Azacyclo-modified dehydrated sugar as well as preparation method and application thereof

Abstract

The invention discloses azacyclo-modified dehydrated sugar as well as a preparation method and application thereof, the structural formula of the azacyclo-modified dehydrated sugar is as follows: # imgabs0 #, and the preparation method of the azacyclo-modified dehydrated sugar comprises the following steps: firstly, adding raw materials 1, 4: 3, 6-dianhydro-D-glucopyranose, chloroacetyl chloride and a heterocyclic compound into a reaction flask, and uniformly stirring a reaction system; sequentially adding a photocatalyst, alkali and a solvent, and replacing the gas in the reaction bottle with nitrogen; uniformly stirring the reaction system, and reacting at 20 DEG C for 12-24 hours under the condition of specific wavelength irradiation of an LED lamp; and after the reaction is finished, adding dichloromethane and a saturated sodium chloride solution, extracting and separating to obtain an organic phase, drying by using anhydrous sodium sulfate, evaporating to remove a reaction solvent, and purifying residues by using silica gel column chromatography to obtain the azacyclo-modified dehydrated sugar compound. According to the invention, 1, 4: 3, 6-dianhydro-D-glucopyranose is used as an initial raw material to synthesize the azacyclo-modified dehydrated sugar. When the spice is added into cigarettes, the cigarette fragrance can be enriched, the cigarettes are endowed with nut fragrance, sweet fragrance and scorch fragrance, and the aftertaste comfort is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a nitrogen heterocycle modified anhydrosugar and a preparation method and application thereof. Background Art

[0002] 1,4:3,6-dianhydro-D-pyranose glucose is commonly found in cigarette smoke and sugar decomposition products. It is a pyran compound generated by sugar degradation. It has the characteristics of volatility, fat solubility and water solubility, and can increase the sweetness of cigarettes.

[0003] Hybrid compounds such as pyrazine and pyridine have prominent aroma characteristics such as nutty aroma and chocolate aroma. They can also increase smoke concentration and improve the mellowness of smoke. They are widely used in cigarette flavoring.

[0004] Therefore, chemical synthesis can be used to design and synthesize compounds that have the advantages of both and add them to cigarettes as tobacco flavorings. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a nitrogen heterocycle modified anhydrosugar and a preparation method and application thereof, which are simple to operate, high in yield and easy to mass produce.

[0006] The technical problem to be solved by the present invention is achieved through the following technical solutions:

[0007] A nitrogen heterocycle-modified anhydrosugar, wherein the nitrogen heterocycle-modified anhydrosugar has the following structural formula:

[0008] .

[0009] A method for preparing a nitrogen heterocycle-modified anhydrosugar comprises the following steps:

[0010]

[0011] (1) In a reaction bottle, first add the raw materials 1,4:3,6-dianhydro-D-pyranose, chloroacetyl chloride and heterocyclic compound, and stir the reaction system evenly; then add the photocatalyst, base and solvent in sequence, and replace the gas in the reaction bottle with nitrogen;

[0012] (2) After the reaction system is stirred evenly, the reaction is carried out at 20°C for 12 to 24 hours under the condition of LED light with a specific wavelength;

[0013] (3) After the reaction is completed, dichloromethane and saturated sodium chloride solution are added, and the organic phase is extracted and separated, and then dried over anhydrous sodium sulfate. The reaction solvent is evaporated, and the residue is purified by silica gel column chromatography to obtain a nitrogen heterocycle-modified anhydrosugar compound.

[0014] Preferably, in the above technical solution, in step (1), the molar ratio of 1,4:3,6-dianhydro-D-pyranose to the photocatalyst and the base is 1:(0.01-0.2):(1.0-3.0).

[0015] Preferably, in the above technical solution, in step (1), the photocatalyst is ferric chloride, ruthenium chloride or cobalt chloride, the base is potassium tert-butoxide, lithium tert-butoxide or sodium tert-butoxide, and the solvent is one or more of N, N-dimethylformamide, N, N-dimethylacetamide or acetonitrile.

[0016] Preferably, in the above technical solution, in step (1), the molar ratio of 1,4:3,6-dianhydro-D-pyranose, chloroacetyl chloride and the heterocyclic compound is 1:(1.0-1.5):(1.0-1.5).

[0017] Preferably, in the above technical solution, in step (2), the wavelength range of light is 300-400 nm.

[0018] Preferably, in the above technical solution, in step (3), the extraction time is: 1-5 min; the volume ratio of dichloromethane to saturated sodium chloride is 1:1; the silica gel column chromatography uses petroleum ether and ethyl acetate as eluents, with a volume ratio of 3:1-1:1, and gradient elution.

[0019] Application of nitrogen heterocyclic modified anhydrosugar in cigarettes.

[0020] Preferably, in the above technical solution, the nitrogen heterocyclic modified anhydrosugar is used as a flavoring in cigarettes, and the added amount is 0.1 to 10 ppm based on the mass of cigarette shreds.

[0021] A cigarette comprising nitrogen heterocycle-modified anhydrosugar.

[0022] The above technical solution of the present invention has the following beneficial effects:

[0023] The present application uses 1,4:3,6-dianhydro-D-pyranose glucose as a starting material to synthesize nitrogen heterocyclic modified anhydrosugar. The flavor is added to cigarettes to enrich the tobacco flavor, give the cigarettes nutty, sweet and caramel flavors, and improve the comfort of the aftertaste. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.

[0025] Figure 1 The compound of Example 1 1 H spectrum.

[0026] Figure 2 The compound of Example 113 C spectrum.

[0027] Figure 3 The compound of Example 2 1 H spectrum.

[0028] Figure 4 The compound of Example 2 13 C spectrum.

[0029] Figure 5 The compound of Example 3 1 H spectrum.

[0030] Figure 6 The compound of Example 3 13 C spectrum. DETAILED DESCRIPTION

[0031] Various exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings. It should be noted that the relative arrangement of components and steps, numerical expressions and numerical values ​​set forth in these embodiments do not limit the scope of the present invention unless otherwise specifically stated.

[0032] Unless otherwise specified, the reagents used in this application are all commercially available or obtained through commercial channels, or can be prepared by referring to existing chemical methods.

[0033] Example 1

[0034] A method for preparing nitrogen heterocycle-modified anhydrosugar:

[0035] (1) In a 100 mL round-bottom flask, add 1.44 g (10 mmol) of 1,4:3,6-dianhydro-D-pyranose, 1.24 g (11 mmol) of chloroacetyl chloride, and 0.94 g (10 mmol) of 4-aminopyridine. Stir the reaction system evenly. Then, add 0.162 g (1 mmol) of ferric chloride, 2.24 g (20 mmol) of potassium tert-butoxide, and 20 mL of acetonitrile in sequence. Replace the gas in the reaction flask with nitrogen.

[0036] (2) After the reaction system is stirred evenly, it is reacted at 20°C for 12 hours under the condition of irradiation with a specific wavelength of 400nm by LED light.

[0037] (3) After the reaction, dichloromethane and saturated sodium chloride solution were added, and the organic phase was extracted and separated, and then dried over anhydrous sodium sulfate. The reaction solvent was evaporated and the residue was purified by silica gel column chromatography to obtain 1.80 g of the target compound with a yield of 64.8%.

[0038] The structural formula of the target compound is as follows:

[0039]

[0040] Structural characterization of compounds:

[0041] 1 H NMR (400 MHz, CDCl3) δ 8.53 (dd, J = 4.9, 1.4 Hz, 2H), 8.40 (s,1H), 7.53 (dd, J = 4.8, 1.6 Hz, 2H), 5.58 (d, J = 1.2 Hz, 1H), 5.25 (dd, J =4.7, 3.3 Hz, 1H), 4.34 – 4.17 (m, 4H), 4.11 (d, J = 15.6 Hz, 1H), 4.04 (d, J= 10.8 Hz, 1H), 3.96 (dd, J = 10.8, 2.3 Hz, 1H), 3.65 (s, 1H); 13 C NMR (400MHz, CDCl3) δ 167.58, 150.82, 143.83, 113.72, 98.85, 86.84, 79.70, 76.07,71.76, 68.43; MS (ESI): m / z 279.09 [M + H + ].

[0042] Example 2

[0043] A method for preparing nitrogen heterocycle-modified anhydrosugar:

[0044] (1) In a 100 mL round-bottom flask, add 1.44 g (10 mmol) of 1,4:3,6-dianhydro-D-pyranose, 1.24 g (11 mmol) of chloroacetyl chloride, and 0.95 g (10 mmol) of 2-aminopyrazine. Stir the reaction system evenly. Then, add 0.162 g (1 mmol) of ferric chloride, 2.24 g (20 mmol) of potassium tert-butoxide, and 20 mL of acetonitrile in sequence. Replace the gas in the reaction flask with nitrogen.

[0045] (2) After the reaction system is stirred evenly, it is reacted at 20°C for 16 h under the condition of irradiation with a specific wavelength of 400 nm by LED light.

[0046] (3) After the reaction, dichloromethane and saturated sodium chloride solution were added, and the organic phase was extracted and separated, and then dried over anhydrous sodium sulfate. The reaction solvent was evaporated and the residue was purified by silica gel column chromatography to obtain 2.10 g of the target compound with a yield of 75.2%.

[0047] The structural formula of the target compound is as follows:

[0048]

[0049] Structural characterization of compounds:

[0050] 1 H NMR (400 MHz, CDCl3) δ 9.56 (d, J = 1.3 Hz, 1H), 8.76 (s, 1H), 8.39 (d, J = 2.5 Hz, 1H), 8.29 (dd, J = 2.4, 1.6 Hz, 1H), 5.60 (d, J = 1.1 Hz,1H), 5.24 (dd, J = 4.7, 3.2 Hz, 1H), 4.27 (m, 3H), 4.17 (d, J = 15.5 Hz, 1H), 4.04 (d, J = 10.8 Hz, 1H), 3.96 (dd, J = 10.8, 2.4 Hz, 1H), 3.65 (s, 1H); 13 CNMR (400 MHz, CDCl3) δ 167.19, 147.20, 142.25, 140.84, 137.04, 98.82, 86.83,79.86, 79.61, 75.99, 71.81, 68.27; MS (ESI): m / z 280.10[M+H + ].

[0051] Example 3

[0052] A method for preparing nitrogen heterocycle-modified anhydrosugar:

[0053] (1) In a 100 mL round-bottom flask, add 1.44 g (10 mmol) of 1,4:3,6-dianhydro-D-pyranose, 1.24 g (11 mmol) of chloroacetyl chloride, and 1.10 g (11 mmol) of 2-aminothiazole. Stir the reaction system evenly. Then, add 0.324 g (2 mmol) of ferric chloride, 3.36 g (30 mmol) of potassium tert-butoxide, and 30 mL of acetonitrile in sequence. Replace the gas in the reaction flask with nitrogen.

[0054] (2) After the reaction system is stirred evenly, it is reacted at 20°C for 24 h under the condition of irradiation with a specific wavelength of 400 nm by LED light.

[0055] (3) After the reaction was completed, dichloromethane and saturated sodium chloride solution were added, and the organic phase was extracted and separated and dried over anhydrous sodium sulfate. The reaction solvent was evaporated and the residue was purified by silica gel column chromatography to obtain 2.03 g of the target compound with a yield of 71.6%.

[0056] The structural formula of the target compound is as follows:

[0057]

[0058] Structural characterization of compounds:

[0059] 1 H NMR (400 MHz, CDCl3) δ 9.85 (s, 1H), 7.48 (d, J = 3.5 Hz, 1H), 7.02(d, J = 3.5 Hz, 1H), 5.57 (s, 1H), 5.23 (dd, J = 4.6, 3.4 Hz, 1H), 4.34 (d, J = 15.5 Hz, 1H), 4.24 (dd, J = 9.1, 6.4 Hz, 3H), 4.03 (d, J = 10.7 Hz, 1H), 3.95 (dd, J = 10.8, 2.3 Hz, 1H), 3.64 (s, 1H); 13 C NMR (400 MHz, CDCl3) δ166.47, 156.93, 137.62, 114.07, 98.76, 86.80, 79.81, 79.61, 76.00, 71.79,67.74; MS (ESI): m / z 285.06 [M + H + ].

[0060] Flavor performance test:

[0061] Weigh a certain amount of nitrogen heterocyclic modified dehydrated sugar, dilute it with ethanol to a 1% solution, and set aside. Weigh 100 g of blank cigarette shreds without flavoring or adding materials, evenly spread them on a clean tray, and evenly spray the ethanol solution of the compound on the shredded tobacco to obtain shredded tobacco with a compound to shredded ratio of 0.1 ppm, 1 ppm, 10 ppm, and 20 ppm. Seal and place for 4 hours, put in a 50℃ oven to dry, humidify with distilled water to the standard moisture (12%), roll into standard cigarettes, balance the moisture (humidity 60%±2%, temperature 22±1℃) for 48 hours, and then evaluate. The control sample is a blank cigarette, and the control sample is balanced for 48 hours under the same temperature and humidity conditions.

[0062] Table 1 Sensory evaluation results

[0063]

[0064] It can be seen from Table 1 that nitrogen heterocyclic modified anhydrosugar can significantly improve and modify the aroma of cigarettes, give cigarettes nutty, sweet and caramel aromas, and improve the taste of smoking. The appropriate dosage is 0.1-10 ppm.

[0065] Although the present invention has been disclosed as above by the embodiments, it is not intended to limit the present invention. Any person skilled in the art may make various choices and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention is limited by the claims and their equivalents.

Claims

1. A nitrogen heterocycle modified anhydrosugar, characterized in that: The structural formula of the nitrogen heterocycle modified anhydrosugar is as follows:

2. The method for preparing the nitrogen heterocycle modified anhydrosugar according to claim 1, characterized in that: The following steps are involved: (1) In a reaction bottle, first add the raw materials 1,4:3,6-dianhydro-D-pyranose, chloroacetyl chloride and heterocyclic compound, and stir the reaction system evenly; then add the photocatalyst, alkali and solvent in sequence, and replace the gas in the reaction bottle with nitrogen; (2) After the reaction system is stirred evenly, the reaction is carried out at 20°C for 12 to 24 hours under the condition of irradiation with a specific wavelength of LED light; (3) After the reaction is completed, dichloromethane and saturated sodium chloride solution are added, and the organic phase is extracted and separated and dried over anhydrous sodium sulfate. The reaction solvent is evaporated and the residue is purified by silica gel column chromatography to obtain a nitrogen heterocycle modified anhydrosugar compound.

3. The method for preparing the nitrogen heterocycle modified anhydrosugar according to claim 2, characterized in that: In step (1), the molar ratio of 1,4:3,6-dianhydro-D-pyranose glucose to the photocatalyst and the base is 1:(0.01-0.2):(1.0-3.0).

4. The method for preparing the nitrogen heterocycle modified anhydrosugar according to claim 2, characterized in that: In step (1), the photocatalyst is ferric chloride, ruthenium chloride or cobalt chloride, the base is potassium tert-butoxide, lithium tert-butoxide or sodium tert-butoxide, and the solvent is one or more of N, N-dimethylformamide, N, N-dimethylacetamide or acetonitrile.

5. The method for preparing the nitrogen heterocycle modified anhydrosugar according to claim 2, characterized in that: In step (1), the molar ratio of 1,4:3,6-dianhydro-D-pyranose, chloroacetyl chloride and the heterocyclic compound is 1:(1.0-1.5):(1.0-1.5).

6. The method for preparing the nitrogen heterocycle modified anhydrosugar according to claim 2, characterized in that: In step (2), the light wavelength range is 300 to 400 nm.

7. The method for preparing the nitrogen heterocycle modified anhydrosugar according to claim 2, characterized in that: In step (3), the extraction time is 1-5 min; the volume ratio of dichloromethane to saturated sodium chloride is 1:1; the silica gel column chromatography uses petroleum ether and ethyl acetate as eluents, with a volume ratio of 3:1-1:1, and gradient elution.

8. Use of the nitrogen-heterocyclic modified anhydrosugar according to claim 1 or the nitrogen-heterocyclic modified anhydrosugar prepared according to the preparation method according to any one of claims 2 to 7 in cigarettes.

9. The use according to claim 8, characterized in that: The nitrogen heterocyclic modified dehydrated sugar is used as a flavor in cigarettes, and the added amount is 0.1 to 10 ppm of the mass of the cigarette shreds.

10. A cigarette, characterized in that: The cigarette contains the nitrogen heterocycle modified anhydrosugar according to claim 1 or the nitrogen heterocycle modified anhydrosugar prepared by the preparation method according to any one of claims 2 to 7, and the preparation method and application thereof.

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