CN115611717A - Preparation method of polyfluorobenzaldehyde - Google Patents
Preparation method of polyfluorobenzaldehyde Download PDFInfo
- Publication number
- CN115611717A CN115611717A CN202211357870.5A CN202211357870A CN115611717A CN 115611717 A CN115611717 A CN 115611717A CN 202211357870 A CN202211357870 A CN 202211357870A CN 115611717 A CN115611717 A CN 115611717A
- Authority
- CN
- China
- Prior art keywords
- dichlorofluorobenzene
- substituted
- formula
- reaction
- chloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- -1 chloromethyl-substituted dichlorofluorobenzene Chemical class 0.000 claims abstract description 85
- 238000006243 chemical reaction Methods 0.000 claims abstract description 60
- NPXCSDPOOVOVDQ-UHFFFAOYSA-N 1,2-dichloro-3-fluorobenzene Chemical class FC1=CC=CC(Cl)=C1Cl NPXCSDPOOVOVDQ-UHFFFAOYSA-N 0.000 claims abstract description 39
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 31
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 26
- 238000007265 chloromethylation reaction Methods 0.000 claims abstract description 23
- 238000003682 fluorination reaction Methods 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 20
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims abstract description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 10
- 150000003935 benzaldehydes Chemical class 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 20
- 239000003054 catalyst Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229920002866 paraformaldehyde Polymers 0.000 claims description 11
- 235000003270 potassium fluoride Nutrition 0.000 claims description 10
- 239000011698 potassium fluoride Substances 0.000 claims description 10
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 10
- CYIFJRXFYSUBFW-UHFFFAOYSA-N 2,4,5-trifluorobenzaldehyde Chemical group FC1=CC(F)=C(C=O)C=C1F CYIFJRXFYSUBFW-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 claims description 9
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 8
- 235000019253 formic acid Nutrition 0.000 claims description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 8
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 claims description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 8
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 8
- UQEDGFZRPSAHLC-UHFFFAOYSA-N 2,3,4-trifluorobenzaldehyde Chemical group FC1=CC=C(C=O)C(F)=C1F UQEDGFZRPSAHLC-UHFFFAOYSA-N 0.000 claims description 7
- KPJIEPBITZLHPQ-UHFFFAOYSA-N 2,4,6-trifluorobenzaldehyde Chemical group FC1=CC(F)=C(C=O)C(F)=C1 KPJIEPBITZLHPQ-UHFFFAOYSA-N 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 239000011261 inert gas Substances 0.000 claims description 7
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 7
- 229910052725 zinc Inorganic materials 0.000 claims description 7
- 239000011701 zinc Substances 0.000 claims description 7
- 235000005074 zinc chloride Nutrition 0.000 claims description 7
- 239000011592 zinc chloride Substances 0.000 claims description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- 239000012320 chlorinating reagent Substances 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- CURILSCKLROVMZ-UHFFFAOYSA-N 1,5-dichloro-2-(chloromethyl)-3-fluorobenzene Chemical compound Fc1cc(Cl)cc(Cl)c1CCl CURILSCKLROVMZ-UHFFFAOYSA-N 0.000 claims description 5
- FKRWWHUGFKOPRN-UHFFFAOYSA-N 1,5-dichloro-2-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC(CCl)=C(Cl)C=C1Cl FKRWWHUGFKOPRN-UHFFFAOYSA-N 0.000 claims description 5
- SABAFIAZCVXLNN-UHFFFAOYSA-N 2,4-dichloro-3-fluorobenzaldehyde Chemical compound FC1=C(Cl)C=CC(C=O)=C1Cl SABAFIAZCVXLNN-UHFFFAOYSA-N 0.000 claims description 5
- WGCCHXURNGWJIW-UHFFFAOYSA-N 2,4-dichloro-5-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=C(Cl)C=C1Cl WGCCHXURNGWJIW-UHFFFAOYSA-N 0.000 claims description 5
- KDTLZLPZFUJFRU-UHFFFAOYSA-N 2,4-dichloro-6-fluorobenzaldehyde Chemical compound FC1=CC(Cl)=CC(Cl)=C1C=O KDTLZLPZFUJFRU-UHFFFAOYSA-N 0.000 claims description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 5
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 claims description 5
- 239000003444 phase transfer catalyst Substances 0.000 claims description 5
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 claims description 4
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 4
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 4
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 claims description 4
- BRKFQVAOMSWFDU-UHFFFAOYSA-M tetraphenylphosphanium;bromide Chemical compound [Br-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BRKFQVAOMSWFDU-UHFFFAOYSA-M 0.000 claims description 4
- CEYYIKYYFSTQRU-UHFFFAOYSA-M trimethyl(tetradecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)C CEYYIKYYFSTQRU-UHFFFAOYSA-M 0.000 claims description 4
- YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 claims description 4
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 3
- JORVCRLRRRRLFI-UHFFFAOYSA-N 1,3-dichloro-2-fluorobenzene Chemical compound FC1=C(Cl)C=CC=C1Cl JORVCRLRRRRLFI-UHFFFAOYSA-N 0.000 claims description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 3
- BLWGKIXZAUOECS-UHFFFAOYSA-N 1,3-dichloro-5-fluorobenzene Chemical compound FC1=CC(Cl)=CC(Cl)=C1 BLWGKIXZAUOECS-UHFFFAOYSA-N 0.000 claims description 3
- BDJZCCWUSOZUQG-UHFFFAOYSA-N 2,4-dichloro-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1Cl BDJZCCWUSOZUQG-UHFFFAOYSA-N 0.000 claims description 3
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 3
- ICXVJVVYSULERR-UHFFFAOYSA-L dichlorozinc hexahydrate Chemical compound O.O.O.O.O.O.Cl[Zn]Cl ICXVJVVYSULERR-UHFFFAOYSA-L 0.000 claims description 3
- 230000000977 initiatory effect Effects 0.000 claims description 3
- 229910052743 krypton Inorganic materials 0.000 claims description 3
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052754 neon Inorganic materials 0.000 claims description 3
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004246 zinc acetate Substances 0.000 claims description 3
- RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 claims description 2
- XILPLWOGHPSJBK-UHFFFAOYSA-N 1,2-dichloro-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Cl)C(Cl)=C1 XILPLWOGHPSJBK-UHFFFAOYSA-N 0.000 claims description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- 150000003983 crown ethers Chemical class 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 claims description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000001256 steam distillation Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical class C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 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 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001944 continuous distillation Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 239000005457 ice water 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
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940072132 quinolone antibacterials Drugs 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/14—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the side-chain of aromatic 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
- C07C17/32—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by introduction of halogenated alkyl groups into ring compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/42—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis
- C07C45/43—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis of >CX2 groups, X being halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/55—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing halogen
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Abstract
The invention relates to the technical field of organic synthesis, in particular to a preparation method of polyfluorobenzaldehyde, which comprises the following steps: 1) Carrying out chloromethylation reaction on substituted dichlorofluorobenzene shown as a formula I to obtain chloromethyl substituted dichlorofluorobenzene shown as a formula II; 2) Carrying out chlorination reaction on the chloromethyl-substituted dichlorofluorobenzene provided by the step 1) shown in the formula II to obtain dichloromethyl-substituted dichlorofluorobenzene shown in the formula II'; 3) Carrying out hydrolysis reaction on dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' provided by the step 2) to obtain formyl-substituted dichlorofluorobenzene shown in the formula III; 4) Carrying out fluorination reaction on the formyl group substituted dichlorofluorobenzene provided by the step 2) and shown in the formula III to obtain the polyfluorinated benzaldehyde shown in the formula IV. The method has the advantages of short reaction route, high conversion rate and universal applicability.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of polyfluorobenzaldehyde.
Background
Trifluorobenzaldehyde is an important fine chemical intermediate and can be used for synthesizing various medical liquid crystal materials. For example, 2,4,5-trifluorobenzaldehyde can be used for synthesizing hypotensor sitagliptin, 2,4,6-trifluorobenzaldehyde can be used for synthesizing medicines Bicteravir developed by Gilidide corporation for treating HIV, 2,3,4-trifluorobenzaldehyde can be used for synthesizing various 2,3,4-trifluorodiphenylacetylene liquid crystal compounds, and can also be used for synthesizing quinolone antibacterial medicines such as widely used sarcin antibiotics like ofloxacin, lomefloxacin, norfloxacin and the like. The prior art has the defects of long reaction route, low conversion rate and the like in the preparation of the trifluorobenzaldehyde.
Disclosure of Invention
In view of the above-mentioned disadvantages of the prior art, the present invention aims to provide a method for preparing polyfluorobenzaldehyde, which is used for solving the problems in the prior art.
In order to achieve the above objects and other related objects, one aspect of the present invention provides a method for preparing polyfluorobenzaldehyde represented by formula IV, comprising the steps of:
1) Performing chloromethylation reaction on the substituted dichlorofluorobenzene shown in the formula I to obtain chloromethyl substituted dichlorofluorobenzene shown in the formula II,
wherein R is 1 、R 2 、R 3 One of which is fluorine and the remainder hydrogen;
2) Carrying out chlorination reaction on the dichlorofluorobenzene substituted by chloromethyl shown in the formula II provided in the step 1) to obtain dichloromethyl-substituted dichlorofluorobenzene shown in a formula II';
3) Carrying out hydrolysis reaction on dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' provided by the step 2) to obtain formyl-substituted dichlorofluorobenzene shown in a formula III;
4) Carrying out fluorination reaction on the dichloro fluorobenzene substituted by the formyl group shown in the formula III provided by the step 3) to obtain polyfluorinated benzaldehyde shown in the formula IV;
on the other hand, the invention provides polyfluorobenzaldehyde shown as a formula IV, which is prepared by the preparation method.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a brand-new preparation method of polyfluorobenzaldehyde, which adopts easily-purchased chemical raw materials, adopts a short reaction route, and has the advantages of good reaction positioning property, safe, simple and easy reaction, less three wastes, high conversion rate and universal applicability by a series of green, environment-friendly and safe reaction processes.
Detailed Description
The inventor of the invention provides a preparation method of polyfluorobenzaldehyde shown as a formula IV through a large amount of researches, and the polyfluorobenzaldehyde is prepared through chloromethylation reaction, hydrolysis reaction and fluorination reaction.
The invention provides a preparation method of polyfluorobenzaldehyde shown as a formula IV in a first aspect, which comprises the following steps:
1) Performing chloromethylation reaction on the substituted dichlorofluorobenzene shown in the formula I to obtain chloromethyl substituted dichlorofluorobenzene shown in the formula II,
wherein R is 1 、R 2 、R 3 One of which is fluorine and the remainder hydrogen;
2) The dichlorofluorobenzene substituted by chloromethyl shown in the formula II provided in the step 1) is further subjected to chlorination reaction to obtain dichloromethyl substituted dichlorofluorobenzene shown in a formula II',
3) Carrying out hydrolysis reaction on dichloromethyl-substituted dichlorofluorobenzene provided by the step 2) to obtain formyl-substituted dichlorofluorobenzene shown in a formula III;
4) Carrying out fluorination reaction on the dichloro fluorobenzene substituted by the formyl group shown in the formula III provided by the step 3) to obtain polyfluorinated benzaldehyde shown in the formula IV;
in one embodiment of the present invention, when R 1 Is fluorine, R 2 、R 3 When hydrogen is present, the substituted dichlorofluorobenzene represented by the formula I is
2,6-dichlorofluorobenzene, the chloromethyl-substituted dichlorofluorobenzene shown in the formula II is
2,6-dichloro-3-chloromethylfluorobenzene (also named 2,4-dichloro-3-fluorobenzyl chloride), wherein the dichloromethyl-substituted dichlorofluorobenzene represented by the formula II' is
2,4-dichloro-3-fluorodichlorobenzyl (also known under the name 1,3-dichloro-4-dichloromethyl-2-fluorobenzene). The formyl-substituted dichlorofluorobenzene shown in the formula III is
2,6-dichloro-3-formylfluorobenzene (which may also be named 2,4-dichloro-3-fluorobenzaldehyde), wherein the polyfluorobenzaldehyde shown in the formula IV is
2,3,4-trifluorobenzaldehyde;
in another embodiment of the present invention, when R 2 Is fluorine, R1 2 、R 3 When hydrogen is present, the substituted dichlorofluorobenzene represented by the formula I is
2,4-dichlorofluorobenzene, the chloromethyl-substituted dichlorofluorobenzene shown in the formula II is
2,4-dichloro-5-chloromethylfluorobenzene (also named 2,4-dichloro-5-fluorobenzyl chloride), wherein the dichloromethyl-substituted dichlorofluorobenzene represented by the formula II' is
2,4-dichloro-5-fluorodichlorobenzyl. The formyl-substituted dichlorofluorobenzene shown in the formula III is
2,4-dichloro-5-formylfluorobenzene (which may also be named 2,4-dichloro-5-fluorobenzaldehyde), wherein the polyfluorobenzaldehyde shown in the formula IV is
2,4,5-trifluorobenzaldehyde.
In still another embodiment of the present invention, when R 3 Is fluorine, R 1 、R 2 When hydrogen is present, the substituted dichlorofluorobenzene represented by the formula I is
3,5-dichlorofluorobenzene, the chloromethyl-substituted dichlorofluorobenzene shown in the formula II is
3,5-dichloro-2-chloromethylfluorobenzene (also named 2,4-dichloro-6-fluorobenzyl chloride), wherein the dichloromethyl-substituted dichlorofluorobenzene represented by the formula II' is
2,4-dichloro-6-fluorodichlorobenzyl, the formyl-substituted dichlorofluorobenzene shown in the formula III is
3,5-dichloro-2-formylfluorobenzene (which may also be named 2,4-dichloro-6-fluorobenzaldehyde), wherein the polyfluorobenzaldehyde shown in the formula IV is
2,4,6-trifluorobenzaldehyde.
In the preparation method of the polyfluorobenzaldehyde shown as the formula IV, the step 1) is to perform chloromethylation reaction on substituted dichlorofluorobenzene shown as the formula I to obtain chloromethyl-substituted dichlorofluorobenzene shown as the formula II;
wherein R is 1 、R 2 、R 3 One of which is fluorine and the remainder hydrogen.
In step 1) of the present invention, the chloromethylation reaction is carried out in the presence of paraformaldehyde. The molecular formula of paraformaldehyde is HO- (CH) 2 O) n -H, n =10-100. In some embodiments, the molar ratio of the paraformaldehyde to the substituted dichlorofluorobenzene of formula I can be, for example, 1 to 5:1. 1-1.2: 1. 1.2-2:1. or 2 to 5:1, etc. Preferably, the molar ratio of the paraformaldehyde to the substituted dichlorofluorobenzene shown in the formula I is 1.2-2:1.
in step 1) of the present invention, the chloromethylation reaction is usually carried out at a certain temperature and for a certain time. For example, the chloromethylation reaction temperature may be, for example, 10 to 80 ℃, 10 to 20 ℃, 20 to 50 ℃, or 50 to 80 ℃. Preferably, the chloromethylation reaction temperature may be, for example, 20 to 50 ℃. The reaction time of the chloromethylation reaction is 2 to 10 hours.
In step 1) of the present invention, the chloromethylation reaction is carried out in the presence of a chlorinating agent selected from hydrogen chloride gas and/or chlorosulfonic acid, etc. In some embodiments, the molar ratio of the chlorinating agent to the substituted dichlorofluorobenzene represented by the formula I may be, for example, 0.9 to 4:1. 0.9-1.5: 1. 1.5-2.5: 1. or 2.5-4:1, etc. Further, when the chlorinating agent is selected from hydrogen chloride, the chloromethylation reaction is carried out in the presence of an acid selected from sulfuric acid.
In step 1) of the invention, the chloromethylation reaction is carried out under the condition of a catalyst, and the catalyst is selected from one or more of anhydrous zinc chloride, zinc chloride hexahydrate and tetramethylammonium chloride. The molar ratio of catalyst to substituted dichlorofluorobenzene represented by the formula I may be 0.01 to 0.1: 1. 0.01-0.02: 1. 0.02-0.05:1. or 0.05-0.1:1, etc. The molar ratio of catalyst to substituted dichlorofluorobenzene represented by the formula I is preferably 0.02 to 0.05:1.
in the preparation method of the polyfluorobenzaldehyde shown as the formula IV, the step 2) is to perform chlorination reaction on the dichlorofluorobenzene substituted by chloromethyl shown as the formula II provided by the step 1) to obtain dichloromethyl substituted dichlorofluorobenzene shown as the formula II',
in the step 2), the chlorination reaction is carried out in the presence of chlorine gas. The chlorination reaction can adopt a photoinitiation method, and the reaction temperature can be 30-60 ℃, 30-40 ℃, 40-50 ℃, or 50-60 ℃ and the like during the photoinitiation chlorination reaction. The chlorination reaction can also adopt a thermal initiation method, and the reaction temperature can be 70-100 ℃, 70-80 ℃, 80-90 ℃, or 90-100 ℃ and the like during the thermal initiation chlorination reaction. The chlorination reaction is carried out in the presence of a catalyst AIBN or BPO, and the dosage of the catalyst is 1 per thousand-1%, 1 per thousand-5 per thousand, 5 per thousand-1% and the like of the weight of the chloromethyl substituted dichlorofluorobenzene shown in the formula II. The chlorination reaction can be carried out in the presence of a solvent, and can be carried out in the absence of a solvent, and is selected from one or more of benzotrifluoride, p-chlorotrifluoromethane, nitrobenzene, 3,4-dichlorobenzotrifluoride, chlorobenzene, dichlorobenzene, trichlorobenzene, dichloroethane, and the like; the dosage of the solvent is 0.5 to 10 times, 0.5 to 1 time, 1 to 3 times, 3 to 5 times, 5 to 8 times, 8 to 10 times, and the like of the weight of the chloromethyl substituted dichlorofluorobenzene shown in the formula II. The content of dichloromethyl-substituted dichlorofluorobenzene shown in formula II 'is detected by GC in the chlorination reaction, and when the content of dichloromethyl-substituted dichlorofluorobenzene shown in formula II' is detected to be close to 50%, for example, the content is 45% -55%, or the content is 48% -52%, the reaction can be stopped, and the post-treatment can be carried out. The system can be cooled to room temperature, nitrogen is introduced to blow to remove the residual chlorine, then the system is distilled, and the separated chloromethyl substituted dichlorofluorobenzene shown as the formula II can be used for recycling and reusing; continuously separating and collecting dichloromethyl-substituted dichlorofluorobenzene shown in the formula II'; the residual kettle bottom materials are not used. When the content of dichloromethyl-substituted dichlorofluorobenzene shown as a formula II' is lower than 45% by GC detection in the chlorination reaction, the chlorination reaction is insufficient, and the conversion rate is low; when the content of dichloromethyl-substituted dichlorofluorobenzene shown in the formula II ' is higher than 55%, more than 3% of over-chlorinated compound II ' is generated in the reaction system, and the compound II ' causes difficulty in separation and purification of dichloromethyl-substituted dichlorofluorobenzene shown in the formula II ' and remains in the dichloromethyl-substituted dichlorofluorobenzene shown in the formula II ' to further influence the purity of subsequent products.
In the preparation method of the polyfluorobenzaldehyde shown as the formula IV, the step 3) is to perform hydrolysis reaction on dichloromethyl-substituted dichlorofluorobenzene shown as the formula II' provided by the step 2) to obtain formyl-substituted dichlorofluorobenzene shown as the formula III;
in step 3), the hydrolysis reaction is performed in the presence of a zinc reagent, wherein the zinc reagent is selected from one or more of zinc chloride, zinc acetate, and zinc acetate dihydrate. In the step 3), the molar ratio of the zinc reagent to the dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' can be 0.02-1: 1. 0.02-0.03: 1. 0.03-0.08:1. 0.08-0.1: 1. 0.1-1:1, etc. Preferably, the molar ratio of the zinc reagent to the dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' is 0.03-0.08:1.
in step 3), the hydrolysis is carried out in the presence of water, wherein the molar ratio of the water to dichloromethyl-substituted dichlorofluorobenzene shown as a formula II' is 0.9-2: 1. 0.9-1: 1. 1-1.5:1 or 1.5-2:1, etc. Preferably, the molar ratio of the water to the dichloromethyl-substituted dichlorofluorobenzene represented by the formula II' is 1 to 1.5:1.
in step 3), the hydrolysis reaction is carried out in the presence of formic acid, and the molar ratio of the formic acid to dichloromethyl-substituted dichlorofluorobenzene shown in II' is 3-10: 1. 3-4: 1. 4-6:1. or 6-10:1, etc. Preferably, the molar ratio of the formic acid to the dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' is 4-6:1.
in step 3) of the present invention, it is usually necessary to carry out the hydrolysis reaction at a temperature of 100 to 150 ℃, 100 to 115 ℃, 115 to 135 ℃, 135 to 150 ℃ or the like. Preferably, the temperature of the hydrolysis reaction is 115-135 ℃. The reaction time may be, for example, 3 to 10 hours, 3 to 5 hours, 5 to 8 hours, 8 to 10 hours, or the like.
In step 3), the hydrolysis reaction may be performed in the presence of a phase transfer catalyst selected from one or more of tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogen sulfate, tetramethylammonium chloride, tetrabutylammonium bromide, tetraethylammonium bromide, tetraphenylphosphonium bromide, 4-dimethylaminopyridine, polyethylene glycol, benzyltriethylammonium chloride, tetra-n-butylammonium fluoride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, and hexadecyltrimethylammonium bromide. In some embodiments, the phase transfer catalyst may be used in a molar ratio of the amount of the phase transfer catalyst to the dichloromethyl-substituted dichlorofluorobenzene represented by the formula II' of from 0.05 to 0.3:1. 0.05-0.1: 1. 0.1-0.15: 1. 0.15-0.2: 1. 0.2-0.25: 1. or 0.25 to 0.3:1, etc.
In step 3), the hydrolysis reaction is carried out under the protection of inert gas. The inert gas may be, for example, one or a combination of nitrogen, neon, argon, krypton, and the like.
In the preparation method of the polyfluorobenzaldehyde shown as the formula IV, the dichloro fluorobenzene substituted by the formyl group shown as the formula III in the step 4) is subjected to a fluorination reaction to obtain the polyfluorobenzaldehyde shown as the formula IV;
in the step 4), the fluorination reaction is carried out in an inert gas atmosphere; the inert gas may be, for example, one or a combination of nitrogen, neon, argon, krypton.
In the step 4), the fluorination reaction further comprises potassium fluoride; the molar ratio of the potassium fluoride to the formyl-substituted dichlorofluorobenzene represented by the formula III can be 2 to 5:1. 2-3: 1. 4-5: 1. or 4-5:1, etc.
In step 4) of the present invention, the fluorination reaction is usually carried out at a temperature of 100 to 180 ℃, 100 to 120 ℃, 120 to 150 ℃, or 150 to 180 ℃.
In step 4), the fluorination reaction further comprises a catalyst. The catalyst is selected from one or more of tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogen sulfate, tetramethylammonium chloride, tetrabutylammonium bromide, tetraethylammonium bromide, tetraphenylphosphonium bromide, 4-dimethylaminopyridine, polyethylene glycol, benzyltriethylammonium chloride, tetra-n-butylammonium fluoride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, crown ethers, and PEG. In some embodiments, the weight ratio of the catalyst to the formyl-substituted dichlorofluorobenzene represented by the formula III may be from 0.001 to 0.1: 1. 0.001-0.01: 1. 0.01-0.05: 1. or 0.05-0.1:1, etc.
In step 4), the invention further comprises a solvent selected from organic solvents, wherein the organic solvents are selected from one or more of 1,3-dimethyl imidazolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone, DMAc, DMF, DMSO, NMP, sulfolane, MIBK, imidazolidinone and the like. In some embodiments, the solvent is 0.5 to 10 times, 0.5 to 3 times, 3 to 8 times, 8 to 10 times, 0.5 to 2 times, 2 to 5 times, 5 to 8 times, 8 to 10 times, or the like, the weight of the formyl-substituted dichlorofluorobenzene represented by the formula III.
The invention provides polyfluorobenzaldehyde shown in a formula IV, which is prepared by the preparation method of the polyfluorobenzaldehyde according to the first aspect of the invention.
In conclusion, the invention provides a brand-new preparation method of polyfluorobenzaldehyde, which adopts easily-purchased chemical raw materials, adopts a short reaction route, passes through a series of green, environment-friendly and safe reaction processes, and has the advantages of good reaction positioning property, safe, simple and easy reaction, less three wastes, high conversion rate and universal applicability.
The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
It is to be understood that the processing equipment or apparatus not specifically identified in the following examples is conventional in the art.
Furthermore, it is to be understood that one or more method steps mentioned in the present invention does not exclude that other method steps may also be present before or after the combined steps or that other method steps may also be inserted between these explicitly mentioned steps, unless otherwise indicated; it is also to be understood that a combined connection between one or more devices/apparatus as referred to in the present application does not exclude that further devices/apparatus may be present before or after the combined device/apparatus or that further devices/apparatus may be interposed between two devices/apparatus explicitly referred to, unless otherwise indicated. Moreover, unless otherwise indicated, the numbering of the various method steps is merely a convenient tool for identifying the various method steps, and is not intended to limit the order in which the method steps are arranged or the scope of the invention in which the invention may be practiced, and changes or modifications in the relative relationship may be made without substantially changing the technical content.
Example 1
1) Chloromethylation reaction
Under nitrogen atmosphere at 20 + -3 deg.C, 10g paraformaldehyde, 100g 77% H 2 SO 4 And 5g of anhydrous ZnCl 2 Sequentially adding the mixture into a reaction bottle, stirring and adding 165g of 2, 6-dichlorofluorobenzene, and heating to 30-35 ℃. The hydrogen chloride gas was started. After 1h, the remaining 40g of paraformaldehyde and 400g 77% are added in portions 2 SO 4 . After the reaction is finished, stopping introducing hydrogen chloride gas, cooling to 20 +/-3 ℃, standing for liquid separation, washing an upper organic phase with brine, concentrating and rectifying to obtain 186.6g of GC99.92% and the yield of 87.4%.1H NMR (400MHZ, DMSO-d 6): δ 7.624-7.663= (m, 1h, ar-H), δ =7.520-7.545 (m, 1h, ar-H), δ =4.872 (s, 2h, ch) 2 )
2) Chlorination reaction
Mixing 2,4-dichloro-3-fluorobenzyl chloride 180g with dichloroethane 100g, adding catalyst AIBN 1g, heating and stirring to 70-80 deg.C; chlorine is slowly introduced into the saturated system, and after 16 hours of reaction, the content of 2,4-dichloro-3-fluorodichlorobenzyl is detected to be 49.6 percent. The temperature is reduced to room temperature, nitrogen purging is carried out for 30 minutes, and 105.1g of 2,4-dichloro-3-fluorodichlorobenzyl and 80g of raw material 2,4-dichloro-3-fluorobenzyl chloride are obtained by rectification. (yield in the chlorination reaction was 50.2%, and a reduced yield, that is, a yield after 80g of the starting material was recovered, was 90.5%)
1H NMR(400MHZ,DMSO-d6)：δ7.765-7.782＝(m,1H，Ar-H)，δ＝7.638-7.654(m,1H，Ar-H)，δ＝4.877(s,1H，CH)
Example 2
1) Chloromethylation reaction
12g of paraformaldehyde and 100g 77% of the total weight of the mixture at 20 + -3 ℃ under a nitrogen atmosphere 2 SO 4 And 9g of zinc chloride hexahydrate are sequentially added into a reaction bottle, 165g of 2, 4-dichlorofluorobenzene is added under stirring, and the temperature is increased to 30-35 ℃. The hydrogen chloride gas was started. Adding the remaining 48g of paraformaldehyde and 400g 77% in portions after the start of the reaction 2 SO 4 . After the reaction is finished, stopping introducing hydrogen chloride gas, cooling to 20 +/-3 ℃, standing for liquid separation, and separating an upper organic phaseAfter washing with brine, the product is concentrated and rectified to obtain 183.0g, GC98.89% and 85.7% yield.
1H NMR(400MHZ,DMSO-d6)：δ＝7.872-7.889(d,1H，Ar-H)，δ＝7.766-7.790(d,1H，Ar-H)，δ＝4.802(s,2H，CH 2 )。
2) Chlorination reaction
Adding 180g of 2,4-dichloro-5-fluorobenzyl chloride into 1g of AIBN catalyst, and heating and stirring to 40-50 ℃; ultraviolet fluorescence is started, chlorine is slowly introduced into the saturated system, and after 20 hours of reaction, the content of 2,4-dichloro-5-fluorodichlorobenzyl is detected to be 51.7 percent. Turning off the ultraviolet lamp, cooling to room temperature, purging with nitrogen for 30 minutes, and rectifying to obtain 2,4-dichloro-5-fluorodichlorobenzyl 108.9g and raw material 2,4-dichloro-5-fluorobenzyl chloride 74g. The starting material was recovered as above (yield 52.1% by chlorination reaction, 88.5% by reduced yield).
1H NMR(400MHZ,DMSO-d6)：δ＝7.885-7.901(d,1H,Ar-H)，δ＝7.787-7.808(d,1H,Ar-H)，δ＝4.822(s,1H,CH)
Example 3
1) Chloromethylation reaction
165g of 3, 5-dichlorofluorobenzene and 40g of paraformaldehyde (1.3 eq) are added into a reaction bottle, stirred and cooled to about 20 ℃, and 130g of chlorosulfonic acid (1.1 eq) is added dropwise, stirred and reacted for 2 hours at the temperature of 20-30 ℃. After the reaction is finished, the reaction solution is slowly poured into ice water under the condition of continuous stirring, the mixture is stirred and then stands for layering, the lower layer is a yellow organic phase, and distillation under reduced pressure is carried out to obtain 179.5g of distillate, the yield is 84.1%, and the GC detection content is 99.28%.
1 H NMR(DMSO-d 6 ,400MHz):δ7.509-7.613(m,2H,Ar-H),δ4.807(d,J＝1.2Hz,2H,CH 2 )。
2) Chlorination reaction
Adding 180g of 2,4-dichloro-6-fluorobenzyl chloride into 1g of AIBN catalyst, and heating and stirring to 40-50 ℃; ultraviolet fluorescence is started, chlorine is slowly introduced into the saturated system, and after reacting for 18 hours, the content of 2,4-dichloro-6-fluorodichlorobenzyl is 51.2 percent through GC sampling detection. And (3) turning off the ultraviolet lamp, cooling to room temperature, purging with nitrogen for 30 minutes, and distilling to obtain 2,4-dichloro-6-fluorodichlorobenzyl 108.3g and raw material 2,4-dichloro-6-fluorobenzyl chloride 71g. (yield in chlorination reaction 51.8%, conversion yield 85.6%)
1H NMR(DMSO-d6,400MHz):δ7.527-7.621(m,2H,Ar-H),δ4.819(d,J＝1.2Hz,1H,CH)
Example 4
And (3) hydrolysis reaction:
171g of 2, 4-dichloro-3-fluorodichlorobenzyl and 6g of zinc acetate are added at room temperature (20 +/-5 ℃), stirring is started, the mixture is heated to 120-130 ℃ in an oil bath, and water is slowly added dropwise while maintaining the temperature. After the reaction is finished, the temperature of the system is reduced to 25 +/-5 ℃, 30g of water is added for washing once, and the lower organic phase is washed by 10% sodium bicarbonate water solution until the pH value is about 7-8. Separating to obtain an organic phase, concentrating and purifying to obtain 120.4g of the product with the GC content of 99.96 percent and the yield of 90.4 percent.
Nuclear magnetism: 1H NMR (400MHZ, CDCl3): δ =10.392-10.395 (d, J =0.8hz,1h, cho), δ =7.685-7.709 (m, 1h, ar-H), δ =7.440-7.480 (m, 1h, ar-H).
Example 5
And (3) hydrolysis reaction:
171g of 2, 4-dichloro-3-fluorodichlorobenzyl and 7g of zinc acetate dihydrate are put into a four-neck flask, when the temperature is raised to be higher than 130 ℃, water is slowly dripped, the internal temperature of the four-neck flask is kept to be higher than 130 ℃, and the dripping is finished within about 30 min. After stirring for 1 hour, the temperature is reduced to 25 ℃, 100ml of dichloroethane and 100ml of water are added into the reaction solution, and the reaction solution is stirred and washed for half an hour. The organic phase of the lower layer was separated, distilled under reduced pressure, and the distillate was cooled to obtain 116.3g of a white solid, GC.
Example 6
And (3) hydrolysis reaction:
2,4-dichloro-5-fluoro-dichlorobenzyl (149g, 0.6mol, 1.00eq) and 3.4g anhydrous zinc chloride (0.041 eq) are put into a reaction bottle at room temperature, stirred under the protection of nitrogen, heated to 125 ℃, added with water dropwise, the temperature is controlled to 125-135 ℃, the reaction is very quick, and the reaction takes 2-3 hours to complete. The reaction can be stopped and the temperature can be reduced. A vacuum distillation device is built, and the product is distilled out, wherein the product is white crystal, the weight is 98.8g, the GC content is 99.94%, and the yield is 85.3%.
Nuclear magnetism: 1H NMR (DMSO-d 6, 400 MHz) δ 10.226-10.172 (m, 1H, CHO), δ 8.020-7.822 (m, 1H, ar-H), δ 7.794-7.651 (m, 1H, ar-H).
Example 7
And (3) hydrolysis reaction:
2,4-dichloro-5-fluoro-dichlorobenzyl (149g, 0.6mol, 1.00eq), 8g zinc acetate dihydrate and 100g formic acid are added, stirred, heated and reacted to 100 ℃, when the reaction temperature is less than or equal to 2 percent of raw materials, the heating is stopped, the mixture is naturally cooled to room temperature, dichloroethane is added for extraction, the dichloroethane phase is washed by water and then distilled, 101.6g of product is obtained, the GC detection shows that the yield is 99.28 percent, and the yield is 87.7 percent.
Example 8
And (3) hydrolysis reaction:
2,4-dichloro-6-fluoro-dichlorobenzyl (171g, 0.7mol, 1.00eq) and 3.9g anhydrous zinc chloride (0.041 eq) are put into a four-port reaction bottle, stirred and heated to 115-125 ℃ under the protection of nitrogen, the internal temperature is controlled to be more than or equal to 115 ℃, water is slowly dripped into the system, and the reaction is carried out for 5 hours. After the reaction, the temperature is reduced to room temperature, 60g of ethyl acetate is added and stirred, then the solvent and the water are distilled off, and the white crystals are obtained by continuous distillation, 112.9g of white crystals are obtained, and the yield is 83.6 percent by GC detection and 99.53 percent.
Example 9
And (3) hydrolysis reaction:
in a drying reaction vessel, 2,4-dichloro-6-fluoro-dichlorobenzyl (171g, 0.7mol, 1.00eq), 160g formic acid, 6g anhydrous zinc chloride and 1g tetrabutyl ammonium bromide are added under the protection of nitrogen, and the mixture is heated to 85 to 95 ℃ for reaction. After about 5 hours of reaction, the temperature is reduced to 20 to 30 ℃, dichloroethane is added for extraction at 150ml, the organic phase is separated, the organic phase is washed by water and NaHCO is used 3 The solution is washed until the pH value is neutral, an organic phase is separated, dichloroethane is removed, and the product 117.8g is obtained by distillation, the GC detection is 99.64 percent, and the yield is 87.2 percent.
1H NMR(DMSO-d 6 ,400MHz):δ10.247(s,1H,CHO),δ7.678～7.748(m,2H,Ar-H)。
Example 10
Fluorination reaction
Preparation of 2,3,4-trifluorobenzaldehyde
Under the protection of nitrogen, 80g of potassium fluoride, 3.5g of tetramethylammonium chloride and 500g of DMF500g are sequentially added into a reaction bottle, the stirring temperature is 150-155 ℃ for refluxing, 123g of 2,4-dichloro-3-fluorobenzaldehyde is added in batches, and the mixture is stirred, heated and refluxed for 2 hours. After the reaction is finished, the reaction product is cooled to room temperature, and after filtration, filtrate is directly distilled to obtain 2,4,5-trifluorobenzaldehyde, 91.9g of colorless transparent liquid, 99.01 percent of GC content and 90.1 percent of yield. 1 H NMR(400MHZ，CDCl3)：δ＝10.284(s，1H,CHO)，δ＝7.671-7.729(m，1H,Ar-H)，δ＝7.124-7.185(m，1H,Ar-H)
Example 11
Fluorination reaction
Preparation of 2,3,4-trifluorobenzaldehyde
Under the protection of nitrogen, 80g of potassium fluoride, 5.5g of tetrabutylammonium bromide and 600g of sulfolane are sequentially added into a reaction bottle, the temperature is raised to 150-155 ℃ by stirring, 2,4-dichloro-3-fluorobenzaldehyde 123g is added in batches, and the reaction is carried out at 150-155 ℃. After the reaction, the reaction mixture was cooled to room temperature (20 to 25 ℃), insoluble materials were removed by filtration, and the filtrate was distilled to give 2,4,5-trifluorobenzaldehyde as a colorless transparent liquid (92.3g, GC content 98.78%, yield 90.5%).
Example 12
Fluorination reaction
Preparation of 2,4,5-trifluorobenzaldehyde
Under the protection of nitrogen, 80g of potassium fluoride, 3g of tetramethylammonium chloride and 500g of DMF are sequentially added into a reaction bottle, stirred and heated to 150-155 ℃ for reflux, 123g of 2,4-dichloro-5-fluorobenzaldehyde is added in batches, and the mixture is stirred, heated and refluxed for 2 hours. After the reaction, the reaction mixture was cooled to room temperature, filtered, and the filtrate was distilled to obtain 2,4,5-trifluorobenzaldehyde as a colorless transparent liquid 91.6g, having a GC content of 98.90% and a yield of 89.8%.
1H NMR(DMSO-d6，400MHz):δ10.135(d，1H，CHO)，δ7.912～7.845(m，1H，Ar-H)，δ7.843～7.775(m，1H，Ar-H)
Example 13
Fluorination reaction
Preparation of 2,4,5-trifluorobenzaldehyde
Under the protection of nitrogen, 90g of potassium fluoride, 5g of tetrabutylammonium bromide and 550g of DMF are sequentially added into a reaction bottle, the stirring temperature is 150-155 ℃, reflux is carried out, 123g of 2,4-dichloro-5-fluorobenzaldehyde is added in batches, stirring and heating are carried out, and reflux is carried out for 2 hours. After the reaction is finished, the reaction product is cooled to room temperature, filtered, and the filtrate is subjected to steam distillation to obtain a mixed solution of 2,4,5-trifluorobenzaldehyde and water, 93.8g of colorless transparent liquid is obtained after layering, 92.5g of product is obtained after drying, the GC content is 99.17%, and the yield is 90.7%.
Example 14
Fluorination reaction
Preparation of 2,4,6-trifluorobenzaldehyde
Under the protection of nitrogen, 80g of potassium fluoride, 5.5g of tetrabutylammonium chloride and 550g of sulfolane are sequentially added into a reaction bottle, the temperature is raised to 150-155 ℃ by stirring, 123g of 2,4-dichloro-6-fluorobenzaldehyde is added in batches, the mixture is stirred and heated, and the reaction is carried out for 2 hours at the temperature of 150-155 ℃. After the reaction, the reaction mixture was cooled to room temperature, insoluble materials were removed by filtration, and the filtrate was subjected to steam distillation with water to give 2,4,6-trifluorobenzaldehyde, which was cooled to give 93.1g of a white solid with 98.73% GC content and 91.3% yield.
1H NMR(DMSO，400MHz):δ10.138(s，1H，CHO)，δ7.439～7.368(m，2H，Ar-H)
Example 15
Fluorination reaction
Preparation of 2,4,6-trifluorobenzaldehyde
Under the protection of nitrogen, 85g of potassium fluoride, 3.5g of tetramethylammonium chloride and 600g of DMF are sequentially added into a reaction bottle, stirred and refluxed, 123g of 2,4-dichloro-6-fluorobenzaldehyde is added in batches, stirred and heated, and refluxed for 2 hours. After the reaction, the reaction mixture was cooled to room temperature (about 25 ℃), filtered, and the filtrate was subjected to steam distillation with water, and the distillate was cooled to give 2,4,6-trifluorobenzaldehyde 94.0g, having a GC content of 99.31% and a yield of 92.2%.
In conclusion, the present invention effectively overcomes various disadvantages of the prior art and has high industrial utilization value.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which may be made by those skilled in the art without departing from the spirit and scope of the present invention as defined in the appended claims.
Claims (10)
1. A preparation method of polyfluorobenzaldehyde shown as a formula IV comprises the following steps:
1) Carrying out chloromethylation reaction on substituted dichlorofluorobenzene shown in a formula I to obtain chloromethyl substituted dichlorofluorobenzene shown in a formula II;
wherein R is 1 、R 2 、R 3 One of which is fluorine and the remainder hydrogen;
2) Carrying out chlorination reaction on the chloromethyl-substituted dichlorofluorobenzene provided by the step 1) shown in the formula II to obtain dichloromethyl-substituted dichlorofluorobenzene shown in the formula II';
3) Carrying out hydrolysis reaction on dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' provided by the step 2) to obtain formyl-substituted dichlorofluorobenzene shown in the formula III;
4) Carrying out fluorination reaction on the dichloro fluorobenzene substituted by the formyl group shown in the formula III provided by the step 3) to obtain polyfluorinated benzaldehyde shown in the formula IV;
2. the method of claim 1, wherein in step 1), the chloromethylation reaction is carried out in the presence of paraformaldehyde in a molar ratio of 1 to 5 of substituted dichlorofluorobenzene of formula I: 1;
and/or, in the step 1), the temperature of the chloromethylation reaction is 10-80 ℃;
and/or, in step 1), the chloromethylation reaction is carried out in the presence of a chlorinating agent selected from hydrogen chloride gas and/or chlorosulfonic acid.
3. The method of claim 2, wherein in step 1), the molar ratio of paraformaldehyde to substituted dichlorofluorobenzene having a formula I is 1.2 to 2:1;
and/or, in the step 1), the temperature of the chloromethylation reaction is 20-50 ℃;
and/or, in the step 1), the molar ratio of the dosage of the chlorinating reagent to the substituted dichlorofluorobenzene shown in the formula I is 0.9-4:1.
4. the process of claim 3, wherein in step 1), when the chlorinating agent is selected from the group consisting of hydrogen chloride, the chloromethylation reaction is carried out in the presence of an acid selected from the group consisting of sulfuric acid;
and/or, in the step 1), the chloromethylation reaction is carried out under the condition of a catalyst, and the catalyst is selected from one or more of anhydrous zinc chloride, zinc chloride hexahydrate and tetramethylammonium chloride.
5. The method of claim 1, wherein in step 2), the chlorination reaction is carried out in the presence of chlorine gas;
and/or the chlorination reaction is a photo-initiated chlorination reaction and/or a thermal-initiated chlorination reaction; preferably, the temperature of the photoinitiated chlorination reaction is 30-60 ℃; the reaction temperature of the thermal initiation chlorination reaction is 70-100 ℃;
and/or, the chlorination reaction further comprises a catalyst selected from AIBN or BPO; preferably, the amount of the catalyst is 1 per mill-1% of the weight of the chloromethyl substituted dichlorofluorobenzene shown in the formula II;
and/or, the chlorination reaction is carried out under the condition of solvent or no solvent; when the chlorination reaction includes a solvent, the solvent is selected from one or more of trifluorotoluene, p-chlorotrifluoromethane, nitrobenzene, 3,4-dichlorotrifluorotoluene, chlorobenzene, dichlorobenzene, trichlorobenzene, dichloroethane; preferably, the amount of the solvent is 0.5-10 times of the weight of the chloromethyl substituted dichlorofluorobenzene shown in the formula II;
and/or stopping the reaction when the content of dichloromethyl-substituted dichlorofluorobenzene shown as the formula II' is detected to be 45-55% in the chlorination reaction.
6. The method of claim 1, wherein in step 3), the hydrolysis reaction is carried out in the presence of a zinc reagent selected from the group consisting of zinc chloride, zinc acetate, and a combination of one or more of zinc acetate dihydrate;
and/or, in step 3), the hydrolysis reaction is carried out in the presence of water;
and/or, in step 3), the hydrolysis reaction is carried out in the presence of formic acid.
7. The method according to claim 6, wherein in step 3), the molar ratio of the zinc reagent to the dichloromethyl-substituted dichlorofluorobenzene represented by the formula II' is 0.02 to 1:1;
and/or, in the step 3), the molar ratio of the water to the dichloromethyl-substituted dichlorofluorobenzene shown as the formula II' is 0.9-2:1;
and/or, in the step 3), the molar ratio of the formic acid to the dichloromethyl-substituted dichlorofluorobenzene shown in the II' is 3-10:1;
and/or, in the step 3), the temperature of the hydrolysis reaction is 100-150 ℃;
and/or, in step 3), the hydrolysis reaction may be carried out in the presence of a phase transfer catalyst selected from one or more of tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogen sulfate, tetramethylammonium chloride, tetrabutylammonium bromide, tetraethylammonium bromide, tetraphenylphosphonium bromide, 4-dimethylaminopyridine, polyethylene glycol, benzyltriethylammonium chloride, tetra-n-butylammonium fluoride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide;
and/or, in the step 3), the hydrolysis reaction is carried out under the protection of inert gas.
8. The method according to claim 7, wherein in step 3), the molar ratio of the zinc reagent to the dichloromethyl-substituted dichlorofluorobenzene represented by II' is from 0.03 to 0.08:1;
and/or, in the step 3), the molar ratio of the water to the dichloromethyl-substituted dichlorofluorobenzene shown in the II' is 1-1.5:1;
and/or, in the step 3), the molar ratio of the formic acid to the dichloromethyl-substituted dichlorofluorobenzene shown in the II' is 4-6:1;
and/or, in the step 3), the temperature of the hydrolysis reaction is 115-135 ℃;
and/or, in the step 3), the molar ratio of the dosage of the phase transfer catalyst to the dichloromethyl-substituted dichlorofluorobenzene shown in the II' is 0.05-0.3:1.
9. the method of claim 1, wherein in step 4), the fluorination reaction is carried out under an inert gas atmosphere; preferably, the inert gas is selected from one or more of nitrogen, neon, argon and krypton;
and/or, in the step 4), potassium fluoride is also included in the fluorination reaction; the molar ratio of the potassium fluoride to the formyl-substituted dichlorofluorobenzene shown in the formula III is 2-5:1;
and/or, in the step 4), the temperature of the fluorination reaction is 100-180 ℃;
and/or, in the step 4), a catalyst is also included in the fluorination reaction; the catalyst is selected from one or more of tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogen sulfate, tetramethylammonium chloride, tetrabutylammonium bromide, tetraethylammonium bromide, tetraphenylphosphonium bromide, 4-dimethylaminopyridine, polyethylene glycol, benzyltriethylammonium chloride, tetra-n-butylammonium fluoride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, crown ethers, and PEG; preferably, the weight ratio of the catalyst to the formyl-substituted dichlorofluorobenzene shown in the formula III is 0.001 to 0.1:1;
and/or, in the step 4), a solvent is further included, wherein the solvent is selected from organic solvents, and the organic solvents are selected from one or more of 1,3-dimethyl imidazolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone, DMAc, DMF, DMSO, NMP, sulfolane, MIBK and imidazolidinone; preferably, the solvent is 0.5 to 10 times of the weight of the formyl-substituted dichlorofluorobenzene shown in the formula III.
10. The method of any one of claims 1 to 9, wherein when R is 1 Is fluorine, R 2 、R 3 When the fluorine is hydrogen, the substituted dichlorofluorobenzene shown in the formula I is 2,6-dichlorofluorobenzene, the chloromethyl-substituted dichlorofluorobenzene shown in the formula II is 2,6-dichloro-3-chloromethyl fluorobenzene, the dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' is 2,4-dichloro-3-fluorodichlorobenzyl, the formyl-substituted dichlorofluorobenzene shown in the formula III is 2,6-dichloro-3-formylfluorobenzene, and the polyfluorobenzaldehyde shown in the formula IV is 2,3,4-trifluorobenzaldehyde;
and/or when R 2 Is fluorine, R1 2 、R 3 When the fluorine is hydrogen, the substituted dichlorofluorobenzene shown in the formula I is 2,4-dichlorofluorobenzene, the chloromethyl-substituted dichlorofluorobenzene shown in the formula II is 2,4-dichloro-5-chloromethyl fluorobenzene, the dichloromethyl-substituted dichlorofluorobenzene shown in the formula II' is 2,4-dichloro-5-fluorodichlorobenzyl, the formyl-substituted dichlorofluorobenzene shown in the formula III is 2,4-dichloro-5-formylfluorobenzene, and the polyfluorobenzaldehyde shown in the formula IV is 2,4,5-trifluorobenzaldehyde;
and/or when R 3 Is fluorine, R 1 、R 2 When the fluorine is hydrogen, the substituted dichlorofluorobenzene shown as the formula I is 3,5-dichlorofluorobenzene, the chloromethyl substituted dichlorofluorobenzene shown as the formula II is 3,5-dichloro-2-chloromethyl fluorobenzene, and the formulaThe dichloromethyl-substituted dichlorofluorobenzene shown in II' is 2,4-dichloro-6-fluorodichlorobenzyl, the formyl-substituted dichlorofluorobenzene shown in the formula III is 3,5-dichloro-2-formylfluorobenzene, and the polyfluorobenzaldehyde shown in the formula IV is 2,4,6-trifluorobenzaldehyde.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN85101737A (en) * | 1984-06-04 | 1987-01-31 | 拜尔股份公司 | Preparation 2,4,5-trihalogenated benzene and 2,3,4, the derivative method of 5-tetrahalogeno-benzene |
| CN1212674A (en) * | 1996-03-07 | 1999-03-31 | 德国赫彻斯特研究技术两合公司 | Process for producing fluorinated aromatics and fluorinated nitrogen-containing hetero-aromatics |
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| CN85101737A (en) * | 1984-06-04 | 1987-01-31 | 拜尔股份公司 | Preparation 2,4,5-trihalogenated benzene and 2,3,4, the derivative method of 5-tetrahalogeno-benzene |
| CN1212674A (en) * | 1996-03-07 | 1999-03-31 | 德国赫彻斯特研究技术两合公司 | Process for producing fluorinated aromatics and fluorinated nitrogen-containing hetero-aromatics |
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