Ch 22(18) Reactions at the alpha carbon of a carbonyl compounds Flashcards
A nucleophile can… to the what carbon
a nucleophile can add to the carbonyl carbon
A…. can remove a proton from an alpha carbon
a base can remove a proton from an alpha carbon
(an alpha carbon is a carbon that is adjacent to a carbonyl carbon)
What is the pKa of one of the hydrogens in CH3CH3
the pKa is greater than 60
Hydrogens attacehd to sp3 carbons have very____pKa values
hydeogens attached to sp3 carbons have very high pKa values
What is a carbon acid? What is the range of their pKa’s?
a compound that contains a relatively acidic hydrogen bonded to an sp3 carbon. The pKa’s range from 16~20 and 25
The electrons left behind when a proton is removed from an alpha carbon are _____ onto the ____. Draw a picture
the electrons left behind when a proton is removed from an alpha carbon are delocalized onto an oxygen.
Why are alpha carbons more acidic than other sp3 carbons
the electrons left behind when a proton is removed from an sp3 carbon are localized on the carbon.
The electrons left behind when a proton is removed from an alpha carbon are delocalized onto an oxygen.
deloocalization increases stability
(the more stable the base, the stronger its conjugate acid)
oxygen is better able to accommodate the electrons than carbon
Why are protons on an alpha carbon of an aldehyde or ketone more acidic than a proton on an alpha carbon of an ester? What are their pKa’s? Draw a picture
esters are less acidic thal aldehydes and ketone because delocalization of the electrons left behind when the proton is removed has to compete with the delocalization of the lone pair onto the carbonyl oxygen
aldehydes and ketones 16-20
ester-25
What happens when electrons can he delocalized onto two oxygens? Draw a picture.
The acidity of the alpha hydrogen increases
How do tautomes differ? Draw a picture
tautomers differ in the location of the double bond and a hydrogen.
For most ketones the ___ tautomer is more stable than the ___ tautomer. In what caseis the oppsite true.
For most ketones the keto tautomer is more stable than the enol tautomer. When the enol tautomer is aromatic it is more stable.
What is the mech for a base catalyzed keto-enol interconversion? Draw it.
- removal of a proton from the alpha carbon
- protonnation on oxygen
What is the mech for an acid catalyzed keto-enol interconversion? Draw it.
- protionation on the oxygen
- removal of a proton from the alpha carbon
What happens when an alpha carbon is treated with a halogan and an acid catalyst?
one of the alpha carbons is replace by an halogen and HX is produced.
What happen when an alpha carbon is treated with excess halogen and a base catalyst? Draw it.
all of the alpha hydrogens are replaced by the halogen and 2X- is produced
What happens when a carboxylic acid is treated with 1.PBr3 (or P),Br. 2.H2O
The HVZ reaction is used to replace the alpha carbon of a carboxylic acid with Br.
What happen when the bromine of the alpha carbon of an aldehyde or ketone is treated with a waek base?
the Br is replaced by the weak base and Br is released as an ion.
What happens when bromine of the alpha carbon of a carboxylic acid is treated with a weak or strong base?
The Br is replaced by the base.
What can be used to form the enolate ion so the equilibrium lies to the right?
LDA can be use since DIA is produced in the reaction and it is a weaker acid then aldehydes and ketones.
How is LDA synthesized ?
With diisopropylamine ,butyllithium and THF at -78ºC
How do you alkylate the alpha carbon of ketones, esters and nitriles?
With 1. LDA/THF 2. alkyl halide with the desried alkyl group
Polyakylation will occur if a weak base (HO-) is used
How do you snthesize an enamine?
When a ketone or aldehyde is treated with a secondary amine and trace acid an enamine and water are produced.
How can you alkylate an alpha carbon via an enamine?
- secondary amine,trace acid
- akyl halide or acyl halide (eletrophile)(Sn2 Reaction)
- HCl/H2O
enamines react with electrophiles like enolates do
alpha, beta-unsaturated aldehydes and ketones under go _______ and _____
alpha, beta unsaturated aldehydes and ketone undergo direct addation and conjugate?
-poor nucleophiles form the conjugate addation product
Whan alpha beta unsaturated aldehyde or ketone is treated with a beta -diester what does the product look like and what are the reagents used?
the beta carbon of the alpha beta carbon is boned to the alpha carbon of the diester.
An same ester ion must be used and along wih methol(same alkyl alchol)
In the presence of catalytic acid or base, a ketone will exist in equilibrium with an ___
enol
What are the factors that effect the equilibrium concentrations of an diketone and the enol
(1) The enol has a conjugated p system, which is a stabilizing factor , and (2)
the enol can form an intramolecular H-bonding interaction between the hydroxyl proton and the
nearby carbonyl group (shown with a gray dotted line above). Both of these factors serve to stabilize
the enol.
When treated with a strong base, the a position of a ketone is deprotonated to give a resonance-stabilized
intermediate called an ____
enolate
Enolates are ambident nucleophiles (ambi is Latin for “both” and dent is Latin for “teeth”), because they possess two nucleophilic sites, each of which can attack an electrophile. When the oxygen atom attacks an electrophile, it is called O-attack; and when the a carbon attacks an electrophile, it is called __-attack.
C- attack
C-attack is nevertheless
more common than O-attack. All of the reactions presented in this chapter will be examples
of C-attack. When drawing the mechanism of an enolate undergoing C-attack, it is technically more
appropriate to draw the resonance structure of the enolate in which the negative charge appears
on the oxygen atom
Why are enolates more usful than enols
(1)enolates possess a full negative charge and are
therefore more reactive than enols and (2) enolates can be isolated and stored for short periods of
time, unlike enols, which cannot be isolated or stored. For these two reasons, the vast majority of
reactions in this chapter proceed via enolate intermediates.
What is an aldol
hydroxyl group is located specifically at the b position
relative to the carbonyl group. The product of an aldol addition reaction is always a b-hydroxy
aldehyde or ketone
aldol addation mech
Retro aldol reaction mech
When heated in acidic or basic conditions, the product of an aldol addition reaction will undergo
elimination to produce unsaturation between the alpha and _____ positions.
beta
What is an aldol condensation
mech for an aldol condensation
Crossed aldol reactions
Intermolecular aldol reactions
Compounds that possess two carbonyl groups can undergo intramolecular aldol reactions. Consider
the reaction that occurs when 2,5-hexanedione is heated in the presence of aqueous sodium hydroxide.
Claison condensation
Like aldehydes and ketones, esters also exhibit reversible condensation reactions.
mech for claisen condensation
A directed Claisen condensation can be performed in which LDA is used as a base to irreversibly
form an ester enolate, which is then treated with a different ester.
Claisen condensation
under acidic conditions, ketones and aldehydes will undergo halogenation at the ____ position
alpha position
this reaction is observed from chlorin, bromine and iodine
Mech for acid catalyzed halogenations of ketones
with unsymmertical ketones bromination occurs primarily at the more substituted side of the ketone, the less substituted is observed as a minor product
halogenated products can under go elimination when treated with a ____
base
Li2CO3
pyridine
tert-butoxide
carboxyclic acids undergo alpha halogenation when treated with bromine in the presence of ____
PBr3
Hell-Volhard-Zelinsky reaction
alpha halogenation in basic conditions
if more than one alpha hydrogen is present then it is difficult to achive monobromination
haloform reaction mech
1)NaOH,Br2/2)H3O+
the reaction ust be followed bt a proton source
x
Dickmann cyclzation
1)NaOEt/2) H3O+
regionselective alkylation
malonic ester synthesis trans forms a halide in to a _____
carboxylic acid with the introduction of two new carbon atoms
acetoacetic ester synthesis is used to conert a alkyl halide into a ______.
methyl ketone with the introduction of three new carbons atoms
