JPS58144377A - Preparation of 5-mercaptotetrazolyl-1-acetic acid - Google Patents

Abstract

PURPOSE:To prepare the titled compound in high purity and yield, by dissolving carboxymethyldithiocarbamic acid benzyl ester in an alkaline aqueous solution, adding a specific organic solvent and an alkali metal azide to the solution, reacting the components with each other under heating, and neutralizing the water layer. CONSTITUTION:Carboxymethyldithiocarbamic acid benzyl ester used as a starting material is dissolved n an alkaline aqueous solution, and the mixture is added with an organic solvent having low polarity and capable of dissolving the by-produced benzyl mercaptan (especially preferably, toluene, xylene, mesitylene, halogenated hydrocarbon having low polarity, ketone having low polarity, and ester having low polarity) and an alkali metal azide. The mixture is made to react under heating, and separated into the water layer and the organic solvent layer. The titled compound can be prepared by neutralizing the water layer with a mineral acid or an organic acid. EFFECT:The objective compound can be prepared easily in an industrial scale.

Description

【発明の詳細な説明】 本発明は工業的に容易に製造可能な収率尚く、純度穴な
る５−メルカプトテトラゾリル−１−酢酸の新規な製造
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 5-mercaptotetrazolyl-1-acetic acid with a high yield and purity that can be easily produced industrially.

従来の５−メルカプトテトラゾリル−１−ば［酸の製造
法は げ）　原料が高価である。Conventional 5-mercaptotetrazolyl-1-ba [method for producing acid] Raw materials are expensive.

（ロ）危険な原料薬品上使用するため工業的でない。(b) It is not suitable for industrial use because it is used as a dangerous raw material for chemicals.

ｅフ　　製造工程が複雑なうえ非常に困難な単位操作が
ある。eF The manufacturing process is complex and there are extremely difficult unit operations.

に）収率が低い。) low yield.

（ホ）製品の純度が低く、また肴色の度合が大きい。(e) The purity of the product is low and the degree of discoloration is large.

などの問題があり、実際に工業化できないか又はコスト
が著しく高くつ（欠点がめった。Due to these problems, it may not be possible to actually industrialize it, or the cost is extremely high (shortcomings are rare).

本発明者等は上記の問題を解決すべく鋭息吋光した結果
、炙くべきことに純度、収率共に篩く、工業的に容易に
製造り能な本発明を完１祝するに至った。The inventors of the present invention have worked hard to solve the above problems, and as a result have completed the present invention, which has excellent purity and yield, and can be easily manufactured industrially. Ta.

本発明はカルボキシメチルジチオカルパミ／酸ベンジル
エステル（以下単にエステルと略称する）を出発原料と
して便用し、先づアルカリ水溶液Ｖこエステルを溶解し
、ついでトルエン等の極性が低く、副生ずるペンジルメ
ル力プタ／倉溶解する有機溶媒とアルカリ金属のアジ化
物を加え、加熱して反応させ、更に反り後水層と有機溶
媒屑とを分離し、水層全塩酸等の鉱酸又は＠濃酸で中和
して５−メルカプトテトラゾリル−１−酢酸を製造する
方法を提供するもので化学反応式で示すと下記の通りで
ある。The present invention conveniently uses carboxymethyldithiocarpami/acid benzyl ester (hereinafter simply referred to as ester) as a starting material, first dissolves the ester in an alkaline aqueous solution, and then uses low polarity such as toluene to dissolve the by-produced pennzyl ester. Add the organic solvent to be dissolved and the alkali metal azide, heat to react, and after warping, separate the aqueous layer and organic solvent waste, and soak the entire aqueous layer with a mineral acid such as hydrochloric acid or @concentrated acid. It provides a method for producing 5-mercaptotetrazolyl-1-acetic acid by neutralization, and the chemical reaction formula is as follows.

ＨＯＯＣ（！Ｈ２ＮＨＣＢ２ＣＨ２Ｃ６Ｈ５＋Ｍ（工’
、）Ｏｉ４→Ｍ（Ｉ）００１：’ＣＨ，ＮＨＣ６２Ｃ！
Ｈ２Ｃ６Ｈ５＋Ｈ２０（１）ＣＭ（１）：　ア・レカリ
金属〕 Ｍ（Ｉ）ＱＯＣＣＨ２ＮＨＣ８２Ｃ１２Ｌ”６Ｈ５＋Ｍ
（１）Ｎ３→　　　Ｎ　−Ｎ ＩＩ　　　　Ｉｆ　　　　　＋Ｃ６Ｈ５σｕ２ｓＨ（２
１ＣＨ２ＣＯＯＣＨ２Ｃ ０ＯＮ　　　　　　　　　　　　　Ｎ−Ｎ＋　　　　　
　　　　　　　　　　１ ０Ｈ２ＣＯＯ１４Ｉ）　　　　　　　　Ｃ！Ｈ２ＣＯＯ
Ｈ以下上記反応式（す、（２）、（３）に従って本発明
を更に詳細に説明する。HOOC(!H2NHCB2CH2C6H5+M(工'
,)Oi4→M(I)001:'CH,NHC62C!
H2C6H5+H20(1) CM(1): A Recari Metal〕 M(I)QOCCH2NHC82C12L"6H5+M
(1) N3→ N −N II If +C6H5σu2sH(2
1CH2COOCH2C 0ON N-N+
1 0H2COO14I) C! H2COO
The present invention will be explained in more detail according to the reaction formulas (2) and (3) below.

（１）式の反応ではエステルと等モルのアルカリ水溶液
（水の量は２０Ｑ〜４ｏｏｐ１モルが好ましい）の中に
、エステルの結晶を加えて溶解する。In the reaction of formula (1), ester crystals are added and dissolved in an alkaline aqueous solution having an equimolar amount as the ester (the amount of water is preferably 1 mole of 20Q to 4oop).

（２）式の反応ではペンジルメルカプク〉をよく溶解す
る極性の低い（誘電率の小さい）有機溶媒とエステルの
１．０〜１．５倍モルのアルカリ金属アジ化物を加え、
５０〜１ｓｏ’Ｃ（好ましくは７０〜１００℃）まで昇
温し、同温度で３０分間以上（好ましくは３時間〜１０
時間）保ち、室温まで冷却し、分液して水層を得る。In the reaction of formula (2), a low polarity (low dielectric constant) organic solvent that dissolves Penzylmercapuc well and an alkali metal azide in an amount of 1.0 to 1.5 times the mole of the ester are added.
Raise the temperature to 50 to 1so'C (preferably 70 to 100℃) and keep at the same temperature for 30 minutes or more (preferably 3 hours to 10
time), cool to room temperature, and separate to obtain an aqueous layer.

本発明においては上記有機溶媒の適訳が本発明の重要な
部分の一つであって、有機溶媒としてはトルニジ、キシ
レン、メシチレシなと及び極性の低いハロゲン化炭化ボ
索、極性の低いケト／類、極性の低いエステル蛸など力
ｒ有効である。In the present invention, an appropriate translation of the above-mentioned organic solvent is one of the important parts of the present invention, and examples of organic solvents include torundi, xylene, mesitire, halogenated carbide with low polarity, ketone with low polarity, etc. It is effective to use esters such as esters with low polarity.

また本発明に使用の上記有機溶媒と（り式の反応におけ
るアルカリ水溶液中の水の重量比の割合は（９５：　５
　）〜（ｓ：「ｓ）であシ、好ましくは（８０：２０）
〜（２０：８０）である。Furthermore, the weight ratio of the organic solvent used in the present invention to water in the alkaline aqueous solution in the reaction of formula (2) is (95:5).
) ~ (s: “s)”, preferably (80:20)
~(20:80).

（３）式の反応では水層を塩酸で中８］（ＰＨ２，０〜
ｏ、　ｓ　）　−’１；あさ。In the reaction of formula (3), the aqueous layer is diluted with hydrochloric acid.
o, s) -'1; morning.

次にエステル又はケトン等の適当な有機溶媒で抽出板蒸
発乾固して５−メルカプトテトラゾリル−１−酢１１！
２を得た。この５−メルカプトテトラゾリル−１−酢酸
の結晶は必要に応じて精製すればよい。Next, an extraction plate was evaporated to dryness using a suitable organic solvent such as an ester or ketone to obtain 5-mercaptotetrazolyl-1-vinegar 11!
I got 2. The crystals of 5-mercaptotetrazolyl-1-acetic acid may be purified as necessary.

次Ｖこ実施例によって本発明を説明する。The invention will now be described by way of examples.

ス施ｙ１］１ ７ｉ（８０ｙに水酸化ナトリウム１２ｙ（０，３０モル
）ｆ：　ｔｚ；解した後、室温でカルボキシメチルジチ
オカルバミシｅベア’；ルエステルの結晶７２．３（０
，３モル）を攪拌しながら俗解する。After dissolving sodium hydroxide 12y (0.30 mol) in 80y, crystals of carboxymethyl dithiocarbamic acid ester 72.3(0
, 3 mol) while stirring.

次にトルエン１２０Ｊ／、アジ化ンーダ２１．５ｙ（Ｏ
，ａ３モルンを加え、８０℃まで昇温後、同温度で５時
間保つ、室温まで冷却後、トルエン層と水層とを分離す
る。Next, toluene 120J/, azide 21.5y (O
, a3 morn was added, the temperature was raised to 80°C, and kept at the same temperature for 5 hours. After cooling to room temperature, the toluene layer and the aqueous layer were separated.

水層を塩酸でＰＨ１，Ｏに調整し、活性炭で処理する。The aqueous layer was adjusted to pH 1.0 with hydrochloric acid and treated with activated carbon.

次に酢酸エチル１ｓ　ｏｍｌで４回抽出し、無水硫酸ナ
トリウムで脱湿後、減圧で蒸発乾固し、はぼ白色の５−
メルカプトテトラゾリル−１−酢酸の結晶３７９ｆ得た
。収率は７４％であった。Next, it was extracted four times with 1 s oml of ethyl acetate, dehumidified with anhydrous sodium sulfate, and evaporated to dryness under reduced pressure.
Crystals 379f of mercaptotetrazolyl-1-acetic acid were obtained. The yield was 74%.

この結晶のアルカリ滴定による純度は９１．１％である
。The purity of this crystal determined by alkaline titration is 91.1%.

実施例　２ 実施例１の反応溶媒組成を変えた場合の結果を第１表に
ボした。Example 2 Table 1 shows the results obtained when the reaction solvent composition of Example 1 was changed.

第　　　　１　　　　表 ゛ズ施例　３ 実施例１のトルエンの代９に他のイず機溶媒？用い、溶
媒組成が（ｓＯ：　５０）の場合の結果を第２表しで示
した。Table 1 Example 3 Can other organic solvents be used in place of toluene in Example 1? Table 2 shows the results when the solvent composition was (sO: 50).

ただしメチルアルコールの場合は反応温度を６５０とし
だ。However, in the case of methyl alcohol, the reaction temperature should be 650.

第２表より啄性の嶋い溶媒の場合収率は低い。As shown in Table 2, the yield is low in the case of a flimsy solvent.

第　　　２　　　ｘ 手続補正書（自発） 昭和５７年４月ら日 持ｆＦ庁長官　島田春樹殿 工　事件の表示 ！ｈイ相５７年特許願第２５６２３号 ２、　発ＩＪＩの名称 ５−メルカグトテトクゾリルー１−酢酸の製造法 ３　補正音する者 事件との関係　特計出頗人 住所　大阪？ｉ北区堂島浜１丁目２番６号氏名　東洋化
成工業林式会社 代表取締役社長　小林栄衛 り（細書の発明のｓｒ：　ＩＩＩ　；％説チ］の欄６　
補正の内容 明細書中 （１）４貝下から３行目 「遺沢」を「選択」に訂正 （２）６貝１行目 「トルエ」を「トルエン」に訂正 （３）６負１０行目 「７４％−１を「７５．６％」に訂正 （４）６貝１１行目No. 2 x Procedural Amendment (Voluntary) April 1980, Chief of Japan Agency, Haruki Shimada Indication of the incident! Patent Application No. 25623 of 1957 2, Name of IJI 5 - Process for producing mercagutotetoxolyl 1 - acetic acid 3 Relationship with the case of the amended person Address of the person making the special offer Osaka? i 1-2-6 Dojimahama, Kita-ku Name Eiri Kobayashi, President and Representative Director of Toyo Kasei Industrial Forestry Co., Ltd. Column 6 of Invention SR: III; % theory in the specification
Contents of amendment In the description (1) Corrected “Izawa” in the 3rd line from the bottom of the 4th shell to “selection” (2) Corrected “Tolue” in the 1st line of the 6th shell to “Toluene” (3) 6th negative line 10 Corrected ``74%-1'' to ``75.6%'' (4) 6 shells line 11

Claims (1)

【特許請求の範囲】 １　アルカリ水溶液にカルボキシメチルジチオカルバミ
ン酸ペンジルエステルヲ溶解し、ついで極性が低く、か
つ副生ずるペンジルメルカグク７を溶解する有機溶媒と
アルカリ金属アジ化物とを加え、加熱反応させ、反応後
水層と有機溶媒層とを分離し、水層を鉱酸もしくは刹゛
機鍍によって中和して、５−メルカプトテトラゾリル−
１−酢酸を製造する方法。 ２　極性が低くかつ副生ずるペンジルメル力ブタソ全溶
解する有機酸媒としてトルエン１キシレン、メシチレ／
、極性の低いハロゲン化炭化水素、極性の低いケトン類
、極性の低いエステル類を便用する持ｄＦ請求の範囲第
１項記載の５−メルカプトテトラゾリル−１−酢酸の製
造法。[Scope of Claims] 1. Carboxymethyldithiocarbamic acid pendyl ester is dissolved in an aqueous alkaline solution, then an organic solvent that has low polarity and dissolves by-produced pendyl merkagoku 7 and an alkali metal azide are added, and a heating reaction is carried out. After the reaction, the aqueous layer and the organic solvent layer are separated, and the aqueous layer is neutralized with a mineral acid or a chemical solution to form 5-mercaptotetrazolyl-
1-A method for producing acetic acid. 2 Toluene 1 xylene, mesitilene/
2. A method for producing 5-mercaptotetrazolyl-1-acetic acid according to claim 1, wherein halogenated hydrocarbons having low polarity, ketones having low polarity, and esters having low polarity are used.