04-BS-12 · May 2018
Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)
National Exam 04-BS-12, Organic Chemistry — May 2018. 3 hours, closed-book examination (one Casio/Sharp-approved calculator and one hand-written aid sheet permitted); NOTES on page 1 state that TEN (10) questions constitute a complete exam paper and only the first 10 as they appear in the answer book are marked, but this sitting prints 13 numbered questions — every question and sub-part below is answered in full.
Reference texts: McMurry, Organic Chemistry, 9th ed. (drug acid–base/salt pharmacokinetics, steroid/bile-acid amphiphilicity, arene-oxide metabolism, cyclopropane stereochemistry and CIP assignment, reaction-energy diagrams, ester equilibria and intramolecular effective molarity, SN2 stereochemistry at a common stereocentre, named-drug synthesis design, epoxide ring-opening stereochemistry, mass-spectral formula discrimination, opioid IR/NMR structure elucidation, keto–enol tautomerism and conjugation/acidity, and condensation-polymer monomer identification). Every molecular formula, mass-balance, exact-mass, and stereochemical (R/S) assignment below.
Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.
Cocaine hydrochloride is an ionic solid: the tertiary amine nitrogen is protonated and paired with a chloride counter-ion, so the crystal is held together by strong Coulombic (ion–ion) forces between full positive and negative charges. Crack (the neutral free base) is a covalent molecule held together only by weaker van der Waals/dipole forces. Ionic lattices require far more energy to separate into the gas phase than molecular solids, so cocaine hydrochloride has the much higher boiling/decomposition point — in practice the salt does not boil at all before it chars, whereas the free base has an appreciable vapour pressure and volatilises (sublimes/vaporises) around 90–100 °C without decomposing.
This same ionic-vs.-covalent split governs solubility. The neutral free base is largely non-polar/lipophilic (soluble in organic solvents, poorly soluble in water) — exactly the property needed to cross the lipid membranes of the lungs when its vapour is inhaled by smoking, giving very fast absorption into the bloodstream. The hydrochloride salt is ionic and highly water-soluble, which makes it useless for smoking (it would decompose, not vaporise, and would not cross a lipid membrane efficiently as an ion) but ideal for dissolving in aqueous solution for direct intravenous injection, bypassing the membrane-crossing step entirely. Route of administration for basic drugs is therefore engineered around exactly this free-base/salt solubility contrast.
