JPS63166859A - 2-mercaptoalkylcarboxylic acid aryl esters and production thereof - Google Patents
2-mercaptoalkylcarboxylic acid aryl esters and production thereofInfo
- Publication number
- JPS63166859A JPS63166859A JP31570286A JP31570286A JPS63166859A JP S63166859 A JPS63166859 A JP S63166859A JP 31570286 A JP31570286 A JP 31570286A JP 31570286 A JP31570286 A JP 31570286A JP S63166859 A JPS63166859 A JP S63166859A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- formula
- compound
- ester
- alkali metal
- 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.)
- Pending
Links
- 239000002253 acid Substances 0.000 title claims abstract description 8
- 150000007860 aryl ester derivatives Chemical class 0.000 title claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- -1 2-Mercaptoisobutyric acid 2-methylphenyl ester Chemical class 0.000 claims abstract description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 8
- 238000006177 thiolation reaction Methods 0.000 claims abstract description 5
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 8
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 6
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical group [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 21
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 150000003862 amino acid derivatives Chemical class 0.000 abstract description 2
- BWXULOIABYDCGG-UHFFFAOYSA-N phenyl 2-bromo-2-methylpropanoate Chemical compound CC(C)(Br)C(=O)OC1=CC=CC=C1 BWXULOIABYDCGG-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 abstract description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 2
- VUAFHZCUKUDDBC-BYPYZUCNSA-N Bucillamine Chemical compound CC(C)(S)C(=O)N[C@@H](CS)C(O)=O VUAFHZCUKUDDBC-BYPYZUCNSA-N 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003172 expectorant agent Substances 0.000 abstract 1
- 230000003419 expectorant effect Effects 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 239000004201 L-cysteine Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N alpha-mercaptoacetic acid Natural products OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UDDBRJGGGUMTQZ-UHFFFAOYSA-N (2,6-dimethylphenyl) acetate Chemical compound CC(=O)OC1=C(C)C=CC=C1C UDDBRJGGGUMTQZ-UHFFFAOYSA-N 0.000 description 1
- RPOAKDSMKKNFDR-UHFFFAOYSA-N (2-methylphenyl) 2-bromoacetate Chemical compound CC1=CC=CC=C1OC(=O)CBr RPOAKDSMKKNFDR-UHFFFAOYSA-N 0.000 description 1
- MREWIVZBHYUQSA-UHFFFAOYSA-N (3-methylphenyl) 2-bromo-2-methylpropanoate Chemical compound CC1=CC=CC(OC(=O)C(C)(C)Br)=C1 MREWIVZBHYUQSA-UHFFFAOYSA-N 0.000 description 1
- INTDJCRUCXBZDX-UHFFFAOYSA-N (4-methoxyphenyl) 2-bromo-2-methylpropanoate Chemical compound COC1=CC=C(OC(=O)C(C)(C)Br)C=C1 INTDJCRUCXBZDX-UHFFFAOYSA-N 0.000 description 1
- CFUKJWSPMHCKIJ-UHFFFAOYSA-N (4-methylphenyl) 2-bromo-2-methylpropanoate Chemical compound CC1=CC=C(OC(=O)C(C)(C)Br)C=C1 CFUKJWSPMHCKIJ-UHFFFAOYSA-N 0.000 description 1
- JYUXDXWXTPSAEL-UHFFFAOYSA-N 1,4-dioxane;oxolane Chemical compound C1CCOC1.C1COCCO1 JYUXDXWXTPSAEL-UHFFFAOYSA-N 0.000 description 1
- ABYMGZBIRXNEIB-UHFFFAOYSA-N 2-methyl-2-sulfanylpropanamide Chemical compound CC(C)(S)C(N)=O ABYMGZBIRXNEIB-UHFFFAOYSA-N 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- UEWYUCGVQMZMGY-UHFFFAOYSA-N phenyl 2-bromoacetate Chemical compound BrCC(=O)OC1=CC=CC=C1 UEWYUCGVQMZMGY-UHFFFAOYSA-N 0.000 description 1
- JWAVCRPHRRVUIT-UHFFFAOYSA-N phenyl 2-bromopropanoate Chemical compound CC(Br)C(=O)OC1=CC=CC=C1 JWAVCRPHRRVUIT-UHFFFAOYSA-N 0.000 description 1
- WIYXENRNXXJXCO-UHFFFAOYSA-N phenyl 2-chloro-2-methylpropanoate Chemical compound CC(C)(Cl)C(=O)OC1=CC=CC=C1 WIYXENRNXXJXCO-UHFFFAOYSA-N 0.000 description 1
- SJWWLGBKKYTCAM-UHFFFAOYSA-N phenyl 2-methyl-2-sulfanylpropanoate Chemical compound CC(C)(S)C(=O)OC1=CC=CC=C1 SJWWLGBKKYTCAM-UHFFFAOYSA-N 0.000 description 1
- DPDRAKOKBQWXTQ-UHFFFAOYSA-N phenyl 2-sulfanylpropanoate Chemical compound CC(S)C(=O)OC1=CC=CC=C1 DPDRAKOKBQWXTQ-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- ZOCLAPYLSUCOGI-UHFFFAOYSA-M potassium hydrosulfide Chemical compound [SH-].[K+] ZOCLAPYLSUCOGI-UHFFFAOYSA-M 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、一般式
（ここにＲは水素または０１〜Ｃ４のアルキル基を示す
。）で表わされる新規な２−メルカプトイソ酪酸アリー
ルエステルおよびその製造法を提供するものである。Detailed Description of the Invention (Industrial Application Field) The present invention provides novel 2-mercaptoisobutyric acid aryl esters represented by the general formula (wherein R represents hydrogen or an alkyl group of 01 to 01 to 4 carbon atoms); The present invention provides a method for producing the same.
本発明の新規化合物は、アミン化合物と定量的に反応し
、２−メルカプトイソ酪酸アミドＩｓ体を与える。例え
ば、Ｌ−システィンとの反応では下式で示σれるＮ−
（２−メルカプト−２−メチルプロピ汀ニル）−Ｌ−シ
スティン′を好収率で与える。The novel compound of the present invention quantitatively reacts with an amine compound to give 2-mercaptoisobutyric acid amide Is form. For example, the reaction with L-cysteine gives N-(2-mercapto-2-methylpropyl)-L-cysteine' represented by the following formula in good yield.
ＣＨ３
＞ Ｃ−ＣＯＮＨＣＨＣＯＯＨ
ＣＨ３ ｌ Ｉ
Ｓ Ｈ ＣＨ２Ｓ Ｈ
このものは医薬、特に喀痰溶解剤として有用で必ること
が知られている。（特公昭５６−５３８８ 、特開昭５
４−６３０１７ ）（従来の技術） （発明が解決しよ
うとする問題点）２−メルカプトイソ酪酸アリールエス
テル類は、新規な化合物であって公知の文献には、ぞの
合成法，物性，その他関連技術に関する記載は全く見当
らない。CH3 > C-CONHCHCOOH CH3 I S H CH2S H This compound is known to be useful as a medicine, especially as a sputum dissolver. (Special Publication No. 56-5388, Japanese Patent Publication No. 56-5388)
4-63017) (Prior art) (Problems to be solved by the invention) 2-Mercaptoisobutyric acid aryl esters are new compounds, and known literature does not contain information on their synthesis methods, physical properties, and other related matters. There is no mention of technology at all.
以下、本発明の内容について詳細に説明する。Hereinafter, the content of the present invention will be explained in detail.
（発明の構成）
本発明は一段式（Ｉ＞で表わされる新規な２−メルカプ
トイソ酪酸アリールエステル類およびこの化合物を一般
式（Ｉ）で表わされる２−ハロイソ酪酸アリールエステ
ル類をチオール化することにより製造する方法に関する
。(Structure of the Invention) The present invention relates to novel 2-mercaptoisobutyric acid aryl esters represented by the one-step formula (I>) and thiolation of 2-haloisobutyric acid aryl esters represented by the general formula (I) to this compound. It relates to a method of manufacturing.
さらに詳しくは一般式（ｎ）で表わされる化合物のハロ
ゲン基をチオール化剤を用いることによりチオール化し
、新規な一般式（Ｉ＞で表わされる化合物を製造する方
法に関する。More specifically, the present invention relates to a method for producing a novel compound represented by the general formula (I>) by thiolating the halogen group of the compound represented by the general formula (n) using a thiolating agent.
本発明により得られる化合物を例示すると２−メルカプ
トイソ酪酸フェニルエステル。An example of the compound obtained by the present invention is 2-mercaptoisobutyric acid phenyl ester.
２−メルカプトイソ酪酸２−メチルフェニルエステル、
２−メルカプトイソ酪酸３−メチルフェニルエステル、
２−メルカプトイソ酪＠４ーメチルフェニルエステル
プトイソ酪酸４−エヂルフェニルエステル。2-mercaptoisobutyric acid 2-methylphenyl ester,
2-mercaptoisobutyric acid 3-methylphenyl ester,
2-Mercaptoisobutyric@4-methylphenyl esterPtoisobutyric acid 4-edylphenyl ester.
２−メルカプトイソ酪酸４−ｔｅｒｔ−ブチルフェニル
エステル、２−メルカプトイン醋酸２、６−シメチルフ
エニルエステル、２−メルカプトイソ酪酸４−メトキシ
フェニルエステル等を挙げることができる。Examples include 2-mercaptoisobutyric acid 4-tert-butylphenyl ester, 2-mercaptoin acetic acid 2,6-dimethylphenyl ester, and 2-mercaptoisobutyric acid 4-methoxyphenyl ester.
本発明の方法を利用すれば、ざらにその他２ーメルカプ
トアルキルカルボン
エステル類，例えば２−メルカプトプロピオン酸フェニ
ルエステル、２−メルカプトプロピオン酸２−メチルフ
ェニルエステル、チオグリコール酸フェニルエステル、
チオグリコール酸２−メチルフェニルエステル等を得る
ことができる。If the method of the present invention is used, Zara and other 2-mercaptoalkyl carbon esters, such as 2-mercaptopropionic acid phenyl ester, 2-mercaptopropionic acid 2-methylphenyl ester, thioglycolic acid phenyl ester,
Thioglycolic acid 2-methylphenyl ester and the like can be obtained.
これらを製造する原料である２−ハロアルキルカルボン
酸アリールエステルとしては、２−ブロモイソ酪酸フェ
ニルエステル、２−クロロイソ酪酸フェニルエステル、
２−ヨードイソ酪酸フェニルエステル、２−ブロモイソ
酪Ｆ！！２ーメチルフェニルエステル、２−クロルイソ
酪酸２−メチルフェニルエステル、２−プロモイソ酪酸
３−メチルフェニルエステル、２−ブロモイソ酪酸４−
メチルフェニルエステル、２−ブロモイソ酪酸４−エチ
ルフェニルエステル、２−ブロモイソ酪酸４−ｔｅｒｔ
ブチルフェニルエステル、２−クロロイソｌ￥［４−ｔ
ｅｒｔ−ブチルフェニルエステル。The 2-haloalkylcarboxylic acid aryl esters that are the raw materials for producing these include 2-bromoisobutyric acid phenyl ester, 2-chloroisobutyric acid phenyl ester,
2-Iodoisobutyric acid phenyl ester, 2-bromoisobutyric F! ! 2-methylphenyl ester, 2-chloroisobutyric acid 2-methylphenyl ester, 2-bromoisobutyric acid 3-methylphenyl ester, 2-bromoisobutyric acid 4-
Methylphenyl ester, 2-bromoisobutyric acid 4-ethylphenyl ester, 2-bromoisobutyric acid 4-tert
Butylphenyl ester, 2-chloroisol\[4-t
ert-butylphenyl ester.
２−ブロモイソ酪酸２，６−シメチルフエニルエステル
、２−ブロモイソ酪酸４−メトキシフェニルエステル、
２−ブロモプロピオン酸フェニルエステル、２−ブロモ
プロピオン酸２−メチルフェニルエステル、２−クロロ
プロピオン酸２−メチルフェニルエステル。2-bromoisobutyric acid 2,6-dimethylphenyl ester, 2-bromoisobutyric acid 4-methoxyphenyl ester,
2-bromopropionic acid phenyl ester, 2-bromopropionic acid 2-methylphenyl ester, 2-chloropropionic acid 2-methylphenyl ester.
ブロモ酢酸フェニルエステル、ブロモ酢酸２−メチルフ
ェニルエステル等を挙げることができる。以上の如く種
々の２−ハロアルキルカルボン酸アリールエステル類を
原料とすることができるが、２−ハロイソ酪酸メチルフ
ェニルエステルを用いた場合は、後述のヂオール化反応
における収率が高いため、特に好適に用いられる。Bromoacetic acid phenyl ester, bromoacetic acid 2-methylphenyl ester, etc. can be mentioned. As mentioned above, various 2-haloalkylcarboxylic acid aryl esters can be used as raw materials, but when using 2-haloisobutyric acid methylphenyl ester, the yield in the diolation reaction described below is high, so it is particularly preferred. used.
ヂオール化反応は、下式に従って進行し、チオール化剤
としては水硫化ナトリウム、水硫化カリウム等の水硫化
アルカリ金属を用いるが、硫化水素を常圧おるいは加圧
下で溶媒中に飽和させた状態で反応を行なえば、ざらに
収率よく目的物を得ることができる。The diolation reaction proceeds according to the following formula, and an alkali metal hydrosulfide such as sodium bisulfide or potassium bisulfide is used as the thiolating agent. Hydrogen sulfide is saturated in the solvent at normal pressure or under pressure. If the reaction is carried out in this state, the target product can be obtained in a fairly good yield.
水硫化アルカリ金属は、２−ハロアルキルカルボン酸ア
リールエステル類に対し、１．Ｏ〜２．０倍モル使用す
ると好結果が得られる。The alkali metal hydrosulfide is 1. Good results can be obtained by using O to 2.0 times the mole.
ＣＨ３ＭＳＮ
＞ Ｃ−Ｃ００Ａｒ
ＣＨ３ｌ
一般式（ｎ）
ＣＨ３
＞ Ｃ−ＣＯＯＡｒ
ＣＨ３ｌ
Ｈ
一般式（Ｉ＞
（Ｘはハロゲン原子１Ｍはアルカリ金属を示す。〉
反応溶媒としては、水、メタノール、エタノール、ｎ−
プロパツール、イソプロパツール。CH3MSN > C-C00Ar CH3l General formula (n) CH3 > C-COOAr CH3l H General formula (I> (X is a halogen atom 1M represents an alkali metal.) As a reaction solvent, water, methanol, ethanol, n-
Proper Tools, Isoproper Tools.
ｎ−ブタノール等の低級アルコール類、アセトン、メチ
ルエチルケトン等のケトン煩、テトラヒドロフランジオ
キサン等のエーテル類。Lower alcohols such as n-butanol, ketones such as acetone and methyl ethyl ketone, and ethers such as tetrahydrofuran dioxane.
Ｎ、Ｎ−ジメチルホルムアミド、ジメチルスルホキシド
等の極性溶媒およびこれらの混合物が使用できる。Polar solvents such as N,N-dimethylformamide, dimethylsulfoxide and mixtures thereof can be used.
反応温度は１０°Ｃ〜８０’Ｃ１好ましくは２０’Ｃ〜
６０’Ｃの範囲に保って実施する。The reaction temperature is 10°C to 80'C1, preferably 20'C to
The temperature is maintained within the range of 60'C.
反応温度が低すぎると反応速度がおそく、逆に高すぎる
と副反応が起こり、収率が低下するので好ましくない。If the reaction temperature is too low, the reaction rate will be slow, whereas if it is too high, side reactions will occur and the yield will decrease, which is not preferred.
（実施例）
次に実施例により本発明の詳細な説明するが、本発明は
、これら実施例のみに限定されるものではない。(Examples) Next, the present invention will be explained in detail with reference to Examples, but the present invention is not limited only to these Examples.
！塵史ユ
還流冷却器、温度計、攪拌機、ガス吹き込み管を備えた
四つロフラスコに７０％水硫化ナトリウム１１２．０
！？ （１，４モル）、メタノール６２６．０７を仕込
み、４０’Ｃにて溶解後、硫化水素を５０ｄ／ｍｉｎで
１５分間吹き込み硫化水素飽和状態とした。! 112.0% 70% sodium bisulfide in a four-loaf flask equipped with a reflux condenser, thermometer, stirrer, and gas injection tube.
! ? (1.4 mol) and 626.07 mol of methanol were charged, and after dissolving at 40'C, hydrogen sulfide was blown in at 50 d/min for 15 minutes to bring it into a state of hydrogen sulfide saturation.
また、別途２−ブロモイソ酪酸２−メチルフエニルエス
テル２５７．ＯＬ３（１゜０モル）をメタノール１７４
．ＯｃＪに溶かしたメタノール溶液を４０℃にて、前述
のメタノール溶液に２時間かけて滴下し、ざらに同温度
で４時間撹拌した。Additionally, 2-bromoisobutyric acid 2-methylphenyl ester 257. OL3 (1゜0 mol) in methanol 174
．． A methanol solution dissolved in OcJ was added dropwise to the above methanol solution over 2 hours at 40°C, and the mixture was roughly stirred at the same temperature for 4 hours.
この間、硫化水素を１０ｍ／’ｍｉｒ＋で反応系に吹き
込み、硫化水素飽和状態を保持した。During this time, hydrogen sulfide was blown into the reaction system at 10 m/'mir+ to maintain a hydrogen sulfide saturated state.
反応後、１０％塩酸水溶液でｐＨ＝１とした後、一部メ
タノールを留去した。残留物に水９８５．０！７を添す
ロし、クロロホルムで生成物を抽出した。ざらにクロロ
ホルムを留去した後、残留物を減圧蒸留することにより
、２−メルカプトイソ酪酸２−メチルフェニルエステル
１２８．０！？を得た。２−ブロモイソ酪酸２−メチル
フェニルエステルに対する収率は、６０．０％であった
。After the reaction, the pH was adjusted to 1 with a 10% aqueous hydrochloric acid solution, and then a portion of methanol was distilled off. Water 985.0!7 was added to the residue, and the product was extracted with chloroform. After roughly distilling off the chloroform, the residue was distilled under reduced pressure to obtain 2-mercaptoisobutyric acid 2-methylphenyl ester (128.0%). ? I got it. The yield based on 2-bromoisobutyric acid 2-methylphenyl ester was 60.0%.
１ワられた２−メルカプトイソ酪酸２−メチルフェニル
エステルは以下に示す物性値を有するものである。The 2-mercaptoisobutyric acid 2-methylphenyl ester obtained by the above reaction has the following physical properties.
・沸 点 １０９〜１１２°Ｃ（５＃Ｈｇ）
・元素分析（％）
Ｈ３
測定値 ８２．８ ６．７ １５．１
計算値 ６２．９ ６．７ １５．２
・ＮＭＲスペクトル（δｐｐｍｃｏｃρ３）δ：
１．６５ 〜１．７５５ （６Ｈ＞δ： ２．１
４ 〜２．２１５ （３Ｈ）δ： ２．５５ 〜
２．６１５ （Ｉ Ｈ＞δ： ６．９０ 〜７．２
３ｍ（４Ｈ）・質量分析
分子量 ２１０
実施例２〜実施例６
原料の２−ハロイソ酪醒アリールエステル類を表−１の
化合物に変更した以外は、実施例１と同様に操作し、実
施例２〜実施例７に示す２−メルカプトイソ酪酸アリー
ルエステル類を１仔だ。・Boiling point 109-112°C (5#Hg)
・Elemental analysis (%) H3 Measured value 82.8 6.7 15.1 Calculated value 62.9 6.7 15.2 ・NMR spectrum (δppmcocρ3)δ:
1.65 to 1.755 (6H>δ: 2.1
4 ~ 2.215 (3H) δ: 2.55 ~
2.615 (I H>δ: 6.90 ~ 7.2
3m(4H)・Mass spectrometry molecular weight 210 Examples 2 to 6 The same procedure as in Example 1 was carried out except that the raw material 2-haloisobutyrated aryl esters were changed to the compounds in Table 1, and Example 2 - One offspring of 2-mercaptoisobutyric acid aryl esters shown in Example 7.
（発明の効果）
本発明による２−メルカプトイソ酪酸アリールエステル
類は、全く新規な化合物て市り、これを原料として合成
される＼−（２−メルカプト−２−メチルプロピオニル
）−し−システィンを始めとするチオール基含有アミノ
酸誘導体は、医薬として有用な化合物でおる。(Effects of the Invention) The 2-mercaptoisobutyric acid aryl esters of the present invention are completely new compounds that can be synthesized from \-(2-mercapto-2-methylpropionyl)-cysteine. Thiol group-containing amino acid derivatives are useful compounds as pharmaceuticals.
Claims (1)
示す。）で表わされる２−メル カプトイソ酪酸アリールエステル類。 （２）Ｒがメチル基である特許請求の範囲（１）記載の
化合物。 （３）Ｒが水素である特許請求の範囲（１）記載の化合
物。 （４）一般式 ▲数式、化学式、表等があります▼（II） （ここにＸはハロゲン原子をＲは式（ I ） と同じ意味を示す。）で表わされる２−ハ ロイソ酪酸アリールエステル類をチオール 化することを特徴とする一般式（ I ）で表 わされる化合物の製造法。 （５）Ｘがブロムである特許請求の範囲（４）記載の方
法。 （６）Ｒがメチル基である特許請求の範囲（４）記載の
方法。 （７）Ｒが水素である特許請求の範囲（４）記載の方法
。 （８）チオール化反応のチオール化剤として水硫化アル
カリ金属を用いる特許請求の範囲 （４）記載の方法。 （９）チオール化反応を硫化水素飽和下で水硫化アルカ
リ金属で行なう特許請求の範囲 （８）記載の方法。 （１０）水硫化アルカリ金属が水硫化ナトリウムである
特許請求の範囲（８）記載の方法。[Claims] (1) Aryl 2-mercaptoisobutyrate represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (where R represents hydrogen or an alkyl group of C_1 to C_4) Esters. (2) The compound according to claim (1), wherein R is a methyl group. (3) The compound according to claim (1), wherein R is hydrogen. (4) General formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (II) (where X is a halogen atom and R has the same meaning as in formula (I)) 2-haloisobutyric acid aryl esters A method for producing a compound represented by general formula (I), which is characterized by thiolation. (5) The method according to claim (4), wherein X is bromine. (6) The method according to claim (4), wherein R is a methyl group. (7) The method according to claim (4), wherein R is hydrogen. (8) The method according to claim (4), in which an alkali metal hydrosulfide is used as a thiolating agent in the thiolation reaction. (9) The method according to claim (8), wherein the thiolation reaction is carried out with an alkali metal hydrogen sulfide under saturated hydrogen sulfide conditions. (10) The method according to claim (8), wherein the alkali metal hydrosulfide is sodium hydrosulfide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31570286A JPS63166859A (en) | 1986-12-27 | 1986-12-27 | 2-mercaptoalkylcarboxylic acid aryl esters and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31570286A JPS63166859A (en) | 1986-12-27 | 1986-12-27 | 2-mercaptoalkylcarboxylic acid aryl esters and production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63166859A true JPS63166859A (en) | 1988-07-11 |
Family
ID=18068520
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP31570286A Pending JPS63166859A (en) | 1986-12-27 | 1986-12-27 | 2-mercaptoalkylcarboxylic acid aryl esters and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63166859A (en) |
-
1986
- 1986-12-27 JP JP31570286A patent/JPS63166859A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK1499587T3 (en) | Process for the synthesis of pharmaceutically active disulfide salts | |
| JPS63166859A (en) | 2-mercaptoalkylcarboxylic acid aryl esters and production thereof | |
| KR840000521A (en) | Process for preparing 3-methylflavone-8-carboxylic acid esters | |
| EP0326326B1 (en) | Cysteine derivatives | |
| KR890002427B1 (en) | Synthesis of nizatidine | |
| Lambeth et al. | Oxidative cyclization of 3-(amino) thioethers to form S-substituted isothiazolidinium salts | |
| US2595723A (en) | mu-allyl-oxy-phenyl-isothiocyanate | |
| US3308132A (en) | 6, 8-dithiooctanoyl amides and intermediates | |
| JPS62207268A (en) | Production of 1,3-dithiolane-2-thione derivative | |
| KR100351743B1 (en) | Process for preparation of the n,n-dicyclohexyl-2-benzothiazole sulfenamide | |
| JPH0674250B2 (en) | Method for producing thiocarbamate derivative | |
| JPS607623B2 (en) | 1-Carbamoyl-5-fluorouracil derivative and method for producing the same | |
| JPH0216754B2 (en) | ||
| JPS6310755A (en) | Production of 2-mercaptoalkylcarboxylic acid ester | |
| WO1984000543A1 (en) | Single crystalline dl-cysteine and process for their preparation | |
| JPH04364178A (en) | Production of 1,3-oxathiolium salts | |
| JPS63112557A (en) | L-cysteine derivative and production thereof | |
| JPH0827148A (en) | Production of dithiazolium salt | |
| JPH0219356A (en) | Aminoacetonitrile derivative and production thereof | |
| JPS60258159A (en) | Preparation of cysteine derivative | |
| JPH0482872A (en) | Production of 13carbon-labeled methionine or homolog thereof | |
| JPS63310860A (en) | Novel azoamidine compound and salt thereof | |
| CS276922B6 (en) | 3-azidomethyl-4-hydroxyphenyl alkyl ketones and the preparation method | |
| JPH01261362A (en) | Production of thiuram polysulfide | |
| JPH0383963A (en) | Bisarylsulfonoxymethyl ether and its production |