CN116836061A - Method for separating mixed acid - Google Patents
Method for separating mixed acid Download PDFInfo
- Publication number
- CN116836061A CN116836061A CN202310528975.0A CN202310528975A CN116836061A CN 116836061 A CN116836061 A CN 116836061A CN 202310528975 A CN202310528975 A CN 202310528975A CN 116836061 A CN116836061 A CN 116836061A
- Authority
- CN
- China
- Prior art keywords
- methyl
- acid
- rectification
- nitrobenzoate
- mixed
- 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.)
- Pending
Links
- 239000002253 acid Substances 0.000 title claims abstract description 101
- 238000000034 method Methods 0.000 title claims abstract description 96
- 238000005886 esterification reaction Methods 0.000 claims abstract description 93
- YPQAFWHSMWWPLX-UHFFFAOYSA-N 1975-50-4 Chemical compound CC1=C(C(O)=O)C=CC=C1[N+]([O-])=O YPQAFWHSMWWPLX-UHFFFAOYSA-N 0.000 claims abstract description 89
- 230000007062 hydrolysis Effects 0.000 claims abstract description 70
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 70
- CCXSGQZMYLXTOI-UHFFFAOYSA-N 13506-76-8 Chemical compound CC1=CC=CC([N+]([O-])=O)=C1C(O)=O CCXSGQZMYLXTOI-UHFFFAOYSA-N 0.000 claims abstract description 67
- 230000032050 esterification Effects 0.000 claims abstract description 50
- 150000002148 esters Chemical class 0.000 claims abstract description 48
- 239000007788 liquid Substances 0.000 claims abstract description 38
- -1 3-nitro dimethyl dibenzoate Chemical compound 0.000 claims abstract description 35
- KFIRODWJCYBBHY-UHFFFAOYSA-N 3-nitrophthalic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1C(O)=O KFIRODWJCYBBHY-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000000926 separation method Methods 0.000 claims abstract description 22
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 50
- 238000006243 chemical reaction Methods 0.000 claims description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 238000002156 mixing Methods 0.000 claims description 41
- 238000003756 stirring Methods 0.000 claims description 29
- 239000002994 raw material Substances 0.000 claims description 27
- 230000010933 acylation Effects 0.000 claims description 23
- 238000005917 acylation reaction Methods 0.000 claims description 23
- 239000003054 catalyst Substances 0.000 claims description 23
- 229960001826 dimethylphthalate Drugs 0.000 claims description 22
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 19
- NIQCNGHVCWTJSM-UHFFFAOYSA-N dimethyl benzenedicarboxylate Natural products COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 claims description 17
- FBSAITBEAPNWJG-UHFFFAOYSA-N dimethyl phthalate Natural products CC(=O)OC1=CC=CC=C1OC(C)=O FBSAITBEAPNWJG-UHFFFAOYSA-N 0.000 claims description 17
- 150000001263 acyl chlorides Chemical class 0.000 claims description 15
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 14
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 14
- 239000003377 acid catalyst Substances 0.000 claims description 14
- 230000002378 acidificating effect Effects 0.000 claims description 12
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000011973 solid acid Substances 0.000 claims description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 4
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 4
- 239000005416 organic matter Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 68
- 238000004128 high performance liquid chromatography Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
- XPVBLOOMFDNJTH-UHFFFAOYSA-N methyl 2-methyl-6-nitrobenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1[N+]([O-])=O XPVBLOOMFDNJTH-UHFFFAOYSA-N 0.000 description 22
- 238000004821 distillation Methods 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- FVHAWXWFPBPFOS-UHFFFAOYSA-N 1,2-dimethyl-3-nitrobenzene Chemical class CC1=CC=CC([N+]([O-])=O)=C1C FVHAWXWFPBPFOS-UHFFFAOYSA-N 0.000 description 16
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 16
- 229910017604 nitric acid Inorganic materials 0.000 description 16
- 238000004321 preservation Methods 0.000 description 16
- 239000012065 filter cake Substances 0.000 description 15
- 239000003513 alkali Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 238000007254 oxidation reaction Methods 0.000 description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 11
- 239000003960 organic solvent Substances 0.000 description 11
- 230000003647 oxidation Effects 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 239000008096 xylene Substances 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 238000010533 azeotropic distillation Methods 0.000 description 5
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 5
- 229960002163 hydrogen peroxide Drugs 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 238000005070 sampling Methods 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012295 chemical reaction liquid Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000413 hydrolysate Substances 0.000 description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
- 229940011051 isopropyl acetate Drugs 0.000 description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- CRZGFIMLHZTLGT-UHFFFAOYSA-N methyl 2-methyl-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1C CRZGFIMLHZTLGT-UHFFFAOYSA-N 0.000 description 2
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 2
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 238000004537 pulping Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- KFIRODWJCYBBHY-UHFFFAOYSA-L 3-nitrophthalate Chemical compound [O-]C(=O)C1=CC=CC([N+]([O-])=O)=C1C([O-])=O KFIRODWJCYBBHY-UHFFFAOYSA-L 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000005485 Azilsartan Substances 0.000 description 1
- 239000005874 Bifenthrin Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000005917 Methoxyfenozide Substances 0.000 description 1
- 239000005810 Metrafenone Substances 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940072049 amyl acetate Drugs 0.000 description 1
- PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 description 1
- 229960002731 azilsartan Drugs 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- OMFRMAHOUUJSGP-IRHGGOMRSA-N bifenthrin Chemical compound C1=CC=C(C=2C=CC=CC=2)C(C)=C1COC(=O)[C@@H]1[C@H](\C=C(/Cl)C(F)(F)F)C1(C)C OMFRMAHOUUJSGP-IRHGGOMRSA-N 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012527 feed solution Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 229960004942 lenalidomide Drugs 0.000 description 1
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- QCAWEPFNJXQPAN-UHFFFAOYSA-N methoxyfenozide Chemical compound COC1=CC=CC(C(=O)NN(C(=O)C=2C=C(C)C=C(C)C=2)C(C)(C)C)=C1C QCAWEPFNJXQPAN-UHFFFAOYSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- AMSPWOYQQAWRRM-UHFFFAOYSA-N metrafenone Chemical compound COC1=CC=C(Br)C(C)=C1C(=O)C1=C(C)C=C(OC)C(OC)=C1OC AMSPWOYQQAWRRM-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 229960000688 pomalidomide Drugs 0.000 description 1
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/16—Separation; Purification; Stabilisation; Use of additives
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Abstract
The invention belongs to the technical field of organic matter separation, and particularly relates to a method for separating mixed acid. The invention provides a method for separating mixed acid, which comprises the following steps: carrying out esterification reaction on the mixed acid to obtain mixed ester; the mixed acid comprises 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the mixed ester comprises 3-nitro dimethyl dibenzoate, 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate; rectifying and hydrolyzing the mixed ester to obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively. The invention adopts a method combining esterification and rectification hydrolysis, and can realize the accurate separation of mixed acid; the separation process is simple and does not generate a large amount of waste liquid; meanwhile, the purity and the yield of the acid obtained by separation are higher.
Description
Technical Field
The invention belongs to the technical field of organic matter separation, and particularly relates to a method for separating mixed acid.
Background
In the oxidation reaction of mononitroxylenes, the oxidation of 3-nitroo-xylene has great application value, and the products of the 3-nitroo-xylene are 2-methyl-3-nitrobenzoic acid, 3-nitrophthalic acid and 2-methyl-6-nitrobenzoic acid, which are all very important intermediates. For example, 2-methyl-3-nitrobenzoic acid is an important raw material for the pesticide methoxyfenozide and the antitumor drug lenalidomide; the 3-nitrophthalic acid is an important intermediate of pesticide bifenthrin, medicinal candesartan, azilsartan and pomalidomide; 2-methyl-6-nitrobenzoic acid is an important synthetic raw material of pesticide bactericide metrafenone.
Because the oxidation products 2-methyl-3-nitrobenzoic acid, 2-methyl-6-nitrobenzoic acid and 3-nitrophthalic acid all have the characteristic of high boiling point (> 300 ℃) and the boiling points of the 2-methyl-3-nitrobenzoic acid and the 2-methyl-6-nitrobenzoic acid are approximate, the separation of all the 2-methyl-3-nitrobenzoic acid and the 2-methyl-6-nitrobenzoic acid is very difficult.
The separation method in the prior art is mainly a recrystallization method, but the recrystallization method needs repeated recrystallization, the amount of the generated waste liquid is excessive, and the operation is difficult; and the purity and yield of the obtained acid are low.
Disclosure of Invention
The invention aims to provide a method for separating mixed acid, which can not generate a large amount of waste liquid and is simple to operate; and the purity and yield of the obtained acid are higher.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a method for separating mixed acid, which comprises the following steps:
carrying out esterification reaction on the mixed acid to obtain mixed ester; the mixed acid comprises 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the mixed ester comprises 3-nitro dimethyl dibenzoate, 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate;
Rectifying and hydrolyzing the mixed ester to obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively;
the rectification and hydrolysis comprises a rectification hydrolysis method 1 and a rectification hydrolysis method 2;
the rectification hydrolysis method 1 comprises the following steps:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
performing third rectification on the first rectification product to obtain 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate respectively;
respectively hydrolyzing the 2-methyl-3-nitrobenzoate, the 2-methyl-6-nitrobenzoate and the 3-nitro-dimethyl phthalate to respectively obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid;
the rectification hydrolysis method 2 comprises the following steps:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
Performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
carrying out first hydrolysis on the 3-nitro dimethyl phthalate to obtain 3-nitrophthalic acid;
and carrying out second hydrolysis on the first rectification product to obtain 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively.
Preferably, the esterification reaction comprises direct esterification or indirect esterification;
the direct esterification includes a first process and a second process;
the first method is as follows: mixing the mixed acid, dimethyl carbonate and an alkaline catalyst, and performing esterification reaction;
the second method is as follows: mixing the mixed acid, the raw material alcohol and the acid catalyst to perform esterification reaction;
the indirect esterification comprises:
mixing the mixed acid with thionyl chloride, and performing an acyl chloride reaction to obtain an acyl chloride mixture;
and mixing the acyl chloride mixture with raw alcohol to perform esterification reaction.
Preferably, in the method one, the basic catalyst comprises one or more of potassium carbonate, sodium carbonate, cesium carbonate, triethylamine, tetrabutylammonium bromide, 1, 5-diazabicyclo [4.3.0] non-5-ene and 1, 8-diazabicyclo [5.4.0] undec-7-ene;
In the second method, the raw material alcohol comprises one or more of methanol, ethanol, propanol, n-butanol and n-amyl alcohol;
the acidic catalyst comprises a liquid acid catalyst or a solid acid catalyst.
Preferably, in the first method, the mass ratio of the mixed acid to the dimethyl carbonate is 1:2 to 4; the mass ratio of the mixed acid to the alkaline catalyst is 1:0.01 to 0.4;
in the second method, the mass ratio of the mixed acid to the acid catalyst is 1:0.2 to 0.4;
the mass ratio of the raw material alcohol to the mixed acid is 2-20: 1.
preferably, the esterification reaction conditions in the first method include: the reaction temperature is 160-180 ℃, the time is 2-20 h, and the pressure is 3-5 MPa.
Preferably, the second method comprises normal pressure esterification or high pressure esterification;
the temperature of the normal pressure esterification is 60-140 ℃ and the time is 10-30 h;
the temperature of the high-pressure esterification is 180-220 ℃, the time is more than or equal to 20min, and the pressure is 2-5 MPa.
Preferably, in the indirect esterification, the mass ratio of the mixed acid to the thionyl chloride is 1:3 to 5.
Preferably, the acid chloride reaction comprises performing a first acylation, a second acylation, and a third acylation in sequence;
the temperature of the first acylation is 30 ℃ and the time is 30min;
The temperature of the second acylation is 50 ℃ and the time is 30min;
the temperature of the third acylation is 70 ℃ and the time is 0.5-2 h;
the first, second and third acylations are all carried out under stirring.
Preferably, in the indirect esterification, the raw alcohol comprises one or more of methanol, ethanol, propanol, n-butanol and n-pentanol;
the mass ratio of the raw material alcohol to the acyl chloride mixture is 1:1.
preferably, the esterification reaction conditions of the indirect esterification include: the reaction temperature is 60-70 ℃ and the reaction time is 1-2 h.
The invention provides a method for separating mixed acid, which comprises the following steps: carrying out esterification reaction on the mixed acid to obtain mixed ester; the mixed acid comprises 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the mixed ester comprises 3-nitro dimethyl dibenzoate, 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate; rectifying and hydrolyzing the mixed ester to obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively; the rectification and hydrolysis comprises a rectification hydrolysis method 1 and a rectification hydrolysis method 2; the rectification hydrolysis method 1 comprises the following steps: carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate; performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate; performing third rectification on the first rectification product to obtain 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate respectively; respectively hydrolyzing the 2-methyl-3-nitrobenzoate, the 2-methyl-6-nitrobenzoate and the 3-nitro-dimethyl phthalate to respectively obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the rectification hydrolysis method 2 comprises the following steps: carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate; performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate; carrying out first hydrolysis on the 3-nitro dimethyl phthalate to obtain 3-nitrophthalic acid; and carrying out second hydrolysis on the first rectification product to obtain 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively. The invention adopts a method combining esterification and rectification hydrolysis, and can realize the accurate separation of mixed acid; the separation process is simple and does not generate a large amount of waste liquid; meanwhile, the purity and yield of the separated acid are higher.
Detailed Description
The invention provides a method for separating mixed acid, which comprises the following steps:
carrying out esterification reaction on the mixed acid to obtain mixed ester; the mixed acid comprises 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the mixed ester comprises 3-nitro dimethyl dibenzoate, 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate;
rectifying and hydrolyzing the mixed ester to obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively;
the rectification and hydrolysis comprises a rectification hydrolysis method 1 and a rectification hydrolysis method 2;
the rectification hydrolysis method 1 comprises the following steps:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
performing third rectification on the first rectification product to obtain 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate respectively;
Respectively hydrolyzing the 2-methyl-3-nitrobenzoate, the 2-methyl-6-nitrobenzoate and the 3-nitro-dimethyl phthalate to respectively obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid;
the rectification hydrolysis method 2 comprises the following steps:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
carrying out first hydrolysis on the 3-nitro dimethyl phthalate to obtain 3-nitrophthalic acid;
and carrying out second hydrolysis on the first rectification product to obtain 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively.
In the present invention, all raw materials are commercially available products well known to those skilled in the art unless specified otherwise.
The invention carries out esterification reaction on mixed acid to obtain mixed ester; the mixed acid comprises 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the mixed ester comprises 3-nitro dimethyl dibenzoate, 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate.
In the invention, the mixed acid is preferably obtained by oxidizing 3-nitro-o-xylene serving as a raw material.
In the present invention, the oxidation preferably includes:
and simultaneously introducing 3-nitro-o-xylene, nitric acid and an auxiliary oxidant into a microchannel reactor for oxidation to obtain the mixed acid.
In the present invention, the acidity of the nitric acid is preferably 35 to 75%. In the present invention, the molar ratio of nitric acid to 3-nitroo-xylene is preferably 1 to 10:1. in a specific embodiment of the invention, the flow rate of the 3-nitroo-xylene is preferably 6.5mL/min, and the flow rate of the nitric acid is preferably 39mL/min.
In the present invention, the auxiliary oxidizer preferably includes oxygen or hydrogen peroxide. In the present invention, the molar ratio of the auxiliary oxidizing agent to 3-nitroo-xylene is preferably 0 to 5:1, more preferably 1.3 to 3.0:1. in a specific embodiment of the present invention, when the auxiliary oxidant is oxygen, the flow rate of the 3-nitroo-xylene is 4mL/min, the flow rate of the nitric acid is 21mL/min, and the flow rate of the oxygen is 80mL/min; when the auxiliary oxidant is hydrogen peroxide, the flow rate of the 3-nitro-o-xylene is 3mL/min, the flow rate of the nitric acid is 15mL/min, and the flow rate of the hydrogen peroxide is 9mL/min.
In the present invention, the temperature of the oxidation is preferably 200 to 280 ℃, the time is preferably 40 to 120 seconds, and the pressure is preferably 2 to 4MPa.
In the present invention, the outlet (receiving reaction liquid) temperature of the microchannel reactor is preferably 80 to 90 ℃. In the present invention, the above temperature is controlled to prevent precipitation of solids and to block the pipe.
After the oxidation, the invention also preferably comprises the steps of cooling and crystallizing the obtained reaction feed liquid, and filtering to obtain mixed acid and recovered acid liquid respectively.
In the present invention, the temperature of the reduced temperature crystallization is preferably 10 to 30 ℃. The process of the present invention is not particularly limited, and may be performed by a process known to those skilled in the art.
In the present invention, the recovered acid liquid is preferably recycled as a reaction raw material for oxidation.
In the present invention, the esterification reaction preferably includes direct esterification or indirect esterification.
In the present invention, the direct esterification preferably includes a first method and a second method;
the first method is as follows: mixing the mixed acid, dimethyl carbonate and an alkaline catalyst, and performing esterification reaction;
the second method is as follows: and mixing the mixed acid, the raw material alcohol and the acid catalyst, and carrying out esterification reaction.
The present invention mixes the mixed acid, dimethyl carbonate and a basic catalyst to perform an esterification reaction (method one).
In the present invention, the basic catalyst preferably includes one or more of potassium carbonate, sodium carbonate, cesium carbonate, triethylamine, tetrabutylammonium bromide (TBAB), 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN), and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU). In the present invention, the mass ratio of the mixed acid to the dimethyl carbonate is preferably 1:2 to 4; the mass ratio of the mixed acid to the alkaline catalyst is preferably 1:0.01 to 0.4. In a specific embodiment of the present invention, the purity of the dimethyl carbonate is preferably 99.5%; the purity of the 1, 8-diazabicyclo [5.4.0] undec-7-ene is preferably 99%.
In the present invention, the esterification reaction conditions preferably include: the reaction temperature is 160-180 ℃, the time is 2-20 h, and the pressure is 3-5 MPa. The rate of heating up to the reaction temperature is not particularly limited in the present invention, and may be any rate known to those skilled in the art.
In the present invention, the esterification reaction is preferably carried out at a rotation speed of 600 r/min. In the present invention, the esterification reaction is preferably carried out in an autoclave. In the present invention, the esterification reaction is preferably carried out under nitrogen.
After the esterification reaction, the method also preferably comprises the steps of sequentially washing the obtained reaction feed liquid with water and distilling the reaction feed liquid at normal pressure. The process of the present invention for washing with water and atmospheric distillation is not particularly limited, and may be employed as is well known to those skilled in the art. In the present invention, the excess dimethyl carbonate can be removed by atmospheric distillation.
The present invention mixes the mixed acid, the raw material alcohol and the acid catalyst to perform an esterification reaction (method II).
In the present invention, the raw alcohol preferably includes one or more of methanol, ethanol, propanol, n-butanol and n-pentanol. In the invention, the mass ratio of the raw material alcohol to the mixed acid is preferably 2-20: 1.
in the present invention, the acidic catalyst preferably includes a liquid acid catalyst or a solid acid catalyst. In the present invention, the liquid acid catalyst preferably comprises sulfuric acid, and the mass concentration of the sulfuric acid is preferably 98%; the solid acid catalyst preferably comprises p-toluene sulfonic acid, naphthalene sulfonic acid, sulfamic acid, phosphotungstic acid, phosphomolybdic acid, or an acidic resin. In the present invention, the mass ratio of the mixed acid to the acidic catalyst is preferably 1:0.2 to 0.4.
In the present invention, the second preferred method comprises normal pressure esterification or high pressure esterification.
In the present invention, the temperature of the atmospheric esterification is preferably 60 to 140℃and the time is preferably 10 to 30 hours. In the present invention, the atmospheric esterification is preferably carried out in a reaction vessel.
In the present invention, when normal pressure esterification is employed and the starting alcohol is methanol, ethanol or propanol, the esterification preferably includes:
primary mixing the mixed acid, the raw material alcohol and the acid catalyst, and performing primary esterification and alcohol distillation treatment to obtain a primary product;
mixing the first-stage product with an entrainer for the second stage, and sequentially carrying out azeotropic dehydration and entrainer removal to obtain a second-stage product;
and (3) mixing the secondary product with raw alcohol in a three-stage manner, and carrying out re-esterification.
In the present invention, the temperature of the primary esterification is preferably 60 to 70℃and the time is preferably 10 to 30 hours. In the present invention, the temperature of the alcohol distillation treatment is preferably 70 to 100℃and the time is preferably 2 to 5 hours. After the alcohol distillation treatment, the invention also preferably comprises the step of cooling the obtained reaction feed liquid. In the present invention, the temperature of the primary product is preferably 70 ℃.
In the present invention, the entrainer preferably includes hexane, cyclohexane, heptane, octane, ethyl acetate, propyl acetate, butyl acetate or butyl ether. In the invention, the mass ratio of the entrainer to the primary product is preferably 0.2-1: 1. in the present invention, the temperature of azeotropic dehydration is preferably 50 to 70 ℃ and the time is preferably 5 to 10 hours. In the present invention, the temperature of the azeotropic removal agent is preferably 65 to 70 ℃ and the time is preferably 6 hours.
In the present invention, the water content of the secondary product is preferably 0.1 to 0.5%. In the present invention, in the tertiary mixing, the mass ratio of the secondary product to the raw alcohol is preferably 1:0.5 to 1. In the present invention, the re-esterification temperature is preferably 60 to 70℃and the time is preferably 5 to 10 hours.
In the present invention, when normal pressure esterification is employed and the starting alcohol is n-butanol or n-pentanol, the esterification reaction preferably includes:
and mixing the mixed acid, the raw material alcohol and the acid catalyst, and carrying out esterification reaction.
In the present invention, the temperature of the esterification reaction is preferably 90 to 140℃and the time is preferably 20 to 40 hours. In the present invention, the esterification reaction is carried out while azeotropic dehydration is carried out.
In the invention, the temperature of the high-pressure esterification is preferably 180-220 ℃, the time is preferably more than or equal to 20min, and the pressure is preferably 2-5 MPa. In the present invention, the high pressure esterification is preferably carried out in a microchannel reactor or a tubular reactor.
In the present invention, when high-pressure esterification is employed and the acidic catalyst is miscible with the starting alcohol, the esterification reaction preferably comprises:
mixing the mixed acid, the raw material alcohol and the acid catalyst, and introducing the mixture into a reactor for esterification reaction; the acidic catalyst preferably comprises sulfuric acid, naphthalene sulfonic acid, p-toluene sulfonic acid or sulfamic acid.
In the present invention, when high-pressure esterification is employed and the acidic catalyst and the raw alcohol are not miscible, the esterification reaction preferably includes:
introducing the mixed acid and the raw material alcohol into a reactor fixed with an acid catalyst for esterification reaction; the acidic catalyst preferably comprises phosphotungstic acid, phosphomolybdic acid or an acidic resin.
The present invention also preferably includes preheating the reactor prior to introduction into the reactor. In the present invention, the temperature of the preheating is preferably 60 to 110 ℃. In the present invention, the temperature difference between the reaction raw material and the acidic catalyst is reduced by preheating, and the esterification efficiency is improved.
After the esterification reaction (method II), the invention also preferably comprises the steps of sequentially concentrating and layering the obtained reaction feed liquid.
In the present invention, the temperature of the concentration is preferably 60 to 110℃and the time is preferably 2 to 5 hours. In the present invention, a concentrated solution and unreacted raw material alcohol can be obtained by concentration, and the obtained raw material alcohol is recycled as a raw material. In the present invention, the temperature of the concentrated solution is preferably 60 to 95 ℃.
In the present invention, the layering process preferably includes:
mixing the concentrated solution and water for the first time, and carrying out first heat preservation and layering to obtain a first organic layer;
Performing second mixing on the first organic layer and water, and performing second heat preservation layering to obtain mixed ester (recorded as a method 1);
or premixing the concentrated solution, the organic solvent and the alkali liquor, layering by third heat preservation, mixing the obtained organic layer with water, and layering by fourth heat preservation to obtain the mixed ester (marked as a method 2).
In the present invention, in the first mixing, the mass ratio of the concentrated solution to water is preferably 1:0.2 to 1. In the present invention, in the second mixture, the mass ratio of the first organic layer to water is preferably 1:0.2 to 1.
In the present invention, the first mixing and the second mixing are both preferably performed under stirring, and the stirring speed is preferably 300 to 600r/min, and the time is preferably 0.1 to 2 hours.
In the present invention, the temperature of the first insulation layer Wen Fenceng and the second insulation layer is preferably 65-90 ℃.
In the present invention, the organic solvent preferably includes an ester solvent, an ether solvent, a ketone solvent, a chlorinated hydrocarbon or a benzene solvent; the ester solvent preferably includes ethyl acetate, isopropyl acetate or sec-butyl acetate; the ether solvent preferably includes methyl tertiary butyl ether; the ketone solvent preferably includes methyl tertiary butyl ketone or methyl ethyl ketone; the chlorinated hydrocarbon preferably comprises dichloromethane or dichloroethane; the benzene solvent preferably comprises toluene or xylene.
In the present invention, the mass of the organic solvent is preferably 20 to 500% of the mass of the concentrated solution. In the present invention, the alkali liquor preferably comprises sodium hydroxide solution, sodium carbonate solution or sodium bicarbonate solution; the mass concentration of the alkali liquor is preferably 5-20%. The addition amount of the alkali solution and water is not particularly limited in the present invention, and may be known to those skilled in the art.
In the present invention, the premixing and remixing are preferably carried out under stirring conditions, the stirring speed is preferably 300-600 r/min, and the time is preferably 0.5-2 h. In the present invention, the temperature of the third heat preservation layer and the temperature of the fourth heat preservation layer are preferably 65-90 ℃.
In the present invention, the indirect esterification preferably includes:
mixing the mixed acid with thionyl chloride, and performing an acyl chloride reaction to obtain an acyl chloride mixture;
and mixing the acyl chloride mixture with raw alcohol to perform esterification reaction.
The mixed acid and thionyl chloride are mixed and subjected to acyl chloride reaction to obtain an acyl chloride mixture.
In the invention, the mass ratio of the mixed acid to the thionyl chloride is preferably 1:3 to 5. The mixing process is not particularly limited and may be employed as is well known to those skilled in the art.
In the present invention, the acid chloride reaction preferably includes sequentially performing a first acylation, a second acylation, and a third acylation; the temperature of the first acylation is 30 ℃ and the time is 30min; the temperature of the second acylation is 50 ℃ and the time is 30min; the temperature of the third acylation is 70 ℃ and the time is 0.5-2 h; the first acylation, the second acylation and the third acylation are all preferably carried out under stirring, and the stirring rotation speed is preferably 300-600 r/min.
After the acid chloride reaction, the present invention also preferably includes distilling the resulting reaction feed solution. In the present invention, the distillation preferably includes direct distillation or sequential direct distillation and azeotropic distillation. In the present invention, the temperature of the direct distillation is preferably 80 to 90℃and the time is preferably 1 to 4 hours.
In the present invention, the azeotropic distillation preferably includes:
mixing the directly distilled product with an organic solvent, and performing azeotropic distillation.
In the present invention, the organic solvent preferably includes benzene-based solvents, ester-based solvents, ketone-based solvents, chlorinated hydrocarbons or ether-based solvents. In the present invention, the benzene-based solvent preferably includes toluene, xylene or trimethylbenzene; the ester solvent preferably includes isopropyl acetate, n-butyl acetate, sec-butyl acetate or amyl acetate; the ketone solvent preferably includes 2-pentanone, 3-pentanone, methyl isopropyl ketone or methyl tert-butyl ketone; the chlorinated hydrocarbon preferably comprises dichloroethane, dichloropropane or dichloromethane; the ether solvent preferably includes anisole, diethyl ether, dibutyl ether or methyl tertiary butyl ether. In the present invention, the mass ratio of the product obtained by the direct distillation to the organic solvent is preferably 1:0.2 to 1. In the present invention, the temperature of the azeotropic distillation is preferably 90 to 100 ℃ and the time is preferably 2 to 4 hours. In the present invention, unreacted thionyl chloride can be recovered by distillation and recycled as a raw material.
After the acyl chloride mixture is obtained, the acyl chloride mixture and raw material alcohol are mixed for esterification reaction.
In the present invention, the raw alcohol preferably includes one or more of methanol, ethanol, propanol, n-butanol and n-pentanol; the mass ratio of the raw material alcohol to the mixed acid is preferably 1-5: 1.
in the present invention, the temperature of the esterification reaction of the indirect esterification is preferably 60 to 70℃and the time is preferably 1 to 3 hours.
After the esterification reaction (indirect esterification), the present invention also preferably includes subjecting the resulting reaction liquid to reduced pressure distillation and layering treatment. In the present invention, the temperature of the reduced pressure distillation is preferably 60 to 90℃and the time is preferably 2 to 4 hours. In the present invention, the residual azeotropic organic solvent and unreacted raw alcohol can be removed by distillation under reduced pressure.
In the present invention, the layering process preferably includes:
mixing the feed liquid obtained by reduced pressure distillation, dimethylbenzene and alkali liquor at 60-70 ℃ and layering to obtain a water phase and an organic phase;
and washing the organic phase with water, and performing reduced pressure distillation to obtain the mixed ester.
In the present invention, the alkali solution is preferably a 10% strength by mass sodium hydroxide solution. In the present invention, the pH of the mixed solution obtained by the mixing is preferably 8 to 9.
The amount of the xylene to be added and the process of distillation under reduced pressure are not particularly limited in the present invention, and those skilled in the art can be used.
After the mixed ester is obtained, the mixed ester is sequentially rectified and hydrolyzed to respectively obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid.
In the present invention, the rectification and hydrolysis include rectification hydrolysis method 1 and rectification hydrolysis method 2.
In the present invention, the rectification hydrolysis method 1 includes:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
performing third rectification on the first rectification product to obtain 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate respectively;
2-methyl-3-nitrobenzoate, 2-methyl-6-nitrobenzoate and 3-nitro dimethyl phthalate are respectively hydrolyzed to obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid.
In the present invention, the temperature of the first rectification is preferably 110 to 130 ℃, the vacuum pressure is 80 to 100Pa, and the reflux ratio is preferably 2:10; the number of trays for the first rectification is preferably 30 to 50.
In the invention, the temperature of the second rectification is preferably 140-160 ℃ and the vacuum pressure is 80-100 Pa; the number of the rectifying trays of the second rectification is preferably 30 to 50.
In the present invention, the third rectification preferably includes a primary rectification and a secondary rectification; the primary rectification temperature is preferably 120-130 ℃, the vacuum pressure is preferably 80-120 Pa, and the number of rectification tower plates is preferably 50-100; the temperature of the secondary rectification is preferably 120-130 ℃, the vacuum pressure is preferably 80-120 Pa, and the number of rectification tower plates is preferably 50-100.
In a specific embodiment of the present invention, the processes of the first rectification, the second rectification and the third rectification are specifically:
transferring the mixed ester to a rectifying tower 1 for first rectification;
the kettle liquid of the rectifying tower 1 enters a rectifying tower 4 for second rectification, and 3-nitro dimethyl phthalate is extracted from the top of the rectifying tower 4;
the mixed fraction at the top of the rectifying tower 1 enters the rectifying tower 2 for primary rectification;
and (3) feeding the mixed fraction at the top of the rectifying tower 2 into the rectifying tower 3 for secondary rectification, extracting 2-methyl-6-nitrobenzoate from the top of the rectifying tower, and returning the tower bottom liquid into the rectifying tower 2 to obtain 2-methyl-3-nitrobenzoate.
In the present invention, the hydrolysis preferably includes:
after the esterified substance is melted, mixing the melted esterified substance with alkali liquor, and hydrolyzing to obtain a hydrolysate;
and (3) regulating the pH value of the cooled hydrolysate to be acidic, and sequentially filtering, washing and drying to obtain the corresponding acid.
In the present invention, the melting temperature is preferably 60 to 85 ℃.
In the present invention, the alkali liquor is preferably 10 to 40% by mass. In the present invention, the alkali liquor preferably includes one or more of sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution, potassium carbonate solution, sodium bicarbonate solution and ammonium hydroxide solution.
In the present invention, the molar ratio of the ester to the alkali in the alkali solution is preferably 1:1 to 6. In the present invention, when the ester is 2-methyl-3-nitrobenzoate or 2-methyl-6-nitrobenzoate, the molar ratio of the ester to the base is preferably 1:1 to 4; when the ester is dimethyl 3-nitrodibenzoate, the molar ratio of the ester to the base is preferably 1:2 to 6.
In the present invention, the mixing method is preferably: the alkali liquor is added dropwise to the melted esterified substance under stirring.
In the invention, the temperature of the hydrolysis is preferably 50-120 ℃ and the time is preferably 2-4 h; the hydrolysis is preferably carried out under stirring, preferably at a speed of 300 to 600r/min.
In the invention, the acid solution used for the pH value adjustment preferably comprises one or more of hydrochloric acid, sulfuric acid, phosphoric acid, sulfurous acid and sodium bisulfate; the concentration of the acid solution is preferably 10 to 40%. In the present invention, the temperature of the pH adjustment is preferably 20 to 50 ℃.
The invention also preferably includes extracting the hydrolysate prior to the pH adjustment. In the present invention, the extraction reagent used for the extraction preferably includes an ester solvent, an ether solvent, a ketone solvent, a chlorinated hydrocarbon or a benzene solvent; the ester solvent preferably includes ethyl acetate, isopropyl acetate or sec-butyl acetate; the ether solvent preferably includes methyl tertiary butyl ether; the ketone solvent preferably includes methyl tertiary butyl ketone or methyl ethyl ketone; the chlorinated hydrocarbon preferably comprises dichloromethane or dichloroethane; the benzene solvent preferably comprises toluene or xylene. In the present invention, the purity of the acid obtained by hydrolysis can be further improved by extraction.
In the present invention, the rectification hydrolysis method 2 includes:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
carrying out first hydrolysis on the 3-nitro-dimethyl phthalate to obtain 3-nitrophthalic acid;
and carrying out second hydrolysis on the first rectification product to obtain 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively.
In the present invention, the processes of the first rectification and the second rectification are consistent with the methods described in the above technical schemes, and are not described herein.
In the present invention, the first hydrolysis is identical to the hydrolysis method of the 3-nitrodibenzoate dimethyl ester defined in the above technical scheme, and will not be described herein.
In the present invention, the second hydrolysis preferably includes:
mixing the first rectification product with alkali liquor for primary hydrolysis, and layering to obtain 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoate respectively;
And carrying out secondary hydrolysis on the 2-methyl-6-nitrobenzoate to obtain 2-methyl-6-nitrobenzoic acid.
In the present invention, the lye preferably comprises sodium hydroxide solution; the mass concentration of the sodium hydroxide solution is preferably 10%; the mass ratio of the first rectification product to the alkali liquor is preferably 1:0.8 to 1.5. In the present invention, the temperature of the primary hydrolysis is preferably 60 to 100 ℃. In the invention, the hydrolysis process is preferably judged by HPLC (high Performance liquid chromatography) central control sampling analysis, and the hydrolysis is judged to be completed when the normalized content of 2-methyl-3-nitrobenzoate in the organic phase is less than or equal to 5 percent and the normalized content of 2-methyl-6-nitrobenzoic acid in the water phase is less than or equal to 5 percent.
In the present invention, the primary hydrolysis process further preferably includes adding an organic solvent; the organic solvent preferably comprises one or more of toluene, xylene, dichloroethane, dichloropropane and methyl tert-butyl ether. The amount of the organic solvent to be added in the present invention is not particularly limited, and may be any one known to those skilled in the art.
In the present invention, the layering process preferably includes:
carrying out first heat preservation and liquid separation on the reaction liquid obtained by the primary hydrolysis to obtain a first aqueous phase and a first organic phase;
Mixing the first aqueous phase and the organic solvent for second heat preservation and liquid separation to obtain a second aqueous phase and a second organic phase;
mixing the first organic phase, the second organic phase and water for third heat preservation and liquid separation to obtain a third water phase and a third organic phase; the third organic phase comprises 2-methyl-6-nitrobenzoate;
mixing the first water phase, the second water phase and the third water phase to obtain a fourth water phase; the fourth aqueous phase comprises 2-methyl-3-nitrobenzoic acid.
After obtaining the fourth aqueous phase, the invention also preferably comprises post-treating the fourth aqueous phase to obtain 2-methyl-3-nitrobenzoic acid; the post-treatment preferably comprises:
dropwise adding a sulfuric acid solution with the concentration of 20% into the fourth water phase at 65-70 ℃ to adjust the pH value to be less than or equal to 2, stirring for 30min, and carrying out heat preservation and filtration to obtain a first filtrate and a first filter cake; 250g of water is added into the first filter cake, pulping is carried out for 30min at 65-70 ℃, heat preservation and filtration are carried out, a second filter cake and a second filtrate are obtained, and the second filter cake is dried, thus obtaining 2-methyl-3-nitrobenzoic acid.
In the present invention, the secondary hydrolysis process is identical to the hydrolysis method of 2-methyl-6-nitrobenzoate defined in the above technical scheme, and will not be described herein.
The invention adopts a method of combining esterification and rectification hydrolysis to realize the accurate separation of mixed acid, the purity of the separated 2-methyl-6-nitrobenzoic acid is preferably 97.1 to 99.2 percent, and the yield is preferably 48.7 to 54.16 percent; the purity of the 3-nitrodibenzoic acid is preferably 99.18-99.24%, and the yield is preferably 71.4-84.09%; the purity of the 2-methyl-3-nitrobenzoic acid is preferably 99.15% -99.5%, and the yield is preferably 62.8% -79.92%.
In order to further illustrate the present invention, a method for separating a mixed acid according to the present invention will be described in detail with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
1. Nitric acid oxidation
3-nitro-o-xylene (flow rate: 6.5 mL/min) and nitric acid solution (acidity: 50%, flow rate: 39 mL/min) are respectively pumped into a microchannel reactor through a pressure pump, and the two materials are mixed in a mixing zone and then flow into a reaction zone for reaction, wherein the reaction temperature is 240 ℃, the reaction pressure is 3.5MPa, the residence time is 56.7s, the reaction solution is received at 80 ℃, and the receiving time is 30min; cooling the reaction solution to 25 ℃, continuously stirring for 2 hours, and filtering to obtain 200g of filter cake (namely mixed acid, HPLC: 2-methyl-3-nitrobenzoic acid: 60.4%, 2-methyl-6-nitrobenzoic acid: 17.8%, 3-nitrodibenzoic acid: 9.8%); the recovered acid liquor (nitric acid acidity 44%) is collected for preparing the next batch of acid liquor;
2. Base catalyzed esterification
The obtained mixed acid (1.0 kg), dimethyl carbonate (99.5%, 3.0 kg) and DBU (99%, 0.05 kg) are added into a 5L autoclave, nitrogen with the pressure of 0.5Mpa is introduced for three times, stirring is started to 600r/min, the temperature is raised to 170 ℃, the temperature is raised for 1h, the reaction is kept for 4h, the pressure is gradually raised to 3.6Mpa from 0Mpa in the reaction process, the temperature is lowered to the room temperature, the pressure is released, 3.806kg of reddish brown liquid is obtained after discharging, the mixture is washed twice with 500mL of water in sequence, and the excessive dimethyl carbonate is distilled off at normal pressure (applied to the next batch) to obtain 1.094kg of mixed ester. 3 batches were repeated to give a total of 3.24kg of organic layer (i.e. mixed ester, HPLC: methyl 2-methyl-3-nitrobenzoate: 63.3%, methyl 2-methyl-6-nitrobenzoate: 21.1%, dimethyl 3-nitrodibenzoate: 13.8%);
3. rectification hydrolysis method 1
3.1 rectification
At a holding vacuum pressure of 100±2Pa, reflux ratio=2: 10, transferring the obtained mixed ester to a rectifying tower 1 (30 pieces of tower plates) under the condition that the rectifying temperature is 130+/-2 ℃;
feeding the mixed fraction (HPLC: 2-methyl-3-nitrobenzoate: 2-methyl-6-nitrobenzoate=77.4%: 23.6%) at the top of the rectifying tower 1 into the rectifying tower 2 (60 pieces of tower plates), wherein the rectifying temperature is 130+/-2 ℃, the mixed fraction (HPLC: 2-methyl-3-nitrobenzoate: 2-methyl-6-nitrobenzoate=17.3%: 82.6%) at the top of the rectifying tower 2, and 1.56kg (HPLC, 2-methyl-3-nitrobenzoate: 98.0%) of the bottom liquid of the rectifying tower 2 is produced;
The mixed fraction at the top of the rectifying tower 2 enters a rectifying tower 3 (60 pieces of tower plates), the rectifying temperature is 130+/-2 ℃, 0.28kg of fraction (HPLC, 2-methyl-6-nitrobenzoate: 97.9%) is produced at the top of the rectifying tower 3, and the bottom liquid of the rectifying tower 3 enters the rectifying tower 2;
feeding the bottom liquid of the rectifying tower 1 into a rectifying tower 4 (with the number of tower plates of 30), wherein the rectifying temperature is 160+/-2 ℃, and 0.23kg of distillate (HPLC, 3-nitro dimethyl dibenzoate: 99.1%) is produced at the top of the rectifying tower 4;
hydrolysis of dimethyl 2, 3-nitrophthalate
Adding the obtained 3-nitrodimethyl phthalate (100.0 g, 99.1%) into a flask, heating to 70 ℃ to melt, dropwise adding sodium hydroxide solution (167 g, 30%) under stirring, heating to 100 ℃ after the dropwise adding is finished, preserving heat, and stirring for 3 hours, and finishing the reaction; cooling to 30deg.C, adjusting pH to 1 with 10% hydrochloric acid, filtering to obtain crude product, washing filter cake with 100g cold water, and drying to obtain pure 3-nitrophthalic acid 72.8g (HPLC: 99.24%);
hydrolysis of 3, 2-methyl-3-nitrobenzoate
Heating 100g of the obtained 2-methyl-3-nitrobenzoate to 65 ℃ to melt, dropwise adding 103g of sodium hydroxide solution (30%), heating to 100 ℃ after the dropwise adding is finished, preserving heat and stirring for 1h, controlling the temperature to 30 ℃ after the reaction is finished in HPLC, dropwise adding 10% hydrochloric acid to adjust the pH to be less than or equal to 3, preserving heat and filtering, washing a filter cake by using 100g of water, and drying to obtain 86.3g of pure 2-methyl-3-nitrobenzoic acid (HPLC: 99.34%);
Hydrolysis of 4, 2-methyl-6-nitrobenzoate
100g of the obtained 2-methyl-6-nitrobenzoate is heated to 85 ℃ to be melted, 103g of sodium hydroxide solution (30%) is dripped, the temperature is raised to 100 ℃ after the dripping is finished, the mixture is stirred for 3 hours under heat preservation, the mixture is cooled to 30 ℃ after the reaction is finished in HPLC, 10% hydrochloric acid is dripped to adjust the pH to be less than or equal to 3, the mixture is filtered under heat preservation, 100g of 100-g water is used for washing a filter cake, and 72.4g of pure 2-methyl-3-nitrobenzoic acid (HPLC: 97.1%) is obtained after drying.
Example 2
1. Nitric acid oxidation
3-nitro-o-xylene (flow rate: 6.5 mL/min) and nitric acid solution (acidity: 50%, flow rate: 39 mL/min) are respectively pumped into a microchannel reactor through a pressure pump, and the two materials are mixed in a mixing zone and then flow into a reaction zone for reaction, wherein the reaction temperature is 240 ℃, the reaction pressure is 3.5MPa, the residence time is 56.7s, the reaction solution is received at 90 ℃, and the receiving time is 30min; cooling the reaction solution to 25 ℃, continuously stirring for 2 hours, and filtering to obtain 200g of filter cake (namely mixed acid, HPLC: 2-methyl-3-nitrobenzoic acid: 60.4%, 2-methyl-6-nitrobenzoic acid: 17.8%, 3-nitrodibenzoic acid: 9.8%); the recovered acid liquor (nitric acid acidity 44%) is collected for preparing the next batch of acid liquor;
2. acid catalyzed esterification
The obtained mixed acid (2.0 kg), absolute methanol (10.0 kg) and concentrated sulfuric acid (98%, 0.6 kg) are added into a 20L reaction kettle, stirred and heated to 65 ℃ for reflux reaction for 10 hours; evaporating methanol at normal pressure, and cooling to 70deg.C after distillation is completed when the temperature of the kettle liquid is increased to 90deg.C;
Dropping 1.0kg of n-hexane for azeotropic dehydration, measuring the water content of the kettle liquid to be 0.3% when no water drops are generated in an azeotropic distiller, steaming the n-hexane at normal pressure until the kettle liquid is 70 ℃, dropping 5.0kg of anhydrous methanol after distillation is finished, carrying out reflux reaction for 8 hours, and carrying out central control until the reaction is finished;
removing methanol solvent by normal pressure distillation, adding 500g of water when the kettle liquid is 95 ℃, stirring for 10min, preserving heat and layering at 70 ℃, separating a water layer, adding 1.0kg of water again for 10min, preserving heat and layering at 70 ℃ to obtain an oil layer, separating a water layer, and obtaining 2.153kg of an organic layer (namely, mixed ester, HPLC: 2-methyl-3-nitrobenzoic acid: 0.2%, 2-methyl-6-nitrobenzoic acid: 1.3%, 3-nitro-o-dibenzoic acid: 0.3%, 2-methyl-3-nitrobenzoate: 60.3%, 2-methyl-6-nitrobenzoate: 16.7%, 3-nitro-o-dibenzoate: 18.4%);
3. rectification hydrolysis method 2
3.1 rectification
Transferring the obtained mixed ester to a rectifying tower 1, rectifying at a temperature of 130+/-2 ℃ (100+/-5 Pa) and with a rectifying tower plate number of 30 blocks, collecting tower top fraction to obtain 1.356kg of light yellow liquid, and cooling to obtain light yellow solid (namely a first rectifying product, namely, mixed monoester of 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate: 99.5 percent) through GC analysis; feeding the kettle liquid of the rectifying tower 1 into a rectifying tower 2, wherein the rectifying temperature is 160+/-2 ℃ (100+/-5 Pa), the number of rectifying tower plates is 30, collecting 0.19kg of yellow liquid of fraction, and cooling to obtain yellow solid (namely 3-nitro dimethyl dibenzoate, and GC: 99.0%);
Hydrolysis of dimethyl 3, 2, 3-nitrodibenzoate
The procedure was followed in the same manner as in 3.2 in example 1 to give 74.6g (HPLC: 99.15%) of dried 3-nitrodibenzoate.
3.3 first stage hydrolysis of the first rectification product
500g (GC: 99.5%, HPLC analysis, 2-methyl-3-nitrobenzoate: 2-methyl-6-nitrobenzoate=76.5%: 24%) and 500g of xylene are added into a 3000mL four-necked flask, heated to 70 ℃ for dissolution, dropwise added with sodium hydroxide solution (10%, 1020 g), the dropwise added process is kept at 70 ℃, after the dropwise addition is finished, the reaction is kept for 2 hours, HPLC central control sampling analysis is performed, when the normalized content of 2-methyl-3-nitrobenzoate in the organic phase is less than or equal to 5%, the normalized content of 2-methyl-6-nitrobenzoic acid in the aqueous phase is less than or equal to 5%, the heat-preserving liquid-separating liquid is carried out, 250g of xylene is added into the aqueous phase again for stirring for 10 minutes, 70 ℃ for heat-preserving liquid-separating is carried out, 250g of water is added for stirring for 10 minutes, 70 ℃ for heat-preserving liquid-separating is carried out, and the aqueous phase (HPLC, 2-methyl-3-nitrobenzoic acid: 96.6%) is combined;
hydrolysis of 2-methyl-6-nitrobenzoate, as in 3.4 of example 1, gives 2-methyl-6-nitrobenzoic acid: 81.2g, LC:99.2%, yield: 67.7%;
Dropwise adding a sulfuric acid solution with the concentration of 20% into a water phase (HPLC, 2-methyl-3-nitrobenzoic acid: 96.6%) at 70 ℃ to adjust the pH value to be less than or equal to 2, stirring for 30min, and carrying out heat preservation and filtration to obtain a first filtrate and a first filter cake; 250g of water is added into the first filter cake, pulping is carried out for 30min at 70 ℃, heat preservation and filtration are carried out, a second filter cake and a second filtrate are obtained, and the second filter cake is dried, thus obtaining 2-methyl-3-nitrobenzoic acid: 300.3g, LC:99.5% and yield 78.5%.
Example 3
1. Oxygen oxidation
3-nitro-o-xylene (flow rate: 4 mL/min), nitric acid solution (acidity 50%, flow rate: 21 mL/min), oxygen (flow rate: 80 mL/min) were pumped into the mixing zone for mixing, and then pumped into the microchannel reactor at 225 ℃ under 2.8MPa for 44s at 85 ℃ for 30min; cooling the reaction solution to 25 ℃, continuously stirring for 2 hours, and filtering to obtain 65g of mixed acid filter cake (namely mixed acid, HPLC: 2-methyl-3-nitrobenzoic acid: 59.6%, 2-methyl-6-nitrobenzoic acid: 14.5%, 3-nitrodibenzoic acid: 15.5%); layering the filtrate to obtain a recovered organic layer (HPLC: 3-nitro-o-xylene 65%), and collecting and applying to the next esterification; the recovered acid liquor (the acidity of nitric acid is 47.5%) is used for preparing the experimental acid liquor of the next batch;
2. Indirect esterification-thionyl chloride esterification
Adding 1100g of the obtained mixed acid and 2500g of thionyl chloride into a 10L glass reaction kettle, heating the mixture with stirring, stirring for 30min at 30 ℃, heating to 50 ℃ and stirring for 30min, finally heating to 70 ℃ and stirring for 1h, sampling by HPLC until the contents of three acids are respectively smaller than 1.0% (methanol quenching sampling), distilling off excessive thionyl chloride, reducing the kettle temperature to 70 ℃ when the kettle temperature is 90 ℃, dropwise adding 1000g of methanol for reflux reaction for 1h, sampling by HPLC until the contents of three acids are respectively smaller than 1.0%, evaporating methanol at normal pressure, adding 1100g of dimethylbenzene when the kettle temperature is 90 ℃, dropwise adding 300g of sodium hydroxide solution with the mass concentration of 10% at the temperature of 65 ℃ for regulating the pH to 9, using 1000g of water for washing an oil layer after layering, obtaining 2110.4g of organic layer, and decompressing and distilling off the rest 1097.3g of kettle liquid (namely mixed ester, HPLC: 2-methyl-3-nitrobenzoate: 61.6%, 2-methyl-6-nitrobenzoate: 17.8%, 3-nitro-dibenzoate: 20%); repeating the esterification for 2 batches again to obtain 3.29kg of mixed ester;
3. rectification hydrolysis method 1
3.1 rectification
Transferring the obtained mixed ester to a rectifying tower 1 (30 pieces of tower plates) under the condition of keeping vacuum pressure at 100+/-5 Pa and reflux ratio=2:10, wherein the rectifying temperature is 130+/-2 ℃;
Feeding the mixed fraction (HPLC: 2-methyl-3-nitrobenzoate: 2-methyl-6-nitrobenzoate=76.5%: 24%) at the top of the rectifying tower 1 into the rectifying tower 2 (60 pieces of tower plates), wherein the rectifying temperature is 130+/-2 ℃, the mixed fraction (HPLC: 2-methyl-3-nitrobenzoate: 2-methyl-6-nitrobenzoate=17.3%: 82.6%) at the top of the rectifying tower 2, and 1.6kg (HPLC, 2-methyl-3-nitrobenzoate: 98.6%) of the bottom liquid of the rectifying tower 2 is obtained;
the mixed fraction at the top of the rectifying tower 2 enters a rectifying tower 3 (60 pieces of tower plates), the rectifying temperature is 130+/-2 ℃, 0.21kg of fraction (HPLC, 2-methyl-6-nitrobenzoate: 97.5%) is produced at the top of the rectifying tower 3, and the 3 kettle liquid of the rectifying tower enters the rectifying tower 2;
feeding the bottom liquid of the rectifying tower 1 into a rectifying tower 4 (with the number of tower plates being 30), wherein the rectifying temperature is 160+/-2 ℃, and 0.4kg of distillate (HPLC, 3-nitrodimethyl phthalate: 99.3%) is produced at the top of the rectifying tower 4;
hydrolysis of dimethyl 3, 2, 3-nitrodibenzoate
The procedure is as in 3.2 of example 1, giving 75.1g (HPLC: 99.2%) of dry 3-nitrodibenzoic acid;
hydrolysis of 3, 2-methyl-3-nitrobenzoate
The procedure is as in 3.3 of example 1, giving 87.5g (HPLC: 99.18%) of 2-methyl-3-nitrobenzoic acid dry product;
Hydrolysis of 4, 2-methyl-6-nitrobenzoate
The procedure was followed in the same manner as in 3.4 of example 1 to give 75.4g (HPLC: 97.7%) of 2-methyl-6-nitrobenzoic acid as a dry product.
Example 4
1. Oxydol oxidation
3-nitro-o-xylene (flow rate: 3 mL/min), nitric acid solution (acidity 50%, flow rate: 15 mL/min) and 30% hydrogen peroxide (flow rate: 9 mL/min) are pumped into a mixing zone for mixing, and then pumped into a microchannel reactor, wherein the temperature is 225 ℃, the pressure is 2.8MPa, the residence time is 95s, and the receiving time is 30min; cooling the reaction solution to 25 ℃, continuously stirring for 2 hours, and filtering to obtain 55g of mixed acid filter cake (namely, mixed acid, HPLC: 2-methyl-3-nitrobenzoic acid: 64.4%, 3-nitrodibenzoic acid: 16.3%, 2-methyl-6-nitrobenzoic acid: 13.5%); layering the filtrate to obtain a recovered organic layer (HPLC: 70% of 3-nitro-o-xylene), and collecting for later use; recovering acid liquor (34.5% of nitric acid acidity) and collecting the acid liquor for the next batch experiment;
2. microchannel esterification
Mixing and stirring mixed acid, anhydrous methanol and naphthalene sulfonic acid according to a mass ratio of 1:5:0.2 until materials are completely dissolved, pumping the materials into a preheater by a metering pump to be preheated to 100 ℃, then entering a micro-reactor for reaction, wherein the temperature of the reactor is 200 ℃, the pressure is 4.2MPa, the flow rate of the materials is 2mL/min, and the retention time is 21.5min; after flowing through the micro-reactor, the mixture enters a cooling tank and is cooled to 60 ℃; removing methanol solvent by normal pressure distillation, adding water (mixed acid: water=1:0.4) when the kettle liquid is 95 ℃, stirring and cooling to 70 ℃ for heat preservation and delamination, separating out a water layer, adding water again for repeating once again to obtain mixed ester (HPLC: 2-methyl-3-nitrobenzoic acid methyl ester: 55.5%, 3-nitro dimethyl phthalate: 17.6%, 2-methyl-6-nitrobenzoic acid methyl ester: 14.3%);
3. Rectification hydrolysis method 1
3.1 rectification
2kg of the mixed ester was distilled according to 3.1 in example 1 to obtain 2-methyl-3-nitrobenzoate (0.928 kg, 98.13%), 2-methyl-6-nitrobenzoate (0.172 kg, 98.02%), and dimethyl 3-nitrodibenzoate (0.142 kg, 99.24%);
hydrolysis of dimethyl 3, 2, 3-nitrodibenzoate
The procedure is as in 3.2 of example 1, giving 75.9g (HPLC: 99.22%) of dry 3-nitrodibenzoic acid;
hydrolysis of 3, 2-methyl-3-nitrobenzoate
The procedure is as in 3.3 of example 1, yielding 99.7g (HPLC: 98.9%) of dry 2-methyl-3-nitrobenzoic acid;
hydrolysis of 4, 2-methyl-6-nitrobenzoate
The procedure was the same as in 3.4 of example 1, to give 75.6g (HPLC: 97.2%) of 2-methyl-6-nitrobenzoic acid as a dry product.
Although the foregoing embodiments have been described in some, but not all embodiments of the invention, other embodiments may be obtained according to the present embodiments without departing from the scope of the invention.
Claims (10)
1. A method for separating a mixed acid, comprising the steps of:
carrying out esterification reaction on the mixed acid to obtain mixed ester; the mixed acid comprises 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid; the mixed ester comprises 3-nitro dimethyl dibenzoate, 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate;
Rectifying and hydrolyzing the mixed ester to obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively;
the rectification and hydrolysis comprises a rectification hydrolysis method 1 and a rectification hydrolysis method 2;
the rectification hydrolysis method 1 comprises the following steps:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
performing third rectification on the first rectification product to obtain 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate respectively;
respectively hydrolyzing the 2-methyl-3-nitrobenzoate, the 2-methyl-6-nitrobenzoate and the 3-nitro-dimethyl phthalate to respectively obtain 3-nitrophthalic acid, 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid;
the rectification hydrolysis method 2 comprises the following steps:
carrying out first rectification on the mixed ester to obtain a first rectification product and a second rectification product respectively; the first rectification product comprises 2-methyl-3-nitrobenzoate and 2-methyl-6-nitrobenzoate, and the second rectification product comprises 3-nitro dimethyl phthalate;
Performing second rectification on the second rectification product to obtain 3-nitro dimethyl dibenzoate;
carrying out first hydrolysis on the 3-nitro dimethyl phthalate to obtain 3-nitrophthalic acid;
and carrying out second hydrolysis on the first rectification product to obtain 2-methyl-3-nitrobenzoic acid and 2-methyl-6-nitrobenzoic acid respectively.
2. The separation process of claim 1, wherein the esterification reaction comprises direct esterification or indirect esterification;
the direct esterification includes a first process and a second process;
the first method is as follows: mixing the mixed acid, dimethyl carbonate and an alkaline catalyst, and performing esterification reaction;
the second method is as follows: mixing the mixed acid, the raw material alcohol and the acid catalyst to perform esterification reaction;
the indirect esterification comprises:
mixing the mixed acid with thionyl chloride, and performing an acyl chloride reaction to obtain an acyl chloride mixture;
and mixing the acyl chloride mixture with raw alcohol to perform esterification reaction.
3. The separation method according to claim 2, wherein in the method one, the basic catalyst comprises one or more of potassium carbonate, sodium carbonate, cesium carbonate, triethylamine, tetrabutylammonium bromide, 1, 5-diazabicyclo [4.3.0] non-5-ene, and 1, 8-diazabicyclo [5.4.0] undec-7-ene;
In the second method, the raw material alcohol comprises one or more of methanol, ethanol, propanol, n-butanol and n-amyl alcohol;
the acidic catalyst comprises a liquid acid catalyst or a solid acid catalyst.
4. A separation method according to claim 2 or 3, wherein in the first method, the mass ratio of the mixed acid and dimethyl carbonate is 1:2 to 4; the mass ratio of the mixed acid to the alkaline catalyst is 1:0.01 to 0.4;
in the second method, the mass ratio of the mixed acid to the acid catalyst is 1:0.2 to 0.4;
the mass ratio of the raw material alcohol to the mixed acid is 2-20: 1.
5. the separation process of claim 2, wherein the esterification reaction conditions in process one include: the reaction temperature is 160-180 ℃, the time is 2-20 h, and the pressure is 3-5 MPa.
6. The separation process according to claim 2, wherein the second process comprises atmospheric or high pressure esterification;
the temperature of the normal pressure esterification is 60-140 ℃ and the time is 10-30 h;
the temperature of the high-pressure esterification is 180-220 ℃, the time is more than or equal to 20min, and the pressure is 2-5 MPa.
7. The separation method according to claim 2, wherein in the indirect esterification, the mass ratio of the mixed acid to thionyl chloride is 1:3 to 5.
8. The separation process according to claim 2 or 7, wherein the acid chloride reaction comprises performing a first acylation, a second acylation, and a third acylation in this order;
the temperature of the first acylation is 30 ℃ and the time is 30min;
the temperature of the second acylation is 50 ℃ and the time is 30min;
the temperature of the third acylation is 70 ℃ and the time is 0.5-2 h;
the first, second and third acylations are all carried out under stirring.
9. The separation method according to claim 2, wherein in the indirect esterification, the raw alcohol includes one or more of methanol, ethanol, propanol, n-butanol and n-pentanol;
the mass ratio of the raw material alcohol to the acyl chloride mixture is 1:1.
10. the separation process according to claim 2 or 9, wherein the esterification reaction conditions of the indirect esterification comprise: the reaction temperature is 60-70 ℃ and the reaction time is 1-2 h.
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