Pi bonds as Electrophiles: Reactions of Carboxylic Acid Derivatives Flashcards
What do Carboxylic Acid Derivative all have?
They all have heteroatoms (O, N or halides) bonded to their carbonyl carbon
How do carboxylic acids differ from aldehydes and ketones?
Ketones and aldehydes only have C or H bonded to the carbonyl carbon
What is the suffix for carboxylic acids?
oic-acid
What is the suffix of ester carboxylic derivatives?
oate
What is the suffix for acid halide?
oyl halide
what is the suffix for acid anhydride?
oic anhydride
what is the suffix of amide carboxylic acid derivatives?
amide
How do substitution reactions differ from carbonyl additions?
In substitution reactions, the carbonyl has a leaving group, so it maintains its sp^2 hybridization.
What is the other name for carbonyl substitution?
Acyl substitution
Steps in Acyl substitution?
- Nuc. Attack on the Carbonyl
- Elimination of leaving group
Leaving Group
electronegative atoms or functional groups which can leave as a stable group with a pair of electrons when the bond breaks.
What makes a good leaving group?
The leaving group takes the pair of electrons, so a good leaving group can stabilize the additional electrons (they can hold the pair of electrons well.
What is the best leaving group?
Weak bases (halogens) and strong acids because they are very electronegative.
Resonance groups are also good leaving groups.
Do exergonic reactions show a good leaving group or a bad one?
An exergonic process where Δ is negative, indicates a good leaving group
What role do Electronic Effects play in relative reactivity (how fast a reaction occurs?)
Electron withdrawing groups enhance carbonyl reactivity by increasing its electrophilicity at the carbonyl C.
Therefore, groups in which X is a poor electron donor and a good electron withdrawer, reacts the fastest.
What is the order from most to least reactive?
Acid Chloride
Acid anhydride
Carboxylic Acid
Ester
Amide
Acid Chlorides
Cl is a strongly electronegative atom
it does not undergo resonance readily
It stabilizes the negative charge it leaves with its size and electronegativity (ability to pull and haul electron density towards itself)
Acid Anhydrides
The extra lone pair and electron density are shared amongst Oxygens via resonance and induction, stabilizing the charge.
Carboxylic Acids and Esters
O is a strongly electronegative atom but is also a good electron donor (good orbital overlap between O and C)
Amides (least reactive)
N is an excellent electron donor (great orbital overlap between C and N; N is less electronegative)
For the reactions to occur, LG needs to be _ than the Nuc.
X must be a better LG than the Nuc.
Interconversion of Carboxylic acids
Carboxylic acids and their derivatives can be interconverted using a variety of chemical pathways
A more reactive derivative can be used to make a less reactive one, but the reverse is not possible.
What molecules does the synthesis of acid chlorides usually include?
Thionyl Chloride (SOCl2)
and/or CHCl3
Synthesis of esters and amides
Neutral alcohols and amines can be used as nucleophiles to make esters and amides
Fischer Esterification
Acid-catalyzed esterification of carboxylic acids
Transesterification
Acid-catalyzed reaction turning on ester into another.
Ester Hydrolysis (Acidic Conditions)
Carboxylic acids can be prepared from esters under acidic conditions using H2O as a nucleophile.
This is the reverse of the Fischer Esterification
Ester Hydrolysis (Basic Conditions)
Also called Saponification
Amide Hydrolysis
Amides need forcing conditions (strong acids and heat) to promote reaction.
What is nature’s natural catalyst?
Enzymes
Carboxylic acid derivatives, including esters and Grignard
they add 2 equivalents of Grignard reagents to give tertiary alcohols.
Carbonyl reductions
Esters and amides are significantly less reactive than aldehydes and ketones.
Since NaBH4 is a mild hydride source, it can only reduce aldehydes and ketones.
LiAlH4 is a strong hydride source (more reactive) so it can reduce aldehydes, ketones, esters, and amides
DIBAL-H is a unique reducing agent
What are esters reduced to?
Alcohol products with LiAlH4
what are amides reduced to?
Amine products with LiAlH4
How can esters (and some amides) be partially reduced to aldehydes?
Through the usage of DIBAL-H
