CN103755545A - Preparation method of glutaric acid - Google Patents
Preparation method of glutaric acid Download PDFInfo
- Publication number
- CN103755545A CN103755545A CN201410014637.6A CN201410014637A CN103755545A CN 103755545 A CN103755545 A CN 103755545A CN 201410014637 A CN201410014637 A CN 201410014637A CN 103755545 A CN103755545 A CN 103755545A
- Authority
- CN
- China
- Prior art keywords
- acid
- glutamic acid
- hypophosphite
- take
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 title claims abstract description 89
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 87
- 238000000034 method Methods 0.000 claims abstract description 49
- 239000002994 raw material Substances 0.000 claims abstract description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims abstract description 8
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims abstract description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 56
- 229960002989 glutamic acid Drugs 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 19
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical group [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 18
- 230000002829 reductive effect Effects 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 10
- 229910019142 PO4 Inorganic materials 0.000 claims description 10
- 238000002425 crystallisation Methods 0.000 claims description 10
- 238000000605 extraction Methods 0.000 claims description 10
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 10
- 235000021317 phosphate Nutrition 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 9
- 235000010288 sodium nitrite Nutrition 0.000 claims description 9
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 6
- 239000011707 mineral Substances 0.000 claims description 6
- -1 nickelous phosphates Chemical class 0.000 claims description 6
- 229910017604 nitric acid Inorganic materials 0.000 claims description 6
- KWSLGOVYXMQPPX-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2h-tetrazole Chemical compound FC(F)(F)C1=CC=CC(C2=NNN=N2)=C1 KWSLGOVYXMQPPX-UHFFFAOYSA-N 0.000 claims description 5
- BCZXFFBUYPCTSJ-UHFFFAOYSA-L Calcium propionate Chemical compound [Ca+2].CCC([O-])=O.CCC([O-])=O BCZXFFBUYPCTSJ-UHFFFAOYSA-L 0.000 claims description 5
- GJYJYFHBOBUTBY-UHFFFAOYSA-N alpha-camphorene Chemical compound CC(C)=CCCC(=C)C1CCC(CCC=C(C)C)=CC1 GJYJYFHBOBUTBY-UHFFFAOYSA-N 0.000 claims description 5
- 235000010331 calcium propionate Nutrition 0.000 claims description 5
- 239000004330 calcium propionate Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 5
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical class [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- 229910001379 sodium hypophosphite Inorganic materials 0.000 claims description 5
- 229910001380 potassium hypophosphite Inorganic materials 0.000 claims description 4
- CRGPNLUFHHUKCM-UHFFFAOYSA-M potassium phosphinate Chemical compound [K+].[O-]P=O CRGPNLUFHHUKCM-UHFFFAOYSA-M 0.000 claims description 4
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 claims description 3
- 235000010289 potassium nitrite Nutrition 0.000 claims description 3
- 239000004304 potassium nitrite Substances 0.000 claims description 3
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 abstract description 4
- 239000004220 glutamic acid Substances 0.000 abstract description 4
- 235000013922 glutamic acid Nutrition 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 238000006193 diazotization reaction Methods 0.000 abstract 1
- 150000007522 mineralic acids Chemical class 0.000 abstract 1
- 239000011259 mixed solution Substances 0.000 abstract 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 47
- 238000004090 dissolution Methods 0.000 description 21
- 239000000047 product Substances 0.000 description 14
- 230000008569 process Effects 0.000 description 13
- 238000001816 cooling Methods 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 9
- 238000013019 agitation Methods 0.000 description 9
- 238000012544 monitoring process Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 238000005352 clarification Methods 0.000 description 7
- 230000006837 decompression Effects 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 4
- 229960000587 glutaral Drugs 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- 239000001117 sulphuric acid Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001941 cyclopentenes Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- UWJJYHHHVWZFEP-UHFFFAOYSA-N pentane-1,1-diol Chemical compound CCCCC(O)O UWJJYHHHVWZFEP-UHFFFAOYSA-N 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 125000002419 D-glutamo group Chemical group C(=O)(O)[C@@H](CCC(=O)O)N* 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- MHLMRBVCMNDOCW-UHFFFAOYSA-N acetic acid;butan-1-ol;hydrate Chemical compound O.CC(O)=O.CCCCO MHLMRBVCMNDOCW-UHFFFAOYSA-N 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- ZTOMUSMDRMJOTH-UHFFFAOYSA-N glutaronitrile Chemical compound N#CCCCC#N ZTOMUSMDRMJOTH-UHFFFAOYSA-N 0.000 description 1
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 239000003351 stiffener Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/20—Diazonium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of glutaric acid. In the method, glutamic acid is taken as a reaction raw material, a mixed solution of inorganic acid and nitrite is taken as a diazotization reagent, hypophosphorous acid or hypophosphite is taken as a reducing agent, and glutamic acid is converted into glutaric acid by a reaction under a certain condition. The method has the characteristics of easiness, convenience and practicability in operation, low price and ready availability of the reagent, high purity and yield of the glutaric acid and environment-friendly reaction process, thus being suitable for large-scale industrial production.
Description
Technical field
The invention belongs to fine chemical technology field, be specifically related to a kind of method of preparing pentanedioic acid take L-glutamic acid as raw material.
Background technology
Pentanedioic acid (Glutaric Acid, formula I) is a kind of important industrial chemicals and medicine intermediate, has application very widely in fields such as fine chemistry industry, agricultural, medicine and buildings.In plastics chemical industry, pentanedioic acid can be used to produce the important macromolecular materials such as polyvinyl chloride, polyester, polyene amine and resin, synthetic rubber; In pharmaceutical industries, pentanedioic acid not only can be used as the important intermediate of synthetic cardiovascular drug, simultaneously due to its good broad-spectrum bactericidal capacity, can be used for producing various thimerosals and relevant medicine, be used for killing the bacterium that parasitizes on animal, plant, insect etc., also can be used for insect protected; In addition, pentanedioic acid also has important application at aspects such as the many alcohol of synthesizing polyester, preparation scale remover, sulfur-bearing flue washing composition, refrigerant and stiffening agents.As can be seen here, the scale operation of pentanedioic acid has important social value and economic worth.
Existing pentanedioic acid production method mainly comprises absorption method and synthesis method.Absorption method is generally that the by product by separating in hexanodioic acid production process obtains pentanedioic acid, and main separation means has crystallization, organic solvent extraction, urea complexation and straight-forward fractional distillation etc.The method complex process, separation costs are high, and product purification difficulty.Meanwhile, because it depends on the production technique of hexanodioic acid, therefore with larger uncertainty.Due to the progress of Production Processes of Adipic Acid in recent years, the pentanedioic acid that can reclaim from its by product is fewer and feweri.Therefore, by absorption method, produce pentanedioic acid and cannot meet the demand of Vehicles Collected from Market.
Synthesis method is the research direction of tool application prospect during current pentanedioic acid is produced.Synthesis method traditionally comprises multistep synthesis method (the Org. Synth. take gamma-butyrolactone as raw material, 1963, Coll. Vol. 4,496.), oxidizing water solution (Org. Synth., 1963 take dihydropyrane as raw material, Coll. Vol. 4,497.) acid hydrolyzation (Org. Synth., 1941, Coll. Vol. 1 with take trimethylene cyanide as raw material, 289.) etc., but all have the distinct disadvantage such as raw material costliness, reagent toxicity be large.In recent years, take hydrogen peroxide as oxygenant, glutaraldehyde, ring pentanediol or cyclopentenes are oxidized to prepare the method for pentanedioic acid under the catalysis of the precious metals such as palladium, have given prominence to its comparatively eco-friendly feature.Patent application CN 101570479A provides a kind of method of preparing glutaric acid through oxidation of glutaral pentanedial, the method adopts a kind of supported solid catalyst containing active component palladium, take air as oxygenant, under gentle condition, in the mode of gas-liquid-solid three-phase intermittence or successive reaction, glutaraldehyde is oxidized to pentanedioic acid.But the palladium catalyst that the method is used is expensive, recovery utilization rate is low, poor repeatability, and production cost is higher.Patent application CN 1557798A and CN 1546452A, take wolframic acid as catalyzer, take hydrogen peroxide as oxygenant, are oxidized synthesizing glutaric acid to cyclopentenes and 1,2-ring pentanediol respectively, have eco-friendly feature.But its temperature of reaction is higher, and the unsafe factor while using hydrogen peroxide to bring aftertreatment in actual production, be therefore unfavorable for large-scale industrial production.
It is a kind of with L-glutamic acid [Pidolidone (L-Glutamic Acid that the present invention intends providing, formula II), D-Glu or both mixtures] prepare the method for pentanedioic acid for raw material, the raw material using is cheap and easy to get, reaction conditions gentleness, preparation and sepn process are easy, product pentanedioic acid purity and yield are all higher, are conducive to the large-scale industrial production of pentanedioic acid.
Summary of the invention
The object of the present invention is to provide a kind of method of preparing pentanedioic acid take L-glutamic acid as raw material.The method is take L-glutamic acid as raw material, mineral acid and nitrite mixing solutions are diazo reagent, take Hypophosporous Acid, 50 or hypophosphite as reductive agent, stirring reaction 12~72 hours under 0~40 ℃ of condition, glutamic acid rotating is turned to pentanedioic acid, and with the method for crystallization or organic solvent extraction, product pentanedioic acid is separated from reaction system.
The method of preparing pentanedioic acid take L-glutamic acid as raw material that the present invention proposes, its concrete technology is as follows:
In flask, add a certain amount of water (its volume is 10 ~ 60 times of mineral acid volume), it is cooling under cryosel is bathed, slowly drip a certain amount of mineral acid, slowly drip again mass percent concentration and be 5 ~ 20% the nitrite aqueous solution, then add reductive agent Hypophosporous Acid, 50 (mass percentage concentration is 20~50%) or the hypophosphite aqueous solution (concentration is 100 ~ 150 g/L), magnetic agitation 10 ~ 60 minutes, so that it fully mixes, this process need maintains temperature in flask and is-10~0 ℃.Take raw material L-glutamic acid and at room temperature use water dissolution (glutamic acid aqueous solution concentration is 4 ~ 8 g/L), slowly splash in above-mentioned mixed reaction solution, treat that L-glutamic acid adds complete, make mixture stirring reaction 12~72 hours under 0~40 ℃ of condition, with the reaction of thin-layer chromatography chromatogram monitoring; After question response finishes, by reaction solution concentrating under reduced pressure at 30~60 ℃, adopt crystallization process or organic solvent extractionprocess to separate and obtain product pentanedioic acid, its yield can reach 80%~95%.
In the inventive method, the raw material L-glutamic acid of use is Pidolidone or D-Glu or both mixtures, and operation and reaction yield are not had to impact, but considers from cost of material, take Pidolidone as preferred.
In the inventive method, mineral acid can be any one in hydrochloric acid, nitric acid, perchloric acid, sulfuric acid, phosphoric acid, Hydrogen bromide; In concrete use, hydrochloric acid, nitric acid, perchloric acid, Hydrogen bromide addition are 5:1~20:1 with the ratio of the amount of substance of L-glutamic acid, sulfuric acid is 3:1~10:1 with the ratio of the amount of substance of L-glutamic acid, and phosphoric acid is 2:1~10:1 with the ratio of the amount of substance of raw material L-glutamic acid.
The inventive method nitrite can be any one in Sodium Nitrite and potassium nitrite, and nitrite is 3:1~15:1 with the ratio of the amount of substance of L-glutamic acid, is first made into mass percentage concentration and is 5 ~ 20% the aqueous solution during use.
In the inventive method, reductive agent can be Hypophosporous Acid, 50 or hypophosphite, and mass percent concentration when wherein Hypophosporous Acid, 50 is used is 20 ~ 50%; Hypophosphite is any one in sodium hypophosphite, potassium hypophosphite, six waterside nickelous phosphates, a waterside manganous phosphate, ammonium hypophosphite, six waterside trimagnesium phosphates, calcium propionate; In use, Hypophosporous Acid, 50, sodium hypophosphite, potassium hypophosphite, ammonium hypophosphite are 5:1~20:1 with the ratio of the amount of substance of L-glutamic acid, and six waterside nickelous phosphates, a waterside manganous phosphate, six waterside trimagnesium phosphates, calcium propionate are 3:1~10:1 with the ratio of the amount of substance of L-glutamic acid; In use hypophosphite is mixed with to the aqueous solution that concentration is 100 ~ 150 g/L.
In the inventive method, use method separated product pentanedioic acid from reaction system of crystallization, need first reaction solution at 30~60 ℃ after concentrating under reduced pressure, add appropriate frozen water (add-on is 0.5 ~ 1 times of concentrated rear reaction solution volume), standing 1.5~3 h make pentanedioic acid crystallization, repeat 3 crystallisation processs and can make pentanedioic acid purity reach more than 99%, yield reaches more than 80%.
Also extraction process separated product pentanedioic acid from reaction system with an organic solvent in the methods of the invention, needs first reaction solution after concentrating under reduced pressure, with organic solvent extraction, is extracted and can make for 3 times the yield of pentanedioic acid reach more than 80% at 30~60 ℃; The mixture that the organic solvent using is a kind of in propyl carbinol, chloroform, methylene dichloride, ethyl acetate, ether, sherwood oil, toluene or any two kinds, and add at every turn volume be concentrated after reaction solution volume 1/3rd.
The advantage of the inventive method and technique effect: raw material L-glutamic acid and reaction reagent that present method is used are all cheap and easy to get, easy to operation, reaction process is environmental friendliness comparatively, be suitable for large-scale industrial production, the pentanedioic acid yield making by the inventive method can reach 80%~95%, purity >=99%.
Embodiment
Below by embodiment, further method described in the present invention is described; but protection domain of the present invention is not limited by embodiment; the reagent that the reagent using in the present embodiment is if no special instructions conventional commercial reagent or prepares according to a conventional method, the method for use is ordinary method if no special instructions.
Embodiment 1:
Getting 30 mL water adds in 100 mL three-necked flasks, it is cooling under cryosel is bathed, slowly add 0.56 mL hydrochloric acid (mass concentration 37%, 6.8 mmol), treat fully to mix, get Sodium Nitrite 234.6 mg(3.4 mmol) by 4.5 mL water dissolution, be placed in dropping funnel, slowly splash in hydrochloric acid soln.Then take 897.6 mg(6.8 mmol) in ice bath, cooling Hypophosporous Acid, 50 (aqueous solution that mass percent concentration is 50%) splashes into reaction system in advance, add with 5 minutes, add rear continuation magnetic agitation 30 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 50 mg Pidolidones (0.34 mmol) by 12.5 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain between 0~10 ℃, stirring reaction 12 hours, thin-layer chromatography chromatogram (silica gel G F
254, purchased from Haiyang Chemical Plant, Qingdao, propyl carbinol-Acetic Acid-Water (volume ratio 4:1:1) is developping agent, triketohydrindene hydrate and tetrabromo-mcresolsulfonphthalein are developer) and monitoring reaction process.
After reaction finishes, at 30 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when question response liquid is concentrated into approximately 30 mL (reaction solution becomes thickness), stop concentrating, toward wherein adding 15 mL frozen water, standing 1.5 h, suction filtration is collected crystallization, and crystal washs with a small amount of frozen water; After filtrate concentrates again, operation before repeating, obtains second batch crystallization; Carry out after primary crystallization operation again, three gained crystal are merged, after vacuum-drying, obtaining product pentanedioic acid is sheet clear crystal, weighs 40.9 mg, and yield is 91.3 %.Fusing point: 95~98 ℃, high resolution mass spectrum (HR-ESI MS): m/z=155.0316 ([M+Na]
+, calculated value: 155.0314).Proton nmr spectra (
1h NMR) (500 MHz, D
2o): δ 1.80-1.73 (2H, m, HOOC-CH
2-
cH 2 -CH
2-COOH), 2.34-2.27 (4H, m, HOOC-
cH 2 -CH
2-
cH 2 -COOH).Infrared spectra (IR) is (KBr): ν=3033,2956,1697,1444,982; Purity (according to
1h NMR and GC analyze)>=99%.
Embodiment 2:
Getting 150 mL water adds in 2000 mL three-necked bottles, it is cooling under cryosel is bathed, slowly add 11.6 mL phosphoric acid (mass concentrations 85%, 170 mmol), treat fully to mix, get potassium nitrite 8.67 g(102 mmol) by 78 mL water dissolution, be placed in dropping funnel, slowly splash in phosphoric acid solution, then take 18.2 g(170 mmol) sodium hypophosphite, with splashing into reaction system after 150 mL cold-water solutions, add with 30 minutes, after adding, continue magnetic agitation 1 hour, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 5 g D-Glus (34 mmol) by 625 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain between 35 ℃~40 ℃, stirring reaction 56 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 45 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when question response liquid is concentrated into approximately 150 mL, start to occur muddy, now stop concentrating, toward wherein adding 80 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 80 mL) above-mentioned concentrated solution with chloroform, merge organic layer, with 50 mL saturated common salt water washings, anhydrous magnesium sulfate drying 1 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 4.021 g, and yield is 89.6%, and its structural characterization is with embodiment 1.
Embodiment 3:
Getting 70 mL water adds in 500 mL three-necked bottles, it is cooling under cryosel is bathed, slowly add the 3.65 mL vitriol oil (mass concentrations 98%, 68 mmol), treat fully to mix, get Sodium Nitrite 4.69 g(68 mmol) by 20 mL water dissolution, be placed in dropping funnel, slowly splash in sulphuric acid soln, then take 5.78 g(34 mmol) calcium propionate, with splashing into reaction system after 40 mL cold-water solutions, add with 30 minutes, after adding, continue magnetic agitation 45 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 1 g Pidolidone (6.8 mmol) by 150 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain on 0 ℃ of left and right, stirring reaction 56 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 55 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when question response liquid is concentrated into approximately 50 mL, start to occur muddy, now stop concentrating, toward wherein adding 40 mL water, jolting makes reaction solution again become clarification gently; By ethyl acetate, divide three extractions (each 30 mL) above-mentioned concentrated solution, merge organic layer, with 20 mL saturated common salt water washings, anhydrous magnesium sulfate drying 0.5 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 0.766 g, and yield is 85.3%, and its structural characterization is with embodiment 1.
Embodiment 4:
Getting 35 mL water adds in 250 mL three-necked flasks, it is cooling under cryosel is bathed, slowly add 0.88 mL nitric acid (mass concentration 69.2%, 13.6 mmol), treat fully to mix, get Sodium Nitrite 469.2 mg(6.80 mmol) by 5 mL water dissolution, be placed in dropping funnel, slowly splash in salpeter solution.Then take 564.4 mg(6.80 mmol) ammonium hypophosphite, by 5.5 mL water dissolution, slowly splash into reaction system, add with 5 minutes, after adding, continue magnetic agitation 20 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 0.1g Pidolidone (0.68 mmol) by 25 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain between 0~10 ℃, stirring reaction 24 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 35 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when reaction solution is concentrated into approximately to 30 mL, start to occur muddy, now stop concentrating, toward wherein adding 15 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 20 mL) above-mentioned concentrated solution with propyl carbinol, merge organic layer, with 15 mL saturated common salt water washings, anhydrous magnesium sulfate drying 0.5 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 78.7 mg, and yield is 87.7%, and its structural characterization is with embodiment 1.
Embodiment 5:
Getting 180 mL water adds in 1000 mL three-necked bottles, it is cooling under cryosel is bathed, slowly add 15.7 mL Hydrogen bromide (mass concentrations 47%, 136 mmol), treat fully to mix, get Sodium Nitrite 7.04 g(102 mmol) by 65 mL water dissolution, be placed in dropping funnel, slowly splash in above-mentioned mixing solutions, then take 6.41 g(34 mmol) in ice bath, cooling Hypophosporous Acid, 50 (aqueous solution that mass percent concentration is 35%) splashes into reaction system in advance, add with 30 minutes, add rear continuation magnetic agitation 40 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃, get 1 g Pidolidone (6.8 mmol), 125 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain on 10 ℃ of left and right, stirring reaction 60 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 60 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when question response liquid is concentrated into approximately 50 mL, start to occur muddy, now stop concentrating, toward wherein adding 15 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 30 mL) above-mentioned concentrated solution with methylene dichloride, merge organic layer, with 20 mL saturated common salt water washings, anhydrous sodium sulfate drying 1 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 0.792 g, and yield is 88.2%.Its structural characterization is with embodiment 1.
Embodiment 6:
Getting 70 mL water adds in 500 mL three-necked bottles, it is cooling under cryosel is bathed, slowly add the 3.65 mL vitriol oil (mass concentrations 98%, 68 mmol), treat fully to mix, get Sodium Nitrite 7.04 g(102 mmol) by 40 mL water dissolution, be placed in dropping funnel, slowly splash in above-mentioned sulphuric acid soln, then take 6.05 g(20.4 mmol) six waterside nickelous phosphates, by 55 mL water dissolution, slowly splash into reaction system, add with 15 minutes, after adding, continue again magnetic agitation 40 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 1 g Pidolidone (6.8 mmol) by 125 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain between 20 ~ 30 ℃, stirring reaction 48 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 45 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when question response liquid is concentrated into approximately 150 mL, start to occur muddy, now stop concentrating, toward wherein adding 90 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 80 mL) above-mentioned concentrated solution with ether, merge organic layer, with 50 mL saturated common salt water washings, anhydrous magnesium sulfate drying 0.5 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 0.782 g, and yield is 87.1%.Its structural characterization is with embodiment 1.
Embodiment 7:
Getting 35 mL water adds in 250 mL three-necked flasks, it is cooling under cryosel is bathed, slowly add 0.59 mL perchloric acid (mass concentration 70%, 6.8 mmol), treat fully to mix, get Sodium Nitrite 469.2 mg(6.80 mmol) by 8 mL water dissolution, be placed in dropping funnel, slowly splash in nitric acid mixing solutions.Then take 628.7 mg(3.40 mmol) a waterside manganous phosphate, by 4.2 mL water dissolution, slowly splash into reaction system, add with 5 minutes.After adding, continue magnetic agitation 35 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 0.1g Pidolidone (0.68 mmol) by 12 mL water dissolution, splash in above-mentioned mixing solutions.After dropwising, temperature of reaction is remained between 30~40 ℃, stirring reaction 24 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 35 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when reaction solution is concentrated into approximately to 30 mL, start to occur muddy, now stop concentrating, toward wherein adding 15 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 15 mL) above-mentioned concentrated solution with propyl carbinol, merge organic layer, with 15 mL saturated common salt water washings, anhydrous magnesium sulfate drying 0.5 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 79.5 mg, and yield is 88.6%, and its structural characterization is with embodiment 1.
Embodiment 8:
Getting 70 mL water adds in 500 mL three-necked bottles, it is cooling under cryosel is bathed, slowly add the 3.65 mL vitriol oil (mass concentrations 98%, 68 mmol), treat fully to mix, get Sodium Nitrite 7.04 g(102 mmol) by 60 mL water dissolution, be placed in dropping funnel, slowly splash in above-mentioned sulphuric acid soln.Then take 17.84 g(68 mmol) six waterside trimagnesium phosphates, by 125 mL water dissolution, slowly splash into reaction system, add with 20 minutes.After adding, continue magnetic agitation 40 minutes, so that it fully mixes, this process need maintains in flask temperature between-10~0 ℃.Get 1 g Pidolidone (6.8 mmol) by 125 mL water dissolution, splash in above-mentioned mixed reaction solution.After adding, make temperature of reaction remain on 0 ℃ of left and right, stirring reaction 48 hours, thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction finishes, at 60 ℃ on Rotary Evaporators the above-mentioned reaction solution of concentrating under reduced pressure, when question response liquid is concentrated into approximately 150 mL, start to occur muddy, now stop concentrating, toward wherein adding 90 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 80 mL) above-mentioned concentrated solution with ether, merge organic layer, with 50 mL saturated common salt water washings, anhydrous magnesium sulfate drying 0.5 h; Suction filtration, is sheet clear crystal by the product pentanedioic acid obtaining after filtrate decompression evaporate to dryness, weighs 0.774 g, and yield is 86.3%.Its structural characterization is with embodiment 1.
Claims (4)
1. take L-glutamic acid as raw material, prepare the method for pentanedioic acid for one kind, it is characterized in that: take L-glutamic acid as raw material, mineral acid and nitrite mixing solutions are diazo reagent, take Hypophosporous Acid, 50 or hypophosphite as reductive agent, under 0~40 ℃ of condition, react 12~72 hours, after reaction solution is concentrated, crystallization or extraction make pentanedioic acid;
Described mineral acid is the one in hydrochloric acid, nitric acid, perchloric acid, sulfuric acid, phosphoric acid, Hydrogen bromide;
Described nitrite is Sodium Nitrite or potassium nitrite;
Described hypophosphite is the one in sodium hypophosphite, potassium hypophosphite, six waterside nickelous phosphates, a waterside manganous phosphate, ammonium hypophosphite, six waterside trimagnesium phosphates, calcium propionate.
2. the method for preparing pentanedioic acid take L-glutamic acid as raw material according to claim 1, it is characterized in that: hydrochloric acid, nitric acid, perchloric acid, Hydrogen bromide are 5:1~20:1 with the ratio of the amount of substance of L-glutamic acid, sulfuric acid is 3:1~10:1 with the ratio of the amount of substance of L-glutamic acid, and phosphoric acid is 2:1~10:1 with the ratio of the amount of substance of L-glutamic acid.
3. the method for preparing pentanedioic acid take L-glutamic acid as raw material according to claim 1, is characterized in that: nitrite is 3:1~15:1 with the ratio of the amount of substance of L-glutamic acid.
4. the method for preparing pentanedioic acid take L-glutamic acid as raw material according to claim 1, it is characterized in that: Hypophosporous Acid, 50, sodium hypophosphite, potassium hypophosphite, ammonium hypophosphite are 5:1~20:1 with the ratio of the amount of substance of L-glutamic acid, six waterside nickelous phosphates, a waterside manganous phosphate, six waterside trimagnesium phosphates, calcium propionate are 3:1~10:1 with the ratio of the amount of substance of L-glutamic acid.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410014637.6A CN103755545B (en) | 2014-01-14 | 2014-01-14 | Preparation method of glutaric acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410014637.6A CN103755545B (en) | 2014-01-14 | 2014-01-14 | Preparation method of glutaric acid |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103755545A true CN103755545A (en) | 2014-04-30 |
CN103755545B CN103755545B (en) | 2015-06-03 |
Family
ID=50522910
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410014637.6A Expired - Fee Related CN103755545B (en) | 2014-01-14 | 2014-01-14 | Preparation method of glutaric acid |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103755545B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112345475A (en) * | 2020-11-11 | 2021-02-09 | 昆明理工大学 | Method for rapidly detecting nitrite in food |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1066842A (en) * | 1992-06-17 | 1992-12-09 | 成都制药四厂 | The alpha-hydroxy-r-amino-butyric acid synthesis technique |
CN1938254A (en) * | 2004-03-26 | 2007-03-28 | 株式会社德山 | Process for producing aliphatic dicarboxylic acid compound |
-
2014
- 2014-01-14 CN CN201410014637.6A patent/CN103755545B/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1066842A (en) * | 1992-06-17 | 1992-12-09 | 成都制药四厂 | The alpha-hydroxy-r-amino-butyric acid synthesis technique |
CN1938254A (en) * | 2004-03-26 | 2007-03-28 | 株式会社德山 | Process for producing aliphatic dicarboxylic acid compound |
Non-Patent Citations (2)
Title |
---|
G. KUMARASWAMY等: "Stereoselective synthesis of belactosin C and its derivatives using a catalytic proline catalyzed crossed-aldol reaction", 《TETRAHEDRON LETTERS》 * |
邢其毅等: "《基础有机化学》", 30 June 2005, 高等教育出版社 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112345475A (en) * | 2020-11-11 | 2021-02-09 | 昆明理工大学 | Method for rapidly detecting nitrite in food |
Also Published As
Publication number | Publication date |
---|---|
CN103755545B (en) | 2015-06-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7267508B2 (en) | Manufacturing method of losartan | |
EP2754652A1 (en) | Taurine preparation method | |
Colvin et al. | Improved nitroaldol reactions and reductive routes to vicinal aminoalcohols | |
CN103910623A (en) | Preparation method for benzoic acid | |
CN101781235A (en) | Method for preparing 2-cyanophenol | |
CN106496038A (en) | A kind of preparation method of 3 methyl, 2 nitrobenzoic acid of high selectivity | |
CN103342646B (en) | High-selectivity synthesis method of 4-nitro-ortho-xylene | |
CN103755545B (en) | Preparation method of glutaric acid | |
US8754256B2 (en) | Process for preparation of L-Arginine α-ketoglutarate 1:1 and 2:1 | |
Reynolds et al. | The reactions of 2, 3-dichloro-1, 4-naphthoquinone with alkali metal cyanides | |
CN100513402C (en) | Method for producing 2-oxo-1-phenyl-3-oxabicyclo [3.1.0]hexane | |
CN106008599A (en) | Method for preparing pentadecane diethyl phosphate | |
CN102643264A (en) | Synthesizing method of trioxymethylene | |
CN103724275A (en) | 4-nitroimidazole and preparation method thereof | |
CN109721496A (en) | A kind of synthetic method of 3- nitro ortho-xylene | |
CN101759205A (en) | Method for preparing potassium nitrate by extracting n-butyl alcohol | |
CN102241599A (en) | Method for preparing glycine | |
CN102249950B (en) | Synthetic method of p-hydroxybenzonitrile | |
CN104211582A (en) | Synthesis method of resveratrol | |
CN101980997A (en) | Process for production of high-purity trimellitic acid | |
CN101016222B (en) | Method of eliminating boric acid group from alkyl biphenyl boric acid compounds | |
CN101134722A (en) | Method for synthesizing chloroacetic acid | |
CN106083554A (en) | Method for preparing 2-acetyl cyclohexanone by one-pot method | |
US3907883A (en) | Process for production of 1,12-dodecanedioic acid | |
CN110669097B (en) | Synthesis method of oleanoline derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20170705 Address after: 650093 Ring Road in Yunnan city of Kunming province No. 50 Kunming University of Science and Technology Xinying Campus Patentee after: INDUSTRY MANAGEMENT LTD KUNMING University OF SCIENCE AND TECHNOLOGY Address before: 650093 Kunming, Yunnan, Wuhua District Road, No. 253 Patentee before: Kunming University of Science and Technology |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150603 Termination date: 20220114 |