CN105198843A - One-pot synthesizing method of 2-(furan-2-yl)-2-glyoxalic acid - Google Patents

One-pot synthesizing method of 2-(furan-2-yl)-2-glyoxalic acid Download PDF

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Publication number
CN105198843A
CN105198843A CN201510616708.4A CN201510616708A CN105198843A CN 105198843 A CN105198843 A CN 105198843A CN 201510616708 A CN201510616708 A CN 201510616708A CN 105198843 A CN105198843 A CN 105198843A
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furans
reaction
base
furfural
acid
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CN105198843B (en
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战付旭
郑庚修
姜守相
张启龙
杨倩
刘庆东
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University of Jinan
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University of Jinan
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Furan Compounds (AREA)

Abstract

The invention relates to a one-pot synthesizing method of 2-(furan-2-yl)-2-glyoxalic acid and belongs to the technical field of medical intermediate preparation. The invention provides a novel method for synthesizing the 2-(furan-2-yl)-2-glyoxalic acid through two-step one port reaction of furfural and nitromethane. The one-pot synthesizing method of the 2-(furan-2-yl)-2-glyoxalic acid has the advantages that the reaction condition is mild, materials are low in cost and easy to obtain, and the method is suitable for industrial large-scale production.

Description

The One-step Synthesis method of 2-(furans-2-base)-2-Oxoacetic Acid
technical field:
The invention belongs to chemosynthesis technical field, relate to the one pot process of a kind of important medicine intermediate 2-(furans-2-base)-2-Oxoacetic Acid.
background technology:
2-(furans-2-base)-2-Oxoacetic Acid, having another name called furans ketone acid is one of important intermediate of producing microbiotic cephalofruxin, and it has following structure:
Cephalofruxin is a kind of non-wide spectrum Cephalosporin class microbiotic through gastro-intestinal administration, and this medicine need obtain through semi-synthetic aborning, and furans ketone acid is one of its important intermediate.
Patent 201010584693 relate to the method for being synthesized furans ketone acid by 2-furancarboxylic acid.First 2-furancarboxylic acid and phosphorus trichloride are carried out chlorination by the method in enamel reaction still, obtain furoyl chloride.The latter carries out cyanogenation with sodium cyanide more in a kettle., is finally hydrolyzed and can obtains furans ketone acid.This inventive method condition is comparatively harsh, and has used deadly poisonous compound sodium cyanide, has larger danger.
Patent 200910097425 relate to the synthetic method of furans ketone acid.The method is reacted by Sodium Nitrite and acetyl furan, obtains furans ketone acid through oximate, rearrangement, hydrolysis.Present invention employs the oximation reaction temperature of 58 ~ 60oC, the production rate of furancarboxylic acid is less than 1%, improves productive rate.Patent 201210334531 further improves aforesaid method, adds this oximation reaction of metal salt catalyst, and the productive rate of final furans ketone acid is further enhanced.The method is mentioned simultaneously and after oxidation completes, directly can be carried out acidifying to gained solution, and for the novel method that next step reacts, has higher reference value.
But the main raw material acetyl furan price that aforesaid method is used is higher, become the prime cost source producing furans ketone acid.Therefore seek the synthetic route redesigned, producing furanone acid using the furfural that price is more cheap as raw material just becomes significantly thing.
summary of the invention:
The invention provides the one-pot synthesis method (being shown below) of a kind of medicine intermediate 2-(furans-2-base)-2-Oxoacetic Acid.
concrete steps are:
Step 1)
By furfural (0.96 ~ 96.1g, 10.0 ~ 1000mmol) be dissolved in mixing solutions (methyl alcohol and the water of methyl alcohol and water, volume ratio 1:4,20 ~ 2000mL) in, add Nitromethane 99Min. (0.64 ~ 640mL, 12.0 ~ 1200mmol, 1.2eq), alkali (1.0 ~ 100mmol, 0.1eq) and phase-transfer catalyst (1.0 ~ 100mmol, 0.1eq), room temperature carries out reaction 5h.After TLC detection reaction completes, reaction solution is directly used in next step reaction.
Step 2)
Acetic acid (4 ~ 400mL) is added in the reaction solution in step 1), acetic acid in regulation system: methyl alcohol: the ratio of water is 1:1:4, backward system in add mantoquita (1.0 ~ 100mmol, 0.1eq), be warming up to 90oC, and in system, blast air carry out reaction 3h.Question response completes, acetic acid in system and methyl alcohol are removed the suspension liquid obtained containing product by cool to room temperature by Rotary Evaporators, the pH value of hydrochloric acid conditioning solution is used to be 3 afterwards, obtain the solution of 2-(furans-2-base)-2-Oxoacetic Acid, Liquid Detection transformation efficiency is 85 ~ 90%, this solution can be directly used in next step reaction, prepares SMIA product.
beneficial effect of the present invention is:
Use furfural cheap and easy to get for main raw material, under mild conditions through the reaction of two step one pot, synthesize important medicine intermediate 2-(furans-2-base)-2-Oxoacetic Acid.Before present invention obviates, the common method of industrial synthesis 2-(furans-2-base)-2-Oxoacetic Acid, makes the production cost of this product greatly reduce, and is applicable to the production of industrially scalable.
embodiment:
embodiment 1:
Step 1)
By furfural (0.96g, 10.0mmol) be dissolved in the mixing solutions (methyl alcohol and water, volume ratio 1:4,20mL) of methyl alcohol and water, add Nitromethane 99Min. (0.64mL, 12.0mmol, 1.2eq), potassium hydroxide (0.06g, 1.0mmol, 0.1eq) with benzyltriethylammoinium chloride (0.23g, 1.0mmol, 0.1eq), room temperature carries out reaction 5h.After TLC detection reaction completes, reaction solution is directly used in next step reaction.
Step 2)
In the reaction solution in step 1), add acetic acid (4mL), acetic acid in regulation system: methyl alcohol: the ratio of water is 1:1:4, backward system in add a hydration neutralized verdigris (0.20g, 1.0mmol, 0.1eq), be warming up to 90oC, and in system, blast air carry out reaction 3h.Question response completes, acetic acid in system and methyl alcohol are removed the suspension liquid obtained containing product by cool to room temperature by Rotary Evaporators, the pH value using hydrochloric acid conditioning solution is afterwards 3, and obtain the solution of 2-(furans-2-base)-2-Oxoacetic Acid, Liquid Detection transformation efficiency is 88%.
embodiment 2:
Step 1)
By furfural (9.6g, 100.0mmol) be dissolved in the mixing solutions (methyl alcohol and water, volume ratio 1:4,200mL) of methyl alcohol and water, add Nitromethane 99Min. (6.4mL, 120.0mmol, 1.2eq), sodium hydroxide (0.40g, 10.0mmol, 0.1eq) with Dodecyl trimethyl ammonium chloride (2.63g, 10.0mmol, 0.1eq), room temperature carries out reaction 5h.After TLC detection reaction completes, reaction solution is directly used in next step reaction.
Step 2)
In the reaction solution in step 1), add acetic acid (40mL), acetic acid in regulation system: methyl alcohol: the ratio of water is 1:1:4, backward system in add cupric chloride (1.3g, 1.0mmol, 0.1eq), be warming up to 90oC, and in system, blast air carry out reaction 3h.Question response completes, acetic acid in system and methyl alcohol are removed the suspension liquid obtained containing product by cool to room temperature by Rotary Evaporators, the pH value using hydrochloric acid conditioning solution is afterwards 3, and obtain the solution of 2-(furans-2-base)-2-Oxoacetic Acid, Liquid Detection transformation efficiency is 89%.
embodiment 3:
Step 1)
By furfural (96.1g, 1000mmol) be dissolved in the mixing solutions (methyl alcohol and water, volume ratio 1:4,2000mL) of methyl alcohol and water, add Nitromethane 99Min. (640mL, 1200mmol, 1.2eq), sodium hydroxide (4.0g, 100mmol, 0.1eq) with tetrabutylammonium chloride (27.8g, 100mmol, 0.1eq), room temperature carries out reaction 5h.After TLC detection reaction completes, reaction solution is directly used in next step reaction.
Step 2)
In the reaction solution in step 1), add acetic acid (400mL), acetic acid in regulation system: methyl alcohol: the ratio of water is 1:1:4, backward system in add a hydration neutralized verdigris (20.0g, 1.0mmol, 0.1eq), be warming up to 90oC, and in system, blast air carry out reaction 3h.Question response completes, acetic acid in system and methyl alcohol are removed the suspension liquid obtained containing product by cool to room temperature by Rotary Evaporators, the pH value using hydrochloric acid conditioning solution is afterwards 3, and obtain the solution of 2-(furans-2-base)-2-Oxoacetic Acid, Liquid Detection transformation efficiency is 89%.
The specific embodiment of the present invention is described although above-mentioned in conjunction with the embodiments; but not limiting the scope of the invention; one of ordinary skill in the art should be understood that; on the basis of technical scheme of the present invention, those skilled in the art do not need to pay various amendment or distortion that creative work can make still within protection scope of the present invention.

Claims (7)

1. the method for one pot process 2-(furans-2-base)-2-Oxoacetic Acid, with furfural and Nitromethane 99Min. for raw material, in the methanol-water solution of alkalescence, there is Adol-Henry reaction, subsequently to the mantoquita and the acetic acid that add divalence in reaction system, and pass into air and be oxidized, obtain 2-(furans-2-base)-2-Oxoacetic Acid, comprise the following steps:
Under step 1) normal temperature, be dissolved in methanol-water solution by furfural and Nitromethane 99Min., add alkali and the phase-transfer catalyst of catalytic amount wherein, normal temperature reacts, and TLC detection reaction progress, treats that furfural reaction is complete, is directly used in next step reaction
Step 2) in the solution of 1-(furans-2-base)-2-nitroethyl alcohol, add acetic acid and water is adjusted to suitable proportion, add cupric salt afterwards, pass into air heating to react to 90oC, complete through TLC detection reaction, methyl alcohol in Rotary Evaporators removing mixed solution and acetic acid, with extraction into ethyl acetate aqueous phase three times, through activated carbon decolorizing, evaporate to dryness obtains 2-(furans-2-base)-2-Oxoacetic Acid crude product.
2. as right 1 require as described in the synthetic method of 1-(furans-2-base)-2-nitroethyl alcohol, it is characterized in that, in step 1), the mol ratio of furfural, Nitromethane 99Min., alkali and phase-transfer catalyst is 1:1.2:0.1:0.1; The ratio of first alcohol and water is 1:4; Temperature of reaction is room temperature (25oC), and the reaction times is 5h.
3. as right 1 require as described in the synthetic method of 1-(furans-2-base)-2-nitroethyl alcohol, it is characterized in that, the alkali in step 1) can be sodium carbonate, salt of wormwood, sodium hydroxide, potassium hydroxide and cesium carbonate etc., is wherein the best with sodium hydroxide.
4. as right 1 require as described in the synthetic method of 1-(furans-2-base)-2-nitroethyl alcohol, it is characterized in that, phase-transfer catalyst in step 1) can be benzyltriethylammoinium chloride (TEBA), Tetrabutyl amonium bromide, tetrabutylammonium chloride, tri-n-octyl methyl ammonium chloride, Dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride, cetyl trimethylammonium bromide (CTMAB) etc., is wherein the best with Dodecyl trimethyl ammonium chloride.
5. as right 1 require as described in the synthetic method of 2-(furans-2-base)-2-Oxoacetic Acid, it is characterized in that, step 2) in add acetic acid, regulate methyl alcohol: acetic acid: the volume ratio of water is 1:1:4; The mantoquita added is 10% relative to the ratio of furfural in step 1); Temperature of reaction is 90oC; Reaction times is 3h.
6. as right 1 require as described in the synthetic method of 2-(furans-2-base)-2-Oxoacetic Acid, it is characterized in that, step 2) in mantoquita can be copper sulfate, cupric chloride, cupric bromide, cupric nitrate, venus crystals, cuprous iodide etc., be wherein the best with venus crystals.
7. as right 1 require as described in step 1) in the molar weight of furfural can from 10.0 to 1000mmol.
CN201510616708.4A 2015-09-25 2015-09-25 The One-step Synthesis method of 2 (base of furans 2) 2 Oxoacetic Acids Expired - Fee Related CN105198843B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115504947A (en) * 2022-08-23 2022-12-23 山东和源制药有限公司 Preparation method of furanone acid

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CN101830783A (en) * 2010-05-28 2010-09-15 济南大学 Method for preparing aldehyde by oxidizing alcohol with oxygen in presence of Schiff-base complex catalyst
CN104193600A (en) * 2014-08-11 2014-12-10 济南大学 Method for preparing aldehyde or ketone from air oxidized alcohol by using aluminum oxide as co-catalyst

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Publication number Priority date Publication date Assignee Title
JPS5227745A (en) * 1975-08-26 1977-03-02 Mitsubishi Petrochem Co Ltd Method for carbonating aldehydes
CN1571780A (en) * 2001-09-28 2005-01-26 化学生物活动中心 Synthetic method of 2-(2-nitroethylenyl)-furan and its purpose as anti-coccidium agent
CN101830783A (en) * 2010-05-28 2010-09-15 济南大学 Method for preparing aldehyde by oxidizing alcohol with oxygen in presence of Schiff-base complex catalyst
CN104193600A (en) * 2014-08-11 2014-12-10 济南大学 Method for preparing aldehyde or ketone from air oxidized alcohol by using aluminum oxide as co-catalyst

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Title
ANJOY MAJHI ET AL: "TMEDA Catalyzed Henry (Nitroaldol) Reaction under Metal and Solvent-free Conditions", 《BULL. KOREAN CHEM. SOC.》 *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115504947A (en) * 2022-08-23 2022-12-23 山东和源制药有限公司 Preparation method of furanone acid
CN115504947B (en) * 2022-08-23 2024-04-26 山东和源制药有限公司 Preparation method of furanone acid

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