JPS6328056B2 - - Google Patents
Info
- Publication number
- JPS6328056B2 JPS6328056B2 JP11840180A JP11840180A JPS6328056B2 JP S6328056 B2 JPS6328056 B2 JP S6328056B2 JP 11840180 A JP11840180 A JP 11840180A JP 11840180 A JP11840180 A JP 11840180A JP S6328056 B2 JPS6328056 B2 JP S6328056B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- halogen
- general formula
- reaction
- mol
- 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.)
- Expired
Links
- 238000006243 chemical reaction Methods 0.000 claims description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 17
- 239000003054 catalyst Substances 0.000 claims description 13
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical class OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003279 phenylacetic acid Substances 0.000 claims description 7
- 229960003424 phenylacetic acid Drugs 0.000 claims description 7
- IUJAAIZKRJJZGQ-UHFFFAOYSA-N 2-(2-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Cl IUJAAIZKRJJZGQ-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- YXLXNENXOJSQEI-UHFFFAOYSA-L Oxine-copper Chemical compound [Cu+2].C1=CN=C2C([O-])=CC=CC2=C1.C1=CN=C2C([O-])=CC=CC2=C1 YXLXNENXOJSQEI-UHFFFAOYSA-L 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- CCVYRRGZDBSHFU-UHFFFAOYSA-N (2-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1O CCVYRRGZDBSHFU-UHFFFAOYSA-N 0.000 description 14
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 10
- 239000010949 copper Substances 0.000 description 10
- 229910052802 copper Inorganic materials 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 4
- -1 n-octyl Chemical group 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- VTJMSIIXXKNIDJ-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-methylbutyric acid Chemical compound CC(C)C(C(O)=O)C1=CC=C(Cl)C=C1 VTJMSIIXXKNIDJ-UHFFFAOYSA-N 0.000 description 2
- GDBITPXOESTAML-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methylbutyric acid Chemical compound CC(C)C(C(O)=O)C1=CC=C(O)C=C1 GDBITPXOESTAML-UHFFFAOYSA-N 0.000 description 2
- PZVWKCGKIADPAU-UHFFFAOYSA-N 4-(1,3-benzothiazol-2-ylsulfanyl)aniline Chemical compound C1=CC(N)=CC=C1SC1=NC2=CC=CC=C2S1 PZVWKCGKIADPAU-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- 229910000365 copper sulfate Inorganic materials 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 229960003280 cupric chloride Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- DWXSYDKEWORWBT-UHFFFAOYSA-N 2-(2-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Br DWXSYDKEWORWBT-UHFFFAOYSA-N 0.000 description 1
- IVEWTCACRDEAOB-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetic acid Chemical compound COC1=CC=CC=C1CC(O)=O IVEWTCACRDEAOB-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
- YRNDGUSDBCARGC-UHFFFAOYSA-N 2-methoxyacetophenone Chemical compound COCC(=O)C1=CC=CC=C1 YRNDGUSDBCARGC-UHFFFAOYSA-N 0.000 description 1
- JYJIMEQNTHFXMT-UHFFFAOYSA-N 2-nitro-2-phenylacetic acid Chemical compound OC(=O)C([N+]([O-])=O)C1=CC=CC=C1 JYJIMEQNTHFXMT-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical class O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910020366 ClO 4 Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- ZGUNAGUHMKGQNY-UHFFFAOYSA-N alpha-phenylglycine Chemical compound OC(=O)C(N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- GPNKJBLELXHFFQ-UHFFFAOYSA-L copper;ethane-1,2-diamine;sulfate Chemical compound [Cu+2].NCCN.NCCN.[O-]S([O-])(=O)=O GPNKJBLELXHFFQ-UHFFFAOYSA-L 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Description
この発明は、次の一般式（）：
（上式中、R1およびR2は水素原子および低級ア
ルキル基の中から選ばれ、両者は同一であつても
相違してもよい。）で表わされるヒドロキシフエ
ニル酢酸類を製造する方法に関する。
上記式（）で表わされるヒドロキシフエニル
酢酸類は、胆汁分泌活性医薬および農薬の合成に
有用な中間体として公知である。
上記式（）で表わされるヒドロキシフエニル
酢酸類を合成する方法としていくつかの手法が知
られている。例えば、２−メトキシアセトフエノ
ンを２−メトキシフエニル酢酸に変換し、これに
臭化水素酸で処理して２−ヒドロキシフエニル酢
酸とする方法（J.Org.Chem.11（1946）798など）、
ニトロフエニル酢酸を還元してアミノフエニル酢
酸とし、これをジアゾ化および加水分解によつて
ヒドロキシフエニル酢酸に変換する方法（J.
Chem.Soc.（London）1948、150）、２−ブロモフ
エニル酢酸をモルホリン水溶液中でビス（エチレ
ンジアミン）銅サルフエートまたはビス（エチレ
ンジアミン）銅クロリドのような触媒の存在下に
加水分解する方法（V.N.LisitsynおよびE.K.
Lugovskaya：J.O.C.（USSR）1971、p2666−
2668）、および、２−クロロフエニル酢酸のよう
なハロゲン化フエニル酢酸を金属銅および銅塩の
存在下に苛性アルカリと反応せしめて２−ヒドロ
キシフエニル酢酸とする方法（特開昭47−4870号
公報）などが知られている。これら公知方法の中
では、特開昭47−4870号公報記載の方法は比較的
高い収率を以つて２−ヒドロキシフエニル酢酸が
得られる点で優るとされている（同公開公報によ
れば２−ヒドロキシフエニル酢酸の収率は82〜95
％である）。しかしながら、この方法は、反応を
220〜250℃、20〜60気圧と言う高温高圧条件下に
行わねばならず、工業的には決して有利な方法で
はない。
本発明の目的は、特開昭47−4870号公報に記載
される温度および圧力条件より緩やかな条件下に
高収率を以つて、同公開公報に開示されている２
−ヒドロキシフエニル酢酸を含め、前記一般式
（）で表わされるヒドロキシフエニル酢酸類を
製造することができる技術を提供するにある。
本発明は、触媒の存在下に下記一般式（）：
（上記式中、Ｘはハロゲン原子であり、R1およ
びR2は水素原子および低級アルキル基の中から
選ばれ、両者は同一であつても相違してもよく、
R3は水原子および一価炭化水素基の中から選ば
れる。）で表わされるハロゲン置換フエニル酢酸
類をアルカリと反応させて下記一般式（）：
（上式中のR1およびR2は一般式（）について
定義したとおりである。）で表わされるヒドロキ
シフエニル酢酸類を製造する方法において、触媒
として化学式：
で表わされるビス（８−キノリノラト）銅を使用
することを特徴とする方法を提供する。
触媒として使用するビス（８−キノリノラト）
銅は、８−キノリノール（C9H6NOH）を水およ
び／またはメタノールもしくはエタノール中で銅
（）塩、例えば、CuCl2、CuSO4・5H2O、Cu
（NO3）2・3H2O、Cu（ClO4）2・6H2O、Cu
（C2H3O2）・H2Oなどと反応せしめることにより
容易に調製できる。その製法は、例えば、J.C.
FanningおよびH.B.Jonassen：J.Inorg.Nucl.
Chem.、1963、Vol.25、pp29−35に記載されてい
る。
触媒の好適使用量は、反応温度、反応時間、ハ
ロゲン置換フエニル酢酸出発化合物の種類などに
依在して変わるが、通常、ハロゲン置換フエニル
酢酸モル当り0.001〜0.3モル、より好ましくは
0.01〜0.2モルの範囲で選ぶことができる。後記
実施例４の結果からも明らかなように、170℃程
度の比較的低い反応温度において90％を超える収
率を確保するには一般に約0.05モル以上の触媒使
用通が必要となる。
なお、加水分解反応に使用した触媒は、反応終
了後反応混合物中に酸を加えて中和することによ
り触媒を結晶として析出させ、別回収して、再
使用に供することができる。
本発明方法において出発原料として用いられる
ハロゲン置換フエニル酢酸類を表わす前記一般式
（）において、Ｘはハロゲン原子を表わすが、
このハロゲンが塩素であるものは本発明方法に使
用するのに特に有利な原料である。一般に塩素置
換基は高温条件下でないと加水分解し難いからで
ある。また、ハロゲン置換フエニル酢酸類は遊離
酸（R3＝Ｈ）であつてもエステル（R3＝炭化水
素基）であつてもよい。R3となる炭化水素基と
しては、メチル、エチル、ｎ−ブチルなどのアル
キル基、ベンジル、フエネチルなどのアラルキル
基が挙げられる。ハロゲン置換フエニル酢酸類の
具体例としては、２−クロロフエニル酢酸、４−
クロロフエニル酢酸、２−（4′−クロロフエニル）
−３−メチルプタン酸などの遊離酸ならびにそれ
らのメチル、エチル、ｎ−プロピル、イソプロピ
ル、ｎ−ブチル、イソブチル、ｎ−オクチル、ベ
ンジル、α−フエネチル、β−フエネチルなどの
エステルが挙げられる。
ハロゲン置換フエニル酢酸類と反応せしめられ
るアルカリとしては、水酸化ナトリウム、水酸化
カリウム、炭酸ナトリウムおよび炭酸カリウムな
どが用いられる。アルカリの使用量は、ハロゲン
置換フエニル酢酸類モル当り１〜10モル、好まし
くは２〜７モルである。これらのアルカリは水溶
液として用いられ、その濃度は通常50重量％以
下、より好ましくは５〜30重量％である。アルカ
リ水溶液の濃度が約50重量％を超えると反応混合
物の一様な撹拌が困難となり、不均一反応になり
易い。
加水分解反応は一般に100〜300℃、好ましくは
150〜250℃の温度で行う。反応時間は反応温度と
負の相関を有し、概して、150〜170℃のような比
較的低い温度では数時間またはそれ以上が必要で
あり、230〜250℃のような比較的高い温度では２
時間またはそれ以下でよい。後記実施例３の結果
からも窺えるように、反応温度が高いと副生物生
成量が増大し、目的とするヒドロキシフエニル酢
酸類の収率が低減する。特に、反応温度が約300
℃を超えると出発原料、触媒が不安定となり、反
応の制御も困難となる。
加水分解反応はオートクレーブのような耐圧反
応器中自生圧下に行うのが簡便であり、概して、
150〜250℃の反応温度は約４〜約35Kg／cm2の圧力
に対応する。
以下、本発明を実施例について説明する。
実施例 １
オートクレーブに13％水酸化ナトリウム水溶液
124ｇ（0.4モル）、２−クロロフエニル酢酸17.1
ｇ（0.1モル）及びビス（８−キノリノラト）銅
（）3.52ｇ（0.01モル）を仕込み、加圧下170℃
で２時間反応させた。反応圧力は6.5〜７Kg／cm2
であつた。
反応終了後、得られた反応混合物を放冷し、濃
塩酸を加えて中和し、生成したビス（８−キノリ
ノラト）銅を別した。得られた液は、減圧下
に濃縮した後、濃塩酸を加えて析出した結晶を
取し、水洗、乾燥し、白色板状晶、融点142〜144
℃の２−ヒドロキシフエニル酢酸14.4ｇ（収率95
％）を得た。
比較例 １
オートクレーブに13％水酸化ナトリウム水溶液
124ｇ（0.4モル）、２−クロロフエニル酢酸17.1
ｇ（0.1モル）及び硫酸銅（CuSO4・5H2O）2.5
ｇ（0.01モル）を仕込み、加圧下170℃で６時間
反応させた。反応圧力は6.5〜７Kg／cm2であつた。
反応終了後、得られた反応混合物を放冷し、濃
塩酸を加えて酸性にし析出した結晶を取し、水
洗、乾燥した。白色板状晶、融点142−144℃の２
−ヒドロキシフエニル酢酸3.8ｇ（収率25％）を
得た。
比較例 ２
オートクレーブに13％水酸化ナトリウム水溶液
124ｇ（0.4モル）、２−クロロフエニル酢酸17.1
ｇ（0.1モル）、銅粉末0.42ｇ（0.0067モル）及び
塩化第二銅0.44ｇ（0.0033モル）を仕込み、加圧
下170で６時間反応させた。反応圧力は6.5−７
Kg／cm2であつた。
反応終了後、得られた反応混合物を放冷し、水
溶解の銅粉末を別した。得られた液は減圧下
に濃縮した後、濃塩酸を加えて酸性にし、析出し
た結晶を取し、水洗、乾燥した。白色板状晶、
融点142−144℃の２−ヒドロキシフエニル酢酸
4.0ｇ（収率26％）を得た。
実施例 ２
実施例１と同一手法に従つて、ビス（８−キノ
リノラト）銅（）の存在下に４−クロロフエニ
ル酢酸を水酸化ナトリウムと反応させた。反応時
間を６時間に変えた他は反応条件、反応試薬使用
量いずれも実施例１と同様とした。反応生成物を
実施例１とほぼ同様に処理して、白色板状晶、融
点148−149℃の４−ヒドロキシフエニル酢酸14.6
ｇ（収率96％）を得た。
実施例 ３
実施例１と同一手法に従つて、ビス（８−キノ
リノラト）銅（）の存在下に２−（4′−クロロ
フエニル）−３−メチルブタン酸を水酸化ナトリ
ウムと反応させた。２−（4′−クロロフエニル）−
３−メチルブタン酸の使用量を21.2ｇ（0.1モル）
とした他は反応条件は実施例１と同様にした。反
応生成物を実施例１と同様に処理して、白色無定
形粉末、融点167.5−168℃の２−（4′−ヒドロキ
シフエニル）−３−メチルブタン酸19.2ｇ（収率
99％）を得た。
反応温度（従つて、反応圧力）および反応時間
を変えて上記方法を繰返した。結果は次のとおり
であつた。
This invention is based on the following general formula (): (In the above formula, R 1 and R 2 are selected from a hydrogen atom and a lower alkyl group, and both may be the same or different.) . Hydroxyphenylacetic acids represented by the above formula () are known as intermediates useful in the synthesis of bile secretion active pharmaceuticals and agricultural chemicals. Several techniques are known as methods for synthesizing hydroxyphenylacetic acids represented by the above formula (). For example, 2-methoxyacetophenone is converted to 2-methoxyphenylacetic acid, which is then treated with hydrobromic acid to produce 2-hydroxyphenylacetic acid (J.Org.Chem.11 (1946) 798 Such),
A method for reducing nitrophenyl acetic acid to aminophenylacetic acid, which is then converted to hydroxyphenylacetic acid by diazotization and hydrolysis (J.
Chem.Soc. (London) 1948, 150), a method for the hydrolysis of 2-bromophenyl acetic acid in aqueous morpholine in the presence of a catalyst such as bis(ethylenediamine)copper sulfate or bis(ethylenediamine)copper chloride (VNLisitsyn and EK
Lugovskaya: JOC (USSR) 1971, p2666−
2668), and a method in which halogenated phenylacetic acid such as 2-chlorophenylacetic acid is reacted with caustic alkali in the presence of metallic copper and a copper salt to produce 2-hydroxyphenylacetic acid (JP-A No. 47-4870) ) etc. are known. Among these known methods, the method described in JP-A No. 47-4870 is said to be superior in that 2-hydroxyphenylacetic acid can be obtained with a relatively high yield (according to the publication) The yield of 2-hydroxyphenylacetic acid is 82-95
%). However, this method
It must be carried out under high temperature and high pressure conditions of 220 to 250°C and 20 to 60 atmospheres, which is by no means an advantageous method from an industrial perspective. The object of the present invention is to produce the 2-method-containing compound disclosed in JP-A No. 47-4870 with a high yield under conditions that are milder than the temperature and pressure conditions described in JP-A No. 47-4870.
An object of the present invention is to provide a technology capable of producing hydroxyphenylacetic acids represented by the general formula (), including -hydroxyphenylacetic acid. The present invention uses the following general formula () in the presence of a catalyst: (In the above formula, X is a halogen atom, R 1 and R 2 are selected from a hydrogen atom and a lower alkyl group, and they may be the same or different,
R 3 is selected from water atoms and monovalent hydrocarbon groups. ) is reacted with an alkali to form the following general formula (): (R 1 and R 2 in the above formula are as defined for the general formula ().) In the method for producing hydroxyphenylacetic acids represented by the chemical formula: Provided is a method characterized in that copper bis(8-quinolinolato) represented by is used. Bis(8-quinolinolato) used as catalyst
Copper can be prepared by converting 8-quinolinol ( C9H6NOH ) into copper() salts, e.g. CuCl2 , CuSO4.5H2O , Cu in water and/or methanol or ethanol.
(NO 3 ) 2・3H 2 O, Cu (ClO 4 ) 2・6H 2 O, Cu
It can be easily prepared by reacting with (C 2 H 3 O 2 )・H 2 O, etc. The manufacturing method is, for example, JC
Fanning and H.B.Jonassen: J.Inorg.Nucl.
Chem., 1963, Vol. 25, pp 29-35. The preferred amount of the catalyst to be used varies depending on the reaction temperature, reaction time, type of halogen-substituted phenylacetic acid starting compound, etc., but is usually 0.001 to 0.3 mol per mol of halogen-substituted phenylacetic acid, more preferably
It can be selected within the range of 0.01 to 0.2 mol. As is clear from the results of Example 4 below, in order to ensure a yield of over 90% at a relatively low reaction temperature of about 170°C, it is generally necessary to use about 0.05 mol or more of the catalyst. The catalyst used in the hydrolysis reaction can be neutralized by adding an acid to the reaction mixture after the completion of the reaction to precipitate the catalyst as crystals, which can be separately recovered and reused. In the general formula () representing the halogen-substituted phenylacetic acid used as a starting material in the method of the present invention, X represents a halogen atom,
Those in which the halogen is chlorine are particularly advantageous raw materials for use in the process of the invention. This is because, in general, chlorine substituents are difficult to hydrolyze unless under high temperature conditions. Further, the halogen-substituted phenylacetic acid may be a free acid (R 3 =H) or an ester (R 3 =hydrocarbon group). Examples of the hydrocarbon group serving as R 3 include alkyl groups such as methyl, ethyl, and n-butyl, and aralkyl groups such as benzyl and phenethyl. Specific examples of halogen-substituted phenylacetic acids include 2-chlorophenylacetic acid, 4-chlorophenylacetic acid,
Chlorophenyl acetic acid, 2-(4'-chlorophenyl)
Free acids such as -3-methylbutanoic acid and their esters such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-octyl, benzyl, α-phenethyl, β-phenethyl and the like. As the alkali to be reacted with the halogen-substituted phenylacetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc. are used. The amount of alkali used is 1 to 10 mol, preferably 2 to 7 mol, per mol of halogen-substituted phenylacetic acid. These alkalis are used as aqueous solutions, and the concentration thereof is usually 50% by weight or less, more preferably 5 to 30% by weight. If the concentration of the alkaline aqueous solution exceeds about 50% by weight, it becomes difficult to stir the reaction mixture uniformly, and a heterogeneous reaction tends to occur. The hydrolysis reaction is generally carried out at 100-300°C, preferably
Carry out at a temperature of 150-250 ° C. Reaction time is negatively correlated with reaction temperature, generally requiring several hours or more at relatively low temperatures such as 150-170 °C and 2 hours or more at relatively high temperatures such as 230-250 °C.
It may take an hour or less. As can be seen from the results of Example 3 described later, when the reaction temperature is high, the amount of by-products produced increases, and the yield of the desired hydroxyphenylacetic acids decreases. In particular, the reaction temperature is about 300℃.
If the temperature exceeds ℃, the starting materials and catalyst become unstable, and it becomes difficult to control the reaction. The hydrolysis reaction is conveniently carried out under autogenous pressure in a pressure-resistant reactor such as an autoclave, and generally,
Reaction temperatures of 150-250°C correspond to pressures of about 4 to about 35 Kg/cm 2 . Hereinafter, the present invention will be explained with reference to examples. Example 1 13% sodium hydroxide aqueous solution in an autoclave
124g (0.4mol), 2-chlorophenyl acetic acid 17.1
(0.1 mol) and 3.52 g (0.01 mol) of bis(8-quinolinolato)copper () and heated at 170°C under pressure.
The mixture was allowed to react for 2 hours. Reaction pressure is 6.5-7Kg/cm 2
It was hot. After the reaction was completed, the resulting reaction mixture was allowed to cool, neutralized by adding concentrated hydrochloric acid, and the produced copper bis(8-quinolinolato) was separated. The obtained liquid was concentrated under reduced pressure, then concentrated hydrochloric acid was added to collect the precipitated crystals, washed with water, and dried to form white plate-like crystals, melting point 142-144.
14.4 g of 2-hydroxyphenylacetic acid (yield 95
%) was obtained. Comparative example 1 13% sodium hydroxide aqueous solution in autoclave
124g (0.4mol), 2-chlorophenyl acetic acid 17.1
g (0.1 mol) and copper sulfate (CuSO 4 5H 2 O) 2.5
g (0.01 mol) and reacted under pressure at 170°C for 6 hours. The reaction pressure was 6.5-7 Kg/ cm2 . After the reaction was completed, the resulting reaction mixture was allowed to cool, acidified with concentrated hydrochloric acid, and the precipitated crystals were collected, washed with water, and dried. White plate-like crystals, melting point 142-144℃ 2
-Hydroxyphenylacetic acid 3.8g (yield 25%) was obtained. Comparative example 2 13% sodium hydroxide aqueous solution in autoclave
124g (0.4mol), 2-chlorophenyl acetic acid 17.1
(0.1 mol), 0.42 g (0.0067 mol) of copper powder, and 0.44 g (0.0033 mol) of cupric chloride, and reacted under pressure at 170℃ for 6 hours. Reaction pressure is 6.5-7
It was Kg/ cm2 . After the reaction was completed, the resulting reaction mixture was allowed to cool, and the water-soluble copper powder was separated. The obtained liquid was concentrated under reduced pressure, then made acidic by adding concentrated hydrochloric acid, and the precipitated crystals were collected, washed with water, and dried. white plate crystals,
2-Hydroxyphenylacetic acid with melting point 142-144℃
4.0 g (yield 26%) was obtained. Example 2 Following the same procedure as in Example 1, 4-chlorophenylacetic acid was reacted with sodium hydroxide in the presence of copper bis(8-quinolinolato)(). The reaction conditions and the amounts of reaction reagents used were the same as in Example 1, except that the reaction time was changed to 6 hours. The reaction product was treated in substantially the same manner as in Example 1 to give 4-hydroxyphenylacetic acid as white plate-like crystals, melting point 148-149°C.
g (yield 96%) was obtained. Example 3 Following the same procedure as in Example 1, 2-(4'-chlorophenyl)-3-methylbutanoic acid was reacted with sodium hydroxide in the presence of copper bis(8-quinolinolato)(). 2-(4'-chlorophenyl)-
The amount of 3-methylbutanoic acid used was 21.2g (0.1 mol).
Other than that, the reaction conditions were the same as in Example 1. The reaction product was treated as in Example 1 to give 19.2 g of 2-(4'-hydroxyphenyl)-3-methylbutanoic acid as a white amorphous powder, melting point 167.5-168°C (yield
99%). The above procedure was repeated with different reaction temperatures (and therefore reaction pressures) and reaction times. The results were as follows.
【表】
実施例 ４
実施例３と同様な手法に従つて２−（4′−ヒド
ロキシフエニル）−３−メチルブタン酸を合成し
た。但し、反応温度および反応圧力はそれぞれ
170℃および6.5−７Kg／cm2とし、触媒量および反
応時間を次のように変えた。収率は次のとおりで
あつた。[Table] Example 4 2-(4'-hydroxyphenyl)-3-methylbutanoic acid was synthesized according to the same method as in Example 3. However, the reaction temperature and reaction pressure are
The temperature was 170° C. and 6.5-7 Kg/cm 2 , and the amount of catalyst and reaction time were changed as follows. The yield was as follows.
【表】
実施例 ５
実施例１と同一手法に従つて、ビス（８−キノ
リノラト）銅（）の存在下に４−クロロフエニ
ル酢酸メチルを水酸化ナトリウムと反応させた。
４−クロロフエニル酢酸メチルの使用量を18.5ｇ
（0.1モル）とし、13％水酸化ナトリウム水溶液の
使用量を185ｇ（0.6モル）として他は反応条件は
実施例１と同様とした。反応生成物を実施例１と
ほぼ同様に処理して、白色板状晶、融点148−149
℃の４−ヒドロキシフエニル酢酸14.6ｇ（収率96
％）を得た。
比較例 ４および５
実施例３と同じ手法に従つて、２−（4′−クロ
ロフエニル）−３−メチルブタン酸を加水分解し
た。但し、反応温度および反応圧力はそれぞれ
200℃および13−14Kg／cm2とし、また、触媒とし
て、(i)銅粉末を0.0067モル＋塩化第二銅0.0033モ
ル（合計0.01モル、特開昭47−4870号公報記載の
触媒、比較例４）および(ii)ビス（エチレンジアミ
ン）銅サルフエート0.1モル（前記J.O.C.（USSR）
1971、p2666−2668記載の触媒、比較例５）を用
いた。反応は次のとおりであつた。[Table] Example 5 Following the same procedure as in Example 1, methyl 4-chlorophenylacetate was reacted with sodium hydroxide in the presence of copper bis(8-quinolinolato)().
The amount of methyl 4-chlorophenylacetate used was 18.5g.
(0.1 mol) and the amount of 13% sodium hydroxide aqueous solution used was 185 g (0.6 mol), and the other reaction conditions were the same as in Example 1. The reaction product was treated in substantially the same manner as in Example 1 to give white plate-like crystals, melting point 148-149.
14.6 g of 4-hydroxyphenylacetic acid (yield 96
%) was obtained. Comparative Examples 4 and 5 Following the same procedure as in Example 3, 2-(4'-chlorophenyl)-3-methylbutanoic acid was hydrolyzed. However, the reaction temperature and reaction pressure are
The temperature was 200°C and 13-14 Kg/ cm2 , and as a catalyst, (i) 0.0067 mol of copper powder + 0.0033 mol of cupric chloride (total 0.01 mol, catalyst described in JP-A-47-4870, Comparative Example) 4) and (ii) 0.1 mol of bis(ethylenediamine) copper sulfate (JOC (USSR)
1971, p. 2666-2668, Comparative Example 5) was used. The reaction was as follows.
Claims (1)
びR2は水素原子および低級アルキル基の中から
選ばれ、両者は同一であつても相違してもよく、
R3は水素原子および一価炭化水素基の中から選
ばれる。）で表わされるハロゲン置換フエニル酢
酸をアルカリと反応させて下記一般式（）： （上式中のR1およびR2は一般式（）について
定義したとおりである。）で表わされるヒドロキ
シフエニル酢酸類を製造する方法において、触媒
として化学式： で表わされるビス（８−キノリノラト）銅を使用
することを特徴とする方法。 ２ 触媒の使用量が、ハロゲン置換フエニル酢酸
類モル当たり0.001〜0.3モルである特許請求の範
囲第１項記載の方法。 ３ 反応温度が100−300℃である特許請求の範囲
第１項または第２項記載の方法。 ４ アルカリとして、水酸化ナトリウム、水酸化
カリウム、炭酸ナトリウムおよび炭酸カリウムの
中から選ばれた少くとも１種をハロゲン置換フエ
ニル酢酸類モル当り１〜10モル使用する特許請求
の範囲第１項から第３項までのいずれかに記載の
方法。 ５ 一般式（）で表わされるハロゲン置換フエ
ニル酢酸類のハロゲン置換基が塩素原子である特
許請求の範囲第１項から第４項までのいずれかに
記載の方法。 ６ 一般式（）で表わされるハロゲン置換フエ
ニル酢酸類が２−クロロフエニル酢酸、４−クロ
ロフエニル酢酸、２−（4′−クロロフエニル）−３
−メチルブタン酸およびそれらのエステルの中か
ら選ばれる特許請求の範囲第５項記載の方法。[Claims] 1. In the presence of a catalyst, the following general formula (): (In the above formula, X is a halogen atom, R 1 and R 2 are selected from a hydrogen atom and a lower alkyl group, and they may be the same or different,
R 3 is selected from hydrogen atoms and monovalent hydrocarbon groups. ) is reacted with an alkali to form the following general formula (): (R 1 and R 2 in the above formula are as defined for the general formula ().) In the method for producing hydroxyphenylacetic acids represented by the chemical formula: A method characterized by using bis(8-quinolinolato) copper represented by 2. The method according to claim 1, wherein the amount of catalyst used is 0.001 to 0.3 mol per mol of halogen-substituted phenylacetic acid. 3. The method according to claim 1 or 2, wherein the reaction temperature is 100-300°C. 4 Claims 1 to 1 in which at least one type selected from sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate is used as the alkali in an amount of 1 to 10 moles per mole of the halogen-substituted phenylacetic acid. The method described in any of paragraphs up to 3. 5. The method according to any one of claims 1 to 4, wherein the halogen substituent of the halogen-substituted phenylacetic acid represented by the general formula () is a chlorine atom. 6 The halogen-substituted phenylacetic acids represented by the general formula () are 2-chlorophenyl acetic acid, 4-chlorophenyl acetic acid, 2-(4'-chlorophenyl)-3
- The method according to claim 5, wherein the method is selected from among methylbutanoic acid and their esters.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11840180A JPS5742652A (en) | 1980-08-29 | 1980-08-29 | Preparation of hydroxyphenylacetic acid and catalyst for preparing it |
| US06/290,305 US4390723A (en) | 1980-08-29 | 1981-08-05 | Process for producing hydroxyphenyl aliphatic acid derivatives |
| GB8123893A GB2083023B (en) | 1980-08-29 | 1981-08-05 | Hydroxyphenyl aliphatic acid derivatives preparation and quinolivate copper complex catalyst used therein |
| IT23530/81A IT1138153B (en) | 1980-08-29 | 1981-08-14 | PROCEDURE FOR THE PRODUCTION OF A HYDROXYPHENYL DERIVATIVE OF AN ALIPHATIC ACID AND CATALYST FOR SUCH PROCEDURE |
| NL8103815A NL191788C (en) | 1980-08-29 | 1981-08-14 | Process for the preparation of hydroxyphenyl aliphatic acid derivatives. |
| FR8116128A FR2489312A1 (en) | 1980-08-29 | 1981-08-21 | PROCESS FOR THE PREPARATION OF HYDROXYPHENYL ALIPHATIC ACID DERIVATIVES AND CATALYST USEFUL THEREFOR |
| BE0/205754A BE890069A (en) | 1980-08-29 | 1981-08-25 | PROCESS FOR THE PREPARATION OF ALIPHATIC HYDROXY-PHENYL ACID DERIVATIVES AND CATALYST USEFUL THEREFOR |
| DE19813133583 DE3133583A1 (en) | 1980-08-29 | 1981-08-25 | METHOD FOR PRODUCING HYDROXYPHENYL-ALIPHATIC ACID DERIVATIVES AND CATALYST FOR THIS |
| CH5561/81A CH648301A5 (en) | 1980-08-29 | 1981-08-28 | METHOD FOR PRODUCING HYDROXYPHENYL-ALIPHATIC ACID DERIVATIVES AND CATALYST FOR THIS. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11840180A JPS5742652A (en) | 1980-08-29 | 1980-08-29 | Preparation of hydroxyphenylacetic acid and catalyst for preparing it |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5742652A JPS5742652A (en) | 1982-03-10 |
| JPS6328056B2 true JPS6328056B2 (en) | 1988-06-07 |
Family
ID=14735740
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11840180A Granted JPS5742652A (en) | 1980-08-29 | 1980-08-29 | Preparation of hydroxyphenylacetic acid and catalyst for preparing it |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS5742652A (en) |
| BE (1) | BE890069A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0723126B2 (en) * | 1985-12-27 | 1995-03-15 | 大日本印刷株式会社 | Heat seal method |
-
1980
- 1980-08-29 JP JP11840180A patent/JPS5742652A/en active Granted
-
1981
- 1981-08-25 BE BE0/205754A patent/BE890069A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5742652A (en) | 1982-03-10 |
| BE890069A (en) | 1981-12-16 |
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