CN109574825B - Synthetic method of phenylacetic acid - Google Patents
Synthetic method of phenylacetic acid Download PDFInfo
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- CN109574825B CN109574825B CN201811610433.3A CN201811610433A CN109574825B CN 109574825 B CN109574825 B CN 109574825B CN 201811610433 A CN201811610433 A CN 201811610433A CN 109574825 B CN109574825 B CN 109574825B
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- phenylacetic acid
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- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 title claims abstract description 163
- 229960003424 phenylacetic acid Drugs 0.000 title claims abstract description 81
- 239000003279 phenylacetic acid Substances 0.000 title claims abstract description 81
- 238000010189 synthetic method Methods 0.000 title claims abstract description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 228
- 238000006243 chemical reaction Methods 0.000 claims abstract description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000010791 quenching Methods 0.000 claims abstract description 29
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000002253 acid Substances 0.000 claims abstract description 19
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims abstract description 16
- 230000000171 quenching effect Effects 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 230000020477 pH reduction Effects 0.000 claims abstract description 11
- 239000002841 Lewis acid Substances 0.000 claims abstract description 10
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 5
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 3
- 238000000935 solvent evaporation Methods 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 11
- 230000002194 synthesizing effect Effects 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 15
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 abstract description 10
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 abstract description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 abstract description 4
- 231100000481 chemical toxicant Toxicity 0.000 abstract description 3
- 239000003440 toxic substance Substances 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 37
- 239000012043 crude product Substances 0.000 description 22
- 238000004821 distillation Methods 0.000 description 19
- 238000011084 recovery Methods 0.000 description 17
- 239000002826 coolant Substances 0.000 description 16
- 238000010438 heat treatment Methods 0.000 description 16
- 239000002244 precipitate Substances 0.000 description 16
- 238000002390 rotary evaporation Methods 0.000 description 16
- 238000001291 vacuum drying Methods 0.000 description 16
- 230000003197 catalytic effect Effects 0.000 description 6
- 229960004275 glycolic acid Drugs 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 4
- 229940073608 benzyl chloride Drugs 0.000 description 4
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- WWYDYZMNFQIYPT-UHFFFAOYSA-N ru78191 Chemical compound OC(=O)C(C(O)=O)C1=CC=CC=C1 WWYDYZMNFQIYPT-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000005906 dihydroxylation reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 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 description 1
- HCGXLLKTPOWTFZ-UHFFFAOYSA-N 2-(2,3,4-trichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C(Cl)=C1Cl HCGXLLKTPOWTFZ-UHFFFAOYSA-N 0.000 description 1
- WMWRBGOAZXDIDN-UHFFFAOYSA-N 2-(2-hydroxyphenyl)acetonitrile Chemical compound OC1=CC=CC=C1CC#N WMWRBGOAZXDIDN-UHFFFAOYSA-N 0.000 description 1
- QKSGIGXOKHZCQZ-UHFFFAOYSA-N 2-chloro-2-phenylacetic acid Chemical compound OC(=O)C(Cl)C1=CC=CC=C1 QKSGIGXOKHZCQZ-UHFFFAOYSA-N 0.000 description 1
- AWDSCPCHQFTJQT-UHFFFAOYSA-N 3-oxo-2-phenylprop-2-enoic acid Chemical compound OC(=O)C(=C=O)C1=CC=CC=C1 AWDSCPCHQFTJQT-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 239000005734 Benalaxyl Substances 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- 235000016623 Fragaria vesca Nutrition 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
- 241001284615 Frangula californica Species 0.000 description 1
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 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
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 108010073038 Penicillin Amidase Proteins 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 235000004433 Simmondsia californica Nutrition 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 229960000396 atropine 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
- 239000003899 bactericide agent Substances 0.000 description 1
- FFIAPLNALYDYQK-UHFFFAOYSA-L barium(2+);[2,3,4-trihydroxy-5-(hydroxymethyl)oxolan-2-yl]methyl phosphate Chemical compound [Ba+2].OCC1OC(O)(COP([O-])([O-])=O)C(O)C1O FFIAPLNALYDYQK-UHFFFAOYSA-L 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- YXKTVDFXDRQTKV-HNNXBMFYSA-N benzphetamine Chemical compound C([C@H](C)N(C)CC=1C=CC=CC=1)C1=CC=CC=C1 YXKTVDFXDRQTKV-HNNXBMFYSA-N 0.000 description 1
- 229960002837 benzphetamine Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000002848 electrochemical method Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- CJPQIRJHIZUAQP-UHFFFAOYSA-N methyl N-(2,6-dimethylphenyl)-N-(phenylacetyl)alaninate Chemical compound CC=1C=CC=C(C)C=1N(C(C)C(=O)OC)C(=O)CC1=CC=CC=C1 CJPQIRJHIZUAQP-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 description 1
- 229960004719 nandrolone Drugs 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000003408 phase transfer catalysis Methods 0.000 description 1
- XAMUDJHXFNRLCY-UHFFFAOYSA-N phenthoate Chemical compound CCOC(=O)C(SP(=S)(OC)OC)C1=CC=CC=C1 XAMUDJHXFNRLCY-UHFFFAOYSA-N 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 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
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthetic method of phenylacetic acid, which comprises the following steps: the mass ratio is (25-5): 1, reacting benzene and glycolide or oligomeric glycolic acid at the temperature of 35-80 ℃ for 1-24 h under the catalysis of Lewis acid with the amount of oxyacetyl substances being 1.0-1.3 times, and obtaining a phenylacetic acid product through quenching reaction with water, acidification by adding inorganic strong acid, oil-water phase layering, solvent evaporation and drying. The invention does not select highly toxic chemicals such as hydrogen cyanide, carbon monoxide and the like, thereby eliminating the product safety doubt caused by trace or trace raw material residues; the method does not adopt extremely high reaction pressure conditions and does not need high-pressure reaction equipment, thereby improving the safety of the production process; meanwhile, the raw materials used in the invention have good biodegradability, are green and safe, and have high economical efficiency and good economical efficiency.
Description
Technical Field
The invention relates to a synthetic method of phenylacetic acid, namely the synthesis of the phenylacetic acid by the selective Friedel-crafts alkylation reaction of benzene and glycolide or oligomeric glycolic acid, belonging to the technical field of organic compound synthesis.
Background
The phenylacetic acid is an important intermediate for synthesizing hypnotic drugs of luminal, anticonvulsant drug of mexilin, cardiovascular drug of methylmercaptoimidazole, antirheumatic drug of methamphetamine, appetite suppressant of benzphetamine, antiarrhythmic drug of lorkanib, hypolipidemic drug of atorvastatin, anticholinergic drug of atropine and hormone testosterone phenylacetate nandrolone, is also an important substrate for producing penicillin by a fermentation method, and is also an important intermediate for synthesizing insecticide of phenthoate, bactericide of benalaxyl and herbicide of trichlorophenylacetic acid. Natural phenylacetic acid, in the form of its methyl ester, is found in cocoa, coffee and strawberry, and exhibits a slightly sweet, weak honey and musk aroma. However, natural phenylacetic acid exists only in the fruit as a flavor substance, and the content thereof is very small, and the extraction and enrichment are not easy, so that the demand of the market is far from being met. Phenylacetic acid used as a raw material or an intermediate in the pharmaceutical and pesticide industries is obtained by organic synthesis, and has more than ten routes for synthesizing phenylacetic acid with high yield, such as the reaction of benzyl chloride with formic acid catalyzed by noble metals, the reaction of benzyl chloride or benzyl alcohol with carbon monoxide under the action of carbonyl synthesis catalyst at high temperature and high pressure, the reaction of benzyl chloride with carbon dioxide by phase transfer catalysis technology and electrochemical method, the selective oxidation reaction of phenylacetaldehyde or phenethyl alcohol, the catalytic dehydroxylation reaction of mandelic acid or meso-hydroxyacetic acid, the catalytic reduction reaction of carbonyl phenylacetic acid, the catalytic hydrolysis reaction of phenylacetamide, the catalytic thermal decarboxylation reaction of phenylmalonic acid, the dehydroxylation and hydrolysis reaction of hydroxybenzeneacetonitrile, the catalytic reduction reaction of chlorophenyl acetic acid, the hydrolysis reaction of phenylacetate, the catalytic hydrolysis reaction of penicillin amidase, the microbial fermentation method and the like. Considering the raw material source, the reliability of the synthesis technology, the production cost and other factors comprehensively, the current industrial common method for synthesizing phenylacetic acid mainly comprises the hydrolysis reaction of phenylacetonitrile, the catalytic oxo synthesis reaction of benzyl chloride and the catalytic thermal decarboxylation reaction of phenylmalonic acid, the three synthetic methods have the advantages that raw materials are easy to obtain, the conversion rate of reactants and the yield of products are high, and the production cost is relatively low, the defects are that the first route adopts virulent hydrogen cyanide as the raw material to synthesize the phenylacetonitrile, so that the doubtful possibility of residual hydrogen cyanide exists in the products, the second route adopts the virulent carbon monoxide which causes the hemoglobin to lose the oxygen carrying capacity as the raw material, and the high-pressure condition of not less than 5 MPa in the reaction process increases the operation risk, and the third route has harsh conditions and low yield for synthesizing the phenylmalonic acid and has low atom utilization rate of subsequent decarboxylation reaction.
Phenylacetic acid is an important intermediate of medicines and pesticides, but in the existing synthetic method for synthesizing phenylacetic acid with industrial value, either a highly toxic raw material is selected to cause doubts about possible residue of highly toxic chemicals, or extremely high reaction pressure conditions are selected to increase the high pressure resistance requirement of equipment and increase unsafety factors in the production process, or the selected synthetic method has low atom utilization rate, so that the development of a new green and safe synthetic method for producing phenylacetic acid becomes an important research direction of medicine intermediates and pesticide intermediates.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a novel synthetic method for synthesizing phenylacetic acid by utilizing glycolide or polyglycolic acid with good biodegradability, greenness and safety and a large amount of chemical industrial raw material benzene to react under the conditions of normal pressure and Lewis acid catalysis.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: and (2) mixing the following components in a mass ratio of 25-5: 1, reacting benzene and glycolide or oligomeric glycolic acid at the temperature of 35-80 ℃ for 1-24 h under the catalysis of Lewis acid with the amount of oxyacetyl substances being 1.0-1.3 times, quenching with water, adding inorganic strong acid for acidification, layering an oil-water phase, evaporating a solvent and drying to obtain a phenylacetic acid crude product, and further carrying out reduced pressure distillation or reduced pressure fractionation on the phenylacetic acid crude product to obtain the phenylacetic acid product with the content of not less than 99.5 wt%.
Preferably, the Lewis acid is aluminum chloride, zinc chloride, ferric chloride or boron trifluoride.
Preferably, the water used in the quenching reaction is water vapor in a gaseous state, water in a liquid state or ice in a solid state.
Preferably, the inorganic strong acid is sulfuric acid, or hydrochloric acid, or nitric acid, or hydrobromic acid.
Further, the technical scheme adopted by the invention is specifically as follows: uniformly stirring and mixing the benzene and the glycolide in the mass ratio, adding Lewis acid in batches, reacting at the temperature of 35-80 ℃ for 1-24 h, quenching with water, adding inorganic strong acid for acidification, layering an oil-water phase, evaporating a solvent and drying to obtain a phenylacetic acid crude product, and further carrying out reduced pressure distillation or reduced pressure fractionation on the phenylacetic acid crude product to obtain a phenylacetic acid product with the content of not less than 99.5 wt%;
or uniformly mixing the benzene and the Lewis acid in the mass ratio, adding glycolide or polyglycolic acid in batches, reacting at the temperature of 35-80 ℃ for 1-24 h, quenching with water, adding an inorganic strong acid for acidification, layering an oil-water phase, evaporating a solvent, and drying to obtain a phenylacetic acid crude product, and further carrying out reduced pressure distillation or reduced pressure fractionation on the phenylacetic acid crude product to obtain a phenylacetic acid product with the content of not less than 99.5 wt%.
Preferably, the quenching reaction by water and the acidification by adding the inorganic strong acid are that the water is added for quenching reaction firstly, and then the inorganic acid is used for acidification until the solid is completely dissolved; or the water quenching reaction and the acidification by adding the inorganic strong acid are that ice and hydrochloric acid are mixed and then added into the reaction system for quenching reaction and acidification.
The synthesis method of the invention does not select highly toxic chemicals such as hydrogen cyanide, carbon monoxide and the like, thereby eliminating the doubtful product safety caused by trace or trace raw material residues, and does not adopt extremely high reaction pressure conditions and does not need high-pressure reaction equipment, thereby improving the safety of the production process. Compared with other synthetic methods for synthesizing phenylacetic acid with industrial value, the method has the following remarkable beneficial effects:
(1) the method does not select highly toxic hydrogen cyanide as a raw material to synthesize phenylacetic acid, thereby eliminating doubtful worry of product safety caused by possible highly toxic raw material residues from the source;
(2) the invention does not select extremely high reaction pressure condition to synthesize phenylacetic acid, thereby avoiding the problems of high equipment pressure resistance requirement, low operation safety and the like caused by high pressure condition;
(3) the invention selects glycolide or oligoglycollic acid with good biodegradability and environmental protection as raw materials, thus enhancing the environmental friendliness of the total synthesis route;
(4) in the invention, glycolide or oligoglycolic acid is converted into phenylacetic acid with high yield, the source utilization rate of the glycolide and the oligoglycolic acid reaches 100%, and excessive benzene in the raw materials can be recycled by distillation, so the reaction process is environment-friendly;
(5) the invention selects cheap benzene and readily available glycolide or low-polymer glycolic acid as raw materials, has high conversion rate of converting the glycolide or low-polymer glycolic acid into phenylacetic acid and high atom utilization rate of the glycolide or low-polymer glycolic acid, and can still recycle excessive benzene after recovery, so the synthetic method route has good economy.
Detailed Description
The invention is further illustrated by the following specific examples, which are not intended to be limiting in any way, and any alterations and modifications based on the teachings of the invention are intended to be included within the scope of the invention.
Example 1
1740g of benzene with the moisture content lower than 0.05 percent and 116 g of glycolide are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 290g of anhydrous aluminum trichloride is added into the system in batches and is stirred and dispersed uniformly; raising the temperature of the system to 80 ℃, and continuously reacting for 3 hours under the condition of continuous stirring; after the reaction, a mixture of 300g of crushed ice and 208g of 36.5% concentrated hydrochloric acid is added into the system to quench the reaction and dissolve newly generated precipitates; standing for layering, carrying out rotary evaporation on a benzene layer to recover benzene, and carrying out vacuum drying on a product after benzene recovery to obtain 271g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to give 261.4g of phenylacetic acid having a purity of 99.8%.
Example 2
2430g of benzene with the moisture content of less than 0.05 percent and 116 g of glycolide are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 310g of anhydrous aluminum trichloride is added into the system in batches and stirred and dispersed uniformly; raising the temperature of the system to 70 ℃, and continuously reacting for 4 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 821g of 10% concentrated hydrochloric acid is added dropwise to dissolve the newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 274g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to give 263.8g of phenylacetic acid having a purity of 99.7%.
Example 3
Adding 2550g of benzene with the water content of less than 0.05 percent and 318g of anhydrous aluminum trichloride into a reaction kettle with a heating, condensing, stirring and temperature control device, stirring and mixing uniformly, and then adding 116 g of glycolide into the system in multiple batches, stirring and dispersing uniformly; raising the temperature of the system to 45 ℃, and continuously reacting for 16 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and then 410g of 20% concentrated hydrochloric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying after benzene recovery to obtain 272g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 261.0g of phenylacetic acid having a purity of 99.5%.
Example 4
2080g of benzene with the moisture content lower than 0.05 percent and 116.0g of glycolide are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and 283g of anhydrous aluminum trichloride is added into the system in batches and stirred and dispersed uniformly; raising the temperature of the system to 65 ℃, and continuously reacting for 19 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 153g of 70% sulfuric acid is added dropwise to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 272g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 261.0g of phenylacetic acid having a purity of 99.8%.
Example 5
1400g of benzene with the moisture content of less than 0.05 percent and 116.0g of glycolide are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 320.0g of anhydrous aluminum trichloride is added into the system in batches and stirred and dispersed uniformly; raising the temperature of the system to 55 ℃, and continuously reacting for 6 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 1040 g of 10% sulfuric acid is added dropwise to dissolve the newly generated precipitate; standing for layering, carrying out rotary evaporation on a benzene layer to recover benzene, and carrying out vacuum drying on a product after benzene recovery to obtain 271g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to give 260.0g of phenylacetic acid having a purity of 99.9%.
Example 6
Adding 696g of benzene with the water content of less than 0.05 percent and 116 g of glycolide into a reaction kettle with a heating, condensing, stirring and temperature control device, stirring and mixing uniformly, and then adding 275g of anhydrous aluminum trichloride into the system in batches, stirring and dispersing uniformly; raising the temperature of the system to 60 ℃, and continuously reacting for 7 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 340g of 30% sulfuric acid is added dropwise to dissolve the newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 270.9g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to give 260.3g of phenylacetic acid having a purity of 99.7%.
Example 7
2900g of benzene with the moisture content of less than 0.05 percent and 116.0g of glycolide are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 280g of anhydrous aluminum trichloride is added into the system in batches and stirred and dispersed uniformly; raising the temperature of the system to 60 ℃, and continuously reacting for 4 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and then 924g of 15% nitric acid is dropwise added to dissolve the newly generated precipitate; standing for layering, carrying out rotary evaporation on a benzene layer to recover benzene, and carrying out vacuum drying on a product after benzene recovery to obtain 271g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 260.8g of phenylacetic acid having a purity of 99.8%.
Example 8
812g of benzene with the moisture content of less than 0.05 percent and 116 g of glycolide are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 330g of anhydrous ferric trichloride is added into the system in batches and is stirred and dispersed uniformly; raising the temperature of the system to 60 ℃, and continuously reacting for 19 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 277g of 50% nitric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 275g of a phenylacetic acid crude product; 264.0g of phenylacetic acid with the purity of 99.8 percent is obtained by reduced pressure distillation of the crude phenylacetic acid under the condition of 2mmHg by using warm water at 50 ℃ as a cooling medium.
Example 9
Adding 2700g of benzene with the moisture content lower than 0.05 percent and 116 g of glycolide into a reaction kettle with a heating, condensing, stirring and temperature control device, stirring and mixing uniformly, and then adding 307g of zinc chloride into the system in batches, stirring and dispersing uniformly; raising the temperature of the system to 60 ℃, and continuously reacting for 18 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 441 g of 40% hydrobromic acid is added dropwise to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 270g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to give 259.9g of phenylacetic acid having a purity of 99.9%.
Example 10
2900g of benzene with the moisture content lower than 0.05 percent and 280g of anhydrous aluminum trichloride are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 116 g of glycolide is added into the system in multiple batches and is stirred and dispersed uniformly; raising the temperature of the system to 45 ℃, and continuously reacting for 15 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 208g of 36.5% concentrated hydrochloric acid is added dropwise to dissolve the newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 272g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 261.0g of phenylacetic acid having a purity of 99.9%.
Example 11
Adding 1500g of benzene with the water content of less than 0.05 percent and 116 g of glycolide into a reaction kettle with a heating, condensing, stirring and temperature control device, stirring and mixing uniformly, then adding 300g of 50 percent boron trifluoride diethyl etherate into the system in batches, stirring and dispersing uniformly; raising the temperature of the system to 35 ℃, and continuously reacting for 6 hours under the condition of continuous stirring; after the reaction is finished, 400g of crushed ice is added into the system to quench the reaction, and then 218g of 36.5% concentrated hydrochloric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 270g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to give 259.9g of phenylacetic acid having a purity of 99.8%.
Example 12
Adding 1980g of benzene with the moisture content of less than 0.05 percent and 116.8 g of oligoglycolic acid into a reaction kettle with a heating, condensing, stirring and temperature control device, stirring and mixing uniformly, and then adding 300g of anhydrous aluminum trichloride into the system in batches, stirring and dispersing uniformly; raising the temperature of the system to 45 ℃, and continuously reacting for 8 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 228g of 36.5% concentrated hydrochloric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 273.1g of a phenylacetic acid crude product; the crude phenylacetic acid product is distilled under reduced pressure with warm water at 50 ℃ as a cooling medium under 2mmHg to obtain 262.3g of phenylacetic acid with the purity of 99.6 percent.
Example 13
813g of benzene with the moisture content of less than 0.05 percent and 116 g of oligoglycolic acid are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and 293g of anhydrous aluminum trichloride is added into the system in batches and is stirred and dispersed uniformly; raising the temperature of the system to 35 ℃, and continuously reacting for 18 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 226g of 36.5% concentrated hydrochloric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 274g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 263.3g of phenylacetic acid having a purity of 99.7%.
Example 14
Adding 1980g of benzene with the moisture content of less than 0.05 percent and 116 g of oligoglycolic acid into a reaction kettle with a heating, condensing, stirring and temperature control device, stirring and mixing uniformly, and then adding 308g of anhydrous aluminum trichloride into the system in batches, stirring and dispersing uniformly; raising the temperature of the system to 55 ℃, and continuously reacting for 23 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 225g of 36.5% concentrated hydrochloric acid is added dropwise to dissolve the newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 271.8g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 261.0g of phenylacetic acid having a purity of 99.6%.
Example 15
590g of benzene with the moisture content lower than 0.05 percent and 298g of anhydrous aluminum trichloride are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 118 g of oligoglycolic acid is added into the system in batches and is stirred and dispersed uniformly; raising the temperature of the system to 65 ℃, and continuously reacting for 8 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and 228g of 36.5% concentrated hydrochloric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, carrying out rotary evaporation on a benzene layer to recover benzene, and carrying out vacuum drying on a product after benzene recovery to obtain 278.1g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 267.2g of phenylacetic acid having a purity of 99.7%.
Example 16
2440g of benzene with the moisture content of less than 0.05 percent and 116.2 g of oligoglycolic acid are added into a reaction kettle with a heating, condensing, stirring and temperature control device to be stirred and mixed uniformly, and then 280g of anhydrous aluminum trichloride is added into the system in batches and stirred and dispersed uniformly; raising the temperature of the system to 45 ℃, and continuously reacting for 15 hours under the condition of continuous stirring; after the reaction is finished, 200g of crushed ice is added into the system to quench the reaction, and then 222g of 36.5% concentrated hydrochloric acid is dropwise added to dissolve a newly generated precipitate; standing for layering, performing rotary evaporation on a benzene layer to recover benzene, and performing vacuum drying on a product after benzene recovery to obtain 270.3g of a phenylacetic acid crude product; the crude phenylacetic acid product was subjected to distillation under reduced pressure under 2mmHg with warm water at 50 ℃ as a cooling medium to obtain 259.7g of phenylacetic acid having a purity of 99.8%.
Claims (7)
1. A synthetic method of phenylacetic acid is characterized in that: the mass ratio is (25-5): 1, reacting benzene and glycolide or oligomeric glycolic acid at the temperature of 35-80 ℃ for 1-24 h under the catalysis of Lewis acid with the amount of oxyacetyl substances being 1.0-1.3 times, and obtaining a phenylacetic acid product through quenching reaction with water, acidification by adding inorganic strong acid, oil-water phase layering, solvent evaporation and drying.
2. The method for synthesizing phenylacetic acid according to claim 1, wherein: and uniformly stirring and mixing the benzene and the glycolide, and adding Lewis acid in batches.
3. The method for synthesizing phenylacetic acid according to claim 1, wherein: and uniformly mixing the benzene and the Lewis acid, and then adding glycolide or oligomeric glycolic acid in batches.
4. The method for synthesizing phenylacetic acid according to claim 1, wherein: the water quenching reaction and the acidification by adding the inorganic strong acid are that the water quenching reaction is firstly added, and then the acidification is carried out by the inorganic strong acid until the solid is completely dissolved.
5. A process for the synthesis of phenylacetic acid according to any one of claims 1 to 3, characterized in that: the Lewis acid is aluminum chloride, zinc chloride, ferric trichloride or boron trifluoride.
6. A process for the synthesis of phenylacetic acid according to claim 1 or 4, characterized in that: the inorganic strong acid is sulfuric acid, hydrochloric acid, nitric acid or hydrobromic acid.
7. A process for the synthesis of phenylacetic acid according to claim 1 or 4, characterized in that: the water in the water quenching reaction is water vapor in a gaseous state, water in a liquid state or ice in a solid state.
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Denomination of invention: A synthesis method of phenylacetic acid Effective date of registration: 20231124 Granted publication date: 20200414 Pledgee: Bank of Jiangsu Co.,Ltd. Taixing sub branch Pledgor: TAIXING LINGFEI CHEMICAL TECHNOLOGY Co.,Ltd. Registration number: Y2023980067194 |