JPH0135825B2 - - Google Patents
Info
- Publication number
- JPH0135825B2 JPH0135825B2 JP55076827A JP7682780A JPH0135825B2 JP H0135825 B2 JPH0135825 B2 JP H0135825B2 JP 55076827 A JP55076827 A JP 55076827A JP 7682780 A JP7682780 A JP 7682780A JP H0135825 B2 JPH0135825 B2 JP H0135825B2
- Authority
- JP
- Japan
- Prior art keywords
- toluoyl
- methyl
- acetic acid
- pyrrole
- carboxypyrrole
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 150000003512 tertiary amines Chemical class 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- YASSGZAFJWNSPO-UHFFFAOYSA-N 2-(carboxymethyl)-1h-pyrrole-3-carboxylic acid Chemical compound OC(=O)CC=1NC=CC=1C(O)=O YASSGZAFJWNSPO-UHFFFAOYSA-N 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000013078 crystal Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- QLLUGZYSTABSKS-UHFFFAOYSA-N 2-(carboxymethyl)-1-methyl-5-(4-methylbenzoyl)pyrrole-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(C(O)=O)=C(CC(O)=O)N1C QLLUGZYSTABSKS-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- -1 1-methyl-5-(p-toluoyl)-3-ethoxycarbonylpyrrole-2-ethyl acetate Chemical compound 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- GVUHUYQEAGMUNJ-UHFFFAOYSA-N 2-(1h-pyrrol-2-yl)acetic acid Chemical compound OC(=O)CC1=CC=CN1 GVUHUYQEAGMUNJ-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Chemical compound OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- HOPPBOBZKTVAEA-UHFFFAOYSA-N 2-[3-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetic acid Chemical compound C1(=CC=C(C=C1)C(=O)C1=C(NC=C1)CC(=O)O)C HOPPBOBZKTVAEA-UHFFFAOYSA-N 0.000 description 1
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- WIDHUKOADYLKIO-UHFFFAOYSA-N ethyl 2-(2-ethoxy-2-oxoethyl)-1-methylpyrrole-3-carboxylate Chemical compound CCOC(=O)CC1=C(C(=O)OCC)C=CN1C WIDHUKOADYLKIO-UHFFFAOYSA-N 0.000 description 1
- OIQILCRLOSXOMN-UHFFFAOYSA-N ethyl 2-(2-ethoxy-2-oxoethyl)-4-methyl-5-(4-methylbenzoyl)-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=C(CC(=O)OCC)NC(C(=O)C=2C=CC(C)=CC=2)=C1C OIQILCRLOSXOMN-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- RFLLKFAICZHHBA-UHFFFAOYSA-M sodium 2-(1H-pyrrol-2-yl)acetate dihydrate Chemical compound [Na+].O.O.N1C(=CC=C1)CC(=O)[O-] RFLLKFAICZHHBA-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、トルメチンの一般名で知られている
鎮痛・消炎剤、１―メチル―５―（ｐ―トルオイ
ル）ピロール―２―酢酸の新規な製造法に関す
る。更に詳しくは、１―メチル―５―（ｐ―トル
オイル）―３―カルボキシピロール―２―酢酸を
水中で無機塩基または第三アミンの存在下に加熱
することを特徴とする１―メチル―５―（ｐ―ト
ルオイル）ピロール―２―酢酸の製造法に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 1-methyl-5-(p-toluoyl)pyrrole-2-acetic acid, an analgesic and anti-inflammatory agent known by the common name tolmetin. More specifically, 1-methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid is heated in water in the presence of an inorganic base or a tertiary amine. This invention relates to a method for producing (p-toluoyl)pyrrole-2-acetic acid.
本発明の方法を反応式で示せば次の通りであ
る。 The reaction formula of the method of the present invention is as follows.
本発明の方法は、１―メチル―５―（ｐ―トル
オイル）―３―カルボキシピロール―２―酢酸
（）〔以下、ジカルボン酸（）と記す。〕を水
中で無機塩基または第三アミンの存在下に加熱す
ることにより行なわれる。無機塩基の好ましい具
体例としては、水酸化リチウム、水酸化ナトリウ
ム、水酸化カリウムのような水酸化アルカリ、炭
酸リチウム、炭酸ナトリウム、炭酸カリウムのよ
うな炭酸アルカリ、重炭酸リチウム、重炭酸ナト
リウム、重炭酸カリウムのような重炭酸アルカ
リ、水酸化アンモニウム等があげられる。また、
第三アミンの好ましい具体例としては、トリメチ
ルアミン、トリエチルアミン、トリ―ｎ―プロピ
ルアミン、トリ―ｎ―ブチルアミン、Ｎ―メチル
ピペリジン、Ｎ―メチルモルホリン、Ｎ，Ｎ，
N′，N′―テトラメチルエチレンジアミン等があ
げられる。塩基の使用量としては、ジカルボン酸
（）１モルに対して１〜1.3当量が好ましいが、
第三アミンの場合には更に大量を用いてもよい。
反応温度としては、約140℃ないし約230℃の範囲
が用いられるが、好ましくは約180℃ないし約200
℃の範囲である。反応時間は通常１〜４時間であ
る。本反応は必要に応じて加圧下に行なわれる。 The method of the present invention uses 1-methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid () [hereinafter referred to as dicarboxylic acid ()]. ] in water in the presence of an inorganic base or tertiary amine. Preferred specific examples of inorganic bases include alkali hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide, alkali carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate, lithium bicarbonate, sodium bicarbonate, and Examples include alkali bicarbonate such as potassium carbonate, ammonium hydroxide, etc. Also,
Preferred specific examples of the tertiary amine include trimethylamine, triethylamine, tri-n-propylamine, tri-n-butylamine, N-methylpiperidine, N-methylmorpholine, N,N,
Examples include N',N'-tetramethylethylenediamine. The amount of the base used is preferably 1 to 1.3 equivalents per mol of dicarboxylic acid (),
In the case of tertiary amines, even larger amounts may be used.
The reaction temperature used is in the range of about 140°C to about 230°C, preferably about 180°C to about 200°C.
℃ range. The reaction time is usually 1 to 4 hours. This reaction is carried out under pressure if necessary.
反応終了後、目的物の単離・精製は常法により
行なわれる。 After the reaction is completed, isolation and purification of the target product are carried out by conventional methods.
本発明の方法によれば、ジカルボン酸（）か
ら１―メチル―５―（ｐ―トルオイル）ピロール
―２―酢酸（）を好収率で得ることができる。 According to the method of the present invention, 1-methyl-5-(p-toluoyl)pyrrole-2-acetic acid () can be obtained in good yield from dicarboxylic acid ().
ジカルボン酸（）は新規物質であり、例えば
以下の方法により製造することができる。 Dicarboxylic acid () is a new substance, and can be produced, for example, by the following method.
化合物（）と化合物（）との反応は、通常
のFriedel―Crafts反応条件下に実施することが
でき、例えば塩化メチレン、塩化エチレン、二硫
化炭素、ニトロベンゼン等の溶媒中、塩化アルミ
ニウムのようなルイス酸の存在下に、約０℃ない
し約90℃で行なわれる。 The reaction between compound () and compound () can be carried out under the usual Friedel-Crafts reaction conditions, for example in a solvent such as methylene chloride, ethylene chloride, carbon disulfide, nitrobenzene, etc., or in a Lewis compound such as aluminum chloride. It is carried out in the presence of an acid at a temperature of about 0°C to about 90°C.
化合物（）からジカルボン酸（）への加水
分解は、常法に従つて実施することができ、例え
ば含水エタノール等の溶媒中、水酸化ナトリウ
ム、水酸化カリウム等の塩基の存在下に加熱する
ことにより行なわれる。 Hydrolysis of compound () to dicarboxylic acid () can be carried out according to a conventional method, for example, by heating in a solvent such as aqueous ethanol in the presence of a base such as sodium hydroxide or potassium hydroxide. This is done by
以下に参考例および実施例をあげて本発明を更
に具体的に説明するが、本発明はこれらの実施例
に限定されるものではない。 The present invention will be explained in more detail with reference to Reference Examples and Examples below, but the present invention is not limited to these Examples.
参考例 １
１―メチル―３―エトキシカルボニルピロール
―２―酢酸エチル9.6ｇを塩化エチレン30mlに溶
解し、加熱還流させる。この還流溶液に、ｐ―ト
ルオイルクロリド6.80ｇと塩化アルミニウム5.85
ｇとを塩化エチレン30mlに溶解した溶液を30分に
わたつて滴下する。滴下終了後、更に６時間加熱
還流を続ける。反応液を氷―塩酸に注入し、塩化
エチレン層を分離し、10％炭酸ナトリウム水溶
液、次いで水で洗浄する。無水硫酸ナトリウムで
乾燥した後、塩化エチレンを留去して油状の残渣
を得る。これを塩化メチレンに溶解し、シリカゲ
ルカラムクロマトグラフイーを行なう。塩化メチ
レン―ｎ―ヘキサン（２：１）で溶出して、１―
メチル―５―（ｐ―トルオイル）―３―エトキシ
カルボニルピロール―２―酢酸エチル6.27ｇを得
た。イソプロパノールより再結晶すると融点99〜
100℃を示す。Reference Example 1 9.6 g of ethyl 1-methyl-3-ethoxycarbonylpyrrole-2-acetate is dissolved in 30 ml of ethylene chloride and heated to reflux. To this reflux solution, add 6.80 g of p-toluoyl chloride and 5.85 g of aluminum chloride.
A solution prepared by dissolving G and g in 30 ml of ethylene chloride was added dropwise over 30 minutes. After the dropwise addition is completed, heating and refluxing is continued for an additional 6 hours. The reaction solution is poured into ice-hydrochloric acid, and the ethylene chloride layer is separated and washed with a 10% aqueous sodium carbonate solution and then with water. After drying over anhydrous sodium sulfate, ethylene chloride is distilled off to obtain an oily residue. This was dissolved in methylene chloride and subjected to silica gel column chromatography. Elute with methylene chloride-n-hexane (2:1) to obtain 1-
6.27 g of ethyl methyl-5-(p-toluoyl)-3-ethoxycarbonylpyrrole-2-acetate was obtained. Melting point: 99~ when recrystallized from isopropanol
Indicates 100℃.
元素分析値 C20H23NO5として
計算値：C67.21 H6.49 N3.92
実験値：C67.28 H6.59 N3.90
NMR（CDCl3）
δ：1.28（6H、ｔ）、2.42（3H、ｓ）、
3.95（3H、ｓ）、4.00〜4.60（6H、ｍ）、
7.15（1H、ｓ）、7.32（2H、ｄ）、
7.80（2H、ｄ）
参考例 ２
25％水酸化ナトリウム水溶液20mlとエタノール
10mlの混液に、１―メチル―５―（ｐ―トルオイ
ル）―３―エトキシカルボニルピロール―２―酢
酸エチル2.0ｇを加え、95℃に２時間加熱した後、
濃塩酸で酸性にする。析出する結晶を取し、イ
ソプロパノールより再結晶して、１―メチル―５
―（ｐ―トルオイル）―３―カルボキシピロール
―２―酢酸1.43ｇを得た。 Elemental analysis value C 20 H 23 NO 5 Calculated value: C67.21 H6.49 N3.92 Experimental value: C67.28 H6.59 N3.90 NMR (CDCl 3 ) δ: 1.28 (6H, t), 2.42 ( 3H, s), 3.95 (3H, s), 4.00-4.60 (6H, m), 7.15 (1H, s), 7.32 (2H, d), 7.80 (2H, d) Reference example 2 25% sodium hydroxide aqueous solution 20ml and ethanol
Add 2.0 g of 1-methyl-5-(p-toluoyl)-3-ethoxycarbonylpyrrole-2-ethyl acetate to 10 ml of the mixed solution, and after heating to 95°C for 2 hours,
Acidify with concentrated hydrochloric acid. The precipitated crystals were collected and recrystallized from isopropanol to give 1-methyl-5
1.43 g of -(p-toluoyl)-3-carboxypyrrole-2-acetic acid was obtained.
融点 255〜257℃（分解）
元素分析値 C16H15NO5として
計算値：C63.78 H5.02 N4.65
実験値：C63.89 H5.03 N4.61
実施例 １
水酸化ナトリウム0.13ｇを含有する水酸化ナト
リウム水溶液30mlに１―メチル―５―（ｐ―トル
オイル）―３―カルボキシピロール―２―酢酸
0.9ｇを加え、封管中200℃に１時間加熱する。冷
後、反応液を塩化メチレン10mlで抽出する。水層
を希塩酸で酸性とし、析出する結晶を取する。
これを10％水酸化ナトリウム水溶液10mlに加熱溶
解したのち放置すると結晶が析出する。この結晶
を取し乾燥して、１―メチル―５―（ｐ―トル
オイル）ピロール―２―酢酸ナトリウム・二水和
物0.66ｇを得た。融点 300℃以上
元素分析値 C15H14NO3Na・2H2Oとして
計算値：C57.14 H5.75 N4.44
実験値：C56.82 H5.76 N4.34
上記ナトリウム塩を適量の水に溶解し、希塩酸
で酸性とし、析出する結晶を取し乾燥して、１
―メチル―５―（ｐ―トルオイル）ピロール―２
―酢酸を得た。融点 158〜160℃（分解）
このもののIRスペクトルは、特公昭50−37668
に記載の方法に従つて合成して標品のそれに一致
した。Melting point 255-257℃ (decomposition) Elemental analysis value C 16 H 15 NO 5 Calculated value: C63.78 H5.02 N4.65 Experimental value: C63.89 H5.03 N4.61 Example 1 Sodium hydroxide 0.13g 1-methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid in 30 ml of aqueous sodium hydroxide solution containing
Add 0.9g and heat at 200°C for 1 hour in a sealed tube. After cooling, the reaction solution is extracted with 10 ml of methylene chloride. The aqueous layer is made acidic with dilute hydrochloric acid and the precipitated crystals are collected.
If this is heated and dissolved in 10 ml of a 10% aqueous sodium hydroxide solution and then left to stand, crystals will precipitate. The crystals were collected and dried to obtain 0.66 g of 1-methyl-5-(p-toluoyl)pyrrole-2-sodium acetate dihydrate. Melting point 300℃ or higher Elemental analysis value C 15 H 14 NO 3 Na・2H 2 O Calculated value: C57.14 H5.75 N4.44 Experimental value: C56.82 H5.76 N4.34 Add the above sodium salt to an appropriate amount of water. Dissolve it in water, make it acidic with dilute hydrochloric acid, remove the precipitated crystals and dry it.
-Methyl-5-(p-toluoyl)pyrrole-2
- Acetic acid was obtained. Melting point: 158-160℃ (decomposition) The IR spectrum of this product is
It was synthesized according to the method described in , and it matched that of the standard product.
実施例 ２
１―メチル―５―（ｐ―トルオイル）―３―カ
ルボキシピロール―２―酢酸1.0ｇおよびトリエ
チルアミン0.34ｇを水40mlに加え、封管中200℃
に１時間加熱する。少量の析出物を去し、液
を濃塩酸で酸性にすると、結晶が析出する。結晶
を取し、10％水酸化ナトリウム水溶液10mlに加
熱溶解したのち放置すると結晶が析出する。この
結晶を取し乾燥して、１―メチル―５―（ｐ―
トルオイル）ピロール―２―酢酸ナトリウム・二
水和物0.80ｇを得た。Example 2 1.0 g of 1-methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid and 0.34 g of triethylamine were added to 40 ml of water and heated at 200°C in a sealed tube.
Heat for 1 hour. A small amount of precipitate is removed and the solution is made acidic with concentrated hydrochloric acid to precipitate crystals. Take the crystals, heat and dissolve them in 10ml of a 10% aqueous sodium hydroxide solution, and then leave to stand to precipitate crystals. The crystals were collected, dried, and 1-methyl-5-(p-
0.80 g of sodium pyrrole-2-acetate dihydrate (toluoyl) was obtained.
実施例 ３
１―メチル―５―（ｐ―トルオイル）―３―カ
ルボキシピロール―２―酢酸0.9ｇおよび1Nアン
モニア水3.3mlを水40mlに加え、封管中200℃に１
時間加熱する。反応液を実施例２と同様に処理し
て、１―メチル―５―（ｐ―トルオイル）ピロー
ル―２―酢酸ナトリウム・二水和物0.76ｇを得
た。Example 3 0.9 g of 1-methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid and 3.3 ml of 1N ammonia water were added to 40 ml of water, and the mixture was heated to 200°C in a sealed tube.
Heat for an hour. The reaction solution was treated in the same manner as in Example 2 to obtain 0.76 g of 1-methyl-5-(p-toluoyl)pyrrole-2-sodium acetate dihydrate.
以下に、比較として、１―メチル―５―（ｐ―
トルオイル）―３―カルボキシピロール―２―酢
酸を通常の脱炭酸反応条件下（例えば特公昭49−
47752号公報に記載）に処理した実験結果を示す
が、本発明の方法の場合と異なり、２位の酢酸部
分のカルボキシル基の脱炭酸が起こり目的とする
１―メチル―５―（ｐ―トルオイル）ピロール―
２―酢酸を得ることができなかつた。 For comparison, 1-methyl-5-(p-
toluoyl)-3-carboxypyrrole-2-acetic acid under normal decarboxylation reaction conditions (for example,
47752), but unlike the method of the present invention, the carboxyl group of the acetic acid moiety at the 2-position is decarboxylated, resulting in the desired 1-methyl-5-(p-toluoyl). ) Pyrrole-
2-Acetic acid could not be obtained.
参考例 ３（比較例）
１―メチル―５―（ｐ―トルオイル）―３―カ
ルボキシピロール―２―酢酸0.50ｇをキノリン８
mlに加え、160℃に８時間加熱する。冷後、希塩
酸を加えて酸性とし、析出する結晶を取する。
この結晶を乾燥した後、エタノールより再結晶し
て、１，２―ジメチル―５―（ｐ―トルオイル）
ピロール―３―カルボン酸0.32ｇを得た。Reference Example 3 (Comparative Example) 0.50 g of 1-methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid was added to quinoline 8
ml and heat to 160°C for 8 hours. After cooling, add dilute hydrochloric acid to make it acidic and remove the precipitated crystals.
After drying these crystals, they were recrystallized from ethanol to produce 1,2-dimethyl-5-(p-toluoyl).
0.32 g of pyrrole-3-carboxylic acid was obtained.
融点 248〜249℃（分解）
元素分析値 C15H15NO3として
計算値：C70.02 H5.88 N5.44
実験値：C69.87 H5.89 N5.63
参考例 ４（比較例）
１―メチル―５―（ｐ―トルオイル）―３―カ
ルボキシピロール―２―酢酸0.50ｇおよび亜クロ
ム酸銅50mgをキノリン８mlに加え、140℃に３時
間加熱する。冷後、反応液を参考例３と同様に処
理して、１，２―ジメチル―５―（ｐ―トルオイ
ル）ピロール―３―カルボン酸0.34ｇを得た。Melting point 248-249℃ (decomposition) Elemental analysis value C 15 H 15 NO 3 Calculated value: C70.02 H5.88 N5.44 Experimental value: C69.87 H5.89 N5.63 Reference example 4 (comparative example) 1 Add 0.50 g of -methyl-5-(p-toluoyl)-3-carboxypyrrole-2-acetic acid and 50 mg of copper chromite to 8 ml of quinoline and heat to 140°C for 3 hours. After cooling, the reaction solution was treated in the same manner as in Reference Example 3 to obtain 0.34 g of 1,2-dimethyl-5-(p-toluoyl)pyrrole-3-carboxylic acid.
Claims (1)
カルボキシルピロール―２―酢酸を水中で無機塩
基または第三アミンの存在下に加熱することを特
徴とする１―メチル―５―（ｐ―トルオイル）ピ
ロール―２―酢酸の製造法。1 1-Methyl-5-(p-toluoyl)-3-
A method for producing 1-methyl-5-(p-toluoyl)pyrrole-2-acetic acid, which comprises heating carboxylpyrrole-2-acetic acid in water in the presence of an inorganic base or a tertiary amine.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7682780A JPS572270A (en) | 1980-06-06 | 1980-06-06 | Preparation of 1-methyl-5- p-toluoyl pyrrole-2-acetic acid |
| CA000379120A CA1151187A (en) | 1980-06-06 | 1981-06-05 | Process for preparing 1-methyl-5-(p-toluoyl)pyrrole-2- acetic acid |
| AT253581A AT374794B (en) | 1980-06-06 | 1981-06-05 | METHOD FOR PRODUCING 1-METHYL-5 (P-TOLUOYL) -PYRROL-2-ACETIC ACID |
| AT265783A AT375343B (en) | 1980-06-06 | 1983-07-20 | METHOD FOR PRODUCING THE NEW 1-METHYL-5 (P-TOLUOYL) -3-CARBOXYPYRROL-2-ACETIC ACID |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7682780A JPS572270A (en) | 1980-06-06 | 1980-06-06 | Preparation of 1-methyl-5- p-toluoyl pyrrole-2-acetic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS572270A JPS572270A (en) | 1982-01-07 |
| JPH0135825B2 true JPH0135825B2 (en) | 1989-07-27 |
Family
ID=13616503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7682780A Granted JPS572270A (en) | 1980-06-06 | 1980-06-06 | Preparation of 1-methyl-5- p-toluoyl pyrrole-2-acetic acid |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS572270A (en) |
| AT (1) | AT374794B (en) |
| CA (1) | CA1151187A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0230110A1 (en) * | 1985-11-30 | 1987-07-29 | FISONS plc | Pharmacologically active pyrrole and pyrazole derivatives |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4947752A (en) * | 1972-03-24 | 1974-05-09 |
-
1980
- 1980-06-06 JP JP7682780A patent/JPS572270A/en active Granted
-
1981
- 1981-06-05 CA CA000379120A patent/CA1151187A/en not_active Expired
- 1981-06-05 AT AT253581A patent/AT374794B/en not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4947752A (en) * | 1972-03-24 | 1974-05-09 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATA253581A (en) | 1983-10-15 |
| CA1151187A (en) | 1983-08-02 |
| AT374794B (en) | 1984-05-25 |
| JPS572270A (en) | 1982-01-07 |
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