- Kinetic and polarographic study on atropine N-oxide: its obtaining and polarographic reduction
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The work presents the obtaining of atropine N-oxide using various peroxyacids (organic monoperoxyacid, diperoxyacids and inorganic peroxyacids). The kinetics of atropine oxidation with various oxidants, for example Oxone, m-chloroperoxybenzoic acid, diperoxysebasic acid and diperoxyazelaic acid, was studied. The optimal conditions for obtaining of atropine N-oxide (oxidation duration, pH) are given in the work. It was established that the best oxidant was potassium peroxymonosulfate, since 100% yield of atropine N-oxide was achieved within 15?min. In this work, we showed that the oxidation reaction of atropine to N-oxide was a second-order reaction. The rate constants of these reactions were established. The electrochemical behavior of atropine N-oxide obtained using potassium peroxymonosulfate and m-chloroperoxybenzoic acid on a mercury dropping electrode was investigated. Atropine N-oxide was reduced forming two peaks. Each reduction peak involved 1 electron and 1 proton.
- Dubenska, Liliya,Dushna, Olha,Blazheyevskiy, Mykola,Pysarevska, Solomiya,Klymiuk, Iryna
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Read Online
- Synthesis method of atropine sulfate
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The invention belongs to the field of chemical synthesis, and particularly relates to a preparation method of atropine sulfate. The preparation method comprises the following steps: firstly preparing tropine ester, then preparing atropine, salifying to prepare atropine sulfate, and finally refining to obtain the product. In the preparation process of the tropine ester, the reaction temperature is strictly controlled to be 105-111 DEG C, and the crystallization temperature is controlled to be 0-5 DEG C, so that the yield of the tropine ester is improved. In the process of preparing atropine through reduction reaction, palladium-carbon is adopted as a catalyst, and the reaction temperature is strictly controlled to be 10-15 DEG C, so that the product quality is effectively improved. Sulfuric acid is diluted by preparing a sulfuric acid ethanol solution, and the dripping speed of the sulfuric acid ethanol solution is controlled, so that the stable quality of atropine sulfate is ensured.
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- Synthesis method of atropine and atropine sulfate
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The invention provides a synthesis method of atropine and atropine sulfate, which comprises the following steps: carrying out acetylation reaction on tropine acid to form acetyl tropine acid, reactingthe acetyl tropine acid with a chlorination reagent to form acyl chloride, reacting the acyl chloride with tropine alcohol, removing acetyl to obtain atropine, and salifying atropine and sulfuric acid to obtain atropine sulfate. The whole synthesis process can be completed by adopting a one-pot reaction, additional steps for completing the process by isolating intermediates are avoided, the reaction conditions are mild, the steps are simple, the yield is high, the purity is high, and the method is suitable for large-scale industrial production.
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Paragraph 0042; 0046-0048; 0050; 0054-0056; 0058; 0062-0064
(2020/07/02)
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- Method for preparing atropine
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The present invention relates to a method for manufacturing atropine. More specifically, the present invention relates to the method for manufacturing atropine which can manufacture and crystallize atropine by effectively removing impurities remaining in a crude atropine sulfate monohydrate using activated carbon and leaving sulfate by an acid-base reaction, thereby being able to obtain high purity atropine.(AA) 5802/atropine(BB) AtropineCOPYRIGHT KIPO 2020
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Paragraph 0065-0083
(2019/11/19)
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- Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine
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Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9.
- Bédard, Anne-Catherine,Longstreet, Ashley R.,Britton, Joshua,Wang, Yuran,Moriguchi, Hideki,Hicklin, Robert W.,Green, William H.,Jamison, Timothy F.
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supporting information
p. 6233 - 6241
(2017/09/30)
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- An anti-choline medicine preparation method of atropine sulfate
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The invention provides a synchronizing method of atropine sulphate. The method is characterized in that hydrolyzing methyl phenoxyacetate (II) is hydrolyzed to obtain a compound (III); the compound (III) and thionyl chloride are subjected to acylation reaction to obtain a compound (IV); the compound (IV) and 8-methyl-8-azabicyclo[3.2.1]oct-3-alchol are subjected to condensation reaction to obtain a compound (V); the compound (V) and paraformaldehyde are used for producing atropine (VI) under an alkaline condition; the atropine (VI) is salified under an acidic condition to obtain the atropine sulphate (I). The preparation method is simple in technology, high in yield, high in purity, low in monomer impurity and easy for industrial production.
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- Can Accelerated Reactions in Droplets Guide Chemistry at Scale?
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Mass spectrometry (MS) is used to monitor chemical reactions in droplets. In almost all cases, such reactions are accelerated relative to the corresponding reactions in bulk, even after correction for concentration effects, and they serve to predict the likely success of scaled-up reactions performed in microfluidic systems. The particular chemical targets used in these test studies are diazepam, atropine and diphenhydramine. In addition to a yes/no prediction of whether scaled-up reaction is possible, in some cases valuable information was obtained that helped in optimization of reaction conditions, minimization of by-products, and choice of catalyst. In a variant on the spray-based charged droplet experiment, the Leidenfrost effect was used to generate larger, uncharged droplets and the same reactions were studied in this medium. These reactions were also accelerated but to smaller extents than in microdroplets, and they gave results that correspond even more closely to microfluidics data. The fact that MS was also used for online reaction monitoring in the microfluidic systems further enhances the potential role of MS in exploratory organic synthesis.
- Wleklinski, Michael,Falcone, Caitlin E.,Loren, Bradley P.,Jaman, Zinia,Iyer, Kiran,Ewan, H. Samuel,Hyun, Seok-Hee,Thompson, David H.,Cooks, R. Graham
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p. 5480 - 5484
(2016/11/26)
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- PROCESS FOR PREPARATION OF ATROPINE
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A process for the production of atropine is provided. The process provides for a new, efficient and commercially feasible synthetic process for the preparation of atropine and atropine salts. In one aspect, a one pot process for the synthesis of atropine is provided. The process provides excellent yield and can be used to prepare commercial 5 scale batches of atropine or atropine salts. The process avoids the additional steps of having to isolate intermediates to complete the process and has the advantage of proceeding efficiently at ambient temperature for many of the steps. The process includes providing acetyltropoyl chloride and reacting the acetyltropoyl chloride with tropine followed by a contact with an acid to form atropine.
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- CRYSTALLINE ATROPINE SULFATE
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The present invention relates to crystalline polymorph form of Atropine sulfate and process for the preparation thereof.
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- N-Demethylation of N-methyl alkaloids with ferrocene
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Under Polonovski-type conditions, ferrocene has been found to be a convenient and efficient catalyst for the N-demethylation of a number of N-methyl alkaloids such as opiates and tropanes. By judicious choice of solvent, good yields have been obtained for dextromethorphan, codeine methyl ether, and thebaine. The current methodology is also successful for the N-demethylation of morphine, oripavine, and tropane alkaloids, producing the corresponding N-nor compounds in reasonable yields. Key pharmaceutical intermediates such oxycodone and oxymorphone are also readily N-demethylated using this approach.
- Kok, Gaik B.,Scammells, Peter J.
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supporting information; experimental part
p. 4499 - 4502
(2010/09/15)
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- Further investigation of the N-demethylation of tertiary amine alkaloids using the non-classical Polonovski reaction
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The iron salt-mediated Polonovski reaction efficiently N-demethylates certain opiate alkaloids. In this process, the use of the hydrochloride salt of the tertiary N-methyl amine oxide was reported to give better yields of the desired N-demethylated product. Herein, we report further investigation into the use of N-oxide salts in the iron salt-mediated Polonovski reaction. An efficient approach for the removal of iron salts that greatly facilitates isolation and purification of the N-nor product is also described.
- Thavaneswaran, Shanti,Scammells, Peter J.
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p. 2868 - 2871
(2007/10/03)
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- Isotopically labelled tropane alkaloids. The synthesis of (RS)-[3′, 3′-2H2]- and (RS)-[1′-13C, 3′, 3′-2H2]- hyoscyamines for metabolism studies in plants
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A synthetic route to isotopically labelled forms of the tropane alkaloid hyoscyamine, including (RS)-[3′, 3′,-2H2]- (2a) and (RS)-[1′-13C, 3′, 3′,-2H2]- (2b) hyoscyamines, involving the reaction betwe
- Patterson, Stephen,O'Hagan, David
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p. 191 - 198
(2007/10/03)
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- Differential analgesic activity of the enantiomers of atropine derivatives does not correlate with their muscarinic subtype selectivity
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The enantiomers of several tropic and p-substituted tropic acid esters related to atropine obtained by esterification under non-racemizing conditions after resolution of the corresponding racemic acids [(+)- and (-)-18, (+)- and (-)-19] are reported. They were tested in vitro on muscarinic subtype receptors and in vivo for their analgesic activity on mice. As in the case of the lead compound, R-(+)-hyoscyamine, these substances show enantioselectivity in analgesic tests, the eutomers being the R-(+) or R-(+)-p-substituted tropic acid derivatives. However, this property, which is a consequence of increased central release of ACh, seems unrelated to muscarinic subtype selectivity insofar as the compounds are unable to discriminate muscarinic subtype receptors. A possible explanation of these results which does not involve subtype selectivity is proposed, based on the recently developed concept of inverse agonism.
- Dei,Bartolini,Bellucci,Ghelardini,Gualtieri,Manetti,Romanelli,Scapecchi,Teodori
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p. 595 - 605
(2007/10/03)
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- Detection and identification of side reactions of halogenated hydrocarbon solvents with amines of pharmaceutical interest by secondary processes to the neutralizations of sulphonphthaleinic dyes with these amines
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The neutralization reactions between amines and diprotic acid dyes in organic solvents generate {dye-, amineH+} and {dye2-, (amineH+)2} ion associates that show two absorption bands in the visible spectrum. An unidentified third absorption band; which appears with a high amine concentration, proves that halogenated hydrocarbon solvents (dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride) give side reactions with amines (atropine, tropine, quinine, ephedrine, and ajmaline) that generate a quaternary ammonium salt, N-halogenalkylammonium halide ({N+- RX,X-}). The molecular weight of the quaternary ammonium salt is the sum of the amine and that of the solvent. The {N+-RX,X-} ion associated reacts with {dye2-, (amineH+)2} by substitution reactions, forming {dye2-, amineH+, N+-RX} and {dye2-, (N+-RX)2} ion associates that justify the third absorption band. The amine-solvent side reactions are of first order with respect to the amine, being very slow processes with rate constant values from 399.4 h-1 (tropine-dichloromethane reaction) to 15.8 h-1 (atropine-1,2-dichloroethane reaction). Rate constants increase with the basicity of the amine measured in the halogenated hydrocarbons employed. Rate constants also increase with a reduction in the number of the halogen atoms present in the halogenated solvent. The new visible absorption band that appears in the amine-dye neutralization gives a quick colorimetric test to bring to light this kind of side reaction in these solvents.
- Gainza,Konyeaso,Asenjo
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p. 226 - 232
(2007/10/02)
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