Kinetics of the reactions between 1-fluoro-2,6-dinitrobenzene and pyrrolidine and piperidine in binary solvent systems: Influence of the nucleophile structure

Article abstract of DOI:10.1002/poc.704

We studied the kinetics of the reaction between l-fluoro-2,6-dinitrobenzene and pyrrolidine or piperidine in ethyl acetate-chloroform or acetonitrile and acetonitrile-chloroform binary solvent mixtures. The kinetic response of these reactions was compared with that of the reactions with homopiperidine. The aim of this work was to evaluate the influence of the nucleophile structure and of solvent effects on those reactive systems. The amine structure has a great influence on second-order rate constants, especially on the rate constants related to the catalyzed step. In mixtures with chloroform the amine structure is also responsible for the change in the reaction mechanism. Theoretical quantum mechanics calculations confirm that the origin of these results lies in stereoelectronic effects due to the conformational difference between the amino moieties in the intermediate a adducts as they release the nucleofuge. Solvation effects are dominated by non-specific interactions. The order of incidence of the molecular-microscopic solvent properties on the second-order rate coefficient k_A is dipolarity/polarizability > hydrogen-bond donor ability (HBD) > hydrogen-bond acceptor ability (HBA). The (HBA + HBD) and (HBA +-HBA/HBD) solvent systems have similar solvation mechanisms: the critical state is preferentially solvated by the structure formed by intersolvent hydrogen-bonded species. Mixtures of the type (HBA/HBD + HBD) manifest a particular solvation behavior. Among the reactive systems selected there is only one example in which preferential solvation is not operative.

Full text of DOI:10.1002/poc.704

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2004; 17: 138–147
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.704
Kinetics of the reactions between 1-fluoro-2,6-
dinitrobenzene and pyrrolidine and piperidine in binary
solvent systems: Influence of the nucleophile structure
P. M. Mancini,* G. G. Fortunato and L. R. Vottero
´
´
Departamento de Qu ı´ mica, Area Qu ı´ mica Organica, Facultad de Ingenier ı´ a Qu ´ı mica, Universidad Nacional del Litoral,
Santiago del Estero 2829, (3000) Santa Fe, Argentina
Received 26 May 2003; revised 15 July 2003; accepted 27 July 2003
ABSTRACT: We studied the kinetics of the reaction between 1-fluoro-2,6-dinitrobenzene and pyrrolidine or
epoc
piperidine in ethyl acetate–chloroform or acetonitrile and acetonitrile–chloroform binary solvent mixtures. The
kinetic response of these reactions was compared with that of the reactions with homopiperidine. The aim of this work
was to evaluate the influence of the nucleophile structure and of solvent effects on those reactive systems. The amine
structure has a great influence on second-order rate constants, especially on the rate constants related to the catalyzed
step. In mixtures with chloroform the amine structure is also responsible for the change in the reaction mechanism.
Theoretical quantum mechanics calculations confirm that the origin of these results lies in stereoelectronic effects due
to the conformational difference between the amino moieties in the intermediate ꢀ adducts as they release the
nucleofuge. Solvation effects are dominated by non-specific interactions. The order of incidence of the molecular–
microscopic solvent properties on the second-order rate coefficient kA is dipolarity/polarizability > hydrogen-bond
donor ability (HBD) > hydrogen-bond acceptor ability (HBA). The (HBA þ HBD) and (HBA þ HBA/HBD) solvent
systems have similar solvation mechanisms: the critical state is preferentially solvated by the structure formed by
intersolvent hydrogen-bonded species. Mixtures of the type (HBA/HBD þ HBD) manifest a particular solvation
behavior. Among the reactive systems selected there is only one example in which preferential solvation is not
operative. Copyright # 2004 John Wiley & Sons, Ltd.
Additional material for this paper is available in Wiley Interscience
KEYWORDS: nucleophile structure; solvent effects; aromatic nucleophilic substitution; stereoelectronic effects;
correlations; preferential solvation
INTRODUCTION
bond acceptor (HBA) solvent þ potential hydrogen-bond
donor (HBD) co-solvent]; type B [HBA solvent HBA/
potential HBD co-solvent]; and type C [HBA/potential
We have recently reported a study of the solvent effects
on the kinetics of the nucleophilic aromatic substitution
3
HBD solvent þ potential HBD co-solvent].
ðS ArÞ reaction between 1-fluoro-2,6-dinitrobenzene
Here, we extended the analysis to the reactions be-
tween 2,6-DNFB and the secondary amines pyrrolidine
(PYR) and piperidine (PIP), carried out in the solvent
mixtures mentioned above.
N
(
(
2,6-DNFB) and the secondary amine homopiperidine
HPIP) (hexahydro-1H-azepine), in ethyl acetate–
chloroform or acetonitrile and acetonitrile–chloroform
1
binary solvent mixtures.
The mixed solvents chosen were representative of
the types we proposed for mixtures of polar aprotic solvents
where both pure solvents are able to form complexes or
cross-associated species. These mixtures were grouped
on the basis of the molecular–microscopic descriptors
determined in earlier measurements: type A [hydrogen-
The aims of this work were twofold: (i) to investigate
the influence of solvent effects on the selected similar
SNAr processes performed in different mixed solvent
systems; and (ii) to study the influence of the ring size
of the nucleophile, comparing the kinetic response ob-
tained by performing the reaction with the three homo-
logous amines. In this direction, the corresponding results
were analyzed in order to infer possible stereoelectronic
effects related to the ring size of the cyclic amines used.
Additionally, the kinetic results for the reactions with
PYR and PIP carried out in binary mixtures of types A, B
and C were evaluated and related through kinetic re-
sponse patterns, multiparametric correlation analysis and
preferential solvation models.
2,3
´
*
Correspondence to: P. M. Mancini, Departamento de Qu ´ı mica, Area
Qu ´ı mica Org a´ nica, Facultad de Ingenier ´ı a Qu ´ı mica, Universidad
Nacional del Litoral, Santiago del Estero 2829, (3000) Santa Fe,
Argentina.
E-mail: pmancini@fiqus.unl.edu.ar
Contract/grant sponsor: Science and Technology Secretariat, Univer-
sidad Nacional del Litoral; Contract/grant numbers: 2000-17-151;
2
002-21-152; 2002-21-153.
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

KINETICS OF REACTIONS OF 2,6-DNFB WITH PYRROLIDINE AND PIPERIDINE
139
Scheme 1
RESULTS AND DISCUSSION
co-solvent molar fraction, exhibiting a negative deviation
from the ideal response. The highest decrease takes place
in HBD solvent-poor mixtures.
The kinetics of the S Ar reactions between 2,6-DNFB
N
and PYR and PIP respectively, in ethyl acetate (EAc)–
CHCl , ethyl acetate and acetonitrile (AcN) and acetoni-
trile–CHCl solvent systems were determined at 25 C.
3
With respect to the reaction carried out in EAc–AcN
mixtures, the plots also manifest a unique pattern of
kinetic response: kA increases with increase in the
HBA/HBD solvent molar fraction over the whole range
of amine concentration, exhibiting positive deviations
from ideal behavior.
3
ꢀ
Kinetic results
On the other hand, the reaction carried out in AcN–
CHCl3 shows a unique kinetic response pattern: kA
decreases with increase in the CHCl molar fraction,
The gross mechanism of S Ar reactions when primary or
N
secondary amines are the nucleophiles is now well
4–6
3
established (Scheme 1). In aprotic polar solvents, the
reaction follows a second-order kinetic law represented
by the equation
exhibiting negative deviations from ideal response, as
in the case of EAc–CHCl mixtures. The highest decrease
also takes place in HBD-poor mixtures.
3
À
Á
B
3
Table S2 (Supporting Information) gives the
k k =k and k k =k partial rate relations obtained by
the linear regression treatment of the kinetic data. The
k k þ k ½Bꢁ
1
2
kA ¼
ð1Þ
B
1
2
ꢂ1
1
3
ꢂ1
k
þ k þ k ½Bꢁ
ꢂ1
2
3
k k =k values are not statistically significant, so the
1
2
ꢂ1
reactions exhibit zero intercept and are clearly base-
Each reaction was explored at different solvent com-
positions, and the influence of amine concentration was
studied in all cases. The reactions were carried out under
pseudo-first-order conditions: they yielded the expected
products in quantitative yield [N-(2,6-dinitrophenyl)pyr-
rolidine and N-(2,6-dinitrophenyl)piperidine], and pro-
ved to be first order in the corresponding substrate. The
catalyzed in all solvent mixtures (k =k >>100Þ. The
3
2
response of the k k =k values can be considered ap-
3
1
ꢂ1
proximately equivalent to that of the k values.
A
Reaction with PIP. Table S3 (Supporting Information)
gives the k values for the reaction between 2,6-DNFB
A
second-order rate constants, k , were calculated from
A
the experimental pseudo-first-order rate constants k and
’
the appropriate amine concentration.
and PIP in the solvent systems explored, including the
data in the pure solvents. As in the case for the reactions
with PYR, in all instances the kA second-order rate
constant varies linearly with the amine concentration
exhibiting zero intercept.
Reaction with PYR. Table S1 (Supporting Information,
available at the epoc website at http://www.wiley.com/
The plots of k vs X are shown in Fig. 1. The shapes
A
CoS
epoc) gives the k values for the reactions performed in
A
of the curves for the reactions performed in EAc–CHCl3
reveal two different kinetic responses depending on the
co-solvent concentration. In the EAc-rich zone, the kA
values decrease with increase in the co-solvent molar
fraction, giving rise to negative deviations, whereas in the
the explored mixtures. The data in the pure solvents are
additionally presented. For all solvent systems, the ki-
netic results reveal a satisfactory linear dependence of the
rate on amine concentration, showing a zero intercept.
In order to understand the influence of the solvent
effects on the explored reactions with changes in the
CHCl -rich zone the kinetic response tends to an ideal
3
behavior.
The reaction carried out in EAc–AcN mixtures man-
ifests a unique pattern: the k values increase linearly
composition of the mixtures, plots of k vs X
A
at each
CoS
amine concentration are presented in Fig. 1. The shapes
of the curves for the reaction performed in EAc–CHCl3
show a general pattern: the k values decrease from pure
A
with the HBA/HBD solvent molar fraction over the whole
range of amine concentration, clearly yielding an ideal
response.
A
EAc to pure CHCl as a non-linear function of the
3
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

1
40
P. M. MANCINI, G. G. FORTUNATO AND L. R. VOTTERO
Figure 1. Plots of kA vs XCoS for the reaction of 2,6-DNFB with PYR or PIP in EAc–CHCl or AcN and AcN–CHCl mixtures, at
3
3
each amine concentration
With respect to the reaction performed in AcN–CHCl3,
the shape of the curves is similar to that with the EAc–
CHCl mixtures: k decreases with increase in the co-
solvent molar fraction, manifesting a negative deviation
from ideal response, the highest decrease taking place in
the HBD solvent-poor mixtures.
with respect to HPIP in all binary solvent mixtures, at
constant amine concentration.
Table 1 gives the corresponding relations at two amine
concentrations (0.03 and 0.09 M) in the whole range of
solvent composition and for all solvent systems.
3
A
The results corresponding to EAc–CHCl mixtures
3
Table S4 (Supporting Information) gives partial rate
relations k K =k and k k =k obtained by the linear
regression treatment of the kinetic data. As in the case for
suggest the following: (i) The amine with the smallest
ring exhibits the highest rate. These ratios are higher in
EAc-rich than in CHCl -rich mixtures. Thus, when the
1
2
ꢂ1
1
3
ꢂ1
3
the reactions with PYR, relations k k =k are statisti-
1
reactions are performed in the former mixtures, those
with PYR are almost 300 times more reactive than
2
ꢂ1
cally not different from zero, which means that the
reactions are highly base-catalyzed in all solvent mix-
tures (k =k >>100).
PIP
HPIP
those with HPIP; (ii) The kA : kA
ratios decrease
slightly with the co-solvent molar fraction and also
indicate more similar rates for PIP and HPIP; (iii) The
3
2
PYR
A
PIP
k
: kA ratios also decrease with the co-solvent mole
The nucleophile influence
fraction and suggest that the five-membered ring amine is
much more reactive than the six-membered ring amine.
In EAc-rich mixtures, the reactions with PYR are almost
100 times more reactive than those with PIP.
The results corresponding to EAc–AcN binary mix-
tures suggest, as in the previous mixture, that the amine
with the smallest ring exhibits the highest rate, but in this
case the order of magnitude of the ratios remains constant
with the co-solvent concentration.
Comparison of amines. In order to achieve a com-
parative study of the homologous secondary amines PYR,
PIP and HPIP, the kinetic data corresponding to PYR and
PIP were compared with the previously reported data for
1
HPIP.
It is possible to estimate reactivity ratios k AP YR : k AP IP
:
HPIP
A
k
taking into account the k values for each amine
A
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

KINETICS OF REACTIONS OF 2,6-DNFB WITH PYRROLIDINE AND PIPERIDINE
141
Table 1. Relations k AP YR : kA : kA and k AP YR : kA in binary solvent mixtures (including the data in the pure solvents)
PIP
HPIP
PIP
PYR
A
PIP
HPIP
PYR
PIP
: kA
k
: kA : kA
k
A
Solvent
XCoS
[Amine] ¼ 0.03 M
[Amine] ¼ 0.09 M
[Amine] ¼ 0.03 M [Amine] ¼ 0.09 M
EAc
AcN
CHCl3
303 : 3.18 : 1
238 : 4.70 : 1
47.6 : 1.16 : 1
300 : 3.68 : 1
318 : 4.10 : 1
182 : 4.10 : 1
236 : 3.42 : 1
356 : 4.30 : 1
170 : 3.60 : 1
212 : 3.56 : 1
632 : 5.00 : 1
151 : 3.60 : 1
206 : 3.69 : 1
371 : 5.00 : 1
124 : 3.00 : 1
188 : 3.17 : 1
356 : 5.40 : 1
112 : 2.20 : 1
154 : 2.79 : 1
353 : 5.10 : 1
86 : 5.10 : 1
118 : 2.18 : 1
316 : 5.30 : 1
72 : 2.40 : 1
94.8 : 1.84 : 1
308 : 5.00 : 1
71 : 2.10 : 1
86 : 1.65 : 1
279 : 5.00 : 1
63 : 1.96 : 1
280 : 3.30 : 1
236 : 5.44 : 1
87 : 2.30 : 1
95 : 1
51 : 1
41 : 1
81 : 1
76 : 1
44 : 1
69 : 1
82 : 1
47 : 1
59 : 1
72 : 1
42 : 1
57 : 1
74 : 1
41 : 1
59 : 1
66 : 1
39 : 1
55 : 1
69 : 1
69 : 1
54 : 1
60 : 1
30 : 1
51 : 1
62 : 1
34 : 1
52 : 1
56 : 1
32 : 1
85 : 1
43 : 1
38 : 1
74 : 1
76 : 1
39 : 1
66 : 1
74 : 1
38 : 1
60 : 1
70 : 1
37 : 1
61 : 1
66 : 1
39 : 1
58 : 1
61 : 1
40 : 1
52 : 1
59 : 1
43 : 1
51 : 1
56 : 1
41 : 1
49 : 1
53 : 1
43 : 1
48 : 1
50 : 1
36 : 1
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
240 : 3.20 : 1
292 : 3.80 : 1
188 : 4.90 : 1
201 : 3.00 : 1
314 : 4.26 : 1
189 : 4.90 : 1
185 : 3.07 : 1
325 : 4.64 : 1
185 : 4.90 : 1
164 : 2.70 : 1
334 : 5.10 : 1
172 : 4.40 : 1
157 : 2.70 : 1
340 : 5.60 : 1
149 : 3.70 : 1
139 : 2.70 : 1
318 : 5.40 : 1
137 : 3.20 : 1
127 : 2.70 : 1
294 : 5.24 : 1
119 : 2.90 : 1
114 : 2.30 : 1
282 : 5.33 : 1
107 : 2.90 : 1
107 : 2.20 : 1
264 : 5.23 : 1
96 : 2.60 : 1
The relations obtained for AcN–CHCl mixtures allo-
3
to conformational or stereoelectronic effects in the tran-
9
sition state leading to the reaction product. It was
wed us to arrive at conclusions similar to those obtained
for EAc–CHCl mixtures.
suggested that the unshared electron pair on the amine-
ꢂ
3
In order to compare the constants corresponding
AMINE
nitrogen of the anionic ꢀ intermediate (Z ) must be
to the k k =k ðk
Þ catalyzed pathway, relations
antiperiplanar with respect to the rupturing C—F bond
in the transition state, making it possible that the amino
moiety approaches a coplanar geometry, which is a
canonical form of the product. Related to this, it was
also suggested that the carbon-bound amino moiety in the
transition state for that step should be intermediate
1
PIP
3
ꢂ1
PYR
HPIP
k
(
: k : k
were calculated for all solvent systems
Table 2). The results reveal a high incidence of the amine
structure in the catalyzed step, which is favored by the
amine with the smallest ring. The corresponding relations
were calculated for the reactions between these amines
7
ꢂ
and 1-fluoro-2,4-dinitrobenzene, arriving at equivalent
between its conformations in Z (antiperiplanar confor-
conclusions. These results can be related to stereoelec-
tronic effects and to conformational differences depend-
ing on the ring size of the amine.
mation) and in the canonical structure. The structure I is
the respective canonical form of the product correspond-
ing to our reactive system.
Influence of the cyclic amine on the catalyzed
pathway: theoretical calculations. With a view to
explaining the remarkable differences in rates between
the cyclic amines specially related to the rate constants
on the catalyzed pathway, and in order to confirm whether
the ring size of the amine plays a role in that step,
semiempirical molecular orbital calculations at the
8
AM1 (Austin Model 1) level were carried out in a
vacuum with the HyperChem 5.11 systems of programs.
Such huge differences, specifically between PYR and
PIP, were found in similar systems and they were ascribed
If we consider that the SB–GA (Specific Base–General
Acid) mechanism is operative for the ZH intermediate
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

1
42
P. M. MANCINI, G. G. FORTUNATO AND L. R. VOTTERO
Table 2. Relations kPYR : kPIP : kHPIPand kPYR : kPIP in binary
solvent mixtures (including the data in the pure solvents)
that the kinetic differences between the three cyclic
9,10
amines do not arise from the first equilibrium (K )
and provided they have pKa values that do not differ
greatly, the same acidity for the ZH intermediates can be
considered. The previous considerations would imply
1
11
PYR
A
PIP
HPIP
PYR
A
PIP
Solvent
XCoS
k
: kA : k
k
: kA
EAc
AcN
CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
294 : 3.35 : 1
284 : 6.30 : 1
140 : 3.75 : 1
239 : 3.25 : 1
305 : 3.97 : 1
217 : 5.60 : 1
198 : 3.21 : 1
326 : 4.70 : 1
219 : 6.00 : 1
181 : 3.16 : 1
329 : 5.06 : 1
231 : 6.90 : 1
160 : 2.93 : 1
344 : 5.55 : 1
208 : 6.10 : 1
162 : 3.05 : 1
370 : 6.30 : 1
197 : 5.50 : 1
149 : 2.96 : 1
352 : 6.20 : 1
184 : 4.90 : 1
148 : 2.96 : 1
329 : 6.20 : 1
176 : 4.30 : 1
145 : 3.05 : 1
318 : 6.30 : 1
152 : 3.90 : 1
139 : 3.07 : 1
303 : 6.30 : 1
127 : 3.60 : 1
88 : 1
45 : 1
37 : 1
73 : 1
77 : 1
39 : 1
62 : 1
70 : 1
36 : 1
57 : 1
65 : 1
33 : 1
55 : 1
62 : 1
34 : 1
53 : 1
58 : 1
36 : 1
50 : 1
56 : 1
38 : 1
50 : 1
53 : 1
41 : 1
48 : 1
51 : 1
39 : 1
45 : 1
48 : 1
35 : 1
that the differences in the k k =k
parameter must
stem from a difference in the k values. As a conse-
1
3
ꢂ1
4
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
quence, the ring size of the amine would play a critical
role in the transition state for the separation of the
ꢂ
fluorine atom from the Z intermediate.
ꢂ
In this direction, the Z ꢀ-complexes intermediate
geometric structures for PYR, PIP and HPIP were opti-
mized at the AM1 level. From the structures which
represent a local minimum in the potential energy sur-
face, it was possible to determine the total energy (ET),
the heat of formation (ꢀH) and the heat of formation with
respect to reactants (ꢀꢀHReactants) (Table 3). Total en-
ergies and heats of formation corresponding to reactants
(substrate and cyclic amines) are given as Supporting
Information (Table S5). The negative values obtained for
ꢀꢀHReactants indicate that the formation of these com-
AcN–CHCl3
plexes for all amines is exothermic. In order to analyze
ꢂ
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
AcN–CHCl3
EAc–CHCl3
EAc–AcN
the antiperiplanar Z conformations for all intermediates,
a conformational search was carried out [based on the
rotation of a dihedral angle formed by the Cipso—N
(amino group) bond, the Cipso—F bond and the N—Cꢁ
bond of the amino moiety]. The respective energies are
listed in Table 3. The structures obtained are shown in
Figs S1–S3 (Supporting Information). The conforma-
tional search yielded only one antiperiplanar conforma-
tion for PYR and two conformations for PIP and HPIP. In
order to compare the energy between these structures and
those previously optimized, the magnitude of ꢀE was
calculated. This value represents the difference in the ꢀH
values between the structure corresponding to an energy
minimum and the antiperiplanar conformation. It can be
clearly appreciated that both conformations derived from
PYR are equivalent (ꢀE ¼ 0), whereas for PIP and HPIP
derivatives the antiperiplanar conformations correspond
to structures energetically higher than those which con-
stitute a local minimum. This means that reaching the
corresponding antiperiplanar conformation in order to
evolve to the transition state would be easier for PYR
than for PIP and HPIP intermediates.
AcN–CHCl3
decomposition step, the k k =k constants relative to
3
1
ꢂ1
this pathway are equivalent in this case to the product of
the first equilibrium constant (K ), the acid dissociation
1
constant of the zwiterionic intermediate (K ), and the
3
specific rate constant for the general acid-catalyzed
nucleofuge departure (k ) (Scheme 2). It can be assumed
4
Scheme 2
ꢂ
a
Table 3. Total energy and heats of formation at AM1 level corresponding to Z intermediates
ꢂ
ꢂ1
ꢂ1
ꢂ1
ꢂ1
ꢀE (kcal mol )
Z conformation
ET (kcal mol
)
ꢀH (kcal mol
)
ꢀꢀHReactants (kcal mol
ꢂ43.64
)
2
,6-DNFB þ PYR
,6-DNFB þ PIP
Minimum energy
Antiperiplanar
Minimum energy
Antiperiplanar
ꢂ87973.8
ꢂ87973.8
ꢂ59.80
ꢂ59.80
ꢂ67.25
ꢂ67.25
ꢂ66.68
ꢂ69.30
ꢂ69.00
ꢂ68.72
0
2
ꢂ91568.08
ꢂ91568.08
ꢂ91567.52
ꢂ95156.97
ꢂ95156.65
ꢂ95156.30
ꢂ39.71
0
0.57
2
,6-DNFB þ HPIP Minimum energy
Antiperiplanar
ꢂ38.68
0.30
0.58
a
T
E , total energy; ꢀH, heat of formation; ꢀꢀHReactant, heat of formation with respect to reactants; ꢀE, heat of formation difference between the minimum
energy and the antiperiplanar conformations. 1 kcal ¼ 4.184 kJ.
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

KINETICS OF REACTIONS OF 2,6-DNFB WITH PYRROLIDINE AND PIPERIDINE
143
Table 4. Total energy and heats of formation at AM1 level corresponding to product minimum energy and to canonical
structures
ET
(kcal mol
ꢀH
(kcal mol
ꢀꢀH
(kcal mol
ꢀꢀH
(kcal mol ) (kcal mol
ꢀꢀHZ
ꢂ
ꢂ1
Reactants
ꢂ1
Products
ꢂ1
ꢂ1
ꢂ1
Product structure
)
)
)
)
2,6-DNFB þ PYR
2,6-DNFB þ PIP
2,6-DNFB þ HPIP
Minimum energy
Canonical structure
Minimum energy
Canonical structure
Minimum energy
Canonical structure
ꢂ76730.03
ꢂ76729.15
ꢂ80326.11
ꢂ80319.43
ꢂ83916.23
ꢂ83904.60
42.96
43.84
33.72
40.40
30.43
41.82
59.12
59.99
61.26
67.94
61.05
72.44
0.884
6.680
11.39
103.6
107.1
110.5
In order to evaluate the possibility that the carbon-
treatment allowed us to determine the incidence of each
type of solvent property on the kinetics of the reaction.
The results obtained from this correlation are presented in
Tables 5 and 6, corresponding to the reactions with PYR
and PIP, respectively.
The good correlations obtained by multiple regression
analysis (based on least squares) over the whole range of
solvent compositions allow an interpretation of the influ-
ence of any mixed solvent property on the kinetic process.
For the system with PYR, the coefficient b is, in most
cases, not statistically significant at the 90% confidence
level, or higher, according to Student’s t-test. In EAc–
bound amino moiety in the transition state approaches a
coplanar geometry, the respective products and structures
of type I were optimized at AM1 level for each amino
derivatives. As expected, the optimized product struc-
tures [Figs S4(a), S5(a) and S6(a), Supporting Informa-
tion] obtained for the three amines do not exhibit that
coplanar geometry, and the corresponding structures of
type I [Figs S4(b), S5(b) and S6(b), Supporting Informa-
tion] with the carbon-bound amino moiety coplanar are
energetically higher than the former. Table 4 shows the
resultant energies for all structures. The positive values
obtained for ꢀꢀHReactants indicate that the formation of
the products for all amines is endothermic. This allows us
to make some suggestions about the respective transition
states taking into account the product structures. In
this direction, the trends observed for the ꢀH values
CHCl mixtures coefficients s and a are negative at all
3
amine concentrations, which means that an increase in
the dipolarity/polarizability and in the HBD ability of the
mixed solvent decreases the k values. Considering the
A
magnitude of the s and a coefficients for these correla-
tions, it can be inferred that the kA values are more
sensitive to dipolarity/polarizability than to the HBD
of canonical structures with respect to products
ꢂ
(
ꢀꢀHProduct) and with respect to antiperiplanar Z con-
formations (ꢀꢀHZ
ꢂ
) indicate that the structures in the
ability, resulting in 3.3 < s/a < 6.8. In AcN–CHCl mix-
3
transition state derived from the amine with the smallest
ring are energetically favored to approach the coplanar
geometry necessary to progress towards products.
The previous results show that the origin of the
differential behaviors lies in special conformations re-
lated to the ring size of the amine.
tures the coefficients s are also negative but the coeffi-
cients a are positive at all amine concentrations. As in the
previous system, the dipolarity/polarizability of the sol-
vent has a greater effect on the k values than the HBD
A
ability (3.2 < s/a < 5.8). For the reaction performed in
EAc–AcN mixtures, the coefficient s is not statistically
significant, the k values being linearly dependent on the
A
HBD ability of the solvent, thus log k ¼ Y þ aꢁ.
A
The solvent influence
For the system with PIP, in EAc–CHCl mixtures,
3
the coefficients s, a and b are negative and their magni-
tudes follow the order s > a ꢄ b, thus 4.7 < s/a < 8.8,
6.0 < s/b < 10. It must be pointed out that for some amine
concentrations, the coefficients a and b are not statisti-
Correlation analysis of kinetic data with
molecular–microscopic
solvent
properties:
solvent effects on the second-order rate coeffi-
cient k . The kinetic data and the molecular–micro-
cally significant. In AcN–CHCl , the correlation gives
3
A
scopic solvent properties were correlated by means of a
multiparametric approach in order to interpret quantita-
tively the influence of the solvent effects on the explored
reactions. The chosen multiparametric equation was that
negative values for coefficients s and positive values
for coefficients a and b, their order of incidence
being s > a > b, thus 2.1 < s/a < 4.7, 7.0 < s/b < 13,
1.5 < a/b < 6.1. It can be clearly seen that the systems
are also very sensitive to the dipolarity/polarizability of
the solvent. With respect to the EAc–AcN mixtures, the
reactive system is sensitive to dipolarity/polarizability in
addition to the HBD ability of the solvent (1.1 < s/a <
1.7). The coefficient b is not statistically significant
at the 90% or higher confidence level at most amine
concentrations.
12
developed by Kamlet et al.:
ꢃ
log k ¼ Y þ sꢂ þ aꢁ þ bꢃ
ð2Þ
A
where s, a and b measure the relative susceptibilities of
the reactive system with respect to the solvent properties
(
dipolarity/polarizability, HBD and HBA ability). This
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

1
44
P. M. MANCINI, G. G. FORTUNATO AND L. R. VOTTERO
2
Table 5. Correlation coefficient (r and r ), standard deviation (SD), intercept (Y ) and the parameters s, a, and b (and their
standard errors) and the number of data points (n) corresponding to log k ¼ Y þ sꢂ* þ aꢁ þ bꢃ for the reaction between
A
2
,6-DNFB and PYR in binary mixtures (including the data in pure solvents)
2
r (r )
Solvent
[PYR](M)
0.005
SD
Y (sY)
s (ss)
a (sa)
b (sb)
n
EAc–CHCl3
0.975
0.951)
0.978
0.957)
0.973
0.946)
0.967
0.935)
0.974
0.949)
0.976
0.952)
0.975
0.950)
0.978
0.956)
0.976
0.952)
0.989
0.978)
0.987
0.974)
0.984
0.969)
0.991
0.981)
0.992
0.985)
0.990
0.981)
0.993
0.986)
0.982
0.965)
0.993
0.987)
0.986
0.972)
0.987
0.974)
0.988
0.977)
0.985
0.970)
0.048
þ2.220
(0.398)
þ2.415
(0.411)
þ3.552
(0.525)
þ3.942
(0.581)
þ4.281
(0.497)
þ4.155
(0.472)
þ4.061
(0.470)
þ4.345
(0.459)
þ4.315
(0.474)
ꢂ0.819
(0.558)
þ0.025
(0.390)
þ0.741
(0.425)
þ1.133
(0.354)
þ0.971
(0.317)
þ1.378
(0.324)
þ5.122
(0.757)
þ4.880
(1.256)
þ5.042
(0.855)
þ5.667
(1.178)
þ5.104
(1.076)
þ4.526
(0.997)
þ4.681
(1.139)
ꢂ3.522
(0.456)
ꢂ3.410
(0.473)
ꢂ4.175
(0.602)
ꢂ4.359
(0.666)
ꢂ4.527
(0.570)
ꢂ4.252
(0.542)
ꢂ4.061
(0.539)
ꢂ4.329
(0.527)
ꢂ4.201
(0.543)
þ0.617
(0.523)
þ0.444
(0.366)
þ0.517
(0.398)
þ0.288
(0.332)
þ0.533
(0.297)
þ0.304
(0.303)
ꢂ7.197
(0.972)
ꢂ6.526
(1.513)
ꢂ6.170
(1.099)
ꢂ6.687
(1.513)
ꢂ5.719
(1.383)
ꢂ4.839
(1.281)
ꢂ4.957
(1.463)
ꢂ1.079
(0.233)
ꢂ0.814
(0.242)
ꢂ0.875
(0.308)
ꢂ0.685
(0.341)
ꢂ0.703
(0.291)
ꢂ0.624
(0.277)
ꢂ0.655
(0.275)
ꢂ0.727
(0.269)
ꢂ0.762
(0.278)
þ0.734
(0.281)
þ0.437
(0.197)
þ0.381
(0.214)
þ0.559
(0.178)
þ0.436
(0.160)
þ0.476
(0.163)
þ1.241
(0.245)
þ1.433
(0.407)
þ1.815
(0.277)
þ1.404
(0.382)
þ1.405
(0.349)
þ1.661
(0.323)
þ1.567
(0.369)
ꢂ0.479
(0.336)
ꢂ0.151
(0.348)
ꢂ0.449
(0.443)
ꢂ0.665
(0.490)
ꢂ0.914
(0.419)
ꢂ0.717
(0.398)
ꢂ0.629
(0.396)
ꢂ0.713
(0.387)
ꢂ0.628
(0.400)
þ1.159
(0.607)
þ0.447
(0.424)
þ0.04
11
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
0
0
0
0
0
0
0
0
.01
.03
.05
.07
.09
.1
0.050
0.064
0.070
0.060
0.057
0.057
0.056
0.057
0.020
0.014
0.015
0.013
0.011
0.012
0.042
0.070
0.047
0.065
0.060
0.055
0.063
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
.125
.150
EAc–AcN
0.005
0
0
0
0
0
.01
.03
.05
.07
.09
(0.461)
ꢂ0.094
(0.384)
þ0.249
(0.344)
ꢂ0.115
(0.352)
þ0.626
(0.231)
þ0.547
(0.384)
þ0.522
(0.261)
þ0.776
(0.360)
þ0.687
(0.329)
þ0.465
(0.305)
þ0.519
(0.348)
AcN–CHCl3
0.005
0
0
0
0
0
0
.01
.03
.05
.07
.09
.1
Preferential solvation effects on kinetic results:
application of preferential solvation models. In
order to obtain information about the solvation effects on
allowed us to determine the corresponding preferential
solvation parameters f2/1 and f12/1, which measure the
tendency of the solutes to be solvated by co-solvent S2
and by the ‘mixed solvent’ S12 (structure attributed to the
formation of intersolvent complexes or associates by
hydrogen-bond interactions) with reference to solvent
S1. The corresponding results are presented in Table S6
(Supporting Information).
the reagents and/or intermediates of the explored S Ar
N
reaction, we applied the general equation based on
13
solvent exchange theory by Bosh and co-workers:
À Á
À
Á
2
0
2
0
2
0
2
f2=1ðY ꢂ Y Þ x þ f ðY ꢂ Y Þ 1 ꢂ x x
2
1
12=1 12
1
Y ¼ Y þ
À
Á
À Á
À
Á
1
2
2
For the reactions with PYR performed in EAc–CHCl3
0
2
0
2
0
2
0
2
1
ꢂ x þ f
x
þ f12=1 1 ꢂ x x
2=1
mixtures, at all amine concentrations it can be seen that:
(i) f2/1 < 1, indicating that the preferential solvation is
produced by EAc in preference to CHCl ; (ii) f > 1,
ð3Þ
3
12/1
The application of this preferential solvation model to
the k values in the whole range of solvent composition
suggesting preferential solvation by S12 in preference to
EAc and CHCl . As a consequence, the preferential
A
3
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

KINETICS OF REACTIONS OF 2,6-DNFB WITH PYRROLIDINE AND PIPERIDINE
145
2
Table 6. Correlation coefficient (r and r ), standard deviation (SD), intercept (Y ) and the parameters s, a, and b (and their
standard errors) and the number of data points (n) corresponding to log k ¼ Y þ sꢂ* þ aꢁ þ bꢃ for the reaction between
A
2
,6-DNFB and PIP in binary mixtures (including the data in pure solvents)
2
r (r )
Solvent
[PIP] (M)
0.01
SD
Y (sY)
s (ss)
a (sa)
b (sb)
n
EAc–CHCl3
0.980
0.960)
0.971
0.944)
0.970
0.941)
0.972
0.945)
0.965
0.931)
0.963
0.928)
0.967
0.935)
0.978
0.956)
0.989
0.978)
0.994
0.989)
0.996
0.992)
0.996
0.993)
0.998
0.997)
0.997
0.995)
0.997
0.995)
0.998
0.997)
0.995
0.991)
0.992
0.984)
0.990
0.980)
0.989
0.978)
0.995
0.991)
0.991
0.982)
0.995
0.991)
0.995
0.990)
0.027
þ0.175
(0.198)
þ0.542
(0.271)
þ1.020
(0.267)
þ0.910
(0.260)
þ1.201
(0.287)
þ1.156
(0.283)
þ1.131
(0.263)
þ1.379
(0.247)
ꢂ0.787
(0.753)
ꢂ1.492
(0.508)
ꢂ0.818
(0.493)
ꢂ0.449
(0.429)
ꢂ0.748
(0.283)
ꢂ0.578
(0.365)
ꢂ0.847
(0.419)
ꢂ0.798
(0.300)
þ2.740
(0.613)
þ2.973
(0.804)
þ3.137
(0.916)
þ2.888
(0.975)
þ2.848
(0.596)
þ2.255
(0.853)
þ2.899
(0.585)
2.748
ꢂ2.488
(0.246)
ꢂ2.450
(0.336)
ꢂ2.700
(0.332)
ꢂ2.407
(0.323)
ꢂ2.590
(0.357)
ꢂ2.459
(0.351)
ꢂ2.311
(0.326)
ꢂ2.530
(0.306)
þ0.585
(0.706)
þ1.171
(0.477)
þ0.991
(0.462)
þ0.823
(0.402)
þ1.076
(0.266)
þ0.941
(0.343)
þ1.280
(0.393)
þ1.121
(0.281)
ꢂ5.857
(0.788)
ꢂ5.571
(1.033)
ꢂ5.484
(1.177)
ꢂ4.958
(1.253)
ꢂ4.708
(0.766)
ꢂ3.879
(1.096)
ꢂ4.584
(0.751)
ꢂ4.301
(0.813)
ꢂ0.531
(0.133)
ꢂ0.404
(0.182)
ꢂ0.379
(0.179)
ꢂ0.410
(0.175)
ꢂ0.382
(0.193)
ꢂ0.342
(0.191)
ꢂ0.332
(0.177)
ꢂ0.287
(0.166)
þ0.978
(0.380)
þ0.680
(0.257)
þ0.888
(0.249)
þ0.905
(0.216)
þ0.776
(0.143)
þ0.881
(0.184)
þ0.734
(0.211)
þ0.841
(0.151)
þ1.237
(0.199)
þ1.265
(0.260)
þ1.361
(0.297)
þ1.572
(0.316)
þ1.639
(0.193)
þ1.798
(0.276)
þ1.589
(0.1889)
þ1.559
(0.205)
ꢂ0.414
(0.134)
ꢂ0.227
(0.183)
ꢂ0.473
(0.180)
ꢂ0.238
(0.176)
ꢂ0.408
(0.194)
ꢂ0.369
(0.191)
ꢂ0.290
(0.177)
ꢂ0.423
(0.166)
ꢂ2.019
(0.818)
ꢂ0.177
(0.552)
ꢂ0.963
(0.535)
ꢂ1.174
(0.466)
ꢂ0.628
(0.308)
ꢂ0.693
(0.352)
ꢂ0.366
(0.456)
ꢂ0.121
(0.326)
þ0.807
(0.187)
þ0.790
(0.246)
þ0.709
(0.280)
þ0.536
(0.298)
þ0.419
(0.182)
þ0.293
(0.260)
þ0.462
(0.179)
þ0.550
(0.193)
11
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
0
0
0
0
0
0
0
.03
.05
.07
.09
.1
0.037
0.037
0.036
0.039
0.039
0.036
0.034
0.027
0.018
0.018
0.015
0.010
0.013
0.015
0.011
0.034
0.045
0.051
0.054
0.033
0.047
0.032
0.035
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
.125
.150
EAc–AcN
0.01
0
0
0
0
0
0
0
.03
.05
.07
.09
.1
.125
.150
AcN–CHCl3
0.01
0
0
0
0
0
0
0
.03
.05
.07
.09
.1
.125
.150
(0.633)
solvation order is intersolvent complex > EAc > CHCl3.
The results in EAc–AcN mixtures indicate in general
the same preferential solvation order corresponding
to EAc–CHCl : intersolvent complex > EAc > AcN. On
3
the other hand, in AcN–CHCl mixtures the observed
3
preferential solvation order is CHCl > intersolvent
3
complex > AcN.
For the reactions with PIP carried out in EAc–CHCl3
mixtures, the preferential solvation order at most amine
concentrations is intersolvent complex > EAc > CHCl3.
With respect to AcN–CHCl mixtures, as in the case of
3
the reactions with PYR, the critical state of the reaction is
preferentially solvated by the co-solvent with HBD
ability, AcN being the least preferred solvent.
As has been argued, considering the linear kinetic
response observed in EAc–AcN mixtures, the reactive
system constitutes, at first sight, an ideal system. In this
case, Eqn (3) reduces to
0
1
0
Y ¼ x Y þ x Y
ð4Þ
1
2
2
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

1
46
P. M. MANCINI, G. G. FORTUNATO AND L. R. VOTTERO
Table 7. Linear regression treatment of the kA values (Table S3) vs XAcN for each amine concentration, corresponding to the
sr e) aa cc tci oo nr d bi ne gt wt oe e En q 2n , 6( 7- D) NFB and PIP in EAc–AcN mixtures; intercept kEAc (standard error s) and slope (kAcNꢂkEAc) (standard error
[PIP] M
Intercept (s)
Slope (s)
r
SD
n
kEAc
kAcNꢂkEAc
0
0
0
0
0
0
0
0
.01
.03
.05
.07
.09
.1
0.036 (0.003)
0.126 (0.005)
0.190 (0.010)
0.284 (0.012)
0.369 (0.013)
0.438 (0.012)
0.510 (0.011)
0.649 (0.015)
0.081 (0.005)
0.230 (0.009)
0.441 (0.017)
0.613 (0.020)
0.750 (0.022)
0.893 (0.021)
1.100 (0.018)
1.299 (0.025)
0.977
0.993
0.993
0.995
0.996
0.998
0.999
0.998
0.006
0.009
0.018
0.021
0.023
0.022
0.019
0.026
11
11
11
11
11
11
11
11
0.040
0.121
0.205
0.291
0.378
0.420
0.520
0.608
0.088
0.239
0.465
0.659
0.792
0.930
1.110
1.310
.125
.150
which implies a linear relation between the kinetic
property and the solvent composition. As a consequence,
it would imply that there is no preferential solvation and
the corresponding property of the mixed solvent is the
simple average of these properties in the pure solvents.
Applying the corresponding equation to the kinetic data
in EAc–AcN mixtures and as a function of XAcN, it
becomes
HPIP the constants related to the non-catalyzed step
are significant. This behavior can be related to stereo-
electronic effects that come into play during the
catalyzed step.
2. The amine with the smallest ring size exhibits huge
differences in rates with respect to the rest of the
amines. Those differences are more pronounced when
the reaction is carried out in HBA solvent-rich mixtures.
3
. The nucleophile structure has a great influence in the
catalyzed pathway, being also greater in solvents with
high HBA ability. The smaller the ring size of the
nucleophile, the more effective is its catalytic power.
. Theoretical quantum mechanics calculations show
that the origin of previous behavior lies in stereoelec-
tronic effects which come into play during the nucleo-
fuge departure. These effects are forced by differences
in conformation related to the ring size of the amine.
The conformational difference is more crucial be-
tween PYR and PIP and/or PYR and HPIP than
between PIP and HPIP.
kA ¼ XEAckEAc þ XAcNkAcN ¼ kEAc þ ðkAcN ꢂ kEAcÞXAcN
ð5Þ
4
where k is the second-order rate constant for a defined
A
composition of the mixture, and kEAc and kAcN are the
corresponding parameters in the pure solvents.
In order to establish if the experimental data satisfy
Eqn (5), linear regression analysis was applied to the lines
obtained from the k vs X
A
pattern (Fig. 1) at each
AcN
amine concentration. The results are shown in Table 7.
The good correlation coefficients and the probability
P < 0.0001 indicate a linear relationship between kA
and XAcN. The intercept and slope resulting from the
linear regression analysis at each amine concentration
were compared with the experimental kEAc and
5
6
. The nucleophile structure is also responsible for the
change in reaction mechanism in mixtures with
CHCl : while the reactions with PYR and PIP are
catalyzed in the whole range of co-solvent concentra-
tion, those with HPIP are non-catalyzed in HBD-rich
mixtures.
. In all reactive systems, the rate constant is more
susceptible to solvent effects related to dipole and
induced-dipole interactions than those attributed to
hydrogen-bond interactions. Hence the solvation ef-
fects are dominated by non-specific interactions.
3
kAcN ꢂ k
values (Table 7). The good agreement ob-
EAc
tained allow us to confirm that the experimental data
satisfy Eqn (5), so the 2,6-DNFB–PIP/EAc–AcN reactive
system constitutes an ideal system.
CONCLUSIONS
Exceptions are the reactive systems 2,6-DNFB þ
1
HPIP in EAc–CHCl at low amine concentrations
3
This comparative study related to the influence of the
amine structure and solvent effects on the selected
reactive systems allow us to conclude the following.
(for which the kinetic retarding effect takes place) and
2
,6-DNFB þ PYR/PIP in EAc þ AcN. These systems
are dominated by specific interactions related to the
HBD ability of the solvent.
1
. The kinetic results corresponding to the reactions with
PYR and PIP reveal that there is no significant con-
tribution to k from the spontaneous pathway for the
The incidence of the solvation effects ascribed to
the HBA solvent properties has little influence in all
cases.
A
decomposition of the zwitterionic intermediate, the
reactions going exclusively via the base-catalyzed
pathway. It may be argued that, in these reactive
systems, the HBD solvents cannot effectively assist
the fluoride detachment. In contrast, in reactions with
7. If we consider the solvatochromic response patterns
(solvatochromic property vs XCoS), the EAc–CHCl3
mixtures exhibit synergism for ꢁ, a negative devia-
tion from ideality for ꢂ* and a positive deviation for
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147

KINETICS OF REACTIONS OF 2,6-DNFB WITH PYRROLIDINE AND PIPERIDINE
147
1
4a
14
over sodium. The solvents were purified as usual and all
˚
of them were kept over 4 A molecular sieves and stored in
ꢃ. The kinetic response patterns of k values vs
A
XCoS corresponding to the three nucleophiles are
characterized by exhibiting negative deviations
from the ideal response, ꢂ* being the dominant
solvent property. On the other hand, the EAc–AcN
mixtures exhibit a nearly linear response for ꢂ*,
positive deviations for ꢁ and a small synergism for
special vessels that allow delivery without air contamina-
tion. All binary mixtures were prepared prior to use and
stored under anhydrous conditions.
The kinetics of the reactions were studied by UV–
visible spectrophotometry. A Perkin-Elmer Model 124
spectrophotometer was used, equipped with a data-
acquisition system.
The parameters of solvation which minimize the
square residuals of the kA values were computed by
non-linear regressions using the MATLAB 5.2 program.
14b
ꢃ. The corresponding kinetic response patterns of
kA values show positive deviations from the ideal
response in reactions with PYR, for which ꢁ is
dominant, and an ideal response in reactions with
PIP, which are dominated by ꢂ* and ꢁ properties.
Finally, the solvatochromic response for AcN–
CHCl mixtures is characterized by a small syner-
3
14a
gism for ꢂ* and positive deviations for ꢁ and ꢃ.
Acknowledgements
The corresponding kinetic response exhibits negative
deviations from ideal behavior, ꢂ* being the domi-
nant solvent property as in the case of EAc–CHCl3
mixtures.
We are indebted to the Universidad Nacional del Litoral
(UNL), Rep u´ blica Argentina. This work received finan-
cial support from the Science and Technology Secretar-
iat, UNL, CAI þ D Program (Projects 2000-17-151,
2002-21-152 and 2002-21-153).
The above considerations allow us to conclude
that for solvent systems A (HBA þ HBD) and B
(
HBA þ HBA/HBD), the solvatochromic process
and the kinetic process are related to each other.
This correspondence might come from similar solva-
tion mechanisms.
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EXPERIMENTAL
,6-DNFB was synthesized as reported previously.
PYR and PIP were refluxed for 3 h and then fractionated
15
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Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 138–147