Preparation method of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one
阅读说明：本技术 一种2,3-二氢-3,5-二羟基-6-甲基-4h-吡喃-4-酮的制备方法 (Preparation method of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one ) 是由 陈芝飞 席高磊 许克静 赵志伟 蔡莉莉 孙志涛 杨静 马胜涛 刘强 于 2019-11-07 设计创作，主要内容包括：本发明涉及一种2,3-二氢-3,5-二羟基-6-甲基-4H-吡喃-4-酮的制备方法,以单糖为原料,二级胺和酸为催化剂,乙醇为溶剂,采用美拉德反应一锅法合成2,3-二氢-3,5-二羟基-6-甲基-4H-吡喃-4-酮,同时采用硅胶色谱柱-聚酰胺树脂柱-硅胶色谱柱三次层析进行纯化,得到2,3-二氢-3,5-二羟基-6-甲基-4H-吡喃-4-酮纯品,产率最高可达20.31％,远大于文献已报道的3.125％。该合成和纯化方法具有制备工艺简单、产率高、易规模化生产等优点,具有广泛的应用前景。(The invention relates to a preparation method of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone, which takes monosaccharide as a raw material, secondary amine and acid as catalysts, ethanol as a solvent, and adopts a Maillard reaction one-pot method to synthesize the 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone, and adopts a silica gel chromatographic column, a polyamide resin column and a silica gel chromatographic column to carry out three times of chromatography for purification to obtain a pure product of the 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone, wherein the yield can reach 20.31 percent at most and is far more than 3.125 percent reported in the literature. The synthesis and purification method has the advantages of simple preparation process, high yield, easiness in large-scale production and the like, and has wide application prospect.)
1. A method for preparing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one with a structural formula
1) adding monosaccharide, secondary amine and ethanol into a reactor, stirring and dissolving, reacting at 50-70 ℃ for 1-4H, adding acid, reacting at 60-80 ℃ for 10-40H, and removing the solvent by reduced pressure evaporation to obtain a Maillard reaction product A containing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one;
2) purifying the Maillard reaction product A by silica gel chromatographic column-polyamide resin column-silica gel chromatographic column three times to obtain 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone.
2. The method of claim 1, wherein the monosaccharide includes, but is not limited to, glucose, galactose, or mannose.
3. The method of claim 1, wherein the secondary amine comprises but is not limited to pyrrolidine, diethylamine or morpholine.
4. The method for producing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one according to claim 1, wherein said acid is acetic acid or an acetic acid derivative.
5. The method for preparing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one according to claim 4, wherein the acetic acid derivative is thioglycolic acid, chloroacetic acid or oxalic acid, or any combination thereof.
6. The method of claim 1, wherein the molar ratio of the monosaccharide to the secondary amine to the acid is 1: (0.5-2): (0.5-2).
7. The process for preparing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one according to claim 1, wherein in the purification of step 2), maillard reaction product a is applied to a first silica gel column and eluted with a first eluent;
detecting the eluate by a detector, and controlling the effluent to be conveyed into a first-stage concentration device at the upper end of the polyamide resin column by a first conveying pump when the eluate contains 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one which flows out;
when the volume of the effluent in the first-stage concentration device reaches a first set value, starting the stirring and heating device, concentrating the effluent to the first set volume, then flowing into a polyamide resin column, and eluting by using a second eluent;
detecting the effluent passing through the polyamide resin column by a detector, and controlling the effluent to be conveyed into a second-stage concentration device at the upper end of a second silica gel column by a second conveying pump when the effluent containing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone flows out;
and when the volume of the effluent in the second-stage concentration device reaches a second set value, starting the stirring and heating device, concentrating the effluent to the second set volume, then flowing into a second silica gel column, and eluting by using a third eluent.
8. The method for producing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one according to claim 7, wherein the first eluent is any one of dichloromethane/methanol and chloroform/methanol.
9. The method for producing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one according to claim 7, wherein the second eluent is any one of petroleum ether/ethyl acetate, n-hexane/ethyl acetate, and petroleum ether/acetone.
10. The method for producing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one according to claim 7, wherein the third eluent is any one of dichloromethane/methanol, chloroform/methanol.
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one by adopting a Maillard reaction.
Background
The mouthfeel comfort is a key index influencing the sensory quality and the style characteristics of the cigarette, wherein the sweet taste characteristic is one of the difficult-to-distinguish sensory styles. The flavour materials used in the flavour blending of cigarettes to impart "sweet" to the smoke tend to be non-volatile, such as sugars, extractum, maillard reactants, which contribute to the "sweet" of the smoke, mainly in trace amounts or by cracking. For example, saccharides can be cleaved to produce a trace sweet substance, dianhydro glucose, and maillard reaction can produce part of pyrones, but more of the cleavage products are substances which have no effect on "sweet taste". Therefore, in the cigarette flavoring, the sweet substance capable of migrating into the smoke is directly used as the flavoring raw material, so that the flavoring is easier to quantify and master, a large amount of useless substances are removed, the 'sweet' characteristic of the cigarette is obviously improved, and the possible negative influence on the smoke is reduced.
2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone is commonly present in cigarette smoke, Maillard reaction products, sugar cracking products and natural extractum. From the structure, 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone is similar to common caramel flavor substance maltol and belongs to pyranolenone compounds, and the cyclic dicarbonyl compounds with a planar enol-carbonyl substructure often have caramel flavor. 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one was often described in the previous stage as having a caramel-like smell, but in fact its pure product had no aroma, whereas it had better water solubility and exhibited a very pronounced "sweet" character in taste compared to caramel-like fragrant substances such as maltol.
Relevant researches show that 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one is in obvious positive correlation with the 'sweet' of smoke, so that the back sweet of the smoke of the cigarette can be obviously improved, and the 'sweet' and 'moist' taste characteristics of the cigarette are highlighted. However, 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone is used as a Maillard reaction intermediate, so that the problems of low product yield, difficult preparation and purification and the like exist, and the 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone is not commercialized or applied as a sweetening agent. Therefore, the research of synthetic technology which aims at 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone, has high product yield and simple preparation process and can be produced in large scale has important significance for developing novel sweetening agents for cigarettes.
Disclosure of Invention
The invention aims to provide a preparation method of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone, which aims to solve the problems of low product yield, difficult preparation and purification and the like in the prior art because 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone is used as a Maillard reaction intermediate.
The invention is realized by the following technical scheme:
a method for preparing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one with a structural formula
1) adding monosaccharide, secondary amine and ethanol into a reactor, stirring and dissolving, reacting at 50-70 ℃ for 1-4 h, adding acid, reacting at 60-80 ℃ for 10-40 h, and evaporating under reduced pressure to remove a solvent (temperature range: 25-50 ℃ and the pressure range is 5-200 Pa) to obtain a Maillard reaction product A containing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one;
2) purifying the Maillard reaction product A by silica gel chromatographic column-polyamide resin column-silica gel chromatographic column three times to obtain 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone.
The monosaccharide includes, but is not limited to, glucose, galactose, or mannose.
The secondary amine includes, but is not limited to, tetrahydropyrrole, diethylamine, or morpholine.
The acid is acetic acid or an acetic acid derivative.
The acid is thioglycolic acid, chloroacetic acid or oxalic acid, and one or any combination of the three.
The molar ratio of the monosaccharide to the secondary amine to the acid is 1: (0.5-2): (0.5-2).
Purifying step 2), namely adding the Maillard reaction product A into a first silica gel column, and eluting by using a first eluent;
detecting the eluate by a detector, and controlling the effluent to be conveyed into a first-stage concentration device at the upper end of the polyamide resin column by a first conveying pump when the eluate contains 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one which flows out;
when the volume of the effluent in the first-stage concentration device reaches a first set value, starting the stirring and heating device, concentrating the effluent to the first set volume, then flowing into a polyamide resin column, and eluting by using a second eluent;
detecting the effluent passing through the polyamide resin column by a detector, and controlling the effluent to be conveyed into a second-stage concentration device at the upper end of a second silica gel column by a second conveying pump when the effluent containing 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone flows out;
and when the volume of the effluent in the second-stage concentration device reaches a second set value, starting the stirring and heating device, concentrating the effluent to the second set volume, then flowing into a second silica gel column, and eluting by using a third eluent.
The first eluent is any one of dichloromethane/methanol and trichloromethane/methanol.
The second eluent is any one of petroleum ether/ethyl acetate, n-hexane/ethyl acetate and petroleum ether/acetone.
The third eluent is any one of dichloromethane/methanol and trichloromethane/methanol.
The invention has the beneficial effects that:
according to the invention, monosaccharide is used as a raw material, secondary amine and acid are used as catalysts, ethanol is used as a solvent, 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one is synthesized by adopting a Maillard reaction one-pot method, and meanwhile, a silica gel chromatographic column, a polyamide resin column and a silica gel chromatographic column are adopted for three times of chromatography for purification, so that a pure product of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one is obtained, the yield can reach 20.31% at most, and is far greater than 3.125% reported in the literature. The synthesis and purification method has the advantages of simple preparation process, high yield, easiness in large-scale production and the like, and has wide application prospect.
Drawings
FIG. 1 is a schematic diagram of an apparatus for separating and purifying 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one;
FIG. 2 is a NMR chart of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one;
FIG. 3 is a NMR carbon spectrum of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one;
FIG. 4 is a TIC diagram of the 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one;
FIG. 5 is a mass spectrum of the 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one.
Description of the reference numerals
1 a first silica gel column, 2 polyamide resin columns, 3 a second silica gel column, 4 detectors, 51 a first-stage concentration device, 52 a second-stage concentration device, 6 delivery pumps, 7 a liquid storage tank, 8 a liquid inlet of the chromatographic column, 9 a waste liquid outlet and 10 a product outlet.
Detailed Description
The technical solutions of the present invention are described in detail below by examples, and the following examples are only exemplary and can be used only for explaining and explaining the technical solutions of the present invention, but not construed as limiting the technical solutions of the present invention.
As shown in figure 1, the device for separating and purifying 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-ketone in the technical scheme comprises a first silica gel column 1, a
The outlet of the first silica gel column is connected with the inlet of a first delivery pump through a
In the technical scheme of the application, the separation and purification device is used.