CN110627646A - Preparation method of 5-fluoro-2-nitrophenol - Google Patents
Preparation method of 5-fluoro-2-nitrophenol Download PDFInfo
- Publication number
- CN110627646A CN110627646A CN201910993149.7A CN201910993149A CN110627646A CN 110627646 A CN110627646 A CN 110627646A CN 201910993149 A CN201910993149 A CN 201910993149A CN 110627646 A CN110627646 A CN 110627646A
- Authority
- CN
- China
- Prior art keywords
- fluoro
- nitrophenol
- reaction
- producing
- temperature
- 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.)
- Pending
Links
- QQURWFRNETXFTN-UHFFFAOYSA-N 5-fluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC=C1[N+]([O-])=O QQURWFRNETXFTN-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 22
- RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 54
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 20
- 239000003513 alkali Substances 0.000 claims description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 8
- 239000007791 liquid phase Substances 0.000 claims description 7
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 6
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 239000012044 organic layer Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 230000035484 reaction time Effects 0.000 abstract description 11
- 230000036632 reaction speed Effects 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 12
- 239000002994 raw material Substances 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 239000012535 impurity Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- SJTBRFHBXDZMPS-UHFFFAOYSA-N 3-fluorophenol Chemical compound OC1=CC=CC(F)=C1 SJTBRFHBXDZMPS-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- FOUWCSDKDDHKQP-UHFFFAOYSA-N flumioxazin Chemical compound FC1=CC=2OCC(=O)N(CC#C)C=2C=C1N(C1=O)C(=O)C2=C1CCCC2 FOUWCSDKDDHKQP-UHFFFAOYSA-N 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000002194 synthesizing effect Effects 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 5-fluoro-2-nitrophenol. The invention solves the technical problem that the existing method for preparing 5-fluoro-2-nitrophenol has long reaction time and is not beneficial to industrialized operation. The technical scheme adopted by the invention for solving the technical problems is to provide a preparation method of 5-fluoro-2-nitrophenol, which comprises the following steps: reacting 2, 4-difluoronitrobenzene in the presence of a base, water and an organic solvent to obtain 5-fluoro-2-nitrophenol. The invention can accelerate the reaction speed, effectively shorten the reaction time, reduce the energy consumption and is easier to carry out industrial application by adding the organic solvent into the reaction system.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 5-fluoro-2-nitrophenol.
Background
The 5-fluoro-2-nitrophenol is a key intermediate for synthesizing fine chemicals such as herbicide flumioxazin and the like, and the synthetic routes reported in the literature mainly comprise:
(1) m-fluorophenol nitration method
The method is reported in patent WO2009035407 and the like, but the method has low industrial value because m-fluorophenol is expensive, byproducts are more during nitration, the yield is low and the like.
(2) Hydrolysis method of 2, 4-difluoronitrobenzene
The document, synthetic research on novel herbicide flumioxazin, and the like report that the method hydrolyzes 2, 4-difluoronitrobenzene through inorganic strong base such as NaOH and KOH, and then obtains a target product through acidification. Although the method is simple and convenient to operate, the reaction time is long, and the method is not beneficial to industrial operation.
Disclosure of Invention
The invention solves the technical problem that the existing method for preparing 5-fluoro-2-nitrophenol has long reaction time and is not beneficial to industrialized operation.
The technical scheme adopted by the invention for solving the technical problems is to provide a preparation method of 5-fluoro-2-nitrophenol, which comprises the following steps: reacting 2, 4-difluoronitrobenzene in the presence of a base, water and an organic solvent to obtain 5-fluoro-2-nitrophenol.
In the preparation method of the 5-fluoro-2-nitrophenol, the organic solvent is one or more of dimethyl sulfoxide, tetrahydrofuran, N-methylpyrrolidone, acetonitrile, 1, 4-dioxane, 1, 3-dimethyl-2-imidazolidinone or sulfolane; preferably one or more of dimethyl sulfoxide, tetrahydrofuran, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone or sulfolane; more preferably dimethyl sulfoxide or tetrahydrofuran; most preferred is dimethyl sulfoxide.
In the preparation method of the 5-fluoro-2-nitrophenol, the mass ratio of the organic solvent to the 2, 4-difluoronitrobenzene is 0.2-2: 1.
In the preparation method of the 5-fluoro-2-nitrophenol, the mass ratio of the organic solvent to the 2, 4-difluoronitrobenzene is 0.5-1: 1.
In the preparation method of the 5-fluoro-2-nitrophenol, the alkali is inorganic alkali; the preferred base is sodium hydroxide or potassium hydroxide.
In the preparation method of the 5-fluoro-2-nitrophenol, the mass ratio of the alkali to the water is 1: 1-4; the preferable mass ratio is 1: 1.5-2.5.
In the preparation method of the 5-fluoro-2-nitrophenol, the reaction temperature is 52-58 ℃.
The preparation method of the 5-fluoro-2-nitrophenol comprises the step of adjusting the pH value of a system to be acidic by using hydrochloric acid after the reaction is finished, wherein the pH value of the system is 1-6, and the preferable pH value is 3-4.
Wherein, in the preparation method of the 5-fluoro-2-nitrophenol, the temperature of the system is ensured to be more than 30 ℃ before the pH of the system is adjusted by hydrochloric acid.
The preparation method of the 5-fluoro-2-nitrophenol comprises the following steps: adding alkali, water and an organic solvent into a reaction container, heating to 50-54 ℃, dropwise adding 2, 4-difluoronitrobenzene, maintaining the reaction internal temperature at 55-58 ℃ in the dropwise adding process, keeping the temperature of the reaction system to be less than 0.5% after dropwise adding, reacting until the temperature of the reaction system is more than 30 ℃ in a liquid phase, adjusting the pH value of the reaction system to 3-4, standing for layering, and removing the solvent from an organic layer under reduced pressure to obtain the 5-fluoro-2-nitrophenol.
The invention has the beneficial effects that:
the invention can accelerate the reaction speed, effectively shorten the reaction time, reduce the energy consumption and is easier to carry out industrial application by adding the organic solvent into the reaction system.
Detailed Description
Specifically, the preparation method of the 5-fluoro-2-nitrophenol comprises the following steps: reacting 2, 4-difluoronitrobenzene in the presence of a base, water and an organic solvent to obtain 5-fluoro-2-nitrophenol.
The inventor of the invention finds that the addition of dimethyl sulfoxide (DMSO), Tetrahydrofuran (THF), N-methylpyrrolidone (NMP), Acetonitrile (ACN), dioxane, 1, 3-dimethyl-2-imidazolidinone (DMI) or sulfolane can effectively shorten the reaction time and reduce the energy consumption through a large number of screening tests. Wherein dimethyl sulfoxide (DMSO), Tetrahydrofuran (THF), N-methylpyrrolidone (NMP), 1, 3-dimethyl-2-imidazolidinone (DMI) or sulfolane are added in the same reaction time, so that the conversion rate of the product is high; dimethyl sulfoxide or tetrahydrofuran is added, so that the conversion rate of the product is higher; dimethyl sulfoxide is added, and the conversion rate of the product is highest.
In the method, the use amount of the organic solvent is too small, so that the reaction time cannot be effectively shortened; the organic solvent is used in a large amount, and the cost is high. Therefore, the influence of the cost and the solvent on the reaction is comprehensively considered, and the mass ratio of the organic solvent to the 2, 4-difluoronitrobenzene is set to be 0.2-2: 1; preferably, the mass ratio of the organic solvent to the 2, 4-difluoronitrobenzene is 0.5-1: 1.
In the method of the present invention, the alkali is sodium hydroxide or potassium hydroxide. If the mass ratio of the alkali to the water is smaller, the content of the water is too high, the reaction speed is slower, and the amount of the generated wastewater is larger after the reaction is finished; the mass ratio of alkali to water is larger, the conversion rate of the main product is reduced, and the content of generated impurities is increased. Therefore, the mass ratio of the alkali to the water is 1: 1-4, and the preferable mass ratio is 1: 1.5-2.5.
In the method, when the reaction temperature is too low, the reaction process is slow, a large amount of raw materials are accumulated, so that the reaction is incomplete, and meanwhile, the phenomenon of sudden violent rise of the system temperature occurs in the later stage of the reaction; when the reaction temperature is too high, the amount of impurities produced becomes large. Therefore, the temperature of the hydrolysis reaction is set to be 52-58 ℃.
The method of the invention ensures that the reaction temperature is higher than 30 ℃ when hydrochloric acid is dripped after the reaction is finished, otherwise a large amount of solid is separated out and is difficult to stir; the pH was determined because the reaction solution was already separated when the pH was 5 to 6, but further pH was determined to be 4 in order to further increase the amount of product separation, and further lowering the pH increased the amount of acid used and was of little significance.
The terms referred to in the present invention explain:
concentration-mass percentage concentration-solute mass (g)/((solute mass (g) + solvent mass (g)) x 100%.
The present invention is further illustrated in detail by the following test examples and examples, but the scope of the present invention is not limited thereto.
Example 1
274.4g of water is added into a 1L four-mouth bottle, 117.6g (2.1mol) of potassium hydroxide is slowly added, the mixture is stirred until the mixture is dissolved and clarified, 111.36g of tetrahydrofuran is added, the temperature is raised to 52 ℃, 111.36g (0.7mol) of 2, 4-difluoronitrobenzene is started to be dripped, the temperature in the reaction is maintained between 55 and 58 ℃ in the dripping process, the mixture is kept stirring for 1 to 1.5 hours after the dripping is completed within 0.5 hour, the raw material is detected to be less than 0.5 percent in a liquid phase, and the reaction is completed. And (3) ensuring that the temperature of the system is higher than 30 ℃, dropwise adding 36 wt% hydrochloric acid to adjust the pH to be 4, standing for layering, and decompressing an organic layer to remove a solvent to obtain 104g of oily matter, wherein the yield is 95% and the content of a liquid phase is 95.3%.
Test example 1 screening of reaction solvent
3.2g (0.02mol) of raw material 2, 4-difluoronitrobenzene, 7.0g of 40 wt% KOH aqueous solution and 3.2g of solvent are added into a 50mL three-necked flask, the temperature is raised to 55 ℃, the reaction is carried out for 2h, samples are taken, the liquid phase detection is controlled in a middle way, and the detection results are shown in Table 1.
TABLE 1 screening of reaction solvents
As can be seen from Table 1, the reaction speed can be increased and the conversion rate can be increased by adding part of the solvent in the reaction system, and when DMSO and THF are used as the solvents, the reaction speed is the fastest and the conversion rate is the highest.
Test example 2 screening of bases
3.2g (0.02mol) of the raw material 2, 4-difluoronitrobenzene, 3.2g of THF and 2.25eq of alkali are added into a 50mL three-necked flask, the temperature is raised to 55 ℃, the reaction is carried out for 2h, samples are taken, the liquid phase detection is controlled in the middle, and the detection results are shown in Table 2.
TABLE 2 screening of bases
| Serial number | Alkali | Main product (5-fluoro-2-nitrophenol) | Remainder of raw material |
| 1 | 20 wt% KOH aqueous solution | 91.9％ | 2.8％ |
| 2 | 25 wt% aqueous KOH solution | 93.9％ | 1.25％ |
| 3 | 30 wt% KOH aqueous solution | 94.2％ | 0.6％ |
| 4 | 40 wt% aqueous KOH solution | 94％ | 0.4％ |
| 5 | 50 wt% KOH aqueous solution | 92％ | / |
| 6 | Solid KOH | 94.33％ | / |
| 7 | 30 wt% NaOH in water | 91.3％ | 1.1％ |
When solid KOH or NaOH is added, the reaction is severe, 1eq of alkali is consumed firstly to generate phenol, then the phenol continuously reacts with the KOH or the NaOH to generate salt and water, the potassium salt or the sodium salt of the phenol generated by the reaction has poor solubility in an organic solvent and is difficult to stir after being separated out, so a large amount of solvent dispersion system is needed, water is added during post-treatment to further treat salt generated by the system, and the generation of wastewater cannot be avoided subsequently. The initial addition of water in the solid reaction is helpful to improve the single kettle capacity.
As can be seen from Table 2, when the alkali concentration is 30 wt% or 40 wt% KOH aqueous solution, the difference in the main product content is not significant; when the alkali is KOH, the content of the main product is about 3 percent higher than that when the alkali is NaOH, and the reaction by-product potassium fluoride can be well recycled; from the aspects of experimental stirring difficulty, wastewater quantity and main product content in the reaction liquid, the comprehensive effect is best when the concentration of the alkali is 30 wt%.
Test example 3 screening of solvent amount
3.2g (0.02mol) of 2, 4-difluoronitrobenzene as a raw material, 9.3g of a 30 wt% KOH aqueous solution and 3.2g of solvent are added into a 50mL three-necked flask, the temperature is raised to 55 ℃, and the detection results are shown in Table 3.
TABLE 3 screening of solvent dosage
| Serial number | Solvent(s) | Mass ratio of solvent to 2, 4-difluoronitrobenzene | Reaction time | Remainder of raw material |
| 1 | THF | 1:1 | 1h | 0.6％ |
| 2 | THF | 0.5:1 | 2h | 0.5％ |
| 3 | THF | 0.2:1 | 5.5h | 0.44％ |
| 4 | DMSO | 1:1 | 0.3h | 0.57％ |
| 5 | DMSO | 0.5:1 | 1h | 0.39％ |
As can be seen from Table 3, the more the amount of solvent used, the shorter the reaction time required; the reaction time of DMSO is shorter than that of THF under the same solvent dosage; the solvent recovery cost and the influence of the solvent on the reaction are comprehensively considered, and the mass ratio of the solvent to the 2, 4-difluoronitrobenzene is better when being 0.5-1: 1.
Test example 4 screening of reaction temperature
19.1g (0.12mol) of raw material 2, 4-difluoronitrobenzene and 9.5g of THF are added into a 250mL three-necked flask, the temperature is increased, 51g of 30 wt% KOH aqueous solution is dripped, a sample is taken after 2 hours of reaction, the liquid phase detection is controlled in the middle, and the detection results are shown in Table 4.
TABLE 4 screening of reaction temperatures
| Serial number | Dropping temperature | Maximum temperature | Content of major product | Main impurity content |
| 1 | 73℃ | 73℃ | 91.75％ | 3.1％ |
| 2 | 52℃ | 58℃ | 94.5％ | 1.6％ |
| 3 | 45℃ | 68℃ | 92％ | 2.3％ |
As can be seen from Table 4, when the reaction temperature is lower, a large amount of raw materials accumulate due to slow reaction process and are not completely reacted, the temperature of the reaction system is suddenly increased in the later period of the reaction, and the generated impurities are increased due to overhigh reaction temperature, so the reaction temperature is preferably 52-58 ℃.
Test example 5 temperature control of reaction System before neutralization by dropping hydrochloric acid
The procedure of example 1 was followed except that the solvent was replaced with DMSO.
TABLE 5 reaction temperature before neutralization by dropwise addition of hydrochloric acid
| Serial number | Dropping temperature | Maximum temperature | Content of major product | Main impurity content |
| 1 | 33℃ | 38℃ | 93.6％ | 1.7％ |
| 2 | 45℃ | 48℃ | 94.3％ | 1.8％ |
| 3 | 55℃ | 55℃ | 95％ | 2％ |
Before the hydrochloric acid is added for neutralization, the temperature of a reaction system is more than 30 ℃, and when the temperature is lower than 30 ℃, a large amount of solid is separated out from the system, so that the stirring is difficult.
Claims (10)
- The preparation method of the 1.5-fluoro-2-nitrophenol is characterized by comprising the following steps: reacting 2, 4-difluoronitrobenzene in the presence of a base, water and an organic solvent to obtain 5-fluoro-2-nitrophenol.
- 2. The process for producing 5-fluoro-2-nitrophenol according to claim 1, wherein: the organic solvent is one or more than two of dimethyl sulfoxide, tetrahydrofuran, N-methyl pyrrolidone, acetonitrile, 1, 4-dioxane, 1, 3-dimethyl-2-imidazolidinone or sulfolane; preferably one or more of dimethyl sulfoxide, tetrahydrofuran, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone or sulfolane; more preferably dimethyl sulfoxide or tetrahydrofuran; most preferred is dimethyl sulfoxide.
- 3. The method for producing 5-fluoro-2-nitrophenol according to claim 1 or 2, characterized in that: the mass ratio of the organic solvent to the 2, 4-difluoronitrobenzene is 0.2-2: 1.
- 4. The process for producing 5-fluoro-2-nitrophenol according to claim 3, wherein: the mass ratio of the organic solvent to the 2, 4-difluoronitrobenzene is 0.5-1: 1.
- 5. The process for producing 5-fluoro-2-nitrophenol according to any of claims 1 to 4, wherein: the alkali is inorganic alkali; the preferred base is sodium hydroxide or potassium hydroxide.
- 6. The process for producing 5-fluoro-2-nitrophenol according to claim 5, wherein: the mass ratio of the alkali to the water is 1: 1-4; the preferable mass ratio is 1: 1.5-2.5.
- 7. The process for producing 5-fluoro-2-nitrophenol according to any of claims 1 to 6, wherein: the reaction temperature is 52-58 ℃.
- 8. The method for producing 5-fluoro-2-nitrophenol according to any of claims 1 to 7, wherein: and after the reaction is finished, the step of adjusting the pH value of the system to be acidic by using hydrochloric acid is also included, wherein the pH value of the system is 1-6, and the preferable pH value is 3-4.
- 9. The method for producing 5-fluoro-2-nitrophenol according to claim 8, wherein: before adjusting the pH of the system by using hydrochloric acid, the temperature of the system is ensured to be more than 30 ℃.
- 10. The method for producing 5-fluoro-2-nitrophenol according to any of claims 1 to 9, comprising the steps of: adding alkali, water and an organic solvent into a reaction container, heating to 50-54 ℃, dropwise adding 2, 4-difluoronitrobenzene, maintaining the reaction internal temperature at 55-58 ℃ in the dropwise adding process, keeping the temperature of the reaction system to be less than 0.5% after dropwise adding, reacting until the temperature of the reaction system is more than 30 ℃ in a liquid phase, adjusting the pH value of the reaction system to 3-4, standing for layering, and removing the solvent from an organic layer under reduced pressure to obtain the 5-fluoro-2-nitrophenol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910993149.7A CN110627646A (en) | 2019-10-18 | 2019-10-18 | Preparation method of 5-fluoro-2-nitrophenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910993149.7A CN110627646A (en) | 2019-10-18 | 2019-10-18 | Preparation method of 5-fluoro-2-nitrophenol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110627646A true CN110627646A (en) | 2019-12-31 |
Family
ID=68976645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910993149.7A Pending CN110627646A (en) | 2019-10-18 | 2019-10-18 | Preparation method of 5-fluoro-2-nitrophenol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110627646A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116514662A (en) * | 2022-12-12 | 2023-08-01 | 山东京博农化科技股份有限公司 | Preparation method of 5-fluoro-2-nitrophenol |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS572242A (en) * | 1980-06-06 | 1982-01-07 | Kumiai Chem Ind Co Ltd | Preparation of 2-bromo-2-nitro-1,3-propanediol |
| CN1850778A (en) * | 2006-05-26 | 2006-10-25 | 常州市晔泰精细化工研究所 | Method for preparing 2-fluoro-4-nitrophenol |
| CN101037380A (en) * | 2007-04-29 | 2007-09-19 | 上海康鹏化学有限公司 | Preparation method of 2,3-Difluoro-5-Bromophenol |
| CN102285888A (en) * | 2010-11-15 | 2011-12-21 | 江苏威凯尔医药科技有限公司 | New preparation method of 2-fluoro-4-nitrophenol |
| CN106045861A (en) * | 2016-05-26 | 2016-10-26 | 山东润博生物科技有限公司 | Method and system for continuously producing 5-fluoro-2-nitrophenol |
| CN106083536A (en) * | 2016-06-14 | 2016-11-09 | 浙江永太科技股份有限公司 | A kind of preparation method of the bent key intermediate in Ansai |
| CN106632444A (en) * | 2016-12-29 | 2017-05-10 | 千辉药业（安徽）有限责任公司 | Synthesizing method of novel ofloxacin intermediate |
| CN108976129A (en) * | 2018-08-16 | 2018-12-11 | 淮安国瑞化工有限公司 | A kind of fluoro- 2,4- 2,4-dinitrophenoxy of 2-(5-) acetic acid esters preparation method |
-
2019
- 2019-10-18 CN CN201910993149.7A patent/CN110627646A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS572242A (en) * | 1980-06-06 | 1982-01-07 | Kumiai Chem Ind Co Ltd | Preparation of 2-bromo-2-nitro-1,3-propanediol |
| CN1850778A (en) * | 2006-05-26 | 2006-10-25 | 常州市晔泰精细化工研究所 | Method for preparing 2-fluoro-4-nitrophenol |
| CN101037380A (en) * | 2007-04-29 | 2007-09-19 | 上海康鹏化学有限公司 | Preparation method of 2,3-Difluoro-5-Bromophenol |
| CN102285888A (en) * | 2010-11-15 | 2011-12-21 | 江苏威凯尔医药科技有限公司 | New preparation method of 2-fluoro-4-nitrophenol |
| CN106045861A (en) * | 2016-05-26 | 2016-10-26 | 山东润博生物科技有限公司 | Method and system for continuously producing 5-fluoro-2-nitrophenol |
| CN106083536A (en) * | 2016-06-14 | 2016-11-09 | 浙江永太科技股份有限公司 | A kind of preparation method of the bent key intermediate in Ansai |
| CN106632444A (en) * | 2016-12-29 | 2017-05-10 | 千辉药业（安徽）有限责任公司 | Synthesizing method of novel ofloxacin intermediate |
| CN108976129A (en) * | 2018-08-16 | 2018-12-11 | 淮安国瑞化工有限公司 | A kind of fluoro- 2,4- 2,4-dinitrophenoxy of 2-(5-) acetic acid esters preparation method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116514662A (en) * | 2022-12-12 | 2023-08-01 | 山东京博农化科技股份有限公司 | Preparation method of 5-fluoro-2-nitrophenol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3166611B1 (en) | Process for the preparation of 4-alkoxy-3-hydroxypicolinic acids | |
| CN106749072A (en) | The preparation method of clomazone | |
| TWI685488B (en) | Method for preparing intermediate of Azotomin (Azoxystyrin) | |
| CN107857743B (en) | Method for preparing roxatidine acetate hydrochloride and intermediate | |
| US20130137893A1 (en) | Process for preparing and purifying salts of acrylamido-2-methylpropanesulfonic acid | |
| CN110028462A (en) | A method of preparing isoxazoles intermediate and isoxazoline | |
| CN112544621B (en) | Method for preparing 2- (4-chlorophenoxy) -propoxyamine | |
| CN113754647B (en) | Synthesis method of sulfuryl pyraflufen-ethyl and intermediate thereof | |
| CN110627646A (en) | Preparation method of 5-fluoro-2-nitrophenol | |
| CN102875435B (en) | Organic thiosulfuric acid derivative preparation method | |
| CN110337434B (en) | Process for preparing 2-cyanoimidazole compounds | |
| CN111116416B (en) | Preparation method of beta-amino acrylonitrile compound | |
| CN108047208A (en) | A kind of method for reducing Losartan dimer impurity | |
| CN108164423B (en) | Preparation method of naftifine hydrochloride | |
| CN111718370A (en) | Preparation method of O, O' -dimethyl thiophosphoryl amide | |
| UA86284C2 (en) | Process for the production of anilines, use of ammonia in this process and amination process | |
| CN106748796B (en) | The method for preparing the fluoro- 2,4- dinitrobenzene of 1,5- bis- | |
| CN113024479B (en) | Preparation method of clomazone | |
| CN103951590A (en) | Preparation method of N,O-dimethyl-N'-nitroisourea | |
| CN103626695B (en) | New method for preparing fluazinam by using mixed solvent as medium | |
| CN109836344B (en) | Method for producing glycine by organic solvent | |
| CN113336680B (en) | Green process synthesis method of sulfanilamide | |
| CN1467206A (en) | Preparation method of 2-chloro-4, 6-dimethoxypyrimidine | |
| CN103724248A (en) | Preparation method of vildagliptin process impurities | |
| CN108191753A (en) | A kind of preparation method of 5- chloro-8-hydroxyquinolines |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20191231 |
|
| RJ01 | Rejection of invention patent application after publication |