Preparation method of 4-ethyl-2-methylphenol

Abstract

The invention relates to a preparation method of 4-ethyl-2-methylphenol, which comprises the following steps: taking 4-ethylphenol and methanol as raw materials, and carrying out one-step methylation reaction in a fixed bed reactor by adopting an iron-based catalyst Fe2O3-Al2O3. The iron loading capacity of the catalyst is 8-12 wt%, the specific surface area is larger than or equal to 200 m / g, the reaction temperature is 350-380 DEG C, the pressure is 0.1-0.5 MPa, the molar ratio of 4-ethyl phenol to methanol is 1: 3, and the liquid hourly space velocity is 0.5-0.7 h <-1 >. And carrying out reduced pressure rectification on the reaction liquid to obtain a product, wherein the rectification temperature is 120-140 DEG C and the pressure is 10 mmHg. The deactivated catalyst can be regenerated by roasting 5% O2 / N2 mixed gas at 350 DEG C for 4 hours, and the activity recovery rate is greater than or equal to 95%. The method abandons the traditional acylation-reduction two-step process, avoids the use of noble metals and strong corrosive reagents, has the advantages of high selectivity (greater than or equal to 88%), less wastewater, low catalyst cost, continuous operation and the like, and is suitable for green industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to a preparation method of 4-ethyl-2-methylphenol. BACKGROUND

[0002] 4-ethyl-2-methylphenol (CAS: 2219-73-0) as an important pharmaceutical intermediate, the existing synthesis route has significant defects:

[0003] (1) The traditional F-C acylation route (o-cresol + acetyl chloride→4-acetyl-2-methylphenol→Pd catalytic hydrogenation) has a yield of more than 93%, see Chinese patent CN1768050A for details, but a large amount of high-salt wastewater is generated by using anhydrous aluminum chloride, and the cost of Pd catalyst is high;

[0004]

[0005] (2) The acid-catalyzed condensation route of o-cresol and acetaldehyde (J. Am. Chem. Soc., 1937) does not disclose the yield, and the acetic acid-HCl system is highly corrosive, and the product separation is complex.

[0006]

[0007] In addition, the method for preparing phenolic derivatives by biomass pyrolysis, see Chinese patent CN201410559021, although renewable resources are used, but the target product is 4-ethyl-2-methoxyphenol, which is significantly different from the target compound of the present application, and a complex separation process is required. SUMMARY

[0008] The technical problem to be solved by the present application is to provide a preparation method of 4-ethyl-2-methylphenol, which overturns the traditional "acylation-reduction" two-step method, uses 4-ethylphenol as raw material, methanol as methylating agent, and synthesizes the target product in a fixed bed reactor. The selectivity of this route is 88%, no chlorine-containing wastewater is generated, and it meets the requirements of green chemistry.

[0009] To solve the above technical problems, the present application provides a preparation method of 4-ethyl-2-methylphenol, comprising the following steps:

[0010] (1) A 50g iron-based catalyst Fe2O3-Al2O3 is loaded in a fixed bed reactor and preheated to 400℃, the iron-based catalyst Fe2O3-Al2O3 has an iron loading of 8-12wt%, and a specific surface area of ≥200m² / g;

[0011] (2) feeding 4-ethylphenol, methanol and water into a fixed window reactor for a methylation reaction, the molar ratio of the 4-ethylphenol and the methanol being 1:3, the liquid hourly space velocity being 0.5-0.7h -1 , the reaction temperature being 350-380℃, and the pressure being 0.1-0.5Mpa;

[0012]

[0013] (3) the reaction liquid is subjected to vacuum rectification to obtain 4-ethyl-2-methylphenol product, the rectification temperature being 120-140℃, and the pressure being 10mmHg;

[0014] (4) catalyst regeneration: the deactivated catalyst is calcined at 350℃ for 4h in 5% O2 / N2 mixed gas, and the activity recovery rate is ≥95%.

[0015] The advantages of the present application are as follows: the present application overturns the traditional two-step method of "acylation-reduction", uses 4-ethylphenol as raw material and methanol as methylating reagent to synthesize the target product in a fixed bed reactor in one step, uses iron-based catalyst Fe2O3-Al2O3, the catalyst cost is low, the service life is long, the catalyst consumption per ton of product is only 0.8kg after inspection, the whole process does not involve strong acid, strong base and noble metal, the wastewater discharge is reduced by 90%, meets the green production requirements of pharmaceutical intermediates, and the fixed bed continuous production has high operation stability and is suitable for industrialization. DETAILED DESCRIPTION

[0016] Embodiment:

[0017] A preparation method of 4-ethyl-2-methylphenol, comprising the following steps:

[0018] (1) 50g of iron-based catalyst Fe2O3-Al2O3 is loaded in a fixed bed reactor and preheated to 400℃, the iron-based catalyst Fe2O3-Al2O3 has an iron loading of 8-12wt% and a specific surface area of ≥200m² / g;

[0019] (2) 4-ethylphenol, methanol and water are fed into a fixed window reactor for a methylation reaction, the feeding speed of the 4-ethylphenol being 50g / h, the feeding speed of the methanol being 150g / h, the feeding speed of the water being 100g / h, the reaction temperature being 350-380℃, and the pressure being 0.1-0.5Mpa;

[0020]

[0021] (3) the reaction liquid is subjected to vacuum rectification to obtain 4-ethyl-2-methylphenol product, the rectification temperature being 120-140℃, and the pressure being 10mmHg;

[0022] (4) Catalyst regeneration: the deactivated catalyst was calcined at 350°C for 4h with 5% O2 / N2 mixture, and the activity recovery rate was ≥95%.

[0023] The catalyst was tested for 2000 hours, and the methylation selectivity was stable at more than 88% (after 2000 hours of continuous operation, the yield decreased to 87.5%, and after regeneration of the catalyst, the yield recovered to 89.8%).

[0024] The iron-based catalyst Fe2O3-Al2O3 in the above examples was prepared by the method described in the prior patent CN117427693B.

[0025] The general steps are as follows: mixing iron nitrate (Fe (NO3)3 9H2O) with pseudoboehmite, precipitating with ammonia water to pH=9, drying at 120°C, and calcining at 500°C for 4h to obtain Fe2O3-Al2O3 (Fe content 10wt%). Crushed to 20-40 mesh.

[0026] Comparative example:

[0027] The prior patent CN1768050A route: o-cresol 100g was acylated by F-C (AlCl3 150g) to obtain 4-acetyl-2-methylphenol 118g (yield 94%), and the target product 98g (yield 83%) was obtained by Pd (OH)2catalytic hydrogenation (50°C, 5MPa H2). The total yield was 78%, and 2.1L of aluminum-containing wastewater was generated. The catalyst cost was 18 times that of Example 1.

Claims

1. A process for the preparation of 4-ethyl-2-methylphenol, characterized in that, Comprising the following steps: (1) in the fixed bed reactor filled with 50g iron-based catalyst Fe2O3-Al2O3, preheated to 400℃, the iron-based catalyst Fe2O3-Al2O3 iron loading 8-12wt%, specific surface area≥200m² / g; (2) feeding 4-ethylphenol, methanol and water into a fixed window reactor to perform a methylation reaction, the molar ratio of 4-ethylphenol and methanol being 1:3, the liquid hourly space velocity being 0.5-0.7 h -1 -1, the reaction temperature being 350-380℃, and the pressure being 0.1-0.5 MPa (3) feeding 4-ethylphenol, methanol and water into a fixed window reactor to perform a methylation reaction, the molar ratio of 4-ethylphenol and methanol being 1:3, the liquid hourly space velocity being 0.5-0.7 h -1 -1, the reaction temperature being 350-380℃, and the pressure being 0.1-0.5 MPa ； (3) the reaction liquid is obtained by vacuum rectification 4-ethyl-2-methyl phenol product, rectification temperature 120~140℃, pressure is 10mmHg; (4) catalyst regeneration: the deactivated catalyst is calcined at 350℃ for 4h by 5% O2 / N2 mixed gas, and the activity recovery rate is≥95%.

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