WO2017197870A1

WO2017197870A1 - Method for oxidatively synthesizing p-carboxybenzene sulfonamide by means of oxygen

Info

Publication number: WO2017197870A1
Application number: PCT/CN2016/108404
Authority: WO
Inventors: 梁静; 杨会会; 魏贤勇; 宗志敏
Original assignee: 中国矿业大学
Priority date: 2016-05-16
Filing date: 2016-12-02
Publication date: 2017-11-23
Also published as: CN105801455A

Abstract

The present invention belongs to a method for preparing p-carboxybenzene sulfonamide. A method for oxidatively synthesizing p-carboxybenzene sulfonamide by means of oxygen. The method comprises: oxygen is taken as an oxidizing agent, an oxygen pressure is only required to be maintained at 1 atm, and oxidization is carried out in an acetic acid, by taking oxygen as the oxidizing agent under the action of a nitroxide free radical type catalyst and a metal salt or a metallic oxide cocatalyst; and p-methylphenyl sulphonylamine is catalytically oxidized to prepare p-carboxybenzene sulfonamide. The processes comprise: 5 mL of acetic acid, 1 mmol of p-methylphenyl sulphonylamine, the catalyst and a cocatalyst are sequentially added in a round-bottom flask having a magnetic stirring device; oxygen is introduced, and the pressure is maintained at 1 atm; the dosage mole ratio of the catalyst is 3%-8% of the dosage of the p-methylphenyl sulphonylamine, the dosage mole ratio of the cocatalyst is 0.5%-6% of the dosage of the p-methylphenyl sulphonylamine, reaction is finished after stirring is performed for 2-12 hours at the temperature of 40-120 °C, following which cooling is performed, reduced pressure distillation is performed to remove acetic acid, residues are sequentially washed with water and acetone, and drying is performed to obtain p-carboxybenzene sulfonamide. The advantages are mild conditions and high yield.

Description

Method for synthesizing p-carboxybenzenesulfonamide by oxygen oxidation

Technical field

The present invention relates to a process for the preparation of p-carboxybenzenesulfonamide, and more particularly to a process for the oxidation of p-carboxybenzenesulfonamide by oxygen oxidation.

Background technique

p-Carboxybenzenesulfonamide (I) is an important pharmaceutical synthetic intermediate for the synthesis of probenecid, harazin, etc., and its sodium salt can also be used as an inhibitor of carbonic anhydrase. Its structural formula is as follows:

The p-carboxybenzenesulfonamide is prepared by using p-toluenesulfonamide as a raw material and oxidizing the methyl group to a carboxyl group using an oxidizing agent. However, the p-methylbenzenesulfonamide aromatic ring contains a strong electron withdrawing group, which is a substrate which is difficult to oxidize. Therefore, its oxidation often uses more than stoichiometric conventional strong oxidizing agents KMnO ₄ , Na ₂ Cr ₂ O ₇ , CrO _{3 .} , NaIO _4, etc., these oxidants are present in the reaction system in a lower valence state, which not only increases the difficulty of separation and purification of the product, but also discharges the waste liquid to the environment, and also has corrosion equipment. Low efficiency and other drawbacks do not meet the requirements of green chemistry.

In the past, the use of oxygen as an oxidant to oxidize aromatic side chains often needs to be carried out under high temperature and high pressure conditions. For example, Li Tao et al. reported the use of cobalt-based pyrazole complexes as catalysts to oxidize toluene with oxygen as an oxidant to prepare benzoic acid, 150 ° C and 1.5 MPa. The reaction was carried out at (150 atm) for 140 minutes, the yield of benzoic acid was up to 75.96%, and the selectivity of benzoic acid was 89.25%. The reaction is carried out under high temperature and high pressure, which is a process of severe energy consumption, and the requirements for equipment are also high; the preparation of the catalyst cobalt-pyrazole complex required for the reaction is cumbersome and costly; the reaction oxidizes the methyl group to the carboxyl group. Further, an intermediate oxidation product such as a methylol group or an aldehyde group is formed, and a product selectivity of a carboxyl group is 89.25%; the reaction condition can oxidize toluene, but when a methyl group is introduced to a strong electron withdrawing sulfonamide group, The base cannot be oxidized to form p-carboxybenzenesulfonamide. In fact, many novel oxidation catalysts can catalyze the oxidation of toluene to benzoic acid, but not the oxidation of p-toluenesulfonamide.

Summary of the invention

SUMMARY OF THE INVENTION It is an object of the present invention to provide a low cost, environmentally friendly, mild and efficient method for the oxidation of p-carboxybenzenesulfonamide by oxygen oxidation.

The object of the present invention is achieved by using oxygen as an oxidant, oxygen pressure only needs to be maintained at 1 atm, and oxidation by oxygen as an oxidant under the action of a nitroxide type catalyst and a metal salt or a metal oxide promoter. The reaction is carried out in acetic acid; catalytically oxidizing p-toluenesulfonamide to prepare p-carboxybenzenesulfonamide;

R ¹ and R ² represent the same group or different groups, and R ¹ and R ² are hydrogen or a C ₁ -C ₆ alkyl group;

The specific process is as follows: in a round bottom flask equipped with a magnetic stirring device, 5 mL of acetic acid, 1 mmol of p-toluenesulfonamide, a catalyst and a cocatalyst are sequentially added, oxygen is introduced, and the pressure is maintained at 1 atm; the amount of the catalyst is used. The molar ratio is 3% to 8% of the amount of p-toluenesulfonamide, and the molar ratio of the cocatalyst is 0.5% to 6% of the amount of p-toluenesulfonamide, and the mixture is stirred at 2 to 12 at 40 to 120 °C. After the lapse of time, the reaction was stopped, cooled, and acetic acid was distilled off under reduced pressure. The residue was washed successively with water, acetone and dried to give the product p-carboxybenzenesulfonamide.

The catalyst used is a free radical catalyst, which is N-hydroxy-2,2,6,6-tetramethylpiperidine, N-hydroxyphthalimide, N-hydroxy sulfonylbenzoyl Amine, N,N-dihydroxystilbenetetramethyleneimide, 1,3,5-trihydroxyisocyanuric acid, N-hydroxy-N-methylbenzamide, 3,5-dinitro-N -hydroxy-N-methylbenzamide or 1-hydroxy-2,2-diphenyl-3-indanone; molar ratio based on p-toluenesulfonamide is only 3% to 8%; The catalyst is cobalt acetate, manganese acetate, copper acetate, iron acetate or manganese dioxide metal salt, the molar ratio based on p-toluenesulfonamide is only 0.5% to 6%, and the conversion ratio of p-toluenesulfonamide is 80.32~ 99.33%, the yield of the product p-carboxybenzenesulfonamide is 70.83-94.05%, and the selectivity is up to 97.65%; the catalyst and the cocatalyst can be removed by washing after completion of the reaction.

The beneficial effect is that due to the above scheme, the low-cost, environmentally friendly oxygen is used as the oxidant, and the p-toluenesulfonamide is oxidized to the product p-carboxybenzenesulfonamide, the yield is up to 94.05%, and the selectivity is up to 97.65. %, the purity detected by Agilent 1200 high performance liquid chromatography is 92.23～95.35%%, the main product of p-carboxybenzenesulfonamide in the oxidation product, a small amount of 4-hydroxymethylbenzenesulfonamide (II), no 4- Formylbenzenesulfonamide (III) is formed.

Compared with the conventional p-toluenesulfonamide oxidation process, the oxidant used is oxygen, which not only reduces the cost, but also the by-product after oxidation is water, which is environmentally friendly, and is removed by vacuum distillation after the reaction is completed. Acetic acid and acetic acid can be recycled, and the residue can be separated by washing with water and acetone, thereby separating the product from the catalyst, the cocatalyst and the by-product, and the post-treatment is simple and convenient.

The method has mild reaction conditions and is carried out under normal pressure (oxygen pressure maintained at 1 atm) at a medium temperature (40 to 120 ° C), and has high conversion rate and high selectivity, high product purity, and good industrial application prospect.

Compared with the traditional oxidation method, the invention has the essential feature that the method uses low-cost oxygen as an oxidant, greatly reduces the cost, and the by-product is water, and has no pollution to the environment; the reaction only needs to maintain oxygen pressure. 1atm can efficiently oxidize p-methylbenzenesulfonamide to p-carboxybenzenesulfonamide, mild conditions, avoid the use of high temperature and high pressure equipment, and reduce energy consumption. It is an ideal green synthesis method for p-carboxybenzenesulfonamide. Industrial application prospects.

advantage:

1. The reaction is a catalytic oxidation process. The amount of catalyst and cocatalyst is small. Compared with the raw material p-toluenesulfonamide, the amount of catalyst is only 3% to 8%, and the amount of cocatalyst is 0.5% to 6%. The washing of the water and the washing of a small amount of acetone can realize the separation of the catalyst, the cocatalyst, the by-products and the product, and the operation is simple and convenient.

2, without the use of traditional strong oxidants, the use of oxygen as an oxidant, not only greatly reduced costs, and by-products Water, which is not harmful to the environment, is an environmentally friendly process;

3. The reaction has a relatively high selectivity and conversion rate. The reaction oxidizes the methyl group to a carboxyl group, and only a very small amount of p-toluenesulfonamide is oxidized to 4-hydroxymethylbenzenesulfonamide without 4-formylbenzenesulfonate. The formation of amides. Under the optimized conditions, the conversion of p-toluenesulfonamide can reach 99.33%, the yield of p-carboxybenzenesulfonamide can reach 94.05%, and the selectivity can reach 94.68%.

4, the reaction conditions are mild, the reaction is carried out under normal pressure (1 atm) and medium temperature (40 ~ 120 ° C), the equipment requirements are simple, avoiding the disadvantages that must be carried out under high temperature and high pressure when using oxygen for oxidation, reducing energy consumption Easy to industrialize and promote applications.

detailed description

The method comprises the steps of: preparing a p-carboxybenzenesulfonamide by catalytic oxidation of p-toluenesulfonamide under the action of a nitroxide type catalyst and a metal salt or a metal oxide cocatalyst, using oxygen as an oxidant:

R ₁ and R ₂ represent the same group or different groups, and R ₁ and R ₂ are hydrogen or a C ₁ -C ₆ alkyl group.

The catalyst used in the method is a nitrogen oxide radical type catalyst; the promoter is various metal salts and metal oxides, the oxidant is oxygen; and the oxidation reaction uses acetic acid as a solvent at normal pressure (1 atm) and medium temperature (40 to 120 ° C). Under conditions; catalytic oxidation of p-toluenesulfonamide to p-carboxybenzenesulfonamide.

The catalyst may be N-hydroxy-2,2,6,6-tetramethylpiperidine, N-hydroxyphthalimide, N-hydroxy sulfonyl benzoimide, N, N. -dihydroxystilbenetetramethyleneimide, 1,3,5-trihydroxyisocyanuric acid, N-hydroxy-N-methylbenzamide, 3,5-dinitro-N-hydroxy-N- Methyl benzamide or 1-hydroxy-2,2-diphenyl-3-fluorenone; the structural formula of the above catalyst is as follows:

The metal salt or metal oxide cocatalyst may be cobalt acetate, manganese acetate, copper acetate, iron acetate or manganese dioxide;

The reactant used is p-toluenesulfonamide, and the benzene ring containing an electron withdrawing substituent is difficult to undergo oxidation reaction itself; therefore, when the sulfonamide group is substituted with an electron donor group such as a methoxy group or an acetamide group, the oxidation reaction is carried out. More likely to happen.

The specific process is as follows:

In a round bottom flask equipped with a magnetic stirring device, acetic acid, p-toluenesulfonamide, a catalyst and a cocatalyst are sequentially added; the molar ratio of the catalyst is 3% to 8% of the amount of p-toluenesulfonamide, and the cocatalyst The molar ratio is 0.5% to 6%, oxygen is supplied, the oxygen pressure is maintained at 1 atm, and the reaction is stopped after stirring for 2 to 12 hours at 40 to 120 ° C. The acetic acid is removed under reduced pressure, and the solvent acetic acid can be repeatedly used, and the residue is used. The residual acetic acid and the cocatalyst were washed repeatedly with water, and the residue was washed with a small amount of acetone to remove the catalyst and a small amount of by-products, and the filter cake was dried to obtain the product p-carboxybenzenesulfonamide.

The yield of the product p-carboxybenzenesulfonamide was 70.83 to 94.05%, and the purity was 92.23 to 95.35% by analytical analysis by Agilent 1200 high performance liquid chromatography. The oxidation reaction is highly selective, and only a small amount of p-toluenesulfonamide is oxidized to 4-hydroxymethylbenzenesulfonamide (II), and no 4-formylbenzenesulfonamide (III) is formed.

R ₁ and R _{2 in} 4-hydroxymethylbenzenesulfonamide (II) and 4-formylbenzenesulfonamide (III) represent the same group or different groups, and R ₁ and R ₂ are hydrogen or C ₁ -C ₆ alkyl.

The reactant used in the reaction contains an electron withdrawing group sulfonamide group, which is a substrate which is difficult to be oxidized, and therefore the reaction is equally applicable to the oxidation of other aromatic hydrocarbon side chains containing an electron withdrawing group or an electron donating group.

The reaction uses oxygen as the oxidant, but the oxygen is weak when used alone. Therefore, it is the key of the present invention to select a suitable catalytic system to increase the activity of oxygen. The catalyst used in the present invention is a nitroxide-type oxidizing agent N-hydroxy-2,2,6,6-tetramethylpiperidine, N-hydroxyphthalimide, N-hydroxyl-sulfonylbenzophenone Imide, N,N-dihydroxystilbenetetramethyleneimide, 1,3,5-trihydroxyisocyanuric acid, N-hydroxy-N-methylbenzamide, 3,5-dinitro -N-hydroxy-N-methylbenzamide, 1-hydroxy-2,2-diphenyl-3-indolone, etc. The cocatalyst is cobalt acetate, manganese acetate, copper acetate, iron acetate, manganese dioxide Such as a metal salt or a metal oxide; the catalytic system is used in a small amount, and the catalytic efficiency is high. When the p-toluenesulfonamide: catalyst: cocatalyst = 100:3 to 8:0.5 to 6, the atmospheric pressure (oxygen pressure) can be achieved. Maintaining at 1 atm) oxygen oxidizes p-methylbenzenesulfonamide to p-carboxybenzenesulfonamide, and the conversion of p-toluenesulfonamide is up to 99.33%. The yield of the product p-carboxybenzenesulfonamide is up to 94.05%; and after the reaction is completed, the separation and purification of p-carboxybenzenesulfonamide can be achieved by simple filtration, washing and drying.

Example 1: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.06 mmol of N-hydroxy sulfonylbenzamide, 0.03 mmol of manganese dioxide, add 25 mL of reaction flask, add 5 mL of acetic acid, and pass oxygen to maintain The oxygen pressure was 1 atm, and the temperature was raised to 80 ° C for 6 hours. After the reaction was completed, it was cooled to room temperature. The manganese dioxide is filtered off, the acetic acid is removed under reduced pressure, and the acetic acid can be recycled. The residue was washed with water to remove residual acetic acid, washed with a small amount of acetone to remove N-hydroxy sulfonylbenzamide and a small amount of p-hydroxymethylbenzenesulfonamide, and the filter cake was dried to obtain p-carboxybenzenesulfonamide in a yield of 81.86. %, the conversion of p-toluenesulfonamide was 86.32%, the selectivity to p-carboxybenzenesulfonamide was 94.83%, and the purity of the product was 94.20% by Agilent 1200 high performance liquid chromatography.

Example 2: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.03 mmol of N,N-dihydroxystilbenetetramethyleneimide, 0.06 mmol of manganese acetate, add 25 mL of reaction flask, add 5 mL of acetic acid, and introduce oxygen. The oxygen pressure was maintained at 1 atm, and the temperature was raised to 120 ° C for 2 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and co-catalyst manganese acetate, and a small amount of acetone is washed to remove N,N-dihydroxystilbenetetramethyleneimide and a small amount of p-hydroxymethylbenzenesulfonamide, and the filter cake is dried to obtain The yield of p-carboxybenzenesulfonamide was 70.83%, the conversion of p-toluenesulfonamide was 80.32%, and the selectivity to p-carboxybenzenesulfonamide was 88.18%. The purity of the product was analyzed by Agilent 1200 high performance liquid chromatography. It is 92.23%.

Example 3: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.08 mmol of N-hydroxyphthalimide, 0.04 mmol of copper acetate, add 25 mL of reaction flask, add 5 mL of acetic acid, and pass oxygen to maintain oxygen pressure. It was 1 atm, and the temperature was raised to 40 ° C for 12 hours. After the reaction was completed, it was cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst copper acetate. A small amount of acetone is washed to remove N-hydroxyphthalimide and a small amount of p-hydroxymethylbenzenesulfonamide. The filter cake is dried to obtain p-carboxybenzenesulfonate. The yield of the amide was 72.81%, the conversion of p-toluenesulfonamide was 81.55%, the selectivity to p-carboxybenzenesulfonamide was 89.28%, and the purity of the product was 94.42% by Agilent 1200 high performance liquid chromatography.

Example 4: Weigh 1 mmol of p-carboxybenzenesulfonamide, 0.05 mmol of 3,5-dinitro-N-hydroxy-N-methylbenzamide, 0.05 mmol of iron acetate, add to a 25 mL reaction flask, and add 5 mL of acetic acid. Oxygen was supplied, the oxygen pressure was maintained at 1 atm, and the temperature was raised to 100 ° C for 6 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst iron acetate, and a small amount of acetone is washed to remove 3,5-dinitro-N-hydroxy-N-methylbenzamide and a small amount of p-hydroxymethylbenzenesulfonamide, filter cake. When dried, p-carboxybenzenesulfonamide can be obtained in a yield of 74.25%, the conversion of p-toluenesulfonamide is 82.43%, and the selectivity to p-carboxybenzenesulfonamide is 90.08%. The product is subjected to Agilent 1200 high performance liquid phase. The purity of the chromatographic analysis was 93.12%.

Example 5: Weigh 1 m mol of p-carboxybenzenesulfonamide, 1-hydroxy-2,2-diphenyl-3-indanone 0.06 mmol, cobalt acetate 0.005 mmol, add 25 mL reaction flask, add 5 mL of acetic acid, Oxygen was supplied, the oxygen pressure was maintained at 1 atm, and the temperature was raised to 100 ° C for 8 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst cobalt acetate, and a small amount of acetone is washed to remove 1-hydroxy-2,2-diphenyl-3-indolone and the like and a small amount of p-hydroxymethylbenzenesulfonamide, and the filter cake is dried. , the p-carboxybenzenesulfonamide was obtained in a yield of 73.45%, the conversion of p-toluenesulfonamide was 82.12%, and the selectivity to p-carboxybenzenesulfonamide was 89.44%. The product was analyzed by Agilent 1200 high performance liquid chromatography to detect a purity of 95.20%.

Example 6: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.06 mmol of 1,3,5-trihydroxyisocyanuric acid, 0.03 mmol of manganese dioxide, add 25 mL of reaction flask, add 5 mL of acetic acid, and pass oxygen to maintain The oxygen pressure was 1 atm, and the temperature was raised to 90 ° C for 12 hours. After the reaction was completed, it was cooled to room temperature. Filtration removes manganese dioxide, and the filtrate removes acetic acid under reduced pressure, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid, and a small amount of acetone is washed to remove 1,3,5-trihydroxyisocyanuric acid and a small amount of p-hydroxymethylbenzenesulfonamide, and the filter cake is dried to obtain p-carboxybenzenesulfonamide. 90.76%, the conversion of p-toluenesulfonamide was 93.24%, the selectivity to p-carboxybenzenesulfonamide was 97.34%, and the purity of the product was 95.15% by Agilent 1200 high performance liquid chromatography.

Example 7: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.06 mmol of N-hydroxy-2,2,6,6-tetramethylpiperidine, 0.03 mmol of manganese dioxide, add to a 25 mL reaction flask, and add 5 mL of acetic acid. Oxygen was supplied, the oxygen pressure was maintained at 1 atm, and the temperature was raised to 100 ° C for 10 hours. The reaction was completed and cooled to room temperature. Manganese dioxide is removed by filtration, and the filtrate is removed under reduced pressure, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid, and a small amount of acetone is washed to remove N-hydroxy-2,2,6,6-tetramethylpiperidine and a small amount of p-hydroxymethylbenzenesulfonamide, and the filter cake is dried to obtain a carboxyl group. The yield of benzenesulfonamide was 72.87%, the conversion of p-toluenesulfonamide was 80.88%, the selectivity to p-carboxybenzenesulfonamide was 90.10%, and the purity of the product was 95.35 by Agilent 1200 high performance liquid chromatography. %.

Example 8: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.06 mmol of N-hydroxy-N-methylbenzamide, 0.01 mmol of cobalt acetate, add 25 mL of reaction flask, add 5 mL of acetic acid, and pass oxygen to maintain oxygen. The pressure was 1 atm, and the temperature was raised to 100 ° C for 12 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst cobalt acetate. A small amount of acetone is washed to remove N-hydroxy-N-methylbenzamide and a small amount of p-hydroxymethylbenzenesulfonamide. The filter cake is dried to obtain p-carboxybenzene. The yield of sulfonamide was 84.62%, the conversion of p-toluenesulfonamide was 90.23%, the selectivity to p-carboxybenzenesulfonamide was 93.78%, and the purity of the product was 93.42% by Agilent 1200 high performance liquid chromatography. .

Example 9: Weigh 1 m mol of p-carboxybenzenesulfonamide, 1-hydroxy-2,2-diphenyl-3-indanone 0.06 mmol, cobalt acetate 0.02 mmol, add 25 mL reaction flask, add 5 mL of acetic acid, Oxygen was supplied, the oxygen pressure was maintained at 1 atm, and the temperature was raised to 100 ° C for 10 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst cobalt acetate, and a small amount of acetone is washed to remove 1-hydroxy-2,2-diphenyl-3-indanone and a small amount of p-hydroxymethylbenzenesulfonimide, filter cake. After drying, p-carboxybenzenesulfonamide can be obtained in a yield of 84.14%, the conversion of p-toluenesulfonamide is 89.12%, and the selectivity to p-carboxybenzenesulfonamide is 94.41%. The product is subjected to Agilent 1200 high performance liquid phase. The purity of the chromatographic analysis was 95.32%.

Example 10: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.05 mmol of N-hydroxy sulfonylbenzamide, 0.02 mmol of cobalt acetate, add to a 25 mL reaction flask, add 5 mL of acetic acid, and pass oxygen to maintain oxygen. The pressure was 1 atm, and the temperature was raised to 80 ° C for 12 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst cobalt acetate. A small amount of acetone is washed to remove N-hydroxy sulfonylbenzamide and a small amount of p-hydroxymethylbenzenesulfonamide. The filter cake is dried to obtain p-carboxybenzene. Sulfonamide, the yield was 81.89%, the conversion of p-toluenesulfonamide was 87.65%, the selectivity to p-carboxybenzenesulfonamide was 93.43%, and the purity of the product was 94.20% by Agilent 1200 high performance liquid chromatography. .

Example 11: Weigh 1 m mol of p-carboxybenzenesulfonamide, 3,5-dinitro-N-hydroxy-N-methylbenzamide 0.05 mmol, cobalt acetate 0.01 mmol, add 25 mL reaction flask, add acetic acid 5 mL, oxygen was introduced, the oxygen pressure was maintained at 1 atm, and the temperature was raised to 100 ° C for 10 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst cobalt acetate, and a small amount of acetone is washed to remove 3,5-dinitro-N-hydroxy-N-methylbenzamide and a small amount of p-hydroxymethylbenzenesulfonimide. The filter cake is dried to obtain p-carboxybenzenesulfonamide, the yield is 94.05%, the conversion of p-toluenesulfonamide is 99.33%, and the selectivity to p-carboxybenzenesulfonamide is 94.68%. The product is highly efficient by Agilent 1200. The purity of the liquid chromatograph was 95.14%.

Example 12: Weigh 1 m mol of p-carboxybenzenesulfonamide, 0.06 mmol of 1,3,5-trihydroxyisocyanuric acid, 0.02 mmol of cobalt acetate, add to a 25 mL reaction flask, add 5 mL of acetic acid, and pass oxygen to maintain oxygen. The pressure was 1 atm, and the temperature was raised to 100 ° C for 10 hours. The reaction was completed and cooled to room temperature. The filtrate is decompressed to remove acetic acid, and acetic acid can be recycled. The residue is repeatedly washed with water to remove residual acetic acid and cocatalyst cobalt acetate. A small amount of acetone is washed to remove 1,3,5-trihydroxyisocyanuric acid and a small amount of p-hydroxymethylbenzenesulfonimide, and the filter cake is dried to obtain a pair. The yield of carboxybenzenesulfonamide was 85.62%, the conversion of p-toluenesulfonamide was 87.68%, and the selectivity to p-carboxybenzenesulfonamide was 97.65%. The purity of the product was determined by Agilent 1200 high performance liquid chromatography. 93.44%.

Claims

A method for synthesizing p-carboxybenzenesulfonamide by oxygen oxidation, characterized in that: the method uses oxygen as an oxidant, and the oxygen pressure only needs to be maintained at 1 atm, and the role of the nitrogen oxide radical catalyst and the metal salt or metal oxide promoter Next, using oxygen as an oxidant, the oxidation reaction is carried out in acetic acid; catalytically oxidizing p-methylbenzenesulfonamide to prepare p-carboxybenzenesulfonamide;

R 1 and R 2 represent the same group or different groups, and R 1 and R 2 are hydrogen or a C 1 -C 6 alkyl group;

The specific process is as follows: in a round bottom flask equipped with a magnetic stirring device, 5 mL of acetic acid, 1 mmol of p-toluenesulfonamide, a catalyst and a cocatalyst are sequentially added, oxygen is introduced, and the pressure is maintained at 1 atm; the amount of the catalyst is used. The molar ratio is 3% to 8% of the amount of p-toluenesulfonamide, and the molar ratio of the cocatalyst is 0.5% to 6% of the amount of p-toluenesulfonamide, and the mixture is stirred at 2 to 12 at 40 to 120 °C. After the lapse of time, the reaction was stopped, cooled, and acetic acid was distilled off under reduced pressure. The residue was washed successively with water, acetone and dried to give the product p-carboxybenzenesulfonamide.
The method for synthesizing p-carboxybenzenesulfonamide by oxygen oxidation according to claim 1, wherein the catalyst used is a radical catalyst, which is N-hydroxy-2,2,6,6-tetramethyl. Piperidine, N-hydroxyphthalimide, N-hydroxy sulfonyl benzoimide, N,N-dihydroxystilbene tetraimide, 1,3,5-trihydroxyiso Cyanuric acid, N-hydroxy-N-methylbenzamide, 3,5-dinitro-N-hydroxy-N-methylbenzamide or 1-hydroxy-2,2-diphenyl-3-indole Anthrone; based on p-toluenesulfonamide molar ratio of only 3% to 8%; the cocatalyst used is cobalt acetate, manganese acetate, copper acetate, iron acetate or manganese dioxide metal salt based on p-toluenesulfonate The molar ratio of the amide is only 0.5% to 6%, the conversion of p-toluenesulfonamide is 80.32 to 99.33%, the yield of the product p-carboxybenzenesulfonamide is 70.83 to 94.05%, and the selectivity is up to 97.65%; After the reaction with the cocatalyst is completed, it can be removed by washing.