CN112707801A - Preparation method of m-phenoxy benzaldehyde - Google Patents
Preparation method of m-phenoxy benzaldehyde Download PDFInfo
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- CN112707801A CN112707801A CN202011609363.7A CN202011609363A CN112707801A CN 112707801 A CN112707801 A CN 112707801A CN 202011609363 A CN202011609363 A CN 202011609363A CN 112707801 A CN112707801 A CN 112707801A
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- C07—ORGANIC CHEMISTRY
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
Abstract
The invention provides a preparation method of m-phenoxy benzaldehyde, belonging to the technical field of organic synthesis. The preparation method provided by the invention uses m-cresol as a raw material, the m-phenoxy toluene is obtained by condensation with halogenated benzene, then the m-phenoxy toluene is reacted with chlorine to chlorinate methyl to obtain a m-phenoxy toluene chlorinated product, and the m-phenoxy toluene chlorinated product is directly hydrolyzed without separation after an oxide of the m-phenoxy toluene is obtained by Komblum oxidation to obtain the m-phenoxy benzaldehyde product. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, high yield and product quality meeting market demands, solves the problems of expensive raw materials, more side reactions, more impurities, low yield, large wastewater amount and serious environmental pollution in the traditional process, and greatly reduces the production cost of the m-phenoxy benzaldehyde. The data of the examples show that the preparation method provided by the invention can obtain the m-phenoxy benzaldehyde with the total yield of 83.5% and the gas phase content of 99.3%.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of m-phenoxy benzaldehyde.
Background
M-phenoxy benzaldehyde, also known as 3-methoxybenzaldehyde and 3-aldehyde diphenyl ether, is called ether aldehyde for short, is an important intermediate for synthesizing a series of high-efficiency, broad-spectrum, safe and low-toxicity pyrethroid pesticides, is a light yellow liquid, is insoluble in water, is soluble in organic solvents such as alcohol and benzene, and the currently reported synthesis methods of m-phenoxy benzaldehyde are as follows:
(1) benzaldehyde is used as a raw material and is subjected to substitution reaction with bromine to obtain m-bromobenzaldehyde, and the m-bromobenzaldehyde is condensed with sodium phenolate to obtain a product, i.e. m-phenoxybenzaldehyde. In the method, a small amount of p-bromobenzaldehyde is generated during the first step of substitution, m-bromobenzaldehyde is easy to generate disproportionation reaction under the alkaline condition during the second step of condensation to obtain by-products of m-phenoxybenzoic acid and m-phenoxybenzyl alcohol, and the products are difficult to purify. The reaction equation is as follows:
(2) CN101337868A discloses that m-bromobenzaldehyde is used as a raw material, aldehyde group protection is carried out by using ethylene glycol to obtain m-bromobenzaldehyde ethylene glycol, the m-bromobenzaldehyde ethylene glycol is condensed with phenol to obtain m-phenoxybenzaldehyde ethylene glycol, and the m-phenoxybenzaldehyde product is obtained by deprotection under acidic conditions. In the method, the price of the raw material bromobenzaldehyde is high, and the aldehyde group protection and deprotection increase the operation procedures, so that the total yield is reduced, and the generation cost is increased. The reaction equation is as follows:
(3) m-phenoxy benzoic acid is used as a raw material, esterification reaction is firstly carried out to obtain m-phenoxy methyl benzoate, and cerium-based catalyst is adopted to prepare m-phenoxy benzaldehyde through gas-phase catalytic hydrogenation. In the method, the catalyst is expensive, the catalytic hydrogenation reaction temperature is high (300-450 ℃), and great potential safety hazards exist in industrial production. The reaction equation is as follows:
disclosure of Invention
In view of the above, the invention aims to provide a preparation method of m-phenoxy benzaldehyde, which has the advantages of easily available raw materials and low cost; meanwhile, the yield is high.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of m-phenoxy benzaldehyde, which comprises the following steps:
carrying out condensation reaction on m-cresol, halogenated benzene and a first catalyst under an alkaline condition to obtain m-phenoxy toluene;
carrying out substitution reaction on the m-phenoxy toluene and chlorine under the condition of the existence of an initiator to obtain a m-phenoxy toluene chloro-product;
mixing the m-phenoxy toluene chlorination product, an oxidant and a second catalyst, and carrying out Komblum oxidation reaction to obtain Komblum oxidation reaction feed liquid;
mixing the Komblum oxidation reaction material liquid, urotropine and water, and carrying out salt forming reaction; and mixing the obtained salt forming system with acetic acid, and hydrolyzing to obtain the m-phenoxy benzaldehyde.
Preferably, the first catalyst is cuprous chloride; the mass of the cuprous chloride is 1-2% of the mass of the m-cresol.
Preferably, the molar ratio of m-cresol to halogenated benzene is 1: (1-1.2).
Preferably, the temperature of the condensation reaction is 170-190 ℃.
Preferably, the initiator comprises azobisisobutyronitrile, azobisisovaleronitrile or tert-butyl peroxyisobutyrate; the mass of the initiator is 0.8-1.2% of that of m-phenoxy toluene.
Preferably, the substitution reaction is carried out under reflux conditions.
Preferably, the oxidizing agent is dimethyl sulfoxide; the second catalyst is sodium iodide and sodium carbonate; the mass of the sodium iodide is 40-60% of that of the m-phenoxytoluene chlorination product, and the mass of the sodium carbonate is 15-25% of that of the m-phenoxytoluene chlorination product.
Preferably, the temperature of the Komblum oxidation reaction is 100-150 ℃, and the time is 2-5 h.
Preferably, the molar ratio of m-phenoxytoluene to urotropin is 1: (0.2-0.4).
Preferably, the using ratio of the m-phenoxytoluene to the water is 1 g: (4-6 ml); the volume ratio of the acetic acid to the water is 1: 1.
the invention provides a preparation method of m-phenoxy benzaldehyde, which comprises the following steps: carrying out condensation reaction on m-cresol, halogenated benzene and a first catalyst under an alkaline condition to obtain m-phenoxy toluene; carrying out substitution reaction on the m-phenoxy toluene and chlorine under the condition of the existence of an initiator to obtain a m-phenoxy toluene chloro-product; mixing the m-phenoxy toluene chlorination product, an oxidant and a second catalyst, and carrying out Komblum oxidation reaction to obtain Komblum oxidation reaction feed liquid; mixing the Komblum oxidation reaction material liquid, urotropine and water, and carrying out salt forming reaction; and mixing the obtained salt forming system with acetic acid, and hydrolyzing to obtain the m-phenoxy benzaldehyde.
The method comprises the steps of condensing m-cresol serving as a raw material with halogenated benzene to obtain m-phenoxy toluene, reacting with chlorine to chlorinate methyl to obtain a m-phenoxy toluene chlorinated product, oxidizing with Komblum to obtain an oxide of the m-phenoxy toluene, and directly hydrolyzing without separation to obtain the m-phenoxy benzaldehyde product. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, high yield and product quality meeting market demands, solves the problems of expensive raw materials, more side reactions, more impurities, low yield, large wastewater amount and serious environmental pollution in the traditional process, and greatly reduces the production cost of the m-phenoxy benzaldehyde.
The data of the examples show that the preparation method provided by the invention can obtain the m-phenoxy benzaldehyde with the total yield of 83.5% and the gas phase content of 99.3%.
Detailed Description
The invention provides a preparation method of m-phenoxy benzaldehyde, which comprises the following steps:
carrying out condensation reaction on m-cresol, halogenated benzene and a first catalyst under an alkaline condition to obtain m-phenoxy toluene;
carrying out substitution reaction on the m-phenoxy toluene and chlorine under the condition of the existence of an initiator to obtain a m-phenoxy toluene chloro-product;
mixing the m-phenoxy toluene chlorination product, an oxidant and a second catalyst, and carrying out Komblum oxidation reaction to obtain Komblum oxidation reaction feed liquid;
mixing the Komblum oxidation reaction material liquid, urotropine and water, and carrying out salt forming reaction; and mixing the obtained salt forming system with acetic acid, and hydrolyzing to obtain the m-phenoxy benzaldehyde.
The reaction principle of the preparation method is shown as formula I:
m-cresol, halogenated benzene and a first catalyst are subjected to condensation reaction under an alkaline condition to obtain m-phenoxy toluene.
In the present invention, the halogenated benzene is preferably chlorobenzene, bromobenzene or fluorobenzene; the first catalyst is preferably cuprous chloride; the mass of the cuprous chloride is preferably 1-2% of that of m-cresol; the molar ratio of m-cresol to halogenated benzene is preferably 1: (1-1.2), more preferably 1: 1.
in the invention, the pH value of the alkaline condition is preferably 12-14; the substance providing the alkaline condition is preferably potassium hydroxide; the dosage of the potassium hydroxide is not particularly limited, as long as the pH value of a reaction system is 12-14; in a specific embodiment of the present invention, the molar ratio of the potassium hydroxide to the m-cresol is preferably (1.2 to 1.5): 1.
in the invention, the temperature of the condensation reaction is preferably 170-190 ℃; the condensation reaction is preferably carried out under reflux conditions. In the present invention, the time of the condensation reaction is preferably controlled by monitoring the content of m-cresol in the condensation reaction system, and the reaction is stopped when the area normalized content of m-cresol in the condensation reaction system is less than 0.3%; the method for monitoring the m-cresol content in the reaction system is preferably gas-phase detection, and the gas-phase detection preferably comprises the following parameters: chromatograph: fuli9790 gas chromatograph, FID detector; a chromatographic column: SE-543 m.times.0.32 mm.times.0.4 μm; hydrogen gas: 0.06 MPa; nitrogen gas: 0.10 MPa; air: 0.1 MPa; a sample inlet: 200 ℃; a detector: 250 ℃; column temperature: at 150 ℃.
After the condensation reaction is finished, the invention preferably further comprises post-treatment, and the post-treatment preferably comprises the following steps: cooling the obtained condensation reaction system and filtering to obtain filter residue and filtrate; washing the obtained filter residue to be colorless, and collecting washing liquor; combining the washing liquid and the filtrate, washing with acid and layering; and carrying out vacuum distillation on the obtained organic phase to obtain m-phenoxy toluene. In the invention, the temperature of the temperature reduction is preferably less than or equal to 110 ℃; the reagent for washing the filter residue is preferably halogenated benzene, and the dosage of the halogenated benzene is not specifically limited as long as the filter residue can be washed to be colorless; the halogenated benzene is preferably in accordance with the kind of the halogenated benzene as the raw material for the condensation reaction. In the present invention, the acid washing reagent is preferably dilute sulfuric acid having a mass concentration of 10%.
After m-phenoxy toluene is obtained, the m-phenoxy toluene and chlorine are subjected to substitution reaction in the presence of an initiator to obtain a m-phenoxy toluene chloro-product.
In the present invention, the initiator preferably includes azobisisobutyronitrile, azobisisovaleronitrile, or tert-butyl peroxyisobutyrate, and more preferably azobisisobutyronitrile; the mass of the initiator is preferably 0.8-1.2% of that of m-phenoxytoluene. In the present invention, the chlorine gas is preferably blown in the form of a stream of chlorine gas, and the speed and time of blowing of the chlorine gas are not particularly limited in the present invention. In the present invention, the solvent for the substitution reaction is preferably carbon tetrachloride, and the amount of the carbon tetrachloride used is not particularly limited as long as m-phenoxytoluene and the initiator can be sufficiently mixed.
In the present invention, the substitution reaction is preferably carried out under reflux conditions; the time of the substitution reaction is preferably controlled by monitoring the content of the phenoxy toluene in the substitution reaction system, and when the area normalized content of the phenoxy toluene in the substitution reaction system is less than 0.5%, the introduction of chlorine is stopped, namely the substitution reaction is stopped. In the present invention, the method for monitoring the content of phenoxytoluene in the substitution reaction system is preferably gas phase detection, and the parameters of the gas phase detection are preferably consistent with the above technical scheme, and are not described herein again.
In the present invention, the tail gas evolved during the substitution reaction is absorbed with a base.
After the substitution reaction, the present invention preferably further comprises a post-treatment, which preferably comprises the steps of: and cooling the obtained substitution reaction system to room temperature, and distilling under reduced pressure to obtain a m-phenoxy toluene chloro-product. The parameters of the reduced pressure distillation are not particularly limited, as long as the solvent of the substitution reaction can be removed cleanly.
After the m-phenoxy toluene chlorination product is obtained, the m-phenoxy toluene chlorination product, an oxidant and a second catalyst are mixed to carry out Komblum oxidation reaction, and Komblum oxidation reaction feed liquid is obtained.
In the present invention, the oxidizing agent is preferably dimethyl sulfoxide; in the present invention, the dimethyl sulfoxide is used as both the oxidizing agent and the organic solvent, and therefore, the amount of the dimethyl sulfoxide is not particularly limited in the present invention, so that the m-phenoxytoluene chlorination product and the second catalyst can be sufficiently mixed. In the present invention, the second catalyst is preferably sodium iodide and sodium carbonate; the mass of the sodium iodide is preferably 40-60% of that of the m-phenoxytoluene chlorination product; the mass of the sodium carbonate is preferably 15-25% of that of the m-phenoxy toluene chloro-product.
In the invention, the temperature of the Komblum oxidation reaction is preferably 100-150 ℃, and is further preferably 120 ℃; the Komblum oxidation reaction is preferably carried out under the protection of nitrogen and under the condition of stirring, and the parameters of the stirring are not particularly limited in the invention. In the present invention, the time of the Komblum oxidation reaction is preferably controlled by monitoring the content of the m-phenoxytoluene chloro product in the Komblum oxidation reaction system; when the area normalization content of the m-phenoxytoluene chlorinated product in the Komblum oxidation reaction system is 10-20%, terminating the reaction; the method for monitoring the content of the phenoxy toluene chlorinated product in the Komblum oxidation reaction system is preferably gas phase detection, and the parameters of the gas phase detection are preferably consistent with the technical scheme, and are not described again.
After the Komblum oxidation reaction is finished, the invention preferably also comprises that the obtained Komblum oxidation reaction system is cooled to room temperature.
After the Komblum oxidation reaction material liquid is obtained, mixing the Komblum oxidation reaction material liquid, urotropine and water to carry out salt forming reaction; and mixing the obtained salt forming system with glacial acetic acid, and hydrolyzing to obtain the m-phenoxy benzaldehyde.
In the present invention, the molar ratio of m-phenoxytoluene to urotropin is preferably 1: (0.2 to 0.4), and more preferably 1: 0.3. in the present invention, the amount ratio of m-phenoxytoluene to water is preferably 1 g: (4-6) mL. In the present invention, the salt-forming reaction is preferably carried out under reflux.
In the present invention, the volume ratio of acetic acid to water is preferably 1: 1.
in the present invention, the hydrolysis is preferably carried out under reflux. In the present invention, the time of the hydrolysis is preferably controlled by monitoring the content of the phenoxytoluene chloride product in the hydrolysis system, and when the area normalized content of the phenoxytoluene chloride product in the hydrolysis system is less than 0.1%, the hydrolysis is stopped; the method for determining the content of the phenoxyl toluene chlorinated product in the hydrolysis system is preferably gas phase detection, and the parameters of the gas phase detection are preferably consistent with the technical scheme, and are not repeated herein.
After the hydrolysis is completed, the present invention preferably further comprises a post-treatment, which preferably comprises the steps of:
mixing the obtained hydrolysis reaction system with toluene for extraction, and washing the obtained organic phase to be neutral; and carrying out reduced pressure distillation on the washed organic phase to obtain the m-phenoxy benzaldehyde.
In the present invention, the organic phase washing reagent is preferably an aqueous sodium bicarbonate solution, and the concentration and the amount of the aqueous sodium bicarbonate solution are not particularly limited as long as the organic phase can be washed to be neutral. In the present invention, the parameters of the reduced pressure distillation are not particularly limited as long as the solvent can be removed.
The following examples are provided to illustrate the preparation of m-phenoxybenzaldehyde according to the present invention in detail, but they should not be construed as limiting the scope of the present invention.
The gas phase detection conditions used in the following examples include the following parameters:
chromatograph: fuli9790 gas chromatograph, FID detector; a chromatographic column: SE-543 m.times.0.32 mm.times.0.4 μm; hydrogen gas: 0.06 MPa; nitrogen gas: 0.10 MPa; air: 0.1 MPa; a sample inlet: 200 ℃; a detector: 250 ℃; column temperature: at 150 ℃.
Example 1
(1) Preparation of m-phenoxytoluene: a100 mL four-mouth bottle is provided with a stirrer, a thermometer and a water separator, 22.3g (0.206mol) of m-cresol, 23.2g of chlorobenzene (0.206mol), 16.6g (0.296mol) of potassium hydroxide are added to adjust the pH value to be 13, 0.3g of cuprous chloride is added to reflux at 180 ℃ for 5 hours, the reaction is stopped when the area normalization content of the m-cresol is detected to be less than 0.3 percent by gas phase, the temperature is reduced to be below 110 ℃, the filtrate is filtered, the chlorobenzene is washed until the filter residue is colorless, the filtrate and the washing liquid are combined and washed by dilute sulfuric acid (20mL) with the mass concentration of 10 percent, the layers are separated, the organic layer is distilled under reduced pressure, 32.3g of the m-phenoxy toluene is collected, the yield is 85 percent.
(2) Preparation of m-phenoxytoluene chloro-product: adding 32.3g (0.175mol) of m-phenoxytoluene which is a product obtained in the previous step into a 250mL four-mouth bottle, adding an initiator azobisisobutyronitrile (AIBNB 0.3g) and 100mL of carbon tetrachloride, heating to reflux, introducing chlorine gas, absorbing escaped tail gas by using alkali, finishing substitution reaction when the area normalization content of the m-phenoxytoluene in a reaction system is less than 0.5% by gas phase detection, cooling reaction liquid, and removing carbon tetrachloride by reduced pressure distillation to obtain 44g of a mixture of crude m-phenoxytoluene chlorinated products, and carrying out gas phase detection: wherein, the monochloro substituent is 44 percent, the dichloro substituent is 53 percent, and the trichloro substituent is 2 percent.
(3) Preparing Komblum oxidation reaction feed liquid: adding 100mL (1.282mol) of dimethyl sulfoxide, 22g (0.147mol) of sodium iodide and 8.4g (0.079mol) of sodium carbonate into the m-phenoxytoluene chloro-product, stirring and heating to 120 ℃ under the protection of nitrogen, reacting for 3 hours, and stopping the reaction when the area normalization content of the m-phenoxytoluene chloro-product in a gas phase detection reaction system is 10-20%; the excess DMSO was removed by distillation under reduced pressure, and the reaction was carried out directly next.
(4) Preparation of m-phenoxybenzaldehyde: adding the Komblum oxidation reaction material liquid into a reaction bottle, adding 150mL of water and 7.8g (0.056) of urotropine under the protection of nitrogen, and heating and refluxing for 4 hours; supplementing 150mL of glacial acetic acid, and continuously refluxing for 4 h; and (3) stopping the reaction when the chlorinated m-phenoxytoluene product is less than 0.1% by gas phase detection, cooling the reaction feed liquid, extracting twice by using 100mL of toluene 2, combining organic layers, washing the organic phase to be neutral by using a sodium bicarbonate solution, carrying out reduced pressure distillation, and collecting 30.7g of fraction at 170-190 ℃ to obtain the m-phenoxybenzaldehyde product, wherein the total yield is 75.1% by using m-cresol, and the gas phase detection content GC is 99.2%.
The mass spectrum and nuclear magnetism information of the obtained m-phenoxy benzaldehyde are as follows:
mass Spectrometry MS (ESI), m/z: 199.3[ M + H]+.
Nuclear magnetism1H NMR(400MHz，CDCl3)，δ＝7.22(2H，ArH)，6.98(H，ArH)，6.92(2H，ArH)，7.20(H，ArH)，7.41(H，ArH)，7.53(H，ArH)，7.47(H，ArH)，9.87(H，CHO).
Example 2
(1) Preparation of m-phenoxytoluene: a 100mL four-mouth bottle is provided with a stirring bottle, a thermometer and a water separator, 22.3g (0.206mol) of m-cresol, 32.3g of bromobenzene (0.206mol) and 16.6g (0.296mol) of potassium hydroxide are added to adjust the pH value to be 13, 0.3g of cuprous chloride is added to carry out reflux reaction at 180 ℃ for 5 hours, the reaction is stopped and cooled to below 110 ℃ when the area normalization content of the m-cresol is detected to be less than 0.3 percent by gas phase, the filtration is carried out, the filter residue is washed by the bromobenzene until the filter residue is colorless, the filtrate and the washing liquid are combined and washed by dilute sulfuric acid (20mL) with the mass concentration of 10 percent, the layers are separated, the organic layer is distilled under reduced pressure, 32.1g of; the gas phase content GC is 99.1%.
(2) Preparation of m-phenoxytoluene chloro-product: adding 32.1g (0.174mol) of m-phenoxy toluene, an initiator azodiisobutyronitrile (AIBN0.3g) and 100mL of carbon tetrachloride into a 250mL four-mouth bottle, heating to reflux, introducing chlorine gas, absorbing escaped tail gas by using alkali, cooling reaction feed liquid after the area normalization content of the m-phenoxy toluene in a reaction system is less than 0.5%, removing the solvent carbon tetrachloride by reduced pressure distillation after the substitution reaction is finished, obtaining 49.2g of a mixture of crude m-phenoxy toluene chloro products, and performing gas phase detection: wherein, the monochloro substituent is 43 percent, the dichloro substituent is 54 percent, and the trichloro substituent is 2 percent.
(3) Preparing Komblum oxidation reaction feed liquid: adding 100mL (1.282mol) of dimethyl sulfoxide, 22g (0.147mol) of sodium iodide and 8.4g (0.079mol) of sodium carbonate into the m-phenoxytoluene chloro-product, stirring and heating to 120 ℃ under the protection of nitrogen, reacting for 3 hours, and stopping the reaction when the area normalization content of the m-phenoxytoluene chloro-product in a gas phase detection reaction system is 10-20%; the excess DMSO was removed by distillation under reduced pressure, and the reaction was carried out directly next.
(4) Preparation of m-phenoxybenzaldehyde: adding the Komblum oxidation reaction material liquid into a reaction bottle, adding 150mL of water under the protection of nitrogen, heating and refluxing 7.5g of urotropine for 4h, adding 150mL of glacial acetic acid, continuously refluxing for 4h, stopping the reaction when the m-phenoxy toluene chlorination product is less than 0.1% through gas phase detection, extracting the reaction material liquid twice with 100mL of toluene 2 after cooling, combining organic layers, washing the organic phase to be neutral with a sodium bicarbonate solution, performing reduced pressure distillation, and collecting 30.3g of fractions at 170-190 ℃ to obtain the product m-phenoxy benzaldehyde, wherein the total yield is 74.1% by m-cresol, and the gas phase detection content GC is 99.3%.
The mass spectrum and nuclear magnetism information of the obtained m-phenoxy benzaldehyde are as follows:
MS(ESI)，m/z：199.3[M+H]+.
1H NMR(400MHz，CDCl3)，δ＝7.22(2H，ArH)，6.98(H，ArH)，6.92(2H，ArH),7.20(H，ArH)，7.41(H，ArH)，7.53(H，ArH)，7.47(H，ArH)，9.87(H，CHO).
example 3
(1) Preparation of m-phenoxytoluene: a 100mL four-mouth bottle is provided with a stirrer, a thermometer and a water separator, 22.3g (0.206mol) of m-cresol, 19.8g of fluorobenzene (0.206mol), 12.4g (0.296mol) of sodium hydroxide are added to adjust the pH value to be 13, 0.3g of cuprous chloride is added, the mixture is refluxed at 180 ℃ for 5 hours, when the area normalization content of the m-cresol is detected to be less than 0.3 percent by a liquid phase, the reaction is stopped and the temperature is reduced to be below 110 ℃, the mixture is filtered, the fluorobenzene washes filter residues to be colorless, the filtrate is washed by dilute sulfuric acid (20mL) with the mass concentration of 10 percent, the layers are separated, an organic layer is subjected to reduced pressure distillation, 32.6g of m-; the gas phase detection content GC is 99%.
(2) Preparation of m-phenoxytoluene chloro-product: adding 32.6g (0.177mol) of m-phenoxy toluene, an initiator azodiisobutyronitrile (AIBN0.3g) and 100mL of carbon tetrachloride into a 250mL four-mouth bottle, heating to reflux, introducing chlorine gas, absorbing escaped tail gas by using alkali, cooling reaction feed liquid after the area normalization content of the m-phenoxy toluene in a reaction system is less than 0.5%, removing the solvent carbon tetrachloride by reduced pressure distillation after the substitution reaction is finished, obtaining 50g of a mixture of crude m-phenoxy toluene chloro products, and performing gas phase detection: wherein, the monochloro substituent is 45 percent, the dichloro substituent is 52 percent, and the trichloro substituent is 2 percent.
(3) Preparing Komblum oxidation reaction feed liquid: adding 100mL (1.282mol) of dimethyl sulfoxide, 22g (0.147mol) of sodium iodide and 8.4g (0.079mol) of sodium carbonate into the m-phenoxytoluene chloro-product, stirring and heating to 120 ℃ under the protection of nitrogen, reacting for 3 hours, and stopping the reaction when the area normalization content of the m-phenoxytoluene chloro-product in a gas phase detection reaction system is 10-20%; the excess DMSO was removed by distillation under reduced pressure, and the reaction was carried out directly next.
(4) Preparation of m-phenoxybenzaldehyde: adding the Komblum oxidation reaction material liquid into a reaction bottle, adding 150mL of water and 7.8g of urotropine under the protection of nitrogen, and then heating and refluxing for 4 hours; supplementing 150mL of glacial acetic acid, continuously refluxing for 4h, stopping the reaction when the chlorinated product of m-phenoxytoluene is less than 0.1% by gas phase detection, extracting twice by using 100mL of toluene 2 after the reaction liquid is cooled, combining organic layers, washing the organic phase to be neutral by using a sodium bicarbonate solution, and carrying out reduced pressure distillation to collect 31.1g of fraction at 170-190 ℃, namely the product of m-phenoxybenzaldehyde, wherein the total yield is 76.1% by using m-cresol, and the gas phase detection content GC is 99.2%.
Example 4
(1) Preparation of m-phenoxytoluene: a100 mL four-mouth bottle is provided with a stirrer, a thermometer and a water separator, 22.3g (0.206mol) of m-cresol, 23.2g of chlorobenzene (0.206mol), 16.6g (0.296mol) of potassium hydroxide are added to adjust the pH value to be 13, 0.3g of cuprous chloride is added to reflux at 170 ℃ for 5h, the reaction is stopped when the area normalization content of the m-cresol is detected to be less than 0.3 percent by liquid phase, the temperature is reduced to be below 110 ℃, the mixture is filtered, the chlorobenzene is used for washing filter residue to be colorless, the filtrate and the washing liquid are combined and washed by dilute sulfuric acid (20mL) with the mass concentration of 10 percent, layers are separated, an organic layer is distilled under reduced pressure, 32.3g of the m-phenoxy toluene is collected, the yield is 85.
(2) Preparation of m-phenoxytoluene chloro-product: adding 32.3g (0.175mol) of m-phenoxy toluene, an initiator azodiisobutyronitrile (AIBN0.3g) and 100mL of carbon tetrachloride into a 250mL four-mouth bottle, heating to reflux, introducing chlorine gas, absorbing escaped tail gas by using alkali, cooling reaction feed liquid after the area normalization content of the m-phenoxy toluene in a reaction system is less than 0.5%, removing solvent carbon tetrachloride by reduced pressure distillation after the substitution reaction is finished, obtaining 44g of a mixture of crude m-phenoxy toluene chloro products, and performing gas phase detection: wherein, the monochloro substituent is 44 percent, the dichloro substituent is 53 percent, and the trichloro substituent is 2 percent.
(3) Preparing Komblum oxidation reaction feed liquid: adding 100mL (1.282mol) of dimethyl sulfoxide, 22g (0.147mol) of sodium iodide and 8.4g (0.079mol) of sodium carbonate into the m-phenoxytoluene chloro-product, stirring and heating to 120 ℃ under the protection of nitrogen, reacting for 3 hours, and stopping the reaction when the area normalization content of the m-phenoxytoluene chloro-product in a gas phase detection reaction system is 10-20%; the excess DMSO was removed by distillation under reduced pressure, and the reaction was carried out directly next.
(4) Preparation of m-phenoxybenzaldehyde: adding the Komblum oxidation reaction material liquid into a reaction bottle, adding 150mL of water and 7.8g of urotropine under the protection of nitrogen, and then heating and refluxing for 4 hours; supplementing 150mL of glacial acetic acid, continuously refluxing for 4h, stopping the reaction when the chlorinated product of m-phenoxytoluene is less than 0.1% by gas phase detection, extracting the reaction feed liquid twice by using 100mL of toluene 2 after cooling, combining organic layers, washing the organic phase of the organic layers to be neutral by using a sodium bicarbonate solution, and carrying out reduced pressure distillation to collect 30.2g of fraction at the temperature of 170-190 ℃, namely the product of m-phenoxybenzaldehyde, wherein the total yield is 73.8% by using m-cresol, and the gas phase content GC is 99.1%.
Example 5
(1) Preparation of m-phenoxytoluene: a100 mL four-mouth bottle is provided with a stirrer, a thermometer and a water separator, 22.3g (0.206mol) of m-cresol, 23.2g of chlorobenzene (0.206mol), 16.6g (0.296mol) of potassium hydroxide are added to adjust the pH value to be 13, 0.3g of cuprous chloride is added, the mixture is refluxed at 190 ℃ for 5 hours, when the area normalization content of the m-cresol is detected to be less than 0.3 percent in a liquid phase, the reaction is stopped and cooled to below 110 ℃, the mixture is filtered, the chlorobenzene is used for washing filter residues to be colorless, the filtrate and the washing liquid are combined and washed by dilute sulfuric acid (20mL) with the mass concentration of 10 percent, layers are separated, an organic layer is distilled under reduced pressure, 32.3g of the m-phenoxy toluene is collected, the yield is 85.
(2) Preparation of m-phenoxytoluene chloro-product: adding 32.3g (0.175mol) of m-phenoxy toluene, an initiator azodiisobutyronitrile (AIBN0.3g) and 100mL of carbon tetrachloride into a 250mL four-mouth bottle, heating to reflux, introducing chlorine gas, absorbing escaped tail gas by using alkali, cooling reaction feed liquid after the area normalization content of the m-phenoxy toluene in a reaction system is less than 0.5%, removing solvent carbon tetrachloride by reduced pressure distillation after the substitution reaction is finished, obtaining 44g of a mixture of crude m-phenoxy toluene chloro products, and performing gas phase detection: wherein, the monochloro substituent is 44 percent, the dichloro substituent is 53 percent, and the trichloro substituent is 2 percent.
(3) Preparing Komblum oxidation reaction feed liquid: adding 100mL (1.282mol) of dimethyl sulfoxide, 22g (0.147mol) of sodium iodide and 8.4g (0.079mol) of sodium carbonate into the m-phenoxytoluene chloro-product, stirring and heating to 120 ℃ under the protection of nitrogen, reacting for 3 hours, and stopping the reaction when the area normalization content of the m-phenoxytoluene chloro-product in a gas phase detection reaction system is 10-20%; the excess DMSO was removed by distillation under reduced pressure, and the reaction was carried out directly next.
(4) Preparation of m-phenoxybenzaldehyde: adding the Komblum oxidation reaction material liquid into a reaction bottle, adding 150mL of water and 7.8g of urotropine under the protection of nitrogen, and then heating and refluxing for 4 hours; supplementing 150mL of glacial acetic acid, continuously refluxing for 4h, stopping the reaction when the chlorinated product of m-phenoxytoluene is less than 0.1% by gas phase detection, extracting twice by using 100mL of toluene 2 after the reaction liquid is cooled, combining organic layers, washing the organic phase to be neutral by using a sodium bicarbonate solution, and carrying out reduced pressure distillation to collect 31.7g of fraction at 170-190 ℃, namely the product of m-phenoxybenzaldehyde, wherein the total yield is 77.5% by using m-cresol, and the gas phase content GC is 98.8%.
Comparative example 1
(1) Adding 18.7g of aluminum trichloride and 200mL of 1.2-dichloroethane into a 500mL four-mouth bottle, fully stirring, heating to 45 ℃, dropwise adding 10.6g of benzaldehyde within 1h under stirring, heating to 60 ℃, slowly dropwise adding 16.8g of bromine which is dried by concentrated sulfuric acid in advance, dropwise adding after 5h, continuing to perform heat preservation reaction for 1h, absorbing hydrogen bromide generated by the reaction by using an alkali solution, slowly pouring the reaction mixture into 2mol/L hydrochloric acid (300mL), stirring, standing for layering, washing an organic layer by using a sodium bicarbonate solution (100mL) with the mass concentration of 10%, concentrating under reduced pressure, evaporating to remove the solvent to obtain a yellow liquid, namely the m-bromobenzaldehyde, and directly performing the next step without purification.
(2) Adding 280mL of DMF, 13.2g of phenol and 7.6g of sodium methoxide into a 500mL four-neck flask, stirring and reacting at 70 ℃ for 1h, adding 2.0g of cuprous chloride, heating to 100 ℃, dropwise adding the m-bromobenzaldehyde obtained in the previous step, after 1h of dropwise addition, evaporating to remove low-boiling-point fractions, raising the reaction temperature to 145-150 ℃, carrying out heat preservation and reacting for 5h, after the reaction is finished, carrying out reduced pressure distillation to remove DMF, extracting residues with chloroform (70mL x 3), washing an organic phase with 10% sodium bicarbonate solution (100mL x 2), carrying out reduced pressure distillation to remove a solvent, continuing reduced pressure distillation to collect 170-190 ℃ fractions 10.3g, namely the product m-phenoxybenzaldehyde, wherein the total yield of the two steps is 52%, and the gas phase content GC is 97.8%.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. A preparation method of m-phenoxy benzaldehyde is characterized by comprising the following steps:
carrying out condensation reaction on m-cresol, halogenated benzene and a first catalyst under an alkaline condition to obtain m-phenoxy toluene;
carrying out substitution reaction on the m-phenoxy toluene and chlorine under the condition of the existence of an initiator to obtain a m-phenoxy toluene chloro-product;
mixing the m-phenoxy toluene chlorination product, an oxidant and a second catalyst, and carrying out Komblum oxidation reaction to obtain Komblum oxidation reaction feed liquid;
mixing the Komblum oxidation reaction material liquid, urotropine and water, and carrying out salt forming reaction; and mixing the obtained salt forming system with acetic acid, and hydrolyzing to obtain the m-phenoxy benzaldehyde.
2. The production method according to claim 1, wherein the first catalyst is cuprous chloride; the mass of the cuprous chloride is 1-2% of the mass of the m-cresol.
3. The method according to claim 1, wherein the molar ratio of m-cresol to halogenated benzene is 1: (1-1.2).
4. The method according to any one of claims 1 to 3, wherein the condensation reaction is carried out at a temperature of 170 to 190 ℃.
5. The method of claim 1, wherein the initiator comprises azobisisobutyronitrile, azobisisovaleronitrile, or tert-butyl peroxyisobutyrate; the mass of the initiator is 0.8-1.2% of that of m-phenoxy toluene.
6. The method according to claim 1 or 5, wherein the substitution reaction is carried out under reflux.
7. The production method according to claim 1, wherein the oxidizing agent is dimethyl sulfoxide; the second catalyst is sodium iodide and sodium carbonate; the mass of the sodium iodide is 40-60% of that of the m-phenoxytoluene chlorination product, and the mass of the sodium carbonate is 15-25% of that of the m-phenoxytoluene chlorination product.
8. The preparation method according to claim 1 or 7, wherein the Komblum oxidation reaction is carried out at a temperature of 100-150 ℃ for 2-5 h.
9. The method according to claim 1, wherein the molar ratio of m-phenoxytoluene to urotropin is 1: (0.2-0.4).
10. The production method according to claim 1 or 9, wherein the m-phenoxytoluene and water are used in a ratio of 1 g: (4-6 ml); the volume ratio of the acetic acid to the water is 1: 1.
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| CN115073369A (en) * | 2022-05-31 | 2022-09-20 | 汉瑞药业(荆门)有限公司 | Preparation method of 5-bromoquinoline-8-formaldehyde |
| CN115772072A (en) * | 2022-11-25 | 2023-03-10 | 上海筑裕新材料科技有限公司 | Preparation method of m-phenoxy benzaldehyde |
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