A synthesis method and application of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone

Abstract

The invention discloses a synthesis method of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (acetylformoin) and application thereof. The furanone is dissolved in toluene, lead tetraacetate or manganese triacetate is added, 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone is obtained after reaction, the furanone is placed in a phosphate buffer solution, esterase is added, and after reaction, the 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone is extracted and purified by LH-20 gel to obtain the 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone. The acetylformoin is applied to cigarette flavoring, and the main function of the acetylformoin is to highlight the sweet and caramel aroma of cigarettes and improve the alcohol content and taste of cigarettes.

Description

Technical Field

[0001] The invention belongs to the technical field of spices, and more specifically, relates to a synthesis method of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone and the application of the 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone as a spice in cigarettes. Background Art

[0002] Chinese cigarettes are mainly flue-cured cigarettes, whose style characteristics are mellow taste and prominent caramel-sweet and roasted-sweet aroma. With the in-depth development of tar reduction and harm reduction, the aroma loss of cigarettes is relatively serious, which requires the use of flavoring technology to make up for the aroma loss, thereby strengthening the style characteristics of Chinese cigarettes.

[0003] 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (acetylformoin) belongs to the enol ketone class of compounds and is one of the products of the Maillard reaction. There are two tautomers, 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (Ⅰ-a) and 3,4-dihydroxy-3-hexene-2,5-dione (Ⅰ-b). In the solid phase and polar solvents, the cyclic (Ⅰ-a) structure is dominant, while in the gas phase and non-polar solvents, the (Ⅰ-b) structure is dominant. Engel et al. (Eur Food Res Technol, 2001, 213:104–106) reported that the compound has a strong caramel sweet aroma with a threshold of 10 μg / L, which is much lower than the commonly used caramel sweet flavors maltol and furanone. There is no report on its application in cigarette flavoring, food, etc. Therefore, it has broad application prospects as a new specialty flavor.

[0004] The synthetic methods reported in the literature ( J. Agric. Food Chem. 1998, 46,3918-3928） , which uses acetone aldehyde as raw material and is achieved through a benzoin condensation reaction under the catalysis of potassium cyanide. Although this method only has one step of reaction, the separation and purification operation is cumbersome, the yield is only 10-16%, and it requires the use of highly toxic potassium cyanide, which is not suitable for large-scale production applications. Summary of the invention

[0005] In view of the problems existing in the prior art, the present invention provides a method for synthesizing 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone and the application of the 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone as a flavor in cigarettes. The method of the present invention uses cheap and readily available furanone as a raw material, and can obtain 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone in high yield through a two-step reaction, and the operation method is simple.

[0006] In order to solve the above problems, the present invention adopts the following technical solutions:

[0007] The synthesis method of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone of the present invention comprises the following steps:

[0008] (1) Furanone is dissolved in anhydrous toluene, anhydrous lead tetraacetate or manganese triacetate is added, the temperature is raised to 90°C and the reaction is completed, the reaction is cooled to room temperature, and the resulting organic phase is washed, dried, and concentrated under reduced pressure to obtain 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone, the structural formula of which is as follows:

[0009] ;

[0010] (2) The 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone prepared in step (1) was placed in a phosphate buffer solution, esterase was added, and the reaction was carried out for 5 h. After the reaction was completed, ethyl acetate was added for extraction. The organic layer was washed with saturated NaCl, dried with anhydrous Na2SO4, and the solvent was evaporated. The residue was purified by LH-20 gel to obtain the target product 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone, the structural formula of which is as follows:

[0011]

[0012] The synthetic route is as follows:

[0013] .

[0014] Furthermore, in the step (1), the molar ratio of furanone to lead tetraacetate is 1:3; and the molar ratio of furanone to manganese triacetate is 1:5.

[0015] Furthermore, the amount of ester hydrolase used in step (2) is 2%-20% of the mass of the substrate 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone.

[0016] Furthermore, the ester hydrolase in step (2) is Novozyme 435 lipase, Candida antarctica lipase, immobilized Candida antarctica lipase or porcine liver esterase.

[0017] Furthermore, the reaction temperature in step (2) is 25-40° C., and the reaction time is 8-16 h.

[0018] Furthermore, the specific structure of the target product in step (2) is any one of a cyclic structure and an open chain structure (Ⅰ-a and Ⅰ-b). That is, the target product in step (2) is any one of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (Ⅰ-a) and its tautomer 3,4-dihydroxy-3-hexene-2,5-dione (Ⅰ-b).

[0019] The 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone synthesized by the method of the invention is mixed with a stabilizer or a diluent and used as a flavor in cigarettes.

[0020] Beneficial effects of the present invention: The method of the present invention uses furanone as a raw material, and can obtain 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone through a two-step reaction, with high yield and simple preparation operation method. When 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone is added to cigarettes, it can be vaporized and volatilized and migrate into the mainstream smoke when the cigarette is burned and smoked, and the smoke is mellowed, giving the cigarette a distinct caramel-sweet aroma. DETAILED DESCRIPTION

[0021] The present invention will be further described below in conjunction with specific embodiments. It should be understood that the following embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention, and those skilled in the art in this field can make some non-essential improvements and adjustments based on the content of the above invention.

[0022] Example 1

[0023] The synthesis method of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (I) in this embodiment is as follows:

[0024] (1) Synthesis of 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone (II)

[0025] Furanone (1.28 g, 10 mmol) was dissolved in toluene, and anhydrous lead tetraacetate (13.2 g, 30 mmol) was added. The temperature was raised to 90°C and the reaction was allowed to proceed for 4 h until the reaction was complete. The mixture was cooled to room temperature, and 50 mL of water was added. The organic layer was separated, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain 2.05 g of compound (II).

[0026] Spectral data of compound (II):

[0027] 1 H NMR (600 MHz, CDCl3) δ 2.27 (s, 3H), 2.14 (s, 3H), 2.10 (s, 3H), 1.60 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 191.07, 175.88, 167.58, 167.56,128.59, 100.27, 21.38, 20.38, 20.19, 13.62.

[0028] (2) Synthesis of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (Ⅰ)

[0029] Compound (II) (500 mg) was placed in a flask, and a phosphate buffer solution with a pH of 8.0 was added, followed by the addition of Novozyme 435 lipase (50 mg). The mixture was reacted at 40°C for 12 h. The aqueous phase was extracted three times with ethyl acetate, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was subjected to LH-20 gel column chromatography, eluted with dichloromethane / methanol = 1 / 1, to obtain 250 mg of compound (I).

[0030] Spectral data of compound (I):

[0031] 1 H NMR (600 MHz, CD3OD) δ 2.17 (s, 3H), 1.41 (s, 3H). 13 C NMR (150 MHz, CD3OD) δ 197.83, 175.02, 132.24, 101.89, 22.77, 13.45.

[0032] 1 H NMR (600 MHz, CDCl3) δ 2.49 (s, 6H). 13 C NMR (150 MHz, CDCl3) δ26.05, 139.58, 205.61.

[0033] Example 2

[0034] The synthesis method of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (I) in this embodiment is as follows:

[0035] (1) Synthesis of 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone (II)

[0036] Furanone (1.28 g, 10 mmol) was dissolved in benzene, and manganese triacetate dihydrate (13.4 g, 50 mmol) was added. The temperature was raised to 90°C using a water separator and refluxed for 6 h until the reaction was complete. The mixture was cooled to room temperature, 50 mL of water was added, and the organic layer was separated. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with petroleum ether / ethyl acetate = 7 / 1 to obtain 1.48 g of compound (II).

[0037] (2) Synthesis of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (Ⅰ)

[0038] Compound (II) (500 mg) was placed in a flask, and a phosphate buffer solution with a pH of 7.5 was added, followed by pig liver esterase (10 mg). The mixture was reacted at 25°C for 8 h. The aqueous phase was extracted three times with ethyl acetate, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was subjected to LH-20 gel column chromatography, eluted with dichloromethane / methanol = 1 / 1, to obtain 266 mg of compound (I).

[0039] Example 5

[0040] The synthesis method of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (I) in this embodiment is as follows:

[0041] (1) The synthesis method of 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone (II) is the same as that of Example 1;

[0042] (2) Synthesis of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (Ⅰ)

[0043] Compound (II) (500 mg) was placed in a flask, and a phosphate buffer solution with a pH of 7.8 was added, followed by the addition of Candida antarctica lipase (100 mg). The mixture was reacted at 38°C for 16 h, and the aqueous phase was extracted three times with ethyl acetate, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was subjected to LH-20 gel column chromatography, eluted with dichloromethane / methanol = 1 / 1, to obtain 230 mg of compound (I).

[0044] Example 6

[0045] Application of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone in cigarette flavoring

[0046] Weigh 100 mg of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone, dilute to 2 mL with ethanol, and dilute in sequence. Use a flavor and fragrance injector to evenly add the prepared solutions of different concentrations into cigarettes. The gradient amount of cigarette addition is 0.001%, 0.002%, 0.005%, and 0.01% of the weight of tobacco. Select cigarette samples that meet the requirements and place them in an environment with a temperature of (22±1)℃ and a relative humidity of (60±3)% for more than 48 hours. Compare with the blank sample for smoking evaluation. The results are shown in Table 1.

[0047] Table 1 Comparative evaluation results

[0048]

[0049] It can be seen from Table 1 that the role of the compound 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone in cigarette flavoring is mainly to enhance the caramel-sweet aroma, the aftertaste and the oral comfort.

[0050] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A method for synthesizing 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone, characterized in that The following steps are involved: (1) Furanone is dissolved in anhydrous toluene, anhydrous lead tetraacetate or manganese triacetate is added, the temperature is raised to 90°C and the reaction is completed, the reaction is cooled to room temperature, and the resulting organic phase is washed, dried, and concentrated under reduced pressure to obtain 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone, the structural formula of which is as follows: ； (2) The 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone prepared in step (1) is placed in a phosphate buffer solution, and an esterase is added to react. After the reaction is completed, ethyl acetate is added for extraction, the organic layer is washed with saturated NaCl, dried over anhydrous Na2SO4, the solvent is evaporated, and the residue is purified by LH-20 gel to obtain the target product 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone, the structural formula of which is as follows: ； The ester hydrolase in step (2) is Novozyme 435 lipase, immobilized Candida antarctica lipase or porcine liver esterase.

2. The method for synthesizing 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone according to claim 1, characterized in that: In the step (1), the molar ratio of furanone to lead tetraacetate is 1:3; the molar ratio of furanone to manganese triacetate is 1:

5.

3. The method for synthesizing 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone according to claim 1, characterized in that: The amount of ester hydrolase used in step (2) is 2%-20% of the mass of the substrate 2,4-diacetoxy-2,5-dimethyl-3(2H)-furanone.

4. The method for synthesizing 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone according to claim 1, characterized in that: The reaction temperature in step (2) is 25-40° C. and the reaction time is 8-16 h.

5. The method for synthesizing 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone according to claim 1, characterized in that The synthetic route is as follows: ； The target product in step (2) is any one of 2,4-dihydroxy-2,5-dimethyl-3(2H)-furanone (I-a) and its tautomer 3,4-dihydroxy-3-hexene-2,5-dione (I-b).

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