25 results about "Diazomethane" patented technology

The utility model provides a gas-liquid separator for separating diazomethane from a diazomethane mixed solution, which comprises an upper cylinder body, a middle cylinder body and a lower cylinder body which are sequentially connected from top to bottom, a gas moisture detection port, a diazomethane content detection port, a gas temperature detection port and an upper cylinder explosion venting port are formed around the gas outlet, and a pressure detection port is formed in the side surface; a refrigerant inlet and a refrigerant outlet are formed in the upper portion of the middle barrel, a refrigerant coil is arranged in the middle barrel, an inlet of the refrigerant coil is connected with the refrigerant inlet, and an outlet of the refrigerant coil is connected with the refrigerant outlet. A liquid level upper gas inlet and a liquid level lower gas inlet are formed in the upper portion of the lower barrel, the liquid level upper gas inlet is connected with the liquid level upper gas distributor through a pipeline, the liquid level lower gas inlet is connected with the liquid level lower gas distributor through a pipeline, and a feeding port is formed in the side wall of the middle of the lower barrel. The gas-liquid separator disclosed by the utility model is high in gas-liquid separation efficiency, safe and explosion-proof, and can be used for continuous automatic production.

The invention relates to the field of analysis and detection, and discloses a method for detecting multiple chelating agents in daily chemical products, which comprises the following steps: methylating a to-be-detected sample by using a diazomethane methylation reagent to obtain a to-be-detected solution; carrying out liquid chromatography-mass spectrometry detection on the to-be-detected liquid by adopting a specific elution program to obtain a chromatogram; and performing qualitative and / or quantitative analysis on the chelating agent in the to-be-detected sample according to the chromatogram. By adopting the detection method disclosed by the invention, efficient detection of various chelating agents (including DTPA, DTPMP, EDTMPA, HDTEPA, EGTA, HEDP, EDTA, NTA, GLDA, PBTC, MGDA, IDS, HEEDTA, HPAA, DTPA-OH, CA and ATMP) can be realized, meanwhile, interference of other components in daily chemical products on detection can be avoided, and relatively high detection sensitivity and accuracy of the chelating agents can be realized.

This invention provides a gas-liquid separator for separating diazonium methane from a diazonium methane mixture. The separator comprises an upper cylinder, a middle cylinder, and a lower cylinder connected sequentially from top to bottom. The upper cylinder has a gas outlet at its top center, surrounded by gas moisture detection ports, diazonium methane content detection ports, gas temperature detection ports, and an explosion vent. A pressure detection port is located on the side. The middle cylinder has a refrigerant inlet and a refrigerant outlet at its upper part, and a refrigerant coil is installed inside the middle cylinder. The refrigerant coil inlet is connected to the refrigerant outlet, and the refrigerant coil outlet is connected to the refrigerant outlet. The lower cylinder has a liquid level-above gas inlet and a liquid level-below gas inlet at its upper part. The liquid level-above gas inlet is connected to a gas distributor above the liquid level via a pipe, and the liquid level-below gas inlet is connected to a gas distributor below the liquid level via a pipe. A feed inlet is located on the middle side wall of the lower cylinder. This gas-liquid separator offers high gas-liquid separation efficiency, is explosion-proof, and can be used for continuous automated production.

The application relates to the field of analysis and detection, and discloses a detection method for multiple chelating agents in daily chemical products, which comprises the following steps: methylating a to-be-detected sample by using a diazomethane methylating reagent to obtain a to-be-detected solution; detecting the to-be-detected solution by using a specific elution program to obtain a chromatogram; and qualitatively and / or quantitatively analyzing the chelating agents in the to-be-detected sample according to the chromatogram. By using the detection method, multiple chelating agents (including DTPA, DTPMP, EDTMPA, HDTEPA, EGTA, HEDP, EDTA, NTA, GLDA, PBTC, MGDA, IDS, HEDTA, HPAA, DTPA-OH, CA and ATMP) can be efficiently detected, meanwhile, the detection can be prevented from being disturbed by other components in the daily chemical products, and high detection sensitivity and accuracy can be realized for the chelating agents.

The application relates to the field of biological medicine, and particularly relates to a method for identifying structures of drug carboxylic acid metabolites based on a derivatization reagent and high-resolution mass spectrometry. The method comprises the following steps: performing pretreatment on a biological sample (such as blood plasma, urine, feces and the like), precipitating proteins through an extraction solvent, and then centrifuging to collect supernatant; blowing nitrogen to dry the supernatant and redissolving; reacting with a derivatization reagent trimethylsilyl diazomethane at 30-60 DEG C for 1-60 minutes to make carboxylic acid metabolites generate methylation products; and identifying the carboxylic acid metabolites through molecular weight changes (+14 Da) by using high-resolution mass spectrometry. The method has high accuracy, is simple to operate, and is low in cost, is suitable for a variety of biological matrices and conventional small molecules, polypeptide and other carboxylic acid-containing metabolite structure identification, has important application value for early drug research and development and metabolism research, and can be widely applied to the fields of early drug research and development, drug metabolism research and the like.

The invention discloses a continuous synthesis method of 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone, which comprises the following steps: (1) introducing a trimethylsilylated diazomethane solution and a strong alkali solution into a micro-channel reactor 1 for reaction, introducing the obtained intermediate reaction solution and a 2-chloromethyl benzoate solution into a micro-channel reactor 2 for continuous reaction, the preparation method comprises the following steps: adding 2-chlorophenyl to generate 1-(2-chlorophenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone; and (2) removing a TMS group from the 1-(2-chlorphenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone, and then carrying out post-treatment to obtain the 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone. The continuous synthesis method uses a fluid process, has the advantages of small amplification effect, high production efficiency and environmental protection, improves the selectivity of 2-tetrazole, and avoids partial sensitization of intermediates.

The invention discloses a continuous preparation method for carrying out cyclopropanation reaction by using a microreactor. According to the method, a three-stage series bottom splashing microreactor system is adopted, and efficient and safe cyclopropanation reaction is realized through gradient catalysis design and accurate temperature control. A reaction system comprises olefin, a diazomethane precursor, alkali liquor and a solvent, wherein a catalyst adopts a gradient distribution design of SBA-15 and CeO2 loaded monatomic palladium. And the three-stage series bottom splashing microreactors are respectively controlled at different temperatures. The process is simple, high conversion rate and high safety are realized, and the cost is reduced.

The invention discloses carboxymethylated dehydrated sugar and a preparation method and application thereof.The preparation method of the carboxymethylated dehydrated sugar comprises the following steps that raw materials 1, 4: 3, 6-dianhydro-D-glucopyranose, a diazomethane diethyl ether solution, a catalyst, alkali and dichloromethane are sequentially added into a high-pressure reaction kettle, the mixture is heated to 80-90 DEG C, the mixture is heated to 80-90 DEG C, and the mixture is cooled to room temperature to obtain the carboxymethylated dehydrated sugar with the content of 1, 4: 3, 6-dianhydro-D-glucopyranose and the content of 1, 4: 3, 6-dianhydro-D-glucopyranose. Replacing air in the reaction kettle with carbon dioxide; after uniformly stirring, heating and reacting for 10 hours at the temperature of 100-150 DEG C, then cooling the reaction kettle to room temperature, adding excessive diluted hydrochloric acid into the reaction system, and continuously stirring and reacting for 1 hour; and after the reaction is finished, extracting and separating to obtain an organic phase, drying with anhydrous sodium sulfate, evaporating under reduced pressure to remove the solvent, and performing column chromatography separation on solid residues to obtain carboxymethylated dehydrated sugar. According to the technical scheme, 1, 4: 3, 6-dianhydro-D-glucopyranose is used as an initial raw material to synthesize the carboxymethylated dehydrated sugar. When the fragrant raw material is added into the cigarette, the sweet feeling of the oral cavity can be improved, the smoke permeability and the fine degree are improved, and the aftertaste comfort is improved.

The invention discloses a gas chromatography method for detecting the content of trioctyl phosphate products and impurities, and belongs to the technical field of organic chemical detection. The core of the method is that (trimethylsilyl) diazomethane (TMSCH2N2) is adopted as a derivatization reagent, and dioctyl phosphate (P204) in a sample is subjected to rapid and safe derivatization at room temperature; an optimized dichloromethane-hexane mixed solvent system is adopted for dilution, so that the solubility is remarkably improved, and the toxicity is reduced; a first-order heating rapid screening method (17min) is suitable for industrial quality control, a multi-order heating accurate quantification method (29min) is suitable for small-scale test process research and development, and trioctyl phosphate (TOP), P204, isooctyl alcohol, isooctyl ether and chloro-isooctane can be accurately quantified at the same time. The method solves the problems of high toxicity, low efficiency, narrow detection range, single mode and the like in the prior art, and has the remarkable advantages of safety, high efficiency, accuracy, environmental protection and wide adaptability.

The invention provides a synthetic method of cyclopropyl alcohol, which comprises the following steps: firstly, by taking vinyl acetate as a substrate, carrying out diazomethane catalytic cyclopropanation reaction to obtain cyclopropyl acetate; and secondly, carrying out hydrolysis reaction on the cyclopropyl acetate to obtain cyclopropyl alcohol. The synthetic method for preparing cyclopropyl alcohol has the advantages of simple process, convenient post-treatment, no obvious by-product or waste water, yield of more than 95%, and substantial cost reduction, and is more suitable for industrial large-scale production.

The invention relates to a mono-boratriazole compound as well as a synthesis method and application thereof, positive ion boron-nitrogen alkyne and (trimethylsilyl) diazomethane are subjected to cycloaddition reaction, trimethylsilyl is migrated from carbon atoms to nitrogen atoms to form a positive ion mono-boratriazole framework, trimethylsilyl and counter ions are further removed by using alkali, and the mono-boratriazole compound is obtained. The mono-boratriazole compound is obtained. The mono-boratriazole compound disclosed by the invention has a wide application prospect in the fields of metal coordination reaction, reverse cyclization ring-opening reaction and preparation of unsaturated boron compounds.

The invention discloses a method for identifying unknown organic phosphodiesters in an environment based on a diazomethane derivatization technology. The method comprises the following steps: S1, establishing an OPDEs suspicious database; s2, carrying out methyl derivatization on the OPDEs to be detected; s3, carrying out suspicious screening on the OPDEs; s4, determining characteristic fragments of the derivatization OPDEs; and S5, carrying out non-targeted screening on the OPDEs. According to the suspicious-non-targeted comprehensive screening method for the unknown OPDEs in the environmental sample, the limitation that an OPDEs analysis method in the environment can only recognize known types of OPDEs can be solved, and comprehensive recognition of the unknown OPDEs in the environmental sample can be achieved.

The application discloses a viscosity reducer for exploitation of deep low-permeability heavy oil reservoirs and a preparation method and application thereof. The preparation method comprises the following steps: (1) under the conditions of existence of a solvent and a catalyst and heating, 4-halogenophthalic anhydride and glycol compounds are subjected to nucleophilic addition reaction under the atmosphere of nitrogen or inert gas to obtain a mixed solution containing intermediate A; (2) diazomethane is introduced into the mixed solution containing intermediate A, and diazomethane and intermediate A are subjected to nucleophilic transfer reaction to obtain a mixed solution containing intermediate B; (3) polyethylene glycol or dimethylaluminum is added into the mixed solution containing intermediate B, and after stirring, sodium sulfite is added, and under the condition of heating, intermediate B and sodium sulfite are subjected to sulfonation reaction of nucleophilic displacement, and after reaction, the viscosity reducer is obtained through post-treatment. The application further discloses application of the viscosity reducer as a displacement flow-increasing viscosity reducer in exploitation of deep low-permeability heavy oil reservoirs.

The present invention relates to a preparation method of montelukast sodium intermediate, belonging to the field of pharmaceutical chemistry. In the present invention, crotonic acid is used as the starting material, and ethyl 3-butenoate is generated through esterification rearrangement reaction. The double bond of ethyl 3-butenoate undergoes epoxidation reaction with m-chloroperoxybenzoic acid to obtain an epoxy compound. The epoxy compound reacts with thiourea to obtain a cyclic sulfur compound. The cyclic sulfur compound undergoes ring opening with a cuprous salt reagent and cyclopropylmagnesium bromide, and finally, it is further hydrolyzed under alkaline conditions to obtain 1-mercaptomethylcyclopropylacetic acid. This method has cheap and easily available starting materials, reducing the material cost; in the reaction process, the use of highly toxic cyanide reagents or extremely explosive diazomethane is avoided, improving the production safety, and the technological process is simple and easy to implement; the number of reaction steps is reduced, the production cost can be greatly reduced, which is beneficial to industrial production.

The invention relates to the technical field of organic synthesis, in particular to a method for preparing diazonium ketone by a one-pot method, which comprises the following steps: reacting carboxylic acid active intermediates such as acyl chloride and mixed anhydride with diazomethane precursor N-methyl-N-nitrosourea in an organic solvent under the action of alkali to obtain a corresponding diazonium ketone compound with medium to good yield. According to the method disclosed by the invention, the diazomethane is generated in situ by using the cheap and easily available diazomethane precursor N-methyl-N-nitrosourea to participate in the reaction, so that the direct use of a highly toxic reagent diazomethane is avoided, and the danger in the process of preparing the diazoketone by the Ardt-Eistern reaction is greatly reduced; and the carboxylic acid substrate can be directly converted into corresponding active intermediates for further serial preparation to obtain corresponding diazonium ketone, and the method has the characteristics of wide application range of the substrate, mild and simple reaction conditions, green steps, low pollution, high economic benefit and the like.

The invention provides a preparation method of 2 '-OMe modified pseudouridine and a phosphoramidite monomer of N1-methyl pseudouridine, and belongs to the field of medicine synthesis, and the preparation method comprises the following steps: methylating 2'-OH of pseudouridine / N1-methyl pseudouridine by using trimethylsilyl diazomethane; reacting the methylation product with 4, 4 '-dimethoxytriphenylmethyl chloride to obtain an intermediate with a DMTr protecting group at the 5'position; and reacting the obtained intermediate with bis (diisopropylamino) (2-cyano ethyoxyl) phosphine to obtain a target product. According to the invention, pseudouridine / N1-methyl pseudouridine is taken as a raw material, the 2-OMe modified pseudouridine / N1-methyl pseudouridine phosphoramidite monomer can be prepared by only three steps, the synthesis route is greatly shortened, the total yield is more than 40%, the purity of the target product is more than 99%, and the method is very suitable for large-scale industrial synthesis.

The invention discloses a method for preparing carboxylic acid methyl ester by a one-pot method, which comprises the following step: reacting carboxylic acid with N-methyl-N-nitrosourea in an anhydrous organic solvent under the action of alkali to prepare the target product carboxylic acid methyl ester. According to the preparation method, N-methyl-N-nitrosourea which is high in reaction activity, low in price and easy to obtain is used as a diazomethane precursor to generate diazomethane in situ, the diazomethane reacts with carboxylic acid through a one-pot method to obtain corresponding carboxylic acid methyl ester, and direct use of a highly toxic and explosive diazomethane reagent is avoided. The preparation method disclosed by the invention has the characteristics of simple and mild reaction conditions, convenience in post-treatment, green steps, low pollution, high economic benefit and the like.

The application belongs to the technical field of organic synthesis, and particularly relates to an asymmetric total synthesis method of catharanthine. Commercially available oxazolidinone 1 is used as a starting material, and is condensed with bromoacrylic acid to obtain compound 2. Then, asymmetric DA reaction of compound 2 and compound 3 occurs under the catalysis of scandium triflate to obtain compound 4. Compound 4 is hydrolyzed into a carboxylic acid under the condition of lithium hydroxide and hydrogen peroxide, and is treated by trimethylsilane diazomethane to obtain compound 6. Compound 6 is selectively reacted with sodium methoxide, and after the protective group is removed by treatment of iodo-trimethylsilane, compound 6 is condensed with an acid to obtain compound 9. Compound 9 is subjected to radical annulation under the catalysis of a photocatalyst Ir(ppy)3 to obtain compound 10. Finally, selective reduction of the amide obtains natural product (+) - catharanthine. The asymmetric total synthesis route of the application has a total step of 8 or 9, and a total yield of 17.8% - 23.5%, which is shorter than that of the prior art, and the total yield is significantly improved.

The invention discloses a preparation method of 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone, which comprises the following steps: (1) under the action of an ether solvent and a strong base, enabling methyl 2-chlorobenzoate to react with trimethylsilanized diazomethane to generate 1-(2-chlorphenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone; and (2) removing a TMS group from the 1-(2-chlorphenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone, and then carrying out post-treatment to obtain the 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone. According to the synthesis method, by-product isomers are reduced, the selectivity of 2-tetrazole is improved, and the total yield is further improved.

The invention provides a synthetic method of a cyclopropyl amine compound, which comprises the following steps: by taking a nitroalkene compound as a substrate, carrying out diazomethane catalytic cyclopropanation reaction to obtain a nitrogen-containing cyclopropyl compound; and secondly, carrying out catalytic hydrogenation reaction on the nitrogen-containing cyclopropyl compound to obtain the cyclopropyl amine compound. Or according to the method, an aminoalkene compound is taken as a substrate, diazomethane catalytic cyclopropanation reaction is carried out, and the cyclopropylamine compound is obtained. According to the preparation method disclosed by the invention, the compound with the aminocyclopropane structure is obtained by directly carrying out cyclopropanation reaction on the aminoalkene compound and the nitroalkene compound or then carrying out simple hydrogen hydrogenation reaction, the yield can reach 95% or above, the atom economy is high, and the production cost can be greatly reduced. The synthesis method for preparing the cyclopropylamine compound is simple in process, mild in reaction condition, convenient in post-treatment, free of obvious by-products and wastewater, remarkably reduced in cost and more suitable for industrial large-scale production.

The invention belongs to the technical field of diazomethane derivative synthesis, and relates to a diazomethane derivative continuous preparation method and system.The preparation method comprises the steps that a strong alkali solution in an alkali liquor container and a benzenesulfonyl hydrazone suspension liquid in a suspension liquid container are preheated respectively; conveying the preheated strong alkali solution and benzenesulfonyl hydrazone suspension into a reaction device according to a certain proportion, mixing, and heating for reaction; respectively conveying an extracting agent and a diazomethane derivative crude product mixed solution obtained by the reaction to an online extraction device for mixing, extraction and online separation, and conveying a diazomethane derivative solution obtained by separation to a solid-liquid separation device for solid-liquid separation. By separately preheating reactants, optimizing parameters such as reaction temperature and the like, and communicating a reactant container, a preheating device, a reaction device and the like, the reaction can be continuously carried out, and accumulation of a large number of reactants, intermediate products and final products is reduced, so that side reactions are reduced, the reaction scale is expanded, and the yield and the yield of the products are improved.

The invention belongs to the field of synthetic chemistry and biological medicine, and particularly relates to a difluoromethyl modified chiral diamine derivative as well as a synthetic method and application thereof. The difluoromethyl modified chiral diamine derivative is obtained by taking p-toluenesulfonyl difluoromethyl diazomethane, aromatic amine, organic aldehyde and electron-rich aromatic hydrocarbon as raw materials and taking chiral phosphoric acid as a chiral inducer and an organic reagent as a solvent through a one-step reaction under the catalysis of transition metal. According to the difluoromethyl modified chiral diamine derivative and the synthesis method, the raw materials are cheap and easy to obtain, safe and non-toxic, the reaction condition is mild, the operation is simple and safe, and the synthesized difluoromethyl modified chiral diamine derivative has good anti-tumor activity and has huge development potential in the field of drug research and development.

The invention discloses a method for determining the content of phosphodiesters in phosphate, which comprises the following steps: dissolving a dioctyl phosphate standard substance with a solvent to prepare a series of standard solutions with different concentrations, converting dioctyl phosphate into di (2-ethylhexyl) methyl phosphate through trimethylsilyl diazomethane, and determining the content of the di (2-ethylhexyl) methyl phosphate by adopting a gas chromatography external standard method. Drawing a standard curve; the method comprises the following steps: dissolving a trioctyl phosphate sample with a solvent, adding excessive derivatization reagent trimethylsilyl diazomethane to carry out derivatization reaction, carrying out gas chromatography sample injection detection analysis, and substituting the detected chromatographic peak area into a standard curve to calculate the content of dioctyl phosphate in the sample. The relative standard deviation RSD of the determination result of the method is less than 5%, the precision is high, the analysis and test method is simple, the operation is safe, and the consumed time is short.

The present invention relates to a gas chromatography-mass spectrometry analysis method for haloacetic acids in drinking water, belonging to the technical field of analytical chemistry. Compared with the prior art, the present invention uses GC-MS to establish a quantitative method for haloacetic acids in drinking water, overcomes the drawbacks of the standard method provided by the US Environmental Protection Agency (USEPA, 552.3), the supporting method of the "Drinking Water Quality Standard" in China (GB / T 5749-2006), and the diazomethane derivatization method, realizes one-step liquid-liquid extraction, can be directly analyzed quantitatively after simple derivatization, and obtains high sensitivity, high spiked recovery rate, low method detection limit, and low quantification limit. The method of the present invention can efficiently, rapidly and accurately determine haloacetic acids in drinking water.

The invention belongs to the field of synthetic chemistry and biological medicine, and mainly discloses a difluoromethyl modified polysubstituted chiral tetrahydroquinoline derivative as well as a synthetic method and application thereof. The difluoromethyl modified polysubstituted chiral tetrahydroquinoline derivative is obtained by taking p-toluenesulfonyl difluoromethyl diazomethane, aromatic amine and organic aldehyde as raw materials and taking chiral phosphoric acid as a chiral inducer and an organic reagent as a solvent through a one-step reaction under the catalysis of metal iron. The raw materials are cheap, easy to obtain, safe and non-toxic, the reaction condition of the synthesis method is mild, the operation is simple and safe, and the synthesized difluoromethyl modified polysubstituted chiral tetrahydroquinoline derivative has excellent anti-tumor activity and has bright application prospects in the field of drug research and development.