A method for synthesizing a thermosensitive sensitizer 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate

Abstract

The invention belongs to the field of organic synthesis, and provides a method for synthesizing a thermosensitive sensitizer 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate, wherein m-aminophenol is used as a raw material, and an intermediate is reacted with sodium cyanate to synthesize 3-ureidophenol, and 3-ureidophenol and p-toluenesulfonamide are subjected to amination, esterification, purification and other steps to obtain a target product 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate. The synthesis method of the invention is simple, the raw materials are easily available, the product yield is high, the cost is low, and it is easy to realize industrialization.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis of esterification and amination, and in particular to a method for synthesizing a thermosensitive sensitizer 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate from p-toluenesulfonyl chloride. Background Art

[0002] The compound 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate is a new type of thermal sensitizer for thermal recording paper. In addition to increasing the sensitivity of recording paper to heat and pressure, it also gives the recorded image a high optical density and clarity, and can improve the sensitivity, thermal stability, sensitivity, luminescence and other properties of thermal recording paper.

[0003] At present, the synthesis methods reported in domestic and foreign literature mainly use p-toluenesulfonyl isocyanate, m-aminophenol and p-toluenesulfonyl chloride as raw materials for synthesis. CN107311893 reports that m-aminophenol is first reacted with p-toluenesulfonyl isocyanate to obtain an intermediate 3-p-toluenesulfonyl semicarbazide phenol, and then reacted with p-toluenesulfonyl chloride under alkaline conditions to obtain 3-(3-tolylurea)phenyl 4-methylbenzenesulfonate; in the process of synthesizing the intermediate 3-p-toluenesulfonyl semicarbazide phenol, this method will produce a reaction byproduct of phenolic hydroxyl group and p-toluenesulfonyl isocyanate, resulting in a low product content and a low yield. WO2000035679 and patent JP2010131763 both report a method for synthesizing 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate, which first reacts m-aminophenol with p-toluenesulfonyl chloride to synthesize 3-aminophenyl-4-methylbenzenesulfonate, and then the obtained intermediate 3-aminophenyl-4-methylbenzenesulfonate is dried and dehydrated, and then reacted with p-toluenesulfonyl isocyanate to obtain 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate. This method also has the problem that during the synthesis of the intermediate, the amino group and phenolic hydroxyl group of m-aminophenol react with p-toluenesulfonyl chloride to produce impurities, resulting in a low content of the final product; at the same time, the intermediate of this method needs to be dried, resulting in increased production costs and reduced production capacity. Summary of the invention

[0004] In order to overcome the problem of impurities easily generated in the synthesis of intermediates in the above synthesis, the inventors conducted intensive research and provided a synthesis method suitable for industrial production of high-purity 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate. The yield of 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate in this method reaches more than 85%, and the content reaches more than 99%, which is of great production value.

[0005] A method for synthesizing a thermosensitive sensitizer 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate, the mechanism of the synthesis method is as follows:

[0006] ;

[0007] The synthesis method comprises the following steps:

[0008] Step (1), adding m-aminophenol to a first reaction kettle containing a solvent of pure water, adding hydrochloric acid to the kettle, and adjusting the pH value to 2-4; slowly adding sodium cyanate to the kettle for reaction, filtering after the reaction is completed, washing the filter cake with water and filtering again to obtain an intermediate 3-hydroxyphenyl urea;

[0009] Step (2), adding 3-hydroxyphenylurea to a second reaction kettle, adding p-toluenesulfonyl chloride to the kettle in batches, and controlling the pH value of the reaction solution to 9-11 by using liquid alkali to carry out the reaction;

[0010] Step (3), after the reaction is completed, the reaction temperature is adjusted, p-toluenesulfonyl chloride is continuously added, and the pH of the reaction solution is controlled to be ≥ 13 by alkaline solution to carry out the reaction; after the reaction is completed, acid is added to precipitate the solid, which is filtered, and the filter cake is put into the kettle again and washed with water; in step (3), the molar ratio of m-aminophenol to p-toluenesulfonyl chloride is 1:1.2~1.5;

[0011] Step (4), after filtration, the filter cake obtained is added into a crystallization solvent for purification, centrifugation and drying to obtain the target product.

[0012] Preferably, in step (1), the molar ratio of m-aminophenol to sodium cyanate is 1:1.1-1.5, more preferably 1:1.5, the reaction temperature is 40-60° C., and the reaction time is 2 hours.

[0013] Preferably, in step (1), the solvent containing pure water is pure water, or a mixed solvent of one or both of methanol and dichloromethane and water.

[0014] Preferably, in step (2), the molar ratio of 3-hydroxyphenylurea to p-toluenesulfonyl chloride is 1:1.0-1.3, more preferably 1:1.2; the reaction temperature is 0-30°C, more preferably 0-10°C; and the reaction time is 2 hours.

[0015] Preferably, in step (3), the reaction temperature is 70-90°C, more preferably 75-80°C; and the reaction time is 5 hours.

[0016] Preferably, in step (3), an appropriate amount of organic solvent is added as a co-solvent for p-toluenesulfonyl chloride, and the solvent oil used is dichloroethane, toluene, chloroform, etc., preferably dichloroethane.

[0017] Preferably, in step (4), the crystallization solvent used for the product is methanol, ethanol, dichloromethane or a mixed solvent of one or two of them and water.

[0018] The 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate product obtained in step (4) of the method described in one of the preferred schemes has a purity of more than 99% and a yield of more than 85%.

[0019] The 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate synthesized by the invention can be used as a heat-sensitive sensitizer.

[0020] Compared with the existing technology, the invention provides a method for synthesizing 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate, which has no impurities in the intermediates and is simple to operate and easy to produce. The yield of the product obtained by this method is more than 85% and the content is more than 99%. DETAILED DESCRIPTION

[0021] Example 1: Step 1, add 109.13g of m-aminophenol and 200g of water to a reaction kettle, slowly drop 128g of 30% hydrochloric acid into the kettle until the reaction liquid in the kettle is acidic; weigh 97.5g of sodium cyanate and slowly add it to the kettle in batches. During the addition process, hydrochloric acid needs to be added at the same time to keep the reaction liquid in the kettle acidic; after the addition is completed, control the temperature in the kettle to 50-55°C and keep it warm for 2 hours. After the insulation is completed, use liquid alkali to adjust the reaction liquid to neutral; cool it to room temperature and filter it; obtain 3-hydroxyphenylurea.

[0022] Step 2: Add 3-hydroxyphenylurea to water, lower the temperature of the reaction solution to 0-5°C, add 228.75 g of p-toluenesulfonyl chloride in batches, and at the same time, slowly drop 30% of liquid alkali to control the reaction pH to 9-11; after the addition is completed, continue to keep warm for 2 hours.

[0023] Step 3: After the insulation is completed, the reaction solution is heated to 75°C, and 226.85 g of p-toluenesulfonyl chloride is added in batches, and 30% of liquid alkali is added dropwise to make the pH of the reaction solution ≥ 13. After the addition is completed, the temperature is continued to be kept for 5 hours to allow sufficient reaction. After the insulation is completed, the temperature in the kettle is lowered to room temperature, hydrochloric acid is added to the kettle, the pH value in the kettle is adjusted to neutral, and filtered to obtain a crude product.

[0024] Step 4, adding the obtained crude product into a solution of methanol: water = 1:1, stirring for 30 minutes, filtering, and drying to obtain the fine product 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate;

[0025] According to the above steps, the product yield was 79.62% based on m-aminophenol, the HPLC content was 99.5%, and the melting point was 163-168°C.

[0026] Example 2: The difference between the synthesis method of 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate in this example and that in Example 1 is that:

[0027] Step 3: After the heat preservation is completed, add 20g of dichloroethane to the kettle, heat the reaction solution to 75°C, continue to add 226.85g of p-toluenesulfonyl chloride in batches, and simultaneously drop 30% of liquid alkali to make the pH of the reaction solution ≥ 13. After the dropwise addition is completed, continue to heat for 5 hours to allow for sufficient reaction. After the heat preservation is completed, reduce the temperature in the kettle to room temperature, add hydrochloric acid to the kettle, adjust the pH value in the kettle to neutral, filter, and obtain a crude product. The other steps remain unchanged.

[0028] According to the above steps, the product yield was 85.52% based on m-aminophenol, the HPLC content was 99.48%, and the melting point was 163-168°C.

[0029] Example 3: The difference between the synthesis method of 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate in this example and that in Example 1 is that:

[0030] Step 4: Add the obtained crude product into dichloromethane, stir for 30 minutes, filter, and dry to obtain the fine product 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate; the HPLC content is 98.69%, the melting point is 161-166°C, and the product yield is 86.22% based on m-aminophenol.

[0031] The above are only specific embodiments of the present disclosure, but the protection scope of the present disclosure is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present disclosure, which should be included in the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.

Claims

1. A method for synthesizing a thermosensitive sensitizer 3-(3-tolylureido)phenyl 4-methylbenzenesulfonate, characterized in that: The synthesis method comprises the following steps: Step (1), adding m-aminophenol to a first reaction kettle containing a solvent of pure water, adding hydrochloric acid to the kettle, and adjusting the pH value to 2-4; slowly adding sodium cyanate to the kettle for reaction, filtering after the reaction is completed, washing the filter cake with water and filtering again to obtain an intermediate 3-hydroxyphenyl urea; in step (1), the solvent containing pure water is pure water, or a mixed solvent of one or two of methanol and dichloromethane and water; Step (2), adding 3-hydroxyphenylurea to a second reaction kettle, adding p-toluenesulfonyl chloride to the kettle in batches, and controlling the pH value of the reaction solution to 9-11 by using liquid alkali to react to obtain ； Step (3), after the reaction is completed, the reaction temperature is adjusted, p-toluenesulfonyl chloride is continuously added, and the pH of the reaction solution is controlled to be ≥13 by alkaline solution to carry out the reaction; after the reaction is completed, acid is added to precipitate the solid, which is filtered, and the filter cake is put into the kettle again and washed with water; in step (3), the molar ratio of m-aminophenol to p-toluenesulfonyl chloride is 1:1.2-1.5; in step (3), an appropriate amount of organic solvent needs to be added as a co-solvent for p-toluenesulfonyl chloride, and the organic solvent is one or more of dichloroethane, toluene, and chloroform; Step (4), after filtering, the obtained filter cake is added to a crystallization solvent for purification, centrifugation, and drying to obtain the target product; in step (1), the molar ratio of aminophenol to sodium cyanate is 1:1.1-1.5, the reaction temperature is 40-60°C, and the reaction time is 2 hours; in step (2), the molar ratio of 3-hydroxyphenylurea to p-toluenesulfonyl chloride is 1:1.0-1.3; the reaction temperature is 0-30°C, and the reaction time is 2 hours; in step (3), the reaction temperature is 70-90°C; the reaction time is 5 hours; in step (4), the crystallization solvent used for the product is methanol, ethanol, dichloromethane or a mixed solvent of one or two of them and water; The mechanism of the synthetic method is as follows: ; The yield of the product is more than 85% and the content is more than 99%.

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