CN102702097A - Preparation method of montelukast sodium intermediate - Google Patents
Preparation method of montelukast sodium intermediate Download PDFInfo
- Publication number
- CN102702097A CN102702097A CN2012101562488A CN201210156248A CN102702097A CN 102702097 A CN102702097 A CN 102702097A CN 2012101562488 A CN2012101562488 A CN 2012101562488A CN 201210156248 A CN201210156248 A CN 201210156248A CN 102702097 A CN102702097 A CN 102702097A
- Authority
- CN
- China
- Prior art keywords
- menglusitena
- preparation
- catalyst
- preparation according
- intermediates preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a preparation method of montelukast sodium intermediate, comprising the steps of adding the compound (II), methyl 2-iodobenzoate, alkali and catalyst into organic solvent and blending until reaction is carried out entirely; and performing aftertreatment to obtain the montelukast sodium intermediate represented by formula (I), wherein the catalyst is nano metal catalyst loaded on mesoporous carbon nitride material, and the loading amount of metal is 0.1-90%. The preparation method provided by the invention uses the catalyst with good heat stability and good solubility, and realizes repeated recycle of the catalyst to reduce the use cost of the catalyst, thereby reducing the preparation cost of the compound (II); additionally, the preparation method is simple in operation, fast in reaction speed, high in conversion rate of substrate, and high in yield of products. The aftertreatment method of the method is simple; the preparation method is friendly to environment; the catalyst is recyclable so as to avoid environmental pollution.
Description
Technical field
The invention belongs to organic cpds midbody synthesis technical field, specifically relate to a kind of Singulair intermediates preparation.
Background technology
According to the definition of IUPAC (IUPAC), the aperture is called mesoporous between the 2-50 nanometer.Carbon nitride material with this pore size is called mesoporous carbon nitride material.Mesoporous carbon nitride material (mpg-C
3N
4) be the non-silica-base material of one type of organic polymer.With respect to inorganic hole materials such as common silicon class mesoporous material and gacs, organic polymer materials all demonstrates meliority aspect a lot, has better synthetic handiness and is easy to carry out advantage such as composition optimizes like organic polymeric materials.In addition, owing to itself be to be become by high temperature thermopolymerization, mesoporous carbon nitride material is compared with traditional organic polymer materials and is had a better thermostability.These advantages make it aspect catalyzer and support of the catalyst, have potentiality widely.
Carbon nitride material itself just has some outstanding catalytic properties, some bibliographical informations the application of carbon nitride material as catalyzer or support of the catalyst.Such as: document (Nat.Mater, 2009,8,76-80.) introduced the reaction of carbon nitride material catalytic pyrolysis water in the presence of other reductive agents.Mesoporous carbon nitride material not only has the various chemical characteristics of carbon nitride material, because the existence of meso-hole structure has increased reaction contact area and reactive behavior site, makes it have the better application prospect as catalyzer or support of the catalyst.
Nano-noble metal catalyst receives broad research and application because of its excellent catalytic activity and selectivity in fields such as oil, chemical industry, medicine, agricultural chemicals, the energy.Related to nearly all heterogeneous catalytic reaction, as: hydrogenation, catalyzed oxidation, cyclization, catalytic pyrolysis, linked reaction etc.More and more as the carrier of nano-noble metal catalyst in the last few years, study also more and more deep.As PdHAP (Win 40350) catalyzer of: Kaneda research group of engineering science institute of Osaka, Japan university exploitation in the catalysis dehalogenation reaction its specific activity conventional load in gac, aluminum oxide and TiO
2On the Pd catalyzer to exceed 10 ~ 200 times.The research of the physical chemistry professor GrahamJ Hutchings of Britain Cardiff university shows that Au-Pd is supported on TiO
2Solvent-free oxidation to phenylcarbinol shows outstanding catalytic effect (science, 311,2006,362).We are supported on mpg-C with Pd
3N
4On be used for the selective hydrogenation of phenol, under gentle relatively condition, obtained greater than 99% phenol conversion and greater than 99% pimelinketone selectivity (J.Am.Chem.Soc.2011,133,2362-2365).
Relieving asthma anti-inflammatory and anti-allergy agent that Menglusitena is a kind of efficient, low toxicity, security is good have broad application prospects, and the structural formula of Menglusitena is:
Compound in the following formula (I) is the important intermediate of synthetic Menglusitena.
It is PdCl that the scheme of synthetic compound (I) is gone up in industry at present
2Catalytic cpd (II) is synthetic with the coupling of o-iodobenzoic acid methyl esters.Yet catalyst P dCl
2Can't reclaim after using, and form palladium black easily, increase production cost.The Pd/C catalyzer also once was used for this reaction of catalysis, but experiment proof Pd/C catalyzer once use after complete deactivation, can't realize the repeatedly utilization of Pd.Therefore exploitation can realize that the efficient heterogeneous catalyst of precious metal recycling has important theory and application value.
Summary of the invention
The invention provides a kind of Menglusitena intermediates preparation, this method adopts the metallic catalyst of mesoporous carbon nitride material load, has improved the productive rate of conversion of raw material and Menglusitena midbody, and simple to operate, and preparation cost is low.
The structure of the Menglusitena midbody that will prepare among the present invention is as shown in the formula shown in (I):
A kind of Menglusitena intermediates preparation; Comprise: compound (II), o-iodobenzoic acid methyl esters, alkali and catalyzer are joined in the organic solvent; Be stirred to and react completely, obtain suc as formula the Menglusitena midbody shown in (I) through aftertreatment, reaction process is shown below:
In the above-mentioned reaction process, described catalyzer is the metallic catalyst of mesoporous carbon nitride material load, and wherein the charge capacity of metal is 0.1-90%.
Among the above-mentioned preparation method; The metallic catalyst of described mesoporous carbon nitride material load can be selected existing method preparation for use; For example can select for use MOX, metal halide or metal nitrate are prepared through ordinary methods such as ultrasonic method, deposition-precipitator method, sol-gel method or light deposition methods; When adopting method for preparing; Metal reacts in the molecule aspect, and the atoms metal that obtains at last is carried on the carbon nitride material carrier that the aperture is the 2-50 nanometer uniformly, and metallic particles is nano particle.The massfraction of nitrogen is 45-70% in the described mesoporous carbon nitride material, when preparing the mesoporous carbon nitride material of this composition, can adopt conventional method and raw material, and preparation cost is low, easy control of reaction conditions.Described mesoporous carbon nitride material can be selected the ordinary method preparation for use; For example optional is organic precursor in order to cyanamide, dicyan diamino, trimeric cyanamide or its mixture; With molecular sieve SBA-15, MCM-41 or silicon sol Ludox HS etc. is template, carries out the high temperature hot polymerization, utilizes NH at last
4HF
2Or HF etc. removes template and can obtain described mesoporous carbon nitride material.
In the metallic catalyst of described mesoporous carbon nitride material load, described metal is the metal with catalytic activity common in the metal catalysed reaction, generally comprises among Pd, Au, Ag, Pt, Ru and the Rh one or more.It is good to select for use in the above-mentioned several kinds of metals one or more to prepare the loaded catalyst catalytic activity, and the productive rate of purpose product compound (I) is high, and catalyst levels is less, and preparation cost is low.For further reducing cost; Guarantee advantages of high catalytic activity simultaneously, further optimized technical scheme is that the charge capacity of described metal is 0.5-20%; The charge capacity of metal is too high; Can improve the Preparation of catalysts cost greatly, content of metal is crossed low then catalytic activity and can be reduced, and what be unfavorable for reacting carries out fast.
Among the above-mentioned preparation method, complete for guaranteeing raw material reaction, lower preparation cost simultaneously, described compound (II) is 1:1-2 with the mol ratio of o-iodobenzoic acid methyl esters.For guaranteeing that compound (II) fully reacts completely, the mass ratio of nano metal is 1000-1:1 in described compound (II) and the catalyzer; Guaranteeing that raw material reaction completely under the prerequisite, is the consumption that reduces metal in the catalyzer, reduce reaction cost, the preferred mass ratio of metal is 1000-300:1 in described compound (II) and the catalyzer.
Among the above-mentioned preparation method, for reducing the reaction times, improve reaction efficiency, described temperature of reaction is 0-250 degree centigrade, and the described reaction times is 10-20 hour.For ease of the control of reaction, reduce the generation of side reaction, preferred temperature of reaction is 70-120 degree centigrade.
Among the above-mentioned preparation method, described organic solvent can be selected organic synthesis field common organic solvent for use, and preferred organic solution agent comprises one or more in acetonitrile, DMF and the methyl alcohol etc.
Among the above-mentioned preparation method, described alkali is acid binding agent, can select conventional organic bases or mineral alkali, for example can select triethylamine, also can select mineral alkalis such as salt of wormwood, sodium acetate.The mol ratio that described alkali and compound (II) add is 1-2:1.
Among the above-mentioned preparation method, the reaction solution that reacts completely only need pass through filtration, will filtrate then to concentrate, and liquid concentrator can obtain purity greater than 95% purpose product compound (I) through ordinary method aftertreatments such as recrystallization or column chromatographies.The solid that filtration obtains can be directly as the catalyzer reuse after oven dry.
Beneficial effect of the present invention is:
(1) the present invention adopts the metallic catalyst of mesoporous carbon nitride material load; This catalyzer thermostability and solvability are good; Can realize the repeatedly recycling of catalyzer, reduce the use cost of catalyzer, and then lower the preparation cost of compound (II).
(2) preparation method of the present invention is simple to operate, and speed of response is fast, and the transformation efficiency of substrate is high, and the productive rate of product is high, and post-treating method is simple.
(3) preparing method's environmental protection of the present invention is friendly, and the pollution to environment has been avoided in the recyclable utilization of catalyzer.
Embodiment
Embodiment 1-13
(1) preparation of mesoporous carbon nitride material:
3g organic precursor list cyanogen ammonia is mixed with 7.5g template Ludox HS-40 silica aqueous solution; In 90 ℃ of oil baths, stir to steam in 1 hour and remove moisture,, place crucible solid porphyrize in quartzy mortar; Design temperature polymerization in the temperature programming retort furnace; Wherein the concrete heating schedule of retort furnace is following: rise to 550 ℃ from room temperature (being generally 25 ℃) through 4h, keep this temperature 4h, reduce to room temperature (being generally 25 ℃) naturally.
The polymkeric substance that obtains is ground, place Plastic Bottle, add 55g NH
4HF
2, 240ml water, vigorous stirring two days, suction filtration; Washing, ethanol is washed, and solid is returned Plastic Bottle, adds 240ml water again and stirs one day; Suction filtration returns solid to Plastic Bottle, adds 200ml ethanol again, stirs 3h; Suction filtration, 70 degrees centigrade of dryings 24 hours, nitrogen content is about 60% in the mesoporous carbon nitride material for preparing.
(2) preparation of the metallic catalyst of mesoporous carbon nitride material load: with preparation Pd charge capacity is that the metallic catalyst of the mesoporous carbon nitride material load of 10% (mass percentage content) is that example describes method for preparing catalyst:
The ultrasonic method preparation method prepares 10w%Pdmpg-C
3N
4: with 0.5g mpg-C
3N
4Place beaker, add the ultrasonic about 15min of 50ml water and mix, add the 0.01g/ml PdCl of 10ml
2Solution, ultrasonic about 10min adds 25ml concentration 2mg/ml NaBH
4The aqueous solution, suction filtration behind the ultrasonic 30min, 80 ℃ of dried over night.
In the table 1 metallic catalyst of other mesoporous carbon nitride material loads need according to above-mentioned 10w%Pdmpg-C
3N
4Preparing method's preparation that catalyzer is identical; Concrete proportioning need calculate according to the load content of actual needs, specifically needs the amount of the water of adding, can increase relatively and can reduce; All do not influence the structure and the catalytic performance of the catalyzer that finally prepares, the restriction of unprincipled property.The NaBH that adds
4The aqueous solution is identical with above-mentioned preparation method with the ratio of metal chloride.Here need to prove; Because the load characteristic of metal and solid support material itself; Cause the actual add-on of metal actual negative carrying capacity and metal that certain difference is often arranged; The actual negative carrying capacity generally can be less than the actual metal add-on, and the size of actual negative carrying capacity need be detected by TP and obtain, so the amount of the actual metal that adds need be less times greater than the amount of metal that calculates according to the actual negative carrying capacity in the preparation process; The actual amount of metal that adds is generally 1.1-1.2 times of the amount of metal that calculates according to charge capacity, can adjust according to actual needs.Charge capacity described in the present invention is the catalyzer that finally obtains and detects the numerical value that obtains through overtesting.
(3) ratio according to table 1 adds compound (II), 350ml organic solvent (the actual usage quantity of solvent also can be adjusted according to actual needs, does not have principle to require), o-benzoic acid methyl esters, alkali and catalyzer successively under whipped state; Feeding intake begins to be warming up to the temperature of reaction shown in the table 2 after finishing, according to the reaction times back flow reaction in the table 2; Reaction adds 2.6 times of quantity of solvent acetonitriles after finishing again, and backflow 1h is then at 78 ℃ of filtrations, the catalyzer that solids filtered obtains reclaiming through drying; The filtrating naturally cooling, crystallization under the room temperature, suction filtration washs filter cake with acetonitrile, suction filtration, centrifuge dripping, washing, suction filtration, centrifuge dripping, again with the acetonitrile washing, suction filtration, centrifuge dripping, vacuum-drying can get product, and product purity and productive rate are seen table 2.
Table 1
Table 2
Can be known by table 1 and table 2: utilize method of the present invention, the productive rate and the purity that prepare compound (I) are all higher, and when particularly content of metal was 0.5-20%, the productive rate of compound (I) was all greater than 90%, and the purity of compound (I) is all greater than 95%; And the transformation efficiency of starting compound (II) is near 100%.
Catalyzer reuse embodiment:
Embodiment 1 reclaimed the catalyzer that obtains according to prepare compound (I) preparation result as shown in table 3 with embodiment 1 identical condition:
Table 3
Can be known by table 3: its catalytic activity variation of catalyzer through repeatedly reuse is less, and activity is still higher, has significantly reduced the actual consumption amount of catalyzer, has reduced the cost of production purpose product.
Claims (10)
1. Menglusitena intermediates preparation comprises: compound (II), o-iodobenzoic acid methyl esters, alkali and catalyzer are joined in the organic solvent, be stirred to and react completely, obtain Menglusitena midbody (I) through aftertreatment;
Described catalyzer is the metallic catalyst of mesoporous carbon nitride material load, and the charge capacity of metal is 0.1-90%;
The structure of described compound (II) is shown below:
The structure of described Menglusitena midbody (I) is shown below:
2. Menglusitena intermediates preparation according to claim 1 is characterized in that described metal comprises one or more among Pd, Au, Ag, Pt, Ru and the Rh.
3. Menglusitena intermediates preparation according to claim 1 is characterized in that, the mass percentage content of nitrogen is 45-70% in the described mesoporous carbon nitride material.
4. Menglusitena intermediates preparation according to claim 1 is characterized in that, the charge capacity of described metal is 0.5-20%.
5. Menglusitena intermediates preparation according to claim 1 is characterized in that, described compound (II) is 1:1-2 with the mol ratio of o-iodobenzoic acid methyl esters.
6. Menglusitena intermediates preparation according to claim 1 is characterized in that, the mass ratio of metal is 1000-300:1 in described compound (II) and the catalyzer.
7. Menglusitena intermediates preparation according to claim 1 is characterized in that, the described reaction times is 10-20 hour, and described temperature of reaction is 70-120 degree centigrade.
8. Menglusitena intermediates preparation according to claim 1 is characterized in that, described organic solution agent comprises one or more in acetonitrile, DMF and the methyl alcohol.
9. Menglusitena intermediates preparation according to claim 1 is characterized in that described alkali comprises one or more in triethylamine, salt of wormwood and the sodium acetate.
10. Menglusitena intermediates preparation according to claim 1 is characterized in that, described compound (II) is 1:1-2 with the mol ratio that alkali adds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101562488A CN102702097A (en) | 2012-05-16 | 2012-05-16 | Preparation method of montelukast sodium intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101562488A CN102702097A (en) | 2012-05-16 | 2012-05-16 | Preparation method of montelukast sodium intermediate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102702097A true CN102702097A (en) | 2012-10-03 |
Family
ID=46895208
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101562488A Pending CN102702097A (en) | 2012-05-16 | 2012-05-16 | Preparation method of montelukast sodium intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102702097A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895987A (en) * | 2012-10-12 | 2013-01-30 | 中南大学 | Method for preparing Au/g-C3N4 composite-type micro-nano material |
| CN105197886A (en) * | 2015-10-16 | 2015-12-30 | 安徽工业大学 | Method for catalyzing formic acid for dehydrogenation by use of supported Au-Pd/mpg-C3N4 nano-catalyst |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006021974A1 (en) * | 2004-08-23 | 2006-03-02 | Morepen Laboratories Limited | A process for synthesizing diol (viii)-an intermediate of montelukast sodium |
| WO2008058118A2 (en) * | 2006-11-06 | 2008-05-15 | Dr. Reddy's Labortories, Ltd. | Preparation of montelukast and its salts |
| CN101668745A (en) * | 2007-04-25 | 2010-03-10 | 隆萨股份公司 | Process for the preparation of optically active ethenylphenyl alcohols |
| WO2010064109A2 (en) * | 2008-12-02 | 2010-06-10 | Mayuka Labs Private Limited | An improved process for the preparation of montelukast sodium and its intermediates |
-
2012
- 2012-05-16 CN CN2012101562488A patent/CN102702097A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006021974A1 (en) * | 2004-08-23 | 2006-03-02 | Morepen Laboratories Limited | A process for synthesizing diol (viii)-an intermediate of montelukast sodium |
| WO2008058118A2 (en) * | 2006-11-06 | 2008-05-15 | Dr. Reddy's Labortories, Ltd. | Preparation of montelukast and its salts |
| CN101668745A (en) * | 2007-04-25 | 2010-03-10 | 隆萨股份公司 | Process for the preparation of optically active ethenylphenyl alcohols |
| WO2010064109A2 (en) * | 2008-12-02 | 2010-06-10 | Mayuka Labs Private Limited | An improved process for the preparation of montelukast sodium and its intermediates |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895987A (en) * | 2012-10-12 | 2013-01-30 | 中南大学 | Method for preparing Au/g-C3N4 composite-type micro-nano material |
| CN105197886A (en) * | 2015-10-16 | 2015-12-30 | 安徽工业大学 | Method for catalyzing formic acid for dehydrogenation by use of supported Au-Pd/mpg-C3N4 nano-catalyst |
| CN105197886B (en) * | 2015-10-16 | 2017-04-26 | 安徽工业大学 | Method for catalyzing formic acid for dehydrogenation by use of supported Au-Pd/mpg-C3N4 nano-catalyst |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105294447B (en) | A kind of method for being catalyzed hydrogenation of chloronitrobenzene and preparing aniline | |
| CN109232578B (en) | Method for continuously preparing tetranitrobenzene pyridine tetraazapentalene (BPTAP) by using micro-reaction technology | |
| CN102286804B (en) | Preparation method of titanium dioxide fibers with photocatalysis function and polycrystalline nanostructure | |
| CN103936536B (en) | Application of molecular size selective catalyst in Knoevenagel condensation reaction | |
| CN106362742A (en) | Ag/ZnO nano-composite, preparation method thereof and application of composite | |
| CN106316810A (en) | Preparation method for increasing synthetic yield of 1,1,3-trichloroacetone | |
| CN103143381B (en) | Carbon nitride material immobilized heteropolyacid catalyst and olefin epoxy synthesizing method | |
| CN107486202A (en) | A kind of mesoporous Ag/Ag2O/TiO2The preparation method of microspheres with solid material | |
| CN106179311A (en) | A kind of photocatalyst of Graphene bismuth titanates composite | |
| CN102633581A (en) | Application of nano titanium oxide mesoporous composite loaded platinum catalyst to catalytic hydrogenation | |
| CN102580720B (en) | Visible light response nano zinc oxide-bismuth oxide composite photocatalyst and preparation method thereof | |
| CN102702097A (en) | Preparation method of montelukast sodium intermediate | |
| CN105148935A (en) | Catalyst for producing 2,3,4-trifluoroaniline and preparation method therefor and application thereof | |
| CN104130198A (en) | 2-amino-4,6-dimethoxypyrimidine and preparation method thereof | |
| CN101817545B (en) | Preparation method of mesoporous alumina powder based on saccharides | |
| CN101391228B (en) | Loaded dual-function catalyst and preparation method and use thereof | |
| CN103433079B (en) | Bipyridyl ruthenium complex covalent functionalization graphene photocatalyst and preparation method thereof | |
| CN101941971B (en) | Method for synthesizing evodiamine | |
| CN101723925B (en) | Preparation method of 7-hydroxy-4-methylcoumarin | |
| CN102350337B (en) | Method for preparing ZnO/rectorite/carbon nano tube composite material | |
| CN112337510B (en) | Preparation method of functionalized polythiophene sensitized titanium dioxide composite photocatalyst and application of composite photocatalyst in photocatalytic degradation of organic pollutants | |
| CN104447736B (en) | The synthetic method of a kind of veranamine | |
| CN110252396B (en) | Catalyst used in synthesis process of dimethyl isophthalate-5-sodium sulfonate, preparation method and application | |
| CN102489299A (en) | Catalyst for producing ethyl orthosilicate by silicon powder method and preparation method thereof | |
| CN111203252B (en) | Copper catalyst for preparing glycol and ethanol from oxalate and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121003 |