Post on 11-Jan-2016
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Chapter 18: Enols and EnolatesChapter 18: Enols and Enolates
Overview
Enols :
Enolates :
18.1 – The 18.1 – The Hydrogen and Its p Hydrogen and Its pKaKa
18.2 – The Aldol Condensation18.2 – The Aldol Condensation
When appropriate base is used, both aldehyde and enolate present in solution, this leads to the aldol reaction
18.2 – The Aldol Condensation (loss of H18.2 – The Aldol Condensation (loss of H22O)O)
When the reaction is run at low temperature the aldol product may be isolated; at elevated temperature the elimination occurs
18.3 – Mixed (Crossed) Aldol Reactions18.3 – Mixed (Crossed) Aldol Reactions
all present in solution at same time
2 enolizable substrates leads to multiple products
18.3 – Mixed (Crossed) Aldol Reactions18.3 – Mixed (Crossed) Aldol Reactions
Usually use 1 non-enolizable substrate:
Elimination of H2O common when conjugation results, can also be induced by heating the reaction mixture
18.4 – Alkylation of Enolate Ions18.4 – Alkylation of Enolate Ions
• Greek staphyle meaning “a bunch of grapes” • Greek kokkos meaning “berry” • aureus = yellow
Staphylococcus aureus (MRSA, VRSA)Staphylococcus aureus (MRSA, VRSA)
• Gram-positive, cluster-forming coccus• Cause food poisoning, endocarditis, osteomyelitis• Can cause septiceamia, infections on implants
• Becoming increasingly resistant to antibiotics• MRSA strains appeared in 1961• VRSA first reported in the USA in 2002
Microcapsule (carbohydrate) – defends against phagocytosis
O
OHO
O
OHO
NHAc
O
H3C
OAcNHAc
OO
CH3HO
NHAc
Type 5 Type 8
O
O
HO
O
AcOO
NHAc
O
H3CNHAc
O
OCH3HO
AcHN
HO
n n
Bacterial Capsular Polysaccharides – Bacterial Capsular Polysaccharides – serotypesserotypes
18.5 – Enolization and Enol Content18.5 – Enolization and Enol Content
Tautomers – two structures that differ by placement of an atom or a group
The enol form is usually in low concentration since the C=O is more stable
Tautomerism is acid-catalyzed and base-catalyzed
18.5 – Enolization and Enol Content18.5 – Enolization and Enol Content
18.5 – Base-Catalyzed Enolization18.5 – Base-Catalyzed Enolization
Enolate resonance forms – not tautomers
18.5 – Acid-Catalyzed Enolization18.5 – Acid-Catalyzed Enolization
Sequential proton transfers
18.6 – Stabilized Enols18.6 – Stabilized Enols
18.7 – 18.7 – -Halogenation of Aldehydes and Ketones-Halogenation of Aldehydes and Ketones
• The reaction overall is a substitution• The reaction is regiospecific – only -H is replaced
18.8 – Mechanism of 18.8 – Mechanism of -Halogenation of Aldehydes and Ketones-Halogenation of Aldehydes and Ketones
Very good cation generated (hetero-atom stabilized)
18.9, 18.10 – The Haloform Reaction and 18.9, 18.10 – The Haloform Reaction and -Deuteration-Deuteration
-Deuteration
Iodoform reaction
A methyl ketoneiodoform
18.11 – Conjugation in 18.11 – Conjugation in ,,-Unsaturated Systems-Unsaturated Systems
Carbonyl carbon and -carbon have positive character
AcroleinFigure 18.2
Pi system iscompletelydelocalized
18.12 – Conjugate Addition to 18.12 – Conjugate Addition to ,,-Unsaturated Systems-Unsaturated Systems
More reactive nucleophiles (e.g. RMgX) attack the most +ve C i.e. the carbonyl carbon. These reactions are usually irreversible.
Softer nucleophiles undergo reversible addition and lead to the more stable (thermodynamically favoured) 1,4-addition product.
18.13 – The Michael Reaction18.13 – The Michael Reaction
H alpha to two C=O will be more acidic than next to one C=O,
deprotonation leads to a soft nucleophile that adds 1,4-
18.13 – Michael Addition – Robinson Annulation Sequence18.13 – Michael Addition – Robinson Annulation Sequence
Application:
18.14 – Conjugate Addition of Organocopper Reagents18.14 – Conjugate Addition of Organocopper Reagents