04-BS-12 · December 2019
Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)
National Exam 04-BS-12, Organic Chemistry — December 2019. 3 hours, closed-book examination (no calculator; 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. (functional groups, stereochemistry, SN1/SN2 mechanisms and stereochemistry, steroid/bile-acid amphiphilicity, named-drug synthesis design, reaction-energy diagrams, polymer chemistry, arene-oxide metabolism, and mass-spectral/IR/NMR structure elucidation). Every molecular formula, exact mass, and stereochemical (R/S, cis/trans, meso/chiral) 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 release one water molecule, so at first glance they look thermodynamically similar — but the intermolecular reaction (Eq. 1) must first bring two separate, independently-tumbling molecules (acetic acid and ethanol) together into a single, precisely-oriented encounter complex before reaction can occur. This costs a large amount of translational and rotational entropy (ΔS is strongly negative for combining two particles into one activated complex), which works against the reaction and keeps Keq modest.
In the intramolecular reaction (Eq. 2), the carboxylic acid and the alcohol are already tethered together in the same molecule; the reactive groups have a very high effective local concentration relative to each other (they are always "nearby," connected by a flexible chain) and no translational entropy needs to be sacrificed to bring two separate molecules together — only the much smaller cost of restricting internal rotation to reach the cyclic transition state. Because so much less unfavourable entropy is paid, the intramolecular (lactonisation) equilibrium lies far further toward product, giving the dramatically larger Keq = 1000 for a favourable ring size (here a six-membered lactone, which forms with essentially no ring strain).
