The decomposition of methyl hemiacetals of benzaldehyde in aqueous solution: A study of the effect of aromatic substitution

Article abstract of DOI:10.1139/v99-102

The acid-base catalysed decomposition of hydrates and hemiacetals of carbonyl compounds are classical examples of reactions where (slow) proton transfer is coupled with heavy atom reorganization, i.e., C - O bond breaking and solvent reorganization. We have studied the influence of m- and p-substitution in the carbonyl electrophile on the kinetics of the acid and base catalysis of the decomposition of methyl hemiacetals of benzaldehyde. The experimental data are well described by three-dimensional More O'Ferrall - Jencks energy contour diagrams according to principles developed by Jencks (the BEMA HAPOTHLE). Thus, for acid catalysis, a Cordes cross-interaction coefficient p_xy′ = ?ρ/?pK_a = 0.15 indicates the coupled nature of the rate-limiting step in a class e mechanism, similar to conclusions reached from systematic substitution in the nucleophile. Our more extensive set of data for base catalysis permits a more rigorous analysis according to the BEMA HAPOTHLE. The data are consistent with a class n mechanism as also suggested earlier on the basis of substitution in the nucleophile. A slight upward curvature observed in the Hammett plots for the various catalysts is described by the direct correlation parameter p_y = ?ρ/?σ = -0.11. This second derivative demonstrates the concerted nature of the C - O bond cleavage and O-H formation in the transition state, which changes with changing substituent. A class n mechanism for base catalysis is also supported by the observation of a Cordes cross-interaction parameter p_xy = ?ρ/?pK_a = -?β/?σ = 0.03, which describes the experimentally observed decrease in Hammett ρ with increasing pK_a of the catalyst. This change may be rationalized by the movement of a saddle point on a diagonal reaction coordinate in the energy contour diagram, as a resultant of shifts parallel and perpendicular to the coordinate, when the energy along one side of the diagram is changed. It is concluded that observed rate changes as a result of substitution in the electrophile are consistent with and present further confirmation of earlier suggested mechanisms of hemiacetal decomposition reactions.

Full text of DOI:10.1139/v99-102

9
78
The decomposition of methyl hemiacetals of
benzaldehyde in aqueous solution: a study of
the effect of aromatic substitution
Karen M. Engell, Robert A. McClelland, and Poul E. Sørensen
Abstract: The acid–base catalysed decomposition of hydrates and hemiacetals of carbonyl compounds are classical
examples of reactions where (slow) proton transfer is coupled with heavy atom reorganization, i.e., C—O bond
breaking and solvent reorganization. We have studied the influence of m- and p-substitution in the carbonyl electrophile
on the kinetics of the acid and base catalysis of the decomposition of methyl hemiacetals of benzaldehyde. The
experimental data are well described by three-dimensional More O’Ferrall – Jencks energy contour diagrams according
to principles developed by Jencks (the BEMA HAPOTHLE). Thus, for acid catalysis, a Cordes cross-interaction
coefficient pxy′ = ∂ρ/∂pK = 0.15 indicates the coupled nature of the rate-limiting step in a class e mechanism, similar
a
to conclusions reached from systematic substitution in the nucleophile. Our more extensive set of data for base
catalysis permits a more rigorous analysis according to the BEMA HAPOTHLE. The data are consistent with a class n
mechanism as also suggested earlier on the basis of substitution in the nucleophile. A slight upward curvature observed
in the Hammett plots for the various catalysts is described by the direct correlation parameter p = –∂ρ/∂σ = –0.11.
y
This second derivative demonstrates the concerted nature of the C—O bond cleavage and O-H formation in the
transition state, which changes with changing substituent. A class n mechanism for base catalysis is also supported by
the observation of a Cordes cross-interaction parameter pxy = –∂ρ/∂pK = –∂β/∂σ = 0.03, which describes the
a
experimentally observed decrease in Hammett ρ with increasing pK of the catalyst. This change may be rationalized
a
by the movement of a saddle point on a diagonal reaction coordinate in the energy contour diagram, as a resultant of
shifts parallel and perpendicular to the coordinate, when the energy along one side of the diagram is changed. It is
concluded that observed rate changes as a result of substitution in the electrophile are consistent with and present
further confirmation of earlier suggested mechanisms of hemiacetal decomposition reactions.
Key words: methyl hemiacetals of benzaldehydes, acid–base catalysed breakdown, Hammett plots, More O’Ferrall –
Jencks diagrams. 989
Résumé : La décomposition, catalysée par les acides et les bases, des hydrates et des hémiacétals de composés
carbonylés fourni des exemples classiques de réactions dans lesquelles le transfert (lent) d’un proton est couplé à une
réorganisation des atomes lourds, comme le bris de la liaison C—O et la réorganisation du solvant. Nous avons étudié
l’influence des substituants en m et en p du carbonyle électrophile sur la cinétique des décompositions catalysées par
les acides et les bases d’hémiacétals de méthyle du benzaldéhyde. Les données expérimentales sont bien décrites par
les diagrammes tridimensionnels de contour d’énergie de More O’Ferrall – Jencks selon les principes de Jencks
(
BEMA HAPOTHLE). Ainsi, pour la catalyse acide, un coefficient d’interaction croisée de Cordes, pxy′ = ∂ρ/∂pK =
a
0
,15, est une indication de la nature couplée de l’étape cinétiquement limitante dans un mécanisme de classe e et ceci
est semblable aux conclusions découlant d’une substitution systématique dans le nucléophile. Le large ensemble de nos
données rend possible une analyse rigoureuse en fonction de BEMA HAPOTHLE. Les données sont en accord avec un
mécanisme de classe n, tel qu’il avait été suggéré antérieurement sur la base de substitutions dans le nucléophile. Une
observation directe du paramètre p = –∂ρ/∂σ = –0,11, nous permet aussi de décrire une courbe légèrement remontante
y
dans les droites de Hammett pour les diverses catalyses. Cette deuxième dérivée démontre la nature concertée du
clivage de la liaison C—O et de la formation de la liaison O-H dans l’état de transition qui est accompagnée de
changements lors de changements de substituants. Un mécanisme de classe n pour la catalyse basique est aussi
supporté par l’observation d’un paramètre d’interaction croisée de Cordes, pxy = –∂ρ/∂pK = –∂β/∂σ = 0,03, qui décrit
a
la diminution observée expérimentalement de la constante ρ de Hammett avec une augmentation du pK du catalyseur.
a
On peut rationaliser ce changement par le mouvement d’un point de selle sur une coordonnée de réaction en diagonale
dans le diagramme de contour d’énergie, qui serait le résultat de déplacements parallèle et perpendiculaire à la
Received January 7, 1999.
This paper is dedicated to Jerry Kresge in recognition of his many achievements in chemistry.
1
K.M. Engell and P.E. Sørensen. Department of Chemistry, Technical University of Denmark, DK-2800 Lyngby, Denmark.
R.A. McClelland. Department of Chemistry, University of Toronto, Toronto, ON M5S 1A1, Canada.
1Author to whom correspondence may be addressed. Telephone: +45 45 25 24 14. Fax: +45 45 88 31 36. e-mail: pes@kemi.dtu.dk
Can. J. Chem. 77: 978–989 (1999)
© 1999 NRC Canada

Engell et al.
979
coordonnée, lorsqu’on modifie l’énergie sur un côté du diagramme. On conclut que les changements de vitesse
observés lors de substitutions dans l’électrophile sont en accord avec, et confirment, les mécanismes suggérés
antérieurement pour les réactions de décomposition des hémiacétals.
Mots clés : hémiacétals de méthyle des benzaldéhydes, décomposition catalysée par les acides et les bases, courbes de
Hammett, diagrammes de More O’Ferrall – Jencks.
[
Traduit par la Rédaction]
confirmed by our data give further support to the general va-
lidity of the principle.
The importance of proton transfer reac Et ino gn es lli en te al le. mentary
chemistry and the life sciences is indisputable. Our present
knowledge of the nature of these reactions and their cou-
pling with other (heavy atom) processes or relocations is
originally based on some careful and now almost historical
experimental studies of acid–base catalysis. J.N. Brønsted
Experimental section
Materials
(
1879–1947) and R.P. Bell (1907–1996), who created a
Benzaldehyde dimethyl acetal and all benzaldehydes
needed for the synthesis of corresponding acetals and
hemiacetals were commercially available. Solids were sub-
limed before use. The dimethyl acetals of the substituted
benzaldehydes were made as described by Davis et al. (7)
apart from for 3- and 4-fluoromethylbenzaldehyde, where a
method of Langvad (8) using dimethyl sulphate was applied.
Solid acetal products were recrystallized from methanol, and
liquids were purified by fractional spinning band distillation.
In a few cases for aldehydes of low reactivity, we were not
able to isolate the pure dimethyl acetal, i.e., an equilibrium
mixture of acetal, and the benzaldehyde builds up in metha-
nol. However, samples from these mixtures could still be
used to initiate reaction, although a higher background ab-
sorption was present in these cases from unreacted
benzaldehyde.
school with a large number of pupils, are commonly re-
garded as two of the scientific fathers of this discipline. In
relation to the present paper, it is appropriate to focus on two
of the pupils by mentioning the outstanding contributions by
W.P. Jencks, and by A.J. Kresge, the former through his
studies of the O—H bond, the latter, the C—H bond.
Protons and hydrogen continue to fascinate scientists. Re-
cently, proton flips in thin silica discs have been suggested
as memory units in future “molecular computers” with a
1
000-fold enhancement in memory capacity (1). In addition,
our steadily growing interest in biology (enzymology) keeps
putting a strong demand on the need for knowledge of the
basic nature of proton transfer reactions.
The mechanisms of acid–base catalysed reactions have
been roughly defined in many cases, and our continuous
goal is to improve the understanding of the more intimate
details of all the parameters involved. In (classical) carbonyl
addition reactions like the formation/decomposition of hemi-
acetals, one way of doing this is to introduce small but sys-
tematic variations in the various reactive sites and to observe
the resulting effect on chemical rates. Thus, in a series of pa-
pers published during the period 1960–1990, Jencks has
taught and convinced us that such studies are relevant in re-
lation to understanding and visualizing reaction mechanisms,
especially in coupled systems. Jencks has introduced the ac-
ronym BEMA HAPOTHLE — from the names of some key
physical organic chemists — to characterize the principle of
applying three-dimensional energy contour diagrams (More
O’Ferrall – Jencks diagrams) in explaining complex chemi-
cal mechanisms (2).
The various dimethyl acetals were typically checked and
1
identified in two ways: (i) verification of the H NMR spec-
trum from a solution in CDCl run on a Bruker AD-250 in-
3
strument at 250 MHz (Me Si internal reference). In the
4
NMR spectra of all acetals, a singlet appears at δ = 5.35 ±
0
.05, typical of the aldehyde proton, which is shifted from
around δ = 9.94. For the dimethyl acetal type, the identity is
further supported by a singlet at δ = 3.31 ± 0.05, six times
the intensity of the aldehyde proton peak. (ii) Verification of
the UV spectrum of the corresponding benzaldehyde after a
hydrolysis of the acetal in weak HCl. Details are as follows:
Benzaldehyde dimethyl acetal (1,1-dimethoxy-1-phenyl-
methane): δH (CDCl ): 5.39 (1 H, s, HC(OMe) ), 3.31 (6
3
2
H, s, OMe), 7.3–7.5 (5 H, m, ArH) (lit. (9), δH (CDCl3):
.40, 3.32, 7.20–7.70, respectively); λmax (H O)/nm 250 (lit.
In relation to Scheme 1, several (relatively easy) studies
5
2
of changing R in the nucleophile/leaving group, combined
3
(
9), λmax (C H )/nm 241).
6 12
with systematic series of acid–base catalysts, have been per-
formed and analysed according to the BEMA HAPOTHLE
4
-Methylbenzaldehyde dimethyl acetal (1,1-dimethoxy-1-(4-
(
2–5). However, very few extensive and systematic substitu-
methylphenyl)methane): bp 102–103°C at 18 Torr (1 Torr =
33.3 Pa) (lit. (7), bp 54°C at 1.1 Torr); δ (CDCl ): 5.35 (1
tions in the carbonyl electrophile have been reported so far,
although as for carbon acids (6) such (supplementary) stud-
ies might also bring about important information on transi-
tion state structures.
1
H
3
H, s, HC(OMe) ), 3.31 (6 H, s, OMe), 2.33 (3 H, s, ArMe),
2
7
.1–7.2 (2 H, br d, half of AB system, 2 × ArH), 7.35–7.45
(
2 H, br d, half of AB system, 2 × ArH); λmax (H O)/nm:
2
In continuation of earlier work and as an attempt to fill
this gap, we report in the present paper results from studies
of the decomposition of methyl hemiacetals of a series of m-
and p-substituted benzaldehydes.
It will be obvious from below that our results may be
treated according to the BEMA HAPOTHLE. The fact that
earlier suggestions concerning the reaction mechanisms are
2
61.6 (lit. (7, 9), λmax/nm: 262, λmax (MeOH)/nm: 255).
3-Methylbenzaldehyde dimethyl acetal (1,1-dimethoxy-1-(3-
methylphenyl)methane): bp 95.5–96.5°C at 12 Torr; δH
(CDCl ): 5.32 (1 H, s, HC(OMe) ), 3.32 (6 H, s, OMe), 2.35
(3 H, s, ArMe), 7.1–7.3 (4 H, m, ArH); λmax (H O)/nm:
254.9, 297.3 (lit. (9), λmax (MeOH)/nm: 249, 289).
3
2
2
©
1999 NRC Canada

9
80
Can. J. Chem. Vol. 77, 1999
4
-Methoxybenzaldehyde dimethyl acetal (1,1-dimethoxy-1-
of the hemiacetals with substituents more electron withdraw-
ing than 4-methyl can be obtained by simply dissolving the
appropriate benzaldehyde in methanol and leaving the solu-
tion for about 1 h. Addition of small amounts of base (so-
dium carbonate or calcium hydride) shifts the equilibrium
towards the hemiacetal even further and at the same time
prevents the formation of acetal.
(
(
4-methoxyphenyl)methane): bp 125–126°C at 15 Torr (lit.
7), bp 86°C at 1.6 Torr); δH (CDCl ): 5.32 (1 H, s,
3
HC(OMe) ), 3.32 (6 H, s, OMe), 3.80 (3 H, s, ArOMe),
2
6
.85–6.95 (2 H, br d, half of AB system, 2 × ArH), 7.3–7.4
(
2 H, br d, half of AB system, 2 × ArH); λmax (H O)/nm:
2
2
85.8 (lit. (7, 9), λmax/nm: 283.5, λmax (MeOH)/nm: 273).
3
-Methoxybenzaldehyde dimethyl acetal (1,1-dimethoxy-1-
Kinetics
(
(
(
3-methoxyphenyl)methane): bp 127–128°C at 15 Torr; δH
CDCl ): 5.32 (1 H, s, HC(OMe) ), 3.32 (6 H, s, OMe), 3.80
3 H, s, ArOMe), 6.8–7.5 (4 H, m, ArH); λmax (H O)/nm:
The decomposition of acetals and hemiacetals of the vari-
ous substrates can be easily followed spectrophotometrically
because of the benzaldehyde reaction product, which has
distinct UV absorption maxima deriving from the aromatic
aldehyde group. Three spectrophotometric techniques have
been applied:
3
2
2
2
57.1, 314.3 (lit. (9), λλmax (MeOH)/nm: 218.5, 251.5, 310).
3
-Bromobenzaldehyde dimethyl acetal (1,1-dimethoxy-1-(3-
bromophenyl)methane): bp 121–121.5°C at 14 Torr; δH
(
7
(
CDCl ): 5.36 (1 H, s, HC(OMe) ), 3.32 (6 H, s, OMe), 7.2–
.7 (4 H, m, ArH); λmax (H O)/nm: 254.5 (lit. (9), λλmax
2
MeOH)/nm: 244.5, 291).
3
2
(
a) Conventional spectrophotometry
For reactions with half-lives >30 s. A small sample of the
substrate — usually about a microliter of a methanolic solu-
tion of acetal or hemiacetal was transferred by a micro sy-
ringe to a thermostatted quartz cell containing the aqueous
reaction medium (Shimadzu UV-150-02 spectrophotometer).
The reaction was initiated by quick stirring with a small Tef-
lon stirrer before data collection.
4
-Dimethylaminobenzaldehyde dimethyl acetal (1,1-
dimethoxy-1-(4-dimethylaminophenyl)methane): bp 163.5–
1
3
64.5°C at 18 Torr; δ (CDCl ): 5.30 (1 H, s, HC(OMe) ),
H 3 2
.32 (6 H, s, OMe), 3.10 (6 H, s, ArNMe), 6.65–6.75 (2 H, d
triplet, half of AB system, 2 × ArH), 7.7–7.8 (2 H, d triplet,
half of AB system, 2 × ArH); λmax (H O)/nm: 245.9, 353.2
2
(
b) Conventional stopped-flow spectrophotometry
For reactions with half-lives <30 s. This technique was
(
lit. (9), λmax (MeOH)/nm: 242, 340).
4
-Trifluoromethylbenzaldehyde dimethyl acetal (1,1-
primarily used in our study of the specific acid-catalysed re-
action, through the stepwise decomposition of the full acetal.
This produced s-shaped absorbance–time traces for the
benzaldehyde appearance that could be analysed to give si-
dimethoxy-1-(4-trifluorophenyl)methane): bp 60–62°C at 10
Torr; δH (CDCl ): 5.46 (1 H, s, HC(OMe) ), 3.32 (6 H, s,
3
2
OMe), 7.6–7.75 (4 H, dd, AB system, 2 × 2 × ArH); λmax
H O)/nm: 240.
+
(
multaneously H -catalytic constants for hemiacetal and
2
acetal decomposition. A slightly alkaline aqueous solution of
the acetal was mixed in the instrument (Durrum or HiTech
Scientific stopped-flow spectrophotometer) with varying
concentrations of excess HCl, followed by measuring the
pH in the final mix after each experiment. This stopped-flow
technique was also used in studying the decomposition of
the mixed acetals. A slightly alkaline, aqueous solution of
the substrate was mixed in the apparatus usually with a
buffer containing enough HCl to neutralize the “alkalinity”
of the substrate solution.
-Chlorobenznzaldehyde dimethyl acetal (1,1-dimethoxy-1-
2
-Bromobenzaldehyde dimethyl acetal (1,1-dimethoxy-1-(4-
2
-Nitrobenzaldehyde dimethyl acetal (1,1-dimethoxy-1-(4-
2
max
(
MeOH)/nm: 265).
(
c) Double-mixing stopped-flow spectrophotometry
4
-Hydroxybenzaldehyde dimethyl acetal (1,1-dimethoxy-1-
(HiTech Scientific PQ/SF-53 instrument). As shown ear-
(
(
4-hydroxyphenyl)methane): λmax (H O)/nm: 244.4, 340.0
lit. (9), λmax (MeOH)/nm: 218.5, 253, 314.5).
lier for equivalent studies of acetophenones (11, 12), this
technique, which is essentially a fast pH jump method, of-
fers an advantage in the (fast) recording of absorbance–time
traces for the buffer-catalysed decomposition of aromatic
hemiacetals. As suggested in Scheme 1, a certain percentage
(depending on aromatic substituent) of hemiacetal interme-
diate builds up during acetal hydrolysis in acid. The time of
maximum buildup may be calculated, and if the pH of the
reaction mixture is jumped to a higher value at that time,
further acetal breakdown will stop, and we are left with a
situation where the decomposition of accumulated
hemiacetal can be studied separately. In a typical double-
2
Two mixed acetals were synthesized according to prescrip-
tions by Anderson and Capon (10) where the respective
benzaldehyde dimethyl acetals are initially converted by
thionyl chloride to the corresponding α-chlorobenzyl methyl
ether, which is then reacting with methyl salicylate. The
final products were purified by HPLC and (or) fractional
distillation: the compounds so prepared were benzaldehyde
2
-(carbomethoxy)phenyl methyl acetal (1-methoxy,1-(2-
carbomethoxyphenoxy)-1-phenyl-methane) and 4-methyl-
benzaldehyde 2-(carbomethoxy)phenyl methyl acetal (1-
methoxy, 1-(2-carbomethoxyphenoxy)-1-(4-methylphenyl)meth-
ane). Spectroscopic and kinetic specifications were as de-
scribed by Anderson and Capon (10).
–
4
mixing experiment an aqueous solution of 5 × 10 M acetal
in 0.002 M NaOH was first mixed (1:1) with 0.004 M aque-
ous HCl. After “incubation” for 2–30 s (depending on the
substrate), this mixture was then jumped to a higher pH by a
second mixing in the instrument (1:1) with an appropriate
Methyl hemiacetals of the various benzaldehydes are too
unstable to be isolated. However, sufficient concentrations
©
1999 NRC Canada

Engell et al.
981
Scheme 1.
k1
R OH
k2
R
1
R
1
OH
OR
R
OR
1
3
-
-R OH
3
3
C
O
C
C
+
H O
2
R
R
3
2
R
OR
2
2
3
Acetal
Hemiacetal
Carbonyl
Fig. 1. S-shaped absorbance–time trace (λmax = 250 nm) of the
hydrolysis of the dimethyl acetal of benzaldehyde in weak
hydrochloric acid.
Fig. 2. Specific acid catalysis of the hydrolysis of benzaldehyde
dimethylacetal (closed squares) and methyl hemiacetal (closed
circles).
-1
⌬
Abs
k /s
obs
0
.0
0.5
1.0
1.5
2.0
1
8
-
-
-
-
16
1
1
1
4
2
0
0
.0
0.2
0.4
0.6
0.8
8
Time (s)
6
4
2
0
buffer (acetate, cacodylate, phosphate, or TRIS), and the in-
crease in absorbance with time was recorded.
All experiments are carried out in such a way that ionic
strengths of 1.0 M (KCl) are obtained in the reaction me-
dium. Temperatures were kept at 25.0 ± 0.2°C.
0
5
10
15
20
25
3
0 {H }/M
+
1
Results and discussion
smaller rate constant can be assigned to acetal hydrolysis,
i.e., the first step in Scheme 1. At pH 6, this step is solely
rate-limiting because the hemiacetal step is accelerated by
hydroxide catalysis (vide infra).
Specific acid catalysis
The consecutive reaction in Scheme 1 leads to s-shaped
absorbance–time plots when the appearance of the final (al-
dehyde) product is followed spectrophotometrically. The ex-
ception to this are cases where the rate constant k >>k or
Figure 2 shows a plot of results from experiments at 15
different pH values in the range pH = 1.65–3.13 for the hy-
1
2
+
vice versa, where the reaction will approach a single expo-
nential nature. This is generally what is observed for the
drolysis of benzaldehyde dimethyl hemiacetal ({H } taken
–
pH
as 10 ). It is clear that the (faster) hemiacetal rate con-
(
acidic) hydrolysis of acetals (k << k ). However, as pointed
stants (k ) are not as well defined as the corresponding k
1
2
2
1
out by Jensen and Lenz (13) and Finley et al. (14), for cer-
tain symmetric acetals like the diethyl and dimethyl acetals
of benzaldehydes and of acetophenones, the rate constants k1
values. The observed relative standard deviation on k being
2
5–10%, while it is less than 0.5% for k . Nevertheless, in
1
+
both cases, catalytic constants (k ) for H catalysis may be
H
and k are sufficiently close to cause a detectable accumula-
tion of hemiacetal, and an s-shaped kinetic trace.
derived from Fig. 2 as indicated by the least-squares lines
2
+
based on kobs = k {H } + k . In these plots, the water values
H
w
An example is shown in Fig. 1 for the hydrolysis of the
dimethyl acetal of benzaldehyde, the absorbance recorded
kw are too small to be determined with certainty.
Table 1 summarizes all the results from the acid catalysis
experiments for 11 aromatic substituents (primary data in the
for the appearance of the aromatic carbonyl peak at λmax
=
3
2
50 nm. The trace is an average of six single runs of 600
supplementary Table S1).
+
points per run. The solid line derives from a least-squares
computer fit (MINSQ) based on a double exponential ex-
pression of the type ∆A = Me
The aromatic substituent effects on the H -catalysed
2
breakdown of benzaldehyde acetals and hemiacetals in Ta-
ble 1 are conveniently visualized in a Hammett plot. We
have applied the Young and Jencks (19) version in eq. [1]
where the contributions from polar and resonance effects are
–
k t
–k t
+ Ne
+ P. This procedure
1
2
produces two first-order rate constants, k and k , of which
1
2
one is approximately 10 times bigger than the other. We
know from experience and from a single (slow) acetal hy-
n
separated where possible, i.e., σ (Table 1) are taken for σ or
4
+
drolysis experiment at about pH 6 (t1/2 ≈ 10 s) that the
σ if no specific values are available for those parameters.
2
MicroMath scientific software. P.O. Box 21550, Salt Lake City, UT 84121.
Tables S1–S3 (kinetic data) have been deposited as supplementary material and may be purchased from: The Depository of Unpublished
Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, Canada, K1A 0S2.
3
©
1999 NRC Canada

9
82
Can. J. Chem. Vol. 77, 1999
+
Table 1. Summary of data for the H -catalyzed decomposition of some meta- and para-substituted benzaldehyde dimethyl acetals.
Temperature 25°C, ionic strength = 1.0 M.
Hammett σ
σ + a
Acetal
kH (M–1 s–1)
Hemiacetal
kH (M–1 s–1)
tmaxc
Hemiacetald
(%)
Substituent
σ a
σ nb
(s)
4
3
3
3
4
3
-Nitro
-Nitro
-Bromo
-Chloro
-Bromo
-Methoxy
0.778
0.71
0.79
0.176e
23.7 ± 0.5e
30.4 ± 0.6e
137 ± 6
208
154
25.3
28.4
11.4
0.72
0.92
3.1
2.9
5.5
0.294e
0.391
0.373
0.232
0.115
0
0.405
4.84 ± 0.11
4.04 ± 0.05
16.9 ± 0.2
29.7 ± 0.3
60.5 ± 0.9
125 ± 8
0.15
0.047
0
0.265
255 ± 12
430 ± 15
690 ± 60
6.67
3.85
5.7
6.9
Parent
(
54)f
3
4
4
4
-Methyl
-Methyl
-Methoxy
-Hydroxy
–0.1
–0.066
–0.31
–0.78
–0.92
99.4 ± 1.3
252 ± 5
1614 ± 16
957 ± 13
870 ± 30
1850 ± 100
3600 ± 400
5500 ± 300
2.81
1.24
0.405
0.384
8.6
9.9
23
–0.17
–0.27
–0.37
–0.13
–0.18
–0.2
12
a
Reference 15.
b
Reference 16.
c
+
t
is the time of maximum buildup of hemiacetal B (d[B]/dt = 0) in the reaction scheme A → B → C, calculated as t = (ln (k [H ]) – ln
max 1
+ + +
max
+
(
k [H ]))/(k [H ] – k [H ]) where [H ] is taken as 0.001 M.
2 1 2
d
+
+
+
+
+
Bmax (%) at tmax, calculated as 100[B]/A = 100(k [H ]/((k [H ]) – (k [H ]))(exp (–(k [H ]t ) – exp (–(k [H ]tmax)).
0
1
2
1
1
max
2
e
Reference 17 (T = 298 K, µ = 1.25 M).
f
Reference 18 (T = 298 K, µ = 0.5 M).
al. (20) found ρ(acetal) = –3.16 ± 0.02 with r = 0.34 ± 0.01
(T = 298 K, µ = 0.25 M, correlation coefficient 0.9998).
Similarly, Przystas and Fife (21) found in a less extensive
study for the hemiacetal breakdown of benzaldehyde ethyl
hemiacetals ρ (hemiacetal) = –1.90 ± 0.05 (correlation coef-
ficient 0.9997).
The observed change in hemiacetal buildup (%Bmax in Ta-
ble 1, last column) with the aromatic substituent clearly has
its origin in the differing slopes in Fig. 3, a fact that was also
observed for acetophenone acetal and hemiacetal breakdown
Fig. 3. Modified Hammet plots (Young and Jencks (19)) for the
H -catalysed decomposition of some m- and p-substituted
benzaldehyde dimethyl acetals and methyl hemiacetals. Data
taken from Table 1.
+
log (kH)
Hemiacetal
(
11, 12).
Buffer catalysis
Kinetics of the breakdown of a number of substituted
benzaldehyde methyl hemiacetals were studied rather exten-
sively for general catalysis by buffers. This section describes
measurements in acetate buffer where catalysis can be seen
from both Hac and ac. Experiental techniques (a) and
Acetal
(
(
b) were applied. The double-mixing experimental technique
c) was employed where there was primarily only catalysis
by the basic buffer components. These results are presented
in the next section.
␴n + r(␴ - ␴ )
+
n
Each substrate was typically studied at three different
buffer ratios. As usual, the observed first order rate con-
+
n
r
+
n
n
+
n
stants are given as kobs = k + k {H } + k [Hac] + k [ac]
[
1]
lg (k/k ) = ρ σ + ρ (σ – σ ) = ρ[σ + r(σ – σ )]
w
H
Hac
ac
0
+
kOH{OH}. As an alternative to classical plotting proce-
r
where r (= ρ /ρ) is a parameter ranging from 0 (no reso-
nance) to 1 (full resonance).
dures, we have applied a least-squares multiparameter fitting
2
procedure by MINSQ based on this equation and leading to
The resulting two Hammett plots are shown in Fig. 3 as
two straight lines. A least-squares analysis according to
eq. [1] (MINSQ) gives the following results: acetal hydro-
lysis, ρ = –3.24 ± 0.16 with r = 0.30 ± 0.06 (correlation co-
efficient 0.996); hemiacetal hydrolysis, ρ = –1.89 ± 0.04
with r = 0.35 ± 0.04 (correlation coefficient 0.999). For a
corresponding study of benzaldehyde ethyl acetals, Jensen et
the “best” values for all catalytic constants involved. De-
tailed results from such a calculation for the decomposition
of 3-methylbenzaldehyde methyl hemiacetal are shown in
Table 2, where the derived catalytic constants are given at
the bottom of the table. The pH of the acetate buffers are
low enough to prevent any catalysis of the reaction by hy-
2
droxide ion (vide infra). The value in the table of k = (7.9 ±
H
©
1999 NRC Canada

Engell et al.
983
Table 2. Kinetic data for the buffer-catalysed decomposition of 3-methylbenzaldehyde methyl hemiacetal.
–
Acetate buffer, r = fraction of acid = [HA]/([HA]+[A ]). Temperature 25°C, ionic strength = 1.0, λ
2
=
max
55 nm.a
–
1
–1
Total buffer concentration (M)
pH
k (obs.) (s )
k (calcd.) (s )
2
2
r = 0.250
0
0
0
0
0
.10
.20
.30
.40
.50
5.04
5.04
5.04
5.05
5.07
0.0496 ± 0.0019
0.080 ± 0.005
0.113 ± 0.003
0.147 ± 0.006
0.180 ± 0.006
0.0523
0.084
0.117
0.149
0.181
r = 0.500
0
0
0
0
0
.10
.20
.30
.40
.50
4.59
4.56
4.59
4.57
4.58
0.060 ± 0.002
0.088 ± 0.014
0.120 ± 0.011
0.152 ± 0.008
0.179 ± 0.006
0.061
0.090
0.116
0.145
0.173
r = 0.750
0
0
0
0
0
.10
.20
.30
.40
.50
a
4.08
4.07
4.04
4.04
3.99
0.101 ± 0.002
0.134 ± 0.005
0.159 ± 0.018
0.182 ± 0.008
0.196 ± 0.013
0.102
0.127
0.155
0.178
0.210
–1 –1
–1
–1 –1
2
–1 –1
kW = (0.013 ± 0.008) s ; k = 0.0 M
s (fixed); kH = (7.9 ± 1.1) × 10 M s ; k = (0.37 ± 0.04) M s ; k = (0.19
A HA
OH
–
1
–1
±
0.04) M s ; correlation coefficient = 0.993.
Scheme 2.
R
R
-
A-H
+
O -C-O H
A
+
HO -C-O H
+
R
=
R
R
-
A
HO
(+ )
C
O
H
A
(-)
HO + C= O + H-A
HO -C-O H +
+
2
–1
2
1
M
.1) × 10 M s–1 compares well with k = (8.7 ± 0.3) × 10
and final results are summarized in Table 3 together with
other relevant data from the literature.
H
–
1
–1
s
from the experiments reported previously in more
acidic solution (Table 1).
The supplementary Table S2 contains results for the re-
maining 12 substituents (acetate catalysis), and the final re-
sults are summarized in Table 3.
Acid catalysis and the BEMA HAPOTHLE
The specific as well as general acid-catalysed breakdown
of carbonyl adducts such as hemiacetals and hydrates is be-
lieved to take place by a so-called class e mechanism (24),
where the (concerted) proton transfer takes place from the
electrophile (carbonyl group) in the transition state of the
rate-limiting (second) step as shown in Scheme 2.
Base catalysis
Catalysis by the buffers cacodylate, phosphate, and TRIS
were studied by the double-mixing technique (c) described
in the experimental section. The buildup to a maximum of
hemiacetal takes place in the first mix at a pH around 3 and
at a speed that varies from compound to compound. After
the second mix, the base-catalysed breakdown of the acetal
is followed spectrophotometrically. A drifting infinity line in
most cases is due to a slight background reaction from con-
tinued hydrolysis of acetal even at higher pH. As before, the
observed first-order rate constants depend on the concentra-
According to Jencks and Jencks (4), the mathematical de-
scription of the saddle point in a More O’Ferrall – Jencks
energy contour diagram visualizing this rate-limiting con-
certed step is given in eq. [2], the primes referring to the fact
that “diagonal” substituent effects are involved, i.e., effects
of substituents on the central carbonyl oxygen atom.
2
2
[
2]
–log (k/p) = 1/2p (pK ) + 1/2p (σ) – p (pK )σ
x a y′ xy′ a
tion of the various catalysts as described by equation k
=
+ x (pK ) – y σ + F
o a o
obs
+
k + k {H } + k [Hac] + k [ac] + kOH{OH}. In almost all
w
H
Hac
ac
The chemical interpretation of p , p , and p is as fol-
x
y′
xy′
cases, however, only contributions from k and k were rel-
A
OH
lows:
evant in the pH range studied, and this equation reduces to
2
kobs = k [ac] + k {OH}. Again, a MINSQ procedure was
ac
OH
px = ∂α /∂pKa
direct correlation expressing curvature in the Brønsted plot.
used to evaluate the best values of the catalytic constants.
Primary results are contained in the supplementary Table S3,
©
1999 NRC Canada

Table 3. Collected catalytic constants for the base-catalyzed decomposition of some meta- and para-substituted benzaldehyde methyl and ethyl hemiacetals, and benzaldehyde
hydrates. Numbers in bold are from this work. Temperature 25°C, ionic strength = 1.0.
HPO 2–
H PO
4
–
TRIS base
Hydroxide
Water
Acetate
pKA = 4.65 pKA = 4.65
p, q = 1, 2
Acetic acid
Cacodylate
4
2
Hammett σ
pKA = –1.74
p, q = 3, 1 (s–1) p, q = 1, 2
pKA = 6.29 pKA = 6.49 pKA = 6.49
pKA = 8.36 pKA = 15.74
Substituent
σ
σ+
σn
p, q = 1, 2
p, q = 2, 3
p, q = 2, 3
p, q = 3, 1
p, q = 2, 1 (10–6kOH
)
3
3
4
,5 Dinitro
1.42
0.055 ± 0.009
0.014 ± 0.004
1.21 ± 0.04 –0.10 ± 0.03
3.1a
0.097a
5.2
1.98 ± 0.07
a
a
a
0
0.42
.30
0.03
0.11a
0.77
0.41
a
4.4a
0.36a
0.39a
a
-Nitro,
0.94
0.82
0.79
0.95
4
-chloro
-Nitro
0.778
0.51 ± 0.02 0.08 ± 0.02
7.1 ± 0.5
3.72 ± 0.09
.42 ± 0.01 0.12a
.40
4.4
a
4.07 ± 0.07
e
0
0
a
a
0.49
f
1
.42
0.63 ± 0.03 –0.02 ± 0.03 1.55b
0.10 ± 0.05
c
4.00 ± 0.07
3
-Nitro
0.71
0.08 ± 0.08
7.1 ± 0.3
9.2
a
0.16a
a
a
c
0
0
.39
.24
4.2
2.2
0.46
0.75
0.43
b
b
a
g
0
4
.54
e
.01 ± 0.07
0.25b
0.04 ± 0.01c 1.45b
2.3b
0.15 ± 0.05c
0.78
g
3
3
4
,4-Dichloro
-Cyano
0.6
0.49
0.6
g
0
.46
0.56
0.54
2.97 ± 0.06
d
0
.97
-Trifluormethyl
0.033 ± 0.004
0.026 ± 0.009
0.32 ± 0.02 0.11 ± 0.01
7.0 ± 0.3
0.63a
13
2.13 ± 0.05
a
0.21a
a
d
0
.39
4.3
1.19
a
0
.33
3
3
3
-Trifluormethyl
-Bromo
-Chloro
0.43
0.391
0.373
7.1 ± 0.2
6.5
2.0 ± 0.1
3.6 ± 0.1
3.5 ± 0.1
0.405
4.44
3.67
13
13
6.7
4.6
0.98 a
0.44 ± 0.04 0.12 ± 0.04
a
0.31a
a
f
0
.37
2.0
0
d
.75
0.40
.30
.224b
2.74b
b
a
0
0
3
4
4
-Fluoro
-Bromo
-Chloro
0.337
0.232
0.227
0.033 ± 0.009
0.011 ± 0.008
0.049 ± 0.013
0.32 ± 0.04 0.04 ± 0.04
0.50 ± 0.04 0.07 ± 0.04
0.24 ± 0.07 0.18 ± 0.06
0.15
0.114
0.3
0.2
3.61
3.22
7.6
5.2
16
15
2.4 ± 0.1
2.99
a
1.1d
d
2
0.59
0
0
.34f
.33a
0.47d
3.22b
d
b
a
0
.29
.20
3
4
-Methoxy
-Fluoro
0.115
0.06
0.05
–0.07
0.008 ± 0.011
0.008 ± 0.012
0.40 ± 0.04 0.15 ± 0.04
0.43 ± 0.04 0.26 ± 0.04
6.8 ± 0.2
–0.1 ± 0.2
2.0 ± 0.1

Table 3 (concluded).
Water
Acetate
pKA = 4.65 pKA = 4.65
p, q = 1, 2
Acetic acid
Cacodylate
pKA = 6.29 pKA = 6.49 pKA = 6.49
HPO 2–
H PO
–
TRIS base
Hydroxide
4
2
4
Hammett σ
pKA = –1.74
p, q = 3, 1 (s–1) p, q = 1, 2
pKA = 8.36 pKA = 15.74
Substituent
Parent
σ
σ+
σn
p, q = 1, 2
p, q = 2, 3
p, q = 2, 3
p, q = 3, 1
p, q = 2, 1 (10–6kOH
)
0
0
0
0.012 ± 0.007
.016 ± 0.010
0.26 ± 0.04 0.17 ± 0.03
0.29 ± 0.03 0.21 ± 0.04
3.36
1.41b
6.25 ± 0.15 0.23 ± 0.09
20
1.7 ± 0.2
3.07
2.76b
0.51 ± 0.17
c
d
0
2
.47f
.170b
2.54b
0.72
.34
d
0
b
0
3
4
-Methyl
-Methyl
–0.067 –0.066
0.013 ± 0.008
–0.129 0.029 ± 0.011
0.37 ± 0.04 0.19 ± 0.04
0.23 ± 0.05 0.35 ± 0.05
3.09
4.17
6.6 ± 0.2
0.1 ± 0.2
0.8 ± 0.2
15
19
2.0 ± 0.1
2.8 ± 0.4
–0.17
–0.31
7.7 ± 0.3
b
3.18
d
1
0
.04
.31
b
4
-Methoxy
–0.27
–0.78
–0.175
4.75
9.1 ± 0.3
1.0 ± 0.2
2 ± 1
28
3.4 ± 2.0
d
1
0
.37
.49
b
4
4
-Hydroxy
-Dimethylamino
–0.37
–0.63
–0.92
–1.7
4.20
5.56
10.6
11 ± 1
35
42
4.0 ± 1.1
5.24 ± 0.05
–0.219
a
Reference 22, benzaldehyde hydrate.
Ethyl hemiacetal (J.L. Jensen. Private communication. Unpublished results. 1991.).
b
c
Reference 23, ethyl hemiacetal.
d
Reference 14, ethyl hemiacetal
Reference 17, methyl hemiacetal.
e
f
Reference 21, ethyl hemiacetal.
g
Reference 23, benzaldehyde hydrate.

9
86
Can. J. Chem. Vol. 77, 1999
Scheme 3.
R
R
-
- + H-A
O-C-OH + A
O-C-O
R
O
R
R
-
A H
-)
C
O
(-)
A- +
HO + C= O
A-H + O-C-O
(
Fig. 4. A More O’Ferrall – Jencks diagram for the rate-limiting
step in the acid-catalysed breakdown of benzaldehyde methyl
hemiacetal (step 2 in Scheme 2) in a class e mechanism (24).
The actual value of Hammett ρ throughout the diagram is a
compromise between the values of ρ indicated at the corners of
the diagram. These corner values represent the experimentally
observed or estimated sensitivity of the various carbonyl forms
to aromatic substitution with reference to the upper left corner
to the x and y axes in the More O’Ferrall – Jencks diagram,
leading to a diagonal reaction coordinate. In this case, a
value of pxy′ >0 is required to produce a saddle point in the
diagram in the right direction (4).
A diagram based on data in the present paper for the acid-
catalysed breakdown of hemiacetals is illustrated in Fig. 4.
A value of ρ = –1.6 is estimated from an interpolation based
0
on the data in Table 3. A value of α = 0.55 is estimated
0
(
22). The location of the saddle point (transition state) is shown
from Brønsted α = 0.47 ± 0.01 for 3-nitro- and α = 0.50 ±
with horizontal and vertical level lines (i.e., a diagonal reaction
coordinate). The bold arrow indicates the expected direction of
movement of the transition state for a weaker acid catalyst, i.e.,
toward higher ρ values (pxy′ positive, see text).
0
.01 for 3,4-dichlorobenzaldehyde ethyl hemiacetal break-
down, based on a series of carboxylic acids (23). The coor-
dinates of the saddle point in Fig. 4 are taken as ρ = –1.9 –
+
(
–1) = –0.9 (for H -catalysis) and α = 0.55 (for the parent
compound). Based on Hammond and anti-Hammond effects,
the bold arrow represents the expected resulting movement
of the transition state when a weaker acid catalyst is intro-
duced, i.e., an increase in ρ as observed experimentally and
in accordance with a positive value of pxy′ (see next para-
graph).
The result from a statistical treatment, based on eq. [1]
MINSQ) of our (limited) set of experimental data for acid
2
(
catalysis (Tables 1 and 3), is that a small positive value of
pxy′ is obtained, but with a large standard deviation. Alterna-
tively, a rather crude plot of ρ versus pK for the three acids
a
+
–
H O , HAc, and H PO , according to p = ∂ρ/∂pK , leads
3
2
4
xy
a
to a value of pxy′ = 0.15 for the methyl hemiacetals of
benzaldehyde. This value is in good agreement with a value
of pxy′ = 0.12 found by McClelland and Coe (22) and by Cox
et al. (23) for dehydration of benzaldehyde hydrates.
The literature contains many studies where the effect of
systematic substitution in the nucleophile/leaving group has
been investigated and analysed (2). However, there are not
many equivalent studies dealing with the electrophile. While
we realise that our body of experimental data for acid catal-
ysis is too incomplete to perform a rigorous statistical analy-
sis according to the Jencks formalism, it does show that a
systematic variation by substitution in the electrophile leads
to experimentally observable effects that follow the rules
stated by this formalism.
py′ = –∂ρ/∂σ
direct correlation expressing curvature in the Hammett plot.
pxy′ = ∂ρ/∂pK = -∂α /∂σ
a
Cordes cross-interaction coefficient.
The values x and y are fixpoints defined as x = α (α
0
0
0
0
extrapolated to σ = 0, i.e., for the parent compound); y = ρ
0
0
Base catalysis and the BEMA HAPOTHLE
In this section, we are dealing with a more complete set of
catalytic data (Table 3) and a rather detailed mechanistic
analysis is therefore possible.
(
ρ extrapolated to pK = 0 for the catalyst). The value of F is
a
taken to fit the absolute value of the observed rate constants.
No detailed data for a reliable Brønsted plot analysis is
carried out in this work, but in a similar study by Cox et al.
(
23), no curvature was observed within experimental error in
Figure 5 shows Hammett plots where all bases are in-
cluded. Rate constants are plotted against σ throughout as a
+
the Brønsted plots for acid catalysis. Similarly, the Hammett
plots, as discussed above, are linear, implying that p and p
are both equal to zero. The two “level lines” of the saddle
point are therefore perpendicular to each other and parallel
result of the fact that a (perhaps) more rigorous plot against
σ + r(σ – σ ) leads to values of r ≥1, indicating a predomi-
nant influence of resonance effects by the substituents, as
x
y′
n
+
n
©
1999 NRC Canada

Engell et al.
987
Fig. 5. Hammett plots for the base-catalysed decomposition of
benzaldehyde hemiacetals. Solid lines are simulated by a least-
squares procedure on the basis of eq. [3] and data from Table 3.
curvature in Brønsted plots, i.e., p = 0, and eq. [3] reduces
to eq. [4]
x
[
4]
–log (k/q)
1/2p (σ) + p (pK )σ + x (pK ) – y σ + F
lg(k /q)
B
2
=
y
xy
a
o
a
o
where y = ρ is the slope in the Hammett plot for a theoreti-
0
o
Hydroxide
TRIS
cal base with pK = 0. It may be clear from a quick inspec-
a
tion of Fig. 5 that all the Hammett plots have slopes around
zero, but with a tendency of ρ to increase with decreasing
pK (p positive). Thus, a good starting guess of ρ in eq. [4]
a
xy
o
will be ρo ≈ 0; βo is Brønsted β for the unsubstituted
benzaldehyde methyl hemiacetal. Cox et al. (23) found β =
Phosphate
Cacodylate
Acetate
_
0.52 ± 0.02 for 3 nitro- and β = 0.50 ± 0.02 for 3,4-dichloro-
benzaldehyde ethyl hemiacetal based on carboxylic acids.
Therefore, a good starting guess of β is expected to be β ≈
o
o
0
.5.
Water
All our data for the methyl hemiacetal decomposition,
catalysed by the five general bases in Table 3 (incl. water)
were now fitted to eq. [4] by a least-squares procedure
σ+
2
(
MINSQ) and the following results were obtained, with a
correlation coefficient of 0.993:
+
best reflected by σ . The curves drawn in the figure are sim-
p = 0.0 (fixed), p = –0.11 ± 0.08, p = 0.03 ± 0.02
x
y
xy
ulated based on the statistical analysis reported below.
According to Jencks, the general base-catalysed break-
down of hemiacetals is believed to take place by a class n
mechanism, where the concerted proton transfer in the tran-
sition state occurs to the leaving nucleophile as shown in
Scheme 3 (24).
As for acid catalysis, the saddle point in an energy con-
tour diagram for the rate-limiting (second) step may be char-
acterized by an equation of the type (4):
β = 0.48 ± 0.01, ρ = 0.10 ± 0.10, F = 2.84 ± 0.05
o
o
The direct correlation coefficient p was found to be small
y
and negative in consequence of a slight upward curvature of
the Hammett plots. Experiments on leaving-group effects
substitution in the nucleophile) for formaldehyde and
(
acetaldehyde (3, 5) lead to a value of p = –0.20. The U-
y′
shaped curvature characterized by negative values of p and
y
2
2
py′ represent the balance between the amount of C—O bond
cleavage and O—H bond formation in the transition state,
which changes with changing substituents. This is strong ev-
idence for a concerted mechanism that involves both pro-
cesses in the transition state (2, 4).
[
3]
–log (k/q) = 1/2p (pK ) + 1/2p (σ)
x
a
y
+
p (pK )σ + x (pK ) – y σ + F
xy a o a o
where again the chemical interpretation of p , p , and p is
x
y
xy
as follows:
A positive value of pxy = 0.03 is in accordance with a
class n mechanism and has been observed in several studies
before, as a result of the fact that when the carbonyl
electrophile becomes less stable the observed Brønsted β
value for base catalysis decreases (2). This phenomenon
may be rationalized from and visualized in Fig. 6, which
shows a energy contour diagram for a class n mechanism
corresponding to step two in eq. [3]. A decrease in stability
of the electrophile (carbonyl) by introducing a more
electronegative substituent, as illustrated by an increase in
energy of the electrophile at the bottom of the diagram,
leads to a shift of the transition state toward the upper left
corner, perpendicular to the the reaction coordinate, and to-
wards the lower left corner, parallel to the reaction coordi-
nate. The resultant of these effects moves the transition state
to the left in the diagram, leading to a decrease in Brønsted
β, as observed. The same diagram may be used to demon-
px = –∂β/∂pKa
direct correlation expressing curvature in the Brønsted plot.
py = –∂ρ/∂ σ
direct correlation expressing curvature in the Hammett plot.
pxy = –∂ρ/∂pK = –∂β/δσ
a
Cordes cross-interaction coefficient.
The values x and y are fixpoints defined as x = β (β ex-
0
0
0
0
trapolated to σ = 0, i.e., for the parent compound); y = ρ (ρ
0
0
extrapolated to pK = 0 for the catalyst). The value of F is
a
taken to fit the absolute value of the observed rate constants.
No primes are assigned here because the central oxygen
atom of the transition state is not involved in substitution.
The limited number of catalyst bases implied in this work
means that no reliable Brønsted analysis could be per-
formed, but from the rather extensive investigations by
Jensen (see reference in footnote b, Table 3) and by Cox et
al. (23), including the breakdown of benzaldehyde ethyl
hemiacetals, we are convinced that there is no observable
strate the increase in ρ with decreasing pK of the catalyst,
a
as observed in the present study. A decrease in pK due to
a
introducing a weaker base raises the energy of the right-hand
site of the diagram, leading to a shift of the transition state
toward the upper right corner, parallel to the reaction coordi-
nate, and toward the upper left corner, perpendicular to the
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1999 NRC Canada

9
88
Can. J. Chem. Vol. 77, 1999
Fig. 6. More O’Ferrall – Jencks diagram for the rate-limiting
step in the base-catalysed breakdown of benzaldehyde methyl
hemiacetal (step 2 in Scheme 3) in a class n mechanism (24).
The actual value of Hammett ρ throughout the diagram is a
compromise between the values of ρ indicated at the corners of
the diagram. These corner values represent the experimentally
observed or estimated sensitivity of the various carbonyl forms
to aromatic substitution with reference to the upper left corner
be the result of a change in rate-limiting step for specific
base catalysis. If Scheme 3 is considered, it is plausible that
the pre-equilibrium step (step one) gradually becomes rate-
limiting under such circumstances.
In conclusion, we can state that our experimental data for
general base catalysis show all the essential elements ex-
pected for a concerted class n mechanism. The observation
of a negative value of the direct interaction coefficient p —
y
(
22). The location of an actual saddle point (transition state) is
as a result of upward curvature in the Hammett plots — is
new and represents a further confirmation of this mecha-
nism. It also confirms the general validity of the More
O’Ferrall – Jencks energy contour diagram as a useful tool
in describing a complex chemical system.
shown in the diagram with one vertical level line parallel to the
y-axis (p = 0) and one turned 151° clockwise from vertical.
x
This angle may be calculated according to Jencks and Jencks (4)
when the the parameters p p and p are known. The bold arrow
x, xy,
y
indicates the expected shift in the transition state for a less
stable carbonyl electrophile, i.e., toward lower Brønsted β values
Acknowledgements
(
pxy positive, see text).
This paper is dedicated to Professor A. Jerry Kresge for
his many contributions to understanding the mechanisms of
proton transfer reactions and for his friendship over the
years. The paper is also dedicated to the memory of Profes-
sor James L. Jensen for his interest in our work and support
over the years. This work was supported by a NATO collab-
orative research grant, CRG no. 900990. We also wish to
thank Statens naturvidenskabelige Forskningsraad og
Forskerakademiet for grants (K.M.E.).
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1999 NRC Canada