75 results about "Elimination reaction" patented technology

Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals.

The invention provides a method for preparing p-chloromethyl styrene, which comprises the following steps: (1) in the presence of a catalyst and an assistant, carrying out reaction on paraformaldehyde and hydrogen chloride to obtain a chloromethylation reagent; (2) reacting beta-halogenated ethyl benzene with the chloromethylation reagent obtained in the step (1) to obtain chloromethyl halogenated ethyl benzene; (3) adding an extracting agent into the chloromethyl halogenated ethylbenzene reaction liquid obtained in the step (2) for extraction to obtain an oil layer containing chloromethyl halogenated ethylbenzene and a water-containing acid layer, and crystallizing the oil layer to obtain purified p-chloromethyl halogenated ethylbenzene; and (4) in the presence of a solvent, carrying out elimination reaction on the purified p-chloromethyl halogenated ethyl benzene and alkali to obtain p-chloromethyl styrene.

The invention relates to the technical field of pharmaceutical chemicals, in particular to a preparation method of 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone, and discloses a preparation method of 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone. The method comprises the following steps: S1, adding a 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone crude product into a mixed solution of a solvent A and a solvent B, heating to 25-35 DEG C, and stirring for dissolving until the solution is clear, so as to obtain a 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone crude product; s2, carrying out transposition elimination reaction; s3, carrying out acidification deprotection reaction; s4, adjusting the pH value; s5, standing and layering; s6, decoloring; s7, performing concentration; s8, cooling and crystallizing; s9, carrying out solid-liquid separation; and S10, carrying out vacuum drying, so as to obtain a finished product of the 11beta, 17alpha-dyhydroxyl-6 alpha-methyl pregna-4-ene-3, 20-diketone. The method has the characteristics of high yield and good product quality, is stable and is easy to realize industrial production.

The invention relates to the technical field of catalytic synthesis, in particular to a chloromethylation catalyst, a preparation method of the chloromethylation catalyst and a method for preparing high-purity ortho-position, meta-position and para-position chloromethyl styrene through the chloromethylation catalyst, and the chloromethylation catalyst is prepared by loading sulfonic acid compounds and (or) pyridine compounds and (or) copper salt on a molecular sieve. The method can improve the localization selectivity of chloromethylation. The method for preparing high-purity ortho-position, meta-position and para-position chloromethyl styrene comprises the following steps of: reacting beta-bromophenylethane, paraformaldehyde and lewis acid in the presence of the chloromethylation catalyst to generate chloromethyl beta-bromophenylethane, and then performing elimination reaction under an alkaline condition to generate a chloromethyl styrene crude product; the high-purity ortho-position, meta-position and para-position chloromethyl styrene is obtained after the crude product is rectified, the brand-new catalyst is adopted in the method, the reaction selectivity is enhanced, the process is simple, and industrial production is facilitated.

The invention discloses a synthesis method of piperonone, and relates to the technical field of flavors, fragrances and chemical engineering, and the synthesis method comprises the following steps: taking acrylate as a raw material, and carrying out Michael addition reaction with isobutene under the action of Lewis acid to obtain 5-methyl-5-hexenoic acid ethyl ester; the preparation method comprises the following steps: carrying out nucleophilic substitution reaction on ethyl 5-methyl-5-hexenoate and bromoisopropane under the action of a basic catalyst to obtain ethyl 5-methyl-2-isopropyl-5-hexenoate; carrying out self Friedel-Crafts acylation reaction on the 5-methyl-2-isopropyl-5-hexenoic acid ethyl ester under the action of Lewis acid, so as to obtain 5-methyl-2-isopropyl-5-chloro cyclohexanone; and carrying out elimination reaction on the 5-methyl-2-isopropyl-5-chlorocyclohexanone under the action of alkali to obtain the product piperonone. According to the synthetic route, conventional chemical reagents are used as raw materials, reaction conditions are mild, emission of three wastes is reduced to a great extent, and the synthetic route is more environmentally friendly and suitable for continuous industrial production.

A full continuous-flow preparation method of (+)-biotin, including: subjecting a cyclic anhydride and a chiral biphenyl propylene glycol to asymmetric ring-opening reaction to produce a first intermediate, which undergoes selective reduction with a borohydride and cyclization with an inorganic mineral acid to produce (3aS, 6aR)-lactone; subjecting the (3aS, 6aR)-lactone and a sulfenylating reagent to sulfenylation to produce (3aS, 6aR)-thiolactone, which undergoes Fukuyama coupling with a zinc reagent in the presence of a palladium catalyst and elimination reaction in the presence of an inorganic mineral acid to produce an alkenyl valerate compound; subjecting the alkenyl valerate compound to reduction in the presence of a Pd / C catalyst to produce a valerate ester, which undergoes hydrolysis to produce a valeric acid salt; and subjecting the valeric acid salt to debenzylation in the presence of an inorganic mineral acid to produce the target product (+)-biotin.

The invention discloses a method for preparing halogenated fluorine-containing olefin with high yield as well as a product and application of the halogenated fluorine-containing olefin, dihalogenated perfluoroethane (ICF2CF2I or BrCF2CF2Br) and ethylene are taken as raw materials, under the action of a peroxide initiator TAPP (tert-amyl peroxypivalate, the addition amount of which is 0.2%-0.3% of the weight of the perfluorinated halogenated ethane), the ethylene is continuously introduced to maintain the reaction pressure of 0-5 kg, and the halogenated fluorine-containing olefin with high yield is prepared. Carrying out addition reaction to generate a dihalogenated fluorine-containing alkane intermediate; and heating toluene and sodium hydroxide / potassium hydroxide to 60-80 DEG C in a three-neck flask, superposing the intermediate to carry out elimination reaction, and continuously collecting the generated olefin through a distillation head to finally obtain ICF2CF2CH = CH2 or BrCF2CF2CH = CH2. The method is strong in process controllability, high in ethylene utilization rate and high in product separation efficiency, and adapts to iodination and bromination double-system production.

The application discloses a new method for synthesizing dihydrogibberellin without protecting carboxyl. The application provides a new method for synthesizing dihydrogibberellin without protecting carboxyl, which comprises the following steps: 1) mixing a compound shown in formula II with a catalyst A in an organic solvent B, and carrying out a hydrogen reduction reaction under a hydrogen atmosphere to obtain a compound shown in formula III; 2) mixing the compound shown in formula III with a saturated aqueous solution of a base in an organic solvent C, and carrying out a selective deacetylation reaction to obtain a compound shown in formula IV; and 3) mixing the compound shown in formula IV with triphenyl phosphine and an elimination reagent in an organic solvent D, and carrying out a dehydration elimination reaction to obtain dihydrogibberellin shown in formula V. The application can simplify the synthesis method of dihydrogibberellin and is more beneficial to large-scale production and synthesis.

The invention discloses a preparation method of an intermediate of macloxvir. The preparation method comprises the following steps: step 1, carrying out halogenation reaction; step 2, elimination reaction; step 3, addition reaction; step 4, ring closing reaction; the starting raw materials, the solvent and the catalyst selected in the invention are industrial-grade cheap and easily available products, have the advantage of low production raw material cost, and provide economic feasibility support for industrial large-scale production; reaction conditions of each step in the reaction process are mild, byproducts are few, the yield is high, and a target product can be prepared more efficiently; meanwhile, the synthesis route is high in atom utilization rate and excellent in atom economy, the used solvent and reagent are high in stability and easy to recycle and reuse, generation and emission of industrial three wastes are greatly reduced, the environment-friendly treatment cost is reduced, and the concept of green chemistry and sustainable development is met; the method gives consideration to economy, high efficiency and environmental friendliness, and solves the problems of low yield, violent reaction conditions and high cost of raw materials and auxiliary materials in the existing method.

The invention provides a synthesis method of atavapam, which comprises the following steps: carrying out nucleophilic addition-elimination reaction on commercially available raw materials and 4-methyl-3-trifluoromethylaniline under alkaline conditions, carrying out Suzuki coupling reaction under the action of a catalyst, carrying out pressurized hydrogenation, and carrying out chiral resolution, thereby obtaining the atavapam. And condensing with 2-fluoro-6-methyl benzoyl chloride under an alkaline condition, and further removing a Boc protecting group under an acidic condition to finish synthesis of the atavapam. According to the invention, a convergent synthesis process is adopted, tedious synthesis steps in the original process are shortened, and post-treatment is simpler and more controllable.

The application provides a preparation method of dydrogesterone, which comprises the following steps: performing a selective epoxidation reaction on a compound I in a first solution containing meta-chloroperoxybenzoic acid and hydrogen peroxide to obtain a compound II; the content of the meta-chloroperoxybenzoic acid in the first solution is more than 1 times of the amount of substance of the compound I; performing a reduction reaction on the compound II under the action of hydrogen and a catalyst to obtain a compound III; performing a hydrolysis reaction on the compound III in a dilute acid solution, and then performing a hydroxyl elimination reaction on the compound III in a second solution to obtain the dydrogesterone; the structural formulae of the compound I, the compound II, the compound III and the dydrogesterone are as follows:; and. The preparation method has less by-products and a higher reaction yield.

The invention discloses a pyrazolo [5, 1-a] isoindole derivative as well as a synthesis method and application thereof, and belongs to the technical field of organic chemical synthesis. The invention solves the problems of harsh reaction conditions, limited substrate range and the like of continuous multi-step synthesis of a precursor in the existing pyrazolo [5, 1-a] isoindole compound synthesis process. According to the invention, a polarity reversal strategy is adopted, a cyano group is introduced into 1, 5-enyne to change the electronic characteristics of 1, 5-enyne, diazo, olefin and ethynyl benzene are reacted under mild conditions, two rings and three new chemical bonds are constructed through a series of intermolecular [3 + 2] cycloaddition, intramolecular cycloaddition and elimination reactions, and pyrazolo [5, 5-a]-1, 5-a-phenanthrene is efficiently synthesized. According to the present invention, the 1, 1-a] isoindole derivative has characteristics of good synthesis yield, simple operation of the synthesis method, easily available raw materials, good substrate universality and step economy, and provides the effective strategy for the drug design synthesis.

This invention discloses a method for preparing trifluoromethyl olefins. The method comprises the following steps: (1) in a haloalkane solvent or ether solvent, a compound as shown in Formula I, CuX'2, CF3SO2Na, N(R) 2 (1) 4X undergoes the addition reaction shown below; (2) The product of the addition reaction in step (1) is reacted with a base in an organic solvent to undergo the elimination reaction shown below. The preparation method of trifluoromethyl olefins provided by the present invention has the advantages of being applicable to electron-rich styrene substrates, requiring less metal catalyst, not requiring high pressure conditions, not requiring photocatalysis, having easy-to-control reaction conditions, being relatively convenient for post-processing, and having a high yield.

The application belongs to the field of medicine synthesis, and particularly relates to a preparation method of 2,2-disubstituted-4-phenyl butyronitrile derivative, which comprises the following steps: mixing phenetole, nitrile and alkali agent in a molar ratio of 1.0:3.5-4.5:2.5-3.5 in aprotic solvent with a dielectric constant (epsilon) less than 20 at 60-100 DEG C for 12-30 hours; after the reaction is completed, the cooled reaction system is adjusted to be neutral, and the product is collected and purified. The phenetole is subjected to elimination reaction under alkaline conditions to generate a carbon-carbon double bond, and is subjected to addition reaction with the nitrile to obtain the 2,2-disubstituted-4-phenyl butyronitrile derivative. Meanwhile, the raw materials used are low in price and easy to synthesize, the cost is greatly reduced, the industrialization prospect is wider, and the operation is simple, so that the process technology has more competitive value.

The invention discloses a preparation method and application of a 2, 5-diketopiperazine derivative, and belongs to the field of biological medicine. The preparation method comprises the following steps: by taking 1, 4-diacetyl piperazine-2, 5-diketone (II) as an initial raw material, firstly, carrying out condensation reaction on the initial raw material and isobutyraldehyde to prepare a key intermediate (III); meanwhile, 4-amino-1-butanol (IV) is converted into an intermediate (VI) through acylation and oxidation two-step reaction; and finally, carrying out condensation and elimination reaction on the intermediates (III) and VI to prepare the target compound (I). The preparation method provided by the invention has the advantages of reasonable route design, mild conditions and outstanding stereoselectivity. According to the method, on the basis of easily available raw materials, a product mainly comprising a Z configuration is efficiently constructed through a modular strategy and consistent mild base catalysis conditions. Experimental data show that the compound prepared by the invention can inhibit TG accumulation in nematode bodies and reduce nematode fat accumulation, and can be developed into efficient medicines for preventing and treating obesity.

The invention is directed to self-eliminating cleavable conjugates according to general formula (I) or (II) wherein AR is capable of an elimination reaction upon cleavage of CL.

The application provides an intermediate for synthesizing chlorantraniliprole and cyantraniliprole and a preparation method of the intermediate, and the structural formula of the intermediate is 2-amino-3-methylbenzoic acid. The intermediate is obtained by a -D-A reaction, aromatization and a Hoffmann elimination reaction from a cheap bio-based platform compound 2-methylfuran as a starting material. The whole process does not need a dangerous nitration process and a hydrogenation process, the process has mild reaction conditions, good operability, less wastewater and a high yield of the obtained intermediate, and is very suitable for industrialized preparation of an intermediate required by the high-efficiency insecticides chlorantraniliprole and cyantraniliprole.

This invention discloses a method for synthesizing vinylene carbonate. The method includes: reacting chlorovinyl carbonate with triethylamine in the presence of compounds such as oxanthracene or thioxanthracene to generate a vinylene carbonate reaction solution; and then subjecting the reaction solution to vacuum filtration, distillation, and crystallization to obtain electronically pure vinylene carbonate (purity can reach 99.995% or higher). This method can effectively inhibit the polymerization of vinylene carbonate, avoid the formation of vinylene carbonate polymers, improve the yield of the elimination reaction and the overall heat transfer efficiency of the distillation process, reduce the difficulty of separation and purification, and reduce energy consumption, making it suitable for industrial production.

The application relates to the technical field of pharmaceutical chemistry, and discloses a sulfuryl hydrazone compound, a preparation method thereof and anti-tumor application. The compound is synthesized from isatin derivatives and sulfuryl hydrazine through two-step nucleophilic substitution-elimination reaction, has a chemical structure as shown in formula (I), and is characterized by 1H NMR, 13C NMR and HRMS. The sulfuryl hydrazone compound has significant inhibitory activity on A549 (lung cancer), HepG2 (liver cancer) and Hela (cervical cancer) three human cancer cell strains, the value of some compounds is as low as 0.03 micromole / L, the compound can induce cell apoptosis by mediating ROS generation in tumor cells, inhibiting the NF-kappa B signal pathway and activating Caspase-3 activity, and can effectively inhibit cancer cell migration and colony formation. The compound has a mild synthesis process, simple operation and wide substrate applicability, can be used as a potential anti-tumor active ingredient, can be used for preparing drugs for resisting lung cancer, liver cancer, cervical cancer and other tumors, and can provide new candidate compounds and technical support for cancer treatment.

The invention provides a papaverine hydrochloride intermediate impurity as well as a preparation method and application thereof, and belongs to the technical field of organic compound synthesis. 1-[(3, 4-dimethoxyphenyl) methyl]-7, 8-dimethoxyisoquinoline is used as a raw material, and the papaverine hydrochloride intermediate impurity with the structure shown in the formula I is successfully prepared through hydrogenation reduction, chlorination reaction and elimination reaction. And a scientific basis is provided for analyzing the structure and the content of the impurity, clinical medication safety of papaverine hydrochloride, improvement of a production process and compliance of laws and regulations.

The invention relates to a synthesis method of 2-butadiene sulfone. The synthesis method comprises the following steps: mixing a compound I with an alkaline substance, and carrying out elimination reaction to obtain the 2-butadiene sulfone. According to the method, 3-substituted sulfolane is simply stirred in an alkaline substance for elimination reaction, and then simple separation and extraction are carried out, so that 2-sulfolane can be conveniently prepared. The method is simple to operate, has high selectivity, can specifically generate the target product 2-butadiene sulfone, and does not generate a byproduct 3-butadiene sulfone, so that the synthesis yield and the purification efficiency are greatly improved. The synthesis method of 2-butadiene sulfone provided by the invention has the characteristics of simple and convenient synthesis conditions, high selectivity, high yield and high purity.

The invention provides an ultrasonic response conjugate based on hydroxyl free radicals and application thereof. The conjugate has a structure as shown in a formula I or a salt of the structure as shown in the formula I, according to the research, a plurality of m-disubstituted benzyl alcohol ultrasonic response structures are designed and screened by starting from an active substance such as hydroxyl free radicals generated by an ultrasonic cavitation effect. After the structure and to-be-masked molecules such as drugs or fluorescence contrast molecules form conjugates through covalent bonds, active groups of the molecules and the molecules can be masked, the activity of the molecules and the molecules can be inhibited, the obtained molecules are called prodrugs, and the prodrugs can be small molecules and can also be used for high-molecular drug loading systems. The prodrug can capture hydroxyl radicals generated by an ultrasonic cavitation effect under the condition of no sound-sensitive agent, and release of target molecules is completed through an elimination reaction. The m-phenylenediether structure obtained through experimental screening is the optimal ultrasonic response group.

This invention belongs to the field of pharmaceutical and environmental chemistry, and specifically relates to a method for preparing anacocetate silyl ether. The method for preparing anacocetate silyl ether provided by this invention includes the following steps: (1) 9-hydroxyl elimination reaction, (2) quenching reaction, (3) pH adjustment, (4) dehydration treatment, (5) 17-hydroxyl silyl ether reaction, (6) water washing and layering, (7) concentration and crystallization, (8) solid-liquid separation, and (9) drying. The preparation method provided by this invention achieves a one-pot preparation of anacocetate silyl ether, with a product purity of over 97.5%, isomer content below 0.5%, and molar yield of over 93.4%. This invention features high yield, low pollution, simple and safe operation, and low cost. Furthermore, the preparation method is stable and easily scalable for large-scale industrial production.

The application belongs to the technical field of fine chemical intermediates synthesis, and particularly relates to a preparation method of 2,2-disubstituted-4-pyridyl butyronitrile derivative. A mixture of hydroxyethyl pyridine, nitrile and alkali agent in a molar ratio of 1:3.5-4.5:4-5 is mixed in an aprotic solvent with a dielectric constant (epsilon) less than 20 at 60-100 DEG C for 12-30 hours. After the reaction is completed, the cooled reaction system is adjusted to neutral, and the product is collected and purified. The elimination reaction of hydroxyethyl pyridine under alkaline conditions generates a carbon-carbon double bond, and the addition reaction of the carbon-carbon double bond with nitrile generates 2,2-disubstituted-4-pyridyl butyronitrile derivative. Meanwhile, the raw materials used are low in price and easy to synthesize, the cost is greatly reduced, the industrialization prospect is wider, and the operation is simple, so that the process technology has more competitive value.

The invention provides a stable acetylcysteine solution and a preparation method thereof. According to the method, the hydrogen sulfide generation inhibitor is added, and the beta-elimination reaction of acetylcysteine is competitively inhibited in the sterilization process, so that the hydrogen sulfide content in the injection after terminal sterilization is obviously reduced from the source, and the problem of high hydrogen sulfide content of the product caused by terminal sterilization in the prior art is solved.

According to the preparation method, sodium perborate tetrahydrate is selected as an oxidizing agent, the requirement for preparing the finasteride through an oxidation elimination reaction is met by accurately controlling reaction conditions, the impurity amount is small, a reagent which easily generates a large amount of waste solids or waste liquid is avoided, operation is easy, and the method is suitable for industrial production. Waste liquid generated by post-treatment is easy to treat. Meanwhile, side reactions are reduced, tedious refining steps are avoided, and the yield of the product is increased.

The invention relates to the field of organic synthesis, and particularly discloses a preparation method of kung-fu acid. Comprising the following steps: carrying out an addition reaction on 3-methyl-1-butene and 1, 1, 1-trichlorotrifluoroethane under the action of a catalyst to obtain 2, 2, 4-trichloro-1, 1, 1-trifluoro-5-methylhexane, carrying out an elimination reaction under a strong alkaline condition to obtain 2-chloro-1, 1, 1-trifluoro-5-methyl-2, 4-hexadiene, carrying out a '1 + 2' cycloaddition reaction on the 2-chloro-1, 1, 1-trifluoro-5-methyl-2, 4-hexadiene and a phosphorus ylide reagent to obtain 2-chloro-1, 1, 1-trifluoro-5-methyl-2, 4-hexadiene. And finally, saponifying and acidifying the kung-fu acid methyl ester to obtain the product kung-fu acid. The process is simple to operate, the raw materials are cheap and easy to obtain, the solvent can be recycled, the conversion rate is high, impurities are few, and the method is more suitable for industrial production.

The present application relates to a kind of biological ortho prodrug, composition and its application, specifically disclose a kind of drug prodrug with substituted acrylamide or substituted vinyl sulfonamide structure, is obtained by the reaction of covalent warhead comprising active drug and N-alkyl hydroxylamine.The drug prodrug can be released by Retro-Cope elimination reaction and Cope elimination reaction with tension alkyne, and the release rate can reach more than 90%, to realize on-demand activation active warhead, effectively solve the off-target problem of covalent inhibitor.In addition, by introducing the drug or fluorophore containing hydroxyl / amine group in the propargyl position of tension alkyne, the intermediate produced after Cope elimination reaction of tension alkyne can further undergo elimination reaction, release the drug or fluorophore containing hydroxyl / amine group, realize combined therapy or real-time monitoring of drug release.The above-mentioned drug prodrug and the composition formed by the combination of tension alkyne have good application prospect in the preparation of drug delivery system or active drug.

The invention provides a preparation method of osimertinib, which belongs to the field of chemical synthesis and comprises the following steps: performing palladium-carbon catalytic hydrogenation reduction on a compound I serving as a raw material; after reduction is finished, hydrogen protection is replaced by nitrogen protection, then 3-chloropropionyl chloride and organic alkali are added, after acylation reaction is finished, direct heating is performed to generate elimination reaction, and a compound II osimertinib is obtained through refining. According to the process, reduction acylation elimination is carried out in the same reaction system, meanwhile, 3-chloropropionyl chloride which is cheaper and easier to obtain is used, acryloyl is eliminated and introduced after acylation, and the whole synthesis process is efficient, economical and environmentally friendly. According to the method, a one-pot strategy is utilized for the first time to combine multiple steps of reactions into one step, the reductive acylation elimination reaction of the compound I is simply and efficiently achieved, and synthesis of osimertinib is completed.