78 results about "4-fluoroaniline" patented technology

The invention discloses a preparation method of 5-bromo-1,3-dichloro-2-fluorobenzene, which comprises the following steps: (1) simultaneously feeding ammonium salt and a sodium nitrite aqueous solution into a tubular reactor for tubular diazotization reaction so as to obtain a diazonium salt intermediate, wherein the ammonium salt is prepared through dissolving 3,5-dichloro-4-fluoroaniline in sulfuric acid; (2) dissolving cuprous bromide in hydrobromic acid, heating to 100-130 DEG C, dropwise adding the diazonium salt intermediate prepared in the step (1) for reaction, and after the complete reaction, performing after-treatment to obtain the 5-bromo-1,3-dichloro-2-fluorobenzene. According to the preparation method, the tubular diazotization reaction technology is adopted to prepare diazonium salt, so that the side reaction including diazonium salt coupling and decomposition and the like can be reduced, the diazotization reaction is enabled to be more stable, and the final yield is improved; in addition, the tubular diazotization reaction technology has a series of advantages of continuity in production, safety, short reaction time, energy saving and the like, and is relatively suitable for industrial production in the future.

The invention discloses a preparation method of gefitinib. The preparation method takes 4-methoxyl-5-(3-morpholine propoxyl)-2-nitrobenzonitrile as a raw material, then subjecting the raw material to treatments of reduction and salt forming reactions so as to obtain an intermediate 2-amino-4-methoxyl-5-(3-morpholine propoxyl) benzonitrile hydrochloride, then directly subjecting the intermediate to react with N,N-dimethyl formamide dimethyl acetal so as to obtain N'-(2-cyano-5-methoxyl-4-(3-morpholinyl propoxyl)benzyl)-N,N-dimethyl formamidine, and finally subjecting the formamidine intermediate to carry out rearrangement reactions with 3-chloro-4-fluoroaniline so as to obtain the gefitinib. The preparation method has the advantages of mild reaction conditions, convenient intermediate purification method, and suitability for industrial production.

The invention relates to a technical method for electrochemically synthesizing para-fluoroaniline. An electrochemical reaction of the invention occurs in a double-chamber diaphragm electrolytic cell, and an anode chamber and a cathode chamber of the electrolytic cell are separated by a cation exchange membrane. An anode is made of such anode materials as graphite, DSA or lead and the like; and a cathode is made of such materials as platinum, silver, copper, lead, nickel, a copper nickel alloy, a copper amalgam alloy, carbon steel, stainless steel, the graphite, glassy carbon and the like. Catholyte consists of 1-20% of nitrobenzene, 1-30% of water and ionic liquid; and anolyte is 5-50% of sulfuric acid or other acidic solution, alkali solutions and salt solutions. An electrolysis product of the cathode is the para-fluoroaniline. The technical method for synthesizing the para-fluoroaniline in the ionic liquid has the advantages of simple process, high yield, little pollution and low cost.

The invention relates to an enzymic uric acid detection agent with high interference preventing capacity. The agent is characterized in that an agent R1 includes a buffering solution, 4-ampyrone, sodium nitrite, an ion balancing agent, ascorbic acid oxidase, a heavy metal ion chelator, bovine serum albumin, dodecyl trimethyl betaine, triton-305 and a preservative; an agent R2 includes a bufferingsolution, F-DAOS (N-ethyl-N-(2-hydroxyl-3-sulfopropyl)-3, 5-dimethoxy-4-fluoroaniline), uricase, bovine serum albumin, peroxidase, a preservative, and other components. The agent is high in interference preventing capacity and particularly capable of accurately detecting a sample of a newborn.

The invention discloses a catalyst for continuously preparing N-isopropyl-4-fluoroanilines. The catalyst comprises an activated carbon carrier, Pt, metal M1 and metal M2, wherein the Pt, metal M1 and metal M2 are loaded on the activated carbon carrier; the Pt accounts for 0.3-1.0wt% of the catalyst; the metal M1 accounts for 0.05-0.5wt% of the catalyst; the metal M2 accounts for 0.05-0.5wt% of the catalyst; the metal M1 is selected from Fe, Cu or Sn; the metal M2 is selected from K, Ce, or Ag. In addition, the invention also discloses a preparation method and application of the catalyst. The catalyst disclosed by the invention has the characteristics of being high in activity, high in selectivity and high in stability and can be used for preparing N-isopropyl-4-fluoroanilines in a high-efficiency catalyzing manner; the conversion ratio of a raw material, namely 4-fluoronitrobenzene, is 98% or more, the yield of a product, namely N-isopropyl-4-fluoroanilines, is 95% or more, and the yield of dehydrogenation by-products is not more than 0.1%.

The invention discloses a preparation method of 2, 6-dichlor fluorbenzene, including that diazonium salt is made by taking 3, 5-dichlor-4-fluoroanilines as raw material and the 2, 6-dichlor fluorbenzene is obtained through diazo hydrogen replacement in the presence of reducing agent. The method concretely includes the following steps: (1) 3, 5-dichlor-4-fluorbenzene is taken as raw material and reacts with inorganic acid, so as to obtain solution containing ammonium salt; (2) the solution containing ammonium salt reacts with nitrite aqueous solution, so as to obtain solution containing diazonium salt; (3) reducing agent is dropwise added into the solution containing diazonium salt until reaction product causes starch potassium iodide paper to turn blue; (4) the reaction solution obtained by the step (3) is subject to dispensing, washing and steam distillation, so as to obtain the product 2, 6-dichlor fluorbenzene. The preparation method has the characteristics of simple technology, high yield and low cost.

The invention discloses a preparation method of gefitinib. In the method, isovanillin is taken as a raw material and synthesized to obtain 7-methoxy-6-(3-morpholine-propoxy)quinazoline-4-one which is directly chloridized to obtain a product, the product is allowed to react with 3-chlorine-4-fluoroaniline to obtain gefitinib hydrochloride which neutralized off hydrochloric acid to obtain the gefitinib. The method has mild reaction condition and is applicable to industrialized production.

The invention discloses a flufenacet preparation method, which comprises synthesis of 2-methylsulfonyl-5-trifluoromethyl-1,3,4-thiadiazole, synthesis of 2-hydroxy-N-(4-fluoroaniline)-N-(1-methylethyl)acetamide and synthesis of 4'-fluoro-N-isopropyl-2-[5-(trifluridine)-1,3,4-thiadiazole-2-imide]acetamide. The optimal flufenacet preparation method is screened by a large number of experiments, the whole process is reasonable in design, particularly the steps of screening optimal reaction conditions and the optimal amount ratio, reaction temperature, reaction time and the like of reaction raw materials, the reaction yield (capable of reaching 90 percent or more) can be greatly increased, side reaction can be reduced, the reaction rate can be increased, the reaction raw materials can be recycled, the production cost is greatly reduced, and a broad application prospect is achieved.

The invention relates to a preparation method of 4-(3-chloro-4-fluorophenylamido)-7-methoxy-6-(3-morpholinylpropoxy)quinazoline (Gefitinib, I). The preparation method of Gefitinib is characterized in that etherification reaction is carried out on a Gefitinib intermediate 4-(3-chloro-4-fluorophenylamido)-6-hydroxy-7-methoxy-quinazoline and 4-(3-hydroxypropyl)-morpholine under proper conditions to obtain the target product Gefitinib. Gefitinib (I).

The invention relates to a preparation method of gefitinib. The preparation method comprises the following steps of: reacting under the action of an appropriate solvent and alkali by taking 3-hydroxy-4-methoxybenzonitrile and 4-(3-chloropropyl) morpholine as raw materials to prepare 4-(3-chlorine-4-fluorophenyl amido)-7-methoxyl-6-[3-(4-morpholinyl)propoxy] quinazoline; nitrifying the 4-(3-chlorine-4-fluorophenyl amido)-7-methoxyl-6-[3-(4-morpholinyl)propoxy] quinazoline to obtain 2-nitryl-4-methoxyl-5-[3-(4-morpholinyl)propoxy] methyl benzoate, and then reducing the 2-nitryl-4-methoxyl-5-[3-(4-morpholinyl)propoxy] methyl benzoate to obtain 2-amido-4-methoxyl-5-[3-(4-morpholinyl)propoxy] methyl benzoate; reacting 3-chlorine-4-fluoroaniline with N,N-dimethylformamide dimethylacetal to obtain (3-chlorine-4-fluorophenyl)-N,N-dimethyl dimethyleneimine; and carrying out loop closing on the 2-amido-4-methoxyl-5-[3-(4-morpholinyl)propoxy] methyl benzoate and the (3-chlorine-4-fluorophenyl)-N,N-dimethyl dimethyleneimine to obtain the gefitinib. The preparation method disclosed by the invention has the advantages of short process route, safety and easiness for operation, easiness and convenience for post processing, high reduction transformation ratio and yield, less environment pollution, and safety, reliability and stability in product quality.

The present invention relates to a method for synthesizing halogenated biphenyl, wherein one halogenated aniline of 4-bromium-2-fluoroaniline or 2, 4-difluoro aniline or 2-fluoroaniline or 4-fluoroaniline or the like, and the benzene are used as the principal raw material under a acidic condition, the trichloroacetic acid, the anhydrous magnesium sulphate and homemade composite catalyst containing copper or zinc or iron are added into a same reactor, and a diazotization reaction and a coupling reaction are completed synchronously. The invention also discloses a method for preparing a homemade composite catalyst containing a metal, including the steps: adding the dimethylformamide into a reactor, filling the nitrogen to protect, adding 0.1-1.0 equivalent weight ammonium formate, 0.5-1.0 equivalent weight N, N, N', N'-tetraphenyl ethylene diamine and 0.1-0.3 equivalent weight CuCl2 or ZnCl2 or FeCl3 and 0.01-0.03 equivalent weight PdCl2, then mixing and heating until 30-60 DEG C, agitating thoroughly and holding for 15-24 hours, cooling, filtrating and vacuum drying, the composite catalyst containing a metal will be obtained. By means of using a same reactor, the halogenated biphenyl may be prepared by the diazotization and the coupling reaction completed in one same step, the yield is more than 85% by the halogenated aniline. The product content achieves 99.5%, the production period is shortened greatly, the equipment production capacity is improved, the energy consumption and material consumption are all reduced, and the work intensity of workers is alleviated greatly, thus the method of the invention is very suitable for an industrialization great production.

The invention discloses a method for preparing 2-chloro-N-(4-fluorophenyl)-N-isopropylacetamide. The method comprises the steps as follows: N-isopropyl-4-fluoroaniline and chloroacetyl chloride are taken as raw materials, triethylamine is taken as an acid-binding agent, a reaction is performed under the mild condition, and 2-chloro-N-(4-fluorophenyl)-N-isopropylacetamide is obtained. Triethylamine is recovered with a follow-up simple technology, so that N-alkylate impurities are effectively avoided; and the technology mainly has numerous advantages as follows: the reaction is mild, the operation is simple and convenient, the equipment corrosiveness is small, the yield and the purity are high, and the method is suitable for industrial production.

The invention provides a synthetic method for cabozantinib. The method comprises the following steps: 1,1-cyclopropanedicarboxylic acid is used a starting raw material, acylation is performed, condensation is performed on an acylation product and 4-[6,7-dimethoxy-4-quinolinyl]oxy]aniline, condensation is further performed on an obtained product and 4-fluoroaniline under effects of a polypeptide condensing agent, and therefore the cabozantinib is obtained. According to the method, the reaction conditions are mild, a chlorinating reagent is used just in one step, and the method is suitable for industrialized production.

The invention discloses a preparation method of 2-bromo-4-fluoroacetanilide. The preparation method comprises steps as follows: 4-fluoroaniline is taken as a raw material and subjected to acetylation and bromination to obtain 2-bromo-4-fluoroacetanilide; the bromination reaction is that acetylate is bromized by hydrobromic acid to produce 2-bromo-4-fluoroacetanilide under the presence of an oxidizing agent; a mole ratio of 4-fluoroaniline, hydrobromic acid and the oxidizing agent is 1: (1.0-2.0): (1.0-3.5); the oxidizing agent is one of hydrogen peroxide, sodium hypochlorite, sodium hypobromite and peracetic acid; and the bromination reaction temperature is in a range from 30 DEG C to 60 DEG C. The bromination reaction adopts hydrobromic acid to replace bromine to serve as a bromination reagent, so that very little 2, 6-dibromo-4-fluoroacetanilide is generated in the bromination reaction, and the yield of 2-bromo-4-fluoroacetanilide is increased.

The invention discloses a method for preparing picolinafen, and belongs to the field of pesticide original medicine technology. The method comprises the following steps that (1) 2-chlorine-6-nitrapyrin serves as a raw material, and acid catalysis hydrolysis is carried out to synthesize 2-chlorine-6-pyridine carboxylic acid; (2) under conditions of alkali 1, catalyst and organic solvent 1, etherification reaction is carried out on 2-chlorine-6-pyridine carboxylic acid and m-trifluoromethylphenol to obtain 2-(3-trifluoromethylphenoxy pendant)-6-picolinic acid; (3) the 2-(3-trifluoromethylphenoxypendant)-6-picolinic acid and di(trichloromethyl) dimethyl carboxylate are reacted in alkali 2 and organic solvent 2 to synthesize intermediate 2-(3-trifluoromethylphenoxy pendant)-6-pyridinecarbonylchloride; (4) the intermediate 2-(3-trifluoromethylphenoxy pendant)-6-pyridinecarbonyl chloride and 4-fluoroaniline are reacted in alkali 3 and organic solvent 2 to prepare the picolinafen. The method for preparing the picolinafen has the advantages that the content of the prepared picolinafen product is 98.1%, the yield of the prepared picolinafen product is 83%, synthesis conditions are mild and safe, the operation process is controlled easily, aftertreatment is simple and convenient, the wastewater quantity is less, and the method is a green synthetic method for preparing the picolinafen.

The invention discloses a method for processing tobacco waste or organic fluorine wastewater. The method for processing tobacco waste comprises the following steps: adding tobacco waste into water and uniformly mixing to obtain a mixed liquor, adding activated sludge, an Arthrobacte TW seed liquid and a signal molecule preparation, and carrying out aeration treatment for 18-48h. The method for processing organic fluorine wastewater comprises the following steps: adding activated sludge, an Arthrobacte TW seed liquid and a signal molecule preparation into organic fluorine wastewater, and carrying out aeration treatment for 24-72h, wherein the collection number of the Arthrobacte TW is CGMCC No.7.47; and the signal molecule preparation is prepared by mixing an N-3oxo-caproyl-homoserinelactone solution and an N-caproyl-homoserinelactone solution. According to the method, adding frequency is low. The method is economical and environmentally friendly, can be adopted to preferentially, rapidly and efficiently degrade nicotine in tobacco or 4-fluoroaniline in organic fluorine wastewater so as to reduce the harm, and is of great significance for environmental protection.

The invention discloses a preparation method of flufenacet, and belongs to the technical field of pesticide preparation. The method comprises the steps: adding 2-hydroxy-N-(4-fluoroaniline)-N-(1-methylethyl)acetamide into an alkali-containing organic solvent A, dropping 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole into the reaction liquid, carrying out a reaction at room temperature, adding an organic solvent B, extracting, washing with water, drying, and concentrating to obtain a crude product flufenacet; and refining the crude product to obtain the pure product flufenacet. The preparation method has the advantages that the required raw materials are easy to obtain, less pollution to the environment exists, the synthesis is simple and convenient, the process conditions are not harsh, the yield can reach more than or equal to 85%, the purity can reach more than or equal to 98%, and the preparation method is suitable for industrialized production.

The invention discloses a preparation method of 3-chloro-4-fluoroaniline, and belongs to the technical field of organic chemical industry. The preparation method comprises the following steps of weighing 3-chloro-4-fluoronitrobenzene and 1% Pt/C catalyst and reacting for 1-10 hours at a temperature of 50-100 DEG C and in a hydrogen atmosphere of 0.1-5 MPa, wherein a mass ratio of 3-chloro-4-fluoronitrobenzene to 1% Pt/C catalyst is (200-400):1. The preparation method takes 3-chloro-4-fluoronitrobenzene as a raw material and prepares 3-chloro-4-fluoroaniline by a hydrogenation substitution reaction under catalysis of 1% Pt/C catalyst, has high reaction conversion rate, high yield and high selectivity, adopts no organic solvent, is simple and reasonable in process, and is suitable for large-scale production. The purity of 3-chloro-4-fluoroaniline prepared by the method can reach over 99.5%; and the yield reaches over 94%.

The invention provides a preparation method of 3-chloro-4-fluoroaniline hydrochloride. The 3-chloro-4-fluoroaniline hydrochloride is prepared from a raw material 3,4-dichloronitrobenzene through a three-step reaction comprising the steps of fluorine displacement, hydrogenation reduction and salt formation. The preparation method has the advantages of few byproducts, stable product properties, low reaction apparatus requirements because of the implementation of the nitro group reduction reaction using hydrogen and Pd-C at normal temperature, recycling of a solvent and Pd-C, and avoiding of the environmental pollution by introducing an excess HCl gas into an alkaline solution.

The invention discloses a cabozantinib preparation method. The target product cabozantinib is prepared by performing five-step reaction on diethyl malonate, 4-fluoroaniline, 4-chloro-6,7-dimethoxyquinoline, 4-aminophenol, 1,2-dibromoethane and the like used as raw materials. The preparation method is simple to operate and friendly to environment; the comprehensive yield is more than 50% and is obviously increased in comparison with the yield of 20% in the prior art; and the preparation method greatly lowers the existing medicine production cost, and is suitable for industrial large-scale production.

The invention relates to a novel method for synthesizing an important intermediate 6-chloro-5-fluoroindole for anticancer and weight-reducing medicines. The method comprises the steps that: 3-chloro-4-fluoroaniline is reacted with boron trichloride in a toluene solution under the action of a Lewis acid aluminium trichloride to produce imine which is then hydrolyzed under the action of hydrochloric acid to get an intermediate, a target product is generated by the reduction of the intermediate by sodium borohydride in a dioxane/water system and then by reflux dewatering, and the 6-chloro-5-fluoroindole is produced by reduced pressure distillation of the initial product. The method has the advantages of readily available raw materials, short reaction steps and low costs, and is suitable for industrial production.

The invention relates to the field of paintings and particularly relates to a water-based dispersive polyanion anticorrosive additive and a preparation method thereof. The preparation method comprisesthe following steps: step 1, selecting sodium lignosulfonates, phosphoric acid and de-ionized water, and performing ultrasonic agitation for dissolution; step 2, then adding aniline or 4-fluoroaniline or a mixture of aniline and 4-fluoroaniline, and performing ultrasonic agitation, thereby obtaining a mixture; step 3, reacting ammonium persulfate with the mixture obtained in the step 2, thereby obtaining a reactant liquor; and step 4, separating a solid precipitate out from the reactant liquor obtained in the step 3, and performing vacuum drying on the solid precipitate. The preparation method has the beneficial effects that natural reproduceable papermaking byproduct sodium lignosulfonates is adopted as a modifier and is blended with aniline and derivatives thereof for reaction, so as toobtain the modified water-based dispersive polyanion anticorrosive additive. The additive has favorable water dispersion property and excellent corrosion prevention effect. According to the scheme, adopted reaction conditions are mild, and the raw material cost is low. The preparation method is simple to operate and easy to realize.

The invention discloses a new method for performing microwave synthesis on gefitinib and a derivative thereof. The method comprises the following steps of: at first, synthesizing 6-methoxyl-7-hydroxyl quinazoline-4-one from 2-iodo (bromo)-4-methoxyl-5-hydroxyl cyanophenyl used as an initial raw material and formamidine hydrochloride in a microwave mode; then performing reaction with 4-(3-bromo propyl) morpholine to introduce an alkyl side chain so as to obtain 7-methoxyl-6-[3-(4-morpholinyl) propoxy] quinazoline-4-ketone; in the presence of a catalyst, performing reaction on the obtained product and a chlorination reagent to obtain 4-chloro-7-methoxyl-6-[3-(4-morpholinyl) propoxy] quinazoline; finally, performing reaction on 4-chloro-7-methoxyl-6-[3-(4-morpholinyl) propoxy] quinazoline and 3-chloro-4-fluoroaniline to obtain a final product 4-(3-chloro-4-fluoroanilino)-7-methoxyl-6-(3-morpholinyl propoxy) quinazoline (gefitinib). The whole route steps are simplified into four steps, the yield is high, the method is convenient to carry out, the dangerousness is low, and the application of high-pollution reagents is reduced; moreover, the whole route is high in economy and suitable for industrial production, and the product cost is reduced. The reaction formula is as shown in the specification.

Provided is a preparation method for revaprazan hydrochloride, the method comprising: (1) the preparation of 4-hydroxyl-2-(4-fluoroaniline)-5,6-dimethylpyrimidine; (2) the preparation of 4-chloro-2-(4-fluoroaniline)-5,6-dimethylpyrimidine; (3) the preparation of revaprazan hydrochloride. The method has advantages such as simple operations, high product purity, good yield and suitability for industrial production.