Condensation

Front 1

Basic Aldol reaction
Whats involved
Catalysts
How?

Back 1

Aldehyde or Ketone with alpha hydrogen
HCOCH3 + NaOH/Ethanol > HCOCH2CH(OH)CH3
Base makes enolate ion, attacks electrophillic carbonyl carbon
aldol (aldehyde + alcohol)

Front 2

When will aldol happen (equillibrium)

Back 2

equillibrium favors aldol reaction for monosubstituted aldehydes
favors reactants for disubstituted aldehydes and most ketones

Front 3

When will aldol happen (instead of alpha substitution)

Back 3

for alpha sub, full equiv. of base, low temp
for condensation, catalytic amnt of weak base

Front 4

Driving force for aldol condensation basic conditions

Back 4

E1cB (cb=conj base)

Front 5

Aldol condensation reaction

Back 5

Beta-Hydroxy ketone or aldehyde + base (or acid, but not really) >conjugated enone. Very stable

Front 6

Implications of aldol condensation

Back 6

Even ketones or disubstituted aldehydes that are otherwise reactant favored for aldol, can be immediately condensed, driving the reaction towards completion

Front 7

Mixed aldol reactions, one product condition
otherwise?

Back 7

Normally, mixed aldol leads to two symmetrical and two mixed products.
IF
One partner has no alpha hydrogen and an unhindered carbonyl carbon, other carbonyl will enolize and attack
IF
One partner has a much more acidic alpha H (e.g., keto-ester), will enolize

Front 8

Intramolecular aldol reaction
H3C-COCH2CH2CO-CH3

Back 8

H3C-COCH2CH2CO-CH3 + NaOH/Ethanol > 5 membered enone ring with methyl group at beta position
STERIC FACTORS

Front 9

Claisen condensation
Requirements
reagents
products

Back 9

Requires ester with alpha hydrogen AND FULL EQUIVALENT OF BASE
2(H3C-COOEt )+ NaOEt/Ethanol >> + H3O+>
H3C-COCH2COOEt
Beta-keto ester
Ester on claisen acceptor is leaving group

Front 10

Driving force of claisen condensation

Back 10

deprotonation of flanked carbon's acidic hydrogen,
thermodynamic sink
Conj base removes acidic hydrogen leaving a negative charged shared by flanking O's.
H3O+ workup returns the hydrogen

Front 11

Mixed Claisen

Back 11

Applicable when one compound has no alpha hydrogen, acts as acceptor
not always good idea

Front 12

Claisen like reaction

Back 12

involves a ketone/aldehyde with an alpha hydrogen and an ester with no alpha hydrogen
alpha substitution of ketone, acyl substitution of ester results in B-diketone

Front 13

Intramolecular Claisen(Name?)
Requirement
Reagent
Result

Back 13

Dieckmann Cyclization
requires an alkyl chain with two terminal esters
i.e.
EtO-CO-CH2CH2CH2CH2-CO-OEt +NaOEt/Ethanol >> + H30+ > 5 membered ketone with alpha COOEt

Front 14

Where to go after dieckman cyclization

Back 14

the acidic, flanked alpha carbon can react with R'X group with NaOEt, then H30+ + heat removes the COOEt group via decarboxylation

Front 15

Michael Reaction
Requirement
Reagents
Products

Back 15

Enolate ion will attack B carbon of a/B-unsaturated ketone
H30+ workup yields a ketone with a substituted beta carbon bonded to alpha carbon of donor

Front 16

Good Michael Donors:
Good Michael Acceptors

Back 16

Donors:
any carbon flanked by two carbonyls (assuming an alpha hydrogen), Bketo-nitrile, RCH2NO2 (Hydrogen is very acidic)
Acceptors:
Conjugated enone, R=CHCN, R=CH-NO2

Front 17

Stork reaction
how
example
reagents

Back 17

Enamine "enolizes" for positive N and negative alpha C, attacks conjugated enone, H20 replaces enamine with carbonyl
e.g.
Cyclohexanone + secondary amine + michael acceptor>
1-aminogroup,2alkylketone-cyclohexa1,6-ene > 2alkylketonecyclohexanone
reagent: THF/H3O+

Front 18

Robinson annulation
What does it combine
Reagents
What does it make

Back 18

Michael reaction + intramolecular aldol condensation
NaOEt H30+
will form a ketone ring with substituents