Ch 22 - Carboxylic Acids & Derivatives--Nucleophilic Acyl Substitution

Question 0

What is a lactone? Lactam?

Answer 0

Lactone: cyclic ester
Lactam: cyclic amide

Question 1

Classification of amides?

Answer 1

Primary: CO-NH2
Secondary: CO-NHR
Tertiary: CO-NR2

Question 2

In RCOZ, the more basic Z….

Answer 2

…the more it donates its e- pair, ⬆ resonance stabilization, ⬇reactivity, poorer LG

Question 3

Order of basicity of RCOZ?

Answer 3

[least] Cl- (acid chloride) ➡ RCOO- (anhydride) ➡ -OH/-OR (alcohol/ester) ➡ -NR2 (amide) [most]

Question 4

Mechanism of nucleophilic acyl substitution?

Answer 4

1) Nu:- attack @ carbonyl C

2) elimination of LG (Z)

Question 5

More rxtive acyl compds can be converted to less rxtive acyl compds by nuc substitution. T or F?

Answer 5

T (vice versa F)

Question 6

Acid chloride ➡ anhydride. Nucleophile?

Answer 6

RCOO-

Question 7

Acid chloride ➡ carboxylic acid. Nucleophile & reagents?

Answer 7

H2O/pyridine

Question 8

Acid chloride ➡ ester. Nucleophile & reagent?

Answer 8

ROH/pyridine

Question 9

Acid chloride ➡ primary, secondary, tertiary amides. Nucleophile?

Answer 9

Primary: 2 NH3
Secondary: 2 RNH2
Tertiary: 2 R2NH

Question 10

Rxn of anhydrides: Nuc attacks at one of the carbonyl C. What happens to second carbonyl C?

Answer 10

Becomes LG (RCOO)

Question 11

Anhydride ➡ carboxylic acid + carboxylic acid. Nucleophile?

Answer 11

H2O

Question 12

Anhydride ➡ ester + carboxylic acid. Nucleophile?

Answer 12

ROH

Question 13

Anhydrides ➡ primary, secondary, tertiary amides + RCOO-. Nucleophile?

Answer 13

Primary: NH3
Secondary: RNH2
Tertiary: R2NH
All in excess

Question 14

Rxn of carboxylic acids: What happens when a strong base is used as a nucleophile?

Answer 14

Acid-base rxn occurs first before nuc substitution (nuc will extract a H+ off OH ➡ RCOO-)

Ex) -OH, -OR, NH3, RNH2

Question 15

Carboxylic acid ➡ acid chloride. Reagent?

Answer 15

SOCl2

Question 16

Dicarboxylic acid ➡ cyclic acid anhydride. Reagent?

Answer 16

Heat

Question 17

Carboxylic acid ➡ ester (fischer esterification). Nucleophile & Reagent?

Answer 17

ROH/Acid catalyst (H2SO4)

Question 18

Steps of Fischer esterification (6)?

Answer 18

Part 1: protonate carbonyl O, addn of ROH to carbonyl C, deprotonate ROH
Part 2: protonate carboxylic OH, elim LG (H2O), deprotonate other OH

Question 19

Two options for carboxylic acid ➡ primary, secondary amide?

Answer 19

1) NH3 / heat
or
✳2) DCC

Question 20

Esters + H2O/acid ➡ ?

Esters + H2O/base ➡ ?

Answer 20

In acid: carboxylic acid + alcohol

In base: carboxylate anion + alcohol

Question 21

Mechanism of ester hydrolysis in acid, steps (6)?

Answer 21

Part 1: protonate carbonyl O, addn of H2O to carbonyl C, deprotonate H2O
Part 2: protonate OR, elim of LG (alcohol), deprotonate OH

Question 22

Mechanism of ester hydrolysis in base (saponification), steps (3)?

Answer 22

1) addn of -OH to carbonyl C
2) Elim of LG (alkoxy group)
3) deprotonate OH

Question 23

Amides + H2O/acid ➡ ?

Amides + H2O/base ➡ ?

Answer 23

In acid: carboxylic acid + R2NH2+

In base: carboxylate anion + R2NH

Question 24

Method to synthesize nitriles?

Answer 24

-CN attacks RX (Sn2)

Question 25

Nitriles + H2O/acid ➡?

Nitriles + H2O/base ➡?

Answer 25

In acid: carboxylic acid

In base: carboxylate anion

Question 26

Reduction of nitriles ➡ primary amines, reagent?

Answer 26

LiAlH4 / H2O

strong reagent

Question 27

Reduction of nitriles ➡ aldehydes, reagent?

Answer 27

DIBAL-H / H2O

mild reagent

Question 28

Nitriles ➡ ketones, reagent?

Answer 28

1) RMgX or RLi / H2O

Question 29

Mechanisms to know for Ch. 22!

Answer 29

• esterification
• ester hydrolysis in acid
• ester hydrolysis in base