JPS62185043A - Method for purifying 2-(substituted aryl)propionic acid or salt thereof - Google Patents
Method for purifying 2-(substituted aryl)propionic acid or salt thereofInfo
- Publication number
- JPS62185043A JPS62185043A JP61026248A JP2624886A JPS62185043A JP S62185043 A JPS62185043 A JP S62185043A JP 61026248 A JP61026248 A JP 61026248A JP 2624886 A JP2624886 A JP 2624886A JP S62185043 A JPS62185043 A JP S62185043A
- Authority
- JP
- Japan
- Prior art keywords
- propionic acid
- substituted aryl
- salt
- halogenated
- purifying
- 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
- 150000003839 salts Chemical class 0.000 title claims abstract description 24
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 title claims description 114
- 235000019260 propionic acid Nutrition 0.000 title claims description 58
- 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 57
- 238000000034 method Methods 0.000 title claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000006227 byproduct Substances 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000007791 liquid phase Substances 0.000 claims abstract description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 10
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 7
- 150000003624 transition metals Chemical class 0.000 claims abstract description 7
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 3
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 3
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 15
- -1 phenoxyphenyl Chemical group 0.000 claims description 13
- 238000005695 dehalogenation reaction Methods 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 3
- RXFOZEZNEXKTPJ-UHFFFAOYSA-N 2-(2-methoxynaphthalen-1-yl)propanoic acid Chemical compound C1=CC=CC2=C(C(C)C(O)=O)C(OC)=CC=C21 RXFOZEZNEXKTPJ-UHFFFAOYSA-N 0.000 claims description 2
- XQMPFCWHEKIBNV-UHFFFAOYSA-N 2-(6-methoxynaphthalen-1-yl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=CC2=CC(OC)=CC=C21 XQMPFCWHEKIBNV-UHFFFAOYSA-N 0.000 claims description 2
- 239000010948 rhodium Substances 0.000 claims description 2
- 230000000737 periodic effect Effects 0.000 claims 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 14
- 150000001735 carboxylic acids Chemical class 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000012535 impurity Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 238000001953 recrystallisation Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 150000002366 halogen compounds Chemical class 0.000 description 3
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- KXUHSQYYJYAXGZ-UHFFFAOYSA-N isobutylbenzene Chemical compound CC(C)CC1=CC=CC=C1 KXUHSQYYJYAXGZ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 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 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000006177 alkyl benzyl group Chemical group 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- YFNONBGXNFCTMM-UHFFFAOYSA-N butoxybenzene Chemical group CCCCOC1=CC=CC=C1 YFNONBGXNFCTMM-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003403 chloroformylation reaction Methods 0.000 description 1
- 238000007265 chloromethylation reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910001510 metal chloride Inorganic materials 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000004672 propanoic acids Chemical class 0.000 description 1
- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical group CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- SONJTKJMTWTJCT-UHFFFAOYSA-K rhodium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Rh+3] SONJTKJMTWTJCT-UHFFFAOYSA-K 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-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
- Catalysts (AREA)
- 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、医薬品や、医薬品その他の有機化学薬品の中
間体として使用される２−（置換アリール）プロピオン
酸またはその塩（以下単に「置換プロピオン酸」という
）の精製方法に関するものである。更に詳しくは、合成
の過程で置換プロピオン酸と共に副生ずる置換プロピオ
ン酸のハロゲン化物等のハロゲン化副生物を水素処理す
ることにより精製し、純度の高い置換プロピオン酸を製
造するための精製方法に関するものである。Detailed Description of the Invention [Industrial Application Field] The present invention relates to 2-(substituted aryl)propionic acid or its salt (hereinafter simply "substituted aryl)propionic acid" which is used as an intermediate for pharmaceuticals and other organic chemicals. The present invention relates to a method for purifying propionic acid (referred to as "propionic acid"). More specifically, it relates to a purification method for producing highly pure substituted propionic acid by refining halogenated by-products such as halides of substituted propionic acid, which are produced together with substituted propionic acid during the synthesis process, by hydrogen treatment. It is.
［従来の技術および
発明が解決しようとする問題点］
従来から、プロピオン酸の製造法として多数の方法が提
案されている０例えば、２−（ｐ−イソブチルフェニル
）プロピオン酸に関しては、イソブチルベンゼンを塩化
アルミニウム触媒の存在下で、塩化アセチルによりアセ
チル化したインブチルアセトフェノンを出発原料とする
方法としては。[Prior Art and Problems to be Solved by the Invention] Conventionally, many methods have been proposed for producing propionic acid. For example, for 2-(p-isobutylphenyl)propionic acid, isobutylbenzene is The method uses imbutylacetophenone acetylated with acetyl chloride in the presence of an aluminum chloride catalyst as a starting material.
（１）水酸化アルカリ金属塩の存在下で、α−クロロ酢
酸と反応させてエポキシ化合物とするダルツエン（Ｄａ
ｒｚｅｎ）反応を組み合わせたものとして、特開昭４７
−３９０５１号、特開昭４９−９５３９８号、特開昭４
９−１０８０４０号、特開昭５１−２３２３５号、特開
昭５１−８５７３０号、特開昭５２−７１４３７号、特
開昭５’２−８５１４０号、特開昭５３’−８３３４５
号、特開昭５７−３１８３９号および（２′）第４級ア
ンモニウム塩などの相間移“動触媒の存在下で、クロロ
ホルムと反応させてメチル化する反応を組み合わせたも
のとしては、イギリス特許９７１．７００号、特開昭５
１−１０５０２８号、特開昭５２−１４７４２号、特開
昭５２−１３９０３７号、特開昭５２−１１１５３４号
、特開昭５３−１３０２３７号、特開昭５３−３４７４
４号。(1) Dalzene (Da
As a combination of reactions (rzen),
-39051, JP-A-49-95398, JP-A-4
9-108040, JP 51-23235, JP 51-85730, JP 52-71437, JP 5'2-85140, JP 53'-83345
No., JP-A No. 57-31839 and (2') British Patent No. 971, which combines the reaction with chloroform and methylation in the presence of a phase transfer catalyst such as a quaternary ammonium salt. No. 700, Japanese Patent Application Publication No. 5
1-105028, JP 52-14742, JP 52-139037, JP 52-111534, JP 53-130237, JP 53-3474
No. 4.
特開昭５８−１１３４３７号などの方法が提案されてい
る。Methods such as Japanese Patent Application Laid-Open No. 113437/1983 have been proposed.
また、イソブチルベンゼンから直接出発する方法として
は、
（１）塩化アルミニウム触媒でハロゲン化アシル化合物
と反応させる方法を組み合わせたものとして、イギリス
特許９７１．７００号、特開昭５１−４１３３８号、特
開昭５１−１０００４１号、特開昭５２−１０５１４８
号、特開昭５２−１０８９４９号、特開昭５３−５（１
１３５号、特開昭５３−１８５３２号、特開昭５４−３
９０４２号。In addition, as a method starting directly from isobutylbenzene, (1) a method combining the method of reacting with an acyl halide compound using an aluminum chloride catalyst, British Patent No. 971.700, JP-A-51-41338, JP-A-51-41338; No. 51-100041, JP-A No. 52-105148
No., JP-A-52-108949, JP-A-53-5(1)
No. 135, JP-A-53-18532, JP-A-54-3
No. 9042.
（２）塩融の存在下でホルマリンと反応させるクロロメ
チル化、または直接のハロゲン化によりハロゲン化イソ
ブチルベンゼンとしてグリニヤール反応を組み合わせた
もとしては、特開昭４７−３９０５０号、特開昭５０−
４０５４１号、＃開開５１−１８８３７号、特開昭５１
−１０００４２号、特開昭５２−８５２４３号、特開昭
５１−１０１９４９号、特開昭５２−１３１５５３号、
特開昭５４−３９０４２号、特開昭５８−９７２４８号
、特開昭５８−１’５１．、．４５号およダ（３）塩化
アルミニウムなどの塩化金属触媒でハロゲン化合物を反
応させるアルキル化反応を組み合わせた方法には、特開
昭４９−１３３３５１号、特開昭５１−３８４３２号、
特開昭５１−５４５２５号、特開昭５１−５４５３１号
、特開昭５１−５８４９８号、特開昭５２−１３１５５
１号、特開昭５３−１２８３７号、特開昭５４−１９１
１３２号、特開昭５８−８０４５号などの方法が開示さ
れている。(2) Chloromethylation by reacting with formalin in the presence of salt melt or direct halogenation to form halogenated isobutylbenzene in combination with Grignard reaction, JP-A-47-39050, JP-A-50-
No. 40541, #Kokai No. 51-18837, JP-A-51
-100042, JP 52-85243, JP 51-101949, JP 52-131553,
JP-A-54-39042, JP-A-58-97248, JP-A-58-1'51. ,．． No. 45 and (3) A method combining an alkylation reaction in which a halogen compound is reacted with a metal chloride catalyst such as aluminum chloride is disclosed in JP-A-49-133351, JP-A-51-38432,
JP-A-51-54525, JP-A-51-54531, JP-A-51-58498, JP-A-52-13155
No. 1, JP-A-53-12837, JP-A-54-191
Methods such as No. 132 and Japanese Unexamined Patent Publication No. 58-8045 are disclosed.
また、２−（ｍ−ベンゾールフェニル）プロピオン酸に
関しては、特開昭５”ｉ、７．．４３１１号、特開昭５
５−７２２５号、特開昭５５−３８４５０号、特開昭５
８−１１３７３８号などの方法が提案されている。更に
、特開昭５９−９８０３７号および特開昭５３−１８５
３３号には、その他の２−（置換アリール）プロピオン
酸の製造方法が開示されている。Regarding 2-(m-benzolphenyl)propionic acid, JP-A-5''i, No. 7.4311;
No. 5-7225, JP-A No. 55-38450, JP-A No. 5-7
Methods such as No. 8-113738 have been proposed. Furthermore, JP-A-59-98037 and JP-A-53-185
No. 33 discloses other methods for producing 2-(substituted aryl)propionic acids.
しかしながら、これら各種の反応を組み合わせた従来の
方法は、その合成過程で岬反応を起こし易いハロゲン化
合物を原料として使用するか、あるいは、塩化アルミニ
ウムなどのハロゲン化合物を触媒として使用している。However, conventional methods that combine these various reactions use halogen compounds that tend to cause the Misaki reaction as raw materials in the synthesis process, or use halogen compounds such as aluminum chloride as catalysts.
これらのように、反応の最中に脱ハロゲンをし易く、遊
離ハロゲン分子やハロゲンイオンを放出する傾向のある
反応試薬を使用する製造方法では、遊離ハロゲン分子に
より種々の副反応が生じ、出発原料、合成過程での中間
体、または目的反応生成物が／＼ロゲン化されるなど、
微量とはいえ、目的物の用途にとって不都合なハロゲン
化副生物の生成は避けられない。In production methods that use reaction reagents that tend to dehalogenate and release free halogen molecules and halogen ions during the reaction, various side reactions occur due to the free halogen molecules, resulting in the loss of starting materials. , an intermediate in the synthesis process, or the desired reaction product is /\logogenated, etc.
Although the amount is small, the production of halogenated by-products, which are inconvenient for the intended use, is unavoidable.
高い純度と高い安全性とが要求される分野に使用される
置換プロピオン酸にとって、微量といえども、ハロゲン
化副生物が混入することは好ましくない０通常は不純物
を除く精製操作として再結晶が行なわれる。然しなから
、再結晶による精製では、ハロゲン化副生物のように目
的物に混入することが特に好ましくない成分の場合には
、比較的多量の置換プロピオン酸をろ液へ残留させざる
を得す、結晶置換プロピオン酸の回収率の低下は避けら
れない、また、ハロゲン化副生物を除くためには、再結
晶を繰り返すなど複雑な後処理工程が必要となる。For substituted propionic acid used in fields that require high purity and high safety, it is undesirable for halogenated by-products to be mixed in, even if only in trace amounts.Usually, recrystallization is performed as a purification operation to remove impurities. It will be done. However, in purification by recrystallization, a relatively large amount of substituted propionic acid must remain in the filtrate in the case of components such as halogenated by-products, which are particularly undesirable to mix with the target product. , a decrease in the recovery rate of crystal-substituted propionic acid is unavoidable, and complicated post-treatment steps such as repeated recrystallization are required to remove halogenated by-products.
本発明者らは、遷移金属触媒の存在下に、水素処理を行
なうことにより、置換プロピオン酸中に含まれるハロゲ
ン化副生物が容易に脱ハロゲン化れることを発見し本発
明を完成したものである。The present inventors completed the present invention by discovering that halogenated by-products contained in substituted propionic acid can be easily dehalogenated by hydrogen treatment in the presence of a transition metal catalyst. be.
従って、本発明の目的は、高純度の置換プロピオン酸を
効率良く回収できる方法を提供することにある。Therefore, an object of the present invention is to provide a method for efficiently recovering highly purified substituted propionic acid.
［問題点を解決するための手段］
本発明の目的は、高純度の２−（置換アリール）プロピ
オン酸またはその塩を効率的に製造するための精製方法
を提供するものである。[Means for Solving the Problems] An object of the present invention is to provide a purification method for efficiently producing highly pure 2-(substituted aryl)propionic acid or a salt thereof.
すなわち、ハロゲン化副生物を含む２−（置換アリール
）プロピオン酸またはその塩を、液相で、周期律表第■
族の遷移金属触媒の共存下に、水素と接触させることに
よって、該ハロゲン化副生物を脱ハロゲン化せしめ、高
純度の２−（置換アリール）プロピオン酸またはその塩
を製造するための精製方法を提供するものである。That is, 2-(substituted aryl)propionic acid or its salt containing a halogenated by-product is prepared in a liquid phase according to No.
A purification method for producing high-purity 2-(substituted aryl)propionic acid or a salt thereof by dehalogenating the halogenated by-product by contacting it with hydrogen in the presence of a group transition metal catalyst. This is what we provide.
以下に本発明の精製方法を具体的に説明する。The purification method of the present invention will be specifically explained below.
本発明の方法で得られる２−（置換アリール）プロピオ
ン加は、カルボン酸の２位に置換アリール基を有する総
炭素数が８〜１８のカルボン酸である。The 2-(substituted aryl) propionate obtained by the method of the present invention is a carboxylic acid having a total carbon number of 8 to 18 and having a substituted aryl group at the 2-position of the carboxylic acid.
すなわち、総炭素数が１９以上の（置換アリール）プロ
ピオン酸の場合、塩基性条件下でも水溶性が不足して脱
ハロゲン化の効率が悪くなり好ましくない、置換アリー
ル基は、フェニル基、メチルフェニル基、エチルフェニ
ル基、ジメチルフェニル基、プロピルフェニル基、ブチ
ルフェニル基などのような低級アルキル置換フェニル基
および酸素原子を含むメトキシフェニル基、エトキシフ
ェニル基、プロポキシフェニル基、ブトキシフェニル基
などのフルコキシ基置換フェニル基や、アルキルフェノ
キシフェニル基、アルキルベンジル基などのような置換
フェニル基の他、メチルナフチル基、メトキシナフチル
基などのような置換ナフチル基などである。さらに、本
発明が目的とする２−（置換アリール）プロピオン酸は
、これらの置換アリール基がカルボン酸の２位に導入さ
れており、２位炭素に結合する水素原子が活性なため合
成過程でハロゲン化され易く、本発明の方法の優位性が
特に明らかとなり好ましい。That is, in the case of (substituted aryl) propionic acid having a total carbon number of 19 or more, the undesirable substituted aryl group is a phenyl group, methylphenyl lower alkyl-substituted phenyl groups, such as ethylphenyl, dimethylphenyl, propylphenyl, butylphenyl, etc., and flukoxy groups, such as methoxyphenyl, ethoxyphenyl, propoxyphenyl, butoxyphenyl, containing an oxygen atom; Examples include substituted phenyl groups, substituted phenyl groups such as alkylphenoxyphenyl groups, and alkylbenzyl groups, as well as substituted naphthyl groups such as methylnaphthyl groups and methoxynaphthyl groups. Furthermore, in the 2-(substituted aryl)propionic acid that is the object of the present invention, these substituted aryl groups are introduced at the 2-position of the carboxylic acid, and the hydrogen atom bonded to the 2-position carbon is active, so it is difficult to use during the synthesis process. It is preferable because it is easily halogenated and the superiority of the method of the present invention becomes particularly clear.
２−（置換アリール）プロピオン酸の具体例としては、
２−フェニルプロピオン酸、２− （ｐ−イソブチルフ
ェニル）プロピオン酸のごとき２−（アルキルフェニル
）プロピオン酸、２−（ｍ−フェノキシフェニル）プロ
ピオン酸のごとき２−（アリールオキシフェニル）プロ
ピオン酸、２−（ｍ−ベンゾールフェニル）プロピオン
酸のごとき２−（アリールカルポキシフェこル）プロピ
オン酸および２−（６−メトキシナフチル）プロピオン
酸のごとき２−（メトキシナフチル）プロピオン酸など
が挙げられる。Specific examples of 2-(substituted aryl)propionic acid include:
2-(alkylphenyl)propionic acid such as 2-phenylpropionic acid, 2-(p-isobutylphenyl)propionic acid, 2-(aryloxyphenyl)propionic acid such as 2-(m-phenoxyphenyl)propionic acid, 2-(aryloxyphenyl)propionic acid such as 2-(m-phenoxyphenyl)propionic acid, Examples include 2-(arylcarpoxyphecol)propionic acid such as -(m-benzolphenyl)propionic acid and 2-(methoxynaphthyl)propionic acid such as 2-(6-methoxynaphthyl)propionic acid.
本発明の方法は、従来から知られている公知の方法によ
って合成されたハロゲン化副生物を含む置換プロピオン
酸またはその塩であればいずれの置換プロピオン酸にも
使用できる。The method of the present invention can be used with any substituted propionic acid or salt thereof containing a halogenated by-product synthesized by conventionally known methods.
本発明の方法の出発原料であるハロゲン化副生物を含む
置換プロピオン酸としては、合成反応後単離されたもの
、あるいは再結晶による精製で得られるハロゲン化副生
物が濃縮されたろ液のいずれも使用できる。The substituted propionic acid containing halogenated by-products, which is the starting material for the method of the present invention, may be either one isolated after the synthesis reaction or a filtrate containing concentrated halogenated by-products obtained by purification by recrystallization. Can be used.
本発明の方法では、脱ハロゲン化、すなわち水素処理を
液相で行なう、２−（置換アリール）プロピオン酸また
はその塩を適当な有機溶媒または水に溶解した状態の液
相として用いる。In the method of the present invention, 2-(substituted aryl)propionic acid or a salt thereof is used as a liquid phase dissolved in a suitable organic solvent or water, in which the dehalogenation, ie, hydrogen treatment, is carried out in the liquid phase.
有機溶媒としては、水素処理反応を阻害せず、かつ２−
（置換アリール）プロピオン酸またはその塩を溶解する
ものであれば、上記再結晶操作で使用する溶媒およびそ
の他適宜の溶媒を使用することができる。水素処理後に
反応系から溶媒を容易に除くためには低沸点であること
が望ましい。As an organic solvent, it does not inhibit the hydrogen treatment reaction and 2-
The solvent used in the recrystallization operation described above and other appropriate solvents can be used as long as they dissolve the (substituted aryl)propionic acid or its salt. A low boiling point is desirable in order to easily remove the solvent from the reaction system after hydrogen treatment.
有機溶媒の例としては、ｎ−へキサン、ｎ−へブタンの
ごときパラフィン類、シクロヘキサンなどのシクロパラ
フィン類、メタノール、エタノール。Examples of organic solvents include paraffins such as n-hexane and n-hebutane, cycloparaffins such as cyclohexane, methanol, and ethanol.
エチレングリコールなどのアルコール類、アセトン、ジ
オキサン、テトラヒドロフランなどのエーテル類が代表
的なものである。これらの有機溶媒および水は２種類以
上の混合物として用いることができる。Typical examples include alcohols such as ethylene glycol, and ethers such as acetone, dioxane, and tetrahydrofuran. These organic solvents and water can be used as a mixture of two or more.
２−（置換アリール）プロピオン酸の塩を用いる場合に
は、溶解させるための水が必要となる。When using a salt of 2-(substituted aryl)propionic acid, water is required for dissolution.
この場合、水と共に他の有機溶媒が存在していてもよい
。In this case, other organic solvents may be present together with water.
本発明の方法の水素処理に用いる触媒は１周期律表第■
族の遷移金属であるが、Ｐｔ、 Ｒｈ、 Ｐｄが効率が
良く好ましい触媒である。これらの触媒はいわゆる水素
化活性が有れば、金属状態でもよく。The catalyst used for the hydrogen treatment in the method of the present invention is
Of the group transition metals, Pt, Rh, and Pd are efficient and preferred catalysts. These catalysts may be in a metallic state as long as they have so-called hydrogenation activity.
また、活性炭、アルミナ、シリカ、シリカアルミナなど
の担体に担持された状態でもよい、また、塩化物、酢酸
塩などのように水素処理の条件下で還元され活性な金属
となるような遷移金属の化合物でもよい。In addition, it may be supported on a carrier such as activated carbon, alumina, silica, or silica-alumina, or it may be a transition metal supported on a carrier such as activated carbon, alumina, silica, or silica-alumina. It may also be a compound.
本発明の方法の反応温度は、２０℃〜１７０″Ｃが好ま
しい、２０℃より低い温度では脱ハロゲン化効率が悪く
、処理時間が長くなり実用的ではない、また１７０℃よ
り高い温度では置換プロピオン酸の芳香族環の核水素化
が著しくなり好ましくない、水素処理の圧力は本発明に
とって本質的な要素にはならない、すなわち、常圧以上
任意の圧力でよく１反応系が液相を保つ圧力以上であれ
ばよい、従って、反応圧力は反応温度によって適宜選択
できる。実用上からは８０ ｋｇ／ａｍ”までの圧力範
囲が好ましい。The reaction temperature of the method of the present invention is preferably 20°C to 170"C. If the temperature is lower than 20°C, the dehalogenation efficiency will be poor and the treatment time will be long, making it impractical. If the temperature is higher than 170°C, substituted propion The hydrogenation pressure of the hydrogen treatment is not an essential element for the present invention because it causes significant nuclear hydrogenation of the aromatic ring of the acid.In other words, any pressure above normal pressure may be used as long as the pressure at which one reaction system remains in a liquid phase is sufficient. Therefore, the reaction pressure can be appropriately selected depending on the reaction temperature. Practically speaking, a pressure range of up to 80 kg/am'' is preferable.
本発明の方法では、塩基性の条件下で水素処理を行なう
ことが好ましい、すなわち、脱ハロゲン化により生成す
るハロゲンを塩基性物質で速やかに中和し、不活性なハ
ロゲン酸塩とすることによって、該生成ハロゲンが脱ハ
ロゲン化生成物および２−（置換アリール）プロピオン
酸に再結合することを防ぐことができるからである。こ
の場合中和を速やかに進行させるためには、上記塩基性
物質を水溶液の形で存在させるべく、液相の水の存在が
望ましい。In the method of the present invention, it is preferable to carry out the hydrogen treatment under basic conditions, that is, by quickly neutralizing the halogen produced by dehalogenation with a basic substance and converting it into an inactive halide salt. This is because the generated halogen can be prevented from recombining with the dehalogenated product and 2-(substituted aryl)propionic acid. In this case, in order to rapidly proceed with neutralization, the presence of water in a liquid phase is desirable so that the basic substance is present in the form of an aqueous solution.
このために塩基性物質を添加して塩基性にすることが必
要である。これらの塩基性物質としては、トリメチルア
ミン、トリエチルアミン、トリブチルアミンなどのアミ
ン類のような有ａ７ミン化合物、ナトリウムメトキシド
、カリウムメトキシド、ナトリウムエトキシド、カリウ
ムエトキシドなどのようなアルカリ金属低級アルコラー
ド類、酢酸ナトリウム、酢酸カリウムなどの低級カルボ
ン酸アルカリ金属塩の他、アンモニア、水酸化ナトリウ
ム、水酸化カリウムなどのアルカリ金属水酸化物、炭酸
ナトリウム、炭酸カリウム、炭酸水素ナトリウム、炭酸
水素カリウムなどのアルカリ金属炭酸塩など無機アルカ
リ金属物質が挙げられる。For this purpose, it is necessary to add a basic substance to make it basic. These basic substances include a7-amine compounds such as amines such as trimethylamine, triethylamine, and tributylamine, and alkali metal lower alcoholides such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc. In addition to alkali metal salts of lower carboxylic acids such as sodium acetate and potassium acetate, alkali metal hydroxides such as ammonia, sodium hydroxide and potassium hydroxide, alkalis such as sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate. Examples include inorganic alkali metal substances such as metal carbonates.
実用上は、低級カルボン酸金属塩および無機アルカリ物
質が取り扱いの点で好ましい、塩基物質の添加量は、置
換プロピオン酸の製造方法により、置換スロピオン酸が
遊離の酸で得られる場合には、その斂と脱ハロゲン化に
より生成したハロゲンを中和して塩基性となるような過
剰量、また、置換プロピオン酸が塩として得られる場合
には、単に脱ハロゲン化されたハロゲンを中和して塩基
性とする量７よい。Practically, lower carboxylic acid metal salts and inorganic alkaline substances are preferable from the viewpoint of handling.When substituted slopionic acid is obtained as a free acid by the method for producing substituted propionic acid, the amount of the basic substance added is determined by the amount of the base substance added. If the substituted propionic acid is obtained as a salt, the halogen produced by the dehalogenation is simply neutralized to make it basic. The amount of sex is 7 good.
水は液相で存在すればよく、たとえば、メタノール、エ
タノール、エチレングリコール等のアルコール類や、ア
セトン、ジオキサン、テトラヒドロフランなどの水溶性
有機溶媒が溶解共存していてもよい。Water only needs to exist in a liquid phase, and for example, alcohols such as methanol, ethanol, and ethylene glycol, and water-soluble organic solvents such as acetone, dioxane, and tetrahydrofuran may be dissolved and coexisting therein.
水の量は、上記塩基性物質および２−（置換アリール）
プロピオン酸を溶解し得る量であれば足りる。The amount of water is the basic substance and 2-(substituted aryl)
Any amount that can dissolve propionic acid is sufficient.
［発明の作用］ 以上に述べたごとく、本発明の方法によれば。[Action of the invention] As described above, according to the method of the present invention.
実質的にハロゲン化副生物を含まない高純度の置換プロ
ピオン酸を製造することができる。このために、特別に
精製する必要のある医薬などのような分野に使用される
場合でも、例えば、再結晶処理が容易となり、結晶の回
収を効率よく行なうことができる。更に本発明の方法で
は、ハロゲン化副生物は水素処理によって目的物である
置換プロピオン酸に変化する。従って１本来は不純物で
あるべき成分が、目的物として回収できるという副次的
利益をもたらす。High purity substituted propionic acids can be produced that are substantially free of halogenated by-products. For this reason, even when used in fields such as medicines that require special purification, for example, recrystallization becomes easy and crystals can be recovered efficiently. Furthermore, in the method of the present invention, the halogenated by-product is converted into the target product, substituted propionic acid, by hydrogen treatment. Therefore, a secondary benefit is that components that should originally be impurities can be recovered as desired products.
［実施例］ 以下に実施例により本発明を説明する。[Example] The present invention will be explained below with reference to Examples.
実施例１
第１表に記載した２−（置換アリール）プロピオン酸を
公知の方法により合成した。その結果゛をやはり第１表
に示す。Example 1 The 2-(substituted aryl)propionic acids listed in Table 1 were synthesized by a known method. The results are also shown in Table 1.
第１表
２−（置換アリール）プロピオン酸の合成上記２−（置
換アリール）置換プロピオン酸ｌｏｇを１００ｇの水に
加えてかきまぜながら、２０％水酸化ナトリウム水溶液
を徐々に加えて、ｐＨ８〜８．５のアルカリ性にして完
全に溶解させた後、活性炭に担持したＰｄ触媒（担持量
２．５ｖｔ％）０．５ｇと共にかきまぜ機付きの耐圧容
器に入れた。Table 1 2-Synthesis of (substituted aryl) propionic acid The above log of 2-(substituted aryl) substituted propionic acid was added to 100 g of water, and while stirring, a 20% aqueous sodium hydroxide solution was gradually added to adjust the pH to 8-8. After completely dissolving the mixture in alkaline solution No. 5, it was placed in a pressure-resistant container equipped with a stirrer together with 0.5 g of Pd catalyst supported on activated carbon (supported amount: 2.5 vt%).
水素でｌ Ｏｋｇ／ｃｒｎ”まで加圧して、温度６０℃
で７時間かきまぜて反応させた０反応終了後、Ｐｄ触媒
をＩ過して除き、ろ液に３５％塩酸を徐々に加えてｐＨ
２〜３の酸性にした。このときにろ液は白く濁り生成物
である置換プロピオン酸が析出する。Pressurized with hydrogen to 1 Okg/crn” and heated to 60°C.
After the reaction was completed, the Pd catalyst was removed by filtration, and 35% hydrochloric acid was gradually added to the filtrate to adjust the pH.
I made it acidic 2-3. At this time, the filtrate becomes cloudy and the substituted propionic acid product precipitates out.
これに対して１回２５１のｎ−ヘキサンを加えて析出物
の抽出を４回繰り返した。減圧でｎ−ヘキサンを除去し
て粉末の結晶または液状物を得た。これらの水素処理生
成物について、その回収率、塩素含有量を第２表に示す
。To this, 251 parts of n-hexane was added once, and the extraction of the precipitate was repeated four times. N-hexane was removed under reduced pressure to obtain powder crystals or liquid. Table 2 shows the recovery rate and chlorine content of these hydrogen-treated products.
第２表 水素処理の結果
実施例２
アルミナを塩化白金酸水溶液に浸し、減圧下で水を除い
て乾燥し、水素気流中４５０℃で３時間処理して得られ
た担持量２．５％の触媒を使用し。Table 2 Hydrogen treatment results Example 2 Alumina was immersed in a chloroplatinic acid aqueous solution, water was removed under reduced pressure and dried, and treated in a hydrogen stream at 450°C for 3 hours to obtain a supported amount of 2.5%. using a catalyst.
実施例１の出発原料と同一の２−フェニルプロピオン酸
を、圧力１５ ｋｇ／ｃｒｎ２、温度９０℃、時間８時
間で水素処理をした他は、実施例１と同様の操作を行な
い１回収率９４％で塩素含有量１３ｐｐｍの白色結晶を
得た。The same operation as in Example 1 was carried out, except that 2-phenylpropionic acid, which was the same as the starting material in Example 1, was treated with hydrogen at a pressure of 15 kg/crn2, a temperature of 90°C, and a time of 8 hours. White crystals with a chlorine content of 13 ppm were obtained.
実施例３
塩化ロジウム水溶液を石綿にしみ込ませた後、ホルマリ
ンと水酸化ナトリウムとの混合水溶液に浸して還元処理
を行なって得た担持量２％の触媒を使用し、実施例２と
同様に処理して１回収率９２％で塩素含有ｉ１４ｐｐｍ
の白色結晶を得た。Example 3 The same treatment as in Example 2 was carried out using a catalyst with a supported amount of 2% obtained by impregnating asbestos with an aqueous solution of rhodium chloride and then immersing it in a mixed aqueous solution of formalin and sodium hydroxide for reduction treatment. with a recovery rate of 92% and a chlorine content of 14 ppm.
White crystals were obtained.
比較例
実施例１の出発原料と同一の２−フェニルプロピオン酸
を、ｎ−ヘキサンを用いて実施例１の再結晶操作に準じ
て再結晶した。その結果を第３表に示す。Comparative Example The same 2-phenylpropionic acid as the starting material in Example 1 was recrystallized using n-hexane according to the recrystallization procedure in Example 1. The results are shown in Table 3.
第３表 再結晶の結果
上記の結果から解るように、ハロゲン化副生物を含む２
−２エニルプロビオン酸については、単なる再結晶によ
る精製方法では効率よくハロゲンを除去することができ
ない。Table 3 Results of recrystallization As can be seen from the above results, 2 containing halogenated by-products
Regarding -2enylprobionic acid, halogen cannot be efficiently removed by a purification method using simple recrystallization.
実施例４
実施例１の出発原料の２−（ｐ−インブチルフェニル）
プロピオン酸２．５ｇをｎ−ヘキサン３０１に溶解し、
活性炭に担持したＰｄ触媒（担持量５貿ｔ％）０．１３
ｇと共に、容量２００１のかきまぜ機付き耐圧容器に入
れた。水素圧１０ ｋｇ／ｃｒＩｒＩ：温度６０℃で４
時間反応させた０反応終了後、Ｐｄ触媒をシ戸遇して除
き、ｎ−ヘキサンを減圧で除去して１回収率９６％で、
塩素含有量１０ｐｐｍの２−（ｐ−イソブチルフェニル
）プロピオン酸を得た。Example 4 2-(p-inbutylphenyl), the starting material of Example 1
Dissolve 2.5 g of propionic acid in 301 n-hexane,
Pd catalyst supported on activated carbon (supported amount: 5 t%) 0.13
The mixture was placed in a pressure-resistant container with a capacity of 2,001 liters and equipped with a stirrer. Hydrogen pressure 10 kg/crIrI: 4 at temperature 60°C
After the reaction was completed for 0 hours, the Pd catalyst was carefully removed, and the n-hexane was removed under reduced pressure with a recovery rate of 96%.
2-(p-isobutylphenyl)propionic acid with a chlorine content of 10 ppm was obtained.
［発明の効果］
以上詳しく説明したように、本発明において提案した精
製方法を２−（置換アリール）プロピオン酸またはその
塩の精製に適用すれば、効率よく高純度の２−（置換ア
リール）プロピオン酸またはその塩とすることができる
。従って、目的に応じて更に精製する必要がある場合で
も１例えば、再結晶操作などの後処理工程における回収
が容易で効率も向上できる。[Effects of the Invention] As explained in detail above, if the purification method proposed in the present invention is applied to the purification of 2-(substituted aryl)propionic acid or its salt, highly purified 2-(substituted aryl)propion can be efficiently produced. It can be an acid or a salt thereof. Therefore, even if further purification is required depending on the purpose, recovery in post-processing steps such as recrystallization is easy and efficiency can be improved.
Claims (7)
ロピオン酸またはその塩を、液相で、周期律表第VIII族
金属触媒の存在下に、水素と接触させることにより、該
ハロゲン化副生物を脱ハロゲン化せしめ、高純度２−（
置換アリール）プロピオン酸またはその塩を得ることを
特徴とする２−（置換アリール）プロピオン酸またはそ
の塩の精製方法。(1) By contacting 2-(substituted aryl)propionic acid or its salt containing a halogenated by-product with hydrogen in the liquid phase in the presence of a Group VIII metal catalyst of the Periodic Table, the halogenated by-product is Dehalogenates living organisms to produce highly pure 2-(
A method for purifying 2-(substituted aryl)propionic acid or a salt thereof, the method comprising obtaining substituted aryl)propionic acid or a salt thereof.
ウム、ロジウムおよび白金からなる群から選ばれた少な
くとも１つであ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その塩の精製方法。(2) 2-(substituted aryl)propionic acid according to claim 1, wherein the transition metal catalyst of Group VIII of the Periodic Table is at least one selected from the group consisting of palladium, rhodium, and platinum. Or how to purify the salt.
フェニルプロピオン酸、２−（アルキルフェニル）プロ
ピオン酸、２−（アリールオキシフェニル）プロピオン
酸、２−（アリールカルボキシフェニル）プロピオン酸
および２−（メトキシナフチル）プロピオン酸からなる
群から選ばれた少なくとも１つの化合物である特許請求
の範囲第１項記載の高純度の２−（置換アリール）プロ
ピオン酸またはその塩の精製方法。(3) The 2-(substituted aryl)propionic acid is 2-
At least one selected from the group consisting of phenylpropionic acid, 2-(alkylphenyl)propionic acid, 2-(aryloxyphenyl)propionic acid, 2-(arylcarboxyphenyl)propionic acid, and 2-(methoxynaphthyl)propionic acid. 2. A method for purifying high purity 2-(substituted aryl)propionic acid or a salt thereof according to claim 1, which is a compound.
（ｐ−イソブチルフェニル）プロピオン酸、２−（ｍ−
フェノキシフェニル）プロピオン酸、２−（ｍ−ベンゾ
ールフェニル）プロピオン酸および２−（６−メトキシ
ナフチル）プロピオン酸からなる群から選ばれた少なく
とも１つの化合物であ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その塩の精製方
法。(4) The 2-(substituted aryl)propionic acid is 2-
(p-isobutylphenyl)propionic acid, 2-(m-
2, which is at least one compound selected from the group consisting of phenoxyphenyl)propionic acid, 2-(m-benzolphenyl)propionic acid, and 2-(6-methoxynaphthyl)propionic acid.
- A method for purifying (substituted aryl)propionic acid or a salt thereof.
許請求の範囲第１項記載の２−（置換アリール）プロピ
オン酸またはその塩の精製方法。(5) The method for purifying 2-(substituted aryl)propionic acid or a salt thereof according to claim 1, wherein the dehalogenation is carried out under basic conditions.
特許請求の範囲第１項または第５項記載の２−（置換ア
リール）プロピオン酸またはその塩の精製方法。(6) The method for purifying 2-(substituted aryl)propionic acid or a salt thereof according to claim 1 or 5, wherein the dehalogenation is carried out in the presence of water in a liquid phase.
で行なう特許請求の範囲第１項記載の２−（置換アリー
ル）プロピオン酸またはその塩の精製方法。(7) The dehalogenation is carried out at a reaction temperature of 20°C to 170°C.
A method for purifying 2-(substituted aryl)propionic acid or a salt thereof according to claim 1, which is carried out by:
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61026248A JPH064562B2 (en) | 1986-02-08 | 1986-02-08 | Method for purifying 2- (substituted aryl) propionic acid or a salt thereof |
| CA000529070A CA1286316C (en) | 1986-02-08 | 1987-02-05 | Method for refining 2-(aryl substituted)-propionic acid or its salt |
| DE8787101631T DE3770310D1 (en) | 1986-02-08 | 1987-02-06 | METHOD FOR PURIFYING 2-ARYL SUBSTITUTED PROPIONIC ACID OR ITS SALTS. |
| EP87101631A EP0240665B1 (en) | 1986-02-08 | 1987-02-06 | Process for refining 2-(aryl substituted) propionic acid or its salts |
| US07/011,734 US4709089A (en) | 1986-02-08 | 1987-02-06 | Method for refining 2-(aryl substituted) propionic acid or its salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61026248A JPH064562B2 (en) | 1986-02-08 | 1986-02-08 | Method for purifying 2- (substituted aryl) propionic acid or a salt thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62185043A true JPS62185043A (en) | 1987-08-13 |
| JPH064562B2 JPH064562B2 (en) | 1994-01-19 |
Family
ID=12187982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61026248A Expired - Lifetime JPH064562B2 (en) | 1986-02-08 | 1986-02-08 | Method for purifying 2- (substituted aryl) propionic acid or a salt thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH064562B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015010036A (en) * | 2013-06-26 | 2015-01-19 | Ｊｆｅケミカル株式会社 | Method for decomposing aromatic halide |
-
1986
- 1986-02-08 JP JP61026248A patent/JPH064562B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015010036A (en) * | 2013-06-26 | 2015-01-19 | Ｊｆｅケミカル株式会社 | Method for decomposing aromatic halide |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH064562B2 (en) | 1994-01-19 |
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