89 results about "Hofmann rearrangement" patented technology

The invention discloses a preparation method of an amino pyridine bromide compound, relating to the field of organic synthesis. The amino pyridine bromide compound takes pyridine bromide formamide as raw material, and is prepared according to the following formula of Hofmann degradation reaction which comprising the following steps of: (1) dropping liquid bromine into alkali liquid with the concentration of 2.0-4.0 mol/L at -5-0 DEG C, reacting for 1.0 hour to obtain sodium hypobromite or potassium hypobromite, wherein the alkali is sodium hydroxide, potassium hydroxide or sodium methoxide; (2) adding the pyridine bromide formamide with the general foumula I to the hypobromite solution at room temperature for dissolving, raising temperature to 50-80 DEG C, reacting for 0.5-2 hours, decreasing temperature to 0 DEG C for separating out solids, and filtrating to obtain crude products; extracting the filtrate with an organic solvent, removing the solvent, and merging the crude products; re-crystallizing by using petroleum ether, and drying to obtain amino pyridine bromide. Wherein, the mole ratio of the general formula I to the alkali is 1:4-8, the mole ratio of the general formula I to water is 1:80-160, and the mole ratio of the general formula I to the liquid bromine is 1:1-2; and the organic solvent is dichloromethane, chloroform or normal hexane. The invention has the advantages of one-step reaction, simple process, low requirement on equipment, and high product purity, and the yield coefficient is around 50 percent.

A method for preparing (1R, 2R)-2-(3, 4-difluoro phenyl)cyclopropylamine includes the steps of: taking 1,2-difluorbenzene as a raw material, and introducing chloracetyl on a benzene ring through the Friedel-Crafts reaction; carrying out reduction by using a boron hydrogen compound, then carrying out a dead circulation reaction, and obtaining a racemate 3,4-difluoro phenyl epoxyethane; carrying out hydrolysis reaction on the racemate 3,4-difluoro phenyl epoxyethane and water in the action of a catalyst to form (s)-3,4-difluoro phenyl epoxyethane; and carrying out reaction on the (s)-3,4-difluoro phenyl epoxyethane and phosphoryl triethyl acetate, then carrying out ammonolysis and Hofmann degradation reactions, and obtaining the (1R, 2R)-2-(3, 4-difluoro phenyl)cyclopropylamine. The method can avoid using expensive reagents during chirality redox, and obtains the (s)-3,4-difluoro phenyl epoxyethane through the kinetic resolution. The raw material cost is low, and the catalyst can be recycled. The (s)-3,4-difluoro phenyl epoxyethane can be obtained by configuration conversion of resolution generated R-configuration, and intermediate cost can be reduced.

The invention relates to a Method for preparation of 4-aminopyridine. This invention is based on the Hofmann degradation rezction of iosniacinamide to prepare 4-aminopyridine, making catalyzer by low-cost iodine or alkali metal iodide, sodium hydroxide orporassium hudroxide and bromine according to certain proportion and condition. The productivity of Hofmann degradation rezction of iosniacinamide is improved above 90%, the purity of 4-aminopyridine is higher than 99%. This can not only improve the productivity of 4-aminopyridine which is made by isonicotinic acid, but also reduce the cost of catalyzer greatly. It has important application-value to prepare 4-aminopyridine which is made by isonicotinic acid.

The invention relates to a technology for continuously producing hydrazine hydrate. A two-step method is adopted for reaction in the technology and the two steps is as follows: firstly, urea and sodium hypochlorite are subjected to full oxidization reaction in low temperature, concretely, two or more than two static mixers with freezing brine jackets are adopted for fully mixing materials to ensure the full performance of the oxidization reaction; and secondly, the product of the first step reacts rapidly in high temperature under the action of sodium hydroxide and is subjected to Hofmann rearrangement so as to generate the hydrazine hydrate. The benefits are as follows: the method is simple in technology and can realize continuous production; only the quantity of the static mixers needs to be increased, so that the investment is little; and the content of the obtained hydrazine hydrate is over 85%.

The invention provides a preparation method of pentafluoroaniline. The preparation method is characterized by comprising the following steps of: (1) adding pentafluorobenzonitrile into sulfuric acid with the concentration of 70-98% for hydrolysis, controlling the hydrolysis temperature to be 70-120 DEG C and the reaction time to be 3-5 hours, and then adding the product into water to separate out, and filtering to obtain pentafluorobenzamide; and (2) mixing the pentafluorobenzamide prepared by step (1) with alkali solution and halogen or hypohalite, preserving the heat for 4-6 hours at -10 to 20 DEG C and then heating up to 70-110 DEG C to carry out Hoffman degradation, controlling the reaction time to be 0.5-3 hours, and then performing steam distillation to obtain the pentafluoroaniline. The method provided by the invention has the advantages that the raw materials are easily available, the process is simple, the operation is convenient, the product purity is high (99% or higher), the yield is high (as high as over 80%), the cost is low, and the method is safe and efficient with energy conservation, consumption reduction and little discharge of three wastes, so the method provided by the invention is suitable for industrial production on a large scale.

A process for preparing 2-amino pyridine and its alkyl derivative from 2-cyanopyridine or its alkyl derivative includes incomplete hydrolysis and Hofmann degradation. Its advantage is high output rate (80%) and purity up to 99% or more.

The invention provides a method for preparing phenylaniline, which comprises the following steps: mixing cyanophenyl shown in the formula II, first alkaline compounds, nickel catalysts and borophenylic acid shown in the formula III or borophenylic esters shown in the formula VI to carry out suzuki coupling reaction for obtaining cyanobiphenyl shown in the formula IV; mixing the cyanobiphenyl, second alkaline compounds and oxyful, and hydrolyzing the cyanobiphenyl to obtain amido biphenyl shown in the formula V; and mixing the amido biphenyl, third alkaline compounds and sodium hypohalite to generate Hofmann degradation reaction for obtaining phenylaniline shown in the formula I, wherein R1 is chlorine, bromine, iodine, sulphonic acid ester radicals, carbonic ether radicals or alkyl ester radicals; R2 is alkyl, alkoxy, cyano, amido or hydrogen; R3 is chlorine, bromine or iodine; and R4 is alkyl, alkoxy, cyano, amido or hydrogen. The preparing method provided by the invention has the advantages of mild condition, low cost, cleanness and environment protection.

The invention relates to a method for synthesizing an important intermediate 2-chloro-3-amino-4-methylpyridine for an anti-AIDS medicament Nevirapine, and belongs to the technical field of organic synthesis. The method comprises the following process steps that: ethyl cyanoacetate and acetone are dehydrated and condensed to generate a condensation compound I under the action of a catalyst; dimethyl formamide, dimethyl sulfate and sodium methoxide solution react to generate N,N-dimethylformamiade dimethyl acetal (N,N-dimethyl formamide A), and then the N,N-dimethylformamiade dimethyl acetal reacts with the condensation compound I to generate conjugated enamine, namely a condensation compound II; the condensation compound II is cyclized by hydrochloric acid and ethanol to form a cyclic compound 2-chloro-4-methyl-ethyl nicotinate; the 2-chloro-4-methyl-ethyl nicotinate is ammonolyzed by ammonia gas to form 2-chloro-4-methyl-niacinamide; and the 2-chloro-4-methyl-niacinamide is subjected to Hofmann degradation reaction to form the 2-chloro-3-amino-4-methylpyridine. Compared with the prior synthesizing method, the method of the invention has the remarkable characteristic of reducing the reaction steps, and is suitable for large-scale industrialized production; the molar total yield of the five-step reaction is improved to 27 percent from the prior 24 percent; and the purity of the product reaches over 99 percent.

A method for manufacturing a sheet of paper and/or board having improved retention and drainage properties is provided, according to which, before the formation of the sheet and/or board, at least two retention aids are added to the fibrous suspension. These two retention aids are a main retention aid corresponding to a (co)polymer having a cationic charge density above 2 meq/g, obtained by the Hofmann degradation reaction, and a secondary retention aid corresponding to a water-soluble or water-swellable polymer having an anionic charge density above 0.1 meq/g. The main retention aid is introduced into the fibrous suspension in a proportion of 100 to 800 g/t of dry pulp, and the secondary retention aid is introduced into the fibrous suspension in a proportion of 50 to 800 g/t of dry pulp and has an intrinsic viscosity IV above 3 dl/g.

The invention discloses a synthetic method for 5-bromine-2-methylpyridine: using 6-methyl-3-picolinic acid as the raw material to react with ethyl alcohol to generate 6-methyl-3-picolinic acid ethyl ester; carrying out ammonolysis reaction by aqueous ammonia on the 6-methyl-3-picolinic acid ethyl ester to generate 6-methyl-3-pyridine carboxamide; carrying out Hofmann degradation reaction to obtain 6-methyl-3-aminopyridine; and finally reacting the 6-methyl-3-aminopyridine with a bromizing reagent to generate 5-bromine-2-methylpyridine. In the method, the process reaction condition is mild, the yield is high, the raw material is available, the cost is lower, and no 3-subsidary products are generated in the whole process, the load of post separation is eliminated and the prospect of industrialization is good.

A process for the preparation of Brivaracetam, an anti-convulsion drug, is provided comprising Hofmann rearrangement of (S)-3-(2-(chloroamino)-2-oxoethyl) hexanoic acid, followed by cyclization resulting in (R)-4-propyl-pyrrolidin-2-one which on condensation with bromo butyric acid or ester followed by reaction with ammonia results in Brivaracetam.

The invention discloses a preparation method for an ambroxol hydrochloride intermediate 3,5-dibromo-2-aminobenzoic acid. The method enables the ambroxol hydrochloride intermediate 3,5-dibromo-2-aminobenzoic acid to be obtained through the following two-step reaction: (1) under the action of alkali and bromine, phthalimide undergoes the Hofmann degradation reaction to obtain 2-amino-benzoate and bromine anion; (2) under acidic conditions, the bromine anion is oxidized in situ to be bromine by hydrogen peroxide, and the bromine further undergoes electrophilic substitution reaction on an aromaticring with 2-aminobenzoic acid to obtain the 3,5-dibromo-2-aminobenzoic acid. The method takes phthalic acid imine as an initiating raw material, the raw material is cheap and easy to obtain, and a production process for the raw material is also more environmentally friendly and saves more energy.