CN105330607A - Preparation method of high-purity 1H-1,2,3-triazole - Google Patents
Preparation method of high-purity 1H-1,2,3-triazole Download PDFInfo
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- CN105330607A CN105330607A CN201510818074.0A CN201510818074A CN105330607A CN 105330607 A CN105330607 A CN 105330607A CN 201510818074 A CN201510818074 A CN 201510818074A CN 105330607 A CN105330607 A CN 105330607A
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- triazole
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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Abstract
The invention relates to a preparation method of high-purity 1H-1,2,3-triazole. The preparation method comprises steps as follows: step (1), benzotriazole is taken as a raw material, potassium permanganate is taken as an oxidizing agent, water is taken as a solvent, and high-purity 1H-1,2,3-triazole-4,5-dicarboxylic acid is obtained through an oxidation ring-opening reaction, purification and drying under the alkaline condition; step (2), 1H-1,2,3-triazole-4,5-dicarboxylic acid obtained in the step (1) has a decarboxylic reaction in an N,N-dimethylformamide solvent under the catalytic action of a catalyst, a target product, namely, high-purity 1H-1,2,3-triazole is obtained through purification, and the catalyst is quinolone, pyridine or a mixture of quinolone and pyridine. In the step (2), quinolone or pyridine is taken as a catalyst to replace conventional copper powder or oxide of copper, the reaction selectivity is good, the yield is high, the product purity is high, and the stability is better.
Description
Technical field
The invention belongs to fine chemistry industry preparing technical field, be specifically related to a kind of preparation method of high purity 1 H-1,2,3-triazole.
Background technology
1H-1,2,3-triazole is the important intermediate of beta-lactamase inhibitor Tazobactam Sodium, also can be used for the synthesis of other medicines, and highly purified 1H-1,2,3-triazole is also used on the clean-out system of electronic product in addition.
At present, the synthetic method of known 1H-1,2,3-triazole mainly contains four kinds:
(1) as the oxalic dialdehyde that JP0641092 generates with 2,2-dichloro acetaldehyde and hydroxyl hydrochloride reaction, monoxime hydrazone or oxime acylhydrazone are intermediate synthesis;
(2) as JP05140121 p-toluene sulfonyl hydrazide and 2,2-dichloro acetaldehyde react the sulphonyl hydrazone that generates or acylhydrazone is that intermediate synthesizes;
(3) as CatinoA.1.2.3-Triazole [J] .Ann.chim (Rome) 1968581507-1509. is directly prepared from hydrazoic acid and alkynes or alkene reaction;
(4) as J.Berdtchem.Scand195913 (5) 888-891 and West China pharmaceutical journal 200116 (4): 273-275, by 1,2,3-triazole-4-carboxylic acid or the preparation of 1,2,3-triazole-4,5-dicarboxylic acid high temperature decarboxylation.These synthetic routes are all indirect or direct is above raw material with trinitride, and this compounds not only has severe toxicity, more has strong explosivity, thus technological operation is dangerous and be difficult to control, the finished product purity is not high, and wastewater flow rate is large, is thus difficult to realize industrialized production.
The patent No. is the preparation method that the patent of invention of 200710069580.X specifically discloses a kind of high purity 1 H-1,2,3-triazole, with benzotriazole and potassium permanganate for raw material, by oxidation open loop, more acidified, obtain 1H-1,2,3-triazole-4,5-dicarboxylic acid crude product, after this crude product refining under the effect of the oxide compound of catalyst copper powder or copper, vacuum decarboxylation at 100 DEG C ~ 180 DEG C, obtains 1H-1, the thick oil of 2,3-triazole.The oxide compound of this preparation method's copper powder or copper does catalyst reaction poor selectivity, purity difference, and thus product stability is also poor, and oxidation is low with high temperature carbonization decarboxylation yield, and large production energy consumption is high, and production capacity is little, thus produces this height.
Summary of the invention
Technical problem to be solved by this invention overcomes the deficiencies in the prior art, a kind of high purity 1 H-1 is provided, 2, the preparation method of 3-triazole, make catalyzer with pyridine or quinoline to replace traditional making catalyzer with the oxide compound of copper powder or copper, when doing decarboxylic reaction, good reaction selectivity, yield are high, product purity is high and stability is better.
For solving above technical problem, a kind of technical scheme that the present invention takes is:
A preparation method for high purity 1 H-1,2,3-triazole, concrete synthetic route is as follows:
The preparation of 1,1H-1,2,3-triazole-4,5-dicarboxylic acid (b)
The preparation of 2,1H-1,2,3-triazole (c)
The concrete steps of preparation method are:
Step 1, be raw material with benzotriazole, potassium permanganate is oxygenant, and water is solvent, in the basic conditions, obtains high purity 1 H-1,2,3-triazole-4,5-dicarboxylic acid by oxidative cleavage, purification oven dry;
The 1H-1 obtained in step 2, step 1,2,3-triazole-4,5-dicarboxylic acid is at N, carrying out decarboxylic reaction under the effect of dinethylformamide solvent catalyst neutralisation, obtaining target product high purity 1 H-1,2 by purifying, 3-triazole, wherein, catalyzer is quinoline, pyridine or the mixture of the two.
Preferably, the temperature of reaction in step 1 is 20 DEG C-100 DEG C, and the reaction times is 1.0-5.0h, benzotriazole: sodium hydroxide or potassium hydroxide: the mol ratio of potassium permanganate is 1:0.5-3:5-10, m (benzotriazole): V (H
2o)=1:15-40.
Preferably, adopt following methods to purify: after completion of the reaction in step 1, cross and filter Manganse Dioxide, its solution 30-50% hydrogen peroxide fades, the residual Manganse Dioxide of removing, cooling; PH is regulated to be 1.5-3.0 with concentrated hydrochloric acid or the vitriol oil again; Be cooled to 0-10 DEG C of crystallization 2.0h again, centrifuge dripping, with washing on a small quantity.
Preferably, the oven dry in step 1 for adopt vacuum-drying or forced air drying in 60-80 DEG C of temperature range.
Preferably, the temperature of reaction of step 2 is 100 DEG C-165 DEG C, reaction times 2.0-8.0h, compound (1H-1,2,3-triazole-4,5-dicarboxylic acid): mol ratio=1:0.01-0.1, the m (1H-1 of catalyzer, 2,3-triazole-4,5-dicarboxylic acid): V (DMF)=1:5-30.
Preferably, adopt following methods to purify: cold filtration after completion of the reaction in step 2, first by short rectifying pillar, reclaim under reduced pressure DMF, then reclaim under reduced pressure crude product, finally obtain high purity 1 H-1,2,3-triazole by crude product by rectifying column.
Due to the employing of above technical scheme, the present invention compared with prior art tool has the following advantages:
1, benzotriazole, i.e. BTA, cheap and easy to get, particularly oxidizing reaction is complete in the basic conditions, filters complete except Manganse Dioxide (Manganse Dioxide content >=99% can be used for other reaction oxidation), filtrate is faded with 20 ~ 30% hydrogen peroxide, product Compound 1H-1,2,3-triazole-4,5-dicarboxylic acid does not need refining and decolouring, product colour is very white, and purity is very high, and more particularly oxidizing reaction yield is very high in the basic conditions;
2, in the first step reaction, the filtrate water that needs concentrating under reduced pressure a large amount of before, energy consumption is very high, and we utilize oxidizing reaction in the basic conditions, allow product 1H-1,2,3-triazole-4,5-dicarboxylic acid does not need to concentrate, and just can make complete crystallization, greatly reduce production cost;
3, mother liquor alkali adjusts PH=6-7, can reuse again, thus environmental protection, and basic non-wastewater discharge, decreases environmental pollution;
4, make catalyzer with pyridine or quinoline in second step reaction to replace traditional making catalyzer with the oxide compound of copper powder or copper, good reaction selectivity, yield are high, product purity is high and stability is better.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further details.Should be understood that these embodiments are for illustration of ultimate principle of the present invention, principal character and advantage, and the present invention does not limit by the scope of following examples.The implementation condition adopted in embodiment can do further adjustment according to specific requirement, and not marked implementation condition is generally the condition in normal experiment.
Embodiment 1
The preparation of compound (b) 1H-1,2,3-triazole-4,5-dicarboxylic acid:
Water 3600L is added in the stainless steel cauldron of 6000L, add the benzotriazole of 400 kilograms again, 380 kilograms, sheet alkali, be warmed up to 40 DEG C, slowly add 2800 kilograms of potassium permanganate again, about 2.0h, control temperature is at 40-80 DEG C, finish insulation 2h, TLC follows the tracks of reaction, react rear mistake and filter Manganse Dioxide, its solution 30-50% hydrogen peroxide fades, the residual Manganse Dioxide of removing, filtrate is cooled to 35 DEG C again, PH2.5 is adjusted with concentrated hydrochloric acid, be cooled to 5 DEG C of crystallization 2.0h again, centrifuge dripping, with a small amount of water washing filter cake, at 70 DEG C of vacuum-drying 5.0h, 506.6 kilograms must be expected, HPLC99.5%, molar yield is 96.0%.
The preparation of compound (c) 1H-1,2,3-triazole:
In the glass lined reactor of 5000L, add N, dinethylformamide 3800L, compound (b) 300 kilograms stirring, drip 1L pyridine again, be warmed up to 120 DEG C, reaction 4.0h, HPLC follows the tracks of cool to room temperature after completion of the reaction, filter, filtrate is by short rectifying pillar, the long 3m of short rectifying pillar, reclaim under reduced pressure N, dinethylformamide, raffinate reduces pressure and collects the crude product of compound (c), compound (c) crude product is collected water white fraction by rectifying column decompression, obtain compound (c) finished product 131.4 kilograms, product purity 99.6% (GC), moisture content 0.2%, molar yield 95.2%.
Embodiment 2:
The preparation of compound (b) 1H-1,2,3-triazole-4,5-dicarboxylic acid:
The mother liquor of embodiment 1 is added in 6000L stainless steel cauldron, regulate PH at 6-7 with 30% alkali lye, add 400 kilograms of benzotriazoles again, 300 kilograms of potassium hydroxide, be warmed up to 45 DEG C, slowly add 2800 kilograms of potassium permanganate again, about 3.0-4.0h, temperature control is at 40 ~ 80 DEG C, finish insulation 4h, it is complete that TLC follows the tracks of reaction, cross and filter Manganse Dioxide, its solution 30-50% hydrogen peroxide fades, the residual Manganse Dioxide of removing, filtrate is cooled to 30 DEG C again, PH1.5 is regulated with 40% sulfuric acid, be cooled to 0 DEG C of crystallization 2.0h again, filter, a small amount of water washing filter cake, at 80 DEG C of forced air drying 4.0h, 509.3. kilogram must be expected, HPLC99.2%, molar yield is 96.2%.
The preparation of compound (c) 1H-1,2,3-triazole:
In the glass lined reactor of 5000L, add N, dinethylformamide 3800L, compound (b) 300 kilograms stirring, drip 2L quinoline again, be warmed up to 120 DEG C, reaction 4.0h, HPLC follows the tracks of cool to room temperature after completion of the reaction, filter, filtrate is by short rectifying pillar, the long 3m of short rectifying pillar, reclaim under reduced pressure N, dinethylformamide, raffinate reduces pressure and collects the crude product of compound (c), compound (c) crude product is collected water white fraction by rectifying column decompression, obtain compound (c) finished product 131.4 kilograms, product purity 99.6% (GC), moisture content 0.2%, molar yield 95.2%.
Preparation method of the present invention simplifies technological operation step, shortens reaction time, greatly reduction production cost, decreases environmental pollution, improves the stability of quality product and product.
Above to invention has been detailed description; the explanation of embodiment just understands method of the present invention and core concept thereof for helping; its object is to allow the personage being familiar with this art can understand content of the present invention and implement according to this, can not limit the scope of the invention with this.All equivalences done according to spirit of the present invention change or modify, and all should be encompassed within protection scope of the present invention.
Claims (6)
1. a preparation method for high purity 1 H-1,2,3-triazole, is characterized in that: comprise the following steps:
Step 1, be raw material with benzotriazole, potassium permanganate is oxygenant, and water is solvent, in the basic conditions, obtains high purity 1 H-1,2,3-triazole-4,5-dicarboxylic acid by oxidative cleavage, purification oven dry;
The 1H-1 obtained in step 2, step 1,2,3-triazole-4,5-dicarboxylic acid carries out decarboxylic reaction under the effect of DMF solvent catalyst neutralisation, obtains target product high purity 1 H-1 by purifying, 2,3-triazole, wherein, described catalyzer is quinoline, pyridine or the mixture of the two.
2. high purity 1 H-1 according to claim 1,2, the preparation method of 3-triazole, it is characterized in that: the temperature of reaction in described step 1 is 20 DEG C-100 DEG C, reaction times is 1.0-5.0h, benzotriazole: sodium hydroxide or potassium hydroxide: the mol ratio of potassium permanganate is 1:0.5-3:5-10, m (benzotriazole): V (H
2o)=1:15-40.
3. the preparation method of high purity 1 H-1,2,3-triazole according to claim 1, it is characterized in that: adopt following methods to purify in described step 1: after completion of the reaction, cross and filter Manganse Dioxide, its solution 30-50% hydrogen peroxide fades, the residual Manganse Dioxide of removing, cooling; PH is regulated to be 1.5-3.0 with concentrated hydrochloric acid or the vitriol oil again; Be cooled to 0-10 DEG C of crystallization 2.0h again, centrifuge dripping, with washing on a small quantity.
4. the preparation method of high purity 1 H-1,2,3-triazole according to claim 1, is characterized in that: the oven dry in described step 1 for adopt vacuum-drying or forced air drying in 60-80 DEG C of temperature range.
5. the preparation method of high purity 1 H-1,2,3-triazole according to claim 1, it is characterized in that: the temperature of reaction of described step 2 is 100 DEG C-165 DEG C, reaction times 2.0-8.0h, compound (1H-1,2,3-triazole-4,5-dicarboxylic acid): mol ratio=1:0.01-0.1, the m (1H-1 of catalyzer, 2,3-triazole-4,5-dicarboxylic acid): V (DMF)=1:5-30.
6. high purity 1 H-1 according to claim 1,2, the preparation method of 3-triazole, is characterized in that: adopt following methods to purify in described step 2: cold filtration after completion of the reaction, first by short rectifying pillar, reclaim under reduced pressure N, dinethylformamide, then reclaim under reduced pressure crude product, finally obtain high purity 1 H-1 by crude product by rectifying column, 2,3-triazole.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946803A (en) * | 2017-05-04 | 2017-07-14 | 石家庄万业化工科技有限公司 | A kind of synthetic method of the triazoles of 1H 1,2,3 |
| CN109096213A (en) * | 2018-09-28 | 2018-12-28 | 上海晋景化学有限公司 | A kind of preparation method of 1H-1,2,3- triazole |
Citations (1)
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| WO2014167528A1 (en) * | 2013-04-11 | 2014-10-16 | Novartis Ag | Spiropyrazolopyridine derivatives and uses thereof for the treatment of viral infections |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014167528A1 (en) * | 2013-04-11 | 2014-10-16 | Novartis Ag | Spiropyrazolopyridine derivatives and uses thereof for the treatment of viral infections |
Non-Patent Citations (1)
| Title |
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| 徐卫良等: "微波法合成1H-1,2,3-三氮唑", 《精细化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946803A (en) * | 2017-05-04 | 2017-07-14 | 石家庄万业化工科技有限公司 | A kind of synthetic method of the triazoles of 1H 1,2,3 |
| CN109096213A (en) * | 2018-09-28 | 2018-12-28 | 上海晋景化学有限公司 | A kind of preparation method of 1H-1,2,3- triazole |
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