Organic Synthesis, Separation, and Identification
Organic Synthesis, Separation, and Identification
This domain tests route planning, safe execution of organometallic and protecting-group chemistry, and the practical separation and identification of products.
Core rules
- Work backwards: identify the target, disconnect at C–C or C–heteroatom bonds, and check each synthon is a real reagent. Use protecting groups only where needed and ensure orthogonality (Boc with acid-labile acetal; TBS with fluoride; Cbz with hydrogenolysis).
- Grignard reagents form in Et2O or THF from aryl/alkyl halides with magnesium turnings; exclude water and acidic protons, and initiate with iodine or 1,2-dibromoethane if needed. Organolithiums (n-BuLi, t-BuLi) require low temperature and inert atmosphere.
- Work up by careful quenching, acid–base extraction, drying over MgSO4 or Na2SO4, and concentration without overheating sensitive products.
- TLC is the rapid check: choose an eluent giving target Rf ≈ 0.3–0.4; visualise by UV, KMnO4, ninhydrin, or phosphomolybdic acid. Flash chromatography uses silica and the same eluent, with gradient elution only if needed.
- Recrystallisation: choose a solvent pair, dissolve hot, filter hot, cool slowly, wash with cold solvent. Confirm purity by melting point, NMR, IR, and MS.
Worked example
Bromobenzene (2.00 g, 12.7 mmol) with magnesium (0.35 g, 14.4 mmol) in THF gives PhMgBr. Benzophenone (1.10 g, 6.00 mmol) is added; the Grignard is in excess. The limiting reagent is the ketone, so the theoretical yield of triphenylmethanol (M = 260.3 g mol⁻¹) is 6.00 × 10⁻³ × 260.3 = 1.56 g. Isolating 1.12 g gives 72%. The calculation identifies the ketone as limiting and prevents a false yield above 100%.
Traps
Quenching the Grignard before adding the electrophile; ignoring the actual limiting reagent; overloading a silica column; co-eluting impurities because TLC was run in a different solvent; discarding the aqueous layer before checking it.