Unless otherwise stated, all images in this file have been reproduced from:
Blackman, Bottle, Schmid, Mocerino and Wille,
Chemistry, 2012 (John Wiley & Sons)
ISBN: 9 78047081 0866
1
Reactions of carboxylic
acids and their derivatives
Lecture 11 Lecture 12 Lecture 13
Aldehydes & ketones: More oxidation & Another overview of
Grignard reagents reduction mechanisms
Nucleophilic acyl Synthetic strategies
substitution
Recap: you’ve seen carboxylic acids
Grignards
Oxidation
And you’ve seen how to identify them:
IR
a strong absorption ~ 1700 cm-1 (C=O)
a broad absorption ~ 3000 cm-1 (O-H)
13C NMR
Peak around 200 ppm 3
Carboxylic acids can be reduced
We can form carboxylic acids by oxidising 1º alcohols and aldehydes
The reverse is the reduction of carboxylic acids
The reagent, lithium aluminium hydride, supplies H–.
You don’t need to know the mechanism (though you might be able to guess)
We saw the reduction of ketones/aldehydes with sodium borohydride. That’s not
reactive enough to reduce carboxylic acids. LiAlH4 is “stronger”.
Worksheet Q1 4
Priming carboxylic acids for further reaction
Carboxylic acids can be converted to acyl chlorides (or acid chlorides)
with a specific reagent. This allows them to be transformed into a range
of other things.
(you don’t need to know the mechanism for the formation of acyl chlorides, but it’s an
interesting one)
Worksheet Q2, Q3, Q4 5
Recap: carboxylic acid derivatives
Aldehydes and ketones
Carboxylic acids
Esters
Amides
Acid chlorides Acid anhydrides
6
How will they react?
Worksheet – Q5 7
One mechanism to rule them all – steps 1 and 2
Mechanism: Nucleophilic Acyl Substitution – with Nuy
Step 1: nucleophilic
addition to electrophilic
carbon of acid chloride …
gives a tetrahedral
intermediate
Step 2: collapse of the
tetrahedral intermediate
to regenerate the C=O p
bond with elimination of
chloride anion as the
leaving group
Worksheet – Q6 8
Reactivity of carboxylic acid derivatives
• Rate of reaction depends on the stability of the carboxylic acid
derivative and on the leaving group
O O O O O
C C C C C R"
R Cl R O R R O R' R N
R'
acid chloride acid anhydride ester amide
increasing reactivity
most least
reactive reactive
• A more reactive derivative maybe converted into a less reactive one
(or back to the carboxylic acid) via the nucleophilic acyl substitution
reaction O O
C H Z (or Z ) C H Y (or Y )
R Y R Z
9
One mechanism to rule them all – step 3
Mechanism: Nucleophilic Acyl Substitution – with H-Nu
Step 1: nucleophilic
addition to electrophilic
carbon of acid chloride …
gives a tetrahedral
intermediate
Step 2: acid/base reaction
(deprotonation of the
tetrahedral intermediate)
Step 3: collapse of the
tetrahedral intermediate
to regenerate the C=O p
bond with elimination of
chloride anion as the
leaving group
Worksheet – Q7 10
Learning outcomes
After this lecture you should be able to:
• Convert a carboxylic acid into an acyl chloride
• Recognise carboxylic acid derivative functional groups
• Understand the different reactivity of these derivatives
• Predict conditions for hydrolysis and interconversion of
carboxylic acid derivatives
Further reading: Blackman 23.4-23.5
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