JPS6313425B2 - - Google Patents
Info
- Publication number
- JPS6313425B2 JPS6313425B2 JP7636782A JP7636782A JPS6313425B2 JP S6313425 B2 JPS6313425 B2 JP S6313425B2 JP 7636782 A JP7636782 A JP 7636782A JP 7636782 A JP7636782 A JP 7636782A JP S6313425 B2 JPS6313425 B2 JP S6313425B2
- Authority
- JP
- Japan
- Prior art keywords
- cyclodextrin
- nitrovinylphenol
- reaction
- derivatives
- derivative
- 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
- 229920000858 Cyclodextrin Polymers 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- PMDYAIGGZBRBFX-UHFFFAOYSA-N 2-(2-nitroethenyl)phenol Chemical compound OC1=CC=CC=C1C=C[N+]([O-])=O PMDYAIGGZBRBFX-UHFFFAOYSA-N 0.000 claims description 11
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 6
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000001116 FEMA 4028 Substances 0.000 description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 229960004853 betadex Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明はニトロビニルフエノールおよびその誘
導体の合成法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for the synthesis of nitrovinylphenol and its derivatives.
ニトロビニルフエノールおよびその誘導体は、
抗菌剤、および種々の医薬、農薬などの合成中間
体として、その重要性が最近とみに増している。 Nitrovinylphenol and its derivatives are
Its importance has recently increased as an antibacterial agent and as a synthetic intermediate for various pharmaceuticals and agricultural chemicals.
すでに、アルカリの存在下にフエノールとハロ
ホルムとを反応させてヒドロキシベンズアルデヒ
ドを合成し、これをニトロメタンおよびその誘導
体と反応させてニトロビニルフエノールおよびそ
の誘導体を合成する方法は公知であつた。また、
アルカリの存在下にヒドロキシベンズアルデヒド
を四ハロゲン化炭素と反応させてヒドロキシホル
ミル安息香酸を合成し、これをニトロメタンおよ
ひその誘導体と反応させて、カルボキシル基を有
するニトロビニルフエノール誘導体を合成する方
法も公知であつた。しかしながら、後述の比較例
に見られるように、上述の方法で合成を実施する
と、目的物の収率は非常に小さく、しかも多量の
副生成物が副生する。 A method for synthesizing hydroxybenzaldehyde by reacting phenol and haloform in the presence of an alkali, and reacting this with nitromethane and its derivatives to synthesize nitrovinylphenol and its derivatives has already been known. Also,
Another method involves reacting hydroxybenzaldehyde with carbon tetrahalide in the presence of an alkali to synthesize hydroxyformylbenzoic acid, and reacting this with nitromethane or its derivatives to synthesize a nitrovinylphenol derivative having a carboxyl group. It was publicly known. However, as seen in the Comparative Examples described below, when the synthesis is carried out by the above method, the yield of the target product is very small, and moreover, a large amount of by-products are produced.
本発明は、上記の反応系にシクロデキストリン
を添加することにより、目的生成物であるニトロ
ビニルフエノールおよびその誘導体を高収率およ
び高選択的に合成し、省原料と分離操作の簡素化
を実現したものである。 The present invention synthesizes the target product nitrovinylphenol and its derivatives in high yield and with high selectivity by adding cyclodextrin to the above reaction system, saving raw materials and simplifying the separation operation. This is what I did.
すなわち、本発明者らは、フエノールと水酸化
ナトリウムまたは水酸化カリウムの水溶液にシク
ロデキストリンを加え、溶解せしめた後に、四ハ
ロゲン化炭素、ハロホルム、およびニトロメタン
またはその誘導体を順次加えることにより、芳香
環に直結するカルボキシル基を有するニトロビニ
ルフエノールおよびその誘導体を高収率、高選択
性で合成することに成功した。本発明における目
的物であるニトロビニルフエノールまたはその誘
導体の収率および選択率はいずれもほぼ100％で
ある。 That is, the present inventors added cyclodextrin to an aqueous solution of phenol and sodium hydroxide or potassium hydroxide, dissolved it, and then added carbon tetrahalide, haloform, and nitromethane or a derivative thereof in order to form an aromatic ring. We succeeded in synthesizing nitrovinylphenol and its derivatives having a carboxyl group directly linked to in high yield and with high selectivity. Both the yield and selectivity of nitrovinylphenol or its derivative, which is the target product of the present invention, are approximately 100%.
本発明においては、反応試薬の添加の際には、
それ以前に加えた異種の反応試薬とフエノールあ
るいはそれに由来する反応中間体との反応の反応
率が50〜100％、好ましくは95〜100％であること
が望ましい。 In the present invention, when adding the reaction reagent,
It is desirable that the reaction rate of the reaction between the previously added different reaction reagent and phenol or a reaction intermediate derived therefrom is 50 to 100%, preferably 95 to 100%.
シクロデキストリンとしては、α−シクロデキ
ストリンとβ−シクロデキストリンのいずれも用
いることができる。シクロデキストリンの添加量
としては、ほぼ100％に近い選択率でニトロビニ
ルフエノールまたはその誘導体を得るためには、
反応系中に存在するハロホルム、四ハロゲン化炭
素およびニトロメタンまたはその誘導体に対する
モル比で0.5以上が望ましいが、これ以下の量の
シクロデキストリン使用量でもニトロビニルフエ
ノールまたはその誘導体の生成の選択性の向上は
達成される。 As the cyclodextrin, both α-cyclodextrin and β-cyclodextrin can be used. In order to obtain nitrovinylphenol or its derivatives with a selectivity close to 100%, the amount of cyclodextrin added is as follows:
It is desirable that the molar ratio of haloform, carbon tetrahalide, and nitromethane or its derivatives present in the reaction system is 0.5 or more, but even if the amount of cyclodextrin used is less than this, the selectivity in the production of nitrovinylphenol or its derivatives can be improved. is achieved.
本発明における水酸化ナトリウムあるいは水酸
化カリウムの水溶液の濃度は0.1〜50重量％、好
ましくは５〜20％である。 The concentration of the aqueous solution of sodium hydroxide or potassium hydroxide in the present invention is 0.1 to 50% by weight, preferably 5 to 20%.
シクロデキストリンは反応中に変化せず、反応
後そのまま再使用が可能である。反応後、反応系
を酸性にすると溶解度の減少のためにシクロデキ
ストリンが沈澱する。この簡便な方法でシクロデ
キストリンの８割以上は回収され、回収されたシ
クロデキストリンは完全に再使用にたえる。 Cyclodextrin does not change during the reaction and can be reused as is after the reaction. After the reaction, when the reaction system is made acidic, cyclodextrin precipitates due to decreased solubility. More than 80% of the cyclodextrin can be recovered using this simple method, and the recovered cyclodextrin can be completely reused.
つぎに、本発明を具体的に実施例を挙げて説明
するが、これにより本発明を制限するものではな
い。 Next, the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto.
実施例 １
1.5ｇ（15.9ミリモル）のフエノールと0.9ｇ
（0.80ミリモル）のβ−シクロデキストリンを80
mlの20％水酸化ナトリウム水溶液に溶かし、この
中に0.01ｇ（0.16ミリモル）の銅粉を加えた。こ
こに２ml（20.0ミリモル）の四塩化炭素を滴下し
つつ、反応液を磁気かくはん機を用いてかくはん
し、60℃で10時間反応せしめた。つぎに、２ml
（24.0ミリモル）のクロロホルムを徐々に滴下し
つつ、反応液を磁気かくはん機を用いてかくはん
し、60℃で10時間反応せしめた。つぎに、反応液
を氷で十分に冷却した後に、0.86ml（15.9ミリモ
ル）のニトロメタン（東京化成工業株式会社製、
特級試薬）を徐々に加え、室温で10時間反応せし
めた。その後、反応液を塩酸で酸性にした後、50
mlのエーテルで３回抽出し、エーテル層を水洗し
た後に乾燥し、3.0ｇの生成物を得た。生成物の
赤外吸収および 1H−NMRスペクトルは、いず
れも４−ヒドロキシ−３−（２−ニトロビニル）
安息香酸の標準サンプルのスペクトルと一致し
た。すなわち、目的物の収率は8.7モル％であり、
選択率は100％であつた。Example 1 1.5 g (15.9 mmol) of phenol and 0.9 g
(0.80 mmol) β-cyclodextrin 80
ml of 20% aqueous sodium hydroxide solution, and 0.01 g (0.16 mmol) of copper powder was added thereto. While 2 ml (20.0 mmol) of carbon tetrachloride was added dropwise thereto, the reaction solution was stirred using a magnetic stirrer and allowed to react at 60°C for 10 hours. Next, 2ml
While (24.0 mmol) of chloroform was gradually added dropwise, the reaction solution was stirred using a magnetic stirrer and allowed to react at 60°C for 10 hours. Next, after sufficiently cooling the reaction solution with ice, 0.86 ml (15.9 mmol) of nitromethane (manufactured by Tokyo Chemical Industry Co., Ltd.,
A special grade reagent) was gradually added, and the mixture was allowed to react at room temperature for 10 hours. Then, after making the reaction solution acidic with hydrochloric acid,
ml of ether three times, and the ether layer was washed with water and dried to obtain 3.0 g of product. The infrared absorption and 1 H-NMR spectra of the product both indicate that 4-hydroxy-3-(2-nitrovinyl)
The spectrum matched that of the standard sample of benzoic acid. That is, the yield of the target product is 8.7 mol%,
The selection rate was 100%.
比較例 １
0.9ｇ（0.80ミリモル）のβ−シクロデキスト
リンを使用しない点以外は、実施例１と同様の操
作を行ない、0.3ｇの生成物を得た。生成物の
1H−NMRスペクトルには、ニトロビニルフエノ
ール類に帰属されるビニルプロトンのシグナルは
検出されなかつた。すなわち、目的物の収率は０
％であつた。Comparative Example 1 The same operation as in Example 1 was carried out except that 0.9 g (0.80 mmol) of β-cyclodextrin was not used, and 0.3 g of a product was obtained. of the product
No vinyl proton signal assigned to nitrovinylphenols was detected in the 1 H-NMR spectrum. In other words, the yield of the target product is 0.
It was %.
Claims (1)
在下に、フエノールに対して四ハロゲン化炭素、
ハロホルム、およびニトロメタンまたはその誘導
体を順次反応させるにあたり、シクロデキストリ
ンを触媒として用いることにより、芳香環に直結
するカルボキシル基を有するニトロビニルフエノ
ールまたはその誘導体を高選択的に製造する方
法。1 Carbon tetrahalide, phenol in the presence of sodium hydroxide or potassium hydroxide,
A method for highly selectively producing nitrovinylphenol or a derivative thereof having a carboxyl group directly connected to an aromatic ring by sequentially reacting haloform and nitromethane or a derivative thereof, using cyclodextrin as a catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7636782A JPS58194842A (en) | 1982-05-07 | 1982-05-07 | Synthesis of nitrovinylphenols |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7636782A JPS58194842A (en) | 1982-05-07 | 1982-05-07 | Synthesis of nitrovinylphenols |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58194842A JPS58194842A (en) | 1983-11-12 |
| JPS6313425B2 true JPS6313425B2 (en) | 1988-03-25 |
Family
ID=13603371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7636782A Granted JPS58194842A (en) | 1982-05-07 | 1982-05-07 | Synthesis of nitrovinylphenols |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58194842A (en) |
-
1982
- 1982-05-07 JP JP7636782A patent/JPS58194842A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58194842A (en) | 1983-11-12 |
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