CN115322102A - Synthetic method for producing 2-fluoro-3-nitrobenzoic acid from 2-chloro-3-nitrotoluene - Google Patents
Synthetic method for producing 2-fluoro-3-nitrobenzoic acid from 2-chloro-3-nitrotoluene Download PDFInfo
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- WLGUSLGYTNJJFV-UHFFFAOYSA-N 2-fluoro-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1F WLGUSLGYTNJJFV-UHFFFAOYSA-N 0.000 title claims abstract description 29
- XTSGZXRUCAWXKY-UHFFFAOYSA-N 2-chloro-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1Cl XTSGZXRUCAWXKY-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000010189 synthetic method Methods 0.000 title description 4
- 239000000243 solution Substances 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 39
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 35
- 230000007062 hydrolysis Effects 0.000 claims abstract description 32
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 26
- NBCNUIXYBLFJMI-UHFFFAOYSA-N 2-fluoro-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1F NBCNUIXYBLFJMI-UHFFFAOYSA-N 0.000 claims abstract description 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000000460 chlorine Substances 0.000 claims abstract description 19
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 19
- -1 2-fluoro-3-nitrotrichlorotoluene Chemical compound 0.000 claims abstract description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 239000012670 alkaline solution Substances 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 239000012535 impurity Substances 0.000 claims description 9
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical group [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 8
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical group N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 4
- 229910052753 mercury Inorganic materials 0.000 claims description 4
- 239000011698 potassium fluoride Substances 0.000 claims description 4
- 235000003270 potassium fluoride Nutrition 0.000 claims description 4
- 239000012141 concentrate Substances 0.000 claims description 3
- 239000002351 wastewater Substances 0.000 abstract description 7
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000006396 nitration reaction Methods 0.000 description 10
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- MMZYCBHLNZVROM-UHFFFAOYSA-N 1-fluoro-2-methylbenzene Chemical compound CC1=CC=CC=C1F MMZYCBHLNZVROM-UHFFFAOYSA-N 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 238000004065 wastewater treatment Methods 0.000 description 2
- NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 description 1
- GAKLFAZBKQGUBO-UHFFFAOYSA-N 2-methyl-3-nitrophenol Chemical compound CC1=C(O)C=CC=C1[N+]([O-])=O GAKLFAZBKQGUBO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001546 nitrifying effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/16—Separation; Purification; Stabilisation; Use of additives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of chemical synthesis, in particular to a synthesis method for producing 2-fluoro-3-nitrobenzoic acid from 2-chloro-3-nitrotoluene, which comprises the following steps: adding 2-chloro-3-nitrotoluene and fluoride into a reaction vessel, and reacting at 75-130 ℃ to obtain a 2-fluoro-3-nitrotoluene solution; adding the obtained 2-fluoro-3-nitrotoluene solution into a chlorination kettle, adding a catalyst into the chlorination kettle, turning on a light source, introducing chlorine, and controlling the temperature of the chlorination kettle to be 70-130 ℃ to perform a photochlorination reaction to obtain a 2-fluoro-3-nitrotrichlorotoluene solution; adding the obtained 2-fluoro-3-nitrotrichlorotoluene solution into a hydrolysis kettle, adding an alkaline solution, controlling the temperature of the hydrolysis kettle to be 105-140 ℃ for hydrolysis, and adding hydrochloric acid to adjust the pH value of the solution to obtain a 2-fluoro-3-nitrobenzoic acid product. The method has the advantages of cheap and easily-obtained raw materials, easily-controlled reaction process, high product purity and yield, less generated wastewater, easy treatment and higher economic and environmental benefits.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a synthesis method for producing 2-fluoro-3-nitrobenzoic acid from 2-chloro-3-nitrotoluene.
Background
2-fluoro-3-nitrobenzoic acid is light yellow solid, is slightly soluble in water, is an important organic synthesis intermediate, and is widely applied to the synthesis of medicaments, active biological enzymes and other medicaments. At present, the reports about the synthesis process of 2-fluoro-3-nitrobenzoic acid mainly include:
(1) 2-fluorotoluene is taken as a raw material. The 2-fluorotoluene is firstly nitrified to obtain the 2-fluoro-3-nitrotoluene and then oxidized to obtain the target product 2-fluoro-3-nitrobenzoic acid, or the 2-fluorotoluene is firstly oxidized to the 2-fluorobenzoic acid and then subjected to nitration reaction to obtain the target product 2-fluoro-3-nitrobenzoic acid. In the method of firstly carrying out nitration and then carrying out oxidation in the route, when the direct nitration is carried out in the first step, various nitration products can appear, the separation of intermediates is difficult, and the yield of target products is low in the whole reaction route. The method of first oxidation and then nitration has more rigorous reaction conditions because the fluorine atom is a passivating group, and has more three wastes in production and larger environmental protection pressure because of nitration by using mixed acid. (2) O-methyl phenol is taken as a raw material. The method comprises the steps of preparing 2-methyl-nitrophenol by nitrifying o-methylphenol with nitrate/p-toluenesulfonic acid, converting hydroxyl into chlorine atoms by chlorination, converting the chlorine atoms into fluorine atoms under the action of cesium fluoride, and finally oxidizing to obtain a target product 2-fluoro-3-nitrobenzoic acid. The two synthetic processes have long routes, low total yield, more three wastes generated in production links, and difficult treatment of organic wastewater generated by nitration and oxidation reactions.
Disclosure of Invention
The invention aims to provide a synthetic method for producing 2-fluoro-3-nitrobenzoic acid from 2-chloro-3-nitrotoluene aiming at the defects of the prior art, which solves the problems of more organic wastewater generated by nitration and oxidation reaction, difficulty in treatment of wastewater and low product yield in the production process of the prior 2-fluoro-3-nitrobenzoic acid.
The technical scheme adopted by the invention for solving the technical problems is as follows: a synthetic method for producing 2-fluoro-3-nitrobenzoic acid from 2-chloro-3-nitrotoluene comprises the following steps:
(1) Adding 2-chloro-3-nitrotoluene and fluoride into a reaction container, reacting at 75-130 ℃ by taking acetonitrile as a solvent, and after reacting for a period of time, performing suction filtration and concentration to obtain a 2-fluoro-3-nitrotoluene solution;
(2) Adding the obtained 2-fluoro-3-nitrotoluene solution into a chlorination kettle, adding a catalyst into the chlorination kettle, turning on a light source, introducing chlorine, controlling the temperature of the chlorination kettle to be 70-130 ℃ to perform a photochlorination reaction, and stopping introducing the chlorine after the reaction is performed for a period of time to obtain a 2-fluoro-3-nitrotrichlorotoluene solution;
(3) Adding the obtained 2-fluoro-3-nitrotrichlorotoluene solution into a hydrolysis kettle, adding an alkaline solution, controlling the temperature of the hydrolysis kettle to be 105-140 ℃ for hydrolysis, adding hydrochloric acid into the hydrolysis kettle after a period of time to adjust the pH value of the solution to be 5-7, and then cooling, crystallizing, filtering, recrystallizing and drying to obtain the 2-fluoro-3-nitrobenzoic acid product.
Specifically, in the step (1), after the reaction is carried out for 6-8 hours, insoluble substances are removed through suction filtration, the filtrate is subjected to reduced pressure concentration, the solvent is removed, the concentrate is subjected to silica gel column chromatography separation to obtain a 2-fluoro-3-nitrotoluene solution, and through chromatographic column chromatography separation, impurities in the 2-fluoro-3-nitrotoluene solution can be removed, so that the raw materials are prevented from generating side reactions in the photochlorination process, and the purity of the product is prevented from being influenced.
Specifically, the fluoride in the step (1) is potassium fluoride or cesium fluoride, and the molar ratio of the 2-chloro-3-nitrotoluene to the fluoride is 1: (1-3).
Specifically, in the step (2), after the reaction is carried out for a period of time, when the content of the 2-fluoro-3-nitrodichlorotoluene in the chlorination kettle is analyzed and detected to be less than or equal to 0.5%, the introduction of the chlorine gas is stopped.
Specifically, in the step (2), the photochlorination light source is a fluorescent lamp, an ultraviolet lamp or a high-pressure mercury lamp.
Specifically, in the step (2), the chlorine gas is firstly treated by the silica gel particle column to remove impurities in the chlorine gas, and then the chlorine gas is introduced into the reaction kettle, wherein the chlorine gas contains impurities such as ferric chloride and the like, and the impurities can influence the photochlorination and cause the photochlorination to generate more byproducts.
Specifically, the catalyst in the step (2) is azobisisobutyronitrile or azobisisoheptonitrile, and the dosage of the catalyst is 0.05-0.5% of the mass of the 2-fluoro-3-nitrotoluene.
Specifically, the molar ratio of the chlorine dosage in the step (2) to the dosage of the reaction raw material 2-fluoro-3 nitrotoluene is (4-10): 1.
specifically, in the step (3), 25-35% by mass of sodium hydroxide solution and 20-30% by mass of sodium carbonate solution are sequentially added into a hydrolysis kettle, the pH value in the hydrolysis process is adjusted to 9-14, and hydrochloric acid is added into the hydrolysis kettle after hydrolysis reaction is carried out for 4-6 hours.
Compared with the prior synthesis process, the invention has the beneficial effects that: the process route of the invention does not need to be subjected to nitrification or oxidation treatment, thereby avoiding the generation of organic wastewater in nitrification or oxidation reaction and reducing the difficulty of wastewater treatment; compared with the prior art, the method takes the 2-chloro-3-nitrotoluene as the raw material, obtains the intermediate 2-fluoro-3-nitrotoluene through the reaction with the fluoride, obtains the 2-fluoro-3-nitrotrichlorotoluene through the photochlorination of the intermediate, obtains the 2-fluoro-3-nitrobenzoic acid through the hydrolysis of the trichloride, and has the advantages of high hydrolysis efficiency, high product yield, less amount of generated process wastewater, easy treatment, more economy and environmental protection; the invention has the advantages of cheap and easily obtained raw materials, easily controlled reaction process, high product purity and high product yield of more than 90 percent.
Detailed Description
The present invention will be described in further detail with reference to specific examples, but the scope of the present invention is not limited thereto.
A synthetic process method of 2-fluoro-3-nitrobenzoic acid comprises the following steps:
(1) Adding 2-chloro-3-nitrotoluene and fluoride into a reaction container, reacting at 75-130 ℃ by taking acetonitrile as a solvent, and after reacting for a period of time, carrying out suction filtration and concentration to obtain a 2-fluoro-3-nitrotoluene solution;
(2) Adding the obtained 2-fluoro-3-nitrotoluene solution into a chlorination kettle, adding a catalyst into the chlorination kettle, turning on a light source, introducing chlorine, controlling the temperature of the chlorination kettle to be 70-130 ℃ to perform a photochlorination reaction, and stopping introducing the chlorine after the reaction is performed for a period of time to obtain a 2-fluoro-3-nitrotrichlorotoluene solution;
(3) Adding the obtained 2-fluoro-3-nitrotrichlorotoluene solution into a hydrolysis kettle, adding an alkaline solution, controlling the temperature of the hydrolysis kettle to be 105-140 ℃ for hydrolysis, adding hydrochloric acid into the hydrolysis kettle after a period of time to adjust the pH value of the solution to be 5-7, and then cooling, crystallizing, filtering, recrystallizing and drying to obtain a 2-fluoro-3-nitrobenzoic acid product.
In the step (1), after reaction for 6-8 h, removing insoluble substances through suction filtration, carrying out reduced pressure concentration on the filtrate, removing the solvent, and then carrying out silica gel column chromatography separation on the concentrate to obtain the 2-fluoro-3-nitrotoluene solution.
In the step (1), the fluoride is potassium fluoride or cesium fluoride, and the molar ratio of the 2-chloro-3-nitrotoluene to the fluoride is 1: (1-3).
In the step (2), after reacting for a period of time, stopping introducing chlorine when the content of the 2-fluoro-3-nitrodichlorotoluene in the chlorination kettle is analyzed and detected to be less than or equal to 0.5 percent.
In the step (2), the light chlorination reaction light source is a fluorescent lamp, an ultraviolet lamp or a high-pressure mercury lamp.
And (3) in the step (2), the chlorine is firstly treated by a silica gel particle column to remove impurities in the chlorine, and then the chlorine is introduced into the reaction kettle.
In the step (2), the catalyst is azobisisobutyronitrile or azobisisoheptonitrile, and the dosage of the catalyst is 0.05-0.5% of the mass of the 2-fluoro-3-nitrotoluene.
The mol ratio of the chlorine dosage in the step (2) to the dosage of the reaction raw material 2-fluoro-3 nitrotoluene is (4-10): 1.
and (3) sequentially adding 25-35% by mass of sodium hydroxide solution and 20-30% by mass of sodium carbonate solution into a hydrolysis kettle, adjusting the pH value in the hydrolysis process to 9-14, and adding hydrochloric acid into the hydrolysis kettle after hydrolysis reaction is carried out for 4-6 h.
Example 1
(1) Adding 100g of 2-chloro-3-nitrotoluene (0.583 mol) and 63.9g of potassium fluoride (1.1 mol) into a 500mL round-bottom flask in sequence, adding 120mL of acetonitrile serving as a solvent, controlling the temperature to be 85-95 ℃ for reaction, performing suction filtration after 7 hours of reaction, and removing insoluble substances; concentrating the filtrate under reduced pressure to remove the solvent; the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate =2 = 1), to give 86.7g of a 2-fluoro-3-nitrotoluene solution with a purity of chromatography of 99.2%.
(2) Adding the obtained 2-fluoro-3-nitrotoluene into a chlorination kettle, controlling the temperature of the chlorination kettle to be 65-75 ℃, adding 0.15g of azodiisobutyronitrile serving as a catalyst, starting a high-pressure mercury lamp, introducing chlorine gas treated by a silica gel particle column, controlling the temperature of the chlorination kettle to be 75-85 ℃ for reaction, and stopping introducing the chlorine gas when the content of 2-fluoro-3-nitrodichlorotoluene in the chlorination kettle is analyzed and detected to be less than or equal to 0.5%, so as to obtain 144.5g of 2-fluoro-3-nitrotrichlorotoluene solution.
(3) Adding the chlorinated solution into a hydrolysis kettle, sequentially adding 240g of 30% sodium hydroxide solution and 100g of 25% sodium carbonate solution, and controlling the temperature of the kettle at 120-125 ℃ for hydrolysis. After the reaction is carried out for 5 hours, sampling and detecting that the 2-fluoro-3-nitrotrichlorotoluene is completely converted, and stopping the reaction. Dropwise adding hydrochloric acid into the hydrolysis kettle while stirring, adjusting the solution to be neutral, and then cooling to room temperature. Adding a proper amount of ice blocks into the kettle, cooling to separate out crystalline solid, filtering, recrystallizing a filter cake by using distilled water, filtering the crystallized solid, and drying by using an oven to finally obtain 99.4g of pure 2-fluoro-3-nitrobenzoic acid with the chromatographic purity of 99.1 percent and the total yield of 91.5 percent.
Example 2
(1) Adding 100g of 2-chloro-3-nitrotoluene (0.583 mol) and 136.7g of cesium fluoride (0.9 mol) into a 500mL round-bottom flask in sequence, adding 120mL of acetonitrile as a solvent, controlling the temperature to be between 85 and 95 ℃ for reaction, performing suction filtration after 7 hours of reaction, and removing insoluble substances; concentrating the filtrate under reduced pressure, and removing the solvent; the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate =2 = 1), to give 86.1g of a 2-fluoro-3-nitrotoluene solution with a purity of chromatography of 99.4%.
(2) Adding the obtained 2-fluoro-3-nitrotoluene into a chlorination kettle, controlling the temperature of the kettle to be 65-70 ℃, adding 0.2g of catalyst azodiisoheptanonitrile, starting an ultraviolet lamp, introducing chlorine gas treated by a silica gel particle column, controlling the temperature of the kettle to be 75-80 ℃ for reaction, and stopping introducing the chlorine gas when the content of 2-fluoro-3-nitrodichlorotoluene in the reaction kettle is analyzed and detected to be less than or equal to 0.5%, so as to obtain 143.8g of 2-fluoro-3-nitrotrichlorotoluene solution.
(3) Adding the chlorinated solution into a hydrolysis kettle, sequentially adding 240g of 30% sodium hydroxide solution and 100g of 25% sodium carbonate solution, and controlling the kettle temperature to be 120-125 ℃ for hydrolysis. After the reaction is carried out for 5 hours, sampling and detecting that the 2-fluoro-3-nitrotrichlorotoluene is completely converted, and stopping the reaction. And (3) dropwise adding hydrochloric acid into the hydrolysis kettle while stirring, adjusting the solution to be neutral, and then cooling to room temperature. Adding a proper amount of ice blocks into the kettle, cooling to separate out a crystallized solid, filtering, recrystallizing a filter cake by using distilled water, filtering the crystallized solid, and drying by using an oven to finally obtain 98.9g of pure 2-fluoro-3-nitrobenzoic acid, wherein the chromatographic purity is 99.2 percent, and the total yield is 90.6 percent.
Compared with the prior art, the method has the advantages that the raw materials are cheap and easy to obtain, the reaction process is easy to control, the product purity can reach more than 99%, and the product yield can reach more than 90%; the invention does not need to carry out nitration or oxidation treatment process, thereby avoiding the generation of organic wastewater in nitration or oxidation reaction, reducing the difficulty of wastewater treatment, and easily separating the intermediate product obtained by reaction; during chlorination reaction, the intermediate product 2-fluoro-3-nitrotoluene is subjected to silica gel column chromatography separation treatment to treat impurities in the intermediate product, and chlorine is treated by using a silica gel particle column to remove impurities in the gas, so that the generation of byproducts in the chlorination process caused by the impurities is avoided, the chlorination process is favorably ensured to react towards trichloride, and the product is obtained, and the product with higher purity is ensured to be obtained.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (9)
1. A synthetic process method of 2-fluoro-3-nitrobenzoic acid is characterized by comprising the following steps: the method comprises the following steps:
(1) Adding 2-chloro-3-nitrotoluene and fluoride into a reaction container, reacting at 75-130 ℃ by taking acetonitrile as a solvent, and after reacting for a period of time, performing suction filtration and concentration to obtain a 2-fluoro-3-nitrotoluene solution;
(2) Adding the obtained 2-fluoro-3-nitrotoluene solution into a chlorination kettle, adding a catalyst into the chlorination kettle, turning on a light source, introducing chlorine, controlling the temperature of the chlorination kettle to be 70-130 ℃ to perform a photochlorination reaction, and stopping introducing the chlorine after the reaction is performed for a period of time to obtain a 2-fluoro-3-nitrotrichlorotoluene solution;
(3) Adding the obtained 2-fluoro-3-nitrotrichlorotoluene solution into a hydrolysis kettle, adding an alkaline solution, controlling the temperature of the hydrolysis kettle to be 105-140 ℃ for hydrolysis, adding hydrochloric acid into the hydrolysis kettle after a period of time to adjust the pH value of the solution to be 5-7, and then cooling, crystallizing, filtering, recrystallizing and drying to obtain a 2-fluoro-3-nitrobenzoic acid product.
2. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: in the step (1), after reaction for 6-8 h, removing insoluble substances through suction filtration, carrying out reduced pressure concentration on the filtrate, removing the solvent, and then carrying out silica gel column chromatography separation on the concentrate to obtain the 2-fluoro-3-nitrotoluene solution.
3. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: in the step (1), the fluoride is potassium fluoride or cesium fluoride, and the molar ratio of the 2-chloro-3-nitrotoluene to the fluoride is 1: (1-3).
4. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: in the step (2), after reacting for a period of time, stopping introducing chlorine when the content of the 2-fluoro-3-nitrodichlorotoluene in the chlorination kettle is analyzed and detected to be less than or equal to 0.5 percent.
5. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: in the step (2), the light chlorination reaction light source is a fluorescent lamp, an ultraviolet lamp or a high-pressure mercury lamp.
6. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: and (3) in the step (2), the chlorine is firstly treated by a silica gel particle column to remove impurities in the chlorine, and then the chlorine is introduced into the reaction kettle.
7. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: in the step (2), the catalyst is azobisisobutyronitrile or azobisisoheptonitrile, and the dosage of the catalyst is 0.05-0.5% of the mass of the 2-fluoro-3-nitrotoluene.
8. The synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: the mol ratio of the chlorine dosage in the step (2) to the dosage of the reaction raw material 2-fluoro-3 nitrotoluene is (4-10): 1.
9. the synthesis process method of 2-fluoro-3-nitrobenzoic acid according to claim 1, characterized in that: and (3) sequentially adding 25-35% by mass of sodium hydroxide solution and 20-30% by mass of sodium carbonate solution into a hydrolysis kettle, adjusting the pH value in the hydrolysis process to 9-14, and adding hydrochloric acid into the hydrolysis kettle after hydrolysis reaction is carried out for 4-6 h.
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