JPS63287745A - Production of 2-(substituted aryl) propionic acid or ester thereof - Google Patents
Production of 2-(substituted aryl) propionic acid or ester thereofInfo
- Publication number
- JPS63287745A JPS63287745A JP62122763A JP12276387A JPS63287745A JP S63287745 A JPS63287745 A JP S63287745A JP 62122763 A JP62122763 A JP 62122763A JP 12276387 A JP12276387 A JP 12276387A JP S63287745 A JPS63287745 A JP S63287745A
- Authority
- JP
- Japan
- Prior art keywords
- substituted aryl
- propionic acid
- ester
- salt
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 title claims description 34
- 235000019260 propionic acid Nutrition 0.000 title claims description 18
- 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 title claims description 17
- 150000002148 esters Chemical class 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- -1 halide salt Chemical class 0.000 claims abstract description 21
- 229910052751 metal Inorganic materials 0.000 claims abstract description 17
- 239000002184 metal Substances 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 238000005810 carbonylation reaction Methods 0.000 claims abstract description 10
- 230000006315 carbonylation Effects 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052787 antimony Inorganic materials 0.000 claims abstract description 4
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 4
- VTMSSJKVUVVWNJ-UHFFFAOYSA-N 1-ethenyl-4-(2-methylpropyl)benzene Chemical compound CC(C)CC1=CC=C(C=C)C=C1 VTMSSJKVUVVWNJ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052782 aluminium Inorganic materials 0.000 claims abstract description 3
- 229910052742 iron Inorganic materials 0.000 claims abstract description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 27
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 13
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 13
- 229910052763 palladium Inorganic materials 0.000 claims description 12
- 239000005977 Ethylene Substances 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 claims description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000007795 chemical reaction product Substances 0.000 abstract description 4
- 229910021592 Copper(II) chloride Inorganic materials 0.000 abstract description 2
- 229910052802 copper Inorganic materials 0.000 abstract description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 abstract description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 abstract 1
- 229910002666 PdCl2 Inorganic materials 0.000 abstract 1
- 125000000218 acetic acid group Chemical class C(C)(=O)* 0.000 abstract 1
- 230000000202 analgesic effect Effects 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 125000003963 dichloro group Chemical group Cl* 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical group 0.000 description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
- KETWBQOXTBGBBN-UHFFFAOYSA-N hex-1-enylbenzene Chemical compound CCCCC=CC1=CC=CC=C1 KETWBQOXTBGBBN-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- DZIQUZJSNSZOCH-UHFFFAOYSA-N methyl 2-phenylpropanoate Chemical compound COC(=O)C(C)C1=CC=CC=C1 DZIQUZJSNSZOCH-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- SXIFNAOBIAIYJO-SXVCMZJPSA-N (1E,3E,7E)-cyclododeca-1,3,7-triene Chemical compound C/1=C\CCCC\C=C\C=C\CC\1 SXIFNAOBIAIYJO-SXVCMZJPSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical group C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- VTWKXBJHBHYJBI-SOFGYWHQSA-N (ne)-n-benzylidenehydroxylamine Chemical compound O\N=C\C1=CC=CC=C1 VTWKXBJHBHYJBI-SOFGYWHQSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- BTOVVHWKPVSLBI-UHFFFAOYSA-N 2-methylprop-1-enylbenzene Chemical compound CC(C)=CC1=CC=CC=C1 BTOVVHWKPVSLBI-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229910021120 PdC12 Inorganic materials 0.000 description 1
- 241000907661 Pieris rapae Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000008366 benzophenones Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- MPMBRWOOISTHJV-UHFFFAOYSA-N but-1-enylbenzene Chemical compound CCC=CC1=CC=CC=C1 MPMBRWOOISTHJV-UHFFFAOYSA-N 0.000 description 1
- 229910002090 carbon oxide Inorganic materials 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000004989 dicarbonyl group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- RDJGLLICXDHJDY-UHFFFAOYSA-N fenoprofen Chemical compound OC(=O)C(C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-UHFFFAOYSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- YNZYUHPFNYBBFF-UHFFFAOYSA-N methyl 2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound COC(=O)C(C)C1=CC=C(CC(C)C)C=C1 YNZYUHPFNYBBFF-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- KHMYONNPZWOTKW-UHFFFAOYSA-N pent-1-enylbenzene Chemical compound CCCC=CC1=CC=CC=C1 KHMYONNPZWOTKW-UHFFFAOYSA-N 0.000 description 1
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 150000003151 propanoic acid esters Chemical class 0.000 description 1
- 150000004672 propanoic acids Chemical class 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、医薬品および医薬品を初めとする有機合成分
野での中間体として有用な２−（置換アリール）プロピ
オン酸エステルおよび／または２−（置換アリール）プ
ロピオン酸を製造する方法に関するものである。これら
２−（置換アリール）プロピオン酸エステルおよび／ま
たは２−（置換アリール）プロピオン酸は、消炎鎮痛効
果を有する医薬品として有用な物質を多く含むものであ
る。更に詳しくは、置換アリールエチレンを一酸化炭素
と、水および／またはアルコールと反応させ、カルボン
酸エステルおよび／またはカルボン酸を製造する際に、
特定の金属塩を共存させ、目的物の選択性を高める新規
な方法に関するものである。Detailed Description of the Invention [Industrial Application Field] The present invention provides 2-(substituted aryl)propionate and/or 2-( The present invention relates to a method for producing substituted aryl)propionic acids. These 2-(substituted aryl) propionic acid esters and/or 2-(substituted aryl) propionic acids contain many substances useful as pharmaceuticals having anti-inflammatory and analgesic effects. More specifically, when reacting substituted aryl ethylene with carbon monoxide, water and/or alcohol to produce carboxylic acid ester and/or carboxylic acid,
This invention relates to a novel method for increasing the selectivity of a target product by coexisting a specific metal salt.
［従来の技術および
本発明が解決しようとする問題点］
従来から、置換アリールエチレンをパラジウム触媒の存
在下でカルボニル化して、２−（置換アリール）プロピ
オン酸を得る方法としては、例えば、英国特許第１５６
５２３５号および特許公開第５２−９７９３０号公報等
が提案されている。[Prior art and problems to be solved by the present invention] Conventionally, as a method for obtaining 2-(substituted aryl)propionic acid by carbonylating substituted aryl ethylene in the presence of a palladium catalyst, for example, the method described in the British patent 156th
No. 5235, Japanese Patent Publication No. 52-97930, etc. have been proposed.
一般に末端オレフィンのカルボニル化では、目的とする
アリール基に対して、α位の炭素原子に対してカルボニ
ル基が導入された２−（置換アリール）体の他に、β位
の炭素原子に対してカルボニル基の導入された３−（置
換アリール）体の副生が避けられなかった。従来からこ
の技術分野では、有用で好ましい２−（置換アリール）
体への選択性を高める方法が望まれていた。即ち、２−
（置換アリール）体（α）／３−（置換アリール）体（
β）のモル比で表すと、α／βの比を高めることに努力
が注がれている。In general, in the carbonylation of terminal olefins, in addition to the 2-(substituted aryl) form in which a carbonyl group is introduced to the α-position carbon atom to the target aryl group, the carbonyl group is introduced to the β-position carbon atom. The by-product of a 3-(substituted aryl) body into which a carbonyl group was introduced was unavoidable. Traditionally in this technical field, useful and preferred 2-(substituted aryl)
There has been a desire for a method that increases selectivity to the body. That is, 2-
(Substituted aryl) form (α)/3-(Substituted aryl) form (
Expressed in molar ratio of β), efforts are being focused on increasing the ratio of α/β.
この目的を達成するための方法として、上記提案されて
いる具体的な方法の他に一般的に塩酸を添加する方法も
行なわれているが、装置の腐食、置換アリールエチレン
の重合によるロス、酸触媒によるエーテルの副生などの
ため、必ずしも好ましい方法てはなかった。In addition to the specific method proposed above, a method of adding hydrochloric acid is generally used to achieve this purpose, but this method causes corrosion of equipment, loss due to polymerization of substituted aryl ethylene, This method was not necessarily preferred because of the by-product of ether caused by the catalyst.
本発明者らは、特定の金属塩を共存させることにより２
−（置換アリール）体に対する３−（置換アリール）体
の比を改善できることを見出し、本発明を完成させたも
のである。The present inventors have discovered that by coexisting a specific metal salt,
The present invention was completed by discovering that the ratio of the 3-(substituted aryl) form to the -(substituted aryl) form can be improved.
更に本発明の方法をフローシートで表すと次のようにな
る。Furthermore, the method of the present invention can be expressed as a flow sheet as follows.
ｃ。c.
（α） （β）［問題を解決す
るための手段］
即ち本発明は、に１１． Ｚｎ、 Ａｌ、ｒｅ、 Ｓｂ
からなる群から選ばれる少なくとも一種の金属の塩をパ
ラジウム金属１原子に対して０．０５〜１．５原子の割
合で共存させて、置換アリールエチレンをパラジウム系
カルボニル化触媒の存在下に、一酸化炭素と、水および
／または低級アルコールと反応させることによりとドロ
エステル化し、必要に応じて加水分解することを特徴と
する２−（置換アリール）プロピオン酸の製造方法を提
供し、有用て好ましい２−（置換アリール）体を効率よ
く製造する方法に関するものである。(α) (β) [Means for solving the problem] That is, the present invention has the following features: 11. Zn, Al, re, Sb
A salt of at least one metal selected from the group consisting of 0.05 to 1.5 atoms per 1 atom of palladium metal is allowed to coexist with the substituted aryl ethylene in the presence of a palladium-based carbonylation catalyst. Provided is a method for producing 2-(substituted aryl)propionic acid, which is useful and preferred, characterized in that it is doroesterified by reacting carbon oxide with water and/or a lower alcohol, and optionally hydrolyzed. The present invention relates to a method for efficiently producing a 2-(substituted aryl) form.
本発明の置換アリールエチレンは、スチレンのほか、メ
チルスチレン、エチルスチレン、ジメチルスチレン、プ
ロピルスチレン、ブチルスチレンなどのようなアルキル
スチレン類の他、ジフェニル基、フェノキシフェニル基
、アルコキシナフチル基、ベンゾイルフェニル基の置換
した置換アリールエチレン類などである。これらの置換
アリールエチレンは、従来公知の方法で製造されたもの
であれば何れも使用することができる。製造方法の具体
例としては、
Ｉｎｄｕｓｔｒｉａｌ ａｎｄ Ｅｎｇｉｎｅｅｒｉｎ
ｇ Ｃｈｅｍｉｓｔｒｙ、 Ｖｏｌ。In addition to styrene, the substituted arylethylene of the present invention includes alkylstyrenes such as methylstyrene, ethylstyrene, dimethylstyrene, propylstyrene, butylstyrene, etc., as well as diphenyl, phenoxyphenyl, alkoxynaphthyl, and benzoylphenyl groups. and substituted arylethylenes. Any substituted arylethylene produced by a conventionally known method can be used. Specific examples of manufacturing methods include:
g Chemistry, Vol.
４１３、 Ｎｏ、 ４．６５２（１！１５４）、Ｊｏｕ
ｒｎａｌ ｏｆ Ｃｈｅｍｉｃａｌ ａｎｄ Ｅｎｇｉ
ｎｅｅｒｉｎｇ Ｄａｔａ。413, No, 4.652 (1!154), Jou
rnal of Chemical and Engineering
nering Data.
Ｖｏｌ、９． Ｎｏ、 １．１０４ （１９６４）、Ｉ
＆ ＥＣＰｒｏｄｕｃｔ Ｒｅ５ａｒｃｈ
ａｎｄ Ｄｅｖｅｌｏｐｍｅｒ＋ｔ。Vol.9. No. 1.104 (1964), I
& ECProduct Re5arch
and Developer+t.
Ｖｏｌ、 ３． Ｎｏ、 １．１８ （１９６４）、米
国特許第２，４２０，６８９．２，４２２，３１８．２
，８６４，８７２．２．９５４，４１３および３，０２
５，３３０号などが提案されており、これらの方法によ
る置換アリールエチレンを何れも使用することが出来る
。Vol, 3. No. 1.18 (1964), U.S. Patent No. 2,420,689.2,422,318.2
,864,872.2.954,413 and 3,02
No. 5,330 and the like have been proposed, and any of the substituted aryl ethylenes obtained by these methods can be used.
具体的な本発明の方法で得られる２−（置換アリール）
プロピオン酸には、α−（３−インブチルフェニル）プ
ロピオン酸、α−（３−ジフェニリル）プロピオン酸、
α−（３−フェノキシフェニル）プロピオン酸、α−（
３−アルコキシナフチル）プロピオン酸、α−（３−ベ
ンゾイルフェニル）プロピオン酸等が例示される。2-(substituted aryl) obtained by the specific method of the present invention
Propionic acid includes α-(3-inbutylphenyl)propionic acid, α-(3-diphenylyl)propionic acid,
α-(3-phenoxyphenyl)propionic acid, α-(
Examples include 3-alkoxynaphthyl)propionic acid and α-(3-benzoylphenyl)propionic acid.
本発明の方法において置換アリールエチレンと一酸化炭
素と共に反応させる化合物は、水、低級アルコールまた
はこれらの混合物である。The compound reacted with the substituted arylethylene and carbon monoxide in the method of the invention is water, a lower alcohol or a mixture thereof.
本発明の方法で、水を用いて一酸化炭素と反応させたと
きには、２−（置換アリール）プロピオン酸が遊離のカ
ルボン酸として直接製造できる。In the method of the present invention, when water is used to react with carbon monoxide, 2-(substituted aryl)propionic acid can be directly produced as a free carboxylic acid.
また、低級アルコールを用いて一酸化炭素と反応させた
ときは、２−（置換アリール）プロピオン酸は使用した
アルコールのアルキルエステルとして製造される。Furthermore, when a lower alcohol is used to react with carbon monoxide, 2-(substituted aryl)propionic acid is produced as an alkyl ester of the alcohol used.
このエステルは必要に応じて従来公知の方法で加水分解
することによって遊離のカルボン酸に容易に変換するこ
とが出来る。これら低級アルコールは、炭素数１から４
である低級アルキル基を有する脂肪族アルコールである
。これらの具体例は、メタノール、エタノール、ローブ
ロバノール、イソプロパツール、ｎ−ブタノール、５ｅ
ｃ−ブタノール、インブタノールおよびｔ’ｅｒｔ−ブ
タノールなどである。これらは、単独でもまた２種類以
上のアルコールを混合しても用いることが出来る。その
種類は反応させる置換アリールエチレンに応じて適宜選
択できる。アルコールの使用量は、置換アリールエチレ
ンに対して過剰であれば良いが、モル比で、置換アリー
ルエチレンの１に対して５までで充分である。If necessary, this ester can be easily converted into a free carboxylic acid by hydrolysis using a conventionally known method. These lower alcohols have 1 to 4 carbon atoms.
It is an aliphatic alcohol having a lower alkyl group. Specific examples of these include methanol, ethanol, lobanol, isopropanol, n-butanol, 5e
These include c-butanol, inbutanol and t'ert-butanol. These alcohols can be used alone or in combination of two or more types. The type can be appropriately selected depending on the substituted arylethylene to be reacted. The amount of alcohol used may be in excess of the substituted aryl ethylene, but a molar ratio of up to 5 to 1 of the substituted aryl ethylene is sufficient.
アルコールを用いるとドロエステル化では、一般にエス
テルの異性体としてノルマル体とイソ体との異性体が共
に生成する。これらの異性体を、例えば蒸留により分離
精製する必要があるときには、沸点、融点などの異性体
間の物理恒数に差が生じるように、用いるアルコールの
種類を適宜選択すれば良い。When alcohol is used, droesterification generally produces both normal and isoisomers as ester isomers. When it is necessary to separate and purify these isomers, for example, by distillation, the type of alcohol used may be appropriately selected so that physical constants such as boiling point and melting point differ between the isomers.
本発明のとドロエステル化触媒はパラジウムを活性中心
とするもので、活性金属の酸価数は０から最高位の酸価
数まで使用できる。これらの触媒としては、３価のリン
化合物、π−アリル基、アミン、ニトリル、オキシム、
オレフィン、水素あるいは一酸化炭素を配位子として含
有する錯体も用いることができる。The toroesterification catalyst of the present invention has palladium as its active center, and the acid number of the active metal can range from 0 to the highest acid number. These catalysts include trivalent phosphorus compounds, π-allyl groups, amines, nitriles, oximes,
Complexes containing olefins, hydrogen or carbon monoxide as ligands can also be used.
これらの錯体の具体例としては、ビストリフェニルホス
フィンジクロロ錯体、ビストリブチルホスフィンジクロ
ロ錯体、ビストリシクロへキシルホスフィンジクロロ錯
体、π−アリルトリフェニルホスフィンジクロロ錯体、
トリフェニルホスフィンピペリジンジクロロ錯体、ビス
ベンゾニトリルジクロロ錯体、ビスシクロへキシルオキ
シムジクロロ錯体、１，５．９−シクロドデカトリエン
−ジクロロ錯体、ビストリフェニルホスフィンジカルボ
ニル錯体、ビストリフェニルホスフィンアセテート錯体
、ビストリフェニルホスフィンシナイトレート錯体、ビ
ストリフェニルホスフィンスルフアート錯体、テトラキ
ストリフェニルホスフィン錯体および一酸化炭素を配位
子の一部に持つクロロカルボニルビストリフェニルホス
フィン錯体、ヒドリドカルボニルトリストリフェニルホ
スフィン錯体、ビスクロロテトラカルボニル錯体、ジカ
ルボニルアセチルアセトナート錯体等を挙げることがで
きる。Specific examples of these complexes include bistriphenylphosphine dichloro complex, bistributylphosphine dichloro complex, bistricyclohexylphosphine dichloro complex, π-allyltriphenylphosphine dichloro complex,
Triphenylphosphine piperidine dichloro complex, bisbenzonitrile dichloro complex, biscyclohexyloxime dichloro complex, 1,5.9-cyclododecatriene-dichloro complex, bistriphenylphosphine dicarbonyl complex, bistriphenylphosphine acetate complex, bistriphenylphosphine dichlorocomplex Nitrate complex, bistriphenylphosphine sulfate complex, tetrakistriphenylphosphine complex, chlorocarbonylbistriphenylphosphine complex with carbon monoxide as part of the ligand, hydridocarbonyltristriphenylphosphine complex, bischlorotetracarbonyl complex , dicarbonylacetylacetonate complex, and the like.
また、反応系において上記の錯体を形成し得る化合物も
用いることができる。Further, compounds capable of forming the above-mentioned complexes in the reaction system can also be used.
すなわち、活性中心であるパラジウムに対して配位子と
なり得る化合物、すなわち、ホスフィン、ニトリル、ア
リル化合物、アミン、オキシム、オレフィン、あるいは
一酸化炭素を同時に反応系に存在させる方法でもよい。That is, a method may be employed in which a compound that can serve as a ligand for palladium, which is an active center, such as a phosphine, a nitrile, an allyl compound, an amine, an oxime, an olefin, or carbon monoxide, is simultaneously present in the reaction system.
上記ホスフィンとしては、例えば、トリフェニルホスフ
ィン、トリトリルホスフィン、トリブチルホスフィン、
トリシクロヘキシルホスフィン、トリエチルホスフィン
等：ニトリルとしては、例えば、ベンゾニトリル、アク
リロニトリル、プロピオニトリル、ベンジルニトリル等
；アリル化合物としては、例えば、アリルクロライド、
アリルアルコール等；アミンとしては、例えば、ベンジ
ルアミン、ピリジン、ピペラジン、トリーｎ−ブチルア
ミン等；オキシムとしては、シクロへキシルオキシム、
アセトオキシム、ベンズアルドオキシム等；またオレフ
ィンとしては、１．５−シクロオクタジエン、Ｌ、５．
９−シクロドデカトリエン等がそれぞれ挙げられる。Examples of the above phosphine include triphenylphosphine, tritolylphosphine, tributylphosphine,
Tricyclohexylphosphine, triethylphosphine, etc.: Nitriles include, for example, benzonitrile, acrylonitrile, propionitrile, benzylnitrile, etc.; allyl compounds include, for example, allyl chloride,
Allyl alcohol, etc.; Examples of amines include benzylamine, pyridine, piperazine, tri-n-butylamine, etc.; Examples of oximes include cyclohexyloxime,
Acetoxime, benzaldoxime, etc.; and olefins include 1,5-cyclooctadiene, L, 5.
Examples include 9-cyclododecatriene and the like.
本発明のとドロエステル化反応において共存させるべき
金属塩はＣｕ、 Ｚｎ％Ａ１、Ｆｅ、 Ｓｂからなる群
から選ばれる少なくとも一種の金属の塩で、これはハロ
ゲン塩、硫酸塩、硝酸塩、燐酸塩などの無機酸塩ばかに
、酢酸塩などのように低級カルボン酸の塩でもよい。こ
れらの塩は、無水の塩でも結晶性の含水塩でもよい。更
にこれらは、単独でも混合物の状態で用いてもよい。こ
れらの金属塩は、パラジウム１原子に対し０．０５〜１
．５の原子比て共存させることが好ましい。原子比が０
．０５未満の添加量ては該金属塩の添加効果がない。即
ち、前述のα／β比（ｉ ／ ｏ比）を向上させる効果
がない。また、原子比が１．５を越える添加では、金属
塩それ自体が別な触媒活性を示すようになり、原料であ
る置換アリールエチレンの重合によるロスが著しくなっ
たり、パラジウムの触媒能を抑制するため好ましくない
。The metal salt to be allowed to coexist in the droesterification reaction of the present invention is a salt of at least one metal selected from the group consisting of Cu, Zn%A1, Fe, and Sb, and this includes halogen salts, sulfates, nitrates, and phosphates. In addition to inorganic acid salts such as, salts of lower carboxylic acids such as acetates may also be used. These salts may be anhydrous salts or crystalline hydrated salts. Furthermore, these may be used alone or in the form of a mixture. These metal salts have a concentration of 0.05 to 1 per palladium atom.
．． It is preferable that they coexist at an atomic ratio of 5. Atomic ratio is 0
．． If the amount added is less than 0.05, there is no effect of the addition of the metal salt. That is, there is no effect of improving the α/β ratio (i/o ratio) described above. In addition, if the atomic ratio exceeds 1.5, the metal salt itself will exhibit a different catalytic activity, and the loss due to polymerization of substituted aryl ethylene, which is a raw material, will become significant, and the catalytic ability of palladium will be suppressed. Therefore, it is undesirable.
具体的な本発明の金属塩としては、ＣｕＣｌ２、ＺｎＣ
ｌ２、ＡｌＣｌ３”６Ｈ２０、ＦｅＧ１３、ＦｅＣｌ２
、Ｇｕ （ＮＯ３） ２、Ｃｕ（ＤＣＯＣＨ３）２．５
ｂＣＩ３等が例示される。Specific metal salts of the present invention include CuCl2, ZnC
l2, AlCl3”6H20, FeG13, FeCl2
, Gu (NO3) 2, Cu (DCOCH3) 2.5
bCI3 etc. are exemplified.
ヒドロエステル化触媒の活性中心であるパラジウムの使
用量は、置換アリールエチレン１モルに対して、０．０
００１〜０．５モル、好ましくは０．０００５〜０．１
モルである。配位子となり得る化合物の添加量は、パラ
ジウム１原子に対して０．８〜１０モル、好ましくは１
〜４モルである。The amount of palladium used, which is the active center of the hydroesterification catalyst, is 0.0 per mole of substituted arylethylene.
001-0.5 mol, preferably 0.0005-0.1
It is a mole. The amount of the compound that can be a ligand added is 0.8 to 10 mol, preferably 1 mol per palladium atom.
~4 moles.
ヒドロエステル化反応は、反応温度は４０〜２００℃、
好ましくは５０〜１８０℃で行なう。In the hydroesterification reaction, the reaction temperature is 40 to 200°C,
Preferably it is carried out at 50 to 180°C.
反応温度が４０℃未満では、反応速度が著しく遅くなり
、実用上実施することができない。また、２００℃を越
える温度では、重合等の副反応やパラジウム系カルボニ
ル化触媒の分解が生じ好ましくない。If the reaction temperature is less than 40° C., the reaction rate will be extremely slow and the reaction cannot be carried out practically. Furthermore, temperatures exceeding 200°C are undesirable because side reactions such as polymerization and decomposition of the palladium-based carbonylation catalyst occur.
反応圧力は５ Ｋｇ／ｃｍ２以上あれば、適宜選択でき
る。５ Ｋｇ／ｃｍ２未満では、実用上実施することが
できない程反応が遅くなる。また、圧力は高い程反応が
速やかに進行し好ましいが、高過ぎる圧力は反応器の耐
圧を非常に高する必要があるなど、製造装置の点からお
のずと限界がある。従って、実用上は５００ Ｋｇ／ｃ
ｍ２以下の圧力で充分である。The reaction pressure can be appropriately selected as long as it is 5 Kg/cm2 or more. If it is less than 5 Kg/cm2, the reaction becomes so slow that it cannot be practically carried out. Further, the higher the pressure, the more quickly the reaction proceeds, which is preferable, but too high a pressure naturally has its limits in terms of production equipment, such as the need to make the pressure resistance of the reactor extremely high. Therefore, in practice, 500 Kg/c
A pressure of less than m2 is sufficient.
カルボニル化反応は一酸化炭素の吸収による圧力減少が
みられなくなるまで行なえばよく、通常は４〜２０時間
の反応時間で充分である。The carbonylation reaction may be carried out until no pressure decrease due to absorption of carbon monoxide is observed, and a reaction time of 4 to 20 hours is usually sufficient.
供給する一酸化炭素は単独で供給すればよい。Carbon monoxide may be supplied alone.
しかしカルボニル化反応に不活性な、窒素、ヘリウム、
アルゴン、メタン、エタン等の気体が共存しても良い。However, nitrogen, helium, and
Gases such as argon, methane, and ethane may coexist.
本発明のカルボニル化において、一般には無溶媒の状態
で充分好ましい結果が得られるが、カルボニル化に不活
性な溶媒を反応熱除去などの目的で用いることもできる
。カルボニル化に不活性な溶媒としては、エーテル、ケ
トン、アルコール等の極性溶媒や、パラフィン、シクロ
パラフィン、芳香族炭化水素のような無極性溶媒が挙げ
られる。In the carbonylation of the present invention, satisfactory results can generally be obtained without a solvent, but a solvent inert to carbonylation can also be used for purposes such as removing reaction heat. Examples of solvents inert to carbonylation include polar solvents such as ethers, ketones, and alcohols, and nonpolar solvents such as paraffins, cycloparaffins, and aromatic hydrocarbons.
アルコールと反応させたときには、２−（置換アリール
）プロピオン酸はアルコールエステルの状態で得られる
。これを必要に応じてカルボン酸の形に変換するには、
例えば、アルカリ水溶液と共に加熱して加水分解した後
、適当な酸で酸性にして遊離のカルボン酸に変換し、更
にカルボン酸を溶剤などで抽出分離すれば良い。When reacted with an alcohol, 2-(substituted aryl)propionic acid is obtained in the form of an alcohol ester. To convert this to the carboxylic acid form if necessary,
For example, it may be hydrolyzed by heating with an aqueous alkali solution, acidified with an appropriate acid to convert it into a free carboxylic acid, and then the carboxylic acid may be extracted and separated using a solvent or the like.
反応終了後、再結晶などにより目的とする２−（置換ア
リール）プロピオン酸が得られる。After the reaction is completed, the desired 2-(substituted aryl)propionic acid is obtained by recrystallization or the like.
［発明の効果コ
本発明の方法によれば、実際の使用面で好ましい２−（
置換アリール）プロピオン酸を、選択性良く、効率的に
製造することができる。[Effects of the Invention] According to the method of the present invention, 2-(
Substituted aryl)propionic acid can be efficiently produced with good selectivity.
［実施例］ 以下実施例で本発明を更に詳しく説明する。[Example] The present invention will be explained in more detail below with reference to Examples.
実施例１
一スチレンのとドロエステル化−
容量２００ｍ１のかき混ぜ機付き耐圧容器に、４２ｇの
スチレン（０，４モル）、０．０７１ｇのＰｄＣ１２（
０，４ミリモル）、０．２１３３ｇのトリフェニルフォ
スフイン（０，８ミリモル）、２０ｇのメタノール（０
，６モル）および各々下記に示す量の（：ｕＣＩ□を入
れ、一酸化炭素によって７５にｇ／ｃｍ２まで加圧し、
加圧状態を保った。加圧下で攪拌しながら温度９０℃に
おいて１０時間反応させた。Example 1 Dro-esterification of styrene - 42 g of styrene (0.4 mol) and 0.071 g of PdC12 (
0,4 mmol), 0.2133 g triphenylphosphine (0,8 mmol), 20 g methanol (0
.
The pressurized state was maintained. The reaction was carried out at a temperature of 90° C. for 10 hours while stirring under pressure.
反応終了後冷却し、その後余剰の一酸化炭素を放出し、
得られた反応物をガスクロマトダラムで分析し、α−フ
ェニルプロピオン酸メチルエステルの収率、および選択
性としてβ−位体に対するα−位体のモル比を算出した
。その結果を以下に示す。After the reaction is completed, it is cooled, and then excess carbon monoxide is released.
The obtained reaction product was analyzed by gas chromatography, and the yield of α-phenylpropionic acid methyl ester and the molar ratio of α-position to β-position were calculated as selectivity. The results are shown below.
表 １
（注）選択性：得られたエステルの（α位体／β位体）
のモル比実験例１から５で得られた反応物をまとめて精
密蒸留により１２ｍｍｌ（ｇから２２ｍｍＨｇの圧力に
おける留出温度９８℃から１１９℃の留分であるα−フ
ェニルプロピオン酸メチルエステル（回収率８６％、純
度９８．７％）を得た。Table 1 (Note) Selectivity: (α position/β position) of the obtained ester
The reactants obtained in Experimental Examples 1 to 5 were combined and subjected to precision distillation to obtain 12 mml (g) of α-phenylpropionic acid methyl ester (recovered), which is a fraction with a distillation temperature of 98°C to 119°C at a pressure of 22 mmHg. yield of 86% and purity of 98.7%).
実施例２
一ブチルスチレンのヒドロエステル化−実施例工と同様
に、容量２００ｍ１のかき混ぜ機付き耐圧容器に、８３
ｇのｐ−イソブチルスチレン（０，４モル）、０．０７
１ｇのＰｄＣ：Ｉ２（０，４ミリモル）、０．２１３３
ｇのトリフェニルフォスフイン（０，８ミリモル）、２
０ｇのメタノール（０，６モル）および各々下記に示す
量のＺｎｆｌ：Ｉ２を入れ、一酸化炭素によって圧カフ
５ Ｋｇ／ｃｍ２まで加圧し、加圧状態を保った。加
圧下で、攪拌しながら温度９０℃において１０時間反応
させた。反応終了後冷却した後、余剰の一酸化炭素を放
出し得られた反応物をガスクロマトダラムで分析し、収
率および選択性としてβ位体に対するα位体のモル比を
算出した。その結果を次に示す。Example 2 Hydroesterification of monobutylstyrene - Similar to the example, 83.
g of p-isobutylstyrene (0.4 mol), 0.07
1 g of PdC: I2 (0.4 mmol), 0.2133
g of triphenylphosphine (0.8 mmol), 2
0 g of methanol (0.6 mol) and Znfl:I2 in the amounts shown below were added, pressurized to a pressure cuff of 5 Kg/cm2 with carbon monoxide, and maintained under pressure. The reaction was carried out under pressure at a temperature of 90° C. for 10 hours while stirring. After the reaction was completed and cooled, excess carbon monoxide was released, and the resulting reaction product was analyzed using a gas chromatograph, and the molar ratio of the α-position to the β-position was calculated as the yield and selectivity. The results are shown below.
表 ２
（注）選択性：得られたエステルの（α位体／β位体）
のモル比実験例６〜１０で得られた反応物をまとめて、
精密蒸留により３ ｍｍｍ１（から５ ｍｍＨｇの圧力
における留出温度１２０℃から１２９℃の留分であるα
−（ｐ−インブチルフェニル）プロピオン酸メチルエス
テル（回収率８９％、純度９８．６％）を得た。Table 2 (Note) Selectivity: (α position/β position) of the obtained ester
The molar ratio of the reactants obtained in Experimental Examples 6 to 10 is summarized as
α, which is a fraction with a distillation temperature of 120°C to 129°C at a pressure of 3 mmHg to 5 mmHg, is obtained by precision distillation.
-(p-Inbutylphenyl)propionic acid methyl ester (recovery rate 89%, purity 98.6%) was obtained.
実施例３
一ブチルスチレンのとドロエステル化−実施例２と同様
にして、以下に示す金属Ｐｄ原子に対して０．５原子比
となる量をパラジウムに触媒に対して添加し、α−イソ
ブチルスチレンのとドロエステル化を実施した。また、
同様に収率および選択率を求めた。Example 3 Doroesterification of monobutylstyrene - In the same manner as in Example 2, palladium was added to the catalyst in an amount of 0.5 atomic ratio to the metal Pd atoms shown below, and α-isobutyl Droesterification of styrene was carried out. Also,
Yield and selectivity were determined in the same manner.
表 ３
実施例５
一加水分解一
実施例２の蒸留で得られたα−（ｐ−イソブチルフェニ
ル）プロピオン酸メチルエステル留分１１０ｇを用いて
加水分解を行なった。Table 3 Example 5 Monohydrolysis 110 g of the α-(p-isobutylphenyl)propionic acid methyl ester fraction obtained by distillation in Example 2 was used for hydrolysis.
容量１リツトルの、還流冷却器、攪拌機付きの反応器に
、エステル１７０ｇと１０％苛性ソーダ水溶液を入れ、
かき混ぜながら徐々に加熱し、８０℃から９５℃に保っ
て３時間反応させた。Put 170 g of ester and a 10% aqueous solution of caustic soda into a 1 liter reactor equipped with a reflux condenser and a stirrer.
The mixture was gradually heated while stirring and kept at a temperature of 80°C to 95°C for 3 hours.
反応終了後室温まで冷却し、３５％塩酸を加えて酸性に
した。カルボン酸として遊離した生成物のために白濁し
た反応混合物に３００ｇのトルエンを加えカルボン酸を
抽出した。抽出後、トルエンを蒸留分離して、淡黄色の
α−（ｐ−インブチルフェニル）プロピオン酸９９ｇ（
融点７３．０℃〜７４．５℃）を得た。After the reaction was completed, the mixture was cooled to room temperature and made acidic by adding 35% hydrochloric acid. To the reaction mixture, which became cloudy due to the product liberated as carboxylic acid, 300 g of toluene was added to extract the carboxylic acid. After extraction, toluene was distilled off to obtain 99 g of pale yellow α-(p-inbutylphenyl)propionic acid (
A melting point of 73.0°C to 74.5°C was obtained.
淡黄色結晶をｎ−ヘキサンから再結晶し、融点７５．０
℃から７５．５℃の白色結晶を得た。このものは、標品
との混合融点試験でも同一の融点を示した。The pale yellow crystals were recrystallized from n-hexane and had a melting point of 75.0.
C. to 75.5.degree. C. white crystals were obtained. This product showed the same melting point in a mixed melting point test with the standard product.
実施例６および比較実験例５
−パラジウム錯体触媒によるとドロエステル化−実施例
２、実験例８のＰｃ１ＧＩ２の代わりに、ジクロロパラ
ジウムビストリフェニルフォスフイン（２８１ｍｇ、０
．４ミリモル）を用いて、実施例２と同様にしてブチル
スチレンのとドロエステル化を行なった。α−インブチ
ルフェニルプロピオン酸メチルエステルの収率９７．６
％、α／β比は４４．５であった。Example 6 and Comparative Experimental Example 5 - Droesterification using a palladium complex catalyst - In place of Pc1GI2 in Example 2 and Experimental Example 8, dichloropalladium bistriphenylphosphine (281 mg, 0
．． Butylstyrene was esterified in the same manner as in Example 2 using 4 mmol). Yield of α-inbutylphenylpropionate methyl ester 97.6
% and α/β ratio was 44.5.
また、上記実験において、ＺｎＣｌ２を添加せずにとド
ロエステル化を行なったが、当該エステルの収率は９１
．４％、α／β比は１３．８であった。In addition, in the above experiment, the droesterification was carried out without adding ZnCl2, but the yield of the ester was 91.
．． 4%, and the α/β ratio was 13.8.
実施例７および比較実験例
一ブロビルアルコール、ブチルアルコールによるとドロ
エステル化−
実施例２、実験例８において、メチルアルコールの代り
にイソプロピルアルコール、５ｅＣ−ブチルアルコール
を用いてとドロエステル化を行なった。Example 7 and Comparative Experimental Example 1 Dro-esterification using brobyl alcohol and butyl alcohol - In Example 2 and Experimental Example 8, doro-esterification was carried out using isopropyl alcohol and 5eC-butyl alcohol instead of methyl alcohol. Ta.
更に各々の場合についてＺｎＣｌ２を添加しない系に付
いても実験した。その結果を以下に示す。Furthermore, in each case, experiments were also conducted on a system in which ZnCl2 was not added. The results are shown below.
表 ４Table 4
Claims (3)
ジウム金属１原子に対して０．０５〜１．５原子のＣｕ
、Ｚｎ、Ａｌ、Ｆｅ、Ｓｂからなる群から選ばれる少な
くとも一種の金属の塩を共存させて、置換アリールエチ
レンを、一酸化炭素、水および／または低級アルコール
と反応させ、必要に応じて加水分解することを特徴とす
る２−（置換アリール）プロピオン酸またはエステルの
製造方法。(1) 0.05 to 1.5 atoms of Cu per 1 atom of palladium metal in the presence of a palladium-based carbonylation catalyst
, Zn, Al, Fe, and Sb, the substituted aryl ethylene is reacted with carbon monoxide, water, and/or lower alcohol, and hydrolyzed as necessary. A method for producing 2-(substituted aryl)propionic acid or ester, characterized in that:
スチレンを反応させ、α−（３−イソブチルフェニル）
プロピオン酸を製造する、特許請求の範囲第１項記載の
２−（置換アリール）プロピオン酸またはエステルの製
造方法。(2) Reacting p-isobutylstyrene as the substituted arylethylene to form α-(3-isobutylphenyl)
A method for producing 2-(substituted aryl)propionic acid or ester according to claim 1, which produces propionic acid.
第１項記載の２−（置換アリール）プロピオン酸または
エステルの製造方法。(3) The method for producing 2-(substituted aryl)propionic acid or ester according to claim 1, wherein the metal salt is a halogen salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62122763A JPH0784406B2 (en) | 1987-05-20 | 1987-05-20 | Process for producing 2- (substituted aryl) propionic acid or ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62122763A JPH0784406B2 (en) | 1987-05-20 | 1987-05-20 | Process for producing 2- (substituted aryl) propionic acid or ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63287745A true JPS63287745A (en) | 1988-11-24 |
| JPH0784406B2 JPH0784406B2 (en) | 1995-09-13 |
Family
ID=14844011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62122763A Expired - Lifetime JPH0784406B2 (en) | 1987-05-20 | 1987-05-20 | Process for producing 2- (substituted aryl) propionic acid or ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0784406B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994014744A1 (en) * | 1992-12-28 | 1994-07-07 | Albemarle Corporation | Process for preparing aryl-substituted aliphatic carboxylic acids and their alkyl esters |
| WO2002039815A1 (en) * | 2000-11-18 | 2002-05-23 | Lovesgrove Research Limited | Compositions for, and a method of, exterminating pests using alkyl esters of benzenepropionic acid |
-
1987
- 1987-05-20 JP JP62122763A patent/JPH0784406B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994014744A1 (en) * | 1992-12-28 | 1994-07-07 | Albemarle Corporation | Process for preparing aryl-substituted aliphatic carboxylic acids and their alkyl esters |
| EP0675868A1 (en) * | 1992-12-28 | 1995-10-11 | Albemarle Corporation | Process for preparing aryl-substituted aliphatic carboxylic acids and their alkyl esters |
| WO2002039815A1 (en) * | 2000-11-18 | 2002-05-23 | Lovesgrove Research Limited | Compositions for, and a method of, exterminating pests using alkyl esters of benzenepropionic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0784406B2 (en) | 1995-09-13 |
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