EXPERIMENT 65 NOTES

ABBREVIATIONS USED
Ph = Phenyl group, or

Example: Phenyl chloride

Cl

or

Ar = Aryl group, or

Example: Aryl chloride

Cl

or ArCl

PhCl

S
H3CO

S is a substituent
on the benzene ring
O

The nature and position

of S may remain unspecified
O

Ac = Acyl group, or H3C

Example: Acyl chloride H3C

O
AcO = Acetoxy group, or H3C

Cl

or AcCl

O
O

Example: Acetic acid H3C

OH

or

AcOH

BASE CATALYZED ESTERIFICATION OF ANHYDRIDES

Example: Acetic anhydride plus phenol:

Base

OH
O

Acetic anhydride

Phenol

Phenyl acetate

Mechanism
O
O

O
O

O
+

O
O
OPh
Leaving group

PhO
Phenyl
acetate

ACID CATALYZED ESTERIFICATION OF ANHYDRIDES

Example: Acetic anhydride plus phenol:
O

O
+

H+

OH

Acetic anhydride

Phenol

Phenyl acetate

Mechanism

1)

+ H+

OH

2)

+
O

OH

OH

Ph

H
O

O
O
Ph

H
OH

O
O

O
H

swap
O

O
Ph

Ph

OH

O
4)

OH

O
proton

3)

OH

O
O
H

OH
O

Ph

Ph
O

-H +
loss of
proton

O
Ph
O
phenyl acetate

EXPERIMENT 65 REACTIONS
Experiment 65 uses the reaction between acetic anhydride and vanillin to illustrate the effects of
catalysis (as shown above) and the reactivities of the functional groups present in the
molecules. In order to figure out the puzzle posed by part B of the experiment, we may want to
keep the following in mind.
1. When an anhydride reacts with an alcohol (either under acidic or basic conditions), the
anhydride plays the part of the electrophile, undergoing nucleophilic attack by the
alcohol.

2. The vanillin molecule has several functional groups, among them alcohol, ether, and
aldehyde. When it reacts with acetic anhydride we can predict a reaction pattern similar
to the examples given above, with vanillin acting as the alcohol (nucleophile) and the
anhydride acting as the electrophile. By working out the mechanism you should be
able to arrive at the structure of the esterification product obtained from the acid
and the base catalyzed reactions.
3. The base-catalyzed reaction is a straightforward esterification and doesnt produce any
other significant products. In other words, the esterification stops at the ester. YOUR
LAB REPORT SHOULD INCLUDE THE STRUCTURE OF THIS ESTER (product of
base catalysis) AND SUPPORTING NMR SPECTRUM (with peak assignments).
4. However, the acid-catalyzed esterification does not form only the ester. It forms the
ester, but this ester continues to react because there are other functional groups present
in the molecule that can react with the anhydride under these conditions.
5. The ether functional group (CH3O) attached to the benzene ring, and the benzene ring
itself, are not reactive under these conditions, and therefore do not undergo any kind of
modification.
6. That leaves us with the aldehyde, which is known to be one of the most reactive
functional groups in organic chemistry. How does it react? The presence of the carbonyl
group (C=O) basically sets the tone for aldehyde chemistry. The polarization of the C=O
makes the carbon highly electrophilic. Therefore we need a nucleophile.
7. We only have one other molecule present in the system, namely acetic anhydride. Can it
act as a nucleophile? The answer is yes, due to the presence of unshared electron pairs
on the three oxygen atoms. So the question becomes, are all the oxygen atoms equally
nucleophilic, or is one of them more nucleophilic than the others? Lets look at the
resonance structures of the anhydride to predict the site of the most nucleophilc oxygen.

+
H3 C

O
H3 C

CH3

CH3

8. Resonance structure B reveals that the carbonyl sp2 oxygen is more nucleophilic than
the central sp3 oxygen. So we can use structure B in a nucleophilic attack on the
aldehyde. Lets see how this works in the acid-catalyzed reaction.
9. Under acid catalysis, the aldehyde oxygen becomes protonated first, leaving the sp2
carbon more susceptible to nucleophilic attack:
O
Ar

OH

H+

HO
Ar =

Ar

H3CO

This is then followed by nucleophilic attack from resonance structure B on that carbon:

O
H3 C

O
H3 C
O
O
O

OH

CH3

HO

CH3

Ar

Ar

The positive charge shown on the central oxygen makes the circled part a good leaving
group relative to the rest of the structure. Attack from the alcohol group on the sp2
carbon next to the positive charge results in internal displacement of the leaving group:

O
H3 C
H3 C

O
HO

CH3

Ar

CH3

Ar
H

10. Loss of a proton from the resulting structure above leads to formation of the final
product. Remember, this product contains an ester group that results from reaction
between the alcohol part of vanillin and acetic anhydride. It also contains the product
resulting from the process shown above. Therefore:
11. YOUR LAB REPORT SHOULD INCLUDE THE STRUCTURE OF THE PRODUCT
FROM ACID CATALYSIS, DISCUSSED IN TERMS OF TWO THINGS:
a) the NMR spectrum obtained, with as many peaks assigned as possible, and
b) the paper by Kochlar et. al. (Conversion of aldehydes into geminal diacetates) 1

GOOD LUCK!
1

Kochlar, S.K. et. al. J. Org. Chem., 48, 1765 1767 (1983). Please locate and obtain this paper using SciFinder, as
learned before in the library instruction session.