Efficient one-pot synthesis of 2-alkylquinolines under solvent-free conditions using sulfonic acid functionalized ionic liquid as a recoverable and reusable catalyst

Article abstract of DOI:10.3987/COM-11-12289

Sulfonic acid functionalized ionic liquid (FIL-A) was firstly used as a recoverable and reusable catalyst for the synthesis of 2-alkylquinoline derivatives from simple and readily available alkylaldehydes and arylamines. The method has the advantages of s

Full text of DOI:10.3987/COM-11-12289

HETEROCYCLES, Vol. 83, No. 10, 2011
2289
HETEROCYCLES, Vol. 83, No. 10, 2011, pp. 2289 - 2298. © 2011 The Japan Institute of Heterocyclic Chemistry
Received, 22nd June, 2011, Accepted, 25th July, 2011, Published online, 4th August, 2011
DOI: 10.3987/COM-11-12289
EFFICIENT ONE-POT SYNTHESIS OF 2-ALKYLQUINOLINES UNDER
SOLVENT-FREE
CONDITIONS
USING
SULFONIC
ACID
FUNCTIONALIZED IONIC LIQUID AS A RECOVERABLE AND
REUSABLE CATALYST
Min Zhang,1* Biao Xiong,1 Ting Wang,1 Yu-Qiang Ding,1* and Li Wang2
1School of Chemical and Materials Engineering and 2School of Food Science and
Technology in Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province,
214122, People’s Republic of China. E-mail: zm31289@yahoo.com.cn
Abstract - Sulfonic acid functionalized ionic liquid (FIL-A) was firstly used as a
recoverable and reusable catalyst for the synthesis of 2-alkylquinoline derivatives
from simple and readily available alkylaldehydes and arylamines. The method has
the advantages of simple experimental procedure, easy recovery and reuse of
catalyst, solvent-free and mild reaction conditions, excellent functional group
tolerance, etc. which makes it a highly practical and environmentally benign
pathway for the synthesis of 2-alkylquinolines.
INTRODUCTION
During the past decade, the applications of functionalized ionic liquids (FILs) or so-called “task-specific
ionic liquids” (TSILs)1 have attracted considerable attention due to its notable advantages such as low
volatility and toxicity, high thermal and chemical stability, excellent dissolving ability. The use of FILs as
reaction medium may offer the potentials for developing highly efficient synthetic methods and avoiding
solvent emission and catalyst recycling problems.2
Drawing from the significant virtues of FILs and our recently reported method on p-toluenesulfonic
acid-mediated quinoline formation,3 we were therefore interested in applying sulfonic acid functionalized
ionic liquid as a reusable catalyst in the synthesis of 2-alkylquinolines. 2-alkylquinolines and its
analogues constitute a significant important class of nitrogen-containing heterocycles, and they have
shown a broad spectrum of biological and pharmaceutical activities such as deacetylase inhibitor,4
antileishmanial,5 antimalarial,6 antidepressant,7 etc. In addition, 2-alkylquinolines also serve as valuable
building blocks for manufacturing functionalized materials,8 chemosensors,9 dyes and pigments.10

2290
HETEROCYCLES, Vol. 83, No. 10, 2011
Owing to its useful functions, there has been an increasing demand for developing highly efficient
methods to synthesize 2-alkylquinoline derivatives. To date, except the well-established name reactions
(such as Skraup,11 Friedländer,12 Combes13 and Doebner-Von Miller reactions14) and related improved
methodologies,15 a variety of recent examples have also showed elegant pathways for elaboration of
2-alkylquinolines.16 However, some of these methods still suffer from the limitations such as harsh
reaction conditions, limited substrate scope, low product yields, poor chemo-selectivity or regioselectivity,
usage of volatile organic solvent, multistep manipulations, etc. Notably, the cross-coupling reaction of
two molecules of alkylaldehydes with one molecule of arylamine provides an attractive pathway for
synthesis of 2-alkylquinoline derivatives.3,17 However, the employed catalysts in such a reaction are
generally difficult to be recovered. In the context of these synthetic problems, the search for an effective
catalytic system along with eco-compatible preparation of 2-alkylquinolines from readily available
starting materials is of significant importance.
Herein, we report a sulfonic acid functionalized ionic liquid A (FIL-A) catalyzed method for the synthesis
of 2-alkylquinolines from readily available alkylaldehydes 1 and arylamine 2 (Scheme 1, eq. 2). FIL-A
featuring a n-butyl sulfonic acid group in tri-methyl-ammonium cation (Scheme1, FIL-A) was prepared
initially according to the protocols reported recently (Scheme 1, eq. 1).18 To the best of our knowledge,
such a methodology has not been reported in spite of its importance as described above.
O
O
O
S
rt
H2SO4
N
N
+
SO3
SO3HHSO4
R1
NMe3
R1
(eq. 1)
FIL-A
R2
R2
FIL-A (15 mol%)
80 °C, 3h
O
+
(eq. 2)
2
NH2
N
R1
2
1
3
Scheme 1. Synthesis of sulfonic acid FIL-A and its application in the synthesis of 2-alkylquinoline 3
RESULTS AND DISCUSSION
In order to formulate an effective conversion system, the synthesis of 3-benzyl-2-phenethylquinoline 3c
from 3-phenylpropanal 1a and aniline 2c was chosen as a model reaction to evaluate the influence of
o
different catalyst loadings initially. The reaction was conducted at 80 C for 3 hours under solvent-free
conditions by introducing 10 mol% of FIL-A, a 72% GC yield was detected (Table 1, entry 1); Further
test of different catalyst loadings showed that 15 mol% of FIL-A was sufficient to promote the reaction
(Table 1, entry 2). The combination of 15 mol% of FIL-A with several conventional organic solvents also
showed to be effective in the formation of product 3 (Table 1, entry 3), but the reaction efficiency is

HETEROCYCLES, Vol. 83, No. 10, 2011
2291
relatively lower than that of solvent-free conditions. Reaction under catalyst-free conditions failed to
yield the expected product even after a prolonged reaction time (Table 1, entry 4). Decreasing the reaction
temperature from 80 °C to 60 °C required longer reaction time to give a desired product yield (Table 1,
entry 5). Thus, the optimized reaction conditions are summarized as: 15 mol% of FIL-A catalyst loading,
solvent-free conditions, and at 80 °C.
With the availability of optimal reaction conditions in hand, we tried to recover and reuse the FIL-A
catalyst. After completion of the reaction for the first run, diethylether was added to the reaction mixture
to extract the product, then the remaining oil catalyst was recovered after removal of residual solvent
under vacuum, and it was reused in the next run without further purification. This procedure was repeated
8 times and the results were outlined in Table 1 (entry 6). The detected GC yields were close in the
previous 6 cycles, and subsequently a gradual decrease of yields was observed in the two latter-cycles.
This phenomenon might be attributed to the negative effect of accumulated water generating from the
reactions or partial catalyst decomposition from the seventh cycle. Hence the catalyst could be effectively
recycled for at least 6 times without any loss of activity.
Table 1. Screening optimized conditions for the synthesis of 3ca and investigation on reuse of catalyst
Ph
conditions
O
Ph
+
2
NH2
N
3c
Ph
1a
2c
Entry Catalyst loading
(mol%)
Solvent
Yield %b
72
1
10
-
-
2
3
4
5, 8, 15, 20
58, 59, 86, 85
85, 68, 79, 57
Not foundc
15
-
1,4-dioxane, MeCN, EtOH, (CH2Cl)2
-
5
6
15
15
-
-
82d
(86, 85, 84, 85,
84, 86, 71, 63)e
a Reaction conditions: unless otherwise stated, 1a (2.4 mmol, 321.6 mg) and aniline 2c (1 mmol, 93 mg) along with
FIL-A ( 0.15 mmol, 43.8 mg) were stirred in a open schlenk tube equipped with circulating cooling water at 80 °C
for 3 h.
b GC yields of 3c with hexadecane as internal standard.
c The reaction was carried out for 24 h.
d The reaction was carried out at 60 °C for 6 h.
e GC yields are with respect to catalyst reused from the first to the eighth cycle respectively.

2292
HETEROCYCLES, Vol. 83, No. 10, 2011
Subsequently, we tested the generality of this synthetic method under optimized reaction conditions.
Various alkylaldehydes 1 and arylamines 2 bearing electron withdrawing groups (such as halide) or
electron releasing groups (such as CH3, CH3O) were employed for 2-alkylquinoline syntheses. As shown
in Table 2, all the reactions proceeded smoothly and yielded the expected products in good to excellent
isolated yields. Notably, minor by-products such as mono- and dialkylated anilines were also formed in
the reactions,17 which could lead to the decrease of product yields (see entries 1, 8 and 9 in Table 2). It
was found that substituents on the benzene ring of arylamines had significant influence on the reaction
efficiency. The electron rich ones gave faster reactions and completed the conversion of starting materials
in three hours (Table 2, entries 1, 2, 5, 8, 10), and it might be attributable to the enhanced nucleophilicity
of arylamines favors the formation of products. The halide-containing products have the potentials for
further functionalization by classical cross-coupling reactions (Table 2, entries 4, 7, 8, 9, 12). Products 3j,
3k, 3l containing two terminal vinyl groups have the potentials for preparation of macrocyclic compounds
or long chain polymers via intra- or intermolecular olefin metathesis (Table 2, entries 10-12).19 Notably,
undec-10-enal 1e is renewable resource existing in castor oil, the conversion of this natural product into
quinoline products exhibits one of its applications. Interestingly, various functional groups could be
selectively introduced into the quinoline skeleton by mediating appropriate alkylaldehydes or arylamines
using this FIL-A catalyzed methodology (Table 2).
Table 2. Efficient one-pot synthesis of 2-alkylquinoline derivativesa
R2
R2
R1
R1
FIL-A (15 mol%)
O
+
R1
2
80 °C, solvent-free
NH2
N
3
1
2
Entry
Aldehyde 1
Amine 2
2a: R2 = OMe
2b: R2 = Me
2c: R2 = H
2d: R2 = Br
2a
Reaction Time (h)
Product 3b, Yield %c
3a, 72
1
2
3
4
5
6
7
8
9
1a:R1 = PhCH2
3
3
3
3
3
5
5
3
5
1a
3b, 81
1a
3c, 78
1a
1b: R1 = Ph
1b
3d, 78
3e, 80
2b
3f, 76
1b
2e: R2 = Cl
3g, 73
1c: R1 = 4-Br-C6H4
1d: R1 = Et
2b
3h, 51
2d
3i, 66

HETEROCYCLES, Vol. 83, No. 10, 2011
2293
CHO
10
2a
3
3j, 85
1e
:
8
11
12
1e
1e
2c
3
3
3k, 85
3l, 83
2d
a
Reaction conditions: The mixture of aldehyde 1 (2.4 mmol), arylamine 2 (1 mmol,) and FIL-A (0.15 mmol, 43.8
mg) was stirred in a open schlenk tube equipped with circulating cooling water at 80 °C for appropriate reaction
time according table 2.
b
1
Known compounds were compared with related references, the IR, H NMR spectra were found to be identical
with the one described in reference.3
c Isolated yield after flash chromatography.
m-Anisidine 2f was then employed to investigate the regioselectivity of the reaction. In which could lead
to two possible regioisomers 4, 4’ (Scheme 2). However, product 4 was obtained exclusively, and the
cyclization reaction occurs at less steric hindered position of the aryamine. It shows that the steric factor
is a major contributor to site the regioselectivity in the reactions. And trisubstituted quinoline 4a and 4b
were obtained in 71%, 73% isolated yields respectively.
OMe
R1
R1
FIL-A (15 mol%)
1a
1b
+
or
+
R1
MeO
NH2
R1
80 °C, solvent-free
N
MeO
N
2f
4
4'
, not found
Ph
Ph
Ph
MeO
N
MeO
N
Ph
4a, yield: 71%
4b, yield: 73%
Scheme 2. Regioselective synthesis of trisubstituted quinolines
The proposed mechanism for this cyclization reaction is illustrated in Scheme 3 based on the reported
exampls.17,20,21 Aldehyde 1 activated by the functionalized sulfonic acid group in cation of FIL-A
condenses with aniline 2, and gives imine A and its tautomer enamine A’ initially. Then mutual
nucleophilic addition of A and A’ results in a tetrahydroquinoline intermediate B. The final quinoline
product is formed by FIL-A promoted aniline elimination and air oxidative aromatization of B (Scheme
3). Alternatively, the reaction between two imine A, or two enamine A’, or a Povarov-type reaction22
between imine and enol formed from aldehyde leads to the formation of quinoline 3, could also explain
the outcome of the reaction.

2294
HETEROCYCLES, Vol. 83, No. 10, 2011
R3
FIL-A
O
R2
R3
R1
R1
FIL-A (15 mol%)
H2N
R2
R1
+
2
1
80 °C, solvent-free
N
2
R3
-H2O
3
R2
air oxidative
aromatization
-H2O
R2
NH2
R3
R3
R2
FIL-A
R3
R2
N
N
H
R2
R3
R1
HN
R1
H
A
R1
N
H
R1
B
A'
Scheme 3. Proposed mechanism for FIL-A catalyzed 2-alkylquinoline synthesis
In conclusion, sulfonic acid functionalized ionic liquid (FIL-A) was firstly used as a recoverable and
reusable catalyst for the synthesis of 2-alkylquinoline derivatives from simple and readily available
alkylaldehydes and arylamines. With this method, functional groups such as halides, vinyl groups can be
selectively introduced into the quinoline skeleton by mediating the reactants. Additionally, unsymmetrical
arylamines can be employed for regioselective synthesis of 2-alkylquinolines. The method having the
advantages of simple experimental procedure, easy recovery and reuse of catalyst, solvent-free and mild
reaction conditions, excellent functional group tolerance makes it a highly practical and environmentally
benign pathway for the synthesis of 2-alkylquinolines.
EXPERIMENTAL
1
All the obtained products were characterized by melting points (mp), H-NMR, 13C-NMR, infrared
spectra (IR) and Low-, high-resolution mass spectra (MS and HRMS). Melting points were measured on
an Electrothemal SGW-X4 microscopy digital melting point apparatus and are uncorrected; IR spectra
1
were recorded on a FTLA2000 spectrometer; H-NMR and 13C-NMR spectra were obtained on
Bruker-200 and Avance 300. Chemical shifts were reported in parts per million (ppm, δ) downfield from
tetramethylsilane. Proton coupling patterns are described as singlet (s), doublet (d), triplet (t), quartet (q),
multiplet (m), and broad (br). EI mass spectra (LRMS) were recorded on an MAT 95XP spectrometer (70
eV, Thermo ELECTRON CORPORATION). ESI high resolution mass spectra (HRMS) were recorded on
an Agilent Technologies 6210 TOF LC/MS using H2O + 0.1% formic acid (10%) and methanol (90%) as

HETEROCYCLES, Vol. 83, No. 10, 2011
2295
eluent. All the chemical reagents were purchased from commercial sources (Alfa, Acros, Aldrich), and
used without further purification.
General procedure for synthesis of the quinoline 3a-3l, 4a, and 4b.
A Schlenk tube equipped with a magnetic stirrer bar and also with a provision of circulating cool water
was used in the experimentation, the catalyst FIL-A (0.15 mmol, 43.8 mg), arylamine (1 mmol),
alkylaldehyde (2.4 mmol) were introduced successively, and the reaction mixture formed a homogeneous
system at 80 °C and it was stirred for 3-5 h in an open system. TLC was used to detect the completion of
the reaction. After cooling down to room temperature, Et2O (5 x 15 mL) was added to the reaction
mixture to extract the product, the remaining oil FIL-A catalyst could be recycled for the next run after
removal of the solvent. The combined organic solvent was evaporated to afford the crude product, it was
purified by flash column chromatography on silica, eluting with petroleum ether, ethyl acetate in the ratio
of 30: 1, to provide desired quinoline products (isolated yields ranges from 63% to 86%).
Selected Analytical Data of obtained compounds
3-Benzyl-6-methoxy-2-phenethylquinoline (3a)
Yield: 72%; White solid, mp 136-137 °C; 1H NMR (200 MHz, CDCl3): δ 8.01 (d, J = 9.0 Hz, 1H), 7.67 (s,
1H), 7.13-7.38 (m, 11H), 7.01 (d, J = 2.4 Hz, 1H), 4.08 (s, 2H), 3.93 (s, 3H), 3.18-3.27 (m, 2H), 3.03-3.11
13
(m, 2H); C NMR (50 MHz, CDCl3): δ 158.9, 157.8, 142.5, 139.8, 135.7, 133.2, 130.4, 129.4, 129.1,
129.0, 128.8, 128.4, 126.9, 126.3, 121.8, 105.1, 55.9, 39.1, 37.9, 35.8; IR (KBr, cm-1) νmax = 3018, 2928,
1624, 1601, 1493, 1450, 1363, 1227, 1123, 1028, 940; MS (EI, m/z): 353 [M]+; HRMS (EI): Calcd. for
C25H23NO [M]+: 353.18; Found: 353.17792.
3-Benzyl-6-methyl-2-phenethylquinoline (3b)
Yield: 81%; White solid, mp 124-126 °C; 1H NMR (200 MHz, CDCl3): δ 8.01 (d, J = 8.4 Hz, 1H), 7.70 (s,
1H), 7.51-7.55 (m, 2H), 7.11-7.36 (m, 10H), 4.08 (s, 2H), 3.19-3.28 (m, 2H), 3.03-3.13 (m, 2H), 2.54 (s,
3H); 13C NMR (50 MHz, CDCl3): δ 158.9, 140.7, 138.1, 134.6, 134.4, 131.1, 129.8, 127.6, 127.3, 127.2,
126.8, 125.8, 125.1, 124.7, 124.6, 37.4, 36.3, 34.1, 20.2; IR (KBr, cm-1) νmax = 3021, 2928, 1601, 1493,
1451, 1355, 1132, 1031, 938; MS (EI, m/z): 337 [M]+; HRMS (EI): Calcd. for C25H23N [M]+: 337.18;
Found: 337.18301.
3-Benzyl-2-phenethylquinoline (3c)
Yield: 78%; White solid, mp 94-97 °C; 1H NMR (200 MHz, CDCl3): δ 8.11 (d, J = 8.4 Hz, 1H), 7.66-7.79
(m, 2H), 7.51 (dd, J = 7.2 Hz, 1H), 7.12-7.39 (m, 11H), 4.11 (s, 2H), 3.21-3.30 (m, 2H), 3.06-3.14 (m,

2296
HETEROCYCLES, Vol. 83, No. 10, 2011
2H); 13C NMR (50 MHz, CDCl3): δ 164.9, 142.4, 139.7, 136.9, 132.9, 129.8, 129.3, 129.2, 129.1, 129.0,
128.8, 127.6, 126.9, 126.8, 126.4, 39.1, 38.1, 35.7; IR (KBr, cm-1) νmax = 3060, 2926, 1601, 1493, 1453,
1418, 1074, 1029; MS (EI, m/z): 323 [M]+; HRMS (EI): Calcd. for C24H21N [M]+: 323.17; Found:
323.16738.
3-Benzyl-6-bromo-2-phenethylquinoline (3d)
Yield: 78%; White solid, mp 89-91 °C; 1H NMR (200 MHz, CDCl3): δ 7.98 (d, J = 9.0 Hz, 1H), 7.89 (d, J
= 1.8 Hz, 1H), 7.75 (dd, J = 2.2 Hz, 1H), 7.65 (s, 1H), 7.10-7.39 (m, 10H), 4.08 (s, 2H), 3.21-3.30 (m,
13
2H), 3.06-3.14 (m, 2H); C NMR (50 MHz, CDCl3): δ 161.7, 145.4, 141.8, 138.8, 135.2, 133.7, 132.2,
130.4, 129.2, 129.0, 128.8, 128.6, 128.4, 128.3, 126.7, 126.0, 119.6, 38.6, 37.6, 35.1; IR (KBr, cm-1) νmax
= 3025, 2927, 1595, 1494, 1477, 1453, 1397, 1059, 918; MS (EI, m/z): 400 [M]+; HRMS (EI): Calcd. for
C24H19NBr [M]+: 400.07; Found: 400.07008.
6-Bromo-3-ethyl-2-propylquinoline (3i)
Yield: 66%; Colorless oil; 1H NMR (200 MHz, CDCl3): δ 7.87-7.91 (m, 2H), 7.77 (s, 1H), 7.64-7.70 (m,
13
1H), 2.79-3.00 (m, 4H), 1.84 (q, J = 8.0 Hz, 2H), 1.34 (t, J = 7.4 Hz, 3H), 1.08 (t, J = 7.4 Hz, 3H); C
NMR (50 MHz, CDCl3): δ 162.6, 145.0, 136.4, 132.7, 131.9, 131.7, 130.3, 128.9, 128.5, 119.2, 114.2,
37.7, 25.2, 22.6, 14.3, 14.2; IR (KBr, cm-1) νmax = 2963, 1594, 1477, 1377, 1345, 1184, 911; MS (EI, m/z):
277 [M]+; HRMS (EI): Calcd. for C14H16NBr [M]+: 277.05; Found: 277.04658.
2-(Dec-9-enyl)-6-methoxy-3-(non-8-enyl)quinoline (3j )
Yield: 85%; Colorless oil; 1H NMR (200 MHz, CDCl3): δ 7.93 (d, J = 9.0 Hz, 1H), 7.77 (s, 1H), δ 7.26 (d,
J = 9.0 Hz, 1H), 7.01 (s, 1H), 6.80 (d, J = 9.2 Hz, 1H), 6.61 (d, J = 8.8 Hz, 1H), 5.76-5.91 (m, 3H),
4.93-5.06 (m, 6H), 3.93 (s, 3H), 2.95 (t, J =8.0 Hz, 2H), 2.78 (t, J =8.0 Hz, 2H), 2.06 (m, 4H), 1.19-1,78
13
(br, 17H); C NMR (50 MHz, CDCl3): δ 162.6, 139.9, 139.7, 135.4, 134.7, 129.3, 128.8, 127.6, 127.2,
126.3, 117.6, 114.6, 114.3, 113.2, 59.3, 50.3, 44.6, 36.4, 34.3, 32.5, 30.7, 30.6, 30.5, 30.2, 30.0, 29.9, 29.8,
29.6, 29.3, 29.2, 29.1, 27.6; IR (KBr, cm-1) νmax = 3074, 2925, 1624, 1513, 1493, 1381, 1229, 1165, 1034,
909; MS (EI, m/z): 421 [M]+; HRMS (EI): Calcd. for C29H43NO [M]+: 421.33; Found: 421.33444.
3-benzyl-7-methoxy-2-phenethylquinoline (4a)
1
Yield: 71%; Light yellow oil; H NMR (200 MHz, CDCl3): δ 7.86 (d, J = 8.0 Hz, 1H), 7.71 (s, 1H),
7.12-7.40 (m, 12H), 4.08 (s, 2H), 3.92 (s, 3H), 3.18-3.26 (m, 2H), 3.03-3.12 (m, 2H); 13C NMR (50 MHz,
CDCl3): δ159.0, 142.6, 139.8, 135.8, 133.2, 130.4, 129.5, 129.2, 129.0, 128.6, 128.4, 126.9, 126.3, 121.8,
105.6, 55.9, 39.2, 37.9, 35.8; IR (KBr, cm-1) νmax = 2931, 1640, 1599, 1493, 1361, 1227, 1135, 939; MS

HETEROCYCLES, Vol. 83, No. 10, 2011
2297
(EI, m/z): 353 [M]+; HRMS (EI): Calcd. for C25H23NO [M]+: 353.18; Found: 353. 1786.
2-benzyl-7-methoxy-3-phenylquinoline (4b)
1
Yield: 73%; Light yellow oil; H NMR (200 MHz, CDCl3): δ 7.81 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H),
6.89-7.42 (m, 12H), 4.28 (s, 2H), 3.91 (s, 3H); 13C NMR (50 MHz, CDCl3): δ159.2, 129.6, 128.9, 128.6,
128.5, 128.4, 128.2, 128.1, 127.5, 125.9, 55.6, 42.7; IR (KBr, cm-1) νmax = 2962, 1643, 1592, 1321, 1263,
1180, 909; MS (EI, m/z): 325 [M]+; HRMS (EI): Calcd. for C23H19NO [M]+: 325.15; Found: 325. 14662.
ACKNOWLEDGEMENT
The authors thanks “the Fundamental Research Funds for the Central Universities” (JUSRP10905), and
the “Start-up grant of Jiangnan University” (1045210372090460) for financial support.
REFERENCES AND NOTES
1. M. D. Soutullo, C. I. Odom, E. A. Salter, A. C. Stenson, R. E. Sykora, A. Wierzbicki, and J. H. Davis,
J. Comb. Chem., 2007, 9, 571.
2. J. P. Hallett and T. Welton, Chem. Rev., 2011, 111, 3508.
3. a) M. Zhang, T. Roisnel, and P. H. Dixnefu, Adv. Synth. Catal., 2010, 352, 1896; b) M. Zhang, B.
Xiong, W. Yang, D. N. T. Kumar, and Y. Q. Ding, Monatsh. Chem., 2011, DOI 10.1007/
s00706-011-0590-7.
4. D. Moffat, S. Patel, F. Day, A. Belfield, A. Donald, M. Rowlands, J. Wibawa, D. Brotherton, L.
Stimson, V. Clark, J. Owen, L. Bawden, G. Box, E. Bone, P. Mortenson, A. Hardcastle, S. v. Meurs,
S. Eccles, F. Raynaud, and W. Aherne, J. Med. Chem., 2010, 53, 8663.
5. N. C. Vieira, C. Herrenknecht, J. Vacus, A. Fournet, C. Bories, B. Figadere, L. S. Espindola, and P.
M. Loiseau, Biomed. Pharmacother., 2008, 62, 684.
6. L. Roberts, T. J. Egan, K. A. Joiner, and H. C. Hoppe, Antimicrob. Agents Chemother., 2008, 52,
1840.
7. C. P. Leslie, M. Biagetti, S. Bison, S. M. Bromidge, R. D. Fabio, D. Donati, A. Falchi, M. J. Garnier,
A. Jaxa-Chamiec, G. Manchee, G. Merlo, D. A. Pizzi, L. P. Stasi, J. Tibasco, A. Vong, S. E. Ward,
and L. Zonzini, J. Med. Chem., 2010, 53, 8228.
8. (a) Y. P. Huo, S. Z. Zhu, and S. Hu, Tetrahedron, 2010, 66, 8635; (b) Y. A. Sayapin, B. N. Duong, V.
N. Komissarov, and I. V. Dorogan, N. I. Makarova, I. O. Bondareva, V. V. Tkachev, G. V. Shilov, S.
M. Aldoshin, and V. I. Minkin, Tetrahedron, 2010, 66, 8763.
9. S. Ou, Z. H. Lin, C. Y. Duan, H. T. Zhang, and Z. P. Bai, Chem. Commun., 2006, 4392.

2298
HETEROCYCLES, Vol. 83, No. 10, 2011
10. P. Natasa, H. Marijana, P. Gordana, and K.-Z. Grace, Dyes Pigments., 2011, 91, 79.
11. Z. H. Skraup, Ber. Dtsch. Chem. Ges., 1880, 13, 2086.
12. P. Friedlander, Ber. Dtsch. Chem. Ges., 1882, 15, 2572.
13. A. Combes, Bull. Soc. Chim. Fr., 1888, 49, 89.
14. O. Doebner and W. V. Miller, Ber. Dtsch. Chem. Ges., 1881, 14, 2812.
15. (a) R. N. Monrad and R. Madsen, Org. Biomol. Chem., 2011, 9, 610; (b) H.-M. Wang, R.-S. Hou,
H.-D. Du, I.-J. Kang, and L.-C. Chen, Heterocycles, 2011, 83, 331; (c) A. Chaskar, V. Padalkar, K.
Phatangare, B. Langi, and C. Shah, Synth. Commun., 2010, 40, 2336; (d) C. S. Choa, H. BoKima, W.
X. Rena, and N. S. Yoonb, Appl. Organometal. Chem., 2010, 24, 817; (e) H. V. Mierde, P. V. D.
Voort, D. D. Vos, and F. Verpoort, Eur. J. Org. Chem., 2008, 1625; (f) B. R. McNaughton and B. L.
Miller, Org. Lett., 2003, 5, 4257.
16. (a) B. Karatas and R. Aumann, Organometallics, 2010, 29, 801; (b) C. Ramesh, V. Kavala, C.-W.
Kuo, and C.-F. Yao, Tetrahedron. Lett., 2010, 51, 5234; (c) K. Selvam and M. Swaminathan,
Tetrahedron. Lett., 2010, 51, 4911; (d) C. S. Cho, T. G. Kim, H. W. Kim, Catal. Commun., 2009, 10,
1482; (e) X. F. Lin, S. L. Cui, and Y. G. Wang, Tetrahedron Lett., 2006, 47, 3127; (f) O. B. Familoni,
P. J. Klaas, K. A. Lobb, V. E. Pakade, and P. T. Kaye, Org. Biomol. Chem., 2006, 4, 3960; (g) S.
Anguille, J.-J. Brunet, N. C. Chu, O. Diallo, C. Pages, and S. Vincendeau, Organometallics, 2006, 25,
2943; (h) M. Kitamura, M. Yoshida, T. Kikuchi, and K. Narasaka, Synthesis, 2003, 2415; (i) J. Jacob,
C. M. Cavalier, W. D. Jones, S. A. Godleski, and R. R. Valente, J. Mol. Catal. A-Chem., 2002,
182-183, 565; (j) M. Beller, O. R. Thiel, H. Trauthweinm, and C. G. Hartung, Chem. Eur. J., 2000, 6,
2513.
17. (a) R. G. Bulgakov, S. P. Kuleshov, R. R. Vafin, and U. M. Dzhemilev, Russ. J. Org. Chem., 2009,
45, 944; (b) S.-Y. Tanaka, M. Yasuda, and A. Baba, J. Org. Chem., 2006, 71, 800.
18. (a) J. Akbari, A. Heydari, H. R. Kalhor, and S. A. Kohan, J. Comb. Chem., 2010, 12, 137; (b) D.
Fang, K. Gong, D.-Z. Zhang, and Z.-L. Liu, Monatsh. Chem., 2009, 140, 1325; (c) D. Fang, J. Luo,
X.-L. Zhou, and Z.-L. Liu, Catal. Lett., 2007, 116, 76.
19. G. C. Vougioukalakis and R. H. Grubbs, Chem. Rev., 2010, 110, 1746.
20. X. S. Wang, Q. Li, M. M. Zhang, C. S. Yao, and S. J. Tu, J. Heterocycl. Chem., 2008, 45, 1027.
21. L. Li and W. D. Jones, J. Am. Chem. Soc., 2007, 129, 10707.
22. (a) S. K. Guchhait, K. Jadeja, and C. Madaan, Tetrahedron Lett., 2009, 50, 6861; (b) N. Shindoh, H.
Tokuyama, Y. Takemoto, and K. Takasu, J. Org. Chem., 2008, 73, 7451.