Summary of CH17 Aldehydes and Ketones • Ketone/aldehyde protection as cyclic thioacetal (see VI above): stable to

I. Nomenclature base and H3O+, LiAlH4, RLi, RMgX, etc. (complementary to cyclic acetals)
• Common names • IUPAC name • vic-diol protection as cyclic acetals: stable to base, LiAlH4, RLi, RMgX, etc
II. Synthesis of aldehydes and ketones HO OH H+ R' O CH3
• Oxidation of alcohols (review section 8.6) CH3COCH3
R O CH3
R' R
PCC, CH2Cl2: 1° RCH2OH ––>RCHO
MnO2: allylic or benzylic C=CH–CH2OH ––> C=CH–CHO VIII. Addition of H-NH2 and its derivatives to form imines,
Jones reagent: 2° RR'CHOH ––>RR'C=O enamines, oximes, hydrazones, semicarbazones
• All additions are under acid catalysis.
• Ozonolysis of alkenes (review section 12.11) • Addition of H-HN2 or H-NHR (1° amine) to C=O forms imine
R1R2C=CHR3 ––>R1R2C=O (ketones) + R3CHO (aldehyde) R'
R' H+
• Hydration of alkynes (review section 13.8 & 13.9) R' = alkyl (ketone)
O H–NHR NR
R' = H (aldehyde)
(A) Markovnikov hydration to ketones, (B) anti-Markovnikov hydration to R R
aldehydes • Addition of H-NR1R2 (2° amine) to C=O containing -H forms enamine
1. R2BH
Hg2+, H2SO4, H2O O (B)R C CH RCH2 CHO
(A)R C CH 2. H2O2, HO– R' = alkyl (ketone) R' H+ R'
R CH3
R' = H (aldehyde) O H–NR2 NR''2
•Friedel-Crafts acylation (review section 15.14)
RCH2 RHC
O O
• Additions of H-NHOH, H-NHNHR, or NH2NHCONH2, H+form crystaline
CO, HCl, AlCl3 RCOCl, AlCl3
H R compounds that are often used in identifying unknown aldehydes or ketones
H–NHOH, H+ R'
S S S phenones R'
benzaldehydes N-OH oxime
III. General mechanisms for nucleophilic addition to C=O O R
R R'
• Nucleophilic addition-protonation (if Nu is a strong nucleophile
R' = alkyl (ketone) NH2NHR, H+ NNHR
and the reaction is under basic conditions)
R' = H (aldehyde) R hydrazone
H 2O R'
– O –
C O Nu OH
N-NHCONH 2
Nu Nu
+ R semicarbazone
NH2NHCONH 2, H
• Electrophilic protonation-addition (if Nu is a weak nucleophile and the
reaction is under acidic conditions) • Wolff-Kishner reduction: to reduce C=O to -CH2- under strong basic
H+ conditions
Nu– R' NH2NH2, NaOH, heat H
C O C OH OH R' = alkyl (ketone) R'
O C H
Nu R' = H (aldehyde) R
R
IV. Addition of H-OH to form hydrates Compare the C=O to –CH2-reduction by Wolf-Kishner reduction,
• Acid or base catalysis
Clemmensen reduction, or thioacetal-hydrogenolysis reactions and
• Reversible reaction with the equilibrium favoring aldehyde or ketone
R' their respective limitations.
R H+ or HO–
R' = alkyl (ketone) R IX. Addition of H-CN to form cyanohydrins
C O H 2O OH
R' = H (aldehyde) • Acid-catalyzed addition
R' HO hydrate • Cyanohydrins are versatile synthetic intermediates
V. Addition of H–OR to form acetals HCl RH2C – hydroxy acid
• Acid or base catalysis R'
O RH 2 C CO 2H
• Reversible reaction with the equilibrium favoring aldehyde or ketone H+ HO
R' R'
R H+ or HO– R' CN conc. H2SO4 –unsaturated
R' = alkyl (ketone) R R' CH2R RHC
C O O R'' OH HO acid
R' = H (aldehyde) CO2H
R' H R''O cyanohydrin
hemiacetal H–CN 1. LiAlH4 RH2C
R' –hydroxy
• 5– or 6– membered cyclic hemiacetals are favored and relatively stable 2. H2O CH2NH2 amine
R' = alkyl (ketone)
R H+ or HO– OH HO
cyclic X. Addition of phosphorus ylides: The Wittig reaction
R' = H (aldehyde) OH O O R hemiacetal
• Preparation of phosphorus ylides
• Hemiacetals are further converted into acetals under acidic conditions 1. P(C6H5)3, benzene RHC P(C6H5)3
RCH2X
R' H , + R' (1°, 2° alkyl halide)
2. strong base (ylide)
R O R'' R (RLi, NaH, or RONa/ROH)
hemiacetal OH OR''
R''O H • Synthesis of alkene from C=O compounds
R''O acetal
VI. Addition of H–SR to form thioacetals R' = alkyl (ketone) R' RHC P(C6H5)3 / THF R'
R' = H (aldehyde) O C RHC
• Thioacetal formation requires a Lewis acid catalyst such as BF3, or ZnCl2 R R
• Thioacetals are stable in H3O+ but can be hydrolyzed with a Lewis acid as XI. Addition of H–OOCOR: The Baeyer–Villiger oxidation
catalyst R BF3 or ZnCl2 R'
• Conversion of aldehydes (R'=H) to acids and ketones (R'=alkyl) to esters
R' = alkyl (ketone) R SR''
O
C O + 2 RSH O
R' = H (aldehyde) O
HgCl2, H2O, R''S thioacetal The migratory aptitude of R:
R' C R O OH, CH2Cl2
CH3CN C H > 3° > 2° > 1° > CH3
R' R
• Thioacetal formation - hydrogenolysis provides a method to reduce R' OR
C=O to -CH2– O HS XII. Oxidative chemical tests for aldehydes
Lewis acids S S
R' = alkyl (ketone) C H H • Fehling's test
R' = H (aldehyde) R' Raney Ni, H2
R R Cu2O (s)
R HS R' R Cu+, NaOH, H2O
R C O C O (brick red)
R'
VII. Acetals and thioacetals as protecting groups in synthesis H HO
• ketone/aldehyde protection as cyclic acetal: stable to base, LiAlH4, RLi, • Tollen's test
RMgX HO +
O H O O
R' = alkyl (ketone) Ag+
O O Ag (s)
R' = H (aldehyde) C cyclic acetal C NH3, H2O C (mirror)
R' R HO R' R R H R OH