CN109879769B - Method for preparing aminomethylbenzoic acid by recycling bromine - Google Patents
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Abstract
The invention discloses a method for preparing aminomethylbenzoic acid by recycling bromine, which comprises the following steps: carrying out bromination reaction on methyl benzoic acid and a bromination agent in the presence of a catalyst I and an oxidant to prepare p-bromomethyl benzoic acid, then carrying out ammonolysis on the p-bromomethyl benzoic acid in the presence of a catalyst II to obtain a product aminomethylbenzoic acid, and recovering bromine-containing mother liquor generated by the bromination reaction and the ammonolysis reaction by a method of precipitation, distillation and filtration. The yield of the product aminomethylbenzoic acid after recrystallization is not less than 96 percent, and the product purity is 99 percent. The brominating agent contains bromine element, and is selected from hydrogen bromide and acidic bromine-containing solution. The aminomethylbenzoic acid obtained by the method has high yield and purity, and can recycle bromine and ammonia water in a reaction system, thereby reducing the production cost.
Description
Technical Field
The invention belongs to the technical field of drug synthesis, and particularly relates to a method for preparing aminomethylbenzoic acid by recycling bromine.
Background
Aminomethylbenzoic acid is a procoagulant drug, has excellent effects of stopping bleeding and preventing bleeding, and can prevent and improve pigmentation of skin color, so that the aminomethylbenzoic acid is widely applied to the fields of medicines and daily chemicals. The hemostatic principle of aminomethylbenzoic acid is that under normal conditions, the activity of the natural antagonist (i.e., anti-fibrinolytic substance) of various kinds of plasmin in blood is many times higher than that of fibrinolytic substance, so fibrinolytic bleeding does not occur, but the anti-fibrinolytic substance cannot block plasmin formed by activation of activator adsorbed on fibrin network; plasmin is an endopeptidase which can cleave arginine and lysine peptide chains of fibrin in a neutral environment to form fibrin degradation products and cause thrombolysis bleeding; plasmin is specifically adsorbed on fibrin by neutralizing the binding site of lysine in the molecular structure of plasmin, and lysine can competitively inhibit the adsorption, so as to reduce the adsorption rate of plasmin, thereby reducing the activation degree of plasmin and reducing bleeding; the spatial configuration of aminomethylbenzoic acid is similar to that of lysine, and can competitively inhibit plasmin from being adsorbed on the fibrin network, thereby preventing activation of the plasmin and protecting fibrin from being degraded by the plasmin to achieve hemostasis. The aminomethylbenzoic acid is also the main raw material for preparing the tranexamic acid which is a hemostatic drug, and the market demand is large.
The preparation method of aminomethylbenzoic acid mainly comprises the following steps: (1) the p-nitrobenzoic acid is adopted as a raw material, is reduced by iron powder and hydrochloric acid to obtain p-aminobenzoic acid, then is subjected to diazotization reaction by utilizing sodium nitrite, and then is reacted with sodium cyanide to generate p-cyanobenzoic acid, and finally is reduced by hydrogen under the catalysis of raney nickel to obtain the aminomethylbenzoic acid. (2) The p-xylene is used as a raw material, and the catalytic oxidation, chlorination and ammoniation are carried out to obtain the aminomethylbenzoic acid, but the chlorination reaction is limited more, the byproducts are more, and the yield is lower. (3) The p-cyanobenzyl chloride is used as a raw material, and the p-cyanobenzyl chloride is subjected to acid hydrolysis and ammoniation to obtain the aminomethylbenzoic acid, wherein the method has a short route, but a hydrolysis by-product benzyl chloride is generated during hydrolysis, and the crystal structures of the products are different. Most of the industrial production adopts the chlorination and ammonolysis of p-toluic acid to produce aminomethylbenzoic acid, but in the process of preparing p-chloromethylbenzoic acid by the action of p-toluic acid and chlorine, the calculated yield of p-chloromethylbenzoic acid is only 50 percent, the effective utilization rate of chlorine atoms is only 25 percent, a large amount of polychlorinated products and isomers are generated by chlorination reaction, the by-product components are complex and difficult to treat, and finally, a large amount of waste water, organic waste residues and industrial sodium chloride are generated, thereby causing environmental hazard.
Patent No. cn201510338012.x discloses a preparation method of aminomethylbenzoic acid, which comprises using p-cyanobenzyl halide (especially p-cyanobenzyl chloride) as raw material, carrying out ammonolysis reaction under catalysis of urotropine to obtain intermediate p-cyanobenzylamine, and carrying out acid hydrolysis to obtain final product aminomethylbenzoic acid. Patent CN201810634724.X provides a synthesis method of aminomethylbenzoic acid, which comprises adding dropwise an ethanol-water solution dissolved with 2-amino-5-methyl-1, 3, 4-thiadiazole into 4-halomethyl alkyl benzoate and triethylamine under stirring, evaporating the solution after reaction is completed until a large amount of solid is separated out, cooling, filtering and drying to obtain 4-aminomethyl alkyl benzoate; adding 4-aminomethyl alkyl benzoate into an acid solution, stirring for reaction, cooling, adding water, dropwise adding alkali until the solution becomes alkaline and a large amount of solids are separated out, filtering, washing and drying to obtain aminomethylbenzoic acid.
At present, the preparation method of aminomethylbenzoic acid has a plurality of problems, such as difficult acquisition of raw materials, low product yield, complex preparation process, high cost, more byproducts and difficult treatment, a large amount of waste liquid and waste residue generated in the process, and environmental pollution.
Disclosure of Invention
In order to solve the problems, the invention provides a method for preparing aminomethylbenzoic acid by recycling bromine, which takes p-methylbenzoic acid and a brominating agent as initial raw materials, prepares p-bromomethylbenzoic acid under the combined action of a catalyst and an oxidant, and then reacts with ammonia water to obtain the aminomethylbenzoic acid. The aminomethylbenzoic acid obtained by the method has high yield and purity, and can recycle bromine and ammonia water in a reaction system, thereby reducing the production cost.
In order to achieve the purpose, the technical scheme adopted by the invention is to provide a method for preparing aminomethylbenzoic acid by recycling bromine, which comprises the following steps: carrying out bromination reaction on methyl benzoic acid and a bromination agent in the presence of a catalyst I and an oxidant to prepare p-bromomethyl benzoic acid, then carrying out ammonolysis on the p-bromomethyl benzoic acid in the presence of a catalyst II to obtain a product aminomethylbenzoic acid, and recovering bromine-containing mother liquor generated by the bromination reaction and the ammonolysis reaction by a method of precipitation, distillation and filtration. The brominating agent is selected from hydrogen bromide and acidic bromine-containing solution, and preferably, the brominating agent is HBr solution. The adding mode of the hydrogen bromide can be that hydrogen bromide gas is introduced into a reaction system, and water solution of the hydrogen bromide gas can also be added; preferably, the concentration of the hydrogen bromide solution is 30-40%, and more preferably, the concentration of the hydrogen bromide solution is 35-40%.
The acidic bromine-containing solution is prepared by dissolving a bromine-containing compound in an acid, preferably, the bromine-containing compound is selected from bromine salts such as potassium bromide, sodium bromide, ammonium bromide and the like, and the acid is selected from hydrochloric acid and sulfuric acid.
The mass ratio of the raw material p-methylbenzoic acid to the brominating agent in the bromination reaction is 1 (1-3), and preferably, the mass ratio of the p-methylbenzoic acid to the brominating agent is 1 (1.5-2.5).
The temperature of the bromination reaction is 15-80 ℃, and preferably, the temperature of the bromination reaction is 30-45 ℃.
The bromination reaction time is 8 to 30 hours, and preferably, the bromination reaction time is 10 to 15 hours.
The reaction principle of the invention is that the p-methyl benzoic acid and the brominating agent can carry out bromination reaction in the presence of the catalyst and the oxidant to generate an intermediate product p-bromomethyl benzoic acid, and the intermediate product and ammonia water are subjected to ammonolysis reaction to finally prepare the aminomethylbenzoic acid. Unexpectedly, the invention discovers that the brominating agent is used as a raw material, so that byproducts can be reduced, the yield and the purity of the product are improved, the reaction condition is mild, and the used reagents are conventional chemicals and are simple and easy to obtain; the bromine-containing mother liquor generated after the reaction of the brominating agent can recover the brominating agent through inorganic reaction and conventional chemical treatment, thereby greatly reducing the production cost.
And the catalyst I in the bromination reaction is a free radical initiator or fluorescent irradiation. Preferably, the radical initiator is selected from azo initiators and peroxides, and more preferably, the radical initiator is selected from azobisisobutyronitrile, azobisisoheptonitrile, cyclohexanone peroxide, dibenzoyl peroxide, cumene hydroperoxide, tert-butyl peroxybenzoate, and cumene hydroperoxide. Preferably, the fluorescence is ultraviolet light.
Preferably, when the catalyst I is a radical initiator, the amount of the catalyst I is 0.1 to 5wt% of p-toluic acid, and preferably, the amount of the catalyst I is 2 to 5wt% of p-toluic acid.
The solvent used in the bromination reaction is not particularly limited as long as it is an organic solvent which does not adversely affect the bromination reaction, and examples thereof include chloroalkanes, ethers, ketones, and the like, such as dichloromethane, trichloromethane, carbon tetrachloride, and dichloroethane. For the convenience of recycling the solvent, those having a relatively low boiling point, such as dichloromethane, chloroform, diethyl ether, acetone, etc., are preferable. And an oxidant is also required to be added in the bromination reaction, the oxidant is peroxide, and preferably, the peroxide is selected from hydrogen peroxide, peroxyacetic acid and ammonium persulfate. The mass ratio of the oxidant to the p-toluic acid is 1: (0.5-2.5), preferably, the mass ratio of the oxidant to the p-toluic acid is 1: (0.7-2).
The inventor unexpectedly finds that when the bromination reaction is carried out, the hydrogen bromide or the acidic bromine-containing solution is used as the brominating agent, and the side reaction can be effectively reduced compared with the conventional brominating agent such as N-bromosuccinimide (NBS); meanwhile, unexpectedly, the oxidizing agent with a specified dosage is matched with the brominating agent to carry out the bromination reaction with the p-methyl benzoic acid, so that the byproducts can be effectively reduced, the yield and the purity of the p-bromomethyl benzoic acid can be improved, and the mother liquor after the bromination reaction can be recycled by using the method provided by the invention.
And filtering the reaction liquid obtained by the bromination reaction to obtain a filter cake, namely the intermediate product p-bromomethylbenzoic acid, heating the filtrate and recovering the solvent I, wherein the residual filtrate is used as a part of mother liquor.
And heating the filtrate by adopting a rotary evaporation or distillation method, evaporating the solvent I in the filtrate and recycling the solvent I for the next use.
The ammonolysis reaction is to carry out ammonolysis reaction on an intermediate product bromomethylbenzoic acid and excessive ammonia water under the action of a catalyst II, and the time of the ammonolysis reaction is 4-6 hours.
The temperature of the ammonolysis reaction is 10-80 ℃, and preferably, the temperature of the ammonolysis reaction is 10-20 ℃.
Preferably, the catalyst II is selected from ammonium bicarbonate and urotropin.
The concentration of the ammonia water is 10-28 wt%.
In the ammonolysis reaction, the molar ratio of the p-bromomethylbenzoic acid to the ammonia water to the catalyst II is that of the p-bromomethylbenzoic acid: ammonia water: catalyst ii is 1: (1-10): (1-2), preferably, the molar ratio of the p-bromomethylbenzoic acid to the ammonia water to the catalyst II is p-bromomethylbenzoic acid: ammonia water: catalyst ii is 1: (4-10): (1.3-2).
The present inventors have unexpectedly found that when the catalyst II is used in a predetermined amount during the ammonolysis reaction, the rate of the ammonolysis reaction can be increased and the mother liquor after the ammonolysis reaction can be recovered and reused by the method of the present invention.
And (2) discharging ammonia gas from the reaction liquid obtained in the ammonolysis reaction under negative pressure, recovering the ammonia gas, adding alkali into the reaction liquid until the pH value is 6.8-8.0, filtering, drying the obtained filter cake to obtain a crude product, recrystallizing to obtain a product of aminomethylbenzoic acid, and using the obtained filtrate as the other part of mother liquor.
The process of discharging the ammonia gas under negative pressure can also adopt one or two combination modes of heating and negative pressure, and preferably, the temperature of the discharged ammonia gas is 30-50 ℃.
The alkali is strong alkali or weak alkali, preferably sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, etc.
According to the preparation method of the invention, the yield of the obtained aminomethylbenzoic acid product is not less than 96%, and the product purity is 99%.
The mother liquor obtained by the bromination reaction and the aminolysis reaction is bromine-containing mother liquor, and the bromine-containing mother liquor contains unreacted raw material p-toluic acid, a small amount of product aminomethylbenzoic acid, bromine-containing salt, catalyst I, catalyst II and water.
The bromine-containing mother liquor is recovered by precipitation, distillation and filtration.
The precipitation method is to add alkali into bromine-containing mother liquor to adjust the pH value, so that the raw material p-toluic acid and the product aminomethylbenzoic acid are precipitated from the mother liquor. The alkali is selected from sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, etc. The distillation method is to distill out the water in the bromine-containing mother liquor treated by the precipitation method.
Adding the residual residue of the bromine-containing mother liquor treated by the distillation method into a solvent II, stirring and filtering to obtain a filter cake containing bromine salt, distilling the obtained filtrate to recover the solvent II, adding strong acid into the bromine-containing salt to obtain the brominating agent, and waiting for reuse.
The solvent II is selected from one or a combination of more than two of methanol, ethanol, isopropanol, acetone, diethyl ether, methyl tert-butyl ether, acetonitrile, N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone and tetrahydrofuran, and preferably, the solvent II is selected from one or a combination of more than two of N, N-dimethylformamide, dimethyl sulfoxide, acetonitrile and tetrahydrofuran.
Preferably, the strong acid is sulfuric acid or hydrochloric acid, and the mass ratio of the strong acid to the bromine-containing salt is (0.5-2): 1. the aqueous solution prepared from the bromine-containing salt and strong acid is used as a brominating agent and can react with p-methylbenzoic acid again to prepare p-bromomethylbenzoic acid, so that the cyclic utilization of bromine is realized; meanwhile, the strong acid salt generated by the reaction of the bromine-containing salt and the strong acid is a valuable industrial salt.
Preferably, the method for preparing aminomethylbenzoic acid by recycling bromine comprises the following steps: (a) bromination reaction: dissolving p-methyl benzoic acid in a solvent I, adding a brominating agent, and carrying out bromination reaction in the presence of a catalyst I and an oxidant to obtain p-bromomethyl benzoic acid; (b) ammonolysis reaction: carrying out ammonolysis reaction on the obtained p-bromomethylbenzoic acid and excessive ammonia water under the action of a catalyst II to obtain aminomethylbenzoic acid; (c) recycling of bromine and ammonia water: and (c) heating the mother liquor in the step (b) to enable ammonia gas to overflow, absorbing and recycling, and adding a solvent II and strong acid into the mother liquor in the steps (a) and (b) to generate a brominating agent for recycling.
Preferably, the method comprises the steps of:
(1) adding the raw materials of p-toluic acid, a solvent I, a brominating agent and water into a reactor, stirring and dissolving, adding a catalyst I and an oxidant, and carrying out bromination reaction at the temperature of 15-80 ℃ for 8-30 hours;
(2) filtering the reaction solution obtained in the step (1), wherein a filter cake is p-bromomethylbenzoic acid, heating the filtrate and recovering a solvent I, and the residual filtrate is used as a part of mother liquor;
(3) adding the p-bromomethylbenzoic acid and excessive ammonia water into a reactor, stirring and dissolving, adding a catalyst II, and carrying out an ammonolysis reaction at the temperature of 10-80 ℃ for 4-6 hours;
(4) discharging ammonia gas from the reaction liquid obtained in the step (3) under negative pressure, absorbing and recycling the ammonia gas, and adding alkali into the reaction liquid to be neutral;
(5) filtering the reaction liquid obtained in the step (4), drying the obtained filter cake to obtain aminomethylbenzoic acid, and taking the obtained filtrate as the other part of mother liquor for later use;
(6) adding alkali into the mother liquor obtained in the steps (2) and (5) to separate out p-toluic acid and aminomethylbenzoic acid in the mother liquor, evaporating residual water, adding a solvent II into residual residues, stirring and filtering to obtain a filter cake containing bromine salt, and distilling the obtained filtrate to recover the solvent II;
(7) and (4) adding strong acid into the bromine-containing salt obtained in the step (6) to prepare a brominating agent, and waiting for reuse. Due to the adoption of the technical scheme, the invention has the following beneficial effects:
1. in the bromination reaction, the inventor unexpectedly finds that when the hydrogen bromide or the bromine-containing solution is used as the bromination reagent, compared with the conventional bromination reagent, the method for bromination of p-toluic acid has the advantages of less side reactions, stable reaction, 96% aminomethylbenzoic acid yield and high aminomethylbenzoic acid purity, does not need complicated separation and purification means, and can obtain a product with the purity of 99% by simple recrystallization operation.
2. The technical scheme provided by the invention can realize the cyclic utilization of the brominating agent, the solvent I, the solvent II and the ammonia water, reduces the production cost, basically has no emission of solid waste, waste gas and waste liquid, and belongs to an environment-friendly process.
3. According to the technical scheme provided by the invention, the mother liquor generates brominating agent and strong acid salt, so that the method has double utilization values, can further reduce the production cost, and has good commercial popularization value.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and the contents of the embodiments should not be construed as limiting the scope of the present invention.
Example 1
(1) Adding 108.8g of p-toluic acid, 500g of dichloroethane and 170.5g of 38% aqueous HBr solution into a reactor, stirring for dissolving, adding 2g of azobisisobutyronitrile and 77.7g of hydrogen peroxide (the concentration is 35%) for bromination reaction, wherein the bromination reaction temperature is 40 ℃ and the bromination reaction time is 12 hours;
(2) cooling the reaction liquid obtained in the step (1) to 20 ℃, filtering to obtain a filter cake, namely p-bromomethylbenzoic acid, heating the filtrate and recovering dichloroethane, and using the residual filtrate as a part of mother liquor;
(3) adding p-bromomethylbenzoic acid and 600g of 25% ammonia water into a reactor, stirring and dissolving, adding 150g of urotropine, and carrying out an ammonolysis reaction at the temperature of 10-20 ℃ for 5 hours;
(4) controlling the temperature of the reaction liquid obtained in the step (3) below 50 ℃, discharging excessive ammonia gas under negative pressure, absorbing and recycling the ammonia gas, and adding NaOH into the reaction liquid until the PH value is 6.8-8.0;
(5) filtering the reaction liquid obtained in the step (4), drying the obtained filter cake for 5 hours at 50 ℃ to obtain aminomethylbenzoic acid, and taking the obtained filtrate as the other part of mother liquor for later use;
(6) adding 32g of NaOH into the mother liquor obtained in the steps (2) and (5) to separate out p-toluic acid and aminomethylbenzoic acid in the mother liquor, evaporating the rest water, adding 1000g of anhydrous methanol and 200g of anhydrous ethanol into the rest residues, heating for 3 hours, cooling to below 20 ℃, filtering to obtain a filter cake of NaBr, and distilling the obtained filtrate to recover the anhydrous methanol and the anhydrous ethanol;
(7) 51g of concentrated sulfuric acid was added to NaBr in step (6) to prepare HBr, and the HBr was used again.
Example 2
(1) Adding 50g of p-toluic acid, 110g of dichloromethane and 90g of 40% HBr aqueous solution into a reactor, stirring for dissolving, adding 1.5g of azobisisobutyronitrile and 40g of hydrogen peroxide (the concentration is 35%), and carrying out bromination reaction at the temperature of 45 ℃ for 10 hours;
(2) cooling the reaction liquid obtained in the step (1) to 20 ℃, filtering to obtain a filter cake, namely p-bromomethylbenzoic acid, heating the filtrate and recovering dichloromethane, and using the residual filtrate as a part of mother liquor for later use;
(3) adding p-bromomethylbenzoic acid and 320g of 18% ammonia water into a reactor, stirring and dissolving, adding 80g of urotropine, and carrying out an ammonolysis reaction at the temperature of 10-20 ℃ for 5 hours;
(4) controlling the temperature of the reaction liquid obtained in the step (3) below 50 ℃, discharging excessive ammonia gas under negative pressure, absorbing and recycling the ammonia gas, and adding NaOH into the reaction liquid until the PH value is 6.8-8.0;
(5) filtering the reaction liquid obtained in the step (4), drying the obtained filter cake for 5 hours at 50 ℃ to obtain aminomethylbenzoic acid, and taking the obtained filtrate as the other part of mother liquor for later use;
(6) adding 15g of NaOH into the mother liquor obtained in the steps (2) and (5) to separate out p-toluic acid and aminomethylbenzoic acid in the mother liquor, evaporating the rest water, adding 600g of N, N-dimethylformamide into the rest residues, heating for 3 hours, cooling to below 20 ℃, filtering to obtain a filter cake of NaBr, and distilling the obtained filtrate to recover N, N-dimethylformamide;
(7) adding 25g of concentrated sulfuric acid into NaBr in the step (6) to prepare HBr, and waiting for reuse.
Example 3
(1) Adding 30g of p-toluic acid, 600g of dichloromethane and 60g of 35% HBr aqueous solution into a reactor, stirring for dissolving, adding 6g of peroxyacetic acid, and applying ultraviolet light to perform bromination reaction at the temperature of 30 ℃ for 15 hours;
(2) cooling the reaction liquid obtained in the step (1) to 20 ℃, filtering to obtain a filter cake, namely p-bromomethylbenzoic acid, heating the filtrate and recovering dichloromethane, and using the residual filtrate as a part of mother liquor for later use;
(3) adding p-bromomethylbenzoic acid and 77g of 28% ammonia water into a reactor, stirring and dissolving, adding 40g of urotropine, and carrying out an ammonolysis reaction at the temperature of 10-20 ℃ for 5 hours;
(4) controlling the temperature of the reaction liquid obtained in the step (3) below 50 ℃, discharging excessive ammonia gas under negative pressure, absorbing and recycling the ammonia gas, and adding NaOH into the reaction liquid until the PH value is 6.8-8.0;
(5) filtering the reaction liquid obtained in the step (4), drying the obtained filter cake for 5 hours at 50 ℃ to obtain aminomethylbenzoic acid, and taking the obtained filtrate as the other part of mother liquor for later use;
(6) adding 14g of NaOH into the mother liquor obtained in the steps (2) and (5) to separate out p-toluic acid and aminomethylbenzoic acid in the mother liquor, evaporating the rest water, adding 200g of ethanol into the rest residues, heating for 3 hours, cooling to below 20 ℃, filtering, obtaining a filter cake of NaBr, and distilling the obtained filtrate to recover ethanol;
(7) adding 13g of concentrated sulfuric acid into NaBr in the step (6) to prepare HBr, and waiting for reuse.
Example 4
(1) Adding 80g of p-toluic acid, 1000g of carbon tetrachloride and 160g of 30% HBr aqueous solution into a reactor, stirring for dissolving, adding 8g of ammonium persulfate and 4g of azobisisoheptonitrile, and carrying out bromination reaction at the bromination reaction temperature of 45 ℃ for 15 hours;
(2) cooling the reaction liquid obtained in the step (1) to 20 ℃, filtering to obtain a filter cake, namely p-bromomethylbenzoic acid, heating the filtrate and recovering carbon tetrachloride, wherein the residual filtrate is used as a part of mother liquor;
(3) adding p-bromomethylbenzoic acid and 1000g of 10% ammonia water into a reactor, stirring for dissolving, adding 164.6g of urotropine, and carrying out ammonolysis reaction at the temperature of 10-20 ℃ for 5 hours;
(4) controlling the temperature of the reaction liquid obtained in the step (3) below 50 ℃, discharging excessive ammonia gas under negative pressure, absorbing and recycling the ammonia gas, and adding NaOH into the reaction liquid until the PH value is 6.8-8.0;
(5) filtering the reaction liquid obtained in the step (4), drying the obtained filter cake for 5 hours at 50 ℃ to obtain aminomethylbenzoic acid, and taking the obtained filtrate as the other part of mother liquor for later use;
(6) adding 25g of NaOH into the mother liquor obtained in the steps (2) and (5) to separate out p-toluic acid and aminomethylbenzoic acid in the mother liquor, evaporating the rest water, adding 600g of ethanol into the rest residues, heating for 3 hours, cooling to below 20 ℃, filtering, obtaining a filter cake of NaBr, and distilling the obtained filtrate to recover ethanol;
(7) 38g of concentrated sulfuric acid was added to NaBr in step (6) to prepare HBr, and the HBr was used again.
Comparative example 1
The brominating agent used in this comparative example was N-bromosuccinimide (NBS), and the other preparation steps and amounts were the same as those of example 1.
The yields and purity data by HPLC of the aminomethylbenzoic acids of the products of examples 1 to 4 and comparative example 1 are shown in Table 1.
TABLE 1 product yield and purity of examples 1-4 and comparative example 1
| Yield (%) | Purity (%) | |
| Example 1 | 96 | 99 |
| Example 2 | 96 | 99 |
| Example 3 | 97 | 99 |
| Example 4 | 98 | 99 |
| Comparative example 1 | 73 | 80 |
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and the like that are within the spirit and principle of the present invention are included in the present invention.
Claims (7)
1. A method for preparing aminomethylbenzoic acid by recycling bromine, which is characterized by comprising the following steps: carrying out bromination reaction on methyl benzoic acid and a bromination agent in the presence of a catalyst I and an oxidant to prepare p-bromomethyl benzoic acid, then carrying out ammonolysis on the p-bromomethyl benzoic acid and the bromination agent in the presence of a catalyst II to obtain a product aminomethylbenzoic acid, and recovering bromine-containing mother liquor generated by the bromination reaction and the ammonolysis reaction by a method of precipitation, distillation and filtration; the yield of the product aminomethylbenzoic acid after recrystallization is not less than 96 percent, and the product purity is 99 percent, wherein
The brominating agent is selected from hydrogen bromide and acidic bromine-containing solution; the catalyst I in the bromination reaction is a free radical initiator, and the free radical initiator is an azo initiator; the oxidant is peroxide; the mass ratio of the oxidant to the p-toluic acid is 1: (0.5-2.5); in the ammonolysis reaction, the molar ratio of the p-bromomethylbenzoic acid to the ammonia water to the catalyst II is that of the p-bromomethylbenzoic acid: ammonia water: catalyst ii = 1: (1-10): (1-2).
2. The method according to claim 1, wherein the temperature of the bromination reaction is 30-45 ℃ and the time of the bromination reaction is 10-15 hours.
3. The process according to claim 1, wherein catalyst I is used in an amount of 0.1 to 5wt% based on p-toluic acid.
4. The process of claim 1, wherein the catalyst II in the ammonolysis reaction is selected from the group consisting of ammonium bicarbonate and urotropine, and the concentration of the aqueous ammonia is 10-28%.
5. The method according to claim 1, wherein the molar ratio of the p-bromomethylbenzoic acid, the ammonia water and the catalyst II is p-bromomethylbenzoic acid: ammonia water: catalyst ii = 1: (4-10): (1.3-2).
6. The method as claimed in claim 1, wherein the precipitation method comprises the steps of adding alkali into the bromine-containing mother liquor to adjust the pH value, so that the raw material p-toluic acid and the product aminomethylbenzoic acid are precipitated from the bromine-containing mother liquor; the distillation method is to evaporate water in the bromine-containing mother liquor treated by the precipitation method; adding the residual residue of the bromine-containing mother liquor treated by the distillation method into a solvent II, stirring and filtering to obtain a filter cake containing bromine salt, distilling the obtained filtrate to recover the solvent II, and adding strong acid into the bromine-containing salt to obtain the brominating agent.
7. The process of claim 6, wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium bicarbonate, and potassium bicarbonate, and the strong acid is sulfuric acid.
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| CN113929588B (en) * | 2020-06-29 | 2023-08-15 | 沈阳化工研究院有限公司 | Method for synthesizing 4-aminomethylbenzoic acid |
| CN114057592B (en) * | 2020-08-05 | 2023-08-22 | 沈阳化工研究院有限公司 | Method for preparing 4-aminomethylbenzoic acid |
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