PAPER
Copper(I) Oxide Catalyzed N-Arylation of Azoles and Amines with
Arylboronic Acid at Room Temperature under Base-Free Conditions
Cu2O-Cat lyzedN-ArylationofAzolesandAmines Sreedhar,* Gopaladasu T. Venkanna, Kota Balaji Shiva Kumar, Vura Balasubrahmanyam
Bojja
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160921; E-mail: sreedharb@iict.res.in
Received 17 October 2007
Abstract: N-Arylation of azoles and amines with arylboronic acids
was efficiently carried out with heterogeneous copper(I) oxide in
methanol at room temperature under base-free conditions. The
products N-arylazoles and N-arylamines were isolated in good to
excellent yields. A variety of arylboronic acids and amines were
converted to the corresponding N-arylazoles and N-arylamines,
demonstrating the versatality of the reaction.
Key words: copper(I) oxide, N-arylimidazoles, N-arylamines, N-
arylation, heterogeneous catalyst
N-Arylated azoles and amines are found in many biologi-
cally active compounds.1,2 The standard practice for N-
arylation reactions involves nucleophilic aromatic substi-
tution 3 and traditional Ullmann reactions 4 as well as the
coupling of imidazoles with aryllead, arylbismuth, aryl-
borane, and arylsilane reagantes.5
Previously the Chan and Lam group have developed an
efficient method for coupling of azoles and arylboronic
acids for the synthesis of N-arylated azoles using stoichio-
metric Cu(OAc)2 and pyridine as base.6 Later, Collman
and co-workers has demonstrated the use of diamine cop-
per complex for the coupling of arylboronic acid with im-
idazole in dichloromethane and water at room
temperature.7 Very recently, Xie and co-workers have
shown simple copper salt catalyzed coupling of imida-
zoles with arylboronic acids in protic solvent under reflux
condition without any base.8 Thus, the development of
mild and cost effective catalytic procedures for N-aryla-
tion of imidazoles and amines still remains an active re-
search area.9
Heterogeneous catalysis is particularly attractive as it al-
lows production and ready separation of large quantities
B(OH)2
HN-azoles
R1
Cu2O
R2NH2 MeOH
r.t., air
Scheme 1 N-Arylation of azoles and amine catalyzed by Cu2O
SYNTHESIS 2008, No. 5, pp 0795–0799xx. 208
Advanced online publication: 18.02.2008
DOI: 10.1055/s-2008-1032184; Art ID: P12007SS
© Georg Thieme Verlag Stuttgart · New York
795
of products with the use of a small amount of catalyst. Re-
cently, we reported the preparation of recyclable hetero-
geneous Cu-exchanged fluoroapatite and tert-
butoxyapatite catalysts, by incorporating basic species
F–/t-BuO– in apatite in situ by co-precipitation and subse-
quent exchange with Cu(II) for N-arylation of imidazoles
and other heterocycles with chloroarenes and fluoroarenes
(EW) with good to excellent yields for the first time.10a
We also explored bromo and iodoarenes for such cou-
pling.10b
Thus, in continuation of our work on N-arylation, we
herein report mild and efficient N-arylation of azoles such
as imidazole, substituted imidazole, pyrazole, benzimida-
zole, and amines catalyzed by heterogeneous Cu2O
(Scheme1) at room temperature under base-free condi-
tions. To the best of our knowledge, N-arylation of substi-
tuted imidazole and pyrazole at room temperature has not
been explored previously. Very recently, we were the first
to report N-arylation of imidazole, benzimidazole, and
amines with arylboronic acids at room temperature under
base-free conditions using CuFAP as catalyst.10c
To identify the best catalytic system for N-arylation of im-
idazole and aniline with phenylboronic acid, a variety of
solvents were screened and it was found that the methanol
is the best solvent. A control reaction conducted under
identical conditions devoid of Cu2O gave no coupled
product despite prolong reaction time. Cu2O was recov-
ered quantitatively by simple centrifugation and reused
for four cycles with consistent activity (Table1, entry 1).
We chose a variety of structurally divergent arylboronic
acids possessing a wide range of functional groups to un-
derstand the scope and the generality of the Cu2O promot-
ed N-arylation of azoles to afford N-arylated azoles and
N-azoles
azoles = imidazole,
R1
2-methylimidazole,
pyrazole, benzimidazole
NHR2
R1
796 B. Sreedhar et al. PAPER

Table 1 N-Arylation of Imidazoles with Arylboronic Acidsa Table 2 N-Arylation of Amines with Phenylboronic Acida
Cu2O B(OH)2 H
Cu2O N R1
NH-azole + ArB(OH)2 Ar-N-azole
MeOH, r.t., air
+ R1NH2 MeOH, r.t., air
Entry Arylboronic acid NH-Azole Time Yield
(h) (%)b Entry Amines Time (h) Yield (%)b

B(OH)2 N NH2
1 4 92
c
1 N
5 95, 92
H
2a 1a 2 NH2 4 90
B(OH)2
2 1a 5 95 NH2
Me 3 5 90
2b
B(OH)2
4 NH 6 80
3 1a 6 95
MeO
2c
5 NH 6 85
B(OH)2
4 1a 5 90 O

Me
6 4 95
NH2
O2N B(OH)2
5 1a 6 85 a
Conditions: amine (1.5 mmol), arylboronic acid (1 mmol), Cu2O
(0.055 mmol), MeOH (4 mL), r.t., under air.
b
Isolated yields.
B(OH)2
6 1a 5 92
Br the results are summarized in Table1. Arylboronic acids
B(OH)2 with electron-donating groups such as p-tolylboronic ac-
7 1a 5 90 id, 4-methoxyphenylboronic acid afforded better yields
F (Table1, entries 2 and 3) than with electron-withdrawing
B(OH)2 group such as 3-nitrophenylboronic acid and 4-fluorophe-
8 1a 5 95 nylboronic acid (Table1, entries 5 and 7). 2-Bromo and 4-
Br bromophenylboronic acid react similarly to provide the
N corresponding N-arylated imidazole which shows that
9 2a 12 95
there is not much effect of ortho- and para-substitution on
Me
N
H
phenylboronic acid (Table1, entries 6 and 8). No side
1b products such as anisole or deboronation of phenylboron-
10 2b 1b 12 90 ic acid was observed in N-arylation of imidazole with
phenylboronic acid and the selectivity of 1-phenyl-1H-
11 2c 1b 12 92 imidazole is >99%. It is noteworthy to observe that when
the reaction conducted in the absence of air their was no
12 2a N 12 90
coupled product, which clearly emphasizes that the pro-
N cess is redox.
H
1c Various other azoles such as 2-methylimidazoles, pyra-
13 2b 1c 12 92 zoles, and benzimidazoles were also successfully coupled
14 2c 1c 12 94
with arylboronic acids to give N-arylated products in good
yields. Among these azoles, 2-methylimidazoles, and
N pyrazoles reacted equally good with boronic acids to af-
15 2a 15 90 ford the corresponding N-arylated products, but the reac-
N
H tions took longer when compared to imidazoles (Table1,
1d entries 9–15).
16 2b 1d 15 85 After achieving excellent results with azoles, we further
17 2c 1d 15 88 applied this catalytic system for the N-arylation of amines
a
with phenylboronic acid to afford corresponding N-ary-
Reaction conditions: azole (1.2 mmol), arylboronic acid (1 mmol), lated amines in good yields and the results are summa-
Cu2O (0.055 mmol), MeOH (4 mL), r.t, under air.
b
Isolated yields. rized in Table2.
c
Yield after fourth cycle.

Synthesis 2008, No. 5, 795–799 © Thieme Stuttgart · New York

PAPER
We chose a variety of structurally divergent amines to un-
derstand the scope and generality of N-arylation of
amines. Among the aliphatic amines tested n-butylamine
provided excellent yields of N-butylaniline in short dura-
tion of time (Table2, entry 6), whereas amines such as pi-
peridine and morpholine took long duration of time with
moderate yields (Table2, entries 4 and 5). Aromatic
amine such as aniline reacted very fast to afford diphenyl-
amine with excellent yields in short duration (Table2, en-
try 1). It was interesting to note that the formation of the
conceivable diarylated product is not observed in our con-
ditions.
In conclusion, N-arylation of imidazoles and amines was
performed using Cu2O catalyst under mild conditions.
The following features make this process attractive: (1)
base-free N-arylation, (2) the reaction is carried out at
room temperature, (3) the procedure works well with a va-
riety of azoles and amines, affording good to excellent
yields, (4) ready availability of Cu2O catalyst, and (5) re-
usability of the catalyst.
All chemicals were purchased from Aldrich and were used as re-
ceived. All solvents were of analytical grade from Merck India Pvt.
Ltd. and used as such. The 1H spectra of samples were recorded on
a Gemini 200 MHz and Bruker Avance 300 MHz spectrometer us-
ing TMS as an internal standard in CDCl3.
N-Arylation of Azoles with Arylboronic Acid at Ambient
Conditions; General Procedure
Cu2O (0.055 mmol) was added to a mixture of azole (1.2 mmol) and
arylboronic acid (1 mmol) in MeOH (3 mL) at r.t., and the mixture
was stirred for 5 h under an atmosphere of air. The progress of the
reaction was monitored by TLC and on completion of the reaction,
the mixture was centrifuged and the centrifugate was concentrated
under reduced pressure to give the crude product. The crude product
was purified by column chromatography on silica gel (hexane–
EtOAc, 70:30) to afford the N-arylated azoles.
1-Phenyl-1H-imidazole (Table 1, entry 1)
IR (film): 3424, 3117, 1600, 1509, 1304, 1253, 1110, 1058, 908,
760, 690, 659, 520 cm–1.
1
H NMR (300 MHz, CDCl3): δ = 7.83 (s, 1 H), 7.50–7.30 (m, 5 H),
7.25 (br s, 1 H), 7.18 (br s, 1 H).
C NMR (75 MHz, CDCl3): δ = 137.3, 135.7, 130.3, 129.9, 127.5,
13
121.5, 118.3.
EI-MS: m/z = 144 (100%), 117, 77, 51.
HRMS: m/z calcd for C9H8N2 (M+): 144.069; found: 144.069.
1-(4-Methylphenyl)-1H-imidazole (Table 1, entry 2)
IR (film): 3391, 3115, 2924, 1612, 1522, 1488, 1304, 1249, 1112,
1058, 964, 908, 816, 735, 661, 616, 523 cm–1.
1
H NMR (300 MHz, CDCl3): δ = 7.76 (s, 1 H), 7.24 (m, 4 H), 7.19
(br s, 1 H), 7.13 (br s, 1 H), 2.39 (s, 3 H).
C NMR (75 MHz, CDCl3): δ = 137.4, 135.5, 134.9, 130.3, 130.1,
13
121.3, 118.3, 20.9.
EI-MS: m/z = 158 (100%), 131, 104, 91, 50.
1-(4-Methoxyphenyl)-1H-imidazole (Table 1, entry 3)
IR (film): 3415, 2928, 1675, 1520, 1464, 1302, 1250, 1181, 1113,
1059, 1029, 833, 764, 661, 614, 536 cm–1.
Cu2O-Catalyzed N-Arylation of Azoles and Amines 797
1
H NMR (300 MHz, CDCl3): δ = 7.71 (s, 1 H), 7.28 (d, J = 9.0 Hz,
2 H), 7.15 (br s, 1 H), 7.11 (br s, 1 H), 6.94 (d, J = 9.0 Hz, 2 H), 3.83
(s, 3 H).
C NMR (75 MHz, CDCl3): δ = 159.0, 135.8, 130, 130.8, 123 (2
13
C), 118.5, 114.6, (2 C), 55.2.
EI-MS: m/z = 174 (100%), 159, 147, 132, 120, 77.
HRMS: m/z calcd for C10H10N2O (M+): 174.079; found: 174.078.
1-(2-Methylphenyl)-1H-imidazole (Table 1, entry 4)
1
H NMR (300 MHz, CDCl3): δ = 7.59 (br s, 1 H), 7.37–7.28 (m, 3
H), 7.23–7.20 (m, 2 H), 7.06 (br s, 1 H), 2.19 (s, 3 H).
13
C NMR (75 MHz, CDCl3): δ = 148.2, 138.4, 135.6, 130.7, 130.1,
118.4, 114.0, 111.1, 107.7.
HRMS: m/z calcd for C10H10N2 (M+): 158.084; found: 158.084.
1-(3-Nitrophenyl)-1H-imidazole (Table 1, entry 5)
1
H NMR (200 MHz, DMSO-d6): δ = 8.36 (s, 1 H), 8.24–8.02 (m, 2
H), 7.91 (d, J = 9.4 Hz, 1 H), 7.74 (t, J = 8.6 Hz, 1 H), 7.52 (br s, 1
H), 7.18 (br s, 1 H).
C NMR (75 MHz, CDCl3): δ = 149.1, 138.3, 125.5, 131.5, 131.2,
13
126.9, 122.1, 118.0, 16.2.
EI-MS: m/z = 189 (100%), 132, 116, 89, 76, 63, 50.
HRMS: m/z calcd for C9H8N3O2 (M + H+): 190.0611; found:
190.0600.
1-(4-Bromophenyl)-1H-imidazole (Table 1, entry 6)
1
H NMR (300 MHz, CDCl3): δ = 7.83 (br s, 1 H), 7.63 (m, 2 H),
7.32–7.20 (m, 4 H).
C NMR (75 MHz, CDCl3): δ = 136.3, 135.4, 132.9, 130.7, 122.9,
13
120.8, 118.0.
EI-MS: m/z = 222 (M+).
Anal. Calcd for C9H7BrN2: C, 48.46; H, 3.16; N, 12.56. Found: C,
48.41; H, 3.11; N, 12.53.
1-(4-Fluorophenyl)-1H-imidazole (Table 1, entry 7)
1
H NMR (300 MHz, CDCl3): δ = 7.79 (br s, 1 H), 7.33–7.36 (m, 2
H), 7.14–7.21 (m, 4 H).
C NMR (75 MHz, CDCl3): δ = 163.4, 160, 133.5, 130.4, 123.2 (2
13
C), 118.2, 116.5 (2 C).
EI-MS: m/z = 162 (100%), 141, 135, 129, 108, 95, 83, 71, 57.
HRMS: m/z calcd for C9H7FN2 (M+): 162.059; found: 162.059.
1-(2-Bromophenyl)-1H-imidazole (Table 1, entry 8)
1
H NMR (300 MHz, CDCl3): δ = 7.71 (d, J = 8.3 Hz, 1 H), 7.59 (br
s, 1 H), 7.47–7.26 (m, 3 H), 7.13 (br s, 1 H), 7.01 (br s, 1 H).
13
C NMR (75 MHz, CDCl3): δ = 137.1, 136.3, 133.5, 129.7, 128.9,
128.1, 127.1, 120.1, 119.5.
EI-MS: m/z = 222 (M+).
Anal. Calcd for C9H7BrN2: C, 48.46; H, 3.16; N, 12.56. Found: C,
48.42; H, 3.10; N, 12.51.
2-Methyl-1-phenyl-1H-imidazole (Table 1, entry 9)
1
H NMR (300 MHz, CDCl3): δ = 7.49–7.36 (m, 3 H), 7.30–7.26 (m,
2 H), 6.98–6.93 (m, 2 H), 3.35 (s, 3 H).
C NMR (75 MHz, CDCl3): δ = 144.0, 137.4, 128.9, 127.5, 126.9,
13
124.9, 120.6, 13.0.
Anal. Calcd for C10H10N2: C, 75.92; H, 6.37; N, 17.71. Found: C,
75.88; H, 6.31; N, 17.68.
Synthesis 2008, No. 5, 795–799 © Thieme Stuttgart · New York
798 B. Sreedhar et al. PAPER

2-Methyl-1-p-tolyl-1H-imidazole (Table 1, entry 10) C NMR (75 MHz, CDCl3): δ = 144, 142, 138, 134 (2 C), 130.5,
13
1
H NMR (300 MHz, CDCl3): δ = 7.31–7.12 (m, 5 H), 7.03 (s, 1 H), 124, 123.6, 122.8 (2 C), 120.3, 110.1 (2 C), 21.
2.42 (s, 3 H), 2.30 (s, 3 H). EI-MS: m/z = 209 (M+ + 1), 208 (M+), 192, 179, 151, 91, 65.
C NMR (75 MHz, CDCl3): δ = 138.0, 135.3, 129.7, 126.8, 125.0,
13
Anal. Calcd for C14H12N2: C, 80.74; H, 5.81; N, 13.45. Found: C,
20.7, 13.3. 80.70; H, 5.80; N, 13.40
Anal. Calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.27. Found: C,
76.67; H, 6.97; N, 16.19. 1-(4-Methoxyphenyl)-1H-benzimidazole (Table 1, entry 17)
1
H NMR (300 MHz, CDCl3): δ = 8.06 (br s, 1 H), 7.86–7.88 (m, 1
1-(4-Methoxyphenyl)-2-methyl-1H-imidazole (Table 1, entry H), 7.45–7.47(m, 1 H), 7.41 (d, J = 9.0 Hz, 2 H), 7.30–7.33 (m, 2
11) H), 7.06 (d, J = 9.0 Hz, 2 H), 3.88 (s, 3 H).
1
H NMR (300 MHz, CDCl3): δ = 7.22–7.15 (m, 2 H), 6.97–6.88 (m, EI-MS: m/z = 224 (100%), 209, 192, 181, 141, 121, 117, 82, 77, 55,
4 H), 3.84 (s, 3 H), 2.31 (s, 3 H). 47.
C NMR (75 MHz, CDCl3): δ = 144.5, 137.8, 129.3, 128.0, 127.3,
13
HRMS: m/z calcd for C14H13N2O (M + H): 225.102245; found:
125.3, 120.4, 13.4. 225.10241.
Anal. Calcd for C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found: C,
70.18; H, 6.40; N, 14.86 N-Arylation of Phenylboronic Acid with Amines; General Pro-
cedure
1-Phenyl-1H-pyrazole (Table 1, entry 12) In a typical experimental procedure, Cu2O (0.055 mmol) was added
IR (KBr): 3142, 3121, 3150, 1601, 1521, 1501, 1464, 1393, 1332, to a mixture of amine (1.5 mmol) and phenylboronic acid (1 mmol)
1253, 1198, 1120, 1074, 1046, 1036, 936, 915, 756 cm–1. in MeOH (3 mL) at r.t., and the mixture was stirred for 3 h under an
1
H NMR (300 MHz, CDCl3): δ = 7.84 (s, 1 H), 7.65 (d, J = 8.3 Hz, atmosphere of air. The progress of the reaction was monitored by
3 H), 7.23 (t, J = 8.3 Hz, 2 H), 7.20 (t, J = 7.1 Hz, 1 H), 6.37 (s, 1 TLC and on completion of the reaction, the mixture was centrifuged
H). and the centrifugate was concentrated under reduced pressure to
give the crude product. The crude product was purified by column
C NMR (75 MHz, CDCl3): δ = 141.1, 140.2, 129.4, 126.8, 126.4,
13
chromatography on silica gel (hexane–EtOAc, 20:1) to afford the
119.2, 107.6. diphenylamine.
EI-MS: m/z = 144.
Diphenylamine (Table 2, entry 1)
Anal. Calcd for C9H8N2: C, 74.98; H, 5.59; N, 19.43. Found: C, 1
H NMR (300 MHz, CDCl3): δ = 7.23–7.16 (m, 4 H), 7.02–6.97 (m,
74.96, H, 5.54; N, 19.39. 4 H), 6.89–6.82 (m, 2 H), 5.56 (br s, 1 H).
1-(4-Methylphenyl)-1H-pyrazole (Table 1, entry 13) EI-MS: m/z = 168 (100%), 96, 81, 67, 54, 45.
1
H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 2.26 Hz, 1 H,), 7.63 Anal. Calcd for C12H11N: C, 85.17; H, 6.55; N, 8.28. Found: C,
(s, 1 H), 7.53 (d, J = 8.3 Hz, 2 H), 7.19 (d, J = 8.3 Hz, 2 H), 6.37 85.13; H, 6.52; N, 8.26.
(s, 1 H), 2.33 (s, 3 H).
C NMR (75 MHz, CDCl3): δ = 140.7, 138.02, 136.1, 126.66,
13 N-Phenylbenzylamine (Table 2, entry 2)
129.93, 119.15, 107.3, 20.90.
1
H NMR (300 MHz, CDCl3): δ = 7.37–7.16 (m, 5 H), 7.27–7.20 (m,
1 H), 7.15–7.04 (m, 1 H), 6.70–6.60 (m, 1 H), 6.55 (d, J = 7.81 Hz,
EI-MS: m/z = 158 (100%). 2 H), 4.29 (s, 2 H), 3.90 (br s, 1 H).
Anal. Calcd for C10H10N2: C, 75.92; H, 6.37; N, 17.71. Found: C,
EI-MS: m/z = 183, 135, 91 (100%), 77, 55.
75.90; H, 6.33; N, 17.68.
HRMS: m/z calcd for C13H14N (M + H+): 184.1121; found:
1-(4-Methoxyphenyl)-1H-pyrazole (Table 1, entry 14) 184.1129.
1
H NMR (300 MHz, CDCl3): δ = 7.77 (d, J = 2.26 Hz, 1 H), 7.62
(s, 1 H), 7.54 (d, J = 8.3 Hz, 2 H), 6.90 (d, J = 8.3 Hz, 2 H), 6.37 (s, N-Cyclohexylaniline (Table 2, entry 3)
1 H), 3.70 (s, 3 H).
1
H NMR (300 MHz, CDCl3): δ = 7.07 (t, J = 8.3 Hz, 2 H), 6.58 (t,
J = 7.55 Hz, 1 H), 6.5 (d, J = 7.5 Hz, 2 H), 3.28–3.18 (m, 1 H),
C NMR (75 MHz, CDCl3): δ = 157.52, 140.2, 133.4, 127.31,
13
2.11–2.02 (m, 2 H), 1.82–1.71 (m, 2 H), 1.70–1.60 (m, 1 H), 1.45–
119.90, 114.46, 107.2, 55.29.
1.06 (m, 5 H).
EI-MS: m/z = 174 (100%). EI-MS: m/z = 174 (100%), 148, 132, 119, 97, 83, 71, 57.
Anal. Calcd for C10H10N2O: C, 68.95; H, 5.79; N, 16.08. Found: C, C NMR (75 MHz, CDCl3): δ = 147.3, 129.2, 116.7, 113.3, 51.6,
13
68.91; H, 5.74; N, 16.01. 33.4, 25.9, 25.0.
1-Phenyl-1H-benzimidazole (Table 2, entry 15) HRMS: m/z calcd for C12H18N (M + H+): 176.1434; found:
1
H NMR (300 MHz, CDCl3): δ = 8.09 (s, 1 H), 7.81–7.87 (m, 1 H), 176.1430.
7.43–7.60 (m, 6 H), 7.5–7.3 (m, 2 H).
N-Phenylpiperidine (Table 2, entry 4)
C NMR (75 MHz, CDCl3): δ = 144, 142.2, 136.5, 133.7, 130,
13
1
H NMR (300 MHz, CDCl3): δ = 7.25–7.18 (m, 2 H), 6.93 (d,
127.9, 124, 123.5, 122.8 (2 C), 120.6, 110.5 (2 C). J = 8.0 Hz, 2 H), 6.82–6.79 (m, 1 H), 3.13 (t, J = 8.0 Hz, 4 H),
EI MS: m/z = 194 (100%), 165, 138, 77, 50. 1.72–1.66 (m, 4 H), 1.58–1.52 (m, 2 H).
Anal. Calcd for C13H10N2: C, 80.39; H, 5.19; N, 14.42. Found: C, HRMS: m/z calcd for C11H16N (M + H+): 162.1277; found:
80.30; H, 5.12; N, 14.40. 162.1271.

1-(4-Methylphenyl)-1H-benzimidazole (Table 1, entry 16) 4-Phenylmorpholine (Table 2, entry 5)

1
H NMR (300 MHz, CDCl3): δ = 8.01 (br s, 1 H), 7.78–7.84 (m, 1 1
H NMR (300 MHz, CDCl3): δ = 7.28 (t, J = 7.20 Hz, 2 H), 6.89–
H), 7.39–7.45 (m, 1 H), 7.20–7.31 (m, 6 H), 2.42 (s, 3 H). 6.94 (m, 3 H), 3.86 (t, J = 4.47 Hz, 4 H), 3.17 (t, J = 4.47 Hz, 4 H).

Synthesis 2008, No. 5, 795–799 © Thieme Stuttgart · New York

PAPER
C NMR (75 MHz, CDCl3): δ = 155.8, 129.8, 120.3, 115.4, 67.0,
13
49.6.
HRMS: m/z calcd for C10H14NO (M + H+): 164.0997; found:
164.1001.
N-Butylaniline (Table 2, entry 6)
1
H NMR (300 MHz, CDCl3): δ = 7.10 (t, J = 7.55 Hz, 1 H), 6.61 (t,
J = 7.55 Hz, 1 H), 6.55–6.48 (m, 2 H), 3.10 (t, J = 6.79 Hz, 3 H),
1.67–1.55 (m, 2 H), 1.51–1.37 (m, 2 H), 0.97 (t, J = 7.55 Hz, 3 H).
EI-MS: m/z = 149, 119, 106 (100), 77, 51, 43.
HRMS: m/z calcd for C10H16N (M + H+): 150.1277; found:
150.1268.
Acknowledgment
K.B.S.K, G.T.V, and V.B. thank UGC and CSIR, India for their fel-
lowships.
References
(1) (a) Quan, M. L.; Lam, P. Y. S.; Han, Q.; Pinto, D. J. P.; He,
M. Y.; Li, R.; Ellis, C. D.; Clark, C. G.; Teleha, C. A.; Sun,
J. H.; Alexander, R. S.; Bai, S.; Luettgen, J. M.; Knabb, R.
M.; Wong, P. C.; Wexler, R. R. J. Med. Chem. 2005, 48,
1729. (b) Dyck, B.; Goodfellow, V. S.; Phillips, T.; Grey, J.;
Haddach, M.; Rowbottom, M.; Naeve, G. S.; Brown, B.;
Saunders, J. Bioorg. Med. Chem. Lett. 2004, 14, 1151.
(c) Smallheer, J. M.; Alexander, R. S.; Wang, J.; Wang, S.;
Nakajima, S.; Rossi, K. A.; Smallwood, A.; Barbera, F.;
Burdick, D.; Luettgen, J. M.; Knabb, R. M.; Wexler, R. R.;
Jadhav, P. K. Bioorg. Med. Chem. Lett. 2004, 14, 5263.
(d) Venkatesan, A. M.; Gu, Y.; Santos, O. D.; Abe, T.;
Agarwal, A.; Yang, Y.; Petersen, P. J.; Weiss, W. J.;
Mansour, T. S.; Nukaga, M.; Hujer, A. M.; Bonomo, R. A.;
Knox, J. R. J. Med. Chem. 2004, 47, 6556. (e) Lange, J. H.
M.; van Stuivenberg, H. H.; Coolen, H. K. A. C.; Adolfs, T.
J. P.; McCreary, A. C.; Keizer, H. G.; Wals, H. C.; Veerman,
W.; Borst, A. J. M.; de Looff, W.; Verveer, P. C.; Kruse, C.
G. J. Med. Chem. 2005, 48, 1823. (f) Barchechath, S. D.;
Tawatao, R. I.; Corr, M.; Carson, D. A.; Cottam, H. B. J.
Med. Chem. 2005, 48, 6409. (g) Mano, T.; Stevens, R. W.;
Kazuo, A.; Nakao, Y. O.; Sakakibara, M.; Okumura, T. T.;
Miyamoto, K. Bioorg. Med. Chem. 2003, 11, 3879.
(h) Mano, T.; Okumura, Y.; Sakakibara, M.; Okumura, T.;
Tamura, T.; Miyamoto, K.; Stevens, R. W. J. Med. Chem.
2004, 47, 720. (i) Roppe, J.; Smith, N. D.; Huang, D.;
Tehrani, L.; Wang, B.; Anderson, J.; Brodkin, J.; Chung, J.;
Jiang, X.; King, C.; Munoz, B.; Varney, M. A.; Prasit, P.;
Cosford, N. D. P. J. Med. Chem. 2004, 47, 4645. (j) Voets,
M.; Antes, I.; Scherer, C.; Muller-Viera, U.; Biemel, K.;
Cu2O-Catalyzed N-Arylation of Azoles and Amines 799
Barassin, C.; Marchais-Oberwinkler, S.; Hartmann, R. W. J.
Med. Chem. 2005, 48, 6632.
(2) (a) Iizuka, K.; Akahane, K.; Momose, D. I.; Nakazawa, M.;
Tanouchi, T.; Kawamura, M.; Ohyama, I.; Kajiwara, I.;
Ignchi, Y.; Okada, T.; Taniguchi, K.; Miyamoto, T.;
Hayashi, M. J. Med. Chem. 1981, 24, 1139. (b) Cozzi, P.;
Carganico, G.; Fusar, D.; Grossoni, M.; Menichincheri, M.;
Pinciroli, V.; Tonani, R.; Vaghi, F.; Salvati, P. J. Med.
Chem. 1993, 36, 2964. (c) Wolfe, J.; Marcoux, J.-F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805.
(d) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 853.
(3) (a) Gungor, T.; Fouquet, A.; Teulon, J.-M.; Prevost, D.;
Cazes, M.; Cloarec, A. J. Med. Chem. 1992, 35, 4455.
(b) Venuti, M. C.; Stephenson, R. A.; Alvarez, R.; Bruno, J.
J.; Strosberg, A. M. J. Med. Chem. 1988, 31, 2136.
(c) Ohmori, J.; Shimizu-Sasamata, M.; Okada, M.;
Sakamoto, S. J. J. Med. Chem. 1996, 39, 3971.
(4) (a) Martinez, G. R.; Walker, K. A. M.; Hirshfeld, D. R.;
Bruno, J. J.; Yang, D. S.; Maloney, P. J. J. J. Med. Chem.
1992, 35, 620. (b) Lo, Y. S.; Nolan, J. C.; Maren, T. H.;
Welstead, J. R.; Gripshover, D. F.; Shamblee, D. A. J. Med.
Chem. 1992, 35, 4790. (c) Pavik, W. J. J. W.; Connors, R.
E.; Burns, D. S.; Kurzweil, E. M. J. Med. Chem. 1993, 115,
7645.
(5) (a) Lam, P. Y. S.; Deudon, S.; Averill, K. M.; Li, R.; He, M.
Y.; Deshong, P.; Clark, C. G. J. Am. Chem. Soc. 2000, 122,
7600. (b) Elliott, G. I.; Konopelski, J. P. Org. Lett. 2000, 2,
3055. (c) Lopez-Alvarado, P.; Avendano, C.; Menendez, J.
C. J. Org. Chem. 1996, 61, 5865. (d) Lopez-Alvarado, P.;
Avendano, C.; Menendez, J. C. Tetrahedron Lett. 1992, 33,
659.
(6) (a) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.;
Winters, M. P.; Chan, D. M. T.; Combs, A. Tetrahedron
Lett. 1998, 39, 2941. (b) Combs, A. P.; Saubern, S.;
Rafalski, M.; Lam, P. Y. S. Tetrahedron Lett. 1999, 40,
1623. (c) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams,
J.; Averill, K. M.; Chan, D. M. T.; Combs, A. Synlett 2000,
674.
(7) (a) Collman, J. P.; Zhong, M.; Zeng, L.; Costanzo, S. J. Org.
Chem. 2001, 66, 1528. (b) Collman, J. P.; Zhong, M. Org.
Lett. 2000, 2, 1233.
(8) Lan, J.-B.; Chen, L.; Yu, X.-Q.; You, J.-S.; Xie, R.-G. Chem.
Commun. 2004, 188.
(9) van Berkel, S. S.; van den Hoogenband, A.; Terpstra, J. W.;
Tromp, M.; van Leeuwen, P. W. N. M.; van Strijdonck, G.
P. F. Tetrahedron Lett. 2004, 45, 7659.
(10) (a) Choudary, B. M.; Sridhar, Ch.; Kantam, M. L.;
Venkanna, G. T.; Sreedhar, B. J. Am. Chem. Soc. 2005, 127,
9948. (b) Kantam, M. L.; Venkanna, G. T.; Sridhar, Ch.;
Shiva Kumar, K. B. Tetrahedron Lett. 2006, 47, 3897.
(c) Kantam, M. L.; Venkanna, G. T.; Sridhar, C.; Sreedhar,
B.; Choudary, B. M. J. Org. Chem. 2006, 71, 9522.
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