- Preparation method of amantadine
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The invention discloses a preparation method of amantadine, which belongs to the technical field of organic chemical synthesis, and is characterized by comprising the following steps: taking a compound adamantane as an initial raw material, generating an intermediate 1-acetamido adamantane in the presence of acetonitrile, a polyion liquid PIL catalyst and sulfuric acid, and then hydrolyzing the intermediate into amantadine in a system of alcohol and alkali. The preparation method is environment-friendly, post-treatment is convenient, the use amount of sulfuric acid and acetonitrile is greatly reduced through the catalyst polyion liquid, and post-treatment is simple. The ionic liquid catalyst can be recycled, so that the cost is greatly saved, and the method is suitable for large-scale industrial production.
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- Amantadine hydrochloride and preparation method thereof
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The invention discloses amantadine hydrochloride and a preparation method thereof, and relates to the technical field of amantadine hydrochloride synthesis. The method aims at solving the problems that the reaction time is too long and the yield of amantadine hydrochloride is not high. The amantadine hydrochloride is prepared from the following components, by weight: 5mmol of nitro compound, 5g ofcatalyst, 15ml of absolute ethyl alcohol, 15ml of concentrated hydrochloric acid, 15ml of hydrazine hydrate and 3ml of sodium hydroxide solution, The preparation method of amantadine hydrochloride comprises the following steps: respectively adding a nitro compound, absolute ethyl alcohol and a catalyst into a 50mL flask; in the production process of the hydrazine hydrate catalytic reduction method, no pollution is caused, the yield is high, the reaction conditions are mild, the yield of the nitro compound is 90%, the conversion rate of the nitro compound subjected to hydrazine hydrate catalytic reduction is 98.5%, the yield of the obtained amantadine hydrochloride is 89.5%, and compared with other processes, the yield is higher, the operation is simple, and the efficiency is high.
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Paragraph 0044; 0057-0064
(2021/03/18)
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- Cyclic (Alkyl)(amino)carbene Ligand-Promoted Nitro Deoxygenative Hydroboration with Chromium Catalysis: Scope, Mechanism, and Applications
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Transition metal catalysis that utilizes N-heterocyclic carbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for the retention of various reducible functionalities and the compatibility of sensitive groups toward hydroboration, thereby providing a mild, chemoselective, and facile strategy to form anilines, as well as heteroaryl and aliphatic amine derivatives, with broad scope and particularly high turnover numbers (up to 1.8 × 106). Mechanistic studies, based on theoretical calculations, indicate that the CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin; it serves as an H-shuttle to facilitate deoxygenative hydroboration. The preparation of several commercially available pharmaceuticals by means of this strategy highlights its potential application in medicinal chemistry.
- Zhao, Lixing,Hu, Chenyang,Cong, Xuefeng,Deng, Gongda,Liu, Liu Leo,Luo, Meiming,Zeng, Xiaoming
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supporting information
p. 1618 - 1629
(2021/01/25)
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- Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents
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Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.
- An, Qing,Chen, Yuegang,Liu, Weimin,Pan, Hui,Wang, Xin,Wang, Ziyu,Zhang, Kaining,Zuo, Zhiwei
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supporting information
p. 6216 - 6226
(2020/04/27)
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- Synthetic method of amantadine hydrochloride (by machine translation)
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Compared, the prior art . the synthesis method: the amantadine hydrochloride has an important clinical value and market value Ritter, and the synthesis process, of the hydrochloric acid adamantanamine, effectively improves the industrial application potential, of the hydrochloric acid adamantane hydrochloride synthesis process as, by adopting a special process and a component, on the one hand for preparation of the medicine, for treating and preventing viral infection, through hydrolysis and purification on the other hand, and effectively solves the problem, of environmental pollution in the synthesis process of the hydrochloric acid adamantanamine by adopting a special process and a component technology; through hydrolysis and purification on an aspect, through hydrolysis and, purification of components . The method mainly, comprises, steps of preparation of an amantadine hydrochloride synthesis process by using a special process and a method. (by machine translation)
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Paragraph 0115; 0119-0122; 0145; 0149-0156; 0157; 0162-0184
(2020/05/29)
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- Method for continuous production of adamantanamine hydrochloride
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The invention aims to provide a method for continuous production of adamantanamine hydrochloride by a high-temperature kneading/spiral propelling reactor. In comparison with a traditional batch reactor, the reaction equipment is small in size and has good reaction stability, helps improve production efficiency by continuous reaction production of amantadine products and more importantly helps avoid the temperature runaway problem of the system, and has good safety. The invention has the prominent characteristics as follows: by using the high-temperature kneading/spiral propelling reactor as the reaction equipment, an aminolysis material can be continuously produced, retention time of the aminolysis material in the equipment can be controlled, side effects are reduced, and the aminolysis material can be removed out of the equipment periodically; in the feeding process, dramatic temperature rise of the system is avoided; and under the condition of high reaction yield, the equipment is small in size, is safe and simple to operate, and has good industrial application value.
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Paragraph 0017-0021
(2019/01/24)
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- Synthetic method of amantadine hydrochloride
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The invention discloses a synthetic method of amantadine hydrochloride. The synthetic method comprises the following steps: preparation of 1-acetamido adamantane, preparation of amantadine and preparation of amantadine hydrochloride, wherein the preparation of the 1-acetamido adamantine comprises the steps of dropwise adding acetonitrile into 20 percent of fuming sulfuric acid, adding a nickel-rhodium bimetallic catalyst and adamantane, rising the temperature, slowly and dropwise adding ice salt water for diluting after completing reaction, extracting, washing, drying, and evaporating and removing a solvent, thus obtaining the 1-acetamido adamantine. The synthetic method disclosed by the invention has the beneficial effects that the alumina supported nickel-rhodium bimetallic catalyst is used for catalyzing acetyl ammoniation reaction of the adamantane, nickel and rhodium are in synergistic effect, the catalytic activity is enhanced, reaction is facilitated to proceed, meanwhile, occurrence of side effects is inhibited, and the yield of a target product is increased; a bromine raw material is prevented from being used, corrosion of bromine to equipment and pollution of the bromineto environment can be avoided, the environmental protection property is good, and the synthetic method is mild in condition, simple and feasible in technology and high in product yield.
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Page/Page column 4-6
(2019/02/17)
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- An Improved Synthesis of Amantadine Hydrochloride
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Amantadine hydrochloride 1 is an antiviral drug used in the prevention and treatment of influenza A infections. It has also been used for alleviating early symptoms of Parkinson's disease. Several methods for the preparation of 1 have been reported. These procedures started with adamantane 2 using as many as four reaction steps to produce amantadine hydrochloride with overall yields ranging from 45% to 58%. In this article, we describe a two-step procedure for the synthesis of 1 from 2 via N-(1-adamantyl)acetamide 4 with an improved overall yield of 67%. The procedure was also optimized to reduce the use of toxic solvents and reagents, rendering it more environment-friendly. The procedure can be considered as suitable for large-scale production of amantadine hydrochloride. The structure of amantadine hydrochloride was confirmed by 1H NMR, 13C NMR, IR, and MS.
- Vu, Duong Binh,Nguyen, Thinh Van,Le, Son Trung,Phan, Chau DInh
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supporting information
p. 1758 - 1760
(2017/11/28)
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- Process for preparation of amantadine free amine amantadine by use of amantadine hydrochloride
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The present invention discloses a process for preparation of amantadine free amine amantadine by use of amantadine hydrochloride, and the process is characterized as follows: in a reaction vessel, water and the amantadine hydrochloride are added in order, the mass ratio of water to amantadine hydrochloride is 1:4, and after even stirring, the pH value is adjusted to 10 with sodium hydroxide or sodium carbonate; and after solid precipitation, the stirring is continued for 0.5h, and a pure free amine amantadine product can be obtained by filtering, washing with water, and drying.
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Paragraph 0057-0061
(2017/02/09)
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- Process for preparing amantadine free amine by using amantadine hydrochloride
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The invention discloses a process for preparing amantadine free amine by using amantadine hydrochloride. The process is characterized by being operated according to the following steps of first adding water and amantadine hydrochloride according to the mass ratio being 1:4 into a reaction still; after uniformly stirring, adjusting the pH value to be 10 by using sodium hydroxide or sodium carbonate; after a solid is separated out, continuously stirring for 0.5h, filtering, washing and drying to obtain an amantadine free amine pure product.
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Paragraph 0057; 0058; 0059; 0060; 0061
(2016/12/16)
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- Purifying method for amantadine hydrochloride waste
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The invention discloses a purifying method for amantadine hydrochloride waste. The purifying method comprises the following steps that 510 L of water, 186 Kg waste and 23.6 L of saturate sodium hydroxide are added in a reaction kettle, steam is introduced into a jacket, the mixture is boiled for 2-3 hours, and pH is maintained to be 9-10 in the period; then, hydrochloric acid is slowly added to regulate the pH value to be 3-4, the mixture is directly filtered, residues are removed, the pH value of an obtained mother solution is regulated to be 10 with alkali liquor (sodium hydroxide), solids are separated out and then filtered, washed with water and dried, and pure amantadine is obtained.
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Paragraph 0057; 0058; 0059; 0060; 0061
(2017/03/18)
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- One-Pot Amination of Cage Hydrocarbons
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A one-pot procedure has been proposed for the synthesis of amines directly from cage hydrocarbons. A number of cage amines have been synthesized by treatment of adamantane, its homologs, and structurally related cage hydrocarbons with nitric acid in acetic acid and subsequent addition of urea and heating.
- Leonova,Skomorokhov,Moiseev,Klimochkin
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p. 1703 - 1709
(2016/02/03)
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- Direct Preparation of Amides from Amine Hydrochloride Salts and Orthoesters: A Synthetic and Mechanistic Perspective
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The conversion of a wide range of primary and secondary aliphatic and a few arylamine hydrochloride salts to their corresponding acetamides with trimethyl orthoacetate is described. Mechanistic studies using NMR and gas chromatography-mass spectrometry techniques indicate these reactions proceed via an O-methylimidate intermediate that undergoes in situ demethylation by chloride, affording the corresponding acetamides. Synthetically, this reaction represents a practical, high-yielding protocol with a simple workup for the rapid conversion of amine hydrochloride salts to acetamides.
- Di Grandi, Martin J.,Bennett, Caitlin,Cagino, Kristen,Muccini, Arnold,Suraci, Corey,Saba, Shahrokh
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supporting information
p. 2601 - 2607
(2015/11/28)
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- A facile deprotection of secondary acetamides
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(Chemical Equation Presented) Imidoyl chlorides, generated from secondary acetamides and oxalyl chloride, can be harnessed for a selective and practical deprotection sequence. Treatment of these intermediates with 2 equiv of propylene glycol and warming enables the rapid release of amine hydrochloride salts in good yields. Notably, the reaction conditions are mild enough to allow for a swift deprotection with no observed epimerization of the amino center.
- Koenig, Stefan G.,Vandenbossche, Charles P.,Zhao, Hang,Mousaw, Patrick,Singh, Surendra P.,Bakale, Roger P.
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supporting information; experimental part
p. 433 - 436
(2009/07/04)
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- N-tosyloxycarbamates as reagents in rhodium-catalyzed C-H amination reactions
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Metal nitrenes for use in C-H insertion reactions were obtained from N-tosyloxycarbamates in the presence of an inorganic base and a rhodium(II) dimer complex catalyst. The C-H amination reaction proceeds smoothly, and the potassium tosylate that forms as a byproduct is easily removed by filtration or an aqueous workup. This new methodology allows the amination of ethereal, benzylic, tertiary, secondary, and even primary C-H bonds. The intramolecular reaction provides an interesting route to various substituted oxazolidinones, whereas the intermolecular reaction gives trichloroethoxycarbonyl-protected amines that can be isolated with moderate to excellent yields and that cleave easily to produce the corresponding free amine. The development, scope, and limitations of the reactions are discussed herein. Isotopic effects and the electronic nature of the transition state are used to discuss the mechanism of the reaction.
- Huard, Kim,Lebel, Helene
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scheme or table
p. 6222 - 6230
(2009/05/27)
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- PROCESS FOR THE PREPARATION OF ADAMANTANAMINES
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The invention relates to a process for preparing certain adamantanamines, of formula (IV) wherein R, R' are each methyl and X is halogen, to intermediates used in the process, and to processes for preparing such intermediates.
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Page/Page column 15-16
(2010/11/28)
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- Synthesis of primary amines by the electrophilic amination of Grignard reagents with 1,3-dioxolan-2-one O-sulfonyloxime
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(Chemical equation presented) Primary amines are prepared by the electrophilic amination of Grignard reagents with 4,4,5,5-tetramethyl-1,3- dioxolan-2-one O-phenylsulfonyloxime and the acidic hydrolysis of the resulting imines.
- Kitamura, Mitsuru,Suga, Takahiro,Chiba, Shunsuke,Narasaka, Koichi
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p. 4619 - 4621
(2007/10/03)
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- Preparation of primary amines by the alkylation of O-sulfonyloximes of benzophenone derivatives with Grignard reagents
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Primary amines are prepared by the electrophilic amination of Grignard reagents with benzophenone O-sulfonyloxime derivatives. 4,4'- Bis(trifluoromethyl)benzophenone O-sulfonyloximes react with alkyl Grignard reagents in the presence of a catalytic amount of CuCN in tetrahydrofuran- hexamethylphosphoric triamide to give N-alkylimines, which are readily hydrolyzed to primary amines. 3,3',5,5'-Tetrakis(trifluoromethyl)benzophenone O-p-tolylsulfonyloxime is arylated to the corresponding N-arylimines with aryl Grignard reagents in ether-toluene, and hydrolysis of the resulting imines gives aniline derivatives.
- Tsutsui, Hironori,Ichikawa, Tomoko,Narasaka, Koichi
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p. 1869 - 1878
(2007/10/03)
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- Preparation of primary amines by the copper(I) catalyzed reaction of 4,4'-bis(trifluoromethyl)benzophenone O-methylsulfonyloxime and alkyl Grignard reagents
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Primary amines are prepared by the reaction of 4,4'-bis-(trifluoromethyl)benzophenone O-methylsulfonyloxime and alkyl Grignard reagents in the presence of a catalytic amount of CuCN-2LiCl and the successive acid hydrolysis of the resulting N-alkylimine derivatives.
- Tsutsui, Hironori,Hayashi, Yujiro,Narasaka, Koichi
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p. 317 - 318
(2007/10/03)
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- Thermolysis of N,N-Dihalo Derivatives of Bridgehead and Neopentylamines to the Corresponding Halides.
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N,N-Dihalo derivatives of (1-adamantyl)- and neopentylamine are converted to the corresponding alkyl halides in excellent yields (88-94percent) during GLC at 155-330 deg C.Decomposition apparently occurs by an SNi mechanism or by intramolecular homolytic cleavage.Intermolecular radical and free-ion reactions are eliminated from consideration because of the absence of radical-derived or rearranged products.Steric factors are deemed important in the neopentyl case since pyrolysis of N,N-dihaloamine gave the corresponding carbonitrile in excellent yield(90-97percent). 1-(Haloamino)adamantanes gave fair amounts of 1-haloadamantanes (30-38percent). 1-(Acetylamino)- and 1-(ethylchloroamino)adamantane yielded 1-chloroadamantane (10-17percent), the major products being the acetamide (60percent) and the ethylamine (56percent), respectively. 1-(Dihaloamino)adamantanes were converted to 1-haloadamantanes by neat (64-70percent) or solution (30-41percent) pyrolysis.
- Roberts, John T.,Rittberg, Barry R.,Kovacic, Peter,Scalzi, Francis V.,Seely, Michael J.
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p. 5239 - 5243
(2007/10/02)
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