Carboxylic Acid & Derivative Reactions Flashcards
What can we use to complete this reaction?
LiAlH4 followed by acid workup
What kind of reactants are necessary for a decarboxylation reaction to occur?
Acidic amino acid, beta-keto acid, dicarboxylic acid
Decarboxylation mechanism:
What product will form when the following carboxylate ion (pyruvate) undergoes a decarboxylation reaction in the presence of HS-CoA?
The decarboxylation of pyruvate produces acetyl-CoA. This reaction is an example of enzyme-catalyzed oxidative decarboxylation.
How do you determine the possible reactants when presented with this anhydride product?
- Since this is an anhydride you should know that to form an anhydride requires either the combination of an acyl chloride and carboxylic acid OR a condensation reaction of two carboxylic acids.
- Look at the molecule and draw two lines on each side of the ester O. Number the carbons.
- One side of the line makes up the acyl chloride and the other side makes up the carboxylic acid or vice versa. Different combinations can be made to achieve the same product.
Which is more likely to react (better electrophile), an anhydride or an amide?
Anhydride because it has a strong EWG (stronger inductive effect) due to the adjacent O, whereas an amide has an adjacent N which has less inductive effect.
EWG make better LGs and cause electrophile to be more reactive.
How does the number of electron-withdrawing groups affect the acidity of a carboxylic acid?
The more electron-withdrawing groups, the stronger the acid. These groups stabilize the conjugate base by delocalizing the electron density of the negative charge.
How is the acidity of a carboxylic acid affected by the electronegativity of its substituents?
More electronegative group near a carboxyl group increases the acidity.
IUPAC suffix for an ester:
-oate
How is an ester named according to IUPAC?
The alkyl group from the —o—- (alcohol) side is named first as a substituent whereas the body chain makes up the =O side
When an alcohol and a carboxylic acid are combined in solution and heated, what reaction is expected to occur? What product(s) will form?
An esterification reaction will occur between the alcohol and carboxylic acid. The expected products include an ester and water.
Acid-Catalyzed epoxide opening mechanism
*Nucleophile attaches to more substituted side
Base-Catalyzed epoxide opening mechanism
*strong base+ strong nucleophile attacks less substituted C in an SN2 manner
*Causes inversion of configuration where the nucleophile attacks
Out of all the carboxylic acid derivatives, which is the most reactive?
Acyl halide, which is the least stable because it has no resonance, Also has induction (which increases reactivity, electrophilicity of the C).
NaBH4 is a reducing agent, what happens if it reacts with a carboxylic acid?
NaBH4 is not strong enough to reduce a COOH, therefore it remains the same.
General mechanism of nucleophilic acyl substitution.
Creation of acyl halide mechanism
Starting reactant: carboxylic acid
Reagent: SOCl2, PCl5, PCl3, PBr3
IUPAC naming of an amide rules
-Carbon 1 starts at the carbonyl carbon of the amide
-Any substituents connected to the N in the amide are donated as N–name of substituents numbering from the C closest to N
If you want to create an amide, why can’t you use a carboxylic acid as your starting reactant?
If you react a COOH and an amine (necessary for amide formation), you would get a predominant neutralization reaction.
An amide can be formed when reacting what carboxylic acid derivative with an amine?
acyl halide
During amide formation, using ammonia (NH3), yields a (primary, secondary, tertiary) amide. What about using a primary amine and secondary amine?
Primary amide
Primary amine yields a secondary amide. Secondary amine yields a tertiary amide.
Acid-catalyzed amide hydrolysis
Base-catalyzed amide hydrolysis
Condensation of 2 carboxylic acids, forms what product?
How do we create an anhydride, what reactants and reagents do we need?
*Starting reactant: Carboxylic Acid and Acyl halide
*Reagents: 1)NaOH or another strong base
Anhydride hydrolysis mechanism
What is fischer esterification?
When a COOH and OH react to form an ester. UNDER ACIDIC CONDITIONS ONLY
How to figure out the product of a Fischer esterification?
Add the 2 OH’s together to form the ester
Fischer Esterification mechanism
Question about fischer esterification
The purpose of the acid in this reaction is to protonate which enhances the electrophiles & increases the stability of leaving groups (adding + charge).
In general, for base catalyzed reactions, the base enhances nucleophilicity.
Define transesterification.
When an ester reacts w/ an alcohol to produce a new different ester.
What are the products of saponification? Saponification occurs under what conditions?
Sodium carboxylate salts (soap) and a glycerol backbone.
Strong-base catalyzed conditions. If there are 3 fatty acids, (ester linkages) 3 equivalents of base are needed.
Saponification/ester hydrolysis mechanism
What is lactonization?
Intramolecular reaction between a carboxylic acid & alcohol creating a cyclic ester called a “latone”.
Gabriel synthesis starting reactants
Starting reactant: N-phthalimidomalonic ester
Gabriel synthesis basic steps
-Deprotonation with strong base
-SN2 nucleophilic attack by alkyl halide: addition of alkyl group
-The alkyl group becomes the R group of the amino acid product
-Base catalyzed hydrolysis
-Decarboxylation with heat, CO2 byproduct
The starting reactant of Stecker synthesis is ______?
An aldehyde
The R group of the amino acid produced from Strecker synthesis is originally present in _________.
the starting aldehyde
steps of strecker synthesis
1) Aldehyde condensation – ammonia added to an aldehyde creating an imine intermediate
2) Cyanide Nucleophilic attack forming aminonitrile (non-stereospecific attack so it forms a racemic mixture of L/D amino acids
3) Aminonitrile hydrolysis to form COOH terminus
Gabriel synthesis and strecker synthesis both produce what kind of product ________?
A racemic mixture of amino acids (D & L)
A general rule is that:
Resonance which donates electron density makes a carboxy acid. derivative less reactive.
Induction makes a carboxy acid. derivative more reactive.
Why is a cyclic amide (lactam) more reactive than a regular amide?
A cyclic amide which adopts a ring structure that has a lot of ring strain causes a decrease in resonance character, which makes the compound unstable –> more reactive
