CN103755545B - Preparation method of glutaric acid - Google Patents

Preparation method of glutaric acid Download PDF

Info

Publication number
CN103755545B
CN103755545B CN201410014637.6A CN201410014637A CN103755545B CN 103755545 B CN103755545 B CN 103755545B CN 201410014637 A CN201410014637 A CN 201410014637A CN 103755545 B CN103755545 B CN 103755545B
Authority
CN
China
Prior art keywords
acid
hypophosphite
reaction
waterside
glutamic acid
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.)
Expired - Fee Related
Application number
CN201410014637.6A
Other languages
Chinese (zh)
Other versions
CN103755545A (en
Inventor
廖霞俐
张伟
饶梦云
成忠均
朱小燕
李晨
李明波
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Industry Management Ltd Kunming University Of Science And Technology
Original Assignee
Kunming University of Science and Technology
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Kunming University of Science and Technology filed Critical Kunming University of Science and Technology
Priority to CN201410014637.6A priority Critical patent/CN103755545B/en
Publication of CN103755545A publication Critical patent/CN103755545A/en
Application granted granted Critical
Publication of CN103755545B publication Critical patent/CN103755545B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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

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

A kind of preparation method of pentanedioic acid
Technical field
The invention belongs to technical field of fine, being specifically related to a kind of take L-glutamic acid as the method that pentanedioic acid prepared by raw material.
Background technology
Pentanedioic acid (Glutaric Acid, formula I) is a kind of important industrial chemicals and medicine intermediate, has application widely in fields such as fine chemistry industry, agricultural, medicine and buildings.In plastics chemical industry, pentanedioic acid can be used to produce polyvinyl chloride, polyester, polyene amine and the important macromolecular material such as resin, synthetic rubber; In pharmaceutical industries, pentanedioic acid not only can be used as the important intermediate of synthesis cardiovascular drug, simultaneously due to its good broad-spectrum bactericidal capacity, can be used for producing various thimerosal and relevant medicine, be used for killing the bacterium, insect etc. that parasitize on animal, plant, also can be used for insect protected; In addition, pentanedioic acid also has important application in the many alcohol of synthesizing polyester, preparation scale remover, sulfur-bearing flue washing composition, refrigerant and stiffening agent etc.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 obtain pentanedioic acid by the by product be separated in hexanodioic acid production process, 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 is difficult.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, produce by absorption method the demand that pentanedioic acid cannot meet Vehicles Collected from Market.
Synthesis method is the research direction of most application prospect during current pentanedioic acid is produced.It is multi-step synthetic method (the Org. Synth. of raw material that synthesis method traditionally comprises with gamma-butyrolactone, 1963, Coll. Vol. 4,496.), take dihydropyrane as oxidizing water solution (Org. Synth., 1963 of raw material, Coll. Vol. 4,497.) be and with trimethylene cyanide acid hydrolyzation (Org. Synth., 1941, the Coll. Vol. 1 of raw material, etc., but all there is the distinct disadvantage such as expensive starting materials, reagent toxicity be large 289.).In recent years, be oxygenant with hydrogen peroxide, under the catalysis of the precious metals such as palladium, the method preparing pentanedioic acid be oxidized to glutaraldehyde, ring pentanediol or cyclopentenes, highlight 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, in the mode of airwater mist cooling interval or successive reaction, glutaraldehyde is oxidized to pentanedioic acid under mild conditions.But the palladium catalyst that the method uses is expensive, recovery utilization rate is low, poor repeatability, and production cost is higher.Patent application CN 1557798A and CN 1546452A is catalyzer with wolframic acid, take hydrogen peroxide as oxygenant, carries out oxidative synthesis pentanedioic acid respectively, have eco-friendly feature to cyclopentenes and 1,2-ring pentanediol.But its temperature of reaction is higher, and unsafe factor when using hydrogen peroxide can bring aftertreatment in actual production, be therefore unfavorable for large-scale industrial production.
The present invention intends providing a kind of with L-glutamic acid [Pidolidone (L-Glutamic Acid, formula II), D-Glu or both mixtures] prepare the method for pentanedioic acid for raw material, the cheaper starting materials used is easy to get, reaction conditions is gentle, preparation and sepn process 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 take L-glutamic acid as the method that pentanedioic acid prepared by raw material.The method take L-glutamic acid as raw material, mineral acid and nitrite mixing solutions are diazo reagent, with Hypophosporous Acid, 50 or hypophosphite for reductive agent, stirring reaction 12 ~ 72 hours under 0 ~ 40 DEG C 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.
What the present invention proposed take L-glutamic acid as the method that pentanedioic acid prepared by raw material, and its concrete technology is as follows:
A certain amount of water (its volume is 10 ~ 60 times of mineral acid volume) is added in flask, cooling under cryosel bath, a certain amount of mineral acid of slow dropping, slowly drip the nitrite aqueous solution that mass percent concentration is 5 ~ 20% again, then reductive agent Hypophosporous Acid, 50 (mass percentage concentration is 20 ~ 50%) or the hypophosphite aqueous solution (concentration is 100 ~ 150 g/L) is added, magnetic agitation 10 ~ 60 minutes, to make it fully mix, it is-10 ~ 0 DEG C that this process need maintains pot temperature.Take raw material L-glutamic acid and at room temperature use water dissolution (glutamic acid aqueous solution concentration is 4 ~ 8 g/L), in the above-mentioned mixed reaction solution of slow instillation, treat that L-glutamic acid adds complete, make mixture stirring reaction 12 ~ 72 hours under 0 ~ 40 DEG C of condition, react with thin-layer chromatography chromatogram monitoring; After question response terminates, by reaction solution concentrating under reduced pressure at 30 ~ 60 DEG C, adopt crystallization process or organic solvent extractionprocess to be separated 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 not having impact to operation and reaction yield, but consider from cost of material, is preferred with Pidolidone.
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 in Sodium Nitrite and potassium nitrite any one, and nitrite is 3:1 ~ 15:1 with the ratio of the amount of substance of L-glutamic acid, is first made into the aqueous solution that mass percentage concentration is 5 ~ 20% during use.
In the inventive method, reductive agent can be Hypophosporous Acid, 50 or hypophosphite, and mass percent concentration when wherein Hypophosporous Acid, 50 uses 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; Hypophosphite is mixed with the aqueous solution that concentration is 100 ~ 150 g/L in use.
The method of crystallization separated product pentanedioic acid from reaction system is used in the inventive method, need first by reaction solution at 30 ~ 60 DEG C after concentrating under reduced pressure, add appropriate frozen water (add-on is 0.5 ~ 1 times of concentrated rear reaction solution volume), leave standstill 1.5 ~ 3 h and make pentanedioic acid crystallization, repeating 3 crystallisation processs can make pentanedioic acid purity reach more than 99%, and yield reaches more than 80%.
In the methods of the invention also can with an organic solvent extraction process separated product pentanedioic acid from reaction system, need first reaction solution after concentrating under reduced pressure, with organic solvent extraction, to be extracted and the yield of pentanedioic acid can be made for 3 times to reach more than 80% at 30 ~ 60 DEG C; The organic solvent used is propyl carbinol, the mixture of a kind of in 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 the reaction reagent of present method use 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 obtained by the inventive method can reach 80% ~ 95%, purity >=99%.
Embodiment
Further method described in the present invention is described below by embodiment; but scope does not limit by embodiment; the reagent that the reagent used in the present embodiment is conventional commercial reagent if no special instructions 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, cooling under cryosel bath, slowly add 0.56 mL hydrochloric acid (mass concentration 37%, 6.8 mmol), treat abundant mixing, get Sodium Nitrite 234.6 mg(3.4 mmol) by 4.5 mL water dissolution, be placed in dropping funnel, slowly in instillation hydrochloric acid soln.Then 897.6 mg(6.8 mmol are taken) Hypophosporous Acid, 50 (mass percent concentration is the aqueous solution of 50%) that cools in ice bath in advance instills reaction system, added with 5 minutes, add rear continuation magnetic agitation 30 minutes, to make it fully mix, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 50 mg Pidolidones (0.34 mmol) by 12.5 mL water dissolution, instill in above-mentioned mixed reaction solution.Temperature of reaction is made to remain between 0 ~ 10 DEG C after adding, stirring reaction 12 hours, thin-layer chromatography chromatogram (silica gel G F 254, purchased from Haiyang Chemical Plant, Qingdao, n-Butanol acetic acid-water (volume ratio 4:1:1) is developping agent, and triketohydrindene hydrate and tetrabromo-mcresolsulfonphthalein are developer) and monitor reaction process.
After reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 30 DEG C, when question response liquid is concentrated into about 30 mL (reaction solution becomes thickness), stopping concentrated, toward wherein adding 15 mL frozen water, leaving standstill 1.5 h, collected by suction crystallization, a small amount of frozen water of crystal washs; Filtrate operates before repetition, obtains second batch crystallization after again concentrating; After carrying out primary crystallization operation again, merged by three gained crystal, obtaining product pentanedioic acid after vacuum-drying is sheet clear crystal, weighs 40.9 mg, and yield is 91.3 %.Fusing point: 95 ~ 98 DEG C, 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) (KBr): ν=3033,2956,1697,1444,982; Purity (according to 1h NMR and GC analyzes)>=99%.
Embodiment 2:
Getting 150 mL water adds in 2000 mL three-necked bottles, cooling under cryosel bath, slowly add 11.6 mL phosphoric acid (mass concentrations 85%, 170 mmol), treat abundant mixing, get potassium nitrite 8.67 g(102 mmol) by 78 mL water dissolution, be placed in dropping funnel, in slow instillation phosphoric acid solution, then 18.2 g(170 mmol are taken) sodium hypophosphite, reaction system is instilled with after 150 mL cold-water solutions, added with 30 minutes, magnetic agitation is continued 1 hour after adding, fully mix to make it, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 5 g D-Glus (34 mmol) by 625 mL water dissolution, instill in above-mentioned mixed reaction solution.Temperature of reaction is made to remain between 35 DEG C ~ 40 DEG C after adding, stirring reaction 56 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 45 DEG C, and when question response liquid is concentrated into about 150 mL, start to occur muddy, now stop concentrated, 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 obtained 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, cooling under cryosel bath, slowly add the 3.65 mL vitriol oil (mass concentrations 98%, 68 mmol), treat abundant mixing, get Sodium Nitrite 4.69 g(68 mmol) by 20 mL water dissolution, be placed in dropping funnel, in slow instillation sulphuric acid soln, then 5.78 g(34 mmol are taken) calcium propionate, reaction system is instilled with after 40 mL cold-water solutions, added with 30 minutes, magnetic agitation is continued 45 minutes after adding, fully mix to make it, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 1 g Pidolidone (6.8 mmol) by 150 mL water dissolution, instill in above-mentioned mixed reaction solution.Temperature of reaction is made to remain on about 0 DEG C after adding, stirring reaction 56 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 55 DEG C, and when question response liquid is concentrated into about 50 mL, start to occur muddy, now stop concentrated, toward wherein adding 40 mL water, jolting makes reaction solution again become clarification gently; Divide three extractions (each 30 mL) above-mentioned concentrated solution by ethyl acetate, 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 obtained 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, cooling under cryosel bath, slowly add 0.88 mL nitric acid (mass concentration 69.2%, 13.6 mmol), treat abundant mixing, get Sodium Nitrite 469.2 mg(6.80 mmol) by 5 mL water dissolution, be placed in dropping funnel, slowly in instillation salpeter solution.Then 564.4 mg(6.80 mmol are taken) ammonium hypophosphite, by 5.5 mL water dissolution, slowly instill reaction system, added with 5 minutes, continue magnetic agitation after adding 20 minutes, to make it fully mix, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 0.1g Pidolidone (0.68 mmol) by 25 mL water dissolution, instill in above-mentioned mixed reaction solution.Temperature of reaction is made to remain between 0 ~ 10 DEG C after adding, stirring reaction 24 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 35 DEG C, and start to occur muddy when reaction solution being concentrated into about 30 mL, now stop concentrated, 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 obtained 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, cooling under cryosel bath, slowly add 15.7 mL Hydrogen bromide (mass concentrations 47%, 136 mmol), treat abundant mixing, get Sodium Nitrite 7.04 g(102 mmol) by 65 mL water dissolution, be placed in dropping funnel, in the above-mentioned mixing solutions of slow instillation, then 6.41 g(34 mmol are taken) Hypophosporous Acid, 50 (mass percent concentration is the aqueous solution of 35%) that cools in ice bath in advance instills reaction system, added with 30 minutes, add rear continuation magnetic agitation 40 minutes, fully mix to make it, it is between-10 ~ 0 DEG C that this process need maintains pot temperature, get 1 g Pidolidone (6.8 mmol), 125 mL water dissolution, instill in above-mentioned mixed reaction solution.Temperature of reaction is made to remain on about 10 DEG C after adding, stirring reaction 60 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 60 DEG C, and when question response liquid is concentrated into about 50 mL, start to occur muddy, now stop concentrated, 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 obtained 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, cooling under cryosel bath, slowly add the 3.65 mL vitriol oil (mass concentrations 98%, 68 mmol), treat abundant mixing, get Sodium Nitrite 7.04 g(102 mmol) by 40 mL water dissolution, be placed in dropping funnel, in the above-mentioned sulphuric acid soln of slow instillation, then 6.05 g(20.4 mmol are taken) six waterside nickelous phosphates, by 55 mL water dissolution, slow instillation reaction system, added with 15 minutes, magnetic agitation is continued again 40 minutes after adding, fully mix to make it, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 1 g Pidolidone (6.8 mmol) by 125 mL water dissolution, instill in above-mentioned mixed reaction solution.Temperature of reaction is made to remain between 20 ~ 30 DEG C after adding, stirring reaction 48 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 45 DEG C, and when question response liquid is concentrated into about 150 mL, start to occur muddy, now stop concentrated, 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 obtained 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, cooling under cryosel bath, slowly add 0.59 mL perchloric acid (mass concentration 70%, 6.8 mmol), treat abundant mixing, get Sodium Nitrite 469.2 mg(6.80 mmol) by 8 mL water dissolution, be placed in dropping funnel, slowly in instillation nitric acid mixing solutions.Then 628.7 mg(3.40 mmol are taken) a waterside manganous phosphate, by 4.2 mL water dissolution, slowly instill reaction system, added with 5 minutes.Continue magnetic agitation after adding 35 minutes, to make it fully mix, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 0.1g Pidolidone (0.68 mmol) by 12 mL water dissolution, instill in above-mentioned mixing solutions.After dropwising, temperature of reaction is made to remain between 30 ~ 40 DEG C, stirring reaction 24 hours; Thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 35 DEG C, and start to occur muddy when reaction solution being concentrated into about 30 mL, now stop concentrated, 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 obtained 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, cooling under cryosel bath, slowly add the 3.65 mL vitriol oil (mass concentrations 98%, 68 mmol), treat abundant mixing, get Sodium Nitrite 7.04 g(102 mmol) by 60 mL water dissolution, be placed in dropping funnel, slowly in the above-mentioned sulphuric acid soln of instillation.Then 17.84 g(68 mmol are taken) six waterside trimagnesium phosphates, by 125 mL water dissolution, slowly instill reaction system, added with 20 minutes.Continue magnetic agitation after adding 40 minutes, to make it fully mix, it is between-10 ~ 0 DEG C that this process need maintains pot temperature.Get 1 g Pidolidone (6.8 mmol) by 125 mL water dissolution, instill in above-mentioned mixed reaction solution.After adding, temperature of reaction is made to remain on about 0 DEG C, stirring reaction 48 hours, thin-layer chromatography chromatogram (chromatographic condition is with embodiment 1) monitoring reaction process.
Reaction terminates, the above-mentioned reaction solution of concentrating under reduced pressure on a rotary evaporator at 60 DEG C, and when question response liquid is concentrated into about 150 mL, start to occur muddy, now stop concentrated, 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 obtained after filtrate decompression evaporate to dryness, weighs 0.774 g, and yield is 86.3%.Its structural characterization is with embodiment 1.

Claims (1)

1. one kind is the method that pentanedioic acid prepared by raw material with L-glutamic acid, it is characterized in that: take L-glutamic acid as raw material, mineral acid and nitrite mixing solutions are diazo reagent, with Hypophosporous Acid, 50 or hypophosphite for reductive agent, react 12 ~ 72 hours under 0 ~ 40 DEG C of condition, after reaction solution is concentrated, crystallization or the obtained pentanedioic acid of extraction;
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;
Described 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, and 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;
Described nitrite is 3:1 ~ 15:1 with the ratio of the amount of substance of L-glutamic acid;
Described 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.
CN201410014637.6A 2014-01-14 2014-01-14 Preparation method of glutaric acid Expired - Fee Related CN103755545B (en)

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 CN103755545A (en) 2014-04-30
CN103755545B true 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)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112345475B (en) * 2020-11-11 2022-09-20 昆明理工大学 Method for rapidly detecting nitrite in food

Citations (2)

* Cited by examiner, † Cited by third party
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
Title
Stereoselective synthesis of belactosin C and its derivatives using a catalytic proline catalyzed crossed-aldol reaction;G. Kumaraswamy等;《Tetrahedron Letters》;20070101;第48卷(第10期);1708页scheme 1-2 *
邢其毅等.基础有机化学.《基础有机化学》.高等教育出版社,2005,(第3版), *

Also Published As

Publication number Publication date
CN103755545A (en) 2014-04-30

Similar Documents

Publication Publication Date Title
JP7267508B2 (en) Manufacturing method of losartan
US8680329B2 (en) Process for preparation of α-ketoglutaric acid
CN101781235A (en) Method for preparing 2-cyanophenol
CN106496038A (en) A kind of preparation method of 3 methyl, 2 nitrobenzoic acid of high selectivity
CN103755545B (en) Preparation method of glutaric acid
US8754256B2 (en) Process for preparation of L-Arginine α-ketoglutarate 1:1 and 2:1
CN109232259A (en) A kind of preparation method of nitro-acetophenone
CN101270063A (en) Method for preparing high purity solid cyanoacetic acid
CN106008599A (en) Method for preparing pentadecane diethyl phosphate
CN109721496A (en) A kind of synthetic method of 3- nitro ortho-xylene
CN101891757B (en) Preparation method of catalyst for producing cephalosporin
CN103724275A (en) 4-nitroimidazole and preparation method thereof
CN110407740A (en) A kind of synthetic method of the bromo- 2- ethylpyridine of 3-
CN105820054A (en) Preparation method of 3-methoxy-2-nitrobenzoate
CN108752218B (en) Route for preparing dolutegravir key intermediate 2, 4-difluorobenzylamine
CN106588698A (en) Preparation method of N-Boc biphenyl alaninal
CN104211582A (en) Synthesis method of resveratrol
CN105541656A (en) Preparation method of benzamide
CN106905161A (en) A kind of synthetic method of the nitrobenzoic acid of 2 chlorine, 4 fluorine 5
CN104370807B (en) The synthetic method of a kind of 6-hydroxyl-5-nitronicotinic acid and process for separation and purification thereof
CN108929226B (en) Method for preparing benzoyl formate derivative
CN108218649B (en) Synthetic method of pregabalin and intermediate thereof
CN105669539A (en) Preparation method of 2-amino-3-fluoropyridine
JP4372242B2 (en) Method for producing isochromanone derivative
CN106083554A (en) A kind of one kettle way prepares the method for 2 acetyl cyclohexanones

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