18.6 base-catalyzed enolization: enolate anions
DESCRIPTION
18.6 Base-Catalyzed Enolization: Enolate Anions. ••. O. • •. R 2 C. CR'. H. Acidity of a -Hydrogen. ••. O. • •. –. R 2 C. CR'. + H +. ••. p K a = 16-20. ••. ••. O. O. • •. • •. –. R 2 C. R 2 C. CR'. CR'. ••. H. ••. –. O. • •. • •. R 2 C. CR'. - PowerPoint PPT PresentationTRANSCRIPT
18.618.6Base-Catalyzed Enolization:Base-Catalyzed Enolization:
Enolate AnionsEnolate Anions
Acidity of Acidity of -Hydrogen-Hydrogen
+ + HH++RR22CC CR'CR'
OO•••• ••••
––
••••
OO••••
RR22CC CR'CR'
••••
HH
ppKKaa = 16-20 = 16-20
Acidity of Acidity of -Hydrogen-Hydrogen
+ + HH++
RR22CC CR'CR'
OO•••••••• ••••
––
••••
RR22CC CR'CR'
OO ••••––
••••
OO••••
RR22CC CR'CR'
••••
HH
ppKKaa = 16-20 = 16-20
Acidity of Acidity of -Hydrogen-Hydrogen
OO••••
RR22CC CR'CR'
••••
HH
ppKKaa = 16-20 = 16-20
enolate ionenolate ion
+ + HH++
••••
RR22CC CR'CR'
OO•••• ••••––
RR22CC CR'CR'
OO•••• ••••
––
••••
Mechanism of EnolizationMechanism of Enolization(Base-catalyzed)(Base-catalyzed)
OO••••
RR22CC CR'CR'
HH
OOHH
•••••••••••• ––
••••
Mechanism of EnolizationMechanism of Enolization(Base-catalyzed)(Base-catalyzed)
HHOOHH
••••••••
OO••••
RR22CC CR'CR'
––••••••••
Mechanism of EnolizationMechanism of Enolization(Base-catalyzed)(Base-catalyzed)
OO
HH
HH ••••OO••••
RR22CC CR'CR'
––••••••••••••
Mechanism of EnolizationMechanism of Enolization(Base-catalyzed)(Base-catalyzed)
OO
HH
HH ••••
OO••••
RR22CC CR'CR'
––••••••••••••
Mechanism of EnolizationMechanism of Enolization(Base-catalyzed)(Base-catalyzed)
HHOO••••
RR22CC CR'CR'
•••• OO
HH••••
––••••
••••
Acidity of Acidity of -Hydrogen-Hydrogen
ppKKaa = 15.5 = 15.5 ppKKaa = 15.8 = 15.8
(CH(CH33))22CCHHCHCH
OO
CCCCHH33
OO
-Diketones are much more acidic-Diketones are much more acidic
CHCH33CCCCHH22CCHCCH33
OO OO
ppKKaa = 9 = 9
HH33CCCC
CHCH33
OO
CCCC
OO
HH HH
HH33CCCC
CHCH33
OO
CCCC
OO
HH
HH++++••••––
-Diketones are much more acidic-Diketones are much more acidic
KKaa = 10 = 10–9–9
HH33CCCC
CHCH33
OO
CCCC
OO
HH
••••––
-Diketones are much more acidic-Diketones are much more acidic
enolate of enolate of -diketone is stabilized; negative -diketone is stabilized; negative charge is shared by both oxygenscharge is shared by both oxygens
-Diketones are much more acidic-Diketones are much more acidic
HH33CCCC
CHCH33
OO
CCCC
OO
HH
••••––
•••• ••••••••••••
HH33CCCC
CHCH33
OO
CCCC
OO
HH
–– •••• •••••••••••• ••••
-Diketones are much more acidic-Diketones are much more acidic
HH33CCCC
CHCH33
OO
CCCC
OO
HH
••••––
•••• ••••••••••••
HH33CC
––
HH
CCCHCH33
OO
CCCC
OO•••• ••••
•••••••• ••••
18.718.7The Haloform ReactionThe Haloform Reaction
Under basic conditions, halogenation of a Under basic conditions, halogenation of a methyl ketone often leads to carbon-carbon methyl ketone often leads to carbon-carbon bond cleavage.bond cleavage.Such cleavage is called the haloform reaction Such cleavage is called the haloform reaction because chloroform, bromoform, or iodoform because chloroform, bromoform, or iodoform is one of the products.is one of the products.
The Haloform ReactionThe Haloform Reaction
ExampleExample
(CH(CH33))33CCCCCCHH33
OO
BrBr22, NaOH, H, NaOH, H22OO
CCHBrHBr33++(CH(CH33))33CCONaCCONa
OO
(CH(CH33))33CCOHCCOH
OO
HH++
(71-74%)(71-74%)
The haloform reaction is sometimes used as a The haloform reaction is sometimes used as a method for preparing carboxylic acids, but method for preparing carboxylic acids, but works well only when a single enolate can works well only when a single enolate can form.form.
The Haloform ReactionThe Haloform Reaction
ArCArCCHCH33
OO
(CH(CH33))33CCCCCHCH33
OO
RRCHCH22CCCHCH33
OO
yesyes yesyes nono
RCCHRCCH33
OO
XX22, HO, HO––
RCCHRCCH22XX
OOXX22, HO, HO––
RCCHRCCHXX22
OO
XX22, HO, HO––
RCCRCCXX33
OO
MechanismMechanism
First stage is substitution of all available First stage is substitution of all available hydrogens by halogenhydrogens by halogen
MechanismMechanism
Formation of the trihalomethyl ketone is Formation of the trihalomethyl ketone is followed by its hydroxide-induced cleavagefollowed by its hydroxide-induced cleavage
HOHO •••• ––••••••••
•••• ––
RCRC
OO ••••
HOHO ••••••••
••••
CCXX33RCRC
OO ••••••••
CCXX33
––•••• CCXX33
••••
RCRC
OO ••••
OHOH••••
••••
++
++––•••• HCHCXX33
••••
RCRC
OO ••••
OO••••
••••++
18.818.8Some Chemical and StereochemicalSome Chemical and Stereochemical
Consequences of EnolizationConsequences of Enolization
Hydrogen-Deuterium ExchangeHydrogen-Deuterium Exchange
OO
HH
HH HHHH
++ 44DD22OO
OO
DD
DD DDDD
++ 44DDOHOH
KOKODD, heat, heat
MechanismMechanism
OODD••••––
••••••••++
HOHODD••••••••++HH
OO
HH
HH
••••––•••• ••••
OO
HH
HHHH
••••••••
HH
MechanismMechanism
HH
OO
HH
HH
••••––•••• ••••
MechanismMechanism
OODD••••––
••••••••++
HH
OO
HH
HH
••••––•••• ••••
OO
HH
HHDD
••••••••
HH
OODD••••••••
DD
Stereochemical Consequences of EnolizationStereochemical Consequences of Enolization
CC CCCC66HH55
OOHH
CHCH33CHCH22
HH33CC
100% R
HH33OO++
HH22O, HOO, HO––
50% R50% S
50% R50% S
Enol is achiralEnol is achiral
CC CCCC66HH55
OOHH
CHCH33CHCH22
HH33CC
R
CCCC66HH55
OHOH
CC
HH33CC
CHCH33CHCH22
Enol is achiralEnol is achiral
CC CCCC66HH55
OOHH
CHCH33CHCH22
HH33CC
R
CCCC66HH55
OHOH
CC
HH33CC
CHCH33CHCH22
CC CCCC66HH55
OOHH
CHCH33CHCH22
HH33CC
S50%50%
50%50%
Results of Rate StudiesResults of Rate Studies
CC CCCC66HH55
OOHH
CHCH33CHCH22
HH33CC
Equal rates for:Equal rates for:racemizationracemizationH-D exchangeH-D exchangebrominationbrominationiodinationiodination
Enol is intermediate Enol is intermediate and its formation is and its formation is rate-determiningrate-determining