Hydroxycarboxylic acid-menthol carbonate as well as synthesis method and application thereof

Abstract

The invention discloses hydroxycarboxylic acid-menthol carbonate as well as a synthesis method and application thereof, dimethyl malate and menthyl chloroformate are taken as raw materials, and malic acid monomethyl ester-menthol carbonate and malic acid-menthol carbonate are obtained through esterification and enzyme hydrolysis two-step reaction; dimethyl tartrate and menthyl chloroformate are used as raw materials, monomethyl tartrate-menthol carbonate is obtained through esterification and enzyme hydrolysis two-step reaction, dibenzyl tartrate and menthyl chloroformate are used as raw materials, tartaric acid-menthol carbonate is obtained through esterification and palladium carbon hydrolysis two-step reaction, and the operation method is simple and convenient. Hydroxycarboxylic acid-menthol carbonate is stable and non-volatile at room temperature, can be cracked to release menthol at the working temperature of cigarettes after being added to the cigarettes, can be efficiently cracked to release menthol at the temperature of 150-300 DEG C, and is suitable for heating the cigarettes, products released by malic acid-menthol carbonate at the high temperature mainly comprise menthol, the generated menthene is less, and the safety of the cigarettes is improved. The method is suitable for traditional cigarettes.

Description

Technical Field

[0001] This invention belongs to the field of tobacco flavoring technology, and more specifically, relates to a menthol carbonate, its preparation method and its application as a flavoring in cigarettes. Background Technology

[0002] Menthol is widely used in the cigarette industry as a flavoring agent or in the manufacture of menthol-based cigarettes. However, menthol is highly volatile, which can easily cause environmental pollution during cigarette production and also leads to a decrease in cigarette quality due to its volatilization during the shelf life of cigarettes.

[0003] Reports indicate that menthol has been prepared into a non-volatile latent aroma compound, with the aim of releasing menthol through the breaking of chemical bonds during cigarette combustion. For example, Jie Wancui et al. synthesized menthol glycosides (Journal of Food and Biotechnology, 2006); Chen Zhifei et al. synthesized menthyl glutarate ester by reacting glutaric acid with menthol (Henan Science, 2016); Zhu Haijun et al. synthesized menthyl malate ester by reacting malic acid with menthol (Fine Chemicals, 2004); Shen Yi et al. prepared galactose-based menthyl carbonate ester (2021, Synthetic Chemistry); and a Japanese patent also describes the preparation of menthol as menthyl carbonate diester (WO2009 / 123355A2).

[0004] The aforementioned aroma compounds can reduce the volatility of menthol to some extent, but they also have many problems. For example, the preparation of menthol glycosides uses the Koenigs-Knorr synthesis method, which involves expensive reagents such as silver salts and is cumbersome and not suitable for production. In addition, their decomposition temperature is high, making them unsuitable for use in heated cigarettes. The carboxylic acid ester bonds formed between glutaric acid, malic acid, and other carboxylic acids and menthol are relatively stable. When heated, the menthol portion preferentially dehydrates to form menthene, making it difficult to decompose and release menthol. Galactose-based menthyl carbonate does not decompose at 200℃ and 300℃, making it difficult to use in heated cigarettes. Furthermore, at high temperatures, the decomposition product menthene accounts for a large proportion. Menthol carbonate diester itself is also highly volatile. It volatilizes directly into the smoke without decomposition, making it difficult to play its intended role. Summary of the Invention

[0005] To address the problem of menthol dicarbonate directly volatilizing and transferring into cigarette smoke without pyrolysis in existing technologies, this invention provides a hydroxycarboxylic acid-menthol carbonate, its synthesis method, and its application as a flavoring in cigarettes. This invention uses dimethyl malate and menthyl chloroformate as raw materials, and obtains monomethyl malate-menthol carbonate and malic acid-menthol carbonate through a two-step reaction of esterification and enzymatic hydrolysis; it also uses dimethyl tartrate and menthyl chloroformate as raw materials, and obtains monomethyl tartrate-menthol carbonate through a two-step reaction of esterification and enzymatic hydrolysis; and it uses dibenzyl tartrate and menthyl chloroformate as raw materials, and obtains tartaric acid-menthol carbonate through a two-step reaction of esterification and palladium carbon hydrogenolysis. The operation methods are simple.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0007] The hydroxycarboxylic acid-menthol carbonates of this invention include malic acid-menthol carbonate, malic acid monomethyl ester-menthol carbonate, tartaric acid monomethyl ester-menthol carbonate, and tartaric acid-menthol carbonate, and their racemic and enantiomers are shown in Formulas 1-4:

[0008]

[0009] Malic acid has a hydroxyl group at the β-position of its carboxylic acid, which is a β-hydroxy acid structure. One of the properties of β-hydroxy acids is that their hydroxyl group is easily dehydrated by heat to form an olefin. Taking advantage of this property, menthol can be linked to its hydroxyl position through a carbonate bond. This achieves the goal of preferentially dehydrating and breaking the hydroxyl group of malic acid at the working temperature of cigarettes, and decomposing the carbonate bond to release menthol.

[0010] The preparation method of the hydroxycarboxylic acid-menthol carbonate of the present invention includes the following steps: dissolving dimethyl malate in CH2Cl2, adding 4-dimethylaminopyridine (DMAP), and then adding menthyl chloroformate; after the reaction, dimethyl malate-menthol carbonate is obtained; the dimethyl malate-menthol carbonate is placed in a phosphate buffer solution and treated with lipase to obtain malate-menthol carbonate or monomethyl malate-menthol carbonate, and the reaction route is shown below:

[0011]

[0012] The preparation method of dimethyl malate-menthol carbonate is as follows: L-dimethyl malate is dissolved in dichloromethane (CH2Cl2), 4-dimethylaminopyridine (DMAP) is added, and menthol chloroformate is added dropwise at -5 to 5°C. After the addition is complete, the reaction is carried out at room temperature for 2 to 4 hours. After the reaction is complete, 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-menthol carbonate, with the following structural formula:

[0013]

[0014] The molar ratio of L-malic acid dimethyl ester, DMAP, and menthol chloroformate is 1:1.2:1 to 1:2:1, preferably 1:1.5:1.

[0015] The preparation method of malic acid-menthol carbonate is as follows: Dimethyl malate-menthol carbonate is placed in a phosphate buffer solution with a pH of 7.6-8.0, lipase is added, and the mixture is stirred at 38-42℃ for 12-20 h. The reaction solution is first extracted with petroleum ether 1-2 times, and then extracted with ethyl acetate 2-3 times. The ethyl acetate phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain malic acid-menthol carbonate, with the following structural formula:

[0016]

[0017] The mass ratio of lipase to dimethyl malate-menthol carbonate is 1:4 to 1:10; the lipase is derived from Candida antarcticis or Novozymes 435.

[0018] The preparation method of monomethyl malate-menthol carbonate is as follows: Dimethyl malate-menthol carbonate is placed in a phosphate buffer solution with a pH of 6.5-7.0, lipase is added, and the mixture is stirred at 20-25℃ for 10-14 hours. The reaction solution is first extracted with petroleum ether 1-2 times, and then extracted with CH2Cl2 2-3 times. The CH2Cl2 phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain monomethyl malate-menthol carbonate, with the following structural formula:

[0019]

[0020] The mass ratio of the lipase to dimethyl malate-menthol carbonate is 1:5 to 1:10; the lipase is derived from Candida antarctica or Novozymes 435.

[0021] Tartaric acid has a β-hydroxy acid structure, and its hydroxyl unit is easily dehydrated by heat. Taking advantage of this property, menthol can be linked to its hydroxyl position through a carbonate bond. This achieves the goal of preferentially dehydrating and breaking tartaric acid at the working temperature of heated cigarettes, and decomposing the carbonate bond to release menthol.

[0022] The preparation method of the hydroxycarboxylic acid-menthol carbonate of the present invention includes the following steps:

[0023] Dimethyl tartrate or dibenzyl tartrate is dissolved in CH₂Cl₂, and the base DMAP is added, followed by the addition of menthyl chloroformate. The reaction yields dimethyl tartrate-menthol carbonate or dibenzyl tartrate-menthol carbonate. Dimethyl tartrate-menthol carbonate is then placed in a phosphate buffer solution and treated with lipase to obtain monomethyl tartrate-menthol carbonate. Dibenzyl tartrate-menthol carbonate is dissolved in methanol and hydrogenated under Pd / C catalysis to remove the benzyl group, yielding tartaric acid-menthol carbonate. The reaction route is shown below:

[0024] The preparation method of dimethyl tartrate-menthol carbonate is as follows: L-dimethyl tartrate is dissolved in CH2Cl2, DMAP is added, and menthyl chloroformate is added dropwise at -5 to 5℃. After the addition is complete, the reaction is carried out at room temperature for 2 to 4 hours. After the reaction is complete, dichloromethane is evaporated, petroleum ether is added, the petroleum ether phase is washed with saturated NaCl, dried over anhydrous Na2SO4, the solvent is evaporated, and the residue is subjected to silica gel column chromatography to obtain dimethyl tartrate-menthol carbonate, with the following structural formula:

[0025]

[0026] The molar ratio of L-dimethyl tartrate, DMAP, and menthyl chloroformate is 1:1.5:1.2 to 1:2:1.2.

[0027] The preparation method of monomethyl tartrate-menthol carbonate is as follows: Dimethyl tartrate-menthol carbonate is placed in a phosphate buffer solution with a pH of 7.6-8.0, lipase is added, and the mixture is stirred at 38-42℃ for 20-30 h. The reaction solution is first extracted with petroleum ether 1-2 times, and then extracted with ethyl acetate 2-3 times. The ethyl acetate phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain monomethyl tartrate-menthol carbonate, with the following structural formula:

[0028]

[0029] The mass ratio of the lipase to dimethyl tartrate-menthol carbonate is 1:5 to 1:8, and the lipase is derived from Candida antarcticis or Novozymes 435.

[0030] The preparation method of tartaric acid-menthol carbonate is as follows:

[0031] (1) Dibenzyl tartrate was dissolved in CH2Cl2, DMAP was added, and menthyl chloroformate was added dropwise at 0-5℃. After the addition was complete, the reaction was carried out at room temperature for 2-4 hours. After the reaction was completed, dichloromethane was evaporated, and petroleum ether was added. The petroleum ether phase was washed with saturated NaCl, dried over anhydrous Na2SO4, and the solvent was evaporated to obtain dibenzyl tartrate-menthol carbonate, with the following structural formula:

[0032]

[0033] (2) Dibenzyl tartrate-menthol carbonate was dissolved in methanol, Pd / C was added, and the reaction was carried out at room temperature for 2-4 hours under a hydrogen atmosphere. After the reaction was completed, the mixture was filtered and the solvent was evaporated to obtain tartaric acid-menthol carbonate, with the following structural formula:

[0034]

[0035] The molar ratio of L-dibenzyl tartrate, DMAP, and menthyl chloroformate is 1:3:2 to 1:4:2; the mass of Pd / C accounts for 3-7% of the mass of dibenzyl tartrate-menthol carbonate, preferably 5%.

[0036] The present invention also provides the application of the aforementioned hydroxycarboxylic acid-menthol carbonate as a latent flavoring that releases menthol in heated or conventional cigarettes.

[0037] The beneficial effects of this invention are as follows: 1. This invention uses dimethyl malate and menthyl chloroformate as raw materials to obtain malic acid-menthol carbonate through a two-step reaction, which is simple to operate. Malic acid-menthol carbonate is stable and non-volatile at room temperature. When added to cigarettes, it can decompose and release menthol at the cigarette's operating temperature. Its advantages are: 1) It can efficiently decompose and release menthol at relatively low heating temperatures (150-300℃), making it suitable for heated cigarettes; 2) At high temperatures, the released product is mainly menthol, with less menthene produced, making it suitable for traditional cigarettes. 2. This invention uses dimethyl tartrate or dibenzyl tartrate and menthyl chloroformate as raw materials to obtain monomethyl tartrate-menthol carbonate and tartaric acid-menthol carbonate through a two-step reaction, which is simple to operate. Monomethyl tartrate-menthol carbonate and menthol tartrate carbonate are stable and non-volatile at room temperature. When added to cigarettes, they can decompose and release menthol at the cigarette's operating temperature. Their advantage lies in their efficient decomposition and release of menthol at temperatures between 150 and 300°C, making them suitable for heated cigarettes. 3. Compared to existing technologies that condense menthol with the carboxyl groups of hydroxy acids to form carboxylic acid esters, this invention condenses menthol with the hydroxyl groups of hydroxy acids to form carbonates. On one hand, the carboxyl hydrogen bonding in the structure makes menthol carbonate more stable and less volatile at room temperature; on the other hand, the carbonate bonds of hydroxy acids are more easily broken by heat, releasing menthol, thereby reducing the formation of menthene. Detailed Implementation

[0038] The present invention will be further described below with reference to specific embodiments. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Those skilled in the art can make some non-essential improvements and adjustments based on the above-described invention.

[0039] Example 1

[0040] Synthesis of dimethyl malate-menthol carbonate

[0041] L-dimethyl malate (1.62 g, 1 mmol) was dissolved in 30 mL of CH2Cl2, DMAP (1.83 g, 1.5 mmol) was added, and menthol chloroformate (2.18 g, 1 mmol) was added dropwise at 0 °C. After the addition was complete, the reaction was carried out at room temperature for 3 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-menthol carbonate.

[0042] Spectral data of dimethyl malate-menthol carbonate prepared in this embodiment:

[0043] 1 H NMR(600MHz, CDCl3)δ5.41(dd,J=7.1,5.3Hz,1H),4.57(td,J=11.0,4.4Hz,1H),3.78(s,1H),3.72(s,1H),2.93-2.92(m,2H),2.08-2.0 1(m,2H),1.70-1.67(m,2H),1.47-1.42(m,2H),1.09-1.05(m,2H),0.92(d,J=3.8Hz,3H),0.91(d,J=4.2Hz,3H),0.81(d,J=7.0Hz,3H). 13 C NMR (150MHz, CDCl3) δ169.44,169.30,153.94,79.50,71.02,52.73,52.25,47.05,40.61,35.92,34.06,31.43,26.10,23.38,21.96,20.64,16.24.

[0044] Example 2

[0045] Synthesis of monomethyl malate-menthol carbonate

[0046] In Example 1, 1.0 g of dimethyl malate-menthol carbonate was placed in a flask, and 30 ml of phosphate buffer solution (pH 7.0) was added. Lipase (0.15 g) from *Candida antarctica* or Novozymes 435 (0.1 g) was also added, and the reaction was carried out at room temperature for 12 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 dichloromethane was removed by vacuum distillation to obtain a white powder with a yield of 92%.

[0047] Spectral data of the malic acid monomethyl ester-menthol carbonate prepared in this embodiment:

[0048] 1H NMR (600MHz, CDCl3) δ5.41(dd,J=7.5,4.7Hz,1H),4.58(td,J=11.0,4.4Hz,1H),3.79(s,3H),3.00-2.97(m,2H),2.08-2.01(m,2 H),1.70-1.68(m,2H),1.48-1.42(m,2H),1.12-1.03(m,2H),0.93(d,J=4.6Hz,3H),0.92(d,J=5.0Hz,3H),0.81(d,J=7.0Hz,3H). 13 C NMR (150MHz, CDCl3) δ174.13,169.05,153.88,79.58,70.59,52.83,46.99,40.55,35.69,34.01,31.41,26.04,23.30,21.95,20.64,16.18.

[0049] Example 3

[0050] Synthesis of malic acid-menthol carbonate

[0051] In Example 1, dimethyl malate-menthol carbonate (1.0 g) was dissolved in phosphate buffer solution (30 ml) at pH 7.8, and lipase (0.2 g) or Novozymes 435 (0.15 g) derived from Candida antarctica was added. The mixture was reacted at 40 °C for 16 h. The reaction solution was first extracted with dichloromethane (20 ml × 2), and then with ethyl acetate (30 ml × 2). The ethyl acetate phase was dried over anhydrous sodium sulfate, and the ethyl acetate was evaporated to obtain a white powder.

[0052] 1 H NMR (600MHz, CDCl3) δ5.41(t,J=5.8Hz,1H),4.58(td,J=10.9,4.3Hz,1H),3.03(d,J=5.3Hz,2H),2.08-1.98(m,2H),1.68(d ,J=10.8Hz,2H),1.48-1.42(m,2H),1.12-1.05(m,2H),0.93(d,J=6.5Hz,3H),0.90(d,J=7.0Hz,3H),0.78(d,J=6.9Hz,3H). 13 C NMR (150MHz, CDCl3) δ174.88,174.33,153.90,79.86,70.08,47.05,40.56,35.66,34.04,31.45,25.99,23.29,21.97,20.65,16.11.

[0053] Example 4

[0054] Synthesis of dimethyl tartrate-menthol carbonate

[0055] L-Dimethyl tartrate (1.79 g, 1 mmol) was dissolved in 30 mL of CH2Cl2, DMAP (1.83 g, 1.5 mmol) was added, and menthol chloroformate (2.62 g, 1.2 mmol) was added dropwise at 0 °C. After the addition was complete, the reaction was carried out at room temperature for 3 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 × 2), dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain dimethyl tartrate-menthol carbonate.

[0056] Spectral data of dimethyl tartrate-menthol carbonate prepared in this embodiment:

[0057] 1 H NMR(600MHz, CDCl3) δ5.38(d,J=2.2Hz,1H),4.77(dd,J=8.0,2.2Hz,1H),4.52(td,J =11.0,4.4Hz,1H),3.84(s,3H),3.82(s,3H),3.14(d,J=8.0Hz,1H,OH),2.09-2.07(m ,1H),1.89-1.84(m,1H),1.70-1.67(m,2H),1.45-1.41(m,2H),1.15-1.04(m,2H),0. 92(d,J=6.6Hz,3H),0.89(d,J=7.0Hz,3H),0.87-0.85(m,1H),0.78(d,J=7.0Hz,3H). 13 CNMR(150MHz,CDCl3)δ170.82,167.02,153.79,79.91,75.52,70.63,53.1 6,52.98,46.84,40.46,34.01,31.42,26.37,23.62,21.92,20.52,16.54.

[0058] Example 5

[0059] Synthesis of monomethyl tartrate-menthol carbonate

[0060] In Example 4, 1.0 g of dimethyl tartrate-menthol carbonate was placed in a flask, and 30 ml of phosphate buffer solution at pH 7.8 was added. Lipase (0.2 g) from *Candida antarctica* or 0.15 g of Novozymes 435 was also added, and the reaction was carried out at 38°C for 24 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 Na₂SO₄, and dichloromethane was removed by vacuum distillation to obtain a white powder.

[0061] Spectral data of monomethyl tartrate-menthol carbonate prepared in this embodiment:

[0062] 1 H NMR (600MHz, CDCl3) δ5.39 (d, J = 2.2Hz, 1H), 4.79-4.77 (m, 1H), 4.55-4.51 (m, 1H), 3.84 (s, 3H), 3.82 (s, 3H), 2.09-2.06 (m, 1H), 1.89- 1.85(m,1H),1.69-1.67(m,2H),1.45-1.41(m,2H),1.14-1.02(m,2H),0.93(d,J=6.6Hz,3H),0.90-0.87(m,4H),0.77(d,J=7.0Hz,3H). 13 C NMR (150MHz, CDCl3) δ170.88,167.09,153.80,79.95,75.53,70.62,53.21,46.82,40.44,34.00,31.41,26.36,23.59,21.93,20.54,16.52.

[0063] Example 6

[0064] Synthesis of dibenzyl tartrate-menthol carbonate

[0065] L-Dibenzyl tartrate (3.3 g, 1 mmol) was dissolved in 50 mL of CH2Cl2, DMAP (3.66 g, 3 mmol) was added, and menthyl chloroformate (4.36 g, 2 mmol) was added dropwise at 0 °C. After the addition was complete, the reaction was carried out at room temperature for 3 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 dibenzyl tartrate-menthol carbonate.

[0066] Spectral data of dibenzyl tartrate-menthol carbonate prepared in this embodiment:

[0067] 1H NMR (600MHz, CDCl3) δ5.66 (s, 1H), 5.18 (d, J = 5.4Hz, 2H), 4.50 (td, J = 10.9, 4.4Hz, 1H), 1.99-1.97 (m, 1H), 1.88-1.84 (m, 1H), 1.67-1.6 5(m,2H),1.42-1.40(m,2H),1.05-1.00(m,2H),0.90-0.85(m,1H),0.89(d,J=6.5Hz,3H),0.86(d,J=7.0Hz,4H),0.74(d,J=6.9Hz,3H). 13 C NMR (150MHz, CDCl3) δ165.69,153.78,134.50,128.64,128.59,128.16,79.86, 73.57,68.00,46.78,40.35,34.01,31.36,26.22,23.49,21.94,20.59,16.47.

[0068] Example 7

[0069] Synthesis of tartaric acid-menthol carbonate

[0070] The dibenzyl tartrate-menthol carbonate (2.0 g) prepared in Example 6 was dissolved in methanol, and 5% Pd / C (0.1 g) was added. The mixture was reacted at room temperature for 4 h under a hydrogen atmosphere. After the reaction was completed, the mixture was filtered and the solvent was evaporated to obtain tartaric acid-menthol carbonate.

[0071] Spectral data of the tartaric acid-menthol carbonate prepared in this embodiment:

[0072] 1 H NMR(600MHz, CDCl3)δ5.64(s,1H),4.54(td,J=10.9,4.4Hz,1H),2.08-2.07(m,1H),1.91-1.86(m,1H),1.68-1.66(m,2H),1 .47-1.40(m,2H),1.12-1.00(m,2H),0.92(d,J=6.5Hz,3H),0.88(d,J=7.0Hz,3H),0.90-0.85(m,1H),0.77(d,J=7.0Hz,3H). 13 C NMR (150MHz, CDCl3) δ169.57,153.73,80.17,72.97,46.85,40.41,34.04,31.40,26.24,23.54,21.94,20.53,16.40.

[0073] Application Example 1

[0074] Thermal decomposition of malic acid-menthol carbonate

[0075] Sample preparation: First, a small amount of quartz wool was inserted into a hollow quartz tube. Then, approximately 0.1 mg of sample was weighed and added to the quartz tube using a glass spotting capillary. The tube was then filled with more quartz wool and allowed to undergo pyrolysis analysis. Oxygen-free pyrolysis conditions: Initial temperature: 50℃; the temperature was increased to 150℃, 200℃, 250℃, 300℃, 600℃, and 900℃ at a rate of 20℃ / ms, held for 15s, and then the pyrolysis products were introduced into GC-MS for analysis. The pyrolysis products are shown in Table 1.

[0076] Table 1. Major thermal decomposition products of malic acid-menthol carbonate

[0077]

[0078] Application Example 2

[0079] Thermal decomposition of monomethyl malate-menthol carbonate

[0080] Sample preparation: First, a small amount of quartz wool was inserted into a hollow quartz tube. Then, approximately 0.1 mg of sample was weighed and added to the quartz tube using a glass spotting capillary. The tube was then filled with more quartz wool and allowed to undergo pyrolysis analysis. Oxygen-free pyrolysis conditions: Initial temperature: 50℃; the temperature was increased to 150℃, 200℃, 250℃, 300℃, 600℃, and 900℃ at a rate of 20℃ / ms, held for 15s, and then the pyrolysis products were introduced into GC-MS for analysis. The pyrolysis products are shown in Table 2.

[0081] Table 2. Major thermal decomposition products of monomethyl malate-menthol carbonate

[0082]

[0083] Application Example 3

[0084] The role of malic acid-menthol carbonate (1) and monomethyl malic acid-menthol carbonate (2) in conventional cigarette flavoring

[0085] Weigh 200 mg each of compound 1 and compound 2, and dilute them to 1 mL with 95% ethanol solution. Inject the prepared solutions evenly into conventional cigarettes, with an addition amount of 0.5 mg and 1.0 mg per cigarette. The evaluation results are shown in Table 3.

[0086] Table 3. Evaluation results of two menthol carbonates in regular cigarettes.

[0087]

[0088] As shown in Table 3, the two types of menthol carbonates used in the flavoring of regular cigarettes can significantly improve the cooling sensation of regular cigarettes and increase the minty aroma.

[0089] Application Example 4

[0090] The role of malic acid-menthol carbonate (1) and malic acid monomethyl ester-menthol carbonate (2) in flavoring heated cigarettes

[0091] Weigh 200 mg each of compound 1 and compound 2, and dilute each to 1 mL with 95% ethanol solution. Inject the prepared solutions evenly into heated cigarettes, adding 2 mg per cigarette. Simultaneously, use cigarettes containing menthol as a control, adding 1 mg of menthol per cigarette. Sensory evaluations were conducted on the cigarettes after different storage periods, and the results are shown in Table 3.

[0092] Table 3. Comparative evaluation results of heated cigarettes with added menthol carbonate and menthol.

[0093]

[0094] As shown in Table 3, the two types of menthol carbonates used to flavor heated cigarettes can significantly improve the cooling sensation of the cigarettes and can be preserved for a long time with stable release.

[0095] Application Example 5

[0096] Thermal decomposition of tartaric acid-menthol carbonate

[0097] Sample preparation: First, a small amount of quartz wool was inserted into a hollow quartz tube. Then, approximately 0.1 mg of sample was weighed and added to the quartz tube using a glass spotting capillary. Another amount of quartz wool was then inserted, and the tube was ready for pyrolysis analysis. Anaerobic pyrolysis conditions: Initial temperature: 50℃; the temperature was increased to 150℃, 200℃, 250℃, and 300℃ at a rate of 20℃ / ms, held for 15s, and then the pyrolysis products were introduced into GC-MS for analysis. The pyrolysis products are shown in Table 1. As can be seen from the table, tartaric acid-menthol carbonate can pyrolyze at 150℃, and the pyrolysis product is mainly menthol. The pyrolysis temperature is consistent with the heating temperature of heated cigarette tobacco.

[0098] Table 4. Major thermal decomposition products of tartaric acid-menthol carbonate

[0099]

[0100] Application Example 6

[0101] The role of monomethyl tartrate-menthol carbonate (compound 3) and tartrate-menthol carbonate (compound 4) in flavoring heated cigarettes.

[0102] Weigh 300 mg each of compound 3 and compound 4, and dilute each to 2 mL with ethanol. Inject the prepared solutions evenly into heated cigarettes, adding 1.5 mg per cigarette. Simultaneously, use cigarettes containing menthol as a control, adding 1 mg of menthol per cigarette. Sensory evaluations were conducted on the cigarettes after different storage periods, and the results are shown in Table 2.

[0103] Table 5. Comparative evaluation results of heated cigarettes with added menthol carbonate and menthol.

[0104]

[0105]

[0106] As shown in Table 5, the two types of menthol carbonates used to flavor heated cigarettes can significantly improve the cooling sensation of the cigarettes and can be preserved for a long time with stable release.

[0107] The foregoing has shown and described the basic principles and main features of the present invention, as well as its advantages. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. Hydroxycarboxylic acid-menthol carbonate, characterized in that, Including malic acid-menthol carbonate, malic acid monomethyl ester-menthol carbonate, tartaric acid monomethyl ester-menthol carbonate, and tartaric acid-menthol carbonate, whose racemic and enantiomers are shown in Formulas 1-4:

2. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 1, characterized in that, Dimethyl malate was dissolved in CH2Cl2, 4-dimethylaminopyridine (DMAP) was added, followed by the addition of menthyl chloroformate. The reaction yielded dimethyl malate-menthol carbonate. Dimethyl malate-menthol carbonate was then placed in a phosphate buffer solution and treated with lipase to obtain malate-menthol carbonate or monomethyl malate-menthol carbonate. The reaction route is shown below:

3. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 2, characterized in that, The preparation method of dimethyl malate-menthol carbonate is as follows: L-dimethyl malate is dissolved in dichloromethane (CH2Cl2), 4-dimethylaminopyridine (DMAP) is added, and menthol chloroformate is added dropwise at -5 to 5°C. After the addition is complete, the reaction is carried out at room temperature for 2 to 4 hours. After the reaction is complete, 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-menthol carbonate, with the following structural formula: The molar ratio of L-malic acid dimethyl ester, DMAP, and menthol chloroformate is 1:1.2:1 to 1:2:

1.

4. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 2, characterized in that, The preparation method of malic acid-menthol carbonate is as follows: Dimethyl malate-menthol carbonate is placed in a phosphate buffer solution with a pH of 7.6-8.0, lipase is added, and the mixture is stirred at 38-42℃ for 12-20 h. The reaction solution is first extracted with petroleum ether, and then extracted with ethyl acetate. The ethyl acetate phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain malic acid-menthol carbonate, with the following structural formula: The mass ratio of lipase to dimethyl malate-menthol carbonate is 1:4 to 1:10; the lipase is derived from Candida antarcticis or Novozymes 435.

5. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 2, characterized in that, The preparation method of monomethyl malate-menthol carbonate is as follows: Dimethyl malate-menthol carbonate is placed in a phosphate buffer solution with a pH of 6.5-7.0, lipase is added, and the mixture is stirred at 20-25℃ for 10-14 h. The reaction solution is first extracted with petroleum ether, and then extracted with CH2Cl2. The CH2Cl2 phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain monomethyl malate-menthol carbonate, with the following structural formula: The mass ratio of the lipase to dimethyl malate-menthol carbonate is 1:5 to 1:10; the lipase is derived from Candida antarctica or Novozymes 435.

6. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 2, characterized in that, Dimethyl tartrate or dibenzyl tartrate is dissolved in CH₂Cl₂, and the base DMAP is added, followed by the addition of menthyl chloroformate. The reaction yields dimethyl tartrate-menthol carbonate or dibenzyl tartrate-menthol carbonate. Dimethyl tartrate-menthol carbonate is then placed in a phosphate buffer solution and treated with lipase to obtain monomethyl tartrate-menthol carbonate. Dibenzyl tartrate-menthol carbonate is dissolved in methanol and hydrogenated under Pd / C catalysis to remove the benzyl group, yielding tartaric acid-menthol carbonate. The reaction route is shown below:

7. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 6, characterized in that, The preparation method of dimethyl tartrate-menthol carbonate is as follows: L-dimethyl tartrate is dissolved in CH2Cl2, DMAP is added, and menthyl chloroformate is added dropwise at -5 to 5℃. After the addition is complete, the reaction is carried out at room temperature for 2 to 4 hours. After the reaction is complete, dichloromethane is evaporated, petroleum ether is added, the petroleum ether phase is washed with saturated NaCl, dried over anhydrous Na2SO4, the solvent is evaporated, and the residue is subjected to silica gel column chromatography to obtain dimethyl tartrate-menthol carbonate, with the following structural formula: The molar ratio of L-dimethyl tartrate, DMAP, and menthyl chloroformate is 1:1.5:1.2 to 1:2:1.

2.

8. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 6, characterized in that, The preparation method of monomethyl tartrate-menthol carbonate is as follows: Dimethyl tartrate-menthol carbonate is placed in a phosphate buffer solution with a pH of 7.6-8.0, lipase is added, and the mixture is stirred at 38-42℃ for 20-30 h. The reaction solution is first extracted with petroleum ether 1-2 times, and then extracted with ethyl acetate 2-3 times. The ethyl acetate phase is dried over anhydrous Na2SO4, and the solvent is evaporated to obtain monomethyl tartrate-menthol carbonate, with the following structural formula: The mass ratio of the lipase to dimethyl tartrate-menthol carbonate is 1:5 to 1:8, and the lipase is derived from Candida antarcticis or Novozymes 435.

9. The method for preparing hydroxycarboxylic acid-menthol carbonate according to claim 6, characterized in that, The preparation method of tartaric acid-menthol carbonate is as follows: (1) Dibenzyl tartrate was dissolved in CH2Cl2, DMAP was added, and menthyl chloroformate was added dropwise at 0-5℃. After the addition was complete, the reaction was carried out at room temperature for 2-4 hours. After the reaction was completed, dichloromethane was evaporated, and petroleum ether was added. The petroleum ether phase was washed with saturated NaCl, dried over anhydrous Na2SO4, and the solvent was evaporated to obtain dibenzyl tartrate-menthol carbonate, with the following structural formula: (2) Dibenzyl tartrate-menthol carbonate was dissolved in methanol, Pd / C was added, and the reaction was carried out at room temperature for 2-4 hours under a hydrogen atmosphere. After the reaction was completed, the mixture was filtered and the solvent was evaporated to obtain tartaric acid-menthol carbonate, with the following structural formula: The molar ratio of L-dibenzyl tartrate, DMAP, and menthyl chloroformate is 1:3:2 to 1:4:2; the mass of Pd / C accounts for 3-7% of the mass of dibenzyl tartrate-menthol carbonate, preferably 5%.

10. The use of the hydroxycarboxylic acid-menthol carbonate according to claim 1 as a latent flavoring that releases menthol in heated or conventional cigarettes.

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