CN1242996C - Method for synthesizing 1H-1, 2,3 triazole - Google Patents
Method for synthesizing 1H-1, 2,3 triazole Download PDFInfo
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- CN1242996C CN1242996C CN 03116646 CN03116646A CN1242996C CN 1242996 C CN1242996 C CN 1242996C CN 03116646 CN03116646 CN 03116646 CN 03116646 A CN03116646 A CN 03116646A CN 1242996 C CN1242996 C CN 1242996C
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Abstract
The present invention relates to a method for synthesizing 1H-1, 2, 3 triazole and belongs to the technical field of synthesis of fine chemical industry. The present invention is characterized in that ion exchange resin is adopted for preprocessing glyoxal water solution in a deacidifying mode, which suppresses the polymerization phenomenon in synthesis; after a mixture of ethanediol monooximido hydrazone, bioxime and bihydrazone, reaction liquid is not dewatered by butyl acetate in an azeotropic mode, the reaction liquid is extracted by ethyl acetate, ethyl acetate solution is distilled in a pressure reduction mode so that solvent is removed, steps, such as a rearrangement step, etc., are simultaneously finished, and single ethanediol monooximido hydrazone is obtained; steps, such as a dehydration step of the butyl acetate in an azeotropic mode, a heating rearrangement step of toluene, etc., are cancelled, decomposition danger, deterioration danger, etc. which are caused by the phenomenon that a product is heated for a long time, are reduced, the equipment and the energy source are saved, the reaction time and the processing time are shortened, and the present invention effectively prevents a human body from being harmed by toluene; reaction conditions and a separation method of final products in the synthetic route can be completely adopted in industrial production. The measured content of 1H-1, 2, 3 triazole which is final products prepared by the present invention is equal to 98% through high pressure liquid phase analysis.
Description
Technical field
The present invention relates to a kind of 1H-1,2, the synthetic method of 3-triazole belongs to technical field of fine chemical synthesis.
Background technology
1H-1,2, the 3-triazole is a kind of main intermediate of novel penicillin synergistic agent-Tazobactam Sodium, in addition, the triazole of replacement also can be as multiple other drug of preparation or sterilant.1998, [Harada, K. such as K.Harada; Oda, M, etal., A Convenient Synthesis of 1,2; 3-Triazole With Glyoxal, Synlett., 1998,431] reported by oxalic dialdehyde through oxalic dialdehyde monoxime hydrazone and acetylize-1; 2, key intermediates such as 3-triazole synthesize 1,2, the method for 3-triazole.The maximum characteristics of this method are to have minimum molecular weight, to be raw material at industrial oxammonium hydrochloride as basic raw material, hydrazine hydrate etc., and production cost is lower, meets the Atom economy principle.
Its route is as follows:
Through experiment, we find that there is following shortcoming in this route in implementation process: (1) is being prepared oxalic dialdehyde monoxime hydrazone regular meeting's polymerization reaction take place often by oxalic dialdehyde, and generation is difficult in a large number identify the yellow polymer of structure and can't obtains oxalic dialdehyde monoxime hydrazone.The preparation process of the key intermediate oxalic dialdehyde monoxime hydrazone that (2) provides in the document is comparatively loaded down with trivial details, needs to remove a large amount of n-butyl acetates (boiling point is up to 125 ℃), crystallization by reaction, azeotropic water removing, steaming and filters, adds toluene and heat and reset in nearly 20 hours and final product filters and six steps such as collects and operate and just can finish.Raw material, intermediate and product all need to stand 150 ℃ of pyritous and heat for a long time during this, can cause very big influence to the performance of product; Adopt a large amount of toluene in the reaction, influence operator's health; Simultaneously, equipment and energy consumption have been increased.
In a word, this route operability is not strong, is difficult to use in suitability for industrialized production, needs badly and is improved.
Summary of the invention
The objective of the invention is in order to overcome 2 deficiencies in the aforesaid method, provide a kind of suitable suitability for industrialized production, economical and convenient synthetic 1,2, the method for 3-triazole.
For this purpose, the present invention adopts following technical scheme, and the characteristics of its method are the steps include:
1, spent ion exchange resin carries out pre-treatment to glyoxal water solution;
2, the mixture that in via the glyoxal water solution after the ion exchange resin treatment, adds oxammonium hydrochloride, hydrazine hydrate prepared in reaction oxalic dialdehyde monoxime hydrazone, the two oximes of oxalic dialdehyde and two hydrazones, mixture adds ethyl acetate extraction, most of ethyl acetate is removed in the solution decompression distillation, separate out solid, analysis revealed mixture major part in the heating concentration process has been reset and has been oxalic dialdehyde monoxime hydrazone;
3, in the ethyl acetate solution of oxalic dialdehyde monoxime hydrazone, add diacetyl oxide and obtain N-acetylize oxalic dialdehyde monoxime hydrazone;
4, ethyl acetate solution adding sodium acetate and the diacetyl oxide to N-acetylize oxalic dialdehyde monoxime hydrazone prepares 2-ethanoyl triazole;
5,2-ethanoyl triazole directly adds ethanol and carries out alcoholysis, obtains 1H-1, and 2, the 3-triazole.
Adopt the present invention, realized following breakthrough: 1. by adopting ion exchange resin that glyoxal water solution is carried out the depickling pre-treatment, method of purification is easy and effective, and glyoxal water solution after processing stability improves, good restraining the polymerism in synthetic.2. in the method, after forming monoxime hydrazone, two oxime and two hydrazone mixture with oxammonium hydrochloride and hydrazine hydrate, add ethyl acetate extraction by oxalic dialdehyde, in removing the process of solvent under reduced pressure, heating finishes rearrangement process at extraction liquid simultaneously, obtain single oxalic dialdehyde monoxime hydrazone, exempted the process that toluene is reset, avoid the harm of toxic reagent human body, simultaneously, enrich in, source low with boiling point, the positive butyl ester of low-cost ethyl acetate substituted acetic acid, more convenient operation, and cost reduces.By saving the step that wherein steaming desolventizes, increase substantially the product yield on the one hand, reduce product be heated for a long time decomposition that brings, danger such as rotten, save the equipment and the energy on the other hand.3. reaction conditions in the synthetic route and final product separation means may adopt in industrial production fully.
Embodiment
(1) pre-treatment of glyoxal water solution: the glyoxal water solution of getting the anionite-exchange resin of glyoxal weight ratio between 1: 0.5 to 1: 1.5 and weight percent concentration and be 30-40% mixes, stirred 0.5 to 3.5 hour down at 10-30 ℃, decompression or normal pressure filter down, filtrate is the glyoxal water solution after the purification, can directly carry out next step reaction.
(2) preparation of oxalic dialdehyde monoxime hydrazone: add appropriate hydrochloric acid azanol, water in the reaction flask, cryosel is bathed and is dripped 85% hydrazine hydrate down, drip then and handled glyoxal solution, cryosel is bathed and was stirred two hours after adding, reaction solution ethyl acetate extraction, filtration, the ethyl acetate layer anhydrous magnesium sulfate drying, distillation removes and desolvates, obtain oxalic dialdehyde monoxime hydrazone, productive rate is 64.16%.
(3) in the ethyl acetate solution of oxalic dialdehyde monoxime hydrazone, drip diacetyl oxide, regulate rate of addition, make temperature of reaction be no more than 40 ℃.At room temperature reacted three hours after dripping end,, obtain N-acetylize oxalic dialdehyde monoxime hydrazone then with the reaction solution decompress filter.
(4) in there-necked flask, add an amount of N-acetylize oxalic dialdehyde monoxime hydrazone, sodium acetate, ethyl acetate, drip diacetyl oxide.Be warming up to 86-95 ℃ after dropwising rapidly, reacted about 1-4 hour.After reaction finished, reaction solution decompress filter, reaction solution be not treated directly to enter next step reaction.
(5) adding weight percent in the above-mentioned garnet liquid that contains the acetylize triazole is the ethanol of 10%-40%; continuation steaming ethyl acetate and ethanol below 100 ℃, obtains containing 1H-1 then 45-75 ℃ of reaction 1-4 hour; 2, the raffinate of 3-triazole.The raffinate underpressure distillation, collecting boiling point is the cut of 80 degree/12mmHg, and final product is the liquid of transparent faint yellow, and productive rate is 46.0%, and it is 98% that high-pressure liquid phase is measured product purity.
Embodiment:
The pre-treatment of 1.40% glyoxal water solution:
Get 32 gram HCO
3 -Type anionite-exchange resin mixes with isopyknic 40% glyoxal water solution, at room temperature stirs 1 hour, filters, and filtrate can directly be carried out next step reaction for the glyoxal water solution after purifying.
2. be feedstock production oxalic dialdehyde monoxime hydrazone with oxammonium hydrochloride, hydrazine hydrate, oxalic dialdehyde:
Add 92g oxammonium hydrochloride, 68ml water in the there-necked flask, cryosel is bathed and to be dripped 162 milliliters of 85% hydrazine hydrates (t＜15 ℃) down, drip then and handled 200 milliliter of 40% oxalic dialdehyde (t＜10 ℃), cryosel is bathed and was stirred two hours after adding, reaction solution ethyl acetate extraction, filtration, ethyl acetate layer anhydrous magnesium sulfate drying, distillation removes and desolvates, finish the rearrangement of two oximes, two hydrazones simultaneously, obtain 58.8 gram oxalic dialdehyde monoxime hydrazones, productive rate is 64.16%.
3.N-the preparation of acetylize oxalic dialdehyde monoxime hydrazone
Oxalic dialdehyde monoxime hydrazone 43.5 grams and 1000 milliliters of ethyl acetate are joined in 2000 milliliters of there-necked flasks that thermometer, agitator are housed.Stirring makes its dissolving, drips 76 ml acetic anhydride, regulates rate of addition, makes temperature of reaction be no more than 40 ℃.At room temperature reacted three hours after dripping end, then with the reaction solution decompress filter, obtain 47 gram oxalic dialdehyde monoxime hydrazone N-acetylates, productive rate is 72.07%
4.2-the preparation of ethanoyl triazole
In the 500ml there-necked flask, add the monoacylated monoxime hydrazone of 37.8 grams, 5 gram sodium acetates, 100ml ethyl acetate, drip the 60ml diacetyl oxide.Be warming up to rapidly after dropwising about 90 ℃ and reacted 2 hours.After reaction finished, the reaction solution decompress filter was removed insoluble substance.Reaction solution is not treated directly to enter next step reaction.
5.1H-1,2, the preparation of 3-triazole
In the above-mentioned garnet liquid that contains the acetylize triazole, add the 10ml dehydrated alcohol,, about 100 ℃, steam ethyl acetate and ethanol subsequently 55 ℃ of reactions 2 hours.The raffinate underpressure distillation that obtains, collecting boiling point is the cut of 80 degree/12mmHg, finally obtains 9.3 gram 1H-1,2, the 3-triazole is the liquid of transparent faint yellow, and productive rate is 46.0%, and purity is 98%.
Claims (2)
1,1H-1,2, the synthetic method of 3-triazole is characterized in that, method steps is:
(1) spent ion exchange resin carries out pre-treatment to glyoxal water solution;
(2) prepare oxalic dialdehyde monoxime hydrazone by glyoxal water solution adding oxammonium hydrochloride, the hydrazine hydrate handled through spent ion exchange resin, after reaction finishes, reaction mixture removes n-butyl acetate without n-butyl acetate azeotropic water removing, steaming and toluene adds steps such as thermal rearrangement, obtains oxalic dialdehyde monoxime hydrazone solid but adopt ethyl acetate extraction, underpressure distillation to remove ethyl acetate and at distillatory rearrangement takes place simultaneously;
(3) add diacetyl oxide by oxalic dialdehyde monoxime hydrazone and obtain N-acetylize monoxime hydrazone;
(4) ethyl acetate solution by N-acetylize monoxime hydrazone adds sodium acetate, diacetyl oxide prepares 2-acetylize triazole;
(5) directly to add temperature be 45-75 ℃ dehydrated alcohol reaction 1-4 hour to above-mentioned 2-acetylize triazole, and reaction finishes and collects final 1H-1,2,3-triazole through underpressure distillation.
2,1H-1 according to claim 1,2, the synthetic method of 3-triazole, it is characterized in that, describedly glyoxal water solution is carried out pretreated process be: getting with the anionite-exchange resin of glyoxal weight ratio between 1: 0.5 to 1: 1.5 and weight percent concentration is that the glyoxal water solution of 30-40% mixes, stirred 0.5 to 2.5 hour down at 10-30 ℃, decompression or normal pressure filter the glyoxal water solution after obtaining purifying down.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 03116646 CN1242996C (en) | 2003-04-25 | 2003-04-25 | Method for synthesizing 1H-1, 2,3 triazole |
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| CN 03116646 CN1242996C (en) | 2003-04-25 | 2003-04-25 | Method for synthesizing 1H-1, 2,3 triazole |
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| CN1539829A CN1539829A (en) | 2004-10-27 |
| CN1242996C true CN1242996C (en) | 2006-02-22 |
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| CN102335568B (en) * | 2011-07-22 | 2013-12-04 | 浙江大学 | Triazole ring-containing quaternary ammonium salt type cationic surfactant and synthesis method thereof |
| CN102830118B (en) * | 2011-12-26 | 2014-07-16 | 重庆紫光化工股份有限公司 | Method for determining mass fraction of triazole in industrial sodium triazole |
| CN113121461A (en) * | 2021-04-15 | 2021-07-16 | 山东泓瑞医药科技股份公司 | Method for preparing high-purity 1H-1,2, 3-triazole |
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