CN107118088A - A kind of preparation method of m-hydroxy acetophenone - Google Patents
A kind of preparation method of m-hydroxy acetophenone Download PDFInfo
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- CN107118088A CN107118088A CN201710451177.7A CN201710451177A CN107118088A CN 107118088 A CN107118088 A CN 107118088A CN 201710451177 A CN201710451177 A CN 201710451177A CN 107118088 A CN107118088 A CN 107118088A
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- C—CHEMISTRY; METALLURGY
- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
- C07C45/676—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton by elimination of carboxyl groups
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- C07—ORGANIC CHEMISTRY
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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Abstract
The invention discloses a kind of preparation method of m-hydroxy acetophenone, comprise the following steps:M-hydroxybenzoic acid acetylation is obtained into an acetoxy-benzoic acid, then chloride obtains an acetoxyl group chlorobenzoyl chloride, then obtains 3 acetyloxy phenyl formylmaloic acid diethylesters with the reaction of diethyl malonate sodium salt solution, last decarboxylation obtains m-hydroxy acetophenone.The present invention is simple to operate, and raw material is cheap and easily-available, and synthesis is easy, and side reaction is few, with higher yield.
Description
Technical field
The present invention relates to chemical substance preparing technical field, more particularly to a kind of preparation method of m-hydroxy acetophenone.
Background technology
Phyenlephrinium (Phenylephrine) is a kind of new drug, is a kind of vasoactive drug of Hemorrhagic shock, for infecting
Poisoning and anaphylactic shock, supraventricular tachycardia, low blood pressure, mydriasis inspection when preventing and treating general anesthesia and lumbar anesthesia, it is tied
Structure formula is as follows:
Wherein, m-hydroxy acetophenone is its crucial synthesis fragment intermediate.At present it is known that m-hydroxy acetophenone synthesis
Method has:The synthetic route of Hangzhou literature of the chemical engineering report, its synthetic route is as follows:
Using acetophenone as raw material, m-hydroxy acetophenone has been synthesized by a nitrated in position, reduction and diazotising hydrolysis.This
The yield of route is relatively low, and total recovery is only about 42.3%, and each step of this route is both needed to using a large amount of difficult recovered solvents,
Environmental pollution is larger, and the purity of the m-hydroxy acetophenone prepared is relatively low.
The content of the invention
The technical problem existed based on background technology, the present invention proposes a kind of preparation method of m-hydroxy acetophenone, this
Invention is simple to operate, and raw material is cheap and easily-available, and synthesis is easy, and side reaction is few, with higher yield.
A kind of preparation method of m-hydroxy acetophenone proposed by the present invention, comprises the following steps:By m-hydroxybenzoic acid second
Acylation obtains an acetoxy-benzoic acid, then chloride obtains an acetoxyl group chlorobenzoyl chloride, then with diethyl malonate sodium
Salting liquid reaction obtains 3- acetyloxy phenyl formylmaloic acid diethylesters, and last decarboxylation obtains m-hydroxy acetophenone.
Preferably, in acetylation, m-hydroxybenzoic acid carries out acetylization reaction with acetylation reagent, wherein, second
Acylating reagent is acetic anhydride.
Preferably, the mol ratio of m-hydroxybenzoic acid and acetylation reagent is 1-1.5:1.
Preferably, in acetylation also need add acetylation catalyst, wherein, acetylation catalyst be sodium acetate,
At least one of ammonium acetate, zinc acetate, lead acetate.
Preferably, the mol ratio of acetylation catalyst and m-hydroxybenzoic acid is 0.1-0.5:100.
Preferably, the reaction dissolvent of acetylation is in toluene, dichloromethane, ether, dichloroethanes, water, tetrahydrofuran
It is at least one.
Preferably, the weight ratio of the reaction dissolvent of acetylation and m-hydroxybenzoic acid is 2-10:1.
Preferably, the temperature of acetylation is 30-100 DEG C, and the time is 2-4h.
Preferably, during chloride, an acetoxy-benzoic acid carries out acyl chloride reaction with chloride reagent, its
In, chloride reagent is thionyl chloride.
Preferably, the mol ratio of an acetoxy-benzoic acid and chloride reagent is 1-2.5:1.
Preferably, also need to add chloride catalyst during chloride, wherein, chloride catalyst is N, N- diformazans
Base formamide.
Preferably, the mol ratio of chloride catalyst and an acetoxy-benzoic acid is 1-5:100.
Preferably, the reaction dissolvent of chloride is toluene, ether, dichloromethane, dichloroethanes, water, tetrahydrofuran, ethanol
At least one of.
Preferably, the reaction dissolvent of chloride is high boiling solvent.
Preferably, the reaction dissolvent of chloride is ethanol or/and tetrahydrofuran.
Preferably, the temperature of chloride is 25-80 DEG C, and the time is 2-8h.
Preferably, in the preparation process of diethyl malonate sodium salt solution, diethyl malonate and alkaline matter containing sodium
Reaction obtains diethyl malonate sodium salt solution in the first solvent.
Preferably, alkaline matter containing sodium is at least one of caustic alcohol, sodium methoxide, sodium hydroxide, sodium acid carbonate.
Preferably, the first solvent is at least one in toluene, dichloromethane, dichloroethanes, ether, tetrahydrofuran, ethanol
Kind.
Preferably, the first solvent is tetrahydrofuran or/and ether.
Preferably, the mol ratio of diethyl malonate and the alkaline matter containing sodium is 1:1-5.
Preferably, the weight ratio of the first solvent and diethyl malonate is 1-10:1.
Preferably, the temperature of diethyl malonate and the alkali substance reaction containing sodium is 30-100 DEG C, and the time is 3-8h.
Preferably, in diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride course of reaction, malonic acid two
Ethyl ester sodium salt solution and an acetoxyl group chlorobenzoyl chloride solution are reacted, wherein, an acetoxyl group chlorobenzoyl chloride solution it is molten
Agent is the first solvent.
Preferably, the mass fraction of an acetoxyl group chlorobenzoyl chloride solution is 16.7-33.3wt%.
Preferably, volume weight (L/kg) ratio of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride is
15:2.7-2.8.
Preferably, the temperature that diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride react is -10 to 0 DEG C,
Time is 30min-2h.
Preferably, decarboxylation need to be carried out in sour environment.
Preferably, maintain sour environment with acidic materials, wherein, acidic materials be hydrochloric acid, sulfuric acid, acetic acid, to toluene
At least one of sulfonic acid.
Preferably, the weight ratio of acidic materials and 3- acetyloxy phenyl formylmaloic acid diethylesters is 5-10:1.
Preferably, decarboxylation need to be carried out in acidic aqueous solution.
Preferably, the temperature of decarboxylation is 90-110 DEG C, and the time is 1-5h.
Preferably, the concrete operations of acetylation are:M-hydroxybenzoic acid is added in acetylization reaction solvent and dissolved, is added
Acetylation reagent and acetylation catalyst, heat up, insulation, and cooling separates out solid, and filtering, drying obtains an acetyloxy phenyl first
Acid.
Preferably, the concrete operations of chloride are:In nitrogen atmosphere, acetoxy-benzoic acid, acyl chloride reaction by between
Solvent is mixed, and adds chloride catalyst, and chloride reagent is added dropwise, and is heated up, and insulation is concentrated to give an acetoxyl group benzoyl
Chlorine.
Preferably, the concrete operations for preparing diethyl malonate sodium salt solution are:First solvent, diethyl malonate are mixed
Even, stirring adds alkaline matter containing sodium, and heating, insulation obtains diethyl malonate sodium salt solution.
Preferably, the concrete operations for preparing 3- acetyloxy phenyl formylmaloic acid diethylesters are:Take diethyl malonate sodium
Salting liquid, cooling, acetoxyl group chlorobenzoyl chloride solution between dropwise addition, insulation, then reaction is quenched in watery hydrochloric acid, and stratification has taken
Machine is mutually spin-dried for obtaining 3- acetyloxy phenyl formylmaloic acid diethylesters.
Preferably, the concrete operations of decarboxylation are:3- acetyloxy phenyl formylmaloic acids diethylester is added into acidic aqueous solution
It is middle to mix, backflow, cool crystallization, and centrifugation obtains m-hydroxy acetophenone.
The reaction dissolvent consumption of chloride is not provided during above-mentioned chloride, its consumption is determined according to concrete operations.
M-hydroxybenzoic acid of the present invention is raw material, cheap and easy to get, and reaction condition is gentle, and energy consumption is low, high income, prepares
M-hydroxybenzoic acid purity it is good, it is environmentally friendly, it is simple to operate, be adapted to industrialized production.
Brief description of the drawings
Fig. 1 is a kind of synthetic route chart of the preparation method of m-hydroxy acetophenone proposed by the present invention.
Fig. 2 is the nuclear magnetic spectrum of acetoxy-benzoic acid between the present invention is prepared.
Fig. 3 is the gas phase collection of illustrative plates of acetoxy-benzoic acid between the present invention is prepared.
The nuclear magnetic spectrum for the m-hydroxy acetophenone that Fig. 4 prepares for the present invention.
Embodiment
As shown in figure 1, Fig. 1 is a kind of synthetic route chart of the preparation method of m-hydroxy acetophenone proposed by the present invention.
A kind of reference picture 1, preparation method of m-hydroxy acetophenone proposed by the present invention, comprises the following steps:The hydroxyl by between
Benzoic acid acetylation obtains an acetoxy-benzoic acid, then chloride obtains an acetoxyl group chlorobenzoyl chloride, then with malonic acid
The reaction of diethylester sodium salt solution obtains 3- acetyloxy phenyl formylmaloic acid diethylesters, and last decarboxylation obtains m-hydroxy acetophenone.
Below, technical scheme is described in detail by specific embodiment.
Embodiment 1
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added to the water dissolving, plus
Enter acetic anhydride and sodium acetate, be warming up to 80 DEG C, be incubated 2h, cooling separates out solid, and filtering, drying obtains an acetyloxy phenyl first
Acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1:1, the mol ratio of sodium acetate and m-hydroxybenzoic acid is 0.5:
100, the weight ratio of water and m-hydroxybenzoic acid is 10:1;
In nitrogen atmosphere, acetoxy-benzoic acid, ethanol are mixed by between, add DMF, are added dropwise two
Chlorine sulfoxide, is warming up to 70 DEG C, is incubated 4h, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, an acetoxy-benzoic acid and two
The mol ratio of chlorine sulfoxide is 1:1, the mol ratio of DMF and an acetoxy-benzoic acid is 1:100;
Toluene, diethyl malonate are mixed, stirring adds sodium hydroxide, are warming up to 80 DEG C, insulation 3h obtains malonic acid
Diethylester sodium salt solution, wherein, the mol ratio of diethyl malonate and sodium hydroxide is 1:1, toluene and diethyl malonate
Weight ratio is 5.9:1;
Diethyl malonate sodium salt solution is taken, -10 DEG C are cooled to, it is acetyloxy phenyl first between 20wt% that mass fraction, which is added dropwise,
The toluene solution of acyl chlorides, is incubated 30min, and then reaction is quenched in watery hydrochloric acid, and stratification takes organic phase to be spin-dried for obtaining 3- acetyl oxygen
Base benzoyl diethyl malonate, wherein, the volume weight of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride
(L/kg) than being 15:2.7;
3- acetyloxy phenyl formylmaloic acids diethylester is added mass fraction to mix in 10wt% aqueous hydrochloric acid solutions, risen
Temperature is to 105 DEG C, and flow back 5h, is cooled to 10 DEG C of crystallizations, and centrifugation obtains m-hydroxy acetophenone, wherein, hydrochloric acid and 3- acetyloxy phenyls
The weight ratio of formylmaloic acid diethylester is 5:1.
Embodiment 2
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added in dichloroethanes
Dissolving, adds acetic anhydride and ammonium acetate, is warming up to 80 DEG C, is incubated 2h, and cooling separates out solid, and filtering, drying obtains an acetyl oxygen
Yl benzoic acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1:1, the mol ratio of ammonium acetate and m-hydroxybenzoic acid
For 0.5:100, the weight ratio of dichloroethanes and m-hydroxybenzoic acid is 8:1;
In nitrogen atmosphere, acetoxy-benzoic acid, dichloroethanes are mixed by between, add DMF, drop
Plus thionyl chloride, 60 DEG C are warming up to, 5h is incubated, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, an acetoxy-benzoic acid
Mol ratio with thionyl chloride is 1:1, the mol ratio of DMF and an acetoxy-benzoic acid is 5:100;
Ethanol, diethyl malonate are mixed, stirring adds caustic alcohol, are warming up to 75 DEG C, insulation 5h obtains malonic acid two
Ethyl ester sodium salt solution, wherein, the mol ratio of diethyl malonate and caustic alcohol is 1:2.5, the weight of ethanol and diethyl malonate
Amount is than being 5.4:1;
Diethyl malonate sodium salt solution is taken, -10 DEG C are cooled to, it is acetyloxy phenyl first between 20wt% that mass fraction, which is added dropwise,
The ethanol solution of acyl chlorides, is incubated 30min, and then reaction is quenched in watery hydrochloric acid, and stratification takes organic phase to be spin-dried for obtaining 3- acetyl oxygen
Base benzoyl diethyl malonate, wherein, the volume weight of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride
(L/kg) than being 15:2.8;
3- acetyloxy phenyl formylmaloic acids diethylester is added mass fraction to mix in 30wt% aqueous sulfuric acids, risen
Temperature is to 110 DEG C, and flow back 5h, is cooled to 10 DEG C of crystallizations, and centrifugation obtains m-hydroxy acetophenone, wherein, sulfuric acid and 3- acetyloxy phenyls
The weight ratio of formylmaloic acid diethylester is 5:1.
Embodiment 3
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added in toluene and dissolved,
Acetic anhydride and zinc acetate are added, 80 DEG C are warming up to, 2h is incubated, cooling separates out solid, and filtering, drying obtains an acetyloxy phenyl first
Acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1:1, the mol ratio of zinc acetate and m-hydroxybenzoic acid is 0.5:
100, the weight ratio of toluene and m-hydroxybenzoic acid is 6:1;
In nitrogen atmosphere, acetoxy-benzoic acid, dichloromethane are mixed by between, add DMF, drop
Plus thionyl chloride, 35 DEG C are warming up to, 5h is incubated, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, wherein, an acetoxyl group
The mol ratio of benzoic acid and thionyl chloride is 1:1, the mol ratio of DMF and an acetoxy-benzoic acid is 3:
100;
Tetrahydrofuran, diethyl malonate are mixed, stirring adds sodium acid carbonate, are warming up to 60 DEG C, insulation 5h obtains third
Diethyl adipate sodium salt solution, wherein, the mol ratio of diethyl malonate and sodium acid carbonate is 1:2, tetrahydrofuran and malonic acid
The weight ratio of diethylester is 6.1:1;
Diethyl malonate sodium salt solution is taken, -10 DEG C are cooled to, it is acetyloxy phenyl first between 20wt% that mass fraction, which is added dropwise,
The tetrahydrofuran solution of acyl chlorides, is incubated 30min, and then reaction is quenched in watery hydrochloric acid, and stratification takes organic phase to be spin-dried for obtaining 3- second
Acyloxy benzoyl diethyl malonate, wherein, the volume of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride
Weight (L/kg) is than being 15:2.8;
3- acetyloxy phenyl formylmaloic acids diethylester is added into mass fraction in the 10wt% p-methyl benzenesulfonic acid aqueous solution
Mix, be warming up to 100 DEG C, flow back 5h, be cooled to 10 DEG C of crystallizations, centrifugation obtains m-hydroxy acetophenone, wherein, sulfuric acid and 3- acetyl
The weight ratio of epoxide benzoyl diethyl malonate is 5:1.
Embodiment 4
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added in dichloromethane
Dissolving, adds acetic anhydride and lead acetate, is warming up to 30 DEG C, is incubated 4h, and cooling separates out solid, and filtering, drying obtains an acetyl oxygen
Yl benzoic acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1.5:1, mole of lead acetate and m-hydroxybenzoic acid
Than for 0.1:100, the weight ratio of dichloromethane and m-hydroxybenzoic acid is 2:1;
In nitrogen atmosphere, acetoxy-benzoic acid, ether are mixed by between, add DMF, are added dropwise two
Chlorine sulfoxide, is warming up to 25 DEG C, is incubated 8h, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, an acetoxy-benzoic acid and two
The mol ratio of chlorine sulfoxide is 2.5:1, the mol ratio of DMF and an acetoxy-benzoic acid is 2:100;
Dichloromethane, diethyl malonate are mixed, stirring adds sodium methoxide, is warming up to 30 DEG C, insulation 8h obtains the third two
Diethyl phthalate sodium salt solution, wherein, the mol ratio of diethyl malonate and sodium methoxide is 1:5, dichloromethane and malonic acid diethyl
The weight ratio of ester is 10:1;
Diethyl malonate sodium salt solution is taken, 0 DEG C is cooled to, it is acetyloxy phenyl first between 16.7wt% that mass fraction, which is added dropwise,
The dichloromethane solution of acyl chlorides, is incubated 2h, and then reaction is quenched in watery hydrochloric acid, and stratification takes organic phase to be spin-dried for obtaining 3- acetyl
Epoxide benzoyl diethyl malonate, wherein, the volume weight of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride
(L/kg) is measured than being 15:2.73;
3- acetyloxy phenyl formylmaloic acids diethylester is added in aqueous acetic acid and mixed, 90 DEG C are warming up to, flow back 4h,
Cool crystallization, and centrifugation obtains m-hydroxy acetophenone, wherein, the weight ratio of acetic acid and 3- acetyloxy phenyl formylmaloic acid diethylesters
For 10:1.
Embodiment 5
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added in toluene and dissolved,
Acetic anhydride and ammonium acetate are added, 100 DEG C are warming up to, 3h is incubated, cooling separates out solid, and filtering, drying obtains an acetyloxy phenyl
Formic acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1.3:1, the mol ratio of ammonium acetate and m-hydroxybenzoic acid is
0.3:100, the weight ratio of toluene and m-hydroxybenzoic acid is 4:1;
In nitrogen atmosphere, acetoxy-benzoic acid, toluene are mixed by between, add DMF, are added dropwise two
Chlorine sulfoxide, is warming up to 80 DEG C, is incubated 2h, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, an acetoxy-benzoic acid and two
The mol ratio of chlorine sulfoxide is 1.5:1, the mol ratio of DMF and an acetoxy-benzoic acid is 4:100;
Toluene, diethyl malonate are mixed, stirring adds caustic alcohol, are warming up to 100 DEG C, insulation 3h obtains malonic acid two
Ethyl ester sodium salt solution, wherein, the mol ratio of diethyl malonate and caustic alcohol is 1:3, the weight of toluene and diethyl malonate
Than for 1:1;
Diethyl malonate sodium salt solution is taken, -5 DEG C are cooled to, it is acetyloxy phenyl between 33.3wt% that mass fraction, which is added dropwise,
The toluene solution of formyl chloride, is incubated 1h, and then reaction is quenched in watery hydrochloric acid, and stratification takes organic phase to be spin-dried for obtaining 3- acetyl oxygen
Base benzoyl diethyl malonate, wherein, the volume weight of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride
(L/kg) than being 15:2.77;
3- acetyloxy phenyl formylmaloic acids diethylester is added in aqueous hydrochloric acid solution and mixed, 110 DEG C, backflow are warming up to
1h, cool crystallization, and centrifugation obtains m-hydroxy acetophenone, wherein, the weight of hydrochloric acid and 3- acetyloxy phenyl formylmaloic acid diethylesters
Amount is than being 7.5:1.
Embodiment 6
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added in ether and dissolved,
Acetic anhydride and sodium acetate are added, 32 DEG C are warming up to, 2.5h is incubated, cooling separates out solid, and filtering, drying obtains an acetyloxy phenyl
Formic acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1.4:1, the mol ratio of sodium acetate and m-hydroxybenzoic acid is
0.4:100, the weight ratio of ether and m-hydroxybenzoic acid is 5:1;
In nitrogen atmosphere, acetoxy-benzoic acid, tetrahydrofuran are mixed by between, add DMF, drop
Plus thionyl chloride, 50 DEG C are warming up to, 7h is incubated, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, an acetoxy-benzoic acid
Mol ratio with thionyl chloride is 2:1, the mol ratio of DMF and an acetoxy-benzoic acid is 3:100;
Ether, diethyl malonate are mixed, stirring adds sodium hydroxide, are warming up to 31 DEG C, insulation 6h obtains malonic acid
Diethylester sodium salt solution, wherein, the mol ratio of diethyl malonate and sodium hydroxide is 1:2, ether and diethyl malonate
Weight ratio is 2:1;
Diethyl malonate sodium salt solution is taken, -8 DEG C are cooled to, it is acetyloxy phenyl first between 30wt% that mass fraction, which is added dropwise,
The diethyl ether solution of acyl chlorides, is incubated 1.5h, and then reaction is quenched in watery hydrochloric acid, and stratification takes organic phase to be spin-dried for obtaining 3- acetyl oxygen
Base benzoyl diethyl malonate, wherein, the volume weight of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride
(L/kg) than being 15:2.75;
3- acetyloxy phenyl formylmaloic acids diethylester is added in aqueous sulfuric acid and mixed, 95 DEG C are warming up to, flow back 4h,
Cool crystallization, and centrifugation obtains m-hydroxy acetophenone, wherein, the weight ratio of sulfuric acid and 3- acetyloxy phenyl formylmaloic acid diethylesters
For 6:1.
Embodiment 7
A kind of preparation method of m-hydroxy acetophenone, comprises the following steps:M-hydroxybenzoic acid is added to the water dissolving, plus
Enter acetic anhydride and zinc acetate, be warming up to 90 DEG C, be incubated 2.5h, cooling separates out solid, and filtering, drying obtains an acetyloxy phenyl first
Acid, wherein, the mol ratio of m-hydroxybenzoic acid and acetic anhydride is 1.2:1, the mol ratio of zinc acetate and m-hydroxybenzoic acid is
0.2:100, the weight ratio of water and m-hydroxybenzoic acid is 9:1;
In nitrogen atmosphere, acetoxy-benzoic acid, water are mixed by between, add DMF, and dichloro is added dropwise
Sulfoxide, is warming up to 85 DEG C, is incubated 4h, is concentrated to give an acetoxyl group chlorobenzoyl chloride, wherein, an acetoxy-benzoic acid and dichloro
The mol ratio of sulfoxide is 1.8:1, the mol ratio of DMF and an acetoxy-benzoic acid is 1.5:100;
Dichloroethanes, diethyl malonate are mixed, stirring adds sodium methoxide, is warming up to 75 DEG C, insulation 7h obtains the third two
Diethyl phthalate sodium salt solution, wherein, the mol ratio of diethyl malonate and sodium methoxide is 1:3, dichloroethanes and malonic acid diethyl
The weight ratio of ester is 7:1;
Diethyl malonate sodium salt solution is taken, the dichloroethanes for being cooled to acetoxyl group chlorobenzoyl chloride between -2 DEG C, dropwise addition is molten
Liquid, is incubated 2.2h, and then watery hydrochloric acid is quenched reaction, stratification, takes organic phase to be spin-dried for obtaining 3- acetoxyl groups benzoyl the third two
Diethyl phthalate, wherein, the volume weight (L/kg) of diethyl malonate sodium salt solution and an acetoxyl group chlorobenzoyl chloride is than being 15:
2.75;
3- acetyloxy phenyl formylmaloic acids diethylester is added in the p-methyl benzenesulfonic acid aqueous solution and mixed, 100 DEG C are warming up to,
Flow back 3h, and cool crystallization, and centrifugation obtains m-hydroxy acetophenone, wherein, p-methyl benzenesulfonic acid and 3- acetyloxy phenyl formylmaloic acids
The weight ratio of diethylester is 7:1.
Purity to the embodiment 1-7 m-hydroxy acetophenones prepared is detected, and counts yield, as a result as follows:
High income of the present invention as can be seen from the above table, the purity of the m-hydroxy acetophenone prepared is good.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto,
Any one skilled in the art the invention discloses technical scope in, technique according to the invention scheme and its
Inventive concept is subject to equivalent substitution or change, should all be included within the scope of the present invention.
Claims (10)
1. a kind of preparation method of m-hydroxy acetophenone, it is characterised in that comprise the following steps:By m-hydroxybenzoic acid acetylation
An acetoxy-benzoic acid is obtained, then chloride obtains an acetoxyl group chlorobenzoyl chloride, it is then molten with diethyl malonate sodium salt
Liquid reaction obtains 3- acetyloxy phenyl formylmaloic acid diethylesters, and last decarboxylation obtains m-hydroxy acetophenone.
2. the preparation method of m-hydroxy acetophenone according to claim 1, it is characterised in that in acetylation, a hydroxyl
Yl benzoic acid carries out acetylization reaction with acetylation reagent, wherein, acetylation reagent is acetic anhydride;Preferably, a hydroxy benzenes first
The mol ratio of acid and acetylation reagent is 1-1.5:1.
3. the preparation method of m-hydroxy acetophenone according to claim 1 or claim 2, it is characterised in that in acetylation also
Acetylation catalyst need to be added, wherein, acetylation catalyst is at least one in sodium acetate, ammonium acetate, zinc acetate, lead acetate
Kind;Preferably, the mol ratio of acetylation catalyst and m-hydroxybenzoic acid is 0.1-0.5:100.
4. according to the preparation method of any one of the claim 1-3 m-hydroxy acetophenones, it is characterised in that the reaction of acetylation
Solvent is at least one of toluene, dichloromethane, ether, dichloroethanes, water, tetrahydrofuran;Preferably, the reaction of acetylation
The weight ratio of solvent and m-hydroxybenzoic acid is 2-10:1;Preferably, the temperature of acetylation is 30-100 DEG C, and the time is 2-4h.
5. according to the preparation method of any one of the claim 1-4 m-hydroxy acetophenones, it is characterised in that in chloride process
In, an acetoxy-benzoic acid carries out acyl chloride reaction with chloride reagent, wherein, chloride reagent is thionyl chloride;It is preferred that
The mol ratio of ground, an acetoxy-benzoic acid and chloride reagent is 1-2.5:1.
6. according to the preparation method of any one of the claim 1-5 m-hydroxy acetophenones, it is characterised in that in chloride process
In also need add chloride catalyst, wherein, chloride catalyst be DMF;Preferably, chloride is catalyzed
The mol ratio of agent and an acetoxy-benzoic acid is 1-5:100.
7. according to the preparation method of any one of the claim 1-6 m-hydroxy acetophenones, it is characterised in that the reaction of chloride
Solvent is at least one of toluene, ether, dichloromethane, dichloroethanes, water, tetrahydrofuran, ethanol;Preferably, chloride
Reaction dissolvent be high boiling solvent;Preferably, the reaction dissolvent of chloride is ethanol or/and tetrahydrofuran;Preferably, acyl chlorides
The temperature of change is 25-80 DEG C, and the time is 2-8h.
8. according to the preparation method of any one of the claim 1-7 m-hydroxy acetophenones, it is characterised in that in malonic acid diethyl
In the preparation process of ester sodium salt solution, diethyl malonate reacts with alkaline matter containing sodium in the first solvent obtains malonic acid two
Ethyl ester sodium salt solution;Preferably, alkaline matter containing sodium is at least one in caustic alcohol, sodium methoxide, sodium hydroxide, sodium acid carbonate
Kind;Preferably, the first solvent is at least one of toluene, dichloromethane, dichloroethanes, ether, tetrahydrofuran, ethanol;It is excellent
Selection of land, the first solvent is tetrahydrofuran or/and ether;Preferably, the mol ratio of diethyl malonate and the alkaline matter containing sodium is
1:1-5;Preferably, the weight ratio of the first solvent and diethyl malonate is 1-10:1;Preferably, diethyl malonate is with containing sodium
The temperature of alkali substance reaction is 30-100 DEG C, and the time is 3-8h.
9. according to the preparation method of any one of the claim 1-8 m-hydroxy acetophenones, it is characterised in that in malonic acid diethyl
In ester sodium salt solution and an acetoxyl group chlorobenzoyl chloride course of reaction, diethyl malonate sodium salt solution and an acetyloxy phenyl first
Solution of acid chloride is reacted, wherein, the solvent of an acetoxyl group chlorobenzoyl chloride solution is the first solvent;Preferably, malonic acid two
The volume weight (L/kg) of ethyl ester sodium salt solution and an acetoxyl group chlorobenzoyl chloride is than being 15:2.7-2.8;Preferably, malonic acid
The temperature that diethylester sodium salt solution and an acetoxyl group chlorobenzoyl chloride react is -10 to 0 DEG C, and the time is 30min-2h.
10. according to the preparation method of any one of the claim 1-9 m-hydroxy acetophenones, it is characterised in that decarboxylation need to be in acid
Property environment in carry out;Preferably, sour environment is maintained with acidic materials, wherein, acidic materials are hydrochloric acid, sulfuric acid, acetic acid, right
At least one of toluenesulfonic acid;Preferably, the weight ratio of acidic materials and 3- acetyloxy phenyl formylmaloic acid diethylesters is
5-10:1;Preferably, decarboxylation need to be carried out in acidic aqueous solution;Preferably, the temperature of decarboxylation is 90-110 DEG C, and the time is 1-
5h。
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CN108530277A (en) * | 2018-05-21 | 2018-09-14 | 江西永通科技股份有限公司 | A kind of preparation method of m-hydroxy acetophenone |
CN113666819A (en) * | 2020-05-14 | 2021-11-19 | 帕潘纳(北京)科技有限公司 | Method for preparing chlorofluoromethrizole intermediate |
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CN105967986A (en) * | 2016-05-30 | 2016-09-28 | 北京旭阳科技有限公司 | 3-hydroxyacetophenone synthesis method |
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Cited By (3)
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CN108530277A (en) * | 2018-05-21 | 2018-09-14 | 江西永通科技股份有限公司 | A kind of preparation method of m-hydroxy acetophenone |
CN113666819A (en) * | 2020-05-14 | 2021-11-19 | 帕潘纳(北京)科技有限公司 | Method for preparing chlorofluoromethrizole intermediate |
CN113666819B (en) * | 2020-05-14 | 2024-06-21 | 帕潘纳(北京)科技有限公司 | Method for preparing penconazole intermediate |
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