Chapter 13: High-Yield Cheat Sheet
This is the MCAT organic chemistry cheat sheet you wish you had the week before test day. Every functional group, every reaction arrow, every spectroscopy value from all 12 chapters, compressed into one page. Nomenclature, stereochemistry, SN1/SN2/E1/E2, carbonyl chemistry, carboxylic acid derivatives, amines, IR and NMR reference tables, separations. The MCAT does not ask you to name every obscure reagent - it asks you to recognize what changes in a reaction and why. That is what this page condenses.
1. Bonding and Structure Review
Hybridization from steric number: sp = 2 (linear, 180°), sp² = 3 (trigonal planar, 120°), sp³ = 4 (tetrahedral, 109.5°).
- s character ↑ → shorter, stronger bond; more acidic terminal H (sp-H is most acidic of C-H bonds)
- π bonds come from unhybridized p orbitals, not hybrids
- Rotation free around σ bonds, restricted around π bonds (gives rise to cis/trans)
- Resonance delocalizes electrons without moving atoms - use curved arrows for electron pairs
- Aromaticity (Hückel’s rule): cyclic, planar, fully conjugated, (4n+2) π electrons. Benzene = 6 π e⁻ (n=1).
Inductive vs resonance effects: inductive = through σ bonds, falls off with distance; resonance = through π system, requires overlap geometry. Electron-donating groups (EDG): alkyl, -OR, -NR₂, -NHR (via resonance). Electron-withdrawing groups (EWG): -NO₂, -CN, -COR, -COOR, halogens (σ-withdrawing, π-donating).
2. IUPAC Nomenclature (Quick Rules)
Priority for principal chain / suffix:
Carboxylic acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne > alkane (and > substituent halides/alkyl groups).
Lowest locants go to (in order): principal group, then multiple bonds, then substituents.
Common functional group suffixes:
| Functional Group | Suffix | Example |
|---|---|---|
| Carboxylic acid | -oic acid | ethanoic acid (acetic) |
| Ester | -oate | methyl ethanoate |
| Amide | -amide | ethanamide |
| Aldehyde | -al | ethanal |
| Ketone | -one | propan-2-one (acetone) |
| Alcohol | -ol | ethanol |
| Amine | -amine | ethanamine |
| Alkene | -ene | ethene |
| Alkyne | -yne | ethyne |
E/Z designation (alkenes): assign CIP priorities to each substituent on each sp² carbon. Z = higher priorities on same side (“zusammen” = together). E = opposite sides.
3. Stereochemistry and Isomers
Isomer hierarchy:
- Constitutional (structural) isomers: different connectivity
- Stereoisomers: same connectivity, different 3D arrangement
- Enantiomers: non-superimposable mirror images (all chiral centers inverted)
- Diastereomers: stereoisomers that are NOT mirror images (some but not all chiral centers differ, or cis/trans, or conformational)
- Meso compounds: have chiral centers but an internal mirror plane → achiral overall
Chirality: a carbon is chiral (stereogenic) if it has four different groups. Compound is chiral if it lacks any improper symmetry element (no mirror plane, no inversion center).
CIP (R/S) assignment:
- Assign priorities 1-4 to the four groups (highest atomic number wins; use isotope mass to break ties; use point of first difference).
- Orient lowest priority (4) away from you.
- Trace 1 → 2 → 3: clockwise = R, counterclockwise = S.
- If lowest priority is toward you, determine direction as usual, then reverse the answer.
Fischer projection rules: horizontal bonds point toward you, vertical away. Switching two groups inverts the stereocenter. D/L sugars: look at the highest-numbered chiral center - OH on right = D, on left = L.
| Relationship | Physical Properties | Optical Activity |
|---|---|---|
| Enantiomers | Identical (except rotating polarized light opposite directions) | Equal magnitude, opposite sign |
| Diastereomers | Different (mp, bp, solubility, reactivity) | Generally different |
| Meso | - | Achiral, does not rotate light |
| Racemic mixture | Same as pure enantiomer (except optics) | Net zero rotation |
Max # stereoisomers for a molecule with n chiral centers = (reduced by meso forms).
Newman projections: along a C-C bond. Staggered (60°/180° dihedrals) lower energy than eclipsed. Anti > gauche > eclipsed > fully eclipsed (rising energy).
4. Acids and Bases in Orgo (pKa table)
Orgo thinks about acidity/basicity as a proxy for reactivity. The lower the pKa of the conjugate acid, the weaker the base - so a good leaving group has a low conjugate-acid pKa.
| Compound | Approx. pKa of relevant H |
|---|---|
| HI, HBr, HCl | -10 to -6 (strong acids) |
| H₂SO₄ (1st H) | -3 |
| H₃O⁺ | -1.7 |
| HF | 3 |
| Carboxylic acid (RCOOH) | 4-5 |
| β-diketone α-H | ~9 |
| Ammonium (R-NH₃⁺) | ~9-11 |
| Thiol (RSH) | ~10 |
| Phenol (C₆H₅OH) | 10 |
| H₂O | 15.7 |
| Alcohol (ROH) | 16-18 |
| α-H of ketone/aldehyde | 19-20 |
| Terminal alkyne (RC≡CH) | 25 |
| Ammonia (NH₃) | 38 |
| Alkene (vinyl H) | 44 |
| Alkane (RH) | ~50 |
Factors that stabilize the conjugate base (and therefore increase acidity):
- ARIO: Atom (size + EN), Resonance, Induction, Orbital (s-character).
- Resonance delocalization (phenol > alcohol).
- Electronegative adjacent groups stabilize negative charge (trifluoroacetic acid ≫ acetic acid).
- More s character → more stable anion (sp > sp² > sp³).
- Larger atom better stabilizes negative charge (HI ≫ HF by the time you factor in bond strength and polarizability).
5. Common Reaction Intermediates (Stability)
Carbocation stability: 3° > 2° > 1° > methyl. Also stabilized by resonance (allylic, benzylic) and by adjacent heteroatoms with lone pairs.
Carbanion stability: methyl > 1° > 2° > 3° (opposite of cations). Stabilized by EWGs and s-character.
Radical stability: 3° > 2° > 1° > methyl (same order as cations, for the same hyperconjugation reasons, but less pronounced).
Leaving group ability: weak bases leave best. I⁻ > Br⁻ > Cl⁻ > F⁻ > TsO⁻ (tosylate) > H₂O > ROH > NH₂⁻ > R⁻ (last two basically never leave).
6. SN1 / SN2 / E1 / E2 (the Big Four)
Rules of thumb:
- Strong bulky base (KOtBu, LDA) → E2 (Hofmann product - less substituted alkene).
- Strong unhindered nucleophile, polar aprotic → SN2.
- Weak nucleophile / weak base, polar protic, 3° substrate → SN1/E1 mix.
- 1° substrate does NOT do SN1 or E1 (primary carbocation too unstable).
- Allylic / benzylic substrates activate SN1 and E1 via resonance-stabilized cation.
SN2 inversion: called Walden inversion - incoming nucleophile pushes leaving group out from the opposite face, “umbrella flips.”
E2 anti-periplanar: H and LG must be ~180° apart. Critical for cyclohexanes - both must be axial (trans-diaxial).
7. Alkene and Alkyne Reactions
Markovnikov’s rule: in H-X addition, H goes to the carbon with more Hs (the less substituted C); X goes to the more substituted C → more stable carbocation.
Anti-Markovnikov: radical H-Br with peroxides (HBr/ROOR); also hydroboration-oxidation.
| Reaction | Reagent | Product | Stereo |
|---|---|---|---|
| Hydrogenation | H₂, Pd/Pt/Ni | Alkane | Syn |
| Halogenation | X₂ (Br₂, Cl₂) | Vicinal dihalide | Anti |
| Halohydrin | X₂, H₂O | β-haloalcohol | Anti, Markovnikov |
| Hydrohalogenation | HX | Alkyl halide | Markovnikov |
| Hydration (acid-cat.) | H₂O, H⁺ | Alcohol | Markovnikov |
| Oxymercuration | Hg(OAc)₂, H₂O; then NaBH₄ | Alcohol | Markovnikov, no rearrangement |
| Hydroboration | BH₃; then H₂O₂/OH⁻ | Alcohol | Anti-Markovnikov, syn |
| Epoxidation | mCPBA | Epoxide | Syn |
| Dihydroxylation | OsO₄/KMnO₄ (cold) | syn-diol | Syn |
| Ozonolysis | O₃; then Zn/H₂O or Me₂S | 2 carbonyls (cleaves C=C) | - |
Terminal alkynes can be deprotonated (pKa ~25) by NaNH₂ → acetylide (strong nucleophile for SN2 on 1° alkyl halides).
8. Alcohols, Phenols, Ethers
Alcohol preparations: see alkene hydration, Grignard + carbonyl, reduction of carbonyls.
Alcohol oxidation:
| Starting material | Reagent | Product |
|---|---|---|
| 1° alcohol | PCC | Aldehyde |
| 1° alcohol | CrO₃ / K₂Cr₂O₇ / KMnO₄ | Carboxylic acid |
| 2° alcohol | PCC, CrO₃, K₂Cr₂O₇ | Ketone |
| 3° alcohol | None of the above | No reaction |
Alcohol → halide: SOCl₂ (→ R-Cl), PBr₃ (→ R-Br), HX (Markovnikov on alkene-forming intermediates).
Phenols are more acidic than alcohols (pKa ~10 vs 16-18) because of resonance stabilization of the phenoxide.
Ether synthesis (Williamson): alkoxide + alkyl halide (SN2). Use 1° alkyl halide to avoid E2.
Epoxide ring-opening:
- Acidic conditions: nucleophile attacks more substituted C (stabler partial carbocation).
- Basic conditions: nucleophile attacks less substituted C (steric control).
9. Carbonyl Chemistry (Aldehydes and Ketones)
Electrophilic carbonyl C: the C=O dipole makes the carbon δ⁺ - nucleophiles attack here.
Key nucleophilic addition reactions:
| Nucleophile | Product |
|---|---|
| Grignard (RMgX) / organolithium (RLi) | Alcohol (adds R group) |
| NaBH₄ | 1° or 2° alcohol (mild, won’t touch esters/carboxylic acids) |
| LiAlH₄ | 1° or 2° alcohol (strong; reduces esters, acids, amides) |
| H₂O + acid/base cat. | Hydrate (gem-diol) - unfavorable for most |
| 1 alcohol, acid cat. | Hemiacetal/hemiketal |
| 2 alcohols, acid cat. | Acetal/ketal (protecting group) |
| Primary amine (RNH₂) | Imine (Schiff base) |
| Secondary amine (R₂NH) | Enamine |
| HCN | Cyanohydrin |
| PPh₃=CR₂ (Wittig) | Alkene |
Aldehyde vs ketone reactivity: aldehydes > ketones (less steric hindrance, fewer electron-donating alkyls).
α-carbon chemistry:
- Enol ↔ keto tautomerization (acid or base catalyzed). Keto dominates; enol needed for halogenation/aldol.
- α-halogenation: α-H replaced with X.
- Aldol condensation: enolate of one carbonyl attacks another carbonyl; dehydration gives α,β-unsaturated carbonyl.
- Haloform reaction: methyl ketone + X₂ + base → CHX₃ + carboxylate.
10. Carboxylic Acids and Derivatives
Reactivity order (Nu attack, via addition-elimination):
Each derivative can be made from something higher in reactivity, not lower.
Key transformations:
| Starting | Reagent | Product |
|---|---|---|
| Carboxylic acid + alcohol | H⁺, heat | Ester (Fischer esterification, reversible) |
| Carboxylic acid | SOCl₂ or PCl₃ | Acid chloride |
| Acid chloride + alcohol | - | Ester |
| Acid chloride + amine | - | Amide |
| Ester + H₂O | acid or base | Carboxylic acid + alcohol (saponification with base) |
| Amide + H₂O | acid or base, heat | Acid + amine (slow) |
| Ester + LiAlH₄ | - | 1° alcohol + alcohol |
| Amide + LiAlH₄ | - | Amine |
| RCOOH | LiAlH₄ | 1° alcohol |
Decarboxylation: β-keto acids and β-diacids lose CO₂ on heating. Key in aldol/Claisen variants.
Nitriles (R-C≡N): hydrolysis gives carboxylic acid; reduction with LiAlH₄ gives 1° amine; Grignard addition gives ketone after hydrolysis.
11. Amines and Nitrogen Chemistry
Amine basicity: aliphatic amines (pKa of conjugate acid ~10-11) are basic (N lone pair available). Aromatic amines (aniline, pKa ~4.6) are less basic - lone pair delocalized into ring. Amides are essentially non-basic (lone pair conjugated to carbonyl).
Preparation:
- Reductive amination: ketone/aldehyde + amine → imine → reduction (NaBH₃CN) → amine
- Gabriel synthesis: phthalimide + alkyl halide → 1° amine (after hydrolysis)
- Hofmann/Curtius rearrangement: amide → amine with loss of a carbon
- Nitrile reduction (LiAlH₄) → 1° amine
Hofmann elimination: quaternary ammonium + base → less-substituted alkene (Hofmann product).
Phosphorus compounds (brief): phosphate groups are the key linkage in DNA/RNA and ATP. Pyrophosphate (PPi) is a great leaving group. Phosphorus is sp³ in phosphate esters.
12. Spectroscopy Reference
IR (Infrared)
IR shows functional groups via bond-vibration frequencies (cm⁻¹).
| Absorption (cm⁻¹) | Bond | Shape/Notes |
|---|---|---|
| 3200-3600 | O-H (alcohol) | Broad |
| 2500-3300 | O-H (carboxylic acid) | Very broad |
| 3300-3500 | N-H | Sharper than O-H; 1° amine = 2 peaks |
| ~3300 | C≡C-H (terminal alkyne) | Sharp |
| 3000-3100 | =C-H (alkene), sp² C-H | |
| 2850-3000 | C-H (sp³) | |
| 2200-2260 | C≡N (nitrile) | Sharp, small |
| 2100-2260 | C≡C | Weak |
| 1700-1750 | C=O (aldehyde, ketone, ester) | Strong |
| 1700-1720 | C=O (carboxylic acid) | Strong |
| 1630-1680 | C=O (amide) | |
| 1600-1680 | C=C (alkene) | Medium |
| 1450-1600 | C=C (aromatic) | Multiple peaks |
Key diagnostic: C=O at ~1700 cm⁻¹ (very strong) and broad O-H.
NMR (¹H)
Chemical shift (δ, ppm from TMS):
| δ (ppm) | Proton Environment |
|---|---|
| 0.5-2.0 | Alkyl (sp³ C-H) |
| 1.5-2.5 | Allylic, α to carbonyl |
| 2.0-3.0 | Aromatic CH₃ (benzylic) |
| 2.5-4.0 | α to electronegative atom (O, N, halide) |
| 3.0-4.0 | C-H next to -OH, -OR, or halide |
| 4.5-6.5 | Vinyl (=CH) |
| 6.5-8.5 | Aromatic |
| 9-10 | Aldehyde H |
| 10-13 | Carboxylic acid H (very broad) |
Four pieces of NMR information:
- Number of signals = number of chemically unique H environments
- Chemical shift (δ) = electronic environment
- Integration = ratio of H atoms per signal
- Splitting (multiplicity) = n + 1 rule for neighboring H: singlet (0 neighbors), doublet (1), triplet (2), quartet (3), multiplet (≥4)
OH and NH protons: often broad; exchange with D₂O disappears.
¹³C NMR: similar logic, but always referred to as decoupled (singlets only), δ 0-220 ppm. Carbonyl C at 170-220.
Mass Spectrometry (MS)
- M⁺ (molecular ion peak) = molecular mass
- M+1 peak from ¹³C natural abundance (~1.1% per carbon) - lets you count Cs
- M+2 peak of ~1:1 or ~3:1 with M → Br or Cl present
- Characteristic fragments: loss of -15 (methyl), -17 (OH), -18 (H₂O), -29 (CHO), -43 (COCH₃), -45 (COOH)
UV-Vis
Absorption by π → π* and n → π* transitions. Longer conjugation → lower energy → higher λ. Useful for polyenes, aromatics, carbonyls.
13. Separation and Purification
| Technique | Separates based on | When used |
|---|---|---|
| Extraction (liq-liq) | Solubility (polarity) | Pull a compound into one solvent layer |
| Acid-base extraction | Ionization state | Separate acids, bases, neutrals by pH adjustment |
| Filtration | Solid vs liquid | Remove insoluble solid |
| Recrystallization | Solubility at different T | Purify solids |
| Distillation (simple) | Boiling point (large ΔBP) | Volatile from non-volatile |
| Fractional distillation | Boiling point (close BPs) | Separate miscible liquids |
| Vacuum distillation | Lower pressure → lower BP | Heat-sensitive compounds |
| TLC (thin layer) | Adsorption to silica (polarity) | Quick analytical check; polar compounds have lower Rf |
| Column chromatography | Adsorption | Preparative separation |
| Size-exclusion (gel filtration) | Molecular size | Big elutes first |
| Ion-exchange | Charge | Resin binds opposite charge |
| Affinity | Specific binding | Pure target molecule via its receptor |
| HPLC / GC | Partition / vapor pressure | Quantitative analysis |
| Electrophoresis | Charge-to-mass ratio, size | Proteins, nucleic acids |
Acid-base extraction flowchart:
- Mixture in organic + aqueous. Wash with dilute HCl → protonates amines → amines go to aqueous.
- Wash remaining organic with NaHCO₃ (weak base) → deprotonates carboxylic acids → go to aqueous. Leaves phenols behind.
- Wash remaining organic with NaOH (strong base) → deprotonates phenols → go to aqueous.
- Neutrals stay in organic layer.
TLC Rf: . More polar compound = lower Rf (sticks harder to silica). Reverse on reverse-phase.
14. Reaction-Type Master Sheet
Nucleophilic substitution: alkyl halide + Nu. SN1 (3°, protic solvent) vs SN2 (1°, aprotic).
Elimination: alkyl halide + base → alkene. E1 vs E2 mirror the S rules; base strength + steric bulk are the deciding factors.
Addition to C=C: electrophile (H⁺, X⁺) attacks π bond → carbocation → Nu traps. Markovnikov = H/OH/X goes to carbon giving stabler cation.
Addition to C=O: nucleophile attacks carbonyl C → tetrahedral intermediate. Aldehydes > ketones.
Addition-elimination (at carboxylic acid derivatives): same tetrahedral intermediate, then the leaving group leaves. Reactivity order set by LG stability.
Oxidation/reduction: oxidation adds O or loses H; reduction does the opposite. Key reagents: LiAlH₄ (strongest), NaBH₄ (mild, selective), H₂/Pd (alkenes→alkanes), PCC (mild, stops at aldehyde), CrO₃ / KMnO₄ (strong).
Grignard / organolithium: strong C nucleophile. Adds to any carbonyl. Destroys anything with acidic H (OH, NH, SH, terminal alkyne).
Aromatic substitution: EAS (electrophilic) replaces ring H. Activators (EDGs) ortho/para; deactivators (EWGs) meta; halogens are deactivating but ortho/para directors.
15. Top 25 Facts to Memorize
- Hybridization sets geometry: sp (180°), sp² (120°), sp³ (109.5°).
- Aromatic = cyclic + planar + conjugated + (4n+2) π electrons (Hückel).
- More s character = shorter, stronger bond, more acidic H (sp-H > sp²-H > sp³-H).
- Chirality requires 4 different groups at a carbon; meso compounds have internal mirror plane.
- Enantiomers differ in optical rotation; diastereomers differ in all physical properties.
- CIP R/S: lowest priority back, 1→2→3 clockwise = R.
- Racemic mixture = no net optical rotation.
- Staggered > eclipsed (Newman projections). Anti > gauche.
- SN2: 1°, strong Nu, polar aprotic, inversion.
- SN1: 3°, weak Nu, polar protic, racemization.
- E2: strong base, anti-periplanar H and LG, Zaitsev (unless bulky → Hofmann).
- E1: 3°, heat, Zaitsev.
- Markovnikov: H to C with more Hs; X to C with fewer Hs (more stable cation).
- Anti-Markovnikov: HBr/peroxides (radical) or hydroboration/oxidation.
- Reducing agents: LiAlH₄ (strong, reduces esters/acids/amides); NaBH₄ (mild, only aldehyde/ketone).
- Grignards destroyed by acidic H (OH, NH, SH) - must be anhydrous.
- Aldol: enolate + carbonyl → β-hydroxy carbonyl → dehydration → α,β-unsaturated.
- Carboxylic acid derivative reactivity: acid chloride > anhydride > ester > acid > amide.
- Fischer esterification: acid + alcohol + H⁺ ⇌ ester + H₂O (reversible; drive by excess or remove water).
- Saponification: ester + NaOH → carboxylate + alcohol (irreversible).
- IR: broad ~3300 = O-H; sharp ~1700 = C=O; broad 2500-3300 = carboxylic acid O-H.
- NMR n+1 rule: peaks split into (neighbor Hs + 1) peaks.
- M+2 in MS of ~1:1 → Br; of ~3:1 → Cl.
- Phenols more acidic than alcohols (pKa ~10 vs ~16-18) due to resonance.
- Acid-base extraction hierarchy: dilute HCl (amines) → NaHCO₃ (acids only) → NaOH (phenols) → neutrals remain.
16. Test-Day Mnemonics
Next Steps
If something on this page feels unfamiliar, open the corresponding chapter and re-walk the mechanism with curved arrows. Orgo rewards mechanism intuition over list memorization - every correct answer has a story about electron flow. This cheat sheet gets you 80% recall on test day; the full chapters get you the reasoning to predict products you have never seen before. Bookmark this page and return to it the night before every practice test and on the morning of the real thing.