JPS5934712B2 - 7-Hydroxy-2-nitrobenzofuran - Google Patents
7-Hydroxy-2-nitrobenzofuranInfo
- Publication number
- JPS5934712B2 JPS5934712B2 JP14938975A JP14938975A JPS5934712B2 JP S5934712 B2 JPS5934712 B2 JP S5934712B2 JP 14938975 A JP14938975 A JP 14938975A JP 14938975 A JP14938975 A JP 14938975A JP S5934712 B2 JPS5934712 B2 JP S5934712B2
- Authority
- JP
- Japan
- Prior art keywords
- nitrobenzofuran
- hydroxy
- hydroxysalicylaldehyde
- reaction
- yield
- 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
Landscapes
- Furan Compounds (AREA)
Description
【発明の詳細な説明】
本発明は医薬として有用な７−ヒドロキシー２−ニトロ
ベンゾフランの新規な製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 7-hydroxy-2-nitrobenzofuran, which is useful as a pharmaceutical.
式” □〜００
（Ｉ）
で示される７−ヒドロキシー２−ニトロベンゾフラン（
Ｉ）はそれ自身抗菌作用を示し化学療法剤として有用で
あり、また医薬中間体としても有用である。7-Hydroxy-2-nitrobenzofuran (
I) itself exhibits antibacterial activity and is useful as a chemotherapeutic agent, and is also useful as a pharmaceutical intermediate.
１５この化合物の製法としては下記の反応式に示される
ごとき７−メトキシー２−ニトロベンゾフラン（Ｈ）の
メトキシ基をヒドロキシ基に変換する方法が知られてい
る〔ルネ・ロワイエ（ＲｅｎざＲｏｙｅｒ）らのブレタ
ン・トウ・ラ・リンエア・シミク・ド２０ウ・フランス
（ＢｕｌｌｅｔｉｎｄｅｌａＳｏｃｉｅｔムＣｈｉｍｉ
ｑｕｅｄｅＦｒａｎｃｅ）、１９７２年、４１５８〜４
１６０頁参照〕。15 As a method for producing this compound, a method is known in which the methoxy group of 7-methoxy-2-nitrobenzofuran (H) is converted to a hydroxyl group as shown in the reaction formula below [Renza Royer et al. The Bulletin de la Society of France
France), 1972, 4158-4
See page 160].
２５□Ｎｏ、一□ＮＯ２
０ＣＨ３ＯＨ
（■） （Ｉ）
この反応は化合物（■）をピリジン塩酸塩の存在下３０
において１５０〜２００℃で１０分〜２４時間加熱する
ことによつて行なわれており、その収率は１７〜４５．
５％と報告されている。25□No, 1□NO2 0CH3OH (■) (I) This reaction consists of compound (■) in the presence of pyridine hydrochloride.
It is carried out by heating at 150 to 200°C for 10 minutes to 24 hours, and the yield is 17 to 45.
It is reported to be 5%.
前記反応における出発物質である化合物（Ｈ）は下記の
反応式に示されるごとき３−メトキシサリチルアルデヒ
ド（１１［）３５をニトロ臭化メチルと反応させること
によつてえられている（ルネ・ロワイエらのブレタン・
トウ・ラ・リンエア・シミク・トウ・フランス、１９７
０年、３７４０〜３７４１頁参照）。この反応は水酸化
ナトリウムの存在下水溶液中で行なわれており、その収
率は１２％と報告されている。Compound (H), which is the starting material in the above reaction, is obtained by reacting 3-methoxysalicylaldehyde (11[)35 with methyl nitrobromide as shown in the reaction formula below (Rene Royer) Ra's Bulletin・
Tou La Rinair Simique Tou France, 197
0, pp. 3740-3741). This reaction is carried out in an aqueous solution in the presence of sodium hydroxide, and the yield is reported to be 12%.
したがつて３−メトキシサリチルアルデヒド（１１）か
ら出発して７ーヒドロキシ一２−ニトロベンゾフラン（
１）をうるには従来法においてはその全収率がわずかに
数％程度であるにすぎない。Therefore, starting from 3-methoxysalicylaldehyde (11), 7-hydroxy-12-nitrobenzofuran (
In conventional methods, the total yield of 1) is only about a few percent.
しかるに本発明者らは、７ーヒドロキシ一２−ニトロベ
ンゾフランの工業的にすぐれた製造法を開発すべく種々
研究を重ねた結果、３−ヒドロキシサリチルアルデヒド
をニトロ臭化メチルと反応させるときは直接７ーヒドロ
キシ一２−ニトロベンゾフランがきわめて容易にかつ高
収率でえられることを見出し本発明を完成するにいたつ
た。However, as a result of various studies aimed at developing an industrially superior method for producing 7-hydroxy-2-nitrobenzofuran, the present inventors found that when 3-hydroxysalicylaldehyde is reacted with nitromethyl bromide, 7 -Hydroxy-2-nitrobenzofuran was found to be extremely easy to obtain in high yield, leading to the completion of the present invention.
従来３−ヒドロキシサリチルアルデヒドなどのごときベ
ンゼン環上に１〜２個の水酸基を有するサリチルアルデ
ヒドは反応性が低くニトロ臭化メチルと反応してベンゾ
フラン環を形成しえないと考えられていた。たとえば４
−ヒドロキシサリチルアルデヒド、５−ヒドロキシサリ
チルアルデヒド、３，４−ジヒドロキシサリチルアルデ
ヒドなどはニトロ臭化メチルと反応しない。ところが本
発明に用いる３−ヒドロキシサリチルアルデヒドのみが
ニトロ臭化メチルと好適に反応することが見出されたの
である。本発明の方法はつぎの反応式で示される。It was conventionally believed that salicylaldehydes having one or two hydroxyl groups on the benzene ring, such as 3-hydroxysalicylaldehyde, have low reactivity and cannot react with methyl nitrobromide to form a benzofuran ring. For example 4
-Hydroxysalicylaldehyde, 5-hydroxysalicylaldehyde, 3,4-dihydroxysalicylaldehyde, etc. do not react with nitromethyl bromide. However, it was discovered that only 3-hydroxysalicylaldehyde used in the present invention reacts favorably with methyl nitrobromide. The method of the present invention is shown by the following reaction formula.
しかして本発明の方法においては出発物質として３−ヒ
ドロキシサリチルアルデヒド（ＪＶ）を用いることによ
つて３−メトキシサリチルアルデヒド（）を出発物質と
して用いる２段階の反応からなる従来法にくらべて１段
階の反応で目的化合物がえられ、しかもその収率がたと
えば７０％以上という高収率であるので、本発明の方法
は工業的にきわめてすぐれた方法である。Therefore, in the method of the present invention, by using 3-hydroxysalicylaldehyde (JV) as a starting material, one step is reduced compared to the conventional method consisting of a two-step reaction using 3-methoxysalicylaldehyde (JV) as a starting material. The method of the present invention is an industrially excellent method because the desired compound can be obtained by the reaction described above, and the yield is as high as, for example, 70% or more.
前記反応は３−ヒドロキシサリチルアルデヒド１モルと
ニトロ臭化メチル約１．２〜１．５モルとを無機塩基の
存在下において溶媒中で反応させることによつて好適に
行なわれる。The reaction is preferably carried out by reacting 1 mole of 3-hydroxysalicylaldehyde with about 1.2 to 1.5 moles of methyl nitrobromide in a solvent in the presence of an inorganic base.
溶媒としては水、アセトン、ジメチルスルホキシドおよ
びこれらの混合物が用いられる。溶媒としてジメチルス
ルホキシドを用いるばあいはチツ素気流中で反応を行な
うとより好ましい結果がえられる。無機塩基としては水
酸化ナトリウム、水酸化カリウム、炭酸ナトリウム、炭
酸カリウムなどが好ましく用いられる。無機塩基の使用
量は３−ヒドロキシサリチルアルデヒド１モルに対して
約１〜１．５モルの範囲から選ばれる。反応温度は１５
〜６０℃の範囲から、反応時間は３０分〜数時間の範囲
から適宜選ばれる。つぎに本発明の方法を実施例をあげ
て説明する。Water, acetone, dimethyl sulfoxide and mixtures thereof are used as solvents. When dimethyl sulfoxide is used as a solvent, more favorable results can be obtained if the reaction is carried out in a nitrogen gas stream. As the inorganic base, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc. are preferably used. The amount of the inorganic base to be used is selected from the range of about 1 to 1.5 mol per 1 mol of 3-hydroxysalicylaldehyde. The reaction temperature is 15
The reaction time is appropriately selected from the range of 30 minutes to several hours. Next, the method of the present invention will be explained by giving examples.
実施例 Ｊ３−ヒドロキシサリチルアルデヒド６．５９
をアセトン２００ｍ１に溶解し、これに炭酸カリウム７
．８９を加えて室温で１時間撹拌したのちニトロ臭化メ
チル９．１９を室温にて２０分間に滴下し、その後５時
間還流した。Example J3-hydroxysalicylaldehyde 6.59
was dissolved in 200 ml of acetone, and 7 ml of potassium carbonate was added to this.
．． After stirring at room temperature for 1 hour, 9.19 g of methyl nitrobromide was added dropwise at room temperature over 20 minutes, followed by refluxing for 5 hours.
反応液を済過し、枦液を濃縮し、えられた残渣をベンゼ
ンから再結晶して融点１５５．５〜１５７℃の黄色結晶
状の７ーヒドロキシ一２−ニトロベンゾフラン５．９９
（収率７０（ｆ））をえた。元素分析値：Ｃ８Ｈ５Ｏ４
Ｎとして
計算値（支））：Ｃ５３．６４Ｈ２．８ｌ実測値（鉤：
Ｃ５３．７９Ｈ２．６６
実施例 ２
３−ヒドロキシサリチルアルデヒド１９９をジメチルス
ルホキシド２５０ｄに溶解し、これに炭酸カリウム２２
．８９を加えてチツ素気流中で室温下に３０分間撹拌し
たのち、ニトロ臭化メチル２３．１９を３０分間で滴下
し、その後１時間攪拌した。After the reaction solution was removed, the liquid was concentrated and the resulting residue was recrystallized from benzene to give 7-hydroxy-12-nitrobenzofuran in the form of yellow crystals with a melting point of 155.5-157°C (5.99%).
(Yield 70(f)) was obtained. Elemental analysis value: C8H5O4
Calculated value (support) as N: C53.64H2.8l Actual measurement value (hook:
C53.79H2.66 Example 2 3-hydroxysalicylaldehyde 199 was dissolved in dimethyl sulfoxide 250d, and potassium carbonate 22
．． 89 was added thereto and the mixture was stirred at room temperature for 30 minutes in a nitrogen gas flow, and then 23.19 g of methyl nitrobromide was added dropwise over 30 minutes, followed by stirring for 1 hour.
反応液に水１．５１を加えたのちろ過し、炉液をエーテ
ル抽出し、エーテル層を濃縮した。えられた残渣をベン
ゼンから再結晶して融点１５５．５〜１５７℃の黄色結
晶状の７ーヒドロキシ一２−ニトロベンゾフラン１９９
（収率７６％）をえた。After adding 1.5 liters of water to the reaction solution, it was filtered, the filtrate was extracted with ether, and the ether layer was concentrated. The obtained residue was recrystallized from benzene to obtain 7-hydroxy-12-nitrobenzofuran 199 in the form of yellow crystals with a melting point of 155.5-157°C.
(yield 76%).
Claims (1)
チルと反応させることを特徴とする式▲数式、化学式、
表等があります▼で示される７−ヒドロキシ−２−ニト
ロベンゾフランの製造法。1 Formula characterized by reacting 3-hydroxysalicylaldehyde with nitromethyl bromide ▲ Mathematical formula, chemical formula,
There are tables etc.Production method of 7-hydroxy-2-nitrobenzofuran shown by ▼.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14938975A JPS5934712B2 (en) | 1975-12-12 | 1975-12-12 | 7-Hydroxy-2-nitrobenzofuran |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14938975A JPS5934712B2 (en) | 1975-12-12 | 1975-12-12 | 7-Hydroxy-2-nitrobenzofuran |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5273859A JPS5273859A (en) | 1977-06-21 |
| JPS5934712B2 true JPS5934712B2 (en) | 1984-08-24 |
Family
ID=15474046
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14938975A Expired JPS5934712B2 (en) | 1975-12-12 | 1975-12-12 | 7-Hydroxy-2-nitrobenzofuran |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5934712B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6112417U (en) * | 1984-06-29 | 1986-01-24 | オクス工業株式会社 | compact |
| JPS6151106U (en) * | 1984-09-11 | 1986-04-05 | ||
| JPS6346025Y2 (en) * | 1984-06-26 | 1988-11-30 |
-
1975
- 1975-12-12 JP JP14938975A patent/JPS5934712B2/en not_active Expired
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6346025Y2 (en) * | 1984-06-26 | 1988-11-30 | ||
| JPS6112417U (en) * | 1984-06-29 | 1986-01-24 | オクス工業株式会社 | compact |
| JPS6151106U (en) * | 1984-09-11 | 1986-04-05 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5273859A (en) | 1977-06-21 |
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