04-BS-12 · December 2016
Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)
National Exam 04-BS-12, Organic Chemistry — December 2016. 3 hours, closed-book examination (no non-communicating calculator restriction beyond the standard aid sheet, 8.5×11", hand-written both sides). Ten questions constitute a complete exam paper (only the first 10 questions as they appear in the answer book are marked, each of equal value) — the source paper in fact prints thirteen questions; all thirteen are answered in full below.
Reference texts: McMurry, Organic Chemistry, 9th ed. (acid/base theory of drugs, SN1/SN2 stereochemistry, carbocation rearrangements, alkyne synthesis via acetylide alkylation, IR/NMR structure elucidation, electrophilic aromatic substitution and synthesis design, amino-acid pKa); Clayden, Organic Chemistry, 2nd ed. (amide resonance and β-lactam reactivity, radical vs. ionic HBr addition mechanisms); a standard biomaterials reference for the poly(ester amide) drug-delivery polymer chemistry of Question 13 (Katsarava-type AABB poly(ester amide)s built from diacids, diols, and protected diamino acids).
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.
Approach. Every target is reached by choosing an installation order for the ring substituents that respects each existing group's directing effect (o,p- vs. meta-director) and the well-known limitations of Friedel–Crafts chemistry (alkyl halides prone to carbocation rearrangement – use acylation + reduction instead; FC reactions fail outright on a ring already bearing NO2; free anilines poison the AlCl3 catalyst – protect first).
(a) 4-Bromoaniline. Br must be installed before nitration, because Br (o,p-director) then directs the incoming NO2 para (major product); nitrating first would put NO2 on (a meta-director), sending any subsequent Br meta to it instead of the required para relationship.
(b) 2-Bromo-4-nitrotoluene. Methylate first (FC alkylation is safe here – CH3Cl cannot rearrange), then nitrate para to CH3 (major), then brominate: with both CH3 (o,p-director) and NO2 (meta-director) present, the position ortho to CH3 and meta to NO2 is doubly reinforced.
(c) 1-(2-Isopropyl-5-nitrophenyl)ethanone. Install the isopropyl group first (FC alkylation is safe – a secondary cation is already the most stable arrangement, no further rearrangement pathway), then acylate ortho to it (the minor FC-acylation regiochemical outcome – para is statistically major, so the ortho isomer must be isolated from the mixture), then nitrate: isopropyl (o,p-director) and the newly installed acetyl (meta-director) both reinforce the same position (para to isopropyl, meta to acetyl).
(d) 4-Aminobenzoic acid (PABA). The methyl group must be installed and nitrated before being oxidised to –COOH, because –COOH itself is a meta-director and would send NO2 to the wrong (meta) position; oxidising the methyl only at the very end, after NO2 is already correctly placed para to it, sidesteps that problem entirely.
(e) Sodium 4-propylbenzenesulfonate. A straight-chain propyl group cannot be installed by direct FC alkylation (the intermediate 1° propyl cation would hydride-shift to the more stable 2° isopropyl cation) — acylate then reduce the carbonyl completely instead, which locks in the unrearranged straight chain.
(f) 4-Bromo-2-propylaniline. This target needs Br meta to the propyl group, which no single o,p-director can ever deliver directly (an o,p-director's own meta position is always disfavoured). The resolution is to install NH2 (ortho to propyl, via nitration and reduction) before brominating: the free/protected amine is such a powerful o,p-director that it completely dominates the ring's regiochemistry once installed, sending Br to its own para position — which happens to be exactly the propyl group's meta position.
(g) Reconstructed target.
A vinyl (styryl) group is installed by the standard acylate→reduce-to-alcohol→dehydrate sequence, since there is no direct FC method to attach –CH=CH2 itself:
| Part | Key strategic choice |
|---|---|
| a | halogenate before nitrate (Br directs para cleanly; NO2 would not) |
| b | alkylate→nitrate(para)→halogenate (both directors reinforce) |
| c | alkylate→acylate(minor ortho)→nitrate (both directors reinforce) |
| d | alkylate→nitrate(para)→oxidise CH3→COOH last→reduce |
| e | acylate+reduce (avoid FC-alkylation rearrangement) then sulfonate |
| f | install NH2 before Br so the amine's dominant directing effect controls regiochemistry; protect as acetanilide to avoid polybromination |
| g | (reconstructed) acylate→reduce→dehydrate for the vinyl group; halogenate last |
