CN110950764A - Method for synthesizing 2-amino-4-chloro-5 nitrophenol in microchannel reactor - Google Patents
Method for synthesizing 2-amino-4-chloro-5 nitrophenol in microchannel reactor Download PDFInfo
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Abstract
The invention discloses a synthetic method of 2-amino-4-chloro-5-nitrophenol. The synthesis method comprises the following steps: 5-chloro-2-methylbenzoxazole is taken as a raw material, and a microchannel reactor and a batch reactor are connected in series for reaction to synthesize the 2-amino-4-chloro-5 nitrophenol. By applying the technical scheme of the invention, the 2-amino-4-chloro-5-nitrophenol is synthesized by utilizing the microchannel reactor, so that the adverse effects of difficult control of the process, easy local overheating to cause danger, easy generation of side reaction and the like in the conventional kettle type reactor are avoided, the intrinsic safety of the process is improved, and the method has the advantages of high production efficiency, strong economy, easy industrialization and continuous production realization. And the microchannel reaction device has the characteristics of low price, convenient transportation, convenient cleaning, higher heat and mass transfer efficiency, easier industrial amplification and the like. Meanwhile, the synthesis method has the advantages of simple, cheap and easily-obtained starting materials and simple process, can effectively reduce the production cost, and is suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of synthesis of photosensitive materials and drug intermediates, and particularly relates to a method for synthesizing 2-amino-4-chloro-5 nitrophenol in a microchannel reactor.
Background
The 2-amino-4-chloro-5 nitrophenol is an important intermediate for synthesizing photosensitive materials, dyes, medicines and pesticides, has wide application and is an intermediate with development prospect, but the 2-amino-4-chloro-5 nitrophenol has no ideal industrial production method. At present, two main production methods of the intermediate are available, one is to synthesize 2-amino-4-chloro-5-nitrophenol by phosgene and 2-amino-4-chlorophenol; the other is a traditional kettle type closed loop, nitration and hydrolysis three-step method or a two-step method. The two methods have the disadvantages of laggard process, long flow, low yield and great pollution. There is a literature in the photosensory society that discloses a conventional reactor nitration process for obtaining 3, 4-dinitropyrazole, which may result in production safety and environmental pollution, and is not conducive to continuous production. And because the traditional batch type reaction kettle often has the problem of low mass transfer and heat transfer efficiency of the reactor due to the relation of the size of equipment, the defects of low yield, low production efficiency, poor quality stability of batch operation products and the like are easily caused due to uneven temperature and concentration, especially when dangerous processes such as nitration and hydrogenation reduction are treated, the potential safety hazard of the kettle type reaction process is large and is limited by the factors of reaction atom economy, process practicability and the like, and the substitution methods of the dangerous processes are often high in cost and longer in route.
Disclosure of Invention
Aiming at the technical problems, the method for synthesizing the 2-amino-4-chloro-5 nitrophenol in the microchannel reactor is provided, the microchannel reactor and the batch reactor are connected in series for synthesis, the problem that the digestion reaction is violent in the early stage of the reaction and difficult to control is solved, and the intrinsic safety of the process is improved.
The purpose of the invention is realized by the following technical scheme:
the invention relates to a method for synthesizing 2-amino-4-chloro-5 nitrophenol in a microchannel reactor, which takes 5-chloro-2-methylbenzoxazole as a raw material, and the microchannel reactor and a batch reactor are connected in series for reaction to synthesize the 2-amino-4-chloro-5 nitrophenol, and comprises the following steps:
step one, synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole: under an ice water bath, slowly mixing concentrated sulfuric acid and fuming nitric acid according to a molar ratio of 1-1.8:1 to obtain mixed nitric-sulfur acid, respectively conveying the mixed nitric-sulfur acid and a sulfuric acid solution of 5-chloro-2-methylbenzoxazole prepared according to a ratio of 1.5-1:1 to two inlets of a microchannel reactor, controlling the molar ratio of the nitric acid to the 5-chloro-2-methylbenzoxazole to be 1-1.2: 1, instantly mixing and contacting two liquid streams in the microchannel reactor at 0-20 ℃ and reacting, and then pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole:
discharging the 5-chloro-2-methyl-6-nitro-benzoxazole obtained after the reaction of the microchannel reactor in the step one to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain a 2-amino-4-chloro-5 nitrophenol crystal:
preferably, in the first step, the molar ratio of the concentrated sulfuric acid to the fuming nitric acid is 1-1.8:1, the molar ratio of the fuming nitric acid to the 5-chloro-2-methylbenzoxazole is 1-1.2: 1, and the molar ratio of the concentrated sulfuric acid to the 5-chloro-2-methylbenzoxazole is 1-1.5: 1.
Preferably, in the step 1, the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is delivered by a high-pressure constant flow pump with accurately controlled flow, and the flow rate is controlled to be 0.1-1 mL/min.
Preferably, in the step 1, the mixed nitric acid and sulfuric acid is delivered by a high-pressure constant flow pump with accurately controlled flow, and the flow rate is controlled to be 0.2-1 mL/min.
Preferably, in the step 1, the reaction temperature is 0-20 ℃.
Preferably, in the step 1, the reaction retention time is 1-20 min.
The invention has the beneficial effects that:
the synthesis method of the 2-amino-4-chloro-5 nitrophenol is synthesized by connecting the microchannel reactor and the batch reactor in series, avoids the problem that the control is difficult due to violent digestion reaction in the early stage of the reaction, improves the intrinsic safety of the process, and has the advantages of high production efficiency, strong economy, easy industrialization and continuous production. The microchannel reactor can realize rapid heat transfer and keep constant temperature, reaction materials are instantly mixed, the reaction time is shortened from traditional hours to dozens of seconds to several minutes, heat can be timely led out, local overheating is eliminated, the production danger is reduced, the production efficiency is improved, and the possibility of safety accidents caused by improper operation is reduced. The short-time high efficiency of the unreacted system can reduce the generation of acid wastewater and byproducts, and the selectivity of the product is improved. The energy consumption is reduced, and the environment is protected.
Detailed Description
The present invention will be described in detail with reference to examples.
Examples 1 to 5: the synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole of the invention: under the ice-water bath, 11g of concentrated sulfuric acid and 7g of 65% fuming nitric acid are slowly mixed according to the molar ratio of 1.1:1 to obtain mixed nitric-sulfur acid, under the ice-water bath, 16.7g (0.1mol) of 5-chloro-2-methylbenzoxazole is dissolved in 98% sulfuric acid according to the molar ratio of 1:1, the mixed nitric-sulfur acid and the sulfuric acid solution of 5-chloro-2-methylbenzoxazole are respectively pumped into a microchannel reactor, the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.5mL/min, the flow rate of the mixed nitric-sulfur acid is 0.3mL/min, the retention time is 10min, and the reaction temperature is 10 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1-1.2: 1, instantly mixing and contacting two streams of liquid in a microchannel reactor at 10 ℃ and reacting, and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to a batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals, wherein 1H NMR (400MHz, CDCl3) is 6.686ppm (s, phenolic hydroxyl ortho hydrogen); δ 6.686ppm (s, hydrogen meta to phenolic hydroxyl); δ 6.334ppm (s, anilinohydrogen); δ 10.311ppm (s, phenolic hydroxyl hydrogen):
TABLE 1
| Examples | 1 | 2 | 3 | 4 | 5 |
| n (5-chloro-2-methylbenzoxazole)/n (nitric acid) | 1.0:1.0 | 1.0:1.05 | 1.0:1.1 | 1.0:1.15 | 1.0:1.2 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.1:1.0 | 1.1:1.0 | 1.1:1.0 | 1.1:1.0 | 1.1:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1:1 | 1:1 | 1:1 | 1:1 | 1:1 |
| Reaction temperature (. degree.C.) | 10 | 10 | 10 | 10 | 10 |
| Flow rate of sulfuric acid solution (ml/min) | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| Flow rate of mixed acid (ml/min) | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 |
| Residence time (min) | 10 | 10 | 10 | 10 | 10 |
| Purity (%) | 99.1 | 98.9 | 98.5 | 98.6 | 98.1 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 91.5 | 91 | 89.4 | 87.6 | 88.2 |
Examples 6 to 10: the difference between this example and example 1 is: synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole in this example: under the condition of ice-water bath, slowly mixing concentrated sulfuric acid and 65% fuming nitric acid according to the molar ratio of 1-1.8:1 to obtain mixed nitric acid and sulfur acid, under the condition of ice-water bath, dissolving 16.7g (0.1mol) of 5-chloro-2-methylbenzoxazole in 98% sulfuric acid according to the molar ratio of 1:1, respectively pumping the mixed nitric acid and sulfur acid solution of 5-chloro-2-methylbenzoxazole into a microchannel reactor, wherein the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.4L/min, the flow rate of the mixed nitric acid and sulfur acid is controlled to be 0.5mL/min, the retention time is 8min, and the reaction temperature is 10 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1:1, instantly mixing and contacting two liquids in a microchannel reactor at 10 ℃ and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals.
TABLE 2
| Examples | 6 | 7 | 8 | 9 | 10 |
| n (5-chloro-2-methylbenzoxazole)/n (nitric acid) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.1:1.0 | 1.2:1.0 | 1.4:1.0 | 1.6:1.0 | 1.8:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1:1 | 1:1 | 1:1 | 1:1 | 1:1 |
| Reaction temperature (. degree.C.) | 10 | 10 | 10 | 10 | 10 |
| Flow rate of sulfuric acid solution (ml/min) | 0.4 | 0.4 | 0.4 | 0.4 | 0.4 |
| Flow rate of mixed acid (ml/min) | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| Residence time (min) | 8 | 8 | 8 | 8 | 8 |
| Purity (%) | 98.1 | 98.8 | 97.5 | 96.6 | 96.1 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 88.5 | 90.1 | 89.4 | 87.6 | 88.7 |
Examples 11 to 15: the difference between this example and example 1 is: synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole in this example: under the ice-water bath, 24g of concentrated sulfuric acid and 14g of 65% fuming nitric acid are slowly mixed according to the molar ratio of 1.2:1 to obtain mixed nitric-sulfur acid, under the ice-water bath, 33.4g (0.2mol) of 5-chloro-2-methylbenzoxazole is dissolved in 98% sulfuric acid according to the molar ratio of 1:1-1.5, the mixed nitric-sulfur acid and the sulfuric acid solution of 5-chloro-2-methylbenzoxazole are respectively pumped into a microchannel reactor, the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.5mL/min, the flow rate of the mixed nitric-sulfur acid is 0.4mL/min, the retention time is 5min, and the reaction temperature is 5 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1:1, instantly mixing and contacting two liquids in a microchannel reactor at the temperature of 5 ℃ and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals.
TABLE 3
| Examples | 11 | 12 | 13 | 14 | 15 |
| n (5-chloro-2-methylbenzoxazole)N (nitric acid) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1.0:1.0 | 1.1:1.0 | 1.2:1.0 | 1.4:1.0 | 1.5:1.0 |
| Reaction temperature (. degree.C.) | 5 | 5 | 5 | 5 | 5 |
| Flow rate of sulfuric acid solution (ml/min) | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| Flow rate of mixed acid (ml/mi)n) | 0.4 | 0.4 | 0.4 | 0.4 | 0.4 |
| Residence time (min) | 5 | 5 | 5 | 5 | 5 |
| Purity (%) | 99.2 | 98.9 | 98.5 | 97.5 | 98.1 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 89.6 | 87.8 | 88.4 | 89.1 | 88.5 |
Examples 16 to 20: the difference between this example and example 1 is: synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole in this example: under the ice-water bath, 24g of concentrated sulfuric acid and 14g of 65% fuming nitric acid are slowly mixed according to the molar ratio of 1.2:1 to obtain mixed nitric-sulfur acid, under the ice-water bath, 33.4g (0.2mol) of 5-chloro-2-methylbenzoxazole is dissolved in 98% sulfuric acid according to the molar ratio of 1:1, the mixed nitric-sulfur acid and the sulfuric acid solution of 5-chloro-2-methylbenzoxazole are respectively pumped into a microchannel reactor, the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.6mL/min, the flow rate of the mixed nitric-sulfur acid is 0.4mL/min, the retention time is 10min, and the reaction temperature is 1-20 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1:1, instantly mixing and contacting two liquids in a microchannel reactor at the temperature of 1-20 ℃ and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals.
TABLE 4
| Examples | 16 | 17 | 18 | 19 | 20 |
| n (5-chloro-2-methylbenzoxazole)/n (nitric acid) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| Reaction temperature (. degree.C.) | 0 | 5 | 10 | 15 | 20 |
| Flow rate of sulfuric acid solution (ml/mi)n) | 0.6 | 0.6 | 0.6 | 0.6 | 0.6 |
| Flow rate of mixed acid (ml/mi)n) | 0.4 | 0.4 | 0.4 | 0.4 | 0.4 |
| Residence time (mi)n) | 10 | 10 | 10 | 10 | 10 |
| Purity (%) | 98.1 | 98.5 | 99.2 | 98.6 | 97.1 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 87.6 | 89.2 | 89.1 | 89.7 | 89.2 |
Examples 21 to 25: the difference between this example and example 1 is: synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole in this example: under the ice-water bath, 60g of concentrated sulfuric acid and 35g of 65% fuming nitric acid are slowly mixed according to the molar ratio of 1.2:1 to obtain mixed nitric-sulfur acid, under the ice-water bath, 83.5g (0.5mol) of 5-chloro-2-methylbenzoxazole is dissolved in 98% sulfuric acid according to the molar ratio of 1:1, the mixed nitric-sulfur acid and the sulfuric acid solution of 5-chloro-2-methylbenzoxazole are respectively pumped into a microchannel reactor, the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.1-1mL/min, the flow rate of the mixed nitric-sulfur acid is 0.4mL/min, the retention time is 10min, and the reaction temperature is 10 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1:1, instantly mixing and contacting two liquids in a microchannel reactor at 10 ℃ and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals.
TABLE 5
| Examples | 21 | 22 | 23 | 24 | 25 |
| n (5-chloro-2-methylbenzoxazole) </orn(nitric acid) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| Reaction temperature (. degree.C.) | 10 | 10 | 10 | 10 | 10 |
| Flow rate of sulfuric acid solution (ml/mi)n) | 0.1 | 0.3 | 0.5 | 0.8 | 1.0 |
| Flow rate of mixed acid (ml/mi)n) | 0.4 | 0.4 | 0.4 | 0.4 | 0.4 |
| Residence time (min) | 10 | 10 | 10 | 10 | 10 |
| Purity (%) | 96.2 | 97.5 | 98.7 | 97.7 | 96.9 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 85.6 | 87.2 | 88.1 | 87.8 | 86.2 |
Examples 26 to 30: the difference between this example and example 1 is: synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole in this example: under the ice-water bath, 60g of concentrated sulfuric acid and 35g of 65% fuming nitric acid are slowly mixed according to the molar ratio of 1.2:1 to obtain mixed nitric-sulfur acid, under the ice-water bath, 83.5g (0.5mol) of 5-chloro-2-methylbenzoxazole is dissolved in 98% sulfuric acid according to the molar ratio of 1:1, the mixed nitric-sulfur acid and the sulfuric acid solution of 5-chloro-2-methylbenzoxazole are respectively pumped into a microchannel reactor, the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.5mL/min, the flow rate of the mixed nitric-sulfur acid is 0.2-1mL/min, the retention time is 10min, and the reaction temperature is 10 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1:1, instantly mixing and contacting two liquids in a microchannel reactor at 10 ℃ and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals.
TABLE 6
| Examples | 26 | 27 | 28 | 29 | 30 |
| n (5-chloro-2-methylbenzoxazole)/n (nitric acid) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| Reaction temperature (. degree.C.) | 10 | 10 | 10 | 10 | 10 |
| Flow rate of sulfuric acid solution (ml/min) | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| Flow rate of mixed acid (ml/min) | 0.2 | 0.4 | 0.6 | 0.8 | 1.0 |
| Residence time (min) | 10 | 10 | 10 | 10 | 10 |
| Purity (%) | 97.2 | 99.0 | 98.6 | 97.4 | 96.5 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 87.5 | 88.9 | 89.4 | 87.3 | 85.1 |
Examples 31 to 35: the difference between this example and example 1 is: synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole in this example: under the ice-water bath, 120g of concentrated sulfuric acid and 70g of 65% fuming nitric acid are slowly mixed according to the molar ratio of 1.2:1 to obtain mixed nitric-sulfur acid, under the ice-water bath, 167g (1mol) of 5-chloro-2-methylbenzoxazole is dissolved in 98% sulfuric acid according to the molar ratio of 1:1, the mixed nitric-sulfur acid and the sulfuric acid solution of 5-chloro-2-methylbenzoxazole are respectively pumped into a microchannel reactor, the flow rate of the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is controlled to be 0.5mL/min, the flow rate of the mixed nitric-sulfur acid is 0.4mL/min, the retention time is 1-20min, and the reaction temperature is 10 ℃.
Controlling the molar ratio of nitric acid to 5-chloro-2-methylbenzoxazole to be 1:1, instantly mixing and contacting two liquids in a microchannel reactor at 10 ℃ and pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole. Discharging the obtained 5-chloro-2-methyl-6-nitro-benzoxazole to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain 2-amino-4-chloro-5-nitrophenol crystals.
TABLE 7
| Examples | 31 | 32 | 33 | 34 | 35 |
| n (5-chloro-2-methylbenzoxazole)/n (nitric acid) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| n (concentrated sulfuric acid)/n (fuming nitric acid) | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 | 1.2:1.0 |
| n (concentrated sulfuric acid)/n (5-chloro-2-methylbenzoxazole) | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 | 1.0:1.0 |
| Reaction temperature (. degree.C.) | 10 | 10 | 10 | 10 | 10 |
| Flow rate of sulfuric acid solution (ml/mi)n) | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| Flow rate of mixed acid (ml/mi)n) | 0.4 | 0.4 | 0.4 | 0.4 | 0.4 |
| Residence time (mi)n) | 1 | 5 | 10 | 15 | 20 |
| Purity (%) | 96.2 | 97.0 | 98.9 | 96.4 | 97.5 |
| Yield% (based on 5-chloro-2-methyl-6-nitrobenzoxazole) | 86.5 | 87.8 | 89.8 | 89.3 | 88.1 |
It should be understood that the detailed description of the present invention is only for illustrating the present invention and is not limited by the technical solutions described in the embodiments of the present invention, and those skilled in the art should understand that the present invention can be modified or substituted equally to achieve the same technical effects; as long as the use requirements are met, the method is within the protection scope of the invention.
Claims (6)
1. A method for synthesizing 2-amino-4-chloro-5 nitrophenol in a microchannel reactor is characterized in that 5-chloro-2-methylbenzoxazole is used as a raw material, the microchannel reactor and a batch reactor are connected in series for reaction, and the 2-amino-4-chloro-5 nitrophenol is synthesized, and the method comprises the following steps:
step one, synthesis of 5-chloro-2-methyl-6-nitro-benzoxazole: under an ice water bath, slowly mixing concentrated sulfuric acid and fuming nitric acid according to a molar ratio of 1-1.8:1 to obtain mixed nitric-sulfur acid, respectively conveying the mixed nitric-sulfur acid and a sulfuric acid solution of 5-chloro-2-methylbenzoxazole prepared according to a ratio of 1.5-1:1 to two inlets of a microchannel reactor, controlling the molar ratio of the nitric acid to the 5-chloro-2-methylbenzoxazole to be 1-1.2: 1, instantly mixing and contacting two liquid streams in the microchannel reactor at 0-20 ℃ and reacting, and then pouring the reaction solution into crushed ice to obtain the 5-chloro-2-methyl-6-nitro-benzoxazole:
discharging the 5-chloro-2-methyl-6-nitro-benzoxazole obtained after the reaction of the microchannel reactor in the step one to the batch reactor, hydrolyzing in the batch reactor, decoloring by active carbon, and filtering to obtain a 2-amino-4-chloro-5 nitrophenol crystal:
2. the synthesis method according to claim 1, wherein in the first step, the molar ratio of the concentrated sulfuric acid to the fuming nitric acid is 1-1.8:1, the molar ratio of the fuming nitric acid to the 5-chloro-2-methylbenzoxazole is 1-1.2: 1, and the molar ratio of the concentrated sulfuric acid to the 5-chloro-2-methylbenzoxazole is 1-1.5: 1.
3. The synthesis method according to claim 1, wherein in the step 1, the sulfuric acid solution of 5-chloro-2-methylbenzoxazole is delivered by a high-pressure constant flow pump with accurately controlled flow, and the flow rate is controlled to be 0.1-1 mL/min.
4. The synthesis method according to claim 1, wherein in the step 1, the mixed nitric acid and sulfuric acid is delivered by a high-pressure constant flow pump with accurately controlled flow, and the flow rate is controlled to be 0.2-1 mL/min.
5. The synthesis method according to claim 1, wherein in the step 1, the reaction temperature is 0-20 ℃.
6. The synthesis method according to claim 1, wherein in the step 1, the reaction retention time is 1-20 min.
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| CN105753730A (en) * | 2016-04-06 | 2016-07-13 | 宜兴市新宇化工有限公司 | Method for preparing 2-amino-4-chloro-5-nitrophenol |
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