Solvolytic Behavior of Aryl and Alkyl Carbonates. Impact of the Intrinsic Barrier on Relative Reactivities of Leaving Groups

Article abstract of DOI:10.1021/acs.joc.7b00885

The effect of negative hyperconjugation on the solvolytic behavior of carbonate diesters has been investigated kinetically by applying the LFER equation log k = s_f(E_f + N_f). The observation that carbonate diesters solvolyze faster than the corresponding carboxylates and that the enhancement of aromatic carbonates is more pronounced indicates that the negative hyperconjugation and π-resonance within the carboxylate moiety is operative in TS. The plots of ΔG^? vs approximated Δ_rG° for solvolysis of benzhydryl aryl/alkyl carbonates and benzhydryl carboxylates reveal that a given carbonate solvolyzes over the higher Marcus intrinsic barrier and over the earlier transition state than carboxylate that produces an anion of similar stability. Due to the lag in development of the electronic effects along the reaction coordinate, the impact of the intrinsic barrier on solvolytic behavior of carbonates is more important than in the case of carboxylates and phenolates. Consequently, the solvolytic reaction constants (s_f) are generally lower for carbonates than for carboxylates. Because of considerable lower reaction constants of carbonates, an inversion of relative reactivities between aryl/alkyl carbonate and another leaving group of similar nucleofugality (N_f) may occur if the electrofuge moiety of a substrate is switched.

Full text of DOI:10.1021/acs.joc.7b00885

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Article
Solvolytic Behavior of Aryl and Alkyl Carbonates. Impact of
the Intrinsic Barrier on Relative Reactivities of Leaving Groups
Mirela Mati#, Matija Kati#, Bernard Denegri, and Olga Kronja
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00885 • Publication Date (Web): 07 Jul 2017
Downloaded from http://pubs.acs.org on July 7, 2017
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Solvolytic Behavior of Aryl and Alkyl Carbonates. Impact of the Intrinsic Barrier on
Relative Reactivities of Leaving Groups.
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Mirela Matić, Matija Katić, Bernard Denegri* and Olga Kronja*
University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kovačića 1,
10000 Zagreb, Croatia
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E-mail: bdenegri@pharma.hr, kronja@pharma.hr
TOC graphic
ABSTRACT
The effect of negative hyperconjugation on the solvolytic behavior of carbonate diesters has
been investigated kinetically by applying the LFER equation log k = sf(Ef + Nf). The
observation that carbonate diesters solvolyze faster than the corresponding carboxylates and that
the enhancement of aromatic carbonates is more pronounced, indicates that the negative
hyperconjugation and π-resonance within the carboxylate moiety is operative in TS. The plots
of ΔG‡ vs. approximated ΔrG° for solvolysis of benzhydryl aryl/alkyl carbonates and
benzhydryl carboxylates reveal that a given carbonate solvolyzes over the higher Marcus
intrinsic barrier and over the earlier transition state than carboxylate that produces an anion of
similar stability. Due to the lag in development of the electronic effects along the reaction
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coordinate, the impact of the intrinsic barrier on solvolytic behavior of carbonates is more
important than in the case of carboxylates and phenolates. Consequently, the solvolytic reaction
constants (sf) are generally lower for carbonates than for carboxylates. Because of considerable
lower reaction constants of carbonates, an inversion of relative reactivities between aryl/alkyl
carbonate and other leaving group of similar nucleofugality (Nf) may occur if the electrofuge
moiety of a substrate is switched.
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INTRODUCTION
Organic carbonates, diesters of carbonic acid, are commonly used as reagents for
carbonylation and alkylation, and as solvents in organic synthesis.1 Since the oxycarbonyl group
can easily be introduced and removed, they also frequently serve as protecting groups in organic
synthesis.2 Therefore, it would be useful to examine the heterolytic reactivity of various
carbonate diesters as well as structural features that determine it. Furthermore, it also seems
interesting to compare solvolytic behavior of carbonates and other substrates.
In our previous study we have examined the SN1 solvolytic reactivity of benzhydryl
methyl and phenyl carbonates in a series of aqueous solvents.3 Kinetic measurements have
showed that the differences in reactivity between X,Y-substituted benzhydryl phenyl carbonates
(aryl ester, karyl in Scheme 1) and X,Y-substituted benzhydryl methyl carbonates (alkyl ester,
kalkyl in Scheme 1) are one order of magnitude,3 whereas the ratio of rates of aromatic and
corresponding aliphatic carboxylates4 and sulfonates5 are practically the same. The rate constant
ratios obtained for solvolysis in 80% ethanol are presented in Scheme 1.3–5
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karyl/kalkyl
O
O S
O
O
0.8
(C6H5)2CH
CH3
O
S
(C6H5)2CH
CH3
O
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O
O
1.4
(p-MeO-C6H4)2CH O C
(p-MeO-C6H4)2CH O C CH3
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O
O
(p-MeO-C6H4)2CH O C
O CH3 13.8
O
(p-MeO-C6H4)2CH O C
Scheme 1. Rate effect of the aromatic ring on the leaving group of various esters
We have also investigated recently the mechanism of decomposition of a series of the
model methyl aryl carbonates and methyl alkyl carbonates computationally in the gas phase as
well as in the presence of the IEFPCM solvation model (water).6 Similarly as it occurs in the
rate determining heterolysis step of SN1 solvolysis in aqueous solvents, in that study, the
computed first step of the decomposition path in the gas phase and water involves heterolysis of
carbonate diesters. The calculations have revealed that the negative hyperconjugation stabilizes
aryl and alkyl carbonate anions toward a recombination with a cation, causing a partial transfer
of the anionic charge out of the carboxylate moiety of the anions and considerable elongation
and polarization of the O2C―OR(Ar) σ-bond, as depicted with the resonance structure in
Scheme 2 (blue). The negative hyperconjugation occurs via two orbital interactions where lone
pair orbitals of both oxygens O1 and O2, which lie in the carboxylic plane, donate electron
density into σ*(C–O3) antibonding orbital located between the carboxylate carbon atom and the
aryloxy (alkoxy) oxygen atom O3 (Scheme S1b).6 While the donation from O1 already exists in
a neutral substrate, the donation from O2 develops along the heterolytic reaction coordinate and
achieves its full strength in free anions.
In aryl carbonate anions, the negative hyperconjugation enables further delocalization of
the anionic charge to the aromatic ring by resonance and an additional contribution to the
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stabilization of the anions (Scheme S1c). Calculations have also indicated that the magnitude of
the negative hyperconjugation depends on the electron-accepting ability of the Ar(R) substituent
attached to O3 (Scheme 2), and that the effect is somewhat suppressed in a solvent in
comparison to the gas phase.
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The above results prompted us to examine the solvolytic behavior of a series of
benzhydryl aryl and alkyl carbonates to establish the effects of the negative hyperconjugation
on their solvolytic reactivity experimentally. We have chosen to determine the leaving group
abilities (nucleofugalities) of various aryl and alkyl carbonates and to examine the effects of
their structural varieties by applying the special LFER approach, which was earlier used for
analogous investigations of numerous leaving groups, including phenyl, methyl and tert-butyl
carbonates.3,5
Accordingly, the absolute heterolysis rate constant for SN1 solvolysis reaction can be
expressed with the following three-parameter LFER equation:5
log k = sf(Ef + Nf)
(1)
in which k is a first-order rate constant (s−1) at 25 °C, sf (the slope parameter) and Nf
(nucleofugality) are the nucleofuge-specific parameters for a given leaving group in a given
solvent, and Ef is the electrofugality parameter (independent variable) of carbocation generated
in heterolysis. Nucleofugality and electrofugality are kinetic terms that describe abilities of the
leaving group and carbocation moieties, respectively, to depart from a substrate. The
nucleofuge-specific parameters (sf and Nf) can be determined from the log k vs. Ef plot, for the
series of substituted benzhydryl substrates with a given leaving group, for which sf represents
the slope parameter, and Nf corresponds to the negative intercept on the abscissa.5 Such an
approach is established to separate the contributions of an electrofuge and a nucleofuge to the
overall solvolytic reactivity of a substrate. This method enables the practical application of
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equation (1) in estimating the solvolytic reactivity of any substrate constituted from an
electrofuge and a nucleofuge of known reactivity parameters.5,7
RESULTS AND DISCUSSION
X
X
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1
1
1
O
O
O
C
k
3
C
+
3
3
O Ar(R)
C
O
2
solvent
O
2
O Ar(R)
O Ar(R)
O
2
Y
Y
Ar = p-NO2−C6H4, p-CN−C6H4, p-Cl−C6H4, p-F−C6H4, p-CH3O−C6H4, p-CH3−C6H4;
R = CH3CH2, (CH3)2CH,
1: X = Y = CH3O
2: X = CH3O, Y = C6H5O
3: X = CH3O, Y = CH3
4: X = CH3O, Y =H
5: X = Y = CH3
6: X = CH3, Y = H
7: X = F, Y = H
8: X = Y = H
Scheme 2. The heterolytic step in solvolysis of benzhydryl carbonates
The series of X,Y-substituted carbonates (Scheme 2) have been prepared from the
corresponding benzhydrols according to the methods presented in Experimental Section.
Substrates 1–8 with different aryl/alkyl carbonate leaving groups (total of 38 substrates) have
been subjected to solvolysis in 80% and 60% aq. ethanol, 60% aq. acetone, and 60% aq.
acetonitrile (details are given in Kinetic Methods and Tables S1–S3). First-order rate constants
(measured at 25 °C and extrapolated from data obtained at higher temperatures) are presented in
Table S1. The logarithms of first-order rate constants of substrates of benzhydryl series with a
given aryl/alkyl carbonate leaving group were plotted against corresponding electrofugalities
(Ef) and the nucleofuge-specific parameters have been extracted. The plots of log k against Ef
obtained in 80% ethanol are presented in Figure 1. The nucleofuge-specific parameters,
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nucleofugalities (Nf) and slope parameters (sf) along with corresponding standard errors and
correlation coefficients are presented in Table 1. These parameters can further be used to
estimate the solvolytic reactivity of a large number of carbonate diesters5,7 as well as to relate
the reactivities of aryl and alkyl carbonates to numerous leaving groups, whose nucleofuge-
specific parameters have already been determined.4,5,8,9
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In Figure 2 the nucleofugalities of various aryl/alkyl carbonates determined here (shown
right) are compared with those of selected leaving groups on the nucleofugality scale (shown
left). The scale that covers up to 12 orders of magnitude is particularly useful for easy
determination of the relative reactivities of various leaving groups. For example, it is easy to
observe that chloride is more than six orders of magnitude more reactive leaving group than
isopropyl carbonate, or that p-nitrophenyl carbonate is more than four orders of magnitude more
reactive than benzoate.
It should also be emphasized that due to excellent correlations (Table 1, Figure 1), the
estimated solvolytic rate constants for benzhydryl derivatives are very accurate, so such
calculated rate constants are reliable. Although for substrates that are not benzhydryl
derivatives, the estimated rate constants are generally less accurate, equation (1) still gives good
predictions of solvolytic reactivities of structurally diverse substrates in a wide range of
reactivity.5,7 Throughout this work, only in a few cases the calculated rate constants for
benzhydryl derivatives have been considered.
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Figure 1. Plots of log k (25 °C) vs. Ef for solvolyses of substituted benzhydryl aryl and alkyl
carbonates in 80% ethanol (v/v). Ef parameters were taken from reference 5.
Table 1. Nucleofuge-specific Parameters Nf and sf for Some Aryl and Alkyl Carbonates in
Various Solvents
b
b
Leaving group
Solvent a
80E20W
60E40W
60AN40W
60A40W
80E20W
60E40W
60AN40W
60A40W
80E20W
60E40W
60AN40W
Nf
sf
r c
p-NO2-C6H4OCO2
0.31 ± 0.06 0.80 ± 0.01 0.9996
1.05 ± 0.07 0.80 ± 0.01 0.9997
0.27 ± 0.15 0.80 ± 0.03 0.9986
0.12 ± 0.12 0.81 ± 0.02 0.9991
0.24 ± 0.06 0.84 ± 0.01 0.9997
0.82 ± 0.14 0.80 ± 0.03 0.9989
0.10 ± 0.15 0.80 ± 0.03 0.9986
–0.03 ± 0.11 0.83 ± 0.02 0.9992
–0.46 ± 0.09 0.84 ± 0.02 0.9996
0.00 ± 0.11 0.80 ± 0.02 0.9993
–0.62 ± 0.11 0.79 ± 0.02 0.9990
p-CN-C6H4OCO2
p-Cl-C6H4OCO2
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b
b
Leaving group
Solvent a
60A40W
80E20W
60E40W
60AN40W
60A40W
Nf
sf
r c
–0.80 ± 0.09 0.84 ± 0.02 0.9995
–0.49 ± 0.07 0.90 ± 0.01 0.9996
–0.08 ± 0.15 0.84 ± 0.03 0.9988
–0.79 ± 0.11 0.81 ± 0.02 0.9991
–0.94 ± 0.07 0.87 ± 0.01 0.9997
–0.88 ± 0.04 0.91 ± 0.01 0.9999
–0.57 ± 0.07 0.82 ± 0.01 0.9996
–1.24 ± 0.07 0.81 ± 0.02 0.9996
–1.52 ± 0.02 0.84 ± 0.01 1.0000
–0.80 ± 0.07 0.92 ± 0.02 0.9997
–0.52 ± 0.12 0.84 ± 0.03 0.9989
–1.26 ± 0.08 0.80 ± 0.02 0.9994
–1.55 ± 0.08 0.84 ± 0.02 0.9995
–2.04 ± 0.02 0.99 ± 0.01 1.0000
–1.80 ± 0.10 0.92 ± 0.03 0.9989
–2.54 ± 0.17 0.90 ± 0.04 0.9978
–2.72 ± 0.18 0.93 ± 0.04 0.9978
– 2.26 ± 0.02 1.00 ± 0.01 1.0000
– 2.03 ± 0.11 0.93 ± 0.03 0.9987
–2.94 ± 0.13 0.88 ± 0.03 0.9989
–2.86 ± 0.12 0.97 ± 0.03 0.9991
p-F-C6H4OCO2
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p-CH3O-C6H4OCO2 80E20W
60E40W
60AN40W
60A40W
p-CH3-C6H4OCO2
CH3CH2OCO2
80E20W
60E40W
60AN40W
60A40W
80E20W
60E40W
60AN40W
60A40W
80E20W
60E40W
60AN40W
60A40W
(CH3)2CHOCO2
a Binary solvents are v/v at 25 °C. E = ethanol, AN = acetonitrile, A = acetone, W = water.
b Errors shown are standard errors. c Correlation coefficient.
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Figure 2. Carbonate leaving groups in the nucleofugality scale for 80% aqueous ethanol along
with other leaving groups. Experimental sf values are given in parentheses. Data for a, b, c, d, e
and f were taken from references 5, 4b, 9a, 8a, 4a and 9b, respectively.
Rate effects
All organic carbonates measured here solvolyze about two or three orders of magnitude
faster than the corresponding carboxylates (esterified with the same substituents as carbonates).
Thus, the nucleofugalities (Nf) are about 1.5 – 3 units larger than those of the corresponding
carboxylates (e.g. in 80% aq. ethanol for p-NO2-benzoate Nf = –2.78,5 while for p-NO2-phenyl
carbonate Nf = 0.31; for isobutyrate Nf = –3.97,4b while for isopropyl carbonate Nf = – 2.26). In
our previous investigation we have demonstrated that the solvolytic rate constants of 4-
methoxybenzhydryl aryl/alkyl carbonates correlate well with the corresponding standard free
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energies for heterolysis, calculated at the IEFPCM-MP2/6-311+G(2d,p) level of theory (r =
0.995), indicating that the electronic effects that stabilize the free aryl and alkyl carbonate
anions are operative in the transition states in solvolysis as well.6 Hence, enhanced reactivity of
carbonates in comparison to corresponding carboxylates is consistent with the previous
conclusion that in aryl/alkyl carbonate anions additional electron-stabilizing effects exist,
particularly the negative hyperconjugation, which delocalizes the negative charge generated on
the carboxylates moiety to O3 (Scheme 2), causing additional stabilization of the TS, and
lowering ∆G‡ for heterolysis.
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Distinct gap between the two bottom correlation lines that belong to benzhydryl alkyl
carbonates and the other lines that correspond to benzhydryl aryl carbonates, presented in
Figure 1, shows that the later solvolyze noticeably faster. Therefore, in line with the rate effect
of the phenyl group in carbonates observed earlier (karyl/kalkyl = 13.8, Scheme 1)3, a general rule
can be set that the substrates with aromatic carbonate leaving groups solvolyze considerably
faster than those with aliphatic LG. It should also be mentioned that enhancement of a substrate,
if the alkyl group is replaced with the aromatic group, does not exist at both carboxylates and
sulfonates,4,5 i.e., such solvolytic behavior is a specific feature of carbonate leaving groups. The
nucleofugality parameters (Nf) for the investigated aromatic carbonates are between one and
three units larger than those for aliphatic carbonates, i.e., monoubstituted aromatic carbonates
solvolyze one to three orders of magnitude faster in all solvents measured (Figure 2). The
smallest rate ratios have been obtained between aliphatic carbonates and phenyl carbonates
carrying electron-donating groups (p-CH3 or p-CH3O), and the ratios expectedly increase as the
electron-accepting ability of the substituent on the aromatic ring increases. Furthermore,
aromatic carbonates with very strong electron-accepting abilities, as are p-NO2-phenyl and p-
CN-phenyl groups (the top two correlation lines), solvolyze considerably faster than other
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aromatic carboxylates, producing a smaller but still observable gap between the lines shown in
Figure 1. Experimental rate effects are supported with previous theoretical findings about the
importance of the negative hyperconjugation in TS, in which the negative charge is delocalized
further by resonance into the aromatic ring, causing the rate enhancement in aromatic
carbonates.6 The degree of this delocalization, i.e. aryl carbonate anion stabilization toward the
recombination with a cation, depends on the electron-accepting ability of the substituent on the
aryl ring.
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Accordingly, enhanced reactivity of aryl/alkyl carbonates in comparison to corresponding
carboxylates indicates that additional electron stabilization occurs in the former due to the
transfer of the anionic charge onto O3, i.e., out of the carboxylate moiety, while the differences
in reactivities between aryl and alkyl carbonates reveal that the orbital delocalization of the
negative charge to the aromatic ring occurs.
While carbonates solvolyze noticeably faster than the corresponding carboxylates, the
influence of the substituents at the aromatic ring on reactivity is less pronounced than in
carboxylates. For instance, in 80% ethanol, k(1-p-NO2-phenyl carbonate)/(1-phenyl carbonate)
= 8.2, whereas k(1-p-NO2-benzoate)/k(1-benzoate) = 21.0. The similar behavior is also found
for the cyano substituent; k(1-p-CN-phenyl carbonate)/k(1-phenyl carbonate) = 7.4 and k(1-p-
CN-benzoate)/k(1-benzoate) = 15.5. Less pronounced substituent effects in aryl carbonates
might seem surprising since they additionally delocalize the negative charge from O3 via
resonance in corresponding aryl carbonate free anions,6 while in benzoates the ring substituents
stabilize both TS and free anions via generally weaker polar effects.4a
To examine the influence of the substituents effect in free anions in solution, standard
free energies for heterolysis of three 8-aryl carbonates and three 8-benzoates (R = H, p-CN and
p-NO2, Scheme 2) were calculated at the M06-2X/6-311+G(3df,2pd) level of theory with the
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SMD solvation model that mimics water (Table S7). The energy column diagrams presented in
Figure 3 correspond to differences in experimental activation free energies (ΔΔG‡) for
solvolysis in 80% ethanol between the substrates (aryl carbonates or benzoates) with the
substituted (R = p-CN or p-NO2) and not substituted (R = H) aromatic ring (a) and to
corresponding differences in calculated standard free energies (ΔΔrG°) for heterolysis (b).
Similar patterns of diagrams show similar modes of stabilization caused with substituents in TS
and the ground state of the both substituted free anions. The calculated ΔΔrG°s support the
experimental findings, showing that indeed the electron-accepting substituents on the aromatic
ring in benzoates lower the energy of both TS and free anion more than in aryl carbonates.
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Figure 3. The impact of electron-accepting substituents (in kcal mol−1) on (a) activation free
energy of 1-benzoates (red columns) and 1-phenyl carbonates (blue columns) in 80% ethanol at
25 °C and (b) stability of free benzoate (red) and phenyl carbonate (blue) anions toward the
benzhydrylium cation (8+), calculated at the SMD-M06-2X/6-311+G(3df,2pd) level (solvent =
water). Experimental data for 1-benzoates and 1-phenyl carbonate were taken from references
4a, 11 and 3. All data are presented in Tables S5, S6 and S7.
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Two effects can mainly account for less pronounced substituent effects in solvolysis of
carbonates: the limited orbital overlap in the transition state and the strong stabilizing effects in
the TS. It has already been shown that the overlap between the O3 lone pair orbitals and the ring
π-system is only partial in free aryl carbonate anions due to steric and electrostatic repulsions
between the carboxylate moiety and the ring which prevents complete resonance.6 On the
contrary, the magnitude of polar effects of substituents in benzoates do not depend on dihedral
angles between the moieties in both TS and free anions, so their impact on the relative
solvolysis rate is larger than in carbonates. The other variable that contributes to less
pronounced substituent effect is the strong complex stabilizing mode in the TS (negative
hyperconjugation and π-resonance within the carboxylate moiety, Scheme S1), which appears to
cover to some extent the substituent effects, i.e., leveling occurs.10
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Variation of the reaction constants
Analogously to the Hammett–Brown ρ+ parameter, the sf parameter (equation 1) indicates
the charge generated in heterolytic transition states of a series of related substrates (ρ+ ≈ 4.4
sf).11 In our previous study, we correlated log k of 4,4'-dimethoxybenzhydryl aliphatic
carboxylates (a series of carboxylates with a common electrofuge) with corresponding sf
values.4b The correlation has shown a slight decrease in sf value of a series with an increased
reactivity of a carboxylate leaving group. This observation was rationalized in terms of relative
position of the transition states on the reaction. Faster reactions solvolyze over earlier transition
states, in which the cleavage of a C–LG bond is less advanced, consequently, the TS is more
reactant-like than those of the slower reactions, in which the charge separation is more
progressed. This is, hence, consistent with the Hammond postulate that the endergonicity of
solvolyses decreases within the series with increasing reactivity of a leaving group.12
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Figure 4. Correlation of sf values of aryl/alkyl carbonates (blue circles) and aliphatic
carboxylates (red circles) against log k (25 °C) for solvolysis of appropriate 4,4'-
dimethoxybenzhydryl aryl/alkyl carbonates and carboxylates in 80% ethanol. The values of log
k and sf for phenyl and methyl carbonates and aliphatic carboxylates were taken from references
3, 5 and 4b (details are given in Tables S5 and S6).
However, when the data for sf vs. log k for aryl/alkyl carbonates are included, the
correlation becomes poor (r = 0.84), due to separation of the data into two sets, the one for
aryl/alkyl carboantes and the other for caraboxylates. Treatment of the data for aryl/alkyl
carbonates and carboxylates individually gives much better correlation, as it is depicted in
Figure 4. Although the experimental points are somewhat scattered and the linear correlations
are not very good, the log k vs. sf plots unambiguously reveal that the trend of decreasing sf
values with increasing reactivity exists for both series, aryl/alkyl carbonates and carboxylates,
and that the line that corresponds to carbonates stretches bellow the line for aliphatic
carboxylates.
The separation of data in the log k vs. sf correlation (shown in Figure 4) implies
inapplicability of both the Hammond postulate12 and the Bell–Evans–Polanyi principle13 if
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carbonates and carboxylates are considered together. Inapplicability of the Hammond postulate
and the Bell–Evans–Polanyi principle was also observed with other types of organic reactions.14
The separation of data into the two lines reveals that carboxylates and carbonates, whose rates
(k) of heterolysis are similar (e.g., 4,4'-dimethoxybenzhydryl chloroacetate and 4,4'-
dimethoxybenzhydryl ethyl carbonate), produce transition states with a different extent of the
charge generated at the reaction center (different sf values). This observation implies that the
solvolytic reactivities in the series of benzhydryl substrates with different types of the leaving
groups do not satisfactory correlate with corresponding stabilities of the free anions.
Consequently, as aryl/alkyl carbonates generally have lower sf values (Figure 4), their transition
states are supposed to be earlier than those of carboxylates of similar reactivities, i.e., they
solvolyze via less endergonic process.
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According to Marcus theory (eq 2), the free energy of activation (ΔG‡) depends on the
free energy of reaction (ΔrG°) and the intrinsic barrier (ΔG‡ ).15,16
0
‡
‡
ΔG‡ = ΔG0 + 0.5ΔrG° + (ΔrG°)2/16ΔG0 )
(2)
Thus, when solvolysis reactions occur with the similar rates (solvolyze over the similar
barrier, ΔG‡), equation 2 predicts higher intrinsic barriers for those that produce more stable
products (less endergonic processes), here for carbonates (Scheme 3a). In both aryl/alkyl
carbonates and carboxylates, leaving groups contain the carboxylate moiety, which stabilizes
both TS and free anions by π-resonance (Scheme S1a), but, as mentioned above, the anionic
charge is further delocalized by the negative hyperconjugation in aryl and alkyl carbonates
(Scheme S1b), and additionally by resonance to the phenyl ring in aryl carbonates (Scheme
S1c). Lag of developing the electronic stabilizing effects along the reaction coordinate, can
account for higher intrinsic barriers for solvolysis of carbonates, compared with carboxylates of
similar reactivity.
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(a)
ΔG
(b)
TS
carbonate
TS
ΔG
carboxylate
carbonate
7
carboxylate
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R LG
R LG
Scheme 3. Free energy profiles for solvolysis of aryl/alkyl carbonates and carboxylates of (a)
the same reactivities and (b) the same free anion stabilities
Variation in rates of development of the complex stabilizing effects along the reaction
coordinate causes variation of the intrinsic barriers.17 The lack of synchronization of resonance
and polar effects have been observed and investigated at proton-transfer reactions and
summarized by The Principle of Nonperfect Synchronization.18 Accordingly, the lag in
development of the charge delocalization, i.e. resonance stabilization of the transition state,
leads to the increase of the intrinsic barrier. It has also been established that resonance
interactions, in comparison with polar stabilization effects, develop relatively slowly during
heterolysis reactions.17,18 Since both aryloxy and alkoxy substituents attached to the carboxylate
moiety at carbonates enable additional delocalization of the anionic charge by the negative
hyperconjugation,6 higher intrinsic barriers for solvolysis of carbonates may be rationalized by
slower development of this stabilizing effect along the reaction coordinate in comparison with
inductive effects in carboxylates. This lag of the stabilizing effects in carbonates is manifested
by their additional stabilization after passing through TS, i.e. by lower free energy of a free
anion (Scheme 3a). An increase in magnitude of the negative hyperconjugation, i.e. donation of
electron density from O2, along the reaction coordinate does not depend only on a degree of the
bond cleavage but also on a degree of the rehybridization at O2 and the change in geometry in
vicinity of O2. It appears that the complexity of developing the stabilization effect causes the
lag in stabilization.
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Impact of the intrinsic barrier on nucleofugality
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The slow heterolytic step in solvolysis of numerous compounds occurs over a barrier
(Scheme 4a). However, if the backward recombination reaction between a generated
nucleophile and an electrophile is a diffusion-controlled process, it occurs without the barrier,
thus, according to the principle of microscopic reversibility, formation of free anions in the
forward reaction is also barrierless (Scheme 4b).5 In such case, ΔG‡ values obtained from the
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solvolytic rate constants are considered to be equal to ΔrG°s for heterolysis.
(a)
(b)
>
ΔrG°
≈
ΔG
ΔG
ΔrG°
TS
TS
ΔG
ΔG
R
LG
R
LG
R LG
R LG
Scheme 4. Energy profiles for heterolytic step of SN1 reactions that occur (a) via barrier
and (b) without barrier
It has been shown previously that the nucleophilicities of chloride and acetate anions are
similar.19a,b Since the 4,4'-dimethoxybenzhydrilium cation (1) recombines with chloride over a
barrier,19a it can be presumed that it recombines with various carboxylate anions, which are
better stabilized than acetate, also via a barrier. Furthermore, methyl carbonate anion is a
weaker nucleophile than both chloride and acetate for one order of magnitude.19c Consequently,
it can also be presumed that the series of carbonate anions presented in Figure 5 combine with
4,4'-dimethoxybenzhydrilium cation (1) over a barrier (Scheme 4a). Further, the difference
between electrophilicities of benzhydrylium cation (8) (E
=
5.90) and 4,4'-
dimethoxybenzhydrilium cation (1) (E = 0) indicates that the former recombines with
nucleophiles approximately six orders of magnitude faster.20 Even though it cannot be predicted
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that the anions produced in solvolyses of benzhydryl (8) aryl/alkyl carbonates and benzhydryl
carboxylates recombine with the benzhydrylium cation (8) without a barrier, according to the
Hammond postulate for each series (8-carboxylates and 8-aryl/alkyl carbonates), the
corresponding transition states should be appreciable more ion pair-like than those for
heterolysis of the 4,4'-dimethoxybenzhydrilium series (energy profile similar to Scheme 4b).
Consequently, the activation free energies for 8-carboxylates and 8-aryl/alkyl carbonates are
considerably closer to the values of the corresponding standard free energies for heterolysis than
those for 1-carboxylates and 1-aryl/alkyl carbonates, thus, for the purposes of consideration
given below, the values of ΔG‡ for 8-carboxylates and 8-aryl/alkyl carbonates can roughly be
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approximated for ΔrG°.
Figure 5. Correlation of activation free energies (in kcal mol−1) for solvolysis of 4,4'-
dimethoxybenzhydryl (1) aryl/alkyl carbonates (blue circles) and carboxylates (red circles) in
80% ethanol at 25 °C against activation free energies for solvolysis of corresponding
benzhydryl (8) aryl/alkyl carbonates and carboxylates. Data for phenyl and methyl carbonates
and for aliphatic carboxylates were taken from references 3 and 4b, respectively (details are
given in Tables S5 and S6).
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Taking advantage from the excellent correlation according to equation (1) if using
benzhydryl derivatives (Figure 1 and Table 1), we correlated the activation free energies for
solvolysis of 4,4'-dimethoxybenzhydryl (1) aryl/alkyl carbonates and carboxylates (ΔG‡) against
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the activation free energies for benzhydryl (8) aryl/alkyl carbonates and carboxylates (ΔG‡
≈ ΔrG°) in an extended range of reactivity (Figure 5). The striking feature of the correlation is a
separation of the data into two very good correlation lines, one for aryl/alkyl carbonates (blue)
and the other for carboxylates (red). Because of the above mentioned approximation of ΔG‡ for
ΔrG° for the benzhydyl (8) series of carbonates and carboxylates, the slopes of correlation lines
can approximately be taken as a Hammond–Leffler α values (α = ΔΔG‡/ΔΔrG°).12 The slopes of
both plots given in Figure 5 are, as expected, smaller than unity. Importantly, the slope of the
line for aryl/alkyl carbonates is noticeably lower than the one for carboxylates (0.69 vs. 0.78),
indicating the higher exergonicity of the 1-aryl/alkyl carbonates series and, consequently, earlier
corresponding transition states. Although the slopes of the lines do not truly represent the
Hammond–Leffler α value because of the approximation introduced (ΔG‡ ≈ ΔrG° for
benzhydryl series), they indicate that given aryl/alkyl carbonate solvolyze over an earlier
transition state than carboxylate of the same or similar reactivity (Scheme 3a).
The separation of the lines in this correlation also demonstrates the inapplicability of the
Hammond postulate12 and the Bell–Evans–Polanyi13 principle if carbonates and carboxylates
are treated together, which has already been concluded from the sf vs. log k correlation
presented in Figure 4. The separation of data can be attributed to the impact of the height of the
Marcus intrinsic barrier15 on nucleofugality of different types of leaving groups. The lines
presented in Figure 5 clearly show that if aryl/alkyl carbonates and carboxylates produce anions
of similar stability (abscissa), aryl/alkyl carbonates solvolyze slower, i.e., over a higher barrier.
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Marcus equation 2 implies that if two substrates produce products of similar stability, the slower
reaction proceeds over a higher intrinsic barrier (Scheme 3b). For example, even though ΔrG°s
for p-NO2-phenyl carbonate and trichloroacetate are similar (the abscissa in Figure 5), the later
solvolyze about one order of magnitude faster (the ordinate).
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In summary, the existence of complex electronic stabilization in a heterolytic transition
state causes carbonates to solvolyze faster than the corresponding carboxylates (e.g. methyl
carbonate vs. acetate) for up to three orders of magnitude. However, this rate enhancement is
somewhat suppressed, due to the higher intrinsic barriers of carbonates caused by slower
development of the stabilizing effects along the reaction coordinate.
Relative reactivity of carbonates
It is well-known that relative reactivities of leaving groups vary with variation in the
structure of an electrofuge, mostly due to different steric demands adjacent to the reaction
center21 and differential solvation of electrofuges.7 However, even in the series of structurally
related substrates, whose steric demands in the vicinity of the reaction center are similar (e.g.
benzhydryl series), the relative reactivities of leaving groups can vary due to different
contribution of both electronic effects (e.g. resonance and inductivity) and intrinsic barriers.9b
This is also observable in the correlation shown in Figure 5. For instance, trichloroacetate is for
more than 1 kcal mol−1 more reactive than p-NO2-phenyl carbonate when an electrofuge is 4,4'-
dimethoxybenzhydrilium (ordinate). Switching the electrofuge with less reactive benzhydrilium
(abscissa) appreciably decreases the difference to 0.2-0.3 kcal mol−1. This occurs because the
transition states in slower reactions of the benzhydrylium series are more ion pair-like (the
Hammond postulate), ultimately approaching the barrierless process (Scheme 4b), so the impact
of the intrinsic barrier on reactivity becomes less important. In such slower processes, in which
the intrinsic barrier is lower, the stability of the ions generated becomes the rate determining
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variable. The decrease of the intrinsic barrier in the series of the benzhydryl derivatives, which
carry a common carboxylate leaving group, with decreasing electrofugality (i.e., with increasing
electrophilicity of a cation generated in solvolysis) was indicated previously.19b Since the same
conclusions have been drawn from the correlations presented in Figures 4 and 5, it is evident
that information on variation of intrinsic barriers for the heterolytic step of SN1 reactions is
included in the sf parameter of equation (1), i.e., the reaction constant.
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Figure 6. Plots of log k (25 °C) vs. Ef for solvolyses of substituted benzhydryl aryl carbonates,
2,4-dinitrophenolates (DNPh)9a and pentafluorophenolates (PFPh)9b in 80% ethanol (v/v). Ef
parameters were taken from reference 5.
It has been shown that phenolates solvolyze over lower intrinsic barriers than carboxylates
within the same region of reactivity,9b so they represent an appropriate models for investigating
how differences in intrinsic barriers effect the relative reactivities of the leaving groups. The
nucleofugalities of p-NO2-phenyl carbonate (Nf = 0.31, sf = 0.80 in 80% aq. EtOH) and 2,4-
dinitrophenolate (DNPh) (Nf = 0.22, sf = 1.03 in 80% aq. EtOH)9a are almost the same, but the
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sf value for the former is considerably lower. This implies relatively higher intrinsic barrier for
p-NO2-phenyl carbonate in heterolysis and in the reverse combination of the ions than it is for
DNPh. In Figure 6 some selected log k vs. Ef correlation lines (equation 1) are presented. The
lines that correspond to p-NO2-phenyl carbonate (line A) and 2,4-dinitrophenolate (DNPh, line
B)9a indicate similar reactivity of the two leaving groups in the region of definition of Nf value
(log k = 0). For substrates that solvolyze with rates k ≈ 1, the heterolytic step and its reversible
recombination reaction proceed over a barrier (Scheme 4a). In the region of less reactive
substrates (weaker electrofuges), divergence of the correlation lines occurs and p-NO2-phenyl
carbonate becomes more reactive than DNPh. As the reaction in the series becomes slower, the
intrinsic barrier becomes lower, approaching the barrierless process, in which a transition state
is ion pair-like (Scheme 4b). In a slower region, the relative reactivities are mostly determined
with the stability of anions generated in heterolysis. Consequently, the correlation implies that
the p-NO2-phenyl carbonate free anion is better stabilized than the DNPh free anion. On the
other hand, in the region of faster reactions, right from the intersection of the correlation lines
(higher electrofugality), the intrinsic barrier is an important variable in determining relative
reactivities, rendering p-NO2-phenyl carbonates in heterolysis less reactive than DNPh.
Figure 6 also reveals other cases of inversion in relative reactivities. For example, lines
for p-CH3O-phenyl carbonate (line C) and pentafluorophenolate (PFPh, line D)9b intersect in the
region of electrofugality Ef ≈ 1, while those for 2,4-dinitrophenolate (DNPh, line B)9a and p-
chlorophenyl carbonate (line E) at Ef ≈ –3. An example of inversion of relative reactivities in
the region of kinetic measurements is also shown with intersection of lines of ethyl carbonate
(line F) and pentafluorophenolate (line D), which intersect at Ef ≈ –2.5. Inversion of relative
reactivities in the experimental region was also observed earlier with phenolates and
carboxylates.9b The intersections of the lines that indicate the inversion of relative reactivities of
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the leaving groups can be rationalized similarly as above for p-NO2-phenyl carbonates and 2,4-
dinitrophenolates: from the intersection point toward the more reactive region (higher
electrofugality), the intrinsic barrier is important in determining the relative reactivates, while
toward the region of lower heterolytic reactivities (lower electrofugality), relative reactivities
are mostly determined with stabilities of generated free anions.
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The difference in solvolytic intrinsic barriers of carbonates and phenolates can be
attributed to the non-synchronous development of several orbital effects in aryl and alkyl
carbonate leaving groups (resonance within the carboxylate moiety, the negative
hyperconjugation and additional resonance in aryl carbonates)6 during the heterolysis process at
carbonate diesters. This behavior is consistent with the principle of nonperfect
synchronization.18 On the other hand, only resonance constitutes a dominant electronic effect at
phenolate leaving groups in both transition states and free anions.
These examples do not only repeatedly demonstrate inapplicability in employing pKa
values for predicting relative reactivities of diverse leaving groups, but also indicate
shortcomings of method in which the solvolysis rates of series of substrates with different
leaving groups and a common electrofuge are used for determining nucleofugalities, since the
inversion of reactivities cannot be predicted. The shortcomings can be overcome if the LFER
approach presented by equation (1)5 is employed.
Conclusion
Kinetic data revealed that the negative hyperconjugation in combination with π-resonance
within the carboxylate moiety that was computationally established to stabilize free aryl and
alkyl carbonate anions also exists in transition states of heterolysis of the carbonate diesters.
Such mode of stabilization of the TS of carbonates contributes to their enhanced solvolytic
reactivity in comparison to corresponding carboxylates. Enhancement of reactivity of aryl
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carbonates is even more pronounced than that of alkyl carbonates due to additional negative
charge delocalization into the aromatic ring by resonance.
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However, as a consequence of slower development of the complex stabilizing electronic
effects during heterolysis in carbonates than in carboxylates, carbonates solvolyze over the
higher intrinsic barrier, causing those that produce anions of similar stability as carboxylates to
solvolyze slower. Due to the impact of the higher intrinsic barrier on the solvolytic behavior of
carbonates, an increase of reactivity with increasing electrofugality is somewhat suppressed in
comparison to carboxylates or phenolates. Consequently, the reaction constants (sf) for
aryl/alkyl carbonates are generally lower than those for carboxylates and particularly those for
phenolates which in turn can account for the inversion of relative reactivities of aryl/alkyl
carbonates and phenolates if the electrofuge moiety of a substrate is varied.
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EXPERIMENTAL SECTION
Substrate preparation. 4-Fluorobenzhydrol, 4-methylbenzhydrol, 4,4'-dimethylbenzhydrol,
and 4,4'-dimethoxybenzhydrol were prepared by the reduction of the commercially available
corresponding substituted benzophenones with sodium borohydride in methanol.
4-Methoxy-4'-methylbenzhydrol, and 4-methoxy-4'-phenoxybenzhydrol were prepared according
to the procedure given in reference 3.
General Procedure for the Synthesis of Benzhydryl 4-Nitrophenyl Carbonates
A solution of 4-nitrophenyl chloroformate (4.2 mmol) in anhydrous benzene (10 mL) was
added dropwise to the previously prepared vigorously stirring solution of appropriate
benzhydrol (3.3 mmol) and pyridine (9.7 mmol) in anhydrous benzene (20 mL). The reaction
mixture was stirred overnight under the atmosphere of argon at ambient temperature, except in
the case of 4-methoxybenzhydryl 4-nitrophenyl carbonate, when the reaction time was 15
minutes. Precipitated pyridinium chloride was removed by filtration and the excess of pyridine
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was removed by 10% hydrochloric acid. The benzene layer was separated and washed with 30
% NaOH (3 ×) and water (3 ×). After drying over anhydrous sodium sulfate, benzene was
evaporated in vacuo to give white crystals (yield 58–78%).
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Benzhydryl 4-Nitrophenyl Carbonate: from benzhydrol (0.60 g; 3.3 mmol), pyridine (0.77 g;
1
9.7 mmol), and 4-nitrophenyl chloroformate (0.85 g; 4.2 mmol); yield 0.89 g; 78%; H NMR
(400 MHz, CDCl3, 25 şC): ä/ppm = 6.81 (s, 1H; Ar2CH), 7.33-7.43 (m, 12H; ArH + Ar-NO2),
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8,22 (d, J = 9.3 Hz, 2H; Ar-NO2); C NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 82.4 (Ar2CH),
121.8, 125.3, 127.1, 128.6, 128.8, 138.7, 145.4 (Ar-NO2), 151.9 (C=O), 155.5 (Ar-NO2);
Collection of HRMS data or elemental analysis was not possible for this compound due to its
limited stability.
4-Fluorobenzhydryl 4-Nitrophenyl Carbonate: from 4-fluorobenzhydrol (0.80 g; 4.0 mmol),
pyridine (0.94 g; 11.9 mmol), and 4-nitrophenyl chloroformate (1.04 g; 5.2 mmol); yield 0.84 g;
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58%; H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 6.79 (s, 1H; Ar2CH), 7.06 (t, J = 8.7 Hz,
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2H; Ar-F), 7.34-7.41 (m, 9H; ArH + Ar-F + Ar-NO2), 8,24 (d, J = 9.3 Hz, 2H; Ar-NO2); C
NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 81.7 (Ar2CH), 115.7 (d, J = 21.7 Hz, Ar-F), 121.7,
125.3, 126.9, 128.7, 128.8 (Ar), 129.1 (d, J = 8.3 Hz, Ar-F), 134.7 (d, J = 3.4 Hz, Ar-F), 138.5,
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145.4 (Ar-NO2), 151.8 (C=O), 155.4 (Ar-NO2), 162.7 (d, J = 247.8 Hz, Ar-F); F NMR (282
MHz, CDCl3, 25 şC): ä/ppm = – 112.95. HRMS (MALDI-TOF/TOF) m/z: [M – H]- Calcd for
C20H13O5NF 366.0777; Found 366.0794.
4-Methylbenzhydryl 4-Nitrophenyl Carbonate: from 4-methylbenzhydrol (0.80 g; 4.0 mmol),
pyridine (0.96 g; 12.1 mmol), and 4-nitrophenyl chloroformate (1.06 g; 5.3 mmol); yield 0.93 g;
63%; 1H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.34 (s, 3H; Ar-CH3), 6.78 (s, 1H; Ar2CH),
7.18 (d, J = 8.0 Hz, 2H; Ar-CH3), 7.29-7.42 (m, 9H; ArH + Ar-CH3 + Ar-NO2), 8,23 (d, J = 9.0
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Hz, 2H; Ar-NO2); C NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 21.2 (Ar-CH3), 82.4 (Ar2CH),
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121.8, 125.2, 126.9, 127.1, 128.4, 128.7, 129.4, 135.8, 138.5, 138.9, 145.3 (Ar-NO2), 151.9
(C=O), 155.6 (Ar-NO2). HRMS (MALDI-TOF/TOF) m/z: [M – H]- Calcd for C21H16O5N
362.1028; Found 362.1017.
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4,4'-Dimethylbenzhydryl 4-Nitrophenyl Carbonate: from 4,4'-dimethylbenzhydrol (0.80 g; 3.8
mmol), pyridine (0.89 g; 11.3 mmol), and 4-nitrophenyl chloroformate (0.99 g; 4.9 mmol);
yield 0.93 g; 66%; 1H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.33 (s, 6H; Ar-CH3), 6.75 (s,
1H; Ar2CH), 7.17 (d, J = 7.9 Hz, 4H; Ar-CH3), 7.29 (d, J = 8.1 Hz, 4H; Ar-CH3), 7.33 (d, J =
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9.1 Hz, 2H; Ar-NO2), 8.21 (d, J = 9.2 Hz, 2H; Ar-NO2); C NMR (75 MHz, CDCl3, 25 şC):
ä/ppm = 21.2 (Ar-CH3), 82.4 (Ar2CH), 121.8, 125.2, 127.0, 129.4, 136.0, 138.3, 145.3 (Ar-
NO2), 151.9 (C=O), 155.6 (Ar-NO2). HRMS (MALDI-TOF/TOF) m/z: [M + (e–)] Calcd for
C22H19O5N 377.1263; Found 377.1270.
4-Methoxybenzhydryl 4-Nitrophenyl Carbonate: data are given in reference 6.
General Procedure for the Synthesis of Benzhydryl 4-Cyanophenyl Carbonates
In a solution of potassium 4-cyanophenoxyde (2.6 mmol) in DMSO (15 ml), a solution of
appropriate benzhydryl 4-nitrophenyl carbonate (0.9 mmol) in DMSO was added. The reaction
mixture was stirred at ambient temperature for one hour, except in the case of 4-
methoxybenzhydryl 4-cyanophenyl carbonate, when the reaction time was 2 minutes. 15 ml of
benzene was added to the mixture and after being stirred for a few minutes, the mixture was
washed with water (3 ×). After drying over anhydrous sodium sulfate, benzene was evaporated
in vacuo to give white crystals (yield 71–89%).
Benzhydryl 4-Cyanophenyl Carbonate: from potassium 4-cyanophenoxyde (0.41 g; 2.6 mmol),
1
and benzhydryl 4-nitrophenyl carbonate (0.30 g; 0.9 mmol); yield 0.20 g; 71%; H NMR (400
MHz, CDCl3, 25 şC): ä/ppm = 6.79 (s, 1H; Ar2CH), 7.28-7.42 (m, 12H; ArH + Ar-CN), 7.64 (d,
J = 8.5 Hz, 2H; Ar-CN); 13C NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 82.3 (Ar2CH), 110.0 (Ar-
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CN), 118.1 (Ar-CN), 122.1 (Ar-CN), 127.0, 128.5, 128.7 (Ar), 133.7 (Ar-CN), 138.8 (Ar),
152.0 (C=O), 154.1 (Ar-CN). Collection of HRMS data or elemental analysis was not possible
for this compound due to its limited stability.
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4-Fluorobenzhydryl 4-Cyanophenyl Carbonate: from potassium 4-cyanophenoxyde (0.39 g; 2.5
mmol), and 4-fluorobenzhydryl 4-nitrophenyl carbonate (0.30 g; 8.2 mmol); yield 0.22 g; 79%;
1H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 6.79 (s, 1H; Ar2CH), 7.08 (t, J = 8.5 Hz, 2H; Ar-
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F), 7.31-7.41 (m, 9H; ArH + Ar-F + Ar-CN), 7.67 (d, J = 8.3 Hz, 2H; Ar-CN); C NMR (75
MHz, CDCl3, 25 şC): ä/ppm = 81.6 (Ar2CH), 110.0 (Ar-CN), 115.7 (d, J = 21.7 Hz, Ar-F),
118.0 (Ar-CN), 122.0 (Ar-CN), 126.9, 128.6, 128.8 (Ar), 129.1 (d, J = 8.4 Hz, Ar-F), 133.7
(Ar-CN), 134.7 (d, J = 3.2 Hz, Ar-F), 138.5 (Ar), 151.9 (C=O), 154.1 (Ar-CN), 162.7 (d, J =
248.0 Hz, Ar-F); 19F NMR (282 MHz, CDCl3, 25 şC): ä/ppm = – 113.0. HRMS (MALDI-
TOF/TOF) m/z: [M – H]- Calcd for C21H13O3NF 346.0880; Found 346.0872.
4-Methylbenzhydryl 4-Cyanophenyl Carbonate: from potassium 4-cyanophenoxyde (0.39 g; 2.5
mmol), and 4-methylbenzhydryl 4-nitrophenyl carbonate (0.30 g; 0.8 mmol); yield 0.24 g; 86%;
1H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.34 (s, 3H; Ar-CH3), 6.76 (s, 1H; Ar2CH), 7.18
(d, J = 8.0 Hz, 2H; Ar-CH3), 7.27-7.41 (m, 9H; ArH + Ar-CH3 + Ar-CN), 7.64 (d, J = 8.8 Hz,
2H; Ar-CN); 13C NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 21.2 (Ar-CH3), 82.3 (Ar2CH), 109.9
(Ar-CN), 118.1 (Ar-CN), 122.1 (Ar-CN), 126.9, 127.1, 128.4, 128.7, 129.4 (Ar), 133.7 (Ar-
CN), 135.9, 138.5, 139.0 (Ar), 152.0 (C=O), 154.2 (Ar-CN). HRMS (MALDI-TOF/TOF) m/z:
[M – H]- Calcd for C22H16O3N 342.1130; Found 342.1133.
4,4'-Dimethylbenzhydryl 4-Cyanophenyl Carbonate: from potassium 4-cyanophenoxyde (0.37
g; 2.4 mmol), and 4,4'-dimethylbenzhydryl 4-nitrophenyl carbonate (0.30 g; 0.8 mmol);yield
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0.25 g; 89%; H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.33 (s, 6H; Ar-CH3), 6.73 (s, 1H;
Ar2CH), 7.17 (d, J = 8.1 Hz, 4H; Ar-CH3), 7.28 (d, 6H; J = 7.8 Hz, Ar-CH3 + Ar-CN), 7.64 (d, J
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= 8.7 Hz, 2H; Ar-CN); 13C NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 21.2 (Ar-CH3), 82.3
(Ar2CH), 109.9 (Ar-CN), 118.1 (Ar-CN), 122.1 (Ar-CN), 127.0, 129.4 (Ar), 133.7 (Ar-CN),
136.0, 138.3 (Ar), 152.0 (C=O), 154.2 (Ar-CN). HRMS (MALDI-TOF/TOF) m/z: [M – H]-
Calcd for C23H18O3N 356.1286; Found 356.1283.
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4-Methoxybenzhydryl 4-Cyanophenyl Carbonate: data are given in reference 6.
General Procedure for the Synthesis of Benzhydryl 4-Chlorophenyl Carbonates
The procedure for 4-chlorophenyl carbonates was almost the same as for 4-nitrophenyl
carbonates, except 4-chlorophenyl chloroformate was used instead of 4-nitrophenyl
chloroformate, and the reactants were used in different ratios (appropriate benzhydrol : pyridine
: 4-chlorophenyl chloroformate = 1.0 : 3.0 : 1.4). Furthermore, benzene layer was separated and
washed with 50% NaOH. All 4-chlorophenyl carbonates were obtained as white crystals (yield
62–80%).
4-Fluorobenzhydryl 4-Chlorophenyl Carbonate: from 4-fluorobenzhydrol (0.50 g; 2.5 mmol),
pyridine (0.59 g; 7.5 mmol), and 4-chlorophenyl chloroformate (0.66 g; 3.5 mmol); yield 0.70
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g; 80%; H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 6.76 (s, 1H; Ar2CH), 7.02-7.10 (m, 4H;
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Ar-F + Ar-Cl), 7.29-7.39 (m, 9H; ArH + Ar-F + Ar-Cl); C NMR (75 MHz, CDCl3, 25 şC):
ä/ppm = 81.1 (Ar2CH), 115.6 (d, J = 21.7 Hz, Ar-F), 122.4, 126.9, 128.5, 128.8 (Ar), 129.1 (d,
J = 8.3 Hz, Ar-F), 129.5, 131.5, 135.0 (d, J = 3.3 Hz, Ar-F), 138.9, 149.5 (Ar), 152.7 (C=O),
162.6 (d, J = 247.6 Hz, Ar-F); 19F NMR (75 MHz, CDCl3, 25 şC): ä/ppm = – 113.3. Collection
of HRMS data or elemental analysis was not possible for this compound due to its limited
stability.
4-Methylbenzhydryl 4-Chlorophenyl Carbonate: from 4-methylbenzhydrol (0.50 g; 2.5 mmol),
pyridine (0.60 g; 7.6 mmol), and 4-chlorophenyl chloroformate (0.67 g; 3.5 mmol); yield 0.55
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g; 62%; H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.32 (s, 3H; Ar-CH3), 6.75 (s, 1H;
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Ar2CH), 7.08 (d, J = 8.9 Hz, 2H; Ar-Cl), 7.16 (d, J = 8.0 Hz, 2H; Ar-CH3), 7.28-7.36 (m, 7H;
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ArH + Ar-Cl), 7.40 (d, J = 6.9 Hz, 2H; Ar-CH3); C NMR (75 MHz, CDCl3, 25 şC): ä/ppm =
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21.2 (Ar-CH3), 81.8 (Ar2CH), 109.9, 118.1 (Ar), 122.4, 127.0, 127.2, 128.3, 128.7, 129.4,
129.5, 131.4, 136.2, 138.3, 139.3, 140.7 (Ar), 152.8 (C=O). HRMS (MALDI-TOF/TOF) m/z:
[M – H]- Calcd for C21H16O3Cl 351.0788; Found 351.0800.
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4,4'-Dimethylbenzhydryl 4-Chlorophenyl Carbonate: from 4,4'-Dimethylbenzhydrol (0.50 g;
2.4 mmol), pyridine (0.56 g; 7.1 mmol), and 4-chlorophenyl chloroformate (0.63 g; 3.3 mmol);
yield 0.57 g; 65%; 1H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.32 (s, 6H; Ar-CH3), 6.72 (s,
1H; Ar2CH), 7.08 (d, J = 8.8 Hz, 2H; Ar-Cl), 7.15 (d, 4H; J = 8.0 Hz, Ar-CH3), 7.28 (d, J = 8.4
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Hz, 6H; Ar-Cl + Ar-CH3); C NMR (75 MHz, CDCl3, 25 şC): ä/ppm = 21.2 (Ar-CH3), 81.8
(Ar2CH), 122.4, 127.0, 129.3, 129.4, 131.3, 136.3, 138.1, 149.6 (Ar), 152.8 (C=O). HRMS
(MALDI-TOF/TOF) m/z: [M – H]- Calcd. for C22H18O3Cl 365.0944; Found 365.0937.
4-Methoxybenzhydryl 4-Chlorophenyl Carbonate: data are given in reference 6.
4-Methoxy-4'-Methylbenzhydryl 4-Chlorophenyl Carbonate: from 4-methoxy-4`-methyl
benzhydrol (0.50 g; 2.2 mmol), pyridine (0.52 g; 76.6 mmol), and 4-chlorophenyl
chloroformate (0.59 g; 3.1 mmol); yield 0.53 g; 63%;
1H NMR (400 MHz, CDCl3, 25 şC): ä/ppm = 2.33 (s, 3H; Ar-CH3), 3.76 (s, 3H; Ar-OCH3),
6.72 (s, 1H; Ar2CH), 6.87 (d, 2H, J = 8.7 Hz, Ar-OCH3), 7.08 (d, 2H, J = 8.9 Hz, Ar-Cl), 7.16
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(d, 2H, J = 7.9 Hz, Ar-CH3), 7.27-7.34 (m, 6H; Ar-OCH3 + Ar-CH3 + Ar-Cl); C NMR (75
MHz, CDCl3, 25 şC): ä/ppm = 21.2 (Ar-CH3), 55.3 (Ar-OCH3), 81.7 (Ar2CH), 114.0, 122.5,
126.8, 128.7, 129.3, 129.5, 131.3, 131.4, 136.4, 138.0, 149.7, 152.8 (C=O), 159.6. Collection of
HRMS data or elemental analysis was not possible for this compound due to its limited
stability.
General Procedure for the Synthesis of Benzhydryl 4-Fluorophenyl Carbonate
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