Process for the preparation of 1,4-anhydro-D-glucopyranose and its use

Abstract

The application belongs to the technical field of organic synthesis and particularly relates to a preparation method and application of 1,4-dehydrated-D-glucopyranose. The preparation method is that 1,4-dehydrated-D-glucopyranose is synthesized from methyl-alpha-D-glucopyranoside as a starting material through three-step reactions. Compared with the synthesis method reported in the prior art, the reaction of the application adopts a more accurate hydroxyl protection strategy, the process is simpler, the atom utilization rate is high, the total yield of the three-step reaction is higher than 60%, the method is suitable for large-scale production, and has a wide application prospect. The flavor raw material added into cigarettes can increase the oral sweet and smooth feeling, enrich the tobacco aroma, increase the smoke transmittance and delicacy, and improve the aftertaste comfort, and has potential application value.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 1,4-dehydrated-D-pyranose and its application as a sweet flavoring ingredient in cigarettes. Background Technology

[0002] 1,4-Dehydro-D-glucopyranose, a pyran compound formed from sugar degradation, is volatile, lipid-soluble, and water-soluble. However, there are few reports on the synthesis of 1,4-dehydro-D-glucopyranose to date. In 2010, Neil R. Thomas synthesized 1,4-dehydro-D-glucopyranose from methyl glucoside via a six-step reaction with an overall yield of 23.8%. This synthetic method is cumbersome, involving multiple hydroxyl protection steps and low atom utilization. Therefore, research into novel synthetic methods for 1,4-dehydro-D-glucopyranose is of great significance. Summary of the Invention

[0003] The purpose of this invention is to provide a simple, high-yield, and easily scalable method for preparing 1,4-dehydrated-D-pyranose and its application as a specialty sweet flavoring ingredient in cigarettes, in order to solve the problem of low overall yield of currently synthesized 1,4-dehydrated-D-pyranose.

[0004] To achieve the above objectives, this application employs the following technical solution:

[0005] A method for preparing 1,4-dehydrated-D-glucopyranose, comprising the following steps:

[0006]

[0007] Step 1, Preparation of intermediate compound (II): In a reaction flask, the raw material methyl-α-D-glucopyranoside (I), benzyl bromide, catalyst and solvent were added in sequence. The mixture was stirred at 60-120℃ for 10-24 h. After the reaction was completed, the mixture was washed with saturated sodium chloride solution, extracted and separated to obtain the organic phase, dried with anhydrous Na2SO4, and the solvent was removed by vacuum evaporation to obtain intermediate compound (II).

[0008] Step 2, preparation of compound (III): In a reaction flask, intermediate compound (II), catalyst, additive and solvent were added in sequence and reacted at 40-80℃ for 4-12 h. After the reaction was completed, saturated sodium chloride solution and dichloromethane were added, and the organic phase was extracted and separated. The organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum evaporation, and the intermediate compound (III) was purified by column chromatography.

[0009] Step 3, Preparation of target product (IV): In a reaction flask, intermediate compound (III), catalyst and solvent are added sequentially, and the reaction is carried out at 20-50℃ for 24-72 h. After the reaction is completed, the solvent is removed by vacuum distillation, and the crude product is separated by silica gel column chromatography to obtain the target product 1,4-dehydrated-D-pyranose (IV).

[0010] Preferably, in step 1, the catalyst is one of silver oxide, tin oxide, or dibutyltin oxide, and the solvent is one of benzene, toluene, or o-xylene.

[0011] Preferably, the molar ratio of methyl-α-D-glucopyranoside (I), catalyst and benzyl bromide is 1:(0.5-1.5):(1.0-2.0).

[0012] Preferably, in step 2, the catalyst is one of ferric trifluoromethanesulfonate, ferric chloride, or ferric tribromide, the additive is one of anhydrous calcium chloride or anhydrous sodium sulfate, and the solvent is one of acetonitrile, methanol, or tetrahydrofuran.

[0013] Preferably, the molar ratio of intermediate compound (II), catalyst and additive is 1:(0.5-3):(1-2).

[0014] Preferably, in step 3, the catalyst is one of Raney nickel or zinc powder, and the solvent is one of acetonitrile, dichloromethane or ethanol.

[0015] Preferably, the mass ratio of compound (III) to catalyst is 1:(0.1-1).

[0016] One application is that the 1,4-dehydrated-D-pyranose prepared according to any of the above methods is used as a sweet flavoring ingredient in cigarettes.

[0017] Preferably, the amount of 1,4-dehydrated-D-pyranose glucose added as a sweet flavoring ingredient for tobacco is 1 to 100 ppm of the weight of the cigarette tobacco.

[0018] The beneficial effects of this invention are:

[0019] This technical solution synthesizes 1,4-dehydro-D-glucopyranoside as a starting material through a three-step reaction. Compared with the synthesis methods reported in existing literature, the reaction of this invention employs a more precise hydroxyl protection strategy, resulting in a simpler process, higher atom utilization, and an overall yield of over 60% in the three-step reaction. It is suitable for large-scale production and has broad application prospects. Adding this flavoring ingredient to cigarettes can increase the sweetness in the mouth, enrich the aroma, improve the permeability and smoothness of the smoke, and enhance the comfort of the aftertaste, demonstrating potential application value. Detailed Implementation

[0020] The technical solutions of the present invention will be described in detail below through embodiments. The following embodiments are merely exemplary and can only be used to explain and illustrate the technical solutions of the present invention, and should not be construed as limiting the technical solutions of the present invention.

[0021] The synthetic steps for the 1,4-dehydro-D-pyranose glucose structure of this application are as follows:

[0022]

[0023] Unless otherwise specified, all reagents and instruments used in the synthesis process of this application are obtainable through normal commercial channels.

[0024] Example 1

[0025] A method for preparing 1,4-dehydrated-D-glucopyranose, comprising the following steps:

[0026] Step 1: Preparation of intermediate compound (II): In a 100 mL round-bottom flask, 1.94 g (10 mmol) of methyl-α-D-glucopyranoside, 3.73 g (15 mmol) of dibutyltin oxide, 2.05 g (12 mmol) of benzyl bromide, and 30 mL of toluene were added, and the mixture was reacted at 110 °C for 12 hours. After the reaction was completed, the mixture was washed with 20 mL of dichloromethane and 20 mL of saturated sodium chloride solution, and the organic phase was extracted and dried over anhydrous Na₂SO₄. The solvent was removed under reduced pressure, and the mixture was purified by column chromatography to obtain 2.25 g of intermediate compound (II), with a yield of 79.2%.

[0027] Step 2, Preparation of intermediate compound (III): In a reaction flask, 1.42 g (5 mmol) of intermediate compound (II), 1.03 g (5 mmol) of ferric trifluoromethanesulfonate, 0.55 g (5 mmol) of anhydrous calcium chloride and 10 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 50 °C for 8 h. After the reaction was completed, the solvent was removed by vacuum distillation. The crude product was separated by silica gel column chromatography to obtain 1.07 g of intermediate compound (III), with a yield of 85.2%.

[0028] Step 3, Preparation of target product (IV): In a reaction flask, 252 mg (1 mmol) of intermediate compound (III), 50.4 mg of Ranney nickel, and 5 mL of ethanol were added sequentially. The reaction was carried out at 25 °C for 48 h. After the reaction was completed, the mixture was filtered, and the solvent was removed by vacuum distillation. The crude product was separated by silica gel column chromatography to obtain 154 mg of target product (IV), with a yield of 95.1%. The overall yield of the three-step reaction was 64.1%.

[0029] Example 2

[0030] A method for preparing 1,4-dehydrated-D-glucopyranose, comprising the following steps:

[0031] Step 1: Preparation of intermediate compound (II): In a 100 mL round-bottom flask, 1.94 g (10 mmol) of methyl-α-D-glucopyranoside, 2.49 g (10 mmol) of dibutyltin oxide, 2.56 g (15 mmol) of benzyl bromide, and 30 mL of toluene were added, and the mixture was reacted at 110 °C for 12 hours. After the reaction was completed, the mixture was washed with 20 mL of dichloromethane and 20 mL of saturated sodium chloride solution, and the organic phase was extracted and dried over anhydrous Na₂SO₄. The solvent was removed under reduced pressure, and the mixture was purified by column chromatography to obtain 2.31 g of intermediate compound (II), with a yield of 81.3%.

[0032] Step 2, Preparation of intermediate compound (III): In a reaction flask, 1.42 g (5 mmol) of intermediate compound (II), 1.03 g (5 mmol) of ferric trifluoromethanesulfonate, 0.71 g (5 mmol) of anhydrous sodium sulfate and 10 mL of tetrahydrofuran were added sequentially. The reaction was carried out at 50 °C for 8 h. After the reaction was completed, the solvent was removed by vacuum distillation. The crude product was separated by silica gel column chromatography to obtain 1.01 g of intermediate compound (III), with a yield of 80.1%.

[0033] Step 3, Preparation of target product (IV): In a reaction flask, 252 mg (1 mmol) of intermediate compound (III), 25.2 mg of Ranney nickel, and 5 mL of ethanol were added sequentially. The reaction was carried out at 25 °C for 48 h. After the reaction was completed, the mixture was filtered, and the solvent was removed by vacuum distillation. The crude product was separated by silica gel column chromatography to obtain 150 mg of target product (IV), with a yield of 92.6%. The overall yield of the three-step reaction was 60.3%.

[0034] Flavor performance test: A certain amount of 1,4-dehydrated-D-glucopyranose (IV) was weighed and diluted with ethanol to prepare a 5% solution for later use. 100g of unflavored blank cigarette tobacco was weighed and evenly spread on a clean tray. The ethanol solution of compound IV was evenly sprayed onto the tobacco to obtain cigarette tobacco with specific gravities of 0.5ppm, 1ppm, 5ppm, 10ppm, 50ppm, and 100ppm of compound IV to tobacco. The tobacco was sealed and left to stand for 4 hours, then dried in a 50℃ oven. The tobacco was then humidified with distilled water to the standard moisture content (12%), rolled into standard cigarettes, and equilibrated for 48 hours (humidity 60% ± 2%, temperature 22 ± 1℃) before evaluation. The control sample was a blank cigarette, equilibrated for 48 hours under the same temperature and humidity conditions.

[0035] Table 1 Sensory evaluation results

[0036]

[0037]

[0038] As shown in Table 1, 1,4-dehydrated-D-pyranose has a significant effect on improving and modifying the aroma of cigarettes, reducing irritation, improving the taste, and making the aftertaste clean and comfortable. Its prominent "sweetness" enhances the "sweetness" of cigarette smoke, highlighting the "sweet" and "smooth" flavor characteristics of cigarettes. Recommended dosage: 1-100 ppm.

[0039] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing 1,4-dehydrated-D-glucopyranose, characterized in that, The steps are as follows: ， Step 1, Preparation of intermediate compound (II): In a reaction flask, the raw material methyl-α-D-glucopyranoside (I), benzyl bromide, catalyst and solvent were added in sequence. The mixture was stirred at 60-120 °C for 10-24 h. After the reaction was completed, the mixture was washed with saturated sodium chloride solution, extracted and separated to obtain the organic phase, dried with anhydrous Na2SO4, and the solvent was removed by vacuum evaporation to obtain intermediate compound (II). Step 2, Preparation of compound (III): In a reaction flask, intermediate compound (II), catalyst, additive and solvent were added in sequence and reacted at 40-80 °C for 4-12 h. After the reaction was completed, saturated sodium chloride solution and dichloromethane were added, and the organic phase was extracted and separated. The organic phase was dried with anhydrous Na2SO4, the solvent was removed by vacuum evaporation, and the intermediate compound (III) was purified by column chromatography. Step 3, Preparation of target product (IV): In a reaction flask, intermediate compound (III), catalyst and solvent were added sequentially, and the reaction was carried out at 20-50 °C for 24-72 h. After the reaction was completed, the solvent was removed by vacuum distillation, and the crude product was separated by silica gel column chromatography to obtain the target product 1,4-dehydrated-D-pyranose (IV). In step 1, the catalyst is one of silver oxide, tin oxide or dibutyltin oxide, and the solvent is one of benzene, toluene or o-xylene; In step 2, the catalyst is one of ferric trifluoromethanesulfonate, ferric chloride or ferric tribromide, the additive is one of anhydrous calcium chloride or anhydrous sodium sulfate, and the solvent is one of acetonitrile, methanol or tetrahydrofuran. In step 3, the catalyst is either Raney nickel or zinc powder, and the solvent is either acetonitrile, dichloromethane, or ethanol.

2. The method for preparing 1,4-dehydrated-D-pyranose according to claim 1, characterized in that, The molar ratio of methyl-α-D-glucopyranoside (I), catalyst and benzyl bromide is 1:(0.5-1.5):(1.0-2.0).

3. The method for preparing 1,4-dehydrated-D-pyranose according to claim 1, characterized in that, The molar ratio of intermediate compound (II), catalyst and additive is 1:(0.5-3):(1-2).

4. The method for preparing 1,4-dehydrated-D-glucopyranose according to claim 1, characterized in that, The mass ratio of compound (III) to catalyst is 1:(0.1-1).

5. An application characterized in that, The 1,4-dehydrated-D-pyranose prepared according to any one of claims 1 to 4 is used as a sweet flavoring ingredient in cigarettes.

6. The application according to claim 5, characterized in that, The amount of 1,4-dehydrated-D-pyranose glucose added as a sweet flavoring ingredient for tobacco is 1 to 100 ppm of the weight of cigarette tobacco.

Images