CN103224473B - Preparation method of triazine ring - Google Patents
Preparation method of triazine ring Download PDFInfo
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- CN103224473B CN103224473B CN201310182074.7A CN201310182074A CN103224473B CN 103224473 B CN103224473 B CN 103224473B CN 201310182074 A CN201310182074 A CN 201310182074A CN 103224473 B CN103224473 B CN 103224473B
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Abstract
The invention relates to a preparation method of a triazine ring. The invention solves the problems that conventional preparation method of the triazine ring has the defects of many byproducts, high cost, low yield, inconvenient aftertreatment and unsuitability for large-scale production. The triazine ring is prepared from 2-methyl thiosemicarbazide and diethyl oxalate serving as starting raw materials through direct cyclization of a Lewis acid catalyst without any solvent system under the protection of nitrogen. The preparation method has the advantages of cheap and readily available raw materials, high yield, low cost and environment friendliness, and is suitable for industrial amplification. The preparation method is applied in the technical field of preparation of organic intermediates.
Description
Technical field
The present invention relates to the preparation method of triazine ring, belong to technical field prepared by organic intermediate, to receive etc. the intermediate of medicine as ceftriaxone sodium, rocephin.
Background technology
Triazine ring is a kind of important organic intermediate, and macromolecular material, dyestuff, agricultural chemicals, medicine industry have a wide range of applications, and has very important Development volue.
English name: Thiotrzinone
CASNO：58909-39-0
Molecular formula: C
4h
5n
3o
2s;
At present, the preparation method of triazine ring mainly contains following two kinds:
Method one (Lu Songlin is permitted to mass troops, Lu Qunshan. the synthetic method of triazine ring, CN200910223937.4,2009-11-20):
This route with 2-methylthiosemicarbazone and oxalic acid diethyl ester for raw material with methyl alcohol for solvent, sodium methylate makees catalyzer, and during cyclization, by product is many, and yield is low, is not suitable for industry's enlarging production.
Method two (Cai Jie. the synthetic method of triazine ring, CN201110443145.5,2011-12-27):
This route with 2-methylthiosemicarbazone and oxalic acid diethyl ester for raw material with ethanol for solvent, catalyzer is the mixture of ammonium chloride and 10%wt hydrochloric acid soln, but still yield is lower, by product is more, product is not easily refined, and is not suitable for suitability for industrialized production.
Summary of the invention
The object of the invention is to solve existing method that to prepare triazine ring by product many, cost is high, and productive rate is low, and aftertreatment is inconvenient, is not suitable for amplifying the problem of producing, and provides a kind of preparation method of triazine ring.
The preparation method of a kind of triazine ring of the present invention, carries out according to following steps:
One, with 2-methylthiosemicarbazone and oxalic acid diethyl ester for raw material, adopt Louis acid catalysis, under nitrogen protection, heating and melting, then carries out ring-closure reaction, is down to room temperature after ring-closure reaction terminates, and obtains triazine ring crude product;
Two, after triazine ring crude product step one obtained mixes with water, reflux, filters, and collects filtrate, then crystallisation by cooling, filters, and collects filter cake, dries, obtains triazine ring;
Wherein, the 2-methylthiosemicarbazone described in step one and oxalic acid diethyl ester, lewis acidic mol ratio are 1:(1 ~ 1.2): (0.01 ~ 0.05); The temperature of ring-closure reaction is 120 DEG C ~ 150 DEG C, and the ring-closure reaction time is 2 ~ 6h;
The quality of the water described in step 2 is 5 ~ 8 times of triazine ring crude product quality.
Synthetic route of the present invention is as follows:
The present invention comprises following beneficial effect:
1, under the inventive method is heated to molten state under nitrogen protection, reacted by catalyzed cyclization, do not need to add any solvent, thus greatly reduce production cost, simplify operating procedure;
2, the triazine ring crude product purity that obtains of the present invention is high, is easy to recrystallization purifying.
Accompanying drawing explanation
Fig. 1 be embodiment 1 prepare triazine ring proton nmr spectra (
1h NMR) figure;
Fig. 2 be embodiment 1 prepare triazine ring carbon-13 nmr spectra (
13c NMR) figure.
Embodiment
Embodiment one: the preparation method of a kind of triazine ring of present embodiment, carry out according to following steps:
One, with 2-methylthiosemicarbazone and oxalic acid diethyl ester for raw material, adopt Louis acid catalysis, under nitrogen protection, heating and melting, then carries out ring-closure reaction, is down to room temperature after ring-closure reaction terminates, and obtains triazine ring crude product;
Two, after triazine ring crude product step one obtained mixes with water, reflux, filters, and collects filtrate, then crystallisation by cooling, filters, and collects filter cake, dries, obtains triazine ring;
Wherein, the 2-methylthiosemicarbazone described in step one and oxalic acid diethyl ester, lewis acidic mol ratio are 1:(1 ~ 1.2): (0.01 ~ 0.05); The temperature of ring-closure reaction is 120 DEG C ~ 150 DEG C, and the ring-closure reaction time is 2 ~ 6h;
The quality of the water described in step 2 is 5 ~ 8 times of triazine ring crude product quality.
Embodiment two: present embodiment and embodiment one unlike: the Lewis acid described in step one is aluminum chloride, iron trichloride, boron trifluoride, titanium tetrachloride or zinc chloride.Other is identical with embodiment one.
Embodiment three: present embodiment and embodiment one or two unlike: the Lewis acid described in step one is aluminum chloride.Other is identical with embodiment one or two.
Embodiment four: one of present embodiment and embodiment one to three unlike: the 2-methylthiosemicarbazone described in step one and oxalic acid diethyl ester, lewis acidic mol ratio are 1:(1 ~ 1.2): (0.01 ~ 0.05).Other is identical with one of embodiment one to three.
Embodiment five: one of present embodiment and embodiment one to four unlike: the temperature of the ring-closure reaction described in step one is 120 DEG C ~ 130 DEG C.Other is identical with one of embodiment one to four.
Embodiment six: one of present embodiment and embodiment one to five unlike: the time of the ring-closure reaction described in step one is 4 ~ 5h.Other is identical with one of embodiment one to five.
Embodiment seven: one of present embodiment and embodiment one to six unlike: the quality of the water described in step 2 is 6 times of triazine ring crude product quality.Other is identical with one of embodiment one to six.
Beneficial effect of the present invention is verified by following examples:
Following enforcement is just for illustration of the present invention, and unrestricted the present invention.
Embodiment 1
The preparation method of a kind of triazine ring of the present embodiment, carries out according to following steps:
One, at room temperature, add 2-methylthiosemicarbazone 50.0g(0.48mol), oxalic acid diethyl ester 69.5g(0.48mol), aluminum chloride 6.30g(0.048mol), under nitrogen protection, room temperature stirs, direct heating melting, then at 120 DEG C of insulated and stirred reaction 4h, be then slow cooling to room temperature, obtain triazine ring crude product;
Two, after triazine ring crude product step one being obtained 43.9g mixes with 260mL distilled water, reflux, filters, and collects filtrate, then crystallisation by cooling, filters, and collects filter cake, dries, obtains the triazine ring of 43.9g.
The triazine ring yield that the present embodiment obtains is 57%, and purity is 99%.
The hydrogen spectrogram of the triazine ring that the present embodiment obtains as shown in Figure 1, carbon spectrogram as shown in Figure 2, from Fig. 1 and Fig. 2,
1hNMR (400MHz, D
2o) δ 3.36 (s, 2H);
13cNMR (101MHz, D
2o) δ=190.57,178.96,168.21,42.60, illustrate that the present embodiment obtains triazine ring.
Embodiment 2
The preparation method of a kind of triazine ring of the present embodiment, carries out according to following steps:
One, at room temperature, add 2-methylthiosemicarbazone 100g(0.95mol), oxalic acid diethyl ester 138.9g(0.95mol), aluminum chloride 12.7g(0.095mol), under nitrogen protection, room temperature stirs, direct heating melting, then at 130 DEG C of insulated and stirred reaction 5h, be then slow cooling to room temperature, obtain triazine ring crude product;
Two, after triazine ring crude product step one being obtained 90.8g mixes with 540mL distilled water, reflux, filters, and collects filtrate, then crystallisation by cooling, filters, and collects filter cake, dries, obtains the triazine ring of 90.8g.
The triazine ring yield that the present embodiment obtains is 60%, and purity is 99%.
Finally, it is also to be noted that what enumerate above is only specific embodiments of the invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be had.All distortion that those of ordinary skill in the art can directly derive from content disclosed by the invention or associate, all should think protection scope of the present invention.
Claims (5)
1. a preparation method for triazine ring, is characterized in that the preparation method of described triazine ring carries out according to following steps:
One, with 2-methylthiosemicarbazone and oxalic acid diethyl ester for raw material, adopt Louis acid catalysis, under nitrogen protection, heating and melting, then carries out ring-closure reaction, is down to room temperature after ring-closure reaction terminates, and obtains triazine ring crude product;
Two, after triazine ring crude product step one obtained mixes with water, reflux, filters, and collects filtrate, then crystallisation by cooling, filters, and collects filter cake, dries, obtains triazine ring;
Wherein, the 2-methylthiosemicarbazone described in step one and oxalic acid diethyl ester, lewis acidic mol ratio are 1:(1 ~ 1.2): (0.01 ~ 0.05); The temperature of ring-closure reaction is 120 DEG C ~ 150 DEG C, and the ring-closure reaction time is 2 ~ 6h;
The quality of the water described in step 2 is 5 ~ 8 times of triazine ring crude product quality; Lewis acid described in step one is aluminum chloride, iron trichloride, boron trifluoride, titanium tetrachloride or zinc chloride.
2. the preparation method of a kind of triazine ring according to claim 1, is characterized in that the 2-methylthiosemicarbazone described in step one and oxalic acid diethyl ester, lewis acidic mol ratio are 1:1:0.05.
3. the preparation method of a kind of triazine ring according to claim 1, is characterized in that the temperature of the ring-closure reaction described in step one is 120 DEG C ~ 130 DEG C.
4. the preparation method of a kind of triazine ring according to claim 1, is characterized in that the time of the ring-closure reaction described in step one is 4 ~ 5h.
5. the preparation method of a kind of triazine ring according to claim 1, is characterized in that the quality of the water described in step 2 is 6 times of triazine ring crude product quality.
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| CN109293590A (en) * | 2018-11-23 | 2019-02-01 | 山东汇海医药化工有限公司 | A method of promoting triazine ring product quality |
| CN109336831B (en) * | 2018-11-23 | 2020-07-28 | 山东汇海医药化工有限公司 | Method for recovering triazine ring from triazine ring wastewater |
| 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 |
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