Download - Chemistry of Carbonyl Compounds (McM 19-12)
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Chemistry of Carbonyl Compounds (McM 19-12)
OH
δ+
δ-
Nucleophile
ElectrophileBase
Nucleophilic addition / substitutionAldehydes / Ketones
O
R'R
R, R': H, alkyl, aryl - Not good leaving groups
NuR R'
O Nu H
R R'
HO Nu
Addition reactions
O
R R'
H
O
R'RNu-H
H
R R'
HO NuH
HR R'
HO Nu
_
Acid catalyzed
Better electrophileWeaker nucleophile
Carboxylic acid derivatives
Substitution
O
LR
L - Good leaving groups
Nu
-X > -OCOR > -OR > -NR2X: Halogen, R: H, alkyl, aryl
R LO Nu
- L
O
NuR May also be acid cat.
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Aldehydes / Ketones
O
R'R
R, R': H, alkyl, aryl - Not good leaving groups
NuR R'
O Nu H
R R'
HO Nu
Addition reactions
The Cannizzarro reaction (McM 19.13)
Hydride as leaving group!
O
R H
R: No acidic a-Hex -H, -Ph. -But
OH
R H
O OH
O
R HO
R OH
H
+R
HO
H
H
2 Aldehyde Carboxylic acid + prim. alcohol
N
N N
NNH2
O
ORHO
OP
O
OOH
P
OO
OHHO
N
OHO
O
NH2
N
N N
NNH2
O
ORHO
OP
O
OOH
P
OO
OHHO
N
OHO
O
NH2
NADH
H H
Nicotinamid adenine dinucleotide
NADR=H
R=Phosphate: NADP+, NADPH
R-OH
prim or sec.
Alchohol dehydrogenase(NAD cont.)
aldehyde / ketone
R
O
H
Aldehyde dehydrogenaseR
O
OH
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Conjugate Addition (McM 19.14)
O
R
O
R
O
R
O
R
1,2-addition, Ex: •Alchohols•Organolithium
1,4-addition, Ex: •Amines•Organocuprates
O
Rδ+
δ+
δ-
δ-
Nu
1,2-aδδition
1,4-aδδ ition(conjugate aδδ ition / MIchael aδδition)
Michael reaction (McM 23.11)
Michael acceptorEWG
O O
R
O
ORN S
ONO
O OR
CN NO2 SO2R
R' R
O OBase
R' R
O O
H H H
NB! resonance formsWell stabilized enolate anion
O
R''O
R''
HO
R''
OR
O
ROR
O
R
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Robinson Annulation (McM 23.13)
R' R
O OBase
R' R
O O
H H H
O O
OR
O
R
H H
1,5-diketoneacidic a-H
Michael react.
Base
O
OR
O
R
O
O
RO R
- H2O
O
OH
RO R
O
O R
R
Alδol conδensation
Ring forming react.annulus (lat.) = ring
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OH
δ+
δ-
Nucleophile
ElectrophileBase
OH
BaseO O Enolate anion
Nucleophilic species
O
E
OE
E
OE
E: - Alkyl halides- Carbonyl compounds (Aldol, Claissen condens.)- Halides
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EWG
O O
R
O
ORN S
ONO
O OR
CN NO2 SO2R
Michael acceptor
Enolizable
Alkylation of enolate anions (McM 22.8)
OHBase
O O
R-X
OR
X
Ketones, esters, nitriles(Aldehydes: condensation)
Base: Strong, sterical hindrance
N H + n-Bu-LI N Li + n-BuH
Litium Diisopropyl AmidepKa ca 40
EWG
O O
R
O
ORCN NO2 SO2R
H
HHHHHH
1019 2517 25ca pKa: 30
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Alkylation of 1,3-dicarbonyl compounds followed by decarboxylation
O O
ORROBase O O
ORRO
R-X O O
ORROR
BaseR-X
O O
ORROR R
H+/H2O O O
OHOR
H OCO
OH
OHR
+O
OHR
O
OHR
R
O O
R'RO
O O
R'ROR
H+/H2O O O
ROR
H
´- CO2
O
R'R
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Enamines as enolate equivalents (McM 23.12, Lab ex. 11)
Synthesis of enamines (cf McM 19.9)
O
ketone / aldehyde
R-NH2
prim. amine
O NH2-R HO NH-R
H
NRH
- H
NR
ImineIminium ion
O
ketone / aldehyde
sec. amine
NRR'
Iminium ion
RNH
R'HH
Base NR R'
Enamine
Neutral imine
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Reactivity of enamines
•Alkylation (alkyl halides)•Conjugate addition (Michael acceptors)•Acylation (acid halides)
•Monoalkylation•No strong base
NR R'
Enamine
E NE
R R'
O E OE
H2OH2O N
R'
RHO N
R'
RH OH
+ RR'NH
O
E EEE
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Halogenation of enolate anions (McM 22.7)
O
RH
H
O
RH
O
RH
X-BX
O
RX
HX
Reacts further in the presence of base and halgen source
H H
H
H
OH
O
RX
XX
OH
OHX
XX
O R
O
HO RCX3Fairly good leaving group +
O
O RHCX3+
pKa X=I: 14
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Halogenation of neutral enols (McM 22.3)
OH
H OH
X-XO
X
H
X
OX + HX
Aldehyde or ketone
(acid, ester, amide - not enolization)
H H HH
E2- HX
O
mainly monohalogenated prod.
a-Bromination of acids (McM 22.4)
O
OHH
PBr
BrBr
O
OH
PBr
BrH
Br
O
BrH
+
HO PBr
Br
P-O bondcf Wittig
OH
Br
Acid bromide generated in situEnolize more easily than acid
Br2O
BrBr
H2O
O
OHBr
cf McM 17.7
Hell Volhart Zelinskii React.Intro of Cl also possible
R-OH + PBr3 R-Br
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Carbonyl condensations in nature (McM 21.8, 23.14)
Acetyl-CoA (Acetyl co-enzyme A)
N
N N
N
NH2
O
OHPO3
OP
OP
OHN
O OO OOH
O
HN
SH3CO
O
Acetyl-CoA
Nu
BaseNature's
O
Clor
O
O
O
Synthesis of Acetylcholine (neurotransmittor)
NOH
Choline
Acetylcholineesterase
CoAS
O
NO
O
Acetylcholine
Acyl-CoA
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CoAS
ODegradation / oxidation of fatty acids +
O
HO2CCO2H
Oxaloacetic acid
≈ Aldol Hydrol.Acyl-CoA
OH
HO2CCO2H
OOH
Citric acid
Citrate cycle Energy
CO2
Carbohydrates
* +
CoAS
ODegradation / oxidation of fatty acids
Metab. with little carbohydrates(Diabetes, starvation, diets)
CoAS
OO O
SCoA
Acetoacetyl-CoA
BiosynthesisSteroids, Lipids etc
Acetone
≈ Claissencondes.
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Polyesters, polyamides etc (McM 21.9)
OHHO
OOOO *O
n
+ n HXO
XO
X
Polyester
NH2H2N
OO HN
HN *H
Nn
+ n HXO
XO
X
Polyamid
OHHO
Polycarbonate
O
O OR R
Carbonate
OHHO OO
OO O
O*
n
+ 2n ROH
Acyl subst react
Step-Growth polymers (Chain-Growth polymers: Polyenes)
OHHO NN NHO
OOn
Polyurethane(Carbamide)
C OCO
isocyanate
NHO