CN106883147B - A kind of preparation method of phenyl-pentafluoride formonitrile HCN - Google Patents
A kind of preparation method of phenyl-pentafluoride formonitrile HCN Download PDFInfo
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- CN106883147B CN106883147B CN201710075294.8A CN201710075294A CN106883147B CN 106883147 B CN106883147 B CN 106883147B CN 201710075294 A CN201710075294 A CN 201710075294A CN 106883147 B CN106883147 B CN 106883147B
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- chloro
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- formonitrile hcn
- fluorobenzonitriles
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- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 239000002994 raw material Substances 0.000 claims abstract description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000001879 copper Chemical class 0.000 claims abstract description 7
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052802 copper Inorganic materials 0.000 claims abstract description 5
- 239000010949 copper Substances 0.000 claims abstract description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims abstract description 5
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical group I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims abstract description 3
- 238000007333 cyanation reaction Methods 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 10
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 8
- 239000011698 potassium fluoride Substances 0.000 claims description 8
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 8
- -1 2,3,4,6- tetra- chloro- 5- fluorobenzene Formonitrile Chemical compound 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 claims description 4
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 claims description 4
- 238000003682 fluorination reaction Methods 0.000 claims description 4
- 235000003270 potassium fluoride Nutrition 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000005660 chlorination reaction Methods 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical group Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 claims description 2
- UGWKCNDTYUOTQZ-UHFFFAOYSA-N copper;sulfuric acid Chemical compound [Cu].OS(O)(=O)=O UGWKCNDTYUOTQZ-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 229960001699 ofloxacin Drugs 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229960004954 sparfloxacin Drugs 0.000 description 2
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- IPWBFGUBXWMIPR-UHFFFAOYSA-N 1-bromo-2-fluorobenzene Chemical compound FC1=CC=CC=C1Br IPWBFGUBXWMIPR-UHFFFAOYSA-N 0.000 description 1
- NOXLGCOSAFGMDV-UHFFFAOYSA-N 2,3,4,5,6-pentafluoroaniline Chemical compound NC1=C(F)C(F)=C(F)C(F)=C1F NOXLGCOSAFGMDV-UHFFFAOYSA-N 0.000 description 1
- MEXUTNIFSHFQRG-UHFFFAOYSA-N 6,7,12,13-tetrahydro-5h-indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one Chemical compound C12=C3C=CC=C[C]3NC2=C2NC3=CC=C[CH]C3=C2C2=C1C(=O)NC2 MEXUTNIFSHFQRG-UHFFFAOYSA-N 0.000 description 1
- ARGBYBNTLCRTCX-UHFFFAOYSA-N C#N.BrC1=CC=CC=C1I Chemical compound C#N.BrC1=CC=CC=C1I ARGBYBNTLCRTCX-UHFFFAOYSA-N 0.000 description 1
- HHOXWPCTCQMHNN-UHFFFAOYSA-N C1(=CC=CC=C1)I.[F] Chemical class C1(=CC=CC=C1)I.[F] HHOXWPCTCQMHNN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229960002422 lomefloxacin Drugs 0.000 description 1
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000003408 phase transfer catalysis Methods 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/24—Preparation of carboxylic acid nitriles by ammoxidation of hydrocarbons or substituted hydrocarbons
- C07C253/28—Preparation of carboxylic acid nitriles by ammoxidation of hydrocarbons or substituted hydrocarbons containing six-membered aromatic rings, e.g. styrene
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a kind of preparation methods of phenyl-pentafluoride formonitrile HCN, include the following steps：(1) by raw material 2, bis- chloro- 3- fluoro acetophenones of 6-, copper salt catalyst, phase transfer catalyst tetrabutylammonium bromide and solvent A are added in autoclave, it is passed through ammonia and oxygen carries out cyanation, wherein, the copper salt catalyst is cuprous iodide or copper trifluoromethanesulfcomposite or copper sulphate or copper acetate；(2) bis- chloro- 3- fluorobenzonitriles of 2,6- are subjected to perchlorinating under the action of catalyst and obtain tetra- chloro- 5- fluorobenzonitriles of 2,3,4,6-；(3) 2,3,4,6- tetra- chloro- 5- fluorobenzonitriles, KF and phase transfer catalyst are added in solvent B, it is perfluorinated that phenyl-pentafluoride formonitrile HCN is obtained by the reaction.It is production 2 that 2,6-, bis- chloro- 3- fluoro acetophenones are utilized in the present invention, and the by-product of bis- chloro- 5- fluoro acetophenones of 4-, single cycle total recovery is up to 83%；Raw material is cheap and easy to get, has saved cost, protects environment；This synthesis technology is simple, easy to operate, and yield is higher, and purity is good, is suitable for industrialized production.
Description
Technical field
The invention belongs to chemical intermediate preparation method technical fields, and in particular to a kind of preparation of phenyl-pentafluoride formonitrile HCN
Method.
Background technology
Phenyl-pentafluoride formonitrile HCN (No. CAS：773-82-0), it is a kind of important medicine, pesticide and liquid shown in structure such as formula (I)
Brilliant intermediate, colourless liquid, fusing point：2.4 DEG C, boiling point is 162-164 DEG C, can be volatilized under room temperature, due to contain active fluorine ions compared with
It is more, become pentafluoro benzoic acid after hydrolysis, becomes tetrafluorobenzoic aid using hydro-reduction.Tetrafluorobenzoic aid is synthesis third
For quinoline ketone drug Lomefloxacin (Lomefloxain), Ofloxacin (Ofloxacin), fourth generation quinolone is left-handed
The starting material of Ofloxacin (Levofloxacin), sparfloxacin (Sparfloxacin) etc.；It can also be by hydrolyzing then
Hofmann degradation obtains pentafluoroaniline, then can synthesize a series of phenyl-pentafluoride class compounds through diazotising.
The disclosed preparation method in relation to phenyl-pentafluoride formonitrile HCN both at home and abroad, is mainly the following：(1) with five fluorine iodobenzenes and five
Bromofluorobenzene is raw material, with cuprous cyanide under pyridine or DMF high temperature, synthesizes phenyl-pentafluoride formonitrile HCN.Such as United States Patent (USP) US3150163 and
US3284484；Although this method reaction step is shorter, starting material price is somewhat expensive, the yield of reaction and product it is pure
Degree is not satisfactory.(2) using five bromo-iodobenzene formonitrile HCNs as raw material, using benzonitrile it is solvent in 300 DEG C of autoclave with KF, passes through within 20 hours
Fluorination reaction synthesizes phenyl-pentafluoride formonitrile HCN.Such as US4684734.This method starting material price is somewhat expensive, and reaction condition is harsher,
There is no practical value.(3) using five chloroiodobenzone formonitrile HCNs as raw material, fluorine occurs with KF and in polyethylene glycol or sulfolane equal solvent
Change reaction synthesis phenyl-pentafluoride formonitrile HCN, such as patent GB1026290, JP60036453, JP59222463, JP60184057,
JP59152361 and JP2005112745 etc..Five chloroiodobenzone formonitrile HCN of raw material used in this method compares in the market to be easy to get, and
Yield is also relatively high, is a kind of method the most commonly used in prepared by current five fluorine iodobenzene formonitrile HCN.
Invention content
The present invention provides a kind of preparation method of phenyl-pentafluoride formonitrile HCN, the preparation method is directly chloro- using production 2,4- bis-
The by-product 2 of 5- fluoro acetophenones, bis- chloro- 3- fluoro acetophenones of 6- are raw material, and phenyl-pentafluoride is prepared through acetophenone nitrilation, chlorination and fluorination
Formonitrile HCN；The route has the advantages that raw material is cheap and easy to get, operating procedure is simple, product yield high, cost is relatively low, while realizing pair
The comprehensive utilization of product, has saved resource, protects environment, has higher industrial value.
The technical proposal for solving the technical problem of the invention is：
A kind of preparation method of phenyl-pentafluoride formonitrile HCN, includes the following steps：
(1) by bis- chloro- 3- fluoro acetophenones of raw material 2,6-, copper salt catalyst, phase transfer catalyst tetrabutylammonium bromide and molten
Agent A's is added in autoclave, is passed through ammonia and oxygen carries out cyanation, under 100~200 DEG C, 2~10atm pressure, instead
Answer 5~10h to obtain 2,6-, bis- chloro- 3- fluorobenzonitriles, wherein the copper salt catalyst be cuprous iodide or copper trifluoromethanesulfcomposite or
Copper sulphate or copper acetate；
(2) the bis- chloro- 3- fluorobenzonitriles of 2,6- that step (1) obtains under catalyst are subjected to chlorination reaction and obtain 2,3,
4,6- tetra- chloro- 5- fluorobenzonitriles, reaction temperature are 80~120 DEG C, and the reaction time is 8~12h；
(3) 2,3,4,6- tetra- chloro- 5- fluorobenzonitriles, potassium fluoride and the phase transfer catalyst for obtaining step (2), in solvent
Fluorination reaction is carried out in B, obtains final product phenyl-pentafluoride formonitrile HCN, and reaction temperature is 150~270 DEG C, and the reaction time is 6~20h.
The synthetic route that the present invention uses can indicate as follows with chemical equation：
Preferably, the quality of the copper salt catalyst is the 5%~20% of the quality of 2,6-, bis- chloro- 3- fluoro acetophenones.
Preferably, the volume ratio of the ammonia and oxygen described in step (1) is 2:3.
Preferably, the solvent A described in step (1) is sulfolane, DMSO, DMF, NMP or DMAC, the dosage of solvent A
For 0.5~2mL/g 2,6-, bis- chloro- 3- fluoro acetophenones.
Preferably, the catalyst described in step (2) is ferric trichloride or ferric bromide, the quality of catalyst is 2,
The 5%~20% of bis- chloro- 3- fluorobenzonitriles quality of 6-.
Preferably, the amount of the substance of potassium fluoride described in step (3) is 2,3,4,6- tetra- chloro- 5- fluorobenzonitriles substances
4.0~5.0 times of amount.
Preferably, the solvent B described in step (3) is sulfolane, DMSO, DMF, NMP or DMAC, the dosage of solvent B
For 1~3mL/g 2,3,4,6-, tetra- chloro- 5- fluorobenzonitriles.
Preferably, the method that step (3) uses the distillation of side border ring, in time steams product phenyl-pentafluoride formonitrile HCN from system
It distillates and, collect 162~164 DEG C of fractions, when flowing out without cut goes out, that is, think that reaction terminates；After reaction, reaction system first drops
Warm cold filtration removes a large amount of inorganic salts, then collect organic phase (including a small amount of unreacted raw material and solvent B) into
Enter next batch to apply mechanically.
Compared with the existing technology, advantage is embodied in the present invention：
(1) with produce 2,4-, bis- chloro- 5- fluoro acetophenones by-product be raw material, it is not only cheap and easy to get, even more turn waste into wealth,
The recycling of by-product reduces the discharge of waste, improves the competitiveness of product in market, is conducive to industrialize extensive life
Production；
(2) each step involved in synthetic route reaction is common reaction, and operating condition is stablized, and yield is preferable；
(3) the organic solvent boiling point used in each step reaction involved in synthetic route is all higher, and high temperature loss is smaller,
And it can be effectively reduced the discharge of pollutant with recycled, operation is simplified, environment is protected；
(4) have raw material easy using phenyl-pentafluoride formonitrile HCN made from this law compared to the synthetic method of traditional phenyl-pentafluoride formonitrile HCN
, impurity is few, the high advantage of purity.
Specific implementation mode
The invention will be further described below, but technical parameter involved in scheme cannot be interpreted as to the present invention
Limitation.
Embodiment 1：The preparation of bis- chloro- 3- fluorobenzonitriles of 2,6-
In the autoclave of 500mL, solvent sulfolane 100mL, 19.1g cuprous iodide and 16.0g phase transfer catalysis (PTC)s is added
Agent tetrabutylammonium bromide, bis- chloro- 3- fluoro acetophenones of 200g2,6-, is vigorously stirred, 110~120 DEG C is warming up to, with 2:3 ratios are logical
Enter oxygen and ammonia, react 6h, reaction terminates to distill to obtain 2,6-, bis- chloro- 3- fluorobenzonitriles 148.2g.
Embodiment 2：The preparation of bis- chloro- 3- fluorobenzonitriles of 2,6-
All steps are same as Example 1 in the present embodiment, and difference lies in be changed to 33.0g trifluoros 19.1g cuprous iodides
Copper methane sulfonate, obtain 2,6-, bis- chloro- 3- fluorobenzonitriles 165.9g.
Embodiment 3：The preparation of bis- chloro- 3- fluorobenzonitriles of 2,6-
All steps are same as Example 1 in the present embodiment, and difference lies in be changed to 16.0g sulfuric acid 19.1g cuprous iodides
Copper obtains 2,6-, bis- chloro- 3- fluorobenzonitriles 101.2g.
Embodiment 4：The preparation of bis- chloro- 3- fluorobenzonitriles of 2,6-
All steps are same as Example 1 in the present embodiment, and difference lies in be changed to 18.0g acetic acid 19.1g cuprous iodides
Copper obtains 2,6-, bis- chloro- 3- fluorobenzonitriles 157.6g.
Embodiment 5：The preparation of tetra- chloro- 5- fluorobenzonitriles of 2,3,4,6-
In tetra- mouthfuls of reaction bulbs of 1000mL, above-mentioned 2,6-, bis- chloro- 3- fluorobenzonitriles 200g and ferric trichloride 16g are added, rise
Temperature is vigorously stirred to 120~125 DEG C, while being passed through chlorine, is reacted 8h, is then evaporated under reduced pressure to 2,3,4,6- tetra- chloro- 5- fluorobenzene
Formonitrile HCN 242.8g.
Embodiment 6：The preparation of tetra- chloro- 5- fluorobenzonitriles of 2,3,4,6-
All steps are same as Example 5 in the present embodiment, and difference lies in react 12h, obtain 2,3,4,6- tetra- chloro- 5- fluorine
Benzonitrile 262.6g.
Embodiment 7：The preparation of tetra- chloro- 5- fluorobenzonitriles of 2,3,4,6-
All steps are same as Example 5 in the present embodiment, and difference lies at 160~165 DEG C, react 8h, filter
Tetra- chloro- 5- fluorobenzonitriles 265.2g of 2,3,4,6-.
Embodiment 8：The preparation of tetra- chloro- 5- fluorobenzonitriles of 2,3,4,6-
All steps are same as Example 7 in the present embodiment, react 12h, obtain 2,3,4,6- tetra- chloro- 5- fluorobenzonitriles
271.5g。
Embodiment 9：The preparation of phenyl-pentafluoride formonitrile HCN
In tetra- mouthfuls of reaction bulbs of 1000mL, above-mentioned 2,3,4,6- tetra- chloro- 5- fluorobenzonitriles 200g, KF196g is added, phase turns
Shifting catalyst tetrabutylammonium bromide 16.0g and sulfolane 200mL is warming up to 160 DEG C, and flow back 8h, then collects 162~164 DEG C
Fraction, until flowing out without cut goes out, cooling down, the fraction received is phenyl-pentafluoride formonitrile HCN crude product, and liquid phase is catalyst and sulfolane
Mixed system recyclable apply mechanically next batch；The phenyl-pentafluoride formonitrile HCN crude product of gained is subjected to air-distillation and obtains the production of phenyl-pentafluoride formonitrile HCN
Product 104.8g, (HPLC detects phenyl-pentafluoride formonitrile HCN content 99.7%, and retention time is consistent with standard items).
Embodiment 10：The preparation of phenyl-pentafluoride formonitrile HCN
All steps are same as Example 9 in the present embodiment, and difference lies in be changed to 217g KF dosages, obtain phenyl-pentafluoride
Formonitrile HCN product 107.8g (HPLC detects phenyl-pentafluoride formonitrile HCN content 99.7%, and retention time is consistent with standard items).
Embodiment 11：The preparation of phenyl-pentafluoride formonitrile HCN
All steps are same as Example 9 in the present embodiment, difference lies in, reaction temperature is changed to 240 DEG C by 160 DEG C,
Obtain phenyl-pentafluoride formonitrile HCN product 137.8g (HPLC detects phenyl-pentafluoride formonitrile HCN content 99.7%, and retention time is consistent with standard items).
Embodiment 12：The preparation of phenyl-pentafluoride formonitrile HCN
All steps are identical as embodiment 11 in the present embodiment, and difference lies in be changed to 217g, phenyl-pentafluoride formonitrile HCN KF dosages
Product 145.9g (HPLC detects phenyl-pentafluoride formonitrile HCN content 99.7%, and retention time is consistent with standard items) or more only lists this hair
Bright preferred embodiment, protection scope of the present invention are not restricted to this, and those skilled in the art are in the claims in the present invention
Any change made by range is each fallen in the scope of the present invention.
The preferred embodiments of the invention are only listed above, and protection scope of the present invention is not restricted to this, this field
Technical staff within the scope of the invention as claimed made by it is any change each fall in the scope of the present invention.
Claims (7)
1. a kind of preparation method of phenyl-pentafluoride formonitrile HCN, which is characterized in that include the following steps：
（1）Bis- chloro- 3- fluoro acetophenones of raw material 2,6-, copper salt catalyst, phase transfer catalyst tetrabutylammonium bromide and solvent A are added
Enter into autoclave, is passed through ammonia and oxygen carries out cyanation, under 100~200 DEG C, 2~10atm pressure, reaction 5~
10h obtains 2,6-, bis- chloro- 3- fluorobenzonitriles, wherein the copper salt catalyst is cuprous iodide or copper trifluoromethanesulfcomposite or sulfuric acid
Copper or copper acetate；
（2）By step（1）Obtained bis- chloro- 3- fluorobenzonitriles of 2,6- carry out chlorination reaction under catalyst and obtain 2,3,4,6-
Four chloro- 5- fluorobenzonitriles, reaction temperature are 80~120 DEG C, and the reaction time is 8~12h；
（3）By step（2）2 obtained, 3,4,6- tetra- chloro- 5- fluorobenzonitriles, potassium fluoride and phase transfer catalyst, in solvent B
Fluorination reaction is carried out, final product phenyl-pentafluoride formonitrile HCN is obtained, reaction temperature is 150~270 DEG C, and the reaction time is 6~20h.
2. a kind of preparation method of phenyl-pentafluoride formonitrile HCN according to claim 1, which is characterized in that step（1）Described in
Solvent A is sulfolane, DMSO, DMF, NMP or DMAC, and the dosage of solvent A is 0.5~2mL/g 2, bis- chloro- 3- fluorophenethyls of 6-
Ketone.
3. a kind of preparation method of phenyl-pentafluoride formonitrile HCN according to claim 1, which is characterized in that step（1）Described in
The volume ratio of ammonia and oxygen is 2:3.
4. a kind of preparation method of phenyl-pentafluoride formonitrile HCN according to claim 1, which is characterized in that step（2）Described in
Catalyst is ferric trichloride or ferric bromide, and the quality of catalyst is the 5%~20% of 2,6-, bis- chloro- 3- fluorobenzonitriles quality.
5. a kind of preparation method of phenyl-pentafluoride formonitrile HCN according to claim 1, which is characterized in that step（3）Described in
The amount of the substance of potassium fluoride is 4.0~5.0 times of the amount of tetra- chloro- 5- fluorobenzonitriles substances of 2,3,4,6-.
6. a kind of preparation method of phenyl-pentafluoride formonitrile HCN according to claim 1, which is characterized in that step（3）Described in
Solvent B is sulfolane, DMSO, DMF, NMP or DMAC, and the dosage of solvent B is 1~3 mL/g, 2,3,4,6- tetra- chloro- 5- fluorobenzene
Formonitrile HCN.
7. a kind of preparation method of phenyl-pentafluoride formonitrile HCN according to claim 1, which is characterized in that step（3）It is anti-using side
The method for answering side to distill, in time distills product phenyl-pentafluoride formonitrile HCN from system, collects 162~164 DEG C of fractions, no fraction
When outflow, that is, think that reaction terminates；After reaction, reaction system elder generation cooling down is filtered to remove a large amount of inorganic salts, then
Collection organic phase enters next batch and applies mechanically.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1026290A (en) * | 1964-03-17 | 1966-04-14 | Robert Neville Haszeldine | Aromatic fluorine compounds |
| CN104151196A (en) * | 2014-07-16 | 2014-11-19 | 上海华谊（集团）公司 | Preparation method of 2,3,4,5,6-pentafluorobenzonitrile |
| CN105732429A (en) * | 2014-12-12 | 2016-07-06 | 江苏维尤纳特精细化工有限公司 | Pentafluorobenzonitrile production method |
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2017
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1026290A (en) * | 1964-03-17 | 1966-04-14 | Robert Neville Haszeldine | Aromatic fluorine compounds |
| CN104151196A (en) * | 2014-07-16 | 2014-11-19 | 上海华谊（集团）公司 | Preparation method of 2,3,4,5,6-pentafluorobenzonitrile |
| CN105732429A (en) * | 2014-12-12 | 2016-07-06 | 江苏维尤纳特精细化工有限公司 | Pentafluorobenzonitrile production method |
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