85 results about "Diphosgene" patented technology

The invention discloses a method for preparing a compound of formula (5). The method comprises the following steps: 1, reacting a compound of formula (2) with triphosgene, diphosgene or phosgene in a non-polar solvent in the presence of an organic alkali to obtain a product, reacting the obtained product with a compound of formula (3) to obtain a compound of formula (1); and 2, reacting the compound of formula (1) with a compound of formula (6) in 1,4-dioxane to obtain a substance, reacting the substance with HCl to form a salt which is the compound of formula (5), wherein R in the compound of formula (3) and the compound of formula (5) is a methyl group or an ethyl group.

The invention discloses a novel synthesis method of palonosetron hydrochloride, which comprises that (1) (S)-tetralin formic acid is reacted with thionyl chloride and (S)-3-amido-quinine cyclic amine, to obtain (S, S)-quinuclidine tetralin formamide, (2), (S, S)-quinuclidine tetralin formamide is reacted with reductant and boron trifluoride diethyl etherate, to obtain (S, S)-tetralin methyl quinine cyclic amine, (3), (S, S)-tetralin methyl quinine cyclic amine is reacted with diphosgene to be added and reacted in boron trifluoride diethyl etherate solution, while the product is added and reacted with alcaine and water, to obtain palonosetron hydrochloride. And the synthesis route is represented as above: a: SOCI2, (S)-3-aminoquinuclidine, b: NaBH4, BF3OEt2, c: BF3OEt2, CICO2CCI3.

The invention provides alicyclic diisocyanate with a novel chemical structure, which is C23-38 alicyclic diisocyanate and has the same excellent performance with other traditional aliphatic isocyanates. The invention also provides a preparation method of this type of substance, which comprises the following steps that: (a) unsaturated dicarboxylic acid with the special structure or the solution of ester thereof are aminated and dehydrated to prepare binary Aliphatic cyanide; (b) the binary aliphatic cyanide is catalyzed and hydrogenised to prepare corresponding saturated diamine; and (c) the solution of the saturated diamine is slowly added into pre-cooled phosgene, diphosgene or triphosgene, the heat is maintained for a period of time and then goes up, the phosgene, the diphosgene or the triphosgene are continued to be added in, until the reaction solution becomes transparent, to prepare the alicyclic diisocyanate. The method is characterized by easily available production raw materials, lower condition requirements, safety, environmental-friendliness, low cost, high efficiency and easy wide popularization in industry.

The present invention relates to a method capable of using diphosgene or triphyosgene to chlorinate 4,6-dihydroxypyrimidine to obtain 4,6-dichloropyrimidine in the presence of proper alkali and a certain solvent or mixed solvent.

The invention relates to a synthesis method for 2-chloro-5-chloromethyl pyridine, in particular to an innovation on a chlorination addition and cyclization reaction. In the method, the insufficient of preparing the 2-chloro-5-chloromethyl pyridine in a cyclopentadiene-acrolein route is solved; the purpose of utilizing less DMF (Dimethyl Formamide) in the chlorination addition and the cyclization reaction is realized; solid triphosgene or diphosgene or phosgene are adopted to substitute phosphorus oxychloride and other phosphorous chlorination cyclization reagents, therefore, the problem of mass discharge of the DMF and phosphorous waste water in the production course is thoroughly solved; the production cost is reduced; and the cleaner production is realized.

The invention discloses application of oridonin powder aerosol in treatment of acute lung injury. The oridonin powder aerosol is prepared by an oridonin nano-drug delivery system, wherein the dosage form of the nano-drug delivery system is selected from lipidosome, nanoparticles, nanosuspension, nanoemulsion and micro-emulsion. The medicines in the oridonin powder aerosol are stable, easily enter the deep parts of lung tissues, are positioned in a targeted mode and are convenient to carry and use, and the treatment of acute lung injury is promoted. The oridonin powder aerosol is used for treating the acute lung injury caused by infection, shock, smoking, trauma, toxin poisoning, inhalation of irritant gases, radiation, high oxygen and low oxygen, wherein the inhaled irritant gases comprise phosgene, diphosgene, triphosgene, chlorine, nitric oxides, formaldehyde, dimethyl sulfate, hydrogen chloride, hydrogen bromide, hydrogen fluoride, ammonia, ozone and sulfur dioxide.

The invention discloses a synthesizing method of 2, 4-dichloro-5-methoxy pyrimidine and belongs to the technical field of pesticide intermediate chemical process. The synthesizing method includes: adding 2, 4-dyhydroxy-5-methoxy pyrimidine, solvent and catalyst into a reaction system, stirring, and performing heating reflux reaction under the condition that phosgene, diphosgene or triphosgene is used as the chlorinating agent; performing simple quenching post-treatment after the reaction to obtain the high-yield and high-purity target product. The synthesizing method is mild in reaction condition, economical and efficient, green as compared with an existing target product synthesizing process, and easy in industrial production.

The invention relates to a method for synthetizing di-tert-butyl bicarbonic ester, comprising the steps as follows: tertiary butyl alcohol natrium is used as the raw material, toluol or heptane is used as the solvent, the raw material and the solvent are heated and mixed to dissolve, carbon dioxide gas is inlet under 40 to 80 DEG C, the additive latent solvent of tertiary butyl alcohol or tetrahydrofuran are additionally added to reduce the viscosity of the solution, the temperature is reduced to 0 to 40 DEG C, the catalyst N, N, , -tetramethyl quadrol and cocatalyst of crownether are added in, toluene solution containing diphosgene is dripped in for reacting for 2 to 3 hours, the acquired oil phase liquid is cleaned in alkali and water, decompressed and distilled to produce the di-tert-butyl bicarbonic ester. The method of the invention is characterized in low production cost, short reaction period, stable product quality and good applicability for industrialized production.

The invention relates to a method for preparing dimethylphenyl isocyanate. Dimethylaniline and solid phosgene are used as raw materials; the molar ratio of the dimethylaniline to the solid phosgene is 2.0 to 2.4; the reaction time is between 3 and 6 hours; a reaction solvent is 1,2-ethylene dichloride; and the reaction temperature is the refluxing temperature of the 1,2-ethylene dichloride. The method, which prepares the dimethylphenyl isocyanate by using the solid phosgene to replace traditional phosgene or diphosgene, and reacting the solid phosgene with the dimethylaniline, has the advantages of simple and reasonable process course, safe and reliable operation, high reaction yield and low production cost, operating environment improvement, environmental pollution reduction, and easy realization of industrialized production.

The invention relates to a preparation method of di-tert-butyl dicarbonate and belongs to the technical field of synthesis of pharmaceutical intermediates. The preparation method comprises the following steps: adding metal sodium into xylol; heating to obtain sodium sand; then dropwise adding tert-butyl alcohol and carrying out pumping filtration to obtain sodium tert-butoxide; dissolving the sodium tert-butoxide into petroleum ether; introducing carbon dioxide and reacting to obtain a monoester sodium salt solution; adding a catalyst and slowly dropwise adding diphosgene to react; after reacting, standing and carrying out the pumping filtration; and washing with water, drying, distilling, cooling and crystallizing to obtain the di-tert-butyl dicarbonate. According to the preparation method, the sodium tert-butoxide is prepared from the metal sodium and the di-tert-butyl dicarbonate is prepared from the sodium tert-butoxide; a pumping filtration method is used for replacing a previous distillation method, so that the process is simpler and more energy is saved; the petroleum ether is used for replacing n-hexane and toluene, so that the production cost is reduced and a product is easier to purify; and finally, after the reaction, the pumping filtration is carried out and then water washing is carried out, so that the amount of wastewater is reduced and the environment-friendly treatment cost is reduced.

The invention provides a synthesis method of 4,6-dichloropyrimidine, comprising the following steps: 1) mixing 4,6-dihydroxypyrimidine with phosphorus oxychloride, and adding phosgene, diphosgene and triphosgene One or several combinations for reaction; 2) Separation and purification of the reaction solution obtained in step 1) to obtain phosphorus oxychloride and 4,6-dichloropyrimidine, and the recovered phosphorus oxychloride is used as a raw material for step 1) 4,6‑dichloropyrimidine synthesis reaction. The invention avoids the cumbersome process of organic alkali recovery and reuse, does not use expensive catalysts, avoids resource waste and product loss, is environmentally friendly, does not generate additional solid waste, and does not generate a large amount of phosphorus-containing waste liquid and waste residue, and the product yield is high, the purity is good, and it can meet the requirements of the market without secondary purification, and can be used for large-scale industrial production.

The invention provides a method for producing diphosgene or triphosgene from phosgene. The method comprises the following steps: preparing a solution, performing solution decontamination, performing catalytic decomposition, performing phosgene refining and recycling a solvent. A diphosgene or triphosgene solution is adopted to contact and react with a catalyst, and the reaction velocity can be flexibility controlled by controlling the concentration of the solution. Before contacting the catalyst, the diphosgene or triphosgene solution is firstly purified, catalyst poisoning is avoided, the service life of the catalyst is prolonged, and the cost is lowered. Moisture and the solvent mixed with phosgene are removed by using a phosgene decomposition refining tower, so that the situations that side reactions and equipment erosion are increased as moisture carried in the solvent and raw materials is fed into a phosgene use unit along with the phosgene can be avoided.

A method for preparing 2-(N-substituted)-amino-benzimidazole derivatives is provided, which comprises the following steps: (1) reacting a compound of 2-(N-protecting group)-O-aryl diamine with a compound of N-phenoxycarbonyl monosubstituted amine to obtain a compound of 2-(N-protecting group)-amino aryl urea; (2) in a suitable organic solvent, performing dehydrating cyclization reaction of the compound of 2-(N-protecting group)-amino aryl urea in the presence of an organic base and dichloro triphenylphosphine prepared by triphenylphosphine oxide with oxalyl chloride or diphosgene or triphosgene, or dibromo triphenylphosphine prepared by triphenylphosphine oxide with bromine, to produce a compound of 1-protecting group-2-(N-substituted)-amino-benzimidazole; (3) deprotecting the resulting compound of 1-protecting group-2-(N-substituted)-amino-benzimidazole to obtain the compound 2-(N-substituted)-amino-benzimidazole.

The invention discloses an application of a chlorogenic acid nano powder inhalation in a medicine for treating acute lung injury. The chlorogenic acid nano powder inhalation is prepared with a chlorogenic acid nano medicine delivery system selected from the dosage forms of lipidosomes, nano-particles, nano-emulsions and micro-emulsions with or without addition of an auxiliary material. The medicine delivery system is dried into solid powder and is then mixed with a carrier to prepare the chlorogenic acid nano powder inhalation. The nano powder inhalation is stable, is easy to enter the deep parts of lung tissue, allows targeted positioning, is convenient to carry and use and has advantages on treatment of the acute lung injury. The chlorogenic acid nano powder inhalation is used for treating acute lung injuries caused by infection, shock, smoking, wound, poisoning, inhalation of simulative gas, irradiation, high-oxygen and low-oxygen atmospheres and the like. The simulative gas herein comprises phosgene, diphosgene, triphosgene, chlorine, nitrogen oxides, formaldehyde, dimethyl sulfate, hydrogen chloride, hydrogen bromide, hydrogen fluoride, ammonia, ozone and sulfur dioxide.

The invention discloses a preparation method of a 3-trifluoromethylpyrazole intermediate. The preparation method is characterized by comprising the following step: carrying out reaction on trifluoroacetic acid, an acylation reagent and vinyl alkyl ether disclosed as Formula 1 in an organic solvent in the presence of an acid-binding agent to obtain 4-alkoxy-1,1,1-trifluoro-3-butenyl-2-one, wherein the acylation reagent is one or more of phosgene, diphosgene and triphosgene, and R is C1-C6 alkyl group. The preparation method has the advantages of fewer reaction steps, mild reaction conditions, environment friendliness, simple after-treatment steps, high reaction yield, high product purity and low production cost, and is suitable for industrial production.

The invention relates to a method for preparing an oxazole compound. The method comprises the steps: adding an assistant represented by a formula (I) or (II) or (III) into an organic solvent and organic alkali (especially triethylamine), dropwise adding an organic solution of phosgene or diphosgene or triphosgene to carry out cyclization reaction with a compound (IV), and thus obtaining the product (V) at high yield and greatly inhibiting the generation of byproducts. The reaction conditions are mild, and compared with a method without addition of additives, the method provided by the invention can improve the yield of the product (V) to 95% or above and reduce the yield of byproducts by 10% or above.

The invention relates to the technical field of a preparation method of 5-penphene-2-formyl chloride. The preparation method is characterized in that 5-penphene-2-carboxylic acid is taken as an initial raw material to react with chloro-reagent diphosgene or triphosgene in the presence of an organic amine catalyst, so as to prepare the 5-penphene-2-formyl chloride. The preparation method has the advantages that the process is simple, the production is safe and reliable, the reaction yield is high, the production cost is low, three wastes are not basically generated, a product is high in purity and has few impurities, and the preparation method is very suitable for industrial production. The 5-penphene-2-formyl chloride prepared by utilizing the preparation method is taken as an intermediate to prepare Rivaroxaban.

The invention provides a simple and convenient production method of avibactam. The simple and convenient production method of the avibactam comprises the steps of using piperidyl-5-keto-2S-formate IIas a raw material, making the piperidyl-5-keto-2S-formate II and O-protecting group hydroxylamine hydrochloride subjected to condensation reaction, and then obtaining 5R-substituted oxyaminopiperidyl-2S-formic acid V through reduction, chiral resolution and hydrolysis under an alkaline condition; and then making the 5R-substituted oxyamino piperidyl-2S-formic acid V and phosgene or triphosgene ordiphosgene subjected to cyclic urea reaction reaction, acylating chlorination reaction and amidation reaction through a one-pot method, obtaining {[(2S,5R)-2-formamyl-7-oxo-1,6-diazetidine[3.2.1]octane-6-yl]oxy}sulfonyl tetra-n-butylammonium salt VII through protecting group take-off, sulphating and tetrabutyl amination salification, and producing the avibactam I finally through ion exchange. Thesimple and convenient production method of the avibactam is simple and convenient in production route, easy to operate, low in raw material price, low in cost, small in three waste discharge, high inatom utilization rate, economical and environmentally friendly, and the yields of the various steps are high, so that the simple and convenient production method of the avibactam benefits industrial production of the avibactam.

The present invention relates to a preparation method of benzoyl urea derivative. In particular, it relates to a chemical synthesis method for preparing benzoyl urea derivative by using bis (trichloromethyl) carbonate instead of phosgene, diphosgene or oxalyl chloride to directly react with substituted aniline and substituted benzamide. Its reaction temperature is 20-200deg.C and reaction time is 1-20h.

The invention discloses a synthetic method for 4,6-dichloropyrimidine. The synthetic method comprises the following steps: (1) mixing 4,6-dihydroxypyrimidine with a catalyst, adding one or two selected from a group consisting of diphosgene and triphosgene, and carrying out a reaction; and (2) after the reaction is completed, separating and purifying a reaction solution so as to obtain the product4,6-dichloropyrimidine. The catalyst is a compound of organic phosphine and cobalt phthalocyanine. The synthetic method of the invention does not use any organic alkali, avoids the cumbersome processof recovery and recycling of the organic alkali, prevents the waste of resources and product loss, and is friendly to environment and free of additional solid waste and considerable phosphorus-containing waste liquid and waste residues; and a specific catalyst combination is used in the invention, the usage amount of the catalyst is small, and cost is low.

The invention relates to a nitration method having the following principles: a phosgene species is converted with two equivalent silver nitrates into a double-mixed anhydride of carbonic acid and nitric acid, known here as carbonic acid dinitrate (I). Said operation is carried out in situ, and the formed dinitrate decomposes spontaneously. In addition to carbon dioxide, nitrate ions and nitronium ions are formed, said ions comprising electrophiles which are necessary for nitration. The solution which is used is acetonitrile, and is insignificant if the alcohol species is dissolved or suspended. The necessary equivalent silver nitrates are introduced into the system and optionally heated or cooled to the desired temperature. Subsequently, the acid chloride is introduced slowly, drop by drop or slowly little by little. Phosgene, diphosgene, triphosgene and chloroformic acid ester can be used as carbonic acid dichloride and monochloride, and their thiocarbonic acid analogues. A brown colouration and precipitated silver chloride display the formation of the carbonic acid reactants, said brown colouration rapidly discolouring due to an immediate reaction of the nitronium ions with the substrate with is to be nitrated. Towards the end of the addition of phosgene, the brown colouration remains for longer and longer until it no longer disappears. Then, it is stirred for another hour at room temperature. In the event of high acid-sensitive educts, non-nucleophilic nitrogen bases such as DBU can be added to the system in order to intercept the formation of nitric acid.

The invention discloses a preparation method for ditertbutyl dicarbonate. In the method, the ditertbutyl dicarbonate is prepared from self-made sodium tert-butoxide solution, diphosgene and a catalyst under a certain condition. The preparation method has the advantages of simple process, high yield, high purity, capability of raising reaction temperature by substituting normal hexane with toluene(normal hexane is used in the conventional method) and higher safety.

The invention discloses a method for synthesizing a pymetrozine intermediate (oxadiazole ketone) by utilizing carbonate ester. According to the method, hydrazine hydrate and an acetic acid ester are utilized as raw materials for hydrazine-ester condensation to synthesize acethydrazide; oxadiazole ketone is generated through a ring-closure reaction between acethydrazide and carbonate ester under certain conditions. Such environmental-friendly non-toxic or low-toxic dimethyl carbonate, diphenyl carbonate or dibenzyl carbonate is utilized for replacing previously common virulent phosgene, diphosgene or triphosgene as a carbonylation ring-closure reagent; under the action of catalysts, a ring-closure cyclization reaction is performed for preparation of oxadiazole ketone; virulent phosgene and a great amount of inorganic solid hazardous waste are prevented from generating during a production process, so that major hidden dangers are reduced; the method has the advantages that the process is safe and reliable, reaction conditions are mild and easy to control, after-treatment is convenient, and an environmental-friendly effect is achieved.

The invention herein provides for the detection of certain organic halogen-containing agents or toxicants such as sarin, chloropicrin, mustard gas, mustard chlorohydrin, phosgene, chlorine, soman, lewisite, diphosgene and others by, in one embodiment, first reacting the agents with superoxide free radical anion (.O{overscore (2)}) to produce light pulses which can be detected by a standard photon counter. The superoxide may be available from a dimethyl sulfoxide superoxide (.O{overscore (2)}) liquid solution, from lecithin coated beads charged with superoxide (.O{overscore (2)}) in a reaction vessel or from a quarternary ammonium ion exchange resin charged with superoxide anion (.O{overscore (2)}) in a reaction vessel.

The invention relates to a synthesis method for co-producing p-chloroaniline and p-chlorophenol isocyanate. The method comprises the following steps of: reducing parachloronitrobenzene by using iron powder, separating water, dehydrating, adding a solvent, reacting with a bis(trichloromethyl) carbonate solution, distilling to recover the solvent, and distilling to obtain a p-chlorophenol isocyanate finished product. The method has the advantages that a process is advanced; process conditions are reasonable; the production of p-chloroaniline is organically combined with that of p-chlorophenol isocyanate; the environment pollution and an intoxicating phenomenon which are brought by p-chloroaniline used as an industrial product in the processes of aftertreatment, conveying, carrying and feeding can be avoided; virulent phosgene and diphosgene are avoided during production of p-chlorophenol isocyanate, and production is safe and reliable; the residual bis(trichloromethyl) carbonate is removed by normal-pressure reflux; the improvement on the quality of a product is facilitated; and the method has great implementation value and social and economic benefits.

The invention discloses an application of a dry curcumin nano-powder inhalant in treatment of acute lung injury. The dry curcumin nano-powder inhalant is prepared from a curcumin nanometer administration system. The dosage form of the curcumin nanometer administration system is selected from a liposome, a nano-particle, a nano-emulsion and a micro-emulsion. The curcumin nanometer administration system with or without auxiliary materials is dried to form a solid powder, and the solid powder is mixed with a carrier to obtain the dry curcumin nano-powder inhalant. The dry curcumin nano-powder inhalant has the advantages of stable drugs, easy entrance of the deep portion of lung tissues, targeted positioning, carrying and use convenience, and benefiting for the treatment of the acute lung injury. The dry curcumin nano-powder inhalant is used for treating acute lung injury caused by infection, shock, smoking, wounds, poisoning, irritating gas inhalation, radiation, high oxygen and low oxygen. Irritating gases comprise phosgene, diphosgene, triphosgene, chlorine, nitrogen oxide, formaldehyde, dimethyl sulfate, hydrogen chloride, hydrogen bromide, hydrogen fluoride, ammonia, ozone and sulfur dioxide.

The invention discloses (S)-N-ethyl-N-methyl-3[1-(dimethylamino) ethyl]-carbamidbenzoate (I) and preparing method of tartrate (II), which comprises the following steps: reacting compound (III) or salt and phosgene, diphosgene or triphosgene to obtain compound (IV); preparing compound (I) through reacting non-purifying compound (IV) and N-methyl-N-ethyl ammonium; reacting compound (I) and L-(+)-tartaric acid to obtain tartrate (II).

3-(2-chlorophenyl)-5-methyl-4-isoxazole formyl chloride is a key intermediate body of cloxacillin. It uses bis (trichloromethyl) carbonate and makes it directly be reacted with 3-(2-chlorophenyl)-5-methyl-4-isoxazole formic acid instead of sulfur oxycchloride or phosphorus oxychloride or phosphorus pentachloride or phosphorus trichloride or phosgene or diphosgene to synthesize 3-(2-chlorophenyl)-5-methyl-4-isoxazole formyl chloride.

The invention provides a 4,6-dichloropyrimidine production process which comprises the following steps: 1) mixing 4,6-dyhydroxyl pyrimidine with phosphorus oxychloride, and adding one or a combinationof more of phosgene, diphosgene and triphosgene to implement a reaction; 2) separating and purifying the reaction liquid obtained in the step 1), thereby obtaining phosphorus oxychloride and 4,6-dyhydroxyl pyrimidine, wherein the recycled phosphorus oxychloride is used as a raw material of the step 1) to implement 4,6-dyhydroxyl pyrimidine synthesis reactions. By adopting the process, the tediousprocess of organic alkali recycling and reuse is avoided, no expensive catalyst is used, resource waste and product loss are avoided, the environment can be protected, no extra solid waste is generated, a great amount of phosphorus-containing waste liquids and waste residues are not generated, either, in addition, a high product yield is achieved, good purity is achieved, market sale requirementscan be met without secondary purification, and the process can be applied to large-scale industrial production.

The invention relates to a method for preparing chiral drug intermediate L-prolinamide and an intermediate thereof. The method comprises the following steps of: firstly, reacting L-proline as an initial raw material with triphosgene, diphosgene or phosgene in solvents of anhydrous tetrahydrofuran, 1,4-dioxane, dichlormethane, chloroform, acetonitrile and the like to synthesize L-proline carbamyl chloride of an intermediate state; secondly, further condensing in the presence of triethylamine to generate L-proline-N-carboxyl-anhydride; and finally, performing ammonolysis, and thus obtaining the L-prolinamide. By adopting the method, the yield of the L-prolinamide is improved, the generation quantity of impurities is reduced, the whole reaction time is shortened, cost of treatment on discharge of three wastes and sewage is reduced, the production cost of the L-prolinamide is comprehensively reduced, and industrialized production is easier to realize.