Generated by AskSia.ai — graphs, formulas, traps
The carbonyl C is partially positive (δ+) — attacked by nucleophiles. The O is partially negative (δ−). Polarity drives nearly all carbonyl chemistry.
Reactivity ranking: acid chloride > anhydride > aldehyde > ketone > ester > carboxylic acid > amide| Class | R-CO-X | X is | pKa α-H |
|---|---|---|---|
| Aldehyde | R-CHO | H | ~17 |
| Ketone | R-CO-R' | R' | ~19 |
| Ester | R-COO-R' | OR' | ~25 |
| Carboxylic acid | R-COOH | OH (very acidic OH itself) | ~5 (OH); ~25 (α-H) |
| Amide | R-CO-NR₂ | NR₂ | ~30 |
| Acid chloride | R-COCl | Cl | ~16 |
α-Carbon acidity: H next to C=O is acidic because the resulting enolate is resonance-stabilized. pKa ~ 19-20 for typical ketones.
Acid chloride > anhydride > aldehyde > ketone > ester > amide. Memorize. Used to predict who reacts first when multiple carbonyls are present, and to determine inter-conversion direction (always more → less reactive).
Lone pair on N makes amines basic and nucleophilic. Conjugate acid pKa ~ 10 (for RNH₃⁺). Aromatic amines (aniline, pKa 4.6) much weaker than aliphatic — N lone pair donates into ring.
| Class | Structure | Examples |
|---|---|---|
| 1° | R-NH₂ | methylamine |
| 2° | R₂NH | dimethylamine |
| 3° | R₃N | triethylamine |
| Quaternary | R₄N⁺ | permanently charged |
Amide bond: RCOOH + R'NH₂ → RCONHR' (peptide bond)Amides: resonance stabilization gives partial double bond character to C-N (planar, restricted rotation). Foundation of protein structure.
Aniline (C₆H₅NH₂) is much weaker base than methylamine. The N lone pair conjugates into the ring, lowering availability for protonation. Adding electron-withdrawing groups to the ring (NO₂) further reduces basicity. Don't assume all amines have similar pKa.
(1) Nu⁻ attacks carbonyl C from above or below the plane. (2) Proton (workup) gives alcohol.
R₂C=O + Nu⁻ → R₂C(O⁻)Nu →[H₂O] R₂C(OH)Nu| Nucleophile | Product | Notes |
|---|---|---|
| NaBH₄, LiAlH₄ | 1° or 2° alcohol | NaBH₄ mild, LAH strong |
| RMgX (Grignard) | alcohol, R adds | tetrahedral product |
| HCN | cyanohydrin | α-OH α-CN |
| H₂O / H⁺ | hydrate (gem-diol) | usually unstable |
| R'OH / H⁺ (1 equiv) | hemiacetal | unstable |
| R'OH / H⁺ (2 equiv) | acetal | stable, protects carbonyl |
| RNH₂ | imine (R-N=R') | via hemiaminal, lose H₂O |
Reactivity: aldehydes > ketones (less steric, less electron donation). Aromatic carbonyls less reactive than aliphatic (resonance with ring).
Grignard (RMgX) attacks any carbonyl C. Don't forget: ester gives tertiary alcohol with TWO new R groups (Grignard adds twice — once to ester, once to ketone intermediate). Aldehyde gives 2° alcohol; ketone → 3° with one new R.
(1) Electrophile E⁺ attacks ring → arenium ion (Wheland intermediate, loss of aromaticity). (2) Loss of H⁺ → restores aromaticity. Net: H replaced by E.
Ar-H + E⁺ → Ar-H-E⁺ → Ar-E + H⁺| Rxn | Reagent | Product |
|---|---|---|
| Halogenation | Cl₂ or Br₂ + FeCl₃ / FeBr₃ | Ar-Cl, Ar-Br |
| Nitration | HNO₃ + H₂SO₄ | Ar-NO₂ |
| Sulfonation | SO₃ + H₂SO₄ | Ar-SO₃H (reversible) |
| F-C alkylation | R-Cl + AlCl₃ | Ar-R (rearrangement risk!) |
| F-C acylation | RCOCl + AlCl₃ | Ar-COR (no rearrangement) |
F-C alkylation pitfalls: rearrangement of carbocation, polyalkylation (since alkyl is activator). Use F-C acylation then reduce to get straight-chain alkylated product.
F-C alkylation and acylation don't work on rings with strong deactivators (NO₂, NR₃⁺) — the ring is too electron-poor. Plan multi-step syntheses to install the alkyl/acyl group before the deactivator.
| Feature | Tells you |
|---|---|
| chemical shift δ (ppm) | chemical environment |
| # of signals | # distinct H environments |
| integration | relative # of H per signal |
| multiplicity (n+1) | # neighboring H's |
δ ranges: alkyl ~1 OH/NH ~2-5 broad aromatic 6-8 aldehyde 9-10 COOH 10-13Mass spec: M⁺ peak = molecular weight. Common fragments: M-15 (loss of CH₃), M-29 (CHO or C₂H₅), M-43 (C₃H₇ or COCH₃). Isotope patterns reveal Cl (M:M+2 = 3:1) and Br (1:1).
¹³C NMR: # of unique C environments. Ranges: alkyl 0-50, alkene 100-140, aromatic 120-140, carbonyl 170-220.
For -CH₂-CH₃: the CH₂ sees 3 H's on CH₃ → quartet. The CH₃ sees 2 H's on CH₂ → triplet. You don't count your own H's. Off-by-one multiplicities lose questions reliably.
Different from aldehyde/ketone addition: NAS proceeds via tetrahedral intermediate that kicks out a leaving group instead of just being protonated. Net: replaces LG with Nu.
R-CO-LG + Nu⁻ → [tetrahedral] → R-CO-Nu + LG⁻| From | To | Reagent |
|---|---|---|
| Acid chloride | anhydride | RCOO⁻ |
| Acid chloride | ester | R'OH (or NaOR') |
| Acid chloride | amide | R'NH₂ (excess) |
| Anhydride | ester | R'OH |
| Anhydride | amide | R'NH₂ |
| Ester | amide | R'NH₂ + heat |
| Ester | acid (saponification) | NaOH then H⁺ |
Carboxylic acid → ester: use Fischer (acid + alcohol) OR convert to acid chloride first then ROH (faster, irreversible).
You can convert acid chloride to anything below it in reactivity. You can't go uphill directly (e.g. amide → ester). To go up the ladder, hydrolyze fully to acid, then re-derivatize. Plan synthesis routes accordingly.
α-pKa ~20 (ketone, aldehyde) ~25 (ester) ~5 (1,3-dicarbonyls)The α-H is between two electron-withdrawing groups (or next to one). Conjugate base (enolate) is resonance-stabilized — charge spreads onto O.
| Rxn | Setup | Product |
|---|---|---|
| Aldol | 2 carbonyls + base, mild | β-hydroxy carbonyl |
| Aldol condensation | aldol + heat / strong base | α,β-unsaturated carbonyl (lose H₂O) |
| Claisen | 2 esters + NaOEt | β-keto ester |
| Michael addition | enolate + α,β-unsat acceptor | 1,5-dicarbonyl |
| α-halogenation | X₂ + acid OR base | α-haloketone |
1,3-Dicarbonyls (acetoacetate, malonate): pKa ~ 5-13. Strong enough to deprotonate with NaOEt. Used in syntheses (acetoacetic ester synthesis, malonic ester synthesis).
For unsymmetric ketones: LDA (bulky, low T) deprotonates the less-substituted α (kinetic). NaOH/heat gives the more-substituted enolate (thermodynamic, more stable). Different conditions = different products.
| Question says… | Use § from | Approach |
|---|---|---|
| 'rank reactivity of carbonyls' | § ① | acid chloride > anhydride > aldehyde > ketone > ester > amide |
| 'aldehyde vs ketone' | § ② | aldehyde more reactive; oxidizes to acid (Tollens, Jones) |
| 'add Grignard to ester' | § ② | 2 equiv → 3° alcohol with two new R |
| 'protect a carbonyl' | § ② | form acetal with 2 R'OH/H⁺; remove with aq. acid |
| 'C=C from C=O' | § ② | Wittig (Ph₃P=CHR') |
| 'convert acid to ester' | § ③ | Fischer (acid + alcohol + H⁺) OR via acid chloride |
| 'saponify' / 'hydrolyze ester base' | § ③ | NaOH → carboxylate + alcohol (irreversible) |
| 'acid chloride + amine' | § ③ | amide formation (use excess amine to absorb HCl) |
| 'aldol condensation' | § ④ | base + 2 carbonyls → β-hydroxy → heat → α,β-unsat |
| 'crossed aldol' | § ④ | use no-α-H partner OR LDA-controlled enolate |
| 'Michael addition' | § ④ | enolate Nu + α,β-unsat C=O electrophile |
| '1,3-dicarbonyl synthesis' | § ④ | malonic / acetoacetic ester routes |
| 'EAS, predict product' | § ⑤ | identify EDG/EWG, o/p vs meta director |
| 'NO₂ before or after?' | § ⑤ | plan: Bromine first if you want o/p; nitrate first if you want meta |
| 'F-C alkylation' | § ⑤ | watch rearrangement; use F-C acylation + reduce |
| 'aniline basicity' | § ⑥ | much weaker than alkyl amine (lone pair into ring) |
| 'reductive amination' | § ⑥ | aldehyde/ketone + amine + NaBH₃CN |
| 'Hofmann elimination' | § ⑥ | quaternary ammonium → least subst alkene |
| NMR triplet 1.0 + quartet 4.0 | § ⑦ | ethyl group next to electronegative atom |
| IR 1715 + 2.1 ppm singlet | § ⑦ | methyl ketone |
| IR broad 3000 + 1715 sharp | § ⑦ | carboxylic acid |
Mechanisms earn partial credit per arrow. Skipping arrow notation = losing 50% even with right product. Source → sink, two electrons each.
Whenever a carbocation forms (SN1, E1, F-C alkylation, HX addition to alkenes), watch for 1,2-H or 1,2-alkyl shifts to a more stable C⁺. The 'expected' product may be wrong because the cation rearranged.