Preparation process of oximido acetanilide

Abstract

The invention discloses a preparation process of oximido acetanilide, which comprises the following specific steps: (1) dissolving hydroxylamine sulfate or hydroxylamine hydrochloride in water, neutralizing with alkali, adding methyl glyoxylate, and heating for reaction to prepare 2-oximido methyl acetate; and (2) reacting 2-oximido methyl acetate with aniline under the action of a catalyst to generate oximido acetanilide. In the reaction process, high-concentration sodium sulfate is not adopted as a solution, a large amount of salt-containing wastewater is not generated, the environmental protection property is high, the yield is good, and a new method is provided for production of oximido acetanilide.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a preparation process of oxime acetanilide. Background Art

[0002] Oxime acetanilide is an intermediate for the preparation of indigo carmine, which can be used for dyes such as Yellow 54, Yellow 64, and Quinaldine. It is also in demand in the pharmaceutical and analytical reagent markets and has a good prospect.

[0003] There are many methods for synthesizing oxime acetanilide, and most of them are produced in the following way in industry: hydroxylamine sulfate (or hydroxylamine hydrochloride) is added to a sodium sulfate solution with a concentration of 15-35%, and then trichloroacetaldehyde and aniline are added, and the product is obtained by cooling and filtering after heating to boiling. This method has a fierce reaction, a large fluctuation in yield, and a large amount of highly concentrated sodium sulfate wastewater is generated, such as patents CN109111401A, CN108484437A, CN108017570A, etc. Summary of the invention

[0004] In view of the above problems existing in the prior art, the present invention provides a preparation process of oxime acetanilide.

[0005] The technical solution of the present invention is as follows:

[0006] The present invention discloses a preparation process of oxime acetanilide, which is carried out according to the following synthesis route:

[0007]

[0008] The specific steps are:

[0009] (1) Hydroxylamine sulfate or hydroxylamine hydrochloride is dissolved in water, neutralized with alkali, and then methyl glyoxylate is added and the temperature is raised to react to obtain methyl 2-oxime acetate;

[0010] (2) Methyl 2-hydroxyethyl acetate reacts with aniline in the presence of a catalyst to generate hydroxyethyl anilide.

[0011] In one embodiment of the present invention, in step (1), the molar ratio of methyl glyoxylate to hydroxylamine sulfate or hydroxylamine hydrochloride is 1:(1-3).

[0012] Preferably, the molar ratio of methyl glyoxylate to hydroxylamine sulfate or hydroxylamine hydrochloride is 1:(1.05-2).

[0013] In one embodiment of the present invention, in step (1), the temperature is raised to 40-90° C. and the reaction is carried out for 3-10 hours.

[0014] Preferably, the reaction temperature is 50-80°C.

[0015] In one embodiment of the present invention, in step (1), after the reaction is completed, the temperature is cooled to room temperature, and then the upper layer is separated and washed with water to obtain the target product.

[0016] In one embodiment of the present invention, in step (1), the base is neutralized to pH=7.

[0017] In one embodiment of the present invention, in step (2), the molar ratio of methyl 2-hydroxyiminoacetate, aniline and catalyst is (1-2):1:(0.01-0.3).

[0018] Preferably, the molar ratio of methyl 2-oxime acetate, aniline and catalyst is (1.1-1.5):1:(0.05-0.2).

[0019] In one embodiment of the present invention, in step (2), the catalyst is one or more of KOH, NaOH, NaOCH3, MgO, CaO, and NaAC.

[0020] Preferably, the catalyst is one of KOH, NaOH, NaAC, and NaOCH3.

[0021] In one embodiment of the present invention, in step (2), the reaction temperature is 50-100° C., and the reaction time is 3-15 h.

[0022] Preferably, the reaction temperature is 60-90°C.

[0023] In one embodiment of the present invention, in step (2), methanol is evaporated during the reaction, and water is added after the reaction is completed. The mixture is cooled to room temperature, filtered, washed with water, and dried to obtain the target product.

[0024] Since the reaction temperature is higher than the boiling point of methanol and methanol is volatile, the methanol generated during the reaction will also evaporate as the reaction proceeds.

[0025] The beneficial technical effects of the present invention are:

[0026] In the reaction process of the invention, high-concentration sodium sulfate is not used as a solution, a large amount of salt-containing wastewater will not be generated, the invention has high environmental protection and good yield, and provides a new method for the production of oxime acetanilide. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of the synthetic route of the present invention;

[0028] Figure 2 is the liquid phase spectrum of 2-oximidoacetic acid methyl ester in Example 1;

[0029] Figure 3 It is the liquid phase spectrum of oxime acetanilide in Example 1. DETAILED DESCRIPTION

[0030] The present invention is described in detail below in conjunction with the accompanying drawings and embodiments.

[0031] Example 1

[0032] Add 75g of water to the flask, add 19g of hydroxylamine hydrochloride, neutralize with soda ash to pH = 7.0, add 22.56g of methyl glyoxylate, heat to 70°C and keep warm for 4h. After the reaction is completed, stir and cool to room temperature, separate the upper layer, wash with water, and obtain 24.3g of methyl 2-oxime acetate; the yield is 92.0% (based on methyl glyoxylate), the purity is 98.47%, and the liquid phase spectrum is as follows Figure 2 shown.

[0033] 46 g of aniline, 54.1 g of 2-oxime acetic acid methyl ester, and 2.1 g of anhydrous sodium hydroxide were added to a flask, and the temperature was raised to 65°C for 10 h. After the reaction, 175 g of 75°C hot water was added, stirred for 0.5 h, cooled to room temperature, filtered, washed with water, and dried to obtain 79.3 g of oxime acetanilide; the yield was 97.8% (based on aniline), the purity was 99.1%, and the liquid phase spectrum was as follows: Figure 3 shown.

[0034] Example 2

[0035] Add 75g of water to the flask, add 37.8g of hydroxylamine sulfate (MW164), neutralize with soda ash to pH = 7.0, add 22.56g of methyl glyoxylate, heat to 60°C and react for 5h. After the reaction is completed, stir and cool to room temperature, separate the upper layer, wash with water, and obtain 25.0g of methyl 2-oxime acetate; yield 94.7%, purity 98.1%.

[0036] 46g aniline, 56.2g 2-oxime acetic acid methyl ester, and 4.2g anhydrous sodium acetate were added to a flask, and the temperature was raised to 75°C for 9h. After the reaction, 175g 75°C hot water was added, stirred for 0.5h, cooled to room temperature, filtered, washed with water, and dried to obtain 77.49g oxime acetanilide; the yield was 95.5%, and the purity was 98.87%.

[0037] Example 3

[0038] Add 75g of water and 30.8g of hydroxylamine sulfate to the flask, neutralize with soda ash to pH = 7.0, add 22.56g of methyl glyoxylate, heat to 65°C and react for 7h. After the reaction is completed, stir and cool to room temperature, separate the upper layer, wash with water, and obtain 24.5g of methyl 2-oxime acetate; the yield is 92.8%, and the purity is 98.15%.

[0039] 43.5 g of aniline, 54.1 g of 2-hydroxymethyl acetate and 1.7 g of potassium hydroxide were added to a flask, and the temperature was raised to 75°C for 8.5 h. After the reaction, 175 g of 75°C hot water was added, stirred for 0.5 h, cooled to room temperature, filtered, washed with water, and dried to obtain 73.1 g of hydroxymethyl acetanilide; the yield was 95.3% and the purity was 99.07%.

[0040] Example 4

[0041] Add 75g of water and 35.8g of hydroxylamine hydrochloride to the flask, neutralize with soda ash to pH = 7.0, add 23.4g of methyl glyoxylate, heat to 70°C and react for 4h. After the reaction is completed, stir and cool to room temperature, separate the upper layer, wash with water, and obtain 25.8g of methyl 2-oxime acetate; the yield is 94.2%, and the purity is 98.38%.

[0042] Add 46g of aniline, 58.4g of 2-hydroxymethyl acetate, and 3.0g of sodium hydroxide into a flask, heat to 85°C and keep warm for 8h. After the reaction, add 175g of 75°C hot water, stir for 0.5h, cool to room temperature, filter and wash with water to obtain 77.08g of hydroxymethyl acetanilide; yield 95.0%, purity 99.13%.

[0043] Example 5

[0044] Add 75g of water and 35.8g of hydroxylamine hydrochloride to the flask, neutralize with soda ash to pH = 7.0, add 23.4g of methyl glyoxylate, heat to 75°C and react for 4h. After the reaction is completed, stir and cool to room temperature, separate the upper layer, wash with water, and dry to obtain 26.4g of methyl 2-oxime acetate; the yield is 96.4% and the purity is 98.18%.

[0045] 46 g of aniline, 57.4 g of methyl 2-oxime acetate, and 2.16 g of sodium methoxide were added to a flask, and the temperature was raised to 90°C for reaction for 5 h. After the reaction, 175 g of 75°C hot water was added, stirred for 0.5 h, cooled to room temperature, filtered, washed with water, and dried to obtain 78.0 g of oxime acetanilide; the yield was 96.2%, and the purity was 99.2%.

[0046] The embodiments provided above are not intended to limit the scope of the present invention, and the steps described are not intended to limit the execution order thereof. Those skilled in the art may make obvious improvements to the present invention in combination with existing common knowledge, which also fall within the scope of protection defined by the claims of the present invention.

Claims

1. A process for preparing oxime acetanilide, characterized in that: Proceed according to the following synthetic route: The specific steps are: (1) Hydroxylamine sulfate or hydroxylamine hydrochloride is dissolved in water, neutralized with alkali, and then methyl glyoxylate is added and the temperature is raised to react to obtain methyl 2-oxime acetate; (2) Methyl 2-oxime acetate reacts with aniline in the presence of a catalyst to generate oxime acetanilide.

2. The preparation process according to claim 1, characterized in that: In step (1), the molar ratio of methyl glyoxylate to hydroxylamine sulfate or hydroxylamine hydrochloride is 1:(1-3).

3. The preparation process according to claim 1, characterized in that: In step (1), the temperature is raised to 40-90°C and the reaction is carried out for 3-10 hours.

4. The preparation process according to claim 1, characterized in that: In step (1), after the reaction is completed, the temperature is cooled to room temperature, the upper layer is separated and washed with water to obtain the target product.

5. The preparation process according to claim 1, characterized in that: In step (2), the molar ratio of methyl 2-oxime acetate, aniline and catalyst is (1-2):1:(0.01-0.3).

6. The preparation process according to claim 1, characterized in that: In step (2), the catalyst is one or more of KOH, NaOH, NaOCH3, MgO, CaO, and NaAC.

7. The preparation process according to claim 1, characterized in that: In step (2), the reaction temperature is 50-100° C. and the reaction time is 3-15 h.

8. The preparation process according to claim 1, characterized in that: In step (2), methanol is evaporated during the reaction. After the reaction is completed, water is added, the mixture is cooled to room temperature, filtered, washed with water, and dried to obtain the target product.

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