JPS6318929B2 - - Google Patents
Info
- Publication number
- JPS6318929B2 JPS6318929B2 JP12555881A JP12555881A JPS6318929B2 JP S6318929 B2 JPS6318929 B2 JP S6318929B2 JP 12555881 A JP12555881 A JP 12555881A JP 12555881 A JP12555881 A JP 12555881A JP S6318929 B2 JPS6318929 B2 JP S6318929B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- cyclodextrin
- acid
- parahydroxybenzoic acid
- product
- 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
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 29
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 229920000858 Cyclodextrin Polymers 0.000 claims description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
- 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 6
- 238000000034 method Methods 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- 241000581652 Hagenia abyssinica Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 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 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 238000007065 Kolbe-Schmitt synthesis reaction Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- -1 cyclic oligosaccharide Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明はパラヒドロキシ安息香酸の合成法に関
する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for the synthesis of parahydroxybenzoic acid.
パラヒドロキシ安息香酸は、耐熱性高分子、農
薬、医薬などの原料として、その重要性が最近と
みに増している。 Parahydroxybenzoic acid has recently become increasingly important as a raw material for heat-resistant polymers, agricultural chemicals, medicines, and the like.
これまでに、フエノールを水酸化カリウムと炭
酸カリウムで処理し、加圧下で二酸化炭素ともも
に加熱することによりパラヒドロキシ安息香酸を
合成する方法は、Kolbe‐Schmitt反応として知
られ公知であつた。しかしながら、この反応は、
高圧反応のために反応装置が高価であること、お
よび反応に不可欠な高度の無水条件を達成するた
めに、水分を蒸発せしめるのに多量の熱エネルギ
ーを必要とすることなどの欠点を有する。 Hitherto, a method for synthesizing parahydroxybenzoic acid by treating phenol with potassium hydroxide and potassium carbonate and heating the mixture with carbon dioxide under pressure has been known as the Kolbe-Schmitt reaction. However, this reaction
Disadvantages include that the reactor is expensive due to the high pressure reaction and that a large amount of thermal energy is required to evaporate water to achieve the highly anhydrous conditions essential for the reaction.
また、アルカリの存在下にフエノールと四塩化
炭素を反応せしめることによりパラヒドロキシ安
息香酸を合成する方法も公知であつた。 Furthermore, a method for synthesizing parahydroxybenzoic acid by reacting phenol with carbon tetrachloride in the presence of an alkali was also known.
しかしながら、後述の比較例に見られるよう
に、上記の反応におけるパラヒドロキシ安息香酸
の生成の選択率は57％で、大量のサリチル酸が副
生する。従つて、この方法でパラヒドロキシ安息
香酸を得るには、大量の原料が必要であると同時
に、分離操作を必要とした。 However, as seen in the Comparative Examples described below, the selectivity for producing parahydroxybenzoic acid in the above reaction was 57%, and a large amount of salicylic acid was produced as a by-product. Therefore, in order to obtain parahydroxybenzoic acid by this method, a large amount of raw materials and a separation operation were required.
本発明は、上記の反応系に環状オリゴ糖である
シクロデキストリンを添加することにより、目的
生成物であるパラヒドロキシ安息香酸の収率およ
び選択性を顕著に向上させ、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 significantly improves the yield and selectivity of parahydroxybenzoic acid, the target product, by adding cyclodextrin, which is a cyclic oligosaccharide, to the above reaction system, thereby saving raw materials and simplifying the separation operation. This is the realization of the
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
ゲン化炭素を加えることにより、パラヒドロキシ
安息香酸を高収率、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パラヒドロ
キシ安息香酸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 to produce parahydroxybenzoic acid in high yield and high selectivity. succeeded in synthesizing it. Both the yield and selectivity of parahydroxybenzoic acid, which is the target product of the present invention, are approximately
It is 100%.
本反応は銅粉触媒の存在下に速やかに進行す
る。しかしながら銅粉触媒を用いずとも、反応の
実施は可能である。 This reaction proceeds rapidly in the presence of a copper powder catalyst. However, it is possible to carry out the reaction without using a copper powder catalyst.
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
いることができるが、β−シクロデキストリンの
方が、より効果が大きい。シクロデキストリンの
添加量としては、ほぼ100％に近い選択率でパラ
ヒドロキシ安息香酸を得るためには、フエノール
に対するモル比で0.01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パラヒド
ロキシ安息香酸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, but β-cyclodextrin is more effective. In order to obtain parahydroxybenzoic acid with a selectivity close to 100%, it is desirable to add cyclodextrin at a molar ratio of 0.01 or more to phenol, but even if the amount of cyclodextrin used is less than this, parahydroxybenzoic acid Increased selectivity of acid production is achieved.
つぎに本発明を具体的に実施例をあげて説明す
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のフエノール（小宗化学薬品株式会社製、
一級試薬）と1.5ｇのβ−シクロデキストリン
（半井化学薬品株式会社製、特級試薬）を20mlの
20％水酸化ナトリウム水溶液に溶かし、ここに３
mlの四塩化炭素（東京化成工業株式会社製、一級
試薬）および0.1ｇの銅粉（米山薬品工業株式会
社製、一級試薬）を加えた。反応液を磁気かくは
ん機を用いてかくはんし、水流還流器を用いて還
流させつつ、80℃で10時間反応せしめた。反応
後、反応液を塩酸で酸性にした後、50ml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、2.1ｇの生成物を得た。生成物の赤外吸収ス
ペクトルは、パラヒドロキシ安息香酸（東京化成
工業株式会社製、特級試薬）のスペクトルと一致
した。さらに、生成物をクロロホルムで処理した
ところ、クロロホルムに可溶な成分は混入してい
なかつた。未反応物であるフエノールおよび副反
応生成物であるサリチル酸はクロロホルムに易溶
である。すなわち、目的物の収率は95％であり、
選択率は100％であつた。Example 1 1.5 g of phenol (manufactured by Koso Chemical Co., Ltd.,
20ml of
Dissolve in 20% sodium hydroxide aqueous solution and add 3
ml of carbon tetrachloride (manufactured by Tokyo Chemical Industry Co., Ltd., first class reagent) and 0.1 g of copper powder (manufactured by Yoneyama Pharmaceutical Co., Ltd., first class reagent) were added. The reaction solution was stirred using a magnetic stirrer and reacted at 80° C. for 10 hours while refluxing using a water reflux device. After the reaction, the reaction solution was made acidic with hydrochloric acid, extracted three times with 50 ml of ether, and the ether layer was washed with water and dried to obtain 2.1 g of product. The infrared absorption spectrum of the product matched that of parahydroxybenzoic acid (manufactured by Tokyo Chemical Industry Co., Ltd., special grade reagent). Furthermore, when the product was treated with chloroform, no components soluble in chloroform were found to be present. Phenol, which is an unreacted product, and salicylic acid, which is a side reaction product, are easily soluble in chloroform. That is, the yield of the target product is 95%,
The selection rate was 100%.
比較例 １
試薬はすべて実施例１に記載したものと同一の
ものを使用した。1.5ｇのフエノールを20mlの20
％水酸化ナトリウム水溶液に溶かし、ここに３ml
の四塩化炭素および0.1ｇの銅粉を加えた。反応
液を磁気かくはん機を用いてかくはんし、水流還
流器を用いて還流させつつ、80℃で10時間反応せ
しめた。反応後、反応液を塩酸で酸性にした後、
50ml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、2.1ｇの生成物を得た。生成物
をクロロホルムで処理し、1.2ｇのクロロホルム
不溶部と0.9ｇのクロロホルム可溶部を得た。ク
ロロホルム不溶部の赤外吸収スペクトルはパラヒ
ドロ安息香酸と一致した。また、クロロホルム可
溶部の赤外吸収スペクトルは、サリチル酸（小宗
化学薬品株式会社製、特級試薬）のスペクトルと
一致した。すなわち、目的物の収率は52％で選択
率は57％であつた。Comparative Example 1 All reagents were the same as those described in Example 1. 20ml of 1.5g of phenol
Dissolve in % sodium hydroxide aqueous solution and add 3ml here.
of carbon tetrachloride and 0.1 g of copper powder were added. The reaction solution was stirred using a magnetic stirrer and reacted at 80° C. for 10 hours while refluxing using a water reflux device. After the reaction, after making the reaction solution acidic with hydrochloric acid,
Extraction was carried out three times with 50 ml of ether, and the ether layer was washed with water and dried to obtain 2.1 g of product. The product was treated with chloroform to obtain 1.2 g of chloroform-insoluble fraction and 0.9 g of chloroform-soluble fraction. The infrared absorption spectrum of the chloroform-insoluble portion was consistent with parahydrobenzoic acid. Furthermore, the infrared absorption spectrum of the chloroform-soluble portion matched the spectrum of salicylic acid (manufactured by Koso Chemical Co., Ltd., special grade reagent). That is, the yield of the target product was 52% and the selectivity was 57%.
Claims (1)
在下に、フエノールに対して四ハロゲン化炭素を
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、パラヒドロキシ安息香
酸を高選択的に製造する方法。1. A method for highly selectively producing parahydroxybenzoic acid by using cyclodextrin as a catalyst in reacting phenol with carbon tetrahalide in the presence of sodium hydroxide or potassium hydroxide.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12555881A JPS5826840A (en) | 1981-08-11 | 1981-08-11 | Synthesizing method of p-hydroxybenzoic acid |
| PCT/JP1982/000066 WO1982003073A1 (en) | 1981-03-09 | 1982-03-09 | Process for introducing substituent to p-position of phenols |
| DE8282900665T DE3274104D1 (en) | 1981-03-09 | 1982-03-09 | Process for selectively producing para-substituted derivatives of phenols |
| DE8484112783T DE3276858D1 (en) | 1981-03-09 | 1982-03-09 | A process for producing a para-substituted phenol derivative |
| EP19840112783 EP0158709B1 (en) | 1981-03-09 | 1982-03-09 | A process for producing a para-substituted phenol derivative |
| EP82900665A EP0073837B1 (en) | 1981-03-09 | 1982-03-09 | Process for selectively producing para-substituted derivatives of phenols |
| US06/530,158 US4523031A (en) | 1981-08-11 | 1983-09-07 | Process for producing a para-substituted phenol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12555881A JPS5826840A (en) | 1981-08-11 | 1981-08-11 | Synthesizing method of p-hydroxybenzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5826840A JPS5826840A (en) | 1983-02-17 |
| JPS6318929B2 true JPS6318929B2 (en) | 1988-04-20 |
Family
ID=14913164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12555881A Granted JPS5826840A (en) | 1981-03-09 | 1981-08-11 | Synthesizing method of p-hydroxybenzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5826840A (en) |
-
1981
- 1981-08-11 JP JP12555881A patent/JPS5826840A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5826840A (en) | 1983-02-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110483275A (en) | A kind of high-selectivity synthesis method of 3 methoxy 4 hydroxymandelic acid | |
| JPS5929180B2 (en) | Method for producing glycolic acid | |
| EP0173748B1 (en) | Process for producing substituted unsaturated six-membered ring compounds from phenol derivatives | |
| JPS6318929B2 (en) | ||
| JPS5815939A (en) | Manufacture of sodium salicylate | |
| US1937477A (en) | Process of preparing para-hydroxybenzoic acid | |
| JPS58110542A (en) | Chlorinated beta-keto ester | |
| JPS6241655B2 (en) | ||
| JPS6245216B2 (en) | ||
| EP0158709B1 (en) | A process for producing a para-substituted phenol derivative | |
| CN102285878B (en) | Method for preparing 2-halo-4,5-dimethoxy benzoic acid | |
| JPS6313425B2 (en) | ||
| CN117486701B (en) | A method for synthesizing vanillin using glyoxylic acid. | |
| KR20140087216A (en) | Method for producing 6-hydroxy-2-naphthoic acid using naphthalene | |
| JPS6232737B2 (en) | ||
| JPS58105961A (en) | Synthesis of indole-3-aldehyde | |
| JPH0136815B2 (en) | ||
| SU412213A1 (en) | ||
| JPH0368019B2 (en) | ||
| CN109232224B (en) | Preparation method of 2-phenylpropionic acid | |
| JPS63162641A (en) | Production of pentaerythritol allyl ether | |
| JPH01106833A (en) | Method for synthesizing p-hydroxymethylphenols | |
| GB2055814A (en) | Process for preparing ???-aryl propionic acids | |
| CN119798087A (en) | A method for synthesizing 2-Cl-3-nitrobenzoic acid by nitric acid oxidation | |
| US2394674A (en) | Process for producing aryl methyl ketones |