CN105859576A - Method for synthesizing phenylbutazone drug intermediate azobenzene - Google Patents
Method for synthesizing phenylbutazone drug intermediate azobenzene Download PDFInfo
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- CN105859576A CN105859576A CN201610292896.4A CN201610292896A CN105859576A CN 105859576 A CN105859576 A CN 105859576A CN 201610292896 A CN201610292896 A CN 201610292896A CN 105859576 A CN105859576 A CN 105859576A
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- azobenzene
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- bute
- synthetic method
- pharmaceutical intermediate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
- C07C245/06—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings
- C07C245/08—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing a phenylbutazone drug intermediate azobenzene. The method comprises the steps of placing aniline into a mixed solution of quinoline, potassium nitrate and potassium bisulfate to react with hafnium chloride, conducting filtration, washing and reduced pressure distillation, conducting a reaction in a sulfolane solution, then lowering the temperature, and conducting suction filtration, washing and recrystallization, so that the azobenzene is obtained. The whole reaction time can be controlled to be within 12 hours, the reaction yield can reach 90% or above, meanwhile, a new synthesis route is provided, and a good foundation is laid for further raising the reaction yield.
Description
Technical field
The present invention relates to the preparation method of a kind of medicine intermediate, belong to organic synthesis field, particularly relate to one
Plant the synthetic method of bute pharmaceutical intermediate azobenzene.
Background technology
Bute medicine is mainly used in rheumatoid arthritis, rheumatic arthritis and gout.The often company of need
Continue and be administered or use with other medicine reciprocal.For acute lymphangitis.The similar aminopyrine of effect.But
Antipyretic effect is more weak, and antiinflammatory action is relatively strong, preferable to inflammatory pain effect.There is promotion uric acid excretion
Effect.Oral absorption is complete, Vd120ml/kg, and when increasing dosage, Vd increases, but blood concentration does not increases, therefore
When reusing, its steady state blood concentration does not linearly increases.T1/2 is 56～86 hours.This product intrahepatic metabolism,
Metabolite is the most active.This medicine has competitive binding effect to plasma protein, causes some drugs to dissociate
And cause excess.As it closes with cumarin anticoagulation, some sulfa drugs, OHA or dilantin sodium etc.
Used time, arise that the excessive response of these medicines.It is when tubular excretion, disturbs penicillin, is administered orally
Antidiabetic drug, aspirin are by renal tubule excretion.When it is applied with aspirin simultaneously, releasing uric acid diuresis is made to make
With substantially weakening.This product can suppress the metabolism of Coumarins anticoagulation and sulfonylurea hypoglycemic agent, and can be by it
Cement out from plasma protein binding site, thus be remarkably reinforced its effect and toxicity, hypoglycemia can be caused
Or bleeding.With the elimination half-life that the drug combination increasing hepatomicrosome enzymatic activity can reduce this medicine.Should
Avoid, with other, there is the drug combination of bone marrow inhibition.This product is share can cause with diuretics triamterene
Kidney function damage.Intestines and stomach easily absorb, blood concentration peak value about 2 hours.Vd is 120ml/kg, and dosage increases
Blood concentration does not increases.98% is combined with plasma protein.Main at the oxidized slow metabolism of liver, metabolin
One of crovaril still have anti-inflammatory activity.This product metabolism is the slowest, mean elimination half life about 70 hours.
Azobenzene is as bute pharmaceutical intermediate, and its synthetic method is good and bad for improving pharmaceutical synthesis product matter
Amount, reduces by-products content and has Important Economic meaning.
Qiu Mingyan (new method [J] of Qiu Mingyan, Hu Zongyan, Zhang Changsong .4,4 '-dihydroxy azobenzene synthesis.
Dyestuff and dyeing, 2006,06:46-47.) with p-nitrophenol as raw material, at formic acid, triethylamine salt and lead
Under effect, it is passed through nitrogen, reacts 2 hours, then filter, with methyl alcohol washing, concentrate, again with ether, salt
Water and water washing, and be dried overnight with sewage magnesium sulfate, eventually pass filter, decompression distillation, volatilization, heavily tie
Brilliant, vacuum drying, obtains 4, and 4 '-dihydroxy azobenzene, yield is 82%.This synthetic method is the most complicated,
Reaction time is long, more than 18 hours, therefore, for shortening the reaction time, improves yield, it is necessary to propose
A kind of new synthetic method.
Summary of the invention
The technical problem existed based on background technology, the present invention proposes a kind of bute pharmaceutical intermediate
The synthetic method of azobenzene.
The synthetic method of a kind of bute pharmaceutical intermediate azobenzene, follows the steps below:
A, in the reaction vessel being provided with agitator, reflux condenser, add aniline (molecular formula 2) 2.3mol,
Quinoline solution 1.6-1.8L, potassium nitrate solution 500-600ml, bisulfite potassium solution 5.1-5.5mol, control
Mixing speed is 190-230rpm, adds hafnium chloride powder 3.2mol, and rising solution temperature, to 65-75 DEG C, returns
Stream reaction 3-5h；
B, filtration, filter cake diethylene glycol solution is washed 3-5 time, merges cleaning solution and filtrate, and decompression is distilled,
Reduction solution temperature, to 10-16 DEG C, separates out solid, is joined by solid in 300ml sulfolane solution, rises
High solution temperature, to 60-66 DEG C, controls mixing speed 110-140rpm, maintains 3-5h；
C, reduce solution temperature to 20-26 DEG C, separate out solid, suction filtration, brine, molten at paracresol
Liquid recrystallizes, obtains crystal azobenzene (molecular formula 1).
Preferably, described quinoline liquid quality fraction is 30-39%.
Preferably, described potassium nitrate solution mass fraction is 20-32%.
Preferably, described potassium bisulfite liquid quality fraction is 41-50%.
Preferably, described diethylene glycol solution mass fraction is 45-55%.
Preferably, the described residing pressure of decompression distillation is 3.5-3.8kPa.
Preferably, described sulfolane solution mass fraction is 52-68%.
Preferably, described salting liquid is any one in KBr, sodium sulphate.
Preferably, described paracresol liquid quality fraction is 80-92%.
Whole course of reaction can represent with following reaction equation:
Compared to synthetic method disclosed in background technology, the bute pharmaceutical intermediate that the present invention provides is even
The synthetic method of pyridine, the reaction time is greatly shortened, and reaction yield is also improved, and the invention provides simultaneously
A kind of new synthetic route, lays a good foundation for promoting reaction yield further.
Accompanying drawing explanation
Fig. 1 is the mass fraction of the quinoline solution normal distribution on the impact of reaction yield.Wherein, horizontal seat
It is designated as the mass fraction of quinoline solution；Ordinate is reaction yield；
Fig. 2 is the mass fraction of the potassium nitrate solution normal distribution on the impact of reaction yield.Wherein, horizontal
Coordinate is the mass fraction of potassium nitrate solution；Ordinate is reaction yield；
Fig. 3 is the mass fraction of the diethylene glycol solution normal distribution on the impact of reaction yield.Wherein, horizontal
Coordinate is the mass fraction of glycol solution；Ordinate is reaction yield；
Fig. 4 is the mass fraction of the sulfolane solution normal distribution on the impact of reaction yield.Wherein, horizontal
Coordinate is the mass fraction of sulfolane solution；Ordinate is reaction yield.
Detailed description of the invention
Embodiment 1:
The synthetic method of x body azobenzene in the middle of a kind of bute medicine, follows the steps below:
A, in the reaction vessel being provided with agitator, reflux condenser, add aniline 2.3mol, quality is divided
Number is the quinoline solution 1.6L of 35%, and mass fraction is 25% potassium nitrate solution 500ml, and mass fraction is 45%
Bisulfite potassium solution 5.5mol, controls mixing speed 190rpm, adds hafnium chloride powder 3.2mol, raises molten
Liquid temp to 65 DEG C, back flow reaction 3h；
B, filtration, filter cake mass fraction is that 50% diethylene glycol solution is washed 3 times, merges cleaning solution and filtrate,
3.7kPa reduces pressure distillation, reduces solution temperature to 10 DEG C, separates out solid, solid joins 300ml mass
Mark is in 57% sulfolane solution, and rising solution temperature, to 60 DEG C, controls mixing speed 110rpm, maintains 4h；
C, reduction solution temperature, to 20 DEG C, separate out solid, suction filtration, and potassium bromide solution washs, at mass fraction
It is that 85% paracresol solution recrystallizes, obtains crystal azobenzene 385.81g, yield 92%.
Embodiment 2:
The synthetic method of a kind of bute pharmaceutical intermediate azobenzene, follows the steps below:
A, in the reaction vessel being provided with agitator, reflux condenser, add aniline 2.3mol, quality is divided
Number is 35% quinoline solution 1.7L, and mass fraction is 27% potassium nitrate solution 550ml, and mass fraction is 46% Asia
Potassium hydrogen sulfate solution 5.3mol, controls mixing speed 210rpm, adds hafnium chloride powder 3.2mol, raises solution
Temperature to 68 DEG C, back flow reaction 3h；
B, filtration, filter cake mass fraction is that 48% diethylene glycol solution is washed 4 times, merges cleaning solution and filtrate,
3.6kPa reduces pressure distillation, reduces solution temperature to 13 DEG C, separates out solid, solid joins 300ml mass
Mark is in 59% sulfolane solution, and rising solution temperature, to 63 DEG C, controls mixing speed 130rpm, maintains 4h；
C, reduction solution temperature, to 23 DEG C, separate out solid, suction filtration, and metabisulfite solution washs, at mass fraction
It is that 85% paracresol solution recrystallizes, obtains crystal azobenzene 364.18g, yield 87%.
Embodiment 3:
The synthetic method of a kind of bute pharmaceutical intermediate azobenzene, follows the steps below:
A, in the reaction vessel being provided with agitator, reflux condenser, add aniline 2.3mol, quality is divided
Number is 39% quinoline solution 1.8L, and mass fraction is 32% potassium nitrate solution 600ml, and mass fraction is 46% Asia
Potassium hydrogen sulfate solution 5.5mol, controls mixing speed 230rpm, adds hafnium chloride powder 3.2mol, raises solution
Temperature to 75 DEG C, back flow reaction 4h；
B, filtration, filter cake mass fraction is that 55% diethylene glycol solution is washed 5 times, merges cleaning solution and filtrate,
3.8kPa reduces pressure distillation, reduces solution temperature to 16 DEG C, separates out solid, solid joins 300ml mass
Mark is in 68% sulfolane solution, and rising solution temperature, to 66 DEG C, controls mixing speed 140rpm, maintains 5h；
C, reduction solution temperature, to 26 DEG C, separate out solid, suction filtration, and potassium bromide solution washs, divides in quality
Number is to recrystallize in 92% paracresol solution, obtains crystal azobenzene 380.93g, yield 91%.
Under the preferred conditions, the reaction time of embodiment 1-3 is all less than 12 hours, and yield is above
85%, therefore synthetic method provided by the present invention contracted significantly than the synthetic method in background technology, reaction time
Short, yield is greatly improved.
Below embodiment 4-9 is contrasted with embodiment 1, the percent mass comparison of each solution in research reaction
Yield and the impact in reaction time.
Embodiment 4:
The mass fraction of the quinoline solution in embodiment 1 is adjusted, remaining preparation condition and raw material proportioning
Same as in Example 1, obtain reaction yield as follows:
Table one: the mass fraction of the quinoline solution impact on reaction yield
From embodiment 4, the mass fraction of quinoline solution is too high or too low all can affect reaction yield, its
Become normal distribution (Fig. 1) with reaction yield, it is 30-39% that peak value occurs in mass fraction.
Embodiment 5:
Being adjusted by the mass fraction of the potassium nitrate solution in embodiment 1, remaining preparation condition is joined with raw material
Ratio is same as in Example 1, obtains reaction yield as follows:
Table two: the mass fraction of the potassium nitrate solution impact on reaction yield
From embodiment 5, the mass fraction of potassium nitrate solution is too high or too low all can affect reaction yield,
It becomes normal distribution (Fig. 2) with reaction yield, and it is 20-32% that peak value occurs in mass fraction.
Embodiment 6:
Being adjusted by the mass fraction of the bisulfite potassium solution in embodiment 1, remaining preparation condition is with former
Material proportioning is same as in Example 1, obtains reaction yield as follows:
Table three: the mass fraction of the bisulfite potassium solution impact on reaction yield
From embodiment 6, the mass fraction of bisulfite potassium solution is little on the impact of reaction yield, but
It is relatively big on the impact of reflux time, and the minimum of a value of reflux time occurs in bisulfite potassium solution
Mass fraction when being 41-50%.
Embodiment 7:
Being adjusted by the mass fraction of the diethylene glycol solution in embodiment 1, remaining preparation condition is joined with raw material
Ratio is same as in Example 1, obtains reaction yield as follows:
Table four: the mass fraction of the diethylene glycol solution impact on reaction yield
From embodiment 7, the mass fraction of diethylene glycol solution is too high or too low all can affect reaction yield,
It becomes normal distribution (Fig. 3) with reaction yield, and it is 45-55% that peak value occurs in mass fraction.
Embodiment 8:
Being adjusted by the mass fraction of the sulfolane solution in embodiment 1, remaining preparation condition is joined with raw material
Ratio is the same as in Example 8, obtains reaction yield as follows:
Table five: the mass fraction of the sulfolane solution impact on reaction yield
From embodiment 8, the mass fraction of sulfolane solution is too high or too low all can affect reaction yield,
It becomes normal distribution (Fig. 4) with reaction yield, and it is 52-68% that peak value occurs in mass fraction.
Embodiment 9:
The mass fraction of the paracresol solution in embodiment 1 is adjusted, remaining preparation condition and raw material proportioning
Same as in Example 1, obtain reaction yield as follows:
Table six: the mass fraction of the paracresol solution impact on reaction yield
From embodiment 9, reaction yield is not affected by the mass fraction of paracresol solution, but counterweight knot
Brilliant time effects is relatively big, and recrystallization minimum of a value occurs in the mass fraction of paracresol solution when being 80-92%.
Embodiment 10 being contrasted with embodiment 1 below, the pressure of distillation of reducing pressure in research reaction is to yield
Impact.
Embodiment 10:
Decompression in embodiment 1 is distilled residing pressure be adjusted, remaining preparation condition and raw material proportioning with
Embodiment 1 is identical, obtains reaction yield as follows:
Table seven: the residing pressure impact on reaction yield of decompression distillation
From embodiment 10, the residing pressure of decompression distillation can affect reaction yield, and it becomes anti-with reaction yield
Ratio, for reducing cost, is chosen as 3.5-3.8kPa by the pressure of decompression distillation.
Described in above example, the only present invention preferably detailed description of the invention, but protection scope of the present invention
Be not limited thereto, any those familiar with the art in the technical scope that the invention discloses,
According to technical scheme and inventive concept equivalent or change in addition thereof, all should contain in the present invention
Protection domain within.
Claims (9)
1. the synthetic method of a bute pharmaceutical intermediate azobenzene, it is characterised in that according to following
Step is carried out:
A, in the reaction vessel being provided with agitator, reflux condenser, add aniline 2.3mol, quinoline is molten
Liquid 1.6-1.8L, potassium nitrate solution 500-600ml, bisulfite potassium solution 5.1-5.5mol, control stirring speed
Degree for 190-230rpm, adds hafnium chloride powder 3.2mol, raises solution temperature to 65-75 DEG C, back flow reaction
3-5h；
B, filtration, filter cake diethylene glycol solution is washed 3-5 time, merges cleaning solution and filtrate, and decompression is distilled,
Reduction solution temperature, to 10-16 DEG C, separates out solid, is joined by solid in 300ml sulfolane solution, rises
High solution temperature, to 60-66 DEG C, controls mixing speed 110-140rpm, maintains 3-5h；
C, reduce solution temperature to 20-26 DEG C, separate out solid, suction filtration, brine, molten at paracresol
Liquid recrystallizes, obtains crystal azobenzene.
2. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described quinoline liquid quality fraction is 30-39%.
3. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described potassium nitrate solution mass fraction is 20-32%.
4. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described potassium bisulfite liquid quality fraction is 41-50%.
5. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described diethylene glycol solution mass fraction is 45-55%.
6. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, the described residing pressure of decompression distillation is 3.5-3.8kPa.
7. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described sulfolane solution mass fraction is 52-68%.
8. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described salting liquid is any one in KBr, sodium sulphate.
9. the synthetic method of bute pharmaceutical intermediate azobenzene as claimed in claim 1, its feature exists
In, described paracresol liquid quality fraction is 80-92%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299232A (en) * | 2018-03-14 | 2018-07-20 | 江苏灼华生物科技有限公司 | It is a kind of to prepare 2-（Dihalotoluene）The method of azobenzene |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4035423A (en) * | 1973-07-03 | 1977-07-12 | Ciba-Geigy Corporation | Process for the preparation of 3,4-dialkoxyanilines |
| CN101215245A (en) * | 2007-01-05 | 2008-07-09 | 浙江龙盛集团股份有限公司 | Monoazo compound containing diester and its preparation, application and dye composition |
| WO2012110745A1 (en) * | 2011-02-15 | 2012-08-23 | Centre National De La Recherche Scientifique (Cnrs) | Photostimulable surfactant |
| WO2012138049A1 (en) * | 2011-04-07 | 2012-10-11 | Korea Research Institute Of Chemical Technology | Non-aqueous fluid marker containing n-benzyl-n-ethylaniline and method for preparing the same |
| CN105017065A (en) * | 2014-04-29 | 2015-11-04 | 中国科学院大连化学物理研究所 | Method for preparing aromatic azobenzene by utilizing aromatic amine oxidation |
| CN105037199A (en) * | 2015-07-10 | 2015-11-11 | 岭南师范学院 | Bromoazobenzene compound and preparation method thereof |
-
2016
- 2016-05-05 CN CN201610292896.4A patent/CN105859576A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4035423A (en) * | 1973-07-03 | 1977-07-12 | Ciba-Geigy Corporation | Process for the preparation of 3,4-dialkoxyanilines |
| CN101215245A (en) * | 2007-01-05 | 2008-07-09 | 浙江龙盛集团股份有限公司 | Monoazo compound containing diester and its preparation, application and dye composition |
| WO2012110745A1 (en) * | 2011-02-15 | 2012-08-23 | Centre National De La Recherche Scientifique (Cnrs) | Photostimulable surfactant |
| WO2012138049A1 (en) * | 2011-04-07 | 2012-10-11 | Korea Research Institute Of Chemical Technology | Non-aqueous fluid marker containing n-benzyl-n-ethylaniline and method for preparing the same |
| CN105017065A (en) * | 2014-04-29 | 2015-11-04 | 中国科学院大连化学物理研究所 | Method for preparing aromatic azobenzene by utilizing aromatic amine oxidation |
| CN105037199A (en) * | 2015-07-10 | 2015-11-11 | 岭南师范学院 | Bromoazobenzene compound and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| SABBASANI RAJASEKHARA REDDY等: "Cu(I) catalyzed dehydrogenative homo coupling of aromatic amines under simple and mild reaction conditions", 《CATALYSIS COMMUNICATIONS》 * |
| WANG, JIAQING等: "Highly Efficient Synthesis of Azos Catalyzed by Common Metal of Copper (0) through Oxidative Coupling Reactions", 《RSC ADVANCES》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299232A (en) * | 2018-03-14 | 2018-07-20 | 江苏灼华生物科技有限公司 | It is a kind of to prepare 2-（Dihalotoluene）The method of azobenzene |
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Application publication date: 20160817 |