CN101161643A - Production technique of 8-hydroxyquinoline - Google Patents
Production technique of 8-hydroxyquinoline Download PDFInfo
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- CN101161643A CN101161643A CNA2007101932728A CN200710193272A CN101161643A CN 101161643 A CN101161643 A CN 101161643A CN A2007101932728 A CNA2007101932728 A CN A2007101932728A CN 200710193272 A CN200710193272 A CN 200710193272A CN 101161643 A CN101161643 A CN 101161643A
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- oxine
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Abstract
The present invention discloses a production technics for a 8-hydroxide quinoline, which includes the following synthetic procedures that: firstly 2-N- p-toluenesulfonyl amino phenol is mixed with ethylamine and methanol, cooled, and dripped with acrolein, after dripping, the mixture is stirred continuously for reaction, then added with hydrochloric acid, stirred for reaction under raised temperature to produce an intermediate of p-toluenesulfonyl-8-hydroxide hydrogenated quinoline, secondly, the solution as above is added with solid sodium hydroxide, the temperature of the mixed solution is raised, and then undergoes circumfluence cooling down, then hydrochloric acid is used to regulate the pH=7.5-7.8 and, thirdly, water is added into the solution as above, temperature is raised and water steam distillation is carried out to obtain the high-purity 8-hydroxide quinoline. Compared with the preparation method in the prior art, the present invention has simple operation, economized investment on the equipment, high yields, low fabrication cost, and suitability for industrialized fabrication. The actual molecular yield of 8-hydroxide can reach to more than 85 percent of that of 8-hydroxyl quinoline, based on the amount of 2-N- p-toluenesulfonyl amino phenol.
Description
Technical field
The present invention relates to the production technique of quinoline, relate in particular to a kind of production technique of oxine.
Background technology
The preparation of well-known oxine mainly is to get for example institution of higher education teaching material " Experiment of Organic Chemistry " Ceng Zhaoqiong chief editor P 175-177 record through the Skraup reaction by Ortho-Aminophenol, o-NP and glycerine under vitriol oil effect.This method temperature of reaction height, reaction is violent, adopts excessive greatly must anhydrous glycerol, the by-product polymer growing amount is many, product separation and purification difficulty, reaction formula as:
Bibliographical information is also arranged, adopt sulfuric acid or hydrochloric acid catalysis Ortho-Aminophenol, o-NP and acrolein reaction to prepare oxine, as DE2545704, JP48012745, US4044011 etc.This method still adopts o-NP as oxygenant, needs to reclaim unreacted o-NP after reaction finishes, and the color of steam distillation gained oxine has light yellowly, influences quality product, and productive rate also is no more than 80% usually.
Oxine also can promptly at first generate quinoline-8-sulfonic acid by the quinoline sulfonation by the preparation of quinoline method, uses the molten generation oxine of sodium hydroxide alkali again.The raw material quinoline source that the quinoline method is adopted is limited, and price is expensive, and this two-step reaction yield is not high yet, adds that pollution is big again, so should not recommend.Reaction formula is:
Therefore how to select cheap starting raw material for use and reduce by product and produce, improve simultaneously the key point that productive rate and quality product are the oxine production technique.
Summary of the invention
The production technique that the purpose of this invention is to provide a kind of oxine.
The production technique synthesis step is as follows:
1) 2-N-tolysulfonyl amido phenol, triethylamine, the methanol mixed postcooling drips propenal down at-20～-5 ℃, and the dropping time is 1～10 hour; After dripping off, continued stirring reaction 1～5 hour down at-20～-5 ℃; Add hydrochloric acid again, be warmed up to 20～50 ℃ of stirring reactions 1～5 hour, generate N-p-toluenesulfonyl-8-hydroxyl hydrogenation quinoline midbody;
2) add solid sodium hydroxide in above-mentioned solution, 1～5 hour postcooling of temperature rising reflux is regulated PH=7.5～8.5 with hydrochloric acid again;
3) in above-mentioned solution, add entry, heat up and carry out steam distillation, obtain highly purified oxine.
The mol ratio of 2-N-tolysulfonyl amido phenol and propenal is preferably 1: 1.2～and 1.4.The mol ratio of N-(2-hydroxy phenyl) benzsulfamide and triethylamine is preferably 1: 0.05～and 0.1.The temperature that drips propenal is preferably-10～-5 ℃.
2-N-tolysulfonyl amido phenol can be made by industrial foundation raw material Tosyl chloride that very easily obtains and Ortho-Aminophenol in condensation in the presence of yellow soda ash.
The present invention compares with existing synthetic method, has the following advantages:
1) reaction conditions safety gentleness, the productive rate height;
2) do not need to make oxygenant, saved the trouble of removing excessive o-NP with steam distillation with o-NP;
3) feed intake and aftertreatment all simple, low equipment investment is easy to realize industrialized production.
Specific implementation method
The production technique building-up reactions equation of oxine:
Following examples will help to understand the present invention, but be not limited to content of the present invention.
Embodiment 1
1) 1 mole of 2-N-tolysulfonyl amido phenol, 0.02 mole of triethylamine, 1000 ml methanol are mixed postcooling, drip 1.0 mol propylene aldehyde down at-20 ℃, and the dropping time is 1 hour; After dripping off, continued stirring reaction 1 hour down at-20 ℃; Add hydrochloric acid again, be warmed up to 20 ℃ of stirring reactions 1 hour, generate N-p-toluenesulfonyl-8-hydroxyl hydrogenation quinoline midbody;
2) add solid sodium hydroxide in above-mentioned solution, 1 hour postcooling of temperature rising reflux is regulated PH=7.5 with hydrochloric acid again;
3) in above-mentioned solution, add entry, heat up and carry out steam distillation, obtain 0.75 mole of highly purified oxine; In 2-N-tolysulfonyl amido phenol, molar yield is 75%.
Embodiment 2
1) 1 mole of 2-N-tolysulfonyl amido phenol, 0.2 mole of triethylamine, 1000 ml methanol are mixed postcooling, drip 1.6 mol propylene aldehyde down at-5 ℃, and the dropping time is 10 hours; After dripping off, continued stirring reaction 5 hours down at-5 ℃; Add hydrochloric acid again, be warmed up to 50 ℃ of stirring reactions 5 hours, generate N-p-toluenesulfonyl-8-hydroxyl hydrogenation quinoline midbody;
2) add solid sodium hydroxide in above-mentioned solution, 5 hours postcooling of temperature rising reflux are regulated PH=8.5 with hydrochloric acid again;
3) in above-mentioned solution, add entry, heat up and carry out steam distillation, obtain 0.80 mole of highly purified oxine; In 2-N-tolysulfonyl amido phenol, molar yield is 80%.
Embodiment 3
1) 1 mole of 2-N-tolysulfonyl amido phenol, 0.05 mole of triethylamine, 1000 ml methanol are mixed postcooling, drip 1.2 mol propylene aldehyde down at-10 ℃, and the dropping time is 5 hours; After dripping off, continued stirring reaction 3 hours down at-20 ℃; Add hydrochloric acid again, be warmed up to 30 ℃ of stirring reactions 3 hours, generate N-p-toluenesulfonyl-8-hydroxyl hydrogenation quinoline midbody;
2) add solid sodium hydroxide in above-mentioned solution, 3 hours postcooling of temperature rising reflux are regulated PH=8.0 with hydrochloric acid again;
3) in above-mentioned solution, add entry, heat up and carry out steam distillation, obtain 0.85 mole of highly purified oxine; In 2-N-tolysulfonyl amido phenol, molar yield is 85%.
Embodiment 4
1) 1 mole of 2-N-tolysulfonyl amido phenol, 0.1 mole of triethylamine, 1000 ml methanol are mixed postcooling, drip 1.4 mol propylene aldehyde down at-5 ℃, and the dropping time is 5 hours; After dripping off, continued stirring reaction 3 hours down at-5 ℃; Add hydrochloric acid again, be warmed up to 30 ℃ of stirring reactions 3 hours, generate N-p-toluenesulfonyl-8-hydroxyl hydrogenation quinoline midbody;
2) add solid sodium hydroxide in above-mentioned solution, 3 hours postcooling of temperature rising reflux are regulated PH=8.5 with hydrochloric acid again;
3) in above-mentioned solution, add entry, heat up and carry out steam distillation, obtain 0.86 mole of highly purified oxine; In 2-N-tolysulfonyl amido phenol, molar yield is 86%.
Claims (4)
1. the invention discloses a kind of production technique of oxine.It is characterized in that this production technique synthesis step is as follows: 1) 2-N-tolysulfonyl amido phenol, triethylamine, the methanol mixed postcooling drips propenal down at-20～-5 ℃, and the dropping time is 1～10 hour; After dripping off, continued stirring reaction 1～5 hour down at-20～-5 ℃; Add hydrochloric acid again, be warmed up to 20～50 ℃ of stirring reactions 1～5 hour, generate N-p-toluenesulfonyl-8-hydroxyl hydrogenation quinoline midbody; 2) add solid sodium hydroxide in above-mentioned solution, 1～5 hour postcooling of temperature rising reflux is regulated PH=7.5～8.5 with hydrochloric acid again; 3) in above-mentioned solution, add entry, heat up and carry out steam distillation, obtain highly purified oxine.
2. the production technique of a kind of oxine according to claim 1, it is characterized in that: the mol ratio of 2-N-tolysulfonyl amido phenol and propenal is 1: 1.0～1.6, be preferably 1: 1.2～1.4.
3. the production technique of a kind of oxine according to claim 1, it is characterized in that: the mol ratio of 2-N-tolysulfonyl amido phenol and triethylamine is 1: 0.02～0.2, be preferably 1: 0.05～0.1.
4. the production technique of a kind of oxine according to claim 1 is characterized in that: the temperature that drips propenal is-20～-5 ℃, is preferably-10～-5 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101932728A CN101161643A (en) | 2007-11-26 | 2007-11-26 | Production technique of 8-hydroxyquinoline |
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| CNA2007101932728A CN101161643A (en) | 2007-11-26 | 2007-11-26 | Production technique of 8-hydroxyquinoline |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101838237A (en) * | 2010-04-27 | 2010-09-22 | 无锡市化工研究设计院宜兴联营实验厂 | Clean production process for separating 8-hydroxyquinoline from quinoline method neutralizing solution |
| CN108752271A (en) * | 2018-06-28 | 2018-11-06 | 江苏新瑞药业有限公司 | A kind of synthetic method of oxyquinoline |
-
2007
- 2007-11-26 CN CNA2007101932728A patent/CN101161643A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101838237A (en) * | 2010-04-27 | 2010-09-22 | 无锡市化工研究设计院宜兴联营实验厂 | Clean production process for separating 8-hydroxyquinoline from quinoline method neutralizing solution |
| CN101838237B (en) * | 2010-04-27 | 2011-11-09 | 无锡市化工研究设计院宜兴联营实验厂 | Clean production process for separating 8-hydroxyquinoline from quinoline method neutralizing solution |
| CN108752271A (en) * | 2018-06-28 | 2018-11-06 | 江苏新瑞药业有限公司 | A kind of synthetic method of oxyquinoline |
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Open date: 20080416 |