Search

CN-121974805-A - Preparation method of 6-nitro-m-cresol

CN121974805ACN 121974805 ACN121974805 ACN 121974805ACN-121974805-A

Abstract

The invention discloses a preparation method of 6-nitro-m-cresol, belonging to the technical field of organic synthesis, the method sequentially carries out esterification, water washing, sulfonation, nitration, desulfonation and refining on the raw materials to obtain the 6-nitro-m-cresol. The method can ensure that the intermediate product is a 6-nitro derivative, greatly reduces the generation of 2-site and 4-site isomer impurities from the source, has definite reaction path and good atom economy. The method of the invention does not need to rely on time-consuming column chromatography or precise fractionation and other complex means, can meet the requirement of high purity only by conventional extraction and crystallization operation, has simple process flow, is very suitable for large-scale production, and can stably reach more than 98% of product purity (such as by HPLC measurement).

Inventors

  • ZHANG HAN

Assignees

  • 张涵

Dates

Publication Date
20260505
Application Date
20260121

Claims (10)

  1. 1. The preparation method of the 6-nitro-m-cresol is characterized by comprising the following steps of: (1) After drying the reaction kettle, adding m-cresol into the reaction kettle, adding aluminum oxide under the condition of stirring, then heating to 45-55 ℃, and preserving heat; (2) Dropwise adding phosphorus oxychloride into a reaction kettle, heating to 80-100 ℃ after the dropwise adding, and carrying out heat preservation reaction for 1-2 hours; (3) Continuously heating to above 120-135 ℃ after the reaction is finished, and carrying out heat preservation reaction for 2.5-4 hours at the temperature, and naturally cooling to 100-90 ℃ after the heat preservation reaction is finished to obtain an esterified substance; (4) Washing the esterified substance with water and dilute alkaline water in sequence, washing the esterified substance with water until the pH value is 5-6, and drying under reduced pressure to remove water; (5) Adding sulfuric acid into the esterified substance after decompression drying, heating to 68-70 ℃, and reacting for 4-6 hours under heat preservation to obtain a sulfonated material; (6) Adding water and sulfuric acid into an acid preparation kettle, adding nitric acid and stirring and cooling to 0-5 ℃ to obtain mixed acid; (7) Adding the sulfonated material into a cold kettle, stirring and cooling to below 0 ℃, then dropwise adding mixed acid into the sulfonated material, and after the heat preservation reaction is completed, obtaining a nitrified material; (8) Adding water into a distillation kettle, adding a nitrifying material, opening jacket steam, heating to 120 ℃, and performing steam distillation to obtain a crude wet material; (9) Mixing the crude wet material with petroleum ether, stirring and heating to 50-55deg.C, and completely and uniformly mixing; (10) Adding 0.8wt% of liquid caustic soda into the mixture obtained in the step (9), keeping warm, stirring uniformly, standing for layering, removing lower alkaline water, and repeating the operation for 1-3 times to obtain a petroleum ether layer; (11) And cooling and crystallizing the petroleum ether layer, and discharging at 5 ℃ to obtain the 6-nitro-m-cresol.
  2. 2. The method for preparing 6-nitro-m-cresol according to claim 1, wherein the mass ratio of m-cresol to aluminum oxide in the step (1) is 200:20.
  3. 3. The preparation method of 6-nitro-m-cresol according to claim 1 or 2, wherein the mass ratio of the m-cresol to phosphorus oxychloride is 200:90-110, and the phosphorus oxychloride is added dropwise for 2-4h to finish the dropwise addition.
  4. 4. The method for producing 6-nitrom-cresol according to claim 1, wherein the mass concentration of the diluted alkaline water in the step (4) is 0.4 to 0.8%.
  5. 5. The process for producing 6-nitrom-cresol according to claim 2, wherein the mass ratio of m-cresol to sulfuric acid used in the step (5) is 200:1100-1300.
  6. 6. The method for producing 6-nitrom-cresol according to claim 1, wherein the mass ratio of water, sulfuric acid and nitric acid in the step (6) is 27:153:66.
  7. 7. The method for preparing 6-nitrom-cresol according to claim 6, wherein the mass ratio of the sulfonated material to the mixed acid in the step (7) is 725:230-260.
  8. 8. The method for preparing 6-nitrom-cresol according to claim 1, wherein the mass ratio of the nitrifying material to water in the step (8) is 970:400-500.
  9. 9. The method for preparing 6-nitro-m-cresol according to claim 1, wherein the mass ratio of the crude wet material to petroleum ether in the step (9) is 280-300:600.
  10. 10. The method for preparing 6-nitrom-cresol according to claim 9, wherein the mass ratio of the liquid alkali to the crude wet material in the step (10) is 400:280-300.

Description

Preparation method of 6-nitro-m-cresol Technical Field The invention relates to the technical field of organic synthesis, in particular to a preparation method of 6-nitro-m-cresol. Background 6-Nitro-m-cresol (6-Nitro-m-cresol), the chemical name of which is 3-methyl-6-nitrophenol, is an important fine chemical intermediate, and is widely applied to the synthesis of dye, pigment, pesticide, medicine and other fields. In the molecular structure of the compound, the nitro (-NO 2) is positioned at the meta position of the phenolic hydroxyl and the ortho position of the methyl, and the specific structure makes the compound a key precursor for synthesizing certain high-performance chemicals. At present, most of the methods for preparing nitrophenol compounds in industry and literature report adopt a direct nitration process of phenol or cresol compounds. Whereas the direct nitration of m-cresol inevitably yields a complex isomer mixture based on 4-nitrom-cresol and 2-nitrom-cresol, the target product 6-nitrom-cresol (nitro meta to hydroxy, ortho to methyl) is produced in very low proportions, usually less than 10%. This inherent regioselectivity problem is a fundamental technical bottleneck that restricts the efficient synthesis of 6-nitrom-cresol. Therefore, it is an urgent need in the art to provide an industrial process for preparing 6-nitrom-cresol with high regioselectivity, high efficiency and simplicity. Disclosure of Invention In view of the above, the invention provides a preparation method of 6-nitrom-cresol with high synthesis efficiency and high purity. In order to achieve the above purpose, the invention adopts the following technical scheme: A preparation method of 6-nitro-m-cresol comprises the following steps: (1) After drying the reaction kettle, adding m-cresol into the reaction kettle, adding aluminum oxide under the condition of stirring, then heating to 45-55 ℃, and preserving heat; (2) Dropwise adding phosphorus oxychloride into a reaction kettle, heating to 80-100 ℃ after the dropwise adding, and carrying out heat preservation reaction for 1-2 hours; (3) Continuously heating to above 120-135 ℃ after the reaction is finished, and carrying out heat preservation reaction for 2.5-4 hours at the temperature, and naturally cooling to 100-90 ℃ after the heat preservation reaction is finished to obtain an esterified substance; (4) Washing the esterified substance with water and dilute alkaline water in sequence, washing the esterified substance with water until the pH value is 5-6, and drying under reduced pressure to remove water; (5) Adding sulfuric acid into the esterified substance after decompression drying, heating to 68-70 ℃, and reacting for 4-6 hours under heat preservation to obtain a sulfonated material; (6) Adding water and sulfuric acid into an acid preparation kettle, adding nitric acid and stirring and cooling to 0-5 ℃ to obtain mixed acid; (7) Adding the sulfonated material into a cold kettle, stirring and cooling to below 0 ℃, then dropwise adding mixed acid into the sulfonated material, and after the heat preservation reaction is completed, obtaining a nitrified material; (8) Adding water into a distillation kettle, adding a nitrifying material, opening jacket steam, heating to 120 ℃, and performing steam distillation to obtain a crude wet material; (9) Mixing the crude wet material with petroleum ether, stirring and heating to 50-55deg.C, and completely and uniformly mixing; (10) Adding 0.8wt% of liquid caustic soda into the mixture obtained in the step (9), keeping warm, stirring uniformly, standing for layering, removing lower alkaline water, and repeating the operation for 1-3 times to obtain a petroleum ether layer; (11) And cooling and crystallizing the petroleum ether layer, and discharging at 5 ℃ to obtain the 6-nitro-m-cresol. Further, the mass ratio of the m-cresol to the aluminum oxide in the step (1) is 200:20. The method for preparing 6-nitrom-cresol according to claim 1 or 2, wherein the mass ratio of the m-cresol to the phosphorus oxychloride is 200:90-110, and the phosphorus oxychloride is added dropwise for 2-4 hours. Further, the mass concentration of the dilute alkaline water in the step (4) is 0.4-0.8%. Further, the mass ratio of m-cresol to sulfuric acid used in step (5) is 200:1100-1300. Further, the mass ratio of water, sulfuric acid and nitric acid in step (6) is 27:153:66. Further, the mass ratio of the sulfonated material to the mixed acid in the step (7) is 725:230-260. Further, the mass ratio of the nitrifying material to the water in the step (8) is 970:400-500. Further, the mass ratio of the crude wet material to petroleum ether in the step (9) is 280-300:600. Further, the mass ratio of the liquid alkali to the crude wet material in the step (10) is 400:280-300. The method has the advantages that the method can ensure that the intermediate product is the 6-nitro derivative, greatly reduces the generation of 2-site and 4-site isomer impurities from th