Cu-Al hydrotalcite: An efficient and reusable ligand-free catalyst for the coupling of aryl chlorides with aliphatic, aromatic, and N(H)-heterocyclic amines

Article abstract of DOI:10.1055/s-0029-1216890

Copper-aluminum hydrotalcite catalysts were effectively used in the coupling of aryl chlorides with aliphatic, aromatic, and N(H)-heterocyclic amines to afford the corresponding N-alkylated/arylated amines in excellent yields. The catalyst was quantitatively recovered from the reaction by simple filtration and reused for a number of cycles with almost consistent activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216890

PAPER
2517
Cu–Al Hydrotalcite: An Efficient and Reusable Ligand-Free Catalyst for the
Coupling of Aryl Chlorides with Aliphatic, Aromatic, and N(H)-Heterocyclic
Amines
C
u–A
l
Hydrotalc
.
ite:
A
n
Effic
S
ient and Reusa
r
ble
L
iga
e
nd-Free
C
a
e
talyst dhar,* R. Arundhathi, P. Linga Reddy, M. Amarnath Reddy, M. Lakshmi Kantam
Indian Institute of Chemical Technology, Inorganic & Physical Chemistry Division, Hyderabad 500007, India
Fax +91(40)27160921; E-mail: sreedharb@iict.res.in
Received 11 March 2009; revised 27 April 2009
over homogeneous systems can make a major impact on
Abstract: Copper–aluminum hydrotalcite catalysts were effective-
ly used in the coupling of aryl chlorides with aliphatic, aromatic,
and N(H)-heterocyclic amines to afford the corresponding N-alky-
lated/arylated amines in excellent yields. The catalyst was quantita-
the environmental performance of a synthesis.10 Our
group reported hydroxyapatite-supported copper (Cu-
HAP)11 and Cu(II)-NaY12 catalyzed coupling of aryl ha-
tively recovered from the reaction by simple filtration and reused lides with heterocyclic amines without the use of addi-
for a number of cycles with almost consistent activity.
tives. Although these results are encouraging, there is
considerable room for improvement. For example, the
above-mentioned are limited in terms of the substrates for
which they can be used; in particular, they are ineffective
for alkylamine derivatives and electron-donating aryl ha-
lides. Therefore, copper-catalyzed C–N cross-coupling
reactions need to be modified to expand the scope of these
methods and to employ more substrates.
Key words: hydrotalcite, copper, aryl chloride, coupling, N-alky-
lated/arylated amines, reusable catalyst
Aliphatic and N-arylheterocycles are common motifs in
pharmaceutical research.1 Usually these compounds are
synthesized by SNAr substitution with aryl halides bearing
electron-withdrawing substituents or by Ullmann-type
coupling at high temperatures.2 After the initial reports of
Chan and Lam, the copper-catalyzed cross coupling be-
tween N-heterocycles and arylboronic acids has become
an important synthetic methodology in modern organic
synthesis.3 However the high cost and poor availability of
functionalized boronic acids precludes its wide applica-
tion. The discovery and development of the catalytic path
for the N-arylation of heterocycles by Buchwald with bro-
mo- and iodoarenes using copper in the presence of basic
ligands generated greater interest in industry. Initially
Buchwald used 1,10-phenanthroline as a ligand and sub-
sequently show that 1,2-diamines were better ligands to
promote this N-arylation.4 Afterwards Cristau et al. re-
ported oxime-type and Schiff base ligands5 and Ma et al.
reported a- and b-amino acids as ligands for effective N-
arylation of N-heterocyclic amines with aryl halides.6
Several ligands7–9 have also been introduced for the N-
arylation of aliphatic amines. However, all of these syn-
thetic protocols suffer from one or more demerits such as
high cost of the ligand, N-arylation of the ligand itself, and
long duration. So there is still scope for further develop-
ment of common catalysts for the N-arylation of aliphatic,
aromatic, and N-heterocyclic amines.
In recent years, layered double hydroxides (LDHs) of
magnesium and aluminum have received considerable at-
tention due to their cation exchange capacity of the brucite
layer, anion exchange by inter layer, and also as good sup-
port in heterogeneous catalysis. By exploiting these prop-
erties of LDHs, we reported N-arylation with chloro-
arenes using layered double hydroxides supported copper
catalyst.13 In continuation of our studies on the catalyst ac-
tivity in organic transformations, we wish to report effi-
cient Cu/Al-HTB catalyzed N-arylation of aryl halides
with various amines under ligand-free conditions. In com-
parison to currently existing methods of C–N bond forma-
tion, our proposed approach has several distinguishing
features that are worth mentioning:
(i) it employs an environmentally friendly and economi-
cally competitive catalytic system;
(ii) it offers experimental simplicity and can be performed
without protection from air or moisture;
(iii) both aliphatic/aromatic and N(H)-heterocyclic
amines and various substituted aryl halides, can be used.
In our preliminary studies to find the best catalyst for the
coupling reaction under ligand-free conditions, we chose
the coupling reaction of octylamine with 1-chloro-2-ni-
trobenzene to give 2-nitro-N-octylaniline (1e) with a cat-
alytic amount of copper catalyst as a model reaction
(Scheme 1, Table 1). From Table 1, it can be seen that Cu/
Al-HTB is the best catalyst amongst the catalysts screened
(Table 1, entry 6).
The development of heterogeneous catalysts for fine
chemicals synthesis has become a major area of research
recently, as the potential advantages of these materials
(simplified recovery and reusability and the potential for
incorporation in continuous reactors and microreactors)
Next we screened different solvent systems and bases
(Scheme 1, Table 2) and it was observed that N,N-dimeth-
ylformamide and potassium carbonate provided the best
yield of the product (Table 2, entry 6) dimethyl sulfoxide,
SYNTHESIS 2009, No. 15, pp 2517–2522
Advanced online publication: 10.07.2009
DOI: 10.1055/s-0029-1216890; Art ID: P03909SS
© Georg Thieme Verlag Stuttgart · New York
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x
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2518
B. Sreedhar et al.
PAPER
catalyst, base
solvent, 100 °C, 6-8 h
H
N
Cl
NH2
7
+
7
NO2
NO2
1e
Scheme 1 C–N Bond formation between aryl chlorides and aliphatic amines
Table 1 Catalyst Screening for the Coupling of 1-Chloro-2-nitro-
dimethylformamide as the solvent albeit in moderate yield
(Table 2, entry 11).
benzene and Octylaminea
In an effort to extend the scope of this current protocol, we
have investigated the N-arylation of aliphatic, aromatic,
and N(H)-heterocyclic amines with a variety of chloro-,
iodo-, and bromoarenes and the results are summarized in
Tables 3 and 4.
Entry
Catalystb
Isolated yield (%)
1
2
3
4
5
6
7
Cu(HAP)
n.r.c
n.r.c
32
Cu(FAP)
Cu(II)-NaY
SiO2-Cu(OAc)2
Cu/Al-HTA
Cu/Al-HTB
Cu/Al-HTC
Under these optimized conditions, several other aryl chlo-
rides and a wide variety of aliphatic (linear, alicyclic)
amines were subjected to this coupling reaction and the
results are summarized in Table 3.
36
65
99, 97d
90
Aryl chlorides with electron-withdrawing and electron-
donating functionalities afforded excellent to good yields
of the corresponding N-alkylated amines 1 (Table 3). The
position of the substituents on the aryl halide play a major
role in the level of reactivity. Electron-withdrawing
groups, such as nitro, cyano, or formyl, in the ortho-posi-
tion of the aryl chlorides gave excellent yields with de-
creased reaction times compared to the corresponding
meta- and para-substituted aryl chlorides, this can be ex-
plained due to the potential of these chelating groups for
the copper provide an activating effect (Table 3, entries 4–
10). It was noticed that the simple formyl substituent was
not inert during the coupling reaction and ultimately was
oxidized to a carboxylic group (Table 3, entries 8 and 9),
but when 2,4-dichlorobenzaldehyde was used for the cou-
pling reaction the formyl group did not undergo oxidation
to the acid (Table 3, entry 11); the chloro group at the
ortho-position was N-arylated to give 1j. The ortho effect
of the chloro group can be visualized when compared with
4-chlorobenzaldehyde (Table 3, entries 8 and 11). Both
primary and secondary cyclic amines reacted with equal
ease to give products 1m–y in excellent yields (Table 3,
entries 16–26). The increased reaction time in the case of
secondary amines may be attributed to steric hindrance
caused by the aliphatic groups at the reacting center.
a 1-Chloro-2-nitrobenzene (1.0 mmol), octylamine (1.2 mmol), cata-
lyst (2.5 mol%), K2CO3 (1.2 mmol), DMF (2.0 mL), stirred, 100 °C.
b Cu-(HAP) = copper hydroxyapatite; Cu-(FAP) = copper fluoro-
apatite; Cu/Al-HT’s (HT, hydrotalcite of Cu/Al in different ratios)
Cu/Al-HTA, 3:1, Cu/Al-HTB, 2.5:1, Cu/Al-HTC, 2:1.
c n.r. = no reaction.
d Isolated yield after five cycles.
Table 2 Effect of the Solvent and Base on the Coupling of 1-Chlo-
ro-2-nitrobenzene and Octylamine Using Cu/Al-HTB Catalysta
Entry Solvent
Base
Time(h) Isolated yield (%)
1
2
DMF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K3PO4
K2CO3
K2CO3
K3PO4
K2CO3
Na2CO3
K2CO3
17
19
21
24
15
8
42
DMSO
NMP
37
3
55
4
1,4-dioxane
DMF
20
5
65
6
DMF
99, 97b
85
7
DMSO
NMP
10
10
9
8
60
A variety of other nitrogen containing heterocycles such
as imidazole, benzimidazole, pyrazole, and morpholine
were successfully coupled with chloro-, iodo-, and bro-
moarenes to give the corresponding N-arylated products 2
in good to excellent yields (Table 4). Chloroarenes con-
taining electron-donating groups afforded the correspond-
ing N-arylated products in diminished yields with longer
reaction times (Table 4, entries 2, 3, 6, and 7). N-Aryla-
tion of imidazole with chloroarenes containing electron-
withdrawing groups, such as nitro, cyano, and trifluoro-
methyl, gave products 2d,e,h–j in high yields (90–99%,
Table 4, entries 4, 5, and 8–10) in short reaction times.
Treatment of 1-chloro-4-bromobenzene and 1-chloro-4-
iodobenzene with imidazole gave selectively 1-(4-chloro-
9
NMP
73
10
11
DMF
12
48
79
DMF
45c
a 1-Chloro-2-nitrobenzene (1.0 mmol), octylamine (1.2 mmol),
Cu/Al-HTB (2.5 mol%), base (1.2 mmol), solvent (2.0 mL), 100 °C.
b Isolated yield after five cycles.
c Isolated yield at r.t.
and N-methylpyrrolidin-2-one were also found to be ef-
fective. It is also noteworthy, even at room temperature
Cu/Al-HTB afforded 45% product in 48 hours with N,N-
Synthesis 2009, No. 15, 2517–2522 © Thieme Stuttgart · New York

PAPER
Cu–Al Hydrotalcite: An Efficient and Reusable Ligand-Free Catalyst
2519
coupling reaction with morpholine it resulted in 4-(4-
chlorophenyl)morpholine (2u) (Table 4, entry 23). Over-
all it was noticed that iodoarenes were more reactive than
chloro- and bromoarenes and this is in line with earlier re-
ports.5b Furthermore, aryl halides bearing electron-with-
drawing functional groups reacted at a faster rate than the
ones containing electron-donating groups.
Table 3 Coupling of Aryl Chlorides with Amines Catalyzed by
Cu/Al-HTBa
Cu/Al-HTB, K2CO3
2
3
NR2R3
Cl
+
HNR R
DMF, 100 °C, 6–8 h
R1
R1
1
Entry R1
R2
R3
Product Time Yield
(h)
24
28
32
8
(%)
n.r.b
52
Table 4 Coupling of Aryl Chlorides with N(H)-Heterocyclic
Amines Catalyzed by Cu/Al-HTBa
1
2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C8H17
n-C12H25
n-C12H25
1a
1b
1c
1d
1e
1f
4-Me
2-Me
Cu/Al-HTB, K2CO3
2
3
NR2R3
X
+
HNR R
DMF, 100 °C, 6–8 h
R1
R1
3
42
2
4
4-NO2
89
Entry X R1
-NR2R3
Prod. Time Yielda
(h) (%)
5
2-NO2
6
99, 97c
78
6
4-CN
12
10
10
8
1
2
3
4
5
6
7
8
9
Cl
H
imidazol-1-yl
imidazol-1-yl
imidazol-1-yl
imidazol-1-yl
imidazol-1-yl
2a 18
2b 12
n.r.b (92, 80)
7
2-CN
1g
1h
1i
75
Cl 4-Me
Cl 2-Me
Cl 4-NO2
Cl 2-NO2
27 (89)
8
4-CO2Hd
2-CO2He
4-CO2H
90
2c
2d
2e
2f
19
8
18 (65)
9
95
90 (95)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
1h
1j
8
97
6
92, 90c (99)
4-Cl-2-CHO
4-NO2
2-NO2
H
8
95
Cl 4-COMe imidazol-1-yl
18 (5) 75 (95)
1k
1l
6
95
Cl 4-OMe
Cl 4-CN
Cl 2-CN
imidazol-1-yl
imidazol-1-yl
imidazol-1-yl
imidazol-1-yl
2g 18
2h 16
59 (90)
95
6
99
cyclopentyl 1m
cyclopentyl 1n
cyclopentyl 1o
cyclopentyl 1p
16
20
8
n.r.b
n.r.b
90
2i
2j
12
7
99
2-Me
10 Cl 2-CF3
97
4-NO2
2-NO2
4-NO2
2-NO2
3-CN
11 Cl 4-CO2Hd imidazol-1-yl
12 Cl 2-CO2He imidazo-l-yl
2k 10
73
8
94
2l
8
8
6
90
cyclohexyl
cyclohexyl
cyclohexyl
cyclohexyl
1q
1r
1s
8
92
13 Br 4-Cl
imidazo-l-yl
imidazo-l-yl
2m
2m
98
6
99
14
15
16
17
18
19
I
I
I
I
I
I
4-Cl
99
14
14
28
24
9
72
4-COMe benzimidazol-1-yl 2n 15
4-COMe pyrazol-1-yl 2o 18
benzimidazol-1-yl 2p 18
88
4-CO2H
4-Me
1t
73
80
–(CH2)5–
–(CH2)5–
–(CH2)5–
–(CH2)5–
–(CH2)5–
1u
1v
1w
1x
1y
52
4-OMe
4-OMe
H
85
2-OMe
4-I
48
pyrazol-1-yl
morpholino
morpholino
2q 20
80
81
2r
2r
8
90
4-Br
10
8
88
20 Cl
H
26
n.r.b
4-NO2
94
21 Cl 4-NO2
22 Cl 2-NO2
23 Br 4-Cl
morpholino
morpholino
morpholino
morpholino
2s
2t
8
6
8
7
92
99
90
99
a ArCl (1 mmol), R2R3NH (1.2 mmol), Cu/Al-HTB (2.5 mol%),
K2CO3 (1.2 mmol), DMF (2.0 mL), 100 °C, stirred.
b No reaction.
c Isolated yields after five cycles.
2u
2v
d Substrate had R1 = 4-CHO.
24
I
4-Br
e Substrate had R1 = 2-CHO.
a Isolated yields, yields in parentheses are of iodo and bromoarenes re-
phenyl)-1H-imidazole (2m) (Table 4, entries 13 and 14). spectively.
b n.r. = no reaction.
The reaction with iodoarenes resulted in complete conver-
sion in short reaction times in accordance with the litera-
ture.11 When 1-bromo-4-chlorobenzene is used for the
c Isolated yield after five cycles.
d In substrate R1 = 4-CHO.
e In substrate R1 = 2-CHO.
Synthesis 2009, No. 15, 2517–2522 © Thieme Stuttgart · New York

2520
B. Sreedhar et al.
PAPER
Anal. Calcd for C9H7N3O2: C, 57.14; H, 3.73; N, 22.21. Found: C,
57.15; H, 3.69; N, 22.30.
The Cu/Al-HTB catalyst was separated from the reaction
mixture by centrifugation, washed with N,N-dimethyl-
formamide to make the catalyst free from organic matter,
then with water, and finally with acetone, dried, and used
in the next cycle. Almost consistent activity was noticed
even after the fifth cycle (Table 1, entry 6). Copper con-
tent (2.5 mol%) of the fresh and used (after 5th cycle) cat-
alyst was found to be almost the same (by ICP-AES). To
check the heterogeneity of the catalyst, a reaction between
1-chloro-2-nitrobenzene and octylamine was terminated
at 16% conversion (after 30 min) and the catalyst was sep-
arated by simple filtration. The reaction was continued for
an additional 12 hours and the conversion remained al-
most unchanged. Moreover, the filtrate was tested for cop-
per by ICP-AES after the 6th cycle and it was almost the
same (only 2% difference) and no copper was found for
the five consecutive cycles. These studies clearly demon-
strate that no leaching of copper has taken place from the
catalyst.
4-Nitro-N-octylaniline (1d)
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 6.79 Hz, 3 H), 1.20–
1.43 (m, 10 H), 1.59–1.71 (m, 2 H), 3.12–3.26 (m, 2 H), 6.48 (d,
J = 9.06 Hz, 2 H), 8.06 (d, J = 9.06 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 22.8, 27.3, 29.5, 30.2, 32.0,
45.1, 114.1, 121.9, 137.3, 153.9.
MS (EI): m/z = 43, 57, 83, 105, 119, 138, 151, 250 (M+).
Anal. Calcd for C14H22N2O2: C, 67.17; H, 8.86; N, 11.19. Found: C,
67.09; H, 8.90; N, 11.18.
2-Nitro-N-octylaniline (1e)
1H NMR (300 MHz, CDCl3): d = 0.92 (t, J = 6.6 Hz, 3 H), 1.31–
1.54 (m, 10 H), 1.68–1.83 (m, 2 H), 3.24–3.33 (m, 2 H), 6.60 (t,
J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 7.38 (t, J = 8.82 Hz, 1
H), 7.96–8.10 (br s, 1 H), 8.15 (dd, J = 8.82, 10.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 26.8, 30.2, 31.6, 44.2, 114.6,
118.2, 121.9, 132.2, 135.5, 138.6.
MS (EI): m/z = 40, 41, 43, 78, 93, 104, 119, 135, 151, 161, 175, 189,
In summary, we have developed a practical and promising
protocol for the N-alkylation/arylation of various amines
with differently substituted aryl halides using Cu/Al-
HTB. The versatility, convenient operation, low cost,
ligand-free, and environmental friendliness of this meth-
od, in addition to the high yields, make it viable for use
both in laboratory research and on a larger industrial scale.
Currently, we are exploring the scope and application of
the proposed Cu/Al-HTB-catalyzed N-alkylation/aryla-
tion with regard to the synthesis of pharmaceutical mole-
cules.
204, 215, 250 (M+), 252 (M + 2 H).
Anal. Calcd for C14H22N2O2: C, 67.17; H, 8.86; N, 11.19. Found: C,
67.15; H, 8.85; N, 11.62.
N-Dodecyl-4-nitroaniline (1k)
1H NMR (300 MHz, CDCl3): d = 0.90 (t, J = 6.59 Hz, 3 H), 1.20–
1.50 (m, 20 H), 3.20–3.35 (m, 2 H), 6.80 (d, J = 8.03 Hz, 2 H), 8.09
(br s, 1 H), 8.15 (d, J = 8.03 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 22.9, 27.2, 29.4, 30.1, 30.4,
31.8, 44.9, 114.5, 122.6, 137.8, 153.8.
GC-MS: m/z = 307 (M + H).
Anal. Calcd for C18H30N2O2: C, 70.55; H, 9.87; N, 9.14. Found: C,
71.09; H, 9.90; N, 9.38.
The 1H NMR (300 MHz, Bruker Avance or 400 MHz, Varian Ino-
va) chemical shifts were measured relative to tetramethylsilane
(TMS). The 13C NMR (75 MHz, Bruker Avance or 100 MHz, Vari-
an Inova) chemical shifts are given using CDCl3 as the internal stan-
dard. Mass spectra (MS) were obtained by EI [VG-7070H
Micromass (3 KeV, xenon)] or GC-MS [Thermo Finnigan TRACE
DSQ MS spectrophotometer, using a BP-1 (30 × 0.25 × 1.0) capil-
lary column]. Solvents were dried by refluxing for at least 24 h over
CaH2 (DMF or DMSO), and freshly distilled prior to use. Unless
otherwise indicated, all syntheses and manipulations were carried
out under atmospheric conditions. All the reactants were commer-
cially available and used without purification. The spectroscopic
data for all known products compared well with reported da-
ta.5,11,14,15
N-Cyclopentyl-2-nitroaniline (1p)13
1H NMR (300 MHz, CDCl3): d = 1.62–1.81 (m, 6 H), 2.00–2.20 (m,
2 H), 3.90–4.01 (m, 1 H), 6.61 (t, J = 8.31 Hz, 1 H), 6.85 (d, J = 9.82
Hz, 1 H), 7.40 (t, J = 8.31 Hz, 1 H), 8.10–8.40 (d, J = 9.82 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 20.7, 31.6, 56.0, 113.3, 117.6,
124.6, 131.9, 136.0, 140.8.
MS (EI): m/z = 43, 69, 83, 85, 105, 121, 149, 164, 177, 191, 206
(M+).
Anal. Calcd for C11H14N2O2: C, 64.06; H, 6.84; N, 13.58. Found: C,
64.00; H, 6.85; N, 13.60.
N-Cyclohexyl-4-nitroaniline (1q)
1H NMR (300 MHz, CDCl3): d = 1.01–1.99 (m, 10 H), 3.01–3.21
(m, 1 H), 6.85 (d, J = 8.31 Hz, 2 H), 7.99 (d, J = 8.31 Hz, 2 H), 8.05
(br s, 1 H).
1-(2-Nitrophenyl)-1H-imidazole (2e); Typical Procedure
A mixture of 1-chloro-2-nitrobenzene (1 mmol), 1H-imidazole (1.2
mmol), K2CO3 (1.2 mmol), and Cu/Al-HTB (100 mg, 2.5 mol%) in
DMF (2 mL) was stirred in a round-bottomed flask at 100 °C. When
the reaction was complete (TLC), the catalyst was filtered washed
several times with DMF, H2O and acetone and reused for the next
reaction. DMF was removed from the reaction filtrate under re-
duced pressure and crude material was purified by chromatography
(silica gel, 60–120 mesh, hexane–EtOAc) to afford 2e.11
1H NMR (300 MHz, CDCl3): d = 7.36–7.56 (m, 6 H), 7.85 (d,
J = 7.93 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 122.0, 124.1, 124.6, 125.5, 129.9,
132.0, 135.5, 137.4, 139.9.
13C NMR (75 MHz, CDCl3): d = 22.9, 28.2, 34.1, 51.2, 114.6,
121.9, 136.9, 154.1.
GC-MS: m/z = 220 (M+).
Anal. Calcd for C12H16N2O2: C, 65.43; H, 7.32; N, 12.72. Found: C,
64.92; H, 7.25; N, 13.10.
4-(Cyclohexylamino)benzoic Acid (1t)
1H NMR (300 MHz, CDCl3): d = 1.01–1.99 (m, 10 H), 3.01–3.21
(m, 1 H), 7.20 (d, J = 8.31 Hz, 2 H), 7.61 (d, J = 8.31 Hz, 2 H), 8.05
(br s, 1 H).
MS (EI): m/z = 43, 57, 83, 85, 109, 115, 128, 149, 164, 171, 189
(M+).
Synthesis 2009, No. 15, 2517–2522 © Thieme Stuttgart · New York

PAPER
Cu–Al Hydrotalcite: An Efficient and Reusable Ligand-Free Catalyst
2521
13C NMR (75 MHz, CDCl3): d = 23.2, 28.1, 33.9, 51.0, 113.6,
118.9, 131.0, 153.1, 169.5.
13C NMR (75 MHz, CDCl3): d = 49.4, 66.9, 117.0, 125.0, 129.1,
150.0.
GC-MS: m/z = 219 (M+).
GC-MS: m/z = 198 (M + H).
Anal. Calcd for C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C,
71.25; H, 7.17; N, 6.41.
Anal. Calcd for C10H12ClNO: C, 60.76; H, 6.12; N, 7.09; Found: C,
60.68; H, 5.99; N, 7.10.
1-Phenyl-1H-imidazole (2a)11
4-(4-Bromophenyl)morpholine (2v)
1H NMR (300 MHz, CDCl3): d = 7.21 (br s, 1 H), 7.29 (br s, 1 H),
7.34–7.40 (m, 3 H), 7.46–7.51 (m, 2 H), 7.87 (s, 1 H).
1H NMR (300 MHz, CDCl3): d = 3.12 (t, J = 4.47 Hz, 4 H), 3.81 (t,
J = 4.47 Hz, 4 H), 6.71 (d, J = 8.80 Hz, 2 H), 7.35 (d, J = 8.80 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 118.2, 121.3, 127.4, 129.7, 130.1,
135.5, 137.1.
GC-MS: m/z = 144 (M+).
13C NMR (75 MHz, CDCl3): d = 46.2, 66.9, 112.9, 118.1, 133.8,
148.7.
MS (EI): m/z = 95, 115, 133, 138, 164, 166, 186, 208, 223, 242
Anal. Calcd for C9H8N2: C, 74.98; H, 5.59; N, 19.43. Found: C,
75.15; H, 5.58; N, 19.41.
(M+), 244 (M + 2 H).
Anal. Calcd for C10H12BrNO: C, 49.61; H, 5.00; N, 5.79; Found: C,
49.62; H, 5.01; N, 5.88.
1-(4-Methoxyphenyl)-1H-imidazole (2g)11
1H NMR (400 MHz, CDCl3): d = 3.87 (s, 3 H), 6.99–7.02 (m, 2 H),
7.21 (s, 1 H), 7.23 (s, 1 H), 7.29–7.34 (m, 2 H), 7.80 (s, 1 H).
Acknowledgment
13C NMR (100 MHz, CDCl3): d = 55.6, 114.8, 118.7, 123.1, 130.0,
130.7, 135.8, 158.9.
GC-MS: m/z = 174 (M+).
R.A. wishes to thank DST (GAP-0152) for financial support and
Department of Science and Technology for providing research fel-
lowship.
Anal. Calcd for C10H10N2O: C, 68.95; H, 5.79; N, 16.08. Found: C,
68.99; H, 5.78; N, 16.41.
References and Notes
4-Phenylmorpholine (2r)14c
1H NMR (300 MHz, CDCl3): d = 3.17 (t, J = 4.47 Hz, 4 H), 3.63 (t,
J = 4.47 Hz, 4 H), 6.57–6.60 (m, 3 H), 6.85 (t, J = 7.20 Hz, 2 H).
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Rafalski, M.; Lam, P. Y. S. Tetrahedron Lett. 1999, 40,
1623. (c) Lam, P. Y. S.; Vincent, G.; Clark, C. G.; Deudon,
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40, 2657. (c) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
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13C NMR (75 MHz, CDCl3): d = 45.8, 99.9, 113.9, 117.0, 126.0,
126.9, 129.0, 133.1, 143.7, 148.2.
GC-MS: m/z = 164 (M + H).
Anal. Calcd for C10H13NO: C, 73.59; H, 8.03; N, 8.58; Found: C,
73.62; H, 8.05; N, 8.61.
4-(4-Nitrophenyl)morpholine (2s)
1H NMR (300 MHz, CDCl3): d = 3.20 (t, J = 4.49 Hz, 4 H), 3.67 (t,
J = 4.49 Hz, 4 H), 6.89 (d, J = 8.39 Hz, 2 H), 8.02 (d, J = 8.39 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 46.4, 66.7, 115.2, 123.2, 138.3,
156.1.
MS (EI): m/z = 51, 57, 77, 91, 104, 120, 134, 150, 161, 177, 1293,
208 (M+).
Anal. Calcd for C10H12N2O3: C, 57.68; H, 5.81; N, 13.45; Found: C,
57.66; H, 5.79; N, 13.60.
4-(2-Nitrophenyl)morpholine (2t)
1H NMR (300 MHz, CDCl3): d = 3.15 (t, J = 4.24 Hz, 4 H), 3.85 (t,
J = 4.24 Hz, 4 H), 7.10 (t, J = 7.63 Hz, 1 H), 7.15 (d, J = 8.49 Hz, 1
H), 7.51 (t, J = 6.78 Hz, 1 H), 7.80 (d, J = 8.49 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 51.9, 66.7, 120.8, 122.1, 125.7,
133.4, 143.5, 145.6.
MS (EI): m/z = 51, 65, 77, 92, 105, 119, 133, 145, 161, 174, 191,
208 (M+).
Anal. Calcd for C10H12N2O3: C, 57.68; H, 5.81; N, 13.45; Found: C,
58.01; H, 5.80; N, 13.41.
4-(4-Chlorophenyl)morpholine (2u)15c
1H NMR (300 MHz, CDCl3): d = 3.11 (t, J = 4.80 Hz, 4 H), 3.85 (t,
J = 4.80 Hz, 4 H), 6.80–6.84 (d, J = 8.94 Hz, 2 H), 7.21 (d, J = 8.94
Hz, 2 H).
Synthesis 2009, No. 15, 2517–2522 © Thieme Stuttgart · New York

2522
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