39

Suggested solutions for Chapter 39

PROBLEM 1
Propose three fundamentally different mechanisms (other than variations of
the same mechanism with different kinds of catalysis) for this reaction. How
would (a) D labelling and (b) 18O labelling help to distinguish the mechanisms?
What other experiments would you carry out to rule out some of these
mechanisms?
O2N

O2N

NaOH

CO2

H2O

OH

Purpose of the problem

Investigating a reaction where there are several reasonable
mechanisms.

Suggested solution
The reaction is an ester hydrolysis so the obvious mechanism is to
attack the carbonyl group with hydroxide. Notice that we draw out each
stage of the mechanism and do not use any summary or shorthand.
Mechanism 1: Normal ester hydrolysis

O2N

OH

O2N

OH

O
O

O2N

O2N

CO2H

CO2

OH

But the ester oxygen atom is attached to an aromatic ring with a para
nitro group. Nucleophilic aromatic substitution would give the same
product.
Mechanism 2: Nucleophilic aromatic substitution

O
O

N
O

O2N

O
OH

CO2

O
O
OH

OH

Solutions Manual to accompany Organic Chemistry 2e

Finally, the ester can be transformed into an enolate, using hydroxide

as a base. Elimination gives a ketene that can be attacked by hydroxide
as a nucleophile to give the product.
Mechanism 2: Enolate elimination to give a ketene

H H

O2N

OH

O2N

O2N

O
O

OH
O

HO
O2N

O2N

OH

CO2H

O2N

CO2
OH

Mechanism 3 requires the exchange of at least one hydrogen atom

with the solvent so, if D2O were used as the solvent, or better
deuterated starting material were used, the exchange of one whole
deuterium atom would indicate mechanism 3 while no exchange, or
only minor amounts from the inevitable enolization, would show
mechanisms 1 or 2. In mechanisms 1 and 3, the added OH group ends
up in in CO2H but in mechanism 2 it ends up as the phenol. Using H218O
as solvent, or better labelling the ester oxygen as 18O would separate
mechanisms 1 and 3 from 2.
D

O2N

O2N

CO2
OH

O2N

mech
3

CO2
OH

O2N

O2N
O

mech
1 or 3

*
= 18O

O2N
O

mech
1 or 2

CO2
OH

mech
2

CO2
OH

Other experiments we could do might include trying to trap the

ketene intermediate in a [2 + 2] cycloaddition, studying the reaction by
UV, hoping to see the realease of p-nitrophenolate in mechanism 3,
changing the structure of the starting material so that one or other of
the mechanisms would be difficult, even measuring the effects of the
substituent on the benzene ring on the rate, or looking for a deuterium
isotope effect in the labelled lactone.

Solutions for Chapter 39 Determining reactions mechanisms

PROBLEM 2
Explain the stereochemistry and labelling pattern in this reaction.
t-Bu

enantiomerically
pure

t-Bu

* = 18O

H2SO4

HOAc

racemic

Purpose of the problem

A combination of labelling and stereochemistry reveals the details of a
surprisingly interesting rearrangement.

Suggested solution
The randomization of the label and the racemisation suggest that the
carboxylate falls off the allyl cation and then comes back on again at
either end. While they are detached the distinction between the two
ends of both cation and anion disappears as they are delocalized.
t-Bu

t-Bu

t-Bu

t-Bu

O
O

*O

*O
O

*O
O

This a
question is based on more
The product is racemic because the two intermediates each have
complex chemistry described by H.
plane of symmetry and are achiral. The retention of relative
L. Goering et al., J. Am. Chem. Soc.,
stereochemistry (formation of the trans product from trans starting
1964, 86, 1951.
material) could result from stereoselective recombination (the two
faces of the allyl cation are not the same) or from the two ions sticking
together as an ion pair so that the acetate slides across one face of the
cation. An alternative [3,3] sigmatropic rearrangement would not
randomize the labels in the same way.

Solutions Manual to accompany Organic Chemistry 2e

t-Bu

t-Bu

[3,3]sigmatropic

*O

PROBLEM 3
The Hammett value for migrating aryl groups in the acid-catalysed Beckmann
rearrangement is 2.0. What does that tell us about the rate-determining step?

Me
N

N
H

Me

OH

Purpose of the problem

The Hammett relationship gives an intimate picture of the Beckmann
rearrangement.

Suggested solution
The normal mechanism for the Beckmann rearrangement (p. 958-960)
involves protonation at OH and migration of the group anti to the NO
bond: in this case the substituted benzne ring.

Me H
N

OH

Me
N

OH2

OH2

etc

N
H

Me

amide

If this mechanism is correct here, we should expect the migration

itself to be the slow step. The first step is just a proton transfer to
oxygen and must be fast. The steps after the migration involve attack of
water on a carbocation and proton transfers to O and N and these must
all be fast. The migration breaks a CC bond, forms a CN bond and
creates an unstable cation. But does this agree with the evidence?
Starting material and product in the migration step are cations so the
transition state must be a cation too. Any contribution to cation stability
made by the migrating group should help and we should therefore
expect electron-donating groups to migrate faster. This is what we see:

Solutions for Chapter 39 Determining reactions mechanisms

a value of 2.0 shows a modest acceleration by electron-donating

groups (p. 1041 ff.).
In the Beckmann rearrangement, the anti group migrates but in other
rearrangements the migrating group is chosen for a very different
reason: it is normally the group that is best able to stabilize a positive
charge and benzene rings can do this by participation. This would be
the participation mechanism:
Me

Me
N

OH2

etc.

X
N

OH2

N
H

amide

Me

Tthat
his is the early work of D. E.
The Hammett value of 2.0 gives very definite evidence
Pearson and group, J. Org. Chem.,
participation does not occur. If it did the closure of the unstable three-
1952, 17, 1511; 1954, 19, 957.
membered ring would be the slow step and a positive charge would
form on the benzene ring itself. This would give a much larger value of
something like 5.0. One reason that participation does not occur is that
the starting material is planar and the p orbitals in the benzene ring
cannot point in the right direction to interact with the * orbital of the
NO bond. They are orthogonal to it.

PROBLEM 4
Between pH 2 and 7 the rate of hydrolysis of this ester is independent
of pH. At pH 5 the rate is proportional to the concentration of acetate
ion (AcO) in the buffer solution and the reaction goes twice as fast in
H2O as in D2O. Suggest a mechanism for the pH-independent hydrolysis.
Above pH 7 the rate increases with pH. What kind of change is this?
O
F3C

NaOAc
SEt

H2O

F3 C

OH

EtSH

Purpose of the problem

Time for you to try your skill at interpreting pH-rate profiles.

Suggested solution
The second part of the question is easily dealt with. In alkaline solution
the rate of hydrolysis simply increases with pH and we have the normal

Solutions Manual to accompany Organic Chemistry 2e

specific base-catalysed reaction in which hydroxide ion attacks the

carbonyl group.
ratedetermining
step

O
F3C

SEt

O
F3C

OH

F3C

OH
SEt

OH + EtS

But this is no ordinary ester. The leaving group is a thiol (pKa about
8) not the usual alcohol (pKa about 16) and so the thiolate anion is a
much better leaving group than EtO. Also the CF3 group is very
electron-withdrawing so nucleophilic attack on the carbonyl group will
be unusually fast. This is why there is a region of pH-independent
hydrolysis not found with EtOAc. You might have suggested that acetate
is a nucleophile or a general base catalyst but the solvent deuterium
isotope effect suggests that it is a general base. The change at pH 7 is a
change of mechanism as the faster of two mechanisms appliesa
sketch of the pH-rate profile will show you the upward curve.
O
F3C
H

SEt
O

rate-determining step
general base catalysis

F3 C
OAc

OH
SEt

F3 C

OH + EtS

PROBLEM 5
In acid solution, the hydrolysis of this carbodiimide has a Hammett
value of 0.8. What mechanism might account for this?
Ar

Ar

H
H2O

ArNH2

Purpose of the problem

Interpretation of a small Hammett value.

Suggested solution
The most obvious explanation for a low Hammett value, that the
aromatic ring is too far away from the reaction, will not wash here as
the aromatic rings are joined directly to the reacting nitrogen atoms of
the carbodiimide. The reaction must surely start with the protonation
of one of the nitrogens. This cannot be the slow step and it would in any
case have a large negative value. The small value observed suggests

Solutions for Chapter 39 Determining reactions mechanisms

that the rate-determining step must have a large positive value that
nearly cancels out the large negative value for the first step. Attack by
water on the protonated carbodiimide looks about right.
ratedetermining
step

H
Ar

H
C

Ar

Ar

fast

Ar

H
Ar

N
OH2

H2O
H
Ar

Ar

Ar

fast

H
N

H2O

Ar

Ar

fast

The hydrolysis of carbdiimides

in acid and base was studied by S.

OH CO2
Hnig
et al., Liebigs Annalen, 1953,
ArNH
2
579, 87.

Ar

The expected equilibrium Hammett value for the protonation

would be about 2.5 to 3 so the kinetic Hammett value for the attack
of water would have to be about +2 to give a net Hammett value of
0.8. This looks fine. The rest of the mechanism involves proton
transfers, hydrolysis of an imide, and decarboxylation.

PROBLEM 6
Explain the difference between these Hammett values by mechanisms for the
two reactions. In both cases the ring marked with the substituent X is varied.
When R = H, = 0.3 but when R = Ph, = 5.1.
R
X

R
Cl

NaOH
X
H2O, EtOH

OH

Purpose of the problem

Interpretation of a variation in Hammett value with another
structural variation.

Suggested solution
The reaction is obviously nucleophilic substitution at the benzylic
centre so we are immediately expecting SN1 or SN2. When R = H, the
reaction occurs at a primary alkyl group and SN2 is expected. When R =
Ph, the reaction occurs at a secondary benzylic centre and SN1 is
expected.

Solutions Manual to accompany Organic Chemistry 2e

OH
SN 2

Cl

ratedetermining
step

Ph

OH

Ph

Ph
SN1

Cl

or

rateX
determining
step

OH

fast

OH

OH2

Since SN1 produces a cation delocalized round the benzene ring in the
slow step, a large negative Hammett value is reasonable. It is not
obvious what sign the Hammett value would have in the SN2 reaction
but as there is no build-up of negative charge on the carbon atom in the
transition state, a small value is reasonable. The actual value (0.3) is
very small indeed but, if we can read anything into it, it suggests a loose
SN2 transition state with a small positive charge on carbon.
HO ()

OH

+?

Cl

Cl ()

OH

PROBLEM 7
Explain how chloride catalyses this reaction.
O

O
Cl
O2N

MeOH, Cl
MeCN

OMe
O2N

Purpose of the problem

An extreme example of surprising catalysis.

Suggested solution
At first you might ask how chloride can catalyse anything at all. It is a
weak base and not a very good nucleophile for the carbonyl group.
However, in polar aprotic solvents like acetonitrile (MeCN), chloride is
not solvated and is both more basic and more nucleophilic. In this
reaction it cannot be a nucleophilic catalyst as attack on the carbonyl

Solutions for Chapter 39 Determining reactions mechanisms

group simply regenerates starting material. It cannot be a specific base

as it is too weak, even in acetonitrile, to remove a proton from
methanol. But it can act as a general base. As methanol attacks the
carbonyl group its proton becomes more acidic and, in the transition
state, chloride is at last able to act.
O

Cl

Cl Me

OMe

OMe
Cl

O2N

O2N

O2N

PROBLEM 8
The hydrolysis of this oxaziridine in 0.1M sulfuric acid has k(H2O)/k(D2O) = 0.7
and an entropy of activation of S = 76 J mol1K1. Suggest a mechanism.
O
Ph

t-Bu

PhCHO + t-BuNHOH

H2O

Purpose of the problem

Deducing a mechanism from isotope effects and entropy of activation.

Suggested solution
The inverse solvent deuterium isotope effect indicates specific acid
catalysis and the modest negative entropy of activation suggests some
bimolecuar involvement. There are various mechanisms you might
have proposed and a likely one involves cleavage of the three-
membered ring in the protonated amine. The second or possibly the
third step could be rate-determining.
O
Ph

t-Bu

H
fast

Ph

t-Bu

H2O

N
H

t-Bu

H
O

Ph
OH

H2O

H
Ph

Ph

N
H

t-Bu

N
H

Ph
+

t-Bu

HO

N
H

t-Bu

Once the three-membered ring is opened, the rest of the mechanism

amounts to acid-catalysed hemiacetal hydrolysis. The original workers

10

Solutions Manual to accompany Organic Chemistry 2e

favoured an alternative mechanism that starts with protonation of the

oxygen atom and ends up with the hydrolysis of an imine. Again, the
second or third step could be rate-determining.
H2O

H
O
Ph

t-Bu

fast Ph

H2O
Ph

Ph

t-Bu

OH

OH
t-Bu

Ph

t-Bu

Ph
+

H OH

OH

t-Bu

HO

N
H

t-Bu

PROBLEM 9
Explain how both methyl groups in the product of this reaction come to be
labelled. If the starting material is reisolated at 50% reaction, its methyl group
is also labelled.
O

OMe
+

Cl

CD3

Ag

partly
deuterated

OMe

Me

partly
deuterated

Purpose of the problem

Exploring a mechansim through labelling.

Suggested solution
The role of silver ion (Ag+) is the removal of the halide to give an
acylium ion that reacts, not at the carbonyl group, but at the methyl
group to give CO2 and a methylated benzene ring. The simple Friedel-
Crafts route cannot be the whole story: it explains how the added
methyl group is labelled, but not why it is only partly labelled and how
label gets into the other methyl group.

Ag

Cl

OMe

OMe

O
O

CD3

O
O

CD3

CO2 +

D 3C

OMe

D3C

The only way in which we can explain those extra features is to

suggest that methylation initially occurs on the oxygen atom and that a

 We hope you didnt suggest a

methyl cation as an intermediate.

Solutions for Chapter 39 Determining reactions mechanisms

methyl group is transferred from there to the benzene ring. We should

never have detected this detail without the labelling experiment.
Alkylation on oxygen provides an alkylating agent that can transfer
either CH3 or CD3 and also explains the formation of trideuterotoluene.
Me

CD3

CO2

O
O

Me

CD3

intermediate
can transfer
either CH3 or CD3

CD3
Me

Me

D3CO
+

MeO

MeO

PROBLEM 10
The pKa values of some protonated pyridines are as follows:
X
H
3-Cl
3-Me
4-Me
3-MeO 4-MeO
pKa

5.2

2.84

5.68

6.02

4.88

6.62

3-NO2
0.81

X
N
H

Can the Hammett correlation be applied to pyridines using the values for
benzene? What equilibrium value does it give and how do you interpret it?
Why are no 2-substituted pyridines included in the list?

Purpose of the problem

Making sure you understand the ideas behind the Hammett
relationship.

Suggested solution
The obvious thing to do is to plot the pKa values against the values for
the substituents using the meta values for the 3-substituted and para
values for the 4-substituted compounds (see table on p. 1042 of the
textbook). This gives quite a good straight line and we get a slope
(Hammett value) of +5.9. The sign is of course positive as the same
electronic effects that make benzoic acids more acidic will also make
pyridinium ions more acidic. The large value may have surprised you,
but reflect: ionization of benzoic acids occurs outside the ring and the
charge isnt deocalized round the ring. Deprotonation of pyridinium

11

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Solutions Manual to accompany Organic Chemistry 2e

ions occurs on the ring and the charge (positive this time) is delocalized
round the ring.
O
X

O
OH

There are no 2-substituted pyridines on the list since, like ortho-

substituted benzenes, they cannot be expected to give a good
correlation because of steric effects.

PROBLEM 11
These two reactions of diazo compounds with carboxylic acids give gaseous
nitrogen and esters as products. In both cases the rate of reaction is
proportional to [diazo compound][RCO2H]. Use the data for each reaction to
suggest mechanisms and comment on the difference between them.
Ar

Ar

RCO2H
Ar

EtO2C

Ar

= 1.6
k(RCO2H)/ k(RCO2D) = 3.5

RCO2H
N

+ N2

+ N2
EtO2C

k(RCO2D)/ k(RCO2H) = 2.9

Purpose of the problem

Application of contrasting isotope effects to detailed mechanistic
analysis.

Suggested solution
The first reaction has a normal kinetic isotope effect (RCO2H reacts
faster than RCO2D) while the second has an inverse deuterium isotope
effect (RCO2H reacts slower than RCO2D). This suggests that there is a
rate-determining proton transfer in the first reaction but specific acid
catalysis in the second (i.e. fast equilibrium proton transfer followed by
slow reaction of the protonated species). Protonation occurs at carbon
in both reactions, and this can be a slow step.

13

Solutions for Chapter 39 Determining reactions mechanisms

Ar
Ar

rate
determining
step

Ar

Ar

N2
N

Ar

Ar
O

Ar

Ar

O
O

The second reaction follows much the same pathway except that loss
of nitrogen is now difficult because the cation would be very unstable
(primary and next to a CO2Et group) so the second step is SN2 and rate
determining. .
R

O
EtO2C

H
N

EtO2C

fast

rate
determining
step

O
EtO2C

PROBLEM 12
Suggest mechanisms for these reactions and comment on their relevance to the
Favorskii family of mechanisms.
CO2Et

O
1. Br2
2. EtO , EtOH
Ph
O

MeO , MeOH Br
bromoketone Ph
added to base

Ph

Ph
Me MeO , MeOH
O

base added to
bromoketone

Ph
CO2Me

Purpose of the problem

Extension of a section of the chapter (p. 1061-3) into new reactions
with internal trapping of intermediates.

Suggested solution
In the first reaction the bromination must occur on the alkene to give a
dibromide. We cannot suggest stereochemistry at this stage and it is
better to continue with the standard Favorskii mechanism and see what
happens. Everything follows until the very last step when the opening
of the cyclopropane provides electrons in just the right place to
eliminate the second bromide and put the alkene back where it was.

+ N2

14

Solutions Manual to accompany Organic Chemistry 2e

This alternative behaviour of a proposed intermediate gives us

confidence that the intermediate really is involved.
O

Br2

EtO
EtOH

Br
O

Br

two-electron
disrotatory
electrocyclic

Br

Br
O
EtO

OEt
Br

Br

Br

gives
product

The stereochemistry of the initial bromination turns out to be

irrelevant as it disappears when the oxyallyl cation is formed. We know
the stereochemistry of the final product so we know the
stereochemistry of the cyclopropanone: it must be on the opposite face
of the five-membered ring to the methyl group. The disrotatory closure
of the oxyallyl cation evidently goes preferentially one way with the H
and the CMe2Br substituents going upwards and the carbonyl group
going down.
H

H
O

CO2Et

O
EtO

OEt

Br

Br

Br

The second reaction to the right is a normal Favorskii. The only point
of interest is the way the three-membered ring breaks up. The more
stable carbanion is the doubly benzylic one so that leaves.
Ph

Br

Me

Ph
O

MeO , MeOH
base added to
bromoketone

Ph

MeO

Ph

Ph

Ph
O

Ph

Ph
O

two-electron
disrotatory
electrocyclic

Ph

Ph
MeO

Ph

Br

MeO

Ph

CO2Me

The reaction with excess bromoketone starts the same way but the
oxyallyl cation is intercepted by one of the benzene rings in a four-

Solutions for Chapter 39 Determining reactions mechanisms

electron conrotatory electrocyclic reaction like the Nazarov reaction (p.

927).
Ph

Ph

MeO

Ph

Ph

O
This work was part of a O
thorough investigation into the
mechanism of the Favorskii

rearrangement by F. G. Bordwell
and group, J. Am. Chem. Soc., 1970,
happening.
92, 2It
172.

You may wonder how excess MeO stops this from

doesnt. The oxyallyl cation and the cyclopropanone are in equilibrium
and excess MeO captures the cyclopropanone and drives the normal
Favorskii onwards. If there is no excess MeO the oxyallyl cation lasts
long enough for the five-membered ring to be the main product.

PROBLEM 13
A typical Darzens reaction involes the base-catalysed formation of an epoxide
from an -haloketone and an aldehyde. Suggest a mechanism consistent with
the data below.
O
Ph

ArCHO
Cl

EtO , EtOH

Ph

O
Ar

(a) The rate expression is: rate = k3[PhCOCH2Cl][ArCHO][EtO]

(b) When Ar is varied, the Hammett value is +2.5.
(c) The following attempted Darzens reactions produced unexpected results:

Cl

Ph

EtO , EtOH

OHC
Cl

Ph

Ph
OMe

O
Ph

OHC

HO

Cl
O

EtO , EtOH
O

Ph

Purpose of the problem

Trying to get a complete picture of a reaction using physical data and
structural variation.

15

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Solutions Manual to accompany Organic Chemistry 2e

Suggested solution
The ethoxide is not incorporated into the product but appears in the
rate expression. Its role must be as a base and there is only one set of
enolizable protons. We start by making the enolate of the chloroketone.
This cannot be the slow step as the aldehyde appears in the rate
expression. Then we can attack the aldehyde with the enolate and
finally close the epoxide ring by nucleophilic displacement of chloride
ion.
O
Cl

Ph
EtO

K1

Ph

k2

Ar

Cl

k3

Ph

Ph

Cl

Ar

If this mechanism is right, the kinetic data show that the second step
is rate-determining (a reasonable deduction as it is a bimolecular step)
and that the first step is a pre-equilibrium. We can write:
rate = k2[enolate][ArCHO]
And we know from the pre-equilibrium that
K1 =

[enolate]
[PhCOCH2Cl][EtO]

So the rate expression becomes when we substitute for [enolate]:

rate = K1k2[PhCOCH2Cl][EtO][ArCHO]
and this matches the observed rate expression though the apparently
third order rate constant is revealed as the product of an equilibrium
constant and a second order rate constant.
The Hammett value shows a modest gain of electrons near the Ar
group in the rate-determining step. We must not take the pre-
equilibrium into account as ArCHO is not involved in this step. In fact a
Hammett value of +2.5 is typical of nucleophilic attack on a carbonyl
group conjugated to the benzene ring.
The unexpected products come from variations in this mechanism.
para-Methoxybenzaldehyde is conjugated and unreactive so the enolate
ignores it and reacts with the unenolised version of itself.

17

Solutions for Chapter 39 Determining reactions mechanisms

O
Ph
EtO

Cl
H

Ph

O
Ph

Cl

Cl

Cl

Cl

With salicylaldehyde, the second example, the phenolic OH group will

exist as an anion under the reaction conditions. Alkylation by the
chloroketone allows enolate formation leading to an intramolecular
aldol reaction.
CHO

CHO

EtO

CHO

Cl

EtO

OH

O
Ph

Ph

OH
O

H
O

Ph

Ph

Ph

PROBLEM 14
If you believed that this reaction went by elimination followed by conjugate
addition, what experiments would you carry out to try and prove that the enone
is an intermediate?
O
Ph

NaCN
Cl

H2O, EtOH

Ph

Ph

Ph

Ph

Ph
Cl

CN

Purpose of the problem

Turning the usual question backwards: what evidence do you want,
rather than how to interpret what you are given.

Suggested solution
The suggested mechanism of elimination followed by conjugate
addition might be contrasted with direct SN2 to see what evidence is
needed.

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Solutions Manual to accompany Organic Chemistry 2e

CN

mechanism 1:
simple SN2 displacement

Ph

O
Ph

Cl

CN

mechanism 2:
elimination - addition
(a) elimination

Ph

Cl
H

(b) addition

Ph

Cl

Ph

CN

O
CN

Ph

Ph
HO

O
CN

Ph

CN

There are many types of evidence you might suggest: here are some
of them.
Exchange of protons in D2O/EtOD would suggest
elimination/addition.
Kinetic evidence (tricky as you cannot be sure which is the
slow step.
A Hammett plot with substituted benzene rings. The SN2
mechanism would have a small as the benzene ring is a long
way from the action.
Base catalysis: mechanism 2 is base catalysed, mechanism 1
isnt.
Kinetic isotope effect might be found in mechanism 2.
Stereochemistry. If a substituent were added to make the
terminal carbon chiral, inversion would be expected for
mechanism 1 and racemization for mechanism 2. But choose a
small substituent otherwise it would be a very different
compound.
O
Ph

SN2
CN inversion Ph

addition/
elimination

Cl

Ph

O
R

achiral

Ph
racemic

CN