Nucleophilic addition to aldehydes and ketones

Grignard addition: 1-tetralone (an aryl ketone) with 1) PhMgBr, CH3CH2OCH2CH3, Δ; 2) aq. HCl gives 1-phenyltetralin-1-ol (the benzylic alcohol).

Acetal formation: 3-nitrobenzaldehyde (an aromatic aldehyde) with CH3OH, acid cat. gives 3-nitrobenzaldehyde dimethyl acetal.

Hydrate formation: 2-hydroxy-2-cyclohexen-1-one (an enol) with HClO4; H2O gives 2,2-dihydroxycyclohexan-1-one (the hydrate (gem-diol)).

Organolithium addition: (+)-2-methylpentanoic acid (a carboxylic acid) with 1) 2 equiv EtLi, Et2O; 2) NH4Cl / H2O gives (4S)-4-methylheptan-3-one (the dialkyl ketone).

Acetal hydrolysis: 3-ethoxy-1,2-dihydronaphthalene (an enol ether) with H2O; HCl, Δ gives 2-tetralone (the six-membered cyclic ketone).

Cyanohydrin formation: acetophenone (an aryl ketone) with 1) NaCN, H2O; HCl, ether; 2) H2O, HCl gives atrolactamide.

Hydride reduction of carbonyl: fluorenone (an aryl ketone) gives fluoren-9-ol (the benzylic alcohol).

Imine formation: m-toluidine (an aniline) gives the imine.

Reductive amination: 2,3-dimethoxybenzaldehyde (an aromatic aldehyde) with CH3NH2, H2 (45 psi), Raney nickel; aq. CH3CH2OH, 70 °C gives 1-(2,3-dimethoxyphenyl)-N-methylmethanamine (the secondary amine).

Strecker: acetophenone (an aryl ketone) with 1) NaCN, NH4Cl; H2O, CH3OH; 2) aq. HCl, Δ; 3) pyridine gives 2-amino-2-phenylpropanoic acid (the α-amino acid).

Aminal formation: a secondary amine gives the aminal.

Cannizzaro: furfural (an aromatic aldehyde) with 1) 33% NaOH; 2) H2SO4 (workup) gives 2-furancarboxylic acid (the acid and the alcohol) and furfuryl alcohol (the acid and the alcohol).

Strecker: benzaldehyde (an aromatic aldehyde) with 1) NaCN, NH4Cl; H2O, CH3OH; 2) aq. HCl, Δ; 3) NH4OH gives 2-phenylglycine (the α-amino acid).

Acetal formation: acrolein (an α,β-unsaturated aliphatic aldehyde) and triethyl orthoformate (an acetal) with NH4NO3; CH3CH2OH gives 3,3-diethoxy-1-propene (the acetal).

Grignard addition: a Grignard reagent with CO2 gives 2,4,6-trimethylbenzoic acid (the addition product).

Organolithium addition: cyclohexanecarboxylate and lithium ion with Li; 1) CH3Li, ether; 2) aq. HCl gives cyclohexyl methyl ketone.

Acetal hydrolysis: 5,9-dithiaspiro[3.5]nonane (a thioacetal) with HgCl2, CdCO3; H2O, triethylene glycol, 90-110 °C gives cyclobutanone (the four-membered cyclic ketone).

Hydride reduction of carbonyl: 4-tert-butylcyclohexanone (a six-membered cyclic ketone) with 1) LiAlH4, AlCl3, ether; 2) t-BuOH, Δ; 3) H2SO4, H2O gives the secondary alcohol.

Cyanohydrin formation: acetone (a methyl ketone) with NaCN; H2SO4, H2O gives acetone cyanohydrin.

Grignard addition: a Grignard reagent with 1) CO2; 2) aq. H2SO4 gives 2-methylbutanoic acid (the addition product).

Grignard addition: tert-butyl 3-(5-methylfuran-2-yl)propanoate (an ester) with 1) propargylmagnesium bromide (2 equiv), Et2O; 2) NH4Cl / H2O gives 4-[2-(5-methylfuran-2-yl)ethyl]hepta-1,6-diyn-4-ol (the tertiary alcohol).

Grignard addition: N-methoxy-N,2-dimethylpropanamide with 1) allylmagnesium chloride, THF; 2) NH4Cl / H2O gives 2-methylhex-5-en-3-one (the dialkyl ketone).

Grignard addition: ethyl acetate (an ester) with 1) PhMgBr (2 equiv), Et2O; 2) NH4Cl / H2O gives 1,1-diphenylethanol (the benzylic alcohol).

Organolithium addition: a carboxylic acid with 1) 2 equiv PhLi, Et2O; 2) NH4Cl / H2O gives the aryl ketone.

Grignard addition: gamma-butyrolactone (a five-membered lactone) with 1) 2-thienylmagnesium bromide (2 equiv), THF; 2) HCl / H2O gives 1,1-dithiophen-2-ylbutane-1,4-diol (the primary alcohol).

Organolithium addition: ethyl methacrylate (an α,β-unsaturated ester) with 1) 2.2 equiv MeLi, Et2O; 2) NH4Cl / H2O gives 2,3-dimethyl-3-buten-2-ol (the allylic alcohol).

Grignard addition: ethyl benzoate (an ester) with 1) PhMgBr (2 equiv.), CH3CH2OCH2CH3, benzene, Δ; 2) aq. H2SO4 gives triphenylcarbinol (the benzylic alcohol).

Cyanohydrin formation: ethyl ketone (a dialkyl ketone) with NaCN; NH4Cl gives 2-ethyl-2-hydroxybutyronitrile (the cyanohydrin).

Grignard addition: 9-phenanthrenecarbonitrile with CH3MgI; CH3CH2OCH2CH3; Δ gives the addition product.

Grignard addition: a Grignard reagent with 1) CO2; 2) 20% HCl gives the addition product.

Imine formation: benzaldehyde (an aromatic aldehyde) and ethylamine (a primary amine) gives the imine.

Grignard addition: gamma-nonalactone (a five-membered lactone) with 1) CH3MgBr (2 equiv.), ether, Δ; 2) HCl, H2O, benzene gives 2-methyldecane-2,5-diol (the secondary alcohol).

Grignard addition: an α,β-unsaturated ketone with PhMgBr; 1); Et2O; 2) H+ gives the benzylic alcohol.

Hydride reduction of carbonyl: a six-membered cyclic ketone with 1) NaBH4; EtOH; 2) H+ gives the secondary alcohol.

Acetal hydrolysis: 3,3-diethoxy-1,2-propanediol (an acetal) with H2SO4; H2O gives glyceraldehyde (the aliphatic aldehyde).

Acetal formation: isatin (a five-membered cyclic ketone) gives spiro(1,3-dioxolane-2,3'-(3H)indol)-2'(1'H)-one (the acetal).

Hemiacetal formation: an aliphatic aldehyde gives the hemiacetal.

Acetal formation: trimethylolmethane (a primary alcohol) gives (2,2-dimethyl-1,3-dioxan-5-yl)methanol (the acetal).

Reductive amination: cyclohexanone (a six-membered cyclic ketone) and dimethylamine (a secondary amine) with Me2NH·HCl, NaBH3CN, KOH; CH3OH gives N,N-dimethylcyclohexylamine (the tertiary amine).

Grignard addition: a Grignard reagent with CO2; −7 °C gives the addition product.

Imine formation: benzaldehyde (an aromatic aldehyde) with PhNH2 gives the imine.

Organolithium addition: cyclohexanone (a six-membered cyclic ketone) and an organolithium with 1); 2) H+ workup gives 1-[methoxy(trimethylsilyl)methyl]cyclohexan-1-ol (the tertiary alcohol).

Acetal formation: a hemiacetal with CH3OH, HCl; Δ gives the acetal.

Grignard addition: cyclohexanone (a six-membered cyclic ketone) with 1); 2) H+ workup gives the benzylic alcohol.

Acetal formation: methyl pyruvate (an α-keto ester) gives the acetal.

Hydrate formation: pyruvic acid (an α-keto acid) with H2O gives 2,2-dihydroxypropanoic acid (the hydrate (gem-diol)).

Hydrate formation: 2-bromobutanal (an α-halo aldehyde) with H2O gives 2-bromobutane-1,1-diol (the hydrate (gem-diol)).

Hydrate formation: acetone (a methyl ketone) gives 2,2-propanediol (the hydrate (gem-diol)).

Grignard addition: a Grignard reagent with 1) CO2, 0 °C; 2) H3O+ gives pivalic acid (the addition product).

Acetal formation: benzaldehyde (an aromatic aldehyde) gives 2-phenyl-1,3-dioxolane (the acetal).

Hydrate formation: 1,3-dichloroacetone (an α-halo ketone) with H2O gives 1,3-dichloropropane-2,2-diol (the hydrate (gem-diol)).

Hydrate formation: methyl pyruvate (an α-keto ester) with H2O gives methyl 2,2-dihydroxypropanoate (the hydrate (gem-diol)).

Grignard addition: an arene and ethyl acetate (an ester) with CH3CH2OCH2CH3; NH4Cl gives 1,1-diphenylethanol (the benzylic alcohol).

Acetal formation: 2,2-dimethoxypropane (an acetal) with BuOH (2 equiv.); p-TsOH, benzene, Δ gives 2,2-dibutoxypropane (the acetal).

Acetal formation: an enol ether with SN2; AcOH; 0.5 eq. gives 2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (the acetal).

Grignard addition: an alkylbenzene and benzophenone (an aryl ketone) with CH3CH2OCH2CH3; Δ gives the addition product.

Reductive amination: acetophenone (an aryl ketone) with H2, Ra(Ni) (3500 - 5000 psi); NH3, 150 °C gives 1-phenylethylamine (the primary amine).

Grignard addition: an ester with PhMgBr; ether, benzene, Δ gives the benzylic alcohol.

Acetal formation: benzaldehyde (an aromatic aldehyde) with HCl, CHCl3, 0 °C gives 2-phenyl-1,3-dithiane (the thioacetal).

Grignard addition: a Grignard reagent with 1) PhCN, ether, Δ; 2) CH3OH gives benzophenone imine (the addition product).