Ch.22 Flashcards
What is alpha substitution?
the substitution of one of the hydrogens attached to the alpha carbon for an electrophile
Alpha substitution occurs through an _____ ion intermediate.
enolate
What is tautomerization?
an interconversion of isomers that occurs through the migration of a proton and the movement of a double bond
Are tautomers resonance forms?
no
Describe base-catalyzed tautomerism.
A proton on the a carbon is abstracted to form a resonance-stabilized enolate ion with the negative charge spread over a carbon atom and an oxygen atom
Equilibrium in base-catalyzed tautomerism favors which form?
favors keto form over the enolate ion
Describe acid-catalyzed tautomerism.
the oxygen is first protonated, and then a proton from the a carbon is removed
Describe reacemization.
If a chiral a carbon has an enolizable hydrogen atom, a trace of acid or base allows that carbon to invert its configuration, with the enol serving as the intermediate.
What is the pKa for alpha H of aldehyde or ketone?
around 20
Which is more acidic, and aldehyde/ketone or alkane/alkene?
aldehyde/ketone
What is the approximate pKa of water?
15.7
what is the pKa of an alkyne?
25
what is the pKa of an alcohol?
16-19
Even though the keto–enol tautomerism equilibrium favors the keto form, addition of an ______ ______ the equilibrium toward the formation of more enol
electrophile shifts
How is LDA made?
by using an alkyllitium reagent to deprotonate diispropylamine
What can LDA do?
convert a carbonyl compound completely to its enolate
what happens when LDA reacts with a ketone?
it abstracts the a proton to form the lithium salt of the enolate
Ketones or aldehydes react with a secondary amine to form _________.
enamines
The enamine has a nucleophilic a carbon, which can be used to attack ___________.
electrophiles
The electrostatic potential map (EPM) of a simple enamine shows a what (red) near the a carbon atom of the double bond?
high negative electrostatic potential
Enamines displace halides from reactive alkyl halides, giving alkylated _____ __________.
iminium salts
The alkylated iminium salt can be hydrolyzed to the ketone under _____ conditions.
acidic
Hydrolysis of the iminium salt produces the ______ as the final product.
beta-diketone
When a ketone is treated with a halogen and a base, an ____________ reaction occurs.
alpha halogenation
What reaction is called base-promoted?
the alpha halogenation of ketone
In multiple halogenation, which halogenation occurs faster?
second halogenation
In haloform reaction, when Cl2 is used, what is formed?
chloroform
In haloform reaction, when Br2 is used, what is formed?
bromoform
In haloform reaction, when I2 is used, what is formed?
iodoform
What is the iodoform test used to identify?
methyl ketones (or secondary alcohols)
Alcohols can give a _____ iodoform test.
positive
What is iodoform (CHI3)?
a yellow solid that participates out of solution
The _____ reaction replaces a hydrogen atom with a bromine atom on the a carbon of a carboxylic acid (a-bromoacid).
HVZ
what do condensations do?
combine two or more molecules, often with the loss of a small molecule such as water or an alcohol
what is the aldol condensation?
the addition of an enolate ion to another carbonyl group. It occurs under basic conditions
In aldol condensations, When the reaction is carried out at _____ temperatures, the beta-hydroxy carbonyl compound can be isolated
low
In aldol condensation, what will heating do?
Heating will dehydrate the aldol product to the alpha,beta-unsaturated compound.
what is crossed aldol condensation?
When the enolate of one aldehyde (or ketone) adds to the carbonyl group of a different aldehyde or ketone
Intramolecular aldol reactions of diketones are often used for making what?
five- and six-membered rings
Is stereo control possible for Mukaiyama Aldol Addition and Alkylation?
yes
Is stereo control possible for Henry Reaction?
yes
Describe the mannich reaction.
formation of the iminium ion of aldehyde
The claisen condensation results when what happens?
when an ester molecule undergoes nucleophilic acyl substitution by an enolate
What is an internal Claisen cyclization is called?
a Dieckmann condensation or a Dieckmann cyclization
What are useful esters?
benzoates, formates, carbonates, and oxalates
_________ may also react with an ester to form a beta-diketone.
ketones
What happens in a crossed claisen condensation?
an ester without alpha hydrogens serves as the electrophilic component
Which are more acidic, and more likely to deprotonate and serve as the enolate component in the condensation, ketones or esters?
ketones
What does malonic ester synthesis make?
substituted derivatives of acetic acids.
______ takes place through a cyclic transition state, initially giving an enol form that quickly tautomerizes to the product.
Decarboxylation
What are the final products of acetoacetic ester synthesis?
ketones
_____ ion completely deprotonates acetoacetic ester.
Ethoxide
alpha,beta-Unsaturated carbonyl compounds have unusually _______ double bonds.
electrophilic
describe hard nucleophiles.
have low energy HOMO’s and a high charge + have high energy LUMO’s and a high charge
describe soft nucleophiles.
have high energy HOMO’s and are polarizable + low energy LUMO’s and are polarizable
What dominates the reactivity of hard nucleophiles?
charge
What dominates the reactivity of soft nucleophiles?
orbital interactions
Hard nucleophiles tend to react well with ___ electrophiles.
hard
Soft electrophiles tend to react well with ____ nucleophiles.
soft
What are some hard basic nucleophiles?
H20, HO-, RCO2-, Cl-, ROH, RO-, NH3, RNH2
What are some hard acidic electrophiles?
H+, Li+, Na+, K+, Mg2+, BF3
What are some soft basic nucleophiles?
I-, RS-, RSe-, S2-, RSH, RSR, R3P, alkenes, aromatics, R-
What are some soft acidic electrophiles?
Ag+, Pd2+, I2, Br2, radicals
An enolate will do a ___,___-attack on the a,b-unsaturated ketone (MVK).
1,4
Describe robinson annulation.
With enough base, the product of the Michael reaction undergoes a spontaneous intramolecular aldol condensation, usually with dehydration, to give a six-membered ring—a conjugated cyclohexenone
