Regioselective N-alkylation of 2-aminoimidazoles with alcohols to 2-(N-Alkylamino)imidazoles catalyzed by the [Cp*IrCl2] 2/K2CO3 system

Article abstract of DOI:10.1002/ejoc.201200698

The direct N-alkylation of 2-aminoimidazoles to give the corresponding 2-(N-alkylamino)imidazoles was accomplished using alcohols as alkylating agents in the presence of a [Cp*IrCl₂]₂/K ₂CO₃ system. The iridium-catalyzed regioselective reaction is simple, efficient, general, and environmentally benign. The direct N-alkylation of 2-aminoimidazoles to give the corresponding 2-(N-alkylamino) imidazoles was accomplished using alcohols as alkylating agents in the presence of a [Cp*IrCl₂]₂/K₂CO₃ system. The iridium-catalyzed regioselective reaction is simple, efficient, general, and environmentally benign. Copyright

Full text of DOI:10.1002/ejoc.201200698

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FULL PAPER
DOI: 10.1002/ejoc.201200698
Regioselective N-Alkylation of 2-Aminoimidazoles with Alcohols to 2-(N-
Alkylamino)imidazoles Catalyzed by the [Cp*IrCl2]2/K2CO3 System
Feng Li,*[a] Qikai Kang,[a] Haixia Shan,[a] Lin Chen,[a] and Jianjiang Xie[a]
Keywords: Synthetic methods / Homogeneous catalysis / Iridium / Regioselectivity / Hydrogen transfer / Nitrogen
heterocycles
The direct N-alkylation of 2-aminoimidazoles to give the cor- [Cp*IrCl2]2/K2CO3 system. The iridium-catalyzed regioselec-
responding 2-(N-alkylamino)imidazoles was accomplished
using alcohols as alkylating agents in the presence of a
tive reaction is simple, efficient, general, and environmen-
tally benign.
Introduction
2-Aminoimidazole derivatives are an important class of
nitrogen-containing heterocyclic compounds. In particular,
2-(N-alkylamino)imidazoles display a wide range of bio-
logical activities.[1] Examples of the applications of this class
of compounds include: as a human arginase 1 inhibitor
(A),[1a] small conductance Ca2+-activated K+ (SK) channel
inhibitors (NS8593 and NS11757; B),[1b] antiallergic anti-
histamines (Norastemizole and Astemizole; C),[1c] respira-
tory syncytial virus (RSV) inhibitors (JNJ-2408068;
D),[1d–1e] metal-free artificial nucleases,[1f–1g] and nuclear
Factor-kB activation inhibitors[1h] (Figure 1). The tradi-
tional method for the preparation of 2-(N-alkylamino)imid-
azoles was through SNAr reactions of 2-haloimidazoles
with alkylamines.[1–2]
This procedure requires the multistep synthesis of the
starting materials, and suffers from harsh reaction condi-
tions such as high temperature, high pressure, and micro-
wave irradiation. Over the past few years, transition-metal-
catalyzed methods have been developed for the preparation
of 2-(N-alkylamino)imidazole derivatives. These include Pd-
catalyzed amination of 2-halobenzimidazoles,[3] Pd- or Cu-
catalyzed cyclization of o-halobenzoguanidines,[4] Cu-cata-
lyzed coupling of dihalobenzenes with N-alkylguanidines,[5]
and Cu-catalyzed cascade addition/cyclization of o-haloan-
ilines and carbodiimides.[6] However, these procedures only
allow the synthesis of benzo-fused 2-(N-alkylamino)imid-
azoles, so the scope of reaction was highly restricted. All of
the procedures mentioned above produce a stoichiometric
amount of the hydrogen halide as by-product, resulting in
an environmental hazard.
Figure 1. Biologically active 2-(N-alkylamino)imidazoles.
The direct N-alkylation of 2-aminoimidazoles provides
what is apparently one of the most simple routes to 2-(N-
alkylamino)imidazoles. However, when alkyl halides are
used as alkylating agents, such reactions give the isomeric
3-alkyl-2-iminoazolines as products rather than 2-(N-alk-
ylamino)imidazoles, due to the fact that the endocyclic ni-
trogens are more basic than the exocylic ones[7] (Scheme 1,
top line). Recently, much effort has been put into research
into the N-alkylation of amines using alcohols as alkylating
agents, based on the “hydrogen autotransfer” (or “hydro-
gen-borrowing”) process,[8] using iridium,[9] ruthenium,[10]
or other transition metal catalysts.[11] The methodology is
attractive because of its high atom efficiency and the forma-
tion of water as the only by-product, and it has also been
applied to the N-alkylation of (hetero)aromatic amines.[12]
Very recently, we reported the preparation of 2-(N-alk-
ylamino)thiazoles and 2-(N-alkylamino)oxazoles by direct
[a] School of Chemical Engineering, Nanjing University of Science
and Technology,
Nanjing 210094, P. R. China
Fax: +86-25-84431939
E-mail: fengli@mail.njust.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200698.
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F. Li, Q. Kang, H. Shan, L. Chen, J. Xie
FULL PAPER
N-alkylation of the corresponding amines with primary Table 2. N-alkylation of 2-aminoimidazoles 1 with various alcohols
2.[a]
alcohols, catalyzed by transition metal/base systems.[13,14]
Scheme 1. Direct N-alkylation of 2-aminoimidazoles with alkyl hal-
ides and alcohols.
Realizing the unique potential influence on regioselectiv-
ies of alcohols as non-alkyl halide alkylating agents, and as
part of our continuing interest in exploring regioselective
N-alkylation reactions, in this paper, we wish to describe
our efforts towards the iridium-catalyzed direct N-alkyl-
ation of 2-aminoimidazoles to give the corresponding 2-(N-
alkylamino)imidazoles using alcohols as alkylating agents
(Scheme 1, bottom line). A high reactivity was seen in the
presence of a relatively weak base, and the reaction was
effective not only for primary alcohols, but also for second-
ary alcohols.
Results and Discussion
In an initial experiment, the N-alkylation of 2-amino-
benzimidazole (1a) with benzyl alcohol (2a) was chosen as
a model reaction. The reaction was carried out in the pres-
ence of [Cp*IrCl2]2 (Cp* = pentamethylcyclopentadienyl)
(0.2 mol-%) at 130 °C for 12 h to give the desired N-alkyl-
ated product (i.e., 3aa) in 62% yield (Table 1, entry 1). As
expected, the reaction was improved by the addition of a
Table 1. N-alkylation of 2-aminoimidazole (1a) with benzyl alcohol
(2a) under various conditions.[a]
[a] Reaction conditions: amine (1 mmol), alcohol (4 mmol),
[Cp*IrCl2]2 (0.2 mol-%), K2CO3 (0.1 mmol), 130 °C, 12 h. [b] Iso-
lated yields. [c] 150 °C.
[a] Reaction conditions: 1a (1 mmol), 2a (4 mmol), catalyst
(0.2 mol-%), base (0.1 mmol), 130 °C, 12 h. [b] Isolated yields.
2
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N-Alkylation of 2-Aminoimidazoles with Alcohols
Table 3. N-alkylation of 1-alkyl-2-aminoimidazoles 4 with various
alcohols 2.[a]
Table 3. (Continued)
[a] Reaction conditions: amine (1 mmol), alcohol (4 mmol),
[Cp*IrCl2]2 (0.2 mol-%), K2CO3 (0.1 mmol), 130 °C, 12 h. [b] Iso-
lated yields. [c] K2CO3 (1 mmol). [d] 150 °C.
base (10 mol-%) (Table 1, entries 2–6). Product 3aa could
be obtained in 96% yield when K2CO3 or Cs2CO3 was used
as a base (Table 1, entries 5–6). When [Ir(cod)Cl]2 (cod =
1,5-cyclooctadienyl) or [Cp*RhCl2]2 were used as alterna-
tive catalysts in the presence of K2CO3, the reactions gave
3aa in 91 and 93% yields, respectively (Table 1, entries 7–
8). We also found that no reaction occurred in the presence
of K2CO3 alone (Table 1, entry 9).
Under the optimal conditions (Table 1, entry 5), the N-
alkylation of a series of 2-aminoimidazoles 1 with various
alcohols 2 was examined, and the results are summarized
in Table 2. The N-alkylation of 2-aminobenzimidazole (1a)
with benzylic alcohols bearing an electron-donating group
(i.e., 2b and 2c) or electron-withdrawing group (i.e., 2d) gave
the corresponding products (i.e., 3ab–3ad) in 84–92%
yields. Similarly, the reactions of 1a with benzylic alcohols
bearing a halogen atom (i.e., 2e and 2f) gave the desired
products (i.e., 3ae and 3af) in 90 and 87% yields, respec-
tively. Aliphatic primary alcohols, such as 1-butanol (2g)
and 1-octanol (2h), were also converted into the corre-
sponding products (i.e., 3ag and 3ah) in high yields. Surpris-
ingly, cyclic secondary alcohols with a high degree of steric
hindrance, such as cyclopentanol (2i) and cyclohexanol (2j),
were successfully used, and the desired products (i.e., 3ai
and 3aj) were obtained in 78 and 84% yields, respectively.
N-Alkylation with functionalized alcohols 2k and 2l gave
the corresponding products (i.e., 3ak and 3al) in 87 and
71% yields, respectively. Furthermore, the reactions of sub-
stituted 2-aminobenzimidazole 1b with 2a and 2g gave the
desired products (i.e., 3ba and 3bg) in 95 and 85% yields,
respectively. For non-benzo-fused 2-aminoimidazoles 1c
and 1d, N-alkylation with 1a gave the corresponding prod-
ucts (i.e., 3ca and 3da) in 84 and 89% yields, respectively.
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F. Li, Q. Kang, H. Shan, L. Chen, J. Xie
FULL PAPER
To further expand the scope of the reaction, the N-alkyl- product; see Equation (1). Furthermore, the reaction of 7
ation of 1-alkyl-2-aminoimidazoles 4 with various alcohols with 2g was carried out for 12 h in the presence of
2 was investigated. As shown in Table 3, the reactions of [Cp*IrCl2]2 (0.2 mol-%) and K2CO3 (10 mol-%), and gave
1-benzyl-2-aminobenzimidazole (4a) with various benzylic an almost quantitative yield of 3aa, supporting the hydro-
alcohols gave the desired products (i.e., 5aa–5ap) in 78–91% gen-transfer mechanism; see Equation (2).
yields. The alkylation of 4a with aliphatic alcohols 2g–j gave
the corresponding products (i.e., 5ag–5aj) in 68–87% yields.
Furthermore, the reaction of non-benzo-fused substrate 4b
with 2a gave the corresponding product (i.e., 5ba) in 75%
yield, although an elevated reaction temperature was re-
quired. 2-Aminoimidazoles bearing other substituents at
the 1N position were also shown to be suitable substrates.
The reactions of 4c–h with 2a gave the desired products
(i.e., 5ca–5ha) in 80–90% yields.
It should be noted that no isomeric 1-alkyl-2-iminoazol-
ines or over-alkylated 1,3-dialkyl-2-iminoazolines or 2-(N-
dialkylamino)imidazoles were observed in any reactions.
Only the desired 2-(N-alkylamino)imidazole products were
seen.
A plausible mechanism for this regioselective reaction Conclusions
based on the “hydrogen autotransfer” (or “hydrogen-bor-
We have demonstrated the first example of the prepara-
rowing”) process[8,9] is outlined in Scheme 2. The alcoholate
tion of 2-(N-alkylamino)imidazoles by direct N-alkylation
of the corresponding 2-aminoimidazoles with alcohols. This
is first dehydrogenated to form the aldehyde and the metal
hydride species. Then condensation occurs between the al-
iridium-catalyzed regioselective reaction has advantages
dehyde and 2-aminoimidazole to give the imine intermedi-
over existing methods, such as the ready availability of
ate. Finally, the unsaturated intermediate is hydrogenated,
starting materials, high atom efficiency, and environmental
which consumes the hydride species and gives the desired
friendliness. Efforts to extend the potential of alcohols as
product. The exocyclic nitrogen of 2-aminoimidazole is fa-
electrophiles are currently underway in our laboratory.
vored over the endocyclic one in the condensation with the
aldehyde, and this results in the regioselectivity of the reac-
tion.
Experimental Section
General Methods: Infra-red spectra were recorded with a Nicolet
iS10 FTIR spectrometer. High-resolution mass spectra (HRMS)
were obtained with a HPLC-Q-Tof MS (Micro) spectrometer and
are reported as m/z values. Melting points were measured with a
X-6 micro-melting apparatus (Beijing Tech Instrument Co., Ltd).
Proton nuclear magnetic resonance (1H NMR) spectra were re-
corded at 500 MHz using a Bruker Avance 500 spectrometer.
Chemical shifts are reported on the δ scale in parts per million
(ppm) relative to tetramethylsilane, using residual solvent peaks (δ
= 7.26 ppm for CDCl3; 2.50 ppm for [D6]DMSO; 4.78 and
3.31 ppm for CD3OD) as internal standards. Coupling constants
(J values) are reported in Hertz (Hz), and splitting patterns are
designated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; b, broad. Carbon nuclear magnetic resonance (13C
NMR) spectra were recorded at 125 MHz using a Bruker Avance
500 spectrometer. Chemical shifts are reported on the δ scale in
ppm relative to tetramethylsilane, using solvent peaks (δ
=
77.0 ppm for CDCl3; 39.5 ppm for [D6]DMSO; 49.0 ppm for
CD3OD) as internal standards.
[17]
[Cp*IrCl2]2,[15] [Ir(cod)Cl]2,[16] and [Cp*RhCl2]2
were prepared
according to literature methods. All reactions were run under an
atmosphere of nitrogen, unless otherwise indicated. Anhydrous sol-
vents were transferred by oven-dried syringe. Reaction tubes were
oven-dried and cooled under a stream of nitrogen. Reaction tubes
were purchased from Beijing Synthware Glass Inc. Analytical thin-
layer chromatography (TLC) was carried out using 0.2 mm com-
mercially available silica gel plates. Solvents for chromatography
Scheme 2. Plausible mechanism.
To confirm the proposed mechanism, the condensation
of 2-aminoimidazole with an aldehyde was first examined.
Treatment of 2-aminobenzimidazole (1a) with benzaldehyde
(6) at 130 °C for 12 h gave imine 7 in 55% yield as the only are listed as volume/volume ratios.
4
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N-Alkylation of 2-Aminoimidazoles with Alcohols
General Procedure for Iridium-Catalyzed N-Alkylation of 2-Amino-
imidazoles Using Alcohols as Alkylating Agents: 2-Aminoimidazole
derivative (1 mmol), alcohol (4 mmol), base (0.1 mmol, 10 mol-%)
and iridium complex (0.002 mmol, 0.2 mol-%) were added to an
oven-dried, nitrogen-purged 20 mL Schlenk tube. The reaction mix-
ture was heated at 130 °C for 12 h, and was then allowed to cool
to ambient temperature. The mixture was concentrated in vacuo
and purified by flash column chromatography with hexane/ethyl
acetate to give the corresponding product.
13.6 ppm. HRMS-EI (70 eV): m/z calcd. for C11H16N3 [M + H]+
190.1344; found 190.1346.
N-Octyl-1H-benzo[d]imidazol-2-amine (3ah): M.p. 139–140 °C. 1H
NMR (500 MHz, CD3OD): δ = 7.17–7.16 (m, 2 H, ArH), 6.95–
6.93 (m, 2 H, ArH), 3.34 (t, J = 7.1 Hz, 2 H, CH2N), 1.64 (quint,
J = 7.3 Hz, 2 H, CH2), 1.45–1.30 (m, 10 H, 5 CH2), 0.89 (t, J =
6.6 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, CD3OD): δ = 157.1,
139.1, 121.2, 112.6, 43.9, 33.0, 30.9, 30.5, 30.4, 28.0, 23.7,
14.4 ppm. HRMS-EI (70 eV): m/z calcd. for C15H24N3 [M + H]+
246.1970; found 246.1972.
N-Benzyl-1H-benzo[d]imidazol-2-amine (3aa):[1b] M.p. 164–166 °C
1
(ref.[1b] m.p. 165–166 °C). H NMR (500 MHz, CD3OD): δ = 7.38
N-Cyclopentyl-1H-benzo[d]imidazol-2-amine (3ai): M.p. 205–
206 °C. 1H NMR (500 MHz, CD3OD): δ = 7.18–7.17 (m, 2 H,
ArH), 6.96–6.94 (m, 2 H, ArH), 4.09 (quint, J = 6.4 Hz, 1 H,
CHN), 2.09–2.03 (m, 2 H, CH2), 1.82–1.74 (m, 2 H, CH2), 1.70–
1.64 (m, 2 H, CH2), 1.60–1.53 (m, 2 H, CH2) ppm. 13C NMR
(125 MHz, CD3OD): δ = 156.5, 139.0, 121.2, 112.6, 55.5, 34.2,
24.6 ppm. HRMS-EI (70 eV): m/z calcd. for C12H16N3 [M + H]+
202.1344; found 202.1348.
(br. s, 2 H, ArH), 7.31 (br. s, 2 H, ArH), 7.23–7.18 (m, 3 H, ArH),
6.96 (br. s, 2 H, ArH), 4.57 (s, 2 H, CH2N) ppm. 13C NMR
(125 MHz, CD3OD): δ = 156.9, 140.6, 139.2, 129.5, 128.3, 128.2,
121.3, 112.8, 47.4 ppm. HRMS-EI (70 eV): m/z calcd. for C14H14N3
[M + H]+ 224.1188; found 224.1184.
N-(4-Methoxybenzyl)-1H-benzo[d]imidazol-2-amine (3ab):[18] M.p.
193–195 °C (ref.[18] m.p. 207–208 °C). 1H NMR (500 MHz,
CD3OD): δ = 7.30 (d, J = 7.9 Hz, 2 H), 7.18 (br. s, 2 H), 6.96 (br.
s, 2 H), 6.87 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (125 MHz,
CD3OD): δ = 160.4, 156.9, 139.1, 132.5, 129.7, 121.3, 114.9,
112.8 ppm. HRMS-EI (70 eV): m/z calcd. for C15H16N3O
[M + H]+ 254.1293; found 254.1300.
N-Cyclohexyl-1H-benzo[d]imidazol-2-amine (3aj):[21] M.p. 213-
214 °C (ref.[21] m.p. 215.1–215.5 °C). 1H NMR (500 MHz,
CD3OD): δ = 7.17–7.15 (m, 2 H, ArH), 6.94–6.93 (m, 2 H, ArH),
3.61–3.56 (m, 1 H, CHN), 2.07–2.05 (m, 2 H, CH2), 1.80–1.78 (m,
2 H, CH2), 1.68–1.66 (m, 1 H, CH), 1.49–1.42 (m, 2 H, CH2), 1.32–
1.22 (m, 3 H, CH2 and CH) ppm. 13C NMR (125 MHz, CD3OD):
δ = 156.2, 139.1, 121.1, 112.6, 52.7, 34.6, 26.8, 26.1 ppm. HRMS-
EI (70 eV): m/z calcd. for C13H18N3 [M + H]+ 216.1501; found
216.1493.
N-(4-Methylbenzyl)-1H-benzo[d]imidazol-2-amine (3ac):[19] M.p.
172–173 °C. 1H NMR (500 MHz, CD3OD): δ = 7.26 (d, J = 7.9 Hz,
2 H, ArH), 7.19–7.17 (m, 2 H, ArH), 7.13 (d, J = 7.7 Hz, 2 H,
ArH), 6.96–6.94 (m, 2 H, ArH), 4.51 (s, 2 H, CH2N), 2.29 (s, 3 H,
CH3) ppm. 13C NMR (125 MHz, CD3OD): δ = 156.9, 139.1, 137.9,
137.4, 130.1, 128.3, 121.3, 112.8, 47.3, 21.1 ppm. HRMS-EI
(70 eV): m/z calcd. for C15H16N3 [M + H]+ 238.1344; found
238.1343.
N-(3-Phenylpropyl)-1H-benzo[d]imidazol-2-amine (3ak): M.p. 159–
161 °C. 1H NMR (500 MHz, CD3OD): δ = 7.26–7.20 (m, 4 H,
ArH), 7.18–7.13 (m, 3 H, ArH), 6.96–6.94 (m, 2 H, ArH), 3.37 (t,
J = 7.1 Hz, 2 H, CH2N), 2.73 (t, J = 7.7 Hz, 2 H, CH2Ar), 1.99–
1.93 (m, 2 H, CH2) ppm. 13C NMR (125 MHz, CD3OD): δ = 157.0,
143.1, 139.1, 129.4, 129.3, 126.8, 121.2, 112.7, 43.4, 34.1, 32.8 ppm.
HRMS-EI (70 eV): m/z calcd. for C16H18N3 [M + H]+ 252.1501;
found 252.1503.
N-[4-(Trifluoromethyl)benzyl]-1H-benzo[d]imidazol-2-amine
(3ad):[18] M.p. 222–223 °C (ref.[18] m.p. 222–223 °C). 1H NMR
(500 MHz, CD3OD): δ = 7.62 (d, J = 8.3 Hz, 2 H, ArH), 7.57 (d,
J = 8.1 Hz, 2 H, ArH), 7.20–7.18 (m, 2 H, ArH), 6.97–6.96 (m, 2 H,
ArH), 4.67 (s, 2 H, CH2N) ppm. 13C NMR (125 MHz, CD3OD): δ
N-(2-Methoxyethyl)-1H-benzo[d]imidazol-2-amine (3al): M.p. 151–
152 °C. 1H NMR (500 MHz, CDCl3): δ = 7.28–7.26 (m, 2 H, ArH),
7.05–7.03 (m, 2 H, ArH), 3.60 (t, J = 4.7 Hz, 2 H, CH2O), 3.55 (t,
J = 4.7 Hz, 2 H, CH2N), 3.39 (s, 3 H, OCH3) ppm. 13C NMR
(125 MHz, CDCl3): δ = 155.8, 137.5, 120.7, 112.2, 72.6, 58.9,
43.4 ppm. HRMS-EI (70 eV): m/z calcd. for C10H14N3O [M +
H]+ 192.1137; found 192.1134.
= 156.7, 145.5, 139.1, 130.3 (q, JC,F = 31.2 Hz), 125.8 (q, JC,F
=
269.4 Hz), 126.3, 121.4, 112.9, 46.8 ppm. HRMS-EI (70 eV): m/z
calcd. for C15H13N3F3 [M + H]+ 292.1062; found 292.1070.
N-(4-Bromobenzyl)-1H-benzo[d]imidazol-2-amine (3ae):[19] M.p.
162–163 °C (ref.[19] m.p. 195–197 °C). 1H NMR (500 MHz,
CD3OD): δ = 7.46 (d, J = 8.1 Hz, 2 H, ArH), 7.30 (d, J = 8.1 Hz,
2 H, ArH), 7.19–7.17 (m, 2 H, ArH), 6.97–6.95 (m, 2 H, ArH)
ppm. 13C NMR (125 MHz, CD3OD): δ = 156.7, 140.1, 139.1,
132.5, 130.2, 121.8, 121.4, 112.9, 46.7 ppm. HRMS-EI (70 eV): m/z
calcd. for C14H13N3Br [M + H]+ 302.0293; found 302.0298.
N-Benzyl-5,6-dimethyl-1H-benzo[d]imidazol-2-amine (3ba): M.p.
179–180 °C. 1H NMR (500 MHz, CD3OD): δ = 7.38 (d, J = 7.5 Hz,
2 H, ArH), 7.31 (t, J = 7.5 Hz, 2 H, ArH), 7.23 (t, J = 7.1 Hz, 1
H, ArH), 6.97 (s, 2 H, ArH), 4.54 (s, 2 H, CH2N), 2.26 (s, 6 H, 2
CH3) ppm. 13C NMR (125 MHz, CD3OD): δ = 156.6, 140.7, 137.6,
129.5, 129.4, 128.3, 128.2, 113.6, 47.5, 20.2 ppm. HRMS-EI
(70 eV): m/z calcd. for C16H18N3 [M + H]+ 252.1501; found
252.1504.
N-(2-Chlorobenzyl)-1H-benzo[d]imidazol-2-amine (3af):[18] M.p.
182–184 °C (ref.[18] m.p. 212–214 °C). 1H NMR (500 MHz,
CD3OD): δ = 7.46–7.45 (m, 1 H, ArH), 7.41–7.39 (m, 1 H, ArH),
7.26–7.24 (m, 2 H, ArH), 7.19–7.18 (m, 2 H, ArH), 6.97–6.95 (m, 2
H, ArH), 4.67 (s, 2 H, CH2) ppm. 13C NMR (125 MHz, CD3OD): δ
= 156.7, 139.2, 137.8, 134.3, 130.4, 129.6, 128.1, 121.3, 112.9,
45.3 ppm. HRMS-EI (70 eV): m/z calcd. for C14H13N3Cl [M +
H]+ 258.0798; found 258.0794.
N-Butyl-5,6-dimethyl-1H-benzo[d]imidazol-2-amine (3bg):[1f] M.p.
82–84 °C. 1H NMR (500 MHz, CDCl3): δ = 7.06 (s, 2 H, ArH),
4.51 (br. s, 1 H, NH), 3.38 (t, J = 7.1 Hz, 2 H, CH2N), 2.29 (s, 6
H, 2 CH3Ar), 1.61 (quint, J = 7.3 Hz, 2 H), 1.39 (sext, J = 7.5 Hz,
2 H), 0.92 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 156.6, 140.7, 129.5, 129.4, 128.3, 128.2, 113.6, 47.5,
20.2 ppm. HRMS-EI (70 eV): m/z calcd. for C13H20N3 [M + H]+
218.1657; found 218.1658.
N-Butyl-1H-benzo[d]imidazol-2-amine (3ag):[20] M.p. 145–146 °C.
1H NMR (500 MHz, CDCl3): δ = 7.27–7.26 (m, 2 H, ArH), 7.04–
7.02 (m, 2 H, ArH), 5.19 (br. s, 1 H, NH), 3.39 (t, J = 7.1 Hz, 2
H, CH2N), 1.55 (quint, J = 7.3 Hz, 2 H, CH2), 1.35 (sext, J =
7.5 Hz, 2 H, CH2), 0.84 (t, J = 7.3 Hz, 3 H, CH3) ppm. 13C NMR N-Benzyl-4,5-diphenyl-1H-imidazol-2-amine (3ca):[22] M.p. 176–
(125 MHz, CDCl3): δ = 156.0, 137.8, 120.5, 111.9, 43.0, 31.9, 19.9,
1
177 °C. H NMR (500 MHz, CD3OD): δ = 7.41 (d, J = 7.2 Hz, 2
Eur. J. Org. Chem. 0000, 0–0
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Job/Unit: O20698
/KAP1
Date: 31-07-12 15:57:25
Pages: 9
F. Li, Q. Kang, H. Shan, L. Chen, J. Xie
FULL PAPER
H, ArH), 7.37–7.33 (m, 6 H, ArH), 7.26 (t, J = 7.4 Hz, 5 H, ArH),
7.20 (t, J = 7.2 Hz, 2 H, ArH), 4.50 (s, 2 H, CH2N) ppm. 13C NMR
(125 MHz, CD3OD): δ = 152.1, 140.8, 134.4, 130.3, 129.5, 129.4,
128.8, 128.6, 128.2, 127.8, 48.3 ppm. HRMS-EI (70 eV): m/z calcd.
for C22H20N3 [M + H]+ 326.1657; found 326.1650.
J = 7.7 Hz, 1 H, ArH), 7.30 (d, J = 8.1 Hz, 4 H, ArH), 7.24 (s, 1
H), 7.16–7.06 (m, 6 H, ArH), 5.12 (s, 2 H, CH2N), 4.71 (d, J =
4.9 Hz, 2 H, CH2NH), 4.55 (br. s, 1 H, NH) ppm. 13C NMR
(125 MHz, CDCl3): δ = 153.7, 141.9, 135.2, 134.9, 134.6, 134.0,
133.7, 130.5, 129.2, 129.1, 128.2, 127.1, 126.5, 121.6, 120.0, 116.7,
107.3, 45.7, 44.5 ppm. HRMS-EI (70 eV): m/z calcd. for
C21H18N3Cl2 [M + H]+ 382.0878; found 382.0872.
N-Benzyl-5-methyl-4-phenyl-1H-imidazol-2-amine (3da): M.p. 139–
1
140 °C. H NMR (500 MHz, [D6]DMSO): δ = 7.49–7.47 (m, 4 H,
N-[3-(Trifluoromethyl)benzyl]-1-benzyl-1H-benzo[d]imidazol-2-
amine (5ao): M.p. 136–138 °C. 1H NMR (500 MHz, CDCl3): δ =
7.53 (d, J = 6.6 Hz, 1 H, ArH), 7.50–7.29 (m, 7 H, ArH), 7.18–
7.08 (m, 5 H, ArH), 5.15 (s, 2 H, CH2N), 4.74 (s, 2 H,CH2NH),
4.48 (br. s, 1 H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ =
153.8, 141.9, 139.7, 135.2, 134.9, 130.88 (q, JC,F = 32.1 Hz), 130.9,
129.2, 129.0, 128.3, 126.4, 124.2, 124.00 (q, JC,F = 270.9 Hz),
123.98, 121.6, 120.2, 116.8, 107.4, 46.7, 45.8 ppm. HRMS-EI
(70 eV): m/z calcd. for C22H19N3F3 [M + H]+ 382.1531; found
382.1539.
ArH), 7.41–7.37 (m, 5 H, ArH), 7.31 (br. s, 1 H, ArH), 4.53 (d, J
= 6.8 Hz, 2 H), 2.25 (s, 3 H, CH3) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 146.3, 137.7, 128.8, 128.5, 128.2, 127.8, 127.4,
127.1, 126.8, 121.6, 119.1, 52.7, 45.7 ppm. HRMS-EI (70 eV): m/z
calcd. for C1.7H18N3 [M + H]+ 264.1501; found 264.1505.
N,1-Dibenzyl-1H-benzo[d]imidazol-2-amine (5aa): M.p. 105–106 °C.
1H NMR (500 MHz, CDCl3): δ = 7.55 (d, J = 7.8 Hz, 1 H, ArH),
7.3–7.22 (m, 8 H, ArH), 7.17–7.13 (m, 3 H, ArH), 7.10–7.05 (m, 2
H, ArH), 5.11 (s, 2 H, CH2N), 4.68 (d, J = 5.2 Hz, 2 H, CH2NH),
4.25 (br. s, 1 H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ =
154.1, 142.2, 138.5, 135.3, 134.9, 129.1, 128.6, 128.1, 127.5, 127.4,
126.4, 121.5, 119.9, 116.7, 107.3, 47.4, 45.7 ppm. HRMS-EI
(70 eV): m/z calcd. for C21H19N3 [M + H]+ 314.1657; found
314.1647.
1-Benzyl-N-(naphthalen-2-ylmethyl)-1H-benzo[d]imidazol-2-amine
1
(5ap): M.p. 132–133 °C. H NMR (500 MHz, CDCl3): δ = 7.80 (t,
J = 4.6 Hz, 1 H, ArH), 7.75 (d, J = 8.5 Hz, 1 H, ArH), 7.72 (t, J
= 4.7 Hz, 1 H, ArH), 7.61 (s, 1 H, ArH), 7.56 (d, J = 7.7 Hz, 1 H,
ArH), 7.46–7.45 (m, 2 H, ArH), 7.35 (dd, J = 8.4, J = 1.6 Hz, 1
H, ArH), 7.31–7.30 (m, 3 H, ArH), 7.18–7.07 (m, 5 H, ArH), 5.12
(s, 2 H, CH2N), 4.84 (d, J = 5.0 Hz, 2 H, CH2NH), 4.35 (br. s, 1
H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ = 154.1, 142.2,
135.9, 135.3, 134.9, 133.2, 132.7, 129.1, 128.3, 128.1, 127.7, 127.6,
126.4, 126.1, 125.9, 125.8, 125.7, 121.5, 119.9, 116.7, 107.3, 47.4,
45.6 ppm. HRMS-EI (70 eV): m/z calcd. for C25H22N3 [M + H]+
364.1814; found 364.1811.
N-(4-Methoxybenzyl)-1-benzyl-1H-benzo[d]imidazol-2-amine (5ab):
M.p. 150–151 °C. 1H NMR (500 MHz, CDCl3): δ = 7.55 (d, J =
7.8 Hz, 1 H, ArH), 7.33–7.28 (m, 3 H, ArH), 7.17–7.15 (m, 3 H,
ArH), 7.14–7.11 (m, 2 H, ArH), 7.09–7.04 (m, 2 H, ArH), 6.81 (dt,
J = 8.8, J = 2.6 Hz, 2 H, ArH), 5.09 (s, 2 H, CH2N), 4.61 (d, J =
5.4 Hz, 2 H, CH2NH), 4.17 (br. s, 1 H, NH), 3.78 (s, 3 H, OCH3)
ppm. 13C NMR (125 MHz, CDCl3): δ = 159.0, 154.1, 142.2, 135.4,
134.8, 130.6, 129.1, 128.9, 128.0, 126.4, 121.4, 119.8, 116.6, 114.0,
107.3, 55.2, 46.9, 45.6 ppm. HRMS-EI (70 eV): m/z calcd. for
C22H21N3O [M + H]+ 344.1763; found 344.1751.
1-Benzyl-N-butyl-1H-benzo[d]imidazol-2-amine (5ag): M.p. 86–
1
88 °C. H NMR (500 MHz, CDCl3): δ = 7.53 (d, J = 7.9 Hz, 1 H,
ArH), 7.36–7.31 (m, 3 H, ArH), 7.16 (d, J = 7.0 Hz, 2 H, ArH),
7.13 (t, J = 7.4 Hz, 1 H, ArH), 7.08–7.02 (m, 2 H, ArH), 5.08 (s,
2 H, CH2Ph), 3.89 (br. s, 1 H, NH), 3.48 (q, J = 6.6 Hz, 2 H,
CH2N), 1.54 (quint, J = 7.4 Hz, 2 H, CH2), 1.28 (sext, J = 7.4 Hz, 2
H, CH2), 0.87 (t, J = 7.3 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 154.4, 142.3, 135.4, 134.8, 129.1, 128.1, 126.4, 121.3,
119.6, 116.4, 107.1, 45.6, 43.1, 31.7, 19.8, 13.7 ppm. HRMS-EI
(70 eV): m/z calcd. for C18H22N3 [M + H]+ 280.1814; found
280.1807.
N-(4-Methylbenzyl)-1-benzyl-1H-benzo[d]imidazol-2-amine (5ac):
M.p. 123–124 °C. 1H NMR (500 MHz, CDCl3): δ = 7.55 (d, J =
7.8 Hz, 1 H, ArH), 7.31–7.30 (m, 3 H, ArH), 7.17–7.05 (m, 9 H,
ArH), 5.10 (s, 2 H, CH2N), 4.64 (d, J = 4.1 Hz, 2 H, CH2NH),
4.29 (br. s, 1 H, NH), 2.31 (s, 3 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 154.1, 142.1, 137.2, 135.4, 135.3, 134.8, 129.3, 129.2,
128.1, 127.6, 126.5, 121.5, 119.9, 116.7, 107.3, 47.2, 45.7, 21.0 ppm.
HRMS-EI (70 eV): m/z calcd. for C22H22N3 [M + H]+ 328.1814;
found 328.1806.
1-Benzyl-N-octyl-1H-benzo[d]imidazol-2-amine (5ah): M.p. 82–
N-(4-Bromobenzyl)-1-benzyl-1H-benzo[d]imidazol-2-amine
(5ae):
1
83 °C. H NMR (500 MHz, CDCl3): δ = 7.53 (d, J = 7.9 Hz, 1 H,
M.p. 147–148 °C. 1H NMR (500 MHz, CDCl3): δ = 7.53 (d, J =
7.6 Hz, 1 H, ArH), 7.37 (d, J = 8.3 Hz, 1 H, ArH), 7.38–7.30 (m,
3 H, ArH), 7.18–7.13 (m, 3 H, ArH), 7.11–7.07 (m, 3 H, ArH),
5.14 (d, J = 5.1 Hz, 2 H, CH2N), 4.63 (d, J = 5.6 Hz, 2 H, CH2N),
4.46 (br. s, 1 H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ =
153.8, 141.8, 137.6, 135.3, 134.8, 131.6, 129.2, 129.1, 128.2, 126.5,
121.6, 121.2, 120.1, 116.7, 107.4, 46.6, 45.7 ppm. HRMS-EI
(70 eV): m/z calcd. for C21H19N3Br [M + H]+ 392.0762; found
392.0760.
ArH), 7.36–7.31 (m, 3 H, ArH), 7.17 (d, J = 7.2 Hz, 2 H, ArH),
7.13 (t, J = 7.4 Hz, 1 H, ArH), 7.08–7.02 (m, 2 H, ArH), 5.08 (s,
2 H, CH2N), 3.88 (br. s, 1 H, NH), 3.47 (q, J = 6.6 Hz, 2 H,
CH2NH), 1.55 (quint, J = 7.0 Hz, 2 H, CH2), 1.29–1.23 (m, 10 H,
5 CH2), 0.87 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 154.4, 142.3, 135.5, 134.8, 129.1, 128.1, 126.5, 121.3,
119.6, 116.5, 107.1, 45.7, 43.4, 31.7, 29.6, 29.2, 29.1, 26.7, 22.6,
14.0 ppm. HRMS-EI (70 eV): m/z calcd. for C22H30N3 [M + H]+
336.2440; found 336.2439.
N-(4-Chlorobenzyl)-1-benzyl-1H-benzo[d]imidazol-2-amine (5am):
M.p. 130–132 °C. 1H NMR (500 MHz, CDCl3): δ = 7.52 (d, J =
7.8 Hz, 1 H, ArH), 7.32–7.30 (m, 3 H, ArH), 7.21 (d, J = 8.5 Hz,
2 H, ArH), 7.17–7.06 (m, 7 H, ArH), 5.12 (s, 2 H, CH2N), 4.62 (d,
J = 4.9 Hz, 2 H, CH2NH), 4.43 (br. s, 1 H, NH) ppm. 13C NMR
(125 MHz, CDCl3): δ = 153.9, 141.9, 137.1, 135.3, 134.8, 133.1,
129.2, 128.8, 128.6, 128.1, 126.4, 121.6, 120.0, 116.6, 107.4, 46.5,
45.7 ppm. HRMS-EI (70 eV): m/z calcd. for C21H19N3Cl
[M + H]+ 348.1268; found 348.1270.
1-Benzyl-N-cyclohexyl-1H-benzo[d]imidazol-2-amine (5aj): M.p.
169–171 °C. 1H NMR (500 MHz, CDCl3): δ = 7.52 (d, J = 7.9 Hz,
1 H, ArH), 7.56–7.31 (m, 3 H, ArH), 7.17 (d, J = 7.2 Hz, 2 H,
ArH), 7.12 (d, J = 7.5 Hz, 1 H, ArH), 7.07–7.00 (m, 2 H, ArH),
5.07 (s, 2 H, CH2N), 3.95–3.88 (m, 1 H, CH), 3.78 (d, J = 7.8 Hz,
1 H, NH), 2.03–2.01 (m, 2 H, CH2), 1.62–1.56 (m, 3 H, CH2 and
CH), 1.44–1.36 (m, 2 H, CH2), 1.18–1.06 (m, 3 H, CH2 and CH)
ppm. 13C NMR (125 MHz, CDCl3): δ = 153.7, 142.5, 135.5, 134.7,
129.1, 128.1, 126.5, 121.3, 119.4, 116.4, 107.0, 51.3, 45.6, 33.5, 25.6,
24.5 ppm. HRMS-EI (70 eV): m/z calcd. for C20H24N3 [M + H]+
3061970; found 306.1972.
N-(2,4-Dichlorobenzyl)-1-benzyl-1H-benzo[d]imidazol-2-amine
(5an): M.p. 101–103 °C. 1H NMR (500 MHz, CDCl3): δ = 7.51 (d,
6
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Job/Unit: O20698
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Date: 31-07-12 15:57:25
Pages: 9
N-Alkylation of 2-Aminoimidazoles with Alcohols
N,1-Dibenzyl-4,5-diphenyl-1H-imidazol-2-amine (5ba): M.p. 129–
130 °C. 1H NMR (500 MHz, CDCl3): δ = 7.52 (d, J = 7.6 Hz, 2
H, ArH), 7.34–7.18 (m, 15 H, ArH), 7.11 (d, J = 7.3 Hz, 1 H,
H, ArH), 7.42 (d, J = 7.6 Hz, 2 H, ArH), 7.37 (t, J = 7.4 Hz, 2 H,
ArH), 7.31 (t, J = 7.2 Hz, 1 H, ArH), 7.13 (t, J = 7.1 Hz, 1 H,
ArH), 7.10–7.05 (m, 2 H, ArH), 4.76 (d, J = 5.5 Hz, 2 H, CH2NH),
ArH), 7.07 (d, J = 7.3 Hz, 2 H, ArH), 4.79 (s, 2 H, CH2N), 4.62 4.33 (br. s, 1 H, NH), 3.87 (t, J = 7.2 Hz, 2 H, CH2N), 1.72 (quint,
(d, J = 5.7 Hz, 2 H, CH2NH), 3.61 (br. s, 1 H, NH) ppm. 13C
NMR (125 MHz, CDCl3): δ = 149.5, 139.4, 136.4, 135.1, 133.6,
131.3, 131.0, 129.1, 128.9, 128.4, 128.1, 128.0, 127.8, 127.7, 127.2,
126.6, 126.1, 125.8, 125.1, 47.9, 45.9 ppm. HRMS-EI (70 eV): m/z
calcd. for C29H26N3 [M + H]+ 416.2127; found 416.2133.
J = 7.5 Hz, 2 H, CH2), 1.37 (sext, J = 7.5 Hz, 2 H, CH2), 0.93 (t,
J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
153.8, 142.1, 138.7, 134.5, 128.6, 127.8, 127.5, 121.0, 119.5, 116.4,
107.3, 47.5, 42.0, 31.0, 20.1, 13.6 ppm. HRMS-EI (70 eV): m/z
calcd. for C18H21N3 [M + H]+ 280.1814; found 280.1811.
Procedure for the Condensation of 1H-Benzo[d]imidazol-2-amine
with Benzaldehyde: 1a (1 mmol), benzaldehyde 6 (1 mmol), and 1-
butanol (0.4 mL) were added to an oven-dried, nitrogen-purged
20 mL Schlenk tube. The resulting mixture was then heated at
130 °C for 12 h, at which point the reaction mixture was allowed
to cool to ambient temperature. The mixture was concentrated in
vacuo, and purified by flash column chromatography with hexane/
ethyl acetate to give the corresponding product.
N-Benzylidene-1H-benzo[d]imidazol-2-amine (7):[23] M.p. 183–
184 °C (ref.[23] m.p. 201–203 °C). 1H NMR (500 MHz, [D6]-
DMSO): δ = 12.7 (br. s, 1 H, NH), 9.47 (s, 1 H, N=CHAr), 8.08
(d, J = 7.0 Hz, 2 H, ArH), 7.66–7.58 (m, 4 H, ArH), 7.45–7.42 (m,
1 H, ArH), 7.20–7.18 (m, 2 H, ArH) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 165.4, 155.7, 142.4, 135.1, 134.3, 132.8, 129.5,
129.1, 122.1, 121.9, 118.7, 111.2 ppm.
1-(4-Methylbenzyl)-N-benzyl-1H-benzo[d]imidazol-2-amine (5ca):
M.p. 135–136 °C. 1H NMR (500 MHz, CDCl3): δ = 7.54 (d, J =
7.9 Hz, 1 H, ArH), 7.30–7.24 (m, 3 H, ArH), 7.22 (d, J = 7.8 Hz,
1 H, ArH), 7.15 (t, J = 7.4 Hz, 1 H, ArH), 7.11–7.06 (m, 4 H,
ArH), 7.03 (d, J = 8.1 Hz, 2 H, ArH), 5.06 (s, 2 H, CH2N), 4.68
(d, J = 5.3 Hz, 2 H, CH2NH), 4.27 (br. s, 1 H, NH), 2.32 (s, 3 H,
CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 154.2, 142.2, 138.6,
137.9, 134.9, 132.3, 129.8, 128.5, 127.5, 127.4, 126.4, 121.4, 119.8,
116.6, 107.3, 47.4, 45.5, 21.0 ppm. HRMS-EI (70 eV): m/z calcd.
for C22H22N3 [M + H]+ 328.1814; found 328.1804.
1-(4-Fluorobenzyl)-N-benzyl-1H-benzo[d]imidazol-2-amine (5da):[20]
M.p. 150–152 °C. 1H NMR (500 MHz, CDCl3): δ = 7.54 (d, J =
7.9 Hz, 1 H, ArH), 7.30–7.24 (m, 5 H, ArH), 7.18–7.13 (m, 1 H,
ArH), 7.10 (m, 2 H, ArH), 7.07 (d, J = 4.1 Hz, 2 H, ArH), 6.99 (t,
J = 8.6 Hz, 2 H, ArH), 5.08 (s, 2 H, CH2N), 4.69 (d, J = 4.9 Hz,
2 H, CH2NH), 4.33 (br. s, 1 H, NH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 162.4 (d, JC,F = 245.7 Hz), 154.0, 142.1, 138.4, 134.7,
131.1 (d, JC,F = 11.0 Hz), 128.6, 128.1 (d, JC,F = 32.5 Hz), 127.6,
127.5, 121.5, 120.0, 116.7, 116.1 (d, JC,F = 21.7 Hz), 107.3, 47.4,
45.0 ppm. HRMS-EI (70 eV): m/z calcd. for C21H19N3 [M + H]+
314.1657; found 314.1647.
Procedure for the Reaction of
7 with 2g Catalyzed by the
[Cp*IrCl2]2/K2CO3 System: 7 (1 mmol), 1-butanol 2g (4 mmol),
[Cp*IrCl2]2 (0.002 mmol, 0.2 mol-%), and K2CO3 (0.1 mmol,
10 mol-%) were added to an oven-dried, nitrogen-purged 20 mL
Schlenk tube. The resulting mixture was then heated at 130 °C for
12 h, at which point the reaction mixture was allowed to cool to
ambient temperature. The mixture was concentrated in vacuo, and
purified by flash column chromatography with hexane/ethyl acetate
to give the corresponding product (i.e., 3aa).
1-(4-Chlorobenzyl)-N-benzyl-1H-benzo[d]imidazol-2-amine
(5ea):
M.p. 149–151 °C. 1H NMR (500 MHz, CDCl3): δ = 7.54 (d, J =
8.0 Hz, 1 H, ArH), 7.31–7.24 (m, 7 H, ArH), 7.16 (t, J = 7.1 Hz,
1 H, ArH), 7.08–7.04 (m, 4 H, ArH), 5.07 (s, 2 H, CH2N), 4.69 (d,
J = 4.3 Hz, 2 H, CH2NH), 4.29 (br. s, 1 H, NH) ppm. 13C NMR
(125 MHz, CDCl3): δ = 153.9, 142.2, 138.4, 134.6, 134.0, 133.8,
129.3, 128.6, 127.7, 127.6, 127.5, 121.7, 120.0, 116.8, 107.3, 47.5,
45.0 ppm. HRMS-EI (70 eV): m/z calcd. for C21H18ClN3
[M + H]+ 348.1268; found 348.1269.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H NMR and 13C NMR spectra for all N-alkyl-
ated products.
Acknowledgments
N-Benzyl-1-phenethyl-1H-benzo[d]imidazol-2-amine (5fa): M.p.
122–123 °C. 1H NMR (500 MHz, CDCl3): δ = 7.53 (d, J = 7.7 Hz,
1 H, ArH), 7.32–7.28 (m, 3 H, ArH), 7.21–7.14 (m, 6 H, ArH),
7.13–7.08 (m, 2 H, ArH), 7.01 (t, J = 3.5 Hz, 2 H, ArH), 4.40 (t,
J = 4.7 Hz, 2 H, CH2NH), 4.13 (t, J = 4.9 Hz, 2 H, CH2N), 3.48
(br. s, 1 H, NH), 3.04 (t, J = 6.4 Hz, 2 H, ArCH2) ppm. 13C NMR
(125 MHz, CDCl3): δ = 154.2, 142.1, 138.3, 138.2, 134.1, 129.0,
128.8, 128.5, 128.0, 127.5, 127.2, 121.4, 120.0, 116.7, 107.2, 47.6,
44.5, 35.3 ppm. HRMS-EI (70 eV): m/z calcd. for C22H22N3 [M +
H]+ 328.1814; found 328.1812.
Financial support by National Natural Science Foundation of
China (NSFC) (grant number 20902046), Natural Science Founda-
tion of Jiangsu Province (grant number BK2009384), and Scientific
Research Foundation for Returned Scholars (grant number
KZ03013), Ministry of Education of China, is greatly appreciated.
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2217; g) C. Gnaccarini, S. Peter, U. Scheffer, S. Vonhoff, S.
Klussmann, M. W. Gobel, J. Am. Chem. Soc. 2006, 128, 8063–
N-Benzyl-1-ethyl-1H-benzo[d]imidazol-2-amine (5ga): M.p. 152–
153 °C. 1H NMR (500 MHz, CDCl3): δ = 7.51 (d, J = 7.8 Hz, 1
H, ArH), 7.42 (d, J = 7.5 Hz, 2 H, ArH), 7.36 (t, J = 7.3 Hz, 2 H,
ArH), 7.31 (t, J = 7.2 Hz, 1 H, ArH), 7.13 (t, J = 7.1 Hz, 1 H,
ArH), 7.10–7.06 (m, 2 H, ArH), 4.76 (d, J = 5.0 Hz, 2 H, CH2NH),
4.37 (br. s, 1 H, NH), 3.93 (q, J = 7.3 Hz, 2 H, CH2N), 1.35 (t, J
= 7.3 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 153.5,
142.2, 138.7, 134.0, 128.7, 127.9, 127.6, 121.2, 119.6, 116.5, 107.1,
47.6, 36.8, 14.0 ppm. HRMS-EI (70 eV): m/z calcd. for C16H18N3
[M + H]+ 252.1501; found 252.1508.
N-Benzyl-1-butyl-1H-benzo[d]imidazol-2-amine (5ha): M.p. 134–
135 °C. 1H NMR (500 MHz, CDCl3): δ = 7.51 (d, J = 7.8 Hz, 1
Eur. J. Org. Chem. 0000, 0–0
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F. Li, Q. Kang, H. Shan, L. Chen, J. Xie
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8
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Job/Unit: O20698
/KAP1
Date: 31-07-12 15:57:25
Pages: 9
N-Alkylation of 2-Aminoimidazoles with Alcohols
Synthetic Methods
F. Li,* Q. Kang, H. Shan, L. Chen,
J. Xie ................................................ 1–9
Regioselective N-Alkylation of 2-Amino-
imidazoles with Alcohols to 2-(N-Alkyl-
amino)imidazoles Catalyzed by the
[Cp*IrCl2]2/K2CO3 System
The direct N-alkylation of 2-aminoimid-
azoles to give the corresponding 2-(N-
alkylamino)imidazoles was accomplished
using alcohols as alkylating agents in the
presence of a [Cp*IrCl2]2/K2CO3 system.
The iridium-catalyzed regioselective reac-
tion is simple, efficient, general, and en-
vironmentally benign.
Keywords: Synthetic methods
geneous catalysis / Iridium / Regioselec-
tivity Hydrogen transfer Nitrogen
heterocycles
/ Homo-
/
/
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