Mechanistic studies of amination of ketenimines: Change of rate-determining step by N-substituents through electronic effects

Article abstract of DOI:10.1016/j.tet.2005.09.119

Vinylidenediamine intermediate was not found in amination reactions of N-i-propyl-p-substituted-phenylketenimines 3a-3e with n-BuNH₂, but it was found in amination reactions of N-p-substituted-phenylphenylketenimines 1a-1c with n-BuNH₂

Full text of DOI:10.1016/j.tet.2005.09.119

Tetrahedron 62 (2006) 171–181
Mechanistic studies of amination of ketenimines: change of
rate-determining step by N-substituents through electronic effects
*
Kuangsen Sung, Fu-Lin Chen, Pin-Mei Huang and Shu-Min Chiang
Department of Chemistry, National Cheng Kung University, No.1 University Rd., Tainan, Taiwan, ROC
Received 2 June 2005; revised 26 September 2005; accepted 27 September 2005
Available online 26 October 2005
Abstract—Vinylidenediamine intermediate was not found in amination reactions of N-i-propyl-p-substituted-phenylketenimines 3a–3e with
n-BuNH2, but it was found in amination reactions of N-p-substituted-phenylphenylketenimines 1a–1c with n-BuNH2 by low-temperature 1H
NMR spectrometer, indicating that the rate-determining step is changed from the first step (C]N addition) to the second step
(tautomerization) when N-substituent of the ketenimines is changed from i-propyl group to p-substituted-phenyl group. Amination reactions
of ketenimines 5 and 10 in a solvent with 3Z35.9 were designed to explore electronic effects of N-substituents on the amination reactions by
means of ab initio calculations. Computation results at level of MP2/6-31CG*//HF/6-31CG* (Onsager model) show that significant
electronic stabilization of the first transition state involving C]N addition by N-phenyl group is the major factor causing the change of the
rate-determining step for the amination reactions.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
two steps including an initial addition to C]N, followed by
tautomerization to give amidine 2a.7 The reaction runs fast
at room temperature, so the metastable intermediate of
vinylidenediamine was caught and identified by means of
low-temperature proton NMR. In the low-temperature
proton NMR experiment, it was found that the second step
involving tautomerization is much slower than the first
addition step.7 On the other hand, when we changed
N-substituent of the ketenimine from phenyl group to
i-propyl group 3a and did the same amination reaction,
surprisingly no intermediate was found at all by means of
the low-temperature proton NMR. In this article, we
designed model reactions and used ab initio calculations
to inspect how and why the rate-determining step of these
amination reactions is changed. To our knowledge, this is
the first example to demonstrate change of rate-determining
step in the reactions of ketenimines and ketenes (Scheme 1).
Chemistry of ketenes and ketenimines has been intensely
studied for a century.1 They are important reactive
intermediates, which may occur as transients in many
thermal and photochemical reactions.1,2 There has been
intense interest in their addition reactions, including
cycloadditions,3 nucleophilic additions,2b,f,4 electrophilic
additions,5 and radical additions.6 Both amination of
ketenes2f,4c–f and hydration of ketenimines2b,4h,i generate
the amide functional group, which is a repeating unit in
peptides and other synthetic polymers like nylon.
There was a mechanistic controversy regarding where an
initial addition occurs on ketenes and ketenimines when
they reacts with amines.2f,4c–f,7,8 Recent results2f,4c–f,7
confirm that they are two-step reactions and involve an
initial addition of an amine to C]O or C]N, followed by
tautomerization. In the recent literatures regarding
amination reactions of ketenimines7 or ketenes,2f,4d,e
intermediates of vinylidenediamines or enol amides were
found, indicating that the rate-determining step is the second
step involving tautomerization.
2. Computational details
All the calculations reported here were performed with
Gaussian98 program.9 The Onsager self-consistent reaction
field (SCRF) model has been used to monitor systems in a
solvent with dielectric constant of 35.9 which is close to that
of acetonitrile. The model treats the solvent as a continuum
of uniform dielectric constant (the reaction field) and the
solute is placed into a fixed spherical cavity of radius a0
within the solvent. The radius a0 of the cavity for each solute
was evaluated based on its optimized structure in the gas
In our previous research, we found that reaction of
N-phenylphenylketenimine 1a with n-butylamine involves
Keywords: Amination; Ketenimine; Mechanistic study.
*
Corresponding author. Tel.: C886 62757575 65338; fax: C886
63506303.; e-mail: kssung@mail.ncku.edu.tw
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.119

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K. Sung et al. / Tetrahedron 62 (2006) 171–181
Scheme 1.
phase. SCRF geometry optimizations of 5–14 were carried
out at level of HF/6-31CG* in solvent (3Z35.9) without
any symmetry restriction. Many possible conformations
have been optimized for each of these configurations, and
the conformation with the lowest energy was chosen for
each configuration. Their optimized structures are shown in
Figure 1. An SCRF frequency calculation at each of SCRF
optimized structures was run at the same level and analytical
˚
Figure 1. SCRF optimized structures of 5–14 at level of HF/6-31CG* (Onsager) in a solvent (3Z35.9). Bond lengths are in A.

K. Sung et al. / Tetrahedron 62 (2006) 171–181
173
Table 1. Calculated energies (hartree), imaginary frequencies (cmK1), and spherical cavity of radius a0 (A) of stationary points along amination of ketenimines
in solvent (3Z35.9) at MP2/6-31CG*//HF/6-31CG* Level (Onsager model)
˚
Stationary
point
a0
Energy
Imaginary
frequency
Stationary
point
a0
Energy
Imaginary
frequency
5
3.86
4.29
4.06
4.23
4.22
2.77
K249.66817
K305.95331
K306.02672
K362.31219
K306.05061
K56.33085
10
11(TS)
12
13(TS)
14
4.04
4.66
4.41
4.60
4.46
K362.47773
K418.77114
K418.83987
K475.12451
K418.86874
6(TS)
7
8(TS)
9
NH3
K2109
K1880
K2115
K1825
vibration frequencies were calculated to determine the
nature of the located stationary points. Thus, all the
stationary points found were properly characterized by
evaluation of the harmonic frequencies. The energies of all
the stationary points were calculated at MP2/6-31CG* with
scale zero-point vibration energies included, and population
analyses of 5 and 10 were carried out at the same level.
(Table 1) The scale factor of 0.9135 for zero-point vibration
energies is used according to the literatures.10 As shown in
Table 2,10 it was reported that the Onsager model at MP2/
6-31CG* level gives the best prediction results for the
energy difference between the gauche and trans conformers
of dichloroethane in several solvents.10 Therefore, the
Onsager model at MP2/6-31CG* level was used in this
research to predict the reaction mechanism of the amination
of ketenimines.
The major structure difference between 1a–1c and 3a–3e is
N-substituent. To avoid inaccurate calculations due to too
many atoms,10 the investigated molecules need to be
simplified, so ketenimines 5 and 10 were chosen as model
substrates in order to inspect N-substituent effects on the
amination reactions. Amination reactions of 5 and 10 with
NH3 were monitored at the MP2/6-31CG* level in the
solvent with dielectric constant of 35.9.
In early studies, theoretical8a,b and kinetic studies8c–e of
amination of ketenes were interpreted as involving initial
addition to the C]C bond of ketenes. Later on, high-level
ab initio calculations4c,e and kinetic studies2f,4d–f,l–m over-
threw the previous mechanism and suggested the amination
reactions proceed via amine addition across the C]O bond
of ketenes, followed by tautomerization. Meanwhile, some
labile intermediate of amide enols from amination of
ketenes were caught by IR2f,4e,l and UV4m spectrometers,
and a stable amide enol from the amination of a crowded
diarylketene was even isolated.4f Similarly, the amination of
ketenimines was found to proceed via amine addition across
the C]N bond, followed by tautomerization, much easier
than via amine addition across the C]C bond by high-level
ab initio calculations in both gas phase and solution,7 and
the metastable intermediate of vinylidenediamine was
caught and identified by means of low-temperature proton
NMR spectrometer.7 Therefore, the amination reactions of 5
and 10 were designed to involve the two steps, C]N
addition and tautomerization (Scheme 4).
Table 2. Predicted energy differences (DE) between the gauche and trans
conformers of dichloroethane in four solvent environments
Medium
DE (kcal/mol)
IPCM
Onsager
Exp.
HF/
6-31CG*
MP2/
6-31CG*
B3LYP/
6-31CG*
Gas phase
1.96
1.32
0.50
0.30
1.51
0.99
0.29
0.13
1.76
1.45
0.90
0.73
1.20
0.91
0.31
0.15
Cyclohexane
Pure liquid
Acetonitrile
3. Results and discussion
According to preliminary results of kinetic studies for the
amination reactions of 1a–1c and 3a–3e with n-BuNH2 in
CH3CN, C]N addition of these ketenimines involves one
molecule of n-BuNH2.11 Therefore, C]N addition of 5 and
10 are designed to involve one molecule of NH3. Because
suprafacial 1,3-hydrogen shift is thermally forbidden,12
tautomerization of vinylidenediamines 7 and 12 without
catalyst is unlikely. Therefore, we designed tautomerization
of 7 and 12 to be catalyzed by one molecule of NH3,
forming amidines 9 and 14.
When we studied the amination of N-phenylphenyl-
ketenimine 1a with n-butylamine in CD3CN at K10 8C by
proton NMR spectrometer, the vinylidenediamine inter-
mediate was caught and we found that it involves two steps,
C]N addition and tautomerization, and the second step is
much slower than the first step.7 The same reaction
mechanism was found for amination of other N-p-
substituted-phenyl-phenylketenimines 1b and 1c with
n-BuNH2 by monitoring the reactions with proton NMR
spectrometer in CD3CN at K10 8C Scheme 2). One
representative example is shown in Figure 2.7 On the other
hand, reactions of N-i-propyl-p-substituted-phenylketeni-
mines 3a–3e with n-BuNH2 in CD3CN are much slower than
those of 1a–1c with n-butylamine, so they were monitored by
proton NMR spectrometer at 10 8C Scheme 3). Surprisingly,
there is no intermediate found for each of the reactions, and
one representative example is shown in Figure 3. To find out
this strange result, reactions of ketenimines 5 and 10 with
NH3 were monitored by ab initio calculations in the solvent
with 3Z35.9.
Calculated activation enthalpies, activation entropies,
activation free energies, enthalpies, entropies, and free
energies for the amination reactions of 5 and 10 with NH3
are shown in Table 3. Both C]N addition of 5 and
tautomerization of 7 are exothermic reactions, and
activation free energy of the former is 5.1 kcal/mol more
than that of the latter. This indicates that the first step
involving C]N addition is a rate-determining step in the
amination reaction of 5 with NH3. That is the reason why
there is no intermediate found by low-temperature proton
NMR spectrometer in the amination reactions of 3a–3e with

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K. Sung et al. / Tetrahedron 62 (2006) 171–181
Figure 2. Part of 1H NMR (CD3CN) spectra for the reaction of 1a with n-butylamine in the presence of an internal standard (benzyl phenyl ether) at K10 8C
(a) before adding n-butylamine, (b) at 10 min after mixing the solution, (c) at 14 min, (d) at 45 min, (e) at 19 h, and (f) at 30 min after increasing the
temperature to 25 8C.

K. Sung et al. / Tetrahedron 62 (2006) 171–181
175
Figure 3. Part of 1H NMR (CD3CN) spectra for amination of 3a with n-BuNH2 in the presence of benzyl phenyl ether as an internal standard at 10 8C (A)
before adding n-BuNH2, (B) at 5 min after mixing the solution, (C) at 20 min, (D) at 40 min, (E) at 100 min, (F) at 130 min, (G) at 250 min.

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K. Sung et al. / Tetrahedron 62 (2006) 171–181
Scheme 2.
Scheme 3.
n-BuNH2 in CD3CN. On the other hand, both C]N addition
of 10 and tautomerization of 12 are exothermic reactions,
and activation free energy of the former is 0.33 kcal/mol
less than that of the latter, indicating that the second step
involving taumomerization becomes a rate-determining step
in the amination reaction of 10 with NH3. This is consistent
with the experimental results that the metastable vinylidene-
diamine intermediates were caught by low-temperature
proton NMR spectrometer in the amination reactions of
1a–1c with n-BuNH2 in CD3CN.
Activation free energy for tautomerization of 7 is very close
to that for tautomerization of 12, indicating that electronic
effects of N-substituent make little difference in the
tautomerization processes. In contrast, activation free
energy for C]N addition of 5 with NH3 is 4.69 kcal/mol
more than that for C]N addition of 10 with NH3, indicating
that N-phenyl group strongly stabilizes the transition state in
the C]N addition process of 10 with NH3. This is the major
reason why the rate-determining step is changed from the
first step (C]N addition) to the second step (tautomeriza-
tion) when N-substituent of the ketenimines is changed from
i-propyl group 3a–3e to p-substituted-phenyl group 1a–1c
in the amination reactions. Because steric effect of phenyl
group is very close to that of i-propyl group,13 it turns out
that electronic effects, instead of steric effect, control the
change of the rate-determining step in these amination
reactions.
Scheme 4.

K. Sung et al. / Tetrahedron 62 (2006) 171–181
177
Table 3. Calculated activation enthalpies (kcal/mol), activation entropies (cal/mol K), activation free energies (kcal/mol), enthalpies (kcal/mol), entropies
(cal/mol K), and free energies (kcal/mol) for amination of 5 and 10 in the solvent (3Z35.9) at MP2/6-31CG*//HF/6-31CG* level (Onsager model)
DH‡ (298 K)
DS‡ (298 K)
DG‡ (298 K)
DH (298 K)
DS (298 K)
DG (298 K)
Process: 5CNH3/6(TS)/7
28.25
Process: 7CNH3/8(TS)/9CNH3
25.27
Process: 10CNH3/11(TS)/12
23.46
K40.44
K33.31
K40.78
K34.61
40.30
35.20
35.61
35.94
K13.85
K15.37
K16.07
K18.52
K40.54
1.99
K1.77
K15.96
K4.25
K39.67
3.22
Process: 12CNH3/13(TS)/14CNH3
25.62
K19.48
Rate constants for the amination reactions of ketenimines 1a
and 3a with n-BuNH2 in CD3CN were measured by means
of low-temperature proton NMR spectrometer and their
results are shown in Table 4. The rate constants of the first
steps (C]N addition) for the amination of ketenimines 1a
and 3a were measured by following disappearance of
ketenimines. Their pseudo-first-order rate constants are
1.52!10K3 sK1 (at K10 8C) for the amination of 1a and
9.18!10K5 sK1 (at 10 8C) for the amination of 3a, and
the corresponding second-order rate constants are 3.04!
10K3 MK1 sK1 (at K10 8C) and 1.84!10K4 MK1 sK1 (at
10 8C), respectively, indicating that N-phenyl ketenimine
makes the C]N addition step much faster during the
amination reaction than N-i-propyl ketenimine does. These
experimental results are well consistent with our compu-
tation results that N-phenyl group strongly stabilizes the
transition state in the C]N addition process of amination of
ketenimines.
10K5 MK1 sK1 (at K10 8C), indicating that the tautomer-
ization is much slower than the corresponding C]N
addition, resulting in accumulation of the vinylidene-
diamine intermediate. On the other hand, in the case of
amination of ketenimine 3a, the C]N addition step is very
slow and presumably slower than the next tautomerization
step, leading to no accumulation of the vinylidenediamine
intermediate. All the experimental results are consistent
with our computation results that the rate-determining step
is changed from the first step (C]N addition) to the second
step (tautomerization) when N-substituent of the
ketenimines is changed from i-propyl group to phenyl
group in the amination reactions.
Due to lack of special NMR sample-injection system, we
had problem to inject CD3CN solution of ketenimine into a
thermostated NMR tube inside a NMR spectrometer, which
contained CD3CN solution of n-BuNH2 and internal
standard and had finished shimming. To compensate this
deficiency, we added n-BuNH2, CD3CN, internal standard,
and ketenimine together in a NMR tube at liquid nitrogen
temperature, and let them warm up to a preset temperature
inside a NMR spectrometer for further rate-constant
measurement. As shown in Table 4, this method did provide
The rate constant of the second step (tautomerization)
for the amination of ketenimine 1a was measured by
following appearance of amidine product. The pseudo-first-
order rate constant are 3.00!10K5 sK1 (at K10 8C), and
the corresponding second-order rate constants are 6.00!
Table 4. Pseudo-first-order and second-order rate constants of the C]N addition and tautomerization for the amination reactions of ketenimines 1a and 3a
with n-BuNH2 in CD3CN by means of proton NMR spectrometera
R
Temperature
C]N Addition
k2 (MK1 sK1
Tautomerization
k
obs (sK1
)
)
kobs (sK1
)
k2 (MK1 sK1
)
Ph
i-Pr
K10 8C
10 8C
1.52!10K3
9.18!10K5
3.04!10K3
1.84!10K4
3.00!10K5
—
6.00!10K5
—
a All rate constants were measured at least in duplicate with maximum deviations of G5%.

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K. Sung et al. / Tetrahedron 62 (2006) 171–181
acceptable results in distinguishing N-substituent effects for
the amination of ketenimines. However, this method is not
accurate enough to measure temperature and concentration
effects on the rate constants and linear free energy
relationship (LFER) for the amination of ketenimines.
Therefore, we couldn’t get experimental data of activation
parameters for the amination of ketenimines, which may be
used to fit our computational results. Nevertheless, literature
data can be used for the comparison purpose. Base-
catalyzed hydration of 3a was reported to have observed
first-order rate constant of 1.3!10K3 sK1 at pHZ10 and
25 8C in water,4i which is faster than the amination of 3a in
CD3CN (kobsZ9.18!10K5 sK1 at 10 8C). Presumably, it is
because water concentration in the base-catalyzed hydration
reaction is much more than n-BuNH2 concentration in the
amination reaction. The base-catalyzed hydration of 3a was
reported to have the experimental activation enthalpy of
15.2 kcal/mol,4i which is smaller than that for the amination
of 5 in acetonitrile (calculated DH‡(298 K) Z28.25 kcal/
mol). It was reported that water solvent is involved in the
transition state of base-catalyzed hydration of 3a,4i and it is
likely that involvement of water solvent in the transition
state reduces its activation enthalpy.
these groups can be an evidence for this electron
delocalization. It is very likely that this electron delocaliza-
tion provides one of ways to stabilize 11(TS) significantly.
4. Conclusion
The rate-determining step of the amination reactions of
3a–3e is the first addition step, so the vinylidenediamine
intermediate cannot be found naturally. In contrast, due to
electronic stabilization of the transition state of the first
C]N addition step by N-phenyl group, the rate-determining
step of the amination reactions of 1a–1c switches to the
second tautomerization step, resulting in accumulation of
the vinylidenediamine intermediate. Therefore, the vinyl-
idenediamine intermediate can be caught in the amination
reactions of 1a–1c. N-phenyl substituent decreases LUMO
energy of ketenimine, and that makes N-phenyl ketenimine
more reactive toward nucleophilic amines than N-i-propyl
ketenimine. The transition state 11(TS) for the C]N
addition of N-phenyl ketene 10 is significantly stabilized by
electron delocalization through the system.
5. Experimental
5.1. General
Calculated activation barriers for hydration of ketenimine
with H2O and (H2O)2 addition across C]N bond in solution
by PCM model at MP2/6-31G(d,p) level were reported to be
44.5 and 27.0 kcal/mol, respectively.14 Calculated acti-
vation barriers for amination of ketene with NH3 and
NH3$H2O addition across C]O bond in gas phase at MP2/
6-31G* level were reported to be 30.03 and 2.86 kcal/mol,
respectively.4c These two examples indicate that involve-
ment of additional water molecule in the transition states
significantly reduce activation barrier. Compared with the
experimental rate constants for the amination reactions of
ketenimines 1a and 3a, the calculated activation free
energies for the amination of ketenimines 5 and 10 are
somewhat big, indicating that additional water molecule is
likely involved in the transition states of the amination of
ketenimines 1a and 3a during the NMR studies. Never-
theless, this does not change the finding that N-phenyl group
strongly stabilizes the transition state in the C]N addition
process of amination of ketenimines.
Ketenimines 1a is known and other ketenimines 1b–1c
and 3a–3e were prepared by a known procedure.4h,i,7
5.2. General method to prepare ketenimines 1b–1c
and 3a–3e
Phosphorus pentachloride (7 mmol) was added to a solution
of N-substituted-p-substituted-phenylacetamide (7 mmol)
in dry benzene (20 mL). The solution was refluxed for
1 h, and the benzene and by-product of phosphorus
oxychloride were removed in high vacuum. The green-
yellow residue was dissolved in dry ether (20 mL) and dry
triethylamine (6 mL) was added to the solution to give an
instant color change to red. The reaction was refluxed for
6 h. The solution was filtered to remove insoluble
ammonium chloride under nitrogen atmosphere. After
evaporation of the solvent and triethylamine, crude
ketenimine was obtained as red oil, and it was purified by
sublimation in high vacuum with finger temperature at
K196 8C. The ketenimine was diluted with hexane for
storage.
LUMO of ketenimines lies in the ketenimine plane with a
large coefficient on Ca, so amination of ketenimine involves
an in-plane nucleophilic attack on the ketenimine LUMO at
Ca.7 This can be easily seen from the optimized transition
structures 6(TS) and 11(TS). LUMO energies of 5 and 10
were calculated to be 1.95 and 1.83 eV at MP2/6-31CG*
level in the solvent with dielectric constant of 35.9 (Onsager
model), indicating that N-phenyl substituent decreases
LUMO energy of ketenimine. According to PMO
theory,12,15 N-phenyl ketenimine 10 with low-lying
LUMO is more reactive toward nucleophilic amines than
N-i-propyl ketenimine 5, and this is consistent with both our
experimental and computational results.
5.2.1. N-p-Methoxyphenylphenylketenimine (1b). Yield:
74%; 1H NMR (CDCl3) d 3.83 (3H, s, OCH3), 5.24 (1H, s,
CH), 6.92 (2H, d, JZ8.2 Hz, PhH), 7.19 (2H, d, JZ8.2 Hz,
PhH); 7.26–7.34 (5H, m, PhH); 13C NMR (CDCl3) d 55.5,
60.9, 114.6, 125.1, 125.2, 125.5, 128.9, 132.9, 133.0, 159.2,
189.4; IR (hexane) 2007 (C]C]N) cmK1; HRMS (EI) m/z
calcd for C15H13NO 223.0997, found 223.0999. Anal. Calcd
for C15H13NO: C 80.68, H 5.87, N 6.28. Found: C 80.70, H
5.81, N 6.22.
In the optimized transition structure of 11(TS), dihedral
angle between N-phenyl substituent and ketenimine (or
enamine) plane is 12.88, and the N-phenyl group is
conjugated with the enamine backbone, making electron
delocalization go through these groups. Bond distances in
5.2.2. N-p-Bromophenylphenylketenimine (1c). Yield:
62%; 1H NMR (CDCl3) d 5.30 (1H, s, CH), 7.10–7.53
(9H, m, PhH); 13C NMR (CDCl3) d 61.3, 121.3, 125.4,

K. Sung et al. / Tetrahedron 62 (2006) 171–181
179
125.6, 125.7, 129.0, 131.9, 132.6, 139.6, 191.9; IR (hexane)
2016 (C]C]N) cmK1; HRMS (EI) m/z calcd for
C14H10BrN 270.9996, found 270.9995. Anal. Calcd for
C14H10BrN: C 61.99, H 3.72, N 5.17. Found: C 61.93, H
3.77, N 5.10.
(50 mL, 0.5 mmol) was injected into the NMR tube through
a rubber cap. The solution in the NMR tube was shaken in a
cold bath and then put into the NMR spectrometer. Then the
reaction was monitored by proton NMR spectrometer at
K10 8C for 1b–1c and 10 8C for 3a–3e until all the
ketenimine and most of intermediate (if it exists) were
consumed, and then the temperature was raised to 25 8C.
1
5.2.3. N-i-Propylphenylketenimine (3a). Yield: 78%; H
1
Monitored H NMR spectra for amination of 1a–1c look
NMR (CDCl3) d 1.35 (6H, d, JZ8.5 Hz, CH3), 3.85 (1H, m,
CH), 4.82 (1H, d, JZ2.4 Hz, CH), 7.08–7.30 (5H, m, PhH);
13C NMR (CDCl3) d 23.5, 54.6, 58.4, 124.4, 124.7, 128.7,
134.3, 184.7; IR (hexane) 2026 (C]C]N) cmK1; HRMS
(EI) m/z calcd for C11H13N 159.1048, found 159.1049.
Anal. Calcd for C11H13N: C 82.96, H 8.23, N 8.80. Found: C
82.92, H 8.19, N 8.89.
alike with vinylidenediamine intermediate involved and one
representative of them was shown in Figure 2.7 Monitored
1H NMR spectra for the amination of 3a–3e look alike
without any detected intermediate and one representative of
them is shown in Figure 3. Final products of amidines were
identified as follows.
5.4. Product analysis for amination of 1b–1c and 3a–3e
with n-BuNH2
5.2.4. N-i-Propyl-p-methylphenylketenimine (3b). Yield:
66%; H NMR (CDCl3) d 1.33 (6H, d, JZ5.2 Hz, CH3),
1
2.30 (3H, s, CH3), 3.83 (1H, m, CH), 4.79 (1H, d, JZ1.8 Hz,
CH), 7.00 (2H, d, JZ8.0 Hz, PhH), 7.07 (2H, d, JZ8.0 Hz,
PhH); 13C NMR (CDCl3) d 21.4, 23.5, 54.7, 58.6, 124.7,
129.4, 130.9, 134.1, 185.8; IR (hexane) 2026 (C]C]N)
cmK1; HRMS (EI) m/z calcd for C12H15N 173.1204, found
173.1206. Anal. Calcd for C12H15N: C 83.18, H 8.73, N
8.09. Found: C 83.10, H 8.80, N 8.10.
5.4.1. N-Butyl-N0-(p-methoxyphenyl)-2-phenylaceta-
midine (2b). H NMR (CDCl3) d 0.87 (3H, t, JZ7.2 Hz,
1
CH3), 1.27–1.43 (4H, m, CH2), 3.16 (2H, t, JZ7.0 Hz,
CH2), 3.44 (2H, s, CH2), 6.93–7.30 (9H, m, PhH); 13C NMR
(CDCl3) d 13.77, 20.07, 31.17, 36.19, 41.02, 55.20, 114.21,
114.52, 125.14, 128.28, 128.43, 142.82, 143.88, 151.01,
158.53; IR (thin film) 1655 (N–]N) cmK1; HRMS (EI) m/z
calcd for C19H24N2O 296.1889, found 296.1888.
5.2.5. N-i-Propyl-p-methoxyphenylketenimine (3c).
1
Yield: 71%; H NMR (CDCl3) d 1.30 (6H, d, JZ2.6 Hz,
CH3), 3.80 (3H, s, OCH3), 3.82 (1H, m, CH), 4.79 (1H, d,
JZ2.0 Hz, CH), 6.80 (2H, d, JZ5.0 Hz, PhH), 7.00 (2H, d,
JZ5.0 Hz, PhH); 13C NMR (CDCl3) d 23.5, 54.7, 55.2,
58.3, 114.4, 121.1, 125.8, 157.0, 186.6; IR (hexane) 2026
(C]C]N) cmK1; MS (EI) m/z 196 (30, MC), 140 (45), 99
(100), 84 (25), 57 (70); HRMS (EI) m/z calcd for C12H15NO
189.1154, found 189.1153. Anal. Calcd for C12H15NO: C
76.14, H 7.99, N 7.40. Found: C 76.10, H 8.18, N 7.35.
5.4.2. N-Butyl-N0-(p-bromophenyl)-2-phenylacetamidine
1
(2c). H NMR (CDCl3) d 0.92 (3H, t, JZ7.2 Hz, CH3),
1.29–1.45 (4H, m, CH2), 3.17 (2H, t, JZ6.8 Hz, CH2), 3.46
(2H, s, CH2), 7.11–7.50 (9H, m, PhH); 13C NMR (CDCl3) d
13.70, 20.12, 31.07, 36.39, 41.25, 110.63, 116.29, 125.55,
128.30, 128.74, 131.36, 142.72, 145.04, 157.09; IR (thin
film) 1651 (N–]N) cmK1; HRMS (EI) m/z calcd for
C18H21N2 265.1705, found 265.1703.
1
5.2.6. N-i-Propyl-p-chlorophenylketenimine (3d). Yield:
59%; H NMR (CDCl3) d 1.30 (6H, d, JZ2.6 Hz, CH3),
5.4.3. N-Butyl-N0-i-propyl-2-phenylacetamidine (4a). H
1
NMR (CDCl3) d 0.96 (3H, t, JZ7.2 Hz, CH3), 1.17 (6H, d,
JZ6.4 Hz, CH3), 1.31–1.52 (4H, m, CH2), 3.07 (2H, t, JZ
6.8 Hz, CH2), 3.50 (2H, s, CH2), 3.78 (1H, m, CH), 7.06–
7.15 (5H, m, PhH); 13C NMR (CDCl3) d 13.71, 19.73,
20.11, 31.13, 36.25, 41.30, 46.02, 125.81, 128.02, 128.83,
142.51, 157.91; IR (thin film) 1663 (N–]N) cmK1; HRMS
(EI) m/z calcd for C15H24N2 232.1939, found 232.1941.
3.85 (1H, m, CH), 4.76 (1H, d, JZ2.0 Hz, CH), 7.03 (2H, d,
JZ5.9 Hz, PhH), 7.20 (2H, d, JZ5.9 Hz, PhH); 13C NMR
(CDCl3) d 23.5, 54.7, 58.0, 125.8, 129.1, 130.6, 132.7,
183.7; IR (hexane) 2026 (C]C]N) cmK1; HRMS (EI) m/z
calcd for C11H12ClN 193.0658, found 193.0656. Anal.
Calcd for C11H12ClN: C 68.37, H 6.26, N 7.25. Found: C
68.40, H 6.19, N 7.31.
5.4.4. N-Butyl-N0-i-propyl-2-(p-methylphenyl)aceta-
midine (4b). H NMR (CDCl3) d 0.93 (3H, t, JZ7.2 Hz,
1
5.2.7. N-i-Propyl-p-nitrophenylketenimine (3e). Yield:
1
45%; H NMR (CDCl3) d 1.33 (6H, d, JZ5.2 Hz, CH3),
CH3), 1.17 (6H, d, JZ6.4 Hz, CH3), 1.31–1.52 (4H, m,
CH2), 2.31 (3H, s, CH3), 3.13 (2H, t, JZ7.0 Hz, CH2), 3.64
(2H, s, CH2), 3.80 (1H, m, CH), 7.00 (2H, d, JZ8.0 Hz,
PhH), 7.07 (2H, d, JZ8.0 Hz, PhH); 13C NMR (CDCl3) d
13.75, 20.10, 21.30, 32.34, 36.65, 41.01, 46.82, 126.23,
128.52, 134.73, 141.51, 153.91; IR (thin film) 1662
(N–]N) cmK1; HRMS (EI) m/z calcd for C16H26N2
246.2096, found 246.2095.
3.88 (1H, m, CH), 4.76 (1H, d, JZ1.7 Hz, CH), 7.06 (2H, d,
JZ7.0 Hz, PhH), 7.98 (2H, d, JZ7.0 Hz, PhH); 13C NMR
(CDCl3) d 23.3, 54.6, 57.7, 123.7, 129.9, 134.9, 143.8,
177.3; IR (hexane) 2032 (C]C]N) cmK1; HRMS (EI) m/z
calcd for C11H12NO2 190.0868, found 190.0870. Anal.
Calcd for C11H12NO2: C 69.44, H 6.36, N 7.37. Found: C
69.51, H 6.42, N 7.39.
5.3. NMR study of amination of ketenimines 1b–1c
and 3a–3e
5.4.5. N-Butyl-N0-i-propyl-2-(p-methoxyphenyl)aceta-
midine (4c). H NMR (CDCl3) d 0.96 (3H, t, JZ7.2 Hz,
1
CH3), 1.18 (6H, d, JZ6.5 Hz, CH3), 1.31–1.52 (4H, m,
CH2), 3.06 (2H, t, JZ7.0 Hz, CH2), 3.48 (2H, s, CH2), 3.70
(3H, s, OCH3), 3.80 (1H, m, CH), 6.80 (2H, d, JZ5.0 Hz,
PhH), 7.00 (2H, d, JZ5.0 Hz, PhH); 13C NMR (CDCl3) d
13.95, 19.81, 20.30, 32.13, 36.95, 41.43, 46.71, 113.81,
A NMR tube filled with 1 mL of a CD3CN solution of a
ketenimine (0.01 mmol) and benzyl phenyl ether
(0.033 mmol, serving as an internal standard with d
5.0 ppm) was cooled by liquid nitrogen. Pure n-butylamine

180
K. Sung et al. / Tetrahedron 62 (2006) 171–181
128.82, 129.13, 154.51, 157.91; IR (thin film) 1661
(N–]N) cmK1; HRMS (EI) m/z calcd for C16H26N2O
262.2045, found 262.2044.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.09.
119
5.4.6. N-Butyl-N0-i-propyl-2-(p-chlorophenyl)aceta-
1
midine (4d). H NMR (CDCl3) d 0.97 (3H, t, JZ7.2 Hz,
CH3), 1.08 (6H, d, JZ6.4 Hz, CH3), 1.31–1.52 (4H, m,
CH2), 3.13 (2H, t, JZ7.1 Hz, CH2), 3.61 (2H, s, CH2), 3.80
(1H, m, CH), 7.03 (2H, d, JZ5.9 Hz, PhH), 7.20 (2H, d, JZ
5.9 Hz, PhH); 13C NMR (CDCl3) d 14.05, 19.80, 20.90,
31.83, 36.75, 41.22, 46.53, 128.71, 130.42, 131.11, 136.53,
153.62; IR (thin film) 1662 (N–]N) cmK1; HRMS (EI) m/z
calcd for C15H23ClN2 266.1550, found 266.1549.
References and notes
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(4e). 1H NMR (CDCl3) d 0.90 (3H, t, JZ7.2 Hz, CH3), 1.11
(6H, d, JZ6.5 Hz, CH3), 1.31–91.52 (4H, m, CH2), 3.04
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Setup for the rate-constant measurement is the same as the
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Acknowledgements
Financial support by the National Science Council of
Taiwan (NSC 92-2113-M-006-010) and computer time
from National Center for High-performance Computing of
Taiwan are gratefully acknowledged.
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