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) 1,2-Epoxycyclohexane. Treat cyclohexene with a peroxyacid (e.g. m-CPBA) in one step: the peroxyacid delivers an oxygen atom across the double bond in a concerted syn addition, giving the epoxide directly.
b) Cyclohexanecarbonitrile (two steps). (1) Markovnikov hydrohalogenation: cyclohexene + HBr → bromocyclohexane. (2) SN2 displacement with sodium cyanide (NaCN, a good nucleophile) installs the nitrile, displacing bromide.
c) Cyclohexyl propyl ether (two steps, Markovnikov). Oxymercuration–demercuration of cyclohexene in 1-propanol as solvent/nucleophile (Hg(OAc)2, then NaBH4) adds the alcohol across the double bond with Markovnikov regiochemistry and no carbocation rearrangement, giving the secondary ether directly in effectively one operational step (acid-catalysed direct addition of 1-propanol works too, but is more prone to rearrangement).
d/e) The trans-difunctionalised, racemic ("+enantiomer") pairs — both routed through the same epoxide from part (a). Opening 1,2-epoxycyclohexane with a nucleophile proceeds by backside (SN2-like) attack at one of the two equivalent epoxide carbons, which necessarily places the incoming nucleophile anti to the oxygen that remains as the alcohol — the product is always the trans-1,2-difunctionalised cyclohexane. Because cyclohexene and m-CPBA are both achiral, the epoxidation in part (a) creates the two epoxide enantiomers in equal amounts (a racemate), and the nucleophile is equally likely to open either one from the required backside face — so the ring-opening product is necessarily obtained as the racemic trans pair (+ enantiomer), exactly as stated in both targets.
For (d), open the epoxide with a sulfur nucleophile such as sodium hydrosulfide (NaSH):
For (e), open the epoxide with sodium acetylide (HC≡C–Na, from acetylene + NaNH2):
