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.
a) The keto form. Curcumin's central 1,3-diketone-derived unit –C(=O)–CH=C(OH)– simply tautomerises to –C(=O)–CH2–C(=O)–, moving the enolic proton onto the adjacent carbon and restoring a second carbonyl:
This particular enol is unusually stable, for three compounding reasons: (1) it is a 1,3-dicarbonyl-derived enol, so the C=C of the enol is conjugated with the remaining carbonyl on the other side, not isolated as in a simple enol; (2) that whole enone unit is further conjugated with two styryl (CH=CH–Ar) arms and two aryl rings, extending the π-system across the entire molecule; and (3) the enolic O–H sits perfectly positioned to form a strong intramolecular, six-membered-ring hydrogen bond to the adjacent carbonyl oxygen. All three factors stabilise the enol tautomer far more than they stabilise the keto (diketo) form, so curcumin exists overwhelmingly as the enol shown in the source, unlike a simple ketone (e.g. acetone), whose enol content is negligible.
b) Why the enol O–H is more acidic than a plain alcohol O–H. Deprotonating the enol gives an anion whose negative charge is delocalised by resonance directly onto the adjacent carbonyl oxygen (through the conjugated C=C–C=O system), effectively converting it into an enolate that is stabilised exactly like a carboxylate — the negative charge is shared over two electronegative oxygens rather than being localised on one. Deprotonating a simple alcohol, by contrast, leaves the negative charge entirely localised on a single oxygen with no resonance stabilisation available. Greater delocalisation of the resulting anion means a lower-energy (more stable) conjugate base, which by definition means a stronger acid (lower pKa) for the enol O–H.
c) Why curcumin is coloured. Colour requires a chromophore that absorbs visible light, which in turn requires a HOMO–LUMO gap small enough to fall in the visible range (∼1.8–3.1 eV). Curcumin's fully conjugated system — two aromatic rings linked through an extended chain of alternating double bonds (two styryl C=C's conjugated through the central enol/enone unit) — delocalises its π electrons over a very long path. Extending conjugation lowers the energy gap between the highest occupied and lowest unoccupied molecular orbitals (particle-in-a-box-type reasoning: a longer conjugated system has more closely spaced energy levels), shifting absorption from the UV (where a small isolated chromophore like a single alkene absorbs) into the visible blue region — curcumin absorbs blue light strongly, and the light that is transmitted/reflected (its complementary colour) is perceived as yellow.
d) Why curcumin is an antioxidant. The same phenolic –OH groups on both aromatic rings (as in vitamin E or BHT) can donate a hydrogen atom to a reactive free radical, quenching it. Critically, the resulting phenoxyl radical is itself highly stabilised: the unpaired electron is delocalised by resonance around the aromatic ring and, because the ring is directly conjugated to the rest of curcumin's extended π-system (via the styryl linkage), the radical can delocalise even further into the central enol/diketone unit. A radical that is this well stabilised is much less reactive/dangerous than the radical it just quenched, so the chain reaction of radical damage (e.g. lipid peroxidation) is broken rather than propagated — the hallmark of an effective radical-scavenging antioxidant.
