Synthesis method of 4-oxo-beta-ionone

Abstract

The invention belongs to the field of synthesis of organic matters, and particularly relates to a synthesis method of 4-oxo-beta-ionone, which comprises the following steps: S1, dissolving beta-ionone in a good solvent, and introducing sulfur dioxide; s2, adding water and a catalyst into the solvent, and then adding an oxidizing agent; s3, removing a water phase, and adding an alkaline solution; s4, separating a water phase, recovering the solvent, and distilling to obtain 4-oxo-beta-ionone; according to the method, the beta-ionone is oxidized into the 4-oxo-beta-ionone by using the oxidizing agent, and the sulfur dioxide is introduced to protect conjugated double bonds on a six-membered ring in the beta-ionone before the oxidizing agent is added, so that the oxidation selectivity of the oxidizing agent is improved, and the oxidation efficiency is high.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a method for synthesizing 4-oxo-β-ionone. Background Art

[0002] 4-Oxo-β-ionone is an important chemical that can be used as a flavoring agent in cigarettes and as a raw material for the synthesis of carotenoids such as canthaxanthin and astaxanthin. The specific chemical structure is shown in the figure below. Figure 1 shown.

[0003] In the prior art, there are two main routes for chemical preparation of 4-oxo-β-ionone: 1. Synthesis using α-ionone as raw material, which is generally not used for large-scale production due to its expensive raw materials and low conversion rate; 2. Synthesis using β-ionone as raw material, which is the current industrialized production method. In the route using β-ionone as raw material, U.S. Patent No. 4209450 uses excess sodium chlorate as an oxidant, iodine and potassium iodide to catalyze the oxidation of β-ionone to 4-oxo-β-ionone. Due to the problem of oxidation selectivity, the final yield is only 40%. Chinese patent CN102336641A discloses a method for oxidizing β-ionone with oxygen. In a DMSO system, oxygen is introduced at a reaction temperature of 90 to 125°C, and the flash point of DMSO is 89 to 95°C. This condition is not suitable for large-scale production and is very prone to flash explosion. Chinese patent CN112409155A has made improvements on the basis of US4209450, but there is still the problem of oxidant selectivity. Summary of the invention

[0004] The present invention aims to overcome at least one of the above-mentioned deficiencies of the prior art and provide a method for synthesizing 4-oxo-β-ionone to achieve the technical effect of improving oxidation selectivity.

[0005] The object of the present invention is to provide a method for synthesizing 4-oxo-β-ionone, comprising the following steps:

[0006] S1, dissolving β-ionone in a good solvent and introducing sulfur dioxide;

[0007] S2, adding water and a catalyst to the solvent, and then adding an oxidant;

[0008] S3, separate the water phase and add alkaline solution;

[0009] S4, separating the aqueous phase, recovering the solvent, and distilling to obtain 4-oxo-β-ionone.

[0010] The invention utilizes an oxidant to oxidize beta-ionone into 4-oxo-beta-ionone, and introduces sulfur dioxide before adding the oxidant to protect the conjugated double bonds on the six-membered ring in the beta-ionone, thereby improving the selectivity of the oxidant oxidation and achieving high oxidation efficiency.

[0011] Furthermore, in step S1, the molar amount of sulfur dioxide introduced is 1.05 to 1.3 times the molar amount of β-ionone.

[0012] Furthermore, in step S1, the temperature of the reaction system is maintained at 10°C to 25°C when sulfur dioxide is introduced.

[0013] Furthermore, the oxidant refers to any one of thiourea peroxide and urea peroxide.

[0014] After thiourea peroxide and urea peroxide are used as oxidants to complete the oxidation reaction, the generated thiourea and urea can be recycled and reacted with hydrogen peroxide to regenerate thiourea peroxide and urea peroxide, thereby achieving repeated utilization.

[0015] Furthermore, the molar amount of the oxidant is 1.1 to 2 times the molar amount of β-ionone.

[0016] Furthermore, the good solvent is selected from at least one of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and esters; and / or, the amount of the good solvent is 5 to 10 times the mass of β-ionone. Preferably, the good solvent is at least one of n-heptane and toluene.

[0017] Furthermore, the catalyst is a trivalent iron salt, and the amount of the catalyst used is 0.1% to 0.25% of the mass of β-ionone.

[0018] Further, the alkaline solution is prepared by dissolving at least one alkali raw material in water, and the alkali raw material is selected from at least one of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, and calcium hydroxide; and / or, the molar amount of the alkali raw material is 1 to 2 times the molar amount of β-ionone. Preferably, the alkali raw material is at least one of potassium carbonate and sodium carbonate.

[0019] Furthermore, in step S2, the temperature is controlled at 5°C to 15°C when the oxidant is added; and in step S3, the temperature is controlled at 30°C to 60°C when the alkaline solution is added.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The present invention utilizes an oxidant to oxidize β-ionone to 4-oxo-β-ionone, and introduces sulfur dioxide before adding the oxidant to protect the conjugated double bonds on the six-membered ring in β-ionone, thereby improving the selectivity of the oxidant oxidation and achieving high oxidation efficiency.

[0022] 2. The present invention uses any one or more of thiourea peroxide and urea peroxide as an oxidant. The thiourea and urea generated after the reaction of thiourea peroxide and urea peroxide can be recovered and reused after reacting with hydrogen peroxide, thereby saving costs.

[0023] 3. During the operation of the present invention, the raw materials used are simple and the process is highly operable. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of the chemical structure of 4-oxo-β-ionone.

[0025] Figure 2 This is a schematic diagram of the technical route adopted by the present invention. DETAILED DESCRIPTION

[0026] The object of the present invention is to provide a method for synthesizing 4-oxo-β-ionone, comprising the following steps:

[0027] S1, dissolving β-ionone in a good solvent and introducing sulfur dioxide;

[0028] S2, adding water and a catalyst to the solvent, and then adding an oxidant;

[0029] S3, separate the water phase and add alkaline solution;

[0030] S4, separating the aqueous phase, recovering the solvent, and distilling to obtain 4-oxo-β-ionone.

[0031] The present invention utilizes an oxidant to oxidize β-ionone to 4-oxo-β-ionone, and before oxidation, sulfur dioxide is introduced to react with the conjugated double bonds on the six-membered ring of β-ionone to form a five-membered ring sulfite, and the formed sulfite is more stable than the original double bond and is not easy to react further. This allows the oxidant to oxidize β-ionone without being affected by the conjugated double bonds; after the oxidation reaction, sulfur dioxide is removed from the molecule by adding an alkaline solution, thereby re-obtaining the original conjugated double bond structure. This synthesis method prevents the oxidant from oxidizing the double bonds, improves the selectivity of the oxidant oxidation, and has high oxidation efficiency.

[0032] Preferably, in step S1, the molar amount of sulfur dioxide introduced is 1.05 to 1.3 times the molar amount of β-ionone. When the molar amount of sulfur dioxide introduced is less than 1.05 times or greater than 1.3 times the molar amount of β-ionone, the content of the generated 4-oxo-β-ionone is low and the yield is low.

[0033] In the specific implementation, in step S1, the temperature of the reaction system is maintained at 10°C to 25°C when sulfur dioxide is introduced.

[0034] In a specific implementation, the oxidant refers to any one of thiourea peroxide and urea peroxide.

[0035] After thiourea peroxide and urea peroxide are used as oxidants to complete the oxidation reaction, the generated thiourea and urea can be recycled and reacted with hydrogen peroxide to regenerate thiourea peroxide and urea peroxide, thereby achieving repeated utilization.

[0036] Preferably, the molar amount of the oxidant is 1.1 to 2 times the molar amount of β-ionone.

[0037] In a specific implementation, the good solvent is selected from at least one of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and esters; and / or, the amount of the good solvent is 5 to 10 times the mass of β-ionone. Preferably, the good solvent is at least one of n-heptane and toluene.

[0038] In a specific implementation, the catalyst is a trivalent iron salt, and the amount of the catalyst used is 0.1% to 0.25% of the mass of β-ionone.

[0039] In a specific implementation, the alkaline solution is prepared by dissolving at least one alkali raw material in water, and the alkali raw material is selected from at least one of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, and calcium hydroxide; the molar amount of the alkali raw material is 1 to 2 times the molar amount of β-ionone. Preferably, the alkali raw material is at least one of potassium carbonate and sodium carbonate.

[0040] In specific implementation, in step S2, the reaction temperature is controlled at 5°C to 15°C when the oxidant is added; in step S3, the temperature is controlled at 30°C to 60°C when the alkaline solution is added.

[0041] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0042] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are conventional materials, reagents, methods and instruments in the art unless otherwise specified, and can be obtained through commercial channels by those skilled in the art.

[0043] Example 1

[0044] This embodiment provides a method of using Figure 2 The 4-oxo-β-ionone prepared according to the principle shown in the figure is prepared in the following manner:

[0045] S1, add 19.2 g (0.1 mol) of β-ionone and 150 g of n-heptane into a reactor, and introduce 7 g (0.11 mol) of sulfur dioxide while stirring, maintain the reaction temperature at 10°C, and introduce sulfur dioxide for 1 hour;

[0046] S2. When the raw material point disappears by TLC detection, 100 ml of water and 0.03 g of ferric sulfate are added, and the temperature of the reaction system is lowered to 5°C; then 11.3 g of urea peroxide is dissolved in 100 ml of water to prepare an oxidant aqueous solution, which is added dropwise to the above reaction solution, and the reaction temperature is maintained at 5°C to 8°C; the dropping time is 2.5 hours;

[0047] S3. After the addition is completed, use TLC to detect. When the raw material point disappears, separate the water phase, add 100 ml of water and 16.6 g of potassium carbonate, raise the temperature to 55°C to 60°C, and react for 1 hour;

[0048] S4. Detect by TLC. When the raw material point disappears, separate the water phase, recover the n-heptane, reduce the pressure to 500 Pa, control the temperature at 110°C to 115°C, and collect the product by distillation. After the product is placed at room temperature, weigh it to obtain 19.6 g of light yellow solid, with a gas phase content of 98.8% and a yield of 95%.

[0049] The detected 4-oxo-β-ionone NMR data are:

[0050] 1H-NMR (δ, ppm, 300MHz, CDCl3):

[0051] 1.93(s,6H,2CH3);1.895(t,2H,(CH3)2CCH2);1.803(d,3H,C=CCH3);2.35(s ,3H,CH3C=O); 2.53(t,2H,CH2C=O); 6.25(dd,1H,CHC=O); 7.23(dd,1H,CHC=C)

[0052] Example 2

[0053] This embodiment provides a method of using Figure 2 The 4-oxo-β-ionone prepared according to the principle shown in the figure is prepared in the following manner:

[0054] S1, take 19.2 grams (0.1 mol) of β-ionone and 180 grams of toluene into the reactor, and add 7.7 grams (0.12 mol) of sulfur dioxide while stirring, maintain the reaction temperature at 10 ° C, and add sulfur dioxide for 1 hour;

[0055] S2. When the raw material point disappears by TLC detection, 100 ml of water and 0.02 g of ferric sulfate are added, and the temperature of the reaction system is lowered to 5°C; then 14 g of urea peroxide is dissolved in 100 ml of water to prepare an oxidant aqueous solution, and the aqueous solution is added dropwise to the above reaction solution, and the reaction temperature is maintained at 5°C to 8°C; the dropping time is 3 hours;

[0056] S3, after the addition is completed, use TLC detection, when the raw material point disappears, separate the water phase, add 150ml of water and 20.7g of potassium carbonate, raise the temperature to 50℃~55℃, and react for 1.5 hours;

[0057] S4. Detect by TLC. When the raw material point disappears, separate the water phase, recover toluene, reduce the pressure to 500 Pa, control the temperature at 110°C to 115°C, and collect the product by distillation. After the product is left at room temperature, weigh it to obtain 19.8 g of light yellow solid, with a gas phase content of 98.9% and a yield of 96.1%.

[0058] Example 3

[0059] This embodiment provides a method of using Figure 2 The 4-oxo-β-ionone prepared according to the principle shown in the figure is prepared in the following manner:

[0060] S1, add 19.2 g (0.1 mol) of β-ionone and 100 g of petroleum ether into a reactor, and introduce 8.3 g (0.13 mol) of sulfur dioxide while stirring, maintain the reaction temperature at 25 ° C, and introduce sulfur dioxide for 1.5 hours;

[0061] S2. When the raw material point disappears by TLC detection, 100 ml of water and 0.02 g of ferric bromide are added, and the temperature of the reaction system is lowered to 10°C; then 14 g of urea peroxide is dissolved in 100 ml of water to prepare an oxidant aqueous solution, and the aqueous solution is added dropwise to the above reaction solution, and the reaction temperature is maintained at 5°C to 8°C; the dropping time is 3 hours;

[0062] S3, after the addition is completed, use TLC to detect, when the raw material point disappears, separate the water phase, add 150ml of water and 8g of sodium hydroxide, raise the temperature to 30°C, and react for 1 hour;

[0063] S4. Detect by TLC. When the raw material point disappears, separate the water phase, recover the petroleum ether, reduce the pressure to 500 Pa, control the temperature at 110°C to 115°C, and collect the product by distillation. After the product is placed at room temperature, weigh it to obtain 19.3 g of light yellow solid, with a gas phase content of 97.9% and a yield of 93.7%.

[0064] Comparative Example 1

[0065] This embodiment provides a 4-oxo-β-ionone, and the specific preparation method is as follows:

[0066] S1, add 19.2 g (0.1 mol) of β-ionone and 150 g of n-heptane into a reactor;

[0067] S2. When the raw material point disappears by TLC detection, 100 ml of water and 0.03 g of ferric sulfate are added, and the temperature of the reaction system is lowered to 5°C; then 11.3 g of urea peroxide is dissolved in 100 ml of water to prepare an oxidant aqueous solution, which is added dropwise to the above reaction solution, and the reaction temperature is maintained at 5°C to 8°C; the dropping time is 2.5 hours;

[0068] S3. After the addition is completed, use TLC to detect. When the raw material point disappears, separate the water phase and add 100 ml of water for washing;

[0069] S4, separate the water phase, recover n-heptane, reduce the pressure to 500 Pa, control the temperature at 110°C to 115°C, distill and collect the product, weigh the product after leaving it at room temperature, and obtain 15.8 g of light yellow solid, with a gas phase content of 96.7% and a yield of 76.7%.

[0070] Comparative Example 2

[0071] This embodiment provides a method of using Figure 2 The 4-oxo-β-ionone prepared according to the principle shown in the figure is prepared in the following manner:

[0072] S1, add 19.2 g (0.1 mol) of β-ionone and 150 g of n-heptane into a reactor, and introduce 10.24 g (0.16 mol) of sulfur dioxide while stirring, maintain the reaction temperature at 10°C, and introduce sulfur dioxide for 2 hours;

[0073] S2. When the raw material point disappears by TLC detection, 100 ml of water and 0.03 g of ferric sulfate are added, and the temperature of the reaction system is lowered to 5°C; then 11.3 g of urea peroxide is dissolved in 100 ml of water to prepare an oxidant aqueous solution, which is added dropwise to the above reaction solution, and the reaction temperature is maintained at 5°C to 8°C; the dropping time is 2.5 hours;

[0074] S3. After the addition is completed, use TLC to detect. When the raw material point disappears, separate the water phase, add 100 ml of water and 16.6 g of potassium carbonate, raise the temperature to 55°C to 60°C, and react for 1 hour;

[0075] S4. Detect by TLC. When the raw material point disappears, separate the water phase, recover the n-heptane, reduce the pressure to 500 Pa, control the temperature at 110°C to 115°C, and collect the product by distillation. After the product is placed at room temperature, weigh it to obtain 18.2 g of light yellow solid, with a gas phase content of 95.8% and a yield of 88.3%.

[0076] Comparative Example 3

[0077] This comparative example provides a method of using Figure 2 The 4-oxo-β-ionone prepared according to the principle shown in the figure is prepared in the following manner:

[0078] S1, add 19.2 g (0.1 mol) of β-ionone and 100 g of petroleum ether into a reactor, and introduce 5.76 g (0.09 mol) of sulfur dioxide while stirring, maintain the reaction temperature at 25 ° C, and introduce sulfur dioxide for 1.5 hours;

[0079] S2. When the reaction was unchanged by TLC, 100 ml of water and 0.02 g of ferric bromide were added, and the temperature of the reaction system was lowered to 10°C; 14 g of urea peroxide was dissolved in 100 ml of water to prepare an oxidant aqueous solution, which was added dropwise to the reaction solution, and the reaction temperature was maintained at 5°C to 8°C; the addition time was 3 hours;

[0080] S3, after the addition is completed, use TLC to detect, when the raw material point disappears, separate the water phase, add 150ml of water and 8g of sodium hydroxide, raise the temperature to 30°C, and react for 1 hour;

[0081] S4. Detect by TLC. When the raw material point disappears, separate the water phase, recover the petroleum ether, reduce the pressure to 500 Pa, control the temperature at 110°C to 115°C, and collect the product by distillation. After the product is placed at room temperature, weigh it to obtain 18.3 g of light yellow solid, with a gas phase content of 96.3% and a yield of 88.9%.

[0082] From the comparison between Example 1 and Comparative Example 1, it can be seen that the difference between Comparative Example 1 and Example 1 is that no sulfur dioxide is introduced before adding the oxidant, and no alkaline solution is added in step S3 to reduce sulfur dioxide. Comparative Example 1 produces 15.8 grams of light yellow solid with a yield of 76.7%, and Example 1 produces 19.6 grams of light yellow solid with a yield of 95%. Therefore, introducing sulfur dioxide before oxidizing β-ionone with an oxidant can improve the selectivity of oxidation and the yield, and the yield of 4-oxo-β-ionone prepared by the technical solution of the present invention is higher.

[0083] From the comparison between Example 1 and Comparative Example 2, it can be seen that the difference between Comparative Example 2 and Example 1 is that the molar amount and the introduction time of sulfur dioxide introduced in Comparative Example 2 are different. In Comparative Example 2, 10.24 g (equivalent to 0.16 mol) of sulfur dioxide are introduced for 2 hours. Comparative Example 2 obtains 18.2 g of light yellow solid with a yield of 88.3%, while Example 1 obtains 19.6 g of light yellow solid with a yield of 95%. Therefore, when the molar amount of sulfur dioxide introduced exceeds 1.3 times, the yield of 4-oxo-β-ionone obtained is small and the yield is low.

[0084] From the comparison between Example 3 and Comparative Example 3, it can be seen that the difference between Comparative Example 3 and Example 3 is that the molar amount of sulfur dioxide introduced in Comparative Example 3 is different. 5.76 g (equivalent to 0.09 mol) of sulfur dioxide is introduced in Comparative Example 3, and 18.3 g of light yellow solid is obtained in Comparative Example 3, with a yield of 88.9%, while 19.3 g of light yellow solid is obtained in Example 3, with a yield of 93.7%. Therefore, when the molar amount of sulfur dioxide introduced is less than 1.05 times, the yield of 4-oxo-β-ionone obtained is small and the yield is low.

[0085] In summary, the introduction of sulfur dioxide before using an oxidant to oxidize β-ionone can improve the selectivity of oxidation and the yield. When the molar amount of sulfur dioxide introduced exceeds 1.3 times and when the molar amount of sulfur dioxide introduced is less than 1.05 times, the yield of 4-oxo-β-ionone obtained is small and the yield is low.

[0086] The present invention utilizes an oxidant to oxidize β-ionone to 4-oxo-β-ionone, and before oxidation, sulfur dioxide is introduced to react with the conjugated double bonds on the six-membered ring of β-ionone to form a five-membered ring sulfite, and the formed sulfite is more stable than the original double bond and is not easy to react further. This allows the oxidant to oxidize β-ionone without being affected by the conjugated double bonds; after the oxidation reaction, sulfur dioxide is removed from the molecule by adding an alkaline solution, thereby re-obtaining the original conjugated double bond structure. This synthesis method prevents the oxidant from oxidizing the double bonds, improves the selectivity of the oxidant oxidation, and has high oxidation efficiency.

[0087] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the technical solution of the present invention, and are not intended to limit the specific implementation methods of the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the claims of the present invention shall be included in the protection scope of the claims of the present invention.

Claims

1. A method for synthesizing 4-oxo-β-ionone, characterized in that: The following steps are involved: S1, dissolving β-ionone in a good solvent and introducing sulfur dioxide; S2, adding water and a catalyst to the solvent, and then adding an oxidant; S3, separate the water phase and add alkaline solution; S4, separating the aqueous phase, recovering the solvent, and distilling to obtain 4-oxo-β-ionone.

2. The method for synthesizing 4-oxo-β-ionone according to claim 1, characterized in that: In step S1, the molar amount of sulfur dioxide introduced is 1.05 to 1.3 times the molar amount of β-ionone.

3. A method for synthesizing 4-oxo-β-ionone according to claim 2, characterized in that: In step S1, the temperature of the reaction system is maintained at 10°C to 25°C when sulfur dioxide is introduced.

4. A method for synthesizing 4-oxo-β-ionone according to claim 1, characterized in that: The oxidant is any one of thiourea peroxide and urea peroxide.

5. A method for synthesizing 4-oxo-β-ionone according to claim 3, characterized in that: The molar amount of the oxidant is 1.1 to 2 times the molar amount of β-ionone.

6. The method for synthesizing 4-oxo-β-ionone according to claim 1, characterized in that: The good solvent is selected from at least one of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and esters; and / or, the amount of the good solvent is 5 to 10 times the mass of β-ionone.

7. The method for synthesizing 4-oxo-β-ionone according to claim 6, characterized in that: The good solvent is at least one of n-heptane and toluene.

8. The method for synthesizing 4-oxo-β-ionone according to claim 1, characterized in that: The catalyst is a trivalent iron salt; and / or the amount of the catalyst is 0.1% to 0.25% of the mass of β-ionone.

9. The method for synthesizing 4-oxo-β-ionone according to claim 1, characterized in that: The alkaline solution is prepared by dissolving at least one alkaline raw material in water, wherein the alkaline raw material is selected from at least one of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, and calcium hydroxide; and / or the molar amount of the alkaline raw material is 1 to 2 times the molar amount of β-ionone.

10. The method for synthesizing 4-oxo-β-ionone according to claim 1, characterized in that: In step S2, the temperature is controlled at 5°C to 15°C when the oxidant is added, and / or, in step S3, the temperature is controlled at 30°C to 60°C when the alkaline solution is added.

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