JPS6310142B2 - - Google Patents
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- Publication number
- JPS6310142B2 JPS6310142B2 JP17211883A JP17211883A JPS6310142B2 JP S6310142 B2 JPS6310142 B2 JP S6310142B2 JP 17211883 A JP17211883 A JP 17211883A JP 17211883 A JP17211883 A JP 17211883A JP S6310142 B2 JPS6310142 B2 JP S6310142B2
- Authority
- JP
- Japan
- Prior art keywords
- lower alkyl
- alkyl group
- formula
- acid
- acid derivative
- 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
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- 239000002253 acid Substances 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- -1 alkyl salicylic acid derivative Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000012286 potassium permanganate Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- LNEAPIMQYSWIIK-UHFFFAOYSA-N 2-hydroxy-3-propanoylbenzaldehyde Chemical compound C(CC)(=O)C1=C(C(C=O)=CC=C1)O LNEAPIMQYSWIIK-UHFFFAOYSA-N 0.000 description 2
- BNKPFZVIJZNDLZ-UHFFFAOYSA-N 2-hydroxy-3-propanoylbenzoic acid Chemical compound CCC(=O)C1=CC=CC(C(O)=O)=C1O BNKPFZVIJZNDLZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- WUTVVHZNZHDMNM-UHFFFAOYSA-N 2-hydroxy-1-phenylhex-4-en-1-one Chemical compound CC=CCC(O)C(=O)C1=CC=CC=C1 WUTVVHZNZHDMNM-UHFFFAOYSA-N 0.000 description 1
- AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical compound CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
- KWAGCWPFRUIZLG-UHFFFAOYSA-N 2-methoxy-3-propanoylbenzoic acid Chemical compound CCC(=O)C1=CC=CC(C(O)=O)=C1OC KWAGCWPFRUIZLG-UHFFFAOYSA-N 0.000 description 1
- QNRDKBXSCGZZFV-UHFFFAOYSA-N 2-methoxy-3-propylbenzoic acid Chemical compound CCCC1=CC=CC(C(O)=O)=C1OC QNRDKBXSCGZZFV-UHFFFAOYSA-N 0.000 description 1
- TVYRJQXMQNZLNO-UHFFFAOYSA-N 3-acetyl-2-hydroxybenzoic acid Chemical compound CC(=O)C1=CC=CC(C(O)=O)=C1O TVYRJQXMQNZLNO-UHFFFAOYSA-N 0.000 description 1
- DCARPOVHBQKEJV-UHFFFAOYSA-N 3-butyl-2-hydroxybenzoic acid Chemical compound CCCCC1=CC=CC(C(O)=O)=C1O DCARPOVHBQKEJV-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- SPIUTQOUKAMGCX-UHFFFAOYSA-N flavoxate Chemical compound C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)OCCN1CCCCC1 SPIUTQOUKAMGCX-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- KLZFYWWPVQHTOY-UHFFFAOYSA-N methyl 2-hydroxy-3-propylbenzoate Chemical compound CCCC1=CC=CC(C(=O)OC)=C1O KLZFYWWPVQHTOY-UHFFFAOYSA-N 0.000 description 1
- HXAUZKXZXYPTOP-UHFFFAOYSA-N methyl 2-methoxy-3-propylbenzoate Chemical compound CCCC1=CC=CC(C(=O)OC)=C1OC HXAUZKXZXYPTOP-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は、新規なアシル安息香酸誘導体に関
し、更に詳しくは、一般式
（式中、R1は水素原子または低級アルキル基を
示し、R2は低級アルキル基またはアラアルキル
基を示し、R3は低級アルキル基を示す。）で表わ
されるアシル安息香酸誘導体に関する。
本発明の第１の目的は、前記一般式（）で表
わされる化合物を提供することである。前記一般
式（）を有する化合物は、従来文献未記載の新
規な化合物であり、種々の医薬品の合成中間体と
して極めて有用な化合物である。
すなわち、前記一般式（）を有する本発明の
化合物より導かれるアシルサリチル酸は、種々の
医薬品の前駆体として重要な化合物であつて、例
えば、３−アセチルサリチル酸は胃酸分泌抑制作
用や鎮痛作用を有する７−アセチルスピロ〔ベン
ゾ〔ｂ〕フラン−２（3H）−1′−シクロプロパン〕
−３−オンの前駆体であり（特開昭56−154478号
参照）、３−プロピオニルサリチル酸は排尿機能
改善作用を有する３−メチルフラボン−８−カル
ボン酸２−ピペリジノエチルエステルの前駆体で
ある（特公昭51−4983号参照）。
本発明の他の目的は、上記の如く新規で有用な
化合物の工業的に有利な製造方法を提供すること
である。
従来、３位にアシル基を有するサリチル酸誘導
体の製造法としては、３−プロピオニルサリチル
酸の製法において、２−ヒドロキシ−３−プロペ
ニルプロピオフエノンを酢酸とギ酸との混合溶媒
中でオゾン酸化して得られる３−プロピオニルサ
リチルアルデヒドをアルカリと200℃で加熱酸化
する方法（特公昭51−4983号参照）および２−ア
シロキシ−３−プロペニルプロピオフエノンを酢
酸中過マンガン酸カリウムで酸化する方法（特公
昭54−14104号参照）が知られている。
しかしながら、前者の製法は、プロペニル基の
オゾン酸化および３−プロピオニルサリチルアル
デヒドのアルカリによる200℃と云う高い温度で
の酸化工程があり、後者の製法は、プロペニル基
をカルボキシル基に酸化するため過マンガン酸塩
の使用量が多く、経済的な損失も大きいので、工
業的に有利な方法とは云えない。
本発明者らは、高価な副薬品を多量に使用する
ことなく、且つ緩和な反応条件の下で高い収率で
目的の化合物を製造する方法を鋭意研究した結
果、水酸基を保護したアルキルサリチル酸誘導体
がPH７以上で過マンガン酸塩によつて容易に酸化
されてアシル安息香酸誘導体になることを見出し
て本発明の方法を完成するに至つた。
すなわち、本発明は前記一般式（）を有する
アシル安息香酸誘導体の製造において、
一般式
（式中、R1、R2およびR3は前記と同意義を示
す。）で表わされるアルキル安息香酸誘導体を酸
化することを特徴とするものである。
本発明に使用する式（）で表わされるアルキ
ル安息香酸誘導体において、R1は水素原子また
はメチル、エチル、プロピル、ブチルのような炭
素数１乃至４の低級アルキル基を示し、R2はメ
チル、エチル、プロピル、ブチルのような炭素数
１乃至４の低級アルキル基またはベンジル、ｐ−
ニトロベンジルのようなアラアルキル基を示し、
R3はメチル、エチル、プロピル、ブチルのよう
な炭素数１乃至４の低級アルキル基を示す。
前記式（）で表わされるアルキル安息香酸誘
導体は、対応するアルキルサリチル酸またはアル
キルサリチル酸アルキルエステルの水酸基をジメ
チル硫酸、ジエチル硫酸のようなジアルキル硫酸
またはベンジルブロミドのようなアラアルキルハ
ライドによつてアルコキシ基またはアラアルコキ
シ基に変換することにより容易に得られる。対応
するサリチル酸は３−プロピルサリチル酸
（Beilstein Handbuch der Organischen
Chemie第10巻、270頁）、３−ブチルサリチル酸
（Helvetica Chimica Acta第30巻、１頁、1947
年）などである。
本発明の反応を行うには、一般式（）で表わ
されるアルキル安息香酸誘導体を水に懸濁または
溶解させるが、水酸化カリウムまたは水酸化ナト
リウムのようなアルカリを添加して溶解性を高め
て行うことが好適である。
酸化剤としては過マンガン酸カリウムが好適で
あり、その使用量はアルキル安息香酸誘導体に対
して１乃至３モルであるが、好適には1.2乃至２
モルである。
反応は、反応混合物のPHを調整しながら行うこ
とが望ましく、PH７〜10の範囲が好適であり、最
も好ましくはPH９〜10である。PHの調整は、反応
中に酸を添加するか、または硝酸マグネシウムを
加えて緩衝溶液とすることにより行うことができ
る。反応温度は０〜60℃、好適には５〜30℃の範
囲である。生成したアシル安息香酸誘導体は反応
終了後、二酸化マンガンを別し、液を酸性に
することにより析出する結晶を取することによ
つて得られる。
以下に本発明を実施例により更に詳しく説明す
るが、本発明はこれによつて限定されるものでは
ない。
実施例 １
２−メトキシ−３−プロピオニル安息香酸
２−メトキシ−３−プロピル安息香酸97.0ｇ
（0.5モル）を水500mlに懸濁し、苛性ソーダを加
えて溶解し、PH8.5に調整したのち10℃に冷却す
る。この溶液に、液温を10〜15℃に保ちながら過
マンガン酸カリウム134.3ｇを少量づつ加えて酸
化する。約６時間を要する。この間、4N−硝酸
マグネシウム水溶液でPH9.0〜9.5に保つ。更に４
時間撹拌を継続したのち、二酸化マンガンを別
する。液に濃塩酸50mlを加えてPH１とし、析出
した結晶を別する。得量90.7ｇ（収率87.2％）。
ｎ−ヘキサンより再結晶したものは融点98〜
101℃を示す。
元素分析値（％）C11H12O4として
計算値 Ｃ、63.45；Ｈ、5.81
実測値 Ｃ、63.41；Ｈ、5.92
NMRスペクトル（CDCl3）δ：1.15（3H、ｔ、
Ｊ＝７Hz、−COCH2CＨ 3）、2.95（2H、ｑ、Ｊ
＝７Hz、−COCＨ 2CH3）、3.90（3H、ｓ、−OC
Ｈ3）、7.0〜8.3（Ｈ、ｍ、Ar.Ｈ）、10.8（1H、
ｓ、−COOＨ）．
実施例 ２
２−メトキシ−３−プロピオニル安息香酸メチ
ル
２−メトキシ−３−プロピル安息香酸メチル
41.6ｇを水60ml及びアセトン140mlの混合液に溶
解し、PH8.5に調整したのち、15℃に冷却する。
この溶液に、室温を15〜25℃に保ちながら過マン
ガン酸カリウム158ｇを少量づつ加えて酸化する。
この間、4N−硝酸マグネシウム水溶液で反応液
をPH9.0〜9.5に保つ。反応の進行を薄層クロマト
グラフ法で確認したのち、二酸化マンガンを別
する。
液は濃縮したのち、残留物をベンゼン150ml
で抽出し、抽出液は、硫酸マグネシウムで乾燥
後、溶媒を留去する。残留物は減圧蒸留して沸点
109〜110℃／0.5mmHgの留分を集める。
元素分析値（％）C12H14O4として
計算値 Ｃ、64.85；Ｈ、6.35
実測値 Ｃ、64.46；Ｈ、6.35
NMRスペクトル（CDCl3）δ：1.20（3H、ｔ、
Ｊ＝７Hz、−COCH2CＨ 3）、3.07（2H、ｑ、Ｊ
＝７Hz、−COCH2CH3）、3.97（3H、ｓ、−OCＨ
３）、4.05（3H、ｓ、−OCＨ 3）、7.2〜8.3（3H、
ｍ、Ar・Ｈ）
参考例 １
２−メトキシ−３−プロピル安息香酸メチル
３−プロピルサリチル酸メチル38.8ｇ、炭酸カ
リウム96.6ｇおよびジメチル硫酸75.6ｇをアセト
ン300ml中30〜35℃で10時間反応する。反応終了
後、アセトンを留去し、残留物に水を加え、ベン
ゼン150mlで抽出する。抽出液は硫酸マグネシウ
ムで乾燥後、溶媒を留去する。残留物は減圧蒸留
して沸点105〜106℃／１mmHgの留分を集める。
収量38.7ｇ（93.1％）。
元素分析値（％）C12H16O3として
計算値 Ｃ、69.21；Ｈ、7.74
実測値 Ｃ、69.34；Ｈ、7.69
参考例 ２
２−メトキシ−３−プロピル安息香酸
２−メトキシ−３−プロピル安息香酸メチル
10.4ｇ、95％苛性ソーダ2.53ｇと水30mlの混合物
を75〜80℃で４時間反応する。反応終了後、冷却
し、濃硫酸でPH約１に調整する。析出する結晶を
取し、冷水10mlで洗浄後、50℃で送風乾燥して
融点65〜69℃の結晶を9.22ｇ（95.05％）得た。
本品９ｇを４倍量のｎ−ヘキサンより再結晶する
と、融点69〜70℃の純品が7.8ｇ得られた。
NMRスペクトル（CDCl3）δ：0.97（3H、ｔ、
Ｊ＝７Hz、ＣＨ 3）、1.4〜2.0（2H、ｍ、ＣＨ 2）、
2.68（2H、ｔ、Ｊ＝７Hz、ＣＨ 2）、3.90（3H、
ｓ、OCＨ 3）、7.0〜8.0（3H、ｍ、Ar.Ｈ）、10.63
（1H、ｓ、ＯＨ）。 DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel acylbenzoic acid derivatives, and more particularly, to novel acylbenzoic acid derivatives having the general formula (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a lower alkyl group or an aralkyl group, and R 3 represents a lower alkyl group.) A first object of the present invention is to provide a compound represented by the above general formula (). The compound having the general formula () is a novel compound that has not been previously described in any literature, and is an extremely useful compound as a synthetic intermediate for various pharmaceuticals. That is, acylsalicylic acid derived from the compound of the present invention having the general formula () is an important compound as a precursor of various pharmaceuticals, and for example, 3-acetylsalicylic acid has gastric acid secretion suppressing action and analgesic action. 7-acetylspiro[benzo[b]furan-2(3H)-1'-cyclopropane]
3-propionylsalicylic acid is a precursor of 3-methylflavone-8-carboxylic acid 2-piperidinoethyl ester, which has a urinary function-improving effect. (See Special Publication No. 51-4983). Another object of the present invention is to provide an industrially advantageous method for producing the novel and useful compounds as described above. Conventionally, as a method for producing a salicylic acid derivative having an acyl group at the 3-position, in the production method of 3-propionylsalicylic acid, 2-hydroxy-3-propenylpropiophenone is oxidized with ozone in a mixed solvent of acetic acid and formic acid. A method of heating and oxidizing 3-propionyl salicylaldehyde with an alkali at 200°C (see Japanese Patent Publication No. 51-4983) and a method of oxidizing 2-acyloxy-3-propenylpropiophenone with potassium permanganate in acetic acid (see Japanese Patent Publication No. 51-4983). 54-14104) is known. However, the former method involves ozone oxidation of the propenyl group and oxidation of 3-propionylsalicylaldehyde with an alkali at a high temperature of 200°C, whereas the latter method involves the use of permanganese to oxidize the propenyl group to a carboxyl group. Since the amount of acid salt used is large and the economic loss is also large, it cannot be said to be an industrially advantageous method. As a result of intensive research into a method for producing the desired compound in high yield under mild reaction conditions without using large amounts of expensive auxiliary chemicals, the present inventors discovered an alkyl salicylic acid derivative with a protected hydroxyl group. was easily oxidized by permanganate at a pH of 7 or above to form an acylbenzoic acid derivative, leading to the completion of the method of the present invention. That is, the present invention provides a method for producing an acylbenzoic acid derivative having the general formula () (In the formula, R 1 , R 2 and R 3 have the same meanings as above.) It is characterized by oxidizing an alkylbenzoic acid derivative represented by the formula. In the alkylbenzoic acid derivative represented by the formula () used in the present invention, R 1 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, and butyl, and R 2 represents methyl, Lower alkyl groups having 1 to 4 carbon atoms such as ethyl, propyl, butyl, or benzyl, p-
represents an aralkyl group such as nitrobenzyl,
R 3 represents a lower alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, and butyl. The alkyl benzoic acid derivative represented by the above formula (2) is an alkoxy group or It can be easily obtained by converting it into an aralkoxy group. The corresponding salicylic acid is 3-propyl salicylic acid (Beilstein Handbuch der Organischen
Chemie Vol. 10, p. 270), 3-butylsalicylic acid (Helvetica Chimica Acta Vol. 30, p. 1, 1947
) etc. To carry out the reaction of the present invention, the alkyl benzoic acid derivative represented by the general formula () is suspended or dissolved in water, and an alkali such as potassium hydroxide or sodium hydroxide is added to increase solubility. It is preferable to do so. Potassium permanganate is suitable as the oxidizing agent, and the amount used is 1 to 3 mol, preferably 1.2 to 2 mol, based on the alkylbenzoic acid derivative.
It is a mole. The reaction is desirably carried out while controlling the pH of the reaction mixture, preferably in the range of 7 to 10, and most preferably in the range of 9 to 10. The pH can be adjusted by adding an acid during the reaction or by adding magnesium nitrate to form a buffer solution. The reaction temperature ranges from 0 to 60°C, preferably from 5 to 30°C. The produced acylbenzoic acid derivative can be obtained by separating the manganese dioxide after the reaction is completed, and collecting the precipitated crystals by making the solution acidic. EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto. Example 1 2-Methoxy-3-propionylbenzoic acid 97.0 g of 2-methoxy-3-propylbenzoic acid
(0.5 mol) is suspended in 500 ml of water, dissolved by adding caustic soda, adjusted to pH 8.5, and then cooled to 10°C. To this solution, 134.3 g of potassium permanganate is added little by little while maintaining the liquid temperature at 10 to 15°C for oxidation. It takes about 6 hours. During this time, maintain the pH at 9.0 to 9.5 with a 4N magnesium nitrate aqueous solution. 4 more
After continuing stirring for an hour, the manganese dioxide is separated. Add 50 ml of concentrated hydrochloric acid to the solution to adjust the pH to 1, and separate the precipitated crystals. Amount obtained: 90.7 g (yield 87.2%). Those recrystallized from n-hexane have a melting point of 98~
Shows 101℃. Elemental analysis value (%) as C 11 H 12 O 4 Calculated value C, 63.45; H, 5.81 Actual value C, 63.41; H, 5.92 NMR spectrum (CDCl 3 ) δ: 1.15 (3H, t,
J = 7Hz, -COCH 2 C H 3 ), 2.95 (2H, q, J
=7Hz, -COC H 2 CH 3 ), 3.90 (3H, s, -OC
H3 ), 7.0-8.3 (H, m, Ar. H ), 10.8 (1H,
s, -COO H ). Example 2 Methyl 2-methoxy-3-propionylbenzoate Methyl 2-methoxy-3-propylbenzoate
Dissolve 41.6 g in a mixture of 60 ml of water and 140 ml of acetone, adjust the pH to 8.5, and cool to 15°C.
To this solution, 158 g of potassium permanganate is added little by little while maintaining the room temperature at 15-25°C for oxidation.
During this time, maintain the reaction solution at pH 9.0 to 9.5 with a 4N aqueous magnesium nitrate solution. After confirming the progress of the reaction using thin layer chromatography, the manganese dioxide is separated. After concentrating the liquid, add 150ml of benzene to the residue.
After drying the extract with magnesium sulfate, the solvent is distilled off. The residue is distilled under reduced pressure to the boiling point.
Collect the fraction at 109-110°C/0.5mmHg. Elemental analysis value (%) as C 12 H 14 O 4 Calculated value C, 64.85; H, 6.35 Actual value C, 64.46; H, 6.35 NMR spectrum (CDCl 3 ) δ: 1.20 (3H, t,
J = 7Hz, -COCH 2 C H 3 ), 3.07 (2H, q, J
=7Hz, -COCH2CH3 ), 3.97(3H,s , -OCH
3 ) , 4.05 (3H, s, -OC H3 ), 7.2~8.3 (3H,
m, Ar.H ) Reference Example 1 Methyl 2-methoxy-3-propylbenzoate 38.8 g of methyl 3-propylsalicylate, 96.6 g of potassium carbonate and 75.6 g of dimethyl sulfate are reacted in 300 ml of acetone at 30-35°C for 10 hours. After the reaction is complete, the acetone is distilled off, water is added to the residue, and the mixture is extracted with 150 ml of benzene. After drying the extract over magnesium sulfate, the solvent is distilled off. The residue is distilled under reduced pressure to collect a fraction with a boiling point of 105-106°C/1 mmHg.
Yield: 38.7g (93.1%). Elemental analysis value (%) as C 12 H 16 O 3 Calculated value C, 69.21; H, 7.74 Actual value C, 69.34; H, 7.69 Reference example 2 2-methoxy-3-propylbenzoic acid 2-methoxy-3-propyl Methyl benzoate
A mixture of 10.4 g, 2.53 g of 95% caustic soda and 30 ml of water is reacted at 75-80°C for 4 hours. After the reaction is complete, cool and adjust the pH to approximately 1 with concentrated sulfuric acid. The precipitated crystals were collected, washed with 10 ml of cold water, and dried with air at 50°C to obtain 9.22 g (95.05%) of crystals with a melting point of 65-69°C.
When 9 g of this product was recrystallized from 4 times the amount of n-hexane, 7.8 g of a pure product with a melting point of 69 to 70°C was obtained. NMR spectrum (CDCl 3 ) δ: 0.97 (3H, t,
J=7Hz, CH3 ) , 1.4-2.0 (2H, m, CH2 ) ,
2.68 (2H, t, J=7Hz, C H 2 ), 3.90 (3H,
s, OC H3 ), 7.0-8.0 (3H , m, Ar. H ), 10.63
(1H, s, O H ).
Claims (1)
示し、R2は低級アルキル基またはアラアルキル
基を示し、R3は低級アルキル基を示す。）で表わ
されるアシル安息香酸誘導体。 ２ 式 （式中、R1は水素原子または低級アルキル基を
示し、R2は低級アルキル基またはアラアルキル
基を示し、R3は低級アルキル基を示す。）を有す
るアルキル安息香酸誘導体を酸化することを特徴
とする式 （式中、R1、R2およびR3は前記と同意義を示
す。）で表わされるアシル安息香酸誘導体の製造
法。 ３ 式 （式中、R1は水素原子または低級アルキル基を
示し、R2は低級アルキル基またはアラアルキル
基を示し、R3は低級アルキル基を示す。）を有す
るアルキル安息香酸誘導体をPH７以上で過マンガ
ン酸カリウムにより酸化することを特徴とする式 （式中、R1、R2およびR3は前記と同意義を示
す。）で表わされるアシル安息香酸誘導体の製造
法。[Claims] 1 formula (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a lower alkyl group or an aralkyl group, and R 3 represents a lower alkyl group.) An acylbenzoic acid derivative represented by the following formula. 2 formulas (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a lower alkyl group or an aralkyl group, and R 3 represents a lower alkyl group.) The expression A method for producing an acylbenzoic acid derivative represented by the formula (wherein R 1 , R 2 and R 3 have the same meanings as above). 3 formulas (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a lower alkyl group or an aralkyl group, and R 3 represents a lower alkyl group.) Formula characterized by oxidation by acid potassium A method for producing an acylbenzoic acid derivative represented by the formula (wherein R 1 , R 2 and R 3 have the same meanings as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17211883A JPS6064944A (en) | 1983-09-20 | 1983-09-20 | Acylbenzoic acid derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17211883A JPS6064944A (en) | 1983-09-20 | 1983-09-20 | Acylbenzoic acid derivative and production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6064944A JPS6064944A (en) | 1985-04-13 |
| JPS6310142B2 true JPS6310142B2 (en) | 1988-03-04 |
Family
ID=15935885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17211883A Granted JPS6064944A (en) | 1983-09-20 | 1983-09-20 | Acylbenzoic acid derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6064944A (en) |
-
1983
- 1983-09-20 JP JP17211883A patent/JPS6064944A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6064944A (en) | 1985-04-13 |
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