R R
O
aldehydesketones
R X
O
carboxylic acidand derivatives
Carbonyl Chemistry
Wednesday, April 29, 2009
R R
O
R R
OElectrophiles (eg. H+)
Nucleophiles (eg. CH3MgBr)
O
OH
H
BaseO
O
an enolate
Wednesday, April 29, 2009
O
α
β
O
α
β
O
α
β
O1
2 34
Nuc-H1
2 34
OH Nuc
O1
2 34
1
2 34
NucOH O1
2 34
Nuctautomerize
1,2-addition
1,4-addition (conjugate addition)
Nuc-H
Wednesday, April 29, 2009
1,4-addition
OCH3NH2
O
NHCH3
1,4-addition
O O
Ph
1) Ph2CuLi2) H3O+
1,2-addition
O 1) PhMgBr2) H3O+ HO Ph
1,2-addition
O 1) PhLi2) H3O+ HO Ph
1,2-addition
O 1) NaBH42) H3O+ HO H
1,2-addition
O 1) LiAlH42) H3O+ HO H
Wednesday, April 29, 2009
O
a hemiacetal
+ ROH2H+
HO OR
an acetal
RO OR
(+ ROH) (+ ROH)(- H2O)
O HA
Mechanism for Acetal Formation
OH
OHR
O OHR
H A O OR
H
Hemiacetal-H2O
OR
OR
resonance structures
HA
O OR
H
RAO O
RR
OH
resonance structures
HO R
NEED TO KNOW MECHANISM
O OR
H
H
Wednesday, April 29, 2009
Wittig Reaction
+ Ph3P CH2
phosphoniumylide
+ Ph3P OO
Both aldehydes and ketones participate. The Wittig reagent is made from the alkyl halide by SN2 reactions.
O Ph3P+
Br
+ Ph3P:
PPh3O
+ Br
+ Ph3P:
easier to prepare Wittigreagent - substitution on a primary bromide.
Harder method
easier method
Wednesday, April 29, 2009
R Y
O Nuc
R YO Nuc
R Nuc
O+ Y
Cl
O
Acid Halides(acetyl chloride)
O
Acid anhydrides(acetic anhydride)
OCH3
O
Esters(methyl acetate)
NH2
O
Amides(acetamide)
O
O
More Reactive Less Reactive
Wednesday, April 29, 2009
R Y
O+ Nuc-H General NAS ReactionR Nuc
O+ HY
R Y
O+ HO-H HydrolysisR OH
O+ HY
R Y
O+ R'O-H AlcoholysisR OR'
O+ HY
R Y
O+ NH3 AminolysisR NH2
O+ HY
Wednesday, April 29, 2009
R Y
O H-
R H
O+ Y-
R Y
O R'MgB r
R R'
O+ HY
ReductionH-
R'MgB r
R HO H
R R'O R' Grignard
R Cl
O R'2CuLi
R R'
O
R OCH3
O DIBAL
R H
O
Wednesday, April 29, 2009
OH
OCH3
KMnO4
OH
OKMnO4 2
OH
O
OH
OH
O
H
O
Tollen's Oxidation
CrO3H3O+
Ag2ONH4OH
OH
OC H3O+
N
O
OMgBr
OH
O
H3O+
MgBr
O C OOH
OKMnO4 2
O
Oxidation Methods Other Methods
Wednesday, April 29, 2009
R OH
O SOCl2
R Cl
O
R OH
O NaOH then CH3I
R OCH3
Olimited to primary alkyl halides
SN2
R OH
O HA, CH3OH
R OCH3
O
limited to inexpensive alcohol solvents -methanol and ethanol most practicalFischer Esterification
R OH
O LiAlH4
R OH
H H
then H3O+
R OH
O BH3
R OH
H H
then H3O+
selective for carboxylic acid reduction - will not react with esters
Carboxylic Acids
!
Wednesday, April 29, 2009
R Cl
O H2O
R OH
O
R Cl
O R'CO2Na
R O
O
R Cl
O R'OH, pyridine
R OR'
O
R Cl
O R'NH2, pyridine
Acid Chlorides
+ HCl
R'
O+ NaCl
+ pyridine•HCl
+ pyridine•HClR NHR'
O
R Cl
O LiAlH4
R OH
H H
then H3O+
R Cl
O R'MgBr
R OH
R' R'
then H3O+
R Cl
O R'2CuLi
R R'
Adds Twice
Adds Twice
Adds OnceO
!
Wednesday, April 29, 2009
Acid Anhydrides
O H2O
OH
O
R'OH, pyridine
R OR'
O
R'NH2, pyridine
LiAlH4
R OH
H H
then H3O+
+
+ pyridine•HO2CCH3
+R NHR'
O
R'MgBr
R OH
R' R'
then H3O+
Adds Twice
Adds Twice
HO
O
O
O
O
O
O
O
O
O
pyridine•HO2CCH3
O
O
O
O
O
O
!
Wednesday, April 29, 2009
Esters
R
O H2O, NaOH
OH
O
LiAlH4
R OH
H H
then H3O+
+
R'MgBr
R OH
R' R'
then H3O+
Adds Twice
Adds Twice
OCH3
R
O
OCH3
R
O
OCH3
then H3O+
HOCH3
DIBAL
R H
Adds OnceO
R
O
OCH3then H3O+
!
Amides
R
O H2O, H3O+
OH
O
LiAlH4
R NH2
H H
then H3O+
Adds Twice - Nitrogen is retained.
NH2
R
O
NH2
heat
!
Wednesday, April 29, 2009
O
Acid Catalyzed Enol Equilibrium
OHHA OH OHH
A
O
Base Catalyzed Enol Equilibrium
OHOH O OH
HA
Wednesday, April 29, 2009
O OHH+ Br Br OBr + HBr
OBr2
CH3CO2H
OBr pyridine
O
OH
OR
PBr3Br2
then H2OOH
OR
Br
Wednesday, April 29, 2009
N LiO+
O+
LDAlithium
diisopropyl amide
N H
100%
O 1) LDA2) CH3I
OCH3
Wednesday, April 29, 2009
OpKa = 20
OpKa = 9
O
OEt
OpKa =13
EtO
O
OEt
O
EtO
O NaOEt, EtOH
R BrOEt
O
EtO
O
R
Wednesday, April 29, 2009
H3O+, Heat
HO
O
OEt
O
EtO
O
R
R + CO2
H3O+
O
O
HO
O
R
H Heat
HO
OH
R
-CO2
tautomerize
OpKa = 20
OpKa = 9
O
OEt
OpKa =13
EtO
O
Wednesday, April 29, 2009
OEt
O NaOEtEtOH
+ Br
O CO2EtO
H3O+, Heat
+ CO2
O
Wednesday, April 29, 2009
O HA
Mechanism for Acetal Formation
OH
OHR
O OHR
H A O OR
H
Hemiacetal-H2O
OR
OR
resonance structures
HA
O OR
H
RAO O
RR
OH
resonance structures
HO R
NEED TO KNOW MECHANISM
O OR
H
H
Wednesday, April 29, 2009
H
Fischer Esterification
R OH
O HA
R OH
OH R'OH
R OH
HO OR'H
A
R OH
HO OR'
R OH
HO OR'
HA
R
HO OR'
R OR'
OH
R OR'
O A
NEED TO KNOW MECHANISM
Wednesday, April 29, 2009
OCH3
O OH
OCH3
O OHOH
O
Base Catalyzed Hydrolysis (Saponification)
+ OCH3 O
O+ HOCH3
Rapid acid-base reaction takes place
Carboxylate is a thermodynamic sink and makes the reaction essentiall non-reversible. To get the carboxylic acid, add acid to protonate.
OCH3
O HA
OCH3
OH
OCH3
OH H2O
OCH3
OH OH
H AOCH3
OH O H
HA
OCH3
OH O H
HOH
OH
OH
OH
OH
O A
Acid Catalyzed Hydrolysis
NEED TO KNOW MECHANISMS
BEST METHOD
- HOCH3
Wednesday, April 29, 2009
NH2
O HA
NH2
OH
NH2
OH H2O
NH2
OH OH
H ANH2
OH O H
HA
NH2
OH O H
HOH
OH
OH
OH
OH
O A
Acid Catalyzed Hydrolysis
NEED TO KNOW MECHANISMS
- NH3
R NH2
O
H2O R OH
OHA (cat)Amide Hydrolysis
Wednesday, April 29, 2009
Wednesday, April 29, 2009
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