Acetal = product of carbonyl reacting with 2 equivalents of alcohol (acid catalyst). Reaction is reversible. Acetals are stable to base and nucleophiles — used to PROTECT carbonyls during synthesis.
Acetal = product of carbonyl reacting with 2 equivalents of alcohol (acid catalyst). Reaction is reversible. Acetals are stable to base and nucleophiles — used to PROTECT carbonyls during synthesis.
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⚗️ Aldehydes & Ketones
Nucleophilic addition to carbonyl: Nu attacks C, then protonation
Nucleophilic Addition Mechanism
Carbonyl carbon (C=O) is electrophilic. Nucleophile attacks C from above or below the pi bond → tetrahedral alkoxide intermediate. Protonation (workup) gives the product. Key: nucleophile always attacks carbon, not oxygen. Products depend on nucleophile: H⁻ → alcohol. RMgX → alcohol. CN⁻ → cyanohydrin. H₂O → hydrate (gem-diol). NH₂R → imine.
Primary amines (RNH₂) react with aldehydes/ketones → imines (Schiff bases, C=N). Reaction is reversible; remove water to drive forward. Acid catalysis (pH ~4–5) is optimal — enough acid to protonate intermediate, not too much to protonate amine. Secondary amines (R₂NH) + carbonyl with alpha-H → enamine (C=C-N). Imines and enamines are both useful in synthesis as nucleophilic equivalents.
Cyanohydrin: HCN + carbonyl → R₂C(OH)CN — adds one carbon
Cyanohydrin Synthesis
HCN adds to aldehydes and ketones via CN⁻ nucleophile (use NaCN + HCN or KCN). Product: cyanohydrin R₂C(OH)CN. Useful in synthesis because: (1) adds one carbon, (2) CN group can be hydrolyzed to COOH or reduced to CH₂NH₂. Aldehydes react more readily than ketones. Thermodynamic product with formaldehyde/acetaldehyde; equilibrium disfavors it with hindered ketones.
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🃏 ⚗️ Aldehydes & Ketones
Cyanohydrin formation — reactants and product?
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🃏 Answer
Cyanohydrin: HCN + carbonyl → R₂C(OH)CN — adds one carbon
HCN adds to aldehydes and ketones via CN⁻ nucleophile (use NaCN + HCN or KCN). Product: cyanohydrin R₂C(OH)CN. Useful in synthesis because: (1) adds one carbon, (2) CN group can be hydrolyzed to COOH or reduced to CH₂NH₂. Aldehydes react more readily than ketones. Thermodynamic product with formaldehyde/acetaldehyde; equilibrium disfavors it with hindered ketones.
Wittig converts a carbonyl to an alkene. Phosphorus ylide (Ph₃P=CHR, a stabilized carbanion) reacts with aldehyde or ketone → alkene product + triphenylphosphine oxide byproduct. Highly selective — no rearrangements, specific alkene formed. Non-stabilized ylides → Z (cis) alkene. Stabilized ylides → E (trans) alkene. Used in synthesis to introduce double bonds at specific positions.
Non-stabilized ylide→ Z (cis) alkene major product
Stabilized ylide→ E (trans) alkene major product
ByproductPh₃P=O (triphenylphosphine oxide)
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⚗️ Aldehydes & Ketones
Keto-enol tautomerism: carbonyl ⇌ enol (equilibrium, acid or base catalyzed)
Keto-Enol Tautomerism
Carbonyls with alpha-H exist in equilibrium with their enol form. Keto form is usually dominant (>99%). Enol has OH on the alpha carbon with C=C. Interconverted by acid (protonation of carbonyl O, then deprotonation of C=C) or base (removal of alpha-H → enolate, then protonation of O). Enols and enolates are nucleophilic at the alpha carbon — key to aldol, alkylation, and halogenation reactions.
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🃏 ⚗️ Aldehydes & Ketones
Keto-enol tautomerism?
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🃏 Answer
Keto-enol tautomerism: carbonyl ⇌ enol (equilibrium, acid or base catalyzed)
Carbonyls with alpha-H exist in equilibrium with their enol form. Keto form is usually dominant (>99%). Enol has OH on the alpha carbon with C=C. Interconverted by acid (protonation of carbonyl O, then deprotonation of C=C) or base (removal of alpha-H → enolate, then protonation of O). Enols and enolates are nucleophilic at the alpha carbon — key to aldol, alkylation, and halogenation reactions.
Acid conditionsMono-halogenation at alpha C via enol
Base conditionsMultiple halogenations — no selectivity
Haloform reactionCH₃COR + 3X₂/NaOH → RCOO⁻ + CHX₃
Iodoform testYellow CHI₃ = positive for methyl ketone
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⚗️ Aldehydes & Ketones
Cannizzaro reaction: no alpha-H aldehyde + base → alcohol + carboxylate
Cannizzaro Reaction
Aldehydes with NO alpha-H (formaldehyde, benzaldehyde, trimethylacetaldehyde) undergo Cannizzaro reaction with base: one molecule is oxidized (→ carboxylate) and one is reduced (→ alcohol). Hydride transfer from one molecule to another. Does NOT occur with ketones or aldehydes that have alpha-H (those undergo aldol instead). Crossed Cannizzaro: formaldehyde always gets oxidized, other aldehyde gets reduced.
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🃏 ⚗️ Aldehydes & Ketones
The Cannizzaro reaction?
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Cannizzaro reaction: no alpha-H aldehyde + base → alcohol + carboxylate
Aldehydes with NO alpha-H (formaldehyde, benzaldehyde, trimethylacetaldehyde) undergo Cannizzaro reaction with base: one molecule is oxidized (→ carboxylate) and one is reduced (→ alcohol). Hydride transfer from one molecule to another. Does NOT occur with ketones or aldehydes that have alpha-H (those undergo aldol instead). Crossed Cannizzaro: formaldehyde always gets oxidized, other aldehyde gets reduced.
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⚗️ Aldehydes & Ketones
Conjugate addition (1,4-) vs direct addition (1,2-) to enones
1,2 vs 1,4 Addition to Enones
Alpha,beta-unsaturated carbonyls (enones) have two electrophilic sites: carbonyl C (1,2-position) and beta-C (1,4-position). Hard nucleophiles (RMgX, RLi, NaBH₄) prefer 1,2-addition (kinetic, direct to carbonyl). Soft nucleophiles (organocuprates R₂CuLi, RSH, amines) prefer 1,4-conjugate addition (thermodynamic, to beta-C). Organocuprates = best reagents for conjugate addition.