A method for reducing nitrosobenzene compounds

Abstract

The present invention provides a method for reducing nitrosobenzene compounds, which belongs to the field of organic synthesis. The method for reducing nitrosobenzene compounds provided by the present invention comprises the following steps: compound 1 reacts in the presence of a solvent and a reducing agent to obtain compound 2, wherein the reducing agent is hydrazine hydrate. The method for reducing nitrosobenzene compounds provided by the present invention can obtain aniline compounds in high yield under mild reaction conditions without the need for an additional catalyst.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a method for reducing nitrosobenzene compounds. Background Art

[0002] Aniline compounds are one of the important organic chemical raw materials and are widely used in industries such as fuel, medicine, pesticides, explosives, fragrances, and rubber vulcanization accelerators.

[0003] In the prior art, the preparation methods of aniline compounds mainly include iron powder reduction method, phenol amination method and nitrobenzene catalytic hydrogenation method.

[0004] However, the above three traditional methods all have certain disadvantages, such as: the iron powder reduction method has high energy consumption, serious pollution and difficulty in product separation; the phenol amination method and nitrobenzene catalytic hydrogenation method, although simple in process, not only require the use of relatively expensive catalysts, but also require high temperature and high pressure reaction conditions. Summary of the invention

[0005] The present invention is made to solve the above problems, and aims to provide a method for reducing nitrosobenzene compounds with high yield, mild reaction conditions and environmental friendliness.

[0006] The present invention provides a method for reducing nitrosobenzene compounds, which is used to convert all nitroso groups connected to aromatic rings into amino groups, and has the following characteristics:

[0007]

[0008] In the above formula, compound 1 is Any of

[0009] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 are independently selected from any one of H, alkyl, alkoxy, hydroxy, amino, N-alkylamino, and N,N-dialkylamino,

[0010] X1 is selected from Any of

[0011] X2 is selected from

[0012] X3

[0013] 1≤m≤6,0≤n≤5,0≤p≤5,0≤q≤5,0≤z,0≤x,0≤y,

[0014] z,x,y,m,n,p,q are all integers,

[0015] The steps include:

[0016] Compound 1 reacts in the presence of a solvent and a reducing agent to obtain compound 2.

[0017] Wherein, the reducing agent is hydrazine hydrate.

[0018] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: wherein the R groups substituted on the same benzene ring may be the same or different, such as In the above, the (6-m) R1 groups are selected independently and can be the same group or different groups.

[0019] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: when x, y, z=0, that is, the corresponding group does not exist, two adjacent groups are directly adjacent.

[0020] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following feature: wherein the solvent is an alkaline aqueous solution.

[0021] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: wherein the concentration of hydroxide in the alkaline aqueous solution is 0.25 mmol / mL-1.5 mmol / mL, and preferably, the alkaline aqueous solution is 1 wt%-5 wt% of sodium hydroxide aqueous solution.

[0022] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: wherein the molar ratio of hydrazine hydrate to the nitroso group of compound 1 is (1-5):1.

[0023] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: wherein the mass volume ratio of compound 1 to the solvent is 0.5 g / mL-0.01 g / mL.

[0024] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: during the reaction, an additive is added to the reaction system, and the additive is any one or more of n-hexane, n-heptane, n-octane, petroleum ether, ethyl ether or tert-butyl methyl ether.

[0025] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: wherein the volume ratio of the additive to the solvent is (0.01-0.1):1.

[0026] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: wherein the reaction time is 4h-24h, preferably, the reaction time is 6h-20h.

[0027] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: comprising the following steps:

[0028] Compound 1 and a solvent are mixed, hydrazine hydrate is added at a temperature controlled at 0°C-20°C, and the reaction is carried out at a temperature controlled at 0°C-30°C. After the reaction is completed, the compound 2 is purified and dried to obtain compound 2. Preferably, when compound 2 is solid at room temperature, the purification method includes: controlling the temperature of the reaction system at 0°C-15°C, filtering, and obtaining compound 2.

[0029] The method for reducing nitrosobenzene compounds provided by the present invention may also have the following characteristics: comprising the following steps:

[0030] Compound 1, solvent and additives are mixed, hydrazine hydrate is added at a temperature controlled at 0°C-20°C, and the reaction is carried out at a temperature controlled at 0°C-30°C. After the reaction is completed, the compound 2 is purified, filtered and dried to obtain compound 2. Preferably, when compound 2 is solid at room temperature, the purification method includes: controlling the temperature of the reaction system at 0°C-15°C, filtering, and obtaining compound 2.

[0031] In the method for reducing nitrosobenzene compounds provided by the present invention, the method may also have the following characteristics: Compound 1 is selected from any one of the following compounds:

[0032]

[0033] Functions and Effects of the Invention

[0034] According to the method for reducing nitrosobenzene compounds involved in the present invention, since hydrazine hydrate is used as a reducing agent, the present invention can prepare aniline compounds in high yield under mild reaction conditions without the need for additional catalysts. DETAILED DESCRIPTION

[0035] In order to make the technical means, creative features, objectives and effects achieved by the present invention easier to understand, the present invention is described in detail below in conjunction with embodiments.

[0036] In the following examples, the preparation method of compound 1a is carried out by referring to the following reaction steps:

[0037] 10 g of 2-methylphenol (Compound 1a, 92.5 mmol, 1.0 eq) was dissolved in 50 mL of ethanol, the reaction system was temperature controlled at 5°C-10°C, 50 mL of 36 wt%-38 wt% hydrochloric acid aqueous solution and 20 mL of 0.38 g / mL sodium nitrite aqueous solution (110 mmol, 1.2 eq) were added dropwise in sequence, and the mixture was kept at 5°C-10°C for 7 h to obtain a reaction solution;

[0038] Pour 400 mL of 20° C. water into the reaction solution, keep warm and stir for 1 h, filter, take out the solid, and dry to obtain 10.28 g of 4-nitroso-2-methylphenol with a yield of 81.0% and a purity of 98.7%.

[0039] In the following examples, unless otherwise specified, all reaction raw materials are commercially available.

[0040] In the following examples, unless otherwise specified, the hydrazine hydrate used in the following examples is hydrazine hydrate with a mass fraction of 85%.

[0041] <Example 1>

[0042] Preparation of compound 2a

[0043] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0044]

[0045] The steps include:

[0046] Add 1L 3wt% sodium hydroxide aqueous solution and 100g compound 1a (0.729mol, 1.0eq) to the reaction vessel, cool to 0-5°C, add 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) dropwise, and control the temperature at 0-5°C with stirring to react for 16h. Filter, wash the filter cake with water, and dry to obtain 62.9g compound 2a as a black solid with a yield of 70.1% and a liquid phase purity of 99.6%.

[0047] <Example 2>

[0048] Preparation of compound 2a

[0049] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0050]

[0051] The steps include:

[0052] Add 1L 3wt% sodium hydroxide aqueous solution and 100g compound 1a (0.729mol, 1.0eq) to the reaction vessel, cool to 0-5°C, add 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) dropwise, and control the temperature at 25-30°C to react with stirring for 16h, filter, wash the filter cake with water, and dry to obtain 51.5g compound 2a as a black solid with a yield of 57.4% and a liquid phase purity of 94.2%.

[0053] <Example 3>

[0054] Preparation of compound 2a

[0055] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0056]

[0057] The steps include:

[0058] 1L tetrahydrofuran and 100g compound 1a (0.729mol, 1.0eq) were added to the reaction vessel, and the temperature was lowered to 0-5°C. 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) was added dropwise, and the temperature was controlled at 0-5°C with stirring for 16h. The pH value was adjusted to 7 with 1mol / L hydrochloric acid aqueous solution, and extracted with dichloromethane three times. The organic phases were combined, concentrated under reduced pressure, and subjected to column chromatography to obtain 59.2g of compound 2a as a black solid with a yield of 65.9% and a liquid phase purity of 96.0%.

[0059] <Example 4>

[0060] Preparation of compound 2a

[0061] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0062]

[0063] The steps include:

[0064] Add 1L 3wt% aqueous sodium hydroxide solution, 100g compound 1a (0.729mol, 1.0eq) and 50mL n-heptane to the reaction vessel, cool to 0-5°C, add 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) dropwise, and control the temperature at 25-30°C with stirring to react for 6h, cool to 5°C, filter, wash the filter cake with water, and dry to obtain 78.2g compound 2a as a black solid with a yield of 87.1% and a liquid phase purity of 98.0%.

[0065] <Example 5>

[0066] Preparation of compound 2a

[0067] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0068]

[0069] The steps include:

[0070] Add 1L 3wt% aqueous sodium hydroxide solution, 100g compound 1a (0.729mol, 1.0eq) and 50mL tert-butyl methyl ether to the reaction vessel, cool to 0-5°C, add 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) dropwise, and control the temperature at 25-30°C with stirring to react for 6h, cool to 5°C, filter, wash the filter cake with water, and dry to obtain 72.1g compound 2a as a black solid with a yield of 80.3% and a liquid phase purity of 98.2%.

[0071] <Example 6>

[0072] Preparation of compound 2a

[0073] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0074]

[0075] The steps include:

[0076] 1L 3wt% aqueous sodium hydroxide solution, 100g compound 1a (0.729mol, 1.0eq) and 50mL N,N-dimethylformamide were added to the reaction vessel, and the temperature was lowered to 0-5°C. 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) was added dropwise, and the temperature was controlled to react at 25-30°C with stirring for 6h. The temperature was lowered to 5°C, filtered, the filter cake was washed with water, and dried to obtain 46.7g compound 2a as a black solid with a yield of 52.0% and a liquid phase purity of 93.1%. Only trace amounts of product were present in the filtrate.

[0077] <Example 7>

[0078] Preparation of compound 2a

[0079] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0080]

[0081] The steps include:

[0082] 1L 3wt% aqueous sodium hydroxide solution, 100g compound 1a (0.729mol, 1.0eq) and 50mL ethanol were added to the reaction vessel, cooled to 0-5°C, 68.9g hydrazine hydrate (85wt%, 1.17mol, 1.6eq) was added dropwise, and the temperature was controlled at 25-30°C with stirring for 6h, cooled to 5°C, no solid was precipitated, and the pH value was adjusted to 7 with 1mol / L aqueous hydrochloric acid solution. The mixture was extracted with dichloromethane three times, the organic phases were combined, concentrated under reduced pressure, and subjected to column chromatography to obtain 47.5g compound 2a as a black solid with a yield of 52.9% and a liquid purity of 95.2%.

[0083] <Example 8>

[0084] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0085]

[0086] The steps include:

[0087] 100 mL of 3 wt% aqueous sodium hydroxide solution and 10 g of compound 1a (72.9 mmol, 1.0 eq) were added to the reaction vessel, the temperature was raised to 90°C, 50.8 g of sodium dithionite (291.6 mmol, 4.0 eq) was added, the temperature was controlled at 85-90°C and stirred for 16 h. HPLC detection showed that there were various impurities in the reaction system, and compound 2a was only 26.7%.

[0088] <Example 9>

[0089] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0090]

[0091] The steps include:

[0092] 100 mL of 3 wt % aqueous sodium hydroxide solution and 10 g of compound 1a (72.9 mmol, 1.0 eq) were added to the reaction vessel, and the temperature was controlled at 15-20 ° C. 99.5 g of 20 wt % aqueous ammonium sulfide solution (291.6 mmol, 4.0 eq) was added, and the temperature was controlled at 15-20 ° C. and stirred for 16 h. HPLC detection showed that there were various impurities in the reaction system, and compound 2a was only 53.4%.

[0093] <Example 10>

[0094] This embodiment provides a method for preparing compound 2a, and the reaction formula is as follows:

[0095]

[0096] The steps include:

[0097] 100 mL of methanol, 10 g of compound 1a (72.9 mmol, 1.0 eq) and 1 g of Raney Ni were added to the reaction container, hydrogen was replaced, and the reaction was stirred under hydrogen atmosphere at room temperature for 12 h. HPLC detection showed that various impurities were present in the reaction system, and compound 2a accounted for 76.1%.

[0098] <Example 11>

[0099] Preparation of compound 2e

[0100] This example provides a method for preparing compound 2e, and the reaction formula is as follows:

[0101]

[0102] The steps include:

[0103] Add 100 mL of 3 wt% aqueous sodium hydroxide solution, 10 g of compound 1e (81.2 mmol, 1.0 eq) and 50 mL of n-heptane to the reaction vessel, cool to 0-5°C, add 7.64 g of hydrazine hydrate (85 wt%, 129.9 mmol, 1.6 eq) dropwise, and control the temperature at 25-30°C with stirring to react for 6 h. Cool to 5°C, filter, wash the filter cake with water, and dry to obtain 8.0 g of compound 2e as a black solid with a yield of 90.3% and a liquid phase purity of 97.5%.

[0104] <Example 12>

[0105] Preparation of compound 2v

[0106] This example provides a method for preparing compound 2v, and the reaction formula is as follows:

[0107]

[0108] The steps include:

[0109] 100 mL of 3 wt% aqueous sodium hydroxide solution, 10 g of compound 1v (43.8 mmol, 1.0 eq) and 50 mL of n-heptane were added to the reaction vessel, the temperature was lowered to 0-5°C, 10.3 g of hydrazine hydrate (85 wt%, 175.2 mmol, 4.0 eq) was added dropwise, and the temperature was controlled to react at 25-30°C with stirring for 6 h. The temperature was lowered to 5°C, filtered, the filter cake was washed with water, and dried to obtain 7.9 g of compound 2v as a dark yellow solid with a yield of 90.0% and a liquid phase purity of 96.1%.

[0110] Functions and Effects of the Embodiments

[0111] According to the method for reducing nitrosobenzene compounds involved in the above embodiment, since hydrazine hydrate is used as a reducing agent, the present invention can prepare aniline compounds in high yield under mild reaction conditions without the need for additional catalysts.

[0112] Furthermore, since hydrazine hydrate is used as the reducing agent in the above embodiment, the by-product of the reaction is nitrogen, which greatly simplifies the post-processing process of the entire reaction, reduces environmental pollution, and is conducive to industrial production.

[0113] According to the method for reducing nitrosobenzene compounds involved in the above embodiment, because water is selected as the solvent, when the target product is solid at room temperature, the product can be separated by crystallization by cooling, which greatly improves the production efficiency.

[0114] According to the method for reducing nitrosobenzene compounds involved in the above embodiment, since n-heptane or tert-butyl methyl ether can be used as an additive in the reaction, the reaction can be carried out at room temperature without generating a large amount of impurities, and the reaction time can be further shortened.

[0115] The above-mentioned embodiments are preferred examples of the present invention and are not intended to limit the protection scope of the present invention.

Claims

1. A method for reducing nitrosobenzene compounds, for converting all nitroso groups connected to aromatic rings into amino groups, characterized in that: The reaction formula is: In the above formula, compound 1 is selected from any one of the following compounds: The steps include: Compound 1 reacts in the presence of a solvent and a reducing agent to obtain compound 2. Wherein, the reducing agent is hydrazine hydrate, The solvent is an alkaline aqueous solution, The concentration of hydroxide in the alkaline aqueous solution is 0.25 mmol / mL-1.5 mmol / mL.

2. The method for reducing nitrosobenzene compounds according to claim 1, characterized in that: in, The molar ratio of the hydrazine hydrate to the nitroso group of the compound 1 is (1-5):

1.

3. The method for reducing nitrosobenzene compounds according to claim 1, characterized in that: in, The mass volume ratio of the compound 1 to the solvent is 0.5 g / mL-0.01 g / mL.

4. The method for reducing nitrosobenzene compounds according to claim 1, characterized in that: in, During the reaction, additives were added to the reaction system. The additive is any one or more of n-hexane, n-heptane, n-octane, petroleum ether, ethyl ether or tert-butyl methyl ether.

5. The method for reducing nitrosobenzene compounds according to claim 1, characterized in that: in, The volume ratio of the additive to the solvent is (0.01-0.1):

1.

6. The method for reducing nitrosobenzene compounds according to claim 1, characterized in that: in, The reaction time is 4h-24h.

7. The method for reducing nitrosobenzene compounds according to claim 1, characterized in that: The steps include: Compound 1 and a solvent are mixed, hydrazine hydrate is added at a temperature controlled at 0°C-20°C, and the reaction is carried out at a temperature controlled at 0°C-30°C. After the reaction is completed, the compound 2 is purified.

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