JPS62242642A - Production of alpha-phenylpropionic acid - Google Patents
Production of alpha-phenylpropionic acidInfo
- Publication number
- JPS62242642A JPS62242642A JP61086530A JP8653086A JPS62242642A JP S62242642 A JPS62242642 A JP S62242642A JP 61086530 A JP61086530 A JP 61086530A JP 8653086 A JP8653086 A JP 8653086A JP S62242642 A JPS62242642 A JP S62242642A
- Authority
- JP
- Japan
- Prior art keywords
- rhodium
- reaction
- compound
- phenylpropionic acid
- water
- 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
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 title claims description 20
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 239000010948 rhodium Substances 0.000 claims abstract description 20
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000002497 iodine compounds Chemical class 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical class CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 abstract description 7
- -1 rhodium halide Chemical class 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 6
- 150000001351 alkyl iodides Chemical class 0.000 abstract description 2
- 230000001754 anti-pyretic effect Effects 0.000 abstract description 2
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 2
- 230000000202 analgesic effect Effects 0.000 abstract 1
- 239000002221 antipyretic Substances 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- KXAHUXSHRWNTOD-UHFFFAOYSA-K rhodium(3+);triiodide Chemical compound [Rh+3].[I-].[I-].[I-] KXAHUXSHRWNTOD-UHFFFAOYSA-K 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- VLVILBSSXMZZCB-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]ethanol Chemical compound CC(C)CC1=CC=C(C(C)O)C=C1 VLVILBSSXMZZCB-UHFFFAOYSA-N 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229910002090 carbon oxide Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical compound [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 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 description 3
- 150000003440 styrenes Chemical class 0.000 description 3
- GQEFPXSNRRKUHO-UHFFFAOYSA-N 4-methylpent-1-enylbenzene Chemical compound CC(C)CC=CC1=CC=CC=C1 GQEFPXSNRRKUHO-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 229910000856 hastalloy Inorganic materials 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000037048 polymerization activity Effects 0.000 description 2
- 150000003284 rhodium compounds Chemical class 0.000 description 2
- 238000007086 side reaction Methods 0.000 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 description 2
- 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 description 1
- XMRHRPOYXVMEEP-UHFFFAOYSA-N 1-ethyl-2-(2-methylpropyl)benzene Chemical compound CCC1=CC=CC=C1CC(C)C XMRHRPOYXVMEEP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003426 co-catalyst Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 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
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MHOVAHRLVXNVSD-OIOBTWANSA-N rhodium-100 Chemical compound [100Rh] MHOVAHRLVXNVSD-OIOBTWANSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000005023 xylyl group Chemical group 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、α−フェニルプロピオン酸の工業的製造方法
に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an industrial method for producing α-phenylpropionic acid.
α−フェニルプロピオン酸は鎮痛、消炎、解熱等の薬理
作用を有し、医薬品として有用である。α-Phenylpropionic acid has pharmacological effects such as analgesia, anti-inflammatory, and antipyretic properties, and is useful as a pharmaceutical.
α−フェニルプロピオン酸の製造法については、近年数
多くの合成経路が提示されている。Regarding the production method of α-phenylpropionic acid, many synthetic routes have been proposed in recent years.
例えば、α−フェニルエチルアルコール誘導体、又はス
チレン誘導体と一酸化炭素との反応により一段階でα−
フェニルプロピオン酸を製造する試みが、近年いくつか
なされている。For example, by reacting α-phenylethyl alcohol derivatives or styrene derivatives with carbon monoxide, α-
Several attempts have been made in recent years to produce phenylpropionic acid.
スチレン誘導体を原料とする方法については、パラジウ
ム錯体を触媒とするもの（特開昭５９−１０５４５号公
報）があり、好収率が得られているが、スチレン誘導体
は、α−フェニルエチルアルコール誘導体の脱水反応に
より製造しなければならず、この脱水反応の収率は、ス
チレン誘導体の高重合活性のため低く、α−フェニルエ
チルアルコール誘導体を直接カルボニル化する方法に比
べ不利である。Regarding methods using styrene derivatives as raw materials, there is a method using a palladium complex as a catalyst (Japanese Unexamined Patent Publication No. 59-10545), and a good yield has been obtained. The yield of this dehydration reaction is low due to the high polymerization activity of the styrene derivative, which is disadvantageous compared to the method of directly carbonylating an α-phenylethyl alcohol derivative.
α−フェニルエチルアルコールｇｓ体’ｔｉ−直接カル
ボニル化する方法に関しては、パラジウム錯体を触媒と
した場合、α−（アルコキシフェニル）エチルアルコー
ルのカルボニル化には有効であるが、その他のα−フェ
ニルエチルアルコール誘導体に対しては有効でないこと
（特開昭５９−９５２３８号公報）が知られている。又
、この他に、コバルト又はロジウム錯体を使用し、水の
存在下でカルボニル化する方法（特開昭５２−９７９３
０号公報）があるが、本発明者等の追試によれば、α−
フェニルプロピオン酸は生成せず、有効な方法とは認め
難い（比較例１参照）。Regarding the method of direct carbonylation of α-phenylethyl alcohol gs'ti-, when a palladium complex is used as a catalyst, it is effective for carbonylating α-(alkoxyphenyl)ethyl alcohol, but other α-phenylethyl It is known that it is not effective against alcohol derivatives (Japanese Unexamined Patent Publication No. 59-95238). In addition, there is also a method of carbonylation using a cobalt or rhodium complex in the presence of water (Japanese Patent Laid-Open No. 52-9793).
0), but according to additional tests by the inventors, α-
Phenylpropionic acid was not produced, and it is difficult to recognize this as an effective method (see Comparative Example 1).
一方、原料カα−フェニルエチルアルコール誘導体では
なく、アルコール一般の場合には、ロジウム及びヨウ素
化合物を触媒とするカルボン酸の製造法が知られている
（特公昭４７−３３３４号公報）。しかしながら、この
方法を本発明の実施例に述べられているような、高いヨ
ウ素化合物濃度及び反応温度において、α−フェニルエ
チルアルコール誘導体に適用しても、その極めて高い重
合活性のため、重合物の副生が多く、α−フェニルプロ
ピオン酸は得られない（比較例２参照）。On the other hand, in the case of alcohol in general rather than the raw material α-phenylethyl alcohol derivative, a method for producing carboxylic acid using a rhodium and iodine compound as a catalyst is known (Japanese Patent Publication No. 47-3334). However, even when this method is applied to α-phenylethyl alcohol derivatives at high iodine compound concentrations and reaction temperatures as described in the Examples of the present invention, the polymerization does not occur due to its extremely high polymerization activity. There are many by-products and α-phenylpropionic acid cannot be obtained (see Comparative Example 2).
本発明者らは、かかる情況に鑑み、鋭意研究を重ねた結
果、意外にも、次の反応式
８式％
（式中Ｒは水素、アルキル基、アルケニル基、又はアリ
ール基を表す）
で示される反応を、触媒としてロジウムを使用し、ヨウ
素化合物の添加量をＲｈ：Ｉ原子比がｔ：Ｏ，Ｓ〜ｌ：
６の範囲内になるように抑え、反応液中の水の濃度が２
モル／ｌ以下で、反応温度も１３０℃以下で行った場合
に限り、好収率でα−フェニルプロピオン酸が生成する
ことを見出し、α−フェニルエチルアルコール誘導体と
一酸化炭素より一段階でα−フェニルプロピオン酸を製
造する工業的に有利な方法を確立し、本発明を完成した
。In view of the above circumstances, the inventors of the present invention have conducted extensive research and have unexpectedly found the following reaction formula (wherein R represents hydrogen, an alkyl group, an alkenyl group, or an aryl group). The reaction was carried out using rhodium as a catalyst, and the amount of iodine compound added was set at a Rh:I atomic ratio of t:O,S~l:
The concentration of water in the reaction solution is kept within the range of 2.
It was discovered that α-phenylpropionic acid can be produced in good yield only when the reaction temperature is 130°C or lower and the reaction temperature is 130°C or lower. - An industrially advantageous method for producing phenylpropionic acid was established, and the present invention was completed.
即ち、本発明は、一般式
（式中、Ｒは水素、アルキル基、アルケニル基、又はア
リール基を表す）
で示される化合物を、ロジウム触媒とヨウ素化金物の存
在下、ロジウム触媒とヨウ素化合物のＲｈ：Ｉ原子比が
１：０．５〜１：６の範囲内になるような割合で、反応
液中の水の濃度２モル／ｌ以下、反応温度１３０℃以下
好ましくは３０〜１３０℃の条件で、−酸化炭素と反応
させることを特徴とする一般式
（式中、Ｒは前記と同意義）
で示されるα−フェニルプロピオン酸の製造法に係わる
ものである。That is, the present invention provides a compound represented by the general formula (wherein R represents hydrogen, an alkyl group, an alkenyl group, or an aryl group) in the presence of a rhodium catalyst and a metal iodide. The Rh:I atomic ratio is in the range of 1:0.5 to 1:6, the water concentration in the reaction solution is 2 mol/l or less, and the reaction temperature is 130°C or less, preferably 30 to 130°C. The present invention relates to a method for producing α-phenylpropionic acid represented by the general formula (wherein R has the same meaning as above), which is characterized by reacting with -carbon oxide under the following conditions.
以下、本発明を具体的に説明する。The present invention will be specifically explained below.
（１） 触媒
ロジウム触媒としては、ハロゲン化ロジウム、ロジウム
カルボニル、酢酸ロジウムなどのロジがム化合物が一般
的に用いられる。ロジウム触媒は、反応時に原料と共に
仕込んでも、反応前に、−酸化炭素及び水素加圧下、１
００℃乃至２００℃でカルボニル錯体としたものを使用
してもよい。(1) Catalyst As the rhodium catalyst, rhodium compounds such as rhodium halides, rhodium carbonyl, and rhodium acetate are generally used. Even if the rhodium catalyst is charged together with the raw materials during the reaction, the
A carbonyl complex formed at 00°C to 200°C may be used.
触媒としてヨウ化ロジウム等を使用する場合には、その
可溶化のために反応前処理をすることが好ましい。When rhodium iodide or the like is used as a catalyst, it is preferable to perform a reaction pretreatment to solubilize it.
（２） ヨウ素化合物
助触媒として、Ｉ２、ＩＩ、ヨウ化アルキル等のヨウ素
化合物を、ロジウム原子に対しヨウ素原子が０．５乃至
６グラム当量となるような割合で添加する必要がある。(2) As an iodine compound co-catalyst, it is necessary to add an iodine compound such as I2, II, or alkyl iodide in such a proportion that the iodine atom is 0.5 to 6 gram equivalent to the rhodium atom.
ロジウム触媒としてヨウ化ロジウムを用いる場合は、助
触媒としてヨウ素化合物を必ずしも追加する必要はない
。When rhodium iodide is used as the rhodium catalyst, it is not necessarily necessary to add an iodine compound as a promoter.
（３）原料アルコール
■
で示される原料となるα−フェニルエチルアルコール誘
導体において、置換ｉＲは水素、アルキル基、アルケニ
ル基、又は了り−ル基を表す。アルキル基、アルケニル
基としては、鎖状、分枝状あるいは環状のもの、例えば
、メチル基、エチル基、プロピル基、イソブチル基、イ
ソプレニル基、シクロヘキシル基等が挙げられる。アリ
ール基としては、例えばフェニル基、トリル基、キシリ
ル基、ナフチル基等が挙げられる。(3) Raw material alcohol In the α-phenylethyl alcohol derivative as a raw material represented by (3), the substituted iR represents hydrogen, an alkyl group, an alkenyl group, or an aryl group. Examples of the alkyl group and alkenyl group include chain, branched, or cyclic groups, such as methyl group, ethyl group, propyl group, isobutyl group, isoprenyl group, and cyclohexyl group. Examples of the aryl group include phenyl group, tolyl group, xylyl group, and naphthyl group.
（４）−酸化炭素
一酸化炭素は、純粋なもの又はこれに窒素等の不活性ガ
ス、あるいは水素を含むものが使用可能である。反応圧
力は、常圧でも高圧でも反応は進行するが、反応速度及
び経済的な面からは、常圧〜１００ ｋｇ／ｃｍ”が好
ましい。(4) - Carbon oxide Carbon monoxide may be pure or may contain an inert gas such as nitrogen, or hydrogen. The reaction proceeds at either normal pressure or high pressure, but from the viewpoint of reaction rate and economy, a range of normal pressure to 100 kg/cm'' is preferable.
又、水素を含む場合、その分圧が常圧〜５ｋｇ／Ｃｌ１
１２程度であれば、ロジウム化合物の溶解を助ける意味
でむしろ好ましいが、それ以上の高圧の場合、水素化副
生物を増加させ不利である。In addition, when hydrogen is included, its partial pressure is between normal pressure and 5 kg/Cl1
A pressure of about 12 is rather preferable in the sense that it helps dissolve the rhodium compound, but a pressure higher than that is disadvantageous as it increases hydrogenation by-products.
（５） 反応温度
反応温度は通常１３０℃以下、好ましくは３０〜１３０
℃であるが、経済的な面及び副反応抑制の面から６０〜
１００℃が特に好ましい。(5) Reaction temperature The reaction temperature is usually 130°C or lower, preferably 30 to 130°C.
℃, but from the economic point of view and prevention of side reactions
100°C is particularly preferred.
（６）溶媒
反応は溶媒なしでも進行するが、溶媒を使用する場合は
、１．４−ジオキサン等のエーテル類、ベンゼン、トル
エン等の芳香族炭化水素、あるいはヘキサン、ヘプタン
等の脂肪族炭化水素乃至はそれらの混合物が好ましく用
いられる。又、溶媒を使用する場合の原料アルコール濃
度はｌ乃至５０ｔ１％程度が、経済性及び副反応抑制の
面で有利である。(6) Solvent reaction proceeds without a solvent, but if a solvent is used, ethers such as 1,4-dioxane, aromatic hydrocarbons such as benzene and toluene, or aliphatic hydrocarbons such as hexane and heptane are used. Or a mixture thereof is preferably used. Further, when a solvent is used, it is advantageous in terms of economy and suppression of side reactions that the raw alcohol concentration is about 1 to 50 t1%.
なお、反応液中に２モル／１２を超える水分が存在する
と反応の進行が阻害されるので、水分は２モル／Ｉｌ以
下に押さえることが必要である。Note that the presence of water exceeding 2 mol/12 in the reaction solution inhibits the progress of the reaction, so it is necessary to keep the water content below 2 mol/Il.
（実施例〕
以下、実施例により本発明を更に詳細に説明するが、本
発明はこれらの実施例に限定されるものではない。(Examples) Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.
実施例１
ハステロイ製、容量３００−のオートクレーブにα−（
４−イソブチルフェニル）エチルアルコール９．０ｇ
（５０，６ｍ＋ａｏｌ） 、ヨウ化ロジウム１．５ｇ
（３，１０ｍｓ＋ｏｌ）及び溶媒としてジオキサン１０
０−を入れ、水素圧力１ａｔｓ＋、−酸化炭素圧力６ｋ
ｇ／ｃ＋ｓ”、反応温度８５℃で３時間、攪拌しながら
反応させた。Example 1 α-(
4-isobutylphenyl)ethyl alcohol 9.0g
(50,6m+aol), rhodium iodide 1.5g
(3,10ms+ol) and dioxane 10 as solvent
0-, hydrogen pressure 1ats+, - carbon oxide pressure 6k
g/c+s'' and a reaction temperature of 85° C. for 3 hours with stirring.
冷却後内容物を取り出し、溶媒を減圧留去した。残渣を
ベンゼン５０−に溶解し、２Ｎ−ＮａＯＨ水溶液１００
−を加え酸成分を水層に抽出した。抽出液に塩酸を加え
、遊離した酸をエーテルに抽出した。エーテルを留去し
て得た粗結晶をｎ−ヘキサン中で再結晶させ、α−（４
−イソブチルフェニル）プロピオン酸の白色結晶４．４
ｇを得た。After cooling, the contents were taken out and the solvent was distilled off under reduced pressure. The residue was dissolved in 50% of benzene, and 100% of a 2N aqueous NaOH solution was added.
- was added to extract the acid component into the aqueous layer. Hydrochloric acid was added to the extract, and the liberated acid was extracted into ether. The crude crystals obtained by distilling off the ether were recrystallized in n-hexane to give α-(4
-White crystals of isobutylphenyl)propionic acid 4.4
I got g.
このものの赤外吸収スペクトル及びＮＭＲスペクトルは
標品と一致した。The infrared absorption spectrum and NMR spectrum of this product matched those of the standard product.
実施例２
ハステロイ−Ｃ製、容量３００−のオートクレーブにα
−フェニルエチルアルコール９．３ ｇ （７６，２１
１１１０１） 、ヨウ化ロジウム１．５ ｇ （３，１
０ａｖ＋ｏｌ）及び溶媒としてジオキサンｉｏｏ ａＺ
を入れ、実施例１と同様に反応させ、α−フェニルプロ
ピオン酸及びβ−フェニルプロピオン酸の油状混合物６
．８ｇを得た。このものの液体クロマトグラフィー分析
の結果、混合物の組成はα−フェニルプロピ、ｔン酸８
６重１％、β−フェニルプロピオン酸１４重重量であっ
た。Example 2 α in a Hastelloy-C autoclave with a capacity of 300
-Phenylethyl alcohol 9.3 g (76,21
11101), rhodium iodide 1.5 g (3,1
0av+ol) and dioxane ioo aZ as solvent
and reacted in the same manner as in Example 1 to obtain an oily mixture of α-phenylpropionic acid and β-phenylpropionic acid 6.
．． 8g was obtained. As a result of liquid chromatography analysis of this product, the composition of the mixture was α-phenylpropylene, t-8
The content was 6% by weight and 1% by weight, and the β-phenylpropionic acid was 14% by weight.
実施例３
ハステロイ−（製、容ＭＩ ３００−のオートクレーブ
にヨウ化ロジウム１．５ｇ （３，１０ｍｍｏｌ）及び
溶媒としてジオキサン１００ ｍｌを入れ、水素圧力１
０ｋｇ／ｃｍ”、−酸化炭素圧力３０ｋｇ／ｃｍ”、反
応温度１５０℃で攪拌し、冷却、放圧後、α−（４−イ
ソブチルフェニル）エチルアルコール８．９ ｇ （５
０，０ｍｍｏｌ）及びヨウ素０．４０ ｇ （３，１５
ｍｍｏｌ）を追加し、以降実施例１と同様に反応し、α
−（４−イソブチルフェニル）プロピオン酸４．５ｇを
得た。Example 3 1.5 g (3.10 mmol) of rhodium iodide and 100 ml of dioxane as a solvent were placed in a Hastelloy (MI 300) autoclave, and the hydrogen pressure was 1.
After stirring at a reaction temperature of 150°C, cooling, and pressure release, 8.9 g of α-(4-isobutylphenyl)ethyl alcohol (5
0.0 mmol) and iodine 0.40 g (3,15
mmol), and thereafter reacted in the same manner as in Example 1, and α
4.5 g of -(4-isobutylphenyl)propionic acid was obtained.
比較例１
ハステロイ−Ｃ製、容＠ ３００−のオートクレーブに
α−（４−イソブチルフェニル）エチルアルコール１７
．８ ｇ （１００ｍｍｏｌ） 、水２．７ ｇ （１
５０信ｏ＋ｏｌ）、（Ｒｈ（Ｃｏ）ｚｃｌ）ｚ １９３
ｍｇ（０，５ｍｍｏｌ）、トリフェニルホスフィン５２
．４ｍｇ（０，２ｍｓ＋ｏｌ）及び溶媒としてベンゼン
１７．８−を入れ、−酸化炭素圧力６０ｋｇ／ｃ＋ｎ”
、反応温度８０℃で５時間、攪拌しながら反応させた。Comparative Example 1 α-(4-isobutylphenyl)ethyl alcohol 17 was placed in a Hastelloy-C autoclave with a volume of 300-
．． 8 g (100 mmol), water 2.7 g (1
50 belief o+ol), (Rh(Co)zcl)z 193
mg (0.5 mmol), triphenylphosphine 52
．． 4mg (0.2ms+ol) and benzene 17.8- as a solvent, -carbon oxide pressure 60kg/c+n"
The reaction was carried out at a reaction temperature of 80° C. for 5 hours with stirring.
冷却後、内容物を取り出し、溶媒を減圧留去した。この
ものの赤外吸収スペクトルを測定したところ、カルボン
酸に特有の１７００ｃｏ＋−’付近の吸収は見られずα
−（４−イソブチルフェニル）プロピオン酸の生成は無
いことが確認された。After cooling, the contents were taken out and the solvent was distilled off under reduced pressure. When we measured the infrared absorption spectrum of this product, no absorption near 1700co+-', which is characteristic of carboxylic acids, was observed.
It was confirmed that -(4-isobutylphenyl)propionic acid was not produced.
比較例２
ハステロイ−Ｃ製、容量３００−のオートクレーブにα
−（４−イソブチルフェニル）エチルアルコール９．９
ｇ （５５，７ｍｍｏｌ） 、ＲｈＣ１＊ ・３（Ｈ
ｚＯ）０．２０５ｇ （０，７８０ｍｍｏｌ）、５７％
水性ヨウ化水素酸２５．５ｇ及び溶媒としてベンゼン１
００１ｍ７を入れ、−酸化炭素圧力３０ｋｇ／ｃｏ＋”
、反応温度１８０℃で２時間、攪拌しながら反応させた
。冷却後、内容物を取り出し、溶媒を減圧留去した。こ
のものの赤外スペクトル、ＮＭＲスペクトル、ガスクロ
マトグラフィー分析の結果、カルボン酸の生成はな（、
α−（４−イソブチルフェニル）エチルアルコールは全
量、重合物に変化していることが確認された。Comparative Example 2 α in a Hastelloy-C autoclave with a capacity of 300
-(4-isobutylphenyl)ethyl alcohol 9.9
g (55.7 mmol), RhC1*・3(H
zO) 0.205g (0,780mmol), 57%
25.5 g of aqueous hydroiodic acid and 1 part of benzene as solvent
001m7, -carbon oxide pressure 30kg/co+"
The reaction was carried out at a reaction temperature of 180° C. for 2 hours with stirring. After cooling, the contents were taken out and the solvent was distilled off under reduced pressure. As a result of infrared spectrum, NMR spectrum, and gas chromatography analysis of this product, no carboxylic acid was formed (
It was confirmed that the entire amount of α-(4-isobutylphenyl)ethyl alcohol had changed into a polymer.
比較例３（反応温度が高すぎる場合）
ハステロイ製、容量３００−のオートクレーブにα−（
４−イソブチルフェニル）エチルアルコール９．２ｇ
（５１，７＋ｕｗｏｌ） 、ヨウ化ロジウム１．５ｇ
（３，１０ｗａｏｌ）及び溶媒としてジオキサン１００
−を入れ、反応温度を１８０℃とした他は、実施例１と
同様に反応させた０反応後の内容物を分析した結果、α
−（４−イソブチルフェニル）プロピオン酸生成量は０
．５ｇであり、他はすべてイソブチルスチレン重合物及
びイソブチルエチルベンゼンになっていることが確認さ
れた。Comparative Example 3 (When the reaction temperature is too high) α-(
9.2 g of 4-isobutylphenyl)ethyl alcohol
(51,7+uwol), rhodium iodide 1.5g
(3,10 waol) and dioxane 100 as solvent
- was added and the reaction temperature was 180°C, but the reaction was carried out in the same manner as in Example 1. As a result of analyzing the contents after the 0 reaction, α
-(4-isobutylphenyl)propionic acid production amount is 0
．． It was confirmed that the remaining amount was 5 g, and the rest were all isobutyl styrene polymer and isobutylethylbenzene.
比較例４（ヨウ素過剰の場合）
ハステロイ製、容量３００１Ｉ７のオートクレーブにα
−（４−イソブチルフェニル）エチルアルコール９．０
ｇ （５０，６＋５ｓｏｌ） 、ヨウ化ロジウム１．５
ｇ （３，１０ｍｍｏｌ） 、ヨウ素５．０ ｇ （３
９，４ｍｍｏｌ）（Ｒｈ：Ｉ比＝ １ ： １２．７）
及び溶媒としてジオキサン１００−を入れ、実施例１と
同一の反応条件で反応させた。反応後の内容物を分析し
た結果、α−（４−イソブチルフェニル）プロピオン酸
生成量は１．１ｇであり、他はすべてイソブチルスチレ
ン重合物となっていることが確認された。Comparative Example 4 (in the case of excess iodine) α in a Hastelloy autoclave with a capacity of 3001I7
-(4-isobutylphenyl)ethyl alcohol 9.0
g (50,6+5sol), rhodium iodide 1.5
g (3.10 mmol), iodine 5.0 g (3
9.4 mmol) (Rh:I ratio = 1:12.7)
and dioxane 100- as a solvent, and the reaction was carried out under the same reaction conditions as in Example 1. As a result of analyzing the contents after the reaction, it was confirmed that the amount of α-(4-isobutylphenyl)propionic acid produced was 1.1 g, and that everything else was isobutylstyrene polymer.
比較例５（水が過剰の場合）
ハステロイ製、容ｉｔ ３００−のオートクレーブにα
−（４−イソブチルフェニル）エチルアルコール９．１
ｇ （５１，１ａｖｏｌ） 、ヨウ化ロジウム１．５ｇ
（３，１０ａ＋ｍｏｌ） 、水５．８ ｇ （３２２
ｍｍｏｌ） （反応液中の水の濃度は２．９モル／ｌ’
）及び溶媒としてジオキサン１００１１７を入れ、実施
例１と同様に反応させた０反応後の内容物のガスクロマ
トグラフィー及びＮＭＲ分析の結果、α−（４−イソブ
チルフェニル）エチルアルコールの５９％は未反応で残
り４０％が４−イソブチルスチレンに変化しており、α
−（４−イソブチルフェニル）プロピオン酸の生成は痕
跡量であった。Comparative Example 5 (When water is excessive)
-(4-isobutylphenyl)ethyl alcohol9.1
g (51,1avol), rhodium iodide 1.5g
(3,10a+mol), water 5.8g (322
mmol) (The concentration of water in the reaction solution is 2.9 mol/l'
) and dioxane 100117 as a solvent and reacted in the same manner as in Example 1. As a result of gas chromatography and NMR analysis of the contents after the 0 reaction, 59% of α-(4-isobutylphenyl)ethyl alcohol was unreacted. The remaining 40% is converted to 4-isobutylstyrene, α
-(4-isobutylphenyl)propionic acid was produced in trace amounts.
Claims (1)
リール基を表す） で示される化合物を、ロジウム触媒とヨウ素化合物の存
在下、ロジウム触媒とヨウ素化合物のＲｈ：Ｉ原子比が
１：０．５〜１：６の範囲内になるような割合で、反応
液中の水の濃度２モル／ｌ以下、反応温度１３０℃以下
の条件で、一酸化炭素と反応させることを特徴とする一
般式 ▲数式、化学式、表等があります▼ （式中、Ｒは前記と同意義） で示されるα−フェニルプロピオン酸の製造法。[Claims] 1. A compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents hydrogen, an alkyl group, an alkenyl group, or an aryl group) In the presence of the compound, the Rh:I atomic ratio of the rhodium catalyst and the iodine compound is in the range of 1:0.5 to 1:6, the water concentration in the reaction solution is 2 mol/l or less, and the reaction is carried out. α-phenylpropionic acid, which is characterized by reacting with carbon monoxide at a temperature of 130°C or less, is represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (wherein R has the same meaning as above) manufacturing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61086530A JPH0653705B2 (en) | 1986-04-15 | 1986-04-15 | Method for producing α-phenylpropionic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61086530A JPH0653705B2 (en) | 1986-04-15 | 1986-04-15 | Method for producing α-phenylpropionic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62242642A true JPS62242642A (en) | 1987-10-23 |
| JPH0653705B2 JPH0653705B2 (en) | 1994-07-20 |
Family
ID=13889543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61086530A Expired - Lifetime JPH0653705B2 (en) | 1986-04-15 | 1986-04-15 | Method for producing α-phenylpropionic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0653705B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5166418A (en) * | 1990-06-04 | 1992-11-24 | Hoechst Celanese Corporation | Method for producing ibuprofen |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5629542A (en) * | 1979-07-03 | 1981-03-24 | Nissan Chem Ind Ltd | Preparation of phenylacetic acid derivative |
-
1986
- 1986-04-15 JP JP61086530A patent/JPH0653705B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5629542A (en) * | 1979-07-03 | 1981-03-24 | Nissan Chem Ind Ltd | Preparation of phenylacetic acid derivative |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5166418A (en) * | 1990-06-04 | 1992-11-24 | Hoechst Celanese Corporation | Method for producing ibuprofen |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0653705B2 (en) | 1994-07-20 |
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