was collected and concentrated under reduced pressure to obtain flavanones with a yield of 81.5-89.7%.

The volume ratio of the pyridine to water is 1:0.67-2.5, preferably 1:1.5.

Main advantages of the present invention are as follows:

(1) Using pyridine and water reaction system, the yield of flavanones is high, and the yield of flavanones is 82.8 to 91.1% under heating conditions; the yield of flavanones is 84.5 to 99.6% under visible light. The yield of flavanones is 81.5-89.7%.

(2) No by-products. The reacted mixture has only flavanones and unreacted 2'-hydroxychalcone, and no other by-products are generated.

(3) Pyridine is easy to distill and recover from water, and the product is easy to separate.

(4) Most of the reaction solvent is distilled water, which is economical and easy to get.

(5) The recovered pyridine can be reused without secondary pollution, which is beneficial to environmental protection.

(6) Easy to operate and easy to popularize.

The invention provides a new high-efficiency synthetic method for synthesizing flavanone compounds from the chalcone route, and has great medical value and economic benefit.

Detailed ways

The present invention will be further described below in conjunction with specific embodiments, so as to help understand the contents of the present invention.

Example 1: 2'-hydroxychalcone heating cyclization

Weigh 1mmol of 2'-hydroxychalcone, dissolve it with 40ml of pyridine, add it to a 250ml three-neck round bottom flask, add 60ml of distilled water, stir mechanically, condense and reflux, control the temperature at 90°C, and react for 1h; concentrate under reduced pressure; Column chromatography separation (eluent is benzene: ethyl acetate=30: 1), distillation under reduced pressure; Concentrate is constant volume with methanol, adopts ultraviolet-visible spectrophotometer to measure absorbance at 251nm place of characteristic peak of flavanone, The flavanone content was calculated, and the yield was 91.1%; and the melting point, IR, H-NMR, and HRMS analyzes were carried out.

Other solvent systems (volume ratio is 1: 1.5), are shown in Table 1 to the action effect of heating cyclization of 2'-hydroxychalcone under the above-mentioned same conditions.

Table 1 Effect of different solvent systems on the heating cyclization of 2'-hydroxychalcone

It can be seen from Table 1 that under the same reaction conditions, using pyridine-water as the reaction system, the yield of flavanones is obviously much higher than other reaction systems. It shows that the pyridine-water system is a new and important reaction system for the cyclization of 2'-hydroxychalcones to flavanones.

The effects of different volume ratios of pyridine-water systems on the heating cyclization of 2'-hydroxychalcone under the above conditions are shown in Table 2.

Table 2 Effects of different volume ratios on the heating cyclization of 2'-hydroxychalcone

It can be seen from Table 2 that under the same reaction conditions, different volume ratios of pyridine-water systems have different effects on the heating cyclization of 2'-hydroxychalcone, wherein when the volume ratio of pyridine and water is 1:1.5, the flavanone maximum yield.

Example 2: cyclization of 2'-hydroxychalcone with visible light

Visible light photocyclization of 2'-hydroxychalcone was studied in pyridine-water system. Weigh 1mmol of 2'-hydroxychalcone, dissolve it with 40ml of pyridine, pour it into a quartz glass photoreactor, add 60ml of distilled water, fix the quartz glass photoreactor on a shaker, irradiate with a 500W xenon lamp, and react 4h, the reaction mixture was concentrated under reduced pressure, separated by column chromatography (eluent: benzene:ethyl acetate=30:1), and distilled under reduced pressure; The absorbance was measured at a fixed wavelength at 251nm, the characteristic peak of alkanone, and the content of flavanone was calculated. The yield was 99.6%; and analyzed by melting point, IR, H-NMR, HRMS and so on.

The effects of different reaction systems on the visible light photocyclization of 2'-hydroxychalcone to generate flavanones under the same conditions above are shown in Table 3.

Table 3 Effect of different solvent systems on visible light photocyclization of 2'-hydroxychalcone

It can be seen from Table 3 that under the same reaction conditions, the pyridine-water system is also a new important reaction system for the visible light photocyclization of 2'-hydroxychalcone to generate flavanones.

Example 3: Photocyclization of 2'-hydroxychalcone under natural light

The natural light photocyclization reaction of 2'-hydroxychalcone was studied in pyridine-water system. Weigh 1mmol of 2'-hydroxychalcone, dissolve it with 40ml of pyridine, add it to a 250ml three-necked round-bottomed flask, add 60ml of distilled water, stir mechanically, react for 4 hours under natural light in the room, concentrate the reaction mixture under reduced pressure, and perform column chromatography Separation (eluent is benzene: ethyl acetate = 30: 1), distillation under reduced pressure; Concentrate is distilled to volume with methanol, adopts ultraviolet-visible spectrophotometer to measure absorbance at fixed wavelength at 251nm place of flavanone characteristic peak, calculates Flavanone content, the yield is 89.7%; and analyzed by melting point, IR, H-NMR, HRMS and so on.

Example 4: Cyclization of 2'-hydroxychalcone in dark room

The cyclization reaction of 2'-hydroxychalcone in darkroom was studied in pyridine-water system. Weigh 1mmol of 2'-hydroxychalcone, dissolve it with 40ml of pyridine, add it to a 250ml three-neck round-bottomed flask, then add 60ml of distilled water, stir mechanically, react in a dark room for 4h, concentrate the reaction mixture under reduced pressure, and separate by column chromatography ( The eluent is benzene:ethyl acetate=30:1), distilled under reduced pressure; the concentrate is constant volume with methanol, adopts ultraviolet-visible spectrophotometer to measure absorbance at fixed wavelength at 251nm place of flavanone characteristic peak, calculates flavanone Ketone content, the yield was 87.8%; and analyzed by melting point, IR, H-NMR, HRMS and the like.

Claims (5)

1. method by 2 '-hydroxy-benzalacetophenone heating generating flavanone by cyclization of 2 is characterized in that comprising successively following process:

(1) in reaction kettle, add 2 '-hydroxy-benzalacetophenone, pyridine and water, the volume ratio of described pyridine and water is 1:0.67～2.5, stirs, and is heated to 80～90 ℃, and the reaction times is 0.5～1.5h;

(2) with behind the post reaction mixture concentrating under reduced pressure, chromatographic separation in silicagel column, underpressure distillation then.

2. the method for claim 1, it is characterized in that: the volume ratio of described pyridine and water is 1:1.5.

3. the method by 2 '-hydroxy-benzalacetophenone visible light illumination generating flavanone by cyclization of 2 is characterized in that, comprises following process successively:

(1) in the reaction system of pyridine and water composition, the volume ratio of described pyridine and water is 1:0.67～1.5 or 1:2.5, adds 2 '-hydroxy-benzalacetophenone, stirs, and with 500W xenon lamp photograph, the reaction times is 1～4h;

(2) with the post reaction mixture concentrating under reduced pressure, chromatographic separation in silicagel column, concentrating under reduced pressure after the collection elutant.

4. the method by 2 '-hydroxy-benzalacetophenone natural lighting generating flavanone by cyclization of 2 is characterized in that, comprises following process successively:

(1) in the reaction system of pyridine and water composition, the volume ratio of described pyridine and water is that 1:0.67～2.5 add 2 '-hydroxy-benzalacetophenone, stir, and illumination under indoor natural light, the reaction times is 1～4h;

(2) with the post reaction mixture concentrating under reduced pressure, chromatographic separation in silicagel column, concentrating under reduced pressure after the collection elutant.

5. method as claimed in claim 4 is characterized in that: the volume ratio of described pyridine and water is 1:1.5.