04-BS-12 · December 2018
Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)
National Exam 04-BS-12, Organic Chemistry — December 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. (Brønsted acid–base sites in drugs, SN1/SN2 mechanism selection, Williamson ether synthesis, SN2 stereochemistry at a stereocentre, steroid/bile-acid amphiphilicity, named-drug synthesis design, fatty-acid melting-point trends, epoxide/alkene interconversion chemistry, radical stability and antioxidants, Diels–Alder stereochemistry, bicyclic-ketal pheromone synthesis, arene-oxide metabolism, and mass-spectral/IR/NMR structure elucidation). Every molecular formula, exact mass, and stereochemical (R/S, cis/trans) 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.
a) Classification. Benzene → arene oxide is an oxidation: cytochrome P450 (a mono-oxygenase, using O2 and NADPH) adds one oxygen atom across a ring C=C, and the average carbon oxidation state increases as the new C–O bonds are formed — a textbook Phase I oxidative metabolism step. Arene oxide → phenol is neither oxidation nor reduction: it is an intramolecular rearrangement (the "NIH shift" — the strained epoxide opens, a hydride shifts, and the ring re-aromatises with loss of a proton), and arene oxide and phenol are simply isomers (both C6H6O) — no oxygen is gained or lost and no change in overall oxidation level occurs in this second step.
| Step | Classification | Reasoning |
|---|---|---|
| Benzene → arene oxide | Oxidation | O atom added across a C=C (P450 mono-oxygenase); formula gains one O |
| Arene oxide → phenol | Neither | intramolecular NIH-shift rearrangement; both are C6H6O isomers, no net redox change |
b) Why phenol is more water-soluble, and why it matters. Phenol's –OH group can both donate and accept hydrogen bonds with water, whereas benzene is a purely non-polar hydrocarbon that can only engage water through weak van der Waals contacts (and in fact disrupts water's own hydrogen-bond network, making it thermodynamically unfavourable to dissolve) — "like dissolves like," and the polar O–H makes phenol far more compatible with a polar solvent despite carrying the same aromatic ring. This matters directly for the excretion pathway described in the question stem: the whole point of Phase I oxidative metabolism (P450) is to convert lipophilic, membrane-permeant, hard-to-excrete xenobiotics into more polar, water-soluble metabolites (often taken further still by Phase II conjugation — glucuronidation or sulfation of the new phenolic OH) that can be filtered by the kidney and eliminated in urine rather than re-absorbed and accumulated in fatty tissue.
