Method for reducing production cost of beta-ionone

Abstract

The invention provides a method for reducing the production cost of beta-ionone, which is characterized in that the purity of pseudo-ionone can be reduced to 85% for use by controlling the ratio of a key isomer (A) to a cis-isomer (B) to a trans-isomer (C) in the raw material pseudo-ionone as A / (B + C) = (0.005-0.05): 1.

Description

Technical Field

[0001] The present invention belongs to the field of chemical intermediate synthesis, and particularly relates to a method for reducing the production cost of β-ionone. Background Art

[0002] β-Ionone, also known as ionone, belongs to a kind of terpene fragrance. It is an important essence and fragrance, widely used in the cosmetics, food and beverage industries. At the same time, it is also an important intermediate for synthesizing vitamin A and carotenoids. At the same time, as a representative of cyclized isoprenoids, it has a wide range of biological activities and shows strong anti-cancer effects.

[0003] The most commonly used industrial synthesis method is to synthesize β-ionone from citral through two-step reactions. First, citral and acetone undergo aldol condensation under an alkali catalyst to form pseudoionone, and then pseudoionone undergoes a cyclization reaction under low temperature and an acid catalyst to form β-ionone. This process route is simple, the raw material source is rich, and the conversion rate and yield are relatively high, which is a relatively economical synthesis method. However, generally in the second-step cyclization reaction of this process route, the raw material pseudoionone has a relatively high purity requirement (>94%). The improvement of the purity of this raw material mainly relies on high-temperature rectification. However, pseudoionone is a heat-sensitive substance, and high-temperature rectification will cause product deterioration, yield reduction, and increased production cost. Summary of the Invention

[0004] The purpose of the present invention is to provide a method for reducing the production cost of β-ionone. By controlling the ratios of the key isomer (A), cis-isomer (B), and trans-isomer (C) in the raw material pseudoionone, the purity requirement of the raw material pseudoionone can be reduced to 85%, greatly reducing the energy consumption for separating pseudoionone upstream and reducing the production cost.

[0005] To achieve the above-mentioned invention purpose, the technical solution of the present invention is as follows:

[0006] A method for reducing the production cost of β-ionone, in the presence of an acidic catalyst, pseudoionone undergoes a cyclization reaction to form β-ionone; wherein, the ratios of isomer (A), cis-isomer (B), and trans-isomer (C) in the raw material pseudoionone satisfy A / (B + C) = (0.005 - 0.05):1, preferably (0.01 - 0.02):1; wherein the structures of isomer (A), cis-isomer (B), and trans-isomer (C) are respectively

[0007] Industrially, the initial raw material for the production of β-ionone comes from citral, and there are mainly two common sources of citral: extraction from Litsea cubeba oil and chemical synthesis. Regardless of which method is used, a certain amount of isomeric impurities will be present in the obtained citral. These isomers will be introduced into the product pseudoionone during the reaction of citral and acetone to produce pseudoionone, and ultimately into the cyclization reaction. Therefore, generally, pseudoionone will be rectified and purified, and the purity needs to be increased to more than 94% before it can be used in the second-step cyclization reaction. However, there will be significant product losses during the rectification process. Further research has found that not all impurity isomers in the cyclization reaction will affect the reaction effect, and one of the key impurity isomers, isomer A, has a crucial impact on the reaction effect. The sources of the isomers are as follows:

[0008]

[0009] This isomer can undergo an isomerization reaction with the raw materials during the cyclization reaction. If its content is not controlled, it will lead to the selectivity of β-ionone. Further research has found that if the ratio of this isomer to the cis-trans isomers of pseudoionone can be controlled, then the purity requirement for the raw material pseudoionone in the cyclization reaction does not need to be so strict. In this way, the rectification energy consumption and high-temperature losses during the production of pseudoionone will be reduced, the raw material cost can be greatly reduced, and the production cost of β-ionone can be further reduced.

[0010] To control the key isomer A, generally, pseudoionone can be pretreated before the cyclization reaction. Specifically, before the cyclization reaction, pseudoionone can pass through a cation resin modified with phosphoric acid. The resin can achieve the conversion between isomer A and other isomers according to the different double-bond conjugate systems of isomer A, isomer B, and isomer C, thereby controlling the ratio between the isomers. Other methods that can control the ratio of the key isomer A to the cis-trans isomers of pseudoionone can also be used, such as by adding a pseudoionone sample with a lower content of isomer A to a sample with a higher content of isomer A for regulation.

[0011] Specifically, the method for controlling the key isomer A includes the following steps: Modify the T211 sulfonic acid resin with phosphoric acid in deionized water as the solvent, and wash the modified resin with deionized water after the modification.

[0012] In the present invention, the modification reaction temperature is 70 - 100 °C, preferably 80 - 90 °C; the modification reaction time is 12 - 48 h, preferably 24 - 36 h.

[0013] In the present invention, the dosage of phosphoric acid is 1 - 5 times the mass of the resin, preferably 2 - 3 times.

[0014] In the present invention, the dosage of the reaction solvent deionized water is 0.5 - 5 times the mass of the resin, preferably 1 - 2 times.

[0015] In the present invention, after the reaction combination, the resin is washed with deionized water until the pH of the filtrate is 2 - 7, preferably pH 3 - 4.

[0016] In the present invention, the reaction temperature of pseudoionone through the phosphoric acid modified resin is 30 - 70°C, preferably 40 - 50°C.

[0017] In the present invention, the residence time of pseudoionone through the phosphoric acid modified resin is 1 - 30 min, preferably 5 - 10 min.

[0018] In the present invention, the acidic catalyst for the cyclization reaction is selected from concentrated sulfuric acid with a mass concentration of 90 - 98%, preferably 93 - 95% concentrated sulfuric acid.

[0019] In the present invention, the cyclization reaction temperature is -30 - 20°C, preferably -10 - 0°C; the reaction residence time is 10 - 200 s, preferably 50 - 100 s.

[0020] In the present invention, the cyclization reaction is carried out continuously, and the reactor type is a continuous stirred tank reactor, a shell and tube reactor or a microchannel reactor, preferably a shell and tube reactor.

[0021] In the present invention, the mass ratio of the catalyst to pseudoionone is (0.5 - 3):1, preferably (1 - 2):1.

[0022] In the present invention, the reaction is carried out in a solvent, and the solvent is selected from one or more of n - hexane, n - heptane, dichloromethane, dichloroethane and toluene, preferably n - heptane.

[0023] In the present invention, the mass ratio of the solvent to pseudoionone is (0.5 - 5):1, preferably (2 - 4):1.

[0024] The positive effect of the present invention is as follows:

[0025] Through the research on the raw material composition in the production process of β - ionone, the key impurities that can improve the tolerance of the cyclization reaction raw material pseudoionone are discovered. By controlling the ratio of the key isomer A to the cis - trans isomers of pseudoionone, the purity of the used pseudoionone can be relaxed from 94% to 85%, greatly reducing the production cost of β - ionone. Description of the Drawings

[0026] Figure 1 1H NMR spectrum of isomer A

[0027] Figure 2 13C NMR spectrum of isomer A Detailed Description of the Invention

[0028] The technical solutions of the present invention will be further described below, but are not limited thereto. Any modification or equivalent replacement of the technical solutions of the present invention without departing from the scope of the technical solutions of the present invention shall be covered by the protection scope of the present invention.

[0029] Gas chromatography analysis: Chromatography model: Agilent WAX: 1701.42249; carrier gas: high-purity nitrogen; injection mode: autoinjector; nitrogen flow rate: 55.0 ml / min; vaporization chamber temperature: 290 °C; split injection, split ratio: 1:30; injection volume: 0.5 μl; column flow rate 1.5 ml / min; column temperature: first-order programmed temperature rise, initial temperature 90 °C, hold for 2 minutes, then rise to 290 °C at a rate of 20 °C / min, hold for 15 minutes; detector temperature 300 °C; the proportions of isomer A, isomer B and isomer C in the reaction liquid composition are quantified according to the external gas chromatography standard method.

[0030] Isomer A is separated by rectification of the reaction liquid, with 80 trays, reflux ratio 30:1, top pressure 1 kPaA, and the fraction with a top temperature of 109 - 111 °C is taken out. The product is further characterized by NMR spectrum: Nuclear magnetic resonance data ( 1 H 400 MHz, 13 C 100 MHz) are all measured by a varian 400 NMR nuclear magnetic resonance spectrometer, and the dissolution reagent is CDCl3.

[0031] 1 H NMR (400 MHz, CDCl3) δ: 6.83 - 6.80 (m, 1H), 6.01 - 5.98 (d, 1H), 5.22 - 5.20 (m, 1H), 5.02 - 5.00 (m, 1H), 4.90 - 4.88 (m, 1H), 2.65 - 2.62 (m, 2H), 2.25 (s, 3H), 1.98 - 1.97 (t, 4H), 1.82 (s, 3H), 1.71 (s, 3H).

[0032] 13 C NMR (100 MHz, CDCl3) δ: 197.6, 148.5, 141.3, 132.3, 132.1, 123.6, 110.7, 41.2, 37.7, 27.5, 26.8, 24.1, 18.4.

[0033] Specifications and sources of some reagents in the examples and comparative examples

[0034] Reagent Name Specification Source (Manufacturer) Pseudoionone Industrial Grade Hubei Wande Chemical Industry Sulfuric Acid Industrial Grade Tianjin Reagent Factory T211 Sulfonic Acid Resin Industrial Grade Dandong Mingzhu Dichloromethane, Heptane, Phosphoric Acid AR Aladdin Reagent

[0035] Resin modification: 50 g of T211 sulfonic acid resin, 100 g of phosphoric acid, and 100 g of deionized water were added to a 500 mL reaction flask, heated at 80 °C for 24 h. After the reaction, the temperature was lowered, and the resin was washed with deionized water until the pH of the washing solution was 3.

[0036] Example 1

[0037] Pseudoionone pretreatment: 50 g of the modified resin was loaded into a 100 mL resin column. Commercially purchased pseudoionone (purity 84.88%, isomer A / (isomer B + isomer C) = 0.081) entered through the upper feed port of the resin column, and the treated pseudoionone was collected from the lower discharge port. The feed temperature and the resin insulation temperature were 50 °C, and the residence time was 5 min. The purity and isomer composition of the final product were tested by gas chromatography. The composition of the discharged pseudoionone was purity 85.20%, isomer A / (isomer B + isomer C) = 0.0051.

[0038] The reaction used a microchannel reactor. Pseudoionone, 93% sulfuric acid, and n-heptane were fed simultaneously. The feed rate of pseudoionone (purity 85.20%, isomer A / (isomer B + isomer C) = 0.0051 determined by gas chromatography) was 11.29 kg / h, the feed rate of 93% sulfuric acid was 11.29 kg / h, and the feed rate of n-heptane was 45.14 kg / h. The reaction temperature was -10 °C, and the residence time was 50 s. The reaction effluent was quenched with sulfuric acid in pure water, and the organic phase was sampled for testing. The yield of β-ionone was 94.12%.

[0039] Example 2

[0040] Pseudoionone pretreatment: 50 g of the modified resin was loaded into a 100 mL resin column. Commercially purchased pseudoionone (purity 84.84%, isomer A / (isomer B + isomer C) = 0.093) entered through the upper feed port of the resin column, and the treated pseudoionone was collected from the lower discharge port. The feed temperature and the resin insulation temperature were 60 °C, and the residence time was 8 min. The purity and isomer composition of the final product were tested by gas chromatography. The composition of the discharged pseudoionone was purity 84.90%, isomer A / (isomer B + isomer C) = 0.0201. The reaction used a tubular reactor. Pseudoionone, 95% sulfuric acid, and dichloromethane were fed simultaneously. The feed rate of pseudoionone (purity 84.90%, isomer A / (isomer B + isomer C) = 0.0201) was 11.33 kg / h, the feed rate of 95% sulfuric acid was 33.98 kg / h, and the feed rate of n-heptane was 22.65 kg / h. The reaction temperature was 0 °C, and the residence time was 100 s. The reaction effluent was quenched with sulfuric acid in pure water, and the organic phase was sampled for testing. The yield of β-ionone was 94.23%.

[0041] Example 3

[0042] Pseudoionone pretreatment: 50 g of modified resin was loaded into a 100 mL resin column. Commercially purchased pseudoionone (purity 85.18%, isomer A / (isomer B + isomer C) = 0.101) was fed into the upper feed port of the resin column, and the pretreated pseudoionone was collected from the lower discharge port. The feed temperature and the resin insulation temperature were 65 °C, and the residence time was 15 min. The purity and isomer composition of the final product were tested by gas chromatography. The composition of the discharged pseudoionone was purity 85.30%, isomer A / (isomer B + isomer C) = 0.0105.

[0043] The reaction used a microchannel reactor, and pseudoionone, 98% sulfuric acid, and n-heptane were fed simultaneously. The feed rate of pseudoionone (purity 85.30%, isomer A / (isomer B + isomer C) = 0.0105) was 11.27 kg / h, the feed rate of 98% sulfuric acid was 22.54 kg / h, and the feed rate of n-heptane was 56.36 kg / h. The reaction temperature was 20 °C, and the residence time was 200 s. The reaction effluent was quenched with sulfuric acid in pure water, and the organic phase was sampled for testing. The yield of β-ionone was 94.35%.

[0044] Example 4

[0045] Pseudoionone pretreatment: 50 g of modified resin was loaded into a 100 mL resin column. Commercially purchased pseudoionone (purity 85.07%, isomer A / (isomer B + isomer C) = 0.114) was fed into the upper feed port of the resin column, and the pretreated pseudoionone was collected from the lower discharge port. The feed temperature and the resin insulation temperature were 70 °C, and the residence time was 4 min. The purity and isomer composition of the final product were tested by gas chromatography. The composition of the discharged pseudoionone was purity 85.00%, isomer A / (isomer B + isomer C) = 0.0495.

[0046] The reaction used a microchannel reactor, and pseudoionone, 90% sulfuric acid, and n-heptane were fed simultaneously. The feed rate of pseudoionone (purity 85.00%, isomer A / (isomer B + isomer C) = 0.0495) was 11.31 kg / h, the feed rate of 90% sulfuric acid was 5.66 kg / h, and the feed rate of n-heptane was 5.66 kg / h. The reaction temperature was -30 °C, and the residence time was 10 s. The reaction effluent was quenched with sulfuric acid in pure water, and the organic phase was sampled for testing. The yield of β-ionone was 94.08%.

[0047] Comparative Example 1

[0048] Pseudoionone pretreatment: 50 g of modified resin was loaded into a 100 mL resin column. Commercially purchased pseudoionone (purity 86.84%, isomer A / (isomer B + isomer C) = 0.096) entered through the upper feed port of the resin column, and the pretreated pseudoionone was collected from the lower discharge port. The feed temperature and the resin insulation temperature were 70 °C, and the residence time was 20 min. The purity and isomer composition of the final product were tested by gas chromatography. The composition of the discharged pseudoionone was purity 86.74%, isomer A / (isomer B + isomer C) = 0.0042.

[0049] The reaction used a microchannel reactor, and pseudoionone, 93% sulfuric acid, and n-heptane were fed simultaneously. The feed rate of pseudoionone (purity 86.74%, isomer A / (isomer B + isomer C) = 0.0042) was 11.29 kg / h, the feed rate of 93% sulfuric acid was 11.29 kg / h, and the feed rate of n-heptane was 45.14 kg / h. The reaction temperature was -10 °C, and the residence time was 50 s. The reaction effluent was quenched with sulfuric acid in pure water, and the organic phase was sampled for testing. The yield of β-ionone was 90.74%.

[0050] Compared with Example 1, the purity of pseudoionone was higher, but the ratio of isomer A / (isomer B + isomer C) was lower, resulting in a 3.38% decrease in the yield of β-ionone. This indicates that controlling the content of isomer A / (isomer B + isomer C) helps to increase the yield of β-ionone.

[0051] Comparative Example 2

[0052] The reaction used a microchannel reactor, and pseudoionone, 93% sulfuric acid, and n-heptane were fed simultaneously. Commercially purchased pseudoionone (purity 87.34%, isomer A / (isomer B + isomer C) = 0.0515) was fed at a rate of 11.29 kg / h, 93% sulfuric acid was fed at a rate of 11.29 kg / h, and n-heptane was fed at a rate of 45.14 kg / h. The reaction temperature was -10 °C, and the residence time was 50 s. The reaction effluent was quenched with sulfuric acid in pure water, and the organic phase was sampled for testing. The yield of β-ionone was 88.21%.

[0053] Compared with Example 1, the purity of pseudoionone was higher, but the ratio of isomer A / (isomer B + isomer C) was higher, resulting in a 5.91% decrease in the yield of β-ionone. This indicates that controlling the content of isomer A / (isomer B + isomer C) helps to increase the yield of β-ionone.

[0054] Comparative Example 3

[0055] The reaction uses a microchannel reactor, and pseudoionone, 90% concentrated sulfuric acid, and n-heptane are fed simultaneously. The feed rate of purchased pseudoionone (purity 94.51%, isomer A / (isomer B + isomer C) = 0.055) is 11.31 kg / h, the feed rate of 90% concentrated sulfuric acid is 5.66 kg / h, and the feed rate of n-heptane is 5.66 kg / h. The reaction temperature is -30 °C, the residence time is 10 s, and the reaction product is quenched with sulfuric acid in pure water. The organic phase is sampled and tested, and the yield of β-ionone is 93.19%.

[0056] Compared with Example 4, the purity of pseudoionone reaches more than 94%, the ratio of isomer A / (isomer B + isomer C) exceeds the upper limit, and the yield of β-ionone is closer to that of Example 4. This shows that after exceeding the upper limit, higher-purity pseudoionone is required to obtain a higher yield. However, higher-purity pseudoionone means more stringent separation conditions, higher energy consumption, and a significant increase in raw material costs.

Claims

1. A method for reducing the production cost of β-ionone, in the presence of an acidic catalyst, pseudoionone undergoes a cyclization reaction to produce β-ionone; wherein, In the raw material pseudoionone, the ratio of isomer (A), cis-isomer (B) and trans-isomer (C) satisfies A / (B + C) = (0.005 - 0.05):1, preferably (0.01 - 0.02):1; wherein the structures of isomer (A), cis-isomer (B) and trans-isomer (C) are respectively 2. The method according to claim 1, characterized in that, The acidic catalyst for the cyclization reaction is selected from concentrated sulfuric acid with a mass concentration of 90 - 98%, preferably 93 - 95% concentrated sulfuric acid.

3. The method according to claim 1 or 2, characterized in that, The temperature of the cyclization reaction is -30 - 20°C, preferably -10 - 0°C; the reaction residence time is 10 - 200 s, preferably 50 - 100 s.

4. The method according to any one of claims 1 to 3, characterized in that, The cyclization reaction is carried out continuously, and the reactor type is a continuous stirred tank, a shell-and-tube or a microchannel reactor, preferably a shell-and-tube reactor.

5. The method according to any one of claims 1 to 4, characterized in that The mass ratio of the catalyst to pseudoionone is (0.5 - 3):1, preferably (1 - 2):

1.

6. The method according to any one of claims 1-5, characterized in that, The reaction is carried out in a solvent, and the solvent is selected from one or more of n-hexane, n-heptane, dichloromethane, dichloroethane and toluene, preferably n-heptane.

7. The method according to any one of claims 1 to 6, characterized in that, The mass ratio of the solvent to pseudoionone is (0.5 - 5):1, preferably (2 - 4):1.

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