Kinetic medium effects of cationic cosolutes in aqueous solution: The effects of alkylammonium bromides on the neutral hydrolysis of 1-benzoyl-1,2,4-triazole

Article abstract of DOI:10.1039/a606698d

We have investigated the kinetic effects of alkylammonium, alkyldimethylammonium, alkyltrimethylammonium and tetraalkylammonium bromides on the water-catalysed hydrolysis of 1-benzoyl-1,2,4-triazole at pH 4 and 25 °C. All cosolutes retard the reaction. The retardation is attributed to a dominant stabilisation of the initial state through hydrophobic interactions with the cosolute. The results are analysed in terms of pairwise Gibbs energy interaction parameters. These G(C) values show that alkyl groups shorter than propyl have no significant influence on the medium effect. The extensively hydrated ammonium groups prevent the formation of a well developed hydrophobic hydration shell by methylene moieties in its vicinity. We observe additivity of kinetic effects of methylene groups outside the ionic hydration sphere on the hydrolysis reaction. Pairwise group interaction parameters were obtained for the CH₂-group of the different cosolutes; the contribution of the CH₂-group to the overall cosolute effect is -94 J kg mol^-2 for both alkylammonium bromides and alkyldimethylammonium bromides, and -110 J kg mol^-2 for alkyltrimethylammonium bromides. Ammonium bromide, which is primarily hydrophilic, also retards the reaction. We suggest that competition between ammonium bromide and the transition state for water molecules results in the strict orientational requirements for the water molecules in the activated complex not being met. Hence the hydrolysis is retarded.

Full text of DOI:10.1039/a606698d

View Article Online / Journal Homepage / Table of Contents for this issue
Kinetic medium effects of cationic cosolutes in aqueous solution: the
effects of alkylammonium bromides on the neutral hydrolysis of
1
-benzoyl-1,2,4-triazole
a
a
b
Peter Hol, Lisette Streefland, Michael J. Blandamer and
,
a
Jan B. F. N. Engberts*
a
Department of Organic and Molecular Inorganic Chemistry, University of Groningen,
Nijenborgh 4, 9747 AG Groningen, The Netherlands
Department of Chemistry, University of Leicester, Leicester, UK LE1 7RH
b
We have investigated the kinetic effects of alkylammonium, alkyldimethylammonium,
alkyltrimethylammonium and tetraalkylammonium bromides on the water-catalysed hydrolysis of
1
-benzoyl-1,2,4-triazole at pH 4 and 25 ЊC. All cosolutes retard the reaction. The retardation is attributed
to a dominant stabilisation of the initial state through hydrophobic interactions with the cosolute. The
results are analysed in terms of pairwise G ibbs energy interaction parameters. These G(C) values show
that alkyl groups shorter than propyl have no significant influence on the medium effect. The extensively
hydrated ammonium groups prevent the formation of a well developed hydrophobic hydration shell by
methylene moieties in its vicinity. We observe additivity of kinetic effects of methylene groups outside the
ionic hydration sphere on the hydrolysis reaction. Pairwise group interaction parameters were obtained for
the CH -group of the different cosolutes; the contribution of the CH -group to the overall cosolute effect
2
2
Ϫ2
is Ϫ94 J kg mol for both alkylammonium bromides and alkyldimethylammonium bromides, and Ϫ110
J kg mol for alkyltrimethylammonium bromides. Ammonium bromide, which is primarily hydrophilic,
Ϫ2
also retards the reaction. We suggest that competition between ammonium bromide and the transition
state for water molecules results in the strict orientational requirements for the water molecules in the
activated complex not being met. H ence the hydrolysis is retarded.
Introduction
catalysed hydrolysis of 1-benzoyl-1,2,4-triazole (1) in dilute
aqueous solutions. Using the theory as described above, we can
7
Rate constants for chemical reactions in water often change
dramatically when organic cosolvents or cosolutes are added.
Chemical reactivity in aqueous solutions is influenced by
specific, noncovalent interactions between cosolutes and the
reactants. Noncovalent interactions between apolar alkyl
moieties, the so-called hydrophobic interactions, are respon-
distinguish between the effect of a methylene moiety in the alkyl
chain near the cationic group and that further away from this
polar ionic group. The SWAG approach turned out to be
inapplicable to the methylene moieties inside the hydration
shell of the ammonium headgroup; i.e. the first two methylene
moieties of the alkyl group. This pattern is apparently due to
the incompatibility of the headgroup hydration sphere with
the hydrophobic hydration sphere of the alkyl group. The
SWAG approach is valid for methylene moieties outside this
hydration sphere; i.e. further than two carbon atoms away
from the ionic group. The rate retarding effect of ammonium
bromide on the hydrolysis reaction is substantial, despite the
absence of hydrophobic groups. Previously, we observed that
1
,2
3
sible for, inter alia, the stabilisation of proteins, the assembly of
4
5
lipids in biomembranes, surfactant aggregation and enzyme–
substrate interactions. However, the molecular mechanism of
6
these interactions is still under extensive investigation.
Kinetic medium effects of low concentrations of chemically
inert cosolute molecules on the rates of organic reactions in
dilute aqueous solutions directly reflect pairwise interactions
between these cosolutes and both the initial state and the acti-
vated complex. We have shown how kinetic medium effects
can be described using pairwise Gibbs energy interaction
parameters. By applying the additivity approach of pairwise
group interactions, as proposed by Savage and Wood (SWAG
approach), pairwise group interaction parameters can be
obtained. These pairwise group interaction parameters reveal
the contribution of each functional group in the cosolute to the
overall solvent effect.
11
the anionic sulfate group is also rate retarding. We contend,
15
primarily based on simulation studies, that the two water
molecules involved in the activated complex require a very
specific orientation and, apparently, this is hampered by the
water-demanding ionic groups in these two solutes, including
ammonium bromide.
7
8
Experimental
During the last few years, this analysis has been applied to
different types of cosolutes for pH-independent hydrolysis reac-
tions in dilute aqueous media. These cosolutes vary from
Materials
1-Benzoyl-1,2,4-triazole was synthesised according to literature
7
9
16
monohydric and polyhydric alcohols, (acyclic) carboxamides,
procedures. The alkyl amines, tetraalkylammonium brom-
9
9
9
10
ureas, sulfonamides, sulfones, alkylpyrrolidinones, sodium
ides and methyl bromide were purchased from Janssen Chimi-
ca, Fluka and Sigma. The alkylamines were distilled before use.
The alkylammonium bromides and the dimethylalkyl-
ammonium bromides were prepared in situ by acidifying the
corresponding alkylamines and dimethylalkylamines, respect-
ively, with aqueous hydrogen bromide to pH 4. The alkyldi-
methylamines were synthesised by Esch–Weiler–Clark methyl-
1
1
alkylsulfates to more complex molecules such as carbo-
1
2
13,14
hydrates and α-amino acids.
In the present study, we describe medium effects of tetra-
alkylammonium bromides (R = H to butyl), alkylammonium
bromides, alkyldimethylammonium bromides and alkyl-
trimethylammonium bromides (R = propyl to hexyl). This is the
first study of the effect of this class of cosolutes on the water-
1
7
ation of the corresponding alkylamine.
J. Chem. Soc., Perkin Trans. 2, 1997
485

View Article Online
The alkyltrimethylammonium bromides were synthesised by
methylation of the corresponding alkyldimethylamines with
methyl bromide Ϫ20 ЊC in acetone. The acetone was carefully
removed via a steel tube under moderate nitrogen pressure. The
salts were dried in a drying pistol until no further loss in mass
was observed. The purity of the tetraalkyl- and the alkyl-
Table 1 Pairwise Gibbs energy interaction parameters for tetra-
alkylammonium bromides
Ϫ2
R
H
G(C)/J kg mol
Ϫ307 (±7)
Ϫ324 (±4)
Ϫ389 (±15)
Ϫ655 (±7)
Ϫ1190 (±13)
Methyl
1
trimethylammonium bromides was checked by H NMR and
Ethyl
Propyl
Butyl
1
3
C NMR spectroscopy.
Kinetic measurements
Solutions for the kinetic measurements were prepared by mass
immediately before use using demineralised water, adjusted to
pH 4 with hydrogen chloride. About 5–8 µl of a stock solution
containing 1 in acetonitrile were injected into 2.5 ml of reaction
medium and placed in a thermostatted cell compartment
(25.0 ± 0.05 ЊC) of a Perkin-Elmer λ5 or λ2 spectrophotometer.
The reaction was followed for at least four half-lives and excel-
lent first-order kinetics were obtained by following the change
in absorbance at 250 nm. Rate constants were calculated using a
fitting program and were reproducible to within 1.5%. Reaction
rate constants at each molality were measured in triplicate. A
blank reaction in aqueous solution containing no added salt
was frequently measured. Kinetic data for each set of solutions
were determined at at least four different molalities.†
Results and discussion
Fig. 1 Medium effects on the pseudo-first-order rate constant for
hydrolysis of 1 at 25 ЊC, plotted as ln[k(mc)/k(mc = 0)] versus the molality
of ammonium bromide, *; tetramethylammonium bromide, ᮀ; tetra-
ethylammonium bromide, ᭿; tetrapropylammonium bromide, ᭝ and
tetrabutylammonium bromide, x
Previously, we developed a theory in which rate constants can
be quantitatively linked to pairwise Gibbs energy interaction
1
8,19
parameters,
G(C) values, which reflect the difference in
pairwise interaction Gibbs energy between the cosolute and the
initial state, and the cosolute and the transition state of the
reaction, respectively, see eqn. (1).
The difference in hydrophobicity between the initial state and
the transition state is responsible for the marked changes in rate
constants which are observed when hydrophobic cosolutes are
added. Hydrophobic cosolutes stabilise the initial state to a
larger extent than the transition state which increases the Gibbs
energy of activation leading to a decrease in rate constant.
In the present study we investigated the effect of tetra-
alkylammonium, alkylammonium, alkyldimethylammonium
and alkyltrimethylammonium bromides on the hydrolysis of 1,
up to a concentration of 1 molal of added cosolute, except for
hexylammonium and hexyldimethylammonium bromide. The
effects of the latter two cosolutes were measured up to a limit of
k
(
m
c
)
2
ln ͩ ͪ
=
G(C) Ϫ NM φmc
w
(1)
k
RT
c
(m = 0)
Herein, k(mc = 0) and k(mc) are, respectively, the rate constants
in aqueous solution and in aqueous solution containing mc
molal of cosolute; N is the number of water molecules involved
in the transition state of the hydrolysis reaction; φ is the prac-
tical osmotic coefficient, which equals 1 in highly dilute solu-
tion and Mw is the molar mass of water. The term NφM m
w
c
0
0
.5 molal, because they showed evidence of aggregation above
.5 molal. All cosolutes retard the hydrolysis of 1, as expressed
accounts for the effect of the cosolute on the reactivity of water.
The general-base catalysed hydrolysis of 1-benzoyl-1,2,4-
triazole (1) is water-catalysed in the pH range of 3–5 and pro-
ceeds via a dipolar activated complex containing two water
in negative G(C). These retardations are dominated by stabilis-
ation of the initial state of the hydrolysis by the cosolutes
through hydrophobic interactions. These alkylammonium sol-
1
6,20
molecules [eqn. (1), N = 2] with three protons in flight
Scheme 1).
2
1,22
utes can be viewed
as hydrophobic species. There is con-
(
vincing evidence that even tetramethylammonium chloride is
hydrophobic, according to a neutron diffraction study reported
2
3
by Finney et al.
Medium effects on the neutral hydrolysis of 1, expressed as
the dependence of ln[k(mc)/k(mc = 0)] on the molality of added
tetraalkylammonium bromides are shown in Fig. 1. The tetra-
alkylammonium bromides produced excellent linear corre-
lations between ln[k(mc)/k(mc = 0)] and the molality of added salt,
indicating pairwise (i.e. 1:1) interactions between cosolute and
substrate. G(C) values were obtained from the slopes of these
plots; Table 1.
In terms of the SWAG approach, each functional group in
one molecule interacts with every functional group in the other
molecule. Each of these interactions has a characteristic effect
on the pairwise Gibbs energy interaction parameter, G(C). In
the case of alkyl-substituted ammonium bromides, G(C) is
composed of contributions due to n methylene moieties in the
alkyl chain, the ammonium ion and the bromide ion. In the case
of perfect additivity, the increment in G(C) of the cosolutes
Scheme 1 Reaction mechanism for the water-catalysed hydrolysis of
1
-benzoyl-1,2,4-triazole
†
Supplementary data are available (Suppl. No. 57211) from the British
depends solely on the difference in the number of CH groups.
Library. For details of the Supplementary Publications Scheme, see
Instructions for Authors’, J. Chem. Soc., Perkin Trans. 2, 1997, Issue 1.
2
‘
In Fig. 2, G(C) is plotted versus the number of CH groups (the
2
4
86
J. Chem. Soc., Perkin Trans. 2, 1997

View Article Online
Table 2 Pairwise Gibbs energy interaction parameters for alkyl-
ammonium bromides
Ϫ2
R
G(C)/J kg mol
Propyl
Butyl
Pentyl
Hexyl
Ϫ471 (±26)
Ϫ486 (±4)
Ϫ631 (±6)
Ϫ735 (±7)
Table 3 Pairwise Gibbs energy interaction parameters for alkyl-
dimethylammonium bromides
Ϫ2
R
G(C)/J kg mol
Propyl
Butyl
Pentyl
Hexyl
Ϫ415 (±8)
Ϫ527 (±16)
Ϫ625 (±10)
Ϫ696 (±8)
Fig. 2 Medium effects of tetra-alkylammonium bromides on the
hydrolysis of 1 at 25 ЊC. Plot of G(C) versus number of CH moieties.
2
Table 4 Pairwise Gibbs energy interaction parameters for alkyl-
trimethylammonium bromides
Ϫ2
R
G(C)/J kg mol
Methyl
Propyl
Butyl
Pentyl
Hexyl
Ϫ324 (±4)
Ϫ436 (±6)
Ϫ512 (±14)
Ϫ575 (±13)
Ϫ782 (±6)
2
6,27
ceeds via the same mechanism
as the water-catalysed
1
5
hydrolysis of 1. Berendsen et al. observed that only a few of
the many possible water orientations which lead to reaction can
account for the experimental rate constant. We suggest that the
strict orientational requirements for the water molecules in the
activated complex are further reduced when ammonium brom-
ide is added as a cosolute. Ammonium bromide is extensively
hydrated mainly through hydrogen bonding to the four polar-
ised N᎐H groups, and competes with the transition state for
water molecules. The even larger negative G(C) for sodium
alkylsulfates might also be rationalised on the basis of elec-
trostriction. In anionic sulfates the charge is less shielded and
will have a larger influence on the 3D hydrogen-bond network
of water than the cationic ammonium bromides.
Fig. 3 Medium effects of alkyldimethylammonium bromides on the
hydrolysis of 1 at 25 ЊC. Plot of G(C) versus number of CH moieties.
2
contribution of a CH3 group equals the contribution of 1.5
CH groups and the contribution of three CH groups).
2
Almost no effect on the G(C) value is observed when the alkyl
chains were extended from zero to two carbon atoms per chain;
i.e. from ammonium bromide to tetraethylammonium bromide.
Hence these groups are not available for hydrophobic inter-
action with the initial state of the hydrolysis reaction. We con-
tend that this is due to the hydrophilic hydration sphere of the
ammonium headgroup, which apparently extends to carbon
atom three in the alkyl chain. The influence of ionic hydration
shells on the hydrophobicity of nearby methylene groups has
1
1
In Tables 2, 3 and 4, G(C) values are listed for alkyl-
ammonium bromides, alkyldimethylammonium bromides and
alkyltrimethylammonium bromides, respectively. As an ex-
ample, G(C) values for alkyldimethylammonium bromide are
1
1
also been found in kinetic studies with sodium alkylsulfates,
plotted versus the number of CH moieties in Fig. 3.
2
1
0
24
alkylpyrrolidinones and α-amino acids as cosolutes. Gianni
Good additivity is obtained for alkylammonium and alkyl-
2
5
et al. reviewed partial molal volumes of organic electrolytes at
infinite dilution through a simple additivity scheme from which
they concluded that the region of influence of a polar group
does not extend beyond the β carbon atom. Our results show
that outside the hydrophilic hydration sphere additivity is
dimethylammonium bromides, resulting in the same G(CH )
2
Ϫ2
value of Ϫ94 J kg mol . Satisfactory additivity is found for
alkyltrimethylammonium bromides, resulting in a G(CH )
2
Ϫ2
value of Ϫ110 J kg mol . These values are in good agreement
with G(C) values of monohydric alcohols, G(CH ) = Ϫ90 J kg
7
2
Ϫ2
observed for alkyl groups of alkylammonium bromides,
mol .
Ϫ2
G(CH ) = Ϫ94 J kg mol .
As argued above, only methylene moieties outside the hydra-
tion sphere of the ionic group (i.e. further than two carbon
atoms away from the ionic group) are available for hydrophobic
interactions with the substrate. Therefore, when the alkyl-
dimethylammonium bromide series is considered, the G(C)
2
Remarkably, ammonium bromide has a rate retarding effect
Ϫ2
on the neutral hydrolysis of 1, G(C) = Ϫ307 ± 7 J kg mol ,
despite the absence of hydrophobic groups. One would antici-
pate an increase in rate due to a stabilisation of the transition
state by this primarily ionic solute. However, we observed pre-
viously that ionic groups can have a retarding effect on the
+
Ϫ
value for the CH CH N (H)Me Br group should be similar to
2
2
2
the G(C) value for ammonium bromide. We obtain this value by
1
1
Ϫ
hydrolysis of 1. In the case of sodium alkylsulfates, G(OSO3
)
extrapolation of the linear correlation in Fig. 3 to n(CH ) = 5
2
Ϫ2
15
is approximately Ϫ600 J kg mol . Recently, Berendsen et al.
(Fig. 4).
+
calculated the proton transfer rate constant of the rate deter-
mining step in the water-catalysed hydrolysis of a carboxylic
ester, p-methoxyphenyl dichloroacetate, by means of molecular
dynamics (MD) simulations and density matrix evolution
By extrapolation G(CH CH N (H)Me ) equals Ϫ282 J kg
2
2
2
Ϫ2
mol . Extrapolation of the alkylammonium and alkyltri-
+
methylammonium bromides gives a G(CH CH N H ) value of
2
2
3
Ϫ2
+
Ϫ300 J kg mol and a G(CH CH N Me ) value of Ϫ245 J kg
2
2
3
Ϫ2
(DME). The water-catalysed hydrolysis of this substrate pro-
mol , respectively. These are in satisfactory agreement with the
J. Chem. Soc., Perkin Trans. 2, 1997
487

View Article Online
molecules and their noncovalent interactions with solutes in
aqueous solution.
References
1
2
M. J. Blandamer, J. Burgess and J. B. F. N. Engberts, Chem. Soc.
Rev., 1986, 14, 237.
J. B. F. N. Engberts, Water. A Comprehensive Treatise, ed. F. Franks,
Plenum, New York, 1979, vol. 6, ch. 4.
3
4
H. A. Scherega, Acc. Chem. Res., 1979, 12, 7.
J. H. Fendler, Membrane Mimetic Chemistry, Wiley, New York,
1
982.
5
6
H. Wennerström and B. Lindman, Phys. Rep., 1979, 52, 1.
W. Blokzijl and J. B. F. N. Engberts, Angew. Chem., Int. Ed. Engl.,
1
993, 32, 1545.
7
W. Blokzijl, J. B. F. N. Engberts and M. J. Blandamer, J. Am. Chem.
Soc., 1990, 112, 1197.
8
9
J. J. Savage and R. H. Wood, J. Solution Chem., 1976, 10, 733.
R. P. V. Kerstholt, M. J. Blandamer and J. B. F. N. Engberts,
J. Chem. Soc., Perkin Trans. 2, 1993, 49.
Fig. 4 Medium effects of alkyldimethylammonium bromides on the
hydrolysis of 1 at 25 ЊC. Plot of G(C) versus number of CH moieties.
2
Extrapolation according to the SWAG approach (five CH2 moieties =
10 J. Apperloo, M. J. Blandamer and J. B. F. N. Engberts, unpublished
results.
CH CH N(H)Me ).
2
2
2
1
1
1
1
1 W. H. Noordman, W. Blokzijl, M. J. Blandamer and J. B. F. N.
Engberts, J. Org. Chem., 1993, 58, 7111.
2 S. A. Galema, M. J. Blandamer and J. B. F. N. Engberts, J. Am.
Chem. Soc., 1990, 112, 9665.
3 L. Streefland, M. J. Blandamer and J. B. F. N. Engberts, J. Chem.
Soc., Perkin Trans. 2, in the press.
4 L. Streefland, M. J. Blandamer and J. B. F. N. Engberts, J. Phys.
Chem., 1995, 99, 5769.
experimental G(C) value for ammonium bromide of Ϫ307 ± 7 J
kg mol , which indicates again that hydrophobic groups in
close proximity to a polar group are masked for hydrophobic
Ϫ2
interactions with the substrate. The deviation of the G(C) value
Ϫ2
of Ϫ245 J kg mol for alkyltrimethylammonium bromides is
due to less pronounced additivity.
15 M. F. Lensink, J. Mavri and H. J. C. Berendsen, unpublished results.
16 W. Karzijn and J. B. F. N. Engberts, Tetrahedron Lett., 1978, 1787.
7 S. H. Pine and B. L. Sanchez, J. Org. Chem., 1971, 36, 829.
1
Conclusions
18 W. Blokzijl, J. Jager, J. B. F. N. Engberts and M. J. Blandamer,
J. Am. Chem. Soc., 1986, 108, 6411.
In the present study, the effects of tetraalkylammonium, alkyl-
ammonium, alkyldimethylammonium and alkyltrimethyl-
ammonium bromides on rate of the neutral hydrolysis of
1
9 W. Blokzijl, J. B. F. N. Engberts and M. J. Blandamer, J. Phys.
Chem., 1987, 91, 6022.
20 H. J. Mooij, J. B. F. N. Engberts and M. Charton, Recl. Trav. Chim.
Pays Bas, 1988, 107, 185.
1
-benzoyl-1,2,4-triazole have been measured. All cosolutes
2
1 J. Y. Huot and C. Jolicoeur, The Chemical Physics of Solvation, Part
A, ed. R. R. Dogonadze, Elsevier, New York, 1985.
2 G. Jakli and L. Marko, Models Chem., 1995, 132, 225.
3 J. L. Finney, A. K. Soper and J. Z. Turner, Pure Appl. Chem., 1993,
65, 2521.
retard the hydrolysis reaction which is interpreted as a domin-
ant stabilisation of the hydrophobic initial state through hydro-
phobic interactions with the cosolute. The kinetic results are
expressed in pairwise Gibbs energy interaction parameters
2
2
[
G(C)]. Analysis of these G(C) values suggests that the ionic
24 L. Streefland, M. J. Blandamer and J. B. F. N. Engberts, J. Am.
Chem. Soc., 1996, 118, 9539.
hydration shell of the ammonium group is incompatible with
the hydration shell of the alkyl groups attached to it. The ionic
hydration shell dominates the medium effect up to two carbon
atoms; i.e. the effect of the alkyl groups is only observed for
alkyl groups with more than two carbon atoms. For those
methylene groups outside the ionic hydration sphere, additivity
is observed.
2
2
5 P. Gianni and L. Lepori, J. Solution Chem.,1996, 25, 1.
6 J. F. J. Engbersen and J. B. F. N. Engberts, J. Am. Chem. Soc., 1974,
9
6, 1231.
2
7 J. F. J. Engbersen and J. B. F. N. Engberts, J. Am. Chem. Soc., 1975,
97, 1563.
Paper 6/06693D
Received 30th September 1996
Accepted 19th November 1996
The results presented here provide an important contribution
to the rank of understanding the hydration of polyfunctional
4
88
J. Chem. Soc., Perkin Trans. 2, 1997