Post-treatment method for preparing 1h-tetrazolium acetic acid from triethyl orthoformate

Abstract

The invention discloses a post-processing method for preparing 1H-tetrazole-1-acetic acid through the triethyl orthoformate method by taking glycine, sodium azide and triethyl orthoformate as the raw materials. The method comprises the following steps: firstly, distilling a reaction liquid under the ordinary pressure gradient to sequentially recycle the by-product, namely, ethyl alcohol and acetic acid, a solvent; then adding excessive concentrated hydrochloric acid at the low temperature, and performing acidification and cyclization to remove sodium chloride; finally, performing activated carbon fading on the filter liquor, performing concentration to recycle hydrochloric acid, and cooling for crystallization to obtain 1H-tetrazole-1-acetic acid. The post-processing method has the advantages that the post-processing technology of ethyl acetate extraction, recrystallization of an organic solvent and the like of the traditional process is eliminated, and the purification strategy that a solvent is firstly recycled and then the acidification and salt removal are performed is created, so that the efficient separation and recovery of the by-product ethyl alcohol and the solvent acetic acid are realized, the use of the organic extraction reagent ethyl acetate is avoided, the crystallization and precipitation of the water phase of the 1H-tetrazole-1-acetic acid are ensured, the product purity reaches more than 99%, and the production cost is effectively lowered.

Description

technical field [0001] The invention relates to a post-treatment method of 1H-tetrazolium acetic acid reaction solution obtained by a triethyl orthoformate method, is an optimization and improvement of a traditional post-treatment process, and belongs to the technical field of organic synthesis. Background technique [0002] 1H-tetrazole acetic acid, English name: 1H-tetrazole-1-acetic acid, CAS number: [21732-17-2], molecular formula: C 3 h 4 N 4 o 2 , Molecular weight: 128.09, white crystal, soluble in water, ethyl acetate, isopropanol, etc., melting point: 128.5-131.5 ℃. 1H-tetrazolium acetic acid is an important raw material for the preparation of antibiotics Pioneer V, cefazolin and cefazolin sodium. [0003] At present, the traditional "one-pot" process of 1H-tetrazolium acetic acid only stays in the stage of laboratory experiments. According to reports, the traditional "one-pot method", also known as the triethyl orthoformate method, is as follows: using glycine...

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Problems solved by technology

[0008] However, there are three fatal defects in the post-treatment process of the above method, which makes it impossible to realize the industrial scale-up of the "one-pot method":

[0009] 1. The recovery rate of organic solvents is low, the loss is large, and the pollution is serious

The reaction solution was acidified and ring-closed with hydrochloric acid, concentrated under reduced pressure, and the removal mixture included solvent acetic acid, by-product ethanol and water. Because the solvent acetic acid or by-product ethanol tended to azeotrope with water, effective separation could not be achieved, resulting in solvent acetic acid and by-product ethanol. The by-product ethanol is difficult to recycle and reuse, and a large amount of organic mixed waste solvents are produced, which not only leads to a sharp increase in production costs, but also increases the pressure on environmental protection

[0010] 2. A large amount of ethyl acetate is used

Due to the high water content in the extract, the sodium chloride content is high, which affects the smooth precipitation of 1H-tetrazolium acetic acid crystals. The separation of 1H-tetrazolium acetic acid, sodium chloride and other impurities has always been a problem. craft

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