CN105967974B - A kind of preparation method of 2- methyl -3,4,5- trifluorobromobenzenes - Google Patents
A kind of preparation method of 2- methyl -3,4,5- trifluorobromobenzenes Download PDFInfo
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- CN105967974B CN105967974B CN201610304204.3A CN201610304204A CN105967974B CN 105967974 B CN105967974 B CN 105967974B CN 201610304204 A CN201610304204 A CN 201610304204A CN 105967974 B CN105967974 B CN 105967974B
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- methyl
- added dropwise
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- trifluorobromobenzenes
- insulation reaction
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- PRKLUKBOWDLULS-UHFFFAOYSA-N 1-bromo-3,4,5-trifluoro-2-methylbenzene Chemical class CC1=C(Br)C=C(F)C(F)=C1F PRKLUKBOWDLULS-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 22
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000009413 insulation Methods 0.000 claims abstract description 12
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229940043279 diisopropylamine Drugs 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- IPWBFGUBXWMIPR-UHFFFAOYSA-N 1-bromo-2-fluorobenzene Chemical compound FC1=CC=CC=C1Br IPWBFGUBXWMIPR-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 abstract description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 abstract description 3
- HKJCELUUIFFSIN-UHFFFAOYSA-N 5-bromo-1,2,3-trifluorobenzene Chemical compound FC1=CC(Br)=CC(F)=C1F HKJCELUUIFFSIN-UHFFFAOYSA-N 0.000 abstract description 2
- 238000004064 recycling Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- MUUAQFJJUGVBGB-UHFFFAOYSA-N 1-bromo-2,3,4-trifluorobenzene Chemical compound FC1=CC=C(Br)C(F)=C1F MUUAQFJJUGVBGB-UHFFFAOYSA-N 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000004973 liquid crystal related substance Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- UGEJOEBBMPOJMT-UHFFFAOYSA-N 3-(trifluoromethyl)phenol Chemical class OC1=CC=CC(C(F)(F)F)=C1 UGEJOEBBMPOJMT-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005885 boration reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/02—Lithium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation methods of 3,4,5 trifluorobromobenzene of 2 methyl, it is related to technical field of organic synthesis, using tetrahydrofuran as solvent, n-BuLi is added dropwise into diisopropylamine under low temperature, drips off rear insulation reaction 30min, it then proceedes to cool down, and raw material 3,4,5 is added dropwise, trifluorobromobenzene, rear insulation reaction 2h is dripped off, is heated up after reaction, then dimethyl suflfate is added dropwise, reaction 30min is warmed to room temperature after dripping off, stop reaction, post-treated rear rectification under vacuum is to get 2 methyl 3,4,5 trifluorobromobenzenes.Preparation process of the present invention is simple, at low cost, and can be to solvents tetrahydrofurane recycling, and product purity reaches 99.5% or more, and yield is 60% or so.
Description
Technical field：
The present invention relates to technical field of organic synthesis, and in particular to a kind of 2- methyl -3,4, the preparation side of 5- trifluorobromobenzenes
Method.
Background technology：
2- methyl -3,4,5- trifluorobromobenzenes can prepare novel fluorine liquid crystal material as the intermediate of fluorinated liquid crystal material
Material.2- methyl -3,4 is made through grignard reaction, boration, oxidation in 2- methyl -3,4,5- trifluorobromobenzenes, 5- trifluoromethyl phenols, in recent years
To start to apply on New Liquid Crystal material.
3,4,5- trifluorobromobenzenes due to cannot directly use n-BuLi with the presence of bromine atom, lithiumation process on phenyl ring,
Otherwise bromine atom can be also lithiated, to generate a large amount of by-products.Phenyl ring methylates generally use iodomethane as the examination that methylates
Agent, and the present invention using dimethyl suflfate as methylating reagent, can be to avoid dimethyl by-product by controlling reaction temperature
Generation.
Invention content：
Technical problem to be solved by the present invention lies in providing, a kind of by-product production quantity is few, at low cost and product purity is high
2- methyl -3,4,5- trifluorobromobenzenes preparation method.
The technical problems to be solved by the invention are realized using technical solution below：
A kind of 2- methyl -3,4, the preparation method of 5- trifluorobromobenzenes, using tetrahydrofuran as solvent, to diisopropylamine under low temperature
Middle dropwise addition n-BuLi drips off rear insulation reaction 30min, then proceedes to cool down, and raw material 3 is added dropwise, and 4,5 ,-trifluorobromobenzene, drop
Insulation reaction 2h, heats up, then dimethyl suflfate is added dropwise after reaction after complete, and reaction 30min is warmed to room temperature after dripping off, and stops anti-
It answers, post-treated rear rectification under vacuum is to get 2- methyl -3,4,5- trifluorobromobenzenes.
Described 3, the dropping temperature of 4,5- trifluorobromobenzenes is -80~-60 DEG C, preferably -80~-70 DEG C.
The dropping temperature of the dimethyl suflfate is -60~-10 DEG C, preferably -60~-30 DEG C.
The beneficial effects of the invention are as follows：The present invention first prepares N, N- lithium diisopropyl amidos, then with 3,4,5 ,-trifluorobromobenzene
Lithiation occurs, then reacts with dimethyl suflfate, obtains 2- methyl -3,4,5- trifluorobromobenzenes, preparation process letter
It is single, at low cost, and solvents tetrahydrofurane can be recycled and be reused, to realize recycling for resource, avoid organic solvent dirty
Environment is contaminated, and product purity reaches 99.5% or more, yield is 60% or so.
Specific implementation mode：
In order to make the technical means, the creative features, the aims and the efficiencies achieved by the present invention be easy to understand, tie below
Specific embodiment is closed, the present invention is further explained.
Embodiment 1
2L there-necked flasks, nitrogen protection throw diisopropylamine, and tetrahydrofuran 750g, cool down -40 DEG C of dropwise addition n-BuLis, and drop finishes
Insulation reaction 30min, cools to -78 DEG C, is added dropwise raw material 3, and 4,5,-trifluorobromobenzene, drop finishes, -78 DEG C of heat preservation 2h.Lithium reagent is finished
For use.Another 3 liters of there-necked flasks, nitrogen protection throw dimethyl suflfate, and tetrahydrofuran 600g cools to -40 DEG C, ready-made lithium
Reagent kit is quickly pressed into, and -10 DEG C of temperature control is hereinafter, insulation reaction 30min.Stop reaction, water pump decompression is sloughed tetrahydrofuran, added
400g water, dichloroethanes extraction, organic phase are washed one time, and rectification under vacuum after concentration obtains finished product 2- methyl -3,4,5- trifluoro bromines
Benzene, 99.5% or more purity, yield 56%.
Embodiment 2
2L there-necked flasks, nitrogen protection throw diisopropylamine, and tetrahydrofuran 750g, cool down -40 DEG C of dropwise addition n-BuLis, and drop finishes
Insulation reaction 30min, cools to -78 DEG C, is added dropwise raw material 3, and 4,5,-trifluorobromobenzene, drop finishes, -78 DEG C of heat preservation 2h.It is warming up to -60
DEG C start that dimethyl suflfate is added dropwise, keeps temperature to be not higher than -30 DEG C, nature is added dropwise and is warmed to room temperature, insulation reaction 30min.
Stop reaction, tetrahydrofuran is sloughed in water pump decompression, and 400g water, dichloroethanes extraction, organic phase is added to wash one time, depressurized after concentration
Rectifying obtains finished product 2- methyl -3,4,5- trifluorobromobenzenes, 99.5% or more purity, yield 61%.
Embodiment 3
2 liters of there-necked flasks, nitrogen protection throw diisopropylamine, and tetrahydrofuran 750g, cool down -40 DEG C of dropwise addition n-BuLis, and drop finishes
Insulation reaction 30min, cools to -70 DEG C, is added dropwise raw material 3, and 4,5,-trifluorobromobenzene, drop finishes, -70 DEG C of heat preservation 2h.It is warming up to -50
DEG C start that dimethyl suflfate is added dropwise, keeps temperature to be not higher than -20 DEG C, nature is added dropwise and is warmed to room temperature, insulation reaction 30min.
Stop reaction, tetrahydrofuran is sloughed in water pump decompression, and 400g water, dichloroethanes extraction, organic phase is added to wash one time, depressurized after concentration
Rectifying obtains finished product 2- methyl -3,4,5- trifluorobromobenzenes, 99.5% or more purity, yield 60%.
The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent thereof.
Claims (1)
1. a kind of 2- methyl -3,4, the preparation method of 5- trifluorobromobenzenes, it is characterised in that：Using tetrahydrofuran as solvent, under low temperature
N-BuLi is added dropwise into diisopropylamine, drips off rear insulation reaction 30min, then proceedes to cool down, and raw material 3 is added dropwise, 4,5 ,-three
Bromofluorobenzene drips off rear insulation reaction 2h, heats up after reaction, then dimethyl suflfate is added dropwise, reaction is warmed to room temperature after dripping off
30min stops reaction, and post-treated rear rectification under vacuum is to get 2- methyl -3,4,5- trifluorobromobenzenes；The 3,4,5- trifluoros bromine
The dropping temperature of benzene is -80~-70 DEG C, and the dropping temperature of dimethyl suflfate is -60~-30 DEG C.
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| CN201610304204.3A CN105967974B (en) | 2016-05-06 | 2016-05-06 | A kind of preparation method of 2- methyl -3,4,5- trifluorobromobenzenes |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610304204.3A CN105967974B (en) | 2016-05-06 | 2016-05-06 | A kind of preparation method of 2- methyl -3,4,5- trifluorobromobenzenes |
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| CN105967974A CN105967974A (en) | 2016-09-28 |
| CN105967974B true CN105967974B (en) | 2018-08-31 |
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| CN113121304A (en) * | 2021-04-19 | 2021-07-16 | 河北松辰医药科技有限公司 | Synthetic method of p-bromooctylbenzene and derivatives thereof |
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| US6348624B1 (en) * | 1998-01-09 | 2002-02-19 | The Procter & Gamble Co. | Process for making certain benzoic acid compounds |
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Denomination of invention: A preparation method of 2-methyl-3,4,5-trifluorobromobenzene Granted publication date: 20180831 Pledgee: Bengbu financing guarantee Group Co.,Ltd. Pledgor: CHINA SYNCHEM TECHNOLOGY Co.,Ltd. Registration number: Y2024980010170 |
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