CN102992982B

CN102992982B - Synthesis method of p-hydroxybenzaldehyde

Info

Publication number: CN102992982B
Application number: CN201210534372.3A
Authority: CN
Inventors: 刘鹏; 郭龙龙; 吴文雷; 马韵升; 史庆苓; 门振; 高洪奎
Original assignee: Jingbo Agrochemicals Technology Co Ltd
Current assignee: Beijing Agricultural Chemical Technology Co., Ltd.
Priority date: 2012-12-12
Filing date: 2012-12-12
Publication date: 2015-01-14
Anticipated expiration: 2032-12-12
Also published as: CN102992982A

Abstract

The invention provides a synthesis method of p-hydroxybenzaldehyde. Phenol used as a raw material reacts with a Vilsmeier reagent to synthesize p-hydroxybenzaldehyde. The invention has advantages of easily available raw materials, short reaction period, simple operation, mild reaction conditions, safe reaction process and low requirement on equipment, and is more suitable for industrial production of p-hydroxybenzaldehyde compared to other synthesis method of p-hydroxybenzaldehyde; no by-product is generated in the synthesis process, and separation and purification in a post treatment process is simple, so as to lower the cost of post treatment, and enhance yield and purity of the target product p-hydroxybenzaldehyde, wherein the yield is higher than 90%, and the purity is above 98%; and the synthesis method resolves problems in existing phenol method for p-hydroxybenzaldehyde synthesis, such as difficulties in separation and purification in post treatment, low yield of p-hydroxybenzaldehyde and high cost.

Description

The synthetic method of p-Hydroxybenzaldehyde

Technical field

The invention belongs to technical field of fine, relate to chemical synthetic method, be specifically related to the synthetic method of p-Hydroxybenzaldehyde.

Background technology

P-Hydroxybenzaldehyde is the important intermediate of medicine industry and perfume industry, synthesis amoxycillin (amoxycilline Trihydrate bp), Trimethoprim Trimethyl phosphate (TMP), 3 is can be used in medicine industry, 4,5-TMB, to hydroxyglycine, amoxycillin cephamycin, artificial rhizoma Gastrodiae, farrerol, Ai Siluo etc.; For the synthesis of spices such as vanillin food grade,1000.000000ine mesh, vanirone, piperonal, syringic aldehyde, aubepine and raspberry ketones in perfume industry.Abroad also for the synthesis of pesticide herbicide bromoxynil and chloroxynil, and produce sterilant, photograph emulsifying agent, nickel plating gloss-imparting agent, liquid crystal etc.

Current industrial production p-Hydroxybenzaldehyde is mainly with the operational path that phenol, p-cresol, para-nitrotoluene etc. are raw material.Existing phynol method raw material is easy to get, and manufacturing process is comparatively simple, but the isolation andpurification in later stage is more difficult, and cause the yield of p-Hydroxybenzaldehyde on the low side, cost is higher.

Summary of the invention

The object of the present invention is to provide a kind of is raw material with phenol, by simple technique synthesis p-Hydroxybenzaldehyde, this synthetic method feed stock conversion is high, product yield is high, take phenol as a kind of brand-new method that p-Hydroxybenzaldehyde prepared by raw material, namely Vilsmeier reagent and phenol reactant is adopted to prepare p-Hydroxybenzaldehyde, solve in existing phynol method synthesis p-Hydroxybenzaldehyde technique and there is later stage isolation andpurification difficulty, cause the yield of p-Hydroxybenzaldehyde on the low side, the problem that cost is higher.

The invention provides a kind of synthetic method of p-Hydroxybenzaldehyde, take phenol as raw material, and adopt Vilsmeier reagent and phenol reactant to prepare p-Hydroxybenzaldehyde, reaction equation is as follows:

Concrete steps comprise:

(1) be solvent with toluene, add DMF and reagent I and react at temperature is 10 ~ 30 DEG C, obtain Vilsmeier reagent;

(2) phenol is slowly added in the Vilsmeier reagent generated in step (1) and carry out insulation reaction, be cooled to 25 DEG C-50 DEG C, then the stirring reaction that adds water;

(3) add water after having reacted washing, separatory, desolventizing, drying, obtains faint yellow solid, be target product.

The composition principle of described p-Hydroxybenzaldehyde is:

The synthetic method of the p-Hydroxybenzaldehyde that the present invention relates to take phenol as a kind of brand-new method that p-Hydroxybenzaldehyde prepared by raw material, namely adopts Vilsmeier reagent and phenol reactant to prepare p-Hydroxybenzaldehyde.From thermodynamics, Vilsmeier reagent and phenol reactant generate the contraposition product p-Hydroxybenzaldehyde of phenol at first, and at this moment aldehyde radical occupies the para postion of phenyl ring, and the aldehyde radical in contraposition makes phenyl ring passivation, produce so do not have other by products.

In described step (1), reagent I is POCl ₃or SOCl ₂or PCl ₅or PCl ₃one.

In described step (1), the volumetric usage of toluene is 3 ~ 10 times of DMF.

The mol ratio of described step (1) and step (2) middle phenol: DMF: reagent I is 1:1 ~ 1.2:1 ~ 1.3, and the very few reaction of raw material is incomplete, and excessive cost increases, and by product also can be made to increase.

Order of addition(of ingredients) in described step (1) is add reagent I in toluene to drip DMF again, or reagent I is added drop-wise in the mixed solution of toluene and DMF.This is because the reaction in step (1) is strong exothermal reaction, can only be that a kind of raw material is added drop-wise in another kind of raw material, be conducive to the temperature of reaction of the hierarchy of control like this.

In described step (1), the temperature of reaction of system is 10 ~ 30 DEG C.Because the reaction of system in step (1) is comparatively violent, heat release is many, wayward reaction when temperature is too high, temperature can be made to raise instantaneously and punching material occurs, so temperature is controlled within the scope of this.

In described step (2), the Adding Way of phenol is for adding phenol solid, or adds the toluene solution of phenol.

Temperature of reaction in described step (2) is 60 ~ 110 DEG C, is preferably 110 DEG C.When temperature is lower than 60 DEG C, the meeting augmenting response time, energy consumption increases; Boiling point due to toluene is 110 DEG C, and selection toluene is solvent, and when carrying out back flow reaction, best temperature of reaction is 110 DEG C.

Reaction times in described step (2) is 30min ~ 180min, and this is the Best Times scope of reaction, and the time is too short, and cause reaction not exclusively, product yield is too low, and cost increases; Overlong time, can increase energy consumption, and corresponding cost also can increase.

The temperature of the water added in described step (2) is 0-83 DEG C, and the test a large amount of for a long time through contriver finds, when the temperature of the water added is greater than 83 DEG C, there will be bumping and even rushes material phenomenon.

In described step (3), washing temperature is 40 ~ 80 DEG C, and when washing temperature is too low, the product in toluene can be separated out, and when washing temperature is too high, reaches the azeotropic point of toluene and water, dangerous.General washing two to three times, because product is dissolved in toluene, gets upper toluene phase, under negative pressure desolvation toluene, reclaims toluene and applies mechanically, and finally obtains faint yellow solid, and detecting gained faint yellow solid by liquid matter and nucleus magnetic hydrogen spectrum is p-Hydroxybenzaldehyde.Isolation andpurification in end processing sequences is simple to operate, and the solvent toluene after recovery can be applied mechanically, and reduces the cost of post-processed, thus reduces production cost.

The present invention take phenol as raw material, p-Hydroxybenzaldehyde is prepared with Vilsmeier reagent, raw material is easy to get, reaction time is short, operation steps is simple, and reaction conditions is gentle, reaction process safety, low for equipment requirements, the method for other p-Hydroxybenzaldehydes is more suitable for industrial production p-Hydroxybenzaldehyde relatively; In building-up process, do not have by product to produce, in end processing sequences, separating-purifying is simple, reduce the cost of post-processed, improve yield and the purity of target product p-Hydroxybenzaldehyde, yield is more than 90%, and purity, more than 98%, solves in existing phynol method synthesis p-Hydroxybenzaldehyde method and there is later stage isolation andpurification difficulty, cause the yield of p-Hydroxybenzaldehyde on the low side, the problem that cost is higher.

Embodiment

Below in conjunction with specific embodiment, invention to be described further, but not as the restriction to summary of the invention, all based on purification principle of the present invention technology all belong to integral part of the present invention.

Embodiment one

The synthetic method of p-Hydroxybenzaldehyde, be raw material with phenol, concrete steps comprise:

(1) in the four-hole boiling flask of drying, add 300mL toluene, then add 100mL DMF, measure 93.79mL SOCl ₂in constant pressure funnel, in four-hole boiling flask, drip SOCl ₂, temperature of reaction is 30 DEG C, stirs 30min, obtains Vilsmeier reagent;

(2) taking 121.68g phenol adds in four-hole boiling flask, insulation reaction 80min at temperature is 60 DEG C, then cools to 50 DEG C, adds the water that volume is 250mL, temperature is 83 DEG C and stirs 100min;

(3) leave standstill in the solution immigration separating funnel in step (2) four-hole boiling flask, cut lower floor's aqueous phase, add the water that volume is 300mL, temperature is 80 DEG C and wash; Then cut lower floor's aqueous phase, get toluene and remove toluene under negative pressure, dry, obtain faint yellow solid, namely obtain p-Hydroxybenzaldehyde 143.85g, purity 98.9%, yield 91.1%.

Embodiment two

(1) in the four-hole boiling flask of drying, add 100mL toluene, then add 12.05mL POCL ₃, measure 10mL DMF in constant pressure funnel, in four-hole boiling flask, drip DMF, temperature of reaction is 10 DEG C, stirs 45min, obtains Vilsmeier reagent;

(2) taking 10.15g phenol adds in four-hole boiling flask, insulation reaction 30min at temperature is 110 DEG C, then cools to 25 DEG C, adds the water that volume is 200mL, temperature is 0 DEG C and stirs 100min;

(3) leave standstill in the solution immigration separating funnel in step (2) four-hole boiling flask, cut lower floor's aqueous phase, add the water that volume is 280mL, temperature is 60 DEG C and wash; Then cut lower floor's aqueous phase, get toluene and remove toluene under negative pressure, dry, obtain faint yellow solid, namely obtain p-Hydroxybenzaldehyde 12.21g, purity 98.7%, yield 92.7%.

Embodiment three

(1) in the four-hole boiling flask of drying, add 200mL toluene, then add 48.61mL PCL ₅, measure 50mL DMF in constant pressure funnel, in four-hole boiling flask, drip DMF, temperature of reaction is 20 DEG C, stirs 70min, obtains Vilsmeier reagent;

(2) take 60.84g phenol to be dissolved in 100mL toluene solution and to add in four-hole boiling flask, insulation reaction 180min at temperature is 85 DEG C, then cool to 40 DEG C, add the water that volume is 150mL, temperature is 40 DEG C and stir 65min;

(3) leave standstill in the solution immigration separating funnel in step (2) four-hole boiling flask, cut lower floor's aqueous phase, add the water that volume is 180mL, temperature is 40 DEG C and wash; Then cut lower floor's aqueous phase, get toluene and remove toluene under negative pressure, dry, obtain faint yellow solid, namely obtain p-Hydroxybenzaldehyde 73.18g, purity 98.4%, yield 92.7%.

Embodiment four

(1) in the four-hole boiling flask of drying, add 300mL toluene, then add 60mL DMF, measure 73.33mL PCL ₃in constant pressure funnel, in four-hole boiling flask, drip PCL ₃, temperature of reaction is 15 DEG C, stirs 70min, obtains Vilsmeier reagent;

(2) taking 60.84g phenol adds in four-hole boiling flask, insulation reaction 60min at temperature is 100 DEG C, then cools to 30 DEG C, adds the water that volume is 150mL, temperature is 60 DEG C and stirs 65min;

(3) leave standstill in the solution immigration separating funnel in step (2) four-hole boiling flask, cut lower floor's aqueous phase, add the water that volume is 200mL, temperature is 50 DEG C and wash; Then cut lower floor's aqueous phase, get toluene and remove toluene under negative pressure, dry, obtain faint yellow solid, namely obtain p-Hydroxybenzaldehyde 72.55g, purity 98.1%, yield 91.9%.

As can be seen from embodiment 1-4, take phenol as raw material, adopt the present invention to synthesize p-Hydroxybenzaldehyde, the purity of gained p-Hydroxybenzaldehyde is more than 98%, and yield is more than 90%.

Claims

1. a synthetic method for p-Hydroxybenzaldehyde, is raw material with phenol, it is characterized in that: adopt Vilsmeier reagent and phenol reactant to prepare p-Hydroxybenzaldehyde, reaction equation is as follows:

Concrete steps comprise:

(3) add water after having reacted washing, separatory, desolventizing, drying, obtains faint yellow solid, be target product;

In described step (1), reagent I is POCl ₃or SOCl ₂or PCl ₅or PCl ₃one;

The mol ratio of described step (1) and step (2) middle phenol: DMF: reagent I is 1:1 ~ 1.2:1 ~ 1.3;

Temperature of reaction in described step (2) is 60 ~ 110 DEG C;

Reaction times in described step (2) is 30min ~ 180min;

The temperature of the water added in described step (2) is 0-83 DEG C;

In described step (3), washing temperature is 40 ~ 80 DEG C.

2. the synthetic method of p-Hydroxybenzaldehyde according to claim 1, is characterized in that: in described step (1), the volumetric usage of toluene is 3 ~ 10 times of DMF.

3. the synthetic method of p-Hydroxybenzaldehyde according to claim 1, is characterized in that: the order of addition(of ingredients) in described step (1) is add reagent I in toluene to drip DMF again, or reagent I is added drop-wise in the mixed solution of toluene and DMF.

4. the synthetic method of p-Hydroxybenzaldehyde according to claim 1, is characterized in that: in described step (2), the Adding Way of phenol is for adding phenol solid, or adds the toluene solution of phenol.