34 results about "Cyanopyrazine" patented technology

The invention provides a method of producing 2-cyanopyrazine by biocatalysis to produce pyrazinamide and a new strain, Serratia marcescens ZJB-09104, which is used in the preparation process. In the method, the pyrazinamide is obtained through the catalytic hydration reaction under the conditions that the pH is 6.0-8.0 and the temperature is 20-40 DEG C in a reaction system which uses 2-cyanopyrazine as a substrate and nitrile hydratase which is obtained by the culturing of the Serratia marcescens as a catalyst. The method applies the Serratia marcescens ZJB-09104 to the experiments producing pyrazinamide by biocatalysis. Results show that the strain has a wide application prospect in the field of producing pyrazinamide by biocatalysis as the strain can effectively produce the pyrazinamide by biocatalysis and the transformation ratio of the 2-cyanopyrazine.attains 83.8 percent within 12h.

The invention relates to a favipiravir intermediate and a synthetic method for favipiravir, and specifically discloses a method for synthesizing 3,6-difluoro-2-cyanopyrazine with a formula 4 as shownin the specification. The method comprises the following steps: a) allowing a compound with a formula 1 as shown in the specification to react with a chlorinated reagent or a brominated reagent so asto obtain a compound with a formula 2 as shown in the specification; b) allowing the compound with the formula 2 as shown in the specification to react with phosphorus oxychloride in the presence of organic base so as to obtain a compound with a formula 3 as shown in the specification; and c) allowing the compound with the formula 3 as shown in the specification to react with a fluorinated reagentso as to obtain the compound with the formula 4 as shown in the specification. The invention also relates to a method for synthesizing the favipiravir by using the above-mentioned method.

The catalyst is VMoOP system carried catalyst prepared via soaking process. The catalyst features the carrier alumina, silica gel and silicon carbide and active component V / P / Mo in the molecular ratio of 1 to 1-6 to 0.01-1. When the catalyst is used in synthesizing 2-cyanopyrazine and the user amount of catalyst is 40 g, the introduced amount of 2-methylpyrazine 0.05-2 ml / min, that of ammonia is 100-200 ml / min and that of air is 1000-2000 ml / min; the material feeding molar proportion among 2-methylpyrazine, ammonia and air is 1 to 8-20 to 10-90. The present invention has the advantages of high catalyst activity, long service life, no need of activation period, simple synthesis process, high material conversion rate and high product quality.

The invention provides modification and application of nitrile hydratase amino acid motif, and belongs to the technical field of bioengineering. According to the invention, nitrile hydratase derived from pseudonocardia thermophila is modified, the NO.46 site on a beta subunit and the NO.6 site and NO.126 site on an alpha subunit of a wild type are mutated respectively, and the specific enzyme activity of a constructed mutant is remarkably improved and can be improved by 1-5 times compared with that of the wild type. Moreover, the substrate spectrum is also broadened, the mutant has a very goodcatalytic effect on isobutyronitrile, n-valeronitrile, acrylonitrile, nicotinonitrile, 2-cyanopyrazine, benzonitrile, cinnamonitrile, naphthonitrile and the like, and the catalytic performance on corresponding substrates is also remarkably improved. Therefore, the obtained nitrile hydratase mutant can be suitable for more production scenes, and the production efficiency is improved.

The invention discloses a thermal activity delayed fluorescent organic compound using 2-cyanopyrazine as a receptor, preparation and applications thereof, wherein the structure of the thermal activity delayed fluorescent organic compound is represented by a general formula (1). According to the present invention, the compound as the light emitting layer material is used in organic electroluminescent devices based on TADF light-emitting mechanism, and the device produced from the compound has good photoelectric performance, and can meet the requirements of panel manufacturing enterprises.

The invention relates to a preparation method of 2-aminopyrazine derivatives, and belongs to the technical field of organic synthesis.With 2-cyanopyrazine as the raw material, by adding a sodium hypochlorite solution and alkali, 2-aminopyrazine is prepared through reaction, then 2-amino-3,5-dibromopyrazine is obtained through bromination reaction, and 2-amino-5-bromine-3-morpholinopyrazine, 2-amino-5-bromine-3-piperazinylpyrazine and 2-amino-5-bromine-3-pyrrolidylpyrazine are obtained after substitution reaction is conducted on 2-amino-3,5-dibromopyrazine as the raw material together with morpholine, piperazine and pyrrole respectively.With 2-cyanopyrazine as the raw material, different 2-aminopyrazine derivatives are prepared, the raw materials are low in price and easy to obtain, operation is easy, and target product yield is high.

The invention provides a preparation method of favipiravir, which comprises the following step: by using one or two of 6-fluoro-3-hydroxyl-2-cyanopyrazine and 6-fluoro-3-hydroxyl-2-cyanopyrazine organic amine salt as raw materials, carrying out high-yield preparation in an anhydrous organic solvent under alkaline conditions to obtain favipiravir. Compared with the existing concentrated sulfuric acid hydrolysis process and hydrogen peroxide hydrolysis process, a large amount of acidic wastewater generated in the concentrated sulfuric acid hydrolysis process is avoided, explosion hazards possibly caused by use of hydrogen peroxide are also avoided, meanwhile, hydrolysis and oxygenolysis phenomena of products in the concentrated sulfuric acid hydrolysis process and the hydrogen peroxide hydrolysis process are avoided, and the preparation method is environmentally friendly, simple and safe to operate and relatively high in yield.

The invention relates to the field of chemical organic synthesis, in particular to a method for synthesizing 2-acetyl pyrazine. The method comprises the following steps: (1) preparation of a Grignardreagent: adding metallic magnesium, an anhydrous polar solvent, elemental iodine and methyl chloride into a pressure vessel, and stirring to prepare the Grignard reagent; (2) adding reaction: adding 2-cyanopyrazine, tetrahydrofuran, a catalyst and the Grignard reagent into a reactor, and refluxing and condensing to obtain an intermediate product; (3) hydrolyzing: adding water into the intermediateproduct, adjusting the pH value by using dilute acid, stirring and refluxing, and then adjusting to be neutral; and finally, extracting with toluene; and (4) aftertreatment: desolventizing a tolueneextracting solution, dissolving desolventized solid with ethanol, adding activated carbon, filtering, and cooling to obtain a white solid P1; and recrystallizing with the ethanol to obtain the 2-acetylpyrazine. According to the method, a monovalent copper salt is adopted as a catalyst, the yield of 2-acetylpyrazine is increased to be 69%, meanwhile, the reaction speed is increased, and the synthesis reaction temperature is also reduced.

The invention discloses a modified activated carbon carrier for immobilizing a phorate degradation bacterium. Activated carbon is washed and modified with a mixed liquid prepared from 3-chloro-6-phenyl pyridazine, alcohol, 4-(2-aminoethyl)-tetrahydropyrane, 2-bromo-5-cyanopyrazine and 5-chloro-3-methylbenzothiophene to prepare a substance B; the substance B is modified with a mixed liquid prepared from ZrCl4, CeCl3, Cu(NO3)2 and Sr(NO3)2 to prepare a substance C; and the substance C is modified with a mixed liquid prepared from 3-hydroxyflavone, alcohol, chlorphenyl silane and 2-imidazolidone to obtain a substance which is the modified activated carbon carrier for immobilizing the phorate degradation bacterium.

The invention discloses a nitrile hydratase mutant and application thereof, and belongs to the field of genetic engineering and enzyme engineering. The half-life period of the nitrile hydratase mutantStr.t NHase-betaL48D at the temperature of 65 DEG C is about 43 minutes, and the thermal stability is remarkably improved compared with the thermal stability of other NHase enzymes. By adopting the technical scheme, the substrate tolerance of reaction taking nitrile compounds such as nicotinonitrile, acrylonitrile, benzonitrile, 2-cyanopyrazine nitrile, isobutyronitrile, n-valeronitrile and cinnamonitrile as substrates is obviously improved.

The invention discloses an ammonia-oxidizing bacteria immobilized glass plate. A production method of the ammonia-oxidizing bacteria immobilized glass plate comprises the following steps: cleaning a glass plate, and modifying the cleaned glass plate with a mixed solution formed by potassium bitartrate, potassium tert-butoxide, agarose and potassium hydrogen phthalate in order to obtain a substanceA; modifying the substance A with a mixed solution formed by 2-chloro-3-cyanopyrazine, 2-bromo-5-nitropyridine and 4-bromotetrahydropyran in order to obtain a substance B; modifying the substance B with a mixed solution formed by tetrahydrothiopyran-4-one and 1-aminoanthraquinone in order to obtain a substance C; and immobilizing the ammonia-oxidizing bacteria on the substance C to obtain a substance which is the ammonia-oxidizing bacteria immobilized glass plate. The ammonia-oxidizing bacteria immobilized glass plate has the advantages of high strain activity, and efficient degradation of ammonia nitrogen in wastewater.

The invention relates to a refluxing improved rectifying tower for 2-cyanopyrazine. The refluxing improved rectifying tower comprises a tower body provided with an extraction hole, a plurality of pieces of tower plates and a refluxing system, wherein the refluxing system comprises an extraction pipe connected with the extraction hole, a heat exchanger connected with the extraction pipe and a refluxing main pipe connected with the heat exchanger; each tower plate comprises a hollow shell body, a plurality of sieve holes which are formed in the shell body and penetrate through the shell body, and a plurality of spraying holes which are formed in a non-sieve-hole region of the bottom surface of the shell body; a refluxing auxiliary pipe, which is communicated with the inner part of the shellbody and extends out of the tower body, is arranged on a side face of each tower plate; each refluxing auxiliary pipe is communicated with the refluxing main pipe and an auxiliary pipe valve is arranged on a pipe body; each sieve hole is internally provided with a sealing circular ring which is coaxial with the sieve hole and is fixedly connected with the shell body; a main pipe valve is arrangedat the tail end of the refluxing main pipe. According to the refluxing improved rectifying tower for the 2-cyanopyrazine, the characteristic that positions of the different tower plates correspond todifferent separation efficiency can be sufficiently utilized, so that the purification effect of single-time refluxing is remarkably improved and the refluxing time needed for reaching the effect is effectively shortened, and furthermore, the whole efficiency of refluxing operation is greatly improved.

The invention discloses a method for analyzing and determining relevant substances in pyrazinamide by employing a liquid chromatography. The method comprises the following steps of (1) preparing a contrast solution; (2) preparing a system applicability solution; (3) preparing a test solution; (4) preparing a self-control solution; and (5) carrying out chromatographic analysis and determination, namely injecting taken diluent and prepared contrast solution, system applicability solution, test solution and appropriate self-control solution into a liquid chromatograph, recording a liquid chromatogram, and analyzing and determining the content of pyrazinoic acid, the content of 2-cyanopyrazine, the content of an unknown single impurity and the content of total impurities according to the liquid chromatogram. The method is higher in specificity and pertinence, and the 2-cyanopyrazine and the pyrazinoic acid existing in the pyrazinamide can be quantitatively tested accurately, thereby more effectively controlling the product quality and providing a certain basis for the study of the relevant substances.

A preparation process of pyrazinamide comprises the following steps: (1) synthesis of 2-methylpyrazine: putting a catalyst I into a reactor I, and performing reducing for 4 hours; adding 2-methylpyrazine into the reactor I, then adding ethylenediamine and 1, 2-propylene glycol, carrying out gas-solid phase contact catalytic reaction in the reactor I, cooling a mixture generated by the reaction through a condenser, feeding the mixture into a receiver, taking tail gas, and performing absorbing, emptying and separating to obtain 2-methylpyrazine, (2) chemical base catalysis; putting the catalystII into a reactor II, introducing an aqueous solution of 2-methylpyrazine in a mass ratio of (1:10)-(1:20) into the reactor II through a metering pump, introducing ammonia gas and air, controlling thetemperature of the reaction system to be 3-6 DEG C, maintaining the pH value to be 9-10, performing reacting for 1-2 hours, and performing heating to 20-30 DEG C to obtain 2-cyanopyrazine; and (3) synthesis of pyrazinamide. The preparation process of pyrazinamide has the advantages of the simple process, the high conversion rate, no generation of by-product pyrazinic acid, the good economic benefits and the wide application prospect.

The invention provides a refining method of favipiravir. The method specifically comprises the following steps: 6-fluoro-3-hydroxy-2-cyanopyrazine reacts with hydrogen peroxide under an alkaline condition to obtain 6-fluoro-3-hydroxy-2-pyrazinamide; the 6-fluoro-3-hydroxy-2-pyrazinamide is prepared into an organic alkali salt in an anhydrous organic solvent, and then the pH value in water is adjusted to prepare high-purity 6-fluoro-3-hydroxy-2-pyrazinamide; and 6-fluoro-3-hydroxy-2-pyrazinamide and organic alkali are salified in an organic solvent, the salt has excellent crystallinity, high-purity favipiravir can be prepared with high yield through simple operation, the yield can reach 90% or above, and the HPLC purity reaches 99.9% or above.

The invention discloses a preparation method of acetylpyrazine. Acetylpyrazine is prepared from 8-10 parts of magnesium chips, 180-200 parts of anhydrous tetrahydrofuran, 300-350 parts of chloromethane, 450-500 parts of anhydrous toluene, 20-25 parts of cyanopyrazine, 40-50 parts of alcohol, 2 parts of activated carbon and a plurality parts of chloromethane. Acetylpyrazine has the advantages that the synthesis method is simple, the raw materials are easy to obtain, energy consumption and material losses are low, the safety and the finished product content are high, and acetylpyrazine is suitable for large-scale production.

The invention discloses a microchannel reactor for 2-cyanopyrazine preparation. The microchannel reactor comprises a microchannel plate and a seal plate, the microchannel plate and the seal plate areoverlapped, and one surface, close to the seal plate, of the microchannel plate is provided with an etching groove. The etching groove fits the seal plate to form a microchannel, an inlet end of the etching groove is provided with a gasification groove, and the gasification groove are provided with a liquid inlet and a gas inlet to communicate with the outside. The microchannel reactor has advantages that the microchannel is formed by the seal plate and the microchannel plate with the etching groove, the inlet of the microchannel is provided with the gasification groove for mixing reaction materials, the middle of a reaction channel is filled with a catalyst, and reaction material gas and the catalyst are subjected to gas-solid reaction to synthesize a product; since the microchannel is small in flow through area but large in surface area, long-time mixing reaction of materials can be realized only through a small device while quick heat conduction can be realized, high safety is realized, catalysis is benefited, and accordingly reaction efficiency can be improved.

The invention provides an application of nitrile hydratase in catalyzing a hydration reaction of a cyanopyrazine compound to generate an amide pyrazine compound, and belongs to the technical field ofbiochemical engineering. The nitrile hydratase is derived from Agrobacterium tumefaciens, Stappia aggregata IAM 12614 or Sinorhizobium meliloti. The cyanopyrazine compound is used as a substrate, in-vitro nitrile hydratase or a cell expressing the nitrile hydratase is used as a catalyst, the hydration reaction is carried out, and the amide pyrazine compound can be obtained. The applied raw material is high in conversion rate and free of side reaction, and the product is easy to separate and purify and is relatively high in purity; and compared with a traditional chemical catalysis process, theprocess is environmentally friendly and easy and convenient to operate, and the yield exceeds 99%.

The present invention relates to a favipiravir intermediate 3, 6-dichloro-2-cyanopyrazine synthesis process, which is characterized in that the synthesis route is as follows as described in the specification. The cheap 2-chloropyrazine is used as the raw material, the product 3, 6-dichloro-2-cyanopyrazine can be obtained only through two-step reaction, the total yield is 55% or above, all the used reagents can be common reagents which can be purchased commercially, the production cost is reduced, and a synthesis process for large-scale industrial production of the 3, 6-dichloro-2-cyanopyrazine is achieved. According to the method disclosed by the invention, the synthesis process conditions are optimized, and particularly, the catalyst and the cocatalyst in the step (2) are selected, so that the yield and the purity of the product are further improved.

A process for preparing 2-cyanopyrazine by ammonia oxidizing method features use of a special catalyst VaTibPcDdEeOx, where V and Ti are primary catalyst and P, Fe, Ni, Co, Bi, Mn, Cr, Mo, Cu, Zn, Sn, B, K, Li and Mg are multicomponent catalyst. Its advantages are high activity, selectivity, output rate and purity and simple process.

The invention relates to a preparation method of favipiravir, which comprises the following steps of: reacting 3,6-difluoro-2-cyanopyrazine under an alkaline condition at the temperature of between 40 and 70 DEG C to obtain 6-fluoro-3-hydroxy-2-cyanopyrazine, and then conducting a next-step reaction basically without treatment, and conducting reaction with inorganic alkali and hydrogen peroxide at 45-65 DEG C to obtain favipiravir. The preparation method avoids use of precursor control reagents or dangerous preparations, reduces dangerous factors in production, and has the advantages of simplicity and convenience in operation, high yield, high purity of the prepared product, safety, environmental protection, low cost, suitability for industrial production and the like.

The invention discloses a catalyst for synthesizing 2-cyanopyrazine and preparation and application methods thereof and belongs to the field of preparation of catalysts. The catalyst is a CrVPO systemloaded type catalyst and a carrier is gamma-Al2O3, wherein the amount-of-substance ratio of active components is that Cr to V to P is equal to 0.8 to 1 to (0.8 to 2.6). The catalyst takes a gamma-Al2O3 raw material with low cost as the catalysis carrier, and the catalysis carrier is treated by utilizing a simple and feasible ultrasonic and rotary evaporation technology, so that a CrVPO-gamma Al2O3 catalyst which has a good catalytic effect on the synthesis of the 2-cyanopyrazine and has no production on subsequent production is obtained; the preparation method of the catalyst is simple, feasible, economical and practical and is convenient for industrial production; a test proves that the efficiency of synthesizing the 2-cyanopyrazine in micro-channel reaction of the catalyst prepared by the preparation method can reach 58.92 percent.

The invention discloses a new method for synthesizing 2-amino-3, 5-dibromopyrazine, a product and an application. The method comprises the following steps: step 1, taking 2-cyanopyrazine and sodium hypochlorite as raw materials, carrying out reaction under inorganic alkali aqueous solution conditions, and then carrying out reduced pressure distillation to obtain 2-aminopyrazine; step 2, taking N,N-dimethylacetamide as a solvent, adding 1, 3-dibromo-5, 5-dimethylhydantoin, dropwise adding an N, N-dimethylacetamide solution of 2-aminopyrazine, and carrying out reaction for 15 to 20 h so as to obtain a 2-amino-3, 5-dibromopyrazine crude product; carrying out subsequent treatment on the 2-amino-3, 5-dibromopyrazine crude product with heptane and ethanol to obtain the 2-amino-3, 5-dibromopyrazine disclosed by the invention. The invention provides the new method for synthesizing 2-amino-3, 5-dibromopyrazine, the yield of the product is improved, the purification problem of the product is solved, and meanwhile, the synthesis cost of the product is reduced.

The invention relates to a refluxing improved rectifying tower for 2-cyanopyrazine. The refluxing improved rectifying tower comprises a tower body provided with an extraction hole, a plurality of pieces of tower plates and a refluxing system, wherein the refluxing system comprises an extraction pipe connected with the extraction hole, a heat exchanger connected with the extraction pipe and a refluxing main pipe connected with the heat exchanger; each tower plate comprises a hollow shell body, a plurality of sieve holes which are formed in the shell body and penetrate through the shell body, and a plurality of spraying holes which are formed in a non-sieve-hole region of the bottom surface of the shell body; a refluxing auxiliary pipe, which is communicated with the inner part of the shellbody and extends out of the tower body, is arranged on a side face of each tower plate; each refluxing auxiliary pipe is communicated with the refluxing main pipe and an auxiliary pipe valve is arranged on a pipe body; each sieve hole is internally provided with a sealing circular ring which is coaxial with the sieve hole and is fixedly connected with the shell body; a main pipe valve is arrangedat the tail end of the refluxing main pipe. According to the refluxing improved rectifying tower for the 2-cyanopyrazine, the characteristic that positions of the different tower plates correspond todifferent separation efficiency can be sufficiently utilized, so that the purification effect of single-time refluxing is remarkably improved and the refluxing time needed for reaching the effect is effectively shortened, and furthermore, the whole efficiency of refluxing operation is greatly improved.

The invention discloses a thermally active delayed fluorescence organic compound with 2-cyanopyrazine as an acceptor and its preparation and application. The structure of the thermally active delayed fluorescent organic compound is shown in the general formula (1). The compound is based on the light emitting mechanism of TADF and is used as a light emitting layer material in an organic electroluminescent device. The device produced by the invention has good photoelectric performance and can meet the requirements of panel manufacturers.

The catalyst is VMoOP system carried catalyst prepared via soaking process. The catalyst features the carrier alumina, silica gel and silicon carbide and active component V / P / Mo in the molecular ratio of 1 to 1-6 to 0.01-1. When the catalyst is used in synthesizing 2-cyanopyrazine and the user amount of catalyst is 40 g, the introduced amount of 2-methylpyrazine 0.05-2 ml / min, that of ammonia is 100-200 ml / min and that of air is 1000-2000 ml / min; the material feeding molar proportion among 2-methylpyrazine, ammonia and air is 1 to 8-20 to 10-90. The present invention has the advantages of high catalyst activity, long service life, no need of activation period, simple synthesis process, high material conversion rate and high product quality.