JPH0231703B2 - - Google Patents
Info
- Publication number
- JPH0231703B2 JPH0231703B2 JP57035786A JP3578682A JPH0231703B2 JP H0231703 B2 JPH0231703 B2 JP H0231703B2 JP 57035786 A JP57035786 A JP 57035786A JP 3578682 A JP3578682 A JP 3578682A JP H0231703 B2 JPH0231703 B2 JP H0231703B2
- Authority
- JP
- Japan
- Prior art keywords
- halogenated
- acid
- hydrogen
- hydroxymandelic
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 25
- 239000003054 catalyst Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052763 palladium Inorganic materials 0.000 claims description 13
- VKVOJYUPJRVDPP-UHFFFAOYSA-N 2,2-dihydroxy-2-phenylacetic acid Chemical class OC(=O)C(O)(O)C1=CC=CC=C1 VKVOJYUPJRVDPP-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical class OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 9
- 150000001555 benzenes Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- IYTUKSIOQKTZEG-UHFFFAOYSA-N (3-chloro-4-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C(Cl)=C1 IYTUKSIOQKTZEG-UHFFFAOYSA-N 0.000 description 6
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- VDBWQCRJTMKEMJ-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CC=C(O)C(Cl)=C1 VDBWQCRJTMKEMJ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- WQONPSCCEXUXTQ-UHFFFAOYSA-N 1,2-dibromobenzene Chemical compound BrC1=CC=CC=C1Br WQONPSCCEXUXTQ-UHFFFAOYSA-N 0.000 description 2
- JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 2
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 2
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 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
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- -1 chlorohydroxymandelic acid Chemical compound 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000004246 zinc acetate Substances 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- HWBAYVVTQOPCIR-UHFFFAOYSA-N 2-(2-bromophenyl)-2,2-dihydroxyacetic acid Chemical compound OC(C(=O)O)(O)C1=C(C=CC=C1)Br HWBAYVVTQOPCIR-UHFFFAOYSA-N 0.000 description 1
- MLTHQBJVZAHFFC-UHFFFAOYSA-N 2-chloro-2-(4-hydroxyphenyl)acetic acid Chemical compound OC(=O)C(Cl)C1=CC=C(O)C=C1 MLTHQBJVZAHFFC-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003426 co-catalyst Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明はハロゲン化ヒドロキシマンデル酸をハ
ロゲン化ベンゼン溶媒中で水素還元することによ
りベンジル位の水酸基を還元して、ハロゲン化ヒ
ドロキシフエニル酢酸を製造する方法に関するも
のである。
ハロゲン化ヒドロキシフエニル酢酸は医薬、農
薬の中間原料として有用である。例えば３−クロ
ロ−４−ヒドロキシフエニル酢酸は、消炎鎮痛剤
として広く用いられている３−クロロ−４−アリ
ルオキシフエニル酢酸（商品名；アルクロフエナ
ツク）の中間体として有用な化合物である。
ハロゲン化ヒドロキシフエニル酢酸を得る公知
の方法として、例えば特開昭54−76542号公報に
は、３−クロロ−４−ヒドロキシマンデル酸を赤
リン、錫（すず）、あるいは塩化第一錫を用いて
還元する方法が提案されているが、還元剤を化学
量論量使用する必要があり、工業的規模で行うに
は操業上の困難が大きかつた。
この欠点を解決するために本発明者は工業的に
有利な還元方法として水素を用いる方法を検討し
た。
従来、この種の反応にしばしばアルコール溶媒
が使用されていることから、ハロゲン化ヒドロキ
シマンデル酸、例えば３−クロロ−４−ヒドロキ
シマンデル酸をエチルアルコールなど各種のアル
コール溶媒中、パラジウム触媒による水素還元を
試みたところ、目的とするベンジル位の水酸基の
還元だけでなく、３−位の塩素原子までもが水素
化分解を受けてしまい、その結果、所望する３−
クロロ−４−ヒドロキシフエニル酢酸は全く生成
せず、４−ヒドロキシフエニル酢酸のアルキルエ
ステルが生成した（特開昭56−71043号公報参
照）。
そこで、３−位の塩素原子が水素化分解されな
い条件を見出すべく検討したところ、水溶媒中、
パラジウム触媒および酢酸亜鉛助触媒の存在下、
３−クロロ−４−ヒドロキシマンデル酸を水素還
元すれば、３−クロロ−４−ヒドロキシフエニル
酢酸が収率75％、選択率83％で生成することを見
い出した（特開昭56−81533号公報参照）。
しかしながら、この方法では２種類の触媒を組
み合わせて使用する必要があるため、その触媒の
回収、再使用の面で問題があつた。つまり、一度
使用したパラジウム触媒、酢酸亜鉛助触媒を回収
して次回の反応に用いる場合、反応速度が著しく
低下し長い反応時間を要するだけでなく、目的物
の収率低下が著しいという欠点があつた。
本発明者はパラジウム触媒のみを使用し、ハロ
ゲン化ヒドロキシマンデル酸を水素還元してハロ
ゲン化ヒドロキシフエニル酢酸を製造する方法に
ついて鋭意検討した結果、本発明に到達した。
すなわち、本発明はハロゲン化ヒドロキシマン
デル酸をパラジウム触媒の存在下、ハロゲン化ベ
ンゼン溶媒中で水素還元することを特徴とするハ
ロゲン化ヒドロキシフエニル酢酸の製造法に関す
るものである。
本発明の方法に使用するハロゲン化ヒドロキシ
マンデル酸は次式で表わされる。
（ただし、式中のＸはハロゲン原子を示す）その
例として、クロロヒドロキシマンデル酸、ブロモ
ヒドロキシマンデル酸、ヨウ化ヒドロキシマンデ
ル酸、フルオロヒドロキシマンデル酸などが挙げ
られる。なお、ハロゲン化ヒドロキシマンデル酸
は、例えば、ハロゲン化フエノールとグリオキシ
ル酸とをアルカリ存在下に反応させることによつ
て容易に得ることができる。
本発明の方法で使用するハロゲン化ベンゼンの
例として、クロロベンゼン、ブロモベンゼン、Ｏ
−ジクロロベンゼン、ｍ−ジクロロベンゼン、Ｏ
−ジブロモベンゼン、ｍ−ジブロモベンゼンを挙
げることができるが、その中で、Ｏ−ジクロロベ
ンゼン、ｍ−ジクロロベンゼン、Ｏ−ジブロモベ
ンゼン、ｍ−ジブロモベンゼンが好ましい。
これら溶媒の使用量は原料のハロゲン化ヒドロ
キシマンデル酸１モルに対して0.5〜10、特に
１〜５が好ましい。
また本発明の方法で使用するパラジウム触媒は
金属パラジウムを活性炭、グラフアイト、シリカ
ゲル、炭酸カルシウム、アルミナ等の担体に0.1
〜10重量％、好ましくは0.5〜８重量％の量を担
持させたものが適当である。なお、パラジウム触
媒は塩化パラジウムを濃塩酸に溶解し、前記のよ
うな担体に含浸させた後、必要に応じて水素等で
還元処理し、残存の塩酸を除去処理して調整され
る。パラジウム触媒の使用量は、原料のハロゲン
化ヒドロキシマンデル酸１モルに対して金属パラ
ジウム換算で0.001〜2.0ｇ、特に0.01〜0.5ｇが好
ましい。
水素は純水素または、窒素のような不活性ガス
を混合した水素含有ガスが使用される。水素圧力
は0.1〜５Kg／cm2（ゲージ）、特に１〜３Kg／cm2
（ゲージ）が好ましい。また、反応温度は60〜110
℃、特に70〜90℃が好ましい。反応時間は反応温
度にもよるが、通常30分〜120分間である。
本発明の方法によつて得られる反応生成物は、
ハロゲン化ヒドロキシマンデル酸に対応するハロ
ゲン化ヒドロキシフエニル酢酸であり、次式によ
つて表わされる。
（ただし、式中のＸはハロゲン原子を示す）
本発明の方法に従つて反応して得た反応生成物
は、通常、冷却してパラジウム触媒を別除去
し、液から溶媒を留去して得られた粘性油状物
をベンゼン、トルエン、キシレン等の溶剤で抽出
し、この抽出液から溶剤を留去して目的生成物で
あるハロゲン化ヒドロキシフエニル酢酸を単離す
る。
本発明の方法を実施することによつて、ハロゲ
ン化ヒドロキシマンデル酸から収率よくハロゲン
化ヒドロキシフエニル酢酸を製造することができ
る。
次に、本発明の実施例を示す。
実施例 １〜６
３−クロロ−４−ヒドロキシマンデル酸10.13
ｇ（50ミリモル）、５重量％pd−活性炭触媒0.2ｇ
および溶媒100mlをオートクレーブに仕込み、水
素を２〜2.5Kg／cm2（ゲージ）圧入し、80℃にお
いて撹拌しながら60分間反応させた。反応生成物
を冷却して前記触媒を別分離して反応液を得
た。未反応の３−クロロ−４−ヒドロキシマンデ
ル酸（CHMと略す）を液体クロマトグラフイー
で、また、生成した３−クロロ−４−ヒドロキシ
フエニル酢酸（CHPと略す）をガスクロマトグ
ラフイーでそれぞれ定量し、CMHの反応率、お
よびCHPの収率を計算した。
CHMの反応率＝（仕込みのCHMのモル数）−（未反応
のCHMのモル数）／（仕込みのCHMのモル数）×100
CHPの収率＝生成したCHPのモル数／仕込みのCHMのモル
数×100
その結果を第１表に示す。
The present invention relates to a method for producing halogenated hydroxyphenylacetic acid by reducing the hydroxyl group at the benzyl position by hydrogen reduction of halogenated hydroxymandelic acid in a halogenated benzene solvent. Halogenated hydroxyphenylacetic acid is useful as an intermediate raw material for pharmaceuticals and agricultural chemicals. For example, 3-chloro-4-hydroxyphenylacetic acid is a compound useful as an intermediate for 3-chloro-4-allyloxyphenylacetic acid (trade name: Alcrofenac), which is widely used as an anti-inflammatory analgesic. be. As a known method for obtaining halogenated hydroxyphenylacetic acid, for example, in JP-A-54-76542, 3-chloro-4-hydroxymandelic acid is prepared using red phosphorus, tin, or stannous chloride. A reduction method has been proposed, but it requires the use of a stoichiometric amount of a reducing agent, which poses great operational difficulties if carried out on an industrial scale. In order to solve this drawback, the present inventor investigated a method using hydrogen as an industrially advantageous reduction method. Conventionally, alcoholic solvents are often used in this type of reaction, so halogenated hydroxymandelic acid, such as 3-chloro-4-hydroxymandelic acid, is subjected to hydrogen reduction using a palladium catalyst in various alcoholic solvents such as ethyl alcohol. When attempted, not only the desired reduction of the hydroxyl group at the benzyl position but also the chlorine atom at the 3-position underwent hydrogenolysis, resulting in the desired reduction of the 3-position.
No chloro-4-hydroxyphenylacetic acid was produced, but an alkyl ester of 4-hydroxyphenylacetic acid was produced (see JP-A-56-71043). Therefore, we investigated to find conditions under which the chlorine atom at the 3-position would not be hydrogenolyzed, and found that in an aqueous solvent,
In the presence of a palladium catalyst and a zinc acetate cocatalyst,
It was discovered that when 3-chloro-4-hydroxymandelic acid is reduced with hydrogen, 3-chloro-4-hydroxyphenylacetic acid is produced with a yield of 75% and a selectivity of 83% (JP-A-56-81533). (see official bulletin). However, since this method requires the use of a combination of two types of catalysts, there are problems in recovering and reusing the catalysts. In other words, when the palladium catalyst and zinc acetate co-catalyst that have been used are recovered and used for the next reaction, not only does the reaction rate drop significantly and require a long reaction time, but also the yield of the target product is significantly reduced. Ta. The present inventor has arrived at the present invention as a result of intensive studies on a method for producing halogenated hydroxyphenylacetic acid by reducing halogenated hydroxymandelic acid with hydrogen using only a palladium catalyst. That is, the present invention relates to a method for producing halogenated hydroxyphenylacetic acid, which comprises reducing halogenated hydroxymandelic acid with hydrogen in a halogenated benzene solvent in the presence of a palladium catalyst. The halogenated hydroxymandelic acid used in the method of the present invention is represented by the following formula. (However, X in the formula represents a halogen atom) Examples thereof include chlorohydroxymandelic acid, bromohydroxymandelic acid, iodohydroxymandelic acid, fluorohydroxymandelic acid, and the like. Note that halogenated hydroxymandelic acid can be easily obtained, for example, by reacting a halogenated phenol and glyoxylic acid in the presence of an alkali. Examples of halogenated benzenes used in the method of the invention include chlorobenzene, bromobenzene, O
-dichlorobenzene, m-dichlorobenzene, O
-dibromobenzene and m-dibromobenzene, among which O-dichlorobenzene, m-dichlorobenzene, O-dibromobenzene and m-dibromobenzene are preferred. The amount of these solvents to be used is preferably 0.5 to 10, particularly 1 to 5, per mole of halogenated hydroxymandelic acid as the raw material. In addition, the palladium catalyst used in the method of the present invention is metal palladium in a carrier such as activated carbon, graphite, silica gel, calcium carbonate, alumina, etc.
A loading of up to 10% by weight, preferably 0.5 to 8% by weight, is suitable. Note that the palladium catalyst is prepared by dissolving palladium chloride in concentrated hydrochloric acid, impregnating the carrier as described above, and then subjecting the solution to reduction treatment with hydrogen or the like as necessary to remove residual hydrochloric acid. The amount of palladium catalyst used is preferably 0.001 to 2.0 g, particularly 0.01 to 0.5 g, in terms of metal palladium, per mole of halogenated hydroxymandelic acid as a raw material. The hydrogen used is pure hydrogen or a hydrogen-containing gas mixed with an inert gas such as nitrogen. Hydrogen pressure is 0.1-5Kg/cm 2 (gauge), especially 1-3Kg/cm 2
(gauge) is preferred. Also, the reaction temperature is 60-110
℃, especially 70 to 90℃ is preferred. The reaction time depends on the reaction temperature, but is usually 30 minutes to 120 minutes. The reaction product obtained by the method of the present invention is
It is a halogenated hydroxyphenyl acetic acid corresponding to a halogenated hydroxymandelic acid, and is represented by the following formula. (However, X in the formula represents a halogen atom) The reaction product obtained by the reaction according to the method of the present invention is usually cooled, the palladium catalyst is separately removed, and the solvent is distilled off from the liquid. The resulting viscous oil is extracted with a solvent such as benzene, toluene, or xylene, and the solvent is distilled off from this extract to isolate the desired product, halogenated hydroxyphenylacetic acid. By carrying out the method of the present invention, halogenated hydroxyphenylacetic acid can be produced from halogenated hydroxymandelic acid with good yield. Next, examples of the present invention will be shown. Examples 1-6 3-chloro-4-hydroxymandelic acid 10.13
g (50 mmol), 5 wt% PD-activated carbon catalyst 0.2 g
and 100 ml of the solvent were charged into an autoclave, hydrogen was pressurized at 2 to 2.5 Kg/cm 2 (gauge), and the reaction was carried out at 80° C. for 60 minutes with stirring. The reaction product was cooled and the catalyst was separated to obtain a reaction solution. Quantify unreacted 3-chloro-4-hydroxymandelic acid (abbreviated as CHM) by liquid chromatography and quantify generated 3-chloro-4-hydroxyphenylacetic acid (abbreviated as CHP) by gas chromatography. Then, the reaction rate of CMH and the yield of CHP were calculated. Reaction rate of CHM = (Number of moles of CHM charged) - (Number of moles of unreacted CHM) / (Number of moles of CHM charged) x 100 CHP yield = Number of moles of CHP produced / Number of moles of CHM charged Number of moles x 100 The results are shown in Table 1.
【表】
実施例 ７〜12
各種ハロゲン化ヒドロキシマンデル酸50ミリモ
ル、５重量％Pd−活性炭触媒0.2ｇ、および溶媒
のＯ−ジクロロベンゼン100mlをオートクレーブ
に仕込み、後の操作は実施例１〜６と同様に行つ
た。結果を第２表に示す。反応率、収率は実施例
１〜６に準じて算出した。[Table] Examples 7 to 12 50 mmol of various halogenated hydroxymandelic acids, 0.2 g of 5 wt% Pd-activated carbon catalyst, and 100 ml of O-dichlorobenzene as a solvent were charged into an autoclave, and the subsequent operations were carried out as in Examples 1 to 6. I went in the same way. The results are shown in Table 2. The reaction rate and yield were calculated according to Examples 1-6.
Claims (1)
ム触媒の存在下、ハロゲン化ベンゼン溶媒中で水
素還元することを特徴とするハロゲン化ヒドロキ
シフエニル酢酸の製造法。1. A method for producing halogenated hydroxyphenylacetic acid, which comprises reducing halogenated hydroxymandelic acid with hydrogen in a halogenated benzene solvent in the presence of a palladium catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57035786A JPS58154530A (en) | 1982-03-09 | 1982-03-09 | Preparation of halogenated hydroxylphenylacetic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57035786A JPS58154530A (en) | 1982-03-09 | 1982-03-09 | Preparation of halogenated hydroxylphenylacetic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58154530A JPS58154530A (en) | 1983-09-14 |
| JPH0231703B2 true JPH0231703B2 (en) | 1990-07-16 |
Family
ID=12451586
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57035786A Granted JPS58154530A (en) | 1982-03-09 | 1982-03-09 | Preparation of halogenated hydroxylphenylacetic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58154530A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646181A (en) * | 2015-12-29 | 2016-06-08 | 中山大学 | Preparation method of 2-bromine-4-hydroxyphenylacetic acid |
-
1982
- 1982-03-09 JP JP57035786A patent/JPS58154530A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58154530A (en) | 1983-09-14 |
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