Base behaviour, nucleophilic substitution, condensation.
Amides resistant to hydrolysis.
Aromatic compounds
Electrophilic substitution, side-chain reactions.
Keep aromatic ring intact in most conditions.
Construct your own flowchart linking conversions; exam questions often request multi-step synthesis.
2 Stereochemistry
Chirality: Carbon with four different substituents → enantiomers. Use wedge-dash notation; specify R/S using Cahn-Ingold-Prelog rules.
Optical activity: Enantiomers rotate plane-polarised light in opposite directions; racemates have no net rotation.
Geometric isomerism: Occurs in alkenes with restricted rotation when distinct substituents present. Describe as E/Z using CIP priority.
State stereochemical outcomes in mechanisms (e.g. S_N2 inversion of configuration).
3 Mechanism Templates
3.1 Electrophilic Addition to Alkenes
Electron-rich double bond attacks electrophile EX+.
Carbocation intermediate forms (consider rearrangements).
Nucleophile attacks carbocation.
Include regioselectivity explanation (Markovnikov). Provide energy profile diagram if asked.
3.2 S_N1 vs S_N2
Feature
S_N1
S_N2
Substrate
Tertiary > secondary.
Primary > methyl.
Rate law
rate = \(k [\ce{RX}]\)
rate = \(k [\ce{RX}][\ce{Nu^-}]\)
Mechanism
Carbocation intermediate, racemisation.
One-step backside attack, inversion.
Solvent
Polar protic stabilises carbocation.
Polar aprotic favours nucleophile.
3.3 Electrophilic Aromatic Substitution
Generation of electrophile (e.g. NOX2X+ from HNOX3+HX2SOX4).
Electrophile attacks pi electrons, forming arenium ion.
Deprotonation restores aromaticity.
Remember directing effects: activating (ortho/para) vs deactivating (meta).
4 Oxidation and Reduction Summary
Conversion
Reagent/conditions
Observation
Primary alcohol → aldehyde
\(\ce{K2Cr2O7/H^+}\), heat and distil.
Orange to green solution; collect distillate.
Primary alcohol → carboxylic acid
\(\ce{KMnO4/H^+}\), reflux.
Purple to colourless/brown precipitate.
Aldehyde → carboxylic acid
Tollens' or Fehling's.
Silver mirror or brick-red ppt.
Carbonyl → alcohol
\(\ce{NaBH4}\) (aqueous) or \(\ce{LiAlH4}\) (dry ether).
Reduction; specify work-up.
Carboxylic acid → alcohol
\(\ce{LiAlH4}\), dry ether, followed by water.
Powerful reducing agent (dangerous, exothermic).
Tie observations to qualitative analysis (Paper 4).
5 Spectroscopy Checklist
5.1 Infrared (IR)
Functional group
Stretch
Approx. wavenumber \(\pu{cm-1}\)
O-H (alcohol)
Broad
\(\pu{3200-3550 cm-1}\)
O-H (acid)
Very broad with tail
\(\pu{2500-3300 cm-1}\)
C=O
Strong sharp
\(\pu{1680-1750 cm-1}\) (ketone at lower end, acid higher)
N-H (amine)
Medium
\(\pu{3300-3500 cm-1}\) (one or two peaks)
5.2 Proton NMR
Chemical shift ranges: alkyl (0.5-2.0), protons near electronegative atoms (3-4.5), alkenic (5-6), aromatic (6-8), aldehyde (9-10), carboxylic acid (10-12).
Integration ratio reveals relative number of protons.
Splitting pattern obeys n + 1 rule (ignore exchangeable protons in acids/alcohols).
5.3 Carbon-13 NMR
Supports identification of carbon environments (no splitting). Use along with proton NMR.
5.4 Mass Spectrometry
Molecular ion peak MX+ indicates molar mass.
Fragmentation patterns suggest functional groups (e.g. M−15 implies loss of CHX3).
6 Worked Synthesis Problem
Question:
Propose a synthesis route to convert benzene into 4-nitrobenzoic acid. Include reagents, conditions, and key mechanism justifications.
Outline:
Nitration:CX6HX6HNOX3/HX2SOX4CX6HX5NOX2 at 55∘C. Electrophilic substitution; nitro group is meta-directing.
Friedel-Crafts alkylation not suitable (nitro deactivates ring). Instead, consider side-chain oxidation:
a. Reduce nitrobenzene to phenylamine? Not necessary; choose different route.
Side-chain introduction: Perform Friedel-Crafts acylation before nitration to control directing effects. Revised sequence:
CX6HX6CHX3COCl/AlClX3CX6HX5COCHX3
Better approach:
Nitration first: obtain nitrobenzene (meta-directing). To get 4-substitution, use protecting strategy:
Sulfonation introduces SO3H (meta-directing), used as blocking group.
Improved route:
Sulfonate benzene: CX6HX6fumingHX2SOX4CX6HX5SOX3H (SOX3H is meta-directing, so nitration occurs ortho/para? Actually SOX3H is deactivating meta).
Simplify for exam-friendly answer: start with methylbenzene.
Accepted sequence:
Friedel-Crafts alkylation:CX6HX6CHX3Cl/AlClX3CX6HX5CHX3 (toluene). CHX3 is ortho/para directing.
Discuss isomer mixture (ortho and para). Explain purification (fractional crystallisation) to isolate para isomer due to melting-point difference. Provide mechanistic justification for directing effects.
7 Exam Strategies
Mechanism marks: Include curly arrows, partial charges, and intermediate structures. Label slow step if relevant.
Synthetic planning: Work backwards (retrosynthesis) to identify functional group transformations. Mention reagents, conditions (temperature, catalyst), and by-products.
Spectroscopy interpretation: Combine data types systematically-deduce degree of unsaturation from 22C+2−H; use IR to identify functional groups; match NMR signals to structure.
Paper 4: When planning organic experiments, highlight drying agents, reflux/distillation apparatus, hazard mitigation (e.g. LiAlHX4 reacts violently with water).
8 Common Pitfalls
Forgetting to regenerate catalyst in electrophilic aromatic substitution mechanism.
Confusing reagent choices (e.g. NaBH4 reduces ald/ket but not carboxylic acids).
Ignoring stereochemistry in addition reactions (e.g. hydrogenation produces syn addition).
Misreading NMR integration (ratios must be simplified to whole numbers).
9 Quick Drills
Predict products (with mechanisms) when 2-bromobutane reacts with (a) NaOH(aq) and (b) NaOEt(ethanol) under reflux.
Deduce the structure of compound X (Mr=88) given: IR strong peak at 1715cm−1, 1H NMR shows a quartet at 4.1ppm (integration 2) and a triplet at 1.3ppm (integration 3). Suggest identity and justify.
Outline reagents and conditions to convert propanone to 2-methyl-2-propanol.
Organic chemistry rewards a well-organised reaction map and precise mechanistic language. Continue rehearsing with multi-step synthesis questions and visit https://eclatinstitute.sg/blog/h2-chemistry-notes for supporting practice material.
