Industrial preparation method of p-hydroxybenzonitrile

Abstract

The invention discloses an industrial preparation method of p-hydroxybenzonitrile, and belongs to the technical field of organic synthesis. The method comprises the steps that p-chlorobenzonitrile and organic alkali react in a mixed solvent under the action of a composite catalyst to obtain p-hydroxybenzonitrile, the reaction temperature ranges from 60 DEG C to 100 DEG C, the reaction pH ranges from 5.5 to 6.5, and the reaction time ranges from 8 h to 15 h; the mixed solvent is composed of methanol and a polar aprotic solvent according to a volume ratio of 2-4: 1; the composite catalyst is formed by compounding lithium chloride and an organic catalyst according to the mass ratio of (0.5-3.0): 1, and the organic catalyst is selected from one or more of a quaternary ammonium salt catalyst, a crown ether catalyst and tetrabutylammonium bromide; the molar ratio of the p-chlorobenzonitrile to the organic alkali to the lithium chloride is 1: (2.8-3.2): (0.05-0.2); the organic base is selected from sodium methoxide, potassium ethoxide or potassium tert-butoxide. Compared with the prior art, the reaction is performed under normal pressure, the reaction temperature is low, the reaction time is short, and the method is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to an industrial preparation method of p-hydroxybenzonitrile. BACKGROUND

[0002] P-hydroxybenzonitrile, also known as 4-cyanophenol (CNPO), p-cyanophenol, 4-hydroxybenzonitrile, p-cyanophenol, 4-hydroxybenzonitrile, has a CAS registration number of 767-00-0, a melting point of 110-113℃ and a boiling point of 281℃. The pure product is a shiny flaky white crystal, can be dissolved in various organic solvents, is insoluble in cold water and easily soluble in hot water. It is a liquid crystal material, an organic synthesis intermediate of perfume, nitrile chemical product corrosion inhibitor and a basic raw material of nitrile. It can be used as an intermediate of organophosphorus insecticide cyhexatin and phenyl cyanophosphonate, or an intermediate of herbicide bromoxynil, and also as an intermediate of liquid crystal material, perfume, etc., and is widely used in the synthesis of various medicines, perfumes, pesticides, liquid crystal materials, and can be used as a corrosion inhibitor to slow down the corrosion speed of acid on metal; in medicine synthesis, it can be used to synthesize the gout medicine febuxostat and the functional dyspepsia drug itopride; in pesticide synthesis, it is an intermediate of organophosphorus insecticide cyhexatin and phenyl cyanophosphonate, and also an intermediate of herbicide bromoxynil; in addition, p-hydroxybenzonitrile can also be used to synthesize liquid crystal polymer unit p-allyloxybenzoic acid p-hydroxybenzonitrile, and then to synthesize liquid crystal polymer.

[0003] In the prior art, p-chlorobenzonitrile and sodium methoxide are used as raw materials, and the reaction is carried out in a methanol solution under high temperature and high pressure. For example, the patent with the application number CN202110074058.0 discloses a method for preparing dimethyl ether and co-producing p-hydroxybenzonitrile, which comprises the following steps: using a methanol solution of sodium methoxide with a solution concentration of 28%-51% as raw material, reacting with p-halobenzonitrile under the conditions of a molar ratio of 2-3:1, a reaction temperature of 190℃-220℃, a reaction pressure of 3.5Mpa-6Mpa, and a reaction time of 1-24 hours, cooling to below 60℃, releasing pressure and collecting the discharged dimethyl ether gas, recovering the remaining solid-liquid product by reducing pressure distillation, and then adding water to the distillation residue and acidifying to obtain p-hydroxybenzonitrile solid; or cooling and filtering the remaining solid-liquid product, and then acidifying the filtrate which is a low-concentration methanol solution of sodium methoxide to obtain p-hydroxybenzonitrile solid.

[0004] For example, patent application number CN201110301805.6 discloses a method for preparing p-hydroxybenzonitrile. 258g of a 28.5% sodium methoxide methanol solution and 75g of p-chlorobenzonitrile are added to a 1000ml autoclave. After replacing the air in the autoclave with nitrogen, the temperature is raised to 200°C and the autoclave pressure is increased to 2.8 MPa. The reaction is allowed to proceed for 5-7 hours. The reaction is terminated, the temperature is lowered to below 50°C, and the methanol is recovered under reduced pressure (which can be applied). Cold water is added to dissolve the residual product. After filtering the insoluble matter, the product is acidified with 36% hydrochloric acid to precipitate a white p-hydroxybenzonitrile product with a content of >99.0% after drying and a mass of 62.8g. The yield is 95.9%.

[0005] The above process needs to be carried out at high temperature (190℃-220℃) and high pressure (2.5Mpa-6Mpa); it is not suitable for industrial production. Summary of the Invention

[0006] To address the aforementioned issues, the present invention discloses an industrial preparation method for p-hydroxybenzonitrile. The method comprises: reacting p-chlorobenzonitrile and an organic base in a mixed solvent in the presence of a composite catalyst to produce p-hydroxybenzonitrile. The reaction temperature is 60-100°C, the pH is 5.5-6.5, and the reaction time is 8-15 hours. The mixed solvent comprises methanol and a polar aprotic solvent in a volume ratio of 2-4:1. The composite catalyst comprises lithium chloride and an organic catalyst in a mass ratio of 0.5-3.0:1. The organic catalyst is selected from one or more of a quaternary ammonium salt catalyst, a crown ether catalyst, and tetrabutylammonium bromide; the crown ether catalyst is 18-crown-6; and the quaternary ammonium salt catalyst is selected from trimethylbenzylammonium chloride, triethylbenzylammonium chloride, tripropylbenzylammonium chloride, or tributylbenzylammonium chloride, preferably tributylbenzylammonium chloride. Preferably, the composite catalyst comprises lithium chloride and tetrabutylammonium bromide in a mass ratio of 1.0-1.5:1. The molar ratio of p-chlorobenzonitrile: organic base: lithium chloride is 1: 2.8-3.2: 0.05-0.2. The organic base is selected from sodium methoxide, potassium ethoxide or potassium tert-butoxide, preferably sodium methoxide.

[0007] Further, after the reaction is completed, vacuum distillation is performed, ice water is added for crystallization, solid-liquid separation is performed, water is washed, and recrystallization is performed to obtain p-hydroxybenzonitrile. The gas from the vacuum distillation is collected, condensed, and methanol is recovered by distillation. The methanol is reused as a raw material or a recrystallization solvent, and the number of cycles of methanol is 2-4 times. The recrystallization solvent is selected from toluene, methanol, or DMF, and is preferably methanol.

[0008] Wherein, the sodium methoxide adopts 25-35wt% sodium methoxide methanol solution.

[0009] Wherein, a weak acid is added to adjust the reaction pH to 6; the weak acid is selected from acetic acid or citric acid, and is preferably acetic acid.

[0010] wherein the polar aprotic solvent is DMSO.

[0011] Preferably, the industrial preparation method of p-hydroxybenzonitrile provided by the present application comprises the following steps: (1) Dissolving p-chlorobenzonitrile in methanol, and then mixing with sodium methoxide methanol solution, DMSO and composite catalyst; wherein the volume ratio of methanol (total) to DMSO is 2-4:1; the composite catalyst is lithium chloride and tetrabutylammonium bromide compounded according to the mass ratio of 1.0-1.5:1. The molar ratio of p-chlorobenzonitrile: sodium methoxide: lithium chloride is 1:2.8-3.2:0.05-0.2.

[0012] (2) Reacting at 60-100℃ for 8-15h under nitrogen protection, and adding acetic acid to adjust the pH to 6 during the reaction.

[0013] (3) After the reaction is completed, vacuum distillation is performed, ice water is added for crystallization, solid-liquid separation, water washing and methanol recrystallization to obtain p-hydroxybenzonitrile.

[0014] In the present patent, the use of composite catalyst can accelerate the reaction rate; the mixed solvent system can improve the reaction uniformity. The composite catalyst and the mixed solvent system cooperate to allow the reaction to be carried out at normal pressure and at a relatively low temperature (a common kettle reactor can be used), and the reaction yield is greater than 94% and the purity is greater than 98.5%; in addition, methanol can be reused (after 3 cycles, the yield is greater than 92%), which can reduce waste liquid discharge. DETAILED DESCRIPTION

[0015] In order to make the purpose, technical scheme and advantages of the present application clearer, the embodiments of the present application are described in further detail below.

[0016] Example 1: Solvent: methanol and DMSO, the volume ratio of methanol to DMSO is 3:1, and the amount is appropriate.

[0017] Raw materials: p-chlorobenzonitrile 137.6g (1mol), sodium methoxide 162g (3mol), lithium chloride 4.24g (0.1mol) and tetrabutylammonium bromide 4.0g.

[0018] Reaction: The raw materials are added to the reaction kettle, and the reaction is carried out under nitrogen atmosphere, at normal pressure, and the temperature is raised to 80℃, and the pH is adjusted to 6 by adding acetic acid dropwise. The reaction liquid is vacuum distilled, the residue is crystallized with ice water, filtered and dried to obtain white crystal p-hydroxybenzonitrile, the yield is 96.2%, and the purity of the crude product is 98.8%. After water washing twice and methanol recrystallization, the purity of the fine product is 99.8%.

[0019] After the methanol is recycled once, the yield of the crude product is 95.3%; After methanol is recycled for three times, the crude product yield is 92.1%; the reduction is 4%; After methanol is recycled for four times, the crude product yield is 89.5%; After methanol is recycled for four times, the crude product yield is 89.5%; After methanol is recycled for five times, the crude product yield is 86.7%.

[0020] As can be seen from the above, after methanol is recycled for three times, the yield is still above 90%, which is higher than the prior art.

[0021] Example 2: Solvent: methanol and DMSO, the volume ratio of methanol to DMSO is 3:1, and the amount is appropriate.

[0022] Raw materials: p-chlorobenzonitrile 137.6g (1mol), sodium methoxide 156.5g (2.9mol), lithium chloride 3.39g (0.08mol) and 18-crown-6 5.0g.

[0023] Reaction: the raw materials are added to the reaction kettle, under the nitrogen atmosphere, at normal pressure, the temperature is raised to 82℃, and the stirring reaction is carried out for 12 hours, and then acetic acid is added dropwise to adjust the pH to 6.2. The reaction solution is distilled under reduced pressure, the residue is crystallized with ice water, filtered and dried to obtain white crystal p-hydroxybenzonitrile, the yield is 95%, and the purity of the crude product is 98.5%. After water washing and recrystallization, the purity of the fine product is 99.6%.

[0024] Example 3: Solvent: methanol and DMSO, the volume ratio of methanol to DMSO is 3.5:1, and the amount is appropriate.

[0025] Raw materials: p-chlorobenzonitrile 137.6g (1mol), potassium tert-butoxide 336.6g (3mol), lithium chloride 6.36g (0.15mol) and tributylbenzylammonium chloride 3.8g.

[0026] Reaction: the raw materials are added to the reaction kettle, under the nitrogen atmosphere, at normal pressure, the temperature is raised to 85℃, and the stirring reaction is carried out for 10 hours, and then acetic acid is added dropwise to adjust the pH to 6. The reaction solution is distilled under reduced pressure, the residue is crystallized with ice water, filtered and dried to obtain white crystal p-hydroxybenzonitrile, the yield is 96%, and the purity of the crude product is 98.5%. After water washing and recrystallization, the purity of the fine product is 99.7%.

[0027] Comparative Example 1 The same as Example 1, except that no tetrabutylammonium bromide is added. The reaction time is 4 hours, the crude product yield is 89%, and the purity of the crude product is 96.4%.

[0028] Comparative Example 2 The same as example 1, except that: replace DMSO with equal volume of methanol (i.e. use methanol as solvent). The crude product yield is 90%, and the crude product purity is 98.2%.

[0029] Comparative example 3 The same as example 1, except that: replace tetrabutylammonium bromide with equal mass of tetrabutylammonium chloride, the crude product yield is 88%, and the crude product purity is 96.4%.

[0030] Comparative example 4 The same as example 1, except that: replace DMSO with DMF, the crude product yield is 89%, and the crude product purity is 97.8%.

[0031] Comparative example 5 The same as example 1, except that: replace DMSO with acetone, the crude product yield is 90%, and the crude product purity is 97.9%.

[0032] Comparative example 6 The same as example 1, except that: do not add tetrabutylammonium bromide and lithium chloride, and use methanol as solvent; the reaction time is 10 hours, the crude product yield is 80%, and the crude product purity is 94.5%.

[0033] After one cycle of methanol, the crude product yield is 78.5%; After two cycles of methanol, the crude product yield is 72.1%, with a decrease of 9.9%.

[0034] Comparative example 7 Using the method of CN202110074058.0, the reaction pressure is 6.0Mpa, the reaction temperature is 220℃, the reaction time is 5h, the molar ratio of sodium methoxide to p-chlorobenzonitrile is 2:1, the purity is 98.8%, and the yield is 89%.

[0035] After one cycle of methanol, the crude product yield is 87.3%; After two cycles of methanol, the crude product yield is 85.5%; After three cycles of methanol, the crude product yield is 81.4%, with a decrease of 8.5%.

[0036] Comparative example 8 The same as example 1, except that: replace lithium chloride with zinc chloride, the crude product yield is 82%, and the crude product purity is 95.2%.

[0037] The above is only the preferred embodiment of the present application, and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. An industrial preparation method of p-hydroxybenzonitrile, characterized in that: The method comprises: reacting p-chlorobenzonitrile and an organic base in a mixed solvent under the action of a composite catalyst to obtain p-hydroxybenzonitrile, the reaction temperature being 60-100° C., the reaction pH being 5.5-6.5, and the reaction time being 8-15 hours; the mixed solvent being composed of methanol and a polar aprotic solvent in a volume ratio of 2-4:1; the composite catalyst being compounded of lithium chloride and an organic catalyst in a mass ratio of 0.5-3.0:1, the organic catalyst being selected from one or more of a quaternary ammonium salt catalyst, a crown ether catalyst, and tetrabutylammonium bromide; the molar ratio of p-chlorobenzonitrile:organic base:lithium chloride being 1:2.8-3.2:0.05-0.2; and the organic base being selected from sodium methoxide, potassium ethoxide, or potassium tert-butoxide.

2. The method according to claim 1, characterized in that After the reaction is completed, vacuum distillation is performed, ice water is added for crystallization, solid-liquid separation is performed, water washing and recrystallization are performed to obtain p-hydroxybenzonitrile; the gas from the vacuum distillation is collected, condensed, and methanol is recovered by distillation, and the methanol is reused as a raw material, and the number of methanol cycles is 2-4 times; the recrystallization solvent is selected from toluene, methanol or DMF.

3. The method according to claim 1, characterized in that The organic base is sodium methoxide.

4. The method according to claim 3, characterized in that The sodium methoxide is a 25-35wt% sodium methoxide methanol solution.

5. The method according to claim 1, wherein The crown ether catalyst is 18-crown-6, and the quaternary ammonium salt catalyst is selected from trimethylbenzylammonium chloride, triethylbenzylammonium chloride, tripropylbenzylammonium chloride or tributylbenzylammonium chloride.

6. The method according to claim 1, characterized in that The composite catalyst is prepared by compounding lithium chloride and tetrabutylammonium bromide in a mass ratio of 1.0-1.5:

1.

7. The method according to claim 1, characterized in that A weak acid was added to adjust the reaction pH to 6, wherein the weak acid was acetic acid.

8. The method according to claim 1, characterized in that The polar aprotic solvent is DMSO.

9. The method according to claim 1, characterized in that The method comprises the following steps: (1) dissolving p-chlorobenzonitrile in methanol, and then mixing with a sodium methoxide methanol solution, DMSO and a composite catalyst; (2) Under nitrogen protection, the reaction was carried out at 60-100°C for 8-15 hours. During the reaction, acetic acid was added to adjust the pH to 6; (3) After the reaction is completed, distill under reduced pressure, add ice water for crystallization, separate the solid and liquid, wash with water and recrystallize to obtain p-hydroxybenzonitrile.