JPS6014033B2 - Method for producing 4-methyloxazole - Google Patents
Method for producing 4-methyloxazoleInfo
- Publication number
- JPS6014033B2 JPS6014033B2 JP9935977A JP9935977A JPS6014033B2 JP S6014033 B2 JPS6014033 B2 JP S6014033B2 JP 9935977 A JP9935977 A JP 9935977A JP 9935977 A JP9935977 A JP 9935977A JP S6014033 B2 JPS6014033 B2 JP S6014033B2
- Authority
- JP
- Japan
- Prior art keywords
- methyloxazole
- reaction
- methyl
- yield
- producing
- 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
- PUMREIFKTMLCAF-UHFFFAOYSA-N 4-methyl-1,3-oxazole Chemical compound CC1=COC=N1 PUMREIFKTMLCAF-UHFFFAOYSA-N 0.000 title claims description 14
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- QBOFLCYFXQBLPQ-UHFFFAOYSA-N 4-methyl-3h-1,3-oxazole-2-thione Chemical compound CC1=COC(S)=N1 QBOFLCYFXQBLPQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 239000002994 raw material Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 238000009835 boiling Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WNVAJGCMEDTLIE-UHFFFAOYSA-N 2-oxopropyl formate Chemical compound CC(=O)COC=O WNVAJGCMEDTLIE-UHFFFAOYSA-N 0.000 description 1
- CLEJZSNZYFJMKD-UHFFFAOYSA-N 3h-1,3-oxazole-2-thione Chemical compound SC1=NC=CO1 CLEJZSNZYFJMKD-UHFFFAOYSA-N 0.000 description 1
- ZIXUNDOOBLSXPE-UHFFFAOYSA-N 4-methyl-1,3-oxazole-5-carboxylic acid Chemical compound CC=1N=COC=1C(O)=O ZIXUNDOOBLSXPE-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- KDIDLLIMHZHOHO-UHFFFAOYSA-N prop-2-ynyl formate Chemical compound O=COCC#C KDIDLLIMHZHOHO-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003746 solid phase reaction Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
【発明の詳細な説明】
本発明は４ーメチル−２−オキサゾールチオールの酸化
による４ーメチルオキサゾールの製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the preparation of 4-methyloxazole by oxidation of 4-methyl-2-oxazolethiol.
４−メチルオキサゾールは染料、医薬品等の中間体とし
て、例えばビタミン＆の原料として極めて重要な化合物
であり、これまでいくつかの製造法が公知にされている
。4-Methyloxazole is an extremely important compound as an intermediate for dyes, pharmaceuticals, etc., and as a raw material for vitamins, for example, and several production methods have been known so far.
例えば、（ｉ）４−メチルオキサゾールー５−カルボン
酸の脱炭酸による方法（ジャーナル・オプ・ザ・ケミカ
ル・ソサエティー第９３頁（１９５３））、（ｉｉ）ホ
ルムァミドとギ酸アセトニルェステルの反応による方法
（椿公昭４３一１８９０び号公報）、Ｇｉｉ）ハイドロ
キシアセトンとホルムィミドェーテルの反応による方法
（特開昭５１一６８５６４号公報）などが知られている
。しかしながら、これらの方法は収率、純度の点で満足
できるものではない。即ち、（ｉ）の方法は固相反応に
よるものであり、粉末原料と触媒を乾留し脱炭酸する方
法であるが、生成物が不純であり、実験室内での製法と
してはともかく、到底、工業的製法として採用すること
のできないものである。また、（ｉｉ）の方法はギ酸プ
ロパルギルェステルからの通算収率はわずか７．２％で
あり、中間体ギ酸２一ケトプロピルェステルからの収率
でさえ１５．２％に過ぎない。また、（ｉｉｉ）の方法
は前記（ｉ）（ｉｉ）の方法より工業的価値は高いと考
えられるが原料であるホルムィミドェーテルの浪費が多
く更に、後処理の点においても反応溶媒、残存原料と沸
点の近似する目的化合物を分留によって採取せねばなら
ず、化学操作上、必ずしも合理的な製法とは言えない。
本発明者は上記公知方法に代わる合理的な４ーメチルオ
キサゾールの工業的製法について鋭意研究を重ねた結果
、原料として４−メチル−２一オキサゾールチオールを
使用すれば安価で収率もよく、且つ、後処理が簡単な上
に純度の高い（ガスクロマトグラフイ一による定量では
純度１００％）４ーメチルオキサゾールが得られること
を発見し、本発明を完成した。For example, (i) by decarboxylation of 4-methyloxazole-5-carboxylic acid (Journal of the Chemical Society, p. 93 (1953)), (ii) by reaction of formamide and formic acid acetonyl ester. Methods such as (Tsubaki Publication No. 43-1890) and (Gii) a method by reaction of hydroxyacetone and formimide ether (Japanese Patent Application Laid-Open No. 51-68564) are known. However, these methods are not satisfactory in terms of yield and purity. In other words, method (i) is based on a solid-phase reaction, in which powdered raw materials and catalyst are carbonated and decarboxylated, but the product is impure, and although it can be produced in a laboratory, it is definitely not suitable for industrial use. This cannot be adopted as a standard manufacturing method. Further, in method (ii), the total yield from propargyl formate is only 7.2%, and even the yield from the intermediate 2-ketopropyle formate is only 15.2%. In addition, method (iii) is considered to have higher industrial value than methods (i) and (ii) above, but it wastes much of the raw material, formimide ether. However, the target compound, which has a boiling point similar to that of the remaining raw material, must be collected by fractional distillation, which is not necessarily a rational production method in terms of chemical operations.
As a result of intensive research into a rational industrial method for producing 4-methyloxazole as an alternative to the above-mentioned known method, the present inventor found that using 4-methyl-2-oxazole thiol as a raw material is inexpensive and has a good yield. They discovered that 4-methyloxazole can be obtained with simple post-treatment and high purity (100% purity as determined by gas chromatography), and completed the present invention.
以下、本発明を更に詳細に説明する。本発明は極めて安
価な物質であるロダン塩とオキシアセトンとの反応によ
って容易に高収率（約８０％）で得られる４ーメチル−
２−オキサゾールチオールを嫌料とし、これを酸化する
という簡単な操作により高収率で目的物質４−メチルオ
キサゾールを製造する方法であり、本発明反応は次の反
応式によって示される。The present invention will be explained in more detail below. The present invention provides 4-methyl-
This is a method for producing the target substance 4-methyloxazole in high yield by a simple operation of oxidizing 2-oxazolethiol as a raw material, and the reaction of the present invention is shown by the following reaction formula.
本反応に使用する酸化剤としては過酸化水素、過マンガ
ン酸カリ、硝酸等通常の酸化剤が用いられ、特に硝酸、
過酸化水素が工業的に有利である。As the oxidizing agent used in this reaction, common oxidizing agents such as hydrogen peroxide, potassium permanganate, and nitric acid are used, especially nitric acid,
Hydrogen peroxide is industrially advantageous.
反応は室温でも進行するが、加温によって促進される。
反応には溶媒を使用しても良いが、酸化試剤が溶媒をか
ねることも出来る。溶媒としては水、酢酸、プロピオン
酸などが用いられる。４−メチルオキサゾールは通常そ
の分離、精製が困難であり、特に４ーメチルオキサゾー
ルの沸点に近似の沸点をもつ化合物との分離が困難であ
るが、本発明方法によれば、酸化反応終了後反応液をア
ルカリ水溶液で中和するだけで残存原料は塩として水層
に移行するので４−メチルオキサゾールを油層として容
易に分離することが出来る。Although the reaction proceeds at room temperature, it is accelerated by heating.
A solvent may be used in the reaction, but the oxidizing reagent can also serve as the solvent. Water, acetic acid, propionic acid, etc. are used as the solvent. 4-Methyloxazole is usually difficult to separate and purify, especially from compounds with boiling points close to that of 4-methyloxazole. However, according to the method of the present invention, the reaction after the oxidation reaction is completed. By simply neutralizing the liquid with an alkaline aqueous solution, the remaining raw materials are transferred to the aqueous layer as salt, so that 4-methyloxazole can be easily separated as an oil layer.
油層を脱水後蒸留すればきわめて純度の高い４ーメチル
オキサゾールを得ることが出来る。次に実施例を挙げて
説明する。If the oil layer is dehydrated and then distilled, extremely pure 4-methyloxazole can be obtained. Next, an example will be given and explained.
実施例 １
４−メチル−２−オキサゾールチオール１１．５夕を硝
酸１５の‘、水３０の‘、亜硝酸ソーダ０．０２夕の混
液中に徐々に加える。Example 1 11.5 parts of 4-methyl-2-oxazolethiol are gradually added to a mixture of 15 parts of nitric acid, 30 parts of water, and 0.02 parts of sodium nitrite.
反応液を４５ｑｏで１時間燈拝し、反応液を苛性ソーダ
で中和し、塩析する。油層を分離、蒸留すれば、沸点８
８〜８９ｑｏの４−メチルオキサゾール６．２夕（収率
７４．７％）を得る。実施例 ２４ーメチル−２一オキ
サゾールチオール１１．５夕を硝酸３０の‘、水３０地
、亜硝酸ソーダ０．０２夕の濠液中に５５〜６０℃で徐
々に加える。同温度で１．虫時間鷹拝する。反応液を苛
性ソーダで中和後塩化メチレンで抽出、塩化メチレン層
を分留し、４−メチルオキサゾール６．５夕（収率７８
．３％）を得る。実施例 ３４ーメチル−２一オキサゾ
ールチオール５夕、過酸化水素水４０夕の混液を０〜５
℃にて５時間、室温で１幼時間反応させる。The reaction solution was heated at 45 qo for 1 hour, and the reaction solution was neutralized with caustic soda and salted out. If the oil layer is separated and distilled, the boiling point is 8.
6.2 quarts of 4-methyloxazole (yield 74.7%) of 8 to 89 qo are obtained. Example 2 11.5 parts of 4-methyl-2-oxazolethiol are gradually added to a solution of 30 parts of nitric acid, 30 parts of water and 0.02 parts of sodium nitrite at 55-60 DEG C. 1 at the same temperature. Worship the insect time hawk. The reaction solution was neutralized with caustic soda, extracted with methylene chloride, and the methylene chloride layer was fractionally distilled to give 4-methyloxazole 6.5 hours (yield 78
．． 3%). Example 3 A mixture of 5 days of 4-methyl-2-oxazolethiol and 40 days of hydrogen peroxide solution was added to 0 to 5 minutes.
React for 5 hours at ℃ and 1 hour at room temperature.
反応液を実施例２と同様に処理し、４−メチルオキサゾ
ール３．２９（収率８８．６％）を得る。実施例 ４
４−メチル−２一オキサゾールチオール５夕、酢酸５０
の‘および過酸化水素水３０夕の混液を０〜５℃にて２
４時間、室温にて２４時間反応させる。The reaction solution was treated in the same manner as in Example 2 to obtain 3.29 (yield: 88.6%) of 4-methyloxazole. Example 4 4-methyl-2-oxazolethiol 50%, acetic acid 50%
A mixture of 30% of hydrogen peroxide and 30% of hydrogen peroxide solution at 0 to 5℃
4 hours, and 24 hours at room temperature.
Claims (1)
反応せしめることを特徴とする４−メチルオキサゾール
の製法。1. A method for producing 4-methyloxazole, which comprises reacting 4-methyl-2-oxazolethiol with an oxidizing agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9935977A JPS6014033B2 (en) | 1977-08-19 | 1977-08-19 | Method for producing 4-methyloxazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9935977A JPS6014033B2 (en) | 1977-08-19 | 1977-08-19 | Method for producing 4-methyloxazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5432465A JPS5432465A (en) | 1979-03-09 |
| JPS6014033B2 true JPS6014033B2 (en) | 1985-04-11 |
Family
ID=14245381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9935977A Expired JPS6014033B2 (en) | 1977-08-19 | 1977-08-19 | Method for producing 4-methyloxazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6014033B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63117952U (en) * | 1987-01-27 | 1988-07-30 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS572714A (en) * | 1980-06-10 | 1982-01-08 | Ikeda Bussan Co Ltd | Patterning method and device of sheet cover |
| JPS572713A (en) * | 1980-06-10 | 1982-01-08 | Ikeda Bussan Co Ltd | Patterning method of sheet cover |
| JPS57204997A (en) * | 1981-06-10 | 1982-12-15 | Matsushita Electric Works Ltd | Input signal control circuit |
| JPH0421926Y2 (en) * | 1987-08-11 | 1992-05-19 |
-
1977
- 1977-08-19 JP JP9935977A patent/JPS6014033B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63117952U (en) * | 1987-01-27 | 1988-07-30 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5432465A (en) | 1979-03-09 |
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