CN114790135B - Preparation method of benzoyl formic acid - Google Patents
Preparation method of benzoyl formic acid Download PDFInfo
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- CN114790135B CN114790135B CN202210374611.7A CN202210374611A CN114790135B CN 114790135 B CN114790135 B CN 114790135B CN 202210374611 A CN202210374611 A CN 202210374611A CN 114790135 B CN114790135 B CN 114790135B
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- VTESCYNPUGSWKG-UHFFFAOYSA-N (4-tert-butylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC(C)(C)C1=CC=C(N[NH3+])C=C1 VTESCYNPUGSWKG-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims description 14
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims abstract description 23
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229960002510 mandelic acid Drugs 0.000 claims abstract description 23
- -1 amine salts Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000007800 oxidant agent Substances 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 13
- 150000001879 copper Chemical class 0.000 claims abstract description 11
- 230000001590 oxidative effect Effects 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910017604 nitric acid Inorganic materials 0.000 claims abstract description 7
- 239000002798 polar solvent Substances 0.000 claims abstract description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 23
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 235000011054 acetic acid Nutrition 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 12
- 239000005711 Benzoic acid Substances 0.000 claims description 11
- 235000010233 benzoic acid Nutrition 0.000 claims description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 8
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 8
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical group [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000002024 ethyl acetate extract Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 5
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 5
- LZJJVTQGPPWQFS-UHFFFAOYSA-L copper;propanoate Chemical compound [Cu+2].CCC([O-])=O.CCC([O-])=O LZJJVTQGPPWQFS-UHFFFAOYSA-L 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- NDEMNVPZDAFUKN-UHFFFAOYSA-N guanidine;nitric acid Chemical compound NC(N)=N.O[N+]([O-])=O.O[N+]([O-])=O NDEMNVPZDAFUKN-UHFFFAOYSA-N 0.000 claims description 5
- 239000012452 mother liquor Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229940045803 cuprous chloride Drugs 0.000 claims description 4
- MYGGDSFWCQSVAA-UHFFFAOYSA-N n,n-dibutylbutan-1-amine;nitric acid Chemical compound O[N+]([O-])=O.CCCCN(CCCC)CCCC MYGGDSFWCQSVAA-UHFFFAOYSA-N 0.000 claims description 4
- XRDNFNGIKTYHAN-UHFFFAOYSA-N n,n-diethylethanamine;nitric acid Chemical group O[N+]([O-])=O.CCN(CC)CC XRDNFNGIKTYHAN-UHFFFAOYSA-N 0.000 claims description 4
- GWKNUWRKJUDXAY-UHFFFAOYSA-N n,n-dimethylmethanamine;nitric acid Chemical compound CN(C)C.O[N+]([O-])=O GWKNUWRKJUDXAY-UHFFFAOYSA-N 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000000967 suction filtration Methods 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 7
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 150000007530 organic bases Chemical class 0.000 abstract description 2
- 229910002651 NO3 Inorganic materials 0.000 abstract 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 4
- 229910000365 copper sulfate Inorganic materials 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- GJQBHOAJJGIPRH-UHFFFAOYSA-N benzoyl cyanide Chemical compound N#CC(=O)C1=CC=CC=C1 GJQBHOAJJGIPRH-UHFFFAOYSA-N 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical group [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 2
- CMMUKUYEPRGBFB-UHFFFAOYSA-L dichromic acid Chemical compound O[Cr](=O)(=O)O[Cr](O)(=O)=O CMMUKUYEPRGBFB-UHFFFAOYSA-L 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- ITATYELQCJRCCK-UHFFFAOYSA-N Mandelic Acid, Methyl Ester Chemical group COC(=O)C(O)C1=CC=CC=C1 ITATYELQCJRCCK-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- FCOHEOSCARXMMS-UHFFFAOYSA-N Oxaziclomefone Chemical compound C1OC(C)=C(C=2C=CC=CC=2)C(=O)N1C(C)(C)C1=CC(Cl)=CC(Cl)=C1 FCOHEOSCARXMMS-UHFFFAOYSA-N 0.000 description 1
- ULDJWIXKVBYNMQ-UHFFFAOYSA-N Pimolin Natural products COC1=C2C(=O)C3C4C5=C(OC)C(C(=O)C=C(C)O6)=C6C=C5OC4C3(C)OC2=CC2=C1C=CO2 ULDJWIXKVBYNMQ-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- SAXHIDRUJXPDOD-UHFFFAOYSA-N ethyl hydroxy(phenyl)acetate Chemical compound CCOC(=O)C(O)C1=CC=CC=C1 SAXHIDRUJXPDOD-UHFFFAOYSA-N 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 1
- 229960001785 mirtazapine Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000002351 wastewater Substances 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
- C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for synthesizing benzoyl formic acid, which is prepared by taking mandelic acid or ester thereof as a raw material, taking amine salts formed by nitrate or nitric acid and organic base as an oxidant in the presence of a protonated polar solvent, and taking copper salts as catalysts.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a preparation method of benzoyl formic acid.
Background
The benzoyl formic acid is also called acetophenone acid, the molecular structure of which contains carbonyl and carboxyl, and the structural formula is shown as follows:
active groups in the molecular structure of the benzoyl formic acid make the benzoyl formic acid exhibit special properties, and the benzoyl formic acid is an intermediate for synthesizing a plurality of medicines and pesticides, can be used as a medicine intermediate to synthesize the stomach long ning for treating gastric ulcer, the cyclic mandelate for treating cerebral vascular disease and thrombus, the spasmolytic for treating frequent urination, the anticholinergic, the central nervous system stimulant pimolin, the antidepressant mirtazapine and the like by taking the benzoyl formic acid as raw materials. As a raw material of an intermediate of pesticides, the benzoylformic acid is mainly used for synthesizing triazinones herbicides such as oxaziclomefone, prometryn and the like. In addition, benzoic acid is widely used for the constitution of functional materials, and is used as a sensitizer for fluorescent materials, a catalyst for organic oxidation reactions, and the like by complexing with a metal element.
Although benzoic acid is an important pharmaceutical intermediate, the existing preparation methods are not numerous. PCT patent application number WO2015035051A discloses that diethyl oxalate is used as a raw material, phenyl magnesium bromide is added at the temperature of minus 78 ℃ to obtain ethyl benzoate, and then the ethyl benzoate is hydrolyzed to obtain the benzoyl formic acid. The method needs to be subjected to Grignard reaction and is produced at low temperature, and the conditions are harsh, so that the method is not beneficial to large-scale production.
Patent publication No. CN103103156A discloses a method for obtaining benzoyl formic acid by hydrolysis of benzoyl nitrile as a raw material. Although the reaction condition is relatively warm and the yield is relatively high, the raw material benzoyl nitrile is high in commodity price, benzoyl halide and sodium cyanide are needed for preparation, and the comprehensive cost is high.
Patent publication No. CN101503414A discloses a method for preparing benzoic acid by using styrene as a raw material and potassium permanganate as an oxidant. The method is simple to operate, but a large amount of waste water and manganese mud solid waste can be generated by using a large amount of potassium permanganate as an oxidant, so that the difficulty of three-waste treatment is increased, and the production cost is increased.
Document (Journal Of Applicable Chemistry (Lumami, india), 2017,615), 864-854) reports the preparation of benzoic acid starting from mandelic acid and chromic acid as the oxidizing agent in DMSO solvent. Heavy metal pollution is serious in the dichromic acid and the post-reaction treatment used by the method, and the production of the dichromic acid is difficult to adapt to the current environmental protection requirement.
The synthesis process has the problems of high raw material price, prominent three wastes generated by post-treatment, complex operation, strict reaction condition requirements and the like.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the preparation method of the benzoyl formic acid, which has less three wastes, simple and convenient operation and low cost, by taking the mandelic acid or the ester thereof which is cheap and easy to obtain as the raw material.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
the preparation method of the benzoyl formic acid is characterized in that mandelic acid or ester thereof is used as a raw material, amine salt formed by ammonium nitrate or nitric acid and organic base is used as an oxidant in the presence of a protonated polar solvent, copper salt is used as a catalyst, and the reaction formula is as follows:
r is H or alkyl.
Further, the mandelate is selected from methyl mandelate, ethyl mandelate or propyl mandelate, and the mandelate is analyzed by experimental intermediate process to show that under the reaction conditions, the mandelate is firstly hydrolyzed in the system to form mandelic acid, and is further oxidized to form benzoyl formic acid.
Further, the protonated polar solvent is selected from the group consisting of water in admixture with formic acid, acetic acid, propionic acid, butyric acid or isobutyric acid.
The inventors have found that the reaction is substantially non-reactive with water alone and that the reaction rate is relatively slow with acetic acid as solvent, the latter probably being due to the poor solubility of the amine salt of the oxidising agent in acetic acid. The reaction time can be shortened by adding a certain amount of water, and the solubility of amine salts in the system can be increased by adding water appropriately so as to promote the reaction. However, too much water addition also reduces the solubility of mandelic acid, and the reactant concentration becomes dilute, thereby slowing the reaction.
Further, the amine salt is selected from ammonium nitrate and nitric acid and organic amine forming amine nitrate salts, further, the amine nitrate salts are selected from triethylamine nitrate, guanidine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate.
Further, the copper salt is selected from copper acetate, copper propionate, copper chloride, copper sulfate, copper bromide or copper iodide cupric salt; or a monovalent copper salt selected from the group consisting of cuprous chloride, cuprous iodide, and cuprous bromide.
These monovalent copper salts act under the reaction conditions to form divalent copper salts.
Further, the mol ratio of the reaction material mandelic acid or the ester thereof, the oxidant and the copper salt catalyst is 1:2-30:0.02-0.05; preferably, the molar ratio of the reaction mass mandelic acid or the ester thereof to the oxidant is 1:4-8.
Further, the protonated polar solvent is acetic acid aqueous solution, the volume concentration of the acetic acid aqueous solution is 10-90%, preferably 70-85% under the condition that ammonium nitrate oxidant and copper acetate are used as catalysts, the reaction temperature is 60-200 ℃, preferably 100-120 ℃, and the mole ratio of mandelic acid or ester thereof, ammonium nitrate and copper acetate is 1:4-8:0.02-0.05, with aqueous acetic acid as solvent, preferably copper acetate as catalyst to avoid addition of new anions or new salts as much as possible.
The ammonium nitrate adopted by the invention has better selectivity and the yield can reach more than 90 percent. The ammonium nitrate may be added to the system in solid portions or may be added to the reactor by dissolving it in water droplets. The feeding mole ratio of the ammonium nitrate is mandelic acid or the ester thereof: ammonium nitrate = 1:2-30:1, preferably 1:4 to 1:8, an excess of ammonium nitrate being necessary, during the reaction some of which decomposes to give off NO, which is visible in the air as reddish brown NO 2 This means that the ammonium nitrate fed in ionizes in the system to form nitric acid, which at high concentrations is partly decomposed into NO.
The reaction temperature can be 60-200 ℃, the temperature is low, the reaction is slow, and the rising temperature of the system also depends on the solvent and whether the pressure is closed or not. If acetic acid is used as the solvent, the temperature is preferably 100-120 ℃.
The raw material mandelic acid adopted by the invention can be conveniently obtained by phase transfer catalytic reaction of benzaldehyde and chloroform in alkali. (refer to Jiangsu chemical industry, 1991,3.22-23)
Drawings
FIG. 1 is a 1H NMR spectrum of benzoylformic acid.
Detailed Description
The invention will be further illustrated by the following examples
Example 1
Into a 250ml three-necked flask, mandelic acid (4.0 g,26.0 mmol) was added, followed by a reaction for 12 hours at a temperature of about 105℃under stirring, by an aqueous solution (100 ml) of 80% strength by volume acetic acid, copper acetate monohydrate (0.26 g,1.3 mmol) and ammonium nitrate (14.6 g,182.0 mmol). Cooling to room temperature, suction filtering, concentrating the mother liquor to remove most of the solution, adding 50ml of water into the residue, extracting four times (4 x20 ml) with ethyl acetate, combining ethyl acetate extract, adding anhydrous magnesium sulfate for drying, and concentrating to obtain the benzoic acid with the yield of 3.56g and 91.1%. Benzoic acid: 1H-NMR (DMSO, 400 MHz) δ:7.57-7.63 (m, 2H), 7.70-7.76 (m, 1H), 7.90-7.95 (m, 2H).
MS：[M+H]+：151.0409.
In example 1, copper acetate may be replaced with copper propionate, copper chloride, copper sulfate, copper bromide, or copper iodide; the molar ratio of mandelic acid to ammonium nitrate is in the range of 1:2-30, but the optimum value is a ratio of 1:7; ammonium nitrate may be replaced with triethylamine nitrate, guanidine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate.
Example 2
Into a 250ml three-necked flask, mandelic acid (4.0 g,26.0 mmol), an aqueous acetic acid solution (100 ml) having a volume concentration of 90%, cupric acetate monohydrate (0.104 g,0.52 mmol), guanidine nitrate (12.2 g,100 mmol) were charged, and the temperature was raised to reflux (about 105 ℃ C.) with stirring to react for 12 hours. Cooling to room temperature, suction filtering, concentrating the mother liquor to remove most of the solution, adding 50ml of water into the residue, extracting four times (4 x20 ml) with ethyl acetate, combining ethyl acetate extract, adding anhydrous magnesium sulfate for drying, and concentrating to obtain the benzoyl formic acid, 3.37g, and the yield is 86.5%.
In example 1 guanidine nitrate can also be replaced by triethylamine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate, and mandelic acid can be replaced by methyl, ethyl or propyl mandelate.
Example 3
Into a 250ml three-neck flask, (4.0 g,26.0 mmol) of mandelic acid and 0.78mmol (according to 0.03 proportion) of copper chloride as 10% formic acid aqueous solution (100 ml) are added, the temperature is raised to 105 ℃, a solution prepared by dissolving (14.6 g,182.0 mmol) of ammonium nitrate in 30ml of water is added dropwise, then stirring reflux reaction is carried out for 12 hours, cooling is carried out to room temperature, suction filtration is carried out, the mother solution is concentrated to remove most of the solution, 50ml of water is added into the residue, extraction is carried out four times (4 x20 ml) with ethyl acetate, ethyl acetate extract is combined, anhydrous magnesium sulfate is added for drying, and then concentration is carried out, thus obtaining the benzoic acid, 3.42g and the yield is 87.8%.
In example 3, copper chloride may be replaced with copper propionate, copper sulfate, copper bromide, or copper iodide, or copper chloride, copper iodide, or copper bromide; the aqueous formic acid solution may be replaced by an aqueous solution of propionic acid, butyric acid or isobutyric acid.
Example 4
Into a 250ml three-necked flask were charged (4.0 g,26.0 mmol) of mandelic acid, 85% aqueous acetic acid (100 ml), 0.78mmol of cuprous chloride, 27% aqueous ammonia (23.6 g,182.0 mmol) and 65% concentrated nitric acid (17.64 g,
182.0 mmol) and allowed to warm to reflux (about 105 ℃ C.) with stirring, and allowed to react for 12 hours. Cooling to room temperature, suction filtering, concentrating the mother liquor to remove most of the solution, adding 50ml of water into the residue, extracting four times (4 x20 ml) with ethyl acetate, combining ethyl acetate extract, adding anhydrous magnesium sulfate for drying, and concentrating to obtain the benzoic acid with the yield of 3.44g and 88.3%.
In example 4, cuprous chloride may be replaced with cupric chloride, cupric propionate, cupric sulfate, cupric bromide or cupric iodide, or cuprous iodide or cuprous bromide; the aqueous formic acid solution may be replaced by an aqueous solution of propionic acid, butyric acid or isobutyric acid.
Example 5 (control example)
Into a 250ml three-necked flask, mandelic acid (4.0 g,26.0 mmol), an 80% aqueous acetic acid solution (100 ml), ammonium nitrate (14.6 g,182.0 mmol) were charged, and the mixture was heated to reflux (about 105 ℃ C.) with stirring and reacted for 12 hours. Cooling to room temperature, suction filtering, concentrating the mother liquor to remove most of the solution, adding 50ml of water into the residue, extracting four times (4 x20 ml) with ethyl acetate, combining ethyl acetate extract, adding anhydrous magnesium sulfate for drying, concentrating, and performing silica gel column chromatography (CH 2Cl2: CH3 OH=2:1) to obtain the benzoic acid, wherein the yield is 12.8 percent, and 0.5 g.
The above description is only of the preferred embodiments of the present invention, and is not intended to limit the present invention. Modifications, equivalents, improvements, etc. which fall within the spirit and principles of the invention are intended to be included within the scope of the invention.
Claims (8)
1. Preparation method of benzoyl formic acidThe method is characterized in that mandelic acid is used as a raw material, amine salt formed by ammonium nitrate or nitric acid and organic alkali is used as an oxidant in the presence of a protonated polar solvent, copper salt is used as a catalyst, and the reaction formula is as follows:r is H
The protonated polar solvent is selected from the group consisting of mixtures of water with formic acid, acetic acid, propionic acid, butyric acid or isobutyric acid.
2. A process for the preparation of benzoic acid according to claim 1 characterised in that the amine salt is selected from ammonium nitrate and amine salts of nitric acid and organic amines.
3. A process for the preparation of benzoic acid according to claim 2, characterised in that the amine nitrate salt is selected from triethylamine nitrate, guanidine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate.
4. A process for the preparation of benzoylformic acid according to claim 1, characterized in that the copper salt is selected from copper acetate, copper propionate, copper chloride, copper sulphate, copper bromide or copper iodide cupric salts; or a monovalent copper salt selected from cuprous chloride, cuprous iodide, or cuprous bromide.
5. The preparation method of the benzoyl formic acid, which is characterized in that the mol ratio of the reaction materials mandelic acid, the oxidant and the copper salt catalyst is 1:2-30:0.02-0.05.
6. The method for preparing the benzoyl formic acid, which is characterized in that the mol ratio of the mandelic acid to the oxidant is 1:4-8.
7. The method for preparing the benzoyl formic acid, according to claim 1, wherein after the reaction is finished, the reaction solution is cooled to room temperature, suction filtration is carried out, water is added into the residue, extraction is carried out by using ethyl acetate, and the target product is obtained by concentration.
8. The preparation method of the benzoyl formic acid, which is characterized in that mandelic acid is used as a raw material, ammonium nitrate is used as an oxidant, copper acetate is used as a catalyst in the presence of acetic acid aqueous solution with the volume concentration of 10-90%, the temperature is raised to reflux under stirring to react, after the reaction is finished, the reaction is cooled to room temperature, suction filtration is carried out, mother liquor is concentrated to remove most of the solution, water is added into residues, ethyl acetate is used for extraction, ethyl acetate extract is combined, anhydrous magnesium sulfate is added for drying, and concentration is carried out to obtain the benzoyl formic acid, and the mole ratio of the mandelic acid, the ammonium nitrate and the copper acetate is 1:4-8:0.02-0.05.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101712605A (en) * | 2009-09-17 | 2010-05-26 | 嘉兴市中华化工有限责任公司 | Method for converting 2-hydroxyl-3-methoxy-5-aldehyde mandelic acid into vanillin |
| CN108503545A (en) * | 2018-04-19 | 2018-09-07 | 大连理工大学 | A kind of method that catalysis oxidation mandelate prepares acetophenone acid esters |
| CN109970545A (en) * | 2019-04-26 | 2019-07-05 | 中国科学院成都有机化学有限公司 | The preparation method of aryl formic acid salt and acid |
| CN113831233A (en) * | 2021-08-13 | 2021-12-24 | 江苏禾本生化有限公司 | Synthetic method and application of 2,2,2 (4-bromophenyl) -2-glycolic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101712605A (en) * | 2009-09-17 | 2010-05-26 | 嘉兴市中华化工有限责任公司 | Method for converting 2-hydroxyl-3-methoxy-5-aldehyde mandelic acid into vanillin |
| CN108503545A (en) * | 2018-04-19 | 2018-09-07 | 大连理工大学 | A kind of method that catalysis oxidation mandelate prepares acetophenone acid esters |
| CN109970545A (en) * | 2019-04-26 | 2019-07-05 | 中国科学院成都有机化学有限公司 | The preparation method of aryl formic acid salt and acid |
| CN113831233A (en) * | 2021-08-13 | 2021-12-24 | 江苏禾本生化有限公司 | Synthetic method and application of 2,2,2 (4-bromophenyl) -2-glycolic acid |
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