Leaf alcohol carbonate precursor perfume, and synthesis method and application thereof

Abstract

The invention discloses a leaf alcohol carbonate precursor fragrance spice, and a synthesis method and application thereof. The method comprises the following steps: reacting dimethyl malate with triphosgene and pyridine to obtain dimethyl malate chloroformate; the method comprises the following steps: dissolving leaf alcohol in CH2Cl2, adding alkali DMAP, then adding dimethyl malate chloroformate, and reacting to obtain dimethyl malate-leaf alcohol carbonate; and placing the dimethyl malate-leaf alcohol carbonate in a phosphate buffer solution, and treating with lipase to obtain the malic acid-leaf alcohol carbonate or malic acid monomethyl ester-leaf alcohol carbonate precursor fragrance perfume. The obtained leaf alcohol carbonate precursor fragrance spice is applied to heating cigarettes, and leaf alcohol can be released when the heated cigarettes are smoked, so that green fragrance is increased.

Description

Technical Field

[0001] The present invention belongs to the technical field of tobacco flavorings, and more specifically relates to leaf carbonate derived from malic acid, a preparation method thereof, and the application of the leaf carbonate as a latent flavoring in heated cigarettes. Background Art

[0002] Leaf alcohol has a grassy aroma and is widely used as a green flavoring in cigarette flavoring. However, due to its low boiling point (156-157°C at normal pressure), leaf alcohol is easily lost in cigarettes through volatilization, making it difficult to fully utilize its intended function. To reduce leaf alcohol volatilization, a report has used the Koenigs-Knorr synthesis method to prepare leaf alcohol into non-volatile leaf alcohol glycosides (Journal of Jiangsu University (Natural Science Edition), 2007). This method releases leaf alcohol through cleavage of glycosidic bonds during cigarette combustion. However, this method uses expensive reagents such as silver salts and is cumbersome, making it unsuitable for production. Furthermore, the glycoside cleavage temperature is relatively high (>300°C), making it difficult to release at the heating temperatures of heated cigarette tobacco (100-300°C). In addition to glycosides, carbonate derivatives of hydroxyl-containing flavors have also been reported, such as 3-oxo-α-ionol ethyl carbonate (Journal of the Chinese Tobacco Society, 2001), menthol ethyl carbonate (invention patent application 202100240446.5), and menthol phenol carbonate (Journal of Zhengzhou Institute of Light Industry (Natural Science Edition), 2007). However, since the ligands of these hydroxyl-containing flavor carbonates are still lipophilic and volatile substances, the obtained carbonates are still quite volatile and difficult to use as non-volatile latent flavors.

[0003] In view of this, it is necessary to design a new leaf alcohol latent aroma structure so that it is not easy to volatilize at room temperature, but can also decompose and release leaf alcohol efficiently at the lower heating temperature of tobacco in heated cigarettes. Summary of the Invention

[0004] In view of the problem that leaf alcohol in cigarettes is easily volatile and lost in the prior art, it is difficult to play its due role. The present invention provides a malic acid-leaf alcohol carbonate derived from malic acid, its preparation method and its application as a latent fragrance in cigarettes. The carboxyl group of malic acid has hydrophilicity and strong hydrogen bonding, and is a non-volatile acid. In addition, its β-hydroxy acid structure is easily dehydrated by heat. Utilizing this property, it can be designed to connect leaf alcohol by carbonate bond at its hydroxyl position, thereby achieving stable non-volatility (carboxyl hydrogen bonding), and at the heated temperature of heated cigarette shreds, the malic acid unit is preferentially dehydrated and fractured, and the carbonate bond decomposes and releases the purpose of leaf alcohol. Based on this, the present invention uses dimethyl malate and leaf alcohol as raw materials, and can obtain malic acid-leaf alcohol carbonate by a three-step reaction of chloroformate esterification, esterification and enzymatic hydrolysis, with a simple operating method.

[0005] In order to solve the above problems, the present invention adopts the following technical solutions:

[0006] Leaf carbonate latent fragrance, including malic acid-leaf carbonate or malic acid monomethyl ester-leaf carbonate, its racemate and enantiomer are as follows:

[0007]

[0008] The method for synthesizing the leaf alcohol carbonate latent fragrance of the present invention comprises the following steps:

[0009] (1) reacting dimethyl malate with triphosgene and pyridine to obtain dimethyl malate chloroformate 3;

[0010] (2) Dissolve leaf alcohol in CH2Cl2, add 4-dimethylaminopyridine DMAP, and then add dimethyl malate chloroformate to obtain dimethyl malate-leaf alcohol carbonate 4 after reaction;

[0011] (3) placing dimethyl malate-leaf carbonate in a phosphate buffer solution and treating it with lipase to obtain malic acid-leaf carbonate 1 or monomethyl malate-leaf carbonate 2 latent fragrance;

[0012] The synthetic route is as follows:

[0013]

[0014] The preparation method of dimethyl malate chloroformate in step (1) is as follows: dissolving triphosgene in toluene, adding pyridine dropwise at -5 to 5°C, and then adding dimethyl malate dropwise. After the addition, the temperature is raised to room temperature and reacted for 8 to 12 hours. After the reaction is completed, the reaction solution is washed with saturated NaCl, dried with anhydrous Na2SO4, and the solvent is evaporated to obtain dimethyl malate chloroformate, the structural formula of which is as follows:

[0015]

[0016] The molar ratio of dimethyl malate, triphosgene and pyridine is 1:0.3:1.2 to 1:0.5:2, preferably 1:0.4:1.5.

[0017] The preparation method of dimethyl malate-leaf alcohol carbonate in step (2) is as follows: leaf alcohol is dissolved in CH2Cl2, DMAP is added, dimethyl malate chloroformate is added dropwise at -5 to 5°C, and the reaction is carried out at room temperature for 4 to 6 hours. After the reaction is completed, dichloromethane is evaporated, petroleum ether is added, the petroleum ether phase is washed with saturated NaCl, dried over anhydrous Na2SO4, and the solvent is evaporated to obtain dimethyl malate-leaf alcohol carbonate, the structural formula of which is as follows:

[0018]

[0019] As a preferred technical solution of the present invention, the molar ratio of leaf alcohol, DMAP, and dimethyl malate chloroformate in step (2) is 1:1.2:1 to 1:1.6:1, preferably 1:1.5:1.

[0020] The preparation method of monomethyl malate-leaf alcohol carbonate in step (3) is as follows: the dimethyl malate-leaf alcohol carbonate obtained in step (2) is placed in a phosphate buffer solution with a pH value of 6.5 to 7.0, lipase is added, and the mixture is stirred at 20 to 25° C. for 10 to 16 hours. The reaction solution is first extracted with petroleum ether for 1 to 2 times, and then extracted with dichloromethane for 2 to 3 times. The dichloromethane is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain monomethyl malate-leaf alcohol carbonate, which has the following structural formula:

[0021]

[0022] As a preferred technical solution of the present invention, the lipase for preparing monomethyl malate-leaf carbonate is derived from Candida antarctica, and the mass ratio of lipase to substrate dimethyl malate-leaf carbonate is 1:7 to 1:10.

[0023] The preparation method of malic acid-leaf alcohol carbonate in step (3) is as follows: the dimethyl malate-leaf alcohol carbonate obtained in step (2) is placed in a phosphate buffer solution with a pH value of 7.6 to 8.0, lipase is added, and the mixture is stirred at 38 to 42° C. for 10 to 16 hours. The reaction solution is first extracted with petroleum ether for 1 to 2 times, and then extracted with ethyl acetate for 2 to 3 times. The ethyl acetate phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain malic acid-leaf alcohol carbonate, which has the following structural formula:

[0024]

[0025] As a preferred technical solution of the present invention, the lipase used to prepare malic acid-leaf carbonate is Novozymes 435, and the mass ratio of lipase to substrate dimethyl malate-leaf carbonate is 1:5 to 1:8.

[0026] The present invention also provides the use of the malic acid-leaf alcohol carbonate and the monomethyl malate-leaf alcohol carbonate as latent flavorings for releasing leaf alcohol in heated cigarettes.

[0027] The present invention provides the following benefits: Using dimethyl malate and leaf alcohol as raw materials, a malic acid-derived leaf alcohol carbonate latent aroma fragrance can be obtained through a simple three-step reaction. Adding this to heated cigarettes offers the advantage of stable, non-volatile leaf alcohol latent aroma at room temperature, preventing aroma loss during storage. Furthermore, the leaf alcohol is efficiently decomposed and released at the relatively low heating temperature of the heated tobacco, achieving stable aroma enhancement. DETAILED DESCRIPTION

[0028] The present invention will be further described below with reference to specific examples. It should be understood that the following examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention, and that those skilled in the art may make non-essential improvements and adjustments based on the contents of the above invention.

[0029] The room temperature in the embodiments of the present invention refers to 25°C.

[0030] Example 1

[0031] Synthesis of Dimethyl Malate Chloroformate

[0032] Triphosgene (5.94 g, 20 mmol) was dissolved in 150 mL of anhydrous toluene, and pyridine (2.18 g, 75 mmol) was added dropwise at 0°C. After stirring for 15 minutes, dimethyl malate (8.1 g, 50 mmol) was added dropwise, and then the temperature was raised to room temperature to react for 10 hours. After the reaction was completed, it was washed with saturated NaCl solution (50 mL × 5), and the toluene phase was dried over anhydrous Na2SO4. The solvent was evaporated to obtain dimethyl malate chloroformate.

[0033] Spectral data of dimethyl malate chloroformate prepared in this example:

[0034] 1 H NMR (600MHz, CDCl3) δ5.57-5.55(m,1H),3.83(s,3H),3.76(s,3H),3.00-2.98(m,2H). 13 C NMR (150MHz, CDCl3) δ168.81,167.39,150.38,74.13,53.24,52.47,35.49.

[0035] Example 2

[0036] Synthesis of Dimethyl Malate-Leaf Alcohol Carbonate

[0037] Leaf alcohol (1.0 g, 10 mmol) was dissolved in 50 mL of CH2Cl2, and DMAP (1.83 g, 15 mmol) was added. Dimethyl malate chloroformate (2.24 g, 10 mmol) obtained in Example 1 was added dropwise at 0°C. The mixture was reacted at room temperature for 5 h. After the reaction, dichloromethane was evaporated and 50 mL of petroleum ether was added. The petroleum ether phase was washed with saturated NaCl (30 mL × 3), dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain dimethyl malate-leaf alcohol carbonate.

[0038] Spectral data of dimethyl malate-leaf alcohol carbonate prepared in this example:

[0039] 1H NMR (600MHz, CDCl3) δ5.55-5.51(m,1H),5.40(dd,J=6.9,5.4Hz,1H),5.34-5.29(m,1H),4.19-4.15(m,2H),3 .80(s,3H),3.73(s,3H),2.93-2.92(m,2H),2.44(q,J=7.2Hz,1H),2.08-2.03(m,2H),0.97(t,J=7.5Hz,3H). 13 C NMR (150MHz, CDCl3) δ169.37,169.15,154.21,135.15,122.74,71.16,68.15,52.82,52.25,35.91,26.63,20.60,14.15.

[0040] Example 3

[0041] Synthesis of Monomethyl Malate-Leaf Alcohol Carbonate

[0042] Dimethyl malate-leaf carbonate (1.0 g) prepared in Example 2 was placed in a flask, and phosphate buffer solution (30 ml) with a pH of 7.0 was added. Lipase from Candida antarctica (0.125 g) was also added, and the mixture was allowed to react at room temperature for 12 hours. The reaction solution was first extracted with petroleum ether (20 ml x 2) and then with dichloromethane (30 ml x 2). The dichloromethane phase was dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain monomethyl malate-leaf carbonate.

[0043] Spectral data of monomethyl malate-leaf alcohol carbonate prepared in this example:

[0044] 1 H NMR (600MHz, CDCl3) δ5.56-5.50(m,1H),5.42(dd,J=7.0,5.2Hz,1H),5.33-5.29(m,1H),4.19-4.15(m ,2H),3.74(s,3H),2.97-2.96(m,2H),2.44(q,J=7.2Hz,2H),2.08-2.03(m,2H),0.97(t,J=7.5Hz,3H). 13 C NMR (150MHz, CDCl3) δ172.70,169.41,154.20,135.20,122.70,70.74,68.25,52.35,35.76,26.62,20.60,14.14.

[0045] Example 4

[0046] Synthesis of Malic Acid-Leaf Alcohol Carbonate

[0047] Dimethyl malate-leaf carbonate (1.0 g) prepared in Example 2 was dissolved in a phosphate buffer solution (30 ml) having a pH of 7.8, and Novozymes 435 lipase (0.15 g) was added. The mixture was reacted at 40° C. for 14 h. The reaction solution was first extracted with petroleum ether (20 ml × 2) and then with ethyl acetate (30 ml × 2). The ethyl acetate phase was dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain malic acid-leaf carbonate.

[0048] Spectral data of malic acid-leaf alcohol carbonate prepared in this example:

[0049] 1 H NMR (600MHz, DMSO-d6) δ5.55-5.51(m,1H),5.41-5.39(m,1H),5.33-5.29(m,3H),4.19-4. 16(m,2H),3.03-3.02(m,2H),2.46-2.43(m,2H),2.04-2.07(m,2H),0.92(t,J=7.6Hz,3H). 13 C NMR (150MHz, CDCl3) δ175.00,174.12,154.27,135.18,122.68,70.53,68.35,35.67,26.56,20.56,14.08.

[0050] Example 5

[0051] The synthetic method of monomethyl malate-leaf alcohol carbonate in the present embodiment is as follows:

[0052] (1) Synthesis of dimethyl malate chloroformate

[0053] Triphosgene (15 mmol) was dissolved in 150 mL of anhydrous toluene, and pyridine (60 mmol) was added dropwise at 2°C. After stirring for 15 minutes, dimethyl malate (50 mmol) was added dropwise, and then the temperature was raised to room temperature to react for 12 hours. After the reaction was completed, it was washed with saturated NaCl solution (50 mL × 5), and the toluene phase was dried over anhydrous Na2SO4. The solvent was evaporated to obtain dimethyl malate chloroformate.

[0054] (2) Synthesis of dimethyl malate-leaf alcohol carbonate

[0055] Leaf alcohol (10 mmol) was dissolved in 50 mL of CH2Cl2, and DMAP (12 mmol) was added. Dimethyl malate chloroformate (10 mmol) obtained in step (1) was added dropwise at 0°C. The reaction was continued at room temperature for 5 h. After the reaction was completed, dichloromethane was evaporated and 50 mL of petroleum ether was added. The petroleum ether phase was washed with saturated NaCl (30 mL × 3), dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain dimethyl malate-leaf alcohol carbonate.

[0056] (3) Synthesis of Monomethyl Malate-Leaf Alcohol Carbonate

[0057] The dimethyl malate-leaf carbonate (1.0 g) obtained in step (2) was placed in a flask, phosphate buffer solution (30 ml) with a pH of 7.0 was added, and lipase from Candida antarctica (0.1 g) was added. The mixture was reacted at room temperature for 14 h. The reaction solution was first extracted with petroleum ether (20 ml × 2) and then with dichloromethane (30 ml × 2). The dichloromethane phase was dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain monomethyl malate-leaf carbonate.

[0058] Example 6

[0059] The synthetic method of malic acid-leaf alcohol carbonate of the present embodiment is as follows:

[0060] (1) Synthesis of dimethyl malate chloroformate

[0061] Triphosgene (25 mmol) was dissolved in 150 mL of anhydrous toluene, and pyridine (100 mmol) was added dropwise at 5°C. After stirring for 15 minutes, dimethyl malate (50 mmol) was added dropwise, and then the temperature was raised to room temperature for reaction for 8 hours. After the reaction was completed, it was washed with saturated NaCl solution (50 mL × 5), and the toluene phase was dried over anhydrous Na2SO4. The solvent was evaporated to obtain dimethyl malate chloroformate.

[0062] (2) Synthesis of dimethyl malate-leaf alcohol carbonate

[0063] Leaf alcohol (10 mmol) was dissolved in 50 mL of CH2Cl2, and DMAP (16 mmol) was added. Dimethyl malate chloroformate (10 mmol) obtained in step (1) was added dropwise at 5°C. The reaction was continued at room temperature for 5 h. After the reaction was completed, dichloromethane was evaporated and 50 mL of petroleum ether was added. The petroleum ether phase was washed with saturated NaCl (30 mL × 3), dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain dimethyl malate-leaf alcohol carbonate.

[0064] (3) Synthesis of Malic Acid-Leaf Alcohol Carbonate

[0065] The dimethyl malate-leaf carbonate (1.0 g) obtained in step (2) was dissolved in a phosphate buffer solution (30 ml) having a pH of 7.8, and Novozymes 435 lipase (0.125 g) was added, and the mixture was reacted at 42° C. for 12 h. The reaction solution was first extracted with petroleum ether (20 ml × 2) and then with ethyl acetate (30 ml × 2). The ethyl acetate phase was dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain malic acid-leaf carbonate.

[0066] Application Example 1

[0067] Thermal cracking of malic acid-leaf alcohol carbonate prepared in Example 4

[0068] Sample preparation: First, insert a small amount of quartz wool into a hollow quartz tube. Weigh approximately 0.1 mg of sample and add it to the quartz tube using a glass sampling capillary. Then, insert an appropriate amount of quartz wool and wait for thermal pyrolysis analysis. Pyrolysis conditions in the absence of oxygen: Initial temperature: 50°C; then increase the temperature at 20°C / ms to 150°C, 200°C, 250°C, and 300°C, respectively, hold for 15 seconds, and then analyze the pyrolysis products by GC-MS. The thermal pyrolysis products are shown in Table 1. As shown in the table, malic acid-leaf carbonate releases leaf alcohol at a low temperature of 150°C. Within the heating temperature range of 150°C to 300°C for cigarette cut tobacco, leaf alcohol is the primary product released.

[0069] Table 1 Main thermal decomposition products of malic acid-leaf alcohol carbonate

[0070]

[0071] Application Example 2

[0072] Effects of Malic Acid-Leaf Alcohol Carbonate (Compound 1) Prepared in Example 4 and Monomethyl Malate-Leaf Alcohol Carbonate (Compound 2) Prepared in Example 3 in Flavoring Heat-Reduced Cigarettes

[0073] 100 mg of compound 1 and compound 2 were weighed and diluted to 2 mL with 95% ethanol solution. The prepared solutions were evenly added to heated cigarettes, with an addition rate of 0.2 mg per cigarette. The evaluation results are shown in Table 2. As shown in Table 2, the two leaf alcohol carbonates can significantly enhance the green aroma of heated cigarettes and refine the smoke.

[0074] Table 2 Evaluation of two leaf alcohol carbonates in heated cigarettes

[0075]

[0076] The above cigarettes and cigarettes with added leaf alcohol were stored for different periods of time for sensory evaluation, and the evaluation results are shown in Table 3. As can be seen from the table, the two leaf alcohol carbonates can significantly improve the release stability of leaf alcohol when used for flavoring heated cigarettes.

[0077] Table 3 Comparative smoking results of heated cigarettes with leaf alcohol carbonate and leaf alcohol added

[0078]

[0079] The basic principles, main features, and advantages of the present invention are shown and described above. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are merely illustrative of the principles of the present invention. Various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention. Such changes and modifications are intended to fall within the scope of the present invention. The scope of protection claimed in the present invention is defined by the appended claims and their equivalents.

Claims

1. Leaf alcohol carbonate latent fragrance, characterized in that, Including malic acid-leaf carbonate or malic acid monomethyl ester-leaf carbonate, its racemate and enantiomer are as follows:

2. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 1, wherein The following steps are involved: (1) reacting dimethyl malate with triphosgene and pyridine to obtain dimethyl malate chloroformate; (2) dissolving leaf alcohol in CH2Cl2, adding 4-dimethylaminopyridine DMAP, and then adding dimethyl malate chloroformate to obtain dimethyl malate-leaf alcohol carbonate after reaction; (3) placing dimethyl malate-leaf carbonate in a phosphate buffer solution and treating it with lipase to obtain malic acid-leaf carbonate or monomethyl malate-leaf carbonate latent fragrance; The synthetic route is as follows:

3. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 2, wherein The preparation method of dimethyl malate chloroformate in step (1) is as follows: dissolving triphosgene in toluene, adding pyridine dropwise at -5 to 5°C, and then adding dimethyl malate dropwise. After the addition, the temperature is raised to room temperature and reacted for 8 to 12 hours. After the reaction is completed, the reaction solution is washed with saturated NaCl, dried with anhydrous Na2SO4, and the solvent is evaporated to obtain dimethyl malate chloroformate, the structural formula of which is as follows: The molar ratio of dimethyl malate, triphosgene and pyridine is 1:0.3:1.2 to 1:0.5:

2.

4. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 2, wherein The preparation method of dimethyl malate-leaf alcohol carbonate in step (2) is as follows: leaf alcohol is dissolved in CH2Cl2, DMAP is added, dimethyl malate chloroformate is added dropwise at -5 to 5°C, and the reaction is carried out at room temperature for 4 to 6 hours. After the reaction is completed, dichloromethane is evaporated, petroleum ether is added, the petroleum ether phase is washed with saturated NaCl, dried over anhydrous Na2SO4, and the solvent is evaporated to obtain dimethyl malate-leaf alcohol carbonate, the structural formula of which is as follows:

5. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 2 or 4, wherein: In the step (2), the molar ratio of leaf alcohol, DMAP, and dimethyl malate chloroformate is 1:1.2:1 to 1:1.6:

1.

6. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 2, wherein: The preparation method of monomethyl malate-leaf alcohol carbonate in step (3) is as follows: the dimethyl malate-leaf alcohol carbonate obtained in step (2) is placed in a phosphate buffer solution with a pH value of 6.5 to 7.0, lipase is added, and the mixture is stirred at 20 to 25° C. for 10 to 16 hours. The reaction solution is first extracted with petroleum ether and then with dichloromethane. The dichloromethane is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain monomethyl malate-leaf alcohol carbonate, which has the following structural formula:

7. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 6, wherein: The lipase for preparing monomethyl malate-leaf carbonate is derived from Antarctic Candida, and the mass ratio of the lipase to the substrate dimethyl malate-leaf carbonate is 1:7-1:

10.

8. The method for synthesizing the leaf alcohol carbonate latent fragrance according to claim 2, wherein: The preparation method of malic acid-leaf alcohol carbonate in step (3) is as follows: the dimethyl malate-leaf alcohol carbonate obtained in step (2) is placed in a phosphate buffer solution with a pH value of 7.6 to 8.0, lipase is added, and the mixture is stirred at 38 to 42° C. for 10 to 16 hours. The reaction solution is first extracted with petroleum ether and then with ethyl acetate. The ethyl acetate phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain malic acid-leaf alcohol carbonate, which has the following structural formula:

9. The method for synthesizing malic acid-leaf alcohol carbonate according to claim 8, characterized in that: The lipase used to prepare malic acid-leaf carbonate is Novozymes 435, and the mass ratio of the lipase to the substrate dimethyl malate-leaf carbonate is 1:5-1:

8.

10. Use of the malic acid-leaf carbonate and monomethyl malate-leaf carbonate according to claim 1 as latent flavorings for releasing leaf alcohol in heated cigarettes.

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