Method for preparing o-fluorophenol from stable triazene intermediate

Abstract

The invention provides a method for preparing o-fluorophenol from a stable triazene intermediate, and belongs to the technical field of medical technology (organic synthesis). The method is technically characterized by comprising the following steps of: (1) firstly, adding water and concentrated hydrochloric acid into a reaction bottle to prepare a dilute acid solution; (2) adding a substrate o-fluoroaniline into the prepared dilute acid; (3) continuously dropwise adding isoamyl nitrite into a reaction bottle at low temperature to prepare diazonium salt; (4) dropwise adding an acetonitrile solution of secondary amine into the prepared diazonium salt solution at low temperature to prepare a stable triazene intermediate; (5) dropwise adding the prepared mixed solution and an organic solvent into a preheated copper salt solution at the same time for hydrolysis, and starting distillation at the same time; and (6) finally treating the distillation fraction to obtain the target product o-fluorophenol. According to the preparation method of the target product provided by the invention, the triazene intermediate is adopted to replace diazonium salt for hydrolysis reaction, so that the stability of the reaction intermediate is greatly improved, the potential safety hazard of large-scale production is reduced, and the yield of the product is also improved.

Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for preparing o-fluorophenol from a stable triazene intermediate. Background technique

[0002] O-fluorophenol is an important pharmaceutical and agricultural chemical intermediate, used in the synthesis of fungicides, herbicides, dyes, new fluorine-containing liquid crystal materials, plastic and rubber additives.

[0003] The synthetic method of o-fluorophenol has a lot (for example: CN108558607A, CN108558607A), mainly contains three kinds of methods such as phenol low-temperature fluorination method, o-fluorobromobenzene hydrolysis method, o-fluoroaniline diazotization hydrolysis method by raw material route.

[0004] The first category: low-temperature fluorination of phenol. This method not only requires the use of highly dangerous fluorine gas, but also the two isomer products, p-fluorophenol and o-fluorophenol, are difficult to separate, and tar-like by-products a...

Examples

Embodiment 1

[0035] Put 3L of water into the 10L four-necked bottle 1, then slowly add 978.5g of 36% hydrochloric acid dropwise, and add dropwise while stirring. After the dropwise addition, the temperature of the prepared diluted hydrochloric acid is 40-50°C. Then, the temperature was lowered to 10-15° C., and 500 g of o-fluoroaniline was quickly dropped into bottle 1 to form a salt. Then, continue to lower the temperature to 0-5°C and add 606.1 g of isoamyl nitrite dropwise for 1 hour. After the dropwise addition is completed, keep warm at 0-5°C and react for 0.5h, then take a sample, and use starch potassium iodide test paper to detect that it first turns purple-black, and then turns blue. Then, dropwise add a solution prepared by 510.2 g of morpholine and 500 mL of acetonitrile into the reaction bottle 1 at 0-5° C., after the addition is completed, keep warm at 0-5° C. for 1 hour. Put 2L of water and 561.8g of copper sulfate pentahydrate into the 10L four-necked bottle 2 equipped with...

Embodiment 2

[0037] Put 4L of water into the 10L four-necked bottle 1, then slowly add 1293.6g of 36% hydrochloric acid dropwise, and add dropwise while stirring. After the dropwise addition, the temperature of the prepared dilute hydrochloric acid is 40-50°C. Then, the temperature was lowered to 10-15° C., and 500 g of o-fluoroaniline was quickly dropped into bottle 1 to form a salt. Then, continue to lower the temperature to 0-5°C and add 632.5 g of isoamyl nitrite dropwise for 1 hour. After the dropwise addition is completed, keep warm at 0-5°C and react for 0.5h, then take a sample, and use starch potassium iodide test paper to detect that it first turns purple-black, and then turns blue. Then, dropwise add a solution prepared by 587.8 g of morpholine and 600 mL of acetonitrile into the reaction bottle 1 at 0-5° C., after the addition is completed, keep warm at 0-5° C. for 1 hour. Put 2.5L of water and 702.2g of copper sulfate pentahydrate into the 10L four-neck bottle 2 equipped with...

Embodiment 3

[0039] Put 3.5L of water into the 10L four-necked bottle 1, then slowly add 1140.3g of 36% hydrochloric acid dropwise, and add dropwise while stirring. After the dropwise addition, the temperature of the prepared dilute hydrochloric acid is 40-50°C. Then, the temperature was lowered to 10-15° C., and 500 g of o-fluoroaniline was quickly dropped into bottle 1 to form a salt. Then, continue to lower the temperature to 0-5°C and add 613.2 g of isoamyl nitrite dropwise for 1 hour. After the dropwise addition is completed, keep warm at 0-5°C and react for 0.5h, then take a sample, and use starch potassium iodide test paper to detect that it first turns purple-black, and then turns blue. Then, dropwise add the solution prepared by 498.6 g of hexahydropyridine and 500 mL of acetonitrile into the reaction bottle 1 at 0-5° C., after the addition is completed, keep the temperature at 0-5° C. for 1 hour. Put 2L of water and 561.8g of copper sulfate pentahydrate into the 10L four-necked ...

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for preparing o-fluorophenol from a stable triazene intermediate. Background technique

[0002] O-fluorophenol is an important pharmaceutical and agricultural chemical intermediate, used in the synthesis of fungicides, herbicides, dyes, new fluorine-containing liquid crystal materials, plastic and rubber additives.

[0003] The synthetic method of o-fluorophenol has a lot (for example: CN108558607A, CN108558607A), mainly contains three kinds of methods such as phenol low-temperature fluorination method, o-fluorobromobenzene hydrolysis method, o-fluoroaniline diazotization hydrolysis method by raw material route.

[0004] The first category: low-temperature fluorination of phenol. This method not only requires the use of highly dangerous fluorine gas, but also the two isomer products, p-fluorophenol and o-fluorophenol, are difficult to separate, and tar-like by-products a...

Examples

Embodiment 1

[0035] Put 3L of water into the 10L four-necked bottle 1, then slowly add 978.5g of 36% hydrochloric acid dropwise, and add dropwise while stirring. After the dropwise addition, the temperature of the prepared diluted hydrochloric acid is 40-50°C. Then, the temperature was lowered to 10-15° C., and 500 g of o-fluoroaniline was quickly dropped into bottle 1 to form a salt. Then, continue to lower the temperature to 0-5°C and add 606.1 g of isoamyl nitrite dropwise for 1 hour. After the dropwise addition is completed, keep warm at 0-5°C and react for 0.5h, then take a sample, and use starch potassium iodide test paper to detect that it first turns purple-black, and then turns blue. Then, dropwise add a solution prepared by 510.2 g of morpholine and 500 mL of acetonitrile into the reaction bottle 1 at 0-5° C., after the addition is completed, keep warm at 0-5° C. for 1 hour. Put 2L of water and 561.8g of copper sulfate pentahydrate into the 10L four-necked bottle 2 equipped with...

Embodiment 2

[0037] Put 4L of water into the 10L four-necked bottle 1, then slowly add 1293.6g of 36% hydrochloric acid dropwise, and add dropwise while stirring. After the dropwise addition, the temperature of the prepared dilute hydrochloric acid is 40-50°C. Then, the temperature was lowered to 10-15° C., and 500 g of o-fluoroaniline was quickly dropped into bottle 1 to form a salt. Then, continue to lower the temperature to 0-5°C and add 632.5 g of isoamyl nitrite dropwise for 1 hour. After the dropwise addition is completed, keep warm at 0-5°C and react for 0.5h, then take a sample, and use starch potassium iodide test paper to detect that it first turns purple-black, and then turns blue. Then, dropwise add a solution prepared by 587.8 g of morpholine and 600 mL of acetonitrile into the reaction bottle 1 at 0-5° C., after the addition is completed, keep warm at 0-5° C. for 1 hour. Put 2.5L of water and 702.2g of copper sulfate pentahydrate into the 10L four-neck bottle 2 equipped with...

Embodiment 3

[0039] Put 3.5L of water into the 10L four-necked bottle 1, then slowly add 1140.3g of 36% hydrochloric acid dropwise, and add dropwise while stirring. After the dropwise addition, the temperature of the prepared dilute hydrochloric acid is 40-50°C. Then, the temperature was lowered to 10-15° C., and 500 g of o-fluoroaniline was quickly dropped into bottle 1 to form a salt. Then, continue to lower the temperature to 0-5°C and add 613.2 g of isoamyl nitrite dropwise for 1 hour. After the dropwise addition is completed, keep warm at 0-5°C and react for 0.5h, then take a sample, and use starch potassium iodide test paper to detect that it first turns purple-black, and then turns blue. Then, dropwise add the solution prepared by 498.6 g of hexahydropyridine and 500 mL of acetonitrile into the reaction bottle 1 at 0-5° C., after the addition is completed, keep the temperature at 0-5° C. for 1 hour. Put 2L of water and 561.8g of copper sulfate pentahydrate into the 10L four-necked ...

Images