CN116969887A - Preparation process of intermediate 7-chloro 8-quinolinic acid and synthesis process of quinclorac - Google Patents
Preparation process of intermediate 7-chloro 8-quinolinic acid and synthesis process of quinclorac Download PDFInfo
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- CN116969887A CN116969887A CN202311238634.6A CN202311238634A CN116969887A CN 116969887 A CN116969887 A CN 116969887A CN 202311238634 A CN202311238634 A CN 202311238634A CN 116969887 A CN116969887 A CN 116969887A
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- chloride
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- quinolinic acid
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- XLHOYRWQJYJQGZ-UHFFFAOYSA-N 7-chloroquinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=C(Cl)C=CC2=C1 XLHOYRWQJYJQGZ-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 238000000034 method Methods 0.000 title claims abstract description 56
- 230000008569 process Effects 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- FFSSWMQPCJRCRV-UHFFFAOYSA-N quinclorac Chemical compound ClC1=CN=C2C(C(=O)O)=C(Cl)C=CC2=C1 FFSSWMQPCJRCRV-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 title abstract description 11
- 238000003786 synthesis reaction Methods 0.000 title abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 43
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 32
- 239000003054 catalyst Substances 0.000 claims abstract description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000007800 oxidant agent Substances 0.000 claims abstract description 26
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 24
- NKWDCLXGUJHNHS-UHFFFAOYSA-N 7-chloro-8-methylquinoline Chemical compound C1=CN=C2C(C)=C(Cl)C=CC2=C1 NKWDCLXGUJHNHS-UHFFFAOYSA-N 0.000 claims abstract description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 17
- 230000001590 oxidative effect Effects 0.000 claims abstract description 17
- 235000019270 ammonium chloride Nutrition 0.000 claims abstract description 12
- 239000011780 sodium chloride Substances 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- QMUNOGMHQDOTAP-UHFFFAOYSA-N 7-chloro-8-(chloromethyl)quinoline Chemical compound C1=CN=C2C(CCl)=C(Cl)C=CC2=C1 QMUNOGMHQDOTAP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000009471 action Effects 0.000 claims abstract description 6
- 229940125904 compound 1 Drugs 0.000 claims description 25
- 238000007254 oxidation reaction Methods 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 11
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 10
- ZNOKGRXACCSDPY-UHFFFAOYSA-N tungsten trioxide Chemical compound O=[W](=O)=O ZNOKGRXACCSDPY-UHFFFAOYSA-N 0.000 claims description 10
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 claims description 6
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 6
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 5
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 5
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-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
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 5
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 5
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 5
- FNPNRZLYTIVLNO-UHFFFAOYSA-N Cl(=O)(=O)(=O)O.C1(=C(C(=CC(=C1)C)C)C1C2=CC=CC=C2N(C=2C=CC=CC12)C)C Chemical compound Cl(=O)(=O)(=O)O.C1(=C(C(=CC(=C1)C)C)C1C2=CC=CC=C2N(C=2C=CC=CC12)C)C FNPNRZLYTIVLNO-UHFFFAOYSA-N 0.000 claims description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 5
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 5
- 229910021607 Silver chloride Inorganic materials 0.000 claims description 5
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 5
- 229940011182 cobalt acetate Drugs 0.000 claims description 5
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 claims description 5
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 5
- 229940045803 cuprous chloride Drugs 0.000 claims description 5
- 229940117389 dichlorobenzene Drugs 0.000 claims description 5
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 5
- 229960002089 ferrous chloride Drugs 0.000 claims description 5
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 5
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 5
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 5
- -1 ketone acetate Chemical class 0.000 claims description 5
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 5
- 229910052750 molybdenum Inorganic materials 0.000 claims description 5
- 239000011733 molybdenum Substances 0.000 claims description 5
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 claims description 5
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical group CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 claims description 5
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 claims description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 5
- 229950009390 symclosene Drugs 0.000 claims description 5
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 238000009776 industrial production Methods 0.000 abstract description 6
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 14
- 239000000047 product Substances 0.000 description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 239000002699 waste material Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 239000011206 ternary composite Substances 0.000 description 4
- 238000010924 continuous production Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000002341 toxic gas Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 241000192043 Echinochloa Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 238000006757 chemical reactions by type Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 241000533849 Gleditsia Species 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000010812 mixed waste Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006400 oxidative hydrolysis reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000004065 wastewater treatment Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The application relates to a preparation process of an intermediate 7-chloro-8-quinolinic acid and a synthesis process of quinclorac. The preparation process comprises the following steps: a first chlorination step of carrying out a monochlorination reaction on 7-chloro-8-methylquinoline by using a chlorinating agent under the action of a catalyst to obtain 7-chloro-8-chloromethylquinoline; the chlorinating agent is any chloride generated by the real-time reaction of hydrochloric acid, sodium chloride or ammonium chloride and an oxidant; in the first chlorination step, air or oxygen is introduced to obtain the intermediate 7-chloro-8-quinolinic acid. The process has the advantages of less necessary steps, high yield, high purity, environmental friendliness and suitability for industrial production.
Description
Technical Field
The application belongs to the field of chemical industry, relates to a preparation process of an intermediate 7-chloro-8-quinolinic acid and a synthesis process of quinclorac, and in particular relates to a preparation process of an intermediate 7-chloro-8-quinolinic acid and a synthesis process of quinclorac, which are more environment-friendly and more suitable for industrialization.
Background
The quinclorac, also called 3, 7-dichloro-8-quinolinecarboxylic acid, is used as a herbicide for paddy fields with remarkable drug effect, is used for preventing barnyard grass, gleditsia, armywort and the like in direct seeding paddy fields and transplanted paddy fields, has remarkable effect on barnyard grass, is safe for crops, and has the application time not limited by weed growth stage.
The prior art has a conventional technology of a quinclorac synthesis technology. One of the preparation processes is shown in the following scheme (1), and takes aniline and glycerin as main raw materials, and the process is synthesized through three steps of condensation, chlorination, oxidative hydrolysis
Route (1)
In the synthetic process of quinclorac, a nitric acid solution is dropwise added into a concentrated sulfuric acid medium to oxidize various chlorides of 7-chloro-8-methylquinoline, the time required for dropwise addition and heat preservation is 20-24 hours, and the time required for dropwise addition and heat preservation is 2.5-3 times of the time required for a condensation process or a chlorination process, so that the expansion of productivity is obviously limited by the oxidation process. Meanwhile, when nitric acid is used as an oxidant, the input amount is large. It is calculated that the production of 1 ton of quinclorac requires the elimination of 1.5 tons of 98% concentrated nitric acid, thereby necessarily producing a large amount of spent acid. Because the waste acid is very difficult to process, the mixed waste acid treatment becomes the bottleneck for the expansion production of quinclorac in chemical plants. In addition, nitric acid is used as an oxidant, so that nitro compounds are generated in the product, and the quality of the final product is affected.
In view of the above problems, although the prior patent document CN101337929 provides a new oxidizing agent, the oxidizing agent can effectively improve the problems that the oxidation process time is too long, the productivity is limited, and the generated waste acid is not easy to treat, etc. However, the problem of treating the wastewater produced in this method still remains. In addition, it was found through verification that only chlorinated products of dichloro and trichloro can be oxidized, and that the resulting mono-chlorinated intermediate in which the substituent at the 8-position is substituted with one chlorine atom cannot be oxidized (as shown in the following conventional reaction formula (1)), which results in that post-treatments such as separation, impurity removal and the like are necessary operations of the process.
Existing reaction type (1)
Further, another patent document CN103420909 discloses that the oxidation reaction step is performed in the presence of a Co-Mn-Br ternary composite catalyst; the addition amount of the Co-Mn-Br ternary composite catalyst in the oxidation reaction step is calculated by Co, and the molar ratio of Co to the chloride of 7-chloro-8-methylquinoline is 0.001-0.1:1; the molar ratio of the components of the ternary composite catalyst is Co/Mn of 0.1-10:1, and Br/(Co+Mn) of 0.01-10:1; in the presence of a ternary composite catalyst, introducing gas containing oxygen molecules into a chloride system of 7-chloro-8-methylquinoline taking aliphatic carboxylic acid as a solvent, wherein the reaction temperature is 100-255 ℃, and the reaction pressure is 0.5-3 Mpa. The method utilizes air or oxygen to carry out oxidation reaction, thereby fundamentally solving the wastewater treatment problem of the oxidation process. However, it has been experimentally verified that in the chloride system of 7-chloro-8-methylquinoline, the dichlorinated and trichlorinated products are hardly oxidized (as shown in the existing reaction formula (2)); the ratio of the chloride of the monochloro to the chloride of the dichloro is more than 9:1, and the oxidation can be well carried out.
Existing reaction type (2)
Considering the conventional synthetic process of quinclorac, the reaction process is difficult to stay in the stage of the monochlorinated product, and the separation of the monochlorinated product and the dichlorinated product is difficult and time-consuming. In general, the laboratory usually adopts post-treatment such as chromatographic column separation and the like, and then carries out subsequent reaction, which hardly meets the requirements of industrial production on productivity and efficiency.
It is not difficult to find that the existing synthetic process of the intermediate 7-chloro-8-quinolinic acid (M1) and/or quinclorac described above has the following disadvantages:
1. when chlorine is used for chlorination in the traditional process, the substituent at the 8-position is replaced by chlorine atoms to form monochlorides, dichlorides, trichlorides and the like, and the chloride mixtures have various limiting requirements on subsequent oxidation operation and are easy to chlorinate N heterocycle, so that separation and purification are required after intermediate formation of a organism to enter the next step.
2. The oxidation process of the existing intermediate M1 generates a large amount of waste acid water, and the waste acid water treatment cost is high, so that the production cost is obviously increased; excess and residual sodium hypochlorite also generates toxic gases during the acidification process, which can be harmful to the environment and operators.
3. The purity of the quinclorac product prepared by the traditional process is only 88-92%, and the purity can be improved to be more than 97% only by a complicated purification procedure.
Aiming at the defects existing in the prior art, the inventor aims at providing an environment-friendly preparation process of an intermediate 7-chloro 8-quinolinic acid (M1) and a synthesis process of quinclorac, which are more suitable for industrial production, and meanwhile, the application is expected to greatly reduce the production cost and improve the productivity.
Disclosure of Invention
An object of the present application is to provide a new, more environmentally friendly and lower cost process for the preparation of the intermediate 7-chloro-8-quinolinic acid (M1). Specifically, a preparation process of an intermediate 7-chloro 8-quinolinic acid (M1), the preparation process (as shown in the scheme (2)) comprises:
a first chlorination step of carrying out a monochlorination reaction on 7-chloro-8-methylquinoline (compound 1) by using a chlorinating agent under the action of a catalyst to obtain 7-chloro-8-chloromethylquinoline; wherein: the catalyst is any one selected from N-hydroxyphthalimide, cobalt acetate, cuprous chloride, silver chloride, tetrabutylammonium chloride, azodiisobutyronitrile, 10-methyl-9-mesityl acridine perchlorate, ferrous chloride, ketone acetate, molybdenum hexacarbonyl, benzoyl peroxide, tungsten trioxide and ferric trichloride; the chlorinating agent is any chloride generated by the real-time reaction of hydrochloric acid, sodium chloride or ammonium chloride and an oxidant; and
and in the first chloridizing reaction, air or oxygen is introduced to perform oxidation reaction to obtain the intermediate 7-chloro 8-quinolinic acid (M1).
Route (2)
Wherein in the first chlorination step, the oxidant used for the real-time reaction to generate the chlorinating agent is selected from any one of conventional oxidants, preferably hydrogen peroxide.
Alternatively, in the first chlorination step, the chlorinating agent is any one selected from trichloroisocyanuric acid, chlorosuccinimide, sulfonyl chloride, t-butyl hypochlorite, hypochlorous acid, perchloric acid, and sodium hypochlorite.
Further, in the first chlorination step, the monochlorination reaction is performed in a solvent selected from any one of carbon tetrachloride, chloroform, methylene chloride, dichloroethane, chloropropane, chlorobutane, chlorobenzene, dichlorobenzene, acetic acid, acetonitrile, benzene, propyl ether, butyl ether, methyl tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, anisole, tetrahydrofuran, methyl tetrahydrofuran, dioxane.
Further, the weight ratio of the solvent to the compound 1 is 0.1-10:1; preferably, 0.5-5:1; more preferably 0.8-3:1.
Further, the molar ratio of the compound 1 to the catalyst is 1:0.005-1.0; preferably, 1:0.05-0.5; more preferably, 1:0.05-0.2.
Further, the molar ratio of the compound 1 to the hydrochloric acid or sodium chloride or ammonium chloride is 1:0.5-10; preferably, 1:1-6; more preferably 1:2-4.
Further, the molar ratio of the compound 1 to the oxidant is 1:0.5-10; preferably, 1:1-8; further preferably 1:2-6.
Further, the temperature of the first chlorination reaction and the oxidation reaction is 0-200 ℃; preferably, the temperature is 30-150 ℃; more preferably, the temperature is 50-100 ℃.
Another object of the present application is to provide a new, more environmentally friendly, lower cost process for synthesizing quinclorac, in particular, a process for synthesizing quinclorac, which comprises (as shown in the scheme (3):
a first chlorination step of carrying out a monochlorination reaction on 7-chloro-8-methylquinoline (compound 1) by using a chlorinating agent under the action of a catalyst to obtain 7-chloro-8-chloromethylquinoline; wherein: the catalyst is any one selected from N-hydroxyphthalimide, cobalt acetate, cuprous chloride, silver chloride, tetrabutylammonium chloride, azodiisobutyronitrile, 10-methyl-9-mesityl acridine perchlorate, ferrous chloride, ketone acetate, molybdenum hexacarbonyl, benzoyl peroxide, tungsten trioxide and ferric trichloride; the chlorinating agent is any chloride generated by the real-time reaction of hydrochloric acid, sodium chloride or ammonium chloride and an oxidant; and
an oxidation step, in which air or oxygen is introduced in the first chlorination step to perform an oxidation reaction, thereby obtaining an intermediate 7-chloro 8-quinolinic acid (M1); and
and a second chlorination step, in which the intermediate M1 is subjected to chlorination reaction by using a chlorinating agent under the condition of having a catalyst or not to obtain quinclorac.
Route (3)
Wherein in the first chlorination step, the oxidant used for the real-time reaction to generate the chlorinating agent is selected from any one of conventional oxidants, preferably hydrogen peroxide.
Alternatively, in the first chlorination step, the chlorinating agent is any one selected from trichloroisocyanuric acid, chlorosuccinimide, sulfonyl chloride, t-butyl hypochlorite, hypochlorous acid, perchloric acid, and sodium hypochlorite.
Further, in the first chlorination step, the monochlorination reaction is performed in a solvent selected from any one of carbon tetrachloride, chloroform, methylene chloride, dichloroethane, chloropropane, chlorobutane, chlorobenzene, dichlorobenzene, acetic acid, acetonitrile, benzene, propyl ether, butyl ether, methyl tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, anisole, tetrahydrofuran, methyl tetrahydrofuran, dioxane.
Further, the weight ratio of the solvent to the compound 1 is 0.1-10:1; preferably, 0.5-5:1; more preferably 0.8-3:1.
Further, the molar ratio of the compound 1 to the catalyst is 1:0.005-1.0; preferably, 1:0.05-0.5; more preferably, 1:0.05-0.2.
Further, the molar ratio of the compound 1 to the hydrochloric acid or sodium chloride or ammonium chloride is 1:0.5-10; preferably, 1:1-6; more preferably 1:2-4.
Further, the molar ratio of the compound 1 to the oxidant is 1:0.5-10; preferably, 1:1-8; further preferably 1:2-6.
Further, the temperature of the first chlorination reaction and the oxidation reaction is 0-200 ℃; preferably, the temperature is 30-150 ℃; more preferably, the temperature is 50-100 ℃.
Advantageous effects
According to the technical scheme, the application overcomes the technical defects in the prior art, and obtains a preparation process of an intermediate 7-chloro 8-quinolinic acid (M1) and a synthesis process of quinclorac, wherein the preparation process is more environment-friendly and is more suitable for industrial production. The two processes avoid the use of chlorine for chlorination, the intermediate product of the first step of chlorination is not a complex chloride mixture, but a single chloride with high content, and the oxidation reaction can be carried out without post-treatment, so that the three wastes are obviously reduced, and the pollution to the environment is essentially avoided.
Moreover, the production cost is reduced from the raw materials such as reactants, solvents and the like and the operation conditions, the high-temperature and high-pressure reaction conditions are not needed, a large amount of strong acid and toxic gas are not needed, the amount of generated wastewater is obviously reduced, and the material cost is greatly reduced; the method has the advantages of fewer necessary steps, simple operation, high yield and high purity of the intermediate M1, is suitable for directly carrying out subsequent chlorination reaction, does not need intermediate operations such as separation, purification and the like, greatly reduces the time cost, improves the efficiency, truly realizes continuous production, and is more suitable for industrial production.
In addition, the intermediate M1 prepared by the process has higher yield and purity, the yield is more than 95 percent, and the purity is more than 98 percent.
Detailed Description
The technical solution of the present application is further explained below with reference to the specific embodiments, but the present application is not limited in any way, and any modification, alteration or equivalent substitution method that can be implemented by those skilled in the art to which the present application pertains will fall within the scope of the claims of the present application without departing from the technical solution of the present application.
The experimental methods used in the following examples are conventional methods unless otherwise specified. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
The continuous preparation process of the intermediate 7-chloro 8-quinolinic acid (M1) and the synthesis process of quinclorac are conventional methods without special description by selecting proper catalysts and reactants and controlling specific parameters such as the addition amount and the molar ratio of the reactants at a reduced reaction temperature, thereby improving the reaction rate of different steps, the production amount of the products and the yield and the purity of better intermediate products.
The overall yield in the following examples was obtained according to the following formula:
total yield = molar amount of compound 2 represented by formula (2)/molar amount of compound 1 represented by formula (1) ×100%
In the following examples, the purity of the compound 2 represented by the formula (2) was measured by liquid chromatography.
In the following examples, the reactants 7-chloro-8-methylquinoline, catalyst, oxidant, chlorinating agent, etc. are all commercially available.
In some embodiments, the present application provides a process for preparing an intermediate 7-chloro 8-quinolinic acid (M1), the process (as shown in scheme (2)) comprising:
a first chlorination step of carrying out a monochlorination reaction on 7-chloro-8-methylquinoline (compound 1) by using a chlorinating agent under the action of a catalyst to obtain 7-chloro-8-chloromethylquinoline; wherein: the catalyst is any one selected from N-hydroxyphthalimide, cobalt acetate, cuprous chloride, silver chloride, tetrabutylammonium chloride, azodiisobutyronitrile, 10-methyl-9-mesityl acridine perchlorate, ferrous chloride, ketone acetate, molybdenum hexacarbonyl, benzoyl peroxide, tungsten trioxide and ferric trichloride; the chlorinating agent is any chloride generated by the real-time reaction of hydrochloric acid, sodium chloride or ammonium chloride and an oxidant; and
and in the first chloridizing reaction, air or oxygen is introduced to perform oxidation reaction to obtain the intermediate 7-chloro 8-quinolinic acid (M1).
Route (2)
Wherein in the first chlorination step, the oxidant used for the real-time reaction to generate the chlorinating agent is selected from any one of conventional oxidants, preferably hydrogen peroxide.
Alternatively, in the first chlorination step, the chlorinating agent is any one selected from trichloroisocyanuric acid, chlorosuccinimide, sulfonyl chloride, t-butyl hypochlorite, hypochlorous acid, perchloric acid, and sodium hypochlorite.
Further, in the first chlorination step, the monochlorination reaction is performed in a solvent selected from any one of carbon tetrachloride, chloroform, methylene chloride, dichloroethane, chloropropane, chlorobutane, chlorobenzene, dichlorobenzene, acetic acid, acetonitrile, benzene, propyl ether, butyl ether, methyl tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, anisole, tetrahydrofuran, methyl tetrahydrofuran, dioxane.
Further, the weight ratio of the solvent to the compound 1 is 0.1-10:1; preferably, 0.5-5:1; more preferably 0.8-3:1.
Further, the molar ratio of the compound 1 to the catalyst is 1:0.005-1.0; preferably, 1:0.05-0.5; more preferably, 1:0.05-0.2.
Further, the molar ratio of the compound 1 to the hydrochloric acid or sodium chloride or ammonium chloride is 1:0.5-10; preferably, 1:1-6; more preferably 1:2-4.
Further, the molar ratio of the compound 1 to the oxidant is 1:0.5-10; preferably, 1:1-8; further preferably 1:2-6.
Further, the temperature of the first chlorination reaction and the oxidation reaction is 0-200 ℃; preferably, the temperature is 30-150 ℃; more preferably, the temperature is 50-100 ℃.
In other embodiments, the application provides a process for synthesizing quinclorac, the process comprising (as shown in scheme (3):
a first chlorination step of carrying out a monochlorination reaction on 7-chloro-8-methylquinoline (compound 1) by using a chlorinating agent under the action of a catalyst to obtain 7-chloro-8-chloromethylquinoline; wherein: the catalyst is any one selected from N-hydroxyphthalimide, cobalt acetate, cuprous chloride, silver chloride, tetrabutylammonium chloride, azodiisobutyronitrile, 10-methyl-9-mesityl acridine perchlorate, ferrous chloride, ketone acetate, molybdenum hexacarbonyl, benzoyl peroxide, tungsten trioxide and ferric trichloride; the chlorinating agent is any chloride generated by the real-time reaction of hydrochloric acid, sodium chloride or ammonium chloride and an oxidant; and
an oxidation step, in which air or oxygen is introduced in the first chlorination reaction process to perform an oxidation reaction to obtain an intermediate 7-chloro 8-quinolinic acid (M1); and
and a second chlorination step, in which the intermediate M1 is subjected to chlorination reaction by using a chlorinating agent under the condition of having a catalyst or not to obtain quinclorac.
Route (3)
Wherein in the first chlorination step, the oxidant used for the real-time reaction to generate the chlorinating agent is selected from any one of conventional oxidants, preferably hydrogen peroxide.
Alternatively, in the first chlorination step, the chlorinating agent is any one selected from trichloroisocyanuric acid, chlorosuccinimide, sulfonyl chloride, t-butyl hypochlorite, hypochlorous acid, perchloric acid, and sodium hypochlorite.
Further, in the first chlorination step, the monochlorination reaction is performed in a solvent selected from any one of carbon tetrachloride, chloroform, methylene chloride, dichloroethane, chloropropane, chlorobutane, chlorobenzene, dichlorobenzene, acetic acid, acetonitrile, benzene, propyl ether, butyl ether, methyl tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, anisole, tetrahydrofuran, methyl tetrahydrofuran, dioxane.
Further, the weight ratio of the solvent to the compound 1 is 0.1-10:1; preferably, 0.5-5:1; more preferably 0.8-3:1.
Further, the molar ratio of the compound 1 to the catalyst is 1:0.005-1.0; preferably, 1:0.05-0.5; more preferably, 1:0.05-0.2.
Further, the molar ratio of the compound 1 to the hydrochloric acid or sodium chloride or ammonium chloride is 1:0.5-10; preferably, 1:1-6; more preferably 1:2-4.
Further, the molar ratio of the compound 1 to the oxidant is 1:0.5-10; preferably, 1:1-8; further preferably 1:2-6.
Further, the temperature of the first chlorination reaction and the oxidation reaction is 0-200 ℃; preferably, the temperature is 30-150 ℃; more preferably, the temperature is 50-100 ℃.
Example 1
To a 500ml reaction flask were successively added 17.8g (0.1 mol) of 7-chloro-8-methylquinoline, 50ml of DCE, 0.6g of TBAC, 50g of water, 24.5g (0.2 mol) of 30% hydrochloric acid. Heating to 80℃and flowing 9.7g (0.1 mol) of 35% H 2 O 2 The reaction system was added dropwise. After the completion of the dropwise addition, reaction 4 h was refluxed and incubated.
Sampling HPLC analysis, when the area percentage of 7-chloro-8-methylquinoline is < =0.5%, the sampling is qualified. Neutralizing to pH7 with alkali solution. The aqueous phase was separated off, the organic phase was distilled and DCE recovered. The residue was identified, which was mainly crystallized from methanol, and was suction-filtered and dried to obtain 20.6g of intermediate 7-chloro-8-methylquinoline (M1).
Warp yarn 1 H NM identification, intermediate M1 purity 98%, yield 95%. The nuclear magnetic pattern is as follows:
1 H NMR：(500MHz,CDCl 3 )δ=7.52~8.93(m,5H)，4.64(m,5H);
13 C NMR：(500MHz,CDCl 3 ) δ=155.5(C),150.5(CH),136.5(CH),135.4(C),133.8(C),129.2(CH),126.5(C),124.0(CH),121.0(CH), 36.7(CH2).
comparative examples 1 to 6
Following the procedure of example 1, different solvents, catalysts were selected, and the yield and purity of intermediate M1 were tested and evaluated, with 0.1mol of starting reactant 7-chloro-8-methylquinoline. The specific solvents, catalysts, chlorinating and oxidizing agents and reaction conditions and yields of intermediate M1 are shown in table 1.
TABLE 1 reactions and results for the different comparative examples 1-6
Example 2
To a 500ml reaction flask was added 5g Cu (OAc) in order 2 •H 2 O, N-hydroxyphthalimide 16g,200ml CH 2 Cl 2 17.8g (0.1 mol) of 7-chloro-8-methylquinoline. Stirred at 25 ℃ for 30min, then 0.1 equiv. trichloroisocyanuric acid (TCCA) was added in portions. After addition, the reaction was stirred at 25℃for 17-22h, and ice water was added to the reaction mass, followed by extraction with DCM and MgSO 4 Drying and distilling to recover DCM. The residue was identified, and was subjected to suction filtration and drying, mainly using methanol crystals, to obtain intermediate 7-chloro-8-methylquinoline (M1) and intermediate 7-chloro-8-methylquinoline (M1) 20g.
Warp yarn 1 HNM and 13 c NMR identified that intermediate M1 was 98% pure in 94% yield. Referring to example 1, nuclear magnetic resonance spectroscopy data was supplemented:
1 H NMR：(500MHz,CDCl 3 ) δ=7.52~8.93(m,5H)，4.64(m,5H);
13 CNMR: (500MHz,CDCl 3 )δ=155.5(C),150.5(CH),136.5(CH),135.4(C),133.8(C),129.2(CH), 126.5(C),124.0(CH),121.0(CH), 36.7(CH2)。
comparative examples 7 to 13
Following the procedure of example 2, different solvents, catalysts were selected, and the yield and purity of intermediate M1 were tested and evaluated, with starting reactant 7-chloro-8-methylquinoline being 0.1mol. Specific solvents, catalysts, chlorinating and oxidizing agents and reaction conditions and yields of intermediate M1 are shown in table 2.
TABLE 2 reactions and results for the different comparative examples 7-13
As can be seen from comparing the chlorinating agents used in example 1 and comparative examples 1-6, comparative examples 3-4 respectively used ammonium chloride and sodium chloride as the chlorinating agent, and the provided chloride ions involved in the chlorination reaction, and then subjected to the oxidation reaction, the product yield was significantly lower than that of other comparative examples using hydrochloric acid as the chlorinating agent; the yields of comparative examples 5-6 were significantly higher than the other comparative examples 1-4. Moreover, the product yields of comparative examples 1-6 were all significantly lower than example 1. Comparing the chlorinating agents used in example 2 and comparative examples 7-13, it can be seen that the yields of the products of comparative examples 9-11 are significantly lower than those of the other comparative examples and example 2.
From the above examples and comparative examples, the preparation process of the present application can obtain intermediate M1 with higher purity and yield, and in the preferred embodiment, the purity of intermediate M1 obtained by the preparation process of the present application can reach about 98%, the yield reaches more than 95%, and the operation is simple, so that the process is suitable for one-pot continuous production. When other catalyst and chlorinating agent combinations are selected, the manufacturing process generates hazardous exhaust gases such as chlorine, hydrogen chloride and oxygen, the use of sulfuric acid, acetic acid corrodes the production equipment, and a large amount of waste acid water is generated, so that the process is significantly inferior to the above-described embodiments of the present application in terms of environmental friendliness.
Therefore, the technical conception and the technical scheme of the application improve the preparation process of the existing synthetic intermediate 7-chloro 8-quinolinic acid (M1) and the synthesis process of quinclorac. The two processes avoid chlorine chlorination, the intermediate product of the first step of chlorination is not a complex chloride mixture, but a single chloride with high content, and the oxidation reaction can be carried out without post treatment, so that the three wastes are obviously reduced, the pollution to the environment is essentially avoided, the defects in the prior art are overcome, and the method is more suitable for industrial production. The process has the advantages of low raw material cost, few steps, simple operation, no need of high-temperature high-pressure reaction conditions, no need of using a large amount of waste acid water and toxic gas, and low production cost; in addition, the intermediate step does not need post-treatment operation, and continuous production can be truly realized.
Claims (9)
1. A process for preparing an intermediate 7-chloro 8-quinolinic acid (M1), characterized in that the process comprises, as shown in scheme (2):
route (2)
A first chlorination step of carrying out a monochlorination reaction on 7-chloro-8-methylquinoline by using a chlorinating agent under the action of a catalyst to obtain 7-chloro-8-chloromethylquinoline; wherein:
the catalyst is any one selected from N-hydroxyphthalimide, cobalt acetate, cuprous chloride, silver chloride, tetrabutylammonium chloride, azodiisobutyronitrile, 10-methyl-9-mesityl acridine perchlorate, ferrous chloride, ketone acetate, molybdenum hexacarbonyl, benzoyl peroxide, tungsten trioxide and ferric trichloride;
the chlorinating agent is any chloride generated by the real-time reaction of hydrochloric acid, sodium chloride or ammonium chloride and an oxidant; and
and in the first chloridizing reaction, air or oxygen is introduced to perform oxidation reaction to obtain the intermediate 7-chloro 8-quinolinic acid (M1).
2. Process for the preparation of the intermediate 7-chloro 8-quinolinic acid (M1) according to claim 1, characterized in that in the first chlorination step, alternatively the chlorinating agent is any one selected from trichloroisocyanuric acid, chlorosuccinimide, sulfonyl chloride, t-butyl hypochlorite, hypochlorous acid, perchloric acid, sodium hypochlorite.
3. Process for the preparation of the intermediate 7-chloro 8-quinolinic acid (M1) according to claim 1 or 2, characterized in that in the first chlorination step the monochlorination reaction is carried out in a solvent selected from any one of carbon tetrachloride, chloroform, dichloromethane, dichloroethane, chloropropane, chlorobutane, chlorobenzene, dichlorobenzene, acetic acid, acetonitrile, benzene, propyl ether, butyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, anisole, tetrahydrofuran, methyltetrahydrofuran, dioxane.
4. A process for the preparation of the intermediate 7-chloro 8-quinolinic acid (M1) according to claim 3, characterized in that the weight ratio of solvent to compound 1 is 0.1-10:1.
5. Process for the preparation of the intermediate 7-chloro-8-quinolinic acid (M1) according to claim 1 or 2, characterized in that the molar ratio of compound 1 to catalyst is between 1:0.005 and 1.0.
6. Process for the preparation of the intermediate 7-chloro 8-quinolinic acid (M1) according to claim 1, characterized in that the molar ratio of compound 1 to the hydrochloric acid or sodium chloride or ammonium chloride is 1:0.5-10.
7. The process for the preparation of intermediate 7-chloro 8-quinolinic acid (M1) according to claim 1, characterized in that the molar ratio of compound 1 to oxidizing agent is 1:0.5-10.
8. Process for the preparation of the intermediate 7-chloro 8-quinolinic acid (M1) according to claim 1, characterized in that the temperature of the first chlorination reaction and the oxidation reaction is between 0 and 200 ℃.
9. A process for synthesizing quinclorac, wherein the process comprises, as shown in scheme (3):
route (3)
A process for the preparation of the intermediate 7-chloro-8-quinolinic acid (M1) according to any of the preceding claims 1-8; and
and a second chlorination step, in which the intermediate M1 is subjected to chlorination reaction by using a chlorinating agent under the condition of having a catalyst or not to obtain quinclorac.
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