CN114790135A - Preparation method of benzoylformic acid - Google Patents
Preparation method of benzoylformic acid Download PDFInfo
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- CN114790135A CN114790135A CN202210374611.7A CN202210374611A CN114790135A CN 114790135 A CN114790135 A CN 114790135A CN 202210374611 A CN202210374611 A CN 202210374611A CN 114790135 A CN114790135 A CN 114790135A
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- acid
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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 27
- 238000002360 preparation method Methods 0.000 title description 7
- 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 25
- 229960002510 mandelic acid Drugs 0.000 claims abstract description 25
- 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
- -1 amine salt Chemical class 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 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 10
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 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 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 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 18
- 238000000034 method Methods 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 10
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 10
- 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
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 239000012452 mother liquor Substances 0.000 claims description 6
- 238000010992 reflux Methods 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
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-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
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 5
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-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
- 229940045803 cuprous chloride Drugs 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000002024 ethyl acetate extract Substances 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
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 4
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 4
- DVARTQFDIMZBAA-UHFFFAOYSA-O ammonium nitrate Chemical class [NH4+].[O-][N+]([O-])=O DVARTQFDIMZBAA-UHFFFAOYSA-O 0.000 claims description 4
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 4
- 229960003280 cupric chloride Drugs 0.000 claims description 4
- 238000001914 filtration Methods 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
- ITATYELQCJRCCK-UHFFFAOYSA-N Mandelic Acid, Methyl Ester Chemical group COC(=O)C(O)C1=CC=CC=C1 ITATYELQCJRCCK-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- SAXHIDRUJXPDOD-UHFFFAOYSA-N ethyl hydroxy(phenyl)acetate Chemical compound CCOC(=O)C(O)C1=CC=CC=C1 SAXHIDRUJXPDOD-UHFFFAOYSA-N 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 235000011054 acetic acid Nutrition 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 229940076286 cupric acetate Drugs 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 239000002699 waste material Substances 0.000 abstract description 4
- 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
- 150000007530 organic bases Chemical class 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 3
- FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical class OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 2
- 239000000543 intermediate 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
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- PUQSUZTXKPLAPR-UJPOAAIJSA-N Gastrodin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(CO)C=C1 PUQSUZTXKPLAPR-UJPOAAIJSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 239000005579 Metamitron Substances 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 239000002253 acid Substances 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
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 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
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical group Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 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
- 208000026106 cerebrovascular disease Diseases 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
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- CMMUKUYEPRGBFB-UHFFFAOYSA-L dichromic acid Chemical compound O[Cr](=O)(=O)O[Cr](O)(=O)=O CMMUKUYEPRGBFB-UHFFFAOYSA-L 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- QKLCQKPAECHXCQ-UHFFFAOYSA-N ethyl phenylglyoxylate Chemical compound CCOC(=O)C(=O)C1=CC=CC=C1 QKLCQKPAECHXCQ-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 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
- 230000003301 hydrolyzing effect Effects 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
- 239000000463 material 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
- VHCNQEUWZYOAEV-UHFFFAOYSA-N metamitron Chemical compound O=C1N(N)C(C)=NN=C1C1=CC=CC=C1 VHCNQEUWZYOAEV-UHFFFAOYSA-N 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 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
- 230000003647 oxidation Effects 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
- 239000000575 pesticide Substances 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
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 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
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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-
- 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
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- 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 synthesis method of benzoylformic acid, which is prepared by taking mandelic acid or ester thereof as a raw material, taking nitrate or amine salt formed by nitric acid and organic base as an oxidant and copper salt as a catalyst in the presence of a protonated polar solvent, and has the advantages of mild reaction conditions, simple operation, less three wastes and high yield.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a preparation method of benzoylformic acid.
Background
The benzoylformic acid is also called acetophenone acid, and the molecular structure of the benzoylformic acid contains carbonyl and carboxyl, and the structure formula of the benzoylformic acid is shown as follows:
the benzoyl formic acid is used as a raw material to synthesize gastrodine for treating gastric ulcer, cyclamate for treating cerebrovascular disease and thrombus, urokinase for treating frequent micturition, atropine for resisting choline medicine, pimoline for central nervous system stimulant, mirtazapine as antidepressant and the like. As a pesticide intermediate raw material, the benzoylformic acid is mainly used for synthesizing triazinone herbicides such as metamitron, metamizine and the like. Moreover, benzoylformic acid is widely used in the construction of functional materials, and can be used as a sensitizer for fluorescent materials, a catalyst for organic oxidation, and the like by complexing with a metal element.
Although benzoylformic acid is an important pharmaceutical intermediate, the existing preparation methods are not many. PCT patent application No. WO2015035051A discloses a method for preparing benzoylformic acid by using diethyl oxalate as raw material, adding phenylmagnesium bromide at-78 deg.C to obtain ethyl benzoylformate, and hydrolyzing to obtain benzoylformic acid. The method needs Grignard reaction and low-temperature production, has harsh conditions, and is not favorable for 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 mild and the yield is relatively high, the price of the raw material benzoyl nitrile is high, benzoyl halide and sodium cyanide are needed for preparation, and the comprehensive cost is high.
Patent publication No. CN101503414A discloses a method for preparing benzoylformic acid by using styrene as a raw material and potassium permanganate as an oxidant. Although the method is simple to operate, a large amount of potassium permanganate used as an oxidant can generate a large amount of wastewater and manganese mud solid waste, which not only increases the difficulty of treating the three wastes, but also increases the production cost.
The literature (Journal Of Applicable Chemistry (Lumami, India),2017,615),864-854) reports the preparation Of benzoylcarboxylic acids starting from mandelic acid and using chromic acid as the oxidant in DMSO solvent. Heavy metal pollution in dichromic acid and reaction post-treatment used in the method is serious, and the production of the method is difficult to adapt to the current environmental protection requirement.
The synthesis processes all have a series of problems of high raw material price, prominent three-waste problem generated by post-treatment, complex operation, strict requirements on reaction conditions and the like.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the preparation method of the benzoylformic acid, which uses the mandelic acid or the mandelic acid ester with low price and easy obtainment as a raw material, and has the advantages of less three wastes, simple and convenient operation and low cost.
In order to realize the purpose of the invention, the invention adopts the following technical scheme:
a process for preparing benzoylformic acid from mandelic acid or its ester as raw material includes such steps as reaction between ammonium nitrate or the amine salt of nitric acid and organic alkali as oxidant and copper salt as catalyst in the presence of protonized polar solvent:
r is H or alkyl.
Further, the mandelic ester is selected from methyl mandelate, ethyl mandelate or propyl mandelate, and the intermediate process analysis of the mandelic ester shows that under the reaction condition, the mandelic ester is hydrolyzed in the system to form mandelic acid, and is further oxidized to generate benzoyl formic acid.
Further, the protonated polar solvent is selected from a mixture of water and 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 as the solvent and that the reaction is slower with acetic acid as the solvent, which may be due to the poor solubility of the amine salt of the oxidizing agent in acetic acid. The reaction time can be shortened by adding a certain amount of water, and the reaction can be accelerated by adding a proper amount of water to increase the solubility of the amine salt in the system. However, too much water added also reduces the solubility of mandelic acid, which in turn makes the reactant concentration dilute and the reaction slow.
Further, the amine salt is selected from ammonium nitrate and ammonium nitrate salts formed from nitric acid and organic amines, and further, the ammonium nitrate salt is selected from triethylamine nitrate, guanidine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate.
Further, the copper salt is selected from cupric acetate, cupric propionate, cupric chloride, cupric sulfate, cupric bromide or cupric iodide; or cuprous chloride, cuprous iodide, cuprous bromide, and cuprous bromide.
These monovalent copper salts work by forming divalent copper salts under the reaction conditions.
Further, the molar ratio of the reactant 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 ester thereof to the oxidizing agent is from 1:4 to 8.
Further, the protonized polar solvent is an aqueous acetic acid solution, an ammonium nitrate oxidant and copper acetate are used as catalysts, the volume concentration of the aqueous acetic acid solution is 10-90%, preferably 70-85%, the reaction temperature is 60-200 ℃, preferably 100-120 ℃, the molar ratio of mandelic acid or mandelic acid ester to copper acetate is 1: 4-8: 0.02-0.05, and preferably copper acetate as catalyst to avoid adding new anions or new salts as much as possible, if an aqueous acetic acid solution is used as solvent.
The ammonium nitrate adopted by the invention has better selectivity, and the yield can reach more than 90%. The ammonium nitrate may be added to the system in solid portions or may be added to the reactor in the form of water droplets. The feeding molar ratio of ammonium nitrate is mandelic acid or its ester: ammonium nitrate is 1: 2-30: 1, preferably 1: 4-1: 8, the ammonium nitrate is in excess, and is decomposed into NO which is released in the reaction process, and the NO is generated in the air to form reddish brown NO 2 This means that the ammonium nitrate fed in is ionized in the system to produce nitric acid, which at high concentrations partly decomposes to 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 system is sealed and pressurized. If acetic acid is selected as the solvent, the temperature is preferably 100-120 ℃.
The raw material mandelic acid adopted by the invention can be conveniently obtained by the 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 benzoylcarboxylic acid.
Detailed Description
The invention is further illustrated by the following examples
Example 1
A250 ml three-necked flask was charged with (4.0g,26.0mmol) mandelic acid, an 80% acetic acid aqueous solution (100ml) by volume, copper acetate monohydrate (0.26g, 1.3mmol), ammonium nitrate (14.6g,182.0mmol), and the mixture was heated to reflux (about 105 ℃ C.) with stirring and reacted for 12 hours. Cooling to room temperature, vacuum filtering, concentrating the mother liquor to remove most of the solution, adding 50ml of water into the residue, extracting with ethyl acetate four times (4X20ml), combining ethyl acetate extracts, adding anhydrous magnesium sulfate, drying, and concentrating to obtain 3.56g of benzoylformic acid with yield of 91.1%. Benzoyl formic acid: 1H-NMR (DMSO, 400MHz) delta: 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 may range from 1:2 to 30, but the optimum is a ratio of 1: 7; ammonium nitrate may be replaced by triethylamine nitrate, guanidine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate.
Example 2
A250 ml three-necked flask was charged with (4.0g,26.0mmol) mandelic acid, a 90% strength by volume aqueous acetic acid solution (100ml), copper acetate monohydrate (0.104g, 0.52mmol), guanidine nitrate (12.2g,100mmol), 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 to the residue, extracting with ethyl acetate four times (4X20ml), combining the ethyl acetate extracts, drying with anhydrous magnesium sulfate, and concentrating to obtain 3.37g of benzoylformic acid with a yield of 86.5%.
In example 1, guanidine nitrate may also be replaced with triethylamine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate, and mandelic acid may be replaced with methyl mandelate, ethyl mandelate or propyl mandelate.
Example 3
Adding mandelic acid (4.0g,26.0mmol) into a 250ml three-neck flask, adding 10% formic acid aqueous solution (100ml) with volume concentration and copper chloride (0.78 mmol (according to a proportion of 0.03)), heating to 105 ℃, dropwise adding a solution prepared by dissolving ammonium nitrate (14.6g,182.0mmol) in 30ml of water, stirring and refluxing for 12 hours, cooling to room temperature, carrying out suction filtration, concentrating mother liquor to remove most of solution, adding 50ml of water into residue, extracting for four times with ethyl acetate (4x20ml), combining ethyl acetate extracting solutions, drying with anhydrous magnesium sulfate, and concentrating to obtain benzoylformic acid (3.42 g, yield 87.8%).
In example 3, cupric chloride can be replaced by cupric propionate, cupric sulfate, cupric bromide or cupric iodide, and cuprous chloride, cuprous iodide or cuprous bromide can also be replaced; the aqueous formic acid solution may be replaced by an aqueous solution of propionic acid, butyric acid or isobutyric acid.
Example 4
A250 ml three-necked flask was charged with (4.0g,26.0mmol) mandelic acid, 85% aqueous acetic acid (100ml), cuprous chloride (0.78 mmol), 27% aqueous ammonia (23.6g,182.0mmol) and 65% concentrated nitric acid (17.64g,
182.0mmol), and 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 to the residue, extracting with ethyl acetate four times (4X20ml), combining ethyl acetate extracts, drying with anhydrous magnesium sulfate, and concentrating to obtain 3.44g of benzoylformic acid with a yield of 88.3%.
In example 4, cuprous chloride may be replaced with cupric chloride, cupric propionate, cupric sulfate, cupric bromide or cupric iodide, and 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 (comparative example)
A250 ml three-necked flask was charged with (4.0g,26.0mmol) mandelic acid, 80% aqueous acetic acid (100ml), and ammonium nitrate (14.6g,182.0mmol), and the temperature was raised to reflux (about 105 ℃ C.) with stirring to react for 12 hours. After cooling to room temperature, the reaction mixture was filtered with suction, the mother liquor was concentrated to remove most of the solution, the residue was extracted four times with ethyl acetate (4 × 20ml), the ethyl acetate extracts were combined, dried over anhydrous magnesium sulfate, and concentrated to silica gel column chromatography (CH2Cl2: CH3OH ═ 2:1) to give 0.5g of benzoylcarboxylic acid, yield 12.8%.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. All modifications, equivalents, improvements and the like which come within the spirit and principle of the invention are intended to be included within the scope of the invention.
Claims (10)
1. A process for preparing benzoylformic acid from mandelic acid or its ester as raw material includes such steps as reaction of ammonium nitrate or the amine salt of nitric acid and organic alkali as oxidant and copper salt as catalyst in the presence of protonized polar solvent:
r is H or alkyl.
2. The method of claim 1, wherein the mandelic ester is selected from the group consisting of methyl mandelate, ethyl mandelate and propyl mandelate.
3. The method according to claim 1, wherein the protonated polar solvent is selected from the group consisting of water in admixture with formic acid, acetic acid, propionic acid, butyric acid and isobutyric acid.
4. The method according to claim 1, wherein the amine salt is selected from ammonium nitrate and ammonium nitrate salts of nitric acid and organic amines.
5. The method according to claim 4, wherein the ammonium nitrate salt is triethylamine nitrate, guanidine nitrate, trimethylamine nitrate, tripropylamine nitrate or tributylamine nitrate.
6. The method according to claim 1, wherein said copper salt is selected from the group consisting of cupric acetate, cupric propionate, cupric chloride, cupric sulfate, cupric bromide and cupric iodide; or a monovalent copper salt selected from cuprous chloride, cuprous iodide or cuprous bromide.
7. The method of claim 1, wherein the molar ratio of the reactant mandelic acid or the ester thereof, the oxidizing agent and the copper salt catalyst is 1: 2-30: 0.02-0.05.
8. The method of claim 7, wherein the molar ratio of mandelic acid or its ester to the oxidizing agent is 1: 4-8.
9. The method for preparing benzoylformic acid according to claim 1, wherein after the reaction, the reaction mixture is cooled to room temperature, filtered, and the residue is extracted with water and ethyl acetate, and concentrated to obtain the desired product.
10. The method for preparing benzoylformic acid according to claim 1, wherein mandelic acid or its ester is used as raw material, ammonium nitrate is used as oxidant and copper acetate is used as catalyst in the presence of 10-90 vol% acetic acid aqueous solution, stirring and heating to reflux for reaction, cooling to room temperature after reaction, suction filtering, concentrating mother liquor to remove most of solution, adding water to residue, extracting with ethyl acetate, combining ethyl acetate extract, drying with anhydrous magnesium sulfate, and concentrating to obtain benzoylformic acid, wherein the molar ratio of mandelic acid or its ester, ammonium nitrate and 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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