JPH0653724B2 - Method for producing cysteamine or salts thereof - Google Patents
Method for producing cysteamine or salts thereofInfo
- Publication number
- JPH0653724B2 JPH0653724B2 JP60031412A JP3141285A JPH0653724B2 JP H0653724 B2 JPH0653724 B2 JP H0653724B2 JP 60031412 A JP60031412 A JP 60031412A JP 3141285 A JP3141285 A JP 3141285A JP H0653724 B2 JPH0653724 B2 JP H0653724B2
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen sulfide
- reaction
- cysteamine
- mercaptoethyl
- vinylacetamide
- 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 - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明はＮ−ビニルアセトアミドを出発原料とし、硫化
水素をラジカル付加し、Ｎ−（β−メルカプトエチル）
アセトアミドを合成しこれを加水分解して、システアミ
ン又はその塩類を高収率で製造するための新規な方法に
関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention uses N-vinylacetamide as a starting material to radically add hydrogen sulfide to give N- (β-mercaptoethyl).
The present invention relates to a novel method for synthesizing acetamide and hydrolyzing it to produce cysteamine or a salt thereof in high yield.
（従来技術と問題点） システアミンおよびその塩類は医薬品および農薬の中間
体として、又放射線防護物質として極めて有用な物質で
ある。(Prior Art and Problems) Cysteamine and its salts are extremely useful substances as intermediates for pharmaceuticals and agricultural chemicals, and as a radiation protection substance.
システアミンおよびその塩類の製造法としては、以下の
ような方法がある。The following methods are available for producing cysteamine and its salts.
1.エチレンイミン硫化水素を付加する方法 (J.Chem.Soc.,1994,5.) 2.エチレンイミンとケトンの付加体に硫化水素を反応さ
せこれをハロゲン化水素酸で加水分解する方法 （特公昭54-41569） 3.アミノアルキル硫酸エステルと水硫化アルカリ又は多
硫化アルカリと反応させる方法 （特公昭55-11506） （日化誌，1979，(1)P149〜151） 4.2-アルキル-2-オキサゾリンと硫化水素を反応させこ
れを塩酸水溶液中で加水分解する方法 （特開昭54-128509） 5.2-メルカプトチアゾリンを経由する方法 (J.Org.Chem.,25 869(1960)) （特開昭59-231064） 1.2の方法は発ガン性のあるイミンを原料として使用す
る欠点を有している。1. Method of adding ethyleneimine hydrogen sulfide (J.Chem.Soc., 1994 , 5.) 2. Method of reacting adduct of ethyleneimine and ketone with hydrogen sulfide and hydrolyzing it with hydrohalic acid ( JP-B-54-41569) 3. Method of reacting aminoalkyl sulfate with alkali hydrosulfide or alkali polysulfide (JP-B-55-11506) (Nikka, 1979, (1) P149-151) 4.2-Alkyl-2 -Method of reacting oxazoline with hydrogen sulfide and hydrolyzing it in hydrochloric acid aqueous solution (JP-A-54-128509) 5.2-Method via mercaptothiazoline (J.Org.Chem., 25 869 (1960)) (special The method of Kaisho 59-231064) 1.2 has a drawback that imine having carcinogenicity is used as a raw material.
3.4.5の方法はエタノールアミンを出発原料としうるの
でこの欠点を補っているが、３の方法ではスルフィドの
副生がさけられない事。酸・アルカリ多消費型である
事。4.5は工程数が多い事。など工業的製造法としては
問題点を有し満足しうるものではない。The method of 3.4.5 compensates for this drawback because ethanolamine can be used as a starting material, but the method of 3 does not avoid sulfide by-products. Must be highly acid and alkali consuming. 4.5 has a large number of processes. However, the industrial manufacturing method has problems and is not satisfactory.
（本発明による解決手段） 本発明者らは、これら先行技術の問題点を解決する方法
として入手容易な、Ｎ−ビニルアセトアミドを出発原料
とし、これに位置選択的に硫化水素が付加しうる事を見
い出し、その結果高収率で得られたＮ−（β−メルカプ
トエチル）アセトアミドを加水分解によりシステアミン
又はその塩類を効率的に製造しうる方法を完成した。(Means for Solving by the Present Invention) The present inventors use N-vinylacetamide as a starting material, which is an easily available method for solving the problems of the prior art, and hydrogen sulfide can be regioselectively added thereto. As a result, they have completed a method capable of efficiently producing cysteamine or a salt thereof by hydrolyzing N- (β-mercaptoethyl) acetamide obtained in high yield.
本発明は、一般式 （式中、Ｒはアルキル基を示す。）で表わされるＮ−ビ
ニルアルキルアミドに硫化水素をラジカル付加して、一
般式 （式中、Ｒは前記の通り。）で表わされるＮ−（β−メ
ルカプトエチル）アルキルアミドを合成し、これを加水
分解してシステアミンＨＳ−ＣＨ２ＣＨ２−ＮＨ２又
は、その塩類を製造する方法に関する。The present invention has the general formula (In the formula, R represents an alkyl group.) Hydrogen sulfide is radically added to the N-vinylalkylamide represented by the general formula (In the formula, R is as described above), N- (β-mercaptoethyl) alkylamide is synthesized, and this is hydrolyzed to produce cysteamine HS—CH 2 CH 2 —NH 2 or a salt thereof. On how to do.
本発明に使用する原料のＮ−ビニルアセトアミドは、ア
セトアルデヒドのアセトアミド付加体の熱分解により製
造する事が出来る。The raw material N-vinylacetamide used in the present invention can be produced by thermal decomposition of an acetamide adduct of acetaldehyde.
Ｎ−ビニルアセトアミドに硫化水素をラジカル的に付加
させＮ−（β−メルカプトエチル）アセトアミドを高収
率で製造するためには、原料のＮ−ビニルアセトアミド
の重合、生成物の原料への付加、マルコニコフ型の硫化
水素の付加などの副反応を抑制し、反応条件を最適に設
定することが重要である。In order to radically add hydrogen sulfide to N-vinylacetamide to produce N- (β-mercaptoethyl) acetamide in high yield, polymerization of N-vinylacetamide as a raw material, addition of a product to a raw material, It is important to suppress the side reaction such as addition of Marconnikov type hydrogen sulfide and to set the reaction conditions to the optimum.
反応は、溶媒の存在下又は過剰の液化硫化水素存在下で
実施する方が好ましい。The reaction is preferably carried out in the presence of a solvent or excess liquefied hydrogen sulfide.
溶媒を使用する場合には原料と反応したり、目的の反応
を阻害するような負の影響のある溶媒はさけるべきで炭
化水素溶剤、エステル類、アルコール類など一般的な溶
剤から、前述の条件に合うものを選び使用する。If a solvent is used, it should not react with the raw materials or a solvent that has a negative influence on the reaction of interest, and should avoid the common solvents such as hydrocarbon solvents, esters, alcohols, etc. Select and use the one that suits your needs.
例えば、酢酸ブチル、ベンゼン、メタノール、1.4-ジオ
キサンなどを溶媒として使用しうる。For example, butyl acetate, benzene, methanol, 1.4-dioxane and the like can be used as a solvent.
Ｎ−ビニルアセトアミドと硫化水素の比は、Ｎ−（β−
メルカプトエチル）アセトアミドの選択率を高くするた
めに、硫化水素過剰の方が好ましく、通常２〜100倍の
過剰率で反応を実施する。硫化水素の過剰率が減少する
と重合反応が進行しポリマーが副生する。The ratio of N-vinylacetamide to hydrogen sulfide is N- (β-
In order to increase the selectivity of mercaptoethyl) acetamide, hydrogen sulfide excess is preferable, and the reaction is usually carried out at an excess rate of 2 to 100 times. When the excess ratio of hydrogen sulfide decreases, the polymerization reaction proceeds and the polymer is by-produced.
反応の開始は、ラジカル開始剤を使用すれば十分である
が、これに限ることはない。開始剤は一般に使用される
過酸化物、過酸エステル、アゾ化合物等が使用される。It is sufficient to start the reaction by using a radical initiator, but it is not limited thereto. As the initiator, generally used peroxides, peroxyesters, azo compounds and the like are used.
反応温度は使用するラジカル開始剤により影響を受ける
が、高温で短時間の反応の方が良い成績を示す傾向があ
り、50〜120℃で実施しうる。The reaction temperature is affected by the radical initiator used, but a reaction at a high temperature for a short time tends to give better results, and can be carried out at 50 to 120 ° C.
圧力は硫化水素の量、温度により変化するが、加圧系の
方が好ましく、常圧ないし50Kg/cm2程度の加圧下で実施
する。The pressure varies depending on the amount of hydrogen sulfide and the temperature, but a pressurized system is preferable, and it is carried out under atmospheric pressure or a pressure of about 50 Kg / cm 2 .
Ｎ−（β−メルカプトエチル）アセトアミドの加水分解
は酸又はアルカリの存在下水溶液中で不活性ガス雰囲気
下で通常の方法で実施しうる。Hydrolysis of N- (β-mercaptoethyl) acetamide can be carried out by a conventional method in an aqueous solution in the presence of an acid or an alkali under an inert gas atmosphere.
システアミンの鉱酸塩を得るためにはその鉱酸存在下で
加水分解するのが有利である。To obtain the cysteamine mineral salt, it is advantageous to hydrolyze in the presence of the mineral acid.
この場合、鉱酸はＮ−（β−メルカプトエチル）アセト
アミドに対し、1.0〜10当量好ましくは、1.0〜2.0当量
加え30℃〜200℃で加水分解をおこなう。In this case, the mineral acid is added to N- (β-mercaptoethyl) acetamide in an amount of 1.0 to 10 equivalents, preferably 1.0 to 2.0 equivalents, and hydrolyzed at 30 to 200 ° C.
次に本発明を実施例に基づきさらに詳細に説明する。Next, the present invention will be described in more detail based on examples.
実施例１ 50ccオートクレーブに酢酸ブチル20ｍ、Ｎ−ビニルア
セトアミド12mmo、硫化水素250mmo、ＡＩＢＮ32mg
を充填し、100℃、22〜25Kg/cm220分反応をおこなっ
た。Example 1 Butyl acetate 20m, N-vinylacetamide 12mmo, hydrogen sulfide 250mmo, AIBN 32mg in a 50cc autoclave.
Was charged and the reaction was carried out at 100 ° C. for 22 to 25 Kg / cm 2 for 20 minutes.
反応後反応液を分析したところＮ−ビニルアセトアミド
の変化率は92％、Ｎ−（β−メルカプトエチル）アセト
アミドの選択率は93％であった。When the reaction solution was analyzed after the reaction, the conversion rate of N-vinylacetamide was 92% and the selectivity of N- (β-mercaptoethyl) acetamide was 93%.
この反応液を蒸留し、Ｎ−（β−メルカプトエチル）ア
セトアミドを分離した。The reaction solution was distilled to separate N- (β-mercaptoethyl) acetamide.
このＮ−（β−メルカプトエチル）アセトアミド0.92ｇ
をサンプリングし、水２ｍに溶かし、濃塩酸２ｍを
加え４時間100℃窒素気流下加熱した。0.92 g of this N- (β-mercaptoethyl) acetamide
Was sampled, dissolved in 2 m of water, added with 2 m of concentrated hydrochloric acid, and heated for 4 hours at 100 ° C. under a nitrogen stream.
反応後水、塩酸を除去し、システアミン塩酸塩を分離し
た。After the reaction, water and hydrochloric acid were removed, and cysteamine hydrochloride was separated.
システアミン塩酸塩0.83ｇを得た。0.83 g of cysteamine hydrochloride was obtained.
実施例２ 50ccオートクレーブに酢酸ブチル20ｍ、Ｎ−ビニルア
セトアミド12mmo、硫化水素73mmo、ＡＩＢＮ30mgを
充填し90℃、８Kg/cm260分反応をおこなった。Example 2 A 50 cc autoclave was charged with 20 m of butyl acetate, 12 mm of N-vinylacetamide, 73 mmo of hydrogen sulfide and 30 mg of AIBN, and reacted at 90 ° C. for 8 kg / cm 2 60 minutes.
（反応後反応液を分析したところＮ−ビニルアセトアミ
ドの変化率は98％、選択率は85％であった。） この反応液の溶媒を留去したものに５規定塩酸４ｍを
加え、２時間窒素気流下で100℃に加熱した。(After the reaction, the reaction solution was analyzed, and it was found that the conversion rate of N-vinylacetamide was 98% and the selectivity was 85%.) The solvent of this reaction solution was distilled off, and 4 m of 5N hydrochloric acid was added, followed by 2 hours. Heated to 100 ° C under a stream of nitrogen.
反応後水、塩酸を留去して得られる白色粗結晶をエタノ
ールにて再結晶することによりシステアミン塩酸塩1.03
ｇを得た。After the reaction, water and hydrochloric acid were distilled off, and the white crude crystals obtained were recrystallized from ethanol to give cysteamine hydrochloride 1.03.
g was obtained.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭57−122063（ＪＰ，Ａ) 湊宏訳「フリーラジカルの化学」（株) 東京化学同人発行1968．11．５Ｐ．84 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-57-122063 (JP, A) Translated by Hiroshi Minato "Chemicals of Free Radicals" Tokyo Kagaku Dojin, 1968 / 111.5 P. 84
Claims (1)
ニルアルキルアミドに硫化水素をラジカル付加して、一
般式 （式中、Ｒは前記の通り。）で表わされるＮ−（β−メ
ルカプトエチル）アルキルアミドを合成し、これを加水
分解してシステアミンＨＳ−ＣＨ２ＣＨ２−ＮＨ２又
は、その塩類を製造する方法。1. A general formula (In the formula, R represents an alkyl group.) Hydrogen sulfide is radically added to the N-vinylalkylamide represented by the general formula (In the formula, R is as described above), N- (β-mercaptoethyl) alkylamide is synthesized, and this is hydrolyzed to produce cysteamine HS—CH 2 CH 2 —NH 2 or a salt thereof. how to.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60031412A JPH0653724B2 (en) | 1985-02-21 | 1985-02-21 | Method for producing cysteamine or salts thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60031412A JPH0653724B2 (en) | 1985-02-21 | 1985-02-21 | Method for producing cysteamine or salts thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61191672A JPS61191672A (en) | 1986-08-26 |
| JPH0653724B2 true JPH0653724B2 (en) | 1994-07-20 |
Family
ID=12330539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60031412A Expired - Fee Related JPH0653724B2 (en) | 1985-02-21 | 1985-02-21 | Method for producing cysteamine or salts thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0653724B2 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57122063A (en) * | 1981-12-14 | 1982-07-29 | Dow Chemical Co | Manufacture of 2-mercaptoethylamine hydrochloride |
-
1985
- 1985-02-21 JP JP60031412A patent/JPH0653724B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 湊宏訳「フリーラジカルの化学」（株）東京化学同人発行１９６８．１１．５Ｐ．８４ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61191672A (en) | 1986-08-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |