99-45-6

Usage

Originator

Adrenalone ,Yick-Vic Chemicals and Pharmaceuticals (HK) Ltd.

Uses

Adrenalone is a ketone derivative of Epinephrine (E588585) and a potential dopamine β oxidase inhibitor.

Preparation

Preparation by reaction of excess 33% aqueous methylamine with 3,4-dihydroxy-a-chloroacetophenone.

Manufacturing Process

To a suspension of 1 part ω-chloro-3,4-dihydroxyacetophenone (prerared from chloroacetyl chloride and benzcatechole, see J. Russ. Phys. Chem. Ges., 25, 154) was added dropwise 1 part 60% solution of methylamine. Immediately was formed a residue of the salt of methylamine and ω-chloro-3,4- dihydroxyacetophenone. The dissolution of the salt was carried out by heating of the mixture. Then the salt was converted in crude 3,4-dihydroxy-α- methylaminoacetophenone. The product was dissolved in dilute hydrochloric acid. To this solution was added dropwise aqueous ammonium solution to prepare light yellow crystal of 3,4-dihydroxy-α-methylaminoacetophenone. The base and the hydrochloride of 3,4-dihydroxy-α-methylaminoacetophenone decomposed at temperature near 230°C and 240°C respectively.

Therapeutic Function

Hemostatic, Sympathomimetic, Vasoconstrictor

InChI:InChI=1/C9H11NO3/c1-10-5-9(13)6-2-3-7(11)8(12)4-6/h2-4,10-12H,5H2,1H3

Upstream product

• 29705-77-9 3,4-Dimethoxy-ω-methylaminoacetophenon 
• 74-89-5 methylamine 
• 51-43-4 L-epinephrine 
• 99-40-1 2-chloro-3',4'-dihydroxyacetophenone 
• 858005-73-9 N-(2-(3,4-dimethoxyphenyl)-2-oxoethyl)-4-methylbenzenesulfonamide 
• 7647-01-0 hydrogenchloride 
• 858842-22-5 N-(3,4-dimethoxy-phenacyl)-N-methyl-toluene-4-sulfonamide 
• 619-60-3 4-(N,N-dimethylamino)phenol 
• 29477-55-2 3,4-dihydroxyphenylglyoxal 
• 100945-19-5 2-chloro-1-[3,4-bis(acetyloxy)phenyl]ethanone 

Downstream Products

• 51-43-4 L-epinephrine 
• 150-05-0 (S)-4-[1-hydroxy-2-(methylamino)ethyl]pyrocatechol 
• 62-13-5 1-(3,4-dihydroxyphenyl)-1-oxo-2-methylamino-ethan-hydrochlorid 
• 103565-58-8 (+/-)-2-(acetyl-methyl-amino)-1-(3,4-dihydroxy-phenyl)-ethanol 
• 854886-20-7 (3,4-bis-benzoyloxy-phenacyl)-methyl-carbamic acid ethyl ester 
• 21093-18-5 dl-epinephrine-4-O-sulfate 
• 112346-91-5 dl-epinephrine-3-O-sulfate 
• 619-60-3 4-(N,N-dimethylamino)phenol 
• 80098-05-1 adrenalone-3-O-sulfate 
• 80098-06-2 adrenalone-4-O-sulfate 
• 99855-92-2 N-(2-(3,4-dihydroxyphenyl)-2-oxoethyl)-N-methylacetamide 
• 101878-49-3 benzyl (2-(3,4-dihydroxyphenyl)-2-oxoethyl)(methyl)carbamate 
• 329-65-7 Epinephrine 

Relevant academic research and scientific papers

Visible-Light-Mediated Amination of π-Nucleophiles with N-Aminopyridinium Salts

N-Aminopyridinium salts generate nitrogen-centered radicals by means of photoredox catalysis. Herein, we report that they can be trapped by enol equivalents to give α-amino carbonyl compounds in excellent yields. The broad synthetic utility of this method is demonstrated by functionalization of ketones, aldehydes, esters enol equivalents, vinyl ethers, and 1,3-diketones without the need for prior conversion to enol derivatives. The developed method is easily scalable, offers broad substrate scope, high chemoselectivity.

Preparation method of adrenalone hydrochloride

The invention relates to a preparation method of adrenalone hydrochloride. In a process of preparing the adrenalone hydrochloride from chloracetyl catechol and methylamine, reaction is controlled to be carried out in an alcohol solution and tetrabutylammonium bromide or tetrabutylammonium iodide is selected as a phase transfer catalyst. According to the method provided by the invention, the reaction is controlled to be carried out in the alcohol solution and sufficient proceeding of the reaction is promoted; meanwhile, the tetrabutylammonium bromide or the tetrabutylammonium iodide is added to be used as the phase transfer catalyst, so that the reaction is accelerated, the reaction time is shortened and the accumulation of impurities is reduced. The adrenalone hydrochloride with high quality can be prepared at a single time without the need of refining, and a high-quality intermediate is provided for preparation of L-adrenaline.

Purification and characterization of a novel carbonyl reductase involved in oxidoreduction of aromatic β-amino ketones/alcohols

Aromatic β-amino ketones/alcohols such as adrenalone play an important role in some stereoselective synthesis of pharmaceuticals. Unfortunately, the transformation of aromatic β-amino ketones to their chiral alcohols has been carried out chemically as no corresponding biocatalyst has been available. Here, a novel carbonyl reductase responsible for the reduction of adrenalone to (R)-(-)-epinephrine was identified and characterized from Kocuria rhizophila. This enzyme was purified to homogeneity by ammonium sulfate precipitation followed by ion-exchange column chromatography, hydrophobic chromatography and gel chromatography. The purified enzyme yielded pure (R)-enantiomer product with high activity and utilized NADH as the cofactor. The enzyme had special significance by showing selectivity for many aromatic β-amino ketones/alcohols such as 2-amino-acetophenone, 2-amino-4′- hydroxyacetophenone, isoproterenol and ephedrine. The maximum reaction rate (Vmax) and apparent Michaelis-Menten constant (Km) for adrenalone and NADH were 14.62 μmol/(min mg) protein and 0.189 mM, 11.66 μmol/(min mg) protein and 0.204 mM respectively. These properties ensure the enzyme a promising future for industrial application as a replacement of chemical synthesis of aromatic β-amino chiral alcohols.

Selective hydrogenolysis process

A relatively simple, economical process for the synthesis of epinine and related compounds is described. The process involves subjecting adrenalone, epinephrine or their respective congeners to selective hydrogenolysis using hydrogen and a metal hydrogenolysis catalyst such as palladium, platinum, rhodium or nickel. Preferably the reaction is conducted in a non-oxidizing acidic liquid reaction medium, such as in aqueous hydrochloric acid.

One-Electron Redox Potentials of Phenols. Hydroxy- and Aminophenols and Related Compounds of Biological Interest

The rate constants for reversible electron transfer between a series of substituted phenolate ions and anilines and various substituted phenoxyl or anilino radicals in aqueous solution were measured by observing the formation or depletion of the radicals involved.Nonequilibrium concentrations of the radicals were produced in the presence of the corresponding phenols or anilines by using the pulse radiolysis technique.The relaxation of the system to equilibrium was monitored by optical detection methods.From the equilibrium constants for one-electron transfer, the one-electron redox potentials (E2) for 38 phenolic or anilino type compounds were determined, many of which are natural products.The redox potentials are strongly influenced by electron-donating or -withdrawing substituents at the aromatic system.