2007-11-6

Usage

Uses

Used in Pharmaceutical Industry:
Propranolol N-Acetyl Impurity is used as an impurity in the production of propranolol for its antihypertensive, antianginal, and antiarrhythmic properties. It plays a crucial role in the development and formulation of propranolol-based medications, which are essential in the treatment of various cardiovascular conditions.
As a β-adrenergic blocker, propranolol is effective in managing high blood pressure, angina pectoris (chest pain due to insufficient blood supply to the heart), and certain types of arrhythmias (irregular heartbeats). The presence of Propranolol N-Acetyl Impurity in the production process ensures the quality and efficacy of the final propranolol-based pharmaceutical products.

Upstream product

• 108-24-7 acetic anhydride 
• 525-66-6 propranolol 
• 70153-33-2 N-[2-acetyloxy-3-(1-naphthalenyloxy)propyl]-N-(1-methylethyl)acetamide 
• 318-98-9 Inderal 
• 75-36-5 acetyl chloride 
• 2461-42-9 3-(1-naphthyloxy)-1,2-epoxypropane 
• 90-15-3 α-naphthol 
• 129459-75-2 1-(isopropylamino)-3-(naphthalen-1-yloxy)propan-2-yl acetate 
• 4290-58-8 O-acetylpropranolol hydrochloride 

Relevant academic research and scientific papers

Photodegradation products of propranolol: The structures and pharmacological studies

Recently, single-dose drug packaging systems, allowing the administration of multiple drugs in a single pill, have become popular for the convenience of the patient. The quality of drugs and an accurate measurement of their photostabilities within this system, however, have not been carefully addressed. Drugs that are unstable in light should be carefully handled to protect their potency and ensure their safety. Propranolol (1), a β-adrenergic receptor antagonist, is widely used for angina pectoris, arrhythmia, and hypertension. Due to its naphthalene skeleton, this drug may be both light unstable and a photosensitizing agent. In this study, we isolated three photodegraded products of propranolol (1): 1-naphthol (2), N-acetylpropranolol (3), and N-formylpropranolol (4). The structures of these compounds were determined by spectroscopic methods and chemical syntheses. We also examined the acute toxicities of these substances in mice and their binding to β-adrenergic receptors using rat cerebellum cortex membranes. Although the photoproducts isolated in this study did not exhibit any acute toxicity or significant binding to β-adrenergic receptors, these results serve as a warning to single-dose packaging systems, as propranolol (1) must be handled carefully to protect the compound from light-induced degradation.

Facile Synthesis of Propranolol and Novel Derivatives

Propranolol is one of the first medications of the beta-blocker used for antihypertensive drugs. This study reports the facile route for the synthesis of propranolol and its novel derivatives. Herein, propranolol synthesis proceeded from 1-naphthol and isopropylamine under mild and less toxic conditions. Novel propranolol derivatives were designed by reactions of propranolol with benzoyl chloride, pyridinium chlorochromate, and n-butyl bromide through esterification, oxidation reduction, and alkylation, respectively. The isolation and purity of compounds were conducted using column chromatography and thin-layer chromatography. Mass spectrometry and 1H-NMR spectroscopy were applied to identify new compounds structure. Propranolol derivatives from 2-chlorobenzoyl chloride (compound 3), 2-fluorobenzoyl chloride (compound 5), and especially acetic anhydride (compound 6) manifested high yields and significantly increased water solubility. Six semisynthetic propranolol derivatives promise to improve antioxidative and biological activities.

Acetylation of (R,S)-propranolol catalyzed by Candida antarctica lipase B: An experimental and computational study

The chemo- and enantioselectivity of the Candida antarctica lipase B (CalB)-catalyzed acetylation reaction of (R,S)-propranolol using vinyl acetate as acyl donor and toluene as organic solvent was studied. Because of the poor solubility of propranolol in toluene small quantities of methanol were added as cosolvent. The effects of the propranolol/vinyl acetate ratio, the enzyme purification procedure and the methanol concentration on the reaction were investigated. The reactions occurring in the system were quantitatively investigated using 1H and 13C NMR spectroscopy. The major reactions were the hydrolysis and alcoholysis of vinyl acetate, as a consequence of the presence of residual water and methanol in the reaction medium. Furthermore, the NMR analysis confirmed that O-acetyl-propranolol was formed exclusively. The reaction was also found to be enantioselective favoring the faster transformation of the R-propranolol. In addition to the experiments, molecular modeling was used to study the formation of the reactive Michaelis complexes between propranolol and acetylated CalB, using a combined molecular docking and molecular dynamics (MD) procedure. Only for the O-acetylation we found binding modes of the substrate leading to formation of the product, which explains the experimentally observed chemoselectivity of CalB.

Process for inverting the configuration in optically active compounds

The invention relates to a process for inverting the configuration in optically active compounds of the formula STR1 in which Ar1 represents a monocyclic or polycyclic, carbocyclic or heterocyclic radical that has at least one ring of aromatic character and is bonded to the oxygen atom by way of a ring carbon atom, preferably of the ring of aromatic character, and R1 represents an optionally substituted aliphatic, cycloaliphatic or araliphatic hydrocarbon radical, or the salts thereof, characterised in that an optically active compound of the formula STR2 having a R(+) or S(-) configuration, in which R2 represents a monocyclic or polycyclic, carbocyclic or heterocyclic radical, or an optionally substituted aliphatic, cycloaliphatic or araliphatic hydrocarbon radical, is converted, by treating with a strong oxygen-containing inorganic or organic acid or halides thererof, into an optically active compound of the formula STR3 in which X? represents the anion of a strong, oxygen-containing inorganic or organic acid or of a halogen atom and the resulting compound of the formula III is hydrolysed, optionally by way of the corresponding free base as intermediate, to form a compound of the formula I of a configuration opposite to that of the starting material used and, if desired, a free compound of the formula I is converted into a salt or a resulting salt is converted into the free compound.