Process for the synthesis of p-methoxyphenol by catalytic oxidation of phenol
The synthesis of p-methoxyphenol by catalytic oxidation of phenol in a methanol system using acetic acid, iodobenzene, and an oxidant solves the pollution and equipment corrosion problems of traditional methods, achieving a green synthesis with high yield and high selectivity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- KANG YU LIFE SCI TECH (SUZHOU) CO LTD
- Filing Date
- 2023-11-22
- Publication Date
- 2026-07-21
AI Technical Summary
Existing technologies for the synthesis of p-methoxyphenol suffer from severe pollution and equipment corrosion, especially when using the dimethyl sulfate method and the methanol catalytic method, which result in highly toxic substance pollution and waste pollution, as well as low yields.
The synthesis of p-methoxyphenol was achieved by catalytic oxidation of phenol in a nitrogen atmosphere using acetic acid, iodobenzene, and oxidants (such as hydrogen peroxide, TEMPO, and potassium persulfate). The oxidation reaction was carried out in a methanol system using a self-made composite oxidant by controlling the temperature and pH value. Subsequent treatments included extraction, washing, and vacuum distillation.
A green synthesis with high yield and high selectivity was achieved, with a yield of 50-60% and a selectivity of 90% for p-methoxyphenol, and a product purity of over 99%, avoiding the pollution problems of traditional methods.
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Figure CN117603020B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for the catalytic oxidation of phenol to synthesize p-methoxyphenol, which is used to prepare p-methoxyphenol and belongs to the field of organic synthesis technology. Background Technology
[0002] p-Methoxyphenol (also known as p-hydroxyanisole, hydroquinone monomethyl ether, or hydroquinone monomethyl ether) is not only an important intermediate for fine chemical products such as pharmaceuticals, fragrances, and pesticides, but it can also be used as a polymerization inhibitor, antioxidant, and plasticizer for high molecular weights, making it very versatile.
[0003] Numerous domestic and international reports document the synthesis routes of p-methoxyphenol, with the main methods including the anisole method, hydroquinone method, and benzaldehyde method. These methods range from the catalytic oxidation of p-methoxybenzaldehyde, the hydroxylation of anisole, the reaction of hydroquinone with dimethyl sulfate, hydroquinone with dimethyl carbonate, hydroquinone with methanol, to the diazotization and hydrolysis of p-aminoanisole, and are continuously being optimized. Currently, the hydroquinone method and the diazotization of p-aminoanisole are the primary methods used domestically and internationally. The hydroquinone method uses dimethyl sulfate or methanol as a catalyst. The dimethyl sulfate method has drawbacks: dimethyl sulfate is highly toxic, has a foul odor, easily pollutes the environment, and has a low product yield, leading to its gradual phasing out. The methanol catalytic method uses sulfuric acid or other strong acid catalysts, and like the diazotization of p-aminoanisole, it suffers from severe waste pollution and equipment corrosion during production. Summary of the Invention
[0004] The purpose of this invention is to provide a method for the catalytic oxidation of phenol to synthesize p-methoxyphenol. This synthesis method is green, has high yield and selectivity, and uses inexpensive and readily available raw materials.
[0005] To achieve the above objectives, the technical solution of the present invention is as follows:
[0006] A method for the catalytic oxidation of phenol to synthesize p-methoxyphenol, comprising the following steps:
[0007] (1) Add acetic acid, iodobenzene and oxidant to the reaction vessel, control the temperature at 25-40℃ and react for 4-8 hours, adjust the pH to neutral, extract, and dry the organic phase to prepare a composite oxidant; wherein the molar ratio of iodobenzene and oxidant is 1:2.5-5, and the molar ratio of acetic acid and oxidant is 0.2-0.6:1.
[0008] Specifically, the oxidant is one of 30-35% hydrogen peroxide, TEMPO, or potassium persulfate, with hydrogen peroxide being preferred.
[0009] Specifically, in this step, the reaction is carried out under a nitrogen atmosphere, the pH is adjusted by adding sodium hydroxide solution, and the mixture is extracted with dichloromethane.
[0010] (2) Add phenol, methanol and composite oxidant to the reaction vessel, control the temperature at 25-40℃ and react for 4-6 hours, quench, evaporate methanol, adjust pH to weakly alkaline, extract, wash and evaporate organic phase; wherein, the volume ratio of methanol to phenol is 2-5:1 and the molar ratio of composite oxidant to phenol is 1.2-2:1.
[0011] Specifically, in this step, the sample is quenched with sodium sulfite, the pH is adjusted to weakly alkaline with sodium hydroxide, extracted with dichloromethane, and washed with saturated saline solution.
[0012] (3) Distill under reduced pressure at a vacuum of less than 0.53 kPa and collect the fraction at 110-112℃.
[0013] Using the synthesis method of this invention, the conversion rate of phenol is 50-60%, the selectivity is 90%, and the GC purity of the product is over 99%.
[0014] The advantages of the synthesis method of this invention are: selective catalytic oxidation is used, phenol, which is relatively inexpensive, is used as a raw material, and a self-prepared composite oxidant is used to directly oxidize the methoxy group in a methanol system, resulting in high yield and selectivity of p-methoxyphenol. Moreover, the raw materials are inexpensive and readily available, making it a new green synthesis method. Attached Figure Description
[0015] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments.
[0016] Figure 1 This is the gas phase spectrum of the fraction from Example 1.
[0017] Figure 2 This is the gas phase spectrum of the fraction from Example 2.
[0018] Figure 3 This is the gas phase spectrum of the fraction from Example 3.
[0019] Figure 4 The NMR spectra of the products were obtained for Examples 1-3. Detailed Implementation
[0020] Example 1
[0021] Add 1.225 mol of 30-35% hydrogen peroxide to a 250 ml reaction vessel, maintaining the temperature at 20-25℃. Add 0.68 mol of acetic acid and 0.49 mol of iodobenzene, react for 4 h, adjust the pH to neutral with 10% sodium hydroxide solution, extract three times with dichloromethane, and evaporate the organic phase to dryness. Add the prepared composite oxidant to 0.15 mol of phenol and 10 ml of methanol, maintain the temperature at 35-40℃, stir for 6 h, monitor the GC content of the raw material to be less than 0.5%, quench with sodium sulfite solution, evaporate the methanol to dryness, adjust the pH to 8-9 with 10% sodium hydroxide solution, extract twice with 10 ml of dichloromethane, wash once with saturated brine, and evaporate the organic phase to dryness to obtain the crude product. Distill the crude product under reduced pressure below 0.53 kPa, collect the fraction at 110-112℃, and the GC purity of the fraction is 99.5% (e.g., ...). Figure 1 As shown), the NMR spectrum of the product is as follows. Figure 4 As shown, the conversion rate of phenol was 60%, and the selectivity was 90%.
[0022] Example 2
[0023] Add 2 mol of 30-35% hydrogen peroxide to a 250 ml reaction vessel, maintaining the temperature at 20-25℃. Add 1.1 mol of acetic acid and 0.8 mol of iodobenzene, react for 6 h, adjust the pH to neutral with 10% sodium hydroxide solution, extract three times with dichloromethane, and evaporate the organic phase to dryness. Add the prepared composite oxidant to 0.24 mol of phenol and 20 ml of methanol, maintain the temperature at 35-40℃, stir for 4 h, monitor the GC content of the raw material to be less than 0.5%, quench with sodium sulfite solution, evaporate the methanol to dryness, adjust the pH to 8-9 with 10% sodium hydroxide solution, extract twice with 20 ml of dichloromethane, wash once with saturated brine, and evaporate the organic phase to dryness to obtain the crude product. Distill the crude product under reduced pressure below 0.53 kPa, collect the fraction at 110-112℃, and the GC purity of the fraction is 99.5% (e.g., ...). Figure 2 As shown), the NMR spectrum of the product is as follows. Figure 4 As shown, the conversion rate of phenol was 55%, and the selectivity was 90%.
[0024] Example 3
[0025] Add 5 mol of 30-35% TEMPO to a 250 ml reaction vessel, maintaining the temperature at 20-25℃. Add 2.78 mol of acetic acid and 2 mol of iodobenzene, and react for 8 h. Adjust the pH to neutral with 10% sodium hydroxide solution. Extract three times with dichloromethane, and evaporate the organic phase to dryness. Add the prepared composite oxidant to 0.61 mol of phenol and 40 ml of methanol, maintaining the temperature at 30-40℃ and stirring for 5 h. Monitor the GC content of the raw material to be less than 0.5%. Quench with sodium sulfite solution, evaporate the methanol, adjust the pH to 8-9 with 10% sodium hydroxide solution, extract twice with 30 ml of dichloromethane, wash once with saturated brine, and evaporate the organic phase to dryness to obtain the crude product. Distill the crude product under reduced pressure below 0.53 kPa, collecting the fraction at 110-112℃. The GC purity of the fraction is 99.0% (e.g., ...). Figure 3 As shown), the NMR spectrum of the product is as follows. Figure 4 As shown, the conversion rate of phenol was 53.0%, and the selectivity was 90%.
[0026] The above embodiments do not limit the present invention in any way. All technical solutions obtained by equivalent substitution or equivalent transformation fall within the protection scope of the present invention.
Claims
1. A method for the catalytic oxidation of phenol to synthesize p-methoxyphenol, characterized in that... Includes the following steps: (1) Add acetic acid, iodobenzene and oxidant to the reaction vessel, control the temperature at 25-40℃ and react for 4-8 hours, adjust the pH to neutral, extract, and evaporate the organic phase to prepare a composite oxidant; wherein the molar ratio of iodobenzene to oxidant is 1:2.5-5, and the molar ratio of acetic acid to oxidant is 0.2-0.6:1; (2) Add phenol, methanol, and composite oxidant to the reaction vessel, control the temperature at 25-40℃ and react for 4-6 hours, quench, evaporate methanol, adjust pH to weakly alkaline, extract, wash, and evaporate organic phase; wherein, the volume ratio of methanol to phenol is 2-5:1, and the molar ratio of composite oxidant to phenol is 1.2-2:
1. (3) Distill under reduced pressure at a vacuum of less than 0.53 kPa and collect the fraction at 110-112℃.
2. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (1), the reaction is carried out under a nitrogen atmosphere.
3. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (1), sodium hydroxide solution is added to adjust the pH value.
4. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (1), extraction is performed using dichloromethane.
5. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (2), the quenching is performed with sodium sulfite.
6. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (2), sodium hydroxide is used to adjust the pH to weakly alkaline.
7. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (2), extraction is performed using dichloromethane.
8. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: In step (2), saturated saline solution is added for washing.
9. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 1, characterized in that: The oxidant is one of 30-35% hydrogen peroxide, TEMPO, or potassium persulfate.
10. The method for synthesizing p-methoxyphenol by catalytic oxidation of phenol according to claim 9, characterized in that: The oxidant is hydrogen peroxide.