Hydrogen bond contribution to preferential solvation in SNAr reactions

Article abstract of DOI:10.1021/jp4005295

Preferential solvation in aromatic nucleophilic substitution reactions is discussed using a kinetic study complemented with quantum chemical calculations. The model system is the reaction of a series of secondary alicyclic amines toward phenyl 2,4,6-trinitrophenyl ether in aqueous ethanol mixtures of different compositions. From solvent effect studies, it is found that only piperidine is sensitive to solvation effects, a result that may be traced to the polarity of the solvent composition in the ethanol/water mixture, which points to a specific electrophilic solvation in the aqueous phase.

Full text of DOI:10.1021/jp4005295

Article
pubs.acs.org/JPCB
Hydrogen Bond Contribution to Preferential Solvation in SNAr
Reactions
Rodrigo Ormazabal-Toledo,*,† Jose G. Santos,‡ Paulina Ríos,‡ Enrique A. Castro,‡
́
Paola R. Campodonico,§ and Renato Contreras*,†
́
†Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile
‡Facultad de Química, Pontificia Universidad Catol
́
ica de Chile, Casilla 306, Santiago 6094411, Chile
§Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7710162, Chile
S
* Supporting Information
ABSTRACT: Preferential solvation in aromatic nucleophilic
substitution reactions is discussed using a kinetic study
complemented with quantum chemical calculations. The
model system is the reaction of a series of secondary alicyclic
amines toward phenyl 2,4,6-trinitrophenyl ether in aqueous
ethanol mixtures of different compositions. From solvent effect
studies, it is found that only piperidine is sensitive to solvation
effects, a result that may be traced to the polarity of the solvent
composition in the ethanol/water mixture, which points to a
specific electrophilic solvation in the aqueous phase.
nol mixtures.15 Preferential solvation of 1-halo-2,4-dinitroben-
INTRODUCTION
■
According to Ben-Naim1 and other authors,2−5 preferential
zenes in aromatic nuclephilic substitution reactions with several
amines has also been reported by Mancini et al. in mixtures of
solvation may be defined as the difference between the local
and bulk composition of the solute with respect to the various
components of the solvent, in this case, a binary water/ethanol
dichloromethane with different polar protic and polar aprotic
cosolvents.16−22
In this work, we report an integrated experimental and
theoretical study of the title reactions, to discuss preferential
solvation effects from an electronic point of view. The
theoretical model is developed in terms of electron density-
dependent descriptors of reactivity. The model system is the
reaction of phenyl 2,4,6-trinitrophenyl ether (1) with a series of
secondary alicyclic (SA) amines (2−6), depicted in Scheme 1.
The SNAr reaction occurs in activated substrates, generally
possessing aromatic rings strongly activated by electron-
withdrawing substituents.23−25 In some of the studied reactions
involving highly activated substrates, two types of kinetic data
have been recorded:26 one showing the rapid increase in the
magnitude of of a band near 500 nm associated with a σ-
complex formed by the addition of the nucleophile to one of
the unsubstituted positions of the aromatic ring and the other
showing the decrease in the magnitude of a band corresponding
to the disappearance of the substrate and an increase in the
magnitude of another band corresponding to the final
product.26 It is noteworthy that in most SNAr processes the
mixture. The bulk solvation effects may in general be assessed
using continuum dielectric models framed on the classical
Kirkwood−Onsager theories1,6,7 or using a quantum mechan-
ical model of solvation based on the reaction field theory.8,9 If
we assume that the bulk solvation properties of a mixture of
polar protic solvents may be described by an average of the
effective dielectric constants, preferential solvation may be cast
into the form of specific solute−solvent interactions describing
local solvation, which we may define as a “first solvation shell”.
Local solvation may be further classified as “electrophilic” or
“nucleophilic”.10−13 For a solvent mixture of the general form
ROH (R = H or Et), electrophilic solvation represents the
specific interaction through a H-bond with the hydrogen atom
of the solvent, whereas nucleophilic solvation describes a
specific interaction through a H-bond between an acidic
hydrogen atom of the solute and the heteroatom (oxygen in
this case) of the solvent.
Preferential solvation may result in dramatic changes in
reaction mechanisms. Several examples of this have been
reported for the solvolysis of fluorinated alcohols in
trifluoroethanol/water and trifluoroethanol/ethanol mixtures,11
SN2 reactions of sodium 4-nitrophenoxide and iodomethane in
an acetone/water mixture,14 and solvolysis of acetyl chloride in
methanol/acetone, methanol/acetonitrile, and methanol/etha-
Received: January 16, 2013
Revised: April 17, 2013
Published: April 18, 2013
© 2013 American Chemical Society
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Scheme 1. General Mechanism for a SNAr Reaction of Secondary Alicyclic Amines as Nucleophiles toward Phenyl 2,4,6-
Trinitrophenyl Ether as an Electrophile
former reaction is not observed. The overall pathway for these
reactions with amines as nucleophiles is shown in Scheme 1.27
According to Scheme 1, the first step is the formation of a σ-
complex that occurs after amine attack to the substituted
aromatic ring. In a second step, the σ-complex leads to products
by a catalyzed (k3) or noncatalyzed (k2) route. The process
involves the loss of aromaticity in step 1 and rearomatization in
step 2. For this type of reaction, it is possible that an
equilibrium may be reached between the zwitterionic σ-
complex (T ) and its deprotonated form, the anionic σ-
complex (T−),28 followed by its general acid catalysis
conversion to products, as shown in Scheme 2.
Scheme 3. RLPT Mechanism for the Reaction of 1 with
Secondary Alicyclic Amines in Aqueous Ethanol Mixtures
Scheme 2. Possible Pathways for a SNAr Reaction Involving
a Secondary Amine
Via application of the steady state condition to the
intermediates, eq 1 can be derived, where [N]F is the free
amine concentration.
2
k1k2[N]F + k1k3[N]F
kobs
=
k−1 + k2 + k3[N]F
(1)
Assuming that k2 + k3[N]F ≪ k−1, eq 1 can be simplified to
eq 2, where K1 = k1/k−1.
2
kobs = K1k2[N]F + K1k3[N]F
(2)
Plots of kobs versus [N]F were curved upward for all the
amines studied, in accordance with eq 2. These kinetic data
were fit to eq 2, and the resulting curves are shown in Figures
S1−S4 of the Supporting Information. The good fits reinforce
the fact that the second step in Scheme 3 is dual: catalyzed and
noncatalyzed pathways. For the reactions with all SA amines,
except piperidine, the plots described above were found to be
independent of the composition of the solvent mixture, within
the range studied [25, 50 and 75% (v/v) ethanol]. Namely, a
single parabolic curve is shown for the reactions in the different
mixtures. In contrast, the plots of kobs versus [N]F for the
reaction with piperidine are shown in Figure 1. It can be
observed that in the presence of increasing water content, the
rate coefficients increase, thereby suggesting an increasing
degree of stabilization of the T complex by a preferential
solvation in the aqueous phase.
When the k4 step is rate-determining, this reaction pathway is
called the specific base−general acid mechanism (SB−GA
mechanism).29,30 On the other hand, when the transfer of the
proton from the zwitterionic intermediate is rate-limiting,
followed by the rapid loss of the leaving group, the mechanism
is named rate-limiting proton transfer (RLPT).23,28,31
RESULTS AND DISCUSSION
■
Under the experimental conditions used, the formation of a
single product was spectrophotometrically observed. Therefore,
the possibility of nucleophilic attack at the unsubstituted ring
positions may be safely discarded. For the reactions of 1 with
the SA amine series in aqueous ethanol mixtures, the plots of
kobs against free amine concentration ([N]F) are in accordance
with a second-order polynomial equation (see Figures S1−S4
of the Supporting Information). The results are in agreement
with Scheme 3, which is similar to Scheme 2, but assuming k4
≫ k−3. In Scheme 3, the loss of a proton from the zwitterionic
intermediate is the rate-limiting step (i.e., RLPT mechanism)
and not the expulsion of the phenoxide from the anionic
intermediate.
By non-least-squares fitting of eq 2 to the experimental
points, the values of K1k2 and K1k3 were found for all the SA
amines. These are listed in Table 1. Figure 2 shows the
Brønsted-type plots for the K1k2 and K1k3 values obtained for
the reactions of the SA amine series with ether 1. These plots
are linear with slopes βKk = 1.05 for K1k3 and βKk = 0.80 for
3
2
K1k2, which is in agreement with the stepwise mechanism
shown in Scheme 3, where the proton transfer is the rate-
determining step.
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Figure 1. Plot of kobs vs free piperidine concentration ([piperidine]F)
for the piperidinolysis of 1, in 25, 50, and 75% (v/v) ethanol aqueous
mixtures, at 25 °C and an ionic strength of 0.2 M (KCl).
Figure 2. Brønsted-type plots for the reaction of 1 with SA amines.
Filled circles depict data for the catalyzed pathway and empty circles
data for the uncatalyzed pathway.
To prove the hypothesis of a preferential solvation by water
in the reaction with piperidine, we first evaluated the
electrophilic and nucleophilic sites in ethanol and water. The
local electrophilicity32 and nucleophilicity33 of the solvents are
approached as
Figure 3 illustrates the molecular electrostatic potential
(MEP) plot for the transition state (TS) structure correspond-
ing to the nucleophilic attack of morpholine and piperidine on
ether 1. Figure 3 shows that both structures differ only in the
substituent at position 4 (with respect to the nucleophilic
center). The arrow highlights the position of the substituent at
the amine moiety. The orientation of the amine relative to the
substrate is almost conserved along the whole reaction path
(IRC profile). This substitution pattern is responsible for the
different distribution of the electron density.
Figure 3 also shows that for morpholine, a negative zone in
the MEP (green colored) appears over the oxygen atom.
However, for piperidine, the negative zone is dramatically
diminished. The remaining structure is almost the same for
both amines. This result is relevant because this behavior is
probably responsible for the different interactions between the
transition state and the solvent mixture. It is noteworthy that
the kinetic experiments give information about only the rate-
determining step (k3 step in Scheme 3). Figure 3 adds
information related to the first step of the reaction, which is
structurally maintained along the whole reaction profile, as
discussed later.
μ2
2η
ωG+
=
f +ω+; ω+ =
∑
k
(3)
(4)
k∈ G
ω− =
f −ω−; ω− = εHOMO
∑
G
k
k∈ G
These are expressed in terms of the electronic chemical
potential (μ) and the chemical hardness (η).34 The regional (or
group) quantities are projected by using the appropriate
electrophilic and nucleophilic Fukui functions f+k and fk−,
respectively, using a method described elsewhere.35,36 The
electronic chemical potential and the chemical hardness were
obtained using the frontier molecular orbital HOMO and
LUMO.34
Using eqs 3 and 4, we found that the local electrophilicities at
the hydrogen acidic atom of water and ethanol are 0.35 and
0.21 eV, respectively. Local nucleophilicity at the heteroatom
site of the solvent on the other hand yields values of 13.30 and
6.51 eV for water and ethanol, respectively. These results show
that both electrophilic solvation and nucleophilic solvation play
a significant role in favor of preferential aqueous phase
solvation. To qualitatively explore the sites that are more likely
to be electrophilically and nucleophilically bound by water
molecules, we performed a molecular electrostatic potential
(MEP) calculation for the transition state structures involved in
the reactions being studied (see the computational details
section in the Supporting Information).
It is worth emphasizing that the series of amines 3−6 display
patterns of MEP similar to that of morpholine (see Figures S5−
S7 of the Supporting Information for the remaining amines).
Note that while for morpholine and amines 3−6 there is a net
site at position 4 of the nucleophile ring amenable to
electrophilic solvation, in structure b of Figure 3 corresponding
to piperidine, the system may accept an electrophilic or
nucleophilic H-bond, or both, from the solvent. If we consider
Table 1. Values of K1k2 and K1k3 for the Reaction of SA Amines with 1 in Different Aqueous Ethanol Mixtures at 25°C and an
Ionic Strength of 0.2 M (KCl)
a
b
c
nucleophile
pKa
pKa
pKa
K1k2 (M−1 s−1
)
K1k3 (M−1 s−2
)
2
2
2
3
4
5
6
11.02
−
−
9.86
9.16
8.56
7.71
−
10.82
−
−
10.27
9.61
8.88
8.23
7.47
2.59 0.45
1.75 0.19
0.10 0.06
0.06 0.01
0.03 0.002
416.71 25.84
240.53 10.93
128.01 2.73
28.33 0.63
3.36 0.09
−
9.71
9.09
8.48
7.63
0.038 0.004
0.003 0.001
0.637 0.06
0.154 0.02
a
b
c
In a 25% (v/v) ethanol aqueous mixture. In a 50% (v/v) ethanol aqueous mixture. In a 75% (v/v) ethanol aqueous mixture.
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Figure 3. MEP surface corresponding to the TS structure for the formation of the T intermediate for the reaction of 1 toward morpholine (a) and
piperidine (b). Arrows point to position 4 of the nucleophile. Nucleophilic sites are colored red and electrophilic ones blue. Green zones are regions
of vanishing MEP values.
Figure 4. MEP surface corresponding to the TS structure for the formation of the T intermediate for the reaction of 1 toward morpholine (a) and
piperidine (b). Arrow points to position 4 in the nucleophile. In piperidine, the water molecule is stabilized by the o-NO2 behind the plane.
Nucleophilic sites are colored red and electrophilic ones blue. Green zones are regions of vanishing MEP values.
that ethanol and water show comparable values of local
electrophilicity at the hydrogen atom, site 4 may be equally
disposed to accept binding to either water or ethanol, and in
this sense, there is no selectivity toward electrophilic solvent
binding. However, in piperidine, there is no preferential affinity
for an electrophilic or nucleophilic attachment of solvent
molecules. This means that in piperidine the solvent may bond
the transition state via a hydrogen bond in the electrophilic or
nucleophilic solvation mode. Because the regional nucleophil-
icity of water is approximately twice that of ethanol, it may be
concluded that preferential solvation at the TS stage of the
reaction is driven by the nucleophilic solvation by water.
The effect of solvent on the kinetics for the reactions with
piperidine, summarized in Figure 1, may be attributed to a
different molecular interaction between piperidine and solvent
molecules.37 These results show that the environment of the
Meisenheimer complex (MC) changes for different solvent
compositions. Nevertheless, for the remaining amines, the
environment of the MC is similar because of the polar nature of
the substituents at position 4, thereby suggesting that their
kinetic responses are rather independent of the bulk properties
of the solvent.
nucleophilic deactivation at that site. This effect not only arises
from steric hindrance but also may be induced by electron
density reorganization in the whole structure (electrophilic
solvation effect). This effect may be seen by comparing Figure
3a with the corresponding structure shown in Figure 4a. It is
also interesting to note that for piperidine, in the presence of a
water molecule bound to the O atom in the ortho-nitro moiety,
the electrophilic solvation induces a marginal electronic effect
on the whole structure at the transition state. We must
emphasize that the position of the water molecule in this case
also represents a true stationary point on the potential energy
surface. Note that comparison of panels a and b of Figure 4 also
stresses a nucleophilic activation in the former.
The results obtained by a full exploration of the potential
energy surface are consistently in agreement with the kinetic
study. From Table 1, it may be seen that for piperidine, the rate
coefficient increases when the polarity of the reaction media is
increased. This result highlights the relevance of a protic
reaction medium on the reaction mechanism, specifically, on
the step involving proton transfer processes. In this reaction
pathway, the water molecules compete with the nucleophile
(the catalyzed pathway) for proton abstraction. It seems that a
less favorable proton transfer toward water molecules,
compared to proton transfer toward the second catalyzing
nucleophile, drives the reaction mechanism for the whole series
of amines considered in this study.
Figure 4 shows the MEP at the transition state for
morpholine and piperidine and their possible H-bond
complexes formed with the corresponding amine and a water
molecule. These are the interactions expected for the rate-
determining step in Scheme 3. Note that for morpholine, the
presence of a water molecule bound to position 4 of the
nucleophile moiety at the transition state results in a
Note that for amines 3−6, the kinetic study suggests that
solvation effects of reaction media of varying polarity have a
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marginal effect on the reaction rates (see the Supporting
Information for a detailed description of the kinetic study).
Additionally, the change in the rate constants may be
induced by a hyperconjugative effect around the TS stage. The
interaction between the substituent in position 4 in the
nucleophile and the hydrogen atom that is transferred to the
phenoxide group in the rate-limiting step is favored.
Consequently, when piperidine is the nucleophile, the
interaction is less favorable, destabilizing the T intermediate
and powering the proton transfer. With the other amines, the
situation is similar: when the hyperconjugative effect is
dominant, the T intermediate is more stable and the proton
loss is a slower process as for the 1-formylpiperazine
nucleophile.
where qi is the donor orbital occupancy, εi and εj are diagonal
elements, and F(i,j) is the off-diagonal elements of the Fock
matrix. The main interactions presented are those depicted in
Scheme 4.
Scheme 4. Possible Interactions between the Electrophile
a
and Nucleophile Centers
Table 2 displays the main specific interactions evaluated at
the TS stage of the reaction under study. These interactions
Table 2. Second-Order Perturbation Theory Analysis for the
Reaction between 1 and the Full Set of SAA
a
a
Irrelevant atoms were omitted. (a) Hydrogen bond between the
oxygen’s lone pairs in the o-NO2 group and the N−H antibonding
orbital of the nucleophilic center and (b) interaction between the
substituent at position 4 in the nucleophile and antibonding orbitals of
the amine (see the text for details).
nucleophile
donor
acceptor
E(2)
2
3
4
5
6
LP(O1)
LP(O1)
LP(O1)
LP(O1)
LP(O1)
BD*(N2−H3)
BD*(N2−H3)
BD*(N2−H3)
BD*(N2−H3)
BD*(N2−H3)
8.5
9.4
8.9
11.0
12.6
From the information listed in Table 2, it is possible to note
that the main interaction is that established between the acidic
hydrogen atom in the nucleophilic center and the o-NO2 group
in the substrate.41−43 On the other hand, the homoanomeric
effect44−48 that may be present in the nucleophile is weaker
than the interaction between the nucleophile and the
electrophile. Nevertheless, the energy values observed are
within the range previously reported.48 In this sense, the
nucleophile−electrophile interactions together with the prefer-
ential solvation effects are the dominant stabilizing effects
induced in this type of reaction, and these effects outweigh the
homoanomeric effect present in the nucleophilic ring.
a
The interactions presented are those depicted in Scheme 4a. Energies
are in kilocalories per mole.
have been calculated by performing a second-order perturba-
tion theory calculation using the NBO analysis.38−40 Second-
order perturbation theory analysis is a tool that provides
detailed microscopic information from a localized antibonding
orbital (NBO) analysis of an idealized Lewis structure with an
empty non-Lewis orbital (see Tables 2 and 3). For each donor
and acceptor orbitals i and j say, the energy of stabilization is
denoted by E(2) and is evaluated as
Table 3 displays the interactions between the lone pair in the
heteroatom and different possible accepting orbitals in the
nucleophile. These interactions have been reported to be
relevant for the description of reactivity trends.49 For instance,
when we take into account the interaction between the lone
pair in the nitrogen atom [LP(X1)] and the antibonding orbital
C2−C3, it is possible to note the following features: this
interaction diminishes the energy value downward with the pKa,
thereby suggesting that it is relevant for assisting the
nucleophilic attack. Similar results are obtained for the
interaction between the lone pair in the nitrogen atom
[LP(X1)] and the antibonding orbital associated with the
C5−C6 bond. On the other hand, for the interaction between
the LP(X1) orbital and the Ci−Hj antibonding orbitals, an
opposite trend is obtained: a more efficient interaction of this
kind diminishes the reactivity of the system. Consider, for
instance, the interactions involving the BD*(C2−H2a). In this
case, the E(2) value increases and the nucleophilicity of the
amine decreases. In the case of morpholine, the situation is the
same, but this time, the interaction is established between the
two lone pairs in the oxygen atom. Note that one orbital is
axially oriented while the other is equatorial (see Table 3). The
interactions are different for both orbitals, but in the global
analysis, they can be taken as additive contributions.49
F(i, j)2
εj − εi
E(2) = ΔEij = q
i
(5)
Table 3. Second-Order Perturbation Theory Analysis for the
Reaction between 1 and the Full Set of SAA
a
b
interaction
aceptor
nucleophile
c
d
donor
3
4
5
5
6
LP(X1)
LP(X1)
LP(X1)
LP(X1)
LP(X1)
LP(X1)
LP(X1)
LP(X1)
LP(X1)
LP(X1)
BD*(C2−C3)
BD*(C5−C6)
BD*(C2−H2a)
BD*(C2−H2b)
BD*(C3−H3a)
BD*(C3−H3b)
BD*(C5−H5a)
BD*(C5−H5b)
BD*(C6−H6a)
BD*(C6−H6b)
7.5
8.0
7.8
8.2
0.9
1.1
5.4
5.7
4.1
4.0
2.6
3.0
0.8
6.1
6.5
0.8
0.8
2.6
<0.5
0.6
<0.5
0.5
0.6
<0.5
<0.5
3.3
<0.5
<0.5
0.8
<0.5
2.8
<0.5
6.4
<0.5
6.3
0.7
0.6
2.6
<0.5
0.6
<0.5
0.5
0.6
<0.5
<0.5
<0.5
<0.5
<0.5
<0.5
<0.5
a
The interactions and labeling presented are that depicted in Scheme
4b. Energies are in kilocalories per mole. Piperidine is not included in
this table because the interactions described are all near zero.
b
c
Finally, piperidine does not establish any of the interactions
discussed above. This result may be traced to the presence of a
methylene group at position 4 that does not bear any lone pair
Interaction formed between the axial nonbonding orbital with the
d
antibonding orbital series. Interaction formed between the equatorial
nonbonding orbital with the antibonding orbital series.
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that could interact with other sites of the amine. Note that in
this case, the electrophilic solvation will become more
important, in agreement with the experimental observations.
In summary, the orbital interaction analysis quoted in Table 3
nicely complements the experimental results and can be used to
further provide a semiquantitative hierarchy of nucleophilicity
for the series of amines studied in this work.
level of theory. In addition to the optimized structure, a water
molecule was coordinated and the system was relaxed at the
same level of theory as the previous system. To identify
stationary points as transition state structures, we performed
harmonic analysis to check the presence of a unique imaginary
frequency at the same level of theory. All the calculations were
performed using the Gaussian 03 suite of programs.50
ASSOCIATED CONTENT
CONCLUSIONS
■
■
S
* Supporting Information
The reactions of a series of secondary alicyclic amines toward
phenyl 2,4,6-trinitrophenyl ether in aqueous ethanol mixtures
of different compositions have been examined at the
experimental and theoretical levels to understand specific
solvation effects on the reaction mechanism of the title
reactions. It is found that only piperidine is sensitive to
solvation effects, a result that may be traced to the polarity of
the solvent composition in the ethanol/water mixture that
points to a specific electrophilic solvation in the aqueous phase.
The electronic analysis based on the MEP highlights the effects
that the substituent at the nucleophiles may exert on the
solute−solvent interactions in these systems.
Kinetic results (Tables S1−S15), plots of kobs versus [N]F for all
the reactions (Figures S1−S4), H and 13C NMR spectra for
1
phenyl 2,4,6-trinitrophenyl ether and the final product 2,4,6-
trinitro-1-morpholinobenzene, Cartesian coordinates, energies,
and the number of imaginary frequencies (NIMAG) considered
in this study (Tables S16−S26), and the complete ref 50. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: rcontrer@uchile.cl. Phone: (+56 2) 29787272. Fax:
(+56 2) 2713888.
Notes
■
EXPERIMENTAL SECTION
■
Materials. Amines were purified by distillation or
recrystallization, except piperazine, which was purified by
sublimation. The substrate, phenyl 2,4,6-trinitrophenyl ether
(1), was prepared by the method described previously16−19
[mp 157.1−158.7 °C (lit. 155−156 °C)]. The solid, recrystal-
lized from chloroform, was identified by the following NMR
properties: 1H NMR (400 MHz, CDCl3) δ 6.91 (d, 2H, J = 7.9
Hz), 7.21 (m, 1H, J = 7.3 Hz), 7.34 (d, 2H, J = 8.1 Hz), 8.97 (s,
2H); 13C NMR (400 MHz, CDCl3) δ 115.9 (CH), 124.5
(CH), 125.3 (CH), 130.3 (CH), 142.5 (C-2/6), 144.5 (C-4),
146.9 (C-1), 156.1 (C-7).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by Project ICM- P10-003-F CILIS,
■
granted by Fondo de Innovacion
́
para la Competitividad del
́
Ministerio de Economia, Fomento y Turismo, Chile, and
Fondecyt Grants 1100492, 1110062, and 1095145. R.O.-T.
thanks CONICYT of Chile for a doctoral fellowship.
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Kinetic Measurements. These data were recorded
spectrophotometrically (330−550 nm range) by means of a
diode array spectrophotometer in ethanol aqueous mixtures, at
25.0
0.1 °C, an ionic strength of 0.2 M (KCl), and three
different pH values maintained by partial protonation of the
amines. The reactions, studied under an excess of the amine
over the substrate, were started by injection of a substrate stock
solution in acetonitrile (10 μL) into the amine aqueous ethanol
solution (2.5 mL in the spectrophotometric cell). The initial
substrate concentration was ∼1 × 10−4 M. Pseudo-first-order
rate coefficients (kobs) were found for all reactions; these were
determined by means of the spectrophotometer kinetic
software for first-order reactions at 385−390 nm, correspond-
ing to 2,4,6-trinitro-1-aminobenzene. The experimental con-
ditions of the reactions and the kobs values are listed in Tables
S1−S15 of the Supporting Information.
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