Preparation method of high-selectivity alpha-ionone

Abstract

The invention provides a method for high-selectivity synthesis of alpha-ionone, and the high-selectivity alpha-ionone can be stably obtained by controlling the ratio of cis-isomer to trans-isomer of pseudoionone to (E) / (Z) to be more than or equal to 1 and less than or equal to 4. The method is suitable for stable industrial production of alpha-ionone.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing highly selective methyl-ionone. Background Technology

[0002] Acetonide is a traditional synthetic fragrance with a strong violet aroma, which, when diluted, resembles orris root. It is mainly used to formulate flavorings for longan, raspberry, blackberry, cherry, and citrus. Current synthetic methods primarily use pseudoionone as a raw material, undergoing an acid-catalyzed cyclization reaction to obtain acetonide. However, the ratio of cis-trans isomers varies among different manufacturers due to variations in processing methods or raw materials. For example, CN102070423B uses a TEMPO and cuprous chloride catalytic system to prepare (E)-citral, and then, through a condensation reaction, produces (E)-pseudoionone with a content of 91%.

[0003] Our research found that different cis / trans ratios (E / Z) in the raw materials lead to extremely large fluctuations in the selectivity of methyl ionone in the cyclization reaction (60-85%), affecting the stability of product content and quality.

[0004] In view of this problem, the present invention provides a method for preparing highly selective methyl-ionone that can stably obtain high content of methyl-ionone at low cost. Summary of the Invention

[0005] To address the aforementioned problems in the existing technology, the purpose of this invention is to provide a method for preparing highly selective methyl-ionone. Currently, the E / Z values ​​of commercially available pseudo-ionones range from 0.1 to 99. Through experimental research, we found that the cis-trans ratio (E / Z) of pseudo-ionones in the raw materials significantly affects the selectivity of methyl-ionone. Therefore, by controlling the E / Z value, we can stably obtain highly selective methyl-ionone.

[0006] To achieve the above objectives, the present invention includes the following steps:

[0007] A method for preparing highly selective methyl-ionone, the method comprising:

[0008] The pseudoionone raw material undergoes a cyclization reaction under acid catalysis to obtain methylionone. The pseudoionone raw material has a total pseudoionone isomer content of ≥92%, and the mass content ratio of (E)-pseudoionone to (Z)-pseudoionone satisfies 1≤(E) / (Z)≤4.

[0009] The structure of (E / Z isomer) pseudoionone is as follows:

[0010]

[0011] Z-pseudoionone (left) and E-pseudoionone (right)

[0012] In this invention, the solvent used in the reaction is one or a combination of several of the following: benzene, toluene, xylene, cumene, tetrahydrofuran, chloroform, diethyl ether, and anisole.

[0013] Preferably, the mass ratio of the pseudoionone raw material to the solvent is 1:0.1-5, more preferably 1:0.5-2.

[0014] In this invention, the acid catalyst includes one or more of phosphoric acid, sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, and methanesulfonic acid. Preferably, the acid is prepared as a 20-99% aqueous solution, and the amount of acid solution used is 0.1-1 times the mass of the pseudoionone raw material, for example, 0.1 times, 0.2 times, 0.3 times, 0.5 times, or 1 times.

[0015] In this invention, the cyclization reaction is carried out at a temperature of 40-90℃, such as 50℃, 55℃, 60℃, 75℃, 80℃, or 90℃, preferably 50-80℃; and for a reaction time of 1-12h, such as 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 11h, or 12h, preferably 4-8h.

[0016] In this invention, the preferred reaction step is to first spread the pseudoionone raw material and solvent at a certain ratio at the bottom, and after the reaction temperature is reached, the acid catalyst is fed in the form of dropwise addition for 0.5 to 2 hours. The dropwise addition time is not included in the total reaction time.

[0017] In this invention, after the cyclization reaction is completed, post-processing processes such as washing and distillation are also included. These are all conventional operations in the field and are not particularly required by this invention. For example, in some specific examples, the post-processing method used is as follows: the cyclization reaction solution is washed with water, desolventized, and distilled to obtain α-ionone, with the α-ionone content maintained at 80-99%, such as 80%, 83%, 85%, 88%, 90%, and 95%.

[0018] In this invention, if the cis-trans isomer ratio in the pseudoionone raw material is <1 or >4, the isomer ratio can be adjusted by pre-reaction treatment. The E / Z can be 0.1, 0.5, 0.6, 0.8, 5, 8, 10, 20, 30, 40, 50, 60, 70, 80, 99, etc.

[0019] For example, one pretreatment method involves mixing the pseudoionone raw material with a solvent at a reaction mass ratio, and isomerizing it in a tower reactor. The catalyst can be a weakly basic anion exchange resin, barium hydroxide, lithium hydroxide, aluminum hydroxide, calcium hydroxide, etc. The reaction temperature is 80-100℃, for example, 80℃, 85℃, 90℃, 95℃, or 100℃; the pressure is 0.5-3MPa, for example, 0.5MPa, 0.8MPa, 1MPa, 1.5MPa, 2MPa, 2.5MPa, or 3MPa, preferably 1-2MPa; and the residence time is 5-30 min, for example, 5 min, 10 min, 15 min, 20 min, 25 min, or 30 min, preferably 10-20 min. Because the raw material is heat-sensitive, a residence time exceeding 30 min will lead to a decrease in the raw material content. After pretreatment, the material is heated to the reaction temperature via a heat exchanger and then directly fed into the reactor for the cyclization reaction.

[0020] Preferably, the isomerization reaction is carried out in an inert atmosphere, which is selected from nitrogen, argon, and helium.

[0021] It should be noted that the methods disclosed in this invention are merely illustrative examples of one type of catalytic conversion method used to achieve the isomeric ratio of pseudoionone described in this invention. The source of the pseudoionone raw material described in this invention should not be limited by the steps and parameters in the above methods. Similarly, the method for preparing methylionone described in this invention should not be limited by the examples above.

[0022] Compared with the prior art, the positive effects of the technical solution of this invention are as follows:

[0023] This invention ensures product selectivity and quality stability by controlling the content of pseudoionone cis-trans isomers in raw materials and achieving a selectivity of ≥80% for methylionone. Detailed Implementation

[0024] To better understand the technical solution of the present invention, the following embodiments will further illustrate the method provided by the present invention. However, the present invention is not limited to the listed embodiments, but should also include any other known modifications within the scope of the claims of the present invention.

[0025] The main raw material sources in the embodiments and comparative examples of this invention are as follows; unless otherwise specified, all other raw materials were obtained through ordinary commercial channels:

[0026] Isomer catalysts: Dandong Mingzhu Special Resin Co., Ltd., Innocare Reagent Co., Ltd.;

[0027] Acid catalyst: Aladdin Reagents Company;

[0028] Pseudoionone: Wanhua Chemical (purity >92%, E / Z = 1-4).

[0029] Pseudoionone: Aladdin Reagent Company (purity >92%, E / Z <1 or E / Z >4).

[0030] The performance test parameters and corresponding test methods used in the various embodiments of the present invention are as follows:

[0031] Aroma evaluation: Scored by three experienced perfumers according to GB / T 14454.2-2008, and the average value was taken;

[0032] Product purity was determined using gas chromatography (GC). Specific analytical conditions were as follows: Instrument: Agilent Gas Chromatograph 8890; Column: Polyethylene Glycol WAX column, 60 m length, 0.25 mm inner diameter, 0.25 μm film thickness; Column oven temperature: 100 °C; Injector temperature: 250 °C; FID detector temperature: 260 °C; Split ratio: 50:1; Injection volume: 0.2 μL; Carrier gas flow rate: 1.0 mL / min; Temperature program: Initial temperature 100 °C, then increase to 200 °C at 10 °C / min, hold for 8 min, then increase to 230 °C at 30 °C / min, hold for 10 min. Hydrogen, air, and make-up gas flow rates were set according to the instrument manufacturer's recommended optimal flow rates.

[0033] Example 1

[0034] 1) The pseudoionone raw material has an E / Z ratio of 1.2 and requires no pretreatment.

[0035] 500g of pseudoionone raw material and 400g of xylene solvent were premixed in a glass reactor equipped with a mechanical stirrer and heated to 70℃. 150g of 70% phosphoric acid was then added dropwise to the reactor using a metering pump at a set flow rate over 1 hour. After the addition was complete, the reaction was continued at this temperature for 3 hours. GC analysis of the sample showed a conversion rate >99.5% and a selectivity of 82% for α-ionone. After terminating the reaction, the mixture was allowed to stand for 1 hour, and the acid phase was separated. The mixture was then washed twice with pure water, and the solvent was removed by distillation. The fraction collected at 140℃ / 200PaA yielded 80% α-ionone and 98% total ketone content.

[0036] Scent sensory evaluation: Typical ionone floral scent, free of impurities, pure aroma (39.5 points).

[0037] Example 2

[0038] 1) The pseudo-ionone raw material has an E / Z ratio of 2 and requires no pretreatment.

[0039] 800g of pseudoionone raw material and 800g of anisole solvent were premixed in a glass reactor equipped with a mechanical stirrer and heated to 80℃. 200g of 50% sulfuric acid was added dropwise to the reactor using a metering pump at a set flow rate over 1 hour. After the addition was complete, the reaction was continued at this temperature for 4 hours. GC analysis of the sample showed a conversion rate >99.5% and a selectivity of 83% for α-ionone. After terminating the reaction, the mixture was allowed to stand for 1 hour, and the acid phase was separated. The mixture was then washed twice with pure water, and the solvent was removed by distillation. The fraction collected at 140℃ / 200PaA yielded α-ionone with a content of 81% and a total ketone content of 98%.

[0040] Scent sensory evaluation: Typical ionone floral scent, free of impurities, pure aroma (39.1 points).

[0041] Example 3

[0042] 1) The pseudoionone raw material has an E / Z ratio of 4 and requires no pretreatment.

[0043] 1000g of pseudoionone raw material and 500g of tetrahydrofuran solvent were premixed in a glass reactor equipped with a mechanical stirrer and heated to 60℃. 200g of 40% p-toluenesulfonic acid was added dropwise to the reactor using a metering pump at a set flow rate for 1 hour. After the addition was complete, the reaction was continued at this temperature for 4 hours. GC analysis showed a conversion rate >99.3% and a selectivity of 82% for α-ionone. After terminating the reaction, the mixture was allowed to stand for 1 hour, and the acid phase was separated. The mixture was then washed twice with pure water, and the solvent was removed by distillation. The fraction collected at 140℃ / 200PaA yielded α-ionone with a content of 81% and a total ketone content of 98%.

[0044] Scent sensory evaluation: Typical ionone floral scent, free of impurities, pure aroma (39 points).

[0045] Example 4

[0046] 1) The pseudoionone raw material has an E / Z ratio of 0.5, and it undergoes raw material pretreatment.

[0047] D309 macroporous weakly basic styrene-based anion exchange resin was packed into the reaction tower. Under a nitrogen atmosphere, 1 kg of pseudoionone raw material with an E / Z ratio of 0.5 and 1 kg of toluene were mixed and introduced into the reaction tower. The reaction pressure was 1 MPa, the reaction temperature was 80 °C, and the residence time was maintained at 15 min. A sample was taken at the outlet for gas phase analysis. The pseudoionone isomer ratio E / Z was 1.5.

[0048] 2) Preparation of methyl ionone

[0049] The isomerized reaction solution was collected and directly fed into the bottom of the reactor. Stirring and a circulating oil bath were started. After the system temperature dropped to 70℃, 250g of 80% phosphoric acid was added dropwise to the reactor using a metering pump at the set flow rate for 1 hour. After the addition was complete, the reaction was continued at this temperature for 5 hours. GC analysis showed a conversion rate >99.5%. After terminating the reaction, the mixture was allowed to stand for 1 hour, and the acid phase was separated. The solution was then washed twice with pure water, and the solvent was removed by distillation. The fraction collected at 130℃ / 150PaA yielded 82% methyl ionone and 97.5% total ketones.

[0050] Scent sensory evaluation: Typical ionone floral scent, free of impurities, pure aroma (39.1 points).

[0051] Example 5

[0052] 1) The pseudoionone raw material has an E / Z ratio of 0.8, and it undergoes pretreatment.

[0053] Spherical lithium hydroxide was packed into the reaction tower. Under a nitrogen atmosphere, 10 kg of pseudoionone raw material with E / Z = 0.8 and 5 kg of diethyl ether were mixed and fed into the reaction tower. The reaction pressure was 2 MPa, the reaction temperature was 85℃, and the residence time was maintained at 10 min. A sample was taken at the outlet for gas phase analysis. The pseudoionone isomer ratio E / Z = 1.8.

[0054] 2) Preparation of methyl ionone

[0055] The isomerized reaction solution was collected and directly fed into the bottom of the reactor. Stirring and a circulating oil bath were started. After the system temperature dropped to 80℃, 2 kg of 40% sulfuric acid was added dropwise to the reactor using a metering pump at the set flow rate for 1 hour. After the addition was complete, the reaction was continued at the set temperature for 3.5 hours. GC analysis showed a conversion rate >99.6%. After terminating the reaction, the mixture was allowed to stand for 1 hour, and the acid phase was separated. The mixture was then washed twice with pure water, and the solvent was removed by distillation. Vacuum distillation was then performed, and the fraction collected at 133℃ / 150PaA yielded 83% methyl ionone and 98.5% total ketones.

[0056] Scent sensory evaluation: Typical ionone floral scent, free of impurities, pure aroma (39 points).

[0057] Example 6

[0058] 1) The pseudo-ionone raw material has an E / Z ratio of 10, and the raw material is pretreated.

[0059] Spherical barium hydroxide was packed into the reaction tower. Under an argon atmosphere, 8 kg of pseudoionone raw material with an E / Z = 10 and 6 kg of anisole were mixed and fed into the reaction tower. The reaction pressure was 1.5 MPa, the reaction temperature was 90℃, and the residence time was maintained for 20 min. A sample was taken at the outlet for gas phase analysis. The pseudoionone isomer ratio E / Z = 2.5.

[0060] 2) Preparation of methyl ionone

[0061] The isomerized reaction solution was collected and directly fed into the bottom of the reactor. Stirring and a circulating oil bath were started. After the system temperature dropped to 65℃, 2.5 kg of 30% hydrochloric acid was added to the reactor using a metering pump at a set flow rate over 1 hour. After the addition was complete, the reaction was continued at this temperature for 6 hours. GC analysis showed a conversion rate >99.4%. After terminating the reaction, the mixture was allowed to stand for 1 hour, and the acid phase was separated. The solution was then washed twice with pure water, and the solvent was removed by distillation. The fraction collected at 133℃ / 150 PaA yielded 83% methyl ionone and 98% total ketones.

[0062] Scent sensory evaluation: Typical ionone floral scent, free of impurities, pure aroma (39.1 points).

[0063] Comparative Example 1

[0064] Referring to Example 4, the pseudoionone raw material had an E / Z ratio of 0.5, but unlike Example 4, it was not pretreated. The selectivity for methylionone was 75%, yielding a methylionone content of 78% and a total ketone content of 95%.

[0065] Sensory evaluation of odor structure: The top notes of odor are mixed with ripe fruit aromas, and the floral aroma is weak. The odor is acceptable (28.5 points).

[0066] Comparative Example 2

[0067] Referring to Example 6, the pseudoionone raw material had an E / Z ratio of 10, but unlike Example 6, it was not pretreated. The selectivity for methylionone was 74%, yielding a methylionone content of 76% and a total ketone content of 95%.

[0068] Sensory evaluation of odor: The odor is weakly floral and the odor is acceptable (28 points).

[0069] Although the present invention has been described in detail through the preferred embodiments described above, it should be understood that the above description should not be considered as a limitation of the present invention. Those skilled in the art will understand that modifications or adjustments can be made to the present invention based on the teachings of this specification. These modifications or adjustments should also be within the scope defined by the claims of the present invention.

Claims

1. A method for preparing methyl-ionone, characterized in that, The method includes a cyclization reaction of a pseudoionone raw material under acid catalysis to obtain methylionone, wherein the mass content ratio of (E)-pseudoionone to (Z)-pseudoionone in the pseudoionone raw material satisfies 1≤(E) / (Z)≤4.

2. The preparation method according to claim 1, characterized in that, The pseudoionone raw material has a total pseudoionone isomer content of ≥92%.

3. The preparation method according to claim 1 or 2, characterized in that, The solvent used in the reaction is one or a combination of several of the following: benzene, toluene, xylene, cumene, tetrahydrofuran, chloroform, diethyl ether, and anisole.

4. The preparation method according to claim 3, characterized in that, The mass ratio of the pseudoionone raw material to the solvent is 1:0.1-5.

5. The preparation method according to claim 1, characterized in that, Acid catalysts include one or more of phosphoric acid, sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, and methanesulfonic acid.

6. The preparation method according to claim 5, characterized in that, Prepare an aqueous solution of 20-99% acid, with the amount of acid solution being 0.1-1 times the mass of the pseudoionone raw material.

7. The preparation method according to any one of claims 1-6, characterized in that, The cyclization reaction is carried out at a temperature of 40-90℃, preferably 50-80℃, and for a time of 1-12h, preferably 4-8h.

8. The preparation method according to any one of claims 1-6, characterized in that, In the cyclization reaction, pseudoionone and solvent are first laid at the bottom. After the reaction temperature is reached, the acid catalyst is fed in a dropwise manner. The dropwise addition time is not included in the total reaction time.

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