A compound, its preparation method and application in cigarettes

Abstract

The application provides a compound with a structure of formula (I). The compound is used as a tobacco flavoring agent, reduces loss of flavoring components caused by high-temperature evaporation, and releases more evenly in each puff, meets the puffing taste of consumers, and can significantly increase the added amount in cigarettes without affecting the external aroma of the cigarettes. Meanwhile, the compound is used as a tobacco flavoring agent in cigarettes, can enrich the aroma of the cigarettes, soften the smoke, and improve the roundness and comfort of the smoke of the cigarettes.

Description

Technical Field

[0001] This invention relates to the field of cigarette technology, and in particular to a compound, its preparation method, and its application in cigarettes. Background Technology

[0002] As the public pays increasing attention to the issue of "smoking and health," "low-harm, low-tar" cigarettes are highly sought after by consumers. However, while achieving the effect of "reducing harm and tar" in cigarettes, it is inevitable to affect the release of mainstream aroma substances in the smoke, thereby affecting the smoking quality of the cigarettes. In order to compensate for the loss of aroma caused by reducing harm and tar, adding flavorings and fragrances to cigarettes has become an effective means.

[0003] Currently, the use of many excellent fragrances is limited due to issues with their stability, high-temperature resistance, and long-lasting effects. This has prompted the search for substances that are stable during storage, have low volatility, and can decompose to produce commonly used fragrances for excellent flavoring effects during use. Consequently, research in the field of fragrance precursors has gained significant attention. Fragrance precursors are substances with relatively large molecular weights and high boiling points. They have little or no aroma, but can release aromatic compounds through chemical hydrolysis, enzymatic hydrolysis, microbial action, pyrolysis, photolysis, and other pathways.

[0004] Therefore, it is essential to innovate and synthesize more latent fragrance substances that have long-lasting fragrance, uniform fragrance release, safety, and can decompose to produce a variety of aromas. Summary of the Invention

[0005] In view of this, the technical problem to be solved by the present invention is to provide a compound that can enrich the aroma of cigarettes, make the smoke smooth and delicate, and improve the roundness and comfort of cigarette smoke.

[0006] This invention provides a compound with the structure of formula (I):

[0007]

[0008] Wherein, R is ethyl or phenyl.

[0009] This invention provides a method for preparing the compound of the above-mentioned technical formula (I), comprising the following steps:

[0010] A) Ethyl maltol, sodium hydroxide, water and methanol are dissolved, benzyl chloride is added dropwise and heated to react, and after vacuum distillation, washing and drying, 3-(benzyloxy)-2-ethyl-4H-pyran-4-one with formula (II) is obtained;

[0011]

[0012] B) Mix n-propylamine or benzylamine with 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, add methanol, distilled water and NaOH in sequence, and heat to react to obtain a reaction solution;

[0013] C) After the reaction solution is cooled, it is separated by silica gel thin-layer chromatography to obtain the final product.

[0014] Preferably, the molar ratio of ethyl maltol, sodium hydroxide and benzyl chloride in step A) is 1:1.1:1.16;

[0015] The mass-to-volume ratio of ethyl maltol (g), distilled water (mL), and methanol (mL) is 1:1.5:10.

[0016] Preferably, the reaction temperature in step A) is 55–65°C; and the reaction time is 3.5–4.5 h.

[0017] The washing process involves washing with 5% NaOH solution 3-5 times and then with distilled water 1-3 times; the drying process involves drying with anhydrous Na2SO4; and the parameters for vacuum distillation are 0.1 MPa and 50°C.

[0018] Preferably, in step B), the molar ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, n-propylamine, and NaOH is 1:1.5:1.8; the molar ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, benzylamine, and NaOH is 1:1.5:1.8; and the mass-volume ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, distilled water, and methanol is 1:5:10.

[0019] Preferably, the reaction temperature in step B) is 70–100°C and the time is 6–24 h.

[0020] Preferably, the chromatography solvent for silica gel thin-layer chromatography in step C) is dichloromethane and ethyl acetate; the volume ratio of dichloromethane to ethyl acetate is 1:2.

[0021] The present invention provides a flavoring agent for tobacco, comprising compounds with the structure of formula (I) described in the above technical solution.

[0022] This invention provides a type of tobacco shreds with added flavoring agents as described in the above-mentioned technical solution.

[0023] The present invention provides a cigarette comprising the tobacco shreds described above.

[0024] Compared with existing technologies, this invention provides a compound with the structure of formula (I). As a tobacco flavoring agent, this compound reduces the loss of aroma components caused by high-temperature evaporation and provides a more uniform release with each puff, satisfying consumers' smoking experience. It can significantly increase the amount added to cigarettes without affecting the cigarette's external aroma. Simultaneously, when applied to cigarettes as a tobacco flavoring agent, it enriches the cigarette's aroma, creates a smooth and delicate smoke, and improves the roundness and comfort of the cigarette smoke. Attached Figure Description

[0025] Figure 1 Nuclear magnetic resonance imaging of the aroma-producing substance 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one 1 HNMR image.

[0026] Figure 2 Nuclear magnetic resonance imaging of the aroma-producing substance 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one 13 CNMR image.

[0027] Figure 3 Infrared spectrum of the aromatic compound 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one.

[0028] Figure 4 Mass spectrum of the aromatic compound 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one.

[0029] Figure 5 Nuclear magnetic resonance imaging of the aromatic substance 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one 1 HNMR image.

[0030] Figure 6 Nuclear magnetic resonance imaging of the aromatic substance 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one 13 CNMR image.

[0031] Figure 7 Infrared spectrum of the aromatic compound 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one.

[0032] Figure 8 Mass spectrum of the aromatic compound 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one. Detailed Implementation

[0033] This invention provides a compound, its preparation method, and its application in cigarettes. Those skilled in the art can refer to this document and appropriately modify the process parameters to achieve the desired result. It is particularly important to note that all similar substitutions and modifications are obvious to those skilled in the art and fall within the scope of this invention. The method and application of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately alter and combine the method and application described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0034] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural.

[0035] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or multiple items.

[0036] This invention provides a compound with the structure of formula (I):

[0037]

[0038] Wherein, R is ethyl or phenyl.

[0039] Specifically, the present invention provides 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one of formula (Ia) and 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one of formula (Ib).

[0040]

[0041] This invention innovatively synthesizes more latent fragrance substances that are long-lasting, have uniform fragrance release, are safe, and can decompose to produce multiple aromas. The above are novel sweet-scented latent fragrance substances.

[0042] This invention provides a method for preparing the compound of the above-mentioned technical formula (I), comprising the following steps:

[0043] A) Ethyl maltol, sodium hydroxide, water and methanol are dissolved, benzyl chloride is added dropwise and heated to react, and after vacuum distillation, washing and drying, formula (II) 3-(benzyloxy)-2-ethyl-4H-pyran-4-one is obtained;

[0044]

[0045] B) Mix n-propylamine or benzylamine with 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, add methanol, distilled water and NaOH in sequence, and heat to react to obtain a reaction solution;

[0046] C) After the reaction solution is cooled, it is separated by silica gel thin-layer chromatography to obtain the final product.

[0047] The compound of the above-mentioned technical solution (I) provided by the present invention is first dissolved in ethyl maltol, sodium hydroxide, water and methanol.

[0048] In one preferred embodiment of the present invention, ethyl maltol is first placed in a reaction vessel, and NaOH, distilled water and methanol are added sequentially, followed by ultrasonic dissolution; the ultrasonic power of the present invention is 200W, and the ultrasonic time is 1-2 minutes.

[0049] Benzyl chloride is added dropwise under stirring conditions; the preferred dropping rate according to the present invention is 10 drops / min.

[0050] Add benzyl chloride dropwise and heat to react.

[0051] In one preferred embodiment of the present invention, the reaction temperature is 55–65°C; the reaction time is 3.5–4.5 h.

[0052] In one preferred embodiment of the present invention, the reaction temperature is 60°C and the reaction time is 4 hours.

[0053] In one preferred embodiment of the present invention, the molar ratio of ethyl maltol, sodium hydroxide and benzyl chloride is 1:1.1:1.16;

[0054] In one preferred embodiment of the present invention, the mass-to-volume ratio of ethyl maltol (g), water (mL), and methanol (mL) is 1:1.5:10.

[0055] The reaction solution was subjected to vacuum distillation to remove the solvent, then dissolved in dichloromethane, washed, and the organic phase was dried over anhydrous Na₂SO₄. The solvent was then removed by vacuum distillation, followed by vacuum drying. The vacuum distillation parameters were specifically 0.1 MPa and 50°C. The vacuum drying parameters were specifically 0.1 MPa, 37°C, and 24 h.

[0056] The washing method described in this invention involves washing with 5% NaOH solution 3 to 5 times and then washing with distilled water 1 to 3 times.

[0057] In some embodiments, the washing involves washing five times with 5% NaOH solution and three times with distilled water.

[0058] Mix n-propylamine or benzylamine with 3-(benzyloxy)-2-ethyl-4H-pyran-4-one.

[0059] Specifically, the molar ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, n-propylamine, and NaOH is 1:1.5:1.8; the molar ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, benzylamine, and NaOH is 1:1.5:1.8.

[0060] Mix the ingredients, then add methanol, distilled water, and NaOH sequentially and heat to react, yielding a reaction solution.

[0061] According to the present invention, the mass-volume ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, distilled water and methanol is 1:5:10.

[0062] Specifically, the reaction temperature is 70–100°C, and the reaction time is 6–24 hours. Preferably, the reaction temperature is 80–100°C, and the reaction time is 10–24 hours. More preferably, the reaction temperature is 90–100°C, and the reaction time is 15–24 hours.

[0063] After the reaction solution is cooled, it is separated by silica gel thin-layer chromatography to obtain the final product.

[0064] The above reaction solution was cooled to room temperature and separated by silica gel thin-layer chromatography.

[0065] The chromatography solvent for silica gel thin-layer chromatography of the present invention is dichloromethane and ethyl acetate; the volume ratio of dichloromethane to ethyl acetate is 1:2.

[0066] The present invention provides a flavoring agent for tobacco, comprising compounds with the structure of formula (I) described in the above technical solution.

[0067] This invention provides a type of tobacco shreds with added flavoring agents as described in the above-mentioned technical solution.

[0068] The present invention provides a cigarette comprising the tobacco shreds described above.

[0069] The 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one and 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one prepared by this invention are both tobacco aroma monomers. They reduce the loss of aroma components caused by high-temperature evaporation and release more evenly with each puff, satisfying consumers' smoking taste. They can significantly increase the amount added to cigarettes without affecting the external aroma of cigarettes.

[0070] The present invention features simple experimental steps, high reaction yield, relatively simple post-processing, low production cost, and easy production conversion. The two tobacco monomer flavorings developed in this invention are used for the first time as tobacco flavoring agents in cigarettes, enriching the aroma, smoothing and delicacy of cigarette smoke, and improving the roundness and comfort of cigarette smoke.

[0071] It should be understood that in the various embodiments of this application, the order of the above processes does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0072] The numerical ranges and parameters involved in this invention have been presented as accurately as possible to the relevant values ​​in the specific embodiments. However, any numerical value inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise expressly stated, it should be understood that all numerical ranges or specific data used in this disclosure may have a reasonable deviation within a certain range, for example, within 1% or 0.5%.

[0073] The embodiments and comparative examples of this invention describe some examples, in which the embodiments illustrate certain implementations of the invention. However, this does not mean that the effects of the invention can only be achieved in these examples.

[0074] To further illustrate the present invention, the following describes in detail, with reference to embodiments, a compound provided by the present invention, its preparation method, and its application in cigarettes.

[0075] Example 1:

[0076] Preparation method of 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one:

[0077] 1. Weigh 1.4 g (10 mmol) of ethyl maltol into a 50 mL round-bottom flask, add 0.44 g (11 mmol) of NaOH, 2 mL of distilled water, and 14 mL of methanol sequentially, and dissolve by sonication. Add 1.34 mL (11.6 mmol) of benzyl chloride dropwise under stirring, and react at 60 °C for 4 h. After the reaction stops, remove the solvent by vacuum distillation. Dissolve in 10 mL of dichloromethane, wash 5 times with 5% NaOH solution and 3 times with distilled water. Dry the resulting organic phase with anhydrous Na₂SO₄, remove the solvent by vacuum distillation, and dry under vacuum to constant weight to obtain a brownish-yellow oily liquid, 3-(benzyloxy)-2-ethyl-4H-pyran-4-one (compound 2).

[0078] 2. 0.23 g (1 mmol) of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one and 0.123 mL (1.5 mmol) of n-propylamine were placed in a 25 mL round-bottom flask. 4 mL of methanol, 2 mL of distilled water, and 0.07 g (1.8 mmol) of NaOH were added sequentially. The mixture was dissolved by sonication and reacted at 100 °C for 24 h. After the reaction solution cooled to room temperature, silica gel thin-layer chromatography [V(dichloromethane):V(methanol) = 10:1] was performed to separate compound 3a (0.214 g, 79%).

[0079] Example 2:

[0080] Preparation method of 1-benzyl-3-(benzyloxy)-2-ethylpyridin-4(1H)-one:

[0081] 1. Weigh 1.4 g (10 mmol) of ethyl maltol into a 50 mL round-bottom flask, add 0.44 g (11 mmol) of NaOH, 2 mL of distilled water, and 14 mL of methanol sequentially, and dissolve by sonication. Add 1.34 mL (11.6 mmol) of benzyl chloride dropwise under stirring, and react at 60 °C for 4 h. After the reaction stops, remove the solvent by vacuum distillation. Dissolve in 10 mL of dichloromethane, wash 5 times with 5% NaOH solution and 3 times with distilled water. Dry the resulting organic phase with anhydrous Na₂SO₄, remove the solvent by vacuum distillation, and dry under vacuum to constant weight to obtain a brownish-yellow oily liquid, 3-(benzyloxy)-2-ethyl-4H-pyran-4-one (compound 2).

[0082] 2. 0.23 g (1 mmol) of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one and 0.164 mL (1.5 mmol) of benzylamine were placed in a 25 mL round-bottom flask, and 4 mL of methanol, 2 mL of distilled water, and 0.07 g (1.8 mmol) of NaOH were added sequentially. The mixture was dissolved by sonication and reacted at 100 °C for 24 h. After the reaction solution cooled to room temperature, it was separated by silica gel thin-layer chromatography [V(dichloromethane):V(ethyl acetate) = 1:2], yielding compound 3b (0.226 g, 71%).

[0083] Structural characterization

[0084] The spectral data for 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one are as follows: pale yellow liquid. 1 H NMR (400MHz, CDCl3) δ7.36(d,J=6.4Hz,2H),7.27–7.19(m,3H),7.15(d,J=7.5Hz,1H),6.41(d,J=7.5Hz,1H),5.20 (s,2H),3.70–3.64(m,2H),2.50(q,J=7.5Hz,2H),1.67–1.61(m,2H),0.97(t,J=7.5Hz,3H),0.86(t,J=7.4Hz,3H). 13C NMR (100MHz, CDCl3) δ172.38,144.84,144.74,137.20,136.81,127.71,127.22,126.84,116.27,71.88,53 .71,23.69,18.49,12.23,9.81.IR(KBr)ν:3056,2971,2929,1717,1622,1562,1372,1220,1127,744,692cm -1 .HRMS(ESI)Calcd.for C 17 H 19 NO2[M+Na] + :294.1465,found[M+Na] + 294.1486.

[0085] The spectral data for 1-benzyl-3-(benzyloxy)-2-ethylpyridin-4(1H)-one are as follows: brownish-yellow solid. 1 H NMR (400MHz, CDCl3) δ7.37-7.32(m,2H),7.27-7.18(m,7H),6.85-6.79(m,2H),6.45(d ,J=7.4Hz,1H),5.24(s,2H),4.96(s,2H),2.41(q,J=7.5Hz,2H),0.91(t,J=7.6Hz,3H). 13 CNMR (100MHz, CDCl3) δ173.60,146.52,145.77,139.17,137.59,135.73,129.25,128.93,128.33,128.26,127.94,125.7 0,117.53,72.82,56.45,19.92,13.09.IR(KBr)ν:3420,3070,3030,2970,2920,1710,1630,1570,1450,1080,827,735cm -1 .HRMS(ESI)Calcd.forC 21 H 21 NO2[M+H] + :320.1645,found[M+H] + 320.1635.

[0086] Research on the flavoring of target products in tobacco

[0087] Using 95% ethanol as a solvent, 3-(benzyloxy)-2-ethyl-1-propylpyridine-4(1H)-one and 1-benzyl-3-(benzyloxy)-2-ethylpyridine-4(1H)-one were prepared into 1% (w / w) solutions. 0.01 g, 0.03 g, and 0.05 g (i.e., 10 ppm, 30 ppm, and 50 ppm) of the solutions containing the target products were taken and uniformly sprayed onto 10 g of unflavored tobacco. The tobacco was then rolled, and 10 cigarettes of the same weight were selected and placed in a constant temperature and humidity chamber at 22℃±1℃ and 60%±2% for 48 h for equilibration. The control sample was blank tobacco (without flavoring or additives), which was also equilibrated for 48 h under the same temperature and humidity conditions. The results are shown in Table 1.

[0088] Table 1. Evaluation results of flavoring additives in tobacco products.

[0089]

[0090]

[0091] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A compound with the structure of formula (I): Equation (I); in, R is either ethyl or phenyl.

2. A method for preparing a compound of formula (I) according to claim 1, characterized in that, Includes the following steps: A) Ethyl maltol, sodium hydroxide, water and methanol are dissolved, benzyl chloride is added dropwise and heated to react, and after vacuum distillation, washing and drying, 3-(benzyloxy)-2-ethyl-4H-pyran-4-one with the structure of formula (II) is obtained; Formula (II); B) Mix n-propylamine or benzylamine with 3-(benzyloxy)-2-ethyl-4H-pyran-4-one of formula (II), add methanol, distilled water and NaOH in sequence and heat to react to obtain a reaction solution; C) After the reaction solution is cooled, it is separated by silica gel thin-layer chromatography to obtain the final product.

3. The preparation method according to claim 2, characterized in that, In step A), the molar ratio of ethyl maltol, sodium hydroxide, and benzyl chloride is 1:1.1:1.

16. The mass-to-volume ratio of ethyl maltol (g), water (mL), and methanol (mL) is 1:1.5:

10.

4. The preparation method according to claim 2, characterized in that, The reaction temperature in step A) is 55~65℃; the reaction time is 3.5~4.5h. The washing process involves washing with 5% NaOH solution 3-5 times and then with distilled water 1-3 times; the drying process involves drying with anhydrous Na2SO4; and the parameters for vacuum distillation are 0.1 MPa and 50°C.

5. The preparation method according to claim 2, characterized in that, In step B), the molar ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, n-propylamine, and NaOH is 1:1.5:1.8; the molar ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, benzylamine, and NaOH is 1:1.5:1.8; and the mass-volume ratio of 3-(benzyloxy)-2-ethyl-4H-pyran-4-one, distilled water, and methanol is 1:5:

10.

6. The preparation method according to claim 2, characterized in that, The reaction temperature in step B) is 70~100℃, and the time is 6~24h.

7. The preparation method according to claim 2, characterized in that, In step C), the chromatography solvent for silica gel thin-layer chromatography is dichloromethane and ethyl acetate; the volume ratio of dichloromethane to ethyl acetate is 1:

2.

8. A flavoring agent for tobacco, characterized in that, Compounds of formula (I) prepared by any one of the preparation methods of claims 1 or 2 to 7.

9. A type of tobacco shreds, characterized in that, Add the tobacco flavoring agent as described in claim 8.

10. A cigarette, characterized in that, Includes the tobacco as described in claim 9.

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