Synthesized Procainamide: Clinical Effects

Heart muscles are controlled by neurons in the same way as neurons communicate with one another by action potential process. As the membrane potential reaches -50mV, Sodium channels are triggered to open leading to depolarization of the membrane due to Sodium rush into cytoplasm. The channels are inactivated when membrane potential reaches +40mV. Potassium channels then open releasing potassium into the excellular environment till membrane potential is slightly smaller than -70 mV (the resting potential). Arrythmia occurs when neuron triggers irregularly. Procainamide temporarily blocks sodium channels from the extracellular side. The blocking rate is increased by polarization (Sodium channel opening) and decreased by hyperpolarization. It thus lengthens the time to initiate an action potential cycle and gives nervous system time to adjust to normal heartbeats.

To end up with synthesized Procainamide, two major parts of the Procainamide molecule are produced: p-amino-benzyol bromide and diethyl ethylene diamine. The formation of amide bond can readily occur by SN₂ between NH₂ and COCl terminals. Protection for amine is removed later on by HBr In most preparatory reactions, the stoichiometry is 1:1.

Part1: By nucleophilic aromatic substitution (NAS) and electrophilic aromatic substitution (EAS), amino and methyl groups are added para to each other in the referred order. The para product can be isolated through crystallization. Also, adding NH₂ first will be more effective for addition of the methyl group later due to the fact that the amino group is a strongly activating group. The disubstituted product is oxidized to produce p-amino benzoic acid. Amino terminal of diethyl ethylene diamine is protected by benzyl chloroformate. OH of Carboxylic group is then replaced by bromide with SOBr₂. Acyl bromide terminal will not react with protected amino group.

Part 2: Diethylamine is produced by substitution from alkyl halide and ammonia in an approximately 2:1 ratio to reduce trisubstitution. The product is isolated and then reacts with ethylene bromide in a 1:1 ratio. Diethyl ethylene diamine is finally produced by substituting bromide with amino group in reaction with ammonia.

Finally the result is synthesized Procainamide, which has a structure of IUPAC nomenclature: 4-amino-N-(2-diethylaminoethyl) benzamide

Sources cited:

Brooker, Widmaier, Graham and Stiling. Biology 1^st ed. 2007. McGraw-Hill, NYC.

Goodman and Gilman. 1996. 1793 pages. McGraw-Hill, NYC.

Clayden, Greeves, Warren, Wothers .Organic Chemistry.2001. Oxford University Press.

Zamponi, G.X, Sui, X., Codding, P.W, and French, R.J. 1993. Dual actions of procainamide on batrachotoxin-activated sodium channels: open channel block and prevention of inactivation. Biophys J. 65(6): 2324-2334.