Kinetic study of proton-transfer reactions of phenylnitromethanes. Implication for the origin of nitroalkane anomaly

Article abstract of DOI:10.1021/jo200383f

Measurements of rate constants and substituent effects for three important elementary steps of proton-transfer reactions of phenylnitromethane were reported. The Hammett ? values for the deprotonation of ArCH₂NO ₂ with OH^-

Full text of DOI:10.1021/jo200383f

ARTICLE
pubs.acs.org/joc
Kinetic Study of Proton-Transfer Reactions of Phenylnitromethanes.
Implication for the Origin of Nitroalkane Anomaly
Kenichi Ando, Yu Shimazu, Natsuko Seki, and Hiroshi Yamataka*
Department of Chemistry and the Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro,
Toshima-ku 171-8501 Tokyo, Japan
S Supporting Information
b
ABSTRACT: Measurements of rate constants and substituent effects for
three important elementary steps of proton-transfer reactions of phe-
nylnitromethane were reported. The Hammett F values for the depro-
ꢀ
ꢀ
2
tonation of ArCH NO with OH , protonation of ArCHdNO with
2
2
2
ꢀ
H O, and protonation of ArCHdNO2 with HCl were determined in
aqueous MeOH at 25 °C. Comparison of these experimentally observed
F values with those calculated at B3LYP/6-31G* revealed that aci-nitro species (ArCHdNO H), which is formed on the
2
ꢀ
O-protonation of ArCHdNO2 , does not lie on the main route of the proton-transfer reaction. Analysis of the Brønsted plot
implies that the proton-transfer reaction of most XC H CH NO exhibits nitroalkane anomaly, but not for p-NO C H CH NO ,
6
4
2
2
2
6
4
2
2
and that the transition state charge imbalance is an origin of anomaly.
’
INTRODUCTION
Chart 1
Proton transfer reactions of nitroalkanes are known to show
abnormal reactivity, which is often called nitroalkane anomaly.
1
ꢀ4
The nitroalkane anomaly has been observed in several ways.
Pearson and Dillon reported in 1953 that a logarithmic plot of
deprotonation rate constants of 26 different small carbon acids
against corresponding equilibrium constants in water gave linear
Brønsted plots with the slope of 0.56 and that the points of
CH NO and CH CH NO deviated downward by 2 to 3 log-
2,6
product state. Chart 1 shows the resonance structure of nitronate
anion. In the product anion, the negative charge is largely localized
3
2
3
2
2
1
on the NO
2
group, whereas a partial negative charge developed
within the RCHNO moiety at the TS is in part on the CH
arithmic units from the correlation line. Thus, the proton-transfer
rates for nitroalkanes are slower than expected from their acidities.
Similar anomalous behavior of nitro-substituted compounds in pro-
2
2
subgroup due to electrostatic interaction between the negatively
charged carbon and the positively charged proton in-flight. Thus,
a larger fraction of negative charge is localized on the carbon at
the TS than at the product state, which explains the larger-than-
unity Brønsted R values observed for reaction 1. At the same
2
ton-transfer and other reactions has been reported. In a typical
example, the pK value of RCH NO decreases in the order CH
a
2
2
3
NO > CH CH NO > (CH ) CHNO in water, whereas the rate
2
3
2
2
3 2
2
of proton abstraction by hydroxide ion decreases in the same order.
time, since the ability of resonatively stabilizing effect of the NO
group is not fully operating at the TS, the proton-transfer rates of
2
Here the reaction is slower for a more acidic substrate. An analogous
0
system with an electron-withdrawing CN substituent, i.e., RR CHCN,
5
RNO are slower than expected from their pK ’s. The TS
2
a
was reported to exhibit normal rate-equilibrium relationship in water.
imbalance rationale has been developed by Bernasconi, for
proton-transfer reactions of various substrates. The TS imbal-
ance can be conveniently detected by looking at the charge on CR
and on NO both at the TS and the product anion, and such TS
charge imbalance for nitroalkanes has indeed been confirmed
computationally by several authors.
However, these molecular orbital (MO) calculations gave, at
Another well-known example is shown in eq 1, in which the
Brønsted Rvalues are larger than unity, indicating that the substituent
effect is larger on the rate than on the equilibrium. For example, the R
6
3
a,b
2
value is 1.54 for R = H in H O, 1.37 for R = Me in 50% aqueous
2
3c
3d
MeOH, and 1.18 for R = Me in 50% aqueous dioxane. Unusual
behavior in the rate-equilibrium relationship of nitroalkanes has been
reported not only for proton-transfer reactions but also for substitu-
7ꢀ9
4
the same time, quite normal Brønsted R values, and thus no
tion reactions, in which nitronate anion acts as a nucleophile.
8,9
anomaly was detected in these gas-phase reactions. Smaller R
values, though still large, were observed for reaction 1 in non-
hydroxylic solvents, which suggested important factors, such as
The origin of the anomaly has been interpreted in terms of
different charge distribution at the transition state (TS) and the
Received: February 21, 2011
Published: April 12, 2011
r 2011 American Chemical Society
3937
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|J. Org. Chem. 2011, 76, 3937–3945

The Journal of Organic Chemistry
ARTICLE
1
0
hydrogen-bond solvation, operating only in hydroxylic solvent.
observed large positive F value is consistent with the nature of the
reaction and qualitatively agrees with the value reported by
Bordwell with a limited number of substituents (F = 1.28 for
These results implied that the TS charge imbalance might not be
the sole origin of the nitroalkane anomaly.
Protonation of nitronate anion under acidic conditions has
3a
m-Me, H, m-Cl, and m-NO in water, 26 °C). The difference of
2
been shown experimentally to occur not on the carbon but on the
the F values is ascribed to the solvent effect, since it was reported
that the F value for the deprotonation of XC H CHCH NO
11ꢀ14
oxygen site to give aci-nitro species (eq 2).
This apparently
6
4
3
2
differs from the expectation for the protonation of nitronate
anion with H O, which on the basis of the principle of micro-
was larger in 50% (v/v) aqueous MeOH (1.58) than in water
3b
(1.17). It is noticeable, however, that points of both strongly
2
scopic reversibility has implicitly been assumed proceed via direct
electron-withdrawing (p-NO ) and electron-donating (p-MeO,
2
protonation to the carbon site of the anion to give nitro species
p-Me) substituted derivatives deviated upward from the correla-
tion line. Since the standard σ constants were apparently not
appropriate for the anion-generating reaction, we examined
ꢀ
and OH . Although it was assumed that aci-nitro species was on
a blind alley and that the protonation with acid on nitronate led
to nitro species via C-protonation, the reaction path via O-pro-
tonation and aci-nitro f nitro isomerization could not be
eliminated on the basis of kinetics with a limited number of
substrates. Recent theoretical calculations on the substituent
effects on rate and equilibrium processes of important proton-
transfer steps of ArCH NO pointed out possible involvement of
linear free energy relation (LFER) against pK ’s of substituted
a
phenols. The LFER plot in Figure 2 showed excellent correlation
except for the p-NO derivative, which deviated downward from
2
the correlation. Thus, the resonance of p-NO in the deprotona-
2
tion TS is not as strong as that in the phenoxide ion. The
observed considerable size of the slope (0.74) suggested that a
significant amount of negative charge is developed at the benzylic
carbon at the TS. The observed rate constants and the reported
2
2
9
aci-nitro species in the main course of the reaction.
pK ’s of the four substituted phenylnitromethanes in 50% (v/v)
a
3b
aqueous MeOH gave the Brønsted R coefficient of 1.34, confirm-
ing the existence of anomaly in aqueous MeOH (Figure S1 in
Supporting Information).
Protonation with H O. We have measured the rates of pro-
2
tonation on nitronate anions with water under neutral condi-
tions, which corresponds to the reverse reaction of deprotona-
During preliminary kinetic study on the protonation of nitronate
anion under acidic conditions, we found a possibility that aci-
nitro species isomerizes to nitro species via bimolecular reaction
with nitronate (eq 3). This process becomes competitive with
direct C-protonation under the conditions that the protonation
of nitronate anion is carried out with a deficient amount of acid.
This finding prompted us to kinetically examine the whole
processes involved in the proton-transfer reaction of phenylni-
tromethanes in order to understand the proton-transfer chem-
istry of nitroalkane. In particular, comparison was made between
experimentally observed substituent effects with those derived
computationally for each elementally step, which would allow us
to understand the detailed processes of proton transfer of nitroalk-
ane and the origin of the nitroalkane anomaly.
ꢀ
tion with OH . This was planned because the pK values of
a
XC H CH NO were reported only for a limited number of
6
4
2
2
derivatives and also because we had encountered difficulty in
measuring pK ’s for additional derivatives. The rates of proton-
a
ation could not be measured by a conventional way, since pK of
a
C H CH NO is much smaller than that of water and therefore
6
5
2
2
’
RESULTS AND DISCUSSION
ꢀ
Deprotonation with OH . We added some rate constant
data to a large compilation of rates of base-promoted proton
3
transfer of phenylnitroalkanes. The rates of deprotonation of
XC H CH NO under pseudo-first-order conditions with NaOH
6
4
2
2
in 300ꢀ600 molar excess at four different base concentrations
were measured photometrically in 50% (v/v) aqueous MeOH at
2
5.0 °C by a stopped-flow method. Second-order rate constants
are summarized in Table 1. The Hammett plot of the results in
Figure 1 showed nice linear correlation for meta-points with a
F value of 1.63 with the standard Hammett σ constants. The
Figure 1. Hammett correlation of the deprotonation rate of
ꢀ
XC
6
H
4
CH
2
NO
2
with OH in 50% (v/v) aqueous MeOH at 25 °C.
Table 1. Second-Order Rate Constants for Deprotonation of XC H CH NO with Hydroxide Ion in 50% (v/v) Aqueous MeOH
6
4
2
2
at 25 °C
X
p-MeO
p-Me
m-Me
H
p-Cl
m-Cl
m-F
p-CF
3
m-NO
2
p-NO
2
2
ꢀ1 ꢀ1
k
2
(10 s
M
)
2.08 ( 0.10 2.28 ( 0.07 2.46 ( 0.21 3.43 ( 0.18 8.48 ( 1.2 13.1 ( 1.2 11.4 ( 1.1 23.7 ( 2.4 48.4 ( 3.6 96.4 ( 3.4
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The Journal of Organic Chemistry
ARTICLE
ꢀ
protonation/deuteronation of ArCHdNO with H O and
2
2
H
2
O
2
D O
D O (k
/kp ), which are not bad estimates since k /k
2
p
H D
of 6.11 was reported for the deprotonation of PhCL NO (L = H
2
2
ꢀ
15
or D) with OH in water at 25 °C. The pseudo-first-order rate
constants, k , for X = H determined at 40, 50, and 60 °C gave an
obs
excellent Eyring plot, from which the rate constant at 25 °C was
calculated. For other substituted derivatives, rate constants at
2
5 °C were calculated from rate constants at 40 and 50 °C. The
H O
2
calculated protonation rate constants, k
, and the pseudo-
p
first-order rate constants at 25 °C for nine substituted derivatives
are listed, together with the activation parameters, in Table 2.
Rate constants at higher temperatures are listed in Table S2.
Note that these rate constants were obtained under the assump-
tion that there is no deuteron transfer from CD OD and the
3
deuterium isotope effects are the same (6.0) for all substituted
derivatives. Although the calculated protonation rate constants
may not be absolutely correct, they would be reliable in relative
magnitude and should be useful in analyzing substituent effect.
From the forward and reverse proton-transfer rate constants, the
pK values of XC H CH NO were calculated and are summar-
Figure 2. Correlation of the deprotonation rate of XC
6
H
4
CH
2
NO
2
ꢀ
with OH in 50% (v/v) aqueous MeOH vs pK ’s of phenols.
a
ꢀ
the equilibrium is almost fully on the PhCHNO2 þ H O side.
a
6
4
2
2
2
ized in Table 2. Comparison of these pK ’s with those available in
The rates were determined by running the reaction of nitronate
anion in 50% D O/CD OD and following the uptake of deuterium
a
the literature shows that the pK ’s are reliable at least in their
a
2
3
1
relative strength.
in the anion by H NMR (eq 4a).
With a sufficient number of rate constants for the forward and
reverse proton-transfer reactions of substituted phenylnitro-
methanes in a single solvent system, we now compare the sub-
stituent effects for both reactions. The substituent effects for the
reverse reaction are illustrated in Figure 3. The observed positive
F value of 0.45, calculated on the basis of meta substituents,
The pseudo-first-order rate constant (kobs) is given by eq 4b.
2
D O
The second-order rate constant of deuterium uptake (kp ) is
obtained from the concentration of D O and isotope effect on
2
ODꢀ
ODꢀ
deprotonation step (kdH
/k
). The second-order pro-
dD
H O
2
tonation rate constant (kp ) can then be calculated, if the
H
2
O
2
D O
deuterium isotope effect (kp /kp ) is known. We assigned
6
.0 for both the combined primary and secondary deuterium
ODꢀ
ꢀ
isotope effects for deprotonation of ArCHDNO (k
kdD
/
Figure 3. Hammett plot for the protonation of XC H CHdNO
2
2
dH
6
4
ODꢀ
) and the primary deuterium isotope effect for the
with H O in 50% (v/v) aqueous MeOH at 25 °C.
2
Table 2. Activation Parameters, Pseudo-First-Order Rate Constants, and Second-Order Rate Constants for Protonation of
ꢀ
XC H CHdNO and pK Values of XC H CH NO in 50% (v/v) MeOH at 25 °C
6
4
2
a
6
4
2
2
q
ꢀ1
q
ꢀ1
ꢀ1
a
ꢀ6 ꢀ1
H
2
Ob
ꢀ6 ꢀ1 ꢀ1
c
X
ΔH (kcal mol
)
ΔS (cal K mol
)
k
obs 1(0
s
)
k
p
(10
s
M
)
pK
a
p-MeO
p-Me
m-Me
H
22.5
21.6
21.7
21.8
21.8
21.0
21.0
20.6
19.7
ꢀ6.6
ꢀ9.1
ꢀ8.2
ꢀ7.7
ꢀ7.8
ꢀ9.9
ꢀ9.9
ꢀ10.5
7.23 ( 0.08
9.14 ( 0.14
11.6 ( 0.10
12.1 ( 0.22
13.2 ( 0.07
16.8 ( 0.10
17.8 ( 0.30
21.9 ( 0.17
19.0 ( 0.29
1.82 ( 0.02
2.30 ( 0.04
2.90 ( 0.03
3.03 ( 0.05
3.31 ( 0.08
4.23 ( 0.02
4.48 ( 0.02
5.49 ( 0.04
4.76 ( 0.08
7.69
7.75
7.82 (8.00)
7.69 (7.93)
7.34
p-Cl
m-F
7.31
m-Cl
7.28 (7.48)
7.11
p-CF
3
p-NO
2
ꢀ13.9
6.43 (6.49)
a
b
c
Pseudo-first-order rate constant of deuterium uptake. Second-order rate constant of protonation. Calculated pK
a
from forward and reverse rate
constants. Numbers in parentheses are pK values reported in ref 3b.
a
3
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The Journal of Organic Chemistry
ARTICLE
Chart 2
contrast, when large excess of HCl was added to a nitronate
solution, the absorption maximum shifted within seconds from
2
94 nm (λmax of the nitronate) to 277 nm, and then absorption
of the spectrum decreases slowly (Figure 4B). The shift of the
maximum is likely due to the formation of aci-nitro species. The
ꢀ
rates of the reactions of PhCHdNO2 (0.033 mM) with excess
indicates that not only the forward but also the reverse reaction
is accelerated by electron-withdrawing substituents, as expected
for the reactions with nitroalkane anomaly.
Important and unexpected results in Figure 3, however, are
the observed downward deviations for both electron-donating
para substituents (p-MeO, p-Me, p-Cl) and the strongly electron-
HCl were measured by following the absorbance at 277 nm.
Reactions under pseudo-first-order conditions gave excellent
linear first-order rate plots (Figure S2). However, reactions with
lower acid concentrations did not show linear plots, and there-
fore the rate constants were calculated from the data of low
fractions of reaction, and hence could be less reliable. The
observed rate constants are listed in Table S2 and are plotted
against the acid concentration in Figure 5. The apparent satura-
tion kinetics indicates that the reaction proceeds either one of the
two possible mechanisms. In one mechanism, the aci-nitro species is
on the blind-alley, and phenylnitromethane is generated by
C-protonation on the nitronate anion (eq 5). In the other
mechanism, the nitro form is obtained through isomerization
of the aci-nitro species (eq 6).
withdrawing para substituent (p-NO ). The downward devia-
2
tions for p-MeO, p-Me, and p-Cl can be rationalized by extra
resonance stabilization in the nitronate anions by these substit-
uents as illustrated in Chart 2. Thus, these para electron-donating
substituents stabilize the anions and the protonation reactions
become slower than expected from the meta correlation line. The
downward deviation for p-NO is striking. The TS imbalance
2
rationale assumes that the amount of negative charge on the
benzylic carbon would be larger at the proton-transfer TS than at
the anion state, and hence the effect of substituents on the phenyl
ring is larger at the TS. The TS imbalance operates since the
benzylic NO is a resonatively strong electron-withdrawing group,
2
which accepts a large potion of negative charge in the anion
leaving only partial charge on the benzylic carbon. The down-
ward deviation for p-NO in Figure 3 shows that the nitronate
2
anion is strongly stabilized by the p-NO substituent. It is implied
2
that NO on the phenyl ring competes with the benzylic NO in
2
2
delocalizing the negative charge and that a significant amount of
negative charge resides on the ArCH subgroup in the anion as in
2
normal cases.
Protonation with H O under Low Substrate Concentra-
þ
3
ꢀ
tion. The rates of protonation on XC H CHdNO under
6
4
2
acidic conditions were measured photometrically in 50% (v/v)
aqueous MeOH at 25 °C. The reaction was initiated by two
ways; (1) nitronate anion was generated by the reaction of
XC H CH NO and NaOH, and then allowed to react with
Protonation on nitronate anions under acidic conditions has
6
4
2
2
11ꢀ14,16ꢀ18
11
excess HCl, and (2) XC H CHdNO Na prepared separately
been investigated by several groups.
Bernasconi and
6
4
2
12
was treated with HCl.
With small excess of HCl over nitronate, the absorbance of the
Terrier have carried out kinetic study and successfully calcu-
H
3
Oþ
NOH
lated kp
and Ka
for aliphatic and aromatic nitroalkanes
nitronate decreased without a change in λmax (Figure 4A). By
under the assumption that the reaction proceeds by eq 5a.
2ꢀ
Figure 4. UVꢀvis absorption spectrum for protonation of nitronate anion in 50% (v/v) aqueous MeOH at 25 °C. (A) [PhCHdNO ] = 0.033 mM,
ꢀ
[
HCl] = 0.033 mM, (B) [PhCHdNO
2
] = 0.033 mM, [HCl] = 0.99 mM. Time intervals are 20 s at the initial part of the reaction and 60 min at the later
part in both A and B.
3
940
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The Journal of Organic Chemistry
ARTICLE
Figure 5. Observed rate constant variation with acid concentration for
ꢀ
protonation of PhCHdNO2 (0.033 mM) in 50% (v/v) aqueous
MeOH at 25 °C.
Table 3. Pseudo-First-Order Rate Constants for Protonation
ꢀ
ꢀ
þ
Figure 6. Hammett plot for protonation of XC H CHdNO with
H O in 50% (v/v) aqueous MeOH at 25 °C.
3
of XC H CHdNO with H O in 50% (v/v) Aqueous
6
4
2
6
4
2
3
þ
a
MeOH at 25 °C
4
ꢀ1
X
10 kobs (s )
p-Me
m-Me
H
9.07 ( 0.72
15.0 ( 0.3
17.3 ( 0.7
32.8 ( 0.6
55.9 ( 1.0
64.9 ( 2.0
116 ( 4
p-Cl
m-F
m-Cl
p-CF
3
a
ꢀ
[
XC H CHdNO ] = 0.033 mM.
6 4 2
NOH
Analysis of the present data with eq 5b gave pK
and
a
H
3
Oþ
ꢀ1 ꢀ1
k
as 4.2 and 34 M
s
, whereas analysis with eq 6b
s , respectively. The
value is reasonable compared to the reported
ꢀ
1
NOH
ꢀ3 ꢀ1
gave pK
calculated pKa
and k as 4.2 and 2.1 ꢁ 10
a
iso
NOH
NOH
value (pKa
= 4.75 in 50% DMSO) at 20 °C. In principle,
Figure 7. Observed rate constant variation with acid concentration for
however, the two mechanisms are difficult to distinguish by the
analysis of acid concentration dependence, since the rate is
expressed in similar forms as shown in eqs 5b and 6b, re-
spectively. In the present study, we examined the effect of sub-
stituent on the rate of protonation under high acid concentra-
tions, where the rate is independent of the acid concentration and
the substituent effect was compared with the calculated sub-
stituent effect (vide infra). Under such conditions, the rate
ꢀ
protonation of PhCHdNO
at 15 °C.
2
(5.0 mM) in 50% (v/v) aqueous MeOH
atmospheric CO in order to avoid an influence of CO on the
2 2
rate measurements. Thus, we also used a much higher substrate
concentration (5.0 mM) and examined the effect of acid con-
centration on the reactivity. The rate constants determined with
a batch method at 15 °C (see Supporting Information for details)
are listed in Table S4 and illustrated in Figure 7.
It was found that the protonation rates exhibited peculiar acid-
concentration dependence as shown in Figure 7. Here, the rate
NOH
H
3
Oþ
constant, kobs, would be Ka
k
and kiso for mechanisms
ꢀ1
5
and 6, respectively. The pseudo-first-order rate constants for
protonation of XC H CHdNO under acidic conditions are
ꢀ
6
4
2
listed in Table 3 (and Table S3 in detail). The Hammett plot in
Figure 6 gave a rather large F value of 1.49. It is much larger than
constants at a high acid concentration region are constant at
ꢀ
ꢀ4 ꢀ1
the F value (0.45) for the protonation of XC H CHdNO
about 6.0 ꢁ 10
s , which is in good agreement with the rate
6
4
2
ꢀ
4
ꢀ1
with neutral H O (Figure 3), which reflects that the mechanisms
constant (17.3 ꢁ 10
s ) determined at a lower substrate
2
of protonation under neutral and acidic conditions are different;
the protonation under basic conditions occurs on the nitronate
anion, whereas the effective reactant species under high acidic
concentration (Figure 5) if the difference of reaction temperature
is taken into account. At a low acid concentration region, however,
the rate constants exhibit a sharp increase with a decrease of acid
concentration, instead of showing saturation kinetics.
concentrations is aci-nitro species.
þ
Protonation with H O under High Substrate Concentra-
tion. Since the absorption coefficients of nitronate anions were
Since the reaction under low acid concentration conditions
does not follow pseudo-first-order kinetics, the rates were de-
termined only for the initial part of the reaction, and therefore the
rate constants are less reliable. Nevertheless, the fact that the rate
is faster at a lower acid concentration is clearly seen in the decay
3
quite large, we have normally used a low substrate concentration
(
∼0.03 mM) for the rate measurement. However, the use of such
low concentrations required tedious procedures to eliminate
3
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The Journal of Organic Chemistry
ARTICLE
Table 4. Hammett G Values for Various Proton-Transfer Steps of Substituted Phenylnitromethanes at 25 °C Calculated at
B3LYP/6-31þG*
eq
reaction
F
rate
F
equilibrium
ꢀ
2ꢀ
a
a
a
7
8
9
XC
XC
XC
XC
XC
6
H
6
H
6
H
6
H
6
H
4
4
4
4
4
CH
2
2
NO
2
2
þ OH (H
2
O)
2
f XC
6
H
4
CHdNO þ (H
2
O)
3
6.9
2.3
12.6
a
CH
NO
þ (H
2
O)
2
f XC
6
H
4
CHdNO
2ꢀ
2
H þ (H
CHdNO þ XC
2
O)
2
0.8
2
H þ XC
6
H
4
CHdNO f XC
6
H
4
2ꢀ
6 4 2 2
H CH NO
2
)
2ꢀ
ꢀ2.2
ꢀ6.5
ꢀ5.9
ꢀ0.8
ꢀ12.1
ꢀ13.0
CHdNO
ꢀ
1
0
1
CHdNO
2
þ CH
2
(NO
(NO
2
)
2
2
f XC
f XC
6
H
H
4
CHdNO
2
H þ CH(NO
2ꢀ
2
2
6
4
2
2
2 2
ꢀ
1
CHdNO þ CH
)
CH NO
þ CH(NO
)
a
Data taken from ref 9.
plots in Figure S3 in Supporting Information. The fact suggested
a possibility that the aci-nitro species initially formed by the
O-protonation of nitronate anion reacts with the remaining
nitronate anion to yield the nitronate and nitro species in a
bimolecular reaction as shown in eq 3. This route becomes
possible since the reaction of nitronate with a deficient amount of
acid initially yields preferentially the O-protonated aci-nitro
species, and under such circumstances the reaction of the aci-
nitro and nitronate species to afford the nitro species is an
endergonic process.
We used a carbon acid (CH (NO ) ) in reactions 10 and 11,
2 2 2
þ
since the use of H O or HCl did not allow us to optimize TS
3
structures.
Since the initial protonation of nitronate occurs on O more
rapidly than on C, if an effective aci-nitroꢀnitro transformation
exists, then the protonation of nitronate to nitro may proceed
through the aci-nitro route, especially when the protonation
reaction is carried out at a higher substrate concentration than
that (5 mM) in the protonation reaction here. A question then
arises whether the aci-nitro route may be a significant route for
deprotonation of nitroalkane with a base.
Comparison of Hammett G Values. Previous DFT calcula-
tions suggested on the basis of reaction energetics that the
ꢀ
reaction of ArCHdNO2 and H O proceeds via the direct
2
C-protonation rather than the O-protonated aci-nitro intermedi-
Hammett plots for the rates and equilibria for reactions 9ꢀ11
are illustrated in Figures S4ꢀS6, and the calculated F values are
summarized, together with the F values for reactions 7 and 8 in
9
ate (ArCHdNO H). Although O-protonation is faster than
2
C-protonation, the O-protonated state (ArCHdNO H þ
2
ꢀ
ꢀ
ꢀ
OH ) is a minor component in the equilibrium with ArCHd
Table 4. The F value for the ArCH NO f ArCHdNO
2
2
2
NO2 þ H O, and hence the route via aci-nitro species would be
equilibrium in the present study (13.0) is slightly different from
2
9
less favorable. However, it was also concluded that if there is an
effective isomerization process whose barrier is much lower than
that in reference (12.6, eq 7), due to the difference in the
number of substituents used in the calculations. It is interesting to
(
H O) -mediated isomerization (eq 8), ArCH NO may be
note that the F values for the deprotonation reactions with
2
2
2
2
rate
ꢀ
ꢀ
formed via the aci-nitro route. For the protonation of nitronate
with acid, on the other hand, since the O-protonated state
becomes a major component in the equilibrium, the energetic
consideration suggested that the O-protonationꢀisomerization
route could be well competitive with the direct C-protonation
OH (H O) (eq 7) and CH(NO ) (eq 11) are also similar
2 2 2 2
(6.9 and 7.1 (= 13.0ꢀ5.9), despite the fact that the nature and the
strength of these two bases are different.
Comparison of Calculated and Experimental G Values. The
ꢀ
two mechanisms on the protonation of XC H CHdNO
6
4
2
9
route, if a fast isomerization process is available. With these
with an acid (eqs 5 and 6) could be differentiated by
comparing experimentally observed F values with the F values
for elementary steps determined by the DFT calculations. If the
protonation reaction proceeds via the aci-nitro route (eq 6),
the experimental F value for each step could be assigned as
shown in Scheme 1. Here, the F value (ꢀ1.20) for
arguments in mind, we have calculated F values for reactions
7
ꢀ11, and compared the calculated F values with the F values
determined experimentally in the present study.
Calculated G Values. The substituent effects on the rates
and equilibria for reactions 7 and 8 in the gas phase have
been calculated previously at the B3LYP/6-31þG* level of
ꢀ
XC H CHdNO f XC H CHdNO H equilibrium was
6
4
2
6
4
2
9
NOH
theory. Reaction 8 is an isomerization of XC H CH NO to
calculated from the pKa
and p-NO ) in 50% DMSO,
calculated from pK ’s of XC H CH NO . It is seen that the
values of two substrates (X = H
6
4
2
2
1
1,12
XC H CHdNO H through double proton transfer with
and the F value (ꢀ1.22) was
6
4
2
2
(
H O) as a catalyst. The calculated F values were 6.9 (rate)
2
2
a 6 4 2 2
and 12.6 (equilibrium) for reaction 7 and 2.3 (rate) and 0.8
calculated F values for the nitronate f aci-nitro and the
nitronate f nitro equilibria (ꢀ12.1 and ꢀ13.0) are much
larger than the corresponding experimental values (ꢀ1.20
and ꢀ1.22) in both cases, likely due to the absence of solva-
tion. In the O-protonationꢀisomerization mechanism, since
XC H CHdNO H is the effective reactant under acidic conditions,
(equilibrium) for reaction 8. In the present study, the substituent
effects were calculated for reactions 9ꢀ11 at the same level of
theory. Here, reaction 9 is an aci-nitroꢀnitro isomerization with
the nitronate anion as a mediator, and reactions 10 and 11 are the
O- and C-protonation on substituted nitronate anion by an acid.
6
4
2
3
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The Journal of Organic Chemistry
ARTICLE
Scheme 1
Scheme 2
Figure 8. Brønsted correlation of the deprotonation rates of
XC H CH NO with hydroxide ion in 50% (v/v) aqueous MeOH at
6
4
2
2
a
25 °C. pK data was taken from refs 3a and 3b.
protonation reactions both under neutral and acidic conditions, or
of the deprotonation reactions under basic and neutral conditions.
This, in turn, means that the existence of aci-nitro species is not the
origin of nitroalkane anomaly.
It is interesting to note that the Hammett plots reported in the
literature for the deprotonation reaction of XC H CH NO with
6
4
2
2
ꢀ
3a
OH did not include the data of the p-NO derivative. The
2
Brønsted slope R was calculated as the ratio of the two Hammett
3b
F values, on rate and equilibrium, and thus again the point of
p-NO was eliminated. We have now plotted the deprotonation
2
rates determined in the present study against the pK reported in
a
the literature in Figure 8. The Brønsted plot in Figure 8 clearly
indicates that the point of p-NO deviates downward from the
2
the experimental Fvalue (1.49, Figure 6) is for the isomerization rate
process for XC H CHdNO H f XC H CH NO . The calcu-
lated F value for the same process in the gas phase is ꢀ2.2. These
two values do not match, which clearly indicates that the reaction
does not proceed through the O-protonationꢀisomerization me-
chanism in Scheme 1.
correlation line. The slope gave the R value of 1.34 for all
6
4
2
6
4
2
2
substituents except p-NO and 0.53 for the line connecting
2
m-NO and p-NO . In Figure S7 is shown the Brønsted plot
2
2
against the pK values determined in the present study (Table 2).
a
Here also, the correlation gave nice straight line with an R value
of larger than unity, but the point for the p-NO derivative
2
If, on the other hand, the direct C-protonation mechanism
deviated downward. Thus, the so-called nitroalkane anomaly
(
eq 5) is assumed for the reaction, the F values are evaluated as
does not appear for the p-NO substituted derivative. The two lines
2
shown in Scheme 2. In this mechanism, the substituent effect for
the protonation XC H CHdNO under acidic conditions
ꢀ
in Figure 8 implies that XC H CH NO with a weakly electron-
6
4
2
2
6
4
2
withdrawing or electron-donating X exhibit anomaly due to TS
would be the sum of the F value on the initial deprotonation
ꢀ
imbalance, reflecting small substituent effect on pK , whereas p-
a
equilibrium between XC H CHdNO H and XC H CHdNO
6
4
2
6
4
2
ꢀ
2
NO C H CH NO does not show anomaly because the strongly
2
6
4
2
2
and the F value for the C-protonation of XC H CHdNO , since
the effective reactant is again XC H CHdNO H. The calculated
6
4
electron-withdrawing p-NO C H group can compete with the R-
2
6 4
6
4
2
NO . It should be noted here that such TS imbalance is exalted by
2
overall F value for this route is 6.2 (12.1 þ (ꢀ5.9)). Comparison of
this F value and the experimental value (1.49) shows that the
reaction mechanism illustrated in Scheme 2 is much more accep-
table than the mechanism in Scheme 1. The difference of these two
F values is well explained by the solvation effect. This, in turn, means
that the deprotonation of XC H CH NO with H O occurs via the
solvation to a level of showing nitroalkane anomaly due to an
7,8,10
enhanced electron-withdrawing ability of NO in protic solvents.
2
’
CONCLUSION
The present extensive kinetic study for the proton-transfer reactions
6
4
2
2
2
direct deprotonation route rather than the aci-nitro route. The result
ꢀ
further suggests that the protonation of PhCHdNO2 with H O
of phenylnitromethanes under various reaction conditions revealed
that, although aci-nitro species may form during the proton-transfer
reactions, it is not on the main reaction pathways. The Hammett plot
for protonation of nitronate and a Brønsted plot including p-NO2
showed that the nitroalkane anomaly exists for all substituted phenyl-
2
under neutral conditions proceeds through the direct C-protonation
route, since the initial protonation equilibrium between PhCHd
ꢀ
ꢀ
NO2 þ H O vs PhCHdNO H þ OH should almost com-
2
2
pletely on the nitronate side. In summary, the present kinetic study,
together with previous and present computational results showed
9
nitromethanes except for the p-NO derivative. The result is consistent
2
that the aci-nitro species does not lie on the main course of the
with the notion that TS imbalance is the source of anomaly.
3
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The Journal of Organic Chemistry
ARTICLE
’
EXPERIMENTAL SECTION
Preparation of Phenylnitromethanes from Benzyl Bro-
mides. m-NO
2
C
6
H
4
CH
2
NO
2
. In 500 mL flask were placed AgNO
O (240 mL), and the flask was purged
and covered by aluminum foil. At room temperature, m-
CH Br (6.70 g, 31.1 mmol) in Et O (150 mL) was added
2
Materials. Water (liquid chromatography grade) was fractionally
distilled and degassed before use and mixed with fractionally distilled
methanol (liquid chromatography grade) to make 50% (v/v) aqueous
(5.26 g, 34.1 mmol) and Et
2
by N
2
NO
2
C
6
H
4
2
2
methanol. D
were used as received.
Substituted phenylnitromethanes were prepared from substituted
2 4
O (Merck, 99.9%) and methanol-d (ACROS, 99.8%)
by using a hypodermic syreinge. The reaction solution was stirred for 22
h at room temperature, filtered, washed with H O, and dried over
2
1
MgSO
4
. Yield: 77.4%. Mp 94ꢀ95 °C. H NMR (CDCl
3
, 400 MHz):
19
phenylacetonitriles, from phenylacetic acid or from benzyl bromide.
δ 8.34ꢀ8.36 (m, 2H), 7.82 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H),
Substituted phenylnitromethanes were purified by either column chro-
1
5
8
.56 (s, 2H). H NMR (CD OD, 400 MHz): δ 8.42 (s, 1H),.8.34 (d, J =
.0 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.71 (t, J = 8.0 Hz, 1H), 5.77
3
matography (H, m-Me, p-Me, p-MeO, m-F, m-Cl, p-Cl, and p-CF
derivatives) or recrystallization (m-NO and p-NO ) or both (p-CF ).
3
13
2
2
3
3
(s, 2H). C NMR (CD OD, 400 MHz): δ 144.0, 137.7, 133.8, 131.3,
Sodium salts of phenylnitromethanes were prepared by running the
126.5, 126.4, 78.9.
reaction of phenylnitromethanes with sodium in anhydrous EOH/Et
mixed solvent.
2
O
1
m-ClC CH NO
2
6
H
4
2
. Yield: 81.3%. H NMR (CDCl
3
, 400 MHz):
3
OD, 400 MHz):
1
δ 7.33ꢀ7.47 (m, 2H), 5.41 (s, 2H). H NMR (CD
1
3
Preparation of Phenylnitromethanes from Phenylaceto-
nitriles. C CH NO . To Na metal (6.10 g, 0.265 mol) dissolved in
ice-cooled anhydrous EtOH (75 mL) was added dropwise a mixture of
PhCH CN (29.5 g, 0.252 mol) and MeONO (70.0 g, 0.909 mol) under
δ 7.53 (s, 1H),.7.39ꢀ7.48 (m, 3H), 5.59 (s, 2H). C NMR (CD OD,
3
6
H
5
2
2
400 MHz): δ 135.6, 134.0, 131.5, 131.4, 130.8, 129.7, 79.6.
1
p-NO
2
C
6
H
4
CH
2
NO
2
. Yield: 50.7%. Mp 90ꢀ91 °C. H NMR (CDCl
3
,
2
2
4
00 MHz): δ 8.32 (d, J = 8.7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 5.56
1
stirring at such a rate that the solution temperature stayed at 4ꢀ8 °C.
The stirring was continued for 3 h, and the solution was stored in
refrigerator overnight. The precipitate was collected by filtration and
(s, 2H). H NMR (CD OD, 400 MHz): δ 8.30 (d, J = 8.7 Hz, 2H),.7.75
3
1
3
3
(d, J = 8.7 Hz, 2H), 5.77 (s, 2H). C NMR (CD OD, 400 MHz):
δ 150.1, 138.5, 132.7, 124.9, 79.1.
Preparation of Sodium Salt of Phenylnitromethanes.
CHdNO Na. To a 50% (v/v) mixture of anhydrous EtOH and
washed with anhydrous Et O. The filtrate was condensed by rotary
2
evaporator, and the resultant precipitate was filtered and washed with
C
6
H
5
2
anhydrous Et
dried over silica gel. The combined precipitate was boiled with NaOH
41.6 g, 1.04 mol) in H O (160 mL) for 3 h, allowed to cool to room
2
O. The precipitate was combined with the first lot and
anhydrous Et O (10.8 mL) was added Na (0.460 g, 20.0 mmol), and the
2
mixture was stirred until Na was completely dissolved. To this mixture,
(
2
2 2 2
anhydrous Et O (54 mL) was added, and then PhCH NO (3.01 g, 22.0
temperature, and was added to 10 g of ice. The reaction mixture was
mmol) in anhydrous Et O (13.2 mL) was added dropwise. The resultant
2
cooled at ꢀ20 to ꢀ10 °C and acidified with conc HCl. The solution was
precipitate was collected and washed with anhydrous Et
2
O and dried.
1
extracted with Et O, and the organic layer was washed with aqueous
2
Yield: 95.8%. H NMR (CD OD, 400 MHz): δ 7.87 (d, J = 7.8 Hz, 2H),
3
1
13
2 4
NaHCO and water and dried over MgSO . Yield, 48.8%. H NMR
7
(
.29 (t, J = 7.8 Hz, 2H), 7.16 (t, J = 7.8 Hz, 1H), 6.98 (s, 1H). C NMR
CD OD, 400 MHz): δ 134.4, 129.1, 127.6, 127.5, 116.9.
p-MeOC H CHdNO Na. Yield: 57.6%. H NMR (CD OD, 400
1
(
(
(
CDCl
3
, 400 MHz): δ 7.41ꢀ7.46 (m, 5H), 5.44 (s, 2H). H NMR
3
13
1
CD
CD
3
OD, 400 MHz): δ 7.42ꢀ7.49 (m, 5H), 5.57 (s, 2H). C NMR
6
4
2
3
3
OD, 400 MHz): δ 132.2, 131.2, 130.7, 130.0, 80.6.
MHz): δ 7.83 (d, J = 9.2 Hz, 2H), 6.92 (s, 1H), 6.88 (d, J = 9.2 Hz,
H), 3.79 (s, 3H).
p-MeC H CHdNO Na. Yield: 74.5%. H NMR (CD OD, 400 MHz):
1
p-MeC
6
H
4
CH
2
NO
2
. Yield, 28.9%. H NMR (CDCl
3
, 400 MHz): δ 7.34
2
1
(
d, J = 7.8 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 5.40 (s, 2H), 2.38 (s, 3H).
6
4
2
3
1
m-MeC H CH NO . Yield: 45.5%. H NMR (CDCl , 400 MHz): δ
6
4
2
2
3
δ 7.75 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.94 (s, 1H, CH),
.30 (s, 3H).
m-MeC
MHz): δ 7.72 (s, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.17 (t, J = 7.8 Hz,
1
7
.24ꢀ7.34 (m, 4H), 5.40 (s, 2H), 2.38 (s, 3H). H NMR (CD
3
OD, 400
2
1
3
1
MHz): δ 7.26ꢀ7.32 (m, 4H), 5.52 (s, 2H), 2.36 (s, 3H). C NMR
6 4 2 3
H CHdNO Na. Yield: 74.8%. H NMR (CD OD, 400
(
8
CD OD, 400 MHz): δ 140.0, 132.1, 131.7, 131.4, 129.8, 128.2,
3
13
0.7, 21.3.
m-FC
td, J = 7.8, 5.8 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.14ꢀ7.21 (m, 2H),
.44 (s, 2H).
p-ClC CH
.39ꢀ7.43 (m, 4H), 5.41 (s, 2H).
p-CF CH NO
1
(
1
H), 6.99 (d, J = 7.8 Hz, 1H), 6.94 (s, 1H), 2.32 (s, 3H). C NMR
CD OD, 400 MHz): δ 138.7, 134.2, 129.1, 128.5, 128.6, 124.9,
17.2, 21.6.
m-FC H CHdNO Na. Yield: 60.2%. H NMR (CD OD, 400 MHz):
1
6 4 2 2 3
H CH NO . Yield: 71.1%. H NMR (CDCl , 400 MHz): δ 7.42
3
(
1
5
7
4
6
4
2
3
1
6
H
4
2 2 3
NO . Yield: 40.7%. H NMR (CDCl , 400 MHz): δ
δ 7.93 (d, JHF = 12.0 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.26 (td, J = 8.0,
J
HF = 5.6 Hz, 1H), 6.98 (s, 1H), 6.86 (dd, J = 8.0, JHF = 8.0 Hz, 1H).
1
1
3
C
6
H
4
2
2
. Yield: 71.4%. Mp 41ꢀ42 °C. H NMR (CDCl
3
,
p-ClC H CHdNO Na. Yield: 70.3%. H NMR (CD OD, 400 MHz):
6
4
2
3
00 MHz): δ7.72 (d, J= 8.2 Hz, 2H), 7.60 (d, J= 8.2 Hz, 2H), 5.51 (s, 2H).
Preparation of Phenylnitromethanes from Phenylacetic
δ 7.86 (d, J = 9.2 Hz, 2H), 7.27 (d, J = 9.2 Hz, 2H), 6.96 (s, 1H).
1
m-ClC H CHdNO Na. Yield: 74.2%. H NMR (CD OD, 400 MHz):
6
4
2
3
Acids. p-MeOC H CH NO . To diisopropylamine (12.5 g, 123 mmol)
δ 8.14 (s, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 7.13
(d, J = 7.8 Hz, 1H), 6.95 (s, 1H). C NMR (CD OD, 400 MHz):
6
4
2
2
1
3
in 100 mL of anhydrous THF cooled with a dry ice/EtOH bath were
3
added under N atmosphere n-BuLi (2.6 M, 15.2 mL, 117 mmol) and
HMPA (9.15 g, 51.0 mmol) in 40 mL of anhydrous THF by using a
δ 136.6, 135.2, 130.4, 127.0, 126.7, 125.6, 115.3.
2
1
p-CF C H CHdNO Na. Yield: 62.8%. H NMR (CD OD, 400
3
6
4
2
3
hypodermic syringe, and the solution was allowed to warm up to 0 °C.
MHz): δ 8.03 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.04 (s, 1H).
1
An anhydrous THF (40 mL) solution of p-MeOC
6
H
4
CH
2
CO
2
H
m-NO C H CHdNO Na. Yield: 60.9%. H NMR (CD OD, 400
2
6
4
2
3
(
8.48 g, 51.0 mmol) was added dropwise to the LDA solution at 0 °C,
MHz): δ 9.03 (s, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.8 Hz,
1
3
and the solution was stirred at room temperature for 1.5 h. The
solution was cooled again with a dry ice/EtOH bath, and MeONO2
(
temperature. After addition of CH CO H (7 mL), the reaction
solution was warmed up to 0 °C, HCl (4 M, 60 mL) was added,
and the mixture was extracted with ether. Yield: 81.6%. H NMR
1H), 7.49 (t, J = 7.8 Hz, 1H), 7.09 (s, 1H). C NMR (CD OD, 400
3
MHz): δ 149.9, 136.8, 132.6, 132.6, 130.1, 121.1, 114.3.
1
11.4 g, 153 mmol) was added and kept stirring for 1 h at the same
p-NO C H CHdNO Na. Yield: 74.4%. HNMR(CD OD, 400 MHz):
2
6
4
2
3
13
3
2
δ 8.14 (d, J = 9.2 Hz, 2H), 8.03 (d, J = 9.2 Hz, 2H), 7.08 (s, 1H). C NMR
(CD OD, 400 MHz): δ 145.8, 141.9, 126.7, 124.6. 114.6.
3
1
Rate Measurements. Measurement of Deprotonation Rates.
ꢀ
(
CDCl , 400 MHz): δ 7.38 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz,
Rate constants for the deprotonation of XC H CH NO with OH
3
6
4
2
2
2
H), 5.37 (s, 2H), 3.83 (s, 3H).
in aqueous 50% (v/v) MeOH at 25 ( 0.1 °C were determined by
3
944
dx.doi.org/10.1021/jo200383f |J. Org. Chem. 2011, 76, 3937–3945

The Journal of Organic Chemistry
ARTICLE
following the decay of absorbance of XC
X = p-MeO (295.8 nm, p-Me; 294.5 nm, m-Me; 295.6 nm, H; 303.3 nm,
2
p-Cl; 299.5 nm, m-Cl; 301.2 nm, m-F; 311.4, p-CF ; 304 nm, m-NO ;
6
H
4
CH
2
NO
2
at 297.0 nm for
’ REFERENCES
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3
91.0 nm, p-NO
2
) with a stopped-flow instrument. The initial concen-
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ꢀ
tration of XC H CH NO was 0.050 mM, and that of OH was 1.5, 2.0,
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4
2
2
2.5, or 3.0 mM.
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H
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3
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21, 715.
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Acc. Chem. Res. 1992, 25, 9. Bernasconi, C. F. Adv. Phys. Org. Chem. 1992,
0
.4 mL of D O, and cooled down to freeze in a low-temperature bath
2
(
(
r20 °C). The protonation reaction was practically stopped when the
1
solution was mixed with a large potion of D O, since the protonation is very
2
(
slow in aqueous MeOH with a high H O content. The proton NMR spectra
2
were then recorded, and the relative intensity of the benzylic proton
2
1
1
7, 116. Bernasconi, C. F.; Wenzel, P. J. J. Am. Chem. Soc. 1994,
16, 5405. Bernasconi, C. F.; Wenzel, P. J. J. Am. Chem. Soc. 1996,
18, 11446. Bernasconi, C. F. Adv. Phys. Org. Chem. 2010, 44, 223.
(
3
δ = 7.08) with respect to CH signal of DMSO was used to follow the
reaction.
Measurement of the Rates of Protonation of Nitronate Anion
Low Acid Concentration). Rate constants for the protonation of
(7) (a) Bernasconi, C. F.; Wenzel, P. J.; Keeffe, J. R.; Gronert, S.
(
J. Am. Chem. Soc. 1997, 119, 4008. (b) Bernasconi, C. F.; Wenzel, P. J.
J. Am. Chem. Soc. 2001, 123, 2430.
(8) Yamataka, H.; Mustanir; Mishima, M. J. Am. Chem. Soc. 1999,
121, 10223.
C
0
6
H
5
CHdNO
.1 °C were determined by following the decay of absorbance of the
equilibrium mixture of XC H CHdNO Na and XC H CHdNO H
2
Na with HCl in aqueous 50% (v/v) MeOH at 25 (
6
4
2
6
4
2
at 276.0ꢀ294.0 nm photometrically. The initial concentration of
XC CHdNO Na was 0.033 mM. The rate constants for
C H CHdNO Na with different acid concentrations are listed in
(9) Sato, M.; Kitamura, Y.; Yoshimura, N.; Yamataka, H. J. Org.
Chem. 2009, 74, 1267.
6
H
4
2
(
10) Keeffe, J. R.; Morey, J.; Palmer, C. A.; Lee, J. C. J. Am. Chem. Soc.
979, 101, 1295.
11) Bernasconi, C. F.; Kliner, D. A. V.; Mullin, A. S.; Ni, J. X. J. Org.
Chem. 1988, 53, 3342.
12) Moutiers, G.; Thuet, V.; Terrier, F. J. Chem. Soc., Perkin Trans. 2
997, 1479.
6
5
2
1
Table S3. Rate constants for XC H CHdNO Na are summarized in
6
4
2
(
Table S4. Typical rate plots are illustrated in Figure S2.
Measurement of the Rates of Protonation of PhCHdNO
2ꢀ
(
(
High Substrate Concentration). The reactions at higher substrate
concentrations were carried out in a flask with the concentration of
XC HCHdNO Na of 5 mM at 15 ( 0.1 °C. The rate constants were
1
(13) Turnbull, D.; Maron, S. H. J. Am. Chem. Soc. 1943, 65, 212.
(14) Maron, S. H.; La Mer, V. K. J. Am. Chem. Soc. 1939, 61, 692.
(15) Bordwell, F. G.; Boyle, W. J., Jr. J. Am. Chem. Soc. 1975,
6
2
determined by a batch method, in which 0.1 mL of the reaction solution
was taken out at preset intervals, diluted in a 10 mL volumetric flask, and
subjected to UV measurement. The results are listed in Table S4.
Examples of rate plots are shown in Figure S3.
97, 3447.
(16) Sun, S. F.; Folliard, J. T. Tetrahedron 1971, 27, 323.
(17) Pearson, R. G.; Dillon, R. L. J. Am. Chem. Soc. 1950, 72, 3574.
Calculations. Separated reactants, TSs, and products for reactions
(18) Edward, J. T.; Tremaine, P. H. Can. J. Chem. 1971, 49, 3483.
(19) Organic Synthesis; Wiley: New York, 1943; p 512.
(20) Frisch, M. J. et al. Gaussian 03, Revision C.02; Gaussian, Inc.:
2
0
9
ꢀ11 were calculated at the B3LYP/6-31þG* level of theory. Full
frequency analyses were carried out to confirm that the optimized
structures were minima or saddle points on the potential energy surface.
All activation and reaction energies reported are relative to separated
Wallingford, CT, 2004.
ꢀ
1
reactants in kcal mol . We use enthalpies rather than free energies,
since calculated entropies, and hence free energies as well, are known to
be less reliable and not suitable for linear free energy analyses. Hammett
plots were made by using relative activation or reaction enthalpies at 298 K.
’
ASSOCIATED CONTENT
S
Supporting Information. Kinetic data, Hammett and
b
Brønsted plots, and computational results. This material is
available free of charge via the Internet at http://pubs.acs.org.
’
AUTHOR INFORMATION
Corresponding Author
*E-mail: yamataka@rikkyo.ac.jp.
’
ACKNOWLEDGMENT
The study was in part supported by the Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
3
945
dx.doi.org/10.1021/jo200383f |J. Org. Chem. 2011, 76, 3937–3945