CN102558080B - Method for synthesizing thiotriazinone - Google Patents
Method for synthesizing thiotriazinone Download PDFInfo
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- CN102558080B CN102558080B CN201110443145.5A CN201110443145A CN102558080B CN 102558080 B CN102558080 B CN 102558080B CN 201110443145 A CN201110443145 A CN 201110443145A CN 102558080 B CN102558080 B CN 102558080B
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- triazine ring
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- thiotriazinone
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- UMWWHOXOVPIGFD-UHFFFAOYSA-N CN(C(S)=NC1=O)N=C1O Chemical compound CN(C(S)=NC1=O)N=C1O UMWWHOXOVPIGFD-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention relates to a method for synthesizing a pharmaceutical intermediate, in particular to a method for synthesizing thiotriazinone. The method comprises the following steps of: reacting 2-methylaminothiourea and diethyl oxalate which are taken as raw materials and ethanol which is taken as a solvent to obtain crude thiotriazinone, and recrystallizing the crude thiotriazinone to obtain a final product, wherein a recrystallization solvent is water. The method is characterized in that: a catalyst is added in the reaction of the 2-methylaminothiourea and the diethyl oxalate, and is a mixture of ammonium chloride and a hydrochloric acid solution at the concentration of 10 weight percent. The method has the advantages that: the reaction yield is improved and the reaction time is shortened by selecting the appropriate catalyst; the cost of raw materials is reduced; operation steps are reduced; and the method is more suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of synthetic method of medicine intermediate, be specifically related to a kind of synthetic method of triazine ring.
Background technology
Triazine ring, chemical name: Thiotriazinone, molecular formula: C
4h
5n
3o
2s, structural formula is as follows:
Outward appearance: white or off-white color crystalline powder, fusing point >=245 DEG C.
Triazine ring is a kind of important medicine intermediate, is mainly used in synthetic ceftriaxone sodium.
Triazine ring is to react taking 2-methylthiosemicarbazone and oxalic acid diethyl ester as raw material, generates target compound.Reaction formula is as follows:
But exist reaction yield low, the problems such as general reaction time length, cause the waste of time and raw material, and actual production is existed to larger restriction.
Summary of the invention
The object of this invention is to provide a kind of synthetic method of triazine ring, improve reaction yield, Reaction time shorten, reduces energy consumption, reduces material cost simultaneously, and reduction operation steps is applicable to suitability for industrialized production more.
The synthetic method of a kind of triazine ring of the present invention, comprise the steps: taking 2-methylthiosemicarbazone, oxalic acid diethyl ester as starting material, taking ethanol as solvent, reaction generates triazine ring crude product, and triazine ring crude product is carried out to recrystallization, obtains the finished product, wherein, recrystallization solvent is water, and 2-methylthiosemicarbazone adds catalyzer in reacting with oxalic acid diethyl ester, and this catalyzer is the mixture of ammonium chloride and 10wt% hydrochloric acid soln.
Wherein, the mol ratio between various starting material is preferably 2-methylthiosemicarbazone: oxalic acid diethyl ester: ammonium chloride: ethanol=1: 1～1.2: 2～2.3: 4～6, and the ratio relation between ammonium chloride and 10wt% hydrochloric acid soln is 1g: 3ml.
Concrete synthetic method of the present invention is as follows:
Step (1): reaction mass 2-methylthiosemicarbazone, ethanol and catalyzer are joined in there-necked flask, control temperature and drip oxalic acid diethyl ester in the time of 30～50 DEG C, 30min dropwises, then heating reflux reaction 3h, be cooled to 10 DEG C, filtration drying, obtains triazine ring crude product.
Step (2): add appropriate distilled water and the thick product of triazine ring in reaction flask, heat temperature raising adds a small amount of gac after material is entirely molten, continues to stir after 30min, heat filtering, and cooling, crystallization, filters, and obtains product.
The invention has the advantages that by selecting suitable catalyzer, improve reaction yield with this, Reaction time shorten reduces material cost simultaneously, has reduced operation steps simultaneously, is more applicable to suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1:
(1) mixture of reaction mass 2-methylthiosemicarbazone 10.5g, ethanol 230ml, 10.7g ammonium chloride and 32.1ml 10wt% hydrochloric acid soln is joined in there-necked flask, control temperature and in the time of 40 DEG C, drip oxalic acid diethyl ester 14.7g, 30min dropwises, then heating reflux reaction 3h, be cooled to 10 DEG C, filtration drying, obtains triazine ring crude product.
(2) in reaction flask, add appropriate distilled water and the thick product of triazine ring, heat temperature raising adds a small amount of gac after material is entirely molten, continue to stir after 30min, and heat filtering, cooling, crystallization, filters, and obtains product 12.5g, yield 78.6%.
Embodiment 2:
(1) mixture of reaction mass 2-methylthiosemicarbazone 10.5g, ethanol 240ml, 11.2g ammonium chloride and 33.6ml 10wt% hydrochloric acid soln is joined in there-necked flask, control temperature and in the time of 40 DEG C, drip oxalic acid diethyl ester 16.2g, 30min dropwises, then heating reflux reaction 3h, be cooled to 10 DEG C, filtration drying, obtains triazine ring crude product.
(2) in reaction flask, add appropriate distilled water and the thick product of triazine ring, heat temperature raising adds a small amount of gac after material is entirely molten, continue to stir after 30min, and heat filtering, cooling, crystallization, filters, and obtains product 13.1g, yield 82.4%.
Claims (1)
1. a synthetic method for triazine ring, is characterized in that: adopt the one in following two kinds of methods:
(1) mixture of reaction mass 2-methylthiosemicarbazone 10.5g, ethanol 230ml, 10.7g ammonium chloride and 32.1ml10wt% hydrochloric acid soln is joined in there-necked flask, control temperature and in the time of 40 DEG C, drip oxalic acid diethyl ester 14.7g, 30min dropwises, then heating reflux reaction 3h, be cooled to 10 DEG C, filtration drying, obtains triazine ring crude product
(2) in reaction flask, add distilled water and the thick product of triazine ring, heat temperature raising adds gac after material is entirely molten, continue to stir after 30 min, and heat filtering, cooling, crystallization, filters, and obtains product 12.5g, yield 78.6%;
Or (1) joins the mixture of reaction mass 2-methylthiosemicarbazone 10.5g, ethanol 240ml, 11.2g ammonium chloride and 33.6ml10wt% hydrochloric acid soln in there-necked flask, control temperature and in the time of 40 DEG C, drip oxalic acid diethyl ester 16.2g, 30min dropwises, then heating reflux reaction 3h, be cooled to 10 DEG C, filtration drying, obtains triazine ring crude product
(2) in reaction flask, add distilled water and the thick product of triazine ring, heat temperature raising adds gac after material is entirely molten, continue to stir after 30 min, and heat filtering, cooling, crystallization, filters, and obtains product 13.1g, yield 82.4%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110443145.5A CN102558080B (en) | 2011-12-27 | 2011-12-27 | Method for synthesizing thiotriazinone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110443145.5A CN102558080B (en) | 2011-12-27 | 2011-12-27 | Method for synthesizing thiotriazinone |
Publications (2)
| Publication Number | Publication Date |
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| CN102558080A CN102558080A (en) | 2012-07-11 |
| CN102558080B true CN102558080B (en) | 2014-07-09 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201110443145.5A Active CN102558080B (en) | 2011-12-27 | 2011-12-27 | Method for synthesizing thiotriazinone |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103224473B (en) * | 2013-05-16 | 2015-04-15 | 黑龙江大学 | Preparation method of triazine ring |
| CN103553915A (en) * | 2013-11-01 | 2014-02-05 | 山东汇海医药化工有限公司 | Method for treating organic salt in thiotriazine ring cyclization mother liquid by use of inorganic acid |
| CN103664812B (en) * | 2013-12-16 | 2015-07-15 | 山东汇海医药化工有限公司 | Preparation method of TTZ (thiotriazinone) |
| CN104177305B (en) * | 2014-08-07 | 2017-09-15 | 山东汇海医药化工有限公司 | The new method of triazine ring is synthesized using mixed solvent |
| CN106749063A (en) * | 2016-11-14 | 2017-05-31 | 山东汇海医药化工有限公司 | The method that a kind of self-control organic alkali catalyst of use with Graphene as carrier synthesizes triazine ring |
| CN112759558B (en) * | 2020-12-30 | 2022-06-14 | 山东金城柯瑞化学有限公司 | Process for the preparation of triazine rings |
-
2011
- 2011-12-27 CN CN201110443145.5A patent/CN102558080B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 2-甲基-1, 2, 5, 6-四氢-5, 6-二氧-1, 2, 4-三嗪-3-硫醇的合成研究;傅德才 等;《河北科技大学学报》;19991231;第20卷(第1期);第55-56、86页 * |
| 傅德才 等.2-甲基-1, 2, 5, 6-四氢-5, 6-二氧-1, 2, 4-三嗪-3-硫醇的合成研究.《河北科技大学学报》.1999,第20卷(第1期),第55-56、86页. |
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