61-75-6

Basic information

• Product Name: BRETYLIUM TOSYLATE
• Synonyms: (o-bromobenzyl)ethyldimethyl-ammoniup-toluenesulfonate;2-bromo-n-ethyl-n,n-dimethylbenzenemethanaminium4-methylbenzenesulfonate;2-bromo-n-ethyl-n,n-dimethyl-benzenemethanaminiusaltwith4-methylbenzen;2-bromo-n-ethyl-n,n-dimethyl-benzenemethanaminiusaltwith4-methylbenzenes;asl-603;bretylan;bretylate;bretyliump-toluenesulfonate
• CAS NO: 61-75-6
• Molecular Formula: C₇H₇O₃S*C₁₁H₁₇BrN
• Molecular Weight: 414.36
• EINECS: 200-516-8
• Product Categories: Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 61-75-6.mol
• Article Data: 1

Chemical Properties

• Melting Point: 97-99°
• Appearance: white/
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: H2O: soluble50mg/mL
• CAS DataBase Reference: BRETYLIUM TOSYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: BRETYLIUM TOSYLATE(61-75-6)
• EPA Substance Registry System: BRETYLIUM TOSYLATE(61-75-6)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• RTECS: BO9450000
• Hazardous Substances Data: 61-75-6(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Originator

Bretylate,Wellcome,UK,1973

Uses

Bretylium tosylate has a biphasic response, initially inducing norepinephrine release followed by sympathetic ganglionic blockade. Bretylium tosylate is a class III antiarrhythmic agent and a competitive inhibitor of acetylcholinesterase.

Definition

ChEBI: The tosylate salt of bretylium. It blocks noradrenaline release from the peripheral sympathetic nervous system, and is used in emergency medicine, cardiology, and other specialties for the acute management of ventricular tachycardia and ventricular fibril ation.

Manufacturing Process

N-o-Bromobenzyl-N,N-dimethylamine (100g) and ethyl p-toluenesulfonate (94 g) were mixed and warmed to 50°-60°C; after standing for either (a) a minimum of 96 hours at 15°-20°C or (b) a minimum of 18 hours at 50°-60°C and cooling to room temperature, a hard, crystalline mass was formed. Recrystallization of this product from acetone (2.0 ml/g of crude solid), followed by filtration and drying to 60°C gave N-o-bromobenzyl-N-ethyl-N,Ndimethylammonium p-toluenesulfonate as a white, crystalline solid, MP 97°- 99°C. For this procedure it was necessary that the reactants were substantially colorless and of a high purity.

Therapeutic Function

Adrenergic blocker; Antiarrhythmic

General Description

Bretylium tosylate, (o-bromobenzyl)ethyl dimethylammonium p-toluenesulfonate(Bretylol), is an extremely bitter, white, crystalline powder.The chemical is freely soluble in water and alcohol.Bretylium tosylate is an adrenergic neuronal-blockingagent that accumulates selectively in the neurons anddisplaces norepinephrine. Because of this property,bretylium was used initially, under the trade name ofDarenthin, as an antihypertensive agent. It caused posturaldecrease in arterial pressure. This use was discontinuedbecause of the rapid development of tolerance, erratic oralabsorption of the quaternary ammonium compound, andpersistent pain in the parotid gland on prolonged therapy.

Clinical Use

Currently, bretylium is reserved for use in ventriculararrhythmias that are resistant to other therapy. Bretyliumdoes not suppress phase 4 depolarization, a common actionof other antiarrhythmic agents. It prolongs the effectiverefractory period relative to the action potential durationbut does not affect conduction time and is categorized asa class III antiarrhythmic agent. Because bretylium doesnot have properties similar to those of the other antiarrhythmicagents, it has been suggested that its action is aresult of its adrenergic neuronal-blocking properties; theantiarrhythmic properties of the drug, however, are notaffected by administration of reserpine. Bretylium is also alocal anesthetic, but it has not been possible to demonstratesuch an effect on atria of experimental animals, except atvery high concentrations. Therefore, the precise mechanismof the antiarrhythmic action of bretylium remains tobe resolved.

Side effects

The major adverse effect associated with bretylium tosylate is hypotension, including orthostatic hypotension, which may be very severe.

InChI:InChI=1/C11H17BrN.C7H8O3S/c1-4-13(2,3)9-10-5-7-11(12)8-6-10;1-6-2-4-7(5-3-6)11(8,9)10/h5-8H,4,9H2,1-3H3;2-5H,1H3,(H,8,9,10)/q+1;/p-1

Synthetic route

2-bromo-N,N-dimethylbenzylamine (1976-04-1) + ethyl ester of p-toluenesulfonic acid (80-40-0) → bretylium tosylate (61-75-6)

Conditions	Yield
In acetone for 12h; Reflux;

Upstream product

• 1976-04-1 2-bromo-N,N-dimethylbenzylamine 
• 80-40-0 ethyl ester of p-toluenesulfonic acid 

Relevant articles and documents

Process for the production of bretylium tosylate

A method of producing pharmaceutical grade bretylium tosylate comprising low amounts of mutagenic impurities. The method comprises forming bretylium tosylate having a purity of less than 99.5% and purifying the bretylium tosylate by: i) forming a slurry of the bretylium tosylate with a mixture of acetone and ethyl acetate; ii) filtering the slurry to obtain purified bretylium tosylate. The bretylium tosylate so produced has a purity of at least 99.5%, and suitably comprises less than 0.5 ppm of the potentially mutagenic impurity ethyl p-toluenesulfonate. The bretylium tosylate so produced also suitably comprises less than 0.5 ppm of the potentially mutagenic impurity 2-bromobenzylbromide.