CN114213374B

CN114213374B - Synthesis method of 4-aminofluorene

Info

Publication number: CN114213374B
Application number: CN202111622309.0A
Authority: CN
Inventors: 宋文志; 吴清来; 李显跃; 杨雪
Original assignee: Bangnuo Suzhou New Materials Co ltd
Current assignee: Bangnuo Suzhou New Materials Co ltd
Priority date: 2021-12-28
Filing date: 2021-12-28
Publication date: 2024-05-31
Anticipated expiration: 2041-12-28
Also published as: CN114213374A

Abstract

The invention discloses a method for synthesizing 4-aminofluorene, which comprises the steps of reacting fluorene with organic base and nitrous acid ester in a solvent to generate 4-nitrosofluorene, and then reducing nitroso into amino in the presence of a reducing agent to obtain a target product 4-aminofluorene. The invention synthesizes the 4-aminodibenzofuran through two steps of reactions in the presence of strong alkali (sodium alkoxide or potassium alkoxide), nitrous acid ester and reducing agent, has mild and simple reaction conditions, low-cost and easily obtained raw materials, few reaction byproducts and high product yield, and is favorable for realizing industrial production.

Description

Synthesis method of 4-aminofluorene

Technical Field

The invention belongs to the field of organic luminescent materials, and particularly relates to a synthesis method of 4-aminodibenzofuran.

Background

The dibenzofuran derivative is an important organic compound, can be used as an auxiliary agent of some spices, is also an important model for diesel hydrodesulfurization research, and can be used as a raw material of medicines, disinfectants, preservatives, fuels, synthetic resins and high-temperature lubricating oil. In the field of organic photoelectricity, the dibenzofuran derivative is an important organic luminescent material intermediate because of a plurality of modifiable sites and stable central nucleus. 4-aminofluorene is an important intermediate of organic luminescent material, and its structure is shown in formula 1:

In the prior art, the main method for preparing 4-aminofluorene comprises the following steps:

1. the preparation method comprises the steps of taking fluorene as a raw material, reacting butyl lithium and an azide at ultralow temperature to generate 4-azidofluorene, and carrying out high-temperature high-pressure hydrogenation to obtain 4-aminodibenzofuran. The method has a short route, but the butyl lithium is a flammable chemical raw material, and the butyl lithium needs ultralow temperature reaction at-70 ℃ and high-temperature high-pressure hydrogenation in the reduction reaction, thus belonging to the dangerous process category (US 2012/228583).

2. The preparation method comprises the steps of taking dibenzofuran as a raw material, reacting butyl lithium and borate at ultralow temperature to generate 4-dibenzofuran boric acid, and oxidizing the 4-dibenzofuran boric acid in a methanol solvent by using cuprous oxide and ammonia water through air. Cuprous oxide and ammonia water are used as reducing agents. The butyllithium used in the method is a flammable chemical raw material, and is subjected to ultralow temperature reaction at-70 ℃ and the second oxidation reaction belongs to the dangerous process category and is not suitable for industrialization. [ ANGEWANDTE CHEMIE-International Edition,2009, vol.48, #6, p.1114-1116].

3. The preparation method comprises the steps of taking dibenzofuran as a raw material, reacting butyl lithium and dibromoethane at ultralow temperature to generate 4-bromodibenzofuran, then reacting with acetamide at high temperature, and heating to remove acetyl by hydrochloric acid. The butyllithium used in the method is a relatively flammable chemical raw material, and is subjected to ultralow temperature reaction at-70 ℃, and in addition, the second step is subjected to high temperature reaction, and the relatively expensive 5, 5-dimethylcyclohexanedione is utilized, so that the method is not suitable for industrialization (US 2020/317653).

Therefore, in the prior art, the industrial synthesis method of 4-aminodibenzofuran has more defects, and the development of the preparation method of 4-aminodibenzofuran is particularly important.

Disclosure of Invention

The invention aims to provide a method for synthesizing 4-aminodibenzofuran, which is easy for industrial production.

In order to solve the technical problems, the invention provides a method for synthesizing 4-aminofluorene, which comprises the following steps: in a solvent, the dibenzofuran reacts with organic alkali and nitrous acid ester to generate 4-nitrosodibenzofuran, and then nitroso is reduced to amino in the presence of a reducing agent to obtain the target product 4-aminodibenzofuran.

As an improvement of the synthesis method of the 4-aminofluorene, the method comprises the following steps:

1) Dissolving organic alkali into a solvent to obtain an organic alkali solution;

At room temperature, adding an organic alkali solution and dibenzofuran into a reaction kettle, uniformly stirring, cooling to 0-10 ℃, adding nitrous acid ester, and reacting for 2+/-0.2 h at the temperature of 0-10 ℃; the obtained reaction liquid is subjected to post-treatment to obtain 4-nitrosofluorene;

Dibenzofuran: organic base = 1:1 to 2 (preferably 1:1 to 1.5, more preferably 1:1 to 1.2);

Dibenzofuran: nitrite = 1: a molar ratio of 1 to 1.5 (preferably 1:1 to 1.2);

2) Dissolving 4-nitrosofluorene in a solvent at room temperature, adding a reducing agent, stirring for 12+/-1 h at 50-70 ℃ (preferably 60 ℃), and performing post-treatment on the obtained reaction solution to obtain 4-aminofluorene;

4-nitrosofluorene: reducing agent = 1:1 to 50 (preferably 1:9 to 16).

As a further improvement of the method for synthesizing 4-aminofluorene of the present invention:

The organic base is sodium alkoxide or potassium alkoxide; the sodium alkoxide is sodium methoxide (preferred), sodium ethoxide and sodium tert-butoxide, and the potassium alkoxide is potassium ethoxide and potassium tert-butoxide;

the nitrite is at least one of ethyl nitrite, propyl nitrite, n-butyl nitrite (preferred), isoamyl nitrite and tert-butyl nitrite;

the reducing agent is at least one of iron powder (preferred), hydrazine hydrate, palladium/carbon, lithium aluminum hydride, sodium borohydride, tin dichloride and the like.

The solvent is at least one of methanol, ethanol, isopropanol, propanol, N-butanol, N dimethylformamide, N dimethylacetamide, dimethyl sulfoxide and tetrahydrofuran.

The post-treatment of the step 1) is as follows: extracting, filtering and drying the obtained reaction liquid to obtain 4-nitrosofluorene;

The post-treatment of the step 2) is as follows: the obtained reaction liquid is filtered, extracted and dried to obtain the 4-aminodibenzofuran.

in step 1) of the present invention: about 30-80 ml of solvent is used for each 0.1mol of organic base;

In step 2) of the present invention: about 80 to 150ml of solvent is used per 0.08mol of 4-nitrosofluorene.

In the present invention: the organic base needs to be dissolved in a solvent and then mixed with the dibenzofuran for reaction, and the nitrous acid ester needs to be added after the dibenzofuran.

The preparation method of the 4-aminofluorene comprises the following two steps of reaction:

In the presence of a solvent, sodium (potassium) alkoxide serving as organic base, nitrous acid ester and dibenzofuran react in the first step, and in the presence of a reducing agent, the product 4-nitrosodibenzofuran in the first step reacts to obtain the target product 4-aminodibenzofuran.

In the present invention, the end point of the reaction can be judged by Thin Layer Chromatography (TLC), and if the reaction is not completely ended, the reaction can be continued.

The invention provides an industrial synthesis method of 4-aminodibenzofuran, which aims to solve the problems that the experimental condition for preparing 4-aminodibenzofuran in the prior art is harsh, and the industrialization is not facilitated.

The invention uses sodium alkoxide and other active sites of activated dibenzofuran, and nitrosylation is carried out on the nitrous acid ester, the reaction condition is mild, the reaction steps are short, the product yield is high, and the invention is beneficial to realizing industrial production. In the prior similar technology, butyl lithium is used as an activation raw material, the compound is easy to generate exothermic reaction when meeting water and oxygen, a high-concentration (more than 1.0M) butyl lithium solution is easy to burn rapidly when meeting moist air, a solvent in a packaging container is generally low-boiling-point flammable and explosive liquid, once the packaging container is heated and expanded, explosion is easy to cause, meanwhile, the reaction condition is harsh (-70 ℃), the product yield is low, and the industrial production is not easy to realize.

The invention has the beneficial effects that: the invention synthesizes the 4-aminodibenzofuran through two steps of reactions in the presence of strong alkali (sodium alkoxide or potassium alkoxide), nitrous acid ester and reducing agent, has mild and simple reaction conditions, low-cost and easily obtained raw materials, few reaction byproducts and high product yield, and is favorable for realizing industrial production.

Detailed Description

The invention will be further described with reference to the following specific examples, but the scope of the invention is not limited thereto:

the correctness of the results obtained by each step of each example below was characterized by NMR.

In the following case steps, which are not explicitly stated, the reaction is carried out at room temperature under normal atmospheric pressure.

Example 1, a method for synthesizing 4-aminofluorene, the following steps were performed in sequence:

(1) 50mL of ethanol and 0.1mol (about 5.67 g) of sodium methoxide were added to a glass reaction flask, then 0.1mol (about 16.8 g) of dibenzofuran was added and stirred and cooled to 0℃and then 0.12mol (about 12.63 g) of n-butyl nitrite was added, and stirring was continued for 2 hours at a temperature of 0℃and the sampling point plate was determined to have reached the end of the reaction.

The resulting reaction solution was extracted with methylene chloride (100 mL) and water (200 mL), and the methylene chloride phase was taken and subjected to suction filtration with celite (about 20 g), and the filtrate was dried by spin-drying to obtain 15.8g (0.081 mol) of 4-nitrosodibenzofuran in 81% yield.

(2) 0.081Mol (about 15.8 g) of 4-nitrosofluorene was placed in a glass reaction flask, 100mL of acetic acid and 0.8mol (about 45 g) of iron powder were added, the temperature was raised to 60℃for reaction for 12 hours, and a sampling point plate was used to confirm that the end point of the reaction had been reached.

The resulting reaction solution was filtered using celite (about 20 g), the filtrate was extracted with ethyl acetate (200 mL) and water (3 x 300 mL), the lower ethyl acetate phase was removed, and the solvent (i.e., ethyl acetate) was removed to obtain 14.36g (0.078 mol) of the product 4-aminodibenzofuran in 96.2% yield.

Example 2, a method for synthesizing 4-aminofluorene, the following steps were performed in sequence:

(1) 100mL of ethanol and 0.24mol (about 13 g) of sodium methoxide were introduced into a glass reaction flask, followed by 0.2mol

(About 33.6 g) of dibenzofuran was stirred and cooled to 0deg.C, then 0.21mol of n-butyl nitrite was added, and the mixture was stirred at a temperature of 0deg.C for 2 hours, and the sampling point plate was used to determine that the end point of the reaction had been reached.

The obtained reaction solution was extracted with methylene chloride and water, and the methylene chloride phase was filtered with celite, and the filtrate was dried by spin to obtain 33.3g (0.17 mol) of 4-nitrosofluorene in 85% yield.

(2) 0.17Mol (about 33.3 g) of 4-nitrosofluorene was placed in a glass reaction flask, 200mL of acetic acid and 1.85mol of iron powder were added, the temperature was raised to 60℃for reaction for 12 hours, and the sampling point plate determined that the reaction end point had been reached.

The obtained reaction solution was filtered using celite, the filtrate was extracted with ethyl acetate and water, the lower ethyl acetate phase was taken out, and the solvent was removed to obtain 30g (0.16 mol) of 4-aminofluorene product in 94.1% yield.

Example 3, a method for synthesizing 4-aminofluorene, the following steps were performed in sequence:

(1) 1000mL of ethanol and 2mol of sodium methoxide are added into a glass reaction bottle, 2mol of dibenzofuran are added, the temperature is reduced to 0 ℃, 2.34mol of n-butyl nitrite is added, the temperature is kept at 0 ℃ and the stirring is carried out for 2 hours, and a sampling point plate determines that the reaction end point is reached.

The reaction mixture was extracted with methylene chloride and water, and the methylene chloride phase was filtered through suction with celite, and the filtrate was dried by spin to obtain 338.5g (1.72 mol) of 4-nitrosofluorene in 86% yield.

(2) 1.72Mol of 4-nitrosofluorene was placed in a glass reaction flask, 2000mL of acetic acid and 27mol of iron powder were added, the temperature was raised to 60℃for reaction for 12 hours, and the sampling point plate determined that the end point of the reaction had been reached.

The obtained reaction solution was filtered using celite, the filtrate was extracted with ethyl acetate and water, the lower ethyl acetate phase was taken out, and the solvent was removed to obtain 308g (1.68 mol) of 4-aminodibenzofuran as a product in 97.6% yield.

Example 4, a method for synthesizing 4-aminofluorene, the following steps were performed in sequence:

(1) 50mL of ethanol and 0.11mol (about 7.5 g) of sodium ethoxide were added to a glass reaction flask, 0.1mol of dibenzofuran was added and stirred and cooled to 0℃and then 1.2mol of n-butyl nitrite was added, and stirring was continued for 2 hours at a temperature of (0 ℃) and the sampling spot plate was used to determine that the end point of the reaction was reached.

The obtained reaction solution was extracted with methylene chloride and water, and the methylene chloride phase was filtered with celite, and the filtrate was dried by spin to obtain 12.5g (0.062 mol) of 4-nitrosofluorene in 62% yield.

(2) 0.062Mol of 4-nitrosofluorene is placed in a glass reaction flask, 90mL of acetic acid and 0.61mol of iron powder are added, the temperature is raised to 60 ℃ for maintaining the reaction for 12 hours, and a sampling point plate determines that the reaction end point is reached.

The obtained reaction solution was filtered using celite, the filtrate was extracted with ethyl acetate and water, the lower ethyl acetate phase was taken out, and the solvent was removed to obtain 10.66g (0.058 mol) of 4-aminofluorene product in 93.5% yield.

Example 5, a method for synthesizing 4-aminodibenzofuran, the following steps are sequentially carried out:

(1) 50mL of ethanol and 0.10mol of sodium methoxide are added into a glass reaction bottle, 0.1mol of dibenzofuran is added, the temperature is reduced to 0 ℃, 0.12mol of ethyl nitrite is added, the temperature is kept at 0 ℃ and the stirring is carried out for 2 hours, and a sampling point plate determines that the reaction end point is reached.

The obtained reaction solution was extracted with methylene chloride and water, and the methylene chloride phase was filtered with celite, and the filtrate was dried by spin to obtain 7.69g (0.039 mol) of 4-nitrosofluorene in 39% yield.

(2) 0.039Mol (about 7.69 g) of 4-nitrosofluorene was placed in a glass reaction flask, 50mL of acetic acid and 0.4mol of iron powder were added, the temperature was raised to 60℃for reaction for 12 hours, and the sampling point plate determined that the end point of the reaction had been reached.

The obtained reaction solution was filtered using celite, the filtrate was extracted with ethyl acetate and water, the lower ethyl acetate phase was taken out, and the solvent was removed to obtain 6.7g (0.037 mol) of 4-aminofluorene product in 94.87% yield.

Example 6, a method for synthesizing 4-aminofluorene, the following steps were performed in sequence:

(1) 50mL of ethanol and 0.1mol of sodium methoxide are added into a glass reaction bottle, 0.1mol of dibenzofuran is added, the temperature is reduced to 0 ℃, 0.12mol of n-butyl nitrite is added, the temperature is kept (0 ℃) and stirring is carried out for 2 hours, and a sampling point plate determines that the reaction end point is reached.

The obtained reaction solution was extracted with methylene chloride and water, and the methylene chloride phase was filtered with celite, and the filtrate was dried by spin to obtain 16.0g (0.082 mol) of 4-nitrosofluorene in 82% yield.

(2) 0.08Mol of 4-nitrosofluorene was placed in a glass reaction flask, 100mL of acetic acid and 0.8mol (about 153 g) of tin dichloride were added, the temperature was raised to 60℃for reaction for 12 hours, and the sampling point plate determined that the end point of the reaction had been reached.

The obtained reaction solution was filtered using celite, the filtrate was extracted with ethyl acetate and water, the lower ethyl acetate phase was taken out, and the solvent was removed to obtain 10.4g (0.057 mol) of 4-aminofluorene as a product in 71.25% yield.

Comparative example 1, the "sodium methoxide" in step 1) of example 1 was changed to the organic base as described in Table 1 below, the molar amount was maintained constant, still 0.1mol, and the remainder was identical to step 1) of example 1. The corresponding yields of 4-nitrosofluorene are shown in Table 1 below.

TABLE 1

Comparative example 2, changing the "sodium methoxide" in step 1) of example 1 to butyllithium, the molar amount remained unchanged, still 0.1mol, the remainder being identical to step 1) of example 1. This scheme does not produce 4-nitrosofluorene.

Comparative example 3, the "n-butyl nitrite" in step 1) of example 1 was changed to the nitrite described in Table 2 below, the molar amount remained unchanged, still 0.12mol, and the remainder was identical to step 1) of example 1. The corresponding yields of 4-nitrosofluorene are shown in Table 2 below.

TABLE 2

Comparative example 4, in which "n-butyl nitrite" in step 1) of example 1 was changed to boric acid ester, the molar amount was kept unchanged, still 0.12mol, and the rest was equivalent to step 1) of example 1. This scheme does not produce 4-nitrosofluorene.

Comparative example 5 the iron powder of example 1, step 2) was changed to the reducing agent described in table 3 below, the molar amount was kept constant, still 0.8mol, and the rest was identical to step 2) of example 1. The corresponding yields of 4-aminodibenzofuran are set forth in Table 3 below.

Comparative example 6, changing the iron powder of example 1, step 2) to cuprous oxide, the molar amount remained unchanged, still 0.8mol, the remainder being identical to step 2) of example 1. The yields of the corresponding 4-aminodibenzofurans are set forth in Table 3 below.

Comparative example 7, in which the "iron powder" in step 2) of example 1 was changed to "consisting of cuprous oxide and aqueous ammonia in a molar ratio of 2.5:1", the molar amount was kept unchanged, and the remainder was identical to step 2) of example 1. The yields of the corresponding 4-aminodibenzofurans are set forth in Table 3 below.

TABLE 3 Table 3

Finally, it should also be noted that the above list is merely a few specific embodiments of the present invention. Obviously, the invention is not limited to the above embodiments, but many variations are possible. All modifications directly derived or suggested to one skilled in the art from the present disclosure should be considered as being within the scope of the present invention.

Claims

The synthesis method of the 4-aminodibenzofuran is characterized by comprising the following steps: in a solvent, the dibenzofuran reacts with organic alkali and nitrous acid ester to generate 4-nitrosodibenzofuran, and then nitroso is reduced to amino in the presence of a reducing agent to obtain the target product 4-aminodibenzofuran.
2. The method for synthesizing 4-aminofluorene according to claim 1, characterized by comprising the steps of:

1) Dissolving organic alkali into a solvent to obtain an organic alkali solution;

Adding an organic alkali solution and dibenzofuran into a reaction kettle, uniformly stirring, cooling to 0-10 ℃, adding nitrous acid ester, and carrying out heat preservation reaction for 2+/-0.2 h; the obtained reaction liquid is subjected to post-treatment to obtain 4-nitrosofluorene;

dibenzofuran: organic base = 1:1 to 2 molar ratio;

Dibenzofuran: nitrite = 1:1 to 1.5 molar ratio;

2) Dissolving 4-nitrosofluorene in a solvent, adding a reducing agent, stirring at 50-70 ℃ for 12+/-1 h, and performing aftertreatment on the obtained reaction solution to obtain 4-aminofluorene;

4-nitrosofluorene: reducing agent = 1:1 to 50 molar ratio.
3. The method for synthesizing 4-aminodibenzofuran according to claim 2, characterized in that:

The organic base is sodium alkoxide or potassium alkoxide.
4. A method of synthesizing 4-aminodibenzofuran according to claim 3, characterized in that:

the sodium alkoxide is sodium methoxide, sodium ethoxide and sodium tert-butoxide, and the potassium alkoxide is potassium ethoxide and potassium tert-butoxide.
5. The method for synthesizing 4-aminofluorene according to any one of claims 2 to 4, characterized in that: the nitrite is at least one of ethyl nitrite, propyl nitrite, n-butyl nitrite, isoamyl nitrite and tert-butyl nitrite.
6. The method for synthesizing 4-aminofluorene according to claim 5, wherein: the reducing agent is at least one of iron powder, hydrazine hydrate, palladium/carbon, lithium aluminum hydride, sodium borohydride and tin dichloride.
7. The method for synthesizing 4-aminofluorene according to claim 6, wherein:

The solvent is at least one of methanol, ethanol, isopropanol, propanol, N-butanol, N dimethylformamide, N dimethylacetamide, dimethyl sulfoxide and tetrahydrofuran.
8. The method for synthesizing 4-aminofluorene according to claim 7, wherein:

The post-treatment of the step 1) is as follows: extracting, filtering and drying the obtained reaction liquid to obtain 4-nitrosofluorene;

The post-treatment of the step 2) is as follows: the obtained reaction liquid is filtered, extracted and dried to obtain the 4-aminodibenzofuran.