CN114057592B - Method for preparing 4-aminomethylbenzoic acid - Google Patents
Method for preparing 4-aminomethylbenzoic acid Download PDFInfo
- Publication number
- CN114057592B CN114057592B CN202010776212.4A CN202010776212A CN114057592B CN 114057592 B CN114057592 B CN 114057592B CN 202010776212 A CN202010776212 A CN 202010776212A CN 114057592 B CN114057592 B CN 114057592B
- Authority
- CN
- China
- Prior art keywords
- acid
- reaction
- preparing
- aminomethylbenzoic
- aminomethylbenzoic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
- C07C227/20—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters by hydrolysis of N-acylated amino-acids or derivatives thereof, e.g. hydrolysis of carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
- C07C273/1854—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas by reactions not involving the formation of the N-C(O)-N- moiety
- C07C273/1863—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas by reactions not involving the formation of the N-C(O)-N- moiety from urea
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
Abstract
The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for preparing 4-aminomethylbenzoic acid by using a novel ammoniating agent. Reacting p-halomethylbenzoic acid serving as a raw material by an amination reagent in the presence of a solvent, neutralizing the raw material in water by alkali, and then carrying out amination reaction by urea; acidolysis and crystallization are carried out after the reaction to obtain the 4-aminomethylbenzoic acid. The 4-aminomethylbenzoic acid prepared by the method has high purity and low cost, increases the production safety, reduces the complexity and depreciation rate of equipment, and has great industrial practical value.
Description
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for preparing 4-aminomethylbenzoic acid by using a novel ammoniating agent.
Background
The aminotoluene is a procoagulant, has excellent hemostatic and bleeding-preventing effects, and is suitable for abnormal bleeding during operations of lung, liver, pancreas, prostate, thyroid, adrenal gland and the like, gynecological and postpartum bleeding, hemoptysis of pulmonary tuberculosis, bloody sputum, hematuria, prostatauxe bleeding, upper gastrointestinal bleeding and the like. The aminomethylbenzoic acid also has the function of preventing and improving skin pigmentation, and is widely applied to the fields of medicine and daily chemicals. The tranexamic acid is also a key intermediate for synthesizing tranexamic acid which is a hemostatic with wider application, and the market demand is huge; at present, enterprises processing the product in China break goods successively due to technical reasons and the like, the market is blank for a long time, and the clinical requirements of downstream tranexamic acid products cannot be met, and the products are short. The preparation method of the aminomethylbenzoic acid mainly comprises the following steps:
in a first method, patent CN201110421970.5 discloses an amination reaction of p-chloromethyl benzoic acid with urotropine as a catalyst and ammonia as an ammoniation reagent to obtain 4-aminomethyl benzoic acid. The method has the advantages that the product yield is improved to some extent, but the catalyst urotropine is large in dosage, urotropine and ammonium chloride in waste liquid obtained by the reaction are difficult to separate, the urotropine and the ammonium chloride have good solubility in water, and the urotropine and the ammonium chloride are difficult to purify only by methods such as concentration crystallization and the like, so that solid waste is increased. The ammoniating agent is ammonia water in the reaction, and the ammonia water is distilled off after the ammoniation reaction is finished, so that the equipment requirements are strict, and the ammonia water has certain safety risks.
In the second method, the page 19-20 of the 8 th volume of the 1977 journal of Chinese medicine industry reports that 4-halomethylbenzoic acid is used as a raw material, ammonium carbonate or ammonium bicarbonate is used as a catalyst, ammonia water is used as an ammoniating agent, and the yields are respectively 50% -55% and 35% -40%, but the catalyst in a reaction system is cheap and easy to obtain, has small environmental pollution, but has low ammoniation reaction yield, so that the product cost is high, special production equipment is required when excessive ammonia water is recovered, and the requirements on equipment are strict, so that the method is not suitable for industrial production.
In a third method, patent 201080061651.1 discloses a method for preparing 4-aminomethylbenzoic acid by catalytic hydrogenation under alkaline condition by using 4-formyl benzoyl methyl ester as a raw material and hydroxylamine hydrochloride to react into oxime and palladium-carbon as a catalyst. The method has the advantages of difficult raw material purchase, high price, high catalytic hydrogenation risk, high-pressure hydrogenation kettle requirement and inapplicability to large-scale industrial production. Patent 201810463637.2 discloses a method for directly catalyzing and ammonifying 4-formylbenzoic acid into a product by palladium-carbon under ammonia and hydrogen, and the method has the disadvantages of high-pressure catalytic reduction risk, high raw material price and the like.
In a fourth method, patent CN102718673A and CN105037186A disclose a method for preparing 4-aminomethylbenzoic acid by acid hydrolysis and ammonification of p-cyano benzyl halide as raw material. The raw material p-cyano halobenzyl used in the route has no supplier, and if p-cyano toluene is used for self-synthesizing p-cyano halobenzyl, the raw material p-cyano toluene has fewer domestic suppliers and is high in price.
Disclosure of Invention
The invention aims to solve the problems and provide a method for preparing 4-aminomethylbenzoic acid by using a novel ammoniating agent, which has the advantages of no need of a catalyst, easily available raw materials, low production equipment requirement, small environmental pollution and high safety and is suitable for industrial production.
In order to achieve the above purpose, the invention adopts the technical scheme that:
a process for preparing 4-aminomethylbenzoic acid from p-halomethylbenzoic acid includes such steps as reaction by amination reagent in the presence of solvent, alkali neutralization of raw material in water, and amination by urea; acidolysis and crystallization are carried out after the reaction to obtain the 4-aminomethylbenzoic acid.
The specific reaction formula is as follows:
acidolysis is carried out after the reaction, stirring crystallization is carried out, and filtering is carried out, wherein a filter cake is 4-aminomethylbenzoic acid; the filtrate is returned to the system for application.
The raw materials are added with alkali in solvent water to carry out neutralization reaction for 0.5-3h, preferably 1-2h at 10-40 ℃, preferably 20-30 ℃.
The mass of the solvent water is 2-10 times of that of the raw materials, preferably 3-5 times; the molar amount of the base is 1.00 to 2.00 times, preferably 1.01 to 1.03 times the molar amount of the p-halomethylbenzoic acid.
The raw material p-halomethylbenzoic acid is p-bromomethylbenzoic acid or p-chloromethylbenzoic acid; the base is selected from ammonium bicarbonate or ammonium carbonate.
After the neutralization reaction, carbamide as an amination reagent is added into the system, and the amination reaction is carried out for 2 to 15 hours, preferably 6 to 8 hours at 40 to 100 ℃, preferably 80 to 100 ℃.
The molar amount of urea is 1.00 to 2.00 times, preferably 1.02 to 1.05 times the molar amount of p-halomethylbenzoic acid.
After the amination reaction, acid is added into the system to carry out acidolysis reaction for 0.5-6 hours, preferably 1-2 hours at 50-100 ℃, preferably 60-80 ℃ so that the pH value of the system is 4.0-8.0, preferably 6.5-7.5.
The addition amount of the acid is 2.0 to 3.0 times, preferably 2.2 to 2.5 times of the mole number of the p-halomethylbenzoic acid; wherein the acid is sulfuric acid or hydrochloric acid, preferably hydrochloric acid.
Compared with the prior art, the invention has the following advantages:
1. in the reaction process, the ammoniation agent urea reduces the activity of amino due to the existence of carbonyl in the molecular structure of urea, so that the excessive reaction of the amino is not easy to occur, and the final product does not contain carbamic acid and trimethyl benzoic acid, thereby improving the selectivity of the ammoniation reaction and further improving the yield.
2. In the reaction process, urea is directly used for ammonification, and a catalyst urotropine is not adopted, so that the problem that the catalyst cannot be recovered is solved, and the environmental protection pressure is further reduced.
3. In the reaction process, urea is directly used as an ammoniation reagent, so that a large excess of ammonia water or liquid ammonia is avoided, an ammonia evaporation step is not needed after the reaction is completed, the equipment is simple, and the safety risk of explosive ammonia water is also eliminated.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and the contents of the embodiments should not be construed as limiting the scope of protection of the present invention.
Example 1
1. 85.30g of p-chloromethylbenzoic acid and 256ml of purified water are added into a reaction flask, the temperature is raised to 30 ℃ by stirring, 40.72g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 1h at 30 ℃ by stirring after the addition.
2. 31.53g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 100 ℃ with stirring, and the reaction is carried out for 6h.
3. And cooling the liquid obtained in the second step to 60 ℃, adding 111.41g of 36% hydrochloric acid, and stirring at 60 ℃ for reaction for 2 hours.
4. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 6.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 72.37g of aminomethylbenzoic acid, 8.1% of water content, 99.91% of purity and 88.0% of yield are obtained.
5. 85.30g of p-chloromethyl benzoic acid is added into the filtrate obtained in the step 4, the temperature is raised to 30 ℃ by stirring, 40.72g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 1h at 30 ℃ by stirring after the addition.
6. 31.53g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 100 ℃ with stirring, and the reaction is carried out for 6h.
7. And cooling the liquid obtained in the second step to 60 ℃, adding 111.41g of 36% hydrochloric acid, and stirring at 60 ℃ for reaction for 2 hours.
8. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 6.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 81.01g of aminomethylbenzoic acid, 9.5% of water content, 99.85% of purity and 97.0% of yield are obtained.
The obtained filtrate is reacted according to the steps 5-8 in the reaction process, then the filtrate is filtered, the filtrate is continuously used for application, the application is repeated for three times (as shown in the table below), when the four batches are used for application, the average yield of five batches is 95.1%, and the purity of the five batches is more than 99.0%.
TABLE 1
| Batch of | Mass g | Moisture content% | Purity% | Yield% |
| Applying the second batch | 82.40 | 11.3 | 99.60 | 96.7 |
| Apply the third batch | 79.73 | 8.9 | 99.22 | 96.1 |
| Apply the fourth batch | 80.71 | 8.7 | 99.05 | 97.5 |
Example 2
1. 85.30g of p-chloromethylbenzoic acid and 427ml of purified water are added into a reaction flask, the temperature is raised to 20 ℃ by stirring, 39.93g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 2 hours at 20 ℃ by stirring after the addition.
2. 30.63g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 80 ℃ with stirring, and the reaction is carried out for 8 hours.
3. 126.60g of 36% hydrochloric acid was added to the second reaction mixture, and the mixture was stirred at 80℃for 1 hour.
4. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 7.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 74.40g of aminomethylbenzoic acid, 10.7% of water content, 99.95% of purity and 87.9% of yield are obtained.
5. 85.30g of p-chloromethyl benzoic acid is added into the filtrate obtained in the step 4, the temperature is raised to 20 ℃ by stirring, 39.93g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 2 hours at 20 ℃ by stirring after the addition.
6. 30.63g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 80 ℃ with stirring, and the reaction is carried out for 8 hours.
7. 126.60g of 36% hydrochloric acid was added to the second reaction mixture, and the mixture was stirred at 80℃for 1 hour.
8. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 7.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 80.95g of aminomethylbenzoic acid, 8.6% of water content, 99.86% of purity and 97.9% of yield are obtained. The obtained filtrate can be reused for multiple times.
Example 3
1. 107.52g of p-bromomethylbenzoic acid and 323ml of purified water are added into a reaction bottle, the temperature is raised to 20 ℃ by stirring, 40.72g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 2 hours at 20 ℃ by stirring after the addition.
2. 30.63g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 100 ℃ with stirring, and the reaction is carried out for 6h.
3. And cooling the liquid obtained in the second step to 60 ℃, adding 111.41g of 36% hydrochloric acid, and stirring at 60 ℃ for reaction for 2 hours.
4. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 7.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 72.72g of aminomethylbenzoic acid, 7.6% of water content, 99.93% of purity and 88.9% of yield are obtained.
5. 107.52g of p-bromomethylbenzoic acid is added into the filtrate obtained in the step 4, the temperature is raised to 20 ℃ by stirring, 40.72g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 2 hours at 20 ℃ by stirring after the addition.
6. 30.63g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 100 ℃ with stirring, and the reaction is carried out for 6h.
7. And cooling the liquid obtained in the second step to 60 ℃, adding 111.41g of 36% hydrochloric acid, and stirring at 60 ℃ for reaction for 2 hours.
8. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 7.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 81.96g of aminomethylbenzoic acid, 10.0% of water content, 99.80% of purity and 97.6% of yield are obtained. The obtained filtrate can be reused for multiple times.
Example 4
1. 107.52g of p-bromomethylbenzoic acid and 538ml of purified water are added into a reaction flask, the temperature is raised to 30 ℃ with stirring, 39.93g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 1h at 30 ℃ with stirring after the addition.
2. 31.53g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 80 ℃ with stirring, and the reaction is carried out for 8 hours.
3. 126.60g of 36% hydrochloric acid was added to the second reaction mixture, and the mixture was stirred at 80℃for 1 hour.
4. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 6.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 74.74g of aminomethylbenzoic acid, 9.8% of water content, 99.97% of purity and 89.2% of yield are obtained.
5. 107.52g of p-bromomethylbenzoic acid is added into the filtrate obtained in the step 4, the temperature is raised to 30 ℃ by stirring, 39.93g of solid ammonium bicarbonate is slowly added, and the reaction is carried out for 1h at 30 ℃ by stirring after the addition.
6. 31.53g of urea is added into the neutralization feed liquid in the first step, the temperature is raised to 80 ℃ with stirring, and the reaction is carried out for 8 hours.
7. 126.60g of 36% hydrochloric acid was added to the second reaction mixture, and the mixture was stirred at 80℃for 1 hour.
8. And (3) cooling the liquid obtained in the third step to 25 ℃, adjusting the pH value of the liquid to 6.5 by using ammonia water, stirring at 25 ℃ for 0.5h for crystallization, carrying out suction filtration, leaching by using a small amount of water, and carrying out vacuum drying on a filter cake at 50 ℃ for 5h. 81.18g of aminomethylbenzoic acid, 9.6% of water content, 99.88% of purity and 97.1% of yield are obtained. The obtained filtrate can be reused for multiple times.
Claims (8)
1. A process for preparing 4-aminomethylbenzoic acid from p-halomethylbenzoic acid by reaction with amination reagent in the presence of solvent, characterized in that the raw material is neutralized in water by alkali and then is subject to amination reaction by urea; acidolysis and crystallization are carried out after the reaction to obtain 4-aminomethylbenzoic acid;
acidolysis is carried out after the reaction, stirring crystallization is carried out, and filtering is carried out, wherein a filter cake is 4-aminomethylbenzoic acid; the filtrate is returned to the system for application.
2. A process for preparing 4-aminomethylbenzoic acid according to claim 1, wherein: adding alkali into solvent water to perform neutralization reaction for 0.5-3h at 10-40 ℃.
3. A process for preparing 4-aminomethylbenzoic acid according to claim 2, wherein: the mass of the solvent water is 2-10 times of the mass of the raw materials; the molar amount of the base is 1.00-2.00 times of that of the halomethyl benzoic acid.
4. A process for preparing 4-aminomethylbenzoic acid according to claim 2, wherein: the raw material p-halomethylbenzoic acid is p-bromomethylbenzoic acid or p-chloromethylbenzoic acid; the base is selected from ammonium bicarbonate or ammonium carbonate.
5. A process for preparing 4-aminomethylbenzoic acid according to claim 1, wherein: adding carbamide serving as an amination reagent into the system after the neutralization reaction, and carrying out amination reaction for 2-15h at 40-100 ℃.
6. A process for preparing 4-aminomethylbenzoic acid according to claim 5, wherein: the molar quantity of urea is 1.00-2.00 times of that of the para-halomethyl benzoic acid.
7. A process for preparing 4-aminomethylbenzoic acid according to claim 1, wherein: after the amination reaction, acid is added into the system to carry out acidolysis reaction for 0.5-6h at 50-100 ℃ so that the pH value of the system is 4.0-8.0.
8. The process for preparing 4-aminomethylbenzoic acid according to claim 7, wherein: the addition amount of the acid is 2.0-3.0 times of the mole number of the p-halomethyl benzoic acid; wherein the acid is sulfuric acid or hydrochloric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010776212.4A CN114057592B (en) | 2020-08-05 | 2020-08-05 | Method for preparing 4-aminomethylbenzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010776212.4A CN114057592B (en) | 2020-08-05 | 2020-08-05 | Method for preparing 4-aminomethylbenzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114057592A CN114057592A (en) | 2022-02-18 |
| CN114057592B true CN114057592B (en) | 2023-08-22 |
Family
ID=80232109
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010776212.4A Active CN114057592B (en) | 2020-08-05 | 2020-08-05 | Method for preparing 4-aminomethylbenzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114057592B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101291924A (en) * | 2005-08-31 | 2008-10-22 | 细胞基因公司 | Isoindole-imide compounds and compositions comprising and methods of using the same |
| CN102718673A (en) * | 2011-12-16 | 2012-10-10 | 常江 | Novel technology for synthesis of aminomethylbenzoic acid |
| CN102816077A (en) * | 2012-09-21 | 2012-12-12 | 上海现代哈森（商丘）药业有限公司 | Application of urotropine as catalyst in aminomethylbenzoic acid synthesis |
| JP2013047189A (en) * | 2009-12-25 | 2013-03-07 | Kyorin Pharmaceutical Co Ltd | Novel parabanic acid derivative, and medicine containing the same as effective component |
| CN108912002A (en) * | 2018-06-27 | 2018-11-30 | 周道平 | The preparation method of aminomethylbenzoic acid |
| CN109879769A (en) * | 2019-03-22 | 2019-06-14 | 邯郸市赵都精细化工有限公司 | A kind of bromo element recycles the method for preparing aminomethylbenzoic acid |
| CN111333587A (en) * | 2020-04-11 | 2020-06-26 | 东莞市东阳光新药研发有限公司 | Substituted pyrimidine-2, 4(1H,3H) -dione derivatives and uses thereof |
-
2020
- 2020-08-05 CN CN202010776212.4A patent/CN114057592B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101291924A (en) * | 2005-08-31 | 2008-10-22 | 细胞基因公司 | Isoindole-imide compounds and compositions comprising and methods of using the same |
| JP2013047189A (en) * | 2009-12-25 | 2013-03-07 | Kyorin Pharmaceutical Co Ltd | Novel parabanic acid derivative, and medicine containing the same as effective component |
| CN102718673A (en) * | 2011-12-16 | 2012-10-10 | 常江 | Novel technology for synthesis of aminomethylbenzoic acid |
| CN102816077A (en) * | 2012-09-21 | 2012-12-12 | 上海现代哈森（商丘）药业有限公司 | Application of urotropine as catalyst in aminomethylbenzoic acid synthesis |
| CN108912002A (en) * | 2018-06-27 | 2018-11-30 | 周道平 | The preparation method of aminomethylbenzoic acid |
| CN109879769A (en) * | 2019-03-22 | 2019-06-14 | 邯郸市赵都精细化工有限公司 | A kind of bromo element recycles the method for preparing aminomethylbenzoic acid |
| CN111333587A (en) * | 2020-04-11 | 2020-06-26 | 东莞市东阳光新药研发有限公司 | Substituted pyrimidine-2, 4(1H,3H) -dione derivatives and uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| Guseinov, I. Sh.etal. Preparation of chloro- and aminomethyl derivatives of sterically hindered phenols.《Azerbaidzhanskii Khimicheskii Zhurnal》.2007,114-117. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114057592A (en) | 2022-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US2628889A (en) | Preparation of hydroxylamine | |
| CN101927178B (en) | Solid super basic catalyst and preparation method and application thereof | |
| CN114057592B (en) | Method for preparing 4-aminomethylbenzoic acid | |
| CN102757346A (en) | Preparation method of dimethyl fumarate | |
| CN102040494A (en) | Method for preparing p-fluorobenzaldehyde | |
| CN111808054A (en) | Preparation method of ionic liquid and application of ionic liquid in cyclohexanone synthesis | |
| CN114989044B (en) | Catalytic synthesis method of dicarbamate | |
| US3956387A (en) | Manufacture of concentrated aqueous (meth)acrylamide solutions by catalytic addition of water to (meth)acrylonitrile | |
| CN105218398A (en) | A kind of method of preparing cyclohexanone oxime through cyclohexanone liquid phase ammonia oximate | |
| CN113121368A (en) | Method for preparing gamma-aminopropanol by one-step catalytic hydrogenation and application thereof | |
| CN109824516B (en) | Preparation method of trans-4-hydroxycyclohexanecarboxylic acid tert-butyl ester | |
| CN113929588B (en) | Method for synthesizing 4-aminomethylbenzoic acid | |
| CN104549208B (en) | A kind of catalyst of Synthesis of dimethyl carbonate and its preparation method and application | |
| JP4001937B2 (en) | Aminopropionitrile production process | |
| CN107335439B (en) | Preparation method and application of nitrogen-doped carbon-silicon-based bimetallic catalyst for synthesizing amide by direct dehydrogenation of kinds of alcohol amine | |
| CN113801009B (en) | Method for catalyzing gallic acid methylation by using ionic liquid | |
| CN1055922A (en) | 2,4-xylidine and 2, the preparation method of 6-xylidine | |
| CN111170878A (en) | Method for preparing D-type or L-type tert-leucine | |
| CN101817776B (en) | Method for synthesizing 9-fluorenylmethoxycarbonyloxy succinimide ester | |
| CN101318144A (en) | Catalyst for preparing amide compounds, synthesis and application thereof | |
| CN1023400C (en) | Process for preparing 4-amino-3-methylphenol | |
| CN107118095B (en) | High-content potassium isooctanoate composition and preparation method thereof | |
| CN1333208A (en) | Process for preparing natural vitamin E monomester succinate | |
| CN108623488A (en) | A kind of synthetic method of aminomethylbenzoic acid | |
| CN108117490B (en) | Preparation method of p-nitrobenzyl alcohol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |