Amination of phenylketene revisit. Substituent effect on reactivity

Article abstract of DOI:10.1246/bcsj.20130028

The asymmetric stretching frequencies of the ketene group of the m,p-substituted phenylketenes were found to be correlated with σ The substituent effects for the second-order rate constants of phenylketenes with various amines were not correlated linearly

Full text of DOI:10.1246/bcsj.20130028

856
Bull. Chem. Soc. Jpn. Vol. 86, No. 7, 856-863 (2013)
© 2013 The Chemical Society of Japan
Amination of Phenylketene Revisit. Substituent Effect on Reactivity
Md. Mizanur Rahman Badal, Min Zhang, Shinjiro Kobayashi, and Masaaki Mishima*
Institute for Materials Chemistry and Engineering, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581
Received February 4, 2013; E-mail: mishima@ms.ifoc.kyushu-u.ac.jp
The asymmetric stretching frequencies of the ketene group of the m,p-substituted phenylketenes were found to be
correlated with ·. The substituent effects for the second-order rate constants of phenylketenes with various amines were
not correlated linearly with any single substituent constants. The curved ·°-correlations with a plateau at a high reactivity
region were observed for meta-substituents and p-chloro. The substituent effects including para-³-acceptors were
described in terms of the Yukawa-Tsuno equation modified by a quadratic term as an approximation. The resultant μ
¹
value decreases significantly from 2.92 for 2,2,2-trifluoroethylamine to 0.83 for benzylamine while an r value increases
¹
from 0.50 to 1.10. The opposite change of μ and r with amines was interpreted by the dual electronic interactions
between substituents and positive/negative charges at the zwitterionic transition structure. According to this inter-
¹
pretation, benzylamine with small μ value and large r value attributes to early transition state and larger μ value with
¹
smaller r value for 2,2,2-trifluoroethylamine attributes to late transition state.
Nucleophilic addition to ketenes has been considered to
resolved infrared (TRIR) method was used to measure the rate
constants because ketenes exhibit a very strong and charac-
teristic IR band in the region of 2100 cm¹1, arising from the
asymmetric stretch of the C=C=O moiety.
proceed via a highly polar transition state.1-5 The ability of the
system to stabilize the developing charges at the transition state
would be important in determining the energetic and kinetics
of the reaction. The high reactivity of phenylketene is likely
attributed to electronic properties of the phenyl group. Ana-
lysis of the substituent effects in reactivity provides useful
information on the reaction mechanism and, transition struc-
ture of the rate-determining step. The substituent effect for
hydration of p-substituted phenylketenes was analyzed in terms
Results and Discussion
Structural Effects on the Asymmetric Stretching Fre-
quencies of Phenylketenes. Phenylketenes were generated
by the 266 nm laser irradiation of ¡-diazoacetophenone prec-
ursors, via the Wolff rearrangement of the initial carbene
(Scheme 1).1,9 Figure 1 shows a typical IR spectrum of pho-
tolysis of ¡-diazoacetophenone in acetonitrile.
of ·p substituent constants, giving a μ of 1.19.6 This positive
n
μ value suggested formation of the negative charge on the
ketene moiety at the transition state. More recently, Wagner
et al.7 found much smaller μ values for the amination of
p-substituted phenylketenes in acetonitrile. These μ values
varied with nucleophile amines, 0.43, 0.50, 0.88, 0.63, and
0.83 for diethylamine, piperidine, i-propylamine, butylamine,
and benzylamine, respectively. The change in μ value with
amines would be meaningful though the μ values are small in
magnitude because all kinetic data were obtained by a research
group using the same experimental techniques under the same
conditions. The large μ value suggests the larger negative
charge developed at the transition state, i.e., later transition
state along the reaction coordinate. However, this order is
not consistent with that expected from the nucleophilicity of
amines. The nucleophilicity increases in order of i-propylamine
(N = 13.77) < benzylamine (N = 14.29) < diethylamine (N =
15.10) < butylamine (N = 15.27) < piperidine (N = 17.35).8
This discrepancy may arise from low reliability of the μ values
because of a small data set limited only for para-substituted
derivatives. In order to get more information on the transition
structure, it is necessary to examine in detail the substituent
effect for the nucleophilic addition of phenylketene based on
a wide variation of the substituent. Therefore, in this work
we have determined rate constants for a series of substituted
phenylketenes with various amines in acetonitrile. A time-
A strong sharp band with a maximum at 2120 cm¹1 assigned
as the asymmetric stretching of the C=C=O group is agree-
ment with the literature value (2118 cm¹1).7 A weak bleaching
¹1
observed at 1620 and 2095 cm results from the depletion
of the carbonyl and diazo bands of the ¡-diazoacetophenone
precursor, respectively. Similar strong and well-defined ab-
sorptions were observed for other substrates in the region of
2120 cm¹1. The observed frequencies of the ketene stretching
are given in Table 1. The frequency varies with the substituent
from 2118 to 2128 cm¹1. The data set of 11 substituted phen-
ylketenes may provide useful information on the controversies
over structural effect of the asymmetric stretching frequencies
¹1
of the ketene group7,12,13 though the change is only 10 cm
.
The observed frequencies are correlated with the substituent
constants ·. This suggests nearly equal contributions from the
inductive and resonance effects of the substituent because the
· value involves comparably inductive and resonance effects.
¯ ðcmꢀ1Þ ¼ 2119 þ 5:5· ðR ¼ 0:944Þ
ð1Þ
O
O
hν(266 nm)
Ph
H
Ph-C-CHN2
Ph-C-CH
C
C
O
-N2
Scheme 1. Photolysis of ¡-diazoacetophenone.
Published on the web April 13, 2013; doi:10.1246/bcsj.20130028

M. M. R. Badal et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
857
-1
2120 cm
Table 1. Ketene Stretching Frequencies of Substituted
Phenylketenes in Acetonitrile and Substituent Constants ·
0.003
0.002
0.001
¹1
Frequencies/cm
c)
Calcd.b)
B3LYP/6-311+G(d,p)
Subst.
·
Obsd.
p-MeO
H
p-Cl
2118 (2115)a)
2120 (2118)a)
2120
2120
2122
2197
2200
2202
2204
2205
2206
2206
2208
2208
2211
2217
¹0.268
0.000
0.227
0.391
0.49
0.505
0.670
0.71
ΔOD
0
-0.001
-0.002
m-Cl
m-CF3
p-CF3
p-CN
m-NO2
p-NO2
3,5-(CF3)2
2122
2122 (2120)a)
2124
1600
1680
1760
1840
1920
2000
2080
2160
-1
frequency / cm
2122 (2122)a)
2124
0.81
0.98
1.40
Figure 1. TRIR spectrum of phenylketene observed at
400 ¯s after 266 nm irradiation of ¡-diazoacetophenone
in the absence of nucleophile.
3,5-(NO2)2 2128
a) Taken from Ref. 7. b) Calculated frequencies at B3LYP/
6-311+G(d,p)// B3LYP/6-311+G(d,p). c) Refs. 10 and 11.
1.163Å
(1.158)
1.471Å
(1.460)
-0.020
-0.520
-0.435
X
X
X
(-0.077)
(-0.524)
(-0.406)
-
β
+
C
C
O
C
C
O
H
C
C
O
α
H
1.317Å
(1.321)
H
0.262
(0.269)
0.714
(0.738)
(a)
(b)
Scheme 2. Natural charges and bond distances for p-methoxyphenylketene and p-nitrophenylketene calculated at B3LYP/
6-311+G(d,p). Values in the parentheses are for p-nitrophenylketene.
On the contrary, Wagner et al.7 reported that the frequencies of
four p-substituted phenylketenes and t-butylketene were corre-
lated linearly with Charton’s ·I parameters.14 The different
correlation from the present result seems to arise from a limited
data set because the ·I values of substituents used for their
correlation are proportional to their ·p values.
Theoretical calculations may be helpful to understand the
substituent effect on the frequency because the calculation of
vibrational infrared spectrum of ketene by post-Hartree-Fock
and density functional theory methods was found to agree with
experimental values.15 We have then calculated the frequencies
for a series of phenylketenes at DFT-B3LYP level of theory
using 6-311+G (d,p) basis set. The results are given in Table 1.
The calculated frequencies are correlated linearly with ·, being
consistent with the present experimental result, though the μ
value is larger than the experimental one.
negative charge at C¢ increases slightly. In addition, the C¡=O
and Ph-C¢ bonds shorten and the C¢=C¡ bond lengthens.
The bond distances and the charges of the ketene moiety are
also correlated linearly with · with a satisfactory precision
(Table S2). Such changes in geometry and charge suggest that
the electron-withdrawing substituent enhances the contribu-
tion of resonance form (b in Scheme 2). This would result
in increase of asymmetric stretching frequency as noted by
Wagner et al.7
Substituent Effects on Amination of Phenylketenes.
Figure 2 shows the kinetic traces of the IR band at 2120
¹1
cm of phenylketene (a) in the absence of amine and (b) in
the presence of 1.0 mM benzylamine. In the absence of amine,
all the substituted phenylketenes were stable over the present
experimental time scale. However, the lifetime of phenyl-
ketenes were significantly shortened by added amine, and
the decay of ketene obeyed the first-order rate law well. The
observed first-order rate constants were determined by least-
squares fitting of a single-exponential function. The observed
first-order rate constants proved to be linear functions of amine
concentration as shown in Figure 3, and the observed rate
constants were therefore given by a linear function of added
amine concentration shown as eq 3.
¯ ðcmꢀ1Þ ¼ 2199:5 þ 11:5· ðR ¼ 0:991Þ
ð2Þ
The calculated bond distances and natural charges are also
given in Scheme 2 and Table S1. It is well-known that the
ketene group is significantly polarized. Indeed, Scheme 2
shows that C¢ and O atoms bear the negative charge while the
positive charge appears at C¡ and H. The natural charge
distribution changes with the substituent. When the p-methoxy
group is changed to the strong electron-withdrawing p-nitro
group, the total charge of the ketene moiety becomes more
positive as expected. The charge distribution in the ketene
moiety also changes with the substituent, i.e., the same change
of the substituent results in decrease of the negative charge at
O and in increase of the positive charges at C¡ and H while the
kobs ¼ ko þ k2½amineꢁ
ð3Þ
where ko is the observed decay rate constant in the absence of
amine and k2 is the second-order quenching rate constant. The
values of k2 were obtained from the slopes of the plots of kobs
vs. [amine]. The second-order rate constants k2 determined for
all phenylketenes are summarized in Table 2. The second-order

858
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Amination of Phenylketene Revisit
(b)
(a)
Figure 2. The kinetic traces of phenylketene monitored at 2120 cm¹1 in acetonitrile. (a) in the absence of amine. (b) in the presence
of 1.0 mM benzylamine, the upper trace is residual from the least-squares fitting of a single-exponential function.
8.0
3,5-(NO2)2
p-NO2
3,5-(CF3)2
p-CN
7.0
m-NO2
p-CF3
m-CF3
p-Cl
m-Cl
6.0
5.0
Amine = CF3CH2NH2
H
0.0
0.5
1.0
1.5
σ , σ
°
Figure 3. Plot of the rate constant (kobs) of the first-order
decay of phenylketene vs. the concentration of benzyl-
amine in acetonitrile.
Figure 4. Plot of log k2 for reaction of substituted phenyl-
ketenes with 2,2,2-trifluoroethylamine against ·° (open
and closed circles) and · (squares).
¹
Table 2. Second-Order Rate Constants for Reactions of Phenylketenes with Amines in Acetonitrile at 23 °C
¹1
k2/107 M¹1 s
Phenylketenes
Subst.
CF3CH2NH2 NC(CH2)2NH2 m-ClPhCH2NH2 PhCH2NH2 p-MePhCH2NH2 BuNH2 Et2NH Piperidine
p-OCH3
H
p-Cl
®
2.4
4.0
8.0
5.7
8.3
8.3
14.0
22.6
27.4
31.0
34.7
43.2
51.0
51.6
68.7
66.0
10.0
15.3
27.0
32.3
34.8
39.0
51.8
60.2
59.2
78.1
70.1
20.5
31.2
49.5
55.9
59.8
67.7
74.9
85.2
91.9
97.4
36.0
51.4
70.1
70.8
85.6
86.3
92.0
97.0
98.5
60.5
82.5
111
0.017
0.14
0.18
0.30
0.37
0.89
1.12
2.20
6.36
2.46
15.3
19.1
21.4
24.1
32.7
36.5
38.8
54.4
48.0
m-Cl
9.2
117
130
131
156
162
157
163
175
m-CF3
p-CF3
m-NO2
p-CN
3,5-(CF3)2
3,5-(NO2)2
p-NO2
10.9
12.1
17.6
20.3
22.1
35.1
27.4
104
113
106
kinetics reveals that a single amine molecule is involved at the
transition state of addition of amines to phenylketenes.
Table 1 shows that the secondary amines such as piperi-
dine and diethylamine are highly reactive compared with the
primary amines. This is consistent with the higher nucleo-
philicity of the secondary amines than the primary amines,
suggesting that addition of amine to ketene proceeds through
direct nucleophilic attack to the ketene group.

M. M. R. Badal et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
859
¹
Table 3. Correlation Results in Terms of eq 4 and r Values
¹b)
Nucleophiles
μ
¡
Ra)
r
9.0
8.5
8.0
CF3CH2NH2
NC(CH2)2NH2
m-ClC6H4CH2NH2
C6H5CH2NH2
p-MeC6H4CH2NH2
BuNH2
2.92
1.02
1.01
0.83
0.90
0.73
0.49
0.50
¹0.26
¹0.26
¹0.29
¹0.30
¹0.32
¹0.37
¹0.40
¹0.42
0.995
0.993
0.995
0.997
0.996
0.999
0.988
0.992
0.50
0.70
0.80
1.10
3,5-(NO2)2
3,5-(CF3)2
Et2NH
Piperidine
m-NO2
ꢂ
ꢀ
a) Correlation coefficient. b) Calculated from ·pð¼ · þ
Piperidine
m-CF3
ꢀ
Et2NH
ꢀ ꢀ
r ꢁ·R Þ obtained by eq 6.
BuNH2
m-Cl
-
X
X
p-MeC6H4CH2NH2
C6H5CH2NH2
m-ClC6H4CH2NH2
NCCH2CH2NH2
p-Cl
H
-
O
O
7.5
0
0.5
1.0
1.5
C
C
C
C
σ
°
+
+
H
H
NH2R
NH2R
Figure 5. Plots of log k2 for various amines against ·°.
Scheme 3.
In Figure 4 are plotted log k2 for reaction of substituted
phenylketenes with 2,2,2-trifluoroethylamine against ·° and
· . There is no simple linear relationship covering all sub-
of the methyl group of acetonitrile is found to be stronger
than that between a hydrogen atom of amine and a nitrogen of
acetonitrile. Interestingly, the binding energies of both interac-
tions increase in order of diethylamine < ethylamine < 2,2,2-
trifluoroethylamine. That is, the weaker nucleophile needs
stronger desolvation energy. This is consistent with the change
of the ceiling behavior with amines, the weaker nucleophile
reaches a plateau with a smaller rate constant as seen in
Figure 5. These results suggest that a ceiling behavior of the
rate constant for highly reactive ketenes would be attributed
to the diffusion control and to the desolvation control. Even
though both factors influence their reactivities, the degree of
curvature should be related to the reactivity parameters. Indeed,
these curved substituent effects for meta-substituents and para-
chloro derivatives were found to be described well in terms of
the following quadratic eq 4 as an approximation,
¹
stituents although para-substituents seem to give a fair linear
correlation with ·°. This result indicates clearly that the μ
values reported by Wagner7 based on a limited para-substituent
set are not reliable. Limiting to meta-substituents and p-chloro,
one can find a smoothly curved correlation with a plateau at
a higher reactivity region. Similar curved correlations were
found for all other nucleophiles studied as shown in Figure 5. A
ceiling observed for highly reactive phenylketenes seems to be
similar to a diffusion-limit behavior observed for recombination
reactions of a carbocation and an anion nucleophile.16
However, the rate constants at a plateau are smaller than
an accepted diffusion-controlled rate constant (5 © 109-1010
M
¹1 s¹1).16,17 Also, ceiling behavior seems to depend on prop-
erties of a nucleophile. These results suggest that ceiling
behavior may be caused by alternative factors in addition to
a diffusion control. Another possible cause for this behavior
is that the desolvation-process of amines may control their
reactivities. A plateau with a lower rate constant than a diffu-
sion limit was observed for reaction of benzhydryl cations with
amine nucleophiles in aqueous acetonitrile solution, and the
desolvation process of nucleophile amines was considered to
be a rate-determining step.16 In acetonitrile the amines would
be similarly solvated by acetonitrile molecules though the
solvation energy of acetonitrile is smaller than water. When
the amine attacks C¡ carbon of the ketene group, desolvation
must occur. Therefore, it is interesting to elucidate the binding
energies of amines with acetonitrile. We then calculated the
binding energies of diethylamine, ethylamine, and 2,2,2-tri-
fluoroethylamine with acetonitrile at DFT-B3LYP using several
basis sets. The optimized structures of the amines associated
with acetonitrile and the binding energies are given in Chart S1
and Table S7. For all three amines the binding interaction
between a nitrogen atom of amine and a hydrogen atom
2
logðk=k0Þ ¼ μð·m þ ¡ð·mÞ Þ
ð4Þ
The correlation results are summarized in Table 3. The μ value
decreases from 2.92 for 2,2,2-trifluoroethylamine to 0.5 for
piperidine with increasing nucleophilicity of amine. The «¡«
value that represents a degree of curvature increases in the
same order, i.e., the more reactive system has a small substitu-
ent effect with a large curvature. The same curved correlation
should be held for the para-³-electron-withdrawing groups.
In particular, in the present system there exists an enhanced
contribution of resonance effect of para-³-electron-withdraw-
ing groups because the negative charge developed at an oxy-
gen atom of the ketene moiety at the transition state can be
delocalized into the aromatic ³-system through the ethylene
moiety (Scheme 3).
Indeed, Figure 4 shows that the ³-electron-withdrawing
groups at para-position are more reactive than the reactivity
expected from the curved line given by nonconjugative
substituents. In the ³-conjugative system the contribution of
resonance effect of para-³-electron-withdrawing groups varies

860
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Amination of Phenylketene Revisit
Table 4. Correlation Results in Terms of eq 7
0.8
3,5-(NO2)2
p-NO2
p-CN
Nucleophiles
-
£
Ra)
0.6
0.4
0.2
0.0
CF3CH2NH2
NC(CH2)2NH2
m-ClC6H4CH2NH2
C6H5CH2NH2
p-MeC6H4CH2NH2
BuNH2
1.00
0.37
0.32
0.27
0.28
0.20
0.12
0.12
0.00
0.36
0.49
0.76
0.55
0.91
1.03
0.94
®
0.998
0.996
0.997
0.994
0.991
0.975
0.972
3,5-(CF3)2
p-CF3
m-NO2
m-CF3
m-Cl
Et2NH
Piperidine
p-Cl
H
a) Correlation coefficient.
0.0
0.5
1.0
1.5
2.0
2.5
successfully to other amines except for diethylamine and
piperidine. The correlation parameters are given in Table 4.
The changes of both - and £ with amines resemble those for
log(k/k0)[CF3CH2NH2]
Figure 6. Plot of log(k/k0), C6H5CH2NH2 vs. CF3CH2NH2.
¹
μ and r values in Table 3, i.e., a - value decreases with
depending on the nature of the transition structure. Varying
resonance effect can be described well in terms of Yukawa-
Tsuno eq 5.10,11
increasing nucleophilicity of amines while a £ value increases
in the same order. Since the - and £ parameters represent the
relative magnitude of the substituent effect and the degree of
the resonance effect contribution, respectively, the changes of
- and £ with amines support the reality of the finding that the
ꢂ
ꢀ
ꢀ ꢀ
logðk=k0Þ ¼ μð· þ r ꢁ·R Þ
ð5Þ
¹
where ·° is the normal substituent constant which involves
no additional ³-interaction between the substituent and the
μ and r values vary oppositely in direction with the change
of amines.
¹
ꢀ ꢀ
reaction center, ꢁ·R is the resonance substituent constant of
Large changes in μ and r values suggest frequently the
¹
³-acceptor, r is the resonance demand parameter that is a
change of reaction mechanism. However, the present results
are unlikely the case because the reaction mechanism does
not seem to vary significantly with the present small variation
of nucleophiles. How can we interpret this result? When
a nucleophile (amine) attacks C¡ of the ketene moiety, the
negative charge develops on an oxygen atom of the carbonyl
group and the positive charge would form at a nitrogen atom of
amine, resulting in zwitterionic transition structure. If such a
transition structure is formed, how are the negative and posi-
tive charges stabilized by the substituent? Now, we postulate
that the two independent interactions between substituent and
charges would exist in the zwitterionic transition state. The
substituent effect caused by the interaction with the negative
charge at an oxygen atom of the ketene group can be described
by eq 8 with a positive μ1 because there exists the direct
³-interaction between the para-³-acceptor and the negative
charge in the extended ³-framework as mentioned above.
measure of degree of ³-delocalization, and μ is the reaction
ꢀ
constant. The apparent ꢀ·p for a reaction of interest can be
ꢂ
ꢀ ꢀ
represented by (· þ r ꢁ·R ). Based on this relation, the
reactivities of phenylketenes with para-³-acceptors can be
described in terms of eq 6 in a similar manner to eq 4 for
nonconjugative substituents.
2
ꢀ
ꢀ
logðk=k0Þ ¼ μð·p þ ¡ð·pÞ Þ
ð6Þ
Using μ and ¡ values obtained for nonconjugative substituents,
an application of eq 6 to log(k/k0) for para-³-acceptor-sub-
¹
stituted derivatives gave the r values (Table 3). This analysis
worked only for four amines of which reactivity is relatively
low because the substituent effects for highly reactive amines
¹
were too small to obtain a reliable r parameter. Although
available correlation results are limited, it is obvious that a
μ value decreases significantly with increasing nucleophilicity
¹
of amines while an r value increases in the same order. Such
1
1
1
ꢂ
1
ꢀ ꢀ
logðk =k Þ ¼ μ ð· þ r ꢁ· Þ
ð8Þ
0
¹
R
changes of the μ and r values may be elucidated from another
approach. In Figure 6 are plotted log(k/k0) for benzylamine
against the corresponding values for 2,2,2-trifluoroethylamine.
There is a linear relationship for meta-substituents and p-chloro
with a slope of 0.27 while the para-³-acceptors deviate upward
from the line. The small slope and upward deviations of para-³-
acceptors reveal that the reaction with benzylamine is charac-
terized by a small substituent effect with an exalted resonance
contribution of the para-³-acceptors compared with the reac-
tion with 2,2,2-trifluoroethylamine. This is consistent with the
On the other hand, the positive charge developed at a nitrogen
atom can be stabilized by the electron-releasing groups and its
substituent effect is described by eq 9 with a negative μ2. Since
there is no direct resonance interaction between para-³-donor
and the positive charge, r2 = 0.0.
2
2
2
ꢂ
2
2
ꢂ
ꢀ þ
logðk =k Þ ¼ μ ð· þ r ꢁ· Þ ¼ μ ð· Þ
ð9Þ
0
R
Therefore, the observed substituent effect should be described
in terms of eq 10 given by combining eqs 8 and 9.
¹
differences in μ and r between both systems given in Table 3.
1
ꢂ
1
2
ꢂ
ꢀ ꢀ
logðk=k0Þobs ¼ μ ð· þ r ꢁ·R Þ þ μ ð· Þ
ð10Þ
ꢀ ꢀ
logðk=k0Þ ¼ -½logðk=k0ÞCF3CH2NH2 þ £ꢁ·R ꢁ
ð7Þ
Rearrangement of eq 10 gives the following eq 11
ꢀ
ꢁ
Although this approach is based on an assumption that the
degree of curvature is identical to both reactions with benzyl-
amine and 2,2,2-trifluoroethylamine, eq 7 has been applied
μ1r1
ðμ1 þ μ2Þ
ꢀ ꢀ
ꢁ·R
logðk=k0Þobs ¼ ðμ1 þ μ2Þ ·ꢂ þ
ð11Þ

M. M. R. Badal et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
861
X
X
stituent effect of the frequencies involves the contribution of
the resonance effect of the substituents in addition to the
inductive effect, revealing the increasing contribution of the
resonance form (b in Scheme 2) with electron-withdrawing
ability. This was consistent with the calculated geometric
features and charge distribution of the phenylketenes. The
C¡=O and Ph-C¢ bonds tend to shorten and the C¢=C¡ bond
lengthens when the substituent is the stronger electron-with-
drawing group.
-
-
O
O
C
C
C
C
+
+
N
H NCCH3
NH2CH2Ph
H
H
F3CH2C
H
(a) Early TS
(b) Late TS
Scheme 4. Transition structures of amination of phenyl-
The substituent effects for the second-order rate constants of
phenylketenes with various amines were not correlated linearly
with any single substituent constants. The curved ·°-correla-
tions with a plateau at a high reactivity region were observed
for meta-substituents and p-chloro which are nonconjugative
with the negative charge at a reaction site. The substituent
effects including para-³-acceptors were described in terms of
the Yukawa-Tsuno equation modified by introducing a quad-
ratic term as an approximation. The resultant μ value varied
significantly from 2.92 for 2,2,2-trifluoroethylamine to 0.83
ketenes.
Since the μ1 value is positive and the μ2 is negative as
mentioned above, the sum of μ1 and μ2 should be smaller
in magnitude than μ1 when «μ1« > «μ2«.18 This further leads
to an expectation that the observed r (= μ1r1/(μ1 + μ2) for a
¹
whole reaction should be larger than r1 because the magnitude
of μ1/(μ1 + μ2) is larger than unity. Accordingly, when a μ
(= μ1 + μ2) becomes smaller, an r should be larger. This
¹
¹
¹
expectation of the μ and r values for the zwitterionic tran-
sition state are consistent with the experimental observation
that the μ and r values change oppositely in direction with the
change of amines.
for benzylamine while the r value increased from 0.50 to 1.10.
¹
The opposite change of μ and r with amines is interpreted
¹
as the dual electronic interactions between substituents and
positive/negative charges at the zwitterionic transition struc-
ture. Such changes suggest that the position of the transition
state along a reaction coordinate varies with amines, i.e.,
¹
These changes of the μ and r values with amines can be
explained in the following way. Let consider two amines of
benzylamine and 2,2,2-trifluoroethylamine as strong and weak
nucleophiles, respectively. The reaction with a strong nucleo-
phile, benzylamine, would have a relatively early transition
state (a in Scheme 4) where the negative and positive charges
are developed in a similar extent at O and N atoms. This causes
a small μ value because a difference between «μ1« and «μ2«
¹
benzylamine with small μ value and large r value attributes
¹
to early transition state and larger μ value with smaller r value
for 2,2,2-trifluoroethylamine attributes to late transition state.
Experimental
1
The H NMR spectra were recorded on a JEOL JNM-EX
¹
would be small in magnitude, resulting in a large r value.
400 or JNM ECA-500 FT-NMR spectrometer in CDCl3 or
DMSO-d6 and chemical shifts are given in ppm (¤) downfield
from TMS as an internal standard. The ¡-diazoketones were
purified by medium pressure liquid chromatography (MPLC,
Yamazene Corp.) on Lichroprep Si60 (25-40 ¯m, Merck) with
hexane-ethyl acetate or recycling preparative HPLC, LC-908
(JAPAN ANALYTICAL INDUSTRY CO. LTD.); column
JAIGEL-1H with CHCl3 and column chromatography, silica
gel 60 (0.040-0.063 nm). Ether and tetrahydrofuran were dis-
tilled from sodium/benzophenone under argon.
On the other hand, the transition state for a weak nucleo-
phile, 2,2,2-trifluoroethylamine, would be late. This results
in advanced bond formation between C¡ and N, leading to
anticipation that a hydrogen atom of NH is acidic enough to
form strong hydrogen-bonding with solvent acetonitrile (b in
Scheme 4).
As a result, the positive charge formed at the nitrogen atom
of 2,2,2-trifluoroethylamine shifts considerably to the hydrogen
atom, resulting in a smaller μ2 because of a longer distance
between a center of the positive charge and the substituent
on the benzene ring. On the contrary, the developed negative
charge remains mostly at the oxygen atom, resulting in nearly
constant μ1 value in magnitude. Therefore, in the case of a
weaker nucleophile the sum (= μobs) of μ1 and μ2 should not
differ significantly from μ1, and as a result of this a relatively
large μ value and a small r value are observed.
Thus, a small μ value with a remarkably large r value
observed for reaction with a strong nucleophile and the oppo-
site change of μ and r values with amines in direction could
be explained by the concept of duality of electronic interactions
between substituents and reaction sites at the zwitterionic
transition state.
Chemicals. The substituted ¡-diazoketones used as pre-
cursors for the corresponding phenylketenes were prepared
according to the literature.19
Preparation of diazomethane solution. A 100-mL three-
necked flask was fitted with a Liebig condenser set for distil-
lation and with a 200-mL long-stem dropping funnel. The
condenser was connected by means of an adapter to a 200-mL
round-bottom flask. The bottom of this flask was immersed in
an ice-water bath. The second hole of the adapter was fitted
with a glass tube through a Teflon-tube connector. The outlet
of the glass tube passed below the surface of ether (200 mL)
in a 300 mL Erlenmeyer flask. A mixture of carbitol (42.1 g,
0.30 mol) in ether (10 mL) and potassium hydroxide (6.4 g,
0.11 mol) in water (10 mL) was heated in the three-necked flask
at 75 °C. The solution was stirred by a Teflon-coated magnetic
stirring bar about 5 min. Then, N-methyl-N-nitroso-p-toluene-
sulfonamide (21.4 g) in ether (100 mL) was added from the
dropping funnel over 30 min. As soon as all the nitrosoamide
¹
¹
¹
Conclusion
The frequencies observed for the m,p-substituted phenyl-
ketenes were found to be correlated with · though a small
change with the substituent. This result suggests that the sub-

862
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Amination of Phenylketene Revisit
solution was added, additional ether (50 mL) was placed in
the dropping funnel and added (at the previous rate) until the
distillate was colorless. As a consequence of this procedure,
diazomethane solution was obtained in the round-bottom flask
(100 mL) and the Erlenmeyer flask (200 mL).
(JASCO) is crossed with excitation pulses (266 nm) from a
Continuum cw Q-sw Nd:YAG laser. Changes in IR intensity
were monitored by an MCT photovoltaic IR detector amplified,
and digitized with a Tektronix TDS520A oscilloscope. The
TRIR spectrum was analyzed by the IGOR PRO program
(Wavemetrics Inc.) in the form of a difference spectrum.
Theoretical Calculations. Conformational searches were
carried out using Spartan ’08 (Wavefunction, Inc.), and several
conformers of the lowest energy were further optimized at
the RHF/3-21G* level of theory to search the lowest energy
conformer (global minimum). Finally, the geometries were
fully optimized at the DFT-B3LYP level of theory with normal
convergence using the Gaussian 09 program.20 Vibrational
normal mode analyses were performed at the same level to
obtain the stretching frequencies and to ensure that each opti-
mized structure was a true minimum on the potential energy
surface and to calculate the thermal correction needed to obtain
the Gibbs free energies. The zero point energies used for the
thermal correction were unscaled.
Preparation of 2-diazo-1-phenylethanone. A mixture of the
diazomethane solution (300 mL, 0.050 mol) prepared above
and triethylamine 3.2 g (0.032 mol) was stirred on an ice-water
bath at 0 °C for 5 min. Benzoyl chloride 3.6 g (0.026 mol)
dissolved in dry diethyl ether (10 mL) was added from a
dropping funnel over 5 min. The mixture was stirred for an
additional 2 h at 0 °C and overnight at room temperature.
After the triethylamine hydrochloride formed was removed by
filtration, the solvent was evaporated under reduced pressure.
Purification of the residue by column chromatography (silica
gel, eluent: ethyl acetate-hexane, 15:85) gave 2-diazo-1-phen-
1
ylethanone. H NMR (CDCl3): ¤ 5.90 (s, 1H, CH), 7.43-7.78
(m, 5H, Ar). The other ¡-diazoketones were prepared in a
similar way as mentioned above. 2-Diazo-1-(4-methoxyphen-
1
yl)ethanone: silica gel, ethyl acetate-hexane (10:90), H NMR
(CDCl3): ¤ 3.87 (s, 3H), 5.86 (s, 1H, CH), 6.94 (d, J = 8.5 Hz,
2H, Ar), 7.75 (d, J = 8.5 Hz, 2H, Ar). 2-Diazo-1-(4-chloro-
phenyl)ethanone: silica gel, ethyl acetate-hexane (20:80),
1H NMR (CDCl3): ¤ 5.86 (s, 1H, CH), 7.43 (d, J = 8.8 Hz,
2H, Ar), 7.71 (d, J = 8.8 Hz, 2H, Ar). 2-Diazo-1-(3-chloro-
phenyl)ethanone: silica gel, ethyl acetate-hexane (15:85),
1H NMR (CDCl3): ¤ 5.90 (s, 1H, CH), 7.40 (t, J = 8.0 Hz,
1H, Ar), 7.52 (d, J = 8.0 Hz, 1H, Ar), 7.63 (d, J = 8.0 Hz,
1H, Ar), 7.75 (s, 1H, Ar). 2-Diazo-1-(3-trifluoromethylphenyl)-
ethanone: silica gel, ethyl acetate-hexane (15:85), 1H NMR
(CDCl3): ¤ 5.94 (s, 1H, CH), 7.60 (t, J = 8.0 Hz, 1H, Ar), 7.80
(d, J = 8.0 Hz, 1H, Ar), 7.94 (d, J = 8.0 Hz, 1H, Ar), 8.01 (s,
1H, Ar). 2-Diazo-1-(4-trifluoromethylphenyl)ethanone: silica
We are indebted to Joint Project of Chemical Synthesis Core
Research Institutions from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT) of the Japanese
Government for financial support.
Supporting Information
Details of the kinetic experiments, optimized geometries,
selected bond lengths, and natural charges. This material
is available free of charge on the Web at: http://www.csj.jp/
journals/bcsj/.
References
1
a) The Chemistry of Ketenes, Allenes and Related Com-
1
gel, ethyl acetate-hexane (15:85), H NMR (CDCl3): ¤ 5.94
pounds in PATAI’S Chemistry of Functional Groups, ed. by S.
Patai, John Wiley & Sons, New York, 1980, Vol. 2. doi:10.1002/
9780470771617. b) T. T. Tidwell, Ketenes, 2nd ed., John Wiley &
Sons, Hoboken, New Jersey, 2006. c) R. Miller, C. Abaecherli,
A. Said, Ullmann’s Encyclopedia of Industrial Chemistry, 6th
ed., 2002, Vol. A15, pp. 63-75. d) C. M. Temperley, in Synthesis:
Carbon with One Heteroatom Attached by a Multiple Bond in
Comprehensive Organic Functional Group Transformations II,
ed. by A. R. Katritzky, R. J. K. Taylor, Elsevier, Amsterdam, 2005,
Vol. 3, pp. 573-604. doi:10.1016/B0-08-044655-8/00061-1.
(s, 1H, CH), 7.72 (d, J = 8.0 Hz, 2H, Ar), 7.87 (d, J = 8.0 Hz,
2H, Ar). 2-Diazo-1-(3-nitrophenyl)ethanone: silica gel, ethyl
acetate-hexane (15:85), 1H NMR (CDCl3): ¤ 6.00 (s, 1H, CH),
7.68 (t, J = 8.0 Hz, 1H, Ar), 8.14 (d, J = 8.0 Hz, 1H, Ar),
8.41 (d, J = 8.0 Hz, 1H, Ar), 8.57 (s, 1H, Ar). 2-Diazo-1-(4-
cyanophenyl)ethanone: silica gel, ethyl acetate-hexane (15:85),
1H NMR (CDCl3): ¤ 5.91 (s, 1H, CH), 7.76 (d, J = 8.4 Hz,
2H, Ar), 7.86 (d, J = 8.4 Hz, 2H, Ar). 2-Diazo-1-[3,5-bis(tri-
fluoromethyl)phenyl]ethanone: silica gel, ethyl acetate-hexane
1
2
3
4
5
6
H. R. Seikaly, T. T. Tidwell, Tetrahedron 1986, 42, 2587.
T. T. Tidwell, Acc. Chem. Res. 1990, 23, 273.
B. B. Snider, Chem. Rev. 1988, 88, 793.
T. Ye, M. A. McKervey, Chem. Rev. 1994, 94, 1091.
E. Bothe, H. Meier, D. Schulte-Frohlinde, C. von Sonntag,
(15:85), H NMR (CDCl3): ¤ 6.00 (s, 1H, CH), 8.05 (s, 1H,
Ar), 8.20 (s, 2H, Ar). 2-Diazo-1-(3,5-dinitrophenyl)ethanone:
silica gel, ethyl acetate-hexane (15:85), 1H NMR (CDCl3):
¤ 6.09 (s, 1H, CH), 8.91 (d, J = 2.0 Hz, 2H, Ar), 9.20 (t, J =
2.0 Hz, 1H, Ar). 2-Diazo-1-(4-nitrophenyl)ethanone: silica gel,
ethyl acetate-hexane (15:85), 1H NMR (CDCl3): ¤ 5.96 (s, 1H,
CH), 7.92 (d, J = 9.0 Hz, 2H, Ar), 8.31 (d, J = 9.0 Hz, 2H, Ar).
Time-Resolved Infrared Measurements. TRIR experi-
ments were conducted with a JASCO TRIR-1000 dispersive-
type IR spectrometer. This method allows access to the entire
mid IR spectrum (4000-800 cm¹1) with high sensitivity and
sufficient time (ca. 100 ns) and frequency resolution (4-18
cm¹1) to probe a wide range of transient intermediates in
solution. Solutions were flowed through a CaF2 cell, the path
length of which was adjustable from 0.25 to 1 mm. The broad-
band output of a newly developed MoSi2 infrared source
Angew. Chem., Int. Ed. Engl. 1976, 15, 380.
B. D. Wagner, B. R. Arnold, G. S. Brown, J. Lusztyk,
J. Am. Chem. Soc. 1998, 120, 1827.
T. Kanzian, T. A. Nigst, A. Maier, S. Pichl, H. Mayr, Eur. J.
Org. Chem. 2009, 6379.
7
8
9
Y. Chiang, A. V. Fedorov, A. J. Kresge, I. Onyido, T. T.
Tidwell, J. Am. Chem. Soc. 2004, 126, 9382.
10 Y. Tsuno, M. Fujio, Y. Takai, Y. Yukawa, Bull. Chem. Soc.
Jpn. 1972, 45, 1519.
11 M. Fujio, M. Mishima, Y. Tsuno, Y. Yukawa, Y. Takai, Bull.
Chem. Soc. Jpn. 1975, 48, 2127.
12 J. E. Gano, E. J. Jacob, Spectrochim. Acta, Part A 1987,

M. M. R. Badal et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
863
43, 1023.
20 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B.
Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P.
Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg,
M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida,
T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A.
Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd,
E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R.
Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C.
Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam,
M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J.
Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K.
Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J.
Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B.
Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09
(Revision B.01), Gaussian, Inc., Wallingford CT, 2010.
13 M. A. McAllister, T. T. Tidwell, Can. J. Chem. 1994,
72, 882.
14 M. Charton, J. Org. Chem. 1984, 49, 1997.
15 J. S. Kwiatkowski, J. Leszczyński, THEOCHEM 1995,
342, 43.
16 R. A. McClelland, V. M. Kanagasabapathy, N. S. Banait, S.
Steenken, J. Am. Chem. Soc. 1991, 113, 1009.
17 C. D. Ritchie, P. O. I. Virtanen, J. Am. Chem. Soc. 1972,
94, 4966.
18 The substituent effect on the calculated acidity (B3LYP/
6-311+G(d,p)) of ArCH=C(NEt2)OH was described in terms of
¹¤¦G° = 15.9(· þ 1:44ꢁ·R ) and the substituent effect for the
basicity of ArCH=C(NEt2)OH was correlated with ¹¤¦G° =
¹12.5·°, indicating «μ1« > «μ2«.
19 Y. Nakamura, K. Inamura, R. Oomuro, R. Laurenco, T. T.
Tidwell, J. Nishimura, Org. Biomol. Chem. 2005, 3, 3032.
ꢂ
ꢀ ꢀ