Specific acid catalysis and Lewis acid catalysis of Diels-Alder reactions in aqueous media

Article abstract of DOI:10.1002/poc.711

A comparative study of specific acid catalysis and Lewis acid catalysis of Diels-Alder reactions between dienophiles (1, 4 and 6) and cyclopentadiene (2) in water and mixed aqueous media is reported. The reactions were performed in water with copper(II) nitrate as the Lewis acid catalyst whereas hydrochloric acid was employed for specific acid catalysis. At equimolar amounts of copper(II) nitrate and hydrochloric acid (0.01 M, for example) and under the same reaction conditions, the reaction rate for 1a with 2 is about 40 times faster with copper catalysis than with specific acid catalysis. Moreover, at 32°C and 0.01 M HCl, the reaction of 1b with 2 is about 21 times faster than the same uncatalyzed reaction in pure water under the same reaction conditions. The inverse solvent kinetic isotope effect shows that these Diels-Alder reactions undergo specific acid catalysis. Copyright

Full text of DOI:10.1002/poc.711

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2004; 17: 180–186
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.711
Specific acid catalysis and Lewis acid catalysis of
Diels–Alder reactions in aqueous media
Egid B. Mubofu and Jan B. F. N. Engberts*
Physical Organic Chemistry Unit, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
Received 23 June 2003; revised 14 August 2003; accepted 19 August 2003
ABSTRACT: A comparative study of specific acid catalysis and Lewis acid catalysis of Diels–Alder reactions between
dienophiles (1, 4 and 6) and cyclopentadiene (2) in water and mixed aqueous media is reported. The reactions were
performed in water with copper(II) nitrate as the Lewis acid catalyst whereas hydrochloric acid was employed for
specific acid catalysis. At equimolar amounts of copper(II) nitrate and hydrochloric acid (0.01 M, for example) and
under the same reaction conditions, the reaction rate for 1a with 2 is about 40 times faster with copper catalysis than with
specific acid catalysis. Moreover, at 32 ꢀCand 0.01 M HCl, thereaction of 1b with2 isabout21timesfaster than thesame
uncatalyzed reaction in pure water under the same reaction conditions. The inverse solvent kinetic isotope effect shows
that these Diels–Alder reactions undergo specific acid catalysis. Copyright # 2004 John Wiley & Sons, Ltd.
KEYWORDS: Diels–Alder; catalysis; specific acid catalysis; Lewis acid catalysis; kinetics
INTRODUCTION
Diels and Alder themselves8 and other workers.9 The
breakthrough came, however, with a paper by Rideout
and Breslow in 1980.10 In their study, they observed
that the Diels–Alder reaction of cyclopentadiene
with methyl vinyl ketone in water is about 700 times
faster than the same reaction in isooctane.10 Today,
many organic reactions that are traditionally performed
in organic solvents have successfully been performed in
water or aqueous systems.11 Diels–Alder reactions in
water benefit not only from the increase in reaction rates
but also from the increased endo/exo selectivity.12–15
Although Diels–Alder reactions can proceed without
the need for catalysts, the reactions are sometimes slow
and need to be accelerated by physical methods such as
high pressure, high temperature or ultrasound irradition.
However, the acceleration of the reactions through cata-
lysis is more attractive as it avoids high temperature and
pressure. The most effective catalysts for Diels–Alder
reactions are Lewis acids. Lewis acid-catalysed Diels–
Alder reactions were first reported in the 1960s by Yates
and Eaton.16 Lewis acids catalyse Diels–Alder reactions
by coordinating to the activating group of the dienophile
(for normal electron demand Diels–Alder reactions) and
in this way lower the LUMOdienophile–HOMOdiene energy
gap, accelerating the reaction. Even if Lewis acid cata-
lysis proceeds at room temperature with an excellent
yield and turnover numbers, these reactions are faced
with the problem of the excess amounts of Lewis acids
employed. Normally, an excess of up to 2 molar Lewis
acid catalysts is required to activate a carbonyl group-
containing dienophile. In larger scale production, this
The Diels–Alder reaction is a stereospecific [4 þ 2]
cycloaddition of a dienophile and a conjugated diene
to form a six-membered ring. It is one of the most
important and fundamental stereoselective reactions in
the synthesis of six-membered ring compounds, includ-
ing natural products. The reaction is thermally reversible
and the reverse process is referred to as the retro-Diels–
Alder reaction. A critical survey of reactivity, selectivity
and mechanistic aspects of this reaction in various
organic solvents has been reported.1 After a long, heated
debate on the mechanism of Diels–Alder reactions, there
is now a consensus that bond breaking and bond making
in Diels–Alder cycloaddition is predominantly con-
certed2,3 although not necessarily synchronous.4,5 The
reaction being concerted implies that Diels–Alder reac-
tions undergo only a small charge separation on going
from the initial state to the activated complex. This
means that the rates of Diels–Alder reactions are not
strongly influenced by the nature of the solvent em-
ployed for the reaction. Interestingly, however, there is a
substantial rate acceleration when Diels–Alder reactions
are performed in water.6,7 It is interesting that Diels–
Alder reactions were also performed in water by
*Correspondence to: J. B. F. N. Engberts, Physical Organic Chemistry
Unit, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747
AG Groningen, The Netherlands.
E-mail: j.b.f.n.engberts@chem.rug.nl
Contract grant sponsor: National Research School Combination
Catalysis (NRSCC).
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 180–186

CATALYSIS OF DIELS–ALDER REACTIONS
181
excess Lewis acid poses an environmental problem. The
problem may be overcome by the use of solid protic
acids17 and surfactant-assisted Brønsted acids.18
Brønsted acid catalysis of Diels–Alder reactions was
reported19 almost two decades before Lewis acid cataly-
sis was performed by Yates and Eaton.16 Wassermann
and co-workers reported the reaction rates of Brønsted
acid-catalyzed Diels–Alder reactions of cyclopentadiene
with several dienophiles in both polar and nonpolar
organic solvents.19,20 Their studies established that gen-
eral acid catalysis operated in these typical Diels–Alder
cycloaddition reactions.20 It is unfortunate, however, that
their studies did not use water as a reaction medium
because at that time water was not considered an im-
portant solvent for organic reactions. Since then, no
further interest in the Brønsted acid catalysis of Diels–
Alder reactions was reported until the mid-1990s when
specific acid catalysis of Diels–Alder reactions was
performed in water.14,21 To our knowledge, no compara-
tive studies between Brønsted acid catalysis and Lewis
acid catalysis of Diels–Alder reactions in water have been
reported. The present study provides such a comparison.
Scheme 2
reactions of 1a and 1b with 2 at 32 ꢀC gave reliable
second-order rate constants (Table 1). Figure 1 shows a
full reaction profile of the Diels–Alder reaction of die-
nophile 1b with cyclopentadiene 2 in dilute hydrochloric
acid at 32 ꢀC. The profile levels off at relatively high acid
concentration, indicating that the dienophile becomes
completely protonated. The protonation lowers the
LUMO of the dienophile, causing a decrease in the
energy gap of the frontier molecular orbital and therefore
enhancing the reaction rate with an increase in the acid
strength.
Tables 1 and 2 give a comparison of the reaction rates
of the catalyzed and the uncatalyzed Diels–Alder reac-
tions in water under similar reaction conditions. At 0.01 M
RESULTS AND DISCUSSION
Table 1. Second-order rate constants for Brønsted acid
(0.01 M HCl)-catalyzed (kH) and uncatalyzed (kw) Diels–Alder
reactions in doubly distilled water at 32 ꢀC
Specific acid catalysis of Diels–Alder reactions
of azachalcone dienophiles (1, 4) with
cyclopentadiene (2)
Reaction
kH (M ꢁ 1 sꢁ 1) in
0.01 M HCl
kw
kH=kw
(M ꢁ 1 sꢁ 1
)
Specific acid catalysis of the Diels–Alder reactions of
azachalcone dienophiles (1, 4) with cyclopentadiene (2)
was performed at 32 ꢀC in dilute hydrochloric acid at
different pH (Schemes 1 and 2). These cycloadditions are
known to be efficiently catalyzed by Lewis acid catalysts
in aqueous media.14,21 In both proton and Lewis acid
catalysis, 1b is more reactive than dienophiles 1a, 1c
and 4. The reactivity difference is anticipated for normal
electron demand Diels–Alder reactions on the basis of the
frontier molecular orbital (FMO) theory regarding sub-
stituent effects.1 The presence of an electron-donating
group in the dienophile 1c slows the reaction rates. In
fact, the Diels–Alder reaction of 1c with 2 was too slow to
establish reliable reaction kinetics. On the other hand, the
1a þ 2
1b þ 2
4 þ 2
0.042
0.14
0.024
0.0049
0.0065
0.0041
9
21
6
Figure 1. A specific acid-catalyzed Diels–Alder reaction
profile for 1b with 2 at 32 ꢀC
Scheme 1
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 180–186

182
E. B. MUBOFU AND J. B. F. N. ENGBERTS
Table 2. Second-order rate constants (kH) for Diels–Alder
reaction of 1b with cyclopentadiene (2) at different acid
strengths at 25 ꢀC
[HCl] (M)
kH (M ꢁ 1 sꢁ 1
)
kH=kw
0
0.004
0.038
0.049
0.067
0.086
0.096
0.11
1
9.5
12
18
22
24
28
0.003
0.005
0.010
0.016
0.021
0.043
HCl and 32 ꢀC, for instance, the catalyzed reaction of 1b
with 2 is about 21 times faster than the uncatalyzed
reaction. Table 2 gives a comparison of the uncatalyzed
reaction with specific acid catalysis at 25 ꢀC. When
compared with previous reported results on the uncata-
lyzed reaction of 1b witꢁh 12 performed in acetonitrile at
Figure 2. Copper(II) nitrate catalysis of the Diels–Alder
reaction of 1b with 2 at 32 ꢀC at an ionic strength of 2 M
(KNO3)
25 ꢀC (k ¼ 1.4 ꢂ 10ꢁ 5
M
s )
ꢁ 1 22 and that performed in
0.043 M HCl (k ¼ 0.11 M ꢁ 1 sꢁ 1) at 25 ꢀC, the reaction is
accelerated about 8000-fold.
times faster than proton catalysis. Likewise, copper(II)
catalysis is about 50 times faster than proton catalysis for
the reaction of 1b with 2. In contrast, copper(II) catalysis
for the reaction of 4 with cyclopentadiene 2 does not
occur except for a possible salt effect. It is obvious that
copper catalysis only takes place for the dienophiles that
contain two centers for interaction with the metal ion.
This crucial role of the bidentate character of Lewis acid
catalysts for Diels–Alder reactions in water has been
stressed previously.14,22 In the present study, we estab-
lished that specific acid catalysis of these Diels–Alder
reactions does not depend on the bidentate nature of the
dienophile.
The advantage of the bidentate character for specific
acid Diels–Alder catalysis is clear when dienophiles 1a
and 4 are compared. The reaction of the bidentate
dienophile 1a with 2 is much faster than that of dieno-
phile 4 with 2 under similar reaction conditions (Tables 3
and 4). The reasons for this reactivity difference may be
due to hydrogen-bonding and electronic effects. It is
realistic to consider that the proton attached at the pyridyl
nitrogen of 1a will undergo intramolecular hydrogen
bonding with the oxygen of the carbonyl carbon. This
hydrogen-bonding interaction may lower the LUMO
energy of 1a, enhancing its reactivity. In contrast, the
proton attached at the pyridyl nitrogen of the dienophile 4
Comparison of specific acid and Lewis acid
catalysis of Diels–Alder reactions of azachalcones
(1, 4) with cyclopentadiene (2)
The Diels–Alder reactions of dienophiles 1 and 4 with
cyclopentadiene (2) were performed in aqueous solutions
of copper(II) nitrate and hydrochloric acid at 32 ꢀC for
comparison (Table 3). Equimolar amounts of copper(II)
ions and dilute hydrochloric acid were employed and the
reactions were performed under similar reaction condi-
tions. Although it is an unfair comparison because
copper(II) Lewis acid binds in a bidentate fashion15
whereas the proton binds monodentate, it gives some
insights into the different catalytic efficiencies. It is clear
from Fig. 2 that the reaction profile reaches a plateau at
higher copper(II) concentrations as observed for specific
acid catalysis in the preceding section. The observed
levelling off of the reaction profile is indicative of full
binding of the copper(II) catalyst to the dienophile.
Table 3 shows the corresponding second-order rate
constants for the reaction of dienophiles 1 and 4 with
cyclopentadiene (2). It is apparent from the reaction rates
of reaction 1a with 2 that copper(II) catalysis is about 40
Table 3. Second-order rate constants of Lewis acid [0.015 M
Cu(NO3)2] catalysis compared with Brønsted acid (0.015 M
HCl) catalysis of Diels–Alder reactions in water at 32 ꢀC
Table 4. Second-order rate constants of Lewis acid [0.015 M
Cu(NO3)2] catalyzed reactions relative to uncatalyzed reac-
tions in doubly distilled water at 32 ꢀC
kCu (M ꢁ 1 sꢁ 1
in 0.015 M Cu(NO3)2
)
kw,
kCu=kw
Reaction
k
Cu (M ꢁ 1 sꢁ 1
in 0.015 M Cu(NO3)2
)
kH (M ꢁ 1 sꢁ 1
0.015 M HCl
)
kCu=kH
Reaction
(M ꢁ 1 sꢁ 1
)
1a þ 2
1b þ 2
4 þ 2
1.87
8.5
0.007
0.050
0.159
0.028
37
53
0.25
1a þ 2
1b þ 2
4 þ 2
1.87
8.5
0.007
0.0049
0.0065
0.0041
382
1260
1.6
Copyright # 2004 John Wiley & Sons, Ltd.
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CATALYSIS OF DIELS–ALDER REACTIONS
183
is at too remote a distance from the carbonyl oxygen for
intramolecular hydrogen bonding. This makes dienophile
4 less reactive than dienophile 1a under similar reaction
conditions. In addition to hydrogen bonding, an intramo-
lecular electrostatic interaction between the positive
charge on the pyridyl nitrogen and the lone pair of the
oxygen of the carbonyl carbon is expected to cause this
reactivity difference. The electrostatic interaction is more
likely to occur when the pyridyl group is in close
proximity (ortho-position) than when it is more remote
(para-position). The electrostatic interaction will lead to
electron density withdrawal from the double bond of the
dienophile 1a. The electron withdrawal makes 1a rela-
tively more electrophilic and hence more reactive than 4
for these Diels–Alder reactions.
Determination of the pKa of the dienophile
The basicity of the dienophile was established by deter-
mining the pKa for N-protonation of 1b by UV–visible
spectrophotometry at 32 ꢀC. The difference between the
extinction coefficients of the unprotonated and proto-
nated dienophiles at different acid concentrations was
obtained at the wavelength of maximum difference. The
azachalcone derivative 1b, gave a pKa of 2.55 for N-
protonation, which is in good agreement with the litera-
ture value for the structurally similar 2-phenylacetylpyr-
idine, which has a pKa of 2.30 for N-protonation.23
Reliable data were only possible in the pH range 4.4–
1.4 and there was a clear deviation from the isosbestic
point at pH < 1 or > 4.4, suggesting that there are other
possible chemical processes taking place.
Figure 3. A reaction profile of the reaction of dienophile 1a
with cyclopentadiene 2 in DCl (^) and HCl (~) at 32 ꢀC to
establish kH=kD
reversible protonation of the substrate followed by the
rate-determining cycloaddition step. As expected, the
KDIEs approach a value of unity under conditions of
complete protonation of the dienophile.
The observations indicate that the mechanism of the
specific acid catalysis of these Diels–Alder reactions in
water is similar to that of Lewis acid catalysis.14,22 This
means that the first catalytic step of a specific acid-
catalysed Diels–Alder reaction is a rapid but reversible
pre-equilibrium protonation of the dienophile. The pro-
tonated dienophile is more electrophilic and thus acti-
vated for the reaction with the electron-rich diene. The
product then dissociates to a pure product, leaving the
specific acid available for another catalytic reaction
cycle. At very high acid concentrations, the reaction rates
were irreproducible and this could possibly be due to
other processes such as Michael addition of water to the
dienophile that may take place at low pH.
Elucidation of the mechanism of specific
acid-catalyzed Diels–Alder reactions
In order to obtain information about the nature of the
acid-catalyzed Diels–Alder reactions, the kinetic deuter-
ium isotope effect (KDIE) was measured. Data are
summarized in Table 5 and Figure 3. The inverse primary
KDIE is consistent with specific acid catalysis, involving
Table 5. Solvent kinetic isotope effect (KIE) for reactions of 1a and 1b with 2 at different deuterium chloride and hydrochloric
acid concentrations
Reaction
[D3Oþ] (M)
kD (M ꢁ 1 sꢁ 1
)
[H3Oþ] (M)
kH (M ꢁ 1 sꢁ 1
)
kH=kD
1a þ 2
1a þ 2
1a þ 2
1a þ 2
1b þ 2
1b þ 2
1b þ 2
1b þ 2
1b þ 2
0.014
0.019
0.027
0.050
0.001
0.004
0.008
0.010
0.05
0.059
0.062
0.064
0.068
0.048
0.135
0.169
0.170
0.195
0.014
0.020
0.027
0.050
0.001
0.0038
0.0079
0.0099
0.043
0.048
0.052
0.055
0.061
0.035
0.090
0.118
0.140
0.197
0.81
0.84
0.86
0.90
0.73
0.68
0.70
0.82
1.01
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 180–186

184
E. B. MUBOFU AND J. B. F. N. ENGBERTS
Table 6. Rate constants for the proton-catalyzed Diels–
Alder reaction of 1b with 2 in ethanol–water mixtures
(XH O ¼ 0:8) and in dilute hydrohloric acid
2
EtOH-H2O kEtOHꢁH O
,
)
Dil. HCl
kH
kH=kEtOHꢁH O
2
2
(‘pH’)
(M ꢁ 1 sꢁ 1
(pH) (M ꢁ 1 sꢁ 1
)
1.49
2.16
2.42
3.0
0.032
1.52
2.1
2.41
3.0
0.18
0.118
0.09
0.035
0.027
5.63
12.55
14.30
9.50
0.0094
0.0063
0.0037
0.0029
Scheme 3
3.21
3.2
9.31
Specific acid catalysis of the Diels–Alder reaction
of napthoquinones (6) with cyclopentadiene (2)
interesting (Table 6) that the reaction rates are inhibited
by an average factor of ꢃ10. Assuming that at this
ethanol mole fraction the contribution of enforced hydro-
phobic interaction to the aqueous rate acceleration has
vanished, it is noteworthy that the factor of 10 is in the
region of the theoretical value predicted to be contributed
by hydrophobic effects for Diels–Alder reactions carried
out in water.25 This may indeed be indicative of the
hydrophobic influence on the specific acid-catalysed
Diels–Alder reaction in water. The results suggest that
the hydrophobic contribution to the specific acid-
catalyzed Diels–Alder reaction is more or less of the
same magnitude as in pure water.
The Diels–Alder reactions of naphthoquinones (6) with 2
(Scheme 3) were performed in dilute hydrochloric acid in
the pH range 1–6. The concept is that an electrostatic
interaction between the hydronium ion and the activated
complex might lead to a stabilization of the activated
complex. This stabilization could be similar to that
involving hydrogen bonding to the activated complex in
water and protic solvents as they both lower the LUMO
(dienophile)–HOMO (diene) energy gap. However, the
second-order rate constants did not show any acid cata-
lysis on these reactions. The reaction of 6a with 2, for
instance, gave second-order rate constants of 7.8 and
7.5 M ꢁ 1 sꢁ 1 for the reaction performed at pH 2 and 6,
respectively. Similarly, the second-order rate constants
for the reaction of 6b with 2 were also constant, giving
rates of 13.8 M ꢁ 1 sꢁ 1 for the reactions performed at both
pH 2 and 6. The use of 1,1,1,3,3,3-hexafluoro-2-propanol
(HFP) and 2,2,2-trifluoroethanol (TFE) solvents for the
Diels–Alder reaction of 6b with 2 also showed no
detectable acid catalysis. The second-order rate constants
recorded in HFP and TFE solvents were 3.41 and
1.01 M ꢁ 1 sꢁ 1, respectively.
It is perhaps surprising to observe that no acid catalysis
is detected in these Diels–Alder reactions. This is con-
trary to our hypothesis and to previous studies that have
shown general acid catalysis in some Diels–Alder reac-
tions in organic solvents.20 However, since our reactions
are performed in water, the influence of the specific acid
may not be noticed owing to the strong influence of
hydrogen bonding with water and enforced hydrophobic
interaction in Diels–Alder reactions in water. No attempt
was made to establish copper catalysis of these Diels–
Alder reactions but previous studies for the reaction of 6a
with 2 in aqueous CuCl2 showed a slight enhancement of
the rate constant, probably due to salt effects.24
CONCLUSION
A comparative study between Lewis acid and specific
acid catalysis for Diels–Alder reactions in aqueous media
has been carried out. Dienophiles with basic sites were
reacted with cyclopentadiene in aqueous copper(II) ni-
trate or dilute hydrochloric acid. The kinetic investiga-
tions of these reactions established that the two types of
catalysts have similar reaction mechanisms. Bidentate
reactants are required for Lewis acid catalysts but are not
a necessity for specific acid catalysis to take place.
However, a beneficial effect of a bidentate over a mono-
dentate reactant was also noted for specific acid catalysis.
A comparison between copper(II) Lewis acid catalysis
and specific acid catalysis showed the copper(II) catalyst
to be more efficient. For example, at equimolar amounts
of copper(II) and HCl (0.01 M) catalysts, the reaction rate
for the Diels–Alder reaction of 1a with 2 is about 40 times
faster for copper catalysis than for the specific acid
catalysis. At 32 ꢀC and 0.01 M HCl, the Diels–Alder
reaction of 1b with 2 is 21 times faster than in pure water
under the same reaction conditions.
Acid-catalysed Diels–Alder reactions in
mixed aqueous solutions
EXPERIMENTAL
Materials
The reaction of 1b with 2 was performed in ethanol–
water mixtures (mole fraction of water, XH O ¼ 0:8) at
2
different ‘pH’. The reaction rates were evaluated by
initial rate kinetics and compared with the rates of these
reactions performed in dilute hydrochloric acid. It is
4-Acetylpyridine (Aldrich), 2-acetylpyridine (Aldrich),
benzaldehyde (Aldrich), Cu(NO3)2ꢄ3H2O (Merck),
J. Phys. Org. Chem. 2004; 17: 180–186
Copyright # 2004 John Wiley & Sons, Ltd.

CATALYSIS OF DIELS–ALDER REACTIONS
185
KNO3 (Merck), hydrochloric acid (Merck), deuterium
chloride (Aldrich), CDCl3 (Aldrich), acetonitrile
(Aldrich) and deuterium oxide (Aldrich) were of the
highest purity available. Cyclopentadiene was cracked
from its dimer (Merck) immediately before use. Dimin-
eralized water was doubly distilled in a quartz distillation
unit. Ethanol, 1,1,1,3,3,3-hexafluoro-2-propanol and
2,2,2-trifluoroethanol solvents were of the highest purity
available. The solvents were used as received. Dieno-
philes 1a and 4 were prepared by aldol condensation of
2- and 4-acetylpyridine with the corresponding substi-
tuted benzaldehyde using documented procedures.14,22
Dienophile 1b was purified from a stock sample pre-
prepared in our group.22 Similarly, the dienophile was
purified from a stock sample pre-prepared in our group.24
constants are an average of three runs. The rate constants
determined by the pseudo-first-order method were repro-
ducible to within 3% and the initial rate method gave a
reproducibility of 5%.
Equilibrium constant measurements
The determination of the pKa for 1b was performed by
employing a Perkin-Elmer ꢀ5 or ꢀ12 spectrophotometer
at 32 ꢀC. The equilibrium constant was obtained by
measuring the extinction coefficient of the partially pro-
tonated dienophile ("obs ) as function of the acid con-
centration. After the determination of the extinction
coefficient differences of the unprotonated dienophile
and that of the partially protonated dienophile at the
maximum wavelength, the following expression was
employed for data analysis:28
1a and 4. To 100 ml of water cooled to 5 ꢀC, 16.5 mmol
of the appropriate benzaldehyde and 17 mmol of the
appropriate acetylpyridine were introduced. The mixture
was thoroughly shaken to obtain a finely dispersed
emulsion. This was followed by the addition of 10 ml
of 10% NaOH. The mixture was once again shaken and
left undisturbed overnight at 4 ꢀC. The product, which
was oil-like, solidified upon shaking and was filtered and
washed with water giving good yields: 1a, 93%; 4, 77%.
The products were crystallized from ethanol giving pure
products with melting-points for 1a, 74.8–75.5 ꢀC (lit.22
74.5–75.3 ꢀC, lit.26 74 ꢀC) and for 4, of 89.5–90.0 ꢀC
(lit.22 89.0–89.2 ꢀC, lit.27 87–88 ꢀC). The 1H NMR spec-
tra of the products were checked and were consistent with
the previously reported results.14
½H3Oþꢅ=ð"dienophile ꢁ "obs
Þ
¼ K=ð"dienophile ꢁ "protonated
Þ
þ ½H3Oþꢅ=ð"dienophile ꢁ "protonated
Þ
A plot of [H3Oþ]/("dienophile ꢁ "obs) against [H3Oþ]
yielded a straight line for which the ratio of its intercept
to the slope gives the equilibrium constant. To obtain
accurate results, it is necessary to follow the difference
between the extinction coefficient of protonated and
unprotonated dienophile at the maximum wavelength.
Acknowledgement
Kinetic measurements
The National Research School Combination Catalysis
(NRSCC, The Netherlands) is gratefully acknowledged
for financial support. The University of Dar es Salaam
(Tanzania) is acknowledged for generous study leave for
Egid B. Mubofu.
Kinetic measurements were performed using UV-visible
spectrophotometry (Perkin-Elmer ꢀ2, ꢀ5 or ꢀ12 spectro-
thotometer) by monitoring the disappearance of the
absorption of the dienophile at an appropriate wave-
length. For reactions involving specific acid catalysis,
solutions of hydrochloric acid were prepared by diluting
concentrated hydrochloric acid with doubly distilled
water. The concentrations of the dilute hydrochloric
acid were double checked by using a pH meter. The
solutions were then used to perform the specific acid-
catalyzed Diels–Alder reactions. The dienophile was
introduced into a 1 cm pathlength quartz cuvette contain-
ing 3.5 ml of solution. After equilibration, 10–25 ml of a
concentrated stock solution of cyclopentadiene in acet-
onitrile were added. The rates of the faster reactions were
monitored for at least four half-lives and the pseudo-first-
order rate constants were obtained using a fitting pro-
gram. The rates of slower reactions were determined
using initial rate kinetics. Typical concentrations
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