CN109970535B - Preparation method of beta-ionone - Google Patents
Preparation method of beta-ionone Download PDFInfo
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- CN109970535B CN109970535B CN201910327701.9A CN201910327701A CN109970535B CN 109970535 B CN109970535 B CN 109970535B CN 201910327701 A CN201910327701 A CN 201910327701A CN 109970535 B CN109970535 B CN 109970535B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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Abstract
The invention provides a preparation method of beta-ionone, which is characterized by comprising the following raw materials in percentage by weight: 40-65 parts by weight of fuming sulfuric acid; 10-15 parts by weight of petroleum ether; 5-8 parts by weight of methanol; 25-40 parts of pseudo ionone. In the invention, fuming sulfuric acid in a certain proportion is added into rectified pseudo-ionone as a cyclization agent, petroleum ether and methanol are added as solvents, and the mixture is uniformly stirred at low temperature, so that the selectivity of beta-ionone in the cyclization process is obviously increased, the content reaches more than 97 percent, and the separation difficulty is reduced.
Description
Technical Field
The invention belongs to the field of chemical industry, and relates to a technology for increasing the selectivity of main reaction in the preparation process, in particular to a technology for increasing the selectivity of main reaction for a drug intermediate with high purity requirement, such as beta-ionone.
Background
The current methods for cyclizing pseudoionone in the cyclization process include the following methods:
1.98% concentrated sulfuric acid (density 1.84g/mL), the temperature can not be lower than-20 ℃ (mixed with petroleum ether), otherwise the concentrated sulfuric acid will solidify, the selectivity of beta-ionone in the cyclization does not exceed 85%, and great difficulty is brought to the subsequent separation and purification.
2.85% concentrated phosphoric acid (density 1.84), the temperature can not be lower than-10 ℃ (mixed with petroleum ether), otherwise the concentrated phosphoric acid will solidify, the selectivity of beta-ionone in the cyclization does not exceed 55%, which brings great difficulty to the subsequent separation and purification and can only be used as spice.
As a medical intermediate for preparing vitamin A, the purity of beta-ionone must reach 94%, the higher the selectivity of beta-ionone in production and synthesis is, the easier the separation and purification is, the higher the yield is, the selectivity is improved by one percentage point in synthesis, and finally the yield is improved by at least five percentage points (within the range of 90-99%). Otherwise, it can only be discarded or used as a much less expensive perfume raw material, causing significant losses.
Disclosure of Invention
The invention aims to provide a preparation method of beta-ionone with higher purity.
In order to achieve the above object, the present invention provides a method for preparing beta-ionone, which is characterized in that the raw materials comprise:
preferably, the feedstock also includes dry ice (suitably added at a temperature above-30 ℃ C. in the reaction vessel).
Preferably, the petroleum ether has a boiling point of 30-60 ℃. The petroleum ether comprises various pentanes, hexanes and the like.
Preferably, the preparation method of the beta-ionone comprises the following specific steps:
step 1: pumping 40-65 parts by weight of fuming sulfuric acid into a reaction kettle, adding 5-8 parts by weight of methanol and 8-10 parts by weight of petroleum ether, and cooling to-30 to-35 ℃ under the condition that the stirring speed is 200-;
step 2: adding petroleum ether into 25-40 parts by weight of pseudo ionone to obtain a mixture, wherein the sum of the petroleum ether and the petroleum ether in the step 1 is 10-15 parts by weight, and dropwise adding the obtained mixture into a reaction kettle;
and step 3: and after the dropwise addition is finished, continuing stirring for 5-15 minutes, gradually heating to-5-15 ℃, then putting the mixture obtained by the reaction into ice water which is added with petroleum ether and has the temperature of-8-12 ℃, stirring and extracting, wherein the volume ratio of the petroleum ether to the ice water is 1: and 10-15, separating the liquid, and evaporating the solvent petroleum ether from the obtained organic phase to obtain the beta-ionone.
Preferably, in the step 2, if the temperature exceeds-30 ℃ in the dropping process, the dropping is stopped, and dry ice is added to reduce the temperature to below-30 ℃.
Preferably, the temperature is controlled below-30 ℃ during the dropping process in the step 2.
Preferably, the ice water in step 3 contains an acid.
Preferably, the ice water in the step 3 is the water phase obtained by the liquid separation in the step 3 in the previous preparation method of the beta-ionone, and the water phase contains about 30-50% of sulfuric acid, so that the wastewater discharge is reduced and the energy is saved.
The fuming sulfuric acid can efficiently remove one part of water in the pseudo-ionone to ensure that molecules are cyclized, the probability of cyclizing to synthesize beta-ionone is high at low temperature, the freezing point of the fuming sulfuric acid mixture can be reduced by adding methanol, the fuming sulfuric acid mixture is kept in a liquid state at low temperature and is fully contacted and reacted with the pseudo-ionone, and the addition of the dry ice can ensure that the low temperature is maintained and impurities are not mixed in the reaction process (the reaction is strongly exothermic), wherein the dry ice is completely volatilized by heating.
Compared with the prior art, the invention has the beneficial effects that:
in the invention, fuming sulfuric acid in a certain proportion is added into rectified pseudo-ionone as a cyclization agent, petroleum ether and methanol are added as solvents, and the mixture is uniformly stirred at low temperature, so that the selectivity of beta-ionone in the cyclization process is obviously increased, the content reaches more than 97 percent, and the separation difficulty is reduced.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
Each raw material used in the following examples is a commercially available product.
Example 1
A method for preparing beta-ionone comprises raw materials of oleum, petroleum ether, methanol and pseudoionone, and dry ice, and is specifically shown in the following table 1.
The preparation method comprises the following specific steps:
step 1: pumping 40Kg of oleum (the content of the sulfuric acid is about 150%) into a reaction kettle, adding 5Kg of methanol and 8Kg of petroleum ether, and cooling to-30 to-35 ℃ under the condition of stirring rotation speed of 200 and 250 r/min;
step 2: adding petroleum ether (the boiling point is 30-60 ℃) into 40Kg of pseudo-ionone to obtain a mixture, wherein the sum of the petroleum ether and the petroleum ether in the step 1 is 15Kg, dropwise adding the obtained mixture into a reaction kettle, and keeping the temperature below-30 ℃ in the dropwise adding process; if the temperature exceeds-30 ℃ in the dropping process, stopping dropping and properly adding dry ice to reduce the temperature to below-30 ℃.
And step 3: after the dropwise addition, the mixture is continuously stirred for 10 minutes, the temperature is gradually increased to-10 ℃, then the mixture obtained by the reaction is put into 1000L of ice water (containing about 30-50% of sulfuric acid) with petroleum ether and at the temperature of-10 ℃, the water phase obtained by the liquid separation in the step 3 in the previous preparation method of the beta-ionone is stirred and extracted, and the volume ratio of the petroleum ether to the ice water is 1: 10, separating the liquid, and evaporating the solvent petroleum ether from the obtained organic phase to obtain the high-selectivity beta-ionone. The content of the chromatographic analysis reaches 96.5 percent (deducting the solvent petroleum ether)
Example 2
A method for preparing beta-ionone comprises raw materials of oleum, petroleum ether, methanol and pseudoionone, and dry ice, and is specifically shown in the following table 1.
The preparation method comprises the following specific steps:
step 1: pumping 50Kg of oleum (the content of the sulfuric acid is about 150%) into a reaction kettle, adding 5Kg of methanol and 8Kg of petroleum ether, and cooling to-30 to-35 ℃ under the condition of stirring at the rotating speed of 200 and 250 r/min;
step 2: adding petroleum ether (the boiling point is 30-60 ℃) into 32Kg of pseudo-ionone to obtain a mixture, wherein the sum of the petroleum ether and the petroleum ether in the step 1 is 12Kg, dropwise adding the obtained mixture into a reaction kettle, and keeping the temperature below-30 ℃ in the dropwise adding process; if the temperature exceeds-30 ℃ in the dropping process, stopping dropping and properly adding dry ice to reduce the temperature to below-30 ℃.
And step 3: after the dropwise addition, the mixture is continuously stirred for 10 minutes, the temperature is gradually increased to-10 ℃, then the mixture obtained by the reaction is put into 1000L of ice water (containing 30-50% of sulfuric acid) with petroleum ether at the temperature of-10 ℃ for stirring and extraction, and the volume ratio of the petroleum ether to the ice water is 1: 10, separating the liquid, and evaporating the solvent petroleum ether from the obtained organic phase to obtain the high-selectivity beta-ionone. The chromatogram showed a content of 98.5% (deduction of the solvent petroleum ether).
Example 3
A method for preparing beta-ionone comprises raw materials of oleum, petroleum ether, methanol and pseudoionone, and dry ice, and is specifically shown in the following table 1.
The preparation method comprises the following specific steps:
step 1: pumping 55Kg of oleum (the content of the sulfuric acid is about 150%) into a reaction kettle, adding 5Kg of methanol and 7Kg of petroleum ether, and cooling to-30 to-35 ℃ under the condition of stirring at the rotating speed of 200 and 250 revolutions per minute;
step 2: adding petroleum ether (the boiling point is 30-60 ℃) into 30g of pseudo-ionone to obtain a mixture, wherein the sum of the petroleum ether and the petroleum ether in the step 1 is 10Kg, dropwise adding the obtained mixture into a reaction kettle, and keeping the temperature below-30 ℃ in the dropwise adding process; if the temperature exceeds-30 ℃ in the dropping process, stopping dropping and properly adding dry ice to reduce the temperature to below-30 ℃.
And step 3: after the dropwise addition, the mixture is continuously stirred for 10 minutes, the temperature is gradually increased to-10 ℃, then the mixture obtained by the reaction is put into 1000L of ice water (containing about 30-50% of sulfuric acid) with petroleum ether and at the temperature of-10 ℃, the water phase obtained by the liquid separation in the step 3 in the previous preparation method of the beta-ionone is stirred and extracted, and the volume ratio of the petroleum ether to the ice water is 1: 10, separating the liquid, and evaporating the solvent petroleum ether from the obtained organic phase to obtain the high-selectivity beta-ionone. The chromatogram showed a content of 99.7% (deduction of the solvent petroleum ether).
Example 4
A method for preparing beta-ionone comprises raw materials of oleum, petroleum ether, methanol and pseudoionone, and dry ice, and is specifically shown in the following table 1.
The preparation method comprises the following specific steps:
step 1: pumping 60Kg of oleum (the content of the sulfuric acid is about 150%) into a reaction kettle, adding 5Kg of methanol and 7g of petroleum ether, and cooling to-30 to-35 ℃ under the condition of stirring at the rotating speed of 200 and 250 revolutions per minute;
step 2: adding petroleum ether (the boiling point is 30-60 ℃) into 25Kg of pseudo-ionone to obtain a mixture, wherein the sum of the petroleum ether and the petroleum ether in the step 1 is 10Kg, dropwise adding the obtained mixture into a reaction kettle, paying attention to the temperature rise, and keeping the temperature below-30 ℃ in the dropwise adding process; if the temperature exceeds-30 ℃ in the dropping process, stopping dropping and properly adding dry ice to reduce the temperature to below-30 ℃.
And step 3: after the dropwise addition, the mixture is continuously stirred for 10 minutes, the temperature is gradually increased to-10 ℃, then the mixture obtained by the reaction is put into 1000L of ice water (containing about 30-50% of sulfuric acid) with petroleum ether and at the temperature of-10 ℃, the water phase obtained by the liquid separation in the step 3 in the previous preparation method of the beta-ionone is stirred and extracted, and the volume ratio of the petroleum ether to the ice water is 1: 10, separating the liquid, and evaporating the solvent petroleum ether from the obtained organic phase to obtain the high-selectivity beta-ionone. The chromatogram showed a content of 99.8% (deduction of the solvent petroleum ether).
Comparative example 1: a process for the ring synthesis of beta-ionone from pseudoionone comprises the following steps of 1. The method comprises the following specific steps: pumping 100Kg of concentrated sulfuric acid into a reaction kettle, adding 10Kg of petroleum ether, and cooling to-20 ℃ under the condition of stirring rotation speed of 200 and 250 r/min; 5Kg of petroleum ether is added into 35Kg of pseudoionone, slowly and dropwise added into a reaction kettle, the dropwise addition is stopped when the temperature is raised to be more than-10 ℃, and dry ice is added to ensure that the temperature is reduced and then the dropwise addition is carried out. After the dropwise addition, the reaction mixture is stirred for 10 minutes and slightly heated to-5 ℃, then the reaction mixture is put into 1000L of ice water (containing about 30-50% of sulfuric acid) with petroleum ether at the temperature of-10 ℃ for stirring and extraction, and the solvent petroleum ether is evaporated from an organic phase to obtain crude beta-ionone with low selectivity. The chromatogram showed a content of 84.7% (deduction of the solvent petroleum ether).
TABLE-1 beta-ionone purity (subtraction of the mass of the solution during analysis)
Claims (5)
1. The preparation method of the beta-ionone is characterized by comprising the following raw materials:
the preparation method of the beta-ionone comprises the following specific steps:
step 1: pumping 40-65 parts by weight of fuming sulfuric acid into a reaction kettle, adding 5-8 parts by weight of methanol and 8-10 parts by weight of petroleum ether, and cooling to-30 to-35 ℃ under the condition that the stirring speed is 200-;
step 2: adding petroleum ether into 25-40 parts by weight of pseudo ionone to obtain a mixture, wherein the sum of the petroleum ether and the petroleum ether in the step 1 is 10-15 parts by weight, and dropwise adding the obtained mixture into a reaction kettle;
and step 3: and after the dropwise addition is finished, continuing stirring for 5-15 minutes, gradually heating to-5-15 ℃, then putting the mixture obtained by the reaction into ice water which is added with petroleum ether and has the temperature of-8-12 ℃, stirring and extracting, wherein the volume ratio of the petroleum ether to the ice water is 1: and 10-15, separating the liquid, and evaporating the solvent petroleum ether from the obtained organic phase to obtain the beta-ionone.
2. The method of claim 1, wherein the starting material further comprises dry ice.
3. The method of claim 1, wherein the petroleum ether has a boiling point of 30 to 60 ℃.
4. The method for preparing beta-ionone according to claim 1, wherein in step 2, if the temperature exceeds-30 ℃ during the dropping process, the dropping is stopped and dry ice is added to reduce the temperature to below-30 ℃.
5. The method for preparing beta-ionone according to claim 1, wherein the temperature is controlled to be below-30 ℃ during the dropping in step 2.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1129209A (en) * | 1995-10-05 | 1996-08-21 | 复旦大学 | Process for production of beta-jonone |
| CN1348949A (en) * | 2000-10-18 | 2002-05-15 | 浙江新和成股份有限公司 | Beta-ionone producing process |
| CN1508113A (en) * | 2002-12-19 | 2004-06-30 | 上海应用技术学院 | Industrial method for preparing beta-ionone |
| CN102924254A (en) * | 2012-10-30 | 2013-02-13 | 浙江新和成股份有限公司 | Method for preparing ionone by using super-strong acid or super-strong-acid-based ionic liquid as catalyst |
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- 2019-04-23 CN CN201910327701.9A patent/CN109970535B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1129209A (en) * | 1995-10-05 | 1996-08-21 | 复旦大学 | Process for production of beta-jonone |
| CN1348949A (en) * | 2000-10-18 | 2002-05-15 | 浙江新和成股份有限公司 | Beta-ionone producing process |
| CN1508113A (en) * | 2002-12-19 | 2004-06-30 | 上海应用技术学院 | Industrial method for preparing beta-ionone |
| CN102924254A (en) * | 2012-10-30 | 2013-02-13 | 浙江新和成股份有限公司 | Method for preparing ionone by using super-strong acid or super-strong-acid-based ionic liquid as catalyst |
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