Chemical Properties
Off-White Solid
Uses
Bevantolol is a cardioselective β-adrenergic blocker. Bevantolol is used as an antianginal, antihypertensive, antiarrhythmic.
Definition
ChEBI: The hydrochloride salt of bevantolol.
Brand name
Vantol (Parke-Davis).
Hazard
Moderately toxic by ingestion.
Description
Bevantolol hydrochloride is a cardioselective (β1) adrenergic blocker, devoid of intrinsic
sympathomimetic and local anesthetic activities. As with other agents of this category, it
is useful in the treatment of hypertension and angina.
Originator
Warner-Lambert (USA)
Manufacturing Process
To a solution of 50 g (1.25 mol) of NaOH in 1200 ml H2O was added 108 g (1
mol) of m-cresol freshly distilled and at 15°C in one lot 117ml (1.5 mol) of
epichlorohydrin. The emulsion was stirred at room temperature for 16 hours in
a creased flask. The product was taken up in 1000 ml of toluene and washed
with 500 ml water. Distillation yielded 135.7 g=82% of 3-(m-tolyloxy)-1,2-
epoxypropane, b.p. 61°C at 0.05 mm.
Preparation of bevantolol hydrochloride:
To a suitable reactor under a nitrogen blanket is added 13.7 kg of β-(3,4-
dimethoxyphenyl)ethylamine. The amine is cooled to 5°C and 12.5 kg of 3-
(m-tolyloxy)-1,2-epoxypropane is added maintaining the temperature between
5-10°C. After 10 hours, the mixture is seeded with bevantolol free base;
seeding is repeated approximately every 2 hours until it is evident that
crystallization has started. After stirring for 48 hours at 10°C, 26 L of hexane
is added. The temperature is raised to 25°C and stirring is continued for 48
hours. The slurry is filtered and the collected solid is dried under vacuum. The
product is dissolved in 60 L of isopropyl alcohol and the solution is filtered.
The reactor and filter are rinsed with 186 L of isopropyl alcohol and 2.7 kg of
anhydrous hydrogen chloride is added to the combined filtrate. The batch is
heated to reflux for 2 hours. The temperature is adjusted to 65°C and the
solution is seeded with bevantolol hydrochloride crystals. The mixture is held
at this temperature with stirring until a heavy sand-like slurry is present. The
mixture is allowed to cool to ambient temperature without stirring or artificial
cooling. It is then cooled to 20°C. The slurry is centrifuged and the product
rinsed with isopropyl alcohol until the filtrate is colorless. After being vacuum
dried at 50-55°C the product is milled if necessary; yield of bevantolol
hydrochloride 22.7 kg (78.6%); melting point 137-138°C.
Therapeutic Function
Antiarrhythmic, Beta-adrenergic blocker
Safety Profile
A poison by intraperitoneal andintravenous route. Moderately toxic by ingestion. Whenheated to decomposition it emits toxic vapors of NOx,HCl, and Cl-.
References
[1] Tetrahedron Asymmetry, 2016, vol. 27, # 9-10, p. 397 - 403
[2] Journal of Molecular Structure, 2009, vol. 936, # 1-3, p. 171 - 176
