Hydrolysis method of 4-hydroxy-3, 5-diiodobenzonitrile

Abstract

The invention provides a hydrolysis method of 4-hydroxy-3, 5-diiodobenzonitrile, and relates to the technical field of organic synthesis. Specifically, the method comprises the following steps: hydrolyzing 4-hydroxy-3, 5-diiodobenzonitrile under a strong acid or strong alkali condition in the presence of protective gas and a solvent; according to the hydrolysis method of the 4-hydroxy-3, 5-diiodobenzonitrile, provided by the invention, the 4-hydroxy-3, 5-diiodobenzamide is synthesized through hydrolysis by adopting a one-step reaction; the method comprises the following steps: carrying out hydrolysis reaction on 4-hydroxy-3, 5-diiodobenzonitrile serving as a raw material under a strongly alkaline or strongly acidic condition; the reaction process is controlled by controlling the proportion of the strong base or the strong acid and the reaction temperature, the generated amide is easily hydrolyzed into carboxylic acid, the hydrolysis degree is controlled by controlling the molar ratio and the acid-base concentration of substances, the strong acid and sulfuric acid are optimally used and generally controlled within 2 times, the yield and the content are good, the content is 95% or above, and the yield is 80%-85%.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and more specifically to a method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile. Background Art

[0002] 4-Hydroxy-3,5-diiodobenzamide and 3,5-diiodo-4-hydroxybenzoic acid are degradation metabolites of the broadleaf weed herbicide octanoyliodobenzonitrile. There are few reports on the preparation of these two compounds, and the synthesis routes are unclear. Relevant synthesis schemes were sorted out through literature and patent retrieval.

[0003] 4-Hydroxy-3,5-diiodobenzamide. There is basically no direct synthetic route. There are two design routes. Idea 1: One-step method: Using iodobenzonitrile as raw material to hydrolyze the cyanide, control the degree of hydrolysis, and hydrolyze to amide in one step. If the amide is not controlled, it will continue to hydrolyze to carboxylic acid; Idea 2: Two-step method: Using 3,5-diiodo-4-hydroxybenzoic acid as raw material to undergo chlorination reaction to generate acyl chloride, and then ammoniation of the acyl chloride to generate the target compound 5 as shown in the following equation 1.

[0004]

[0005] Equation 1 Searching for similar literature on 3,5-diiodo-4-hydroxybenzoic acid revealed that there are many one-step reaction routes, and the raw materials used include p-hydroxybenzoic acid, methyl p-hydroxybenzoate, 907, iodobenzonitrile, etc.

[0006] Route 1: Using p-hydroxybenzoic acid as a raw material, the target compound 3,5-diiodo-4-hydroxybenzoic acid is produced through iodination reaction. The reaction route is shown in the following equation 2.

[0007]

[0008] Equation 2 First, the iodination reagent potassium iodide is oxidized to iodine by hydrogen peroxide, and iodine free radicals are generated under the action of catalysts or light. The iodine free radicals attack the ortho position of the hydroxyl group on the benzene ring to generate monoiodine compounds, and the monoiodine compounds react with free radicals to generate diiodine compounds. The guessed reaction mechanism is shown in the following equation 3, so the ratio of iodide is more than 2 times, and the catalyst selected is AIBN for experimental verification.

[0009]

[0010]

[0011] Equation 3 Route 2: Using methyl p-hydroxybenzoate as raw material, an intermediate diiodide compound is generated through iodination reaction, and then hydrolyzed to obtain the target product 6. The details are shown in the following equation 4.

[0012]

[0013]

[0014]

[0015] Equation 4 Summary of the invention The purpose of the present invention is to provide a method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile to solve the problem that the synthesis paths of 4-hydroxy-3,5-diiodobenzamide and 3,5-diiodo-4-hydroxybenzoic acid are complicated. The present invention provides a method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile.

[0016] In order to achieve the above-mentioned purpose, the present invention specifically adopts the following technical solutions: A first aspect of the present invention provides a method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile, comprising: hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile under strong acid or strong base conditions in the presence of a protective gas and a solvent.

[0017] Furthermore, the strong acid is selected from at least one of concentrated sulfuric acid, concentrated hydrochloric acid and concentrated nitric acid; and / or, The strong base is selected from at least one of sodium hydroxide and potassium hydroxide.

[0018] Furthermore, the protective gas is selected from at least one of nitrogen and argon; and / or, The solvent is selected from at least one of toluene, xylene, water, o-xylene, m-xylene, p-xylene and ethylbenzene.

[0019] Further, when the 4-hydroxy-3,5-diiodobenzonitrile is hydrolyzed under strong acid conditions, the molar ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the strong acid is 1:(1.0-1.5), and the amount ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the solvent is 0.1 mol:150-200 mL; and / or, When the 4-hydroxy-3,5-diiodobenzonitrile is hydrolyzed under strong alkaline conditions, the molar ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the strong base is 1:(3.0-5.0), and the usage ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the solvent is 0.1 mol:100-300 g.

[0020] Furthermore, the hydrolysis conditions include: temperature of 80°C to 150°C and time of 8h to 20h.

[0021] In the hydrolysis method of 4-hydroxy-3,5-diiodobenzonitrile of the present invention, the reaction path is as follows: .

[0022] The second aspect of the present invention provides 4-hydroxy-3,5-diiodobenzamide obtained by the above-mentioned method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile.

[0023] The third aspect of the present invention provides 3,5-diiodo-4-hydroxybenzoic acid obtained by the above-mentioned method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile.

[0024] Beneficial effects: In the hydrolysis method of 4-hydroxy-3,5-diiodobenzonitrile provided by the present invention, a one-step reaction is adopted to carry out hydrolysis to synthesize 4-hydroxy-3,5-diiodobenzamide; the raw material used is 4-hydroxy-3,5-diiodobenzonitrile, and a hydrolysis reaction is carried out under strong alkaline or strong acidic conditions; the progress of the reaction is controlled by controlling the ratio of the strong base or the strong acid and the reaction temperature, and the generated amide is easily hydrolyzed into carboxylic acid. The present invention controls the degree of hydrolysis by controlling the molar ratio of the substances and the acid-base concentration, and strong acid is used, preferably sulfuric acid, which is generally controlled within 2 times, and the yield and content are good, the content is more than 95%, and the yield is 80% to 85%.

[0025] In the hydrolysis method of 4-hydroxy-3,5-diiodobenzonitrile provided by the present invention, the raw material 4-hydroxy-3,5-diiodobenzonitrile is used to carry out a hydrolysis reaction under strong alkaline conditions, and 3,5-diiodo-4-hydroxybenzoic acid is synthesized in a one-step method. The reaction steps are reduced and carried out in an aqueous phase, thereby avoiding the use of organic solvents, and the yield content is high, which is beneficial to industrial production. The alkaline reagent used is sodium hydroxide or potassium hydroxide, and the hydrolysis is generally controlled to be more than 3 times complete. The yield and content are good, with a content of more than 98% and a yield of more than 95%. No need for recrystallization and a high content. Passing nitrogen during the reaction is beneficial to protecting the phenolic hydroxyl group from being oxidized and preventing the system color from turning black. DETAILED DESCRIPTION

[0026] The present invention will be further explained below in conjunction with the embodiments.

[0027] In the present invention and the embodiments, the content of concentrated sulfuric acid is 98%; In the present invention and the examples, the content of concentrated hydrochloric acid is 36%; In the present invention and the examples, the content of 4-hydroxy-3,5-diiodobenzonitrile is 98%; In the present invention and the embodiments, the content of sodium hydroxide is 98%; In the present invention and the embodiments, the content of potassium hydroxide is 90%.

[0028] Example 1 A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile Add concentrated sulfuric acid (11g, 0.11mol) and water (4.5g, 0.25mol) to a 250mL four-necked flask, stir and mix evenly, add 4-hydroxy-3,5-diiodobenzonitrile (37.9g, 0.1mol) solid, add solvent xylene (150mL), and pass nitrogen. Heat to reflux reaction, react for 10h, take samples for central control, LC detects 0.8% (liquid area percentage normalized content) of raw material 4-hydroxy-3,5-diiodobenzonitrile, after the central control is qualified, the reaction solution is cooled to 22°C and filtered to obtain a crude product. After drying the crude product, methanol is used for recrystallization. After recrystallization, 4-hydroxy-3,5-diiodobenzamide is obtained as a white solid (33.6g), with a content of 95.3% and a yield of 82.3%.

[0029] Example 2 A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile Add concentrated sulfuric acid (15g, 0.15mol) and water (4.5g, 0.25mol) to a 250mL four-necked flask, stir and mix evenly, add 4-hydroxy-3,5-diiodobenzonitrile (37.9g, 0.1mol) solid, add solvent toluene (150mL), and pass nitrogen. Heat to 110℃ for reflux reaction, react for 8h, take samples for central control, LC detects 0.5% (liquid area percentage normalized content) of raw material 4-hydroxy-3,5-diiodobenzonitrile, after the central control is qualified, the reaction solution is cooled to 25℃ and filtered to obtain a crude product. After drying the crude product, methanol is used for recrystallization. After recrystallization, 4-hydroxy-3,5-diiodobenzamide white solid (33.9g) is obtained, with a content of 95.7% and a yield of 83.4%.

[0030] Example 3 A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile Add concentrated hydrochloric acid (15.2g, 0.15mol) to a 250mL four-necked flask, add 4-hydroxy-3,5-diiodobenzonitrile (37.9g, 0.1mol) solid, add solvent xylene (150mL), and pass nitrogen. Heat to 135℃ for reflux reaction, react for 20h, take samples for central control, LC detects 0.7% of raw material 4-hydroxy-3,5-diiodobenzonitrile (liquid phase area percentage normalized content), after the central control is qualified, the reaction solution is cooled to 20℃ and filtered to obtain a crude product. After drying the crude product, methanol is used for recrystallization. After recrystallization, 4-hydroxy-3,5-diiodobenzamide is obtained as a white solid (32.9g), with a content of 95.2% and a yield of 80.5%.

[0031] Example 4 A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile Put 4-hydroxy-3,5-diiodobenzonitrile (37.9g, 0.1mol) solid, sodium hydroxide (12.2g, 0.3mol), solvent water (100g) into the reactor, start stirring, pass nitrogen and heat to 110℃ for reflux reaction, react for 20h, take samples for central control, LC detects 0.9% (liquid area percentage normalized content) of raw material 4-hydroxy-3,5-diiodobenzonitrile, after the central control is qualified, the reaction liquid is cooled to 23℃, 150g of water is added, and a 30% hydrochloric acid aqueous solution is added dropwise, acidified, pH value is 5, stirred for 10min and filtered, the filter cake is rinsed with 500g of water. Drain the filter cake and put it into a 40℃ oven to dry to obtain 38.2g of 3,5-diiodo-4-hydroxybenzoic acid, with a content of 98.1% and a yield of 96.1%.

[0032] Example 5 A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile Put 4-hydroxy-3,5-diiodobenzonitrile (37.9g, 0.1mol) solid, potassium hydroxide (21.8g, 0.35mol), solvent water (100g) into the reactor, start stirring, pass nitrogen and heat to 110℃ for reflux reaction, react for 10h, take samples for central control, LC detects 1% of raw material 4-hydroxy-3,5-diiodobenzonitrile (liquid phase area percentage normalized content), after the central control is qualified, the reaction solution is cooled to 20℃, 150g of water is added, 30% hydrochloric acid aqueous solution is added dropwise, acidified, pH value is 6, stirred for 10min and filtered, the filter cake is rinsed with 500g of water. Drain the filter cake and put it into a 40℃ oven to dry to obtain 38.1g of 3,5-diiodo-4-hydroxybenzoic acid, with a content of 98.6% and a yield of 96.3%.

[0033] Example 6 A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile Put 4-hydroxy-3,5-diiodobenzonitrile (37.9g, 0.1mol) solid, sodium hydroxide (14.3g, 0.35mol), solvent water (100g) into the reactor, start stirring, pass nitrogen and heat to 110℃ for reflux reaction, react for 16h, take samples for central control, LC detects 0.5% of raw material 4-hydroxy-3,5-diiodobenzonitrile (liquid phase area percentage normalized content), after the central control is qualified, the reaction liquid is cooled to 22℃, 150g of water is added, 30% hydrochloric acid aqueous solution is added dropwise, acidified, pH value is 5, and stirred for 10min. Filter, and rinse the filter cake with 500g of water. Drain the filter cake and put it into a 40℃ oven to dry to obtain 38.2g of 3,5-diiodo-4-hydroxybenzoic acid, with a content of 98.4% and a yield of 96.2%.

[0034] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited by the description of the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

[0035] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile, characterized in that: The method comprises: hydrolyzing 4-hydroxy-3,5-diiodobenzonitrile under strong acid or strong base conditions in the presence of protective gas and solvent.

2. The hydrolysis method according to claim 1, characterized in that The strong acid is selected from at least one of concentrated sulfuric acid, concentrated hydrochloric acid and concentrated nitric acid; and / or, The strong base is selected from at least one of sodium hydroxide and potassium hydroxide.

3. The hydrolysis method according to claim 1, characterized in that The protective gas is selected from at least one of nitrogen and argon; and / or, The solvent is selected from at least one of toluene, xylene, water, o-xylene, m-xylene, p-xylene and ethylbenzene.

4. The hydrolysis method according to claim 1, characterized in that When the 4-hydroxy-3,5-diiodobenzonitrile is hydrolyzed under strong acid conditions, the molar ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the strong acid is 1:(1.0-1.5), and the amount ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the solvent is 0.1 mol:150-200 mL; and / or, When the 4-hydroxy-3,5-diiodobenzonitrile is hydrolyzed under strong alkaline conditions, the molar ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the strong base is 1:(3.0-5.0), and the usage ratio of the 4-hydroxy-3,5-diiodobenzonitrile to the solvent is 0.1 mol:100-300 g.

5. The hydrolysis method according to claim 1, characterized in that The hydrolysis conditions include: temperature of 80° C. to 150° C. and time of 8 h to 20 h.

6. A 4-hydroxy-3,5-diiodobenzamide, characterized in that The method is obtained by the preparation method described in any one of claims 1 to 5.

7. A 3,5-diiodo-4-hydroxybenzoic acid, characterized in that The method is obtained by the preparation method described in any one of claims 1 to 5.

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