CH223 Part 5/6: Carboxylic Acids & Derivatives and Enolate Chemistry (Conceptual) Flashcards
What does a acid-catalyzed esterification reaction do?
changes carboxylic acid to ester
Why does an acid-catalyzed esterification reaction need an acid?
it protonates the carboxylic acid and makes the carbonyl group more electrophilic so that it can be attacked by even alcohols
What are hydroxy acids?
compounds that contain both hydroxyl and carboxylic acid functional groups
What do hydroxyl acids form?
cyclic esters called lactones
When does intramolecular esterification take place spontaneously?
when a five- or six-membered ring can be formed
What is a hydrolysis reaction the reverse of?
ester esterification
Which hydrolysis reaction is irreversible? Why?
base-catalyzed ester hydrolysis because the NaOR base will continue to react with the product in an acid-base mechanism
Describe the reactivity trend of common carboxylic acid derivatives?
acyl chloride > acid anhydride > ester > amide
Why is acyl chloride the most reactive?
acyl chloride is very unstable because Cl is incredibly electronegative (wonāt stable partial positive carbonyl)
Why are acid anhydrides more reactive than esters?
the singular middle oxygen in an acid anhydride has to stabalize both carbonyls
Why are esters more reactive than amides?
the oxygen of an ester is more electronegative than the oxygen of a nitrogen
How can acyl chlorides be made?
by treating carboxylic acids with thionyl chloride (SOCl2)
What is the role of pyridine in nucleophilic acyl substitutions with acyl chloride
pyridine can act as a nucleophile and catalyze a reaction to be more reactive than acyl chloride
What is a āNā amide?
A substituted amide formed during a reaction of an ester with an amine
What bond is very strong in amides?
the CN bond
Why do amides have such high boiling points?
they have strong hydrogen bonding and dipole dipole intermolecular forces
Are acid or base amide hydrolysis reactions irreversible?
both! the ammonium ion formed during the acid reaction is not nucleophilic while the carboxylate anion formed during the base reaction is not electrophilic
What is it called when aldehydes and ketones become enols?
tautomerize
What is the keto form?
double bond between carbon and oxygen
What is the enol form?
double bond between two carbons
Where are is the keto form reactive?
it is electrophilic at the carbonyl carbon
Where is the enol form reactive?
it is nucleophilic at the alpha carbon
Why does alpha-halogenation only occur once?
Cl is an EWG that slows down protonation enough to stop a 2nd halogentation
What is the o-enolate?
there the double bond is between two carbons with a negative charge on the oxygen
Where is the most acidic hydrogen on an ketone/aldehyde/ester?
the alpha halogens due to the inductive effective and resonance stabilization with the enolate
What do enolates usually act as in reactions?
nucleophiles
What do you have to make sure matches when using esters?
the alkoxide bases should match the ester to avoid ester saponification
Reactions with alkoxide bases favor the ____.
reactants
Reactions with LDA favor the ____.
products
Where does LDA remove a proton from?
the less substituted alpha carbon because of steric crowding
What reaction occurs when enolates react with carbonyls of aldehydes and ketones?
aldo condensation
When an aldo reaction is heated, what is the product?
an alpha, beta unsaturated carbonyl compound
When will intramolecular aldol condensation reactions occur?
when five- or six-membered rings can be formed
In mixed aldol reactions, how do you know which one is the nucleophile and which one is the electrophile?
- the nucleophile has an enolizable hydrogen
- aldebydes are always more electrophilic than ketones
What is a Claisen condensation reaction?
when two esters react to form a beta keto ester
What must be true of the ester involved in a claisen condensation?
must have at least two alpha hydrogens (two enolates formed)
When will intramolecular Claisen condensation (dieckmann cyclization) occur?
when a five- or six- membered ring can be formed
What can aldehydes, ketones, and ester enolates be alkylated with?
primary alkyl halides
How can you avoid polyalkylations of enolates?
use an enamie as a enol equivalent or use LDA
What is the micheal reaction?
the addition of enols/enolates to the best carbon
What is the product of a micheal reaction?
1,5 diketone
