CN116987007A - Preparation process of p-hydroxybenzonitrile - Google Patents
Preparation process of p-hydroxybenzonitrile Download PDFInfo
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- CN116987007A CN116987007A CN202311012558.7A CN202311012558A CN116987007A CN 116987007 A CN116987007 A CN 116987007A CN 202311012558 A CN202311012558 A CN 202311012558A CN 116987007 A CN116987007 A CN 116987007A
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- hydroxybenzonitrile
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- sodium methoxide
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- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 66
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000012046 mixed solvent Substances 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 12
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 11
- 238000001816 cooling Methods 0.000 claims description 11
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical group I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 11
- 238000002425 crystallisation Methods 0.000 claims description 11
- 230000008025 crystallization Effects 0.000 claims description 11
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000010025 steaming Methods 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000010979 pH adjustment Methods 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- -1 nitrile compound Chemical class 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
- 238000006297 dehydration reaction Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000004176 ammonification Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- UPMXNNIRAGDFEH-UHFFFAOYSA-N 3,5-dibromo-4-hydroxybenzonitrile Chemical compound OC1=C(Br)C=C(C#N)C=C1Br UPMXNNIRAGDFEH-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- VCZNNAKNUVJVGX-UHFFFAOYSA-N 4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1 VCZNNAKNUVJVGX-UHFFFAOYSA-N 0.000 description 1
- 239000005489 Bromoxynil Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 239000005947 Dimethoate Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- QGMAXWWNHMVHFU-UHFFFAOYSA-N [P].C(C1=CC=CC=C1)#N Chemical compound [P].C(C1=CC=CC=C1)#N QGMAXWWNHMVHFU-UHFFFAOYSA-N 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 238000004939 coking Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960001952 metrifonate Drugs 0.000 description 1
- 239000003750 molluscacide Substances 0.000 description 1
- 230000002013 molluscicidal effect Effects 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/53—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation process of p-hydroxybenzonitrile, which takes p-chlorobenzonitrile as a raw material, adopts a mixed solvent, and reacts with sodium methoxide under the action of a catalyst to obtain the p-hydroxybenzonitrile. The method has the advantages of easily obtained reaction raw materials, simple process, no need of high temperature, easy operation, accurate pH adjustment by using mixed solvent in the reaction, and higher product purity and yield.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation process of p-hydroxybenzonitrile.
Background
P-hydroxybenzonitrile, also known as p-cyanophenol, formula C 7 H 5 NO, white needle-like crystals in the small test, light yellow crystals or crystalline powder in industrial production, with the melting point of 110-113 ℃ and the boiling point of 145 ℃/133Pa, and is easy to dissolve in hot water and slightly dissolve in ice water; dissolving in organic solvent such as methanol, diethyl ether, acetone, chloroform, etc.
The p-hydroxybenzonitrile is an extremely important fine organic chemical raw material and intermediate, is widely used for synthesizing various medicines, spices, pesticides, liquid crystal materials, buffers and the like, particularly as a pesticide intermediate, and can be used for generating benzonitrile pesticide preparations such as molluscicide, benzonitrile phosphorus, bromoxynil, trichlorfon, bai Junqing and the like.
The synthesis of the p-hydroxybenzonitrile mainly comprises the following methods:
(1) Paramynoxybenzoic acid dehydration ammonification method
The reaction mechanism of the carboxylic acid dehydration ammonification method is that acid is connected with ammonia to react, a molecule of water is removed from molecules to form amide, the amide is combined with positive ions under weak acid condition, and then intramolecular dehydration is carried out, so that the nitrile compound p-light benzonitrile is finally formed. The reaction requires high temperature conditions.
(2) Paramygdalin ammonification process
Generally, the process for preparing aromatic nitriles generally comprises two steps: the first step is to dehydrate the aldehyde compartment from acid synthesis and requires a strong acid and strong base dehydrating agent. However, this two-stage dehydration process of aldehyde blemish is gradually replaced by the direct synthesis of nitriles by fermentation, i.e. by the direct reaction of aromatic aldehydes and amines in the same system.
The method has the advantages of easily available raw materials, simple process, high product purity and the like, but the solvent required in the reaction has certain toxicity, can cause certain influence on the environment and the human body, and does not meet the requirements of green chemical production.
(3) Ammonification method of methyl parahydroxybenzoate
The method synthesizes the target product through the intramolecular dehydration after synthesizing the amide. The method is divided into three steps, namely vinegar, amide and aromatic nitrile. Firstly, performing an acetification reaction on p-hydroxybenzoic acid and methanol to synthesize methyl p-hydroxybenzoate, and secondly, ammonifying unitary substance to amide to obtain p-hydroxybenzo amine; finally, the amide is combined with positive ions under weak acid condition to carry out intramolecular dehydration to obtain the required product.
(4) Diazonium salt process
The diazonium salt method is to obtain the target product p-hydroxybenzonitrile through substitution of the halogen phenol and the nitrile group.
The method overcomes the generation and increases the safety of the reaction process, but the reaction condition is not high in etching yield. Further, it has been reported that in the reaction of Dimethoate and cuprous cyanide, the aromatic nitrile formed often combines with cuprous south to form a complex, so that ferric trichloride, ethylenediamine or sodium cyanide must be added to separate the aromatic nitrile from cuprous south, and thus the post-treatment is troublesome. Second, the reaction generally necessitates the use of expensive aprotic polar solvents, and copper recovery is also problematic.
(5) P-cresol process
The methyl- , ammonia, water vapor and air are mixed according to a certain proportion, and the ammonia oxidation reaction is directly carried out on the methyl- , ammonia, water vapor and air at the temperature at the moment, so as to synthesize the cyano group, wherein an oxide or catalyst is generally adopted.
In the p-cresol process, during the reaction process for converting p-tolunitrile, the catalyst is irreversibly deactivated in a short time by the byproducts formed in the oxidation process, so that the key point of the process is to select a better catalyst and solve the coking problem in the reaction process.
Therefore, the synthetic process of the parahydroxybenzonitrile still needs to be optimized.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a synthesis process of parahydroxybenzonitrile. The method comprises the following steps:
(1) The p-chlorobenzonitrile reacts with sodium methoxide in a mixed solvent of DMF and methanol under the action of a catalyst, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
(2) Adding toluene solvent into the intermediate mixture obtained in the step (1), adding aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding hydrochloric acid with the concentration of 31%, adjusting the pH value to 6, stirring and crystallizing for 1h to obtain the p-hydroxybenzonitrile.
The reaction route is as follows:
in the step (1), the mass-volume ratio of the p-chlorobenzonitrile to the mixed solvent is 1:6-12, wherein the volume ratio of DMF to methanol in the mixed solvent is 1:3, the catalyst is cuprous iodide, and the molar ratio of the catalyst to the p-chlorobenzonitrile is 1:6-10, wherein the mass concentration of the sodium methoxide is 30%, and the molar ratio of the sodium methoxide to the p-chloromethane is 2-3:1, the reaction temperature of the parachloromethane and the sodium methoxide is 50-60 ℃ and the reaction time is 4 hours;
in the step (2), the mass-volume ratio of toluene to the p-chloromethane is 1:6-8, wherein the molar ratio of the aluminum trichloride to the parachloromethane is 2.1-2.5:1.
the invention has the following beneficial effects:
(1) The raw materials for reaction are easy to obtain, the process is simple, high temperature is not needed, and the operation is easy;
(2) The mixed solvent is used in the reaction, the pH is accurately regulated, and the purity and the yield of the product are high.
Description of the embodiments
Examples
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:3), 1.9g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 28.0g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 6, stirring for crystallization for 1h, and obtaining 10.64g of p-hydroxybenzonitrile, wherein the yield is 89.3%, and the purity is 99.9% through HPLC detection.
Examples
13.76g of p-chloromethane is dissolved in 110mL of mixed solvent (DMF: methanol=1:3), 2.4g of cuprous iodide is added, 16.2g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
96mL of toluene solvent is added into the intermediate mixture, 33.3g of aluminum trichloride is added, the temperature is raised to 60-80 ℃ for reaction for 12 hours, 31% hydrochloric acid is added into the mixture after the reaction is finished and cooled to room temperature, the pH is regulated to 6, stirring crystallization is carried out for 1 hour, 10.67g of p-hydroxybenzonitrile is obtained, the yield is 89.6%, and the purity is 99.9% detected by HPLC.
Examples
13.76g of p-chloromethane is dissolved in 140mL of mixed solvent (DMF: methanol=1:3), 3.17g of cuprous iodide is added, 13.5g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
110mL of toluene solvent is added into the intermediate mixture, 29.33g of aluminum trichloride is added, the temperature is raised to 60-80 ℃ for reaction for 12 hours, after the reaction is finished, the reaction is cooled to room temperature, 31% hydrochloric acid is added, the pH is regulated to 6, stirring crystallization is carried out for 1 hour, 10.47g of p-hydroxybenzonitrile is obtained, the yield is 87.9%, and the purity is 99.9% by HPLC detection.
Examples
13.76g of p-chloromethane is dissolved in 165mL of mixed solvent (DMF: methanol=1:3), 2.4g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 30.67g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 6, stirring for crystallization for 1h, and obtaining 10.84g of p-hydroxybenzonitrile, wherein the yield is 91.0%, and the purity is 99.9% detected by HPLC.
Comparative example 1
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:1), 1.9g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 28.0g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 6, stirring for crystallization for 1h, and obtaining 10.21g of p-hydroxybenzonitrile, wherein the yield is 85.7%, and the purity is 99.2% through HPLC detection.
Comparative example 2
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:5), 1.9g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 28.0g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 6, stirring for crystallization for 1h, and obtaining 10.24g of p-hydroxybenzonitrile, wherein the yield is 86.0%, and the purity is 99.9% through HPLC detection.
Comparative example 3
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:3), 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 8 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 28.0g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 6, stirring for crystallization for 1h to obtain 10.15g of p-hydroxybenzonitrile, and detecting the purity by HPLC to 99.9%
Comparative example 4
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:3), 1.9g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 13.3g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 6, stirring for crystallization for 1h, and obtaining 7.88g of p-hydroxybenzonitrile, wherein the yield is 66.0%, and the purity is 99.2% detected by HPLC.
Comparative example 5
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:3), 1.9g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 28.0g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 5, stirring for crystallization for 1h, and obtaining 9.87g of p-hydroxybenzonitrile, wherein the yield is 82.9%, and the purity is 99.4% through HPLC detection.
Comparative example 6
13.76g of p-chloromethane is dissolved in 80mL of mixed solvent (DMF: methanol=1:3), 1.9g of cuprous iodide is added, 10.8g of sodium methoxide is added, the temperature is controlled between 50 ℃ and 60 ℃ for reaction for 2 hours, the temperature is reduced to 40 ℃ after the reaction is finished, and methanol is distilled off to obtain an intermediate mixture;
adding 80mL of toluene solvent into the intermediate mixture, adding 28.0g of aluminum trichloride, heating to 60-80 ℃ for reaction for 12h, cooling to room temperature after the reaction is finished, adding 31% hydrochloric acid, adjusting the pH to 7, stirring for crystallization for 1h, and obtaining 9.96g of p-hydroxybenzonitrile, wherein the yield is 83.6%, and the purity is 99.2% through HPLC detection.
Claims (10)
1. The preparation process of the p-hydroxybenzonitrile is characterized by comprising the following steps of:
(1) Dissolving p-chlorobenzonitrile in a mixed solvent, reacting with sodium methoxide under the action of a catalyst, cooling to 40 ℃ after the reaction is finished, and steaming to remove methanol to obtain an intermediate mixture;
(2) Adding toluene solvent into the intermediate mixture obtained in the step (1), adding aluminum trichloride for reaction, cooling to room temperature after the reaction is finished, adding hydrochloric acid to adjust pH, stirring for crystallization, and obtaining the p-hydroxybenzonitrile.
2. The process according to claim 1, wherein the mixed solvent in step (1) is a mixture of methanol and DMF.
3. The preparation process according to claim 2, wherein the volume ratio of DMF to methanol in the mixed solvent is 1:3.
4. the process of claim 1 wherein in step (1) the catalyst is cuprous iodide and the molar ratio of catalyst to p-chlorobenzonitrile is 1:6-10.
5. The preparation process according to claim 1, wherein the mass concentration of sodium methoxide in the step (1) is 30%, and the molar ratio of sodium methoxide to p-chloromethane is 2-3:1.
6. the process according to claim 1, wherein the reaction temperature of the parachloronitrile and the sodium methoxide in the step (1) is 50-60 ℃ and the reaction time is 4 hours.
7. The process according to claim 1, wherein the mass to volume ratio of toluene to p-chloromethane in step (2) is 1:6-8.
8. The process of claim 1, wherein the molar ratio of aluminum trichloride to p-chloromethane nitrile in step (2) is from 2.1 to 2.5:1.
9. the process according to claim 1, wherein the reaction temperature in step (2) is 60 to 80 ℃ and the reaction time is 12 hours.
10. The process of claim 1, wherein the pH in step (2) is 6.
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| CN202311012558.7A CN116987007A (en) | 2023-08-10 | 2023-08-10 | Preparation process of p-hydroxybenzonitrile |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102311364A (en) * | 2011-09-30 | 2012-01-11 | 江苏联化科技有限公司 | Preparation method of o(p)-hydroxybenzonitrile |
| CN107118128A (en) * | 2017-04-25 | 2017-09-01 | 常州佳德医药科技有限公司 | The preparation method of 3,4 dihydroxybenzonitriles |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102311364A (en) * | 2011-09-30 | 2012-01-11 | 江苏联化科技有限公司 | Preparation method of o(p)-hydroxybenzonitrile |
| CN107118128A (en) * | 2017-04-25 | 2017-09-01 | 常州佳德医药科技有限公司 | The preparation method of 3,4 dihydroxybenzonitriles |
Non-Patent Citations (1)
| Title |
|---|
| TLILI等: "A Very Simple Copper- Catalyzed Synthesis of Phenols Employing Hydroxide Salts", ANGEWANDTE CHEMIE，INTERNATIONAL EDITION, vol. 48, no. 46, pages 8725 - 8728, XP002639376, DOI: 10.1002/ANIE.200903639 * |
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