CN102643160A - Preparation method of 1,2,4-trifluorobenzene - Google Patents
Preparation method of 1,2,4-trifluorobenzene Download PDFInfo
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- CN102643160A CN102643160A CN201210117387XA CN201210117387A CN102643160A CN 102643160 A CN102643160 A CN 102643160A CN 201210117387X A CN201210117387X A CN 201210117387XA CN 201210117387 A CN201210117387 A CN 201210117387A CN 102643160 A CN102643160 A CN 102643160A
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Abstract
The invention provides a preparation method of 1,2,4-trifluorobenzene, which comprises the following steps: 1) preparation of fluoboric acid diazonium salt: carrying out diazo-reaction on 2,4-difluoroaniline and sodium nitrate in fluoboric acid to obtain a fluoboric acid diazonium salt intermediate; and 2) preparation of 1,2,4-trifluorobenzene: heating to 100-300 DEG C to decompose the fluoboric acid diazonium salt intermediate while emitting nitrogen gas and boron trifluoride gas. The preparation technique provided by the invention is simple to operate, and has the advantages of low cost, high yield, high product quality and the like; and meanwhile, the quality of the byproduct boron trifluoride organic solvent solution is high, the production cost is greatly lowered, the emission of three wastes is reduced, and thus, the invention is suitable for industrial application.
Description
Technical field
The present invention relates to a kind of chemicals preparation method, particularly 1,2, the preparation method of 4-trifluoro-benzene.
Background technology
1,2, the 4-trifluoro-benzene is a kind of important medical material, can be used for producing the ofhypoglycemic medicine sitagliptin phosphate.
Disclose both at home and abroad multiple 1,2, the preparation method of 4-trifluoro-benzene.CN101817724A discloses a kind of with 3, and the 4-difluoroaniline is a raw material, through diazotization and thermolysis preparation 1,2, and the technology of 4-trifluoro-benzene, the used cost of material of this technology is expensive, and production cost is higher; US2011171112 discloses a kind of with 1,2, and the 4-trichlorobenzene is a raw material, and with the method for anhydrous potassium fluoride fluoro-reaction in high boiling solvent, but this method need be used very expensive catalysts; TetrahedronLetters, 2010, vol:51 (14); 1906-1909 has reported that with 2 the 5-dinitrofluorobenzene is a raw material, the technology of in methyl-sulphoxide, reacting with tetrabutyl ammonium fluoride; But this technology is raw materials used all relatively more expensive, and need use microwave condition; See other in addition with benzoquinone and hydrogen fluoride reaction, 2,4, bibliographical informations such as 5-trifluoro-benzoic acid high temperature decarboxylation, the direct fluoro of two fluorobenzene, but have shortcomings such as productive rate is low, expensive raw materials, operational condition harshness.Therefore, all to be not suitable for industrialized production.
Summary of the invention
Technical problem to be solved: existing 1,2 in order to solve, preparing method's expensive raw materials of 4-trifluoro-benzene, problem such as production cost is high, operational condition is harsh, yield is low, the invention provides a kind of new 1,2, the preparation method of 4-trifluoro-benzene.
Technical scheme: for solving the problems of the technologies described above, the present invention adopts following technical scheme preparation 1,2,4-trifluoro-benzene.
A kind of 1,2, the preparation method of 4-trifluoro-benzene is characterized in that: may further comprise the steps:
1) preparation of NITRODIAZONIUM FLUOROBORATE: 2,4 difluorobenzene amine and Sodium Nitrite carry out diazotization reaction in fluoborate aqueous solution, obtain the NITRODIAZONIUM FLUOROBORATE midbody, and reaction formula is following:
2) 1,2, the preparation of 4-trifluoro-benzene: the NITRODIAZONIUM FLUOROBORATE midbody obtains 1,2 100～300 ℃ of thermal degradation, and the 4-trifluoro-benzene discharges nitrogen and boron triflouride gas simultaneously, and reaction formula is following:
In the step 1), described fluoborate aqueous solution, the mass percentage concentration of fluoroboric acid is 20-40%.
In the step 1), described sodium nitrite in aqueous solution, the mass percentage concentration of Sodium Nitrite is 25-30%.
In the step 1), the mol ratio of fluoroboric acid, Sodium Nitrite and 2,4 difluorobenzene amine is (2.0-5.0): (1.02-11): 1.
In the step 1), room temperature drips 2,4 difluorobenzene amine in fluoborate aqueous solution, drips off back stirring at room 1 hour, is cooled to-5～0 ℃ again, is added dropwise to sodium nitrite in aqueous solution, keeps temperature of reaction and is no more than 5 ℃; Sodium nitrite in aqueous solution dripped continued at-20-10 ℃ insulation reaction 2-6 hour, filtered, and solid promptly gets the NITRODIAZONIUM FLUOROBORATE midbody through washing.
In the step 1), preferably, sodium nitrite in aqueous solution dripped continued at 0-5 ℃ of insulation reaction 2-6 hour.
Step 2) in, the thermal degradation time is 4-8 hour.
Step 2) in, preferably, the NITRODIAZONIUM FLUOROBORATE midbody is heated to 100-120 ℃, thermal degradation 2-4 hour, slowly is warming up to 180-300 ℃ again, thermal degradation 2-4 hour.
Step 2) in, the boron triflouride gas that discharges absorbs with organic solvent, obtains the boron trifluoride organic solvent solution.Wherein, said organic solvent is ether, THF, 1,4-dioxane, methyl alcohol, ethanol or acetic acid, preferred ether or THF.Can realize the recycling of boron triflouride gas in this way.
Beneficial effect: production technique of the present invention has following beneficial effect:
1) the present invention 1,2, the preparation method of 4-trifluoro-benzene, and the raw material of employing is that 2,4 difluorobenzene amine, fluoroboric acid and Sodium Nitrite cheap and easy to get gone up in industry, production cost is low;
2) the present invention absorbs the boron triflouride gas that the NITRODIAZONIUM FLUOROBORATE thermolysis produces with organic solvent, is producing 1,2; In the time of the 4-trifluoro-benzene; The high-quality boron trifluoride organic solvent solution of by-product has not only significantly reduced three waste discharge, has also further reduced production cost;
3) the present invention 1,2, the preparation method of 4-trifluoro-benzene, and reaction conditions requires low, easy and simple to handle, is suitable for industrial application;
4) the present invention 1,2, the preparation method of 4-trifluoro-benzene, and through the preparation and 1,2 of NITRODIAZONIUM FLUOROBORATE, the preparation two-step reaction of 4-trifluoro-benzene promptly gets product, adopts this method productive rate higher;
5) the boron trifluoride organic solvent solution of by-product of the present invention is a kind of cationic polymerisation catalyst commonly used; It also is the catalyzer that manufacturing cis-1,4-polybutadiene rubber and polyoxymethylene are used; Or boron hydrogen high energy fuels and the basic raw material that extracts isotropic substance boron; The catalyzer of doing organic synthesis commonly used has the market requirement very widely.
Embodiment
According to following embodiment, can understand the present invention better.Yet, those skilled in the art will readily understand that the described concrete material proportion of embodiment, processing condition and result thereof only are used to explain the present invention, and the present invention that should also can not limit in claims to be described in detail.
Embodiment 1: the preparation of NITRODIAZONIUM FLUOROBORATE.
In the 3000ml four-hole boiling flask, add 1760g 30% fluoborate aqueous solution (fluoroboric acid content 6mol), room temperature is added dropwise to 258g (2mol) 2,4 difluorobenzene amine, and exothermic heat of reaction dripped off the continued stirring at room 1 hour, was cooled to-5～0 ℃ again.Be added dropwise to the solution that 145g (2.1mol) Sodium Nitrite and 340g water are made into, exothermic heat of reaction, control rate of addition; Keep temperature of reaction and be no more than 5 ℃; Add continued 0～5 ℃ of insulation reaction 2 hours, filter, solid washs with the 300ml water and the 200ml ethanol of precooling to 0 ℃ successively; Obtain NITRODIAZONIUM FLUOROBORATE 410g after the drying, yield 90%.
Embodiment 2: the preparation of NITRODIAZONIUM FLUOROBORATE.
In the 3000ml four-hole boiling flask, add 1760g 20% fluoborate aqueous solution (fluoroboric acid content 4mol), room temperature is added dropwise to 258g (2mol) 2,4 difluorobenzene amine, and exothermic heat of reaction dripped off the continued stirring at room 1 hour, was cooled to-5～0 ℃ again.Be added dropwise to the solution that 141g (2.04mol) Sodium Nitrite and 340g water are made into, exothermic heat of reaction, control rate of addition; Keep temperature of reaction and be no more than 5 ℃; Add continued-10--5 ℃ insulation reaction 4 hours, filter, solid washs with the 300ml water and the 200ml ethanol of precooling to 0 ℃ successively; Obtain NITRODIAZONIUM FLUOROBORATE 415g after the drying, yield 91%.
Embodiment 3: the preparation of NITRODIAZONIUM FLUOROBORATE.
In the 3000ml four-hole boiling flask, add 2200g 40% fluoborate solution (fluoroboric acid content 10mol), room temperature is added dropwise to 258g (2mol) 2,4 difluorobenzene amine, and exothermic heat of reaction dripped off the continued stirring at room 1 hour, was cooled to-5～0 ℃ again.Be added dropwise to the solution that 152g (2.2mol) Sodium Nitrite and 360g water are made into, exothermic heat of reaction, control rate of addition; Keep temperature of reaction and be no more than 5 ℃; Add continued-20～-10 ℃ of insulation reaction 6 hours, filter, solid washs with the 300ml water and the 200ml ethanol of precooling to 0 ℃ successively.
Embodiment 4: the preparation of NITRODIAZONIUM FLUOROBORATE.
With embodiment 1 identical operations, difference is: 141g (2.04mol) Sodium Nitrite and 422g water wiring solution-forming.
Embodiment 5:1,2, the preparation of 4-trifluoro-benzene.
Prepare the 1000ml four-hole boiling flask, band mechanical stirring, reflux condensing tube, TM connect gas tube on the prolong, feed in another 500ml four-hole boiling flask.In the 1000ml four-hole boiling flask, add 410g (1.8mol) NITRODIAZONIUM FLUOROBORATE.Add the 200g ether in the 500ml four-hole boiling flask.
The 1000ml four-hole boiling flask is heated to 120 ℃, is incubated 2 hours, slowly is warming up to 180 ℃ again, is incubated 2 hours, decomposes the gas that produces and is absorbed by ether through gas tube, obtains boron trifluoride ether solution 300g, massfraction 40%.
88～90 ℃ of cuts are collected in the resistates air distillation of decomposing, and obtain 1,2,4-trifluoro-benzene 202g, GC content 99.5%, yield 85%.
Embodiment 6:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: the 1000ml four-hole boiling flask is heated to 100 ℃, is incubated 2 hours, slowly is warming up to 300 ℃ again, is incubated 2 hours.
Embodiment 7:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: the 1000ml four-hole boiling flask is heated to 110 ℃, is incubated 4 hours, slowly is warming up to 250 ℃ again, is incubated 4 hours.
Embodiment 8:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: not segmentation controlled temperature, 1000ml four-hole boiling flask direct heating to 180 ℃ is incubated 6 hours.
Embodiment 9:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: add the 200g THF in the 500ml four-hole boiling flask.
Obtain boron trifluoride THF 310g, concentration 39%.
The resistates underpressure distillation of decomposing obtains 1,2,4-trifluoro-benzene 198g, GC content 99.5%, yield 83%.
Embodiment 10:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: add 200g acetic acid in the 500ml four-hole boiling flask.
Embodiment 11:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: add 200g1 in the 500ml four-hole boiling flask, the 4-dioxane.
Embodiment 12:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: add 200g ethanol in the 500ml four-hole boiling flask.
Embodiment 13:1,2, the preparation of 4-trifluoro-benzene.
With embodiment 5 identical operations, difference is: add 200g methyl alcohol in the 500ml four-hole boiling flask.
Claims (10)
1. one kind 2, the preparation method of 4-trifluoro-benzene is characterized in that: may further comprise the steps:
1) preparation of NITRODIAZONIUM FLUOROBORATE: 2,4 difluorobenzene amine and sodium nitrite in aqueous solution carry out diazotization reaction in fluoborate aqueous solution, obtain the NITRODIAZONIUM FLUOROBORATE midbody, and reaction formula is following:
2) 1,2, the preparation of 4-trifluoro-benzene: the NITRODIAZONIUM FLUOROBORATE midbody obtains 1,2 100～300 ℃ of thermal degradation, and the 4-trifluoro-benzene discharges nitrogen and boron triflouride gas simultaneously, and reaction formula is following:
2. according to claim 11,2, the preparation method of 4-trifluoro-benzene is characterized in that: in the step 1), and described fluoborate aqueous solution, the mass percentage concentration of fluoroboric acid is 20-40%.
3. according to claim 11,2, the preparation method of 4-trifluoro-benzene is characterized in that: in the step 1), and described sodium nitrite in aqueous solution, the mass percentage concentration of Sodium Nitrite is 25-30%.
4. according to claim 11,2, the preparation method of 4-trifluoro-benzene is characterized in that: in the step 1), the mol ratio of fluoroboric acid, Sodium Nitrite and 2,4 difluorobenzene amine is (2.0-5.0): (1.02-1.1): 1.
5. according to claim 11,2, the preparation method of 4-trifluoro-benzene; It is characterized in that: in the step 1), room temperature drips 2,4 difluorobenzene amine in fluoborate aqueous solution; Drip off back stirring at room 1 hour; Be cooled to-5～0 ℃ again, be added dropwise to sodium nitrite in aqueous solution, keep temperature of reaction and be no more than 5 ℃; Sodium nitrite in aqueous solution dripped continued at-20-10 ℃ insulation reaction 2-6 hour, filtered, and solid promptly gets the NITRODIAZONIUM FLUOROBORATE midbody through washing.
6. according to claim 51,2, the preparation method of 4-trifluoro-benzene is characterized in that: in the step 1), sodium nitrite in aqueous solution dripped continued at 0-5 ℃ of insulation reaction 2-6 hour.
7. according to claim 11,2, the preparation method of 4-trifluoro-benzene is characterized in that: step 2) in, the thermal degradation time is 4-8 hour.
8. according to claim 11,2, the preparation method of 4-trifluoro-benzene is characterized in that: step 2) in, the NITRODIAZONIUM FLUOROBORATE midbody is heated to 100-120 ℃, thermal degradation 2-4 hour, slowly is warming up to 180-300 ℃ again, thermal degradation 2-4 hour.
9. according to claim 11,2, the preparation method of 4-trifluoro-benzene is characterized in that: step 2) in, the boron triflouride gas that discharges absorbs with organic solvent, obtains the boron trifluoride organic solvent solution.
10. according to claim 91,2, the preparation method of 4-trifluoro-benzene is characterized in that: said organic solvent is ether, THF, 1,4-dioxane, methyl alcohol, ethanol or acetic acid.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104030882A (en) * | 2014-06-29 | 2014-09-10 | 陈昆 | Method for preparing fluorobenzene |
| CN106008182A (en) * | 2016-03-17 | 2016-10-12 | 维讯化工（南京）有限公司 | Preparation method of 4,4'-difluorobenzophenone |
| CN108821939A (en) * | 2018-08-06 | 2018-11-16 | 江苏沙星化工有限公司 | A kind of synthetic method of Ciprofloxacin intermediate 2,4 dichloro fluorobenzene |
| CN112266317A (en) * | 2020-11-10 | 2021-01-26 | 杭州臻挚生物科技有限公司 | Preparation method of 1,2, 4-trifluorobenzene |
| CN112851493A (en) * | 2020-11-10 | 2021-05-28 | 杭州臻挚生物科技有限公司 | Preparation method of 2,4, 5-trifluorophenylacetic acid |
| CN116730795A (en) * | 2023-08-11 | 2023-09-12 | 山东国邦药业有限公司 | Synthesis method of trifluoro-phenylacetic acid intermediate 1,2, 4-trifluoro-benzene |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104030882A (en) * | 2014-06-29 | 2014-09-10 | 陈昆 | Method for preparing fluorobenzene |
| CN106008182A (en) * | 2016-03-17 | 2016-10-12 | 维讯化工（南京）有限公司 | Preparation method of 4,4'-difluorobenzophenone |
| CN108821939A (en) * | 2018-08-06 | 2018-11-16 | 江苏沙星化工有限公司 | A kind of synthetic method of Ciprofloxacin intermediate 2,4 dichloro fluorobenzene |
| CN112266317A (en) * | 2020-11-10 | 2021-01-26 | 杭州臻挚生物科技有限公司 | Preparation method of 1,2, 4-trifluorobenzene |
| CN112851493A (en) * | 2020-11-10 | 2021-05-28 | 杭州臻挚生物科技有限公司 | Preparation method of 2,4, 5-trifluorophenylacetic acid |
| CN112266317B (en) * | 2020-11-10 | 2023-02-10 | 台州臻挚生物科技有限公司 | Process for preparing 1,2, 4-trifluorobenzene |
| CN116730795A (en) * | 2023-08-11 | 2023-09-12 | 山东国邦药业有限公司 | Synthesis method of trifluoro-phenylacetic acid intermediate 1,2, 4-trifluoro-benzene |
| CN116730795B (en) * | 2023-08-11 | 2023-10-27 | 山东国邦药业有限公司 | Synthesis method of trifluoro-phenylacetic acid intermediate 1,2, 4-trifluoro-benzene |
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Application publication date: 20120822 |