CN104130170A - Synthesis method of 4-Hydroxythiobenzamide - Google Patents
Synthesis method of 4-Hydroxythiobenzamide Download PDFInfo
- Publication number
- CN104130170A CN104130170A CN201410389692.3A CN201410389692A CN104130170A CN 104130170 A CN104130170 A CN 104130170A CN 201410389692 A CN201410389692 A CN 201410389692A CN 104130170 A CN104130170 A CN 104130170A
- Authority
- CN
- China
- Prior art keywords
- synthetic method
- reaction
- hydroxyl thiobenzamide
- methyl
- hydroxyl
- 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.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of 4-Hydroxythiobenzamide. The method comprises the following steps: mixing methyl p-hydroxybenzoate with stronger ammonia water, carrying out high-temperature reaction inside a reaction kettle, and then carrying out vacuum concentration on the mixture, so as to obtain p-hydroxybenzene formamide; and refluxing p-hydroxybenzene formamide and phosphorus pentasulfide in a solvent, and obtaining the 4-Hydroxythiobenzamide. The method disclosed by the invention is mild in reaction, safe to operate, low in raw material price, easy to obtain, high in product purity and yield, and low in handling expense, a novel method is provided for obtaining the 4-Hydroxythiobenzamide, and the method disclosed by the invention is applicable to industrial mass production.
Description
Technical field
The invention belongs to chemical industry, be specifically related to a kind of synthetic method to hydroxyl thiobenzamide.
Background technology
To hydroxyl thiobenzamide, claim again 4-hydroxyl thiobenzamide, molecular formula: C
7h
7nOS, molecular weight: 153.2, it is the important intermediate of anti-gout novel medical Febuxostat.
Synthetic method report to hydroxyl thiobenzamide is a lot, Chinese patent literature CN201210219548.6, a kind of preparation method to hydroxyl thiobenzamide is disclosed, specifically certain water gaging, 4-hydroxybenzonitrile, Sodium sulfhydrate, secondary amine are mixed, at a certain temperature, drip organic monoacid, after reaction finishes, filter, filter cake is dried and obtained hydroxyl thiobenzamide, reaction equation is as follows:
The shortcoming of the method is that the prices of raw and semifnished materials that adopt are expensive.
Shown in patent documentation WO2005012273, in water system, 4-hydroxybenzonitrile, under the catalysis of Sodium sulfhydrate, passes into stink damp precursor reactant, and reaction equation is as follows:
In the method reaction process, there is the hydrogen sulfide of a large amount of foul odours, exist the safety such as toxicity damage and pollution hidden trouble, high to equipment seal request, be difficult for absorbing and processing, and in treating processes, produce a large amount of waste water, cannot process and recycle, production cost is high.
In patent documentation CN201310327512, report, take p-HBN as raw material, in organic solvent ethanol, react, take thiocarbamide as sulphur source.Reaction equation is as follows:
The method raw materials cost is higher, reacts wayward, and needs a large amount of methyl alcohol.All lower to the purity of hydroxyl thiobenzamide and yield, need be through repeatedly just carrying out subsequent reactions after purifying.
The technique of above bibliographical information has and is difficult to industrialized problem, method reaction temperature provided by the invention and, operational safety, the prices of raw and semifnished materials are cheap and easily obtain, product purity and yield are higher, processing costs is low, and for the acquisition of hydroxyl thiobenzamide being provided to a kind of new method, this inventive method can be applied to large-scale industrial production.
Summary of the invention
The object of this invention is to provide a kind of synthetic method to hydroxyl thiobenzamide, purification procedures adopts physical method, and environmental protection, has reduced environmental pollution; The yield that has improved hydroxyl thiobenzamide, has reduced production cost.
A kind of synthetic method to hydroxyl thiobenzamide of the present invention, comprises the following steps:
(1) methyl p-hydroxybenzoate is mixed with strong aqua, in reaction kettle for reaction;
(2) after completion of the reaction, vacuum concentration, cooling, suction filtration obtains para hydroxybenzene methane amide;
(3) para hydroxybenzene methane amide and thiophosphoric anhydride are refluxed in solvent;
(4) after completion of the reaction, distillation, except desolventizing, adds water and ethyl acetate extraction, and it is to hydroxyl thiobenzamide that organic phase evaporate to dryness obtains solid.
Wherein:
In step (1), the mol ratio of methyl p-hydroxybenzoate and strong aqua is 1:(37 ~ 40); The temperature of ammonolysis reaction is 100 ~ 120 ℃.
The middle reaction solution of step (2) is concentrated to 1.5 ~ 3 times of charging capacity.
Solvent in step (3) is THF, methyl alcohol, ethanol, toluene, methylene dichloride, chloroform, methyl-phenoxide; The mol ratio of para hydroxybenzene methane amide and thiophosphoric anhydride is 1:(0.4 ~ 0.8).
What by above-mentioned steps, obtain is 96%, HPLC purity 99.4% to hydroxyl thiobenzamide yield.
In sum, the present invention has the following advantages:
(1) starting material are used more cheap methyl p-hydroxybenzoate, and other starting material are also comparatively cheap;
(2) reaction conditions is gentle, and easy handling, more easily realizes suitability for industrialized production;
(3) yield is higher, and cost is lower, and the purity of the product obtaining is higher.
Embodiment
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1:
By 28% strong aqua 150mL, methyl p-hydroxybenzoate 8.6g (0.060mol) in reactor.Under agitation condition, control temperature 100 ~ 120 ℃ of insulation reaction, TLC detects, react completely, end reaction liquid is concentrated in rotatory evaporator to 2 times of charging capacity, suction filtration is separated dry, obtaining white solid is para hydroxybenzene methane amide 7.63g (0.055mol), and productive rate is 97.8%, HPLC purity 99.1%
Embodiment 2:
By 28% strong aqua 150mL, methyl p-hydroxybenzoate 8.6g (0.060mol) in reactor.Under agitation condition, control temperature 100 ~ 120 ℃ of insulation reaction, TLC detects, react completely, end reaction liquid is concentrated in rotatory evaporator to 1.5 times of charging capacity, suction filtration is separated dry, obtaining white solid is para hydroxybenzene methane amide 7.64g (0.056mol), and productive rate is 98.0%, HPLC purity 96.3%.
Embodiment 3:
By 28% strong aqua 100mL, methyl p-hydroxybenzoate 8.6g (0.060mol) in reactor.Under agitation condition, control temperature 100 ~ 120 ℃ of insulation reaction.TLC detects, and reacts completely.End reaction liquid is concentrated in rotatory evaporator to 2 times of charging capacity, suction filtration is separated dry, and obtaining white solid is para hydroxybenzene methane amide 7.54g (0.055mol), and productive rate is 96.7%, HPLC purity 97.2%.
Example 4
By 28% strong aqua 150mL, methyl p-hydroxybenzoate 8.6g (0.060mol) in reactor.Under agitation condition, control temperature 100 ~ 120 ℃ of insulation reaction, TLC detects, and reacts completely.End reaction liquid is concentrated in rotatory evaporator to 3 times of charging capacity, suction filtration is separated dry, and obtaining white solid is para hydroxybenzene methane amide 7.41g (0.054mol), and productive rate is 95.0%, HPLC purity 99.0%.
Example 5
Para hydroxybenzene methane amide 5.0g (0.036mol) and 4.0g(0.018mol) thiophosphoric anhydride will be added in the there-necked flask of 100mL successively, the THF that adds 36mL under stirring, reflux, TLC detects, after having reacted, vacuum distilling is except desolventizing, add 10mL water and the extraction of (2 * 20mL) ethyl acetate, merge organic phase, it is to hydroxyl thiobenzamide 5.27g that evaporate to dryness obtains solid, productive rate is 94.5%, and purity is 96.2%.
Example 6
Para hydroxybenzene methane amide 5.0g (0.036mol) and 3.59g(0.0162mol) thiophosphoric anhydride will be added in the there-necked flask of 100mL successively, the toluene that adds 36mL under stirring, reflux, TLC detects, after having reacted, vacuum distilling is except desolventizing, add 10mL water and the extraction of (2 * 20mL) ethyl acetate, merge organic phase, it is to hydroxyl thiobenzamide 5.39g that evaporate to dryness obtains solid, productive rate is 96.6%, and purity is 98.7%.
Example 7
Para hydroxybenzene methane amide 5.0g (0.036mol) and 4.0g(0.018mol) thiophosphoric anhydride will be added in the there-necked flask of 100mL successively, the toluene that adds 36mL under stirring, reflux, TLC detects, after having reacted, vacuum distilling is except desolventizing, add 10mL water and the extraction of (2 * 20mL) ethyl acetate, merge organic phase, it is to hydroxyl thiobenzamide 5.44g that evaporate to dryness obtains solid, productive rate is 97.4%, and purity is 99.2%.
Example 8
To in the there-necked flask of 100mL, add successively para hydroxybenzene methane amide 5.0g (0.036mol) and 4.0g(0.018mol) thiophosphoric anhydride, under stirring, add the CH of 36mL
2cl
2, reflux, TLC detection, after having reacted, vacuum distilling, except desolventizing, adds 10mL water and the extraction of (2 * 20mL) ethyl acetate, merges organic phase, and it is that productive rate is 94% to hydroxyl thiobenzamide 5.25g that evaporate to dryness obtains solid, and purity is 96.0%.
Example 9
Para hydroxybenzene methane amide 5.0g (0.036mol) and 4.0g(0.018mol) thiophosphoric anhydride will be added in the there-necked flask of 100mL successively, the chloroform that adds 36mL under stirring, reflux, TLC detects, after having reacted, vacuum distilling is except desolventizing, add 10mL water and the extraction of (2 * 20mL) ethyl acetate, merge organic phase, it is to hydroxyl thiobenzamide 5.40g that evaporate to dryness obtains solid, productive rate is 96.8%, and purity is 96.3%.
Although above-mentioned, the specific embodiment of the present invention is described in conjunction with the embodiments; but be not limiting the scope of the invention; one of ordinary skill in the art should be understood that; on the basis of technical scheme of the present invention, those skilled in the art do not need to pay various modifications that creative work can make or distortion still in protection scope of the present invention.
Claims (6)
1. the synthetic method to hydroxyl thiobenzamide, is characterized in that: comprise the following steps:
(1) methyl p-hydroxybenzoate is mixed with strong aqua; Pyroreaction obtains para hydroxybenzene methane amide;
(2) para hydroxybenzene methane amide and thiophosphoric anhydride are refluxed in solvent;
(3) after completion of the reaction, distill out desolventizing, add water and ethyl acetate extraction, it is to hydroxyl thiobenzamide that organic phase evaporate to dryness obtains solid.
2. a kind of synthetic method to hydroxyl thiobenzamide according to claim 1, is characterized in that: in step (1), the mol ratio of methyl p-hydroxybenzoate and strong aqua is 1:(20-40).
3. a kind of synthetic method to hydroxyl thiobenzamide according to claim 1, is characterized in that: in step (1), the temperature of ammonolysis reaction is 100-120 ℃.
4. a kind of synthetic method to hydroxyl thiobenzamide according to claim 1, is characterized in that: the 1.5-3 that in step (2), reaction solution is concentrated to charging capacity doubly.
5. a kind of synthetic method to hydroxyl thiobenzamide according to claim 1, is characterized in that: the solvent in step (3) is THF, methyl alcohol, ethanol, toluene, methylene dichloride, chloroform, methyl-phenoxide, DMF.
6. a kind of synthetic method to hydroxyl thiobenzamide according to claim 1, is characterized in that: in step (3), the mol ratio of para hydroxybenzene methane amide and thiophosphoric anhydride is 1:(0.4-0.8).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410389692.3A CN104130170A (en) | 2014-08-11 | 2014-08-11 | Synthesis method of 4-Hydroxythiobenzamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410389692.3A CN104130170A (en) | 2014-08-11 | 2014-08-11 | Synthesis method of 4-Hydroxythiobenzamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104130170A true CN104130170A (en) | 2014-11-05 |
Family
ID=51803069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410389692.3A Pending CN104130170A (en) | 2014-08-11 | 2014-08-11 | Synthesis method of 4-Hydroxythiobenzamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104130170A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110818590A (en) * | 2019-11-18 | 2020-02-21 | 湖北大学 | Preparation method of p-hydroxybenzonitrile |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06293746A (en) * | 1993-04-08 | 1994-10-21 | Teijin Ltd | Production of (alkoxycyanophenyl)thiazole derivative |
| CN1382686A (en) * | 2001-04-24 | 2002-12-04 | 中国人民解放军军事医学科学院放射医学研究所 | Process for preparing 3-aminobenzoylamine |
| CN102285937A (en) * | 2011-09-14 | 2011-12-21 | 安润医药科技（苏州）有限公司 | Method for synthesizing febuxostat |
| CN103396347A (en) * | 2013-07-31 | 2013-11-20 | 苏州诚和医药化学有限公司 | Method for synthesizing p-hydroxyl thiobenzamide |
-
2014
- 2014-08-11 CN CN201410389692.3A patent/CN104130170A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06293746A (en) * | 1993-04-08 | 1994-10-21 | Teijin Ltd | Production of (alkoxycyanophenyl)thiazole derivative |
| CN1382686A (en) * | 2001-04-24 | 2002-12-04 | 中国人民解放军军事医学科学院放射医学研究所 | Process for preparing 3-aminobenzoylamine |
| CN102285937A (en) * | 2011-09-14 | 2011-12-21 | 安润医药科技（苏州）有限公司 | Method for synthesizing febuxostat |
| CN103396347A (en) * | 2013-07-31 | 2013-11-20 | 苏州诚和医药化学有限公司 | Method for synthesizing p-hydroxyl thiobenzamide |
Non-Patent Citations (2)
| Title |
|---|
| 潘洁玉: "对羟基苯甲腈生产工艺的研究与开发", 《西北大学专业学位硕士学位论文》, 30 June 2012 (2012-06-30), pages 33 - 34 * |
| 田帅等: "硫代苯甲酰胺类化合物的合成与杀虫活性", 《现代农药》, vol. 13, no. 2, 30 April 2014 (2014-04-30), pages 15 - 18 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110818590A (en) * | 2019-11-18 | 2020-02-21 | 湖北大学 | Preparation method of p-hydroxybenzonitrile |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | The hydroamination of alkenes with sulfonamides catalyzed by the recyclable silica gel supported triflic acid | |
| CN101941928B (en) | Synthesis method of sulfhydryl alkyl alcohol | |
| CN104262273B (en) | Synthesis method of 1,3,5-triazine derivatives | |
| CN113444039B (en) | Method for preparing 2,2, 4-trimethyl-1, 2-dihydroquinoline by using ionic liquid | |
| CN102408430B (en) | Synthetic process and special equipment for substituted bis [tetraphenylporphinatoiron] | |
| CN104193628B (en) | A kind of amino aryl ketone compound and synthetic method thereof being used as medicine intermediate | |
| CN104130170A (en) | Synthesis method of 4-Hydroxythiobenzamide | |
| CN105315232A (en) | Method for preparing acryloyl morpholine | |
| CN104529779A (en) | Synthesis method of D-dibenzoyl tartaric acid | |
| CN109438237B (en) | Preparation method of 3-ethoxy ethyl acrylate | |
| CN103880717B (en) | The preparation method of two (3-allyl group-4-hydroxy phenyl) sulfones and derivative thereof | |
| CN102731684B (en) | Preparation method of urethane molecularly imprinted polymer | |
| CN108558661A (en) | A kind of propandiol butyl ether acetic acid esters synthetic method | |
| CN105198768A (en) | Synthesis method for 2-aminobutanamide | |
| CN104130181A (en) | Continuous synthesis method of 2,2,6,6-tetramethyl-4-piperidone | |
| CN103113261A (en) | Preparation method of metharcylic acid, 2-isocyanatoethyl ester | |
| CN100560564C (en) | A kind of production technique that is fit to industrial tert-butyl glycinate | |
| CN108484526B (en) | Method for synthesizing AE active ester by ester exchange method | |
| CN107445856B (en) | Synthesis process of N-isopropyl acrylamide | |
| CN102659572A (en) | Preparation method of dehydroabietic acid | |
| CN106316894A (en) | Nitro acrylamides compound synthetic method | |
| CN101845055B (en) | Method for purifying dichloromethyl phenylsilane by chemical coordination effect | |
| CN102070455B (en) | Chemical synthesis method for o-chlorobenzoic acid chloro butyl ester | |
| CN101307022A (en) | Green synthetic method for methyl-3-ethyl-4-chlorin-5-pyrazol formyl chloride | |
| CN104311469A (en) | Synthetic method of substituted indole-3-acetic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20141105 |