阅读说明：本技术 一种3-氨基苯酚的制备方法 (Preparation method of 3-aminophenol ) 是由 瞿军 吴宏祥 掌鹏程 沈润溥 于 2020-12-14 设计创作，主要内容包括：本发明涉及有机合成化工领域内的一种3-氨基苯酚的合成方法,其以N,N’-双(3-羟基苯基)硫脲为起始原料,乙腈和水为溶剂,过硫酸钾为氧化剂,经氧化反应制备3-氨基苯酚。本发明提供的反应条件温和,操作简单,具有良好的推广应用价值。本发明的目标产物在化学制药、有机合成等方面具有巨大应用价值。(The invention relates to a method for synthesizing 3-aminophenol in the field of organic synthesis chemical industry, which takes N, N' -bis (3-hydroxyphenyl) thiourea as a starting material, acetonitrile and water as solvents, potassium persulfate as an oxidant, and prepares the 3-aminophenol through oxidation reaction. The method provided by the invention has the advantages of mild reaction conditions, simple operation and good popularization and application values. The target product of the invention has great application value in the aspects of chemical pharmacy, organic synthesis and the like.)

1. A preparation method of 3-aminophenol is characterized in that: the method comprises the following steps of (1) preparing 3-aminophenol by using N, N' -bis (3-hydroxyphenyl) thiourea as a starting material, acetonitrile and water as solvents and potassium persulfate as an oxidant through an oxidation reaction, wherein the reaction formula is as follows:

2. the process according to claim 1, wherein the reaction is carried out in the presence of a catalyst selected from the group consisting of: the molar ratio of the potassium persulfate to the N, N' -bis (3-hydroxyphenyl) thiourea is (1-4): 1.

3. the process according to claim 2, wherein the reaction is carried out in the presence of a catalyst selected from the group consisting of: the molar ratio of the potassium persulfate to the N, N' -bis (3-hydroxyphenyl) thiourea is 3: 1.

4. a process for producing a 3-aminophenol according to any one of claims 1 to 3, characterized in that: the volume ratio of acetonitrile to water in the solvent is 1: 3.

5. A process for preparing 3-aminophenol in accordance with any one of claims 1 to 3, characterized in that the reaction temperature is from 60 ℃ to 90 ℃ and the reaction time is from 6 to 9 hours.

6. The process according to claim 5, wherein the reaction temperature is 80 ℃ and the reaction time is 8 hours.

Technical Field

The invention belongs to the field of organic synthesis chemical industry, and particularly relates to a synthetic method of 3-aminophenol.

Background

The 3-aminophenol (formula I) is an important fine chemical raw material and an organic intermediate, and is widely applied to the fields of medicines, pesticides, dyes, antioxidants, catalysts, developers and the like. In medicine, 3-aminophenol can be used for synthesizing sodium p-aminosalicylate which is an anti-tuberculosis drug, and participates in the preparation of tramadol which is an anti-cancer, tranquilization and pain-relieving drug and an cholinesterase drug-ammonium chloride of the aminophenol; in the aspect of pesticides, m-aminophenol can be used for synthesizing herbicides (betanin and betanin), bactericides (fenamidone and flutolanil) and participating in the preparation of an anticoccidial drug namely mebenzoxyquinoline.

At present, the literature reports the following methods for preparing 3-aminophenol:

(1) at present, the method for producing 3-aminophenol is mainly based on a reduction method, such as a 3-nitrophenol iron powder reduction method and a 3-nitrophenol hydrogenation reduction method. The 3-nitrophenol hydrogenation reduction method is a widely applied process, and the reaction catalyst mainly comprises precious metals such as platinum (Pt), palladium (Pd) and rhodium (Rh) and cheap metals such as copper (Cu), nickel (Ni), lead (Zn) and molybdenum (Mo). Although the catalytic effect is obvious and the reaction yield is high, the noble metal catalyst has overhigh price and cost and limited application in industrial production; the cheap metal supported catalyst has poor stability and is easy to agglomerate in the preparation process.

(2) Caitlin McCarthy et al, with water as the reaction solvent at room temperature, catalyze the selective hydroxylation of 3-aminophenylboronic acid to 3-aminophenol using a copper supported catalyst (Cu (0) NPs-CALB). The method has the reaction yield of 99 percent, but the recycling rate of the catalyst is low, so the method is not suitable for mass production.

(3) Monika Tomanov et al, using water as the reaction solvent, and converting 5-amino-2-bromophenol to 3-aminophenol by sodium sulfite reductive dehalogenation under microwave mediation. The method has high reaction yield of 93 percent, but has long reaction time, needs microwave mediated reaction and has higher requirement on reaction equipment.

In order to overcome the defects of the method, the invention provides a novel method for preparing 3-aminophenol, which takes N, N' -bis (3-hydroxyphenyl) thiourea as a raw material to prepare the 3-aminophenol through a cracking reaction, and has the advantages of short reaction step, mild reaction conditions, low cost and yield of more than 76 percent.

Disclosure of Invention

The invention aims to provide a preparation method of 3-aminophenol, which has the advantages of concise and high-efficiency synthesis, mild reaction conditions and simple operation.

Therefore, the technical scheme adopted by the invention is as follows: a preparation method of 3-aminophenol, which takes N, N' -bis (3-hydroxyphenyl) thiourea (formula II) as a starting material, acetonitrile and water as solvents, potassium persulfate as an oxidant, and prepares the 3-aminophenol through an oxidation reaction, wherein the reaction formula is as follows:

wherein the molar ratio of the potassium persulfate to the N, N' -bis (3-hydroxyphenyl) thiourea is (1-4): 1. the preferred amount of the compound is 3: 1.

the volume ratio of acetonitrile to water in the solvent is 1: 3.

The reaction temperature is 60-90 ℃, and the reaction time is 6-9 hours. The reaction temperature is preferably 80 ℃ and the reaction time is preferably 8 hours.

Compared with the prior art, the invention has the following beneficial effects:

(1) the invention provides a new route for synthesizing 3-aminophenol, which takes N, N' -bis (3-hydroxyphenyl) thiourea as a raw material and potassium persulfate as an oxidant to prepare the 3-aminophenol through oxidation reaction.

(2) The reaction solvents of the preparation route of the invention are acetonitrile and water, thereby reducing the use of organic solvents and meeting the requirements of green chemistry.

(3) The route provided by the invention has the advantages of mild reaction conditions, simple operation and good popularization and application values.

(4) The target product of the invention has great application value in the aspects of chemical pharmacy, organic synthesis and the like.

Drawings

FIG. 1 shows nuclear magnetic hydrogen spectra of target compounds.

FIG. 2 shows nuclear magnetic carbon spectra of the target compound.

Detailed Description

The present invention will be further described with reference to the following embodiments.

Analytical instrumentation and equipment used in the examples: nuclear magnetic resonance apparatus (AVANCE DMXIII 400M, Bruker).

Example 1: preparation of 3-aminophenol

A100 ml round bottom flask was charged with N, N' -bis (3-hydroxyphenyl) thiourea (2.6g,10mmol), 10ml acetonitrile, 30ml water, potassium persulfate (8.1g,30mmol) in this order, heated at 80 ℃ under reflux for 8h (TLC to follow the progress of the reaction, optionally 6-9h), and the reaction formula was as follows:

after the reaction is finished, evaporating acetonitrile; cooling to room temperature, adding 100ml purified water, extracting with dichloromethane, layering, drying the organic phase with anhydrous sodium sulfate, concentrating to obtain crude product, and purifying by column chromatography to obtain pure product 1.657g with yield 76.0%.

The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum data of the product are as follows:

¹H NMR(400MHz,DMSO)δ8.86(s,1H)，6.79(t,J＝7.6Hz,1H),6.03-6.01 (m,2H),5.97-5.95(m,1H),4.88(s,2H).

¹³C NMR(100MHz,DMSO)δ158.50,150.24,129.91,105.90,103.79, 101.42.

the structural formula of the product is:

example 2: screening of oxidizing Agents

The experimental conditions and the charge amount in this example were the same as in example 1, and different oxidizing agents (3 times (molar ratio) of the raw material II) were selected for the experiment, and the specific conditions and charge amounts are shown in table 1:

TABLE 1

	Oxidizing agent	Yield of
			1	tert-Butanol peroxide	48.5％
2	Hydrogen peroxide solution	42.2％
			3	Potassium persulfate	76.0％
4	Sodium persulfate	71.5％

As can be seen from table 1, the reaction yield was lowest when hydrogen peroxide was selected as the oxidant, and was only 42.2%, when sodium persulfate was selected as the oxidant, the reaction yield was 71.5%, and when potassium persulfate was selected as the oxidant, the reaction yield was highest, and was 76.0%; in conclusion, the invention selects potassium persulfate as the reaction oxidant.

Example 3: potassium persulfate (K)₂S₂O₈) Screening of dosage

The experimental conditions and the amount of the feed in this example were the same as in example 1, and different dosages of K were selected₂S₂O₈Experiments were performed as shown in table 2:

TABLE 2

	Dosage (mmol)	Yield of
			1	10	61.5％
2	20	71.1％
			3	30	76.0％
4	40	73.5％

As can be seen from Table 2, when the amount of potassium persulfate used was 10mmol, the reaction yield was only 61.5%; when the amount is 30mmol, the reaction yield is 76.0%, however, the reaction yield is reduced by continuously increasing the amount of potassium persulfate; in conclusion, the invention selects 30mmol potassium persulfate to be optimal.

Example 4: screening of solvents

The experimental conditions and the charge amount of the present example were the same as those of example 1, and different reaction solvents were selected for the experiment, as shown in table 3:

TABLE 3

	Solvent(s)	Yield of
			1	Ethanol	68.0％
2	Acetonitrile	46.2％
			3	Methylene dichloride	23.5％
4	Acetonitrile/water	76.0％
			5	Water (W)	73.5％

As can be seen from table 3, the reaction yield was the lowest when dichloromethane was selected as the solvent and was only 23.5%, while the reaction yield was 73.5% when water was selected as the solvent, and the reaction yield was the highest when a mixed solvent of acetonitrile and water was selected and was 76.0%; in summary, the present invention selects the mixed solution of acetonitrile and water as the reaction solvent.

Example 5: proportional screening of mixed solvent

The experimental conditions and the charge amount in this example were the same as those in example 1, and the experiment was carried out by selecting different solvent mixing ratios, as shown in table 4:

TABLE 4

	Acetonitrile: water (W)	Yield of
			1	1:1	65.5％
2	1:2	73.2％
			3	1:3	76.0％
4	1:4	76.3％

As can be seen from table 4, when the mixing ratio of acetonitrile and water is 1:1, the reaction yield is the lowest, only 65.5%, and when the mixing ratio of acetonitrile and water is 1:2, the reaction yield is 73.2%, when the mixing ratio of acetonitrile and water is 1:3, the reaction yield is the highest, 76.0%, however, when the amount of water is continuously increased, the reaction yield is not significantly improved; in summary, the present invention is optimized when the mixing ratio of acetonitrile to water is 1: 3.

Example 6: screening of reaction temperature

The experimental conditions and the charge amount in this example were the same as those in example 1, and different reaction temperatures were selected for the experiment, as shown in table 5:

TABLE 5

	Temperature of	Yield of
			1	60	55.2％
2	70	71.5％
			3	80	76.0％
4	90	70.5％

As can be seen from table 5, when the reaction temperature is 60 ℃, the reaction yield is the lowest, only 55.2%, the reaction yield is obviously improved with the increase of the reaction temperature, when the selection reaction temperature is 80 ℃, the reaction yield is the highest, and is 76.0%, however, when the temperature is continuously increased, the reaction yield is obviously reduced; in conclusion, the reaction temperature can be selected from 70-90 ℃, and the preferred reaction temperature is 80 ℃.

The present invention is not limited to the above embodiments, and based on the technical solutions disclosed in the present invention, those skilled in the art can make some substitutions and modifications to some technical features without creative efforts according to the disclosed technical solutions, and these substitutions and modifications are all within the protection scope of the present invention.