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Flashcards in Carboxylic Acid Derivatives Deck (27)
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1

Reactivity of Carboxylic Acids

MOST REACTIVE

Acyl halides

Anhydrides

Esters

Amides

LEAST REACTIVE 

2

"Golden Rule" 

(from prev chapters)

H- or C- will attack twice, but all other nucleophiles will only attack once

  • After attacking a carbonyl, always try to reform the carbonyl if you can, but never kick off H- or C-
  • If the second attack is by H- or C-, then the carbonyl will not be able to re-form

3

When can proton transfers happen in an attack?

Between Core steps

Before the attack   ---Attack carbonyl----> Between attacking & reforming ---Reform Carbonyl--> End of mechanism

4

When/Why protonate a carbonyl group?

Why? Makes carbonyl group even more electrophilic

What: 

Do not need to protonate acyl halides and anhydrides (already reactive enought)

Do need to protonate weakly active onces (ie: ester reacting with water)

5

Fischer Esterification of RCO2H

Ingredients: 

  • Carboxylic acid
  • Alcohol

RCO2H --MeOH/TsOH-->   RCO2Me

 

Position of equillibrium is important: 

RO2----[Excess ROH, [H+]]---->  RO2R

RO2----[Excess H2O, [H+]]---->  RO2H

6

How do you make Esters from Acyl Halides and Anhydrides?

ROH

7

Ester Hydrolysis under basic conditions

  1. -OH attacks Carboxylic acid's C (C=O pushes to C-O-)
  2. O- pushes electrons back to C (OR leaves)
  3. OH- depotonates OH so it is O[stabilized by resonance]
  4. Second step to protonate again. [NOTE: use H+, not H2O!]

8

Nitriles

  • R-C≡N
  • Cyano group: [C≡N]
  • Same oxidation level of other carboxylic acid derivatives
  • Hydrolysis of nitrile produces amide (NOT Ox-Red rxn), can be done under acidic or basic conditions

9

Amide Production

  • One core step: Attack the carbonyl
  • Hydrolysis of nitrile produces amide (NOT Ox-Red rxn)

  • can be done under acidic or basic conditions

10

Reactivity of Carboxylic Acid Derivatives

11

Reactivity of Carboxylic Acid Derivatives (alt view)

12

General Reactions of Carboxylic Acid Derivatives

13

Mechanism of amide formation by reaction of a carboxylic acid and an amine with dicyclohexylcarbodiimide (DCC) 

  1. Dicyclohexylcarbodiimide is first protonated by the carboxylic acid to make it a better acceptor. 
  2. Thecarboxylatethenadds to the protonated carbodiimide to yield a reactive acylating agent. 
  3. Nucleophilicattackofthe amine on the acylating agent gives a tetrahedral intermediate. 

    The intermediate loses dicyclohexylurea and gives 4 the amide. 

 

 

 

 

14

Reactions of Acid Halides 

15

Acid Anhydride Reactions

16

Preparation of Esters

17

Preparation of Amides

18

Nomenclature of Carboxylic Acid Derivatives

19

Hydrolysis

Reaction with water to yeild carboxylic acid

20

Alcoholysis

Reaction with an alcohol to yield an ester

21

Aminolysis

reaction with ammonia or an amine to yield an amide

22

Reduction

reaction with a hydride reducing agent to yield an aldehyde or an alcohol

23

Grignard reaction

Reaction with an organometallic reagent to yield a ketone or an alcohol

24

Summary of Reactions (MM Ch 21.a)

25

Summary of Reactions (MM Ch 21.b)

26

Summary of Reactions (MM Ch 21.c)

27