N. M. ROUGIER ET AL.
ꢂ
ꢃ
ꢂ
ꢂ
ꢃꢃ
the CD does not affect the nucleophile reactivity over the
reactions centers of 1. Although there is a weak increase in the
percentage yield of 2 (Table S6), the difference in the ratios
bC/bP (13.60) and aC/aP (9.15) may indicate that there is a
change in the selectivity of the attack of the nucleophile in
the presence of CD.
We have also studied the effect of α-CD on the reaction of 1
with Pip. In the presence of α-CD, there was an inhibition of
the reaction. The presence of this CD changed the product dis-
tribution with an increase on product 2 relative to product 4
(Table S8). This could be attributed to a major protection of
the carbon center by α-CD or a major expose of the P center
to the bulk.
The effect of sucrose, a non-reducing disaccharide, on the
reactions of 1 with Pip was also investigated; almost no
effect on the observed rate constants was found. Instead,
the yield of 2 increases from 10.2% to 13.8% for the reac-
tion with Pip as the concentration of sucrose increases from
0 to 0.020 M (Table S9). The observed effect with sucrose
can be attributed to a medium effect or to some type of
unspecific association of the substrate with the sugar, as it
was mentioned before.
ꢀ
kHO ½HO ꢁ þ kAfb½Aꢁ0 þ K1 k1½HOꢀꢁ þ k1Afb½Aꢁ0 ½CDꢁ
ꢀ
kobs
¼
1 þ K1½CDꢁ
(21)
ꢀ
ꢀ
a ¼ kHO ½HO ꢁ þ kAfb½Aꢁ0
(22)
(23)
ꢂ
ꢃ
b ¼ K1 k1½HOꢀꢁ þ k1Afb½Aꢁ0
For BuNH2, the ratio aC/aP is in good agreement with the ratio
kCobs/kPobs (6.40) obtained in the absence of CDs under the same
conditions ([BuNH2]0 = 0.161 and pH = 11.00)[6] (Table 2). The
ratios aC/aP and bC/bP are nearly the same, 6.37 and 6.02,
respectively. Therefore, the presence of β-CD does not affect
the relative reactivity of BuNH2 toward the P and aliphatic C
reaction centers of the complexed substrate, as it was observed
when the Nu is NH2OH.
The effects of α-CD and γ-CD on the reaction of 1 with BuNH2
were also studied. The presence of α- or γ-CD reduces the
reaction rate slightly in comparison to the effect of β-CD (Table 1,
Table S11), and as it was observed in the reactions with Pip, there
was a change in product distribution increasing product 2 in
detriment to 4.
Reaction with n-butylamine
When the reactions of 1 with BuNH2 were performed in the
presence of sucrose, there was no effect on the reactions
rates. Nevertheless, the yield of 2 increases from 13.5% to
19.6% as the concentration of sucrose increases from 0 to
0.020 M (Table S11). The observed effect with sucrose can be
attributed to a medium effect or to some type of unspecific
association of the substrate with the sugar, as it was men-
tioned before.
The reaction of 1 with BuNH2 was previously studied in a pH
range from 10.57 to 11.42 in 2% 1,4-dioxane/H2O.[6] In all cases,
competition between SN2(P) and SN2(C) was observed, leading
to the formation of the aromatic products 2 and demethyl-
fenitrothion, 4, respectively. At constant pH and increasing
BuNH2 concentrations, the yield of product 4 increases. On the
other hand, the attack at P leading to product 2 increases with
the pH.[6]
We report now a study of the effects of CDs on the reaction of
1 with BuNH2. The reaction in the presence of increasing concen-
trations of β-CD was conducted at pH 11.00 in 2% 1,4-dioxane/
H2O at 25 °C and ionic strength 1.00 M (NaCl) at a constant con-
centration of the amine of 0.161 M. At this pH, the complexes of
ionized CD (CDOꢀ) can be neglected.
The reaction was followed in the same way as it was per-
formed with Pip, by measuring the increase in absorbance of
product 2 at 397 nm. The data of the observed rate constants,
kobs, were obtained and dissected into kPobs and koCbs as shown be-
fore for Pip. The percentages of SN2(P) and SN2(C) and the yield
of 2 obtained for the reactions with the BuNH2 in the presence of
β-CD are presented in Table S10.
At pH = 11.00, the molar fraction of BuNH2 is 0.59, and the
molar fraction of BuNH+3 is 0.41. From the association equilibrium
constants of BuNH2 with β-CD (KACD = 3 Mꢀ1),[27] it can be calcu-
lated that at the maximum β-CD concentration used (0.02 M),
only 4.3% of the amine is complexed, Table S7.
In the reaction of 1 with BuNH2, the presence of β-CD
reduces the reaction rate in comparison with the same reac-
tion in the absence of the receptor, and the yields of reac-
tion products remain unchanged. Therefore, in Scheme 5,
the pathways that imply the complexed amines can be
discarded; the observed rate constant for the mechanism
of the reaction of 1 with BuNH2 is given by Eqn (21), which
has the same mathematical form of Eqn (1) with parameters
a and b given by Eqns (22) and (23), and parameter c is
given by Eqn (20).
CONCLUSIONS
Fenitrothion (1) reacts with O-nucleophiles by SN2(P) pathways,
whereas the reaction with N-based nucleophiles occurs with
competition between SN2(P) and SN2(C) pathways. Pip is more
reactive than BuNH2, as it is generally observed.
In all cases, the highest inhibition is produced by β-CD, the
one that has the highest association constant with 1.
The reactivity of the nucleophiles toward the P centers de-
creases in the order HOOꢀ > NH2Oꢀ > HOꢀ as it is the inhibition
produced by β-CD.
The reactivity toward C and P is not affected by the presence
of β-CD in the reaction of 1 with NH2OH or BuNH2, whereas in
the reaction with Pip, the reactivity toward C increases. This re-
sult may be a consequence of the larger size of piperidine than
the primary amines, which is more evident in a constrained sys-
tem as is the substrate included in the cavity of CDs.
The formation of a complex that stabilizes 1 toward the nucle-
ophilic attack could be the reason of the observed inhibition of
the reaction of 1 with the studied nucleophiles.
Acknowledgements
This research was supported in part by Consejo Nacional de
Investigaciones Científicas y Técnicas. Argentina (CONICET) (PIP
112-200801-01335), Agencia Nacional de Promoción Científica
y Tecnológica (FONCYT) (PICT 2008 0180), Ministerio de Ciencia
y Tecnología de la Provincia de Córdoba (PID 2008) and
wileyonlinelibrary.com/journal/poc
Copyright © 2014 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2014, 27 935–943