Download Carboxylic Acid Derivatives

Section Four - Carboxylic Acids and their Derivatives
Question 4.1
In class we looked at carboxylic acids and four carboxylic acid derivatives. As a whole, they
constitute five related functional groups.
i.) Rank the groups in order of their reactivity (use structures or names).
ii.)
How can your answer to (i.) be useful in determining how some of the carboxylic acid
derivatives can be prepared from others? Give an example.
Answer 4.1
From most reactive to least, they are:
i) Acid halides > anhydrides > esters = carboxylic acids > amides
ii) Any functional group can be prepared from any group to its left. For example, esters can be
prepared by the reaction of an anhydride with an alcohol.
O
OH
O
OH
C
C
O
O
O
CH 3
OH
C
H 3C C O C CH 3
O
Question 4.2
Give the principal organic product expected when propionyl chloride (CH3CH2COCl) reacts with
each of the following reagents:
a.) water
b.) LiHAl[OC(CH3)3]3, Lithium tri-t-butoxyaluminum hydride (1 equiv.)
c.) ethanethiol (CH3CH2SH), pyridine
d.) sodium benzoate (the sodium salt of benzoic acid)
e.) benzene, AlCl3
f. hydrazine, (H2N-NH2)
Answer 4.2
a.)
b.)
O
H 3CH 2C
C
O
OH
H 3CH 2C
d.)
C
O
H
H 3CH 2C
C
SCH 2CH 3
e.)
O
H 3CH 2C
c.)
C
O
f.)
O
O
C
C
O
CH 2CH 3
H 3CH 2C
1
C
NHNH
2
Question 4.3
Aldehydes, ketones, and carboxylic acid derivatives are all carbonyl compounds (i.e. they have C=O
bonds). Despite this similarity, aldehydes/ketones frequently exhibit markedly different reactivity
from carboxylic acid derivatives. The former class of compounds undergo addition or addition
elimination reactions with nucleophiles while the latter undergo substitution reactions. Explain why
by comparing the mechanisms of the reactions of benzaldehyde and benzoyl chloride with the
nucleophile hydrazine.
Answer 4.3
O
C
O
C
H
H2N NH2
Cl
Hydrazine
Benzaldehyde
Benzoyl Chloride
Addition/elimination:
H+
O
C
OH
OH
C
C
H
H
H2N
H
H2N
NH2
NH2
-H+
C
C
H
N
HN
NH2
H
C
N
NH2
2
OH
OH2
H
H+
H
+H+
C
HN
NH2
H
NH2
The addition product is formed because there is no good
leaving group attached to the carbon atom that will allow
for the C=O to form again. Elimination of water occurs
subsequently by conversion of OH into a good leaving
group (acid catalyzed) and promotion by the lone pair on
N. This latter reaction is very much like an E1 reaction (the
acid catalyzed dehydration of alcohols).
Substitution
O
O
C
H2N
C
Cl
H2N
NH2
O
C
-H+
Cl
Cl
HN
NH2
Substitution occurs because the !-bond can be
reformed with the expulsion of Cl-, a good
leaving group.
NH2
O
C
+ Cl
NH
NH2
Question 4.4
Many reactions (acetal formation, addition-elimination reactions) of aldehydes and ketones are
catalyzed by acid (H+). How does this species catalyze addition reactions? Resonance structures of
O
H3 C
C
O
+H+
H
H3 C
C
H
O
H
H3 C
Protonated.
C
H
H
O
H3 C
C
O
H
H3 C
C
H
Non-protonated.
key intermediates would help in your explanation.
Answer 4.4
Above are two sets of resonance structures. In each set, the right-hand structure reflects the positive
polarization of the carbon atom which undergoes attack by nucleophiles. In the protonated
structures, both are charged and the right hand structure has an electron deficient carbon atom. In the
non-protonated structures, one structure is uncharged while the other has an electron deficient carbon
atom and bears two charges. The net result of all this is that in the protonated species, the right-hand
structure is a more significant contributor than the corresponding structure in the non-protonated
species. In short, protonation enhances the positive polarization of the carbon atom.
3
Question 4.5
Aldehydes and ketones undergo addition reactions with nucleophiles whereas carboxylic acid
derivatives undergo substitution reactions. The reaction of esters with Grignard reagents involves
both types of reaction. Give the mechanism for the following reaction and explain the basis for the
difference in the reactivity of the starting ester and the intermediate ketone .
O
C
OCH 3
H3C
+ CH3MgBr
[Ketone
Intermediate]
+ CH3MgBr
C
CH3
OH
2) H +, H2O
Answer 4.5
O
C
O
C
OCH3
O
Leaving group.
OCH3
C
CH3
CH3
CH3O-
CH3
O
C
O
C
CH3
OH
C
H+
CH3
CH3
CH3
CH3
CH3
No leaving groups.
The carbonyl group of carboxylic acid derivatives has a leaving group attached. This group can be
displaced and the C-O pi-bond re-established. The net result is substitution. Aldehydes and ketones
have only carbon or hydrogens attached to the carbonyl which cannot be displaced. Addition to the
C=O bond is the result in this case.
Question 4.6
i.) How would you classify the product of this cyclization?
ii.) Propose a mechanism for the transformation.
O
O
H+
OH
O
+ H2 O
OH
Answer 4.6
4
O
OH
C
C
OH
H+
OH
HO
HO
OH
OH
O
H
OH
OH2
OH
H2O
O
The product is an ester (cyclic esters are known as lactones. The mechanism:
Question 4.7
Ketene can be dimerized to give diketene. Diketene can be use to prepare a wide variety of useful
organics. When reacted with ethanol, ethyl acetoacetate is the product. Give a mechanism for the
formation of the latter product.
O
C
O
+ CH 3CH 2OH
H3C
H2C
O
O
C
C
OCH 2CH3
Answer 4.7
O
H
C
O
CH3CH 2OH
H3CH 2C
O
O
C
O
CH2
Diketene
CH2
O
-H
+
H3CH 2C
O
C
O
O
H3CH 2C
C
O
CH2
H+
H3C
5
O
CH2
O
O
C
C
OCH 2CH3
6
7