CN1297531C - Novel supercritical phase salicylic acid synthesis process - Google Patents
Novel supercritical phase salicylic acid synthesis process Download PDFInfo
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- CN1297531C CN1297531C CNB2005100443477A CN200510044347A CN1297531C CN 1297531 C CN1297531 C CN 1297531C CN B2005100443477 A CNB2005100443477 A CN B2005100443477A CN 200510044347 A CN200510044347 A CN 200510044347A CN 1297531 C CN1297531 C CN 1297531C
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Abstract
The present invention relates to a green and novel process for synthesizing salicylic acid under supercritical condition. Sodium phenolate is made through neutralizing phenol with NaOH aqueous solution, dried and ground to obtain thesolid sodium phenolate (reactant). The sodium phenolate and carbon dioxide are used as reactants to carry out the supercritical homogeneous phase carboxylation reaction (Kolbe-Schmitt reaction) in a heavy pressure reaction kettle to obtain sodium salicylate, and salicylic acid is obtained by acidizing. Salicylic acid products with high purity are obtained by further purification. The gas-solid phase heterogeneous reaction of the Kolbe-Schmitt reaction in the traditional process is converted into homogeneous reaction. The operating temperature is lowered and the reaction speed is high, and therefore, side effects generated by local overheating are avoided, problems of pollution and solvent recovery do not exist, and the present invention relates to a green and novel process which meets the requirement of cycle economic industrialization and has strong practicability.
Description
Technical field:
The present invention relates to a kind of method of salicylate, specifically relate to a kind of under super critical condition the novel process of salicylate.
Background technology:
Whitfield's ointment is important source material and the intermediate in medicine industry, foodstuffs industry and the fine chemistry industry.In medicine industry, Whitfield's ointment is mainly used in medicine production such as ethoxybenzamide, Xantimetten, acetylsalicylic acid (acetylsalicylic acid), sodium salicylate, salicylic amide, glyburide, niclosamide, salol, ethyl p-hydroxybenzoate, bismuth subsalicylate, sulfasalazine; Whitfield's ointment itself is also as Cidex-7.Whitfield's ointment is still produced the important source material of high added value fine chemical products such as high-grade dyestuff, rubber industry additive, spices, fire retardant, fabric protectant, soil improvement agent.
Salicylic synthetic be typical Kolbe-Schmitt reaction, i.e. organic phenolic compound and carbonic acid gas generation electrophilic substitution and the reaction of introducing carboxyl on aromatic ring claims the aromatic nucleus carboxylation reaction again.
Salicylic existing synthesis technique mainly contains non-pressure process and middle-pressure process.Non-pressure process has the branch of low temperature process and pyroprocess, but its technological process is similar: it is raw material with phenol, is reacted into phenol sodium with sodium hydroxide earlier, feeds carbonic acid gas and carry out carboxylation reaction under normal pressure, gets product with sulfuric acid acidation again.Wherein, the pyroprocess controlled temperature is 128 ℃ to 200 ℃; The Whitfield's ointment yield is 50%-70%; The low temperature process controlled temperature is under 50 ℃-100 ℃, and the advantage of this method is an atmospheric operation, and security is better, and the equipment input is also fewer, is applicable to that small business produces; Shortcoming is that the per pass conversion of phenol is lower, though phenol can be recycled, energy consumption is higher.
Middle-pressure process be carbonic acid gas is fed the exsiccant sodium phenylate and keep in depress and carry out carboxylation reaction, generate the carbonic acid phenol ester; Molecular transposition is carried out in pressurization then, generates sodium salicylate; Make Whitfield's ointment through acidification again.Middle-pressure process has two kinds of direct method and solvent methods: direct method still internal pressure is stabilized in 0.7-0.8MPa, 130 ℃ of-140 ℃ of following carboxylations more than 6 hours, yield reaches more than 98%, this method adopts the direct mutually carboxylation technology of gas-solid, be reflected in the heterogeneous medium and carry out, the area that contacts between reactant is little, the mass-and heat-transfer poor performance of process.Carbonic acid gas the time repeatedly imports in reaction, and process control is numerous and diverse, long reaction time, and the transformation efficiency of reaction, yield is low and material is cemented in the reactor easily.Solvent method adds phenol and makees solvent, the gas-liquid phase reaction that carboxylation reaction is become more easily carry out, so just increased the contact-impact between reaction mass, improved the mass-and heat-transfer performance of process, thereby speed of response is accelerated cycle shortening, the transformation efficiency of reaction and yield raising, energy expenditure reduces, and process control is also fairly simple.The per pass conversion of this method phenol is higher, and quality product is better.It is the main method of present industrial employing.But still there are shortcomings such as long reaction time, heat energy consumption is big, the solvent recuperation process is numerous and diverse, seriously polluted in this method.
The Kolbe-Schmitt reaction is a reversible reaction, and temperature influence is remarkable.Because the influence of thermodynamics factor, sodium phenylate and carbonic acid gas obtain vicinal hydroxyl groups acid sodium when lesser temps (100 ℃-200 ℃) reacts, and mainly obtain the contraposition product under comparatively high temps.Simultaneously, traditional Kolbe-Schmitt reaction is a gas-solid phase inhomogeneous reaction, and the mass-transfer performance in the reaction process is directly determining the quality of speed of response and quality product, and it is to need the key issue that solves in synthetic.
The 49th page of " modern chemical industry " 1997 the 9th phase, once delivered the news in brief report, Hokkaido, Japan Industrial Technology Research Institute " is the high yield salicylate of reaction medium with the supercritical co ": reaction pressure 17.5MPa, 120 ℃ of temperature of reaction, 30 minutes reaction times, phenol conversion is 100%, Whitfield's ointment productive rate 90%.Its shortcoming is: the reaction pressure height, and the cost of equipment height, energy consumption is big, and productive rate is low.
Summary of the invention:
The purpose of this invention is to provide a kind of under super critical condition the green production novel process of salicylate.
The particular content of invention is:
A) phenol is made the phenol sodium salt with the neutralization of the NaOH aqueous solution, through the dry intermediate reaction thing solid sodium phenol (reactant) that gets of secondary vacuum;
B) in autoclave, be reactant with sodium phenylate and carbonic acid gas, produce Whitfield's ointment through overcritical Kolbe-Schmitt water generation reaction poplar acid sodium salt, acidifying;
C) after further refining purity is 99.5% to 100% Whitfield's ointment product.
The concrete preparation method of solid sodium phenol in the aforesaid step a) (reactant) is: accurately take by weighing a certain amount of solid-state phenol and be heated to liquid state, under agitation phenol liquid is joined in the sodium hydroxide solution of 40-70%, the mol ratio of phenol and sodium hydroxide is 1: 1.0～1.03.After mixing liquid 10-20 minute, heat temperature raising, water is steamed in decompression.Become when thick to solution, transfer to and carry out the drying under reduced pressure first time in the vacuum drying oven.Control vacuum tightness 0.085Mpa-0.095Mpa, temperature is at 160 ℃-170 ℃, to water outlet more after a little while, cooling.Take out solid sodium phenol, grind to form fine powder, carry out drying second time again, temperature is at 135 ℃-145 ℃, vacuum tightness 0.090MPa-0.095MPa.When not water outlet, lower the temperature, weigh, preserve standby in the dry environment.
The concrete technological operation of overcritical building-up reactions and control method are in the aforesaid step b): sodium phenylate is put into autoclave, seal, vacuumize the back and feed an amount of carbonic acid gas.Heat temperature raising also stirs, reach 80-150 ℃ after, slowly feed carbonic acid gas to 7.5-10MPa, slowly feed an amount of carbonic acid gas again with the carrying out of reaction, make temperature in the kettle and pressure-stabilisation 7.5-10MPa and 80-150 ℃.Behind reaction 60-120min under this supercritical state, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 60 ℃, open purging valve simultaneously carbonic acid gas is entered storage tank (recycle) through filter and moisture eliminator.To normal pressure, open kettle cover, pour an amount of distilled water into, be stirred to whole dissolvings, then solution is produced, acidifying, suction filtration, vacuum-drying, obtain the Whitfield's ointment crude product.
Preferably, aforesaid optimal reaction temperature at overcritical Kolbe-Schmitt reaction salicylate is 115-123 ℃.
Preferably, aforesaid optimum response pressure at overcritical Kolbe-Schmitt reaction salicylate is 7.8-8.3MPa.
Preferably, aforesaid optimum reacting time at overcritical Kolbe-Schmitt reaction salicylate is 80-100min.
Preferably, the process for purification of aforesaid Whitfield's ointment crude product is: successively drop in beaker by weight 1: 5: 0.004～0.005 Whitfield's ointment crude product, water, phosphoric acid, place on the magnetic stirring apparatus and stir, and slowly be warming up to 65 ℃～80 ℃, keep 45-70min.Be cooled to then below 30 ℃, filter, filter cake washs with less water, and vacuum-drying gets high purity bigcatkin willow acid product.Advantage of the present invention:
The present invention adopts the advantage of overcritical Kolbe-Schmitt reaction salicylate to be mainly reflected in: adopt supercritical co as reaction medium and reactant, the Kolbe-Schmitt reaction is become homogeneous reaction by the gas-solid phase inhomogeneous reaction in the traditional technology, its mass transfer, heat transfer characteristic are greatly improved, thereby under suitable temperature of reaction, reaction pressure and reaction times, salicylate.Advantage of the present invention is mainly reflected in: service temperature reduces, speed of reaction is fast, homogeneous system has been avoided because of the side reaction that local superheating produces, good reaction selectivity, reaction conversion ratio height, and do not exist and pollute and the solvent recuperation problem, and can improve the quality of products, be a kind of satisfy recycling economy industrialization demand, green production novel process that practicality is very strong.CO2 can recycle, and product purity can satisfy the pharmaceutical grade standard up to more than 99%.
Description of drawings:
Fig. 1 is the reaction equation of salicylate of the present invention
Fig. 2 is the main side reaction reaction equation of salicylate of the present invention
Embodiment:
Embodiment 1:
Accurate weighing sodium hydroxide 60.40g (1.51mol) is mixed with 50% solution, cooling with distilled water.Accurately take by weighing phenol 141.165g (1.5mol), solid-state phenol is heated to liquid state, under agitation phenol liquid is added in the sodium hydroxide solution.Mix liquid after 15 minutes, heat temperature raising, water is steamed in decompression.Become when thick to solution, transfer to and carry out the drying under reduced pressure first time in the vacuum drying oven.Control vacuum tightness 0.085MPa-0.095MPa, temperature is at 160 ℃-170 ℃, to water outlet more after a little while, cooling.Take out solid sodium phenol, wear into fine powder in the mortar, carry out drying second time again, temperature is at 135 ℃-145 ℃, vacuum tightness 0.090MPa-0.095MPa.When not water outlet, lower the temperature.Take out solid sodium phenol and transfer in the autoclave that induction stirring and automatic temperature control system are housed that volume is 500ml, seal, vacuumize the back and feed an amount of carbonic acid gas.Heat temperature raising also stirs, and the control temperature in the kettle is 120 ℃, slowly feeds carbonic acid gas again to 8.0MPa, slowly feeds an amount of carbonic acid gas again with the carrying out that reacts, and makes temperature in the kettle and pressure-stabilisation at 120 ℃ and 8.0MPa.Behind reaction 90min under this supercritical state, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 60 ℃, open purging valve simultaneously carbonic acid gas is entered storage tank (recycle) through filter and moisture eliminator.To normal pressure, open kettle cover, pour 150ml distilled water into, be stirred to whole dissolvings, then solution is changed in the four-hole bottle of 1000ml, under agitation add 10% dilute sulphuric acid, regulating the pH value is 1-2, after leaving standstill for some time, suction filtration in 50 ℃-60 ℃ times dry 2-3 hour, obtains the Whitfield's ointment crude product in vacuum drying oven.Whitfield's ointment crude product, water, phosphoric acid were dropped in the beaker successively by weight 1: 5: 0.005, place on the magnetic stirring apparatus and stir, and slowly be warming up to 65 ℃～75 ℃, keep 50min.Be cooled to then below 30 ℃, filter, filter cake washs with less water, and vacuum-drying gets Whitfield's ointment elaboration 199.20g.Sampling is carried out GC and is analyzed.Result: Whitfield's ointment purity 99.85%, phenol conversion 100%, selectivity 96.0%.
Embodiment 2:
Accurate weighing sodium hydroxide 410.00g (10.25mol) is mixed with 50% solution, cooling with distilled water.Accurately take by weighing phenol 941.10g (10.0mol), solid-state phenol is heated to liquid state, under agitation phenol liquid is added in the sodium hydroxide solution.Mix liquid after 15 minutes, heat temperature raising, water is steamed in decompression.Become when thick to solution, transfer to and carry out the drying under reduced pressure first time in the vacuum drying oven.Control vacuum tightness 0.085MPa-0.095MPa, temperature is at 160 ℃-170 ℃, to water outlet more after a little while, cooling.Take out solid sodium phenol, in mortar, wear into fine powder after, carry out drying second time again, temperature is at 130 ℃-145 ℃, vacuum tightness 0.090MPa-0.095MPa lowers the temperature when not water outlet.Take out solid sodium phenol and transfer in the autoclave that induction stirring and automatic temperature control system are housed that volume is 5000ml, seal, vacuumize the back and feed an amount of carbonic acid gas.Heat temperature raising also stirs, and the control temperature in the kettle is 120 ℃, slowly feeds carbonic acid gas again to 8.2MPa, slowly feeds an amount of carbonic acid gas again with the carrying out that reacts, and makes temperature in the kettle and pressure-stabilisation at 120 ℃ and 8.2MPa.Behind reaction 90min under this supercritical state, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 60 ℃, open purging valve simultaneously carbonic acid gas is entered storage tank (recycle) through filter and moisture eliminator.To normal pressure, open kettle cover, pour 1000ml distilled water into, be stirred to whole dissolvings, then solution is changed in the four-hole bottle of 5000ml, under agitation add 20% dilute sulphuric acid, regulating the pH value is 1-2, after leaving standstill for some time, suction filtration in 50 ℃-60 ℃ times dry 2-3 hour, obtains the Whitfield's ointment crude product in vacuum drying oven.Whitfield's ointment crude product, water, phosphoric acid were dropped in the beaker successively by weight 1: 5: 0.005, place on the magnetic stirring apparatus and stir, and slowly be warming up to 65 ℃～75 ℃, kept 1 hour.Be cooled to then below 30 ℃, filter, filter cake washs with less water, and vacuum-drying gets Whitfield's ointment elaboration 1326.7g.Sampling is carried out GC and is analyzed.Result: Whitfield's ointment purity 99.84%, phenol conversion 100%, selectivity 95.9%.
Claims (6)
1. the green production novel process of a supercritical phase salicylic acid synthesis is characterized in that the preparation method comprises the steps:
A) phenol is made the phenol sodium salt with the neutralization of the NaOH aqueous solution, through the dry intermediate reaction thing solid sodium phenol that gets of secondary vacuum; Wherein the mol ratio of phenol and sodium hydroxide is 1: 1.0～1.03;
B) in autoclave, be reactant with sodium phenylate and carbonic acid gas, produce Whitfield's ointment through overcritical Kolbe-Schmitt water generation reaction poplar acid sodium salt, acidifying;
C) after further refining purity is 99.5% to 100% Whitfield's ointment product.
2. the green production novel process of a kind of supercritical phase salicylic acid synthesis as claimed in claim 1 is characterized in that the concrete technological operation of overcritical building-up reactions in the described step b) and control method are:
1) sodium phenylate is put into autoclave, seal, vacuumize the back and feed an amount of carbonic acid gas;
2) heat temperature raising and stir, reach 80-150 ℃ after, slowly feed carbonic acid gas to 7.5-10MPa, slowly feed an amount of carbonic acid gas again with the carrying out of reaction, make temperature in the kettle and pressure-stabilisation 7.5-10MPa and 80-150 ℃;
3) behind reaction 60-120min under this supercritical state, feed water of condensation the high pressure temperature in the kettle is quickly fallen to below 60 ℃, open purging valve simultaneously carbonic acid gas is entered storage tank through filter and moisture eliminator, so that recycle;
4) to normal pressure, open kettle cover, pour an amount of distilled water into, be stirred to whole dissolvings, then solution is produced, acidifying, suction filtration, vacuum-drying, obtain the Whitfield's ointment crude product.
3. the green production novel process of supercritical phase salicylic acid synthesis as claimed in claim 1 or 2 is characterized in that the temperature of reaction of described overcritical Kolbe-Schmitt reaction salicylate is 115-123 ℃.
4. the green production novel process of supercritical phase salicylic acid synthesis as claimed in claim 1 or 2 is characterized in that the reaction pressure of described overcritical Kolbe-Schmitt reaction salicylate is 7.8-8.3MPa.
5. the green production novel process of supercritical phase salicylic acid synthesis as claimed in claim 1 or 2 is characterized in that the reaction times of described overcritical Kolbe-Schmitt reaction salicylate is 80-100min.
6. the green production novel process of a kind of supercritical phase salicylic acid synthesis as claimed in claim 1, it is characterized in that the described further process for purification of step c) is: successively drop in beaker by weight 1: 5: 0.004～0.005 Whitfield's ointment crude product, water, phosphoric acid, place on the magnetic stirring apparatus and stir, and slowly be warming up to 65 ℃～80 ℃, keep 45-70min; Be cooled to then below 30 ℃, filter, filter cake washs with less water, and vacuum-drying gets high purity bigcatkin willow acid product.
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| CNB2005100443477A CN1297531C (en) | 2005-08-02 | 2005-08-02 | Novel supercritical phase salicylic acid synthesis process |
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| CN107141215A (en) * | 2017-05-11 | 2017-09-08 | 镇江高鹏药业有限公司 | A kind of salicylic acid preparation method of environmental protection in high yield |
| CN107963963A (en) * | 2017-12-06 | 2018-04-27 | 江西省隆南药化有限公司 | A kind of preparation method of septichen |
| CN110550707A (en) * | 2019-09-06 | 2019-12-10 | 温州捷朴环保科技有限公司 | Electrodialysis water treatment facilities with middle electrode |
| CN113336638A (en) * | 2021-06-22 | 2021-09-03 | 宁夏万香源生物科技有限公司 | Efficient synthesis method of salicylic acid |
| CN114149320B (en) * | 2021-11-15 | 2024-04-16 | 宁夏清研高分子新材料有限公司 | Preparation method of high-yield p-hydroxybenzoic acid |
| CN116267989B (en) * | 2022-09-09 | 2024-05-07 | 兰州大学 | Nanometer iron antibacterial agent for fusarium trilineum |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4376867A (en) * | 1981-07-07 | 1983-03-15 | Gert Jansen | Chemical process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4376867A (en) * | 1981-07-07 | 1983-03-15 | Gert Jansen | Chemical process |
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