JPS58185569A - Preparation of cytosine-5-carboxylic acid - Google Patents
Preparation of cytosine-5-carboxylic acidInfo
- Publication number
- JPS58185569A JPS58185569A JP6895882A JP6895882A JPS58185569A JP S58185569 A JPS58185569 A JP S58185569A JP 6895882 A JP6895882 A JP 6895882A JP 6895882 A JP6895882 A JP 6895882A JP S58185569 A JPS58185569 A JP S58185569A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- cytosine
- carboxylic acid
- ureidomethylenecyanoacetic
- urea
- 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
Abstract
Description
【発明の詳細な説明】
本発明はノドシノー５−カルボン酸の製造方法に関する
ものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing nodocino-5-carboxylic acid.
さらにＪＴシ＜は１本発明はオルト蟻酸エステル及びノ
アン酢酸を尿素と反応させ−Ｃ，ウレイドメチレンン７
ノ酢酸を得、ついでナトリウムアルコラードの存在下に
閉環することを特徴とするノドツノ−５−カルボッ酸の
製造方法に関するものである。Furthermore, the present invention is characterized by reacting orthoformic acid ester and noanacetic acid with urea.
The present invention relates to a method for producing nodotsuno-5-carboxylic acid, which comprises obtaining noacetic acid and then ring-closing it in the presence of sodium alcoholade.
本発明の目的物であるノトンノー５−カルボン酸は、ｔ
ことえばキノリ／中で加熱することにより、容易にノド
ノンとなるところから、工業上極めて角田な化合物であ
り、従来は、オルト蟻酸エステル及び尿素をノアノ酢酸
エステルと反応させて、先ずウレイドメチレノノアン酢
！エステルをＩＵ、ついでアルコラードの存在下に閉環
してノドツノ−５−カルボッ酸エステルを得、さらにこ
れを加水分解して、ようやくシトツノ−５−カルボッ酸
を得るのが常識であった。Notonno-5-carboxylic acid, which is the object of the present invention, is t
For example, it is an extremely industrially difficult compound because it is easily converted to nodonone by heating in an aqueous solution. Conventionally, orthoformate and urea are reacted with noanoacetate to form ureidomethylenoanone. vinegar! It has been common knowledge that the ester is ring-closed in the presence of IU and then alcoholade to obtain a rhino-5-carboxylic acid ester, which is then further hydrolyzed to finally obtain a rhino-5-carboxylic acid.
しかしながら、この方法は冗長であるのみならず、コス
トも安価ではない欠点を有しているので１本発明者らは
、経済的有利なノドノン−５−カルボッ酸の製造方法を
確立する目的をもって検討し、オルト蟻酸エステル及び
尿素をノアン酢酸と反応させたところ、意外にも高収率
をもってウレイドメチレノンアノ酢酸が得られ、さらに
このものをナトリウムアルコラードの存在下で閉環させ
て、高品質のントンノー５−カルボン酸が収率よく得ら
れることを見出し１本頭に及んだ次第である。However, this method is not only tedious but also has the drawbacks that it is not inexpensive. However, when orthoformate and urea were reacted with noanacetic acid, ureidomethyleneoneanoacetic acid was obtained with unexpectedly high yield, and this product was further ring-closed in the presence of sodium alcoholade to produce high-quality They discovered that 5-carboxylic acid could be obtained in good yield and developed one.
本発明方法において用いるオルト蟻酸エステルとしては
、市場に容易に入手しうるメチルエステルまたはエチル
エステルを使用するのが有利である。反応に際しては、
三者を混合し、１００℃付近に加熱すると１反応が進行
して、生成するアルコールによって温度が低下してくる
が・かまわず加熱還流をつづける。反応は８〜４時間で
完結するので、冷後。As the orthoformate ester used in the process of the invention, it is advantageous to use methyl or ethyl esters, which are readily available on the market. When reacting,
When the three components are mixed and heated to around 100°C, one reaction proceeds, and the temperature decreases due to the alcohol produced, but the heating and refluxing is continued regardless. The reaction will be completed in 8 to 4 hours, so cool it down.
生成したウレイドメチレノンアノ酢酸をろ取する。しか
し、必要に応じてウレイドメチレノンアノ酢酸は単離し
ないで２反応混合物にナトリウムアルコラードを添加し
て、ひきつづき閉環反応を実施しても差支えない。こＣ
に使用するナトリウムアルコラードはメチラート、エチ
ラート、ｎ−プロピラード、ｉ−プロピラード、ｎ−ブ
チラードあるいはも一ブチラードなどが適当であり、そ
の使用量はウレイドメチレンツアン酢酸に対し。The produced ureidomethyleneone anoacetic acid is collected by filtration. However, if necessary, the ring-closing reaction may be carried out by adding sodium alcoholade to the two reaction mixtures without isolating the ureidomethyleneone anoacetic acid. This C
The sodium alcoholade to be used is suitably methylate, ethylate, n-propylade, i-propylade, n-butylade or monobutylade, and the amount used is relative to ureidomethylenethaneacetic acid.
１５ないし３モル当量の範囲で使用するのが効果的であ
る。閉環反応においてはアルコール系の溶媒を使用する
と反応が円滑に進行するが、不可欠ではない。It is effective to use it in a range of 15 to 3 molar equivalents. In the ring-closing reaction, the reaction proceeds smoothly if an alcohol-based solvent is used, but it is not essential.
次に実施例を挙げて本発明方法を説明する。Next, the method of the present invention will be explained with reference to Examples.
実施例ｔｌ）
尿素６１Ｎ’とノｉ’ＬＪｌ酸９３５ｙをコルベンに仕
込み、１０５℃に加熱し、かき混ぜつつ、オルト蟻酸メ
チル１２８ｙを３０分要してｉ＆下し、後。Example tl) Urea 61N' and Noi'LJl acid 935y were charged in a Kolben, heated to 105°C, and while stirring, methyl orthoformate 128y was added down over 30 minutes.
８時間還流加熱して反応を完結した。冷後、結晶をろ取
し、メタノールで洗い、乾燥して、ウレイドメチ１ンノ
アン酢酸１１５ｙを得た。融点１５５８℃
元素分析値 ０．８＆４５％； １１．８．４８％
； Ｎ、２６．９１％ｉＪｌ算１ｍ（Ｃ，ｌ＆７２＊
；ＩＩ、３．２５４４５；Ｎ、２７０９％（Ｃ５１！５
Ｎ３０３として）
ウレイドメチレノンアノ酎酸５１ｙを２４９０ナトリウ
ムメチラートメタノール溶液２２５ｙとともに７０〜８
０℃で還流させ、４時間にて閉環反応を完結し、内容物
に水１１を／＋−人、脱色吹２１を加え熱時ろ過し、ろ
液を希硫酸にて酸性にして、シトソノ−５−カルボッ酸
の白色結晶を得た。収晴３０ｙ、融−２５６℃（分解）
。The reaction was completed by heating under reflux for 8 hours. After cooling, the crystals were collected by filtration, washed with methanol, and dried to obtain ureidomethylinoanoacetic acid 115y. Melting point 1558℃ Elemental analysis value 0.8 &45%;11.8.48%
; N, 26.91% iJl calculation 1m (C, l &72*
;II,3.25445;N, 2709% (C51!5
As N303) 51y of ureidomethyleneoneanochuic acid with 225y of 2490 sodium methylate methanol solution 70-8
Reflux at 0°C to complete the ring-closing reaction in 4 hours, add 11 parts of water and 21 parts of decolorizer to the contents, filter while hot, acidify the filtrate with dilute sulfuric acid, and add cytosonol. White crystals of 5-carboxylic acid were obtained. Clearance 30y, melting temperature -256℃ (decomposition)
.
実施例（２）
実施例（りにおいて、オルト蟻酸メチルの代りに、オル
ト蟻酸エチル１７２２を用いて、同様に反応させて、ウ
レイドメチ１ンノアン酢酸を得。Example (2) In Example 2, ethyl orthoformate 1722 was used instead of methyl orthoformate, and the reaction was carried out in the same manner as in Example 1 to obtain ureidomethylinoanoacetic acid.
これを単離することなく、ｌＯ％ナトリウムｎ−ブチラ
ードのｎ−ブタノール溶液３１を加え、４時間還流させ
、後、実施例（１１と同様に後処理して、ントン／−５
−カルボ−・酸を得た。収率８１％（対尿素）。Without isolating this, 10% sodium n-butylade in n-butanol solution 31 was added, refluxed for 4 hours, and then worked up in the same manner as in Example (11) to
-Carbo-acid was obtained. Yield 81% (based on urea).
Claims (1)
て、ウレイドメチレノンノ酢酸を得、ついでナトリウム
アルコラードの存在Ｆに閉環することを特徴とするノド
シノー５−カルボッ酸の製造方法。A method for producing nodocino-5-carboxylic acid, which comprises reacting 4-ruthoformate and turacetic acid with urea to obtain ureidomethylenenoacetic acid, and then ring-closing it in the presence of sodium alcoholade.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6895882A JPS58185569A (en) | 1982-04-24 | 1982-04-24 | Preparation of cytosine-5-carboxylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6895882A JPS58185569A (en) | 1982-04-24 | 1982-04-24 | Preparation of cytosine-5-carboxylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58185569A true JPS58185569A (en) | 1983-10-29 |
Family
ID=13388686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6895882A Pending JPS58185569A (en) | 1982-04-24 | 1982-04-24 | Preparation of cytosine-5-carboxylic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58185569A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103992278A (en) * | 2014-05-23 | 2014-08-20 | 南阳师范学院 | Synthesis method of cytosine |
| WO2021059160A1 (en) | 2019-09-23 | 2021-04-01 | Adama Makhteshim Ltd. | Process for preparing 5-(fluoro-4-imino-3-methyl)-1-tosyl-3,4 dihydropyrimidine -(1h)-one |
-
1982
- 1982-04-24 JP JP6895882A patent/JPS58185569A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103992278A (en) * | 2014-05-23 | 2014-08-20 | 南阳师范学院 | Synthesis method of cytosine |
| WO2021059160A1 (en) | 2019-09-23 | 2021-04-01 | Adama Makhteshim Ltd. | Process for preparing 5-(fluoro-4-imino-3-methyl)-1-tosyl-3,4 dihydropyrimidine -(1h)-one |
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