CN105949075B - A kind of synthetic method of mefenamic acid - Google Patents
A kind of synthetic method of mefenamic acid Download PDFInfo
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- CN105949075B CN105949075B CN201610475862.9A CN201610475862A CN105949075B CN 105949075 B CN105949075 B CN 105949075B CN 201610475862 A CN201610475862 A CN 201610475862A CN 105949075 B CN105949075 B CN 105949075B
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- mefenamic acid
- benzoic acid
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- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960003464 mefenamic acid Drugs 0.000 title claims abstract description 28
- 238000010189 synthetic method Methods 0.000 title claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000006482 condensation reaction Methods 0.000 claims abstract description 8
- 239000012024 dehydrating agents Substances 0.000 claims abstract description 8
- 239000002798 polar solvent Substances 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 6
- 239000011230 binding agent Substances 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical class CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims abstract description 3
- 230000000694 effects Effects 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- VVAKEQGKZNKUSU-UHFFFAOYSA-N 2,3-dimethylaniline Chemical compound CC1=CC=CC(N)=C1C VVAKEQGKZNKUSU-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 claims description 3
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 3
- 229940071125 manganese acetate Drugs 0.000 claims description 2
- 229940099596 manganese sulfate Drugs 0.000 claims description 2
- 239000011702 manganese sulphate Substances 0.000 claims description 2
- 235000007079 manganese sulphate Nutrition 0.000 claims description 2
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 claims description 2
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- 150000002696 manganese Chemical class 0.000 abstract description 5
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- -1 chlorobenzene Formic acid sodium salt Chemical group 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- JONFYSWOLCTYFK-UHFFFAOYSA-N 2-(2,3-dichloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(Cl)=C1Cl JONFYSWOLCTYFK-UHFFFAOYSA-N 0.000 description 1
- YHCIJMVTLQFAPK-UHFFFAOYSA-N Cc(c(Nc1ccccc1C(O)=O)ccc1)c1O Chemical compound Cc(c(Nc1ccccc1C(O)=O)ccc1)c1O YHCIJMVTLQFAPK-UHFFFAOYSA-N 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N OC(c(cccc1)c1Cl)=O Chemical compound OC(c(cccc1)c1Cl)=O IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- VQWQYXBWRCCZGX-UHFFFAOYSA-N acetic acid;manganese Chemical compound [Mn].CC(O)=O.CC(O)=O VQWQYXBWRCCZGX-UHFFFAOYSA-N 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229950009130 clofenamic acid Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229960004643 cupric oxide Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- KNLQKHUBPCXPQD-UHFFFAOYSA-N manganese;sulfuric acid Chemical compound [Mn].OS(O)(=O)=O KNLQKHUBPCXPQD-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a kind of synthetic method of mefenamic acid, using 0-chloro-benzoic acid as raw material, in the presence of acid binding agent, using aprotic polar solvent, 0-chloro-benzoic acid salt is obtained into salt；Under dehydrating agent effect, using manganese powder or manganese salt as catalyst, 0-chloro-benzoic acid salt and 2, the progress condensation reaction of 3 dimethylanilines, then acidified obtain mefenamic acid.The invention provides a kind of synthetic method of mefenamic acid, have the advantages that reaction yield is high, product qualities are high and production cost is low, the problem of solving relatively low product yield present in existing preparation method and deeper product colour.
Description
Technical field
The present invention relates to the technical field of organic synthesis, more particularly to a kind of synthetic method of mefenamic acid.
Background technology
Mefenamic acid, also known as mefenamic acid, flutter hot pain etc., English entitled Mefenamic Acid, chemical entitled N-2,3- bis-
Tolyl ortho-aminobenzoic acid, structural formula is shown below.
Mefenamic acid is a kind of NSAIDs, and main function is the synthesis and suppression albumen by suppressing prostaglandin
Matter catabolic enzyme, so that the protein structure of stabilizing cell membrane, disturbs tissue metabolism's process and play a role.
Compared with the NSAIDs of same type, the antiinflammatory action of mefenamic acid is significantly stronger than flufenamic acid and clofenamic acid,
Therefore it is more widely applied.Clinically it is mainly used in rheumatic, rheumatoid arthritis, dysmenorrhoea, headache, neuralgia, courbature
And the treatment of other postoperative inflammatory pains.In addition, mefenamic acid can be additionally used in the precursor of acridine antimalarial and anticarcinogen.
The synthesis of mefenamic acid traditional in early days, which is mainly first to react 0-chloro-benzoic acid and inorganic base, first generates adjacent chlorobenzene
Formic acid sodium salt, 0-chloro-benzoic acid sodium salt is made with 2,3- dimethylanilines in aqueous phase condensation again, but product yield is relatively low, causes life
Production cost is higher and is eliminated.
Because DMF, DMSO and sulfolane equal solvent have certain dissolubility to 0-chloro-benzoic acid sodium salt, therefore later conjunction
Water substantially is instead of with DMF, DMSO and sulfolane equal solvent into method, and achieves preferable conversion ratio.
The documents such as CN200910154422.3 and CN200910114917.3 refer to 0-chloro-benzoic acid and 2,3- dimethyl
Aniline is achieved very well using copper chloride, copper sulphate, copper nitrate, copper acetate, cupric oxide and copper powder etc. as condensation catalyst
Yield, but in course of reaction particularly reaction the later stage generate a large amount of tar, obtained mefenamic acid crude product color is partially deep, lead to
Often be atropurpureus, and containing certain tar, viscosity is larger, even if by solvent refining lighter, but losing larger, more by
In the factor of copper ion, product often greening, not enough in vain.Therefore the synthetic method also has certain limitation.
The content of the invention
The invention provides a kind of synthetic method of mefenamic acid, with reaction yield is high, product qualities are high and produce
The low advantage of cost, the problem of solving relatively low product yield present in existing preparation method and deeper product colour.
The invention discloses a kind of synthetic method of mefenamic acid, comprise the following steps：
(1) using 0-chloro-benzoic acid as raw material, in the presence of acid binding agent, using aprotic polar solvent, adjacent chlorine is obtained into salt
Benzoate；
(2) under dehydrating agent effect, using manganese powder or manganese salt as catalyst, 0-chloro-benzoic acid salt and 2,3- dimethyl benzene
Amine carries out condensation reaction, then acidified obtains mefenamic acid.
The present invention mainly starts with from the catalyst of condensation reaction, abandons the use of copper powder and copper-containing compound, uses metal instead
Manganese powder or manganese salt, reaction side reaction are significantly reduced, while reducing tar yield, product appearance improves obvious.
Preferably, in above-mentioned synthetic method：
0-chloro-benzoic acid, 23 dimethyl aniline, the mass ratio of acid binding agent and catalyst are 1:0.8~1.0:0.8~
1.2:0.01~0.03；
The mass ratio of aprotic polar solvent and 0-chloro-benzoic acid is 0.3~0.5:1；
The mass ratio of dehydrating agent and 0-chloro-benzoic acid is 0.8~1.2:1.
Preferably, in step (1), described acid binding agent is sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide.
In the present invention, abandon water and make solvent, reaction dissolvent is used as using aprotic polar solvent so that yield is carried
It is high.Preferably, in step (1), described aprotic polar solvent is DMF, DMSO or sulfolane.
To ensure being completely dissolved and abundant into salt for 0-chloro-benzoic acid, preferably, in step (1), dissolving and anti-into salt
It should be carried out in the case where being heated to 80 DEG C.
Because condensation reaction generates water, dehydrating agent is introduced, the water for reacting generation is removed in time using azeotropic, greatly shortened
Reaction time.Preferably, in step (2), described dehydrating agent is benzene or toluene.
Preferably, in step (2), described manganese salt is manganese acetate or manganese sulfate.
Preferably, in step (2), the temperature of the condensation reaction is 120~130 DEG C.
Preferably, in step (2), described acidifying is that to adjust condensation product to pH through dilute sulfuric acid be 1~2, then is passed through
It is filtrated to get described mefenamic acid.
Compared with prior art, the invention has the advantages that：
The present invention is used as catalyst in the synthesis of mefenamic acid using manganese powder or manganese salt first, hence it is evident that reduce pair
The generation of reaction, while reducing tar yield, hence it is evident that improve product appearance.
Use DMF, DMSO or sulfolane etc. for reaction dissolvent in the present invention, improve the yield of product；Also introduce benzene or
Toluene substantially reduces the time of condensation reaction as dehydrating agent.
Embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This：
The preparation of the mefenamic acid of embodiment 1
10gDMF is put into 250mL four-hole boiling flasks, 80 DEG C are warming up to, 27g 0-chloro-benzoic acids are put into, until adjacent chlorobenzene first
It is sour complete it is molten after, add 25g sodium carbonate and carry out into salt, 80 DEG C of insulation half an hour.Water knockout drum is connect, 25g toluene is added and carries out a point water, directly
Separated to anhydrous.Catalyst acetic acid manganese 0.5g and 2,3- dimethylaniline 22.5g is put into afterwards, and temperature is maintained at 120~130 DEG C.
Sample in HPLC and control, work as 0-chloro-benzoic acid<When 1%, 100mL water, plus dilute sulfuric acid regulation pH to 2 are added, suction filtration, drying is obtained
About 39.5g pale solids, molar yield 94.8%, nuclear-magnetism detection data and reaction equation difference are as follows.
1H NMR(DMSO):δ2.10(s,3H,-CH3),2.28(s,3H,-CH3), 6.68~7.90 (m, 7H, Ar-H),
9.46(s,-NH).
The preparation of the mefenamic acid of embodiment 2
10gDMF is put into 250mL four-hole boiling flasks, 80 DEG C are warming up to, 27g 0-chloro-benzoic acids are put into, until adjacent chlorobenzene first
It is sour complete it is molten after, add 25g sodium carbonate and carry out into salt, 80 DEG C of insulation half an hour.Water knockout drum is connect, 25g toluene is added and carries out a point water, directly
Separated to anhydrous.Catalyst sulfuric acid manganese 0.5g and 2,3- dimethylaniline 22.5g is put into afterwards, and temperature is maintained at 120~130 DEG C.
Sample in HPLC and control, work as 0-chloro-benzoic acid<When 1%, 100mL water, plus dilute sulfuric acid regulation pH to 2 are added, suction filtration, drying is obtained
About 38.7g pale solids, molar yield 93.0%, nuclear-magnetism detection data are as follows：
1H NMR(DMSO):δ2.10(s,3H,-CH3),2.28(s,3H,-CH3), 6.68~7.90 (m, 7H, Ar-H),
9.46(s,-NH).
Claims (6)
1. a kind of synthetic method of mefenamic acid, it is characterised in that comprise the following steps：
(1) using 0-chloro-benzoic acid as raw material, in the presence of acid binding agent, using aprotic polar solvent, adjacent chlorobenzene first is obtained into salt
Hydrochlorate；
(2) under dehydrating agent effect, using manganese acetate or manganese sulfate as catalyst, 0-chloro-benzoic acid salt and 2,3- dimethylaniline enter
Row condensation reaction, then acidified obtain mefenamic acid.
2. the synthetic method of mefenamic acid according to claim 1, it is characterised in that
0-chloro-benzoic acid, 23 dimethyl aniline, the mass ratio of acid binding agent and catalyst are 1:0.8~1.0:0.8~1.2:
0.01~0.03；
The mass ratio of aprotic polar solvent and 0-chloro-benzoic acid is 0.3~0.5:1；
The mass ratio of dehydrating agent and 0-chloro-benzoic acid is 0.8~1.2:1.
3. the synthetic method of mefenamic acid according to claim 1 or 2, it is characterised in that in step (1), described ties up
Sour agent is sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide.
4. the synthetic method of mefenamic acid according to claim 1 or 2, it is characterised in that in step (1), described is non-
Proton polar solvent is DMF, DMSO or sulfolane.
5. the synthetic method of mefenamic acid according to claim 1 or 2, it is characterised in that in step (2), described is de-
Aqua is benzene or toluene.
6. the synthetic method of mefenamic acid according to claim 1, it is characterised in that in step (2), the condensation reaction
Temperature be 120~130 DEG C.
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| CN107382754A (en) * | 2017-07-10 | 2017-11-24 | 江苏倍合德化工有限公司 | A kind of quick high-efficiency synthesis method for preparing mefenamic acid |
| EP4295864A3 (en) | 2018-09-28 | 2024-03-13 | Research Institute at Nationwide Children's Hospital | Phenylpropionic acid derivatives for modulating pathogen activity |
| CN110467538B (en) * | 2019-09-20 | 2022-08-26 | 山东道可化学有限公司 | Synthesis method of 2-methyl-4-methoxydiphenylamine |
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| BE789442A (en) * | 1971-10-01 | 1973-03-29 | Ciba Geigy | CHELATES TO COMBAT METAL DEFICIENCY PHENOMENA IN PLANTS |
| JPS62273939A (en) * | 1986-05-22 | 1987-11-28 | Mitsui Toatsu Chem Inc | Method for producing DL-alanine |
| DE10219037A1 (en) * | 2002-04-29 | 2003-11-06 | Bayer Ag | Production and use of iminodisuccinic acid ammonium metal salts |
| CN1458140A (en) * | 2003-05-04 | 2003-11-26 | 厦门市先端科技有限公司 | Process for preparing aniline and its derivatives |
| KR101192519B1 (en) * | 2004-05-12 | 2012-10-17 | 이데미쓰 고산 가부시키가이샤 | Aromatic amine derivative, organic electroluminescent element employing the same, and process for producing aromatic amine derivative |
| CN100336794C (en) * | 2006-01-19 | 2007-09-12 | 中山大学 | N-arylation process with hydrazone as ligand in aqueous phase system |
| CN101475505B (en) * | 2009-02-09 | 2012-08-01 | 宝鸡天新药业有限公司 | Process for preparing mefenamic acid |
| CN101704761B (en) * | 2009-10-23 | 2012-09-05 | 宁波斯迈克制药有限公司 | Synthesis method of mefenamic acid |
| CN102344384B (en) * | 2011-09-02 | 2013-10-16 | 德州博诚制药有限公司 | Production method of mefenamic acid |
| CN103420863A (en) * | 2013-03-25 | 2013-12-04 | 江苏海佳化工有限公司 | Mefenamic acid short-process synthesis preparation and refining method |
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