A method for deprotection of tert-butoxyphenethyl methyl ether

Abstract

The application belongs to the field of fine chemical industry, and discloses a deprotection method of p-tert-butoxyphenethyl methyl ether, which comprises the following steps: heating p-tert-butoxyphenethyl methyl ether under the action of a solid acid catalyst to perform a deprotection reaction, so as to obtain p-(2-methoxy)ethyl phenol; the solid acid catalyst comprises aluminum phosphate and basic metal oxides modified on the aluminum phosphate, and the metal elements contained in the basic metal oxides include one or more of K, Ca, Na, Ba or Mg. The application has the advantages of less three-waste emissions, low operation cost, high production efficiency, and can be used for continuous production of p-(2-methoxy)ethyl phenol, and higher temperature and higher air speed can be adopted.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of fine chemical industry, and relates to a deprotection method of p-tert-butoxyphenylethyl methyl ether. BACKGROUND

[0002] It is a common practice in the synthesis field to protect some active functional groups of reactants with a protective agent such as isobutene, and then perform a deprotection reaction in the last step of the reaction. At present, liquid acid is mainly used as a catalyst for catalyzing the deprotection (tert-butyl) reaction in the field of fine chemical industry. The liquid acid catalyst has the advantages of high catalytic activity and low price, but after the reaction is completed, neutralization, water washing and other operations are required, and there are disadvantages such as more three-waste emissions and complex process. The solid acid catalyst has the advantages of easy separation and less three-waste emissions, and is widely used in the field of petroleum and chemical industry. The reaction molecules of petroleum and chemical products are small and have low boiling points, and are easy to gasify, so the gas-solid phase reaction is usually used; the reaction molecules of fine chemical products are large and have high boiling points, and are not easy to gasify, so the liquid phase reaction is usually used. Therefore, the conventional solid acid catalysts in the field of petroleum and chemical industry are often not suitable for the field of fine chemical industry.

[0003] Patent CN106955687B discloses a catalyst for cracking methyl tert-pentyl ether to prepare iso-pentene. The catalyst is alumina modified by sulfate ions and fluoride ions, the reaction temperature is 160℃, and the conversion rate and selectivity reach more than 95%. Although the catalyst has high catalytic activity, the sulfate ions and fluoride ions are easy to flow out, so the catalyst is only suitable for gas-solid phase reaction. For liquid phase reaction, the sulfate ions and fluoride ions are easy to flow out, which causes the decrease of the activity of the catalyst and the corrosion of the reactor and other equipment. The molecular weight of fine chemical products is large, the boiling point is high, the molecular structure is unstable at high temperature, and the liquid phase reaction is usually used, so it is necessary to develop a solid acid catalyst suitable for liquid phase reaction.

[0004] Patent CN111530379A discloses a process for preparing iso-butene by cracking methyl tert-butyl ether, and the process uses sulfonic acid resin as a catalyst. The sulfonic acid resin catalyst has strong acidity and catalytic activity, but its high-temperature resistance is poor, and when the reaction temperature exceeds 120℃, the active components are easy to decompose and fall off. The sulfonic acid resin has poor high-temperature resistance, so after the sulfonic acid resin catalyst is deactivated, it cannot be regenerated by high-temperature calcination to restore its catalytic activity. The sulfonic acid resin has poor high-temperature resistance and cannot be regenerated after deactivation, which limits its application in the field of fine chemical industry.

[0005] Patent CN100482629C discloses a synthesis method of p-(2-methoxy) ethyl phenol, wherein the last step of tert-butoxy phenethyl methyl ether deprotection reaction uses liquid acid (sulfuric acid, hydrochloric acid, phosphoric acid or nitric acid) as catalyst to catalyze the deprotection reaction. The method has high conversion rate of reactants and product selectivity, but generates a large amount of waste water and waste acid, and requires the use of special material reactor to avoid equipment corrosion problems.

[0006] Patent CN109651094B discloses a preparation method of p-(2-methoxy) ethyl phenol, wherein the last step of tert-butoxy phenethyl methyl ether deprotection reaction is carried out under the action of catalyst thionyl chloride. The method has high conversion rate of reactants and product selectivity, but thionyl chloride is highly toxic, generates a large amount of toxic and harmful substances, and is not environmentally friendly.

[0007] Patent CN116020438B discloses a solid acid catalyst with acid metal oxide modified γ-alumina as carrier, which shows good performance in tert-butoxy phenethyl methyl ether deprotection reaction, and the product selectivity can reach more than 98%, and the catalyst has high stability and does not deactivate after 200 hours of continuous reaction. However, the technology still has some limitations, such as complex catalyst preparation conditions, the need to use transition metals for secondary impregnation to obtain ideal selectivity, which increases the cost of catalyst, and may not fully meet the efficiency and economy requirements of industrial production under certain specific working conditions, for example: under the condition of liquid space velocity of 1h -1 , the conversion rate cannot break through 80%, especially the catalyst is not suitable for high temperature reaction, and at the same time, under the condition of 190℃ or more, although higher liquid space velocity can be used, the catalyst surface will be carbonized, resulting in catalyst deactivation, thus the selectivity will be greatly reduced, and the stability of continuous reaction at high temperature is also affected.

[0008] In summary, at present, in the field of fine chemical industry, the catalyst used for deprotection reaction process is mainly liquid acid, which generates a large amount of waste acid, waste water and toxic and harmful substances, and the deprotection reaction in the synthesis of p-(2-methoxy) ethyl phenol is mostly intermittent process, which has long product production cycle, is easy to cause unstable product quality, and is difficult to realize flexible production. The solid acid catalyst commonly used in petroleum and chemical industry is not suitable for the production of fine chemical products, so it is urgent to develop a solid acid catalyst suitable for the production of fine chemical products and a continuous deprotection reaction production process. SUMMARY

[0009] The present application aims to provide a deprotection method of p-tert-butoxyphenethyl methyl ether, to solve the environmental problems caused by liquid acid catalyst in the deprotection reaction and the low efficiency problem caused by the non-continuous process, and at the same time solve the problems of complex preparation, high cost, poor high temperature resistance and low conversion rate of the existing solid acid catalyst. The present application uses a solid acid catalyst to replace a liquid acid catalyst to catalyze the deprotection reaction of p-tert-butoxyphenethyl methyl ether, has the advantages of less three wastes emission, and in combination with a fixed bed reactor, can realize the continuous production operation of the deprotection reaction of p-tert-butoxyphenethyl methyl ether, and is suitable for the continuous production of p-(2-methoxy)ethyl phenol.

[0010] The technical scheme of the present application is as follows:

[0011] A deprotection method of p-tert-butoxyphenethyl methyl ether, comprising: under the action of a solid acid catalyst, heating p-tert-butoxyphenethyl methyl ether to perform a deprotection reaction, to obtain p-(2-methoxy)ethyl phenol.

[0012] The solid acid catalyst comprises aluminum phosphate and basic metal oxides modified on the aluminum phosphate, and the metal elements contained in the basic metal oxides include one or more of K, Ca, Na, Ba or Mg.

[0013] In the present application, the loading amount of the basic metal oxides such as K, Ca, Na, Ba and Mg is 1-5wt% (calculated based on the alkali metal elements).

[0014] As a preferred, the basic oxide modified aluminum phosphate solid acid catalyst is prepared by an impregnation method, and the specific steps are as follows:

[0015] The aqueous solution containing one or more of K, Ca, Na, Ba and Mg nitrates is heated, aluminum phosphate is added, the impregnation method is used for modification, and drying and calcination are performed to obtain the solid acid catalyst.

[0016] As a preferred, in the preparation process of the solid acid catalyst, the heating temperature is 40-60 DEG C, and the impregnation time is 20-40 minutes.

[0017] As a preferred, in the preparation process of the solid acid catalyst, the drying temperature is 100-120 DEG C, and the drying time is 10-14 hours; the calcination temperature is 350-450 DEG C, and the calcination time is 3-7 hours.

[0018] Aluminum phosphate is the most common catalyst carrier in industry, which is cheap, high thermal stability, strong acidity, and has both L acid and B acid. Alkaline oxides such as K, Ca, Na, Ba, Mg, etc. have strong alkalinity. The modification of aluminum phosphate with alkaline oxides can appropriately reduce the acidity of the catalyst, which is beneficial to improve the selectivity of the product, inhibit the side reactions such as coking, and thus improve the service life of the catalyst. p-(2-methoxy) ethyl phenol is a key intermediate for the synthesis of the drug metoprolol. The last step of the synthesis is the deprotection reaction of p-tert-butoxyphenethyl methyl ether under acid catalysis to obtain the target product p-(2-methoxy) ethyl phenol. In this step, the inventors found that the deprotection reaction of p-tert-butoxyphenethyl methyl ether under atmospheric pressure can be catalyzed by the solid acid catalyst of aluminum phosphate modified with alkaline metal oxides, which has high conversion rate and selectivity.

[0019] The evaluation conditions of the performance of the solid acid catalyst prepared by the above method are as follows: the catalyst with a diameter of 1.2-1.5 mm is loaded into a stainless steel fixed bed reactor with an inner diameter of 15 mm. Start the heating furnace, and after the catalyst bed temperature reaches the set temperature, start the plunger pump to control the feed amount of the reactant p-tert-butoxyphenethyl methyl ether. The reaction liquid passes through the catalyst bed of the fixed bed reactor and enters the gas-liquid separator, and the liquid product is collected, and the gas product (isobutene) is discharged. The liquid product is quantitatively analyzed by gas chromatography, and the conversion rate and selectivity are calculated.

[0020] As preferred, the reaction is carried out in a continuous manner, the solid acid catalyst is filled in a fixed bed continuous reactor, and then p-tert-butoxyphenethyl methyl ether is introduced into the fixed bed continuous reactor for deprotection reaction.

[0021] As further preferred, the reaction temperature is 210-250℃, the liquid space velocity is 1-2h -1 The catalyst of the present application can withstand higher temperature and higher space velocity, and is more convenient for industrial use.

[0022] Compared with the prior art, the present application has the following advantages:

[0023] (1) The solid acid catalyst is used to replace the liquid acid catalyst to catalyze the deprotection reaction, which has less three wastes emission, and can realize continuous production operation of the deprotection reaction in combination with the fixed bed reactor, and is a gas phase reaction, so the process is simple and easy to realize industrialization, which is suitable for the production of large-tonnage chemical products.

[0024] (2) The solid acid catalyst is adopted in the application, and the deprotection reaction of p-tert-butoxyphenethyl methyl ether is catalyzed by combining with a fixed bed continuous reactor, the highest selectivity can reach more than 98%, and the application has the advantages of simple operation, continuous production and the like, and also meets the development direction of future fine chemical industry, green, continuous and intelligent.

[0025] (3) Compared with the complex impregnation, drying and calcination conditions in the prior art, the catalyst preparation process of the application is simpler, the equipment requirement is lower, the raw material is cheap and easy to obtain, and the application is suitable for large-scale industrial production. In addition, the combination of the basic metal oxide modified aluminum phosphate shows a unique synergistic effect on the catalyst performance, and has better stability, can be suitable for higher temperature and higher space velocity, and further improves the comprehensive performance of the catalyst.

[0026] (4) The catalyst of the application not only has the same performance as the prior art, but also has advantages in preparation cost and operation complexity. By optimizing the composition and preparation process of the catalyst, the application can significantly reduce the production cost and improve the production efficiency in actual application, and has higher economy and practicability. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 The nuclear magnetic resonance hydrogen spectrum of the product obtained from the embodiment 6 of the application;

[0028] Figure 2 The catalyst life investigation results of the embodiment 9 of the application. DETAILED DESCRIPTION

[0029] The deprotection reaction formula is as follows:

[0030]

[0031] The evaluation conditions of the catalyst performance are as follows: the catalyst with a diameter of 1.2-1.5 mm is loaded into a stainless steel fixed bed reactor with an inner diameter of 15 mm. The heating furnace is started, and after the catalyst bed temperature reaches the set temperature, the plunger pump is started, and the plunger pump is used to control the feed amount of the reactant p-tert-butoxyphenethyl methyl ether. The reaction liquid is gasified after passing through the preheater and enters the reactor, and the reaction occurs in the catalyst bed, enters the gas-liquid separator, collects the liquid product, and discharges the gas product (isobutene). The liquid product is quantitatively analyzed by using a gas chromatograph, and the conversion rate and selectivity are calculated.

[0032] The calculation method of the catalyst loading of the application is as follows:

[0033] Loading amount = nitrate mass * metal atomic weight / (nitrate molecular weight * aluminum phosphate mass) * 100% Example 1

[0034] K-modified aluminum phosphate catalyst with 1wt% K loading. Catalyst preparation method: 0.21 g of potassium nitrate was dissolved in 8 g of deionized water, heated to 50°C, 8 g of aluminum phosphate was poured into the above solution, and left for 30 minutes, dried at 110°C for 12 hours, and then calcined at 450°C for 4 hours in air or nitrogen atmosphere to prepare a solid acid catalyst. The catalyst performance evaluation results are shown in Table 1, the reaction temperature is 210°C, the liquid space velocity is 1h -1 , and the reaction pressure is normal pressure. Example 2

[0035] Ca-modified aluminum phosphate catalyst with 1wt% Ca loading. Catalyst preparation method: 0.33 g of calcium nitrate was dissolved in 8 g of deionized water, heated to 50°C, 8 g of aluminum phosphate was poured into the above solution, and left for 30 minutes, dried at 110°C for 12 hours, and then calcined at 450°C for 4 hours in air or nitrogen atmosphere to prepare a solid acid catalyst. The catalyst performance evaluation results are shown in Table 1, the reaction temperature is 210°C, the liquid space velocity is 1h -1 , and the reaction pressure is normal pressure. Example 3

[0036] Na-modified aluminum phosphate catalyst with 1wt% Na loading. Catalyst preparation method: 0.3 g of sodium nitrate was dissolved in 8 g of deionized water, heated to 50°C, 8 g of aluminum phosphate was poured into the above solution, and left for 30 minutes, dried at 110°C for 12 hours, and then calcined at 450°C for 4 hours in air or nitrogen atmosphere to prepare a solid acid catalyst. The catalyst performance evaluation results are shown in Table 1, the reaction temperature is 210°C, the liquid space velocity is 1h -1 , and the reaction pressure is normal pressure. Example 4

[0037] Mg-modified aluminum phosphate catalyst with 1wt% Mg loading. Catalyst preparation method: 0.49 g of magnesium nitrate was dissolved in 8 g of deionized water, heated to 50°C, 8 g of aluminum phosphate was poured into the above solution, and left for 30 minutes, dried at 110°C for 12 hours, and then calcined at 450°C for 4 hours in air or nitrogen atmosphere to prepare a solid acid catalyst. The catalyst performance evaluation results are shown in Table 1, the reaction temperature is 210°C, the liquid space velocity is 1h -1 , and the reaction pressure is normal pressure. Example 5

[0038] Aluminum phosphate modified with Ba was used as catalyst, in which the loading of Ba was 1wt%. The catalyst was prepared as follows: 0.16g of barium nitrate was dissolved in 8g of deionized water, heated to 50°C, 8g of aluminum phosphate was poured into the above solution, and left for 30 minutes, dried at 110°C for 12 hours, and then calcined at 450°C for 4 hours in air or nitrogen atmosphere to obtain a solid acid catalyst. The results of catalyst performance evaluation are shown in Table 1, the reaction temperature was 210°C, the liquid space velocity was 1h -1 , and the reaction pressure was normal pressure. Example 6

[0039] Aluminum phosphate modified with Ba was used as catalyst, in which the loading of Ba was 5wt%. The catalyst was prepared as follows: 0.8g of barium nitrate was dissolved in 8g of deionized water, heated to 50°C, 8g of aluminum phosphate was poured into the above solution, and left for 30 minutes, dried at 110°C for 12 hours, and then calcined at 450°C for 4 hours in air or nitrogen atmosphere to obtain a solid acid catalyst. The results of catalyst performance evaluation are shown in Table 1, the reaction temperature was 210°C, the liquid space velocity was 1h -1 , and the reaction pressure was normal pressure. After the reaction, the mixed gas entered a gas-liquid separator, the liquid product was collected, and the gaseous product (isobutene) was discharged. The collected liquid product was separated by vacuum rectification to obtain the deprotection product p-(2-methoxy)phenol and unreacted raw material p-tert-butoxyphenethyl methyl ether, which was reused in the deprotection reaction. The product obtained by rectification was analyzed by gas chromatography and the purity was 99.89%, and its 1H nuclear magnetic resonance spectrum is shown in Figure 1 . Example 7

[0040] Aluminum phosphate modified with Ba was used as catalyst, in which the loading of Ba was 1wt%. The catalyst was prepared as in Example 5. The results of catalyst performance evaluation are shown in Table 1, the reaction temperature was 250°C, the liquid space velocity was 1h -1 , and the reaction pressure was normal pressure. Example 8

[0041] Aluminum phosphate modified with Ba was used as catalyst, in which the loading of Ba was 1wt%. The catalyst was prepared as in Example 5. The results of catalyst performance evaluation are shown in Table 1, the reaction temperature was 250°C, the liquid space velocity was 2h -1 , and the reaction pressure was normal pressure. Example 9

[0042] As in Example 6, the reaction temperature was 210°C, the liquid space velocity was 1h -1 , the reaction pressure was normal pressure, and the reaction time was 150 hours to investigate the service life of the catalyst, and the results are shown in Figure 2 .

[0043] Comparative Example 1

[0044] The γ-alumina modified by Nb+W is used as the catalyst, the loading of Nb and W is both 5wt%, the specific surface area of the γ-alumina is 150m 2 / g, the pore volume is 0.5cm 3 / g, and the average pore diameter is 16nm. The catalyst preparation method is as follows: 1.73g of niobium oxalate is dissolved in 6g of deionized water, heated to 50℃, 6g of γ-alumina is poured into the above solution, and placed for 30 minutes, dried at 110℃ for 12 hours, and calcined at 450℃ in air atmosphere for 4 hours to obtain the Nb modified γ-alumina catalyst. 0.61g of tungsten ammonium pentahydrate is dissolved in 6g of deionized water, heated to 50℃, the Nb modified γ-alumina catalyst is poured into the above solution, and placed for 30 minutes, dried at 110℃ for 12 hours, and calcined at 450℃ in air atmosphere for 4 hours to obtain the catalyst. The catalyst performance evaluation results are shown in Table 1, the reaction temperature is 170℃, the liquid space velocity is 1h -1 , and the reaction pressure is normal pressure.

[0045] Comparative Example 2

[0046] The catalyst of Comparative Example 1 is used, the reaction temperature is 210℃, the liquid space velocity is 1h -1 , and the reaction pressure is normal pressure.

[0047] Table 1 Catalyst performance evaluation results of examples

[0048]

[0049] In summary, the present application can realize the continuous production operation of the tert-butoxyphenethyl methyl ether deprotection reaction, the selectivity of p-(2-methoxy)ethyl phenol can reach more than 98%, and the catalyst has good stability, and the catalyst does not appear to be inactivated after 150 hours of continuous reaction (as shown in Figure 2 , at the same time, the catalyst can tolerate higher temperature and higher space velocity, which is more conducive to industrial application. Although the single-pass conversion rate does not reach 100%, the product and unreacted raw material can be separated by rectification, and the unreacted raw material is continuously fed into the fixed bed reactor.

[0050] The above examples can make the professional technical personnel more comprehensively understand the present application, but do not limit the present application in any way.

Claims

1. A method for deprotection of tert-butoxyphenethyl methyl ether, characterized by, The application relates to a method for preparing p-(2-methoxy)ethyl phenol. The solid acid catalyst comprises aluminum phosphate and basic metal oxide modified on the aluminum phosphate, and the basic metal oxide contains Ba as a metal element; The reaction is carried out as follows: The solid acid catalyst is filled in a fixed-bed continuous reactor, and then p-t-butoxy phenethyl methyl ether is introduced into the fixed-bed continuous reactor to carry out the deprotection reaction; The reaction temperature is 210-250 DEG C; The solid acid catalyst is prepared by the following method: The solid acid catalyst is prepared by the following method: The solid acid catalyst is prepared by the following method:

2. The deprotection method of p-t-butoxyphenethyl methyl ether according to claim 1, characterized by, The loading amount of the metal element on the aluminum phosphate is 1-5 wt%.

3. The deprotection method of p-t-butoxyphenethyl methyl ether according to claim 1, characterized by, In the preparation process of the solid acid catalyst, the heating temperature is 40-60 DEG C, and the impregnation time is 20-40 minutes.

4. The deprotection method of p-t-butoxyphenethyl methyl ether according to claim 1, characterized by, In the preparation process of the solid acid catalyst, the drying temperature is 100-120 DEG C, the drying time is 10-14 hours, the calcination temperature is 350-450 DEG C, and the calcination time is 3-7 hours.

5. The deprotection method of p-tert-butoxyphenylethyl methyl ether according to claim 1, characterized by, The reaction temperature is 210-250°C and the liquid space velocity is 1-2h -1 .

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