JP5008796B2 - Method for producing aromatic carboxylic acid - Google Patents
Method for producing aromatic carboxylic acid Download PDFInfo
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- JP5008796B2 JP5008796B2 JP2001012406A JP2001012406A JP5008796B2 JP 5008796 B2 JP5008796 B2 JP 5008796B2 JP 2001012406 A JP2001012406 A JP 2001012406A JP 2001012406 A JP2001012406 A JP 2001012406A JP 5008796 B2 JP5008796 B2 JP 5008796B2
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- reaction
- acid
- carboxylic acid
- aromatic carboxylic
- producing aromatic
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Description
【０００１】
【産業上の利用分野】
この発明は、抗アレルギー薬の製造上の重要な中間体化合物である式（Ｉ）
【０００２】
【化１】
で表される2-ベンジル安息香酸の製造方法に関する。
【０００４】
【従来の技術】
式（Ｉ）で示される2-ベンジル安息香酸は、市販され容易に入手出来る式（ＩＩ)
【０００５】
【化２】
で示される2-ベンゾイル安息香酸を還元することにより生産されてきた。
それらのうち最も工業的で、一般的に採用されうる還元反応の例としては、触媒的水素化反応を挙げることができる。これまでの触媒的水素添加反応は、パラジウム系触媒を用いる場合、酸性条件下の反応例、中性条件下の２、３の反応例が知られている。しかしながら、経済的かつ工業的に実施するには問題点が有った。即ち、酸性条件下での反応に際しては、特殊で高価な耐酸性の反応槽を必要とする例（ホーニング E.C.ら；ジャーナル・オブ・アメリカン・ケミカル・ソサイエティー、71巻、1036-1037頁、1949年 Honing E.C. et al; J. of American Chemical Society Vol. 71, 1036-1037, 1949）、中性条件での反応に於いては、メタノールまたはエタノール溶媒中、基質に対して２２重量％と云う大量の触媒を使用し、２０ｋｇ/ｃｍ２の水素圧中で反応させることが必要とされている例（ジャン フーシェ ら；ブレティン・デュ・ラ・ソシエテ・キミク・デュ・フランス、3113-3130頁、1972年；（Jean Fouche et al, Bulletin du la Societe Chimique de France 3113-3130, 1972)などが知られているのみであった。またニッケル系触媒を用いる場合では、比較的高い温度と１００ｋｇ/ｃｍ２以上というような高圧条件が必要であった（米国特許第2053430号）。
【０００７】
さらに、式（ＩＩ)で示される化合物を還元して得る他の反応の例としては、塩酸−亜鉛アマルガムによる還元、亜鉛末−硫酸銅−アンモニア水による高温での還元等が知られているが、いずれも製造に際して当該物質生産のための専用設備が必要となるばかりでなく、廃液処理等の面で環境に対する一層の配慮も必要となり、適量を、簡単に実施するには不向きである。
【０００８】
【発明が解決しようとする課題】
抗アレルギー薬製造上の重要中間体である2-ベンジル安息香酸を、汎用設備を用いて、低い水素圧下の工業的に実施し易い方法で容易かつ安価に製造する方法を提供する。
【０００９】
【課題を解決するための手段】
本発明者等は、式（ＩＩ)で示される化合物を触媒的還元する反応について鋭意検討を行った結果、2-ベンゾイル安息香酸をイソプロピルアルコール溶媒中、パラジウムー炭素触媒を用いて接触還元することにより、従来の反応における触媒使用量よりも遥かに少ない量で、かつ遥かに低い水素圧下に反応を行って、2-ベンジル安息香酸が極めて好収率に得られることを見い出だし、この知見に基づいて本発明を完成した。
【００１０】
すなわち、本発明は、 イソプロピルアルコール溶媒中、2-ベンゾイル安息香酸を接触還元反応により還元することを特徴とする2-ベンジル安息香酸の製造方法である。
本発明の接触還元反応においては、パラジウム−炭素触媒を２-１０重量％量、より好ましくは２-５％存在させる。すなわち、従来の接触還元反応に比べて遥かに少量の触媒量で好収率の結果が得られる。
又、接触還元反応における水素圧は、５〜１５ｋｇ/ｃｍ２、より好ましくは、８−１２Ｋｇ/ｃｍ2程度の緩和な条件下であり、そのため特別高価な専用設備を必要としない。
【００１１】
本発明の接触還元反応に当たっては、２-ベンゾイル安息香酸を２-１０重量倍量のイソプロピルアルコールに溶解し、２-１０％量のパラジウムー炭素触媒（炭素上に３-１０％を担持させたもの）を加え、通常の加圧反応容器中で水素を通気しながら反応させる。
反応温度は、７０〜１３０℃、水素圧８-１２Ｋｇ/ｃｍ2程度である。
尚、本発明の出発物質である式(ＩＩ)で示される２−ベンゾイル安息香酸は、塩化アルミニウム等の触媒存在下に、無水フタル酸をベンゼンに作用させる公知の方法によって容易に得られる。
【００１２】
以下、本発明を実施例を用いて説明するが、本発明はこれに限定される物ではない。
【実施例】
実施例1
250ｇの市販の2-ベンゾイル安息香酸を600ｇのイソプロピルアルコールに溶解させ、オートクレーブに仕込んだ。ついで5.8ｇの5％パラジウム−炭素を加え、水素圧10Ｋｇ/ｃｍ２になるよう水素を導入する。温度を上昇させ、90℃程度に昇温させると、徐々に水素の吸収が始まる。約6時間をかけて110℃まで昇温させると水素の吸収が終了した。反応混合物を冷却後、触媒を濾別し、溶媒を濃縮、溜去して、粗2-ベンジル安息香酸240ｇを得た。
これを水から再結晶して融点116℃の白色針状結晶 212ｇを得た(収率90.2％)。
本結晶のＮＭＲ，ＩＲスペクトルを測定し、いずれも既知のスペクトルデータと比較し完全に一致したので2-ベンジル安息香酸であると確認した。｛ジ・アルドリッチ・ライブラリー・オブ・エヌエムアール・スペクトラ、第６巻１８３ページＡ（The ALDRICH LIBRARY of NMR SPECTRA,Vol.6,183 A） 及びジ・アルドリッチ・ライブラリー・オブ・インフラレッド・スペクトラ、８６３ページＡ（The ALDRICH LIBRARY of INFRARED SPECTRA,863 A）など｝。
【００１３】
【発明の効果】
以上の如く、本発明の方法は、2-ベンジル安息香酸が従来技術に比し遥かに少ない触媒量で且つ低い水素圧下で進行し、抗アレルギー薬の重要中間体である2-ベンジル安息香酸が容易かつ好収率に得られる。
また、本方法の還元反応は、反応槽として汎用のものが使用でき、設備コストの面でも有利である。[0001]
[Industrial application fields]
The present invention relates to a compound of formula (I) which is an important intermediate compound in the production of antiallergic drugs.
[0002]
[Chemical 1]
The present invention relates to a method for producing 2-benzylbenzoic acid represented by the formula:
[0004]
[Prior art]
2-Benzylbenzoic acid represented by the formula (I) is commercially available and easily available.
[0005]
[Chemical formula 2]
It has been produced by reducing 2-benzoylbenzoic acid represented by
Among these, as an example of the most industrial and generally employable reduction reaction, a catalytic hydrogenation reaction can be mentioned. As for the conventional catalytic hydrogenation reaction, when a palladium catalyst is used, a reaction example under an acidic condition and a few reaction examples under a neutral condition are known. However, there were problems in implementing economically and industrially. That is, an example in which a special and expensive acid-resistant reaction tank is required for the reaction under acidic conditions (Honing EC et al., Journal of American Chemical Society, 71, 1036-1037, 1949 Honing EC et al; J. of American Chemical Society Vol. 71, 1036-1037, 1949). In the reaction under neutral conditions, a large amount of 22% by weight based on the substrate in methanol or ethanol solvent. Example of using a catalyst and reacting in a hydrogen pressure of 20 kg / cm 2 (Jean Fouchet et al .; Bulletin du la Societye Kimique du France, 3113-3130, 1972 (Jean Fouche et al, Bulletin du la Societe Chimique de France 3113-3130, 1972), etc. Also, when using a nickel-based catalyst, a relatively high temperature and 100 kg / cm 2 or more High pressure strip It was required (U.S. Pat. No. 2,053,430).
[0007]
Further, examples of other reactions obtained by reducing the compound represented by the formula (II) include reduction with hydrochloric acid-zinc amalgam, reduction with zinc powder-copper sulfate-aqueous ammonia at high temperature, and the like. In both cases, not only special equipment for production of the substance is required in production, but also environmental considerations are necessary in terms of waste liquid treatment and the like, which is unsuitable for easily implementing an appropriate amount.
[0008]
[Problems to be solved by the invention]
Provided is a method for easily and inexpensively producing 2-benzylbenzoic acid, which is an important intermediate in the production of antiallergic drugs, using a general-purpose facility and in an industrially easy manner under a low hydrogen pressure.
[0009]
[Means for Solving the Problems]
As a result of intensive investigations on the catalytic reduction of the compound represented by the formula (II), the present inventors have conducted catalytic reduction of 2-benzoylbenzoic acid in a isopropyl alcohol solvent using a palladium-carbon catalyst. We have found that 2-benzylbenzoic acid can be obtained in extremely good yields by carrying out the reaction at a much lower amount of hydrogen than in the conventional reaction and under a much lower hydrogen pressure. Based on this, the present invention has been completed.
[0010]
That is, the present invention is a method for producing 2-benzylbenzoic acid, which comprises reducing 2-benzoylbenzoic acid in an isopropyl alcohol solvent by a catalytic reduction reaction.
In the catalytic reduction reaction of the present invention, the palladium-carbon catalyst is present in an amount of 2-10% by weight, more preferably 2-5%. That is, a good yield can be obtained with a much smaller amount of catalyst compared to the conventional catalytic reduction reaction.
Further, the hydrogen pressure in the catalytic reduction reaction is 5 to 15 kg / cm 2 , more preferably about 8-12 Kg / cm 2 , so that no special expensive special equipment is required.
[0011]
In the catalytic reduction reaction of the present invention, 2-benzoylbenzoic acid is dissolved in 2-10 times by weight of isopropyl alcohol, and 2-10% of palladium-carbon catalyst (3-10% supported on carbon) is obtained. ), And the reaction is carried out while ventilating hydrogen in a normal pressurized reaction vessel.
The reaction temperature is about 70 to 130 ° C. and the hydrogen pressure is about 8 to 12 kg / cm 2 .
The 2-benzoylbenzoic acid represented by the formula (II), which is the starting material of the present invention, can be easily obtained by a known method in which phthalic anhydride is allowed to act on benzene in the presence of a catalyst such as aluminum chloride.
[0012]
EXAMPLES Hereinafter, although this invention is demonstrated using an Example, this invention is not a thing limited to this.
【Example】
Example 1
250 g of commercially available 2-benzoylbenzoic acid was dissolved in 600 g of isopropyl alcohol and charged into an autoclave. Next, 5.8 g of 5% palladium-carbon is added, and hydrogen is introduced so that the hydrogen pressure becomes 10 kg / cm 2 . When the temperature is raised to about 90 ° C, hydrogen absorption begins gradually. When the temperature was raised to 110 ° C. over about 6 hours, hydrogen absorption was completed. After cooling the reaction mixture, the catalyst was filtered off, and the solvent was concentrated and distilled off to obtain 240 g of crude 2-benzylbenzoic acid.
This was recrystallized from water to obtain 212 g of white needle crystals having a melting point of 116 ° C. (yield 90.2%).
NMR and IR spectra of this crystal were measured, and both were confirmed to be 2-benzylbenzoic acid because they were completely consistent with known spectral data. {The ALDRICH LIBRARY of NMR SPECTRA, Vol.6, 183 A) and The Aldrich Library of Infrared Spectra, 863 Page A (The ALDRICH LIBRARY of INFRARED SPECTRA, 863 A)}.
[0013]
【Effect of the invention】
As described above, according to the method of the present invention, 2-benzylbenzoic acid proceeds under a much lower catalytic amount and lower hydrogen pressure than in the prior art, and 2-benzylbenzoic acid, which is an important intermediate for antiallergic drugs, is produced. Easy and good yield.
Moreover, the reduction reaction of this method can use a general-purpose reaction tank, which is advantageous in terms of equipment cost.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001012406A JP5008796B2 (en) | 2001-01-19 | 2001-01-19 | Method for producing aromatic carboxylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001012406A JP5008796B2 (en) | 2001-01-19 | 2001-01-19 | Method for producing aromatic carboxylic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002212134A JP2002212134A (en) | 2002-07-31 |
| JP5008796B2 true JP5008796B2 (en) | 2012-08-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001012406A Expired - Fee Related JP5008796B2 (en) | 2001-01-19 | 2001-01-19 | Method for producing aromatic carboxylic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5008796B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104447300A (en) * | 2014-12-02 | 2015-03-25 | 千辉药业（安徽）有限责任公司 | Synthetic method of 2-benzyl benzoic acid |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0407955A1 (en) * | 1989-07-12 | 1991-01-16 | Boehringer Ingelheim Kg | New hetrazepines acting as PAF antagonists, process for their production and their use as drugs |
| JPH08225482A (en) * | 1995-02-22 | 1996-09-03 | Dai Ichi Seiyaku Co Ltd | Tetralone-related compound and its production |
| JPH11292808A (en) * | 1998-04-10 | 1999-10-26 | Sumitomo Chem Co Ltd | Production of 4-phenylbutyl halide |
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2001
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| Publication number | Publication date |
|---|---|
| JP2002212134A (en) | 2002-07-31 |
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