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Chemistry of Carbonyl Compounds (McM 19-12). Nucleophilic addition / substitution. May also be acid cat . The Cannizzarro reaction (McM 19.13) Hydride as leaving group!. Conjugate Addition (McM 19.14). Michael acceptor. 1,2-addition, Ex: Alchohols Organolithium. 1,4-addition, Ex: - PowerPoint PPT Presentation
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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.
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
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
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
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
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
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
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
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
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
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
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
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.
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
