A method for synthesizing theaspirone in one step

Abstract

The application provides a one-step method for synthesizing theamylone. The method uses alpha-isophorone as a raw material, glycol as a reaction aid, and t-butyl hydroperoxide solution as an oxidant under the condition of concentrated sulfuric acid to prepare the amylone. Compared with the traditional preparation method of the amylone, the method has the advantages of high conversion rate and high selectivity, and can ensure a high yield of the reaction.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis, specifically relating to a one-step method for synthesizing tea aroma ketones. Background Technology

[0002] 4-Oxoisophorone (2,6,6-trimethyl-2-cyclohexene-1,4-dione), also known as tea flavor ketone, is not only used as a flavoring or fragrance in food or cosmetic preparations, but also as an intermediate in the preparation of various carotenoids, vitamins and flavorings.

[0003] Currently, there are two main methods for synthesizing tea flavor ketones: oxidation using α-isophorone or oxidation using β-isophorone. The oxidation of β-isophorone to tea flavor ketones is the most widely used method. β-Isophorone is usually generated from α-isophorone via an isomerization reaction. However, because the equilibrium concentration for the isomerization of α-isophorone to β-isophorone is low, distillation and other methods are needed to separate β-isophorone and promote the reaction. This process is cumbersome and cannot yield high-purity β-isophorone, thus limiting the reaction yield in the oxidation of β-isophorone to tea flavor ketones.

[0004] CN110721696A discloses a method for preparing tea aroma ketones using perovskite-type composite oxides as a catalyst. In a fixed-bed reactor, lanthanide noble metal composite perovskite is used as a catalyst, and air is used as the oxidant to oxidize α-isophorone, achieving a yield of over 70%. However, the preparation process of perovskite-type composite oxides is relatively complex and uses precious metals such as rhodium, resulting in high costs.

[0005] CN115703702A discloses a method for preparing tea aroma ketone using Schiff base metal complexes. The method involves using diamine compounds and salicylaldehyde compounds to generate metal complexes with organometallic salts, using these complexes as catalysts, and using hydrogen peroxide or 70% tert-butyl hydrogen peroxide aqueous solution as oxidants to oxidize α-isophorone. The reaction yield can reach over 77%. However, the preparation process of the metal complexes is relatively complex and costly.

[0006] Based on the existing technologies, if β-isophorone is used as a raw material for oxidation reaction, the process is relatively complex and the reaction yield is low; if α-isophorone is used as a raw material for oxidation reaction, the preparation process of the catalyst is relatively complex and the preparation cost is high. Summary of the Invention

[0007] To address the aforementioned technical problems, one objective of this invention is to provide a one-step method for synthesizing tea aroma ketones. This method uses ethylene glycol as a reaction promoter, generates a cyclic ether intermediate, disrupts the conjugated double bond structure of α-isophorone, and then oxidizes the cyclic ether intermediate with an oxidizing agent to obtain tea aroma ketones in one step. Compared with traditional methods for preparing tea aroma ketones, this invention has the advantages of simple operation, high conversion rate, and high selectivity, ensuring a high yield.

[0008] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0009] A one-step method for synthesizing tea aroma ketone, wherein the method uses α-isophorone as a raw material, under concentrated sulfuric acid conditions, ethylene glycol as a reaction aid, and tert-butyl hydrogen peroxide solution as an oxidant to prepare tea aroma ketone.

[0010] The reaction in this application is the oxidation reaction of α-isophorone, as shown in equation (I). α-Isophorone is converted to tea ketone under oxidizing conditions. However, due to the conjugation between the carbon-oxygen and carbon-carbon double bonds in α-isophorone, the oxidation reaction is relatively difficult. Currently, a common process involves first isomerizing α-isophorone to β-isophorone, and then oxidizing it to tea ketone, as shown in equation (II). However, the isomerization reaction of α-isophorone requires a relatively high temperature, and the equilibrium concentration is low, resulting in a low yield of tea ketone.

[0011]

[0012] In this study, it was surprisingly discovered that adding a certain amount of ethylene glycol to α-isophorone under concentrated sulfuric acid conditions, followed by oxidation with an oxidant, can increase the yield of the product tea aroma ketone. Preliminary inference suggests that ethylene glycol can form a cyclic ether intermediate 1 with α-isophorone, cyclizing the carbon-oxygen double bond of α-isophorone and thus disrupting the conjugated structure between its carbon-oxygen and carbon-carbon double bonds, making α-isophorone more easily oxidized to generate cyclic ether intermediate 2. The yield of cyclic ether intermediate 1 can be controlled by adjusting the amount of ethylene glycol added. After the oxidation reaction, water is added to the reaction system for dilution. Under dilute sulfuric acid conditions, the cyclic ether intermediate reacts in reverse to remove ethylene glycol, thus yielding the final product tea aroma ketone. The possible reaction mechanism after adding ethylene glycol is illustrated in equation (III). After the reaction is completed, the reaction solution is washed with water to separate the phases. The sulfuric acid, ethylene glycol and oxidant added at the beginning of the reaction react to form tert-butanol, which will be distributed into the aqueous phase. Then the reaction solution is subjected to rotary evaporation under reduced pressure, and the fraction is collected.

[0013]

[0014] In one embodiment of the present invention, the method includes the following steps:

[0015] S1: Add α-isophorone and ethylene glycol to the reactor, and then add concentrated sulfuric acid to react;

[0016] S2: Cool the reaction system and add tert-butyl hydrogen peroxide solution to continue the reaction;

[0017] S3: Add water to the phase, wash the oil phase with water, and separate to obtain tea aroma ketone.

[0018] In one embodiment of the present invention, the molar ratio of α-isophorone and ethylene glycol in S1 is 1:(0.1-10), preferably 1:(1.3-1.5).

[0019] In one embodiment of the present invention, the mass ratio of α-isophorone to concentrated sulfuric acid in S1 is (0.1-10):1, preferably (0.5-0.8):1; preferably, the concentration of concentrated sulfuric acid is 70%-98wt%.

[0020] In one embodiment of the present invention, the reaction temperature of S1 is 0-50°C, preferably 30-40°C.

[0021] In one embodiment of the present invention, the molar ratio of α-isophorone and tert-butyl hydroperoxide in S2 is (0.1-10):1, preferably (1.3-1.8):1; preferably, the concentration of the aqueous solution of tert-butyl hydroperoxide is 50-70 wt%.

[0022] In one embodiment of the present invention, the reaction temperature in S2 is 0-50°C, preferably 5-15°C.

[0023] Another object of the present invention is to provide a tea-flavor ketone.

[0024] A tea-fragrant ketone, which is prepared by the above method.

[0025] Compared with the prior art, the beneficial effects of the technical solution of the present invention are as follows:

[0026] Using ethylene glycol as a reaction promoter, the conjugated double bond structure of α-isophorone is disrupted by generating a cyclic ether intermediate. The cyclic ether intermediate is then oxidized with an oxidizing agent to obtain tea-fragrant ketone in a one-step process. Compared with traditional methods for preparing tea-fragrant ketone, this invention has the advantages of simple operation, high conversion rate, and high selectivity, with a product yield of 97-99%. Detailed Implementation

[0027] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0028] Unless otherwise specified, all raw materials used in the following embodiments and comparative examples of this invention were obtained commercially. The α-isophorone, ethylene glycol, concentrated sulfuric acid, and tert-butyl hydrogen peroxide aqueous solution used were all of analytical grade.

[0029] In this embodiment of the invention, an Agilent 7820A gas chromatography system was used to analyze the purity of the product and the content of tea aroma ketones therein, with n-hexane as an internal standard and the internal standard method was used for analysis.

[0030] Example 1

[0031] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 40.3 g (0.65 mol, 1.3 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by 34.55 g (0.5 times the molar amount of α-isophorone) of concentrated sulfuric acid. The mixture was stirred and kept at 30 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 10 °C, and 96.4 g (0.75 mol, 1.5 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop, maintaining the reaction solution temperature at 10 °C during the addition. After the addition was complete, the temperature was maintained at 10 °C for 2 h, then raised to 50 °C and maintained at 50 °C for 2 h to obtain cyclic ether intermediate 2. Then, 500g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was taken and washed with 500g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1kPa / 80-85℃ was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 98.9%.

[0032] Example 2

[0033] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 41.85 g (0.675 mol, 1.35 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by the addition of 41.46 g (0.6 times the mass of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 35 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 5°C, and 115.7 g (0.9 mol, 1.8 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was then opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop. The reaction solution temperature was maintained at 5°C during the addition. After the addition was complete, the temperature was maintained at 5°C for 2 hours, and then the temperature was raised to 50°C and maintained at 50°C for 2 hours to obtain cyclic ether intermediate 2. Then, 500 g of deionized water was added to a three-necked flask, and after stirring, the reaction solution was transferred to a separatory funnel. The upper oil phase was collected, and then washed with 500 g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1 kPa / 80-85°C was collected to obtain a tea aroma ketone product with a purity of 99%, and the total product yield was 98.1%.

[0034] Example 3

[0035] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 43.4 g (0.7 mol, 1.4 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by the addition of 55.28 g (0.8 times the mass of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 40 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 15°C, and 83.6 g (0.65 mol, 1.3 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was then opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop. The reaction solution temperature was maintained at 15°C during the addition. After the addition was complete, the temperature was maintained at 10°C for 2 hours, and then the temperature was raised to 50°C and maintained at 50°C for 2 hours to obtain 2% of the cyclic ether intermediate. Then, 500 g of deionized water was added to a three-necked flask, and after stirring, the reaction solution was transferred to a separatory funnel. The upper oil phase was collected, and then washed with 500 g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction collected at 1 kPa / 80-85°C was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 97.3%.

[0036] Example 4

[0037] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 37.2 g (0.6 mol, 1.2 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by 41.46 g (0.6 times the molar amount of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 33 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 7 °C, and 90 g (0.7 mol, 1.4 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop, maintaining the reaction solution temperature at 7 °C during the addition. After the addition was complete, the temperature was maintained at 7 °C for 2 h, then raised to 50 °C and maintained at 50 °C for 2 h to obtain cyclic ether intermediate 2. Then, 500g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was taken and washed with 500g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1kPa / 80-85℃ was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 95.2%.

[0038] Example 5

[0039] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 46.5 g (0.75 mol, 1.5 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by 69.1 g (1 times the molar amount of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 32 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 9 °C, and 102.9 g (0.8 mol, 1.6 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop, maintaining the reaction solution temperature at 9 °C during the addition. After the addition was complete, the temperature was maintained at 9 °C for 2 h, then raised to 50 °C and maintained at 50 °C for 2 h to obtain cyclic ether intermediate 2. Then, 500g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was taken and washed with 500g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1kPa / 80-85℃ was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 98.1%.

[0040] Example 6

[0041] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 43.4 g (0.7 mol, 1.4 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by the addition of 55.28 g (0.8 times the mass of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 10 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 8°C, and 109.3 g (0.85 mol, 1.7 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was then opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop. The reaction solution temperature was maintained at 8°C during the addition. After the addition was complete, the temperature was maintained at 10°C for 2 hours, and then raised to 50°C and maintained at 50°C for 2 hours to obtain cyclic ether intermediate 2. Then, 500 g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was collected, and then washed with 500 g of deionized water each time. The washed oil phase was subjected to rotary evaporation under reduced pressure, and the fraction at 1 kPa / 80-85°C was collected to obtain a tea aroma ketone product with a purity of 99%, and the total product yield was 74.8%.

[0042] Example 7

[0043] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 44.95 g (0.725 mol, 1.45 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by the addition of 34.55 g (0.5 times the mass of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 38 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 13°C, and 64.3 g (0.5 mol, 1 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was then opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop. The reaction solution temperature was maintained at 13°C during the addition. After the addition was complete, the temperature was maintained at 13°C for 2 hours, and then the temperature was raised to 50°C and maintained at 50°C for 2 hours to obtain cyclic ether intermediate 2. Then, 500 g of deionized water was added to a three-necked flask, and after stirring, the reaction solution was transferred to a separatory funnel. The upper oil phase was collected, and then washed with 500 g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1 kPa / 80-85°C was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 92.5%.

[0044] Example 8

[0045] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 40.3 g (0.65 mol, 1.3 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by 48.37 g (0.7 times the molar amount of α-isophorone) of concentrated sulfuric acid (98 wt%). The mixture was stirred and kept at 40 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then raised to 50 °C, and 90 g (0.7 mol, 1.4 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop. The reaction solution temperature was maintained at 50 °C during the addition. After the addition was complete, the temperature was maintained at 50 °C for another 4 h to obtain cyclic ether intermediate 2. Then, 500g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was taken and washed with 500g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1kPa / 80-85℃ was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 64.4%.

[0046] Example 9

[0047] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 34.1 g (0.55 mol, 1.1 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by 13.82 g (0.2 times the molar amount of α-isophorone) of concentrated sulfuric acid (80 wt%). The mixture was stirred and kept at 33 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 7 °C, and 90 g (0.7 mol, 1.4 times the molar amount of α-isophorone) of 70% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was opened, and the 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop, maintaining the reaction solution temperature at 7 °C during the addition. After the addition was complete, the temperature was maintained at 7 °C for 2 h, then raised to 50 °C and maintained at 50 °C for 2 h to obtain cyclic ether intermediate 2. Then, 500g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was taken and washed with 500g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1kPa / 80-85℃ was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 86.1%.

[0048] Example 10

[0049] At room temperature, 69.1 g (0.5 mol) of α-isophorone and 37.2 g (0.6 mol, 1.2 times the molar amount of α-isophorone) of ethylene glycol were added to a 1 L three-necked flask, followed by 41.46 g (0.6 times the molar amount of α-isophorone) of concentrated sulfuric acid (82 wt%). The mixture was stirred and kept at 33 °C for 2 h to obtain cyclic ether intermediate 1. The solution temperature was then lowered to 7 °C, and 90 g (0.7 mol, 1.4 times the molar amount of α-isophorone) of 65% tert-butyl hydrogen peroxide aqueous solution was added to a constant pressure funnel. The funnel was opened, and 70% tert-butyl hydrogen peroxide aqueous solution was slowly added to the flask at a dropping rate of 5 s / drop, maintaining the reaction solution temperature at 7 °C during the addition. After the addition was complete, the temperature was maintained at 7 °C for 2 h, then raised to 50 °C and maintained at 50 °C for 2 h to obtain cyclic ether intermediate 2. Then, 500g of deionized water was added to a three-necked flask, stirred, and the reaction solution was transferred to a separatory funnel. The upper oil phase was taken and washed with 500g of deionized water each time. The washed oil phase was then subjected to rotary evaporation under reduced pressure, and the fraction at 1kPa / 80-85℃ was collected to obtain a tea aroma ketone product with a purity of 99% and a total product yield of 92.1%.

[0050] Comparative Example 1

[0051] Comparative Example 1 was based on the experiments in Example 1, except that ethylene glycol was not added in Comparative Example 1, while all other experimental conditions were the same. The final total yield of the tea aroma ketone product was 15.3%.

[0052] Comparative Example 2

[0053] Comparative Example 2 was based on Example 2, except that concentrated sulfuric acid was not added; all other experimental conditions were the same. The final total yield of tea aroma ketone product was 3.5%.

[0054] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

[0055] It is readily understood that the above embodiments are merely illustrative examples for clear explanation and do not imply that the invention is limited thereto. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A one-step method for synthesizing tea aroma ketones, characterized in that, The method uses α-isophorone as a raw material, under concentrated sulfuric acid conditions, with ethylene glycol as a reaction aid and tert-butyl hydrogen peroxide solution as an oxidant, to prepare tea aroma ketone. The method includes the following steps: S1: Add α-isophorone and ethylene glycol to the reactor, and then add concentrated sulfuric acid to react; S2: Cool the reaction system and add tert-butyl hydrogen peroxide solution to continue the reaction; S3: Add water to the phase, take the oil phase, wash with water, and separate to obtain tea aroma ketone; Wherein, the molar ratio of α-isophorone and ethylene glycol in S1 is 1:(1.1-1.5); In S1, the mass ratio of α-isophorone to concentrated sulfuric acid is 1:(0.2-1).

2. The method according to claim 1, characterized in that, The concentrated sulfuric acid in S1 has a concentration of 70%-98 wt%; And / or, the reaction temperature of S1 is 0-50℃.

3. The method according to claim 2, characterized in that, The reaction temperature for S1 is 30-40℃.

4. The method according to claim 1 or 2, characterized in that, The molar ratio of α-isophorone to tert-butyl hydroperoxide in S2 is 1:(1.0-1.8); And / or, the reaction temperature in S2 is 0-50℃.

5. The method according to claim 4, characterized in that, The concentration of the tert-butyl hydrogen peroxide aqueous solution in S2 is 50-70 wt%. And / or, the reaction temperature in S2 is 5-15℃.

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