Solvolytic Behavior of Aliphatic Carboxylates

Article abstract of DOI:10.1002/ejoc.201301574

The leaving group abilities (nucleofugalities) of a series of aliphatic carboxylates have been obtained by determining the nucleofuge-specific parameters (N_f and s_f) from solvolysis rate constants of X,Y-substituted benzhydryl carboxylates in a series of aqueous ethanol mixtures by applyication of the linear free energy relationship (LFER) equation: log k = s_f (E_f + N_f). These values can be employed to compare reactivities of carboxylates with those of other leaving groups previously included in the nucleofugality scale, and also to estimate the solvolysis rates of various carboxylates. It is confirmed that the inductive effect is the most important variable governing the reactivities of halogenated carboxylates in solution. Moreover, both the Hammett correlation and the solvolytic activation parameters have revealed a strong influence of the inductive effect on the nucleofugality of alkyl-substituted carboxylates. The reaction constants (s_f) indicate that carboxylate substrates with weaker leaving groups solvolyze via later, more carbocation-like, transition states, which is in accord with the Hammond postulate. In addition, due to the weaker demand for solvation of transition states that produce more strongly stabilized benzhydrylium ions, in which more efficient charge delocalization occurs, the reaction constants (s_f) obtained with most of the leaving groups investigated here increase as the polarity of the solvent decreases.

Full text of DOI:10.1002/ejoc.201301574

FULL PAPER
DOI: 10.1002/ejoc.201301574
Solvolytic Behavior of Aliphatic Carboxylates
Mirela Matic´,[a] Bernard Denegri,*[a] and Olga Kronja*[a]
Keywords: Solvolysis / Kinetics / Linear free energy relationships / Nucleofugality / Inductive effects / Hammond postulate
The leaving group abilities (nucleofugalities) of a series of
aliphatic carboxylates have been obtained by determining
the nucleofuge-specific parameters (Nf and sf) from solvolysis
rate constants of X,Y-substituted benzhydryl carboxylates in
a series of aqueous ethanol mixtures by applyication of the
linear free energy relationship (LFER) equation: logk = sf (Ef
+ Nf). These values can be employed to compare reactivities
of carboxylates with those of other leaving groups previously
included in the nucleofugality scale, and also to estimate the
solvolysis rates of various carboxylates. It is confirmed that
the inductive effect is the most important variable governing
the reactivities of halogenated carboxylates in solution.
Moreover, both the Hammett correlation and the solvolytic
activation parameters have revealed a strong influence of the
inductive effect on the nucleofugality of alkyl-substituted
carboxylates. The reaction constants (sf) indicate that carb-
oxylate substrates with weaker leaving groups solvolyze via
later, more carbocation-like, transition states, which is in ac-
cord with the Hammond postulate. In addition, due to the
weaker demand for solvation of transition states that produce
more strongly stabilized benzhydrylium ions, in which more
efficient charge delocalization occurs, the reaction constants
(sf) obtained with most of the leaving groups investigated
here increase as the polarity of the solvent decreases.
X,Y-substituted benzhydryl carboxylates (Scheme 1, be-
low) were chosen for the substrates because comprehensive
nucleofugality and electrofugality scales, developed on the
basis of solvolytic reactivity of benzhydryl derivatives, al-
ready exist.[4,6] By employing those scales it is possible to
calculate the rate of any SN1 reaction of a benzhydryl deriv-
ative in a given solvent, whereas for some other derivatives
solvolysis rates can be estimated semiquantitatively with the
aid of Mayr’s LFER Equation (1)[4,6]
Introduction
The solvolysis of carboxylates proceeds by two major
pathways: (1) addition of a solvent (nucleophile) to the
carbonyl carbon atom, followed by displacement of an
alcohol/phenol in the stepwise manner, and (2) first-order
heterolysis of the R–O bond in a weakly basic to acidic
medium followed by reaction with a solvent.[1,2] The latter
process occurs if stabilized carbocation intermediates are
produced in the heterolytic step [i.e., if an ester solvolyzes
in the SN1 manner to produce an electrofuge (carbocation)
and a nucleofuge (leaving group; LG) in the first, usually
rate-determining, step].[2]
logk (25 °C) = sf (Ef + Nf)
(1)
in which k is the first-order rate constant for the SN1 reac-
In our previous work we investigated the SN1 solvolytic tion and sf (slope of the logk vs. Ef correlation line) and Nf
behavior of substituted benzoates systematically and deter- (nucleofugality, the negative intercept of the correlation line
mined reactivities of about 90 different benzoates both by on the abscissa, which corresponds to the intercept on the
kinetic measurements and by correlation with barriers of ordinate divided by sf) are the nucleofuge-specific param-
the quantum chemical model reaction.[3] In this work we eters, whereas Ef is the electrofugality parameter.[4,6] Prede-
have chosen to examine the behavior of aliphatic carboxyl- fined parameters are sf = 1.00 for the chloride nucleofuge
ates in general in SN1 solvolysis. Our aim was to provide a in pure ethanol and Ef = 0.00 for the dianisylmethyl carb-
comprehensive insight into the influences of the substitu- enium ion. The reactivity of a given nucleofuge in a given
ents both on leaving group abilities (nucleofugalities) and solvent is thus defined with two variables: the slope param-
on the relative positions of the transition states on the reac- eter (sf) and the nucleofugality parameter (Nf), the product
tion coordinates. So far, systematic data relating to solvo- of which (sf ϫNf) corresponds to logk for solvolysis of its
lytic reactivities of aliphatic carboxylates exist only for tri- dianisylmethyl derivative at 25 °C.
fluoroacetates, heptafluorobutyrates, and, partially, for
acetates.[4,5]
Results and Discussion
[a] University of Zagreb, Faculty of Pharmacy and Biochemistry,
Ante Kovacˇic´a 1, 10000 Zagreb, Croatia
Kinetic Measurements
E-mail: okronja@pharma.hr; bdenegri@pharma.hr
http://www.pharma.unizg.hr/Odsjek.aspx?mhID=3&mvID=51
The series of X,Y-substituted carboxylates were prepared
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301574.
from the corresponding benzhydrols by the methods de-
Eur. J. Org. Chem. 2014, 1477–1486
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M. Matic´, B. Denegri, O. Kronja
FULL PAPER
scribed in the Experimental Section. The substrates 1–8 that poorer leaving groups produce larger reaction con-
(Scheme 1) were subjected to kinetic measurements. Solvol- stants (sf). The dependence of the slope parameter (sf) on
ysis rates were measured conductometrically in a series of reactivity is illustrated in Figure 2, in which the rates (logk)
aqueous ethanol mixtures either at 25 °C or at at least three of various dianisylmethyl carboxylates (1, X = Y = OCH3)
different temperatures and extrapolated to 25 °C. Details in 80% aq. ethanol are correlated with the corresponding
are given in Kinetic Methods (see Exp. Sect.). First-order sf values. This correlation, discussed in detail below, enables
rate constants are presented in Table 1 and activation pa- estimation of the nucleofugalities of poorer carboxylate
rameters in Table S1 in the Supporting Information.
leaving groups such as alkylated carboxylates (acetate, iso-
butyrate, and pivalate). In such cases we were only able to
measure the reaction rates of the dianisylmethyl derivatives
(Ef = 0.00) by conventional methods, because substrates
with poorer electrofuges (Ef Ͻ 0) solvolyze too slowly. With
the aid of the correlation presented in Figure 2, the sf pa-
rameters were estimated from the rate constants of dianisyl-
methyl pivalate, isobutyrate, and acetate, and the nucleo-
fugalities (Nf) were determined by use of Equation (1).
Those values are also included in Table 2.
Scheme 1. The heterolytic step in solvolysis of benzhydryl carboxyl-
ates.
In order to calculate the nucleofugality (Nf) and slope
parameters (sf) for the halogenated carboxylates and for-
mates indicated in Scheme 1 for the series of aqueous eth-
anol mixtures, logarithms of the first-order rate constants
were plotted against the corresponding electrofugalities.
Plots of logk against Ef for benzhydryl fluoroacetates are
given in Figure 1 (correlation lines obtained with other
carboxylates are shown in Figures S1–S6 in the Supporting
Information). Excellent linear correlations were obtained in
all cases, indicating both further applicability of Equation
(1) and reliability of the obtained nucleofugality data. The
nucleofuge-specific parameters obtained from the corre-
lation lines are presented in Table 2.
Figure 2. Correlation of sf values of some carboxylates against logk
(25 °C) for solvolyses of appropriate dianisylmethyl carboxylates in
80% ethanol. The values of logk and sf for trifluoroacetate and
heptafluorobutyrate are taken from ref.[5a] and ref.,[4] respectively.
Solvolytic Behavior of Carboxylates
The data presented in Tables 1 and 2 show that the reac-
tivity of carboxylates can vary considerably with the sub-
stituents introduced. Halogen atoms enhance the reactivity,
whereas bulky alkyl substituents decrease the rates signifi-
cantly. The reactivities of the aliphatic carboxylates exam-
ined thus vary over a range of more than six orders of mag-
nitude.
In Figure 3 the reactivities of the leaving groups deter-
mined in this work are compared with those of numerous
selected leaving groups on the nucleofugality scale. It can be
seen, for example, that the reactivities of monohalogenated
acetates are similar to those of alkyl carbonates, whereas
dihaloacetates solvolyze with rates similar to those of
phenyl carbonate. Further, trihalogenated acetates are al-
most one order of magnitude less reactive than neutral sulf-
ides generated in heterolysis of sulfonium ions. Figure 3 also
reveals that the solvolytic reactivities of alkyl-substituted
Figure 1. Plots of logk (25 °C) versus Ef for solvolyses of substi-
tuted benzhydryl fluoroacetates in aqueous ethanol solvents (v/v).
Ef parameters taken from ref.[4]
A comparison of the reactivities of the leaving groups carboxylates and benzoate are similar, whereas tosylate is
and the corresponding sf values in the same solvent reveals about twelve orders of magnitude more reactive than pival-
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Eur. J. Org. Chem. 2014, 1477–1486

Solvolytic Behavior of Aliphatic Carboxylates
Table 1. Solvolysis rate constants of different X,Y-substituted benzhydryl carboxylates in various solvents at 25°.
Carboxylate
Solvent[a]
Electrofuge
(X,Y)
k /s–1 [b]
Carboxylate
Solvent[a] Electrofuge
(X,Y)
k /s–1 [b]
Fluoroacetate
90E10W
4 (MeO, H)
3 (MeO, Me)
(6.86Ϯ0.10)ϫ10–5
(3.78Ϯ0.01)ϫ10–4
Dichloroacetate 80E20W 4 (MeO, H)
3 (MeO, Me)
(3.43Ϯ0.02)ϫ10–3
(1.89Ϯ0.03)ϫ10–2
(3.31Ϯ0.03)ϫ10–5
(4.15Ϯ0.05)ϫ10–4
(5.99Ϯ0.02)ϫ10–3
(3.18Ϯ0.01)ϫ10–2
(6.98Ϯ0.01)ϫ10–5
(8.18Ϯ0.05)ϫ10–4
(9.90Ϯ0.06)ϫ10–3
(4.84Ϯ0.05)ϫ10–2
(6.70Ϯ0.03)ϫ10–5
(1.41Ϯ0.01)ϫ10–4
(1.05Ϯ0.00)ϫ10–3
(1.20Ϯ0.01)ϫ10–2
2.06ϫ10–5[c]
2 (MeO, PhO) (1.23Ϯ0.01)ϫ10–3
1 (MeO, MeO) (9.83Ϯ0.05)ϫ10–3
70E30W 6 (Me, H)
5 (Me, Me)
4 (MeO, H)
3 (MeO, Me)
60E40W 6 (Me, H)
5 (Me, Me)
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
4 (MeO, H)
(1.55Ϯ0.01)ϫ10–4
(9.18Ϯ0.03)ϫ10–4
3 (MeO, Me)
2 (MeO, PhO) (2.59Ϯ0.02)ϫ10–3
1 (MeO, MeO) (1.93Ϯ0.04)ϫ10–2
4 (MeO, H)
3 (MeO, Me)
(2.95Ϯ0.02)ϫ10–4
(1.69Ϯ0.00)ϫ10–3
4 (MeO, H)
3 (MeO, Me)
Trifluoroacetate 90E10W 8 (H, H)
7 (F, H)
6 (Me, H)
5 (Me, Me)
Trichloroacetate 90E10W 8 (H, H)
7 (F, H)
2 (MeO, PhO) (4.11Ϯ0.03)ϫ10–3
1 (MeO, MeO) (3.05Ϯ0.05)ϫ10–2
4 (MeO, H)
3 (MeO, Me)
(5.46Ϯ0.03)ϫ10–4
(2.94Ϯ0.02)ϫ10–3
2 (MeO, PhO) (6.16Ϯ0.06)ϫ10–3
1 (MeO, MeO) (4.80Ϯ0.05)ϫ10–2
(3.83Ϯ0.01)ϫ10–5
(3.56Ϯ0.02)ϫ10–4
(4.53Ϯ0.02)ϫ10–3
(4.24Ϯ0.02)ϫ10–5
(8.49Ϯ0.01)ϫ10–5
(7.98Ϯ0.03)ϫ10–4
(9.48Ϯ0.01)ϫ10–3
(8.36Ϯ0.05)ϫ10–5
(1.66Ϯ0.00)ϫ10–4
(1.50Ϯ0.01)ϫ10–3
(1.72Ϯ0.01)ϫ10–2
(1.69Ϯ0.01)ϫ10–4
(3.26Ϯ0.02)ϫ10–4
(2.86Ϯ0.02)ϫ10–3
(3.05Ϯ0.03)ϫ10–2
1.73ϫ10–5[c]
Chloroacetate
Bromoacetate
Dichloroacetate
4 (MeO, H)
3 (MeO, Me)
(4.34Ϯ0.10)ϫ10–5
(2.09Ϯ0.05)ϫ10–4
6 (Me, H)
5 (Me, Me)
80E20W 8 (H, H)
7 (F, H)
6 (Me, H)
5 (Me, Me)
70E30W 8 (H, H)
7 (F, H)
6 (Me, H)
5 (Me, Me)
60E40W 8 (H, H)
7 (F, H)
2 (MeO, PhO) (6.99Ϯ0.01)ϫ10–4
1 (MeO, MeO) (5.34Ϯ0.08)ϫ10–3
4 (MeO, H)
3 (MeO, Me)
(8.03Ϯ0.05)ϫ10–5
(5.21Ϯ0.10)ϫ10–4
2 (MeO, PhO) (1.46Ϯ0.01)ϫ10–3
1 (MeO, MeO) (1.06Ϯ0.02)ϫ10–2
4 (MeO, H)
(1.47Ϯ0.01)ϫ10–4
(9.50Ϯ0.08)ϫ10–4
3 (MeO, Me)
2 (MeO, PhO) (2.30Ϯ0.05)ϫ10–3
1 (MeO, MeO) (1.63Ϯ0.02)ϫ10–2
4 (MeO, H)
(2.64Ϯ0.00)ϫ10–4
(1.60Ϯ0.01)ϫ10–3
6 (Me, H)
3 (MeO, Me)
5 (Me, Me)
2 (MeO, PhO) (3.20Ϯ0.05)ϫ10–3
Formate
90E10W 4 (MeO, H)
3 (MeO, Me)
1 (MeO, MeO) (2.47Ϯ0.03)ϫ10–2
(1.04Ϯ0.02)ϫ10–4
4 (MeO, H)
3 (MeO, Me)
(3.27Ϯ0.02)ϫ10–5
(2.18Ϯ0.02)ϫ10–4
2 (MeO, PhO) (3.67Ϯ0.07)ϫ10–4
1 (MeO, MeO) (2.77Ϯ0.01)ϫ10–3
2 (MeO, PhO) (7.37Ϯ0.01)ϫ10–4
1 (MeO, MeO) (5.02Ϯ0.07)ϫ10–3
80E20W 4 (MeO, H)
3 (MeO, Me)
(4.01Ϯ0.04)ϫ10–5
(2.68Ϯ0.03)ϫ10–4
4 (MeO, H)
(7.77Ϯ0.09)ϫ10–5
(4.77Ϯ0.05)ϫ10–4
2 (MeO, PhO) (7.68Ϯ0.09)ϫ10–4
3 (MeO, Me)
1 (MeO, MeO) (6.11Ϯ0.03)ϫ10–3
2 (MeO, PhO) (1.43Ϯ0.02)ϫ10–3
70E30W 4 (MeO, H)
3 (MeO, Me)
(8.47Ϯ0.08)ϫ10–5
(5.29Ϯ0.08)ϫ10–4
1 (MeO, MeO) (1.07Ϯ0.02)ϫ10–2
4 (MeO, H)
(1.46Ϯ0.01)ϫ10–4
(8.49Ϯ0.05)ϫ10–4
2 (MeO, PhO) (1.30Ϯ0.02)ϫ10–3
1 (MeO, MeO) (1.10Ϯ0.02)ϫ10–2
3 (MeO, Me)
2 (MeO, PhO) (2.21Ϯ0.03)ϫ10–3
60E40W 4 (MeO, H)
3 (MeO, Me)
(1.74Ϯ0.01)ϫ10–4
(1.03Ϯ0.01)ϫ10–3
1 (MeO, MeO) (1.65Ϯ0.01)ϫ10–2
4 (MeO, H)
3 (MeO, Me)
(2.61Ϯ0.02)ϫ10–4
(1.42Ϯ0.01)ϫ10–3
2 (MeO, PhO) (2.18Ϯ0.01)ϫ10–3
1 (MeO, MeO) (1.75Ϯ0.01)ϫ10–2
2 (MeO, PhO) (3.27Ϯ0.03)ϫ10–3
1 (MeO, MeO) (2.51Ϯ0.03)ϫ10–2
Isobutyrate
Pivalate
90E10W 1 (MeO, MeO) 1.36ϫ10–5[c]
80E20W 1 (MeO, MeO) 2.73ϫ10–5[c]
70E30W 1 (MeO, MeO) (3.32Ϯ0.03)ϫ10–5
60E40W 1 (MeO, MeO) (4.58Ϯ0.02)ϫ10–5
90E10W 1 (MeO, MeO) 4.73ϫ10–6[c]
80E20W 1 (MeO, MeO) 9.48ϫ10–6[c]
70E30W 1 (MeO, MeO) 1.35ϫ10–5[c]
60E40W 1 (MeO, MeO) 2.09ϫ10–5[c]
6 (Me, H)
5.64ϫ10–6[c]
5 (Me, Me)
4 (MeO, H)
3 (MeO, Me)
6 (Me, H)
(7.88Ϯ0.10)ϫ10–5
(1.56Ϯ0.01)ϫ10–3
(8.87Ϯ0.08)ϫ10–3
1.77ϫ10–5[c]
5 (Me, Me)
(2.05Ϯ0.01)ϫ10–4
[a] Binary solvents are on a volume/volume basis at 25 °C. E = ethanol, W = water. [b] Average rate constants from at least three runs
performed at 25 °C. Errors shown are biased standard deviations. [c] Extrapolated from data at higher temperatures (Table S2 in the
Supporting Information) by use of the Eyring equation.
ate as a leaving group. The existence of the comprehensive the acidities of the corresponding carboxylic acids in solu-
nucleofugality scale thus enables comparisons of reactivities tion. The nucleofugalities of chloroacetate and bromoacet-
of leaving groups regardless of functional group, charge, or ate in all solvents, for example, are the same within the lim-
reactivity range.
its of experimental error, as are the corresponding pKa val-
The influences of substituents on the solvolytic reacti- ues (2.87 for chloroacetic acid vs. 2.90 for bromoacetic acid)
[7]
vities of carboxylates are essentially the same as those on
in water. We correlated the Gibbs free energies of acti-
Eur. J. Org. Chem. 2014, 1477–1486
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M. Matic´, B. Denegri, O. Kronja
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Table 2. Nucleofugality parameters Nf and sf for different carboxyl-
ates in various solvents.
[b]
[b]
Leaving group
Fluoroacetate
Solvent[a]
Nf
sf
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
–1.94Ϯ0.06
–1.72Ϯ0.01
–1.59Ϯ0.06
–1.47Ϯ0.11
–2.27Ϯ0.11
–1.95Ϯ0.04
–1.84Ϯ0.07
–1.75Ϯ0.14
–2.16Ϯ0.08
–1.93Ϯ0.01
–1.83Ϯ0.04
–1.72Ϯ0.09
–0.79Ϯ0.02
–0.59Ϯ0.04
–0.37Ϯ0.04
–0.24Ϯ0.06
1.19Ϯ0.08
0.84Ϯ0.04
1.21Ϯ0.02
1.46Ϯ0.02
1.70Ϯ0.02
–2.41Ϯ0.07
–2.13Ϯ0.03
– 1.96Ϯ0.08
– 1.87Ϯ0.12
–3.79
1.04Ϯ0.02
1.00Ϯ0.01
0.96Ϯ0.02
0.92Ϯ0.04
1.01Ϯ0.03
1.01Ϯ0.01
0.97Ϯ0.02
0.93Ϯ0.04
1.05Ϯ0.03
1.02Ϯ0.01
0.98Ϯ0.01
0.94Ϯ0.03
0.97Ϯ0.01
0.91Ϯ0.01
0.90Ϯ0.01
0.85Ϯ0.01
0.86Ϯ0.02
0.90Ϯ0.01
0.90Ϯ0.01
0.89Ϯ0.01
0.87Ϯ0.01
1.06Ϯ0.02
1.04Ϯ0.01
1.01Ϯ0.03
0.95Ϯ0.04
1.15
Chloroacetate
Bromoacetate
Dichloroacetate 90E10W
80E20W
70E30W
60E40W
Trifluoroacetate 90E10W
Trichloroacetate 90E10W
80E20W
Figure 3. Nucleofugalities of some aliphatic carboxylates in 80%
ethanol relative to nucleofugalities of some selected leaving groups
70E30W
60E40W
(shaded; data for a, b, c, and d are taken from ref.[17], ref.[3], ref.[4]
and ref.[18], respectively).
,
Formate
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
90E10W
80E20W
70E30W
60E40W
Acetate[c]
Isobutyrate[c]
Pivalate[c]
–3.61
–3.60
–3.63
–4.16
–3.97
–4.11
–4.25
–4.44
1.12
1.06
1.00
1.17
1.15
1.09
1.02
1.20
–4.29
–4.43
–4.54
1.17
1.10
1.03
[a] Binary solvents are v/v at 25 °C. E = ethanol, W = water. [b] The
correlation plots are shown in the Supporting Information. Errors
shown are standard errors. [c] sf values were estimated from the
sf/logk correlations of dianisylmethyl carboxylates (Figure 2 and
Figures S7–S9 in the Supporting Information).
vation (obtained from logk values of dianisylmethyl carb-
oxylates determined here) with the standard free energies
for dissociations of the corresponding carboxylic acids in
water (ΔG°; calculated from literature pKa values),[7] and
found a reasonably good fit. The correlation line for solvol-
ysis in 80% ethanol is presented in Figure 4. Accordingly,
the relative reactivities in the series of carboxylates are de-
termined with the relative stabilities of the carboxylate
anions formed in heterolysis rather than with the Marcus
Figure 4. Correlation of experimentally determined free energies of
activation (kcalmol–1) for solvolyses of dianisylmethyl carboxylates
in 80% ethanol at 25 °C against standard free energies (kcalmol–1)
for dissociation of the corresponding carboxylic acids in water. Ref-
erences for literature pKa data are given in the Supporting Infor-
mation.
intrinsic barriers; this implies that the solvolytic behavior of different carboxylate anion/H+ pairs are closer in energy
compounds of this class is in accord with the Hammond– than the transition states of the corresponding benzhydryl
Leffler principle, and consequently that the Hammond– carboxylates in the series: that is, ΔΔG°i,j (H-carboxylates)
Leffler coefficient is 0 Ͻ α Ͻ 1 (α = ΔΔG‡/ΔΔG°).
Ͻ ΔΔG‡ (1-carboxylate). If the above consideration relat-
i,j
Interestingly, the slope of the ΔG‡ versus ΔG° line in Fig- ing to the Hammond–Leffler coefficient is borne in mind,
ure 4 is considerably more than unity. The slope of 1.23, it is evident that the differences between the free energy
obtained on correlating ΔG‡ for heterolysis of the benzhy- levels of the carboxylate anion/benzhydrylium ion pairs (in-
dryl carboxylates with ΔG° for dissociation of the corre- termediates in solvolysis) and the corresponding carboxyl-
sponding carboxylate acids (H-carboxylates) indicates that ate anion/H+ pairs are even larger, and so ΔΔG°i,j (H-carb-
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Solvolytic Behavior of Aliphatic Carboxylates
oxylates) ϽϽ ΔΔG°i,j (1-carboxylate). This observation in- aqueous ethanol and in 90% aqueous ethanol is 8.0,
dicates that expansion of the range of relative Lewis basicit- whereas that of the substrate 1-fluoroacetate (X = Y =
ies of the carboxylate anions occurs if the proton counter- OMe; Ef = 0) in the same solvents is only 4.9. The conver-
ion is replaced with the benzhydrylium ions.
gence of the logk versus Ef plots towards higher electrofu-
galities has been explained in terms of diminished demand
for solvation in transition states for substrates (i.e., electro-
fuges) in which the positive charge is more delocalized, as
in, for example, dianisylmethyl derivatives.[8,10] Conse-
Variation in the Reaction Constant (sf)
Fine differences in the solvolytic behavior of the carb- quently, Grunwald–Winstein plots for solvolysis of series
oxylates due to structural diversity can be demonstrated by of carboxylates with the same leaving group and different
comparison of the slope parameters of the logk versus Ef benzhydrylium electrofuges yield electrofuge-dependent m
lines (Table 2). It has already been shown on several oc- values.[8] Grunwald–Winstein plots for solvolysis of 1, 2, 3,
casions that the fundamentals of the Ef and sf parameters and 4 fluoroacetates, for example, with use of the most ap-
are essentially the same as those for the σ+ and ρ+ param- propriate solvent ionizing power scale for carboxylates,
eters, respectively, of the Hammett–Brown correlation (ρ+ ≈ based on ferrocenylmethyl acetate (YOAc),[5e] gave mOAc val-
–4.4sf).[6,8] Even though Equation (1) is so far mostly lim- ues of 0.62, 0.64, 0.81, and 0.82, respectively. This implies
ited to benzhydryl[4] and trityl[9] derivatives, its advantage that the m value can vary in similar compounds that solvo-
over the Hammett–Brown correlation is that fine effects lyze by the same mechanism (SN1), due to variations in elec-
that change the trends and values of the reaction constant trostatic solvation effects of an electrofuge.[8]
(sf parameter) can be observed due to exceptionally good
Unlike their less reactive counterparts, more reactive
correlations between logk and Ef.[8]
carboxylates (e.g., trichloroacetate, trifluoroacetate,[4] and
Two major trends observed with the slope parameters heptafluorobutyrate[4]) produce almost parallel lines over
can be summarized as follows. Firstly, less reactive carb- the series of aqueous ethanol solvent mixtures (i.e., the
oxylates produce steeper logk versus Ef lines (larger reac- slope parameters in the series of solvents differ only within
tion constant sf) than more reactive ones (Table 2, Fig- the limits of experimental error). It seems that increasing
ure 2). Secondly, less reactive carboxylates produce logk solvent polarity in a series of binary mixtures increases the
versus Ef lines with slopes that decrease as the polarity of solvolysis rates of these benzhydryl carboxylates by the
the solvent increases, whereas more reactive carboxylates same factor (Figure S4 in the Supporting Information,
yield lines with the same slopes (within the limits of experi- Table 2, ref.[4]).
mental error) over the series of aqueous ethanol mixtures.
The consequence of such behavior is that the decreasing
As shown in Figure 2, in 80% ethanol, the slope param- trend in the nucleofugalities with decreasing solvent po-
eter decreases by roughly about 0.05 if the reactivity of a larity (in a given series of aqueous solvents) is less pro-
substrate increases by one order of magnitude. Because the nounced for less reactive carboxylates. For the most reactive
reaction constants (sf) for a series of related compounds heptafluorobutyrate,[4] trifluoroacetate,[4] and trichloro-
indicate the degrees of positive charge developed on the re- acetate (Table 2), for example, the difference in Nf values
action centers in the TSs, an increase in the sf parameter on between 60% and 90% ethanol is about 0.9 units, whereas
going to less reactive leaving groups can be explained if a for less reactive monohalogenated acetates and formate it is
shift of the transition state towards a carbocation-like struc- about 0.5 units. It is therefore not surprising that Nf values
ture is considered. Less reactive carboxylates in the series for the least reactive alkyl carboxylates do not vary signifi-
solvolyze over the later transition state on the reaction co- cantly with changing solvent polarity (Table 2).
ordinate, in which the cleavage of the C–O bond is more
advanced, the charge is more separated, and the reaction
center bears more positive charge. This behavior is in ac-
cord with the Hammond postulate.
Effect of Substituents on Reactivity
It has been shown earlier that for some leaving groups
The acidity of an aliphatic carboxylic acid is mainly de-
the slope parameter sf decreases as the polarity of solvent termined by inductivity and polarizability.[11] In water (and
increases, similarly to the trend shown in Figure 1.[8,10] If it other protic solvents) the inductive effects of substituents
is borne in mind that the logk versus Ef correlation lines on the carboxylate moiety and solvation effects are expected
are obtained with substrates that have the same leaving to be the determining variables, whereas in the gas phase it
group but different electrofuges, this phenomenon shows is the polarizability.[12] In water, for example, fluoroacetic
that in some cases substrates with more reactive electro- acid has the lowest pKa of the monohalogenated acetic ac-
fuges are less sensitive to the solvent change than substrates ids,[7] whereas in the gas phase bromoacetic acid is stronger,
with less reactive electrofuges. Such behavior has also been due to more polarizable large bromine, which, in the ab-
observed with less reactive carboxylates (dichloroacetate, sence of solvent, is more efficient than the smaller fluorine
fluoroacetate, chloroacetate, bromoacetate, and formate, in spreading out the generated electron density over the
Table 2, Figures S1–S6 in the Supporting Information). The anion.[12,13] Similarly, the sizes of unsubstituted alkyl
ratio between the solvolysis rate constants of, for example, groups on the carboxylate moiety influence the acidity dif-
4-fluoroacetate (X = OMe, Y = H, Ef = –2.09) in 60% ferently. In the gas phase, carboxylic acids with bulky sub-
Eur. J. Org. Chem. 2014, 1477–1486
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1481

M. Matic´, B. Denegri, O. Kronja
FULL PAPER
stituents are stronger acids than those with small alkyl ity of alkyl substituents in anions, which in the gas phase is
groups,[12] whereas in water carboxylic acids with bulky the major stabilization effect, is overcome in solution by
alkyl groups are weaker acids.[7]
solvation effects, and inversion of the acidity occurs. Thus,
We have examined the major stabilizing effects of the although the enthalpies of formic and acetic acids for disso-
substituents in solvolysis of carboxylates. Each additional ciation in water are almost the same, formic acid is a notice-
halogen atom introduced onto the carboxylate component ably stronger acid, due to a more favorable entropy of
of a substrate enhances the reaction rate because of the dissociation.[11]
more pronounced negative inductive effect of the substitu-
Although a similar interpretation is consistent with the
ent (Tables 1 and 2). Knowing that a substituent in the meta order of the solvolytic reactivities of benzhydryl alkyl carb-
position on the aromatic ring influences the substrate solvo- oxylates (Tables 1 and 2), the activation parameters (see
lytic reactivity only through the inductive effects,[3] and that Table S1 in the Supporting Information) show that it is not
Hammett σmeta parameters empirically describe inductivity possible to distinguish the contributions of solvation and
best, we plotted the solvolysis rates of the substituted diani- inductive effects to the stabilities of the carboxylate anions
sylmethyl acetates against the sums of the Hammett σmeta in the TSs, because changes in both activation parameters
values (Figure 5).
contribute to the decreases in reactivity with increasing
bulkiness of the alkyl substituents. Because of changes in
the enthalpies of activation it can be concluded that the
inductive effect is to some extent operative in all cases. The
ΔΔH‡ value for solvolysis of dianisylmethyl acetate and for-
mate, for example, is 1.2 kcalmol–1, and TΔΔS‡ is
–1.2 kcalmol–1. The pivalate/formate pair yields ΔΔH‡
=
2.1 kcalmol–1 and TΔΔS‡ = –1.7 kcalmol–1. Similar behav-
ior is observed with both series of the halogenated benz-
hydryl carboxylates (mono- and trisubstituted), for which
the inductive effect is considered to be a dominant stabiliza-
tion effect in anions.[11] Moreover, in the Hammett corre-
lation presented in Figure 5, the decrease in reactivity in the
alkyl-substituted carboxylates correlates fairly well with the
positive inductive effect of the alkyl substituents contrib-
uted through Σσ of the methyl groups. It thus appears that
the inductive influence of the alkyl substituents, which op-
erates in the same direction as solvation effects, cannot be
excluded as a variable that contributes to relative reactivities
of the alkyl-substituted carboxylates. The intrinsic polariz-
Figure 5. Plot of logk for solvolyses of dianisylmethyl acetates in
80% ethanol at 25 °C against the sums of σmeta values (σmeta values
were taken from ref.[1] The values for logk for trifluoroacetate and
acetate were taken from ref.[5a] and ref.[5d], respectively.).
The obtained correlation is exceptionally good (r = ability effect of a substituent, which implies a redistribution
0.993), confirming that the inductive effects are the major of the electron density from the reaction center, is sup-
rate-determining variables in the case of the aliphatic carb- pressed by the electrostatic solvation effects, resulting in an
oxylates studied here. If it is borne in mind that the sums increase in the electron density on the carboxylate moiety of
of σmeta values have been included in the correlation for di- an anion. Consequently, it appears that the inductive effect
and trisubstituted acetates, it appears that the influence of becomes the major variable that determines relative reactiv-
the substituents on reactivity is additive: if the same substit- ities of the aliphatic carboxylates in solution.
uent is once again introduced into the substituted carboxyl-
ate, the impact on reactivity is the same as that of the pre-
vious one (i.e., the effect of the next introduced substituent
does not depend on existing substituents on the carboxylate
Conclusions
moiety). Mono-, di-, and trichloroacetates, for example, lie
on the correlation line as well as the acetate, isobutyrate heterolytic reactivities of simple aliphatic carboxylates are
(dimethylacetate), and pivalate (trimethylacetate). defined here by determining the magnitudes of the nucleo-
The contributions of the leaving groups to the overall
It is widely accepted that the controlling force in ordering fuge-specific parameters Nf and sf. It is now possible to
the acidity of alkyl-substituted carboxylic acids in aqueous compare the abilities of the carboxylates with those of other
solutions (as well as that of alcohols) is the steric hindrance leaving groups included in the most comprehensive nucleo-
to solvation of carboxylate anions with larger alkyl groups fugality scale. Halogen and alkyl substituents on aliphatic
(i.e., more heavily substituted acids are weaker).[11,12,14] The carboxylates alter leaving group reactivities by a range of
demand of carboxylate anions with bulkier substituents for more than six orders of magnitude (six Nf value units),
increasing organization of solvent molecules is manifested mostly due to inductive effects of the substituents intro-
through the more unfavorable entropy of solvation for the duced as indicated both by the Hammett correlation and
anions, and consequently the more unfavorable overall en- by the solvolytic activation parameters. So far, the most re-
tropy of dissociation.[15] In this way the intrinsic polarizabil- active carboxylate for which nucleofugalities in various sol-
1482
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1477–1486

Solvolytic Behavior of Aliphatic Carboxylates
4-Methoxy-4Ј-phenoxybenzhydryl Fluoroacetate: This compound
was obtained from 4-methoxy-4Ј-phenoxybenzhydrol (0.70 g,
2.3 mmol), pyridine (0.55 g, 6.9 mmol), and fluoroacetyl chloride
(0.29 g, 3.0 mmol); yield 0.60 g, 71.4%. 1H NMR (300 MHz,
CDCl3, 20 °C): δ = 3.79 (s, 3 H, ArOCH3), 4.90 (d, J = 47.0 Hz, 2
H, CH2F), 6.86–7.35 (m, 1 H, Ar2CH + 13 H, ArH) ppm. 13C
vents have been quantitatively determined is heptafluoro-
butyrate, whereas pivalate is the poorest leaving group. The
solvolytic behavior of the carboxylates investigated here in-
dicates that relative reactivities in a series of substrates with
the same electrofuge are determined by the relative stabili-
ties of the carboxylate anions generated in heterolytic C-
carboxylate bond cleavage. Moreover, reaction constants
(sf) confirm that substrates with less reactive leaving groups
solvolyze via more product-like transition states than sub-
strates with more reactive leaving groups (Hammond).
Finally, from the nucleofuge-specific parameters of the
11 aliphatic carboxylate leaving groups, the rate of any cor-
responding electrofuge-carboxylate substrate can be esti-
mated by use of Equation (1).
1
NMR (75 MHz, CDCl3, 20 °C): δ = 55.5 (ArOCH3), 77.0 (d, JC,F
= 59.1 Hz, CH2-F), 79.1 (Ar2CH), 114.2, 118.7, 119.4, 123.8, 128.8,
2
130.0, 131.5, 134.3, 156.9, 157.5, 159.7, 167.0 (Ar), 167.2 (d, JC,F
= 21.9 Hz, O=C-CH2F) ppm. HRMS (MALDI-TOF/TOF): calcd.
for C22H19O4F [M + K]+ 405.0898; found 405.0906.
4,4Ј-Dimethoxybenzhydryl Fluoroacetate: This compound was ob-
tained from 4,4Ј-dimethoxybenzhydrol (0.50 g, 2.1 mmol), pyridine
(0.50 g, 6.3 mmol), and fluoroacetyl chloride (0.26 g, 2.7 mmol);
1
yield 0.40 g, 64.5%. H NMR (300 MHz, CDCl3, 20 °C): δ = 3.78
(s, 6 H, ArOCH3), 4.89 (d, J = 47.0 Hz, 2 H, CH2F), 6.87 (d, J =
8.8 Hz, 4 H, ArH), 6.96 (s, 1 H, Ar2CH), 7.26 (d, J = 8.9 Hz, 4 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ = 55.5 (Ar-
Experimental Section
1
OCH3), 77.1 (d, JC,F = 68.0 Hz, CH2-F), 79.1 (Ar2CH), 114.1,
Substrate Preparation: 4-Fluorobenzhydrol, 4-methylbenzhydrol, 4-
methoxybenzhydrol, and 4,4Ј-dimethoxybenzhydrol were prepared
by reduction of the commercially available substituted benzophen-
ones with sodium borohydride in methanol.
2
128.7, 131.8, 159.6, 167.0 (Ar), 167.2 (d, JC,F = 21.9 Hz, O=C-
CH2F) ppm. HRMS (MALDI-TOF/TOF): calcd. for C17H17O4F
[M + K]+ 343.0742; found 343.0750.
General Procedure for the Synthesis of Benzhydryl Chloroacetates:
The procedure for chloroacetates was almost the same as for fluo-
roacetates, except that chloroacetic acid anhydride was used instead
of the fluoroacetyl chloride and reactants were used in different
ratios than for fluoroacetates (appropriate benzhydrol/pyridine/
chloroacetic acid anhydride 1.0:2.0:4.0). All chloroacetates were ob-
tained as pale yellow oils (yields 71.0–86.6%).
4-Phenoxybenzhydrol, 4-methoxy-4Ј-methylbenzhydrol, and 4-
methoxy-4Ј-phenoxybenzhydrol were prepared by the procedure
given in ref.[16]
General Procedure for the Synthesis of Benzhydryl Fluoroacetates: A
solution of fluoroacetyl chloride (2.7 mmol) in anhydrous benzene
(10 mL) was added dropwise to a previously prepared stirred solu-
tion of the appropriate benzhydrol (2.1 mmol) and pyridine
(6.3 mmol) in anhydrous benzene (30 mL). The reaction mixture
was stirred under argon at ambient temperature for 12 h. Precipi-
tated pyridinium chloride was removed by filtration, and the excess
of pyridine was removed with hydrochloric acid (10%). The benz-
ene layer was separated and washed with water. After drying over
anhydrous sodium sulfate, benzene was evaporated in vacuo. 4-
Methoxy-4Ј-methylbenzhydryl fluoroacetate was obtained as white
crystals and the other fluoroacetates were obtained as pale yellow
oils (yield 64.5–83.3%).
4-Methoxybenzhydryl Chloroacetate: This compound was obtained
from 4-methoxybenzhydrol (0.50 g, 2.3 mmol), pyridine (0.73 g,
9.2 mmol), and chloroacetic acid anhydride (0.75 g, 4.6 mmol);
yield 0.57 g, 86.6%. 1H NMR (300 MHz CDCl3 20 °C): δ = 3.77
(s, 3 H, Ar-OCH3), 4.12 (s, 2 H, O=C-CH2Cl), 6.87 (d, J = 8.8 Hz,
2 H, ArH), 6.91 (s, 1 H, Ar2CH), 7.25–7.34 (m, 7 H, ArH) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 41.5 (O=C-CH2Cl), 55.6
(ArOCH3), 78.8 (Ar2CH), 114.3, 127.2, 128.4, 128.9, 129.2, 131.8,
139.9, 159.9 (Ar), 166.7 (C=O) ppm. HRMS (MALDI-TOF/TOF):
calcd. for C16H15O3Cl [M + K]+ 329.0341; found 329.0334.
4-Methoxybenzhydryl Fluoroacetate: This compound was obtained
from 4-methoxybenzhydrol (0.70 g, 3.3 mmol), pyridine (0.78 g,
9.9 mmol), and fluoroacetyl chloride (0.41 g, 4.3 mmol); yield
4-Methoxy-4Ј-methylbenzhydryl Chloroacetate: This compound
was obtained from 4-methoxy-4Ј-methylbenzhydrol (0.50 g,
2.2 mmol), pyridine (0.70 g, 8.8 mmol), and chloroacetic acid anhy-
dride (0.75 g, 4.4 mmol); yield 0.54 g, 80.6%. 1H NMR (300 MHz,
CDCl3, 20 °C): δ = 2.33 (s, 3 H, Ar-CH3), 3.78 (s, 3 H, ArOCH3),
4.12 (s, 2 H, O=C-CH2Cl), 6.85–6.89 (m, 1 H, Ar2CH + 2 H,
CH3O-ArH), 7.14–7.28 (m, 6 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3, 20 °C): δ = 21.5 (ArCH3), 41.5 (O=C-CH2Cl), 55.6 (Ar-
OCH3), 78.8 (Ar2CH), 114.3, 127.3, 129.0, 129.6, 132.0, 136.9,
138.3, 159.8 (Ar), 166.7 (C=O) ppm. HRMS (MALDI-TOF/TOF):
calcd. for C17H17O3Cl [M + Na]+ 327.0758; found 327.0749.
1
0.75 g, 83.3%. H NMR (300 MHz, CDCl3, 20 °C): δ = 3.78 (s, 3
H, ArOCH3), 4.91 (d, J = 47.0 Hz, 2 H, CH2F), 6.87 (d, J = 8.8 Hz,
4 H, ArH), 6.99 (s, 1 H, Ar2CH), 7.25–7.35 (m, 7 H, ArH) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 55.6 (ArOCH3), 77.4 (d,
1JC,F = 85.8 Hz, CH2-F), 79.2 (Ar2CH), 114.3, 127.2, 128.4, 128.9,
2
129.2, 131.8, 139.8, 159.9, 167.2 (Ar), 167.3 (d, JC,F = 21.9 Hz,
O=C-CH2F) ppm. HRMS (MALDI-TOF/TOF): calcd. for
C16H15O3F [M + K]+ 313.0637; found 313.0629.
4-Methoxy-4Ј-methylbenzhydryl Fluoroacetate: This compound was
obtained from 4-methoxy-4Ј-methylbenzhydrol (0.70 g, 3.1 mmol), 4-Methoxy-4Ј-phenoxybenzhydryl Chloroacetate: This compound
pyridine (0.74 g, 9.3 mmol), and fluoroacetyl chloride (0.39 g,
was obtained from 4-methoxy-4Ј-phenoxybenzhydrol (0.50 g,
4.0 mmol); yield 0.69 g, 77.5%, m.p. 79.4–80.9 °C. 1H NMR 1.6 mmol), pyridine (0.51 g, 6.4 mmol), and chloroacetic acid anhy-
(300 MHz, CDCl3, 20 °C): δ = 2.33 (s, 3 H, ArCH3), 3.78 (s, 3 H, dride (0.55 g, 3.2 mmol); yield 0.44 g, 71.0%. 1H NMR (300 MHz,
ArOCH3), 4.90 (d, J = 47.0 Hz, 2 H, CH2F), 6.87 (d, J = 8.8 Hz,
CDCl3, 20 °C): δ = 3.78 (s, 3 H, ArOCH3), 4.12 (s, 2 H, O=C-
CH2Cl), 6.86–7.35 (m, 1 H, Ar2CH + 2 H, ArH + 11 H, Ar) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 41.5 (O=C-CH2Cl), 55.7
4 H, ArH), 6.97 (s, 1 H, Ar2CH), 7.14–7.28 (m, 6 H, ArH) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 21.3 (ArCH3), 55.5 (Ar-
1
OCH3), 77.2 (d, JC,F = 82.1 Hz, CH2-F), 79.1 (Ar2CH), 114.1, (ArOCH3), 78.4 (Ar2CH), 114.4, 118.9, 119.6, 124.0, 128.9, 129.0,
127.1, 128.9, 129.4, 131.8, 136.7, 138.1, 159.7, 167.0 (Ar), 167.2 (d,
2JC,F = 21.9 Hz, O=C-CH2F) ppm. HRMS (MALDI-TOF/TOF): Collection of HRMS data or elemental analysis were not possible
calcd. for C17H17O3F [M + K]+ 327.0793; found 327.0800.
for this compound, due to its limited stability.
130.2, 131.8, 134.5, 157.1, 157.7, 159.9 (Ar), 166.8 (C=O) ppm.
Eur. J. Org. Chem. 2014, 1477–1486
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1483

M. Matic´, B. Denegri, O. Kronja
FULL PAPER
4,4Ј-Dimethoxybenzhydryl Chloroacetate: This compound was ob-
tained from 4,4Ј-dimethoxybenzhydrol (0.50 g, 2.1 mmol), pyridine
(0.66 g, 8.4 mmol), and chloroacetic acid anhydride (0.72 g,
4.2 mmol); yield 0.48 g, 72.7%. 1H NMR (300 MHz, CDCl3,
General Procedure for the Synthesis of Benzhydryl Dichloroacetates:
The procedure was similar to that used for chloroacetates except
that dichloroacetyl chloride was used instead of the chloroacetic
acid anhydride and reactants were used in different ratios (appro-
20 °C): δ = 3.74 (s, 6 H, ArOCH3), 4.07 (s, 2 H, O=C-CH2Cl), 6.83 priate benzhydrol/pyridine/dichloroacetyl chloride 1.0:3.0:1.2). 4-
(d, J = 8.8 Hz, 4 H, ArH), 6.84 (s, 1 H, Ar2CH), 7.22 (d, J =
Methylbenzhydryl dichloroacetate was obtained as white crystals,
whereas the others were obtained as pale yellow oils (yield 73.1–
8.6 Hz, 4 H, ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ =
41.4 (O=C-CH2Cl), 55.5 (ArOCH3), 78.4 (Ar2CH), 114.1, 128.7, 87.8%).
131.8, 159.6 (Ar), 166.6 (C=O) ppm. HRMS (MALDI-TOF/TOF):
4-Methylbenzhydryl Dichloroacetate: This compound was obtained
calcd. for C17H17O4Cl [M + (e–)]: 320.0810; found 320.0809.
from 4-methylbenzhydrol (0.50 g, 2.5 mmol), pyridine (0.59 g,
7.5 mmol), and dichloroacetyl chloride (0.44 g, 3.0 mmol); yield
0.57 g, 73.1%, m.p. 52.6–53.7 °C. 1H NMR (300 MHz, CDCl3,
20 °C): δ = 2.33 (s, 3 H, Ar-CH3), 6.00 (O=C-CHCl2), 6.89 (s, 1 H,
Ar2CH), 7.17 (d, J = 7.7 Hz, 2 H, ArH), 7.24–7.36 (m, 7 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ = 21.5 (ArCH3),
64.9 (O=C-CHCl2), 80.4 (Ar2CH), 127.3, 127.5, 128.7, 129.0, 129.7,
136.0, 138.7, 139.1 (Ar), 163.8 (C=O) ppm. HRMS (MALDI-TOF/
TOF): calcd. for C16H14O2Cl2 [M + K]+ 347.0002; found 347.0015.
General Procedure for the Synthesis of Benzhydryl Bromoacetates:
The procedure for bromoacetates was also almost the same as for
fluoroacetates except that bromoacetyl chloride was used instead
of the fluoroacetyl chloride and reactants were used in different
ratios than for fluoroacetates (appropriate benzhydrol/bromoacetyl
chloride/pyridine 1.0:1.0:2.5). All bromoacetates were obtained as
pale yellow oils (yield 48.7–60.0%).
4-Methoxybenzhydryl Bromoacetate: This compound was obtained
from 4-methoxybenzhydrol (0.50 g, 2.3 mmol), pyridine (0.46 g,
5.8 mmol), and bromoacetyl chloride (0.37 g, 2.4 mmol); yield
4,4Ј-Dimethylbenzhydryl Dichloroacetate: This compound was ob-
tained from 4,4Ј-dimethylbenzhydrol (0.50 g, 2.4 mmol), pyridine
(0.57 g, 7.2 mmol), and dichloroacetyl chloride (0.43 g, 2.9 mmol);
1
0.40 g, 51.3%. H NMR (300 MHz, CDCl3, 20 °C): δ = 3.78 (s, 3
1
yield 0.60 g, 78.9%. H NMR (300 MHz, CDCl3, 20 °C): δ = 2.29
H, ArOCH3), 4.13 (O=C-CH2Br), 6.87 (d, J = 8.8 Hz, 2 H, ArH),
6.91 (s, 1 H, Ar2CH), 7.25–7.35 (m, 7 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3, 20 °C): δ = 41.5 (O=C-CH2Br), 55.6 (ArOCH3),
78.8 (Ar2CH), 114.3, 127.2, 128.4, 128.9, 129.2, 131.8, 139.8, 159.9
(Ar), 166.7 (C=O) ppm. Collection of HRMS data or elemental
analysis were not possible for this compound, due to its limited
stability.
(s, 6 H, Ar-CH3), 5.96 (O=C-CHCl2), 6.83 (s, 1 H, Ar2CH), 7.12
(d, J = 8.0 Hz, 4 H, ArH), 7.20 (d, J = 8.1 Hz, 4 H, ArH) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 21.3 (ArCH3), 64.7 (O=C-
CHCl2), 80.3 (Ar2CH), 127.2, 129.5, 136.0, 138.4 (Ar), 163.6
(C=O) ppm. HRMS (MALDI-TOF/TOF): calcd. for C17H16O2Cl2
[M + K]+ 361.0159; found 361.0172.
4-Methoxybenzhydryl Dichloroacetate: This compound was ob-
tained from 4-methoxybenzhydrol (0.50 g, 2.3 mmol), pyridine
(0.55 g, 6.9 mmol), and dichloroacetyl chloride (0.41 g, 2.8 mmol);
4-Methoxy-4Ј-methylbenzhydryl Bromoacetate: This compound was
obtained from 4-methoxy-4Ј-methylbenzhydrol (0.50 g, 2.2 mmol),
pyridine (0.43 g, 5.5 mmol), and bromoacetyl chloride (0.35 g,
2.2 mmol); yield 0.37 g, 48.7%. 1H NMR (300 MHz, CDCl3,
20 °C): δ = 2.32 (s, 3 H, Ar-CH3), 3.77 (s, 3 H, Ar-OCH3), 4.11
(O=C-CH2Br), 6.84–6.88 (m, 1 H, Ar2CH + 2 H, ArH), 7.13–7.27
(m, 6 H, ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ = 21.5
(ArCH3), 41.5 (O=C-CH2Br), 55.6 (ArOCH3), 78.8 (Ar2CH),
114.3, 127.3, 129.0, 129.6, 132.0, 136.9, 138.3, 159.8 (Ar), 166.7
(C=O) ppm. Collection of HRMS data or elemental analysis were
not possible for this compound, due to its limited stability.
1
yield 0.62 g, 81.6%. H NMR (300 MHz, CDCl3, 20 °C): δ = 3.78
(s, 3 H, Ar-OCH3), 6.00 (O=C-CHCl2), 6.88 (d, J = 8.9 Hz, 2 H,
ArH), 6.89 (s, 1 H, Ar2CH), 7.23–7.36 (m, 7 H, ArH) ppm. 13C
NMR (75 MHz, CDCl3, 20 °C): δ = 55.64 (ArOCH3), 64.92 (O=C-
CHCl2), 80.28 (Ar2CH), 114.41, 127.17, 128.64, 128.97, 129.18,
131.06, 139.16, 160.09 (Ar), 163.77 (C=O) ppm. HRMS (MALDI-
TOF/TOF): calcd. for C16H14O3Cl2 [M + K]+ 362.9951; found
362.9952.
4-Methoxy-4Ј-methylbenzhydryl Dichloroacetate: This compound
was obtained from 4-methoxy-4Ј-methylbenzhydrol (0.50 g,
2.2 mmol), pyridine (0.52 g, 6.6 mmol), and dichloroacetyl chloride
(0.38 g, 2.6 mmol); yield 0.65 g, 87.8%. 1H NMR (300 MHz,
CDCl3, 20 °C): δ = 2.33 (s, 3 H, Ar-CH3), 3.78 (s, 3 H, Ar-OCH3),
5.99 (O=C-CHCl2), 6.86–6.88 (m, 1 H, Ar2CH + 2 H, ArH), 7.14–
7.28 (m, 6 H, ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ =
21.51 (ArCH3), 55.63 (ArOCH3), 64.95 (O=C-CHCl2), 80.29
(Ar2CH), 114.37, 127.24, 129.04, 129.65, 131.24, 136.23, 138.51,
160.02 (Ar), 163.79 (C=O) ppm. HRMS (MALDI-TOF/TOF):
calcd. for C17H16O3Cl2 [M + K]+ 377.0108; found 377.0110.
4-Methoxy-4Ј-phenoxybenzhydryl Bromoacetate: This compound
was obtained from 4-methoxy-4Ј-phenoxybenzhydrol (0.50 g,
1.6 mmol), pyridine (0.32 g, 4.1 mmol), and bromoacetyl chloride
(0.26 g, 1.7 mmol); yield 0.39 g, 55.7%. 1H NMR (300 MHz,
CDCl3, 20 °C): δ = 3.79 (s, 3 H, Ar-OCH3), 4.13 (O=C-CH2Br),
6.89 (d, J = 8.9 Hz, 2 H, ArH), 6.90 (s, 1 H, Ar2CH), 6.95–7.36
(m, 11 H, ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ = 41.5
(O=C-CH2Br), 55.6 (ArOCH3), 78.4 (Ar2CH), 114.4, 118.9, 119.6,
124.0, 128.7, 128.9, 130.2, 131.8, 134.5, 157.1, 157.6, 159.9 (Ar),
166.7 (C=O) ppm. LRMS (ESI+): m/z=426.1 [M + H]+. Collection
of HRMS data or elemental analysis were not possible for this
compound, due to its limited stability.
General Procedure for the Synthesis of Benzhydryl Trichloro-
acetates: The procedure for trichloroacetates, like that for di-
chloroacetates, is similar to that described above for chloroacetates
except that trichloroacetyl chloride was used instead of the chloro-
acetic acid anhydride and reactants were used in different ratios
4,4Ј-Dimethoxybenzhydryl Bromoacetate: This compound was ob-
tained from 4,4Ј-dimethoxybenzhydrol (0.50 g, 2.1 mmol), pyridine
(0.42 g, 5.3 mmol), and bromoacetyl chloride (0.33 g, 2.1 mmol);
1
yield 0.45 g, 60.0%. H NMR (300 MHz, CDCl3, 20 °C): δ = 3.79
(appropriate
benzhydrol/pyridine/trichloroacetyl
chloride
(s, 6 H, Ar-OCH3), 4.11 (O=C-CH2Br), 6.87 (d, J = 8.8 Hz, 4 H,
ArH), 6.88 (s, 1 H, Ar2CH), 7.26 (d, J = 8.4 Hz, 4 H, ArH) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 41.5 (O=C-CH2Br), 55.6
(ArOCH3), 78.6 (Ar2CH), 114.3, 128.9, 132.0, 159.8 (Ar), 166.7
(C=O) ppm. Collection of HRMS data or elemental analysis were
not possible for this compound, due to its limited stability.
1.0:1.3:3.0). All products were obtained as white crystals (yield
63.1–80.9%).
Benzhydryl Trichloroacetate: This compound was obtained from
benzhydrol (0.50 g, 2.7 mmol), pyridine (0.64 g, 8.1 mmol), and tri-
chloroacetyl chloride (0.64 g, 3.5 mmol); yield 0.72 g, 80.9%, m.p.
1484
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Eur. J. Org. Chem. 2014, 1477–1486

Solvolytic Behavior of Aliphatic Carboxylates
51.9–52.6 °C. 1H NMR (300 MHz, CDCl3, 20 °C): δ = 6.92 (s, 1
(Ar), 160.5 (C=O) ppm. HRMS (MALDI-TOF/TOF): calcd. for
H, Ar2CH), 7.31–7.40 (m, 10 H, ArH) ppm. 13C NMR (75 MHz, C16H16O3 [M – H]+ 255.1027; found 255.1026.
CDCl3, 20 °C): δ = 82.4 (Ar2CH), 127.4, 129.1, 138.6 (Ar), 161.2
4-Methoxy-4Ј-phenoxybenzhydryl Formate: This compound was
obtained from 4-methoxy-4Ј-phenoxybenzhydrol (0.50 g,
(C=O) ppm. HRMS (MALDI-TOF/TOF): calcd. for C15H11O2Cl3
[M + K]+ 366.9456; found 366.9466.
1.6 mmol); yield 0.38 g, 69.1%, m.p. 63.5–64.2 °C. 1H NMR
(300 MHz, CDCl3, 20 °C): δ = 3.79 (s, 3 H, Ar-OCH3), 6.89 (d, J
= 9.2 Hz, 2 H, ArH), 6.95–7.36 (m, 6 H, Ar2CH + ArH), 8.21 (s,
1 H, O=C-H) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ = 55.6
4-Fluorobenzhydryl Trichloroacetate: This compound was obtained
from 4-fluorobenzhydrol (0.50 g, 2.5 mmol), pyridine (0.59 g,
7.5 mmol), and trichloroacetyl chloride (0.59 g, 3.3 mmol); yield
0.65 g, 75.6%, m.p. 56.9–57.9 °C. 1H NMR (300 MHz, CDCl3, (ArOCH3), 76.3 (Ar2CH), 114.3, 118.9, 119.5, 123.9, 128.9, 130.1,
20 °C): δ = 6.91 (s, 1 H, Ar2CH), 7.06 (t, JH,F = 17.4 Hz, 2 H,
132.0, 134.8, 157.2, 157.5, 159.8 (Ar), 160.4 (C=O) ppm. HRMS
ArH), 7.34–7.39 (m, 7 H, ArH) ppm. 13C NMR (75 MHz, CDCl3,
(MALDI-TOF/TOF): calcd. for C21H18O4 [M + K]+ 373.0836;
2
20 °C): δ = 81.7 (Ar2CH), 115.1 (d, JC,F = 21.8 Hz), 127.2, 129.1, found 373.0831.
3
4
129.1, 129.5 (d, JC,F = 8.4 Hz), 134.4 (d, JC,F = 3.3 Hz), 138.3
4,4Ј-Dimethoxybenzhydryl Formate: This compound was obtained
from 4,4Ј-dimethoxybenzhydrol (0.50 g, 2.1 mmol); yield 0.35 g,
2
(ArH), 161.1 (C=O), 163.1 (d, JC,F = 248.1 Hz) ppm. HRMS
(MALDI-TOF/TOF): calcd. for C15H10O2FCl3 [M + K]+ 384.9362;
found 384.9355.
1
62.5%. H NMR (300 MHz, CDCl3, 20 °C): δ = 3.78 (s, 6 H, Ar-
OCH3), 6.87 (d, J = 8.8 Hz, 4 H, ArH), 6.94 (s, 1 H, Ar2CH), 6.35
(d, J = 8.8 Hz, 4 H, ArH), 8.19 (s, 1 H, O=C-H) ppm. 13C NMR
(75 MHz, CDCl3, 20 °C): δ = 55.6 (ArOCH3), 76.4 (Ar2CH), 114.2,
128.8, 132.3, 133.2, 159.7 (Ar), 160.5 (C=O) ppm. Collection of
4-Methylbenzhydryl Trichloroacetate: This compound was obtained
from 4-methylbenzhydrol (0.50 g, 2.5 mmol), pyridine (0.59 g,
7.5 mmol), and trichloroacetyl chloride (0.59 g, 3.3 mmol); yield
0.70 g, 80.5%, m.p. 45.3–46.2 °C. 1H NMR (300 MHz, CDCl3, HRMS data or elemental analysis were not possible for this com-
20 °C): δ = 2.34 (s, 3 H, Ar-OCH3), 6.90 (s, 1 H, Ar2CH), 7.16–
7.38 (m, 9 H, ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ =
21.4 (ArCH3), 82.2 (Ar2CH), 127.1, 127.3, 128.7, 128.9, 129.6,
135.4, 138.6, 138.8 (Ar), 161.0 (C=O) ppm. HRMS (MALDI-TOF/
TOF): calcd. for C16H13O2Cl3 [M
364.9872.
pound, due to its limited stability.
4,4Ј-Dimethoxybenzhydryl Isobutyrate: The procedure used for 4,4Ј-
dimethoxybenzhydryl isobutyrate was almost the same as for
fluoroacetates except that isobutyryl chloride was used instead of
the fluoroacetyl chloride. Reactants were used in the ratio 4,4Ј-
dimethoxybenzhydrol/pyridine/isobutyryl chloride 1.0:1.4:3.0. The
product was thus obtained as a pale-yellow oil from 4,4Ј-dimeth-
oxybenzhydrol (0.50 g, 2.1 mmol), pyridine (0.49 g, 6.2 mmol), and
isobutyryl chloride (0.31 g, 2.9 mmol); yield 0.52 g, 78.8%. 1H
NMR (300 MHz, CDCl3, 20 °C): δ = 1.19 [d, J = 7.0 Hz, 6 H,
-C(CH3)2], 2.56–2.70 (m, 1 H, O=C-CH-), 3.77 (s, 6 H, Ar-OCH3),
6.80 (s, 1 H, Ar2CH), 6.86 (d, J = 8.8 Hz, 4 H, ArH), 7.25 (d, J =
8.8 Hz, 4 H, ArH) ppm. 13C NMR (75 MHz, CDCl3, 20 °C): δ =
19.3 [CH(CH3)2], 34.6 [CH(CH3)2], 55.6 (ArOCH3), 76.3 (Ar2CH),
114.2, 128.7, 133.3, 159.5 (Ar), 176.3 (C=O) ppm. HRMS
(MALDI-TOF/TOF): calcd. for C19H22O4 [M + K]+ 353.115;
found 353.1161.
+
Na]+ 364.9873; found
4,4Ј-Dimethylbenzhydryl Trichloroacetate: This compound was ob-
tained from 4,4Ј-dimethylbenzhydrol (0.50 g, 2.4 mmol), pyridine
(0.57 g, 7.2 mmol), and trichloroacetyl chloride (0.56 g, 3.1 mmol);
yield 0.53 g, 63.1%, m.p. 52.3–53.7 °C. 1H NMR (300 MHz,
CDCl3, 20 °C): δ = 2.33 (s, 6 H, Ar-OCH3), 6.87 (s, 1 H, Ar2CH),
7.17 (d, J = 8.0 Hz, 4 H, ArH), 7.27 (d, J = 8.2 Hz, 4 H, ArH) ppm.
13C NMR (75 MHz, CDCl3, 20 °C): δ = 21.54 (ArCH3), 82.46
(Ar2CH), 127.35, 129.71, 135.80, 138.74 (Ar), 161.19 (C=O) ppm.
Collection of HRMS data or elemental analysis were not possible
for this compound, due to its limited stability.
General Procedure for the Synthesis of Benzhydryl Formates: The
appropriate benzhydrol (0.50 g) was dissolved in formic acid
(15 mL). After 1 min, benzene (20 mL) was added to the vigorously
stirred solution to stop the reaction. The benzene layer was sepa-
rated and washed with aqueous NaHCO3 and then with water. Af-
ter drying over anhydrous sodium sulfate, the benzene was evapo-
rated in vacuo. 4-Methoxy-4Ј-phenoxybenzhydryl formate was ob-
tained as white crystals, whereas the other compounds were ob-
tained as yellow oils (yield 62.5–80.4%).
4,4Ј-Dimethoxybenzhydryl Pivalate: 4,4Ј-Dimethoxybenzhydryl piv-
alate was prepared in a similar way as the above-described com-
pounds. Reactants were used in the ratio of 4,4Ј-dimethoxybenz-
hydrol/pyridine/trimethylacetyl chloride = 1.0:1.4:3.0 and the mix-
ture was stirred for 2 d under argon at ambient temperature.
Recrystallization from light petroleum ether afforded white crystals.
The compound was thus obtained from 4,4Ј-dimethoxybenzhydrol
(0.50 g, 2.1 mmol), pyridine (0.49 g, 6.2 mmol), and trimethylacetyl
chloride (0.35 g, 2.9 mmol); yield 0.56 g, 81.2%, m.p. 43.9–44.7 °C.
1H NMR (300 MHz, CDCl3, 20 °C): δ = 1.23 [s, 9 H, C(CH3)3],
3.78 (s, 6 H, Ar-OCH3), 6.76 (s, 1 H, Ar2CH), 6.86 (d, J = 8.7 Hz, 4
H, ArH), 7.24 (d, J = 8.5 Hz, 4 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3, 20 °C): δ = 27.5 [C(CH3)3], 39.2 [C(CH3)3], 55.6 (ArOCH3),
76.3 (Ar2CH), 114.1, 128.5, 133.40, 159.4 (Ar), 177.7 (C=O) ppm.
HRMS (MALDI-TOF/TOF): calcd. for C20H24O4 [M + Na]+
351.1572; found 351.1598.
4-Methoxybenzhydryl Formate: This compound was obtained from
4-methoxybenzhydrol (0.50 g, 2.3 mmol); yield 0.57 g, 70.2%. 1H
NMR (300 MHz, CDCl3, 20 °C): δ = 3.77 (s, 3 H, Ar-OCH3), 6.87
(d, J = 8.7 Hz, 2 H, ArH), 6.97 (s, 1 H, Ar2CH), 7.26–7.35 (m, 7
H, ArH), 8.20 (s, 1 H, O=C-H) ppm. 13C NMR (75 MHz, CDCl3,
20 °C): δ = 55.6 (ArOCH3), 76.7 (Ar2CH), 114.3, 127.3, 128.3,
128.9, 129.1, 132.1, 140.1, 159.8 (Ar), 160.5 (C=O) ppm. HRMS
(MALDI-TOF/TOF): calcd. for C15H14O3 [M + H]+ 243.1016;
found 243.1025.
All heptafluorobutyrates and trifluoroacetates were prepared by
the procedure described in ref.[5a] 4,4Ј-Dimethoxybenzhydryl acet-
ate was prepared by the procedure given in ref.[5d]
4-Methoxy-4Ј-methylbenzhydryl Formate: This compound was ob-
tained from 4-methoxy-4Ј-methylbenzhydrol (0.50 g, 2.2 mmol);
1
yield 0.45 g, 80.4%. H NMR (300 MHz, CDCl3, 20 °C): δ = 2.32
Kinetic Methods: Solvolysis rate constants were measured con-
(s, 3 H, Ar-CH3), 3.77 (s, 3 H, Ar-OCH3), 6.86 (d, J = 8.8 Hz, 2
ductometrically. Freshly prepared solvents (30 mL) were thermo-
H, ArH), 6.94 (s, 1 H, Ar2CH), 7.13–7.28 (m, 6 H, ArH) ppm. 13C statted (Ϯ0.1 °C) at a given temperature for several minutes prior
NMR (75 MHz, CDCl3, 20 °C): δ = 21.5 (ArCH3), 55.6 (ArOCH3), to addition of the substrate. Typically, the substrate (10–40 mg) was
76.6 (Ar2CH), 114.3, 127.3, 129.0, 129.6, 132.3, 137.2, 138.1, 159.8 dissolved in dichloromethane (0.10–0.15 mL) and injected into the
Eur. J. Org. Chem. 2014, 1477–1486
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1485

M. Matic´, B. Denegri, O. Kronja
FULL PAPER
[5] a) B. Denegri, O. Kronja, J. Org. Chem. 2009, 74, 5927–5933;
b) T. W. Bentley, K. Roberts, J. Chem. Soc. Perkin Trans. 2
1989, 1055–1060; c) D. Farcasiu, J. Jaehme, C. Rüchardt, J.
Am. Chem. Soc. 1985, 107, 5717–5722; d) B. Denegri, O.
Kronja, Croat. Chem. Acta 2010, 83, 223–226; e) D. N. Kevill,
A. R. Pinhas, J. Org. Chem. 1993, 58, 197–201.
[6] a) B. Denegri, A. Streiter, S. Juric´, A. R. Ofial, O. Kronja, H.
Mayr, Chem. Eur. J. 2006, 12, 1648–1656; b) Correction: B. De-
negri, A. Streiter, S. Juric´, A. R. Ofial, O. Kronja, H. Mayr,
Chem. Eur. J. 2006, 12, 5415–5415; c) B. Denegri, A. R. Ofial,
S. Juric´, A. Streiter, O. Kronja, H. Mayr, Chem. Eur. J. 2006,
12, 1657–1666.
solvent. Increases in the conductivity during solvolysis were moni-
tored automatically by means of a WTW LF 530 conductometer
and use of a Radiometer 2-pole Conductivity Cell (CDC641 T).
Individual rate constants were obtained by least-squares fitting of
the conductivity data to the first-order kinetic equation for three
to four half-lives. The rate constants were averaged from at least
three measurements. In order to achieve complete ionization of a
liberated acid a proton sponge base [1,8-bis(dimethylamino)-
naphthalene] and lutidine (= 2,6-dimethylpyridine) were added at
a range of concentrations for each given aqueous binary mixture
(presented in Table S3 in the Supporting information). Calibration
showed the linear response of conductivity in the presented ranges
of concentrations of the proton sponge base or lutidine and acids
liberated in the examined solvolyses.
[7] The pKa values taken from the literature and the corresponding
ΔG° values are listed in Table S4 in the Supporting Information
along with references.
[8] M. Matic´, S. Juric´, B. Denegri, O. Kronja, Int. J. Mol. Sci.
2012, 13, 2012–2024.
Supporting Information (see footnote on the first page of this arti-
cle): Solvolytic activation parameters, additional solvolysis rate
constants at various temperatures, correlations of logk versus Ef in
aq. ethanol solvents, sf versus logk correlations, 1H NMR, 13C
NMR, and COSY spectra.
[9] M. Horn, C. Metz, H. Mayr, Eur. J. Org. Chem. 2011, 6476–
6485.
[10] B. Denegri, O. Kronja, J. Phys. Org. Chem. 2009, 22, 495–503.
[11] E. V. Anslyn, D. A. Dougherty, Modern Physical Organic
Chemistry, University Science Books, Sausalito, California,
2006.
[12] G. Caldwell, R. Renneboog, P. Kebarle, Can. J. Chem. 1989,
Acknowledgments
67, 611–618.
[13] K. Hiraoka, R. Yamdagni, P. Kebarle, J. Am. Chem. Soc. 1973,
95, 6833–6835.
The authors gratefully acknowledge financial support of this re-
search by the Ministry of Science, Education and Sport of the Re-
public of Croatia and the University of Zagreb.
[14] J. I. Brauman, L. K. Blair, J. Am. Chem. Soc. 1970, 92, 5986–
5992.
[15] B. Wilson, R. Georgiadis, J. E. Bartmess, J. Am. Chem. Soc.
1991, 113, 1762–1766.
[1] T. H. Lowry, K. S. Richardson, Mechanism and Theory in Or-
ganic Chemistry, 3rd ed., Harper and Row, New York, 1987.
[2] M. Horn, H. Mayr, Chem. Eur. J. 2010, 16, 7469–7477.
[16] B. Denegri, O. Kronja, J. Org. Chem. 2007, 72, 8427–8433.
[17] S. Juric´, B. Denegri, O. Kronja, J. Phys. Org. Chem. 2012, 25,
147–152.
[3] M. Matic´, B. Denegri, O. Kronja, J. Org. Chem. 2012, 77, [18] M. Matic´, B. Denegri, O. Kronja, Eur. J. Org. Chem. 2010,
8986–8998.
6019–6024.
[4] N. Streidl, B. Denegri, O. Kronja, H. Mayr, Acc. Chem. Res.
2010, 43, 1537–1549.
Received: October 18, 2013
Published Online: January 8, 2014
1486
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Eur. J. Org. Chem. 2014, 1477–1486