JPS5915906B2 - Process for producing 1-(4-isopropylthiophenyl)2-n-octylaminopropanol, its esters and salts - Google Patents
Process for producing 1-(4-isopropylthiophenyl)2-n-octylaminopropanol, its esters and saltsInfo
- Publication number
- JPS5915906B2 JPS5915906B2 JP57212827A JP21282782A JPS5915906B2 JP S5915906 B2 JPS5915906 B2 JP S5915906B2 JP 57212827 A JP57212827 A JP 57212827A JP 21282782 A JP21282782 A JP 21282782A JP S5915906 B2 JPS5915906 B2 JP S5915906B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- octylaminopropanol
- salts
- isopropylthiophenyl
- esters
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/31—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/32—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to an acyclic carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Description
【発明の詳細な説明】
本発明は式Ｉで表わされる１−（４−イソプロピルチオ
フェニル） −２−ｎ−オクチルアミノプ・ｏ 口パノ
ール（スルオクチジル）、その塩及びエステルの合成方
法に係わる。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the synthesis of 1-(4-isopropylthiophenyl)-2-n-octylaminop-o-suloctidyl of formula I, its salts and esters.
ＣＨ−ＣＨ−ＮＨ−ｎＣ８Ｈ１７
はく酸、グリコール酸、グルコン酸、乳酸、りんｒｏご
酸、酒石酸、くえん酸、アスコルビン酸、マレイン酸、
フマル酸、ピルビン酸、アスパラギン酸、グルタミン酸
、安息香酸、アントラニル酸、オキシ安息香酸、サリチ
ル酸、フェニル酢酸、マンデル酸、エムボン酸、メチル
スルホン酸、エチルスル’５ ホン酸、パントテン酸、
トルエンスルホン酸、スルフアニル酸、シクロヘキシル
アミノスルホン酸、グルクロン酸などの添加塩である。CH-CH-NH-nC8H17 citric acid, glycolic acid, gluconic acid, lactic acid, phosphoric acid, tartaric acid, citric acid, ascorbic acid, maleic acid,
Fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, oxybenzoic acid, salicylic acid, phenylacetic acid, mandelic acid, embonic acid, methylsulfonic acid, ethylsulfonic acid, pantothenic acid,
These are addition salts of toluenesulfonic acid, sulfanilic acid, cyclohexylaminosulfonic acid, glucuronic acid, etc.
広く使用されているエステルとしては酢酸、プロピオン
酸、シクロヘキサンカルボキシル酸、シクロペンタンカ
ルボキシル酸、ピバリン酸、テルチオブチル酢酸、シク
ロヘキサン酢酸、アルコキシフエニル酢酸、２−メチル
プロピオン酸などのエステルがある。Commonly used esters include acetic acid, propionic acid, cyclohexanecarboxylic acid, cyclopentanecarboxylic acid, pivalic acid, terthiobutylacetic acid, cyclohexaneacetic acid, alkoxyphenylacetic acid, 2-methylpropionic acid, and the like.
本発明の方法が新規な中間化合物を生成する場合、この
新規化合物もその生成に寄与する方法と同様に本発明の
範囲に含まれる。If the process of the invention produces a novel intermediate compound, this novel compound is also included within the scope of the invention, as are the processes contributing to its production.
本発明の化合物は下記方法に従つて調製される。Compounds of the invention are prepared according to the following method.
すなわち、式Ｍで表わされる１−（４−アミノフエーニ
ル）−２−ｎ−オクチルアミノプロパノールを下式に従
い、式で表わされるジアゾニウム塩を経て式１で表わさ
れる１−（４−イソプロピルチオフエニル）−２−ｎ−
オクチルアミノプロパノールに転化する。式で表わされ
るジアゾニウム塩は公知の態様で、低温すなわち、−２
０℃ないし１０℃の温度においてアミン及び塩酸の水溶
液に硝酸ナトリウムを添加することによつで生成する。That is, 1-(4-aminophenyl)-2-n-octylaminopropanol represented by formula M is converted into 1-(4-isopropylthiophenyl) represented by formula 1 through a diazonium salt represented by formula according to the following formula. -2-n-
Convert to octylaminopropanol. The diazonium salt of the formula can be prepared in a known manner at low temperatures, i.e. -2
It is produced by adding sodium nitrate to an aqueous solution of an amine and hydrochloric acid at a temperature of 0°C to 10°C.
得たジアゾニウム塩ぱ分離も精製もせず、塩基性媒質中
で、式で表わされるイソプロピルメルカプタン水溶液と
作用させる。塩基は水酸化ナトリウムまたは水酸化カリ
ウムのような無機塩基かまたはトリエチルアミンまたは
ピリジンのような有機塩基でよい。この第２反応はまず
上記低温で行なうが、反応の終期にはこの温度を約５０
−１００℃、好ましくは７０℃まで上昇させることが好
都合である。実施例（ａ）式で表わされるジアゾニウム
塩の生成。The obtained diazonium salt is not separated or purified, but is allowed to react with an aqueous solution of isopropyl mercaptan represented by the formula in a basic medium. The base may be an inorganic base such as sodium hydroxide or potassium hydroxide or an organic base such as triethylamine or pyridine. This second reaction is first carried out at the above-mentioned low temperature, but at the end of the reaction this temperature is lowered to about 50°C.
It is convenient to raise the temperature to -100°C, preferably to 70°C. Example (a) Production of a diazonium salt represented by the formula.
２５０ｍ１の球形フラスコ内で、式Ｍで表わされる１−
（４−アミノフエニル）−２−ｎ−オクチルアミノプロ
パノール１７７（０．０６モル）及び４Ｎ塩酸６７，５
ｍ１の混合物を攪拌しながら一５℃に冷却する。In a 250 m1 spherical flask, 1-
(4-aminophenyl)-2-n-octylaminopropanol 177 (0.06 mol) and 4N hydrochloric acid 67,5
The mixture of m1 is cooled to -5° C. with stirring.
次いで水７０ｍ１に硝酸ナトリウム９．３７（０．１３
５モル）を溶かした溶液を、温度を−５℃ないしＯ℃に
維持しながら添加し、得た混合物（濁つた黄色溶液）を
低温で２時間攪拌する。得た生成物（中間生成物）は分
離せず、下記段階でそのまま利用する。（ｂ）ジアゾニ
ウム塩のチオアルキル化。窒素雰囲気中で水酸化ナトリ
ウム１１ｆ７及びイソプロピルメルカプタン５．２ｔ（
０．０６８モル）を水１００ｍ１に溶かした溶液を−５
℃に冷却する。Next, add 9.37 (0.13
5 mol) is added, maintaining the temperature between -5°C and 0°C, and the resulting mixture (cloudy yellow solution) is stirred at low temperature for 2 hours. The obtained product (intermediate product) is not separated and is used as it is in the following step. (b) Thioalkylation of diazonium salts. Sodium hydroxide 11f7 and isopropyl mercaptan 5.2t (
A solution of 0.068 mol) dissolved in 100 ml of water is -5
Cool to ℃.
次いで窒素雰囲気中で攪拌しながら上記中間生成物を−
５℃ないしＯ℃の温度において約２時間にわたつて添加
する。さらに周囲温度で１６時間混合物を攪拌してから
徐々に７０℃まで加熱し、再びＯ℃に冷却する。Then, the above intermediate product was mixed with stirring in a nitrogen atmosphere.
The addition takes place over a period of about 2 hours at a temperature of 5°C to 0°C. The mixture is stirred for a further 16 hours at ambient temperature and then gradually heated to 70°C and cooled again to 0°C.
濃塩酸２５ｍ１で酸性化（ＰＨ＝Ｏ）し、３０分間にわ
たつて窒素流を通過させて余分なイソプロピルメルカプ
タンを除去する。Acidify (PH=O) with 25 ml of concentrated hydrochloric acid and remove excess isopropyl mercaptan by passing a nitrogen stream through for 30 minutes.
次いで濃塩酸７５ｍ１に溶かした塩化銅（ＣＵＣｌ）１
２．５ｔを１５分間にわたつて添加し、周囲温度で３０
分間攪拌することによりニトロソアミンを第二アミンに
転化させる。次にトルエン２５０ＷＩＩを添加し、反応
混合物に１５％水酸化ナトリウム２５０ｍ１を添加して
ＰＨ−１４とする。得た混合物をろ過し、ろ液を傾潟し
、減圧下で有機相を蒸発させる。Then 1 cup of copper chloride (CUCl) dissolved in 75 mL of concentrated hydrochloric acid
2.5 t was added over 15 minutes and 30 t was added at ambient temperature.
The nitrosamines are converted to secondary amines by stirring for a minute. Then 250 WII of toluene is added and 250 ml of 15% sodium hydroxide is added to the reaction mixture to give a pH-14. The mixture obtained is filtered, the filtrate is decanted and the organic phase is evaporated under reduced pressure.
残留物をエチルアセテート２５０ｍ１に溶かし、この溶
液をシリカゲル床でろ過し、減圧下で蒸発させる。−１
５℃においてｎ−ヘブタン中で２回再結晶させる。必要
に応じ活性炭で処理し、再結晶させる。隔点：６２℃ｏThe residue is dissolved in 250 ml of ethyl acetate, the solution is filtered through a bed of silica gel and evaporated under reduced pressure. -1
Recrystallize twice in n-hebutane at 5°C. If necessary, treat with activated carbon and recrystallize. Separate point: 62℃o
Claims (1)
ミノプロパノールのジアゾニウム塩をイソプロピルメル
カプタンと、−２０℃と＋１０℃の間の温度で塩基性媒
質中で反応させ、得た生成物を前記温度以上の高い温度
で加水分解し、場合によつては無機もしくは有機の酸を
加えてその塩に変え、また有機酸の活性誘導体を加えて
そのエステルに変える、ことを特徴とする、１−（４−
イソプロピルチオフエニル）−２−ｎ−オクチルアミノ
プロパノール、その塩およびエステルの製法。1 The diazonium salt of 1-(4-aminophenyl)-2-n-octylaminopropanol is reacted with isopropyl mercaptan in a basic medium at a temperature between -20°C and +10°C and the product obtained is 1- (4-
Process for producing (isopropylthiophenyl)-2-n-octylaminopropanol, salts and esters thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU83039A LU83039A1 (en) | 1980-12-24 | 1980-12-24 | METHODS OF SYNTHESIS OF 1- (4 ISOPROPYLTHIOPHENYL) -2-N OCTYLAMINOPROPANOL |
| LU83039 | 1980-12-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58113171A JPS58113171A (en) | 1983-07-05 |
| JPS5915906B2 true JPS5915906B2 (en) | 1984-04-12 |
Family
ID=19729552
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56208270A Expired JPS5912665B2 (en) | 1980-12-24 | 1981-12-24 | Method for synthesizing 1-(4-isopropylthiophenyl)-2-n-octylaminopropanol, its esters and salts |
| JP57212827A Expired JPS5915906B2 (en) | 1980-12-24 | 1982-12-06 | Process for producing 1-(4-isopropylthiophenyl)2-n-octylaminopropanol, its esters and salts |
| JP57212825A Expired JPS5938224B2 (en) | 1980-12-24 | 1982-12-06 | Process for producing 1-(4-isopropylthiophenyl)-2-n-octylaminopropanol, its esters and salts |
| JP57212826A Expired JPS5915905B2 (en) | 1980-12-24 | 1982-12-06 | Process for producing 1-(4-isopropylthiophenyl)-2-n-octylaminopropanol, its esters and salts |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56208270A Expired JPS5912665B2 (en) | 1980-12-24 | 1981-12-24 | Method for synthesizing 1-(4-isopropylthiophenyl)-2-n-octylaminopropanol, its esters and salts |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57212825A Expired JPS5938224B2 (en) | 1980-12-24 | 1982-12-06 | Process for producing 1-(4-isopropylthiophenyl)-2-n-octylaminopropanol, its esters and salts |
| JP57212826A Expired JPS5915905B2 (en) | 1980-12-24 | 1982-12-06 | Process for producing 1-(4-isopropylthiophenyl)-2-n-octylaminopropanol, its esters and salts |
Country Status (11)
| Country | Link |
|---|---|
| JP (4) | JPS5912665B2 (en) |
| KR (1) | KR860000340B1 (en) |
| AR (1) | AR229799A1 (en) |
| AT (1) | AT380872B (en) |
| AU (1) | AU548084B2 (en) |
| CH (2) | CH654296A5 (en) |
| ES (4) | ES8308844A1 (en) |
| IL (1) | IL64631A0 (en) |
| IT (1) | IT1140399B (en) |
| LU (1) | LU83039A1 (en) |
| PT (1) | PT74203B (en) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1321701A (en) * | 1969-10-01 | 1973-06-27 | Continental Pharma | Amino-alcohols their salts and process for prepairing the same |
| GB1390748A (en) * | 1973-04-09 | 1975-04-16 | Continental Pharma | Alkyl and cycloalkylthiophenylalkylaminoalkanols their salts and the preparation thereof |
| LU77237A1 (en) * | 1977-05-03 | 1979-01-18 | ||
| IT1082122B (en) * | 1977-07-11 | 1985-05-21 | Medea Res Srl | PROCESS FOR THE PREPARATION OF 1- (4-ISOPROPILMERCAPTO-FENYL) -2-N.OCTYLAMINE-PROPANOL |
| LU79970A1 (en) * | 1978-07-13 | 1980-02-14 | Continental Pharma | PROCESS FOR THE PREPARATION OF 1-PHENYL-1-PROPANOL DERIVATIVES |
-
1980
- 1980-12-24 LU LU83039A patent/LU83039A1/en unknown
-
1981
- 1981-12-21 AT AT0549881A patent/AT380872B/en not_active IP Right Cessation
- 1981-12-23 IL IL64631A patent/IL64631A0/en unknown
- 1981-12-23 CH CH443/85A patent/CH654296A5/en not_active IP Right Cessation
- 1981-12-23 AR AR287941A patent/AR229799A1/en active
- 1981-12-23 PT PT74203A patent/PT74203B/en unknown
- 1981-12-23 CH CH8259/81A patent/CH653325A5/en not_active IP Right Cessation
- 1981-12-23 ES ES508313A patent/ES8308844A1/en not_active Expired
- 1981-12-24 IT IT25853/81A patent/IT1140399B/en active
- 1981-12-24 JP JP56208270A patent/JPS5912665B2/en not_active Expired
- 1981-12-24 KR KR1019810005129A patent/KR860000340B1/en active
- 1981-12-24 AU AU79025/81A patent/AU548084B2/en not_active Ceased
-
1982
- 1982-12-06 JP JP57212827A patent/JPS5915906B2/en not_active Expired
- 1982-12-06 JP JP57212825A patent/JPS5938224B2/en not_active Expired
- 1982-12-06 JP JP57212826A patent/JPS5915905B2/en not_active Expired
-
1983
- 1983-05-16 ES ES522441A patent/ES8407019A1/en not_active Expired
- 1983-05-16 ES ES522442A patent/ES522442A0/en active Granted
- 1983-05-16 ES ES522440A patent/ES8407018A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ES522440A0 (en) | 1984-08-16 |
| ES8407020A1 (en) | 1984-08-16 |
| IT8125853A0 (en) | 1981-12-24 |
| CH654296A5 (en) | 1986-02-14 |
| JPS5938224B2 (en) | 1984-09-14 |
| ES522441A0 (en) | 1984-08-16 |
| IL64631A0 (en) | 1982-03-31 |
| ES8407018A1 (en) | 1984-08-16 |
| JPS58113171A (en) | 1983-07-05 |
| ES522442A0 (en) | 1984-08-16 |
| JPS58113169A (en) | 1983-07-05 |
| ES8407019A1 (en) | 1984-08-16 |
| ES508313A0 (en) | 1983-10-01 |
| JPS57134459A (en) | 1982-08-19 |
| CH653325A5 (en) | 1985-12-31 |
| JPS5912665B2 (en) | 1984-03-24 |
| IT1140399B (en) | 1986-09-24 |
| KR830007541A (en) | 1983-10-21 |
| AU7902581A (en) | 1982-07-01 |
| ES8308844A1 (en) | 1983-10-01 |
| PT74203A (en) | 1982-01-01 |
| AU548084B2 (en) | 1985-11-21 |
| PT74203B (en) | 1983-05-20 |
| AR229799A1 (en) | 1983-11-30 |
| KR860000340B1 (en) | 1986-04-12 |
| LU83039A1 (en) | 1982-07-07 |
| ATA549881A (en) | 1985-12-15 |
| AT380872B (en) | 1986-07-25 |
| JPS58113170A (en) | 1983-07-05 |
| JPS5915905B2 (en) | 1984-04-12 |
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