PDF: Problems - Paton Research Group

2nd YEAR
ORGANIC CHEMISTRY TUTORIAL SHEET
Orbitals and Mechanism II
Reading:
Lecture notes – Orbitals and Mechanism II
Clayden, Greaves & Warren Edition 1 Chapters 35, 36 and 41 (34, 35 & 39 Ed 2)
Fleming - Frontier Orbitals and Organic Chemical Reactions
Maskill – Structure and Reactivity in Organic Chemistry, OCP no. 81
Topics for notes:
You need to be familiar with the following concepts which are useful in the determination of
reaction mechanisms and will have been covered in lectures: Frontier Molecular Orbital treatment
of pericyclic reactions (the Woodward Hoffmann analysis will come in the 3rd year); the classes of
pericyclic reactions; HOMO and LUMO; conrotatory and disrotatory; entropy and volume of
activation; simple kinetic expressions; Curtin-Hammett principle; principle of microscopic
reversibility; kinetic and thermodynamic control; kinetic isotope effects; solvent effects
Tutorial Problems
1) Predict the outcome of the following reactions using FMO analysis:
Me
Me
heat
?
Me
heat
?
Me
2) Suggest mechanisms for the following reactions and explain the stereochemistry using FMO
analysis.
H
H
heat
H
H
3) Predict the structures of the products in the following reactions, explaining any regio or
stereoselectivity. How would the rate of the reactions be affected by the addition of a Lewis acid
such as AlCl3?
CO2Me
a)
+
MeO2C
Me
b)
Me
+
heat
heat
MeO
O
4) Provide mechanisms for the following reactions explaining aspects of stereoselectivity where
necessary:
a)
O
heat
O
Me
b)
heat
Me
Me
Me
5) Suggest mechanisms for the following reactions. Hint: in part a) the reaction requires an
electrocyclic reaction followed by a cycloaddition.
O
a)
+
O
O
b)
heat
H
H
O
O
O
SO2
CO2Et
heat
CO2Et
2nd YEAR
ORBITALS & MECHANISM II
6) Explain the outcome of the following reactions:
SO3H
H2SO4
H2SO4
80 °C
160 °C
SO3H
7) Hydrolysis of the lactone below could potentially proceed by (at least) three different
mechanisms: i) BAC2 (i.e. standard tetrahedral mechanism), ii) via an SNAr reaction, iii) via
formation of an enolate followed by a ketene. Draw these three possible mechanisms. How would
a) deuterium labelling, b) 18O labelling help to distinguish the mechanisms.
O2N
O
NaOH, water
O2N
O
O
OH
O
8) 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. Hint - Silver(I) ions
will abstract chloride from the chloroformate.
O
OMe
Cl
O
OMe
mixture of CH3 and CD3
Me
mixture of CH3 and CD3
CD3
Ag
9) Conformers A and B of the amine C are in rapid equilibrium. Explain why conformer B is more
stable than conformer A and why the diastereoselective alkylation of C gives the quaternary
ammonium salt D.
N
CH3
H3C
CH3
N
N
H313C
13CH
A
B
C
N
CH3 I
3I
D
10) Explain the following: the hydrolysis of amides typically shows overall third order kinetics. Hint you need to apply pre-equilibrium kinetics to all reactive intermediates.
O
O
HO-, H2O
R
NH2
amide
R
O
rate= k[amide][HO-]2
11) Predict which of the two diastereomers of the carboxylic acids shown has the lower pKa in
water.
CO2H
tBu
CO2H
tBu
-2-
2nd YEAR
ORBITALS & MECHANISM II
12) Provide an explanation for the difference in pKa values for acetic acid when measured in the
listed solvents.
pKa (measured in)
H 2O
MeOH
DMSO
MeCN
CH3CO2H
4.8
9.0
12.5
23.0
13) Explain why compound A is hydrolysed in base 8300 times faster than compound B, and
compound C is hydrolysed in acid 100000 times faster than compound D.
O
H
CO2Me
CO2Me
O
A
MeO
O
C
B
OMe
D
14) What do the measured kinetic isotope effects tell us about the mechanisms of the following
reactions?
Br
O
Ph
HO- / Br2
X
O
Ph
X = H,D; kH/kD = 6.1
O
Br
tBu
Y
S
O O
X
A: X = Y = H
B: X = H, Y = D
C: X = D, Y = H
OH
H2O, heat
tBu
Y
X
solvolysis rates:
kA/kB = 1.44
kA/kC = 1.10
-3-

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