A process for the simultaneous preparation of 3-butoxyphenol and 4-n-butylresorcinol

Abstract

The application discloses a method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol, and belongs to the technical field of organic synthesis. The preparation comprises the following steps: mixing resorcinol and n-butanol to prepare a reaction solution, and feeding the reaction solution into a reactor provided with a solid-phase metal phosphate catalyst, and obtaining 3-butoxyphenol and 4-n-butylresorcinol after heating reaction. The method can simultaneously prepare 3-butoxyphenol and 4-n-butylresorcinol, the combined selectivity of 3-butoxyphenol and 4-n-butylresorcinol can reach 70%, the raw materials are resorcinol and n-butanol which are low in price, the production cost is low, the experiment is simple and easy to implement, and the method has high economic benefits.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol. Background Technology

[0002] 3-Butoxyphenol, also known as m-butoxyphenol, is a colorless to pale orange to yellow liquid. CAS: 18979-72-1, molecular formula C 10 H 14 O2, molecular weight 166.22, melting point 65-66℃, boiling point 269℃, relative density 1.5230 g / cm³ 3 3-Butoxyphenol is an important raw material and organic solvent in organic synthesis, and is an important intermediate in the synthesis of polybenzoxazine resins.

[0003] 4-Butylresorcinol, also known as 4-butylresorcinol, is a white to pale yellow powder. CAS: 18979-61-8, molecular formula: C 10 H 14 O2, molecular weight 166.22, melting point 50-55℃, boiling point 166℃. 4-Butylresorcinol is commonly used as a whitening additive in skin care products. It can be used to synthesize intermediates for FXR agonists, and is used to treat cholestasis, high cholesterol, heart disease, and other diseases. It is mainly used in fragrances, pharmaceuticals, dyes, and other fields.

[0004] Current methods for synthesizing 3-butoxyphenol and 4-n-butylresorcinol have long reaction times, low yields, and high costs. Furthermore, the raw materials used involve strong acids and bases, posing problems such as equipment corrosion and significant experimental hazards.

[0005] The synthesis of 3-butoxyphenol generally employs a single-etherification hydroxyl protection method, which involves reacting a halobutane with resorcinol. However, this method requires too long a reaction time and cannot be used for continuous production. The synthesis process is as follows:

[0006]

[0007] The synthesis of 4-n-butylresorcinol mainly involves first reacting resorcinol with butyric acid under AlCl3 catalysis via Friedel-Crafts acylation, followed by reduction of the carbonyl group to a methylene group using either Huang Minglong or Clemens chemiluminescence reduction reactions to obtain 4-n-butylresorcinol. The carbonyl reduction reaction utilizes large amounts of hydrazine and zinc amalgam, causing environmental pollution, and the availability of mercury reagents is restricted. The synthesis process is as follows:

[0008] Summary of the Invention

[0009] The purpose of this invention is to provide a method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol. This method utilizes inexpensive raw materials and simple preparation steps to simultaneously prepare 3-butoxyphenol and 4-n-butylresorcinol, offering significant economic benefits.

[0010] To achieve the above objectives, the present invention provides the following technical solution:

[0011] A method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol includes the following steps:

[0012] Resorcinol and n-butanol were mixed to prepare a reaction solution, which was then fed into a reactor containing a solid metal phosphate catalyst. After heating and reaction, 3-butoxyphenol and 4-n-butylresorcinol were obtained.

[0013] The reaction formula is as follows:

[0014]

[0015] Preferably, the molar ratio of resorcinol to n-butanol is 1:2 to 8; more preferably, it is 1:6.

[0016] Preferably, the reaction solution passes through each gram of catalyst at a rate of 0.3 to 1.5 mL per hour; more preferably, it passes through 1.2 mL per hour.

[0017] Preferably, the temperature of the heating reaction is 220–300°C; more preferably, it is 250°C.

[0018] Preferably, the metal phosphate is one or more selected from aluminum phosphate, lanthanum phosphate, zirconium phosphate, cerium phosphate, zinc phosphate, calcium phosphate, and magnesium phosphate.

[0019] More preferably, the metal phosphate is one or more of aluminum phosphate, lanthanum phosphate, and cerium phosphate.

[0020] Most preferably, the metal phosphate is aluminum phosphate and / or lanthanum phosphate.

[0021] The beneficial technical effects of the present invention are as follows:

[0022] This invention provides a simple method for the simultaneous preparation of 3-butoxyphenol and 4-n-butylresorcinol. The method achieves a combined selectivity of 70% for 3-butoxyphenol and 4-n-butylresorcinol. The raw materials are inexpensive resorcinol and n-butanol, resulting in low production costs, simple and easy experimental procedures, and high economic benefits. Attached Figure Description

[0023] Figure 1This is a schematic diagram of the self-made fixed-bed reaction device used in the embodiments of the present invention, wherein 1 is a nitrogen cylinder, 2 is a flow stabilizing valve, 3 is a rotor flow meter, 4 is a reaction tube, 5 is a heating furnace, 6 is a catalyst bed, 7 is a power cord, 8 is a thermocouple, 9 is a programmable temperature control cabinet, 10 is a cold trap, 11 is a collection bottle, 12 is a horizontal flow pump, and 13 is a container for holding the reaction liquid. Detailed Implementation

[0024] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0025] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0026] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar to or equivalent to those described herein may be used in the implementation or testing of this invention.

[0027] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0028] Examples 1-6 of this invention use Figure 1 The self-made fixed-bed reaction apparatus shown simultaneously prepares 3-butoxyphenol and 4-n-butylresorcinol. Resorcinol and n-butanol are mixed in a reaction solution container at different molar ratios to obtain a reaction solution. A solid metal phosphate catalyst (20-40 mesh) is placed in a reaction tube (1.4 cm inner diameter). Nitrogen gas released from a nitrogen cylinder is used to purge the air from the reaction tube. The heating furnace is heated to the required reaction temperature using a programmed temperature control cabinet. The nitrogen gas supply device is disassembled, and a horizontal flow pump is connected to inject the reaction solution. The reaction solution is heated in the reaction tube and passes through the catalyst, simultaneously producing 3-butoxyphenol and 4-n-butylresorcinol. A collection bottle placed in a cold trap is connected to the end of the reaction tube.

[0029] Example 1

[0030] In this embodiment, resorcinol and n-butanol were mixed at a molar ratio of 1:6 to prepare a reaction solution. An aluminum phosphate catalyst was placed in the reaction tube, and then the reaction tube was heated to 250°C under a nitrogen atmosphere. A 1.2 mL·g... -1 ·h -1 The reaction solution is pumped into the reaction tube at a flow rate of (per gram of catalyst per hour) to allow resorcinol and n-butanol to undergo alkylation under the action of an aluminum phosphate catalyst. After the reaction is complete, the products 3-butoxyphenol and 4-n-butylresorcinol, along with other byproducts, are collected. In this example, the conversion rate of resorcinol is 40%, the selectivity for 3-butoxyphenol is 15.6%, the selectivity for 4-n-butylresorcinol is 55%, the combined selectivity for both is 70.6%, and the other byproducts account for 29.4%.

[0031] The above steps were repeated to investigate the catalytic effects of equal masses of lanthanum phosphate, zirconium phosphate, cerium phosphate, zinc phosphate, calcium phosphate, and magnesium phosphate. The results showed that lanthanum phosphate and aluminum phosphate had comparable effects, followed by cerium phosphate, and then zirconium phosphate, calcium phosphate, magnesium phosphate, and zinc phosphate.

[0032] Example 2

[0033] In this embodiment, resorcinol and n-butanol were mixed at a molar ratio of 1:6 to prepare a reaction solution. An aluminum phosphate catalyst was placed in the reaction tube, and then the reaction tube was heated to 250°C under a nitrogen atmosphere. A 1.5 mL·g... -1 ·h -1 The reaction solution is pumped into the reaction tube at a flow rate of (per gram of catalyst per hour) to allow resorcinol and n-butanol to undergo alkylation under the action of an aluminum phosphate catalyst. After the reaction is complete, the products 3-butoxyphenol and 4-n-butylresorcinol, along with other byproducts, are collected. In this example, the conversion rate of resorcinol is 31%, the selectivity for 3-butoxyphenol is 18.6%, the selectivity for 4-n-butylresorcinol is 53.6%, the combined selectivity for both is 72.2%, and the other byproducts account for 27.8%.

[0034] Repeat the above steps to investigate space velocities of 1 mL·g⁻¹. -1 ·h -1 and 0.5 mL·g -1 ·h -1 Based on the conversion rate of time-dependent hydroxyl and the selectivity of the product, combined with Example 1, the space velocity was found to be 1.2 mL·g. -1 ·h -1 The best time is when.

[0035] Example 3

[0036] In this embodiment, resorcinol and n-butanol were mixed at a molar ratio of 1:8 to prepare a reaction solution. An aluminum phosphate catalyst was placed in the reaction tube, and then the reaction tube was heated to 250°C under a nitrogen atmosphere. A 1.2 mL·g... -1 ·h -1 The reaction solution is pumped into the reaction tube at a flow rate of (per gram of catalyst per hour) to allow resorcinol and n-butanol to undergo alkylation under the action of aluminum phosphate catalyst. After the reaction is complete, the products 3-butoxyphenol and 4-n-butylresorcinol, along with other byproducts, are collected. In this example, the conversion rate of resorcinol was 51.8%, the selectivity for 3-butoxyphenol was 12.2%, the selectivity for 4-n-butylresorcinol was 35.2%, the combined selectivity for both was 47.4%, and the other byproducts accounted for 52.6%.

[0037] The above steps were repeated, and the conversion rate of resorcinol and the selectivity of the product were investigated when resorcinol and n-butanol were mixed in molar ratios of 1:2, 1:4, and 1:10 as the reaction solution. Based on Example 1, it was found that the optimal molar ratio of resorcinol to n-butanol was 1:6.

[0038] Example 4

[0039] In this embodiment, resorcinol and n-butanol were mixed at a molar ratio of 1:6 to prepare a reaction solution. An aluminum phosphate catalyst was placed in the reaction tube, and then the reaction tube was heated to 290°C under a nitrogen atmosphere. A 1.2 mL·g... -1 ·h -1 The reaction solution is pumped into the reaction tube at a flow rate of (per gram of catalyst per hour) to allow resorcinol and n-butanol to undergo alkylation under the action of an aluminum phosphate catalyst. After the reaction is complete, the products 3-butoxyphenol and 4-n-butylresorcinol, along with other byproducts, are collected. In this example, the conversion rate of resorcinol was 78.7%, the selectivity for 3-butoxyphenol was 6.4%, the selectivity for 4-n-butylresorcinol was 27.7%, the combined selectivity for both was 34.1%, and the other byproducts accounted for 65.9%.

[0040] The above steps were repeated, and the conversion rate of hydroquinone and the selectivity of the product were investigated at reaction temperatures of 220℃, 240℃, 270℃ and 300℃ respectively. Combined with Example 1, it was found that the optimal reaction temperature was 250℃.

[0041] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol, characterized in that, Includes the following steps: Resorcinol and n-butanol were mixed to prepare a reaction solution, which was then fed into a reactor containing a solid metal phosphate catalyst. After heating and reaction, 3-butoxyphenol and 4-n-butylresorcinol were obtained. The temperature of the heating reaction is 220~300℃; The metal phosphate is one or more of aluminum phosphate, lanthanum phosphate, zirconium phosphate, cerium phosphate, zinc phosphate, calcium phosphate, and magnesium phosphate.

2. The method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol according to claim 1, characterized in that, The molar ratio of resorcinol to n-butanol is 1:2~8.

3. The method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol according to claim 1, characterized in that, The reaction solution passes through each gram of catalyst at a rate of 0.3 to 1.5 mL per hour.

4. The method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol according to claim 1, characterized in that, The metal phosphate is one or more of aluminum phosphate, lanthanum phosphate, and cerium phosphate.

5. The method for simultaneously preparing 3-butoxyphenol and 4-n-butylresorcinol according to claim 2, characterized in that, The metal phosphate is aluminum phosphate and / or lanthanum phosphate.

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