CN102040499A - Method for synthesizing 3-hydroxyacetophenone - Google Patents
Method for synthesizing 3-hydroxyacetophenone Download PDFInfo
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- CN102040499A CN102040499A CN2010105941732A CN201010594173A CN102040499A CN 102040499 A CN102040499 A CN 102040499A CN 2010105941732 A CN2010105941732 A CN 2010105941732A CN 201010594173 A CN201010594173 A CN 201010594173A CN 102040499 A CN102040499 A CN 102040499A
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- hydroxy acetophenone
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Abstract
The invention discloses a method for synthesizing 3-hydroxyacetophenone. The method comprises the following steps: adding concentrated sulfuric acid to a reaction vessel, controlling the temperature of the concentrated sulfuric acid in the reaction vessel to be minus 5-0 DEG C, then dropwise adding acetophenone to the reaction vessel, continuously stirring the mixture under minus 5-0 DEG C to react for 20-40 minutes after finishing dropwise adding, then slowly raising the temperature in the reaction vessel to 55-65 DEG C to continue reacting for 18-22 hours, slowly dropwise adding the reaction mixture to ice water after finishing the reaction, and collecting and washing the precipitate to obtain 3-sulfonic acetophenone; and adding the 3-sulfonic acetophenone to an alkaline solution, heating the mixture until the raw material is dissolved, then continuing reacting for 28-32 hours under 95-105 DEG C, cooling the reactant to 8-12 DEG C after finishing the reaction, adjusting the pH value to 4.8-5.2, and filtering and drying the obtained solid, thus obtaining the 3-hydroxyacetophenone. The method has the advantages of mild reaction conditions, less reaction steps, cheap and easily obtained raw materials and low cost.
Description
Technical field
The present invention relates to a kind of synthetic method of 3-hydroxy acetophenone.
Background technology
The 3-hydroxy acetophenone, structural formula is as follows, has another name called m-hydroxy acetophenone, a glycoloyl benzene, between hydroxy-acetophenone, 3-glycoloyl benzene, 3-hydroxy-acetophenone, 3-parahydroxyacet-ophenone, 3-oxyacetic acid benzophenone, mainly as the intermediate of medicine phyenlephrinium, market demand is very big.
Fig. 1 3-hydroxy acetophenone structural formula
With the derivative of benzene or benzene is that the common methods of the synthetic 3-hydroxy acetophenone of raw material is to introduce blocking group earlier on the 3-hydroxyl, and then the protecting group through sloughing on the 3-hydroxyl obtains the 3-hydroxy acetophenone.These protecting groups have methyl [Park, Jiyeon; Chae, Junghyun. Synlett, 2010,11:1651-1656], benzyl [Zhou, Linna; Wang, Wenjing; Et.al., TetrahedronLetters, vol.49,33; (2008); 4876-4878], ethanoyl [Narender, T.; Reddy, K. P.; Madhur, G.; Synthetic Communications, 2009,11:1949-1956], silylation [Wang, Bing; Sun, Hui-Xia; Sun, Zhi-Hua, Journal of Organic Chemistry, 2009,74 (4): 1781-1784; Ohgiya, Tadaaki; Nishiyama, Shigeru, Tetrahedron Letters, 2004,45 (33): 6317-6320] etc., difficulty is all compared in the introducing of hydroxyl in these methods, and also needs to protect and deprotection reaction after introducing, and whole process steps is many, and productive rate is low.Position introducing hydroxyl is a comparatively simple effective method of synthetic 3-hydroxy acetophenone between ethanoyl.The introducing of hydroxyl is divided into two kinds of direct method and indirect methods.Hydroxyl ［ Palmisano, Giovanni are directly introduced in direct method position between methyl phenyl ketone; Addamo, Maurizio, et. al., Chemical Communications, 2006,9:1012-1014; Mita, Shuichi; Sakanoto, Takao; Yamada, Shingo; Sakaguchi, Satoshi; Ishii Yasutaka, Tetrahedron Letters, 2005,46 (45): 7729-7732; Gesson, Jean-Pierre; Jacquesy, Jean-Claude; Jouannetaud, Marie-Paule; Morellet, Guy, Tetrahedron Letters, 1983,24 (30): 3095-3098; Kurata, Tsunehiko; Watanabe, Yasumasa; Katoh, Makoto; Sawaki, Yasuhiko, Journal of the American Chemical Society, 1988,110 (22): 7472-7478; Fujimoto, Kazuo; Tokuda, Yuichiro; Maekawa, Hirofumi; Matsubara, Yoshiharu; Mizuno, Takumi; Nishiguchi, Ikuzo, Tetrahedron, 52 (11): 3889-3896 ］, though this method step is few, productive rate is low, contains a large amount of by products, product complexity, be difficult to separate, and severe reaction conditions, be unsuitable for suitability for industrialized production; Indirect method is that other group on the position between methyl phenyl ketone is converted to hydroxyl, and this method reaction conditions is gentle relatively, is easy to realize suitability for industrialized production.Having of the present reported in literature of this method is converted into hydroxyl [Sun Li with halogen; Pei, Wen; Shen, Chen, Journal of Chemical Research, 2006,6:388-389; Anderson, Kevin W.; Ikawa, Takashi; Tundel, Rachel E.; Buchwald, Stephen L. Journal of the American Chemical Society, 2006,128 (33): 10694-10695], nitro is converted into hydroxyl [King; Mcwhirter; Barton, Journal of the American Chemical Society, 1945,67:2089-2090] and boric acid ester is converted into hydroxyl ［ Jung, Young Chun; Mishra, Ragesh Kumar; Yoon, Cheol Hwan; Jung, Kyung Woon, Organic Letters, 2003,5 (13): 2231-2234 ］.These methods exist raw material comparatively expensive, and reaction process also needs to use the high catalyzer of price such as palladium, production cost height.
Summary of the invention
The present invention is directed to the above-mentioned deficiency of prior art, propose a kind of reaction conditions gentleness, reactions steps is few, the synthetic method of the 3-hydroxy acetophenone that raw material is cheap, be easy to get, cost is low.
In order to solve the problems of the technologies described above, the synthetic route of the synthetic method of 3-hydroxy acetophenone of the present invention is as follows:
Concrete technical scheme of the present invention is: a kind of synthetic method of 3-hydroxy acetophenone, and its synthesis step is:
(1) add the vitriol oil in reaction vessel, the vitriol oil of control in the reaction vessel drips methyl phenyl ketone then to-5-0 ℃ in reaction vessel, dropwise the back and continued stirring reaction 20 ~ 40 minutes down at-5 ~ 0 ℃; Temperature to 55 ~ 65 in the slow then temperature reaction container ℃ continuation reaction 18 ~ 22 hours; Reaction slowly is added drop-wise to reaction mixture in the frozen water after finishing, and has precipitation to separate out, collecting precipitation, wash, 3-sulfonic benzo ethyl ketone (3-acetylbenzene sulfonic acid);
(2) the 3-sulfonic benzo ethyl ketone with step (1) gained joins in the basic solution, is heated to material dissolution, continues reaction 28 ~ 32 hours down at 95 ~ 105 ℃ then; After reaction finishes reaction mixture is cooled to 8 ~ 12 ℃, drips concentrated hydrochloric acid and regulate pH value to 4.8 ~ 5.2, filter, get the 3-hydroxy acetophenone behind the gained solid drying.
The concentration of added methyl phenyl ketone in the added vitriol oil is 2.8 ~ 3.2 mol/l(mol in the above-mentioned steps of the present invention (1)), contain the methyl phenyl ketone of 2.8 ~ 3.2 mol in promptly per 1 liter of vitriol oil.
The vitriol oil in the above-mentioned steps of the present invention (1) is that massfraction is the vitriol oil more than 98%.
Vitriol oil temperature in the above-mentioned steps of the present invention (1) before dripping methyl phenyl ketone preferably is controlled at 0 ℃.
After dripping methyl phenyl ketone in the above-mentioned steps of the present invention (1), preferably continued stirring reaction 30 minutes down at 0 ℃.
The reaction vessel temperature preferably is warming up to 60 ℃ of continuation reactions 20 hours in the above-mentioned steps of the present invention (1).
Basic solution in the above-mentioned steps of the present invention (2) is sodium hydroxide solution or potassium hydroxide solution, is preferably sodium hydroxide solution or the potassium hydroxide solution of concentration 5mol/l.
3-sulfonic benzo ethyl ketone is 0.7 ~ 0.8 mol/l in sodium hydroxide solution or the concentration in the potassium hydroxide solution of 5mol/l in the above-mentioned steps of the present invention (2), contains 3-sulfonic benzo ethyl ketone 0.7 ~ 0.8 mol in promptly per 1 liter 5mol/l sodium hydroxide solution or the potassium hydroxide solution.
After the dissolving of 3-sulfonic benzo ethyl ketone, preferably continue reaction 30 hours down in the step of the present invention (2) at 100 ℃.
React the afterreaction mixture that finishes in the step of the present invention (2) and preferably be cooled to 10 ℃.
Drip concentrated hydrochloric acid in the step of the present invention (2) and regulate pH value preferably to 5.
Advantage of the present invention and beneficial effect:
(1) the present invention is reaction raw materials with the methyl phenyl ketone, low price, acquisition easily; Reaction process does not use expensive materials such as palladium as catalyzer, and therefore, production cost is low.
(2) reaction process of the present invention generates 3-acetylbenzene sulfonic acid earlier, under alkaline condition sulfonic group is replaced into hydroxyl then, need not to introduce protecting group deprotection again on hydroxyl, and product postprocessing is simple, need not crystallization, crosses chromatographic column etc.; Therefore, reaction scheme is short, reaction conditions is gentle, simple to operate, yield is high.
Embodiment
Below by embodiment the present invention is described in further detail, but the present invention not only is confined to following examples.
Embodiment 1
1) in the there-necked flask that mechanical stirrer, constant pressure funnel and thermometer are housed, adds 100 milliliters of vitriol oils, place cryosel to bathe in flask, treat in there-necked flask, to drip methyl phenyl ketone 36 grams (0.30mol) after vitriol oil temperature is reduced to 0 ℃.Dropwise back 0 ℃ and continued stirring reaction 30 minutes down, slowly be warming up to 60 ℃ then and continue reaction 20 hours.After reaction finishes reaction mixture slowly is added drop-wise in 1000 milliliters of frozen water, collecting precipitation, washing gets product 3-sulfonic benzo ethyl ketone 39 grams (0.195mol), productive rate 65%.
2) 3-sulfonic benzo ethyl ketone 30 grams (0.15mol) are joined in the potassium hydroxide solution of 200 milliliters of 5mol/l, heating makes its dissolving back continue reaction 30 hours down at 100 ℃.After reaction finishes reaction mixture is cooled to 10 ℃, drips concentrated hydrochloric acid and regulate pH value to 5, filter, get product 3-hydroxy acetophenone 16.32 grams (0.12mol) behind the gained solid drying, productive rate 80%.
Embodiment 2
Step (1) is with embodiment 1;
Step changes potassium hydroxide into sodium hydroxide in (2), and other is constant, gets solid product 3-hydroxy acetophenone 15.3 grams (0.11mol), productive rate 73%.
Claims (10)
1. the synthetic method of a 3-hydroxy acetophenone, it is characterized in that: its synthesis step is:
(1) add the vitriol oil in reaction vessel, the vitriol oil of control in the reaction vessel drips methyl phenyl ketone then to-5-0 ℃ in reaction vessel, dropwise the back and continued stirring reaction 20 ~ 40 minutes down at-5 ~ 0 ℃; Temperature to 55 ~ 65 in the slow then temperature reaction container ℃ continuation reaction 18 ~ 22 hours; Reaction slowly is added drop-wise to reaction mixture in the frozen water after finishing, and has precipitation to separate out, collecting precipitation, wash, 3-sulfonic benzo ethyl ketone;
(2) the 3-sulfonic benzo ethyl ketone with step (1) gained joins in the basic solution, is heated to material dissolution, continues reaction 28 ~ 32 hours down at 95 ~ 105 ℃ then; After reaction finishes reaction mixture is cooled to 8 ~ 12 ℃, drips concentrated hydrochloric acid and regulate pH value to 4.8 ~ 5.2, filter, get the 3-hydroxy acetophenone behind the gained solid drying.
2. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: the concentration of added methyl phenyl ketone in the added vitriol oil is 2.8 ~ 3.2 mol/l in the step (1).
3. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: the vitriol oil in the step (1) is that massfraction is the vitriol oil more than 98%.
4. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: the vitriol oil temperature in the step (1) before dripping methyl phenyl ketone is controlled at 0 ℃.
5. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: after dripping methyl phenyl ketone in the step (1), continued stirring reaction 30 minutes down at 0 ℃.
6. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: temperature continues reaction 20 hours for being warming up to 60 ℃ in the reaction vessel described in the step (1).
7. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: the basic solution in the step (2) is sodium hydroxide solution or the potassium hydroxide solution of concentration 5mol/l.
8. the synthetic method of 3-hydroxy acetophenone according to claim 7 is characterized in that: the 3-sulfonic benzo ethyl ketone described in the step (2) is 0.7 ~ 0.8 mol/l in sodium hydroxide solution or the concentration in the potassium hydroxide solution of 5mol/l.
9. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: reaction conditions is for reacting 30 hours down at 100 ℃ in the step (2).
10. the synthetic method of 3-hydroxy acetophenone according to claim 1 is characterized in that: react the afterreaction mixture that finishes in the step (2) and be cooled to 10 ℃; Described pH value is 5.
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| CN2010105941732A CN102040499B (en) | 2010-12-18 | 2010-12-18 | Method for synthesizing 3-hydroxyacetophenone |
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| CN2010105941732A CN102040499B (en) | 2010-12-18 | 2010-12-18 | Method for synthesizing 3-hydroxyacetophenone |
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| CN102040499A true CN102040499A (en) | 2011-05-04 |
| CN102040499B CN102040499B (en) | 2013-11-20 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62234058A (en) * | 1986-04-01 | 1987-10-14 | Dainippon Ink & Chem Inc | Production of 5-acetyl-2-alkylbenzenesulfonyl chloride |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62234058A (en) * | 1986-04-01 | 1987-10-14 | Dainippon Ink & Chem Inc | Production of 5-acetyl-2-alkylbenzenesulfonyl chloride |
Non-Patent Citations (4)
| Title |
|---|
| 李克华等: "《精细有机合成》", 31 August 2007, 石油工业出版社 * |
| 温辉梁: "《医药中间体产品生产技术》", 31 May 2005, 江西科学技术出版社 * |
| 苑兴彪: "间羟基苯乙酮的合成", 《辽宁化工》 * |
| 陈新志: "间羟基苯乙酮的合成", 《杭州化工》 * |
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