CN102452957A - Synthesis method of 2,6-difluorobenzonitrile - Google Patents
Synthesis method of 2,6-difluorobenzonitrile Download PDFInfo
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- CN102452957A CN102452957A CN2010105249991A CN201010524999A CN102452957A CN 102452957 A CN102452957 A CN 102452957A CN 2010105249991 A CN2010105249991 A CN 2010105249991A CN 201010524999 A CN201010524999 A CN 201010524999A CN 102452957 A CN102452957 A CN 102452957A
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- difluorobenzonitrile
- reaction
- compound method
- temperature
- difluoro bromobenzene
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Abstract
The invention relates to the technical field of organic synthesis and provides a synthesis method of 2,6-difluorobenzonitrile. The synthesis method comprises the following steps of: adding 2,6-difluorobromobenzene and K4(Fe(CN)6)3H2O, a palladium catalyst and sodium carbonate into aprotic polar solvent to obtain mixed solution; and reacting the mixed solution under the protection of inert gas at the temperature of 100-160 DEG C for 15-30h, and cooling to room temperature to obtain 2,6-difluorobromobenzene. In the synthesis method provided by the invention, non-toxic K4(Fe(CN)6)3H2O is taken as a raw material, no pollution is produced, reaction condition is mild, no ligand is required to be added, and operation is simple.
Description
Technical field
The invention belongs to the organic synthesis field, be specifically related to a kind of 2, the compound method of 6-difluorobenzonitrile.
Background technology
2, (2,6-Difuorobenzonitrile is called for short 2 to the 6-difluorobenzonitrile, 6-DFBN) is the important intermediate of synthetic environment friendly agricultural process for preparation of benzoylurea compounds, also is that synthetic organic electromechanical phosphorescent material is like two [2-(4,6-two fluoro-3-benzonitrile bases) pyridine-N, C
2] (four pyrazoles boron) close iridium and (be called for short FCNIrpz
2Bpz
2) important starting raw material.Organic electromechanical phosphorescent material FCNIrpz
2Bpz
2Being mazarine phosphorescence twinkler efficiently, is important blue-light emitting body in blue or the white doped OLED device.
Present Synthetic 2, the most frequently used method of 6-DFBN is with 2, the 6-dichlorobenzonitrile (is called for short 2,6-DCBN) is raw material, form with the Potassium monofluoride reaction.2,6-DCBN and anhydrous potassium fluoride are catalyzer with rudimentary polyester fat alcohol ether compound in sulfolane solvent, and reaction is 3.5 hours under 250 ℃ of condition of normal pressure, yield 91.5%, purity 99.2%; This reaction time is short, and is simple to operate, but temperature of reaction is higher.2,6-DCBN and the anhydrous potassium fluoride 1.43MPa that under nitrogen, keep-ups pressure is in 350 ℃ of reaction 3h, yield 83%, purity 99%; This reaction need not solvent, and is simple to operate, but temperature of reaction is high, and reaction pressure is big, and is strict to conversion unit.2,6-DCBN and anhydrous potassium fluoride heat temperature-gradient method in sulfolane solvent, and 170 ℃ kept 0.5 hour, and 175 ℃ kept 2.0 hours, and 210～230 ℃ kept yield 95.6% 4.0 hours; But this law part is harsh, needs pyroreaction.
At present adopt 2, the 6-difluoro bromobenzene be raw material through the cyaniding Synthetic 2, the report of 6-DFBN is seldom.2, the synthetic as employing cyanogenation of 6-DFBN analogue makes 2, and in the prior art of 4-DFBN, the cyanating reagent of employing almost is NaCN, KCN or the CuCN of severe toxicity, and is very serious to the pollution of environment.
Summary of the invention
It is a kind of 2 that the embodiment of the invention provides, and the compound method of 6-difluorobenzonitrile is intended to solve complex process in the existing compound method, condition strictness and environmental pollution problems.
It is a kind of 2 that embodiments of the invention are achieved in that, the compound method of 6-difluorobenzonitrile, and said method comprises the steps:
In aprotic polar solvent, add 2,6-difluoro bromobenzene and K
4[Fe (CN)
6] 3H
2O, and palladium catalyst and yellow soda ash.
Above-mentioned mixing solutions is reacted under protection of inert gas, and temperature of reaction is 100-160 ℃, and the reaction times is 15-30h, obtains 2 after the cooling, the 6-difluorobenzonitrile.
2 of the embodiment of the invention, the preparation method of 6-difluorobenzonitrile, raw material adopts K
4[Fe (CN)
6] 3H
2O, nontoxic, cheap and easy to get, and reaction conditions is gentle, need not to add part, and simple to operate, productive rate is higher, is applicable to scientific experiment or batch process.
Description of drawings
Fig. 1 is 2 of the embodiment of the invention, the schema of the compound method of 6-difluorobenzonitrile;
Fig. 2 is the nuclear-magnetism in the embodiment of the invention 1
1H NMR test result collection of illustrative plates.
Embodiment
In order to make the object of the invention, technical scheme and advantage clearer,, the present invention is further elaborated below in conjunction with accompanying drawing and embodiment.Should be appreciated that specific embodiment described herein only in order to explanation the present invention, and be not used in qualification the present invention.
See also Fig. 1, the embodiment of the invention is shown provides a kind of 2, the compound method of 6-difluorobenzonitrile, said method comprises the steps:
S01: in aprotic polar solvent, add 2,6-difluoro bromobenzene and K
4[Fe (CN)
6] 3H
2O), and palladium catalyst and yellow soda ash, mixing solutions got.
S02: above-mentioned mixing solutions is reacted under protection of inert gas, and temperature of reaction is 100-160 ℃, and the reaction times is 15-30h, obtains 2 after the cooling, the 6-difluorobenzonitrile.
In step S01, aprotic polar solvent can be methyl-sulphoxide, MSM, N, at least a in dinethylformamide, the DMAC N,N, and preferably, solvent is a DMAC N,N.Catalyzer is Pd (OAc)
2, Pd (PPh
3)
4, Pd (PPh
3)
2Cl
2In the catalyzer of at least a and yellow soda ash combination, preferably, catalyzer is Pd (OAc)
2With the catalyzer of yellow soda ash combination, wherein, sodium carbonate amount is 2,1 molar equivalent of 6-difluoro bromobenzene, Pd (OAc)
2Mole dosage be 2,0.1～0.5% of 6-difluoro bromobenzene molar weight.Reactant 2,6-difluoro bromobenzene and K
4[Fe (CN)
6] 3H
2The molar equivalent ratio of O is preferably 1: 0.20～and 0.25.Temperature of reaction is preferably 110-135 ℃, can be 120 ℃ for example, and the reaction times is preferably 20-24h.
Among the step S02, rare gas element can be inactive gass such as nitrogen, argon gas.Reaction system is carried out under normal pressure, and preferably, the reaction times is 20-24h.Reaction formula is as follows:
The sampling and measuring conversion of raw material is greater than getting final product stopped reaction at 95% o'clock.Carry out aftertreatment after the reaction again, concrete steps are following: after reaction solution is cooled to room temperature, pour the ETHYLE ACETATE dilution into, filter.Filtrating is successively with washing, 5% NH
4The OH solution washing is used anhydrous Na again
2SO
4Dry organic layer filters, steam desolventize after, the cut of 96～100 ℃/2kPa is collected in underpressure distillation, can obtain 2,6-DFBN weighs simultaneously and calculates productive rate and product is characterized.
It is a kind of 2 that the embodiment of the invention provides, the compound method of 6-difluorobenzonitrile, and used raw material is K
4[Fe (CN)
6] 3H
2O, nontoxic, inexpensive, and conversion unit is simple, and temperature of reaction is lower.Simultaneously, this kind compound method, catalyst levels is few, and post-reaction treatment is simple,
Below in conjunction with specific embodiment concrete realization of the present invention is described in detail:
Embodiment one:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL DMAC N,N, 1.116g (2.64mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 8.082mg Pd (OAc)
2, under the nitrogen protection, be heated to 150 ℃, keep this temperature stirring reaction 24h.When the sampling and measuring conversion of raw material gets final product stopped reaction greater than 95% the time.After being cooled to room temperature, pour the dilution of 40mL ETHYLE ACETATE into, filter.Filtrating is used the washing secondary of 30mL, the 5%NH of 30mL successively
4The OH solution washing once, anhydrous Na
2SO
4Dry organic layer filters, and after steaming desolventized, the cut of 96～100 ℃/2kPa was collected in underpressure distillation, got 2 of 1.386g, 6-DFBN, yield 83%, purity 97%.
As shown in Figure 2, test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment two:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL DMAC N,N, 1.014g (2.4mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 8.082mg Pd (OAc)
2, under the nitrogen protection, be heated to 160 ℃, keep this temperature stirring reaction 22h.Aftertreatment gets 2 of 1.351g, 6-DFBN, yield 81%, purity 97% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment three:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL DMAC N,N, 1.267g (3mmol) K in the 25mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 8.082mg Pd (OAc)
2, under the nitrogen protection, be heated to 140 ℃, keep this temperature stirring reaction 20h.Aftertreatment gets 2 of 1.403g, 6-DFBN, yield 84%, purity 97% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment four:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL DMAC N,N, 1.116g (2.64mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 24.25mg Pd (OAc)
2, under the nitrogen protection, be heated to 110 ℃, keep this temperature stirring reaction 24h.Aftertreatment gets 2 of 1.420g, 6-DFBN, yield 85%, purity 98% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment five:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL DMAC N,N, 1.116g (2.64mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 40.411mg Pd (OAc)
2, under the nitrogen protection, be heated to 120 ℃, keep this temperature stirring reaction 24h.Aftertreatment gets 2 of 1.468g, 6-DFBN, yield 88%, purity 98% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment six:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL N, dinethylformamide, 1.116g (2.64mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 42.114mg Pd (PPh
3)
2Cl
2, under the nitrogen protection, be heated to 150 ℃, keep this temperature stirring reaction 24h.Aftertreatment gets 2 of 1.4g, 6-DFBN, yield 84%, purity 97% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment seven:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL methyl-sulphoxide, 1.116g (2.64mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 69.334mg Pd (PPh
3)
4, under the nitrogen protection, be heated to 160 ℃, keep this temperature stirring reaction 24h.Aftertreatment gets 2 of 1.384g, 6-DFBN, yield 83%, purity 97% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
Embodiment eight:
Magnetic stirring apparatus, prolong and logical N are being housed
2Add 2.316g (12mmol) 2 successively, 6-difluoro bromobenzene, 20mL MSM, 1.116g (2.64mmol) K in the 50mL reaction flask of device
4[Fe (CN)
6] 3H
2O, 1.272g (12mmol) yellow soda ash, 40.411mg Pd (OAc)
2, under the nitrogen protection, be heated to 160 ℃, keep this temperature stirring reaction 24h.Aftertreatment gets 2 of 1.368g, 6-DFBN, yield 82%, purity 97% with embodiment one.
Test result is:
1H NMR (400MHz, CDCl
3, ppm): 7.15 (d, 2H), 7.50 (m, 1H).
The above is merely preferred embodiment of the present invention, not in order to restriction the present invention, all any modifications of within spirit of the present invention and principle, being done, is equal to and replaces and improvement etc., all should be included within protection scope of the present invention.
Claims (9)
1. one kind 2, the compound method of 6-difluorobenzonitrile is characterized in that, said method comprises the steps:
In aprotic polar solvent, add 2,6-difluoro bromobenzene and K
4[Fe (CN)
6] 3H
2O, and palladium catalyst and yellow soda ash obtain mixing solutions;
Above-mentioned mixing solutions is reacted under protection of inert gas, and temperature of reaction is 100-160 ℃, and the reaction times is 15-30h, obtains 2 after the cooling, the 6-difluorobenzonitrile.
2. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, said aprotic polar solvent is methyl-sulphoxide, MSM, N, at least a in dinethylformamide and the DMAC N,N.
3. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, said palladium catalyst is Pd (OAc)
2, Pd (PPh
3)
4And Pd (PPh
3)
2Cl
2In at least a.
4. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, said sodium carbonate amount is 2,1 molar equivalent of 6-difluoro bromobenzene, and the mole dosage of palladium catalyst is 2,0.1～0.5% of 6-difluoro bromobenzene molar weight.
5. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, and is said 2,6-difluoro bromobenzene and K
4[Fe (CN)
6] 3H
2The molar equivalent ratio of O is 1: 0.20～0.25.
6. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, said temperature of reaction is 110-135 ℃.
7. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, said temperature of reaction is 120 ℃.
8. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, the said reaction times is 20-24h.
9. as claimed in claim 12, the compound method of 6-difluorobenzonitrile is characterized in that, also comprises last handling process, and said aftertreatment is with after the reaction solution cooling, pours the ETHYLE ACETATE dilution into, filters, the water successively of filtrating, 5% NH
4The OH solution washing is used anhydrous Na again
2SO
4Dry organic layer filters, and after steaming desolventized, the cut of 96～100 ℃/2kPa was collected in underpressure distillation, obtains 2, the 6-difluorobenzonitrile.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109336924A (en) * | 2018-11-15 | 2019-02-15 | 大连理工大学 | A kind of method that supported Pd complex catalysis halogenated aryl hydrocarbon green is cyanalation |
| CN110396059A (en) * | 2019-08-01 | 2019-11-01 | 苏州汉德创宏生化科技有限公司 | A kind of synthetic method of 5- cyanoindole |
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| CN101648909A (en) * | 2009-09-14 | 2010-02-17 | 南京第一农药集团有限公司 | Method for preparing cyanopyridine by using chloropyridine under the catalysis of ligand-free palladium |
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2010
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Patent Citations (3)
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| CN1962622A (en) * | 2006-11-27 | 2007-05-16 | 浙江大学 | Process for preparing 2,4-difluorocyanobenzene |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109336924A (en) * | 2018-11-15 | 2019-02-15 | 大连理工大学 | A kind of method that supported Pd complex catalysis halogenated aryl hydrocarbon green is cyanalation |
| CN109336924B (en) * | 2018-11-15 | 2021-01-19 | 大连理工大学 | Method for catalyzing green cyanation of halogenated aromatic hydrocarbon by supported Pd complex |
| CN110396059A (en) * | 2019-08-01 | 2019-11-01 | 苏州汉德创宏生化科技有限公司 | A kind of synthetic method of 5- cyanoindole |
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Application publication date: 20120516 |