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.
Both reactions form one new C–O ester bond and expel one water molecule, so at first glance they look like the same reaction with the same expected equilibrium constant. The difference is entropy, specifically the number of independent molecules on each side of the equilibrium. Equation [1] is bimolecular: two separate, freely tumbling molecules (acetic acid and ethanol) must find each other and collide in a favourable orientation before they can react — this costs a large amount of translational and rotational entropy, which opposes the forward reaction and keeps Keq modest (here, 4).
Equation [2] is unimolecular: the carboxylic acid and the alcohol are already tethered together in the same molecule (4-hydroxybutanoic acid), so the "collision" is really just an internal rotation bringing the two ends of a single flexible chain together — no intermolecular collision, and essentially no translational entropy cost, is required. This favourable intramolecular effective molarity (chemists estimate the "effective concentration" of the tethered nucleophile at often 10–105 M, far higher than any real bulk solution concentration) drives the forward cyclisation strongly, and the resulting 5-membered ring lactone (γ-butyrolactone) is itself a low-strain, stable ring — both effects push Keq for the intramolecular reaction dramatically higher (here, 1000, a 250-fold difference) even though the same bond (an ester C–O) is being formed and the same small molecule (water) is being lost in both cases.
