carboxylic acids are abundant in nature and in … organic chemistry 1e 21-6 • carboxylate ions...

• Carboxylic acids are abundant in nature and in

pharmaceuticals.

21.1 Introduction Carboxylic Acids

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Klein, Organic Chemistry 1e 21-1

• The US produces over 2.5 million tons of acetic acid per

year, which is primarily used to produce vinyl acetate.

– Vinyl acetate is used in paints and adhesives.

– Carboxylic acid derivatives, such as vinyl acetate, are

very common, and they play a central role in organic

chemistry.

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Klein, Organic Chemistry 1e 21-2

• Monocarboxylic acids are named with the suffix “oic acid.”

– The carbon of the carboxylic acid moiety is assigned the locant

position 1.

21.2 Nomenclature of Carboxylic Acids

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Klein, Organic Chemistry 1e 21-3

• When the carboxylic acid group is

attached to a ring, it is named as an

alkane carboxylic acid.

• There are also many common names for carboxylic acids.

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-4

• Dicarboxylic acids are named with

the suffix “dioic acid.”

• There are also many common names for dicarboxylic acids:

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Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-5

• The carbon atom of the carboxylic acid

has a trigonal planar geometry.

• The acid moiety is capable of strong hydrogen (H­) bonding

including H-bonding between acid pairs.

– As a result, carboxylic acids generally have high boiling points.

– Consider the BPs of acetic acid (118 C) and isopropanol (82 C).

21.3 Structure/ Properties of Carboxylic Acids

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Klein, Organic Chemistry 1e 21-6

• Carboxylate ions end in the suffix “oate.”

– Compounds that end in the suffix “oate” are often found in food

ingredient lists as preservatives.

– NaOH is a strong base, so it is capable of reacting ≈100% with a

carboxylic acid.

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-7

• In water, the equilibrium generally favors the acid .

• pKa values mostly range between 4 and 5. What is pKa?

Copyright 2012 John

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Klein, Organic Chemistry 1e 21-8

• How does the pKa value for a carboxylic acid compare to a

strong acid like HCl, or a very weak acid like ethanol?

H–Cl

pKa = -7

– How can induction and resonance be used to explain the acidity of a

carboxylic acid?

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-9

• Let’s examine the equilibrium between the carboxylic acid

and the carboxylate at physiological pH (7.3).

• The acid and the conjugate base make a buffer. HOW?

• Recall that the Henderson-Hasselbalch equation can be

used to calculate the pH of a buffer:

• Assuming the pKa is 4.3, calculate the ratio of

carboxylate/acid.

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Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-10

• Many biomolecules exhibit carboxylic acid moieties.

• Biomolecules such as pyruvic acid exist primarily as the

carboxylate under physiological conditions.

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Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-11

• Electron withdrawing substituents have a great effect on

acidity.

Copyright 2012 John Wiley

& Sons, Inc.

Klein, Organic Chemistry 1e 21-12

• Electron withdrawing substituents affect benzoic acid as

well.

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Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-13

21.4 Preparation of Carboxylic Acids

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Klein, Organic Chemistry 1e 21-14

• Two new ways to make carboxylic acids:

1. The hydrolysis of a nitrile can produce a carboxylic acid.

– The mechanism will be discussed later.

– Carboxylic acids can be made from alkyl halides using a two-step

process.

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Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-15

2. Carboxylation of a Grignard reaction can be achieved

using CO2.

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-16

Which of the following will undergo a downhill acid base

reaction when exposed to an amine such as ammonia (NH3)?

1. I only

2. II only

3. I and II I and III

4. I and IV

5. I, II, and IV

6. All of them

7. None of them

8. Not sure

CTQ 7?

1. No errors

2. 1 error

3. 2 errors

4. 3 or more errors

5. Not sure

6. Need more time

• Fischer esterification combines a carboxylic acid

and an alcohol using an acid catalyst.

21.10 Preparation of Esters

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Klein, Organic Chemistry 1e 21-19

– Each step of the Fischer esterification mechanism is equilibrium.

– Under acidic conditions, (–) charges are avoided.

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Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-20

• The overall Fischer esterification reaction is an

equilibrium process.

– How might you use Le Châtelier’s principle to favor

products?

– How might you use Le Châtelier's principle to favor

reactants?

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-21

Which reactions will NOT give a significant amount of product?

O

OH

H3C NH2

O

NH

CH3

H2O

C6H5

O

OH

H2SO4

H3C

HN

excess

C6H5

O

N

H2O

O

OH

O

OEt

H2O

CH2CH3

Et OH

excess

excess

Et ONa H2SO4

O

OH

LiAlH4

O

OH

excessO

O

O

OH

O

OEt

H2O

Et OH

excess

NH3 NH4

H3O

OH

8. Not sure

9. Need more time

I. II.

III. IV.

V. VI.

1. I, II, and III

2. I, II, and IV

3. I, III, and IV

4. I, III, and V

5. II, III, and IV

6. I, II, and V

7. IV, V, and VI

8. Not sure

9. Need more time

• Esters can undergo hydrolysis in the presence of aqueous

hydroxide (SAPONIFICATION).

– Predict the last steps in the mechanism.

– To produce a carboxylic acid, H3O+ must be added at the end.

WHY?

21.11 Reactions of Esters

Copyright 2012 John

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Klein, Organic Chemistry 1e 21-23

• SAPONIFICATION is an equilibrium process.

– Analyze the reversibility of each step in the mechanism.

– How might you use Le Châtelier’s principle to favor

products?

– How might you use Le Châtelier’s principle to favor

reactants?

– Is there an entropy difference that might be exploited?

• Soap is made through the saponification of

triglycerides. EXPLAIN HOW.

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-24

• Nylon is a polyamide.

• Polyester is made similarly. HOW?

21.12 Preparation and Reactions of Amides

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Klein, Organic Chemistry 1e 21-25

• Amides can be hydrolyzed with H3O+, but the

process is slow and requires high temperature.

• The mechanism is very similar to that for the

hydrolysis of an ester.

• Show a complete mechanism.

• WHY is the process generally slow?

Copyright 2012 John

Wiley & Sons, Inc.

Klein, Organic Chemistry 1e 21-26

• LAH can reduce an amide to an amine.

• The mechanism is quite

different from the others

we have seen in this

chapter.

• When the H- attacks,

which is the best leaving

group?

21.12 Preparation and Reactions of Amides

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Klein, Organic Chemistry 1e 21-27

21.8 Preparation and Reaction of Acid Chlorides

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Klein, Organic Chemistry 1e 21-28

21.9 Preparation and Reactions of Acid Anhydrides

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Klein, Organic Chemistry 1e 21-29

CYUQ 15?

1. No errors

2. 1 error

3. 2 errors

4. 3 or more errors

5. Not sure

6. Need more time

21.14 Synthetic Strategies

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Klein, Organic Chemistry 1e 21-31

Pg 117

1. No errors

2. 1 error

3. 2 errors

4. 3 or more errors

5. Not sure

6. Need more time