Pi bonds as Electrophiles: Reactions of Carboxylic Acid Derivatives

Question 1

What do Carboxylic Acid Derivative all have?

Answer 1

They all have heteroatoms (O, N or halides) bonded to their carbonyl carbon

Question 2

How do carboxylic acids differ from aldehydes and ketones?

Answer 2

Ketones and aldehydes only have C or H bonded to the carbonyl carbon

Question 3

What is the suffix for carboxylic acids?

Answer 3

oic-acid

Question 4

What is the suffix of ester carboxylic derivatives?

Answer 4

oate

Question 5

What is the suffix for acid halide?

Answer 5

oyl halide

Question 6

what is the suffix for acid anhydride?

Answer 6

oic anhydride

Question 7

what is the suffix of amide carboxylic acid derivatives?

Answer 7

amide

Question 8

How do substitution reactions differ from carbonyl additions?

Answer 8

In substitution reactions, the carbonyl has a leaving group, so it maintains its sp^2 hybridization.

Question 9

What is the other name for carbonyl substitution?

Answer 9

Acyl substitution

Question 10

Steps in Acyl substitution?

Answer 10

1. Nuc. Attack on the Carbonyl
2. Elimination of leaving group

Question 11

Leaving Group

Answer 11

electronegative atoms or functional groups which can leave as a stable group with a pair of electrons when the bond breaks.

Question 12

What makes a good leaving group?

Answer 12

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.

Question 13

What is the best leaving group?

Answer 13

Weak bases (halogens) and strong acids because they are very electronegative.
Resonance groups are also good leaving groups.

Question 14

Do exergonic reactions show a good leaving group or a bad one?

Answer 14

An exergonic process where Δ is negative, indicates a good leaving group

Question 15

What role do Electronic Effects play in relative reactivity (how fast a reaction occurs?)

Answer 15

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.

Question 16

What is the order from most to least reactive?

Answer 16

Acid Chloride
Acid anhydride
Carboxylic Acid
Ester
Amide

Question 17

Acid Chlorides

Answer 17

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)

Question 18

Acid Anhydrides

Answer 18

The extra lone pair and electron density are shared amongst Oxygens via resonance and induction, stabilizing the charge.

Question 19

Carboxylic Acids and Esters

Answer 19

O is a strongly electronegative atom but is also a good electron donor (good orbital overlap between O and C)

Question 20

Amides (least reactive)

Answer 20

N is an excellent electron donor (great orbital overlap between C and N; N is less electronegative)

Question 21

For the reactions to occur, LG needs to be _ than the Nuc.

Answer 21

X must be a better LG than the Nuc.

Question 22

Interconversion of Carboxylic acids

Answer 22

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.

Question 23

What molecules does the synthesis of acid chlorides usually include?

Answer 23

Thionyl Chloride (SOCl2)

and/or CHCl3

Question 24

Synthesis of esters and amides

Answer 24

Neutral alcohols and amines can be used as nucleophiles to make esters and amides

Question 25

Fischer Esterification

Answer 25

Acid-catalyzed esterification of carboxylic acids

Question 26

Transesterification

Answer 26

Acid-catalyzed reaction turning on ester into another.

Question 27

Ester Hydrolysis (Acidic Conditions)

Answer 27

Carboxylic acids can be prepared from esters under acidic conditions using H2O as a nucleophile. This is the reverse of the Fischer Esterification

Question 28

Ester Hydrolysis (Basic Conditions)

Answer 28

Also called Saponification

Question 29

Amide Hydrolysis

Answer 29

Amides need forcing conditions (strong acids and heat) to promote reaction.

Question 30

What is nature's natural catalyst?

Answer 30

Enzymes

Question 31

Carboxylic acid derivatives, including esters and Grignard

Answer 31

they add 2 equivalents of Grignard reagents to give tertiary alcohols.

Question 32

Carbonyl reductions

Answer 32

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

Question 33

What are esters reduced to?

Answer 33

Alcohol products with LiAlH4

Question 34

what are amides reduced to?

Answer 34

Amine products with LiAlH4

Question 35

How can esters (and some amides) be partially reduced to aldehydes?

Answer 35

Through the usage of DIBAL-H