Simple and convenient methods for N-arylation of heterocycles and diphenylamine

Article abstract of DOI:10.1055/s-0031-1290162

N-Arylation of NH-heterocycles and diphenylamine with various aryl halides, using a readily accessible ligand-free potassium tert-butoxide/iron(III) oxide/dimethyl sulfoxide reagent system, gives the corresponding N-aryl derivatives in 47-97% yields. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0031-1290162

PAPER
▌1063
pSapimer ple and Convenient Methods for N-Arylation of Heterocycles and
Diphenylamine
N-Arylation of Heterocycles
Laxhmaiah Alakonda, Mariappan Periasamy*
School of Chemistry, University of Hyderabad, Central University PO, Hyderabad 500 046, India
Fax +91(40)23012460; E-Mail: mpsc@uohyd.ernet.in
Received: 15.10.2011; Accepted after revision: 09.01.2012
pected, iodobenzene (2a) is more reactive than bromoben-
zene and gave 1-phenyl-1H-imidazole (3a) in higher
yields (entries 9 and 15).
Abstract: N-Arylation of NH-heterocycles and diphenylamine
with various aryl halides, using a readily accessible ligand-free po-
tassium tert-butoxide/iron(III) oxide/dimethyl sulfoxide reagent
system, gives the corresponding N-aryl derivatives in 47–97%
yields.
N
N
additive
Key words: iron(III) oxide, N-aryl heterocycles, N-arylimidazole,
+
Ph-I
N
N
H
1
base, solvent, temp, 24 h
triarylamines
2a
3a
Scheme 1 N-Phenylation of 1H-imidazole
The formation of C–N bonds is one of the most important
transformations; it is useful for the synthesis of compounds
of interest to pharmaceutical and material science applica-
tions. In recent years, several N-arylation methods using
N-Phenylation of 1H-Imidazolea
Table 1
various transition-metal-based catalyst systems have been
1
b
reported. Very recently, we have reported that copper Entry Additive Base
complexes containing certain diimine and bi-2-naphthol
Solvent
Temp (°C) Yield (%)
1
–
–
–
–
–
–
–
–
t-BuOK
t-BuOK
t-BuOK
K PO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
120
25
76
ligands are useful in the N-arylation of chiral diamines
2
and indole. In continuation of these studies, we have ex-
0c
2
amined convenient methods for the N-arylation of hetero-
cycles and diphenylamine for use in the synthesis of
molecules that have potential in energy harvesting and
storage devices. Herein, we wish to report the N-arylation
of NH-heterocycles and diphenylamine using the ligand-
free potassium tert-butoxide/iron(III) oxide/dimethyl
sulfoxide reagent system. Initially, we examined the use
of different reagent systems for the N-phenylation of 1H-
imidazole (1) (Scheme 1, Table 1). The simplest and most
straightforward method involves the use of potassium
tert-butoxide/dimethyl sulfoxide under ligand-free and
transition-metal-free conditions giving 1-phenyl-1H-im-
50c
trace
72
3
80
4
120
120
120
120
120
120
120
120
120
120
120
120
3
4
5
KOH
6
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
–
trace
trace
5
7
toluene
8
H O
2
9
Fe O
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
90
2
3
3
10
FeCl
3
76
idazole (3a) in 76% yield (entry 1). We observed that the
reaction does not take place at 25 °C (entry 2) and the 1-
1
1
1
1
1
2
3
4
5
FeSO4
ZnCl2
NiCl2
Fe O
37
phenyl product 3a is obtained only in 50% yield at 80 °C
19
(
entry 3). The use of potassium tert-butoxide or potassium
hydroxide as the base gave comparable yields, but tri-
potassium phosphate gave the product only in trace (<5%)
amounts (entries 1, 4, and 5). Among the solvents
screened, toluene, N,N-dimethylformamide, and water
were less effective compared to dimethyl sulfoxide (en-
tries 1 and 6–8). Experiments using various additives re-
50
0
2
3
3
81d
1
Fe O
t-BuOK
2
a
Reaction conditions: additive (10 mol%), 1H-imidazole (1, 1 mmol),
vealed that the products are obtained in higher yields iodobenzene (2a, 2 mmol), base (2 mmol), solvent (3 mL), 24 h.
b
when the transformation is carried out using iron(III) ox-
ide as an additive (entries 9–13). There is no reaction in
the absence of potassium tert-butoxide (entry 14). As ex-
Isolated yields of product 3a. The product 3a was identified by
1
13
FTIR, H and C NMR, and MS data.
c
Reaction was carried out for 48 h.
Reaction was carried out using bromobenzene.
d
SYNTHESIS 420 012, 44, 1063–1068
Advanced online publication: 02.03.2012
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8
8
1
1
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DOI: 10.1055/s-0031-1290162; Art ID: SS-2011-Z0977-OP
©
Georg Thieme Verlag Stuttgart · New York

1064
L. Alakonda, M. Periasamy
PAPER
The results revealed that the potassium tert-butoxide/di-
methyl sulfoxide reagent system is essential for this trans-
formation (entry 14). Whereas the recently reported
N
N
Fe2O3 (10 mol%)
+
Ar-X
N
N
H
t-BuOK, DMSO, 120 °C, 24 h
1
g
Ar
iron/graphite system requires a dry nitrogen atmosphere,
1
2a–g
X = Br
3a–g
the present potassium tert-butoxide/iron(III) oxide/di-
methyl sulfoxide reagent system does not require inert
conditions.
We next examined the reaction using various substituted
aryl halides 2a–g with imidazole (1) to give N-arylimid-
azoles 3a–g (Scheme 2). This methodology is equally ef-
fective for aryl halides containing either electron-
donating or -withdrawing substituents, such as in the for-
mation of 3d and 3e. In the case of 2-bromopyridine (2g)
as the coupling partner, the corresponding N-aryl product
N
N
N
N
N
N
Ph
a, 81%
3
3b (1-subst.) 39%
3b' (2-subst.) 37%
3c, 70%
MeO
N
O2N
N
N
N
3
3
g is obtained in 90% yield. Two regioisomers 3b/3b′ and
d/3d′, respectively, are obtained when 1-bromonaphtha-
3
d/3d', 71%
3
e, 76%
N
lene and 4-bromoanisole are used as aryl halide coupling
partners, indicating the intermediacy of arynes in this
N
1f
transformation. However, the pathway involving an
electron-transfer mechanism cannot be ruled out (Scheme
N
N
N
3
) considering some recent reports in this area, especially
F3C
CF3
4
when mild bases are used.
3
f, 82%
3g, 90%
The para-substituted aryl bromide and potassium tert-bu-
toxide in dimethyl sulfoxide would give an aryne interme-
diate, which could in turn react with the deprotonated
imidazole intermediate to give a mixture of regioisomers
Scheme 2 N-Arylation of 1H-imidazole with various aryl halides.
Reagents and conditions: Fe O (10 mol%), 1H-imidazole (1, 1
2
3
mmol), aryl bromide 2 (2 mmol), t-BuOK (2 mmol), DMSO (3 mL),
1
20 °C, 24 h.
3
d and 3d′ (Scheme 3, mechanism 1). In the electron-
transfer mechanism (Scheme 3, mechanism 2), the alkox-
ide would transfer an electron to the aryl halide to give the In these transformations, the aryne intermediates are
corresponding radical anion, which could then react with formed due to the highly basic nature of the potassium
the deprotonated imidazole followed by electron transfer tert-butoxide/dimethyl sulfoxide reagent system. In order
to give the corresponding N-aryl product 3d as a single re- to reduce the basic nature of potassium tert-butoxide, we
gioisomer.
carried out a set of experiments using iron(III) chloride
mechanism 1: aryne intermediate
Br
N
N
N
N
H
N
N
t-BuOK/DMSO
+
KBr + t-BuOH
OMe
OMe
OMe
OMe
2d
3d
3d'
mechanism 2: electron-transfer mechanism
N
N
+
3 4
K PO
N
H
N– K+
K2HPO4
N
N
X
N
X
N
(t-BuO)nM
(t-BuO)nM
(t-BuO)nM
(t-BuO)nM
OMe
OMe
OMe
X–
OMe
X = Br, I
3d
Scheme 3 Plausible mechanistic pathways for the N-arylation of imidazole
Synthesis 2012, 44, 1063–1068
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Arylation of Heterocycles
1065
and three equivalents of potassium tert-butoxide under the
X
N-heterocycle
conditions in which iron alkoxides are expected to form
Fe2O3 (10 mol%)
5
Y
Y
NH-heterocycle
+
(
Scheme 4, Table 2). In all these experiments, only one
t-BuOK, DMSO
regioisomer 3b was obtained albeit in low yields (entries
–3). The N-aryl products are obtained in slightly higher
yields using 4-iodoanisole (2d) as the coupling partner
120 °C, 24 h
1
2a X = I, Y = CH
b X = Br, Y = N
3
a–7a Y = CH
b Y = N
2
4
N
(
entries 4 and 5). Presumably, this transformation goes
N
N
through an electron-transfer mechanism under these con-
ditions (Scheme 3, mechanism 2).
N
N
N
N
Ph
Ph
Br
N
N
3a, 90%
4a, 71%
4b, 97%
N
N
N
2b
N
N
FeCl3, t-BuOK, DMSO
20 °C, 36 h
N
3b
N
H
I
Ph
Ph
Ph
1
5
a, 79%
6a, 58%
7a, 64%
MeO
N
1
N
OMe
Scheme 5 N-Phenylation of various NH-heterocycles. Reagents
and conditions: Fe (10 mol%), NH-heterocycle (1 mmol), aryl
halide 2a or 2b (2 mmol), t-BuOK (2 mmol), DMSO (3 mL), 120 °C,
4 h.
2d
3
d
O
2 3
Scheme 4 N-Arylation using the iron(III) chloride/potassium tert-
2
butoxide reagent system
Table 2 Effect of Iron(III) Chloride/Potassium tert-Butoxide Com-
a
bination
MeCN
N
N
+
Br
N
N
b
0–25 °C, 24 h
Entry Ar-X FeCl
t-BuOK
K PO
4
Product Yield
(%)
–Br
3
3
(
mmol)
(mmol)
(mmol)
8
3
a
9, 70%
1
2
3
4
2b
2b
2b
2d
2d
1
3
–
3b
3b
3b
3d
3d
4
NaBF4, acetone
5 °C, 6 h
N
N
0.1
1
0.3
3
1.5
1.5
1.5
1.5
10
11
37
35
2
–BF4
1
0, 96%
0.1
1
0.3
3
Scheme 6 Synthesis of 3-butyl-1-phenyl-1H-imidazol-3-ium tetra-
fluoroborate (10)
5
a
Reaction conditions: 1H-imidazole (1, 1 mmol), aryl halide (2
We then turned our attention towards the use of the potas-
sium tert-butoxide/iron(III) oxide/dimethyl sulfoxide cat-
alyst system for the N-arylation of diphenylamine (11) to
obtain the corresponding triarylamine derivatives since
mmol), K PO (1.5 mmol), DMSO (5 mL), 120 °C, 36 h.
3
4
b
Isolated yields.
We next examined the use of the potassium tert-butox- such a methodology has potential for exploitation in the
ide/iron(III) oxide/dimethyl sulfoxide reagent system for synthesis of optoelectronic materials. We performed the
the N-phenylation of various NH-heterocycles such as N-arylation of diphenylamine (11) with various aryl bro-
benzimidazole, pyrrole, indole, and benzotriazole. The mides at 130 °C to give various aryldiphenylamines 12a–e
corresponding N-phenyl products 4a–7a were obtained in (Scheme 7). It was observed that the aryl halides contain-
moderate to excellent yields (Scheme 5).
ing electron-donating substituents gave the products in
higher yields compared to the derivatives containing elec-
tron-withdrawing groups, compare the formation of 12c
and 12d with 12e. Again, two regioisomers 12b/12b′,
12c/12c′, and 12d/12d′ are obtained in reactions using
some substituted aryl halides indicating the involvement
of aryne intermediates in this transformation (Scheme 3).
1
-Phenyl-1H-imidazole 3a is readily converted into the
ionic liquid 3-butyl-1-phenyl-1H-imidazol-3-ium tetra-
fluoroborate (10) following a procedure reported for the
6
preparation of N,N′-dialkyl ionic liquids (Scheme 6).
This observation illustrates the synthetic potential of the
N-arylation methodology to access a series of ionic liq-
uids that have proven applications in electricity storage Previously, N-arylation of arylamines was carried out by
7
8
devices.
using palladium and copper catalyst systems under a dry
nitrogen atmosphere. The method described here involves
a simple and inexpensive ligand-free potassium tert-but-
oxide/dimethyl sulfoxide reagent system promoted by
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1063–1068

1066
L. Alakonda, M. Periasamy
PAPER
Ph
Ph
LC-MS (EI): m/z = 143 (M – 1).
Ph
Br
Fe2O3 (10 mol%)
NH
N
+
t-BuOK, DMSO, 130 °C, 36 h
1-Naphthalen-1-yl-1H-imidazole (3b)
Yellow solid; yield: 76 mg (39%); mp 58–60 °C (Lit. 62 °C).
FTIR (KBr): 3109, 3055, 1595, 1489, 1304, 802, 661 cm .
Ph
R
9
R
11
12a–e
–
1
Ph
1
H NMR (400 MHz, CDCl ): δ = 7.27–7.31 (m, 2 H), 7.46–7.63 (m,
N
Ph
Me
3
Ph
5
H), 7.77 (s, 1 H), 7.95–7.97 (m, 2 H).
Ph
N
N
13
C NMR (100 MHz, CDCl ): δ = 121.7, 122.3, 123.7, 125.2, 126.9,
Ph
3
Ph
2a, 83%
1
27.6, 128.3, 129.2, 129.5, 134.1, 138.4.
1
12b (1-subst.)
1
7
12c (p-subst.)
12c' (m-subst.)
84%, ratio 56:44
2b' (2-subst.)
6%, ratio 60:40
LC-MS (EI): m/z = 193 (M – 1).
1
-Naphthalen-2-yl-1H-imidazole (3b′)
1
0
NO2
Yellow solid; yield: 72 mg (37%); mp 122–124 °C (Lit. 122–123
OMe
°C).
Ph
Ph
–
1
N
N
FTIR (KBr): 3094, 1631, 1493, 1307, 1057, 814, 657 cm .
Ph
Ph
1
H NMR (400 MHz, CDCl ): δ = 7.27 (s, 1 H), 7.41 (s, 1 H), 7.53–
3
1
2e, 47%
7.60 (m, 3 H), 7.83–7.98 (m, 5 H).
1
1
7
2d (p-subst.)
2d' (m-subst.)
13
C NMR (100 MHz, CDCl ): δ = 118.5, 119.1, 120.3, 126.5, 127.4,
2%, ratio 61:39
3
1
27.9, 130.1, 130.6, 132.2, 133.5, 134.7, 135.8.
Scheme 7 N-Arylation of diphenylamine with various aryl bro-
mide. Reagents and conditions: Fe O (10 mol%), Ph NH (11, 1
LC-MS (EI): m/z = 193 (M – 1).
2
3
2
mmol), aryl bromide (2 mmol), t-BuOK (2 mmol), DMSO (3 mL),
1-Anthracen-9-yl-1H-imidazole (3c)
1
1
Yellow solid; yield: 86 mg (70%); mp 154–156 °C (Lit. 154–156
1
30 °C, 36 h.
°C).
–
1
FTIR (KBr): 3094, 1626, 1493, 1307, 1059, 733, 659 cm .
iron(III) oxide, which does not require a dry nitrogen at-
mosphere. Accordingly, the methods described here are
1
H NMR (400 MHz, CDCl ): δ = 7.28 (s, 1 H), 7.45–7.54 (m, 7 H),
3
expected to be useful in the synthesis of derivatives which 7.79 (s, 1 H), 8.08–8.1 (m, 2 H), 8.61 (s, 1 H).
1
3
have potential for applications in the synthesis of organic
optoelectronics and electricity storage materials.
C NMR (100 MHz, CDCl ): δ = 122.4, 122.7, 125.9, 127.6, 128.4,
3
128.5, 128.8, 129.7, 131.2, 139.6.
LC-MS (EI): m/z = 245 (M + 1).
t-BuOK (Spectrochem, India), Fe O (J. T. Baker Chemical Co.)
2
3
1-(4-Methoxyphenyl)-1H-imidazole (3d + 3d)
and all solvents (Merck) were used as such without any further pu-
rification. Melting points were determined using a Superfit capillary
point apparatus and are uncorrected. IR (KBr) spectra were record-
ed on Jasco-FT-IR model 5300 spectrophotometer with polystyrene
1
Yellow oil; yield: 123 mg (71%; 83:17 ratio by H NMR). Product
3
d was isolated in pure form (89 mg, 51%).
–
1
FTIR (neat): 3117, 2941, 2839, 1608, 15206, 1249, 831 cm .
1
13
1
as reference. H (400 MHz) and C (100 MHz) spectra were record-
H NMR (400 MHz, CDCl ): δ = 3.86 (s, 3 H), 6.97–7.03 (m, 2 H),
3
ed in CDCl on Bruker Avance 400 spectrometer using TMS as in-
7.20–7.21 (m, 2 H), 7.23–7.35 (m, 2 H), 7.82 (s, 1 H).
3
ternal standard. TLC analysis: silica gel coated plates, hexane–
13
C NMR (100 MHz, CDCl ): δ = 55.6, 109.1, 112.4, 115.0, 123.3,
3
EtOAc mixture, developed in an I chamber; column chromatogra-
2
1
29.8, 130.6, 135.8, 158.9.
phy: gravity and flash, column grade silica gel (100–200 and 230–
LC-MS (EI): m/z = 174 (M + 1).
400 mesh).
1
-(4-Nitrophenyl)-1H-imidazole (3e)
1
-Phenyl-1H-imidazole (3a); Typical Procedure for 3a–g and
1
2
Yellow solid; yield: 143 mg (76%); mp 202–204 °C (Lit. 204.4–
3a–7a
To a 25-mL, round-bottom flask with side arm, containing magnetic
stirring bar equipped with an air condenser (without water circula-
tion), were added Fe O (16 mg, 10 mol%), imidazole (1, 68 mg, 1
205.2 °C).
–1
FTIR (KBr): 2926, 1599, 1510, 1338, 1051, 848, 648 cm .
2
3
1
H NMR (400 MHz, CDCl ): δ = 7.27–7.28 (m, 1 H), 7.38 (s, 1 H),
mmol), t-BuOK (224 mg, 2 mmol), DMSO (3 mL), and iodoben-
zene (2a, 408 mg, 2 mmol) in an open atmosphere. The contents
were stirred for 24 h at 120 °C and allowed to cool to 25 °C. The
3
7
.58–7.60 (m, 2 H), 7.99 (s, 1 H), 8.37–8.40 (m, 2 H).
13
C NMR (100 MHz, CDCl ): δ = 117.6, 121.1, 125.8, 131.7, 135.4,
3
mixture was diluted with EtOAc (5 mL) and H O (5 mL) and stir-
142.0, 146.3.
LC-MS (EI): m/z = 189 (M – 1).
2
ring was continued for a further 10 min. The organic layer was sep-
arated and the aqueous layer was extracted with EtOAc (3 × 10 mL).
The combined organic extracts were washed with H O and brine
2
1-[3,5-Bis(trifluoromethyl)phenyl]-1H-imidazole (3f)
White solid; yield: 229 mg (82%); mp 92–94 °C (Lit. 93–95 °C).
soln and dried (anhyd Na SO ). The solvent was evaporated and the
13
2
4
residue was purified by column chromatography (silica gel 100–
–
1
FTIR (KBr): 3113, 3049, 1626, 1508, 1248, 1124, 1060, 887 cm .
2
00 mesh, EtOAc–hexanes, 1:1) to give 3a as a yellow oil; yield:
1
1
29 mg (90%).
H NMR (400 MHz, CDCl ): δ = 7.30–7.31 (m, 1 H), 7.38–7.39 (m,
3
–
1
1 H), 7.88–7.97 (m, 3 H), 8.23 (s, 1 H).
FTIR (neat): 3113, 1956, 1873, 1674, 1601, 1512, 1249 cm .
13
1
C NMR (100 MHz, CDCl
): δ = 117.9, 120.9–121.4 (quart.),
3
H NMR (400 MHz, CDCl ): δ = 7.22 (s, 1 H), 7.29–7.30 (m, 1 H),
3
1
23.9, 126.6, 133.2–134.2 (quart.), 133.8, 134.2, 135.4, 138.6.
7
.37–7.41 (m, 3 H), 7.47–7.51 (m, 2 H), 7.87 (s, 1 H).
13
LC-MS (EI): m/z = 279 (M – 1).
C NMR (100 MHz, CDCl ): δ = 118.2, 121.5, 127.5, 129.9, 130.4,
3
135.6, 137.4.
2
-(1H-Imidazol-1-yl)pyridine (3g)
Light-yellow oil; yield: 130 mg (90%).
Synthesis 2012, 44, 1063–1068
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Arylation of Heterocycles
1067
–
1
FTIR (neat): 3117, 2592, 1670, 1597, 1304, 1055, 904 cm .
due was washed with hexane and dried under high vacuum to obtain
the desired product 9 as a brown oil; yield: 196 mg (70%). This ma-
terial was used in the next step without further purification of the
product.
3-Butyl-1-phenyl-1H-imidazol-3-ium Tetrafluoroborate (10)6a
In a 25-mL round bottom flask, to a stirred soln of bromide salt 9
1
H NMR (400 MHz, CDCl ): δ = 7.21–7.29 (m, 2 H), 7.36–7.38 (m,
3
1
H), 7.65–7.66 (m, 1 H), 7.81–7.86 (m, 2 H), 8.36 (d, 1 H).
1
3
C NMR (100 MHz, CDCl ): δ = 112.3, 116.1, 121.9, 130.7, 134.9,
3
138.9, 149.1.
LC-MS (EI): m/z = 146 (M + 1).
(
281 mg, 1 mmol) in acetone (10 mL) at 25 °C, was added NaBF
4
(
130.8 mg, 1.2 mmol). The contents were stirred for a further 6 h.
1-Phenyl-1H-benzimidazole (4a)
13
The mixture was filtered through Büchner funnel and the solvent
was evaporated. The residue was diluted with CH Cl (20 mL), fol-
Yellow solid; yield: 137 mg (71%); mp 94–96 °C (Lit. 96–98 °C).
–
1
2
2
FTIR (KBr): 3117, 2592, 1670, 1597, 1304, 1055, 904 cm .
lowed by filtration and concentration of the solvent. The residue
was washed with hexane and dried under high vacuum to give the
desired product 10 as a brown oil; yield: 277 mg (96%).
1
H NMR (400 MHz, CDCl ): δ = 7.32–7.35 (m, 2 H), 7.47–7.60 (m,
3
6
H), 7.88–7.90 (m, 1 H), 8.13 (s, 1 H).
1
3
–1
C NMR (100 MHz, CDCl ): δ = 110.5, 120.6, 122.8, 123.7, 124.1,
FTIR (neat): 3157, 2876, 1746, 1599, 1203, 763 cm .
3
127.8, 130.1, 133.7, 136.3, 142.3, 144.1.
1
H NMR (400 MHz, CDCl ): δ = 0.90–0.94 (m, 3 H), 1.34–1.39 (m,
3
LC-MS (EI): m/z = 195 (M + 1).
2 H), 1.85–1.93 (m, 2 H), 4.32–4.36 (t, 2 H), 7.36–7.52 (m, 4 H),
7
.60–7.69 (m, 3 H), 9.36 (s, 1 H).
1-Pyridin-2-yl-1H-benzimidazole (4b)
13
14
C NMR (100 MHz, CDCl ): δ = 13.3, 19.4, 32.0, 50.2, 121.3,
Yellow solid; yield: 189 mg (97%); mp 54–56 °C (Lit. 59–60 °C).
3
1
21.5, 123.4, 129.9, 130.3, 130.5, 134.38.
–1
FTIR (neat): 1589, 1473, 1371, 1143, 887, 744 cm .
11
B NMR (128.3 MHz, CDCl ): δ = –0.90
3
1
H NMR (400 MHz, CDCl ): δ = 7.24–7.27 (m, 1 H), 7.32–7.38 (m,
3
2
H), 7.52–7.54 (d, 1 H), 7.84–7.87 (m, 2 H), 8.03–8.05 (d, 1 H),
Triphenylamine (12a); Typical Procedure for 12a–e
8
.56–8.58 (s, 2 H).
To a 25-mL, round-bottom flask with side arm, containing magnetic
stirring bar equipped with an air condenser (without water circula-
tion) were added Fe O (16 mg, 10 mol%), Ph NH (11, 169 mg, 1
13
C NMR (100 MHz, CDCl ): δ = 112.6, 114.3, 120.6, 121.8, 123.3,
3
2
3
2
1
24.2, 132.1, 138.9, 141.3, 144.6, 149.4, 149.8.
mmol), t-BuOK (224 mg, 2 mmol), DMSO (3 mL), and iodoben-
zene (408 mg, 2 mmol). The contents were stirred for 36 h at 130 °C
and allowed to cool to 25 °C. The mixture was diluted with EtOAc
LC-MS (EI): m/z = 195 (M + 1).
1-Phenyl-1H-benzotriazole (5a)
(
5 mL) and H O (5 mL) and stirring was continued for a further 10
2
3
a
White solid; yield: 155 mg (79%); mp 84–86 °C (Lit. 85–87 °C).
min. The organic layer was separated and the aqueous layer was ex-
tracted with EtOAc (3 × 10 mL). The combined organic extracts
–
1
FTIR (KBr): 3055, 1595, 1500, 1275, 1057, 572 cm .
1
were washed with H O and brine and dried (anhyd Na SO ). The
2 2 4
H NMR (400 MHz, CDCl ): δ = 7.29–7.47 (m, 1 H), 7.48–7.57 (m,
3
solvent was evaporated and the residue was purified by column
chromatography (silica gel 100–200 mesh, pure hexanes) to obtain
the desired product as a colorless solid; yield: 203 mg (83%) (with
bromobenzene) and 220mg (90%) (with iodobenzene); mp 124–126
2
H), 7.59–7.62 (m, 2 H), 776–7.88 (m, 3 H), 8.16–8.18 (m, 1 H).
13
C NMR (100 MHz, CDCl ): δ = 110.4, 120.3, 122.9, 124.4, 128.3,
3
128.7, 129.9, 132.3, 137.0, 146.5.
3
a
LC-MS (EI): m/z = 196 (M + 1).
°C (Lit. 126–128 °C).
–
1
FTIR (KBr): 1583, 1489, 1329, 1277, 748, 692 cm .
1-Phenyl-1H-pyrrole (6a)
1
5
1
White solid; yield: 82 mg (58%); mp 58–60 °C (Lit. 58–60 °C).
H NMR (400 MHz, CDCl ): δ = 6.98–7.03 (m, 3 H), 7.09–7.11 (d,
3
–
1
6 H), 7.23–7.27 (m, 6 H).
FTIR (KBr): 3138, 2928, 1510, 1253, 1022, 607 cm .
13
1
C NMR (100 MHz, CDCl ): δ = 122.6, 124.2, 129.2, 147.8.
3
H NMR (400 MHz, CDCl ): δ = 6.38–6.39 (m, 2 H), 7.12–7.13 (m,
3
2
H), 7.25–7.31 (m, 1 H), 7.36–7.47 (m, 4 H).
LC-MS (EI): m/z = 246 (M + 1).
1
3
C NMR (100 MHz, CDCl ): δ = 110.4, 119.3, 120.5, 125.6, 129.5,
3
Naphthalen-1-yldiphenylamine (12b) and Naphthalen-2-yldi-
phenylamine (12b′)
140.8.
Colorless solid; yield: 224 mg (76%); regioisomeric ratio was cal-
LC-MS (EI): m/z = 143 (M + 1).
1
culated based on H NMR of 7.08–7.17 and 7.21–7.27; all spectral
1
-Phenyl-1H-indole (7a)
data are for a mixture of regioisomers in 60:40 ratio.
FTIR (KBr): 3057, 1626, 1589, 1493, 1273, 750, 696 cm .
Yellow oil; yield: 124 mg (64%).
–
1
–1
FTIR (neat): 3055, 1888, 1597, 1331, 1014, 740 cm .
1
H NMR (400 MHz, CDCl ): δ = 6.95–7.75.
3
1
H NMR (400 MHz, CDCl ): δ = 6.77 (d, 1 H), 7.24–7.33 (m, 2 H),
3
13
C NMR (100 MHz, CDCl ): δ = 120.3, 120.5, 121.3, 121.7, 121.9,
3
7
.39–7.46 (m, 2 H), 7.56–7.59 (m, 4 H), 7.65–7.67 (d, 1 H), 7.77–
1
22.9, 124.4, 126.3, 126.4, 126.9, 127.3, 127.6, 128.4, 128.9, 129.1,
7
.79 (d, 1 H).
1
29.2, 129.3, 130.1, 134.5, 145.5, 147.8, 148.5, 149.1.
13
C NMR (100 MHz, CDCl ): δ = 103.6, 110.5, 120.4, 121.2, 122.4,
3
LC-MS (EI): m/z = 296 (M + 1).
1
26.5, 128.0, 129.4, 129.7, 135.9, 139.9.
LC-MS (EI): m/z = 194 (M + 1).
Diphenyl(p-tolyl)amine (12c) and Diphenyl(m-tolyl)amine
(
12c′)
3
-Butyl-1-phenyl-1H-imidazol-3-ium Bromide (9)
Colorless solid; yield: 217 mg (84%);regioisomeric ratio was calcu-
6
a
1
A slight modification to a literature procedure was followed. To a
stirred soln of 1-phenyl-1H-imidazole (3a, 144 mg, 1 mmol) and
MeCN (5 mL) in a 25-mL, round-bottom flask with side arm, was
added BuBr (411 mg, 3 mmol) dropwise at 0 °C. The contents were
slowly brought to 25 °C and stirring was continued for a further 24
h. The solvent was evaporated under reduced pressure and the resi-
lated based on H NMR analysis of CH δ = 2.28 and 2.34 ppm; all
3
spectral data are for a mixture of regioisomers in 56:44 ratio.
–1
FTIR (KBr): 3028, 2916, 1593, 1504, 1284, 1024, 754, 694 cm .
1
H NMR (400 MHz, CDCl ): δ = 2.28 (s, 3 H), 2.34 (s, 3 H), 6.85–
3
7
.04 (m, 9 H), 7.09–7.18 (m, 11 H), 7.22–7.28 (m, 8 H).
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1063–1068

1068
L. Alakonda, M. Periasamy
PAPER
1
3
C NMR (100 MHz, CDCl ): δ = 20.8, 21.6, 121.6, 122.2, 122.5,
639. (c) Surry, D. S.; Buchwald, S. L. Angew. Chem. Int. Ed.
2008, 47, 6338. (d) For iron-catalyzed N-arylation of NH-
heterocycles: Xia, N.; Oualli, A. Angew. Chem. Int. Ed.
3
1
23.6, 124.1, 124.9, 132.7, 139.1, 145.3, 147.8, 147.9, 148.1.
LC-MS (EI): m/z = 260 (M + 1).
2
007, 46, 934. (e) See also: Correa, A.; Bolm, C. Angew.
(
4-Methoxyphenyl)diphenylamine (12d) and (3-Methoxylphe-
Chem. Int. Ed. 2007, 46, 8862. (f) See also: Guo, D.; Huang,
H.; Xu, J.; Jiang, H.; Liu, H. Org. Lett. 2008, 10, 4513.
(g) See also: Swapna, K.; Kumar, A. V.; Reddy, V. P.; Rao,
K. R. J. Org. Chem. 2009, 74, 7514.
nyl)diphenylamine (12d′)
Colorless solid; yield: 200 mg (72%); regioisomeric ratio was cal-
1
culated based on H NMR analysis of OCH δ = 3.78–3.8 and 3.87–
3
3
.89; all spectral data are for a mixture of regioisomers in 61:39 ra-
(
(
2) (a) Periasamy, M.; Vairaprakash, P.; Dalai, M.
tio.
Organometallics 2008, 27, 1963. (b) Alakonda, L.;
Periasamy, M. J. Organomet. Chem. 2009, 694, 3859.
3) For transition-metal-free C–N cross-couplings: (a) Liu, Z.;
Larock, R. C. Org. Lett. 2003, 5, 4673. (b) Bolliger, J. L.;
Frech, C. M. Tetrahedron 2009, 65, 1180. (c) Kleist, W.;
Prockl, S. S.; Drees, M.; Kohler, K.; Djakovitch, L. J. Mol.
Catal. A: Chem. 2009, 303, 15. (d) Yuan, Y.; Thomé, I.;
Kim, S. H.; Chen, D.; Beyer, A.; Bonnamour, J.; Zuidema,
E.; Chang, S.; Bolm, C. Adv. Synth. Catal. 2010, 352, 2892.
–
1
FTIR (KBr): 3036, 2951, 1593, 1587, 1485, 1242, 1035, 694 cm .
1
H NMR (400 MHz, CDCl ): δ = 3.78–3.8 (d, 3 H), 3.87–3.89 (d, 3
3
H), 6.63–7.34 (m, 28 H).
13
C NMR (100 MHz, CDCl ): δ = 55.3, 55.6, 108.1, 109.8, 114.8,
3
1
16.5, 121.9, 122.9, 124.5, 127.4, 129.2, 129.3, 129.8, 140.8, 147.8,
1
48.3, 149.2, 156.2, 160.5.
(
4-Nitrophenyl)diphenylamine (12e)
(
e) Cano, R.; Ramón, J. D.; Yus, M. J. Org. Chem. 2011, 76,
Yellow solid; yield: 136 mg (47%).
6
54.
–
1
FTIR (KBr): 1581, 1491, 1313, 1109, 841, 694 cm .
(
4) (a) Kim, J. K.; Bunnett, J. F. J. Am. Chem. Soc. 1970, 92,
7464. (b) Shirakawa, E.; Itoh, K.; Higashino, T.; Hayashi, T.
J. Am. Chem. Soc. 2010, 132, 15537.
1
H NMR (400 MHz, CDCl ): δ = 6.92–6.94 (d, 2 H), 7.18–7.31 (m,
3
6
H), 7.36–7.39 (m, 4 H), 8.03–8.05 (d, 2 H).
(
5) Fuls, P. F.; Rodrique, L.; Fripiat, J. J. Clays Clay Miner.
13
C NMR (100 MHz, CDCl ): δ = 118.1, 125.5, 125.7, 126.5, 129.9,
3
1
970, 18, 53.
1
40.1, 145.6, 153.5.
(
6) (a) Min, G.-H.; Yim, T.; Lee, H. Y.; Huh, D. H.; Lee, F.;
LC-MS (EI): m/z = 291 (M + 1).
Mun, J.; Oh, S. M.; Kim, Y. G. Bull. Korean Chem. Soc.
2
006, 27, 847. (b) Ahrens, S.; Peritz, A.; Strassner, T.
Angew. Chem. Int. Ed. 2009, 48, 7908.
Acknowledgment
(
(
(
7) (a) Surry, D. S.; Buchwald, S. L. J. Am. Chem. Soc. 2007,
1
2
29, 10354. (b) Hirai, Y.; Uozumi, Y. Chem. Commun.
010, 46, 1103.
L.A. is thankful to the CSIR for the research fellowship. This re-
search work was supported by the UGC under the ‘University with
Potential for Excellence (UPE)’ and Centre for Advance Studies
8) (a) Liu, Y.-H.; Chen, C.; Yanga, L.-M. Tetrahedron. Lett.
2
006, 47, 9275. (b) Chavan, S. S.; Sawant, S. K.; Sawant, V.
(
CAS) and UGC-MHRD support under Chemistry Networking
A.; Lahiri, G. K. Inorg. Chim. Acta 2010, 363, 3359.
9) Perry, M. C.; Cui, X.; Powell, M. T.; Hou, D. R.;
Reibenspies, J. H.; Burgess, K. J. Am. Chem. Soc. 2003, 125,
Centre program. This research work was also supported by the DST
under the FIST program and IRHPA program in the School of Che-
mistry and Center for Nanotechnology in the University of Hydera-
bad. Award of the JC Bose Fellowship grant by the DST to M.P. is
also gratefully acknowledged.
1
13.
(
10) Voets, M.; Antes, I.; Scherer, C.; Müller-Vieira, U.; Biemel,
K.; Barassin, C.; Marchais-Oberwinkler, S.; Hartmann, R.
W. J. Med. Chem. 2005, 48, 6632.
Supporting Information for this article is available online at
(11) Yang, X. D.; Li, L.; Zhang, H.-B. Helv. Chim. Acta 2008,
91, 1435.
http://www.thieme-connect.com/ejournals/toc/synthesis.omnoinfrtIangiomnSionurpoatfrInt
giSutpor
(
12) Jonhnson, A. L.; Kaner, J. C.; Sharma, D. C.; Dorfman, R.
L. J. Med. Chem. 1969, 12, 1024.
References
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(
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Synthesis 2012, 44, 1063–1068
© Georg Thieme Verlag Stuttgart · New York