CN103030557B

CN103030557B - Method for generating phenylacetate by acetophenone in one step

Info

Publication number: CN103030557B
Application number: CN201310007372.2A
Authority: CN
Inventors: 孟祥光; 李小红
Original assignee: Sichuan University
Current assignee: Sichuan University
Priority date: 2013-01-09
Filing date: 2013-01-09
Publication date: 2014-10-29
Anticipated expiration: 2033-01-09
Also published as: CN103030557A

Abstract

The invention relates to a method for preparing phenylacetate by acetophenone through oxidation in one step. Acetophenone is used as a raw material, hydrogen peroxide is used as an oxidant, formic acid is used as a solvent, and a copper complex is used as a catalyst. The method for synthesizing phenylacetate in one step is characterized in that the phenylacetate yield is high, the conversion rate and selectivity can reach 100%, the reaction condition is mild, the catalyst is simple to prepare, and the raw material is cheap and obtained easily, so that the method is a green synthetic method which is less in investment consumption, high in yield and simple and feasible.

Description

A kind of method that is generated phenylacetate by methyl phenyl ketone one step

Technical field

The present invention relates to a kind of method that is generated phenylacetate by methyl phenyl ketone one step.

Background technology

Phenylacetate, at the industrial general intermediate as solvent and organic synthesis, also can be used as important fine chemistry industry and medicine intermediate.Phenylacetate can obtain hydroxy acetophenone (mixture of o-hydroxyacetophenone and parahydroxyacet-ophenone) through conversion reaction, can be used for treating the diseases such as acute and chronic icterohepatitis, cholecystitis, and o-hydroxyacetophenone is wherein synthetic I _athe important intermediate of class anti-arrhythmic propafenone hydrochloride (propafenone hydrochloride).

The method of industrial synthesis of acetic acid phenyl ester normally adopts phenol to react with certain density sodium hydroxide and generates sodium phenylate, and then dropping diacetyl oxide further reacts, and then through a plurality of steps such as washing, neutralization, dry, rectifying, the yield with approximately 93% makes.This method, owing to using sodium hydroxide solution, can cause the corrosion of equipment, causes environmental pollution.Make the shortcomings such as utilization ratio reduction of equipment simultaneously.Another kind method is by phenol and diacetyl oxide, to take phosphoric acid to contract and phenylacetate is prepared in reaction as catalyzer, and product yield is 91%.The main raw material diacetyl oxide of these two kinds of methods is raw materials of preparing drugs, has become one of medicine of national restrict sales.Resulting reaction product all needs the steps such as washing, alkali cleaning in addition, and a large amount of phenolic wastewater of generation is not easy to process, and problem of environmental pollution is outstanding.Also someone improves now, by the contracting of phenol and phenyllacetyl chloride acidylate and and obtain, react and carry out in the aqueous solution of sodium hydroxide, because hydrolysis reaction easily occurs phenyllacetyl chloride, need to use excessive phenyllacetyl chloride, even so, the yield of product is also very low.Therefore also have the direct acidylate method of selection to make phenylacetate, just Acetyl Chloride 98Min. and phenol are all toxic, deal with pretty troublesomely, and problem of environmental pollution is outstanding.The ionic liquid that Li Liang skills in 2010 etc. have proposed to generate under the condition at the vitriol oil with zwitter-ion at patent ZL201010154485.1 is as catalyzer, catalysis of phenol and acetic acidreaction generate phenylacetate, high in temperature when being separated, the vitriol oil is easily by organic carbon, and this condition cost is high, and problem of environmental pollution still cannot be eliminated.

Under certain catalyzer, with suitable oxygenant oxidation step methyl phenyl ketone, produce phenylacetate, there is the outstanding advantages such as cost is low, route is short, Atom economy is high, simple to operate, pollution-free.Be considered to be hopeful most the clean preparation method that fortified phenol legal system is got a kind of Green Chemistry of phenylacetate.The oxygenant adopting is generally acknowledged Green Oxidant hydrogen peroxide.Under catalytic condition, the transformation efficiency of methyl phenyl ketone reaches 100%, and selectivity also reaches 100%, all generates phenylacetate.And product and catalyst separating convenience, catalyzer is reproducible.

Summary of the invention

The object of the invention is to adopt cheap methyl phenyl ketone is raw material, and peroxide agent is oxygenant, provides that a kind of working method is simple, reaction conditions is gentle, a step of with low cost, high conversion and highly selective produces the method for phenylacetate.

The present invention is usingd methyl phenyl ketone as raw material, and hydrogen peroxide is as oxygenant, and metal copper complexes is catalyzer.Solvent is acetonitrile, Isosorbide-5-Nitrae-dioxane, formic acid, acetic acid, tertiary butyric acid, a kind of in DMSO.Press concentration ratio methyl phenyl ketone: metal copper complexes=20:0.1 ~ 0.3, metal copper complexes: hydrogen peroxide: solvent=0.1:1 ~ 4:110 ~ 150.Under normal pressure, under 20 ~ 70 ° of C conditions, the first reaction in solvent of hydrogen peroxide and copper complex generates active specy, then adds methyl phenyl ketone stirring reaction 0.5 ~ 8h, and then distillation, steams solvent, collects the phenylacetate of 190 ° of C ~ 195 ° C cuts.

Metal copper complexes is the preparation process of catalyzer: 41.16ml methyl ethyl diketone is dissolved in the single port flask that fills 50ml dehydrated alcohol, is positioned in frozen water cooling; 13.36ml anhydrous ethylenediamine is dissolved in 13.5ml dehydrated alcohol, cooling, then slowly dropwise join in above-mentioned solution, generate immediately yellow-white throw out, temperature of reaction maintains 2 ~ 5 ℃, stirs, and reacts 1 hour.Room temperature is placed and is spent the night.Reaction soln decompression rotary evaporation, places and filters, toluene and CCl for yellow crystals ₄recrystallization twice, obtains clear crystal Isosorbide-5-Nitrae-N respectively, two (methyl ethyl diketone) quadrol parts of N-, productive rate 70%.2g Cu (CH ₃cOO) ₂h ₂o joins in 500ml flask, puts into 150ml Isosorbide-5-Nitrae-dioxane solution, is warming up to 80 ℃ of dissolvings.Then slowly add 2.5 ~ 4.5g Isosorbide-5-Nitrae-N, two (methyl ethyl diketone) quadrol parts of N-, stir, and solution, immediately by blue purpling look, continues to stir, and heats up.Holding temperature, at 100 ℃ of left and right approximately 45 min, adds water 200 ml, and solution is dark purple black, and room temperature was placed after one day, had the needle-like crystal of light cyan to separate out.Filter, successively use sherwood oil, ether recrystallization, obtains silver-colored cyan needle-like crystal. Anal.?Calcd.?For?C ₁₂H ₈O ₂N ₂Cu:?C,?50.4;?H,?6.3;?N,?9.81%.?Found:?C,?49.5;?H,?6.6;?N?9.78%.

In catalyst system of the present invention, best solvent is formic acid, optimum methyl phenyl ketone is methyl phenyl ketone with the ratio of copper complex: copper complex=15:0.1 ~ 0.3, optimum copper complex is copper complex with hydrogen peroxide with the amount of substance ratio of solvent: hydrogen peroxide: solvent=0.1:1 ~ 4:120 ~ 135.Optimum temperature of reaction is 20 ~ 40 ° of C.

The present invention produces phenylacetate method with methyl phenyl ketone one step except have reaction raw materials cheap, be easy to get, process safety, product be easy to generate the advantages such as water, environmental sound after separation, hydroperoxidation, also has following outstanding feature:

(1) reaction conditions is gentle, just can carry out at normal temperatures;

?(2) yield of phenylacetate is high, reaches 100%, the transformation efficiency 100% of methyl phenyl ketone;

(3) preparation method of catalyzer is simple, cost is low;

?(4) in reaction process, added solvent and catalyzer are all recyclable, reuse.

The present invention has good economic benefit and considerable prospects for commercial application.

Embodiment

Embodiment 1 gets respectively copper complex 0.11g and is dissolved in 5ml formic acid, Isosorbide-5-Nitrae-dioxane, and acetonitrile, in DMSO, then adds hydrogen peroxidase 10 .02ml, reacts at normal temperatures after 0.5h, adds methyl phenyl ketone 0.05ml, reaction 8h.The transformation efficiency that obtains the yield methyl phenyl ketone of phenylacetate in different solvents, the results are shown in Table one.

The impact of table one different solvents on the transformation efficiency of phenylacetate yield methyl phenyl ketone

Solvent	Formic acid	Isosorbide-5-Nitrae-dioxane	Acetonitrile	DMSO
					Phenylacetate yield %	100	64	79	58
Acetophenone conversion %	100	75	88	70

Embodiment 2 gets respectively copper complex 0.11g and is dissolved in 5ml formic acid, then adds hydrogen peroxidase 10 .02ml, reacts at normal temperatures after 0.5h, adds methyl phenyl ketone 0.05ml to continue reaction, gets the solution of different time sections and test in reaction process.The transformation efficiency that obtains the yield methyl phenyl ketone of phenylacetate when different time, the results are shown in Table two.

Table two is the yield of different time phenylacetate and the transformation efficiency of methyl phenyl ketone in formic acid

Reaction times (h)	2	4	6	8
					Phenylacetate yield %	34	68	86	100
Acetophenone conversion %	35	68	88	100

Embodiment 3 gets respectively copper complex 0.11g and is dissolved in 5ml formic acid, then adds hydrogen peroxidase 10 .02 ~ 0.06ml, reacts at normal temperatures after 0.5h, adds methyl phenyl ketone 0.05ml to continue reaction, gets the different solution of content of hydrogen peroxide and test after reaction 1h.The transformation efficiency that obtains the yield methyl phenyl ketone of phenylacetate in the different solution of content of hydrogen peroxide, the results are shown in Table three.

The yield of phenylacetate and the transformation efficiency of methyl phenyl ketone in the different solution of table three content of hydrogen peroxide

Content of hydrogen peroxide (ml)	0.02	0.04	0.05	0.06
					Phenylacetate yield %	17	42	61	79
Acetophenone conversion %	19	42	61	79

Claims

1. the method by methyl phenyl ketone single stage method phenylacetate processed, using methyl phenyl ketone as raw material, hydrogen peroxide is as oxygenant, copper complex is catalyzer, solvent is acetonitrile, 1, 4-dioxane, formic acid, acetic acid, tertiary butyric acid, a kind of in DMSO, press concentration ratio methyl phenyl ketone: copper complex=15:0.1 ~ 0.3, copper complex: hydrogen peroxide: solvent=0.1:1 ~ 4:110 ~ 150, under normal pressure, under 20 ~ 70 ° of C conditions, the first reaction in solvent of hydrogen peroxide and copper complex generates active specy, then add methyl phenyl ketone stirring reaction 0.5 ~ 8 h, then distillation, steam solvent, collect the phenylacetate of 190 ° of C ~ 195 ° C cuts, it is characterized in that: described catalyzer copper complex is with neutralized verdigris and Isosorbide-5-Nitrae-N, two (methyl ethyl diketone) quadrol part coordinations of N-form, and catalyzer makes by the following method:

Isosorbide-5-Nitrae-N, the preparation of two (methyl ethyl diketone) quadrol parts of N-:

41.16 ml methyl ethyl diketones are dissolved in the single port flask that fills 50 ml dehydrated alcohols, are positioned in frozen water coolingly, 13.36 ml anhydrous ethylenediamines are dissolved in 13.5 ml dehydrated alcohols, cooling, then slowly dropwise join in above-mentioned solution, generate immediately yellow-white throw out, temperature of reaction maintains 2 ~ 5 ° of C, stir, react 1 hour, room temperature is placed and is spent the night, reaction soln decompression rotary evaporation, place and filter, toluene and CCl for yellow crystals ₄recrystallization twice, obtains clear crystal Isosorbide-5-Nitrae-N respectively, two (methyl ethyl diketone) quadrol parts of N-, productive rate 70%;

Catalyzer copper complex C ₁₂h ₈o ₂n ₂cu's is synthetic:

2 g Cu (CH ₃cOO) ₂ ^.h ₂o joins in 500 ml flasks, put into 150 ml Isosorbide-5-Nitrae-dioxane solution, be warming up to 80 ℃ of dissolvings, then slowly add 2.5 ~ 4.5 g 1,4-N, two (methyl ethyl diketone) quadrol parts of N-, stir, solution is immediately by blue purpling look, continue to stir, heat up, holding temperature is at 100 ° of C 45 min, add water 200 ml, solution is dark purple black, and room temperature was placed after one day, had the needle-like crystal of light cyan to separate out, filter, priority sherwood oil, ether recrystallization, obtains silver-colored cyan needle-like crystal.

2. according to the method described in claim 1, it is characterized in that copper complex: hydrogen peroxide: solvent=0.1:1 ~ 4:120 ~ 135.

3. method according to claim 1, is characterized in that, optimum solvent is formic acid.

4. method according to claim 1, is characterized in that, hydrogen peroxide and the copper complex temperature of reaction that first reaction generates active specy in solvent is at 20 ~ 40 ° of C.