JPS5824432B2 - Benzene sulfone amide - Google Patents
Benzene sulfone amideInfo
- Publication number
- JPS5824432B2 JPS5824432B2 JP49135999A JP13599974A JPS5824432B2 JP S5824432 B2 JPS5824432 B2 JP S5824432B2 JP 49135999 A JP49135999 A JP 49135999A JP 13599974 A JP13599974 A JP 13599974A JP S5824432 B2 JPS5824432 B2 JP S5824432B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- ester
- mono
- general formula
- salts
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【発明の詳細な説明】
この発明は制吐作用、向精神作用等のすぐれた薬理作用
を有し、医薬品として価値の高いベンゼンスルホン酸ア
ミド誘導体の新規な製造方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing benzenesulfonic acid amide derivatives that have excellent pharmacological effects such as antiemetic and psychotropic effects and are highly valuable as pharmaceuticals.
この発明の目的物質のうち、例えば１−エチル−２−（
２−メトキシ−５−スルファモイルベンズアミドメチル
）ピロリジンは公知の化合物であるが、この発明者は目
的物質について種々の製造法を検討した結果、目的物質
（ｍ）を高収率で得る新規製造法を見出しこの発明を完
成した。Among the target substances of this invention, for example, 1-ethyl-2-(
2-Methoxy-5-sulfamoylbenzamidomethyl)pyrrolidine is a known compound, but as a result of investigating various production methods for the target substance, the inventor developed a new method for producing the target substance (m) in high yield. He found a new method and completed this invention.
この発明は、一般式
（式中Ｒ１はアルキル基を意味する）
で示されるサリチル酸誘導体またはその塩類に、３価の
有機燐化合物およびジ（２−ピリジル）ジスルフィドの
存在下、一般式
（式中Ｒ２はアルキル基を意味する）
で示されるアミノ化合物を作用させ、一般式（式中Ｒ１
およびＲ２はそれぞれ前と同じ意味である）
で示されるベンゼンスルホン酸アミド誘導体を得ること
からなるベンゼンスルホン酸アミド誘導体の製造方法に
関するものである。In the present invention, a salicylic acid derivative represented by the general formula (wherein R1 means an alkyl group) or a salt thereof is added to a salicylic acid derivative represented by the general formula (in the formula R2 means an alkyl group) is reacted with an amino compound represented by the general formula (wherein R1
and R2 have the same meanings as above).
この発明で使用される原料物質（Ｉ）は、たとえば特公
昭４４−２３４９６号に記載の方法に従って製造するこ
とができる。The raw material (I) used in this invention can be produced, for example, according to the method described in Japanese Patent Publication No. 44-23496.
この発明は、原料物質（Ｉ）またはその塩類に３価の有
機燐化合物およびジ（２−ピリジル）ジスルフィドの存
在下、アミン化合物（ｎ）を作用させることによって行
なわれる。This invention is carried out by reacting the raw material (I) or its salt with an amine compound (n) in the presence of a trivalent organic phosphorus compound and di(2-pyridyl) disulfide.
原料物質（Ｉ）およびアミン化合物（ｎ）の式の定義に
おいて、Ｒ１およびＲ２で示されるアルキル基としては
メチル、エチル、プロピル、イソプロピル、ブチル、ペ
ンチル等が例示される。In the definition of the formulas of the raw material (I) and the amine compound (n), examples of the alkyl groups represented by R1 and R2 include methyl, ethyl, propyl, isopropyl, butyl, pentyl, and the like.
また、反応に使用される３価の有機燐化合物としては、
例えばホスフィン、亜燐酸エステル、亜ホスホン酸エス
テル等が例示される。In addition, as trivalent organic phosphorus compounds used in the reaction,
Examples include phosphine, phosphorous acid ester, and phosphorous acid ester.
ホスフィンとしてはプロピルホスフィン、インブチルホ
スフィン、フェニルホスフィンの如き第１ホスフイン、
ジエチルホスフィン、ジイソアミルホスフィン、ジフェ
ニルホスフィンの如き第２ホスフイン、トリメチルホス
フィン、トリエチルホスフィン、トＩＪ フェニルホス
フィンの如き第３ホスフィン等カ例示され、亜燐酸エス
テルとしては、亜燐酸のモノ（もしくはジもしくはトリ
）メチルエステル、モノ（もしくはジもしくはトリ）エ
チルエステル、モノ（もしくはジもしくはトリ）プロピ
ルエステル、モノ（もしくはジもしくはトリ）イソプロ
ピルエステル等のモノ（もしくはジもしくはトリ）アル
キルエステル、モノ（もしくはジもしくはトリ）フェニ
ルエステル、モノ（もしくはジもしくはトリ）ニトロフ
ェニルエステル等のモノ（もしくはジもしくはトリ）ア
リールエステル等が例示され、また亜ホスホン酸エステ
ルとしては、メチル亜ホスホン酸のモノ（もしくはジ）
メチルエステル、エチル亜ホスホン酸のモノ（もしくは
ジ）エチルエステル等のアルキル亜ホスホン酸のモノ（
もしくはジ）アルキルエステル、フェニル亜ホスホン酸
のモノ（もしくはジ）メチルエステル、フェニル亜ホス
ホン酸のモノ（もしくはジ）エチルエステル等のアリー
ル亜ホスホン酸のモノ（もしくはジ）アルキルエステル
、フェニル亜ホスホン酸のモノ（もしくはジ）フェニル
エステル等が例示されるが、いずれにしても３価の有機
燐化合物は例示されたものに限定されるものではなく、
本発明に悪影響を及ぼさない被酸化性の３価の有機燐化
合物はいずれを使用してもよい。Examples of the phosphine include primary phosphine such as propylphosphine, inbutylphosphine, and phenylphosphine;
Examples include secondary phosphine such as diethylphosphine, diisoamylphosphine, diphenylphosphine, tertiary phosphine such as trimethylphosphine, triethylphosphine, and phenylphosphine. ) methyl ester, mono (or di or tri) ethyl ester, mono (or di or tri) propyl ester, mono (or di or tri) isopropyl ester, mono (or di or tri) alkyl ester, mono (or di or tri) Mono (or di or tri) aryl esters such as tri) phenyl ester and mono (or di or tri) nitrophenyl ester are exemplified.
Mono() of alkylphosphonic acid such as methyl ester, mono(or di)ethyl ester of ethylphosphonic acid
or di)alkyl ester, mono(or di)alkyl ester of arylphosphonic acid such as mono(or di)methyl ester of phenylphosphonic acid, mono(or di)ethyl ester of phenylphosphonic acid, phenylphosphonic acid Examples include mono (or di) phenyl esters, but the trivalent organic phosphorus compounds are not limited to those exemplified.
Any oxidizable trivalent organic phosphorus compound that does not adversely affect the present invention may be used.
原料物質（Ｉ）の塩類としては、たとえば銅塩、水銀塩
、鉛塩、マンガン塩、クロム塩の如きメルカプタン除去
剤となり得る金属塩が好ましいが、特にこれらに限定さ
れるものではない。The salts of the raw material (I) are preferably metal salts that can serve as mercaptan removing agents, such as copper salts, mercury salts, lead salts, manganese salts, and chromium salts, but are not particularly limited thereto.
この発明の反応は、必要に応じてメルカプタン除去剤の
存在下に行なうと一層高収率に目的物質側）が得られる
ことがある。If the reaction of this invention is carried out in the presence of a mercaptan-removing agent, if necessary, the desired substance may be obtained in even higher yield.
メルカプタン除去剤は、原料物質（Ｉ）としてカルボン
酸の重金属塩を使用する場合に好結果を得ることが多い
。Mercaptan removal agents often give good results when heavy metal salts of carboxylic acids are used as raw material (I).
メルカプタン除去剤としては、塩化第２水銀、塩化亜鉛
、塩化銅、硫酸銅、硫酸鉛、硫酸マンガンの如き重金属
の無機酸塩、尿素、コハク酸イミド、フタル酸イミド、
パラニトロフェノール、２・４−ジニトロフェノール、
Ｎ−ヒドロキシコハク酸イミド、バラメトキシフェノー
ル等の水素供与有機化合物と重金属の結合からなる有機
金属化合物、ピアソン（Ｐｅａｒｓｏｎ ）のハード・
ソフト理論によるソフト酸、代表的なものとしては、０
−ニトロフェニルスルフェン酸のエステル、例エハメチ
ルエステル、エチルエステル、第３級ブチルエステル等
するいは２・４−ジニトロフェニルスルフェン酸のエス
テル、例えばメチルエステル、第３級ブチルエステルの
如きスルフェン酸エステル、または２゜３−ジヒドロヒ
ラン、ｎ−７”チルビニルエーテルの如きオレフィン類
等を例示することができるが、もとより例示されたもの
に限定されず、チオール化合物と反応し、これを除去し
得る化合物はいずれを使用してもよい。Mercaptan removal agents include inorganic acid salts of heavy metals such as mercuric chloride, zinc chloride, copper chloride, copper sulfate, lead sulfate, manganese sulfate, urea, succinimide, phthalic imide,
para-nitrophenol, 2,4-dinitrophenol,
Pearson's Hard
Soft acids based on soft theory, typically 0
- Esters of nitrophenylsulfenic acid, such as ethyl ester, ethyl ester, tertiary butyl ester, etc. or esters of 2,4-dinitrophenylsulfenic acid, such as sulfenes such as methyl ester, tertiary butyl ester, etc. Examples include acid esters, olefins such as 2゜3-dihydrohyran, n-7'' methyl vinyl ether, etc., but are not limited to those exemplified, and can react with and remove thiol compounds. Any compound may be used.
この反応は、通常、例えばジメチルホルムアミド、ピリ
ジン、エーテル、ジオキサン、塩化メチレン、テトラヒ
ドロフラン、ベンゼン、トルエン等、この反応に悪影響
を与えない溶媒中で行なわれる。This reaction is usually carried out in a solvent that does not adversely affect the reaction, such as dimethylformamide, pyridine, ether, dioxane, methylene chloride, tetrahydrofuran, benzene, toluene, and the like.
また、この反応においては、反応は悪影響を与えないピ
バリン酸、Ｎ−ヒドロキシコ・・り酸イミド、フェノー
ル、パラニトロフェノール、ピクリン酸の如き酸、トリ
エチルアミン、Ｎ−アルキルモルホリンの如き塩基の存
在下、更には水の共存下に反応を行なうこともできる。In addition, in this reaction, the reaction is carried out in the presence of acids such as pivalic acid, N-hydroxyco-phosphate imide, phenol, p-nitrophenol, picric acid, and bases such as triethylamine and N-alkylmorpholine, which have no adverse effects. Furthermore, the reaction can also be carried out in the presence of water.
この反応の温度は特に限定されず、室温程度の緩和な条
件で充分進行する。The temperature of this reaction is not particularly limited, and the reaction proceeds sufficiently under mild conditions around room temperature.
こうして得られる目的物質（ＩＩＩ）は必要に応じて塩
酸、臭化水素酸、燐酸、硫酸の如き無機酸、酢酸、プロ
ピオン酸、マレイン酸、酒石酸、クエン酸、サリチル酸
の如き有機酸の酸塩に導びくこともできる。The target substance (III) thus obtained is converted into an acid salt of an inorganic acid such as hydrochloric acid, hydrobromic acid, phosphoric acid, or sulfuric acid, or an organic acid such as acetic acid, propionic acid, maleic acid, tartaric acid, citric acid, or salicylic acid, as necessary. I can also guide you.
この発明において、原料物質（Ｉ）またはその塩類に３
価の有機燐化合物およびジ（２−ピリジル）ジスルフィ
ドの存在下、アミン化合物（ｎ）を作用させる際に、中
間に一般式
（式中、Ｒ２は前と同じ意味、Ｒ３は２−ピリジルを意
味する）
で示されるスルフェンアミド誘導体が生成してから、目
的物質（ｍ）が得られる場合があるものと考えられる。In this invention, the raw material (I) or its salts contains 3
When reacting the amine compound (n) in the presence of a divalent organic phosphorus compound and di(2-pyridyl) disulfide, the general formula (wherein, R2 has the same meaning as before, R3 means 2-pyridyl) It is considered that the target substance (m) may be obtained after the sulfenamide derivative shown in
次にこの発明の代表的な実施例を掲げて、この発明の方
法を一層具体的に示すが、もとよりこの発明の範囲は、
前記各記載及び後記実施例記載の方法に限定されるもの
ではなく、種々の変形した方法を採用することができる
ものである。Next, typical examples of this invention will be listed to illustrate the method of this invention more specifically, but the scope of this invention is
The present invention is not limited to the methods described above and the examples described below, and various modified methods may be employed.
実施例 １
２−メトキシ−５−スルファモイル安息香酸１、１５
Ｐおよびジ（２−ピリジル）ジスルフィド１．２１を４
ｒｒｌｌの精製ジメチルホルムアミドに溶解し、これに
１−エチル−２−アミノメチルピロリジン０．６４Ｐ及
びトリフェニルホスフィン１．４１の精製ジメチルホル
ムアミド溶液６ｒｒＬｌを、室温下に攪拌しつつ添加す
る。Example 1 2-methoxy-5-sulfamoylbenzoic acid 1,15
P and di(2-pyridyl) disulfide 1.21 to 4
rrll of a purified dimethylformamide solution, and 6rrLl of a purified dimethylformamide solution containing 0.64 P of 1-ethyl-2-aminomethylpyrrolidine and 1.41 P of triphenylphosphine are added thereto with stirring at room temperature.
室温で１時間攪拌した後、ジメチルホルムアミドを減圧
留去する。After stirring at room temperature for 1 hour, dimethylformamide was distilled off under reduced pressure.
残渣を酢酸エチルに溶解し、■規定塩酸水を加え抽出す
る。The residue was dissolved in ethyl acetate, and extracted with (1) normal hydrochloric acid.
水層に水冷下１規定水酸化ナトリウム水溶液を加えてア
ルカリ性とする。The aqueous layer is made alkaline by adding a 1N aqueous sodium hydroxide solution while cooling with water.
これに塩化ナトリウムを飽和した後、酢酸エチルで２回
抽出する。After saturating this with sodium chloride, it was extracted twice with ethyl acetate.
抽出液を飽和塩化ナトリウム水で洗浄した後、無水硫酸
ナトリウムを加えて乾燥する。After washing the extract with saturated aqueous sodium chloride, it is dried by adding anhydrous sodium sulfate.
酢酸エチルを除去すると、■−エチ／１／−２−（２−
メトキシ−５−スルファモイルベンズアミドメチル）ピ
ロリジンが定量的に得られる。When ethyl acetate is removed, ■-ethyl/1/-2-(2-
Methoxy-5-sulfamoylbenzamidomethyl)pyrrolidine is obtained quantitatively.
水晶を酢酸エチル・ｎ−ヘキサンの混合溶媒で再結晶す
ると、融点１７６〜１７８℃の無色燐片状晶となる。When the crystal is recrystallized with a mixed solvent of ethyl acetate and n-hexane, it becomes colorless scaly crystals with a melting point of 176 to 178°C.
Claims (1)
機燐化合物およびジ（２−ピリジル）ジスルフィドの存
在下、一般式 （式中Ｒ２はアルキル基を意味する） で示されるアミン化合物を作用させ、一般式（式中、Ｒ
１およびＲ２はそれぞれ前と同じ意味である） で示されるベンゼンスルホン酸アミド誘導体を得ること
を特徴とするベンゼンスルホン酸アミド誘導体の製造方
法。[Scope of Claims] 1 A salicylic acid derivative or a salt thereof represented by the general formula (wherein R1 represents an alkyl group) is combined with a salicylic acid derivative or a salt thereof represented by the general formula ( In the formula, R2 means an alkyl group) An amine compound represented by the general formula (in the formula, R
1 and R2 each have the same meaning as above) A method for producing a benzenesulfonic acid amide derivative, characterized in that a benzenesulfonic acid amide derivative is obtained.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7342266A FR2252336B1 (en) | 1973-11-27 | 1973-11-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5083369A JPS5083369A (en) | 1975-07-05 |
| JPS5824432B2 true JPS5824432B2 (en) | 1983-05-20 |
Family
ID=9128360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP49135999A Expired JPS5824432B2 (en) | 1973-11-27 | 1974-11-25 | Benzene sulfone amide |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5824432B2 (en) |
| AR (1) | AR207577A1 (en) |
| AT (1) | AT360511B (en) |
| CA (1) | CA1042895A (en) |
| DE (1) | DE2452405A1 (en) |
| ES (2) | ES432224A1 (en) |
| FI (1) | FI59088C (en) |
| FR (1) | FR2252336B1 (en) |
| GB (1) | GB1446789A (en) |
| IE (1) | IE41347B1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4189495A (en) * | 1974-09-17 | 1980-02-19 | Synthelabo | 2-Methoxy-benzamide derivatives |
| US4172143A (en) * | 1974-12-18 | 1979-10-23 | Synthelabo | 2-Methoxy-benzamide derivatives |
| US4158060A (en) * | 1974-12-18 | 1979-06-12 | Synthelabo | 2-Methoxy-benzamide derivatives |
| CH614709A5 (en) * | 1975-09-25 | 1979-12-14 | Ciba Geigy Ag | |
| ATE20881T1 (en) * | 1982-04-08 | 1986-08-15 | Ile De France | -N-(1-PROPYL-2-PYRROLIDYLMETHYL-2-METHOXY-5SULFAMOYL-BENZAMIDE AND CURES FOR CERTAIN DEPRESSIONS. |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4829764A (en) * | 1971-08-20 | 1973-04-19 | Fratmann Sa |
-
1973
- 1973-11-27 FR FR7342266A patent/FR2252336B1/fr not_active Expired
-
1974
- 1974-01-01 AR AR25665174A patent/AR207577A1/en active
- 1974-11-05 DE DE19742452405 patent/DE2452405A1/en not_active Withdrawn
- 1974-11-12 AT AT902774A patent/AT360511B/en not_active IP Right Cessation
- 1974-11-22 FI FI339074A patent/FI59088C/en active
- 1974-11-22 CA CA214,437A patent/CA1042895A/en not_active Expired
- 1974-11-23 ES ES432224A patent/ES432224A1/en not_active Expired
- 1974-11-23 ES ES432225A patent/ES432225A1/en not_active Expired
- 1974-11-25 JP JP49135999A patent/JPS5824432B2/en not_active Expired
- 1974-11-25 IE IE241374A patent/IE41347B1/en unknown
- 1974-11-26 GB GB5114074A patent/GB1446789A/en not_active Expired
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4829764A (en) * | 1971-08-20 | 1973-04-19 | Fratmann Sa |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5083369A (en) | 1975-07-05 |
| FI339074A (en) | 1975-05-28 |
| DE2452405A1 (en) | 1975-05-28 |
| GB1446789A (en) | 1976-08-18 |
| AT360511B (en) | 1981-01-12 |
| ES432224A1 (en) | 1976-11-01 |
| CA1042895A (en) | 1978-11-21 |
| ES432225A1 (en) | 1976-11-01 |
| FI59088C (en) | 1981-06-10 |
| IE41347B1 (en) | 1979-12-19 |
| FR2252336B1 (en) | 1977-03-04 |
| IE41347L (en) | 1975-05-27 |
| FR2252336A1 (en) | 1975-06-20 |
| FI59088B (en) | 1981-02-27 |
| AR207577A1 (en) | 1976-10-15 |
| ATA902774A (en) | 1980-06-15 |
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