Chapter 22: Alpha Carbon Chemistry: Enols and Enolates Flashcards
Base With Ketone
Enol: Basic Conditions
H is taken, forms anionic C
-anion goes to C-C bond, pushing ketone bond electrons onto oxygen [resonance]
-oxygen gets proton
-assume tautomerization always occurs
-in base catalyzed, the alpha carbon is very nucleophilic during resonance
[H3O+] With Ketone
Enol: Acidic Conditons
- ketone is protenated
- double bond shifts to oxygen [resonance]
- water deprotenates the alpha carbon and elimination forms double C-C bond
Ketone with Base (NaOH, LDA)
Enolate formation
- when the alpha carbon is deprotenated, the anion is resoance stabilized
- O-attack is when oxygen acts as nuc, C-attack is when C acts as nuc
- oxygen will most likely hold the anionic charge
- the C-attack looks like the anion is attack nuc while the ketone is intact
- more useful because 1) more reactive 2) can be stored compared to enols
[H3O+], Br2 with ketones/aldehydes
Alpha Halogenation in Acidic Conditions
- forms enol under acidic conditions
- double bond attacks Br2, crbonyl reforms
- carbonyl is deprotenated
- HBr is autocatalytic side product
- bromination occurs at more substitued side of ketone
- this is because the double bond from enol is more stable there
- mixture of products, just more of one product
1)Br2, PBr3 2) H2O With Carboxylic Acid
Alpha Bromination of Carboxylic Acids: The Hell-Volhard-Zelinski Reaction
- PBr3 converts carboxylic acid -OH to Br
- forms acid halide
- converts to enol of acid halide
- Br2 reacts with enol double bond, carbonyl reforms from enoll
- H2O converts acid halide (Br) ro carboxylic acid
NaOH, Br2: with ketone
Alpha Halogenation in Basic Conditions: The Haloform Reaction
- a base forms the enolate
- the enolate attacks Br2
- monobromination is hard to occur because the brominated alpha is more acidic
- will form enolate faster
1)NaOH, BR2 2) H3O+ with ketone with methyl side
Haloform
-goes through tribromination
This forms a good LG
-OH can then attack the carbonyl carbon
-carbonyl reforms and expels CBr3 that later forms CHBr3 (Bromoform)
**this is exception to never releasing C- because the induction makes it stable
-most efficient when other alpha position has no protons
NaOH, H2O with aldehyde
Aldol Addition
- aldehyde is deprotenated at the alpha position, forming enolate
- enolateattacks carbonyl carbon
- the alkoxie ion of attacked aldeyde is then protenated
- forms beta-hydroxy -ketone
NaOH, H2O with ketone
Retro Aldol Reaction
- reverse three steps of aldol addition
- beta-hydroxy is deprotenated
- carbonyl reforms, pushes off enolate
- enolate can be reprotenated
- this is exception because enolate is resonance stabbilized and most of electron density is on oxygen
Acid/Basic Conditions, heat with aldol
Aldol Condensation
- aldol addition must occur
- alpha proton is deprotenated
- anion forms double bond, OH is LG
NaOH/LDA, heat, two aldehydes
Crossed Aldol Reactions
Efficient if:
1)One ester has not alpha protons
2) Directed claison condensation is performed
1) NaOR 2) H3O+ with two aldehydes
Claisen Condensations The condensation reaction of esters -ester forms enolate -onolate attacks other ester Ester reforms and pushes O-R off -alpha position between both is deprotenated and resonance stabilized -product is beta-keto-ester
1)LDA, -78 deg C 2) RX with ketone
Alkylation of the Alpha Position: Kinestic Product
-form enaolate ion
-enolate ion attacks alkyl halide in SN2 fashion
-alkyl halide should be methyl/primary
-if secondary or tert, the enolate acts as a base. And alkyl halide is eliminated
-must use strong base like LDA, one equivalent
-this is so that all LDA is used up and none is left over
Kinetic Product:
Less sterically hindered
-lower Ea, less stable final product
1)NaH, 25 deg C 2)RX with ketone
Alkylation of the Alpha Position: Thermodynamic Product
-form enaolate ion
-onolate ion attacks alkyl halide in SN2 fashion
-alkyl halide should be methyl/primary
-if secondary or thert, the enolate acts as a base. And alkyl halide is eliminated
-must use strong base like LDA, one equivalent
-this is so that all LDA is used up and none is left over
Thermodynamic product:
-more substituted position
-Higher Ea
-forms more stable enolate
1) NaOEt
2) RX
3) H3O+, Heat with diethyl malonate
The Malonic Ester Synthesis
- tranforms halide into carboxylic acid with two new carbons
- uses diethyl malonate which is deprotenated between carbonyls
- the is then alkylated with alkyl halide
- aquaeus acid hydrolyzes both ester moieties
- heat allows for decarboxylation forms one subbstitued carboxylic acid and one carbon dioxide
- this occurs through a pericyclic reaction
