A kind of preparation method of 2-allyl-4-nitrophenol

Abstract

The present application relates to the technical field of synthesis of organic optoelectronic intermediate materials, and specifically discloses a method for preparing 2-allyl-4-nitrophenol, comprising the following steps: using 2-allylphenol as a raw material, protecting the phenolic hydroxyl group by a steric hindering agent, nitrating the benzene ring by a nitrating agent, and then reducing the phenolic hydroxyl group by a deprotecting agent to obtain a target product; the present application uses a steric hindering agent to protect the phenolic hydroxyl group, and by protecting the phenolic hydroxyl group, the activity of the ortho-position hydrogen atom of the hydroxyl group is passivated, and the ortho-position steric hindering effect is increased, so that the nitration reaction is carried out at the para-position of the phenolic hydroxyl group, and then the phenolic hydroxyl group is reduced by deprotection to obtain the target product; the preparation method of the present application is simple, the cost of the reaction raw materials is low, the reaction time of the entire reaction process is short, the intermediate 1 and the intermediate 2 obtained in the reaction process do not need to be purified, the reaction yield is high, and the purity of the target product is high.

Description

Technical Field

[0001] The present application relates to the technical field of organic optoelectronic material intermediate synthesis, and more specifically, to a method for preparing 2-allyl-4-nitrophenol. Background Art

[0002] 2-Allyl-4-nitrophenol is an important organic chemical synthesis intermediate, widely used in the preparation of dyes, medicines, and organic optoelectronic materials.

[0003] In the prior art (J. Org. Chem. 2014, 79, 7425−7436), 1-(allyloxy)-4-nitrobenzene is used as a raw material, and then allyl-4-nitrophenol is prepared through Claisen rearrangement. The raw materials used in this method are expensive, the yield of the product obtained by the Claisen rearrangement reaction is low, and the product is prone to isomerization.

[0004] In the prior art (Molecules 2019, 24, 4196), 2-allylphenol is used as a raw material and nitrated using a nitric acid / sulfuric acid mixed acid. The nitration reagent is highly acidic, which is not conducive to industrial production, and the obtained product is 2-allyl-4,6-dinitrophenol.

[0005] Therefore, it is particularly important to develop a novel method for preparing 2-allyl-4-nitrophenol. Summary of the invention

[0006] In order to solve the defects of the existing 2-allyl-4-nitrophenol preparation method, such as expensive raw material cost, low product yield, easy product isomerization, and being unfavorable for industrial production, the present application provides a preparation method of 2-allyl-4-nitrophenol.

[0007] The present application provides a method for preparing 2-allyl-4-nitrophenol, which adopts the following technical scheme:

[0008] A method for preparing 2-allyl-4-nitrophenol comprises the following steps:

[0009] Using 2-allylphenol as the raw material, the phenolic hydroxyl group is protected by a steric agent, and then the benzene ring is nitrated in the presence of a nitrating agent. The phenolic hydroxyl group is then reduced by a deprotecting agent to obtain the target product 2-allyl-4-nitrophenol.

[0010] Preferably, the preparation method specifically comprises the following steps:

[0011] (1) Under an inert atmosphere, 2-allylphenol is added to a reaction bottle, a weak base and solvent A are added, and after stirring, a steric reagent is added, and stirring is continued until the reaction is completed. After post-treatment, intermediate 1 is obtained;

[0012] (2) Place intermediate 1 in a reaction bottle, add a nitrating agent, and obtain intermediate 2 through reaction;

[0013] (3) Add intermediate 2 to a reaction flask, add a deprotection reagent and solvent B, and obtain the target product 2-allyl-4-nitrophenol after reaction and post-treatment.

[0014] Preferably, the weak base in step (1) is selected from an inorganic weak base and / or an organic weak base.

[0015] Preferably, the weak base is at least one of sodium nitrosulfate, sodium thiosulfamate, potassium acetate, aluminum hydroxide, ammonia water, morpholine, imidazole, pyrimidine, pyridine and pyrazole.

[0016] Preferably, in step (1), the molar ratio of 2-allylphenol to weak base is 1:(2.0-10.0).

[0017] Preferably, the solvent A in step (1) is selected from at least one of alkanes, amides, aromatic hydrocarbons and ethers.

[0018] Preferably, the solvent A is at least one of n-hexane, n-heptane, N,N-dimethylformyl, N,N-dimethylacetamide, N-methylpyrrolidone, N-ethylpyrrolidone, N-methylpyrimidine, xylene, 1,4-dioxane, and anisole.

[0019] Preferably, the steric hindering reagent in step (1) is selected from at least one of silane reagents, alcohol reagents, acetone reagents, alkyl halides, and disulfide reagents.

[0020] Preferably, the steric hindering agent is at least one of sodium trimethylsilylhydride, tert-butyldimethylchlorosilane, trimethylsilyl oxide, p-nitrobenzoyl chloride, triphenylmethoxymethanol, N,N-dimethylformyl chloride, and triphenylphosphothiocyanate.

[0021] Preferably, in step (1), the molar ratio of 2-allylphenol to the steric hindered agent is 1:(1.0-5.0).

[0022] Preferably, the nitrating agent in step (2) is selected from at least one of nitro inorganic salts, nitro organic salts, nitro inorganic acids, and nitro organic compounds.

[0023] Preferably, the nitrating agent is at least one of zinc nitrate, bismuth nitrate, urea nitrate, guanidine nitrate, tetramethylammonium nitrate, nitric acid, ethylene glycol nitrate, and acetyl nitrate.

[0024] Preferably, in step (2), the molar ratio of 2-allylphenol to nitrating agent is 1:(0.8-1.2).

[0025] Preferably, the nitration method in step (2) refers to using microwave equipment to assist nitration.

[0026] Preferably, the deprotection reagent in step (3) is selected from at least one of acids, bases and salts.

[0027] Preferably, the deprotection agent is at least one of hydrochloric acid, trifluoroacetic acid, hydrofluoric acid, boron trifluoride, sodium hydroxide, and ferric chloride.

[0028] Preferably, in step (3), the molar ratio of intermediate 2 to deprotection reagent is 1:(1.0-10.0).

[0029] Preferably, the solvent B is selected from at least one of alcohols, acids and aromatic hydrocarbons.

[0030] Preferably, the solvent B is at least one of n-butanol, propanol, acetic acid, phosphoric acid, decalin and chlorobenzene.

[0031] In summary, this application has the following beneficial effects:

[0032] The present application utilizes a steric hindered reagent to protect the phenolic hydroxyl group. By protecting the phenolic hydroxyl group, the activity of the hydrogen atom ortho to the hydroxyl group is passivated, and at the same time, the ortho steric hindered effect is increased, so that the nitration reaction takes place at the para position of the phenolic hydroxyl group, and then the phenolic hydroxyl group is reduced by deprotection to obtain the target product. The preparation method of the present application is simple, the cost of the reaction raw materials is low, no external catalyst is required, the reaction time of the entire reaction process is short, the intermediate 1 and the intermediate 2 obtained in the reaction process do not need to be purified, the reaction yield is high, and the purity of the target product is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the H NMR spectrum of the target product 2-allyl-4-nitrophenol obtained in Example 1 of the present application. DETAILED DESCRIPTION

[0034] The present application is further described in detail below with reference to the embodiments.

[0035] Example 1-6 provides a method for preparing 2-allyl-4-nitrophenol.

[0036] Example 1

[0037] A method for preparing 2-allyl-4-nitrophenol comprises the following steps:

[0038] (1) Preparation of intermediate 1: Under nitrogen atmosphere, 2-allylphenol (1.34 g, 10 mmol) was placed in a glass reaction bottle, followed by the addition of tert-butyldimethylsilyl chloride (1.8 g, 12 mmol), imidazole (1.36 g, 20 mmol) and N,N-dimethylformamide (15 ml) with stirring. The mixture was reacted at room temperature for 3 h. After the reaction, the reaction solution was poured into ice water and stirred for 20 min. The mixture was then extracted with ethyl acetate (100 ml for 1 extraction) and water (100 ml each time for 3 extractions). The organic phase was taken and dried under reduced pressure to obtain intermediate 1.

[0039] (2) Preparation of intermediate 2: bismuth nitrate pentahydrate (4.85 g, 10 mmol) and 20% glacial acetic acid (10 ml) were added to the intermediate 1 obtained above. The mixture was heated in a microwave oven for 4 min at a power of 90 W, a speed of 200 r / min, and a temperature of 25°C in a synthesis reactor. 10 ml of deionized water was added to terminate the reaction. The mixture in the reaction flask was then extracted with ethyl acetate (1 extraction with 120 ml) and water (120 ml each time, 3 extractions). The organic solvent was removed from the organic phase to obtain intermediate 2.

[0040] (3) Preparation of target product: The obtained intermediate 2 was added to a reaction flask, followed by ferric chloride (1.62 g, 11 mmol) and glacial acetic acid (20 ml). The mixture was stirred at 80°C for 2 h. The reaction solution was filtered and the filtrate was extracted with ethyl acetate (150 ml for extraction once) and water (150 ml for extraction once). Silica gel powder (20 g) was added to the extract and stirred for 1 h. The mixture was filtered again and the filtrate was dried to obtain pure 2-allyl-4-nitrophenol (1.5 g, yield 84%).

[0041] Example 2

[0042] Compared with Example 1, the type of steric hindered reagent is changed from tert-butyldimethylsilyl chloride to p-nitrobenzoyl chloride to prepare Intermediate 1, and the other steps remain unchanged. The specific operation is as follows:

[0043] (1) Preparation of intermediate 1: Under nitrogen atmosphere, 2-allylphenol (1.34 g, 10 mmol) was placed in a glass reaction bottle, followed by the addition of p-nitrobenzoyl chloride (2.22 g, 12 mmol), imidazole (1.36 g, 20 mmol) and N,N-dimethylformamide (15 ml) and stirring. The mixture was reacted at room temperature for 3 h. After the reaction, the reaction solution was poured into ice water and stirred for 20 min. The mixture was then extracted with ethyl acetate (100 ml for 1 extraction) and water (100 ml each time for 3 extractions). The organic phase was taken and dried under reduced pressure to obtain intermediate 1.

[0044] (2) Preparation of intermediate 2: bismuth nitrate pentahydrate (4.85 g, 10 mmol) and 20% glacial acetic acid (10 ml) were added to the intermediate 1 obtained above. The mixture was heated in a microwave oven for 4 min at a power of 90 W, a speed of 200 r / min, and a temperature of 25°C in a synthesis reactor. 10 ml of deionized water was added to terminate the reaction. The mixture in the reaction flask was then extracted with ethyl acetate (1 time with 120 ml) and water (120 ml each time, 3 times). The organic solvent was removed from the organic phase to obtain intermediate 2.

[0045] (3) Preparation of target product: The obtained intermediate 2 was added to a reaction flask, followed by ferric chloride (1.62 g, 11 mmol) and glacial acetic acid (20 ml). The mixture was stirred at 80°C for 2 h. The reaction solution was filtered and the filtrate was extracted with ethyl acetate (150 ml for extraction once) and water (150 ml for extraction once). Silica gel powder (20 g) was added to the extract and stirred for 1 h. The mixture was filtered again and the filtrate was dried to obtain pure 2-allyl-4-nitrophenol (1.35 g, yield 74%).

[0046] Example 3

[0047] Compared with Example 1, the weak base is replaced by morpholine from imidazole to prepare Intermediate 1, and the remaining steps remain unchanged. The specific operation is as follows:

[0048] (1) Preparation of intermediate 1: Under nitrogen atmosphere, 2-allylphenol (1.34 g, 10 mmol) was placed in a glass reaction bottle, followed by the addition of tert-butyldimethylsilyl chloride (1.8 g, 12 mmol), morpholine (1.74 g, 20 mmol) and N,N-dimethylformamide (15 ml) and stirring. The mixture was reacted at room temperature for 3 h. After the reaction, the reaction solution was poured into ice water and stirred for 20 min. The mixture was then extracted with ethyl acetate (100 ml for 1 extraction) and water (100 ml each time for 3 extractions). The organic phase was taken and dried under reduced pressure to obtain intermediate 1.

[0049] (2) Preparation of intermediate 2: bismuth nitrate pentahydrate (4.85 g, 10 mmol) and 20% glacial acetic acid (10 ml) were added to the intermediate 1 obtained above. The mixture was heated in a microwave oven for 4 min at a power of 90 W, a speed of 200 r / min, and a temperature of 25°C in a synthesis reactor. 10 ml of deionized water was added to terminate the reaction. The mixture in the reaction flask was then extracted with ethyl acetate (1 time with 120 ml) and water (120 ml each time, 3 times). The organic solvent was removed from the organic phase to obtain intermediate 2.

[0050] (3) Preparation of target product: The obtained intermediate 2 was added to a reaction flask, followed by ferric chloride (1.62 g, 11 mmol) and glacial acetic acid (20 ml). The mixture was stirred at 80°C for 2 h. The reaction solution was filtered and the filtrate was extracted with ethyl acetate (150 ml for extraction once) and water (150 ml for extraction once). Silica gel powder (20 g) was added to the extract and stirred for 1 h. The mixture was filtered again and the filtrate was dried to obtain pure 2-allyl-4-nitrophenol (1.68 g, yield 92%).

[0051] Example 4

[0052] Compared with Example 1, the type of nitrating reagent is changed from bismuth nitrate pentahydrate to nitric acid to prepare intermediate 2, and the other steps remain unchanged. The specific operation is as follows:

[0053] (1) Preparation of intermediate 1: Under nitrogen atmosphere, 2-allylphenol (1.34 g, 10 mmol) was placed in a glass reaction bottle, followed by the addition of tert-butyldimethylsilyl chloride (1.8 g, 12 mmol), imidazole (1.36 g, 20 mmol) and N,N-dimethylformamide (15 ml) with stirring. The mixture was reacted at room temperature for 3 h. After the reaction, the reaction solution was poured into ice water and stirred for 20 min. The mixture was then extracted with ethyl acetate (100 ml for 1 extraction) and water (100 ml each time for 3 extractions). The organic phase was taken and dried under reduced pressure to obtain intermediate 1.

[0054] (2) Preparation of intermediate 2: 30% nitric acid (2.1 g, 10 mmol) and 20% glacial acetic acid (10 ml) were added to the intermediate 1 obtained above. The mixture was heated in a microwave manner for 4 min at a power of 90 W, a speed of 200 r / min, and a temperature of 25°C in a synthesis reactor. 10 ml of deionized water was added to terminate the reaction. The mixture in the reaction flask was then extracted with ethyl acetate (1 time with 120 ml) and water (120 ml each time, 3 times). The organic solvent was removed from the organic phase to obtain intermediate 2.

[0055] (3) The obtained intermediate 2 was added to a reaction flask, followed by ferric chloride (1.62 g, 11 mmol) and glacial acetic acid (20 ml). The mixture was stirred at 80°C for 2 h. The reaction solution was filtered and the filtrate was extracted with ethyl acetate (150 ml for extraction once) and water (150 ml for extraction once). Silica gel powder (20 g) was added to the extract and stirred for 1 h. The mixture was filtered again and the filtrate was dried to obtain pure 2-allyl-4-nitrophenol (0.73 g, yield 40%).

[0056] Example 5

[0057] Compared with Example 1, the type of deprotection reagent is changed from ferric chloride to hydrochloric acid to prepare 2-allyl-4-nitrophenol, and the other steps remain unchanged. The specific operation is as follows:

[0058] (1) Preparation of intermediate 1: Under nitrogen atmosphere, 2-allylphenol (1.34 g, 10 mmol) was placed in a glass reaction bottle, followed by the addition of tert-butyldimethylsilyl chloride (1.8 g, 12 mmol), imidazole (1.36 g, 20 mmol) and N,N-dimethylformamide (15 ml) with stirring. The mixture was reacted at room temperature for 3 h. After the reaction, the reaction solution was poured into ice water and stirred for 20 min. The mixture was then extracted with ethyl acetate (100 ml for 1 extraction) and water (100 ml each time for 3 extractions). The organic phase was taken and dried under reduced pressure to obtain intermediate 1.

[0059] (2) Preparation of intermediate 2: bismuth nitrate pentahydrate (4.85 g, 10 mmol) and 20% glacial acetic acid (10 ml) were added to the intermediate 1 obtained above. The mixture was heated in a microwave oven for 4 min at a power of 90 W, a speed of 200 r / min, and a temperature of 25°C in a synthesis reactor. 10 ml of deionized water was added to terminate the reaction. The mixture in the reaction flask was then extracted with ethyl acetate (1 time with 120 ml) and water (120 ml each time, 3 times). The organic solvent was removed from the organic phase to obtain intermediate 2.

[0060] (3) Preparation of target product: The intermediate 2 was added to a reaction flask, followed by 37% hydrochloric acid (1.08 g, 11 mmol) and glacial acetic acid (20 ml). The mixture was stirred at 80°C for 2 h. The reaction solution was filtered and the filtrate was extracted with ethyl acetate (150 ml for extraction once) and water (150 ml for extraction once). Silica gel powder (20 g) was added to the extract and stirred for 1 h. The mixture was filtered again and the filtrate was dried to obtain pure 2-allyl-4-nitrophenol (1.57 g, yield 88%).

[0061] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed. However, as long as it is within the scope of the claims of the present application, it shall be protected by the patent law.

Claims

1. A method for preparing 2-allyl-4-nitrophenol, characterized in that: The steps include: (1) Under an inert atmosphere, 2-allylphenol is added to a reaction flask, followed by the addition of a steric reagent, a weak base and solvent A, and the mixture is stirred until the reaction is complete. Intermediate 1 is obtained after post-treatment; (2) Place intermediate 1 in a reaction bottle, add a nitrating agent, and obtain intermediate 2 through reaction; (3) Add intermediate 2 to a reaction flask, add a deprotection reagent and solvent B, and obtain the target product 2-allyl-4-nitrophenol through reaction and post-treatment; The nitrating agent in step (2) is bismuth nitrate pentahydrate; the molar ratio of 2-allylphenol to the nitrating agent in step (2) is 1:(0.8-1.2).

2. A method for preparing 2-allyl-4-nitrophenol according to claim 1, characterized in that: The steric hindering reagent in step (1) is selected from at least one of silane reagents, alcohol reagents, acetone reagents, alkyl halides, and disulfide reagents.

3. A method for preparing 2-allyl-4-nitrophenol according to claim 1, characterized in that: The steric hindering agent is at least one of sodium trimethylsilylhydride, tert-butyldimethylchlorosilane, trimethylsilyloxysilane, p-nitrobenzoyl chloride, triphenylmethoxymethanol, N,N-dimethylformyl chloride, and triphenylphosphothiocyanate.

4. A method for preparing 2-allyl-4-nitrophenol according to claim 1, characterized in that: In the step (1), the molar ratio of 2-allylphenol to the steric hindrance agent is 1:(1.0-5.0).

5. A method for preparing 2-allyl-4-nitrophenol according to claim 1, characterized in that: The deprotection reagent in step (3) is selected from at least one of acids, bases and salts.

6. A method for preparing 2-allyl-4-nitrophenol according to claim 1, characterized in that: In the step (3), the molar ratio of the intermediate 2 to the deprotection reagent is 1:(1.0-10.0).

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