Rare-earth metal chlorides catalyzed one-pot syntheses of quinolines under solvent-free microwave irradiation conditions

Article abstract of DOI:10.1002/cjoc.201300047

Under microwave irradiation and solvent-free conditions, rare-earth metal chlorides (RECl₃) have been efficient catalysts for one-pot synthesis of quinoline derivatives to give products in good to excellent yields through the multi-component reactions of aldehydes, amines, and alkynes. The rare-earth metal chlorides can be recycled for six times without notable loss of catalytic activities. This new synthetic approach has prominent features of a short reaction time, high yields of products, operational simplicity, broad substrate scopes, environmentally friendly property and commercially available catalysts. It extends the applications of rare-earth metal compounds as catalysts in organic synthesis. A convenient method for the syntheses of quinoline derivatives through multi-component reactions of aldehydes, amines, and alkynes in the presence of rare-earth metal chlorides as catalysts under microwave irradiation and solvent-free conditions was developed.

Full text of DOI:10.1002/cjoc.201300047

FULL PAPER
DOI: 10.1002/cjoc.201300047
Rare-Earth Metal Chlorides Catalyzed One-pot Syntheses of
Quinolines under Solvent-free Microwave
Irradiation Conditions
Lijun Zhang,*,a Bing Wu,a Yongqing Zhou,a Jing Xia,a Shuangliu Zhou,a and Shaowu Wang*,a,b
a Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based
Materials, Institute of Organic Chemistry, College of Chemistry and Materials Science,
Anhui Normal University, Wuhu, Anhui 241000, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Shanghai 200032, China
Under microwave irradiation and solvent-free conditions, rare-earth metal chlorides (RECl3) have been efficient
catalysts for one-pot synthesis of quinoline derivatives to give products in good to excellent yields through the mul-
ti-component reactions of aldehydes, amines, and alkynes. The rare-earth metal chlorides can be recycled for six
times without notable loss of catalytic activities. This new synthetic approach has prominent features of a short re-
action time, high yields of products, operational simplicity, broad substrate scopes, environmentally friendly prop-
erty and commercially available catalysts. It extends the applications of rare-earth metal compounds as catalysts in
organic synthesis.
Keywords rare earth, quinoline, multi-component reaction, microwave irradiation, recyclable
Introduction
been reported.[13] For example, the AuCl3/CuBr[14] and
[15]
FeCl3
catalyzed three-component reaction of alde-
Quinoline derivatives are ubiquitous structural mo-
tifs in many natural products and biologically active
pharmaceuticals such as anti-ulcerative, anticancer and
antihistaminic.[1] Additionally, substituted quinoline
derivatives have also been employed as ligands for the
preparation of OLED phosphorescent complexes[2] and
fluorescent probes in bioimaging studies.[3] Owing to
various applications of quinoline derivatives, their syn-
theses had been extensively studied. The syntheses of
this type of compounds can be achieved from the classic
Skraup reaction,[4] Skraup-Doebner-Von Miller reaction[5]
Friedländer reaction,[6] Povarov reaction,[7] Morita-
Baylis-Hillman reaction,[8] and the dimerization reac-
tion.[9] However, most of these synthetic methods re-
quired use of complicated or unstable starting materials
such as 2-aminobenzaldehyde, and provided low yields
of products due to low reaction efficiency. Thus, devel-
opment of a new synthetic strategy for the efficient con-
struction of quinolines and some related heterocycles is
still attractive. This leads to the recent development of
cascade (domino) reactions[10] for the generation of qui-
hydes, alkynes, and amines have been reported recently.
However, most of these improved synthetic methods
used expensive catalysts or a long reaction time and
provided relatively low yields of products. To increase
the compatibility with the environment, studies on the
recyclable catalysts in the syntheses of quinolines have
attracted growing research interests. However, only few
reports have been reported and generally required PEG
or ionic liquids as the media.[16]
Rare-earth metal chlorides (RE＝Y, Ln), as simple
Lewis acid catalysts,[17] have shown high catalytic ac-
tivities in many organic reactions such as the Biginelli-
type reaction for the synthesis of 1,5-benzodiazepine
derivatives,[18] the condensation reaction for the synthe-
sis of α-amino phosphonate,[19] the C-acylation of
1,3-dicarbonyl compounds,[20] the reductive dehaloge-
nation of halogen-containing hydrocarbons with diiso-
butylaluminum hydride.[21] Our previous studies have
shown that rare-earth metal chlorides displayed high
catalytic activities on the Cannizzaro-reaction of alde-
hydes and lithium amide giving amides and alcohols,[22]
and the introduction of microwave irradiation can im-
prove the performance of these catalysts.[23] Herein, we
report a RECl3-catalyzed one-pot syntheses of quinoline
＋
[11]
nolines, including Rh(cod)2 BF4/2 PPh3
and solid
acid[12] catalyzed domino reactions. Meanwhile, the us-
age of simple substrates as starting materials has also
*
E-mail: zljun@mail.ahnu.edu.cn; swwang@mail.ahnu.edu.cn; Tel.: (86)553-3869310; Fax: (86)553-3883517
Received January 17, 2013; accepted March 4, 2013; published online April 3, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300047 or from the author.
Chin. J. Chem. 2013, 31, 465—471
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465

Zhang et al.
FULL PAPER
derivatives under microwave irradiation and solvent-
free conditions.
118.9; MS (EI) calcd for C21H14NCl (M＋) 315.6, found
316.1.
2-(4-Nitrophenyl)-4-phenylquinoline (4e)[25] Yield
1
61%; white solid. H NMR (CDCl3, 300 MHz) δ: 8.40
Experimental
(s, 3H), 8.27 (d, J＝7.8 Hz, 2H), 7.95 (d, J＝7.74 Hz,
1H), 7.87 (s, 1H), 7.80 (s, 2H ), 7.57 (s, 5H); 13C NMR
(CDCl3, 75.0 MHz) δ: 154.1, 149.9, 148.8, 148.4, 145.5,
137.9, 130.3, 130.1, 129.5, 128.7, 128.4, 127.3, 126.2,
125.8, 124.0, 119.1; MS (EI) calcd for C21H14N2O2 (M＋)
326.1, found 327.2.
General experimental procedures
The reagents were purchased and used without fur-
ther purification unless otherwise stated. All of the mi-
crowave-assisted reactions were performed in a CEM
Discover monomode apparatus at the indicated maxi-
mum temperature and power setting. H and 13C NMR
1
2-(2-Methoxyphenyl)-4-phenylquinoline
(4f)
1
Yield 79%; white solid. H NMR (CDCl3, 300 MHz) δ:
8.87 (s, 1H), 7.94－7.84 (m, 3H), 7.74－7.72 (m, 1H),
7.57－7.41 (m, 7H), 7.17－7.14 (m, 1H), 7.04 (d, J＝
7.89 Hz, 1H), 3.86 (s, 3H); 13C NMR (CDCl3, 75.4
MHz) δ: 157.2, 156.7, 148.8, 147.4, 138.6, 131.5, 130.4,
130.0, 129.7, 129.1, 128.5, 128.2, 126.3, 125.6, 123.7,
121.3, 111.4, 55.7; HRMS (EI) calcd for C22H17NO (M＋)
311.1310, found 311.1304.
spectra were recorded on a Bruker AV-300 MHz spec-
trometer in CDCl3. Mass spectra were performed on a
Micromass GCT-MS.
General procedure for the RECl3-catalyzed synthe-
ses of quinoline derivatives
To a 10 mL flask were charged with RECl3 (0.15
mmol), aldehyde (1.0 mmol), amine (1.0 mmol) and
alkyne (1.50 mmol) under atmosphere. The mixture was
stirred at room temperature for a few minutes then it
was exposed to the MW (700 W) irradiation condition
in Al2O3 bath at 180 ℃ for 8 min. The mixture was
cooled to room temperature and extracted with Et2O.
The residue was purified by flash column chromatogra-
phy (petroleum ether/ethyl acetate＝100/1, V/V) to af-
ford compounds 4a－4q.
2-(2,4-Dichlorophenyl)-4-phenylquinoline
(4g)
1
Yield 74%; white solid. H NMR (CDCl3, 300 MHz) δ:
8.24 (d, J＝7.71 Hz, 1H), 7.99 (d, J＝8.37 Hz, 1H),
7.77－7.69 (m, 3H), 7.55－7.40 (m, 6H), 7.26－7.22
(m, 2H); 13C NMR (CDCl3, 75.0 MHz) δ: 156.8, 148.6,
148.3, 138.1, 137.9, 135.2, 133.2, 132.7, 130.8, 130.0,
129.9, 129.7, 129.6, 128.7, 128.6, 127.6, 127.0, 125.8,
122.8; HRMS (EI) calcd for C21H13Cl2N (M＋) 349.0425,
found 349.0419.
2,4-Diphenylquinoline (4a)[24] Yield 92%; yellow
1
solid. H NMR (CDCl3, 300 MHz) δ: 8.28－8.19 (m,
2-Mesityl-4-phenylquinoline (4h)
Yield 78%;
3H), 7.93－7.72 (m, 4H), 7.56－7.50 (m, 8H); 13C
NMR (CDCl3, 75.0 MHz) δ: 156.9, 153.5, 149.3, 148.8,
139.6, 138.4, 130.1, 129.6, 129.4, 128.9, 128.6, 128.4,
127.6, 126.4, 125.7, 119.4, 115.1; HRMS (EI) calcd for
C21H15N (M＋) 281.1204, found 281.1196.
1
yellow oil. H NMR (CDCl3, 300 MHz) δ: 8.25 (d, J＝
6.72 Hz, 1H), 8.01 (d, J＝8.16 Hz, 1H), 7.75－7.73 (m,
1H), 7.54 (dd, J＝6.09, 6.09 Hz, 5H), 7.33 (s, 2H), 6.97
(s, 2H), 2.34 (s, 3H), 2.12 (s, 6H); 13C NMR (CDCl3,
75.0 MHz) δ: 160.2, 148.7, 148.6, 138.1, 137.8, 137.7,
135.7, 130.0, 129.7, 129.4, 128.6, 128.5, 128.4, 126.4,
125.7, 125.2, 123.1, 21.1, 20.3; HRMS (EI) calcd for
C24H21N (M＋) 323.1674, found 323.1670.
2-(4-Methoxyphenyl)-4-phenylquinoline (4b)[25]
Yield 91%; yellow solid. 1H NMR (CDCl3, 300 MHz) δ:
8.24－8.17 (m, 3H), 7.88 (d, J＝8.25 Hz, 1H), 7.78－
7.69 (m, 2H), 7.56－7.39 (m, 5H), 7.20 (d, J＝7.92 Hz,
1H), 7.06 (d, J＝8.37 Hz, 2H), 3.90 (s, 3H); 13C NMR
(CDCl3, 75.0 MHz) δ: 160.7, 156.5, 149.1, 148.8, 138.5,
132.2, 129.9, 129.6, 129.5, 128.9, 128.6, 128.4, 126.0,
125.6, 125.5, 118.9, 114.2, 55.4; MS (EI) calcd for
C22H17NO (M＋) 311.1, found 312.2.
2-Cyclopentyl-4-phenylquinoline (4i) Yield 50%;
1
yellow oil. H NMR (CDCl3, 300 MHz) δ: 8.13 (d, J＝
8.31 Hz, 1H), 7.83 (d, J＝8.28 Hz, 1H), 7.71 (dd, J＝
7.50, 7.50 Hz, 1H), 7.54－7.43 (m, 5H), 7.30－7.29 (m,
2H), 3.48－3.41 (m, 1H), 2.25－2.23 (m, 4H), 1.93－
1.79 (m, 4H); 13C NMR (CDCl3, 75.0 MHz) δ: 165.8,
148.5, 148.2, 138.5, 129.6, 129.3, 129.2, 128.5, 128.3,
125.7, 125.6, 125.5, 120.2, 48.9, 33.7, 26.1; HRMS (EI)
calcd for C21H19N (M＋) 273.1517, found 273.1509.
4-Phenyl-2-(p-tolyl)quinoline (4c)[26] Yield 89%;
white solid. 1H NMR (CDCl3, 300 MHz) δ: 8.25 (d, J＝
7.65 Hz, 2H), 8.11 (d, J＝6.69 Hz, 2H), 7.90 (d, J＝
7.74 Hz, 2H), 7.81 (s, 1H), 7.73 (s, 1H), 7.56－7.47 (m,
5H), 7.34 (d, J＝6.57 Hz, 1H), 2.44 (s, 3H); 13C NMR
(CDCl3, 75.0 MHz) δ: 156.9, 149.1, 148.8, 139.5, 138.5,
136.9, 130.1, 129.6, 129.5, 128.6, 128.4, 127.5, 126.2,
125.7, 125.6, 119.2, 21.4; MS (EI) calcd for C21H17N
(M＋) 295.1, found 296.2.
6-Methyl-2,4-diphenylquinoline (4j)[27]
Yield
93%; yellow solid. 1H NMR (CDCl3, 300 MHz) δ: 8.17
(dd, J＝7.64, 7.64 Hz, 3H), 7.78 (s, 1H), 7.65 (s, 1H),
7.56－7.46 (m, 9H), 2.49 (s, 3H); 13C NMR (CDCl3,
75.0 MHz) δ: 156.0, 148.5, 147.4, 139.8, 138.7, 136.3,
131.8, 129.8, 129.6, 129.2, 128.8, 128.6, 128.3, 127.5,
125.7, 124.4, 119.5, 21.8; MS (EI) calcd for C22H17N
(M＋) 295.1, found 296.2.
2-(4-Chlorophenyl)-4-phenylquinoline
(4d)[24]
1
Yield 82%; white solid. H NMR (CDCl3, 300 MHz) δ:
8.24－8.15 (m, 3H), 7.89 (s, 2H), 7.79－7.75 (m, 3H),
7.56－7.49 (m, 6H); 13C NMR (CDCl3, 75.0 MHz) δ:
155.6, 149.5, 148.8, 138.3, 138.0, 135.6, 130.1, 129.7,
129.6, 129.0, 128.9, 128.7, 128.5, 126.6, 125.8, 125.7,
6-Methoxy-2,4-diphenylquinoline (4k)[24] Yield
1
91%; white solid. H NMR (CDCl3, 300 MHz) δ: 8.16
(d, J＝7.8 Hz, 3H), 7.78 (s, 2H), 7.58－7.39 (m, 8H),
7.20 (s, 1H), 3.81 (s, 3H); 13C NMR (CDCl3, 75.0 MHz)
466
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Chin. J. Chem. 2013, 31, 465—471

Rare-Earth Metal Chlorides Catalyzed One-pot Syntheses of Quinolines
δ: 157.8, 154.7, 147.8, 144.9, 139.8, 138.8, 131.6, 129.4,
129.0, 128.8, 128.7, 128.4, 127.3, 126.7, 121.9, 119.7,
103.7, 55.5; MS (EI) calcd for C22H17N (M＋) 311.1,
found 312.2.
Results and Discussion
Optimization of the reaction conditions.
Initially, benzaldehyde, aniline and phenylacetylene
were used as model substrates for optimization of the
reaction conditions, which include the reaction tem-
perature, microwave oven power, time of irradiation,
and reactant ratios, results were summarized in Table 1.
Raising the reaction temperature under conventional
thermal conditions leads to an increased yield of the
target product (Table 1, Entries 1－3). Microwave irra-
diation presents a powerful tool toward this reaction
(Table 1, Entries 4－6). The microwave oven power
influences the reaction efficiency of this reaction, and a
79% yield of product was achieved at 700 W (180 ℃)
(Table 1, Entry 8). Increment of the microwave oven
power to 800 W (180 ℃) showed no significant in-
creasing of the yield of the product (Table 1, Entry 9).
Performance of this reaction with irradiation times of 6,
8, and 10 min at 700 W (180 ℃) afforded the corre-
sponding products with yields of 60%, 79% and 80%,
respectively (Table 1, Entries 8 and 10－12). Thus the
optimized microwave irradiation was set at 700 W for 8
min. Under these conditions, we then obtained that the
best ratio of the substrates was 1∶1∶1.5 under sol-
vent-free in the presence of 10 mol% YCl3 as a catalyst
(Table 1, Entry 17). Reaction of benzaldehyde, aniline
and phenylacetylene catalyzed by hydrated lanthanide
chloride, YCl3•6H2O, was tested. The reaction pro-
ceeded highly efficiently (Table 1, Entry 19). So our
microwave assisted reactions were performed at atmos-
pheric condition without the usage of Schlenck tech-
nique.
6-Bromo-2,4-diphenylquinoline (4l)[28]
Yield
82%; white solid. m.p. 157－159 ℃; 1H NMR (CDCl3,
300 MHz) δ: 8.19 (d, J＝7.11 Hz, 2H), 8.12 (d, J＝8.88
Hz, 1H), 8.04 (s, 1H), 7.84－7.79 (m, 2H), 7.56－7.51
(m, 8H); 13C NMR (CDCl3, 75.0 MHz) δ: 157.2, 148.4,
147.4, 139.2, 137.7, 133.0, 131.8, 129.7, 129.5, 128.9,
128.8, 128.7, 127.8, 127.6, 127.0, 120.5, 120.1; MS (EI)
calcd for C21H14NBr (M＋) 359.0, found 360.1.
8-Methyl-2,4-diphenylquinoline (4m)[29]
Yield
73%; yellow oil. 1H NMR (CDCl3, 300 MHz) δ: 8.30 (d,
J＝7.05 Hz, 2H), 7.85 (s, 1H), 7.74 (d, J＝8.22 Hz, 1H),
7.61－7.47 (m, 9H), 7.37 (dd, J＝7.56, 7.56 Hz, 1H),
2.97 (s, 3H); 13C NMR (CDCl3, 75.0 MHz) δ: 155.0,
149.3, 147.7, 139.8, 139.0, 138.0, 132.6, 129.6, 129.3,
128.8, 128.5, 128.3, 127.5, 126.0, 125.7, 123.6, 118.7,
18.4; MS (EI) calcd for C22H17N (M＋) 295.1, found
296.2.
6-Nitro-2,4-diphenylquinoline (4n)[24] Yield 63%;
1
Yellow solid. H NMR (CDCl3, 300 MHz) δ: 8.87 (s,
1H), 8.51 (d, J＝7.71 Hz, 1H), 8.36－8.26 (m, 4H),
7.99 (s, 1H), 7.61 (s, 7H); 13C NMR (CDCl3, 75.0 MHz)
δ: 160.1, 151.3, 149.1, 145.4, 138.5, 136.9, 131.8, 130.5,
129.5, 129.3, 129.2, 129.1, 127.9, 124.8, 123.1, 122.9,
120.7; MS (EI) calcd for C22H17NO (M＋) 326.1, found
327.2.
7-Nitro-2,4-diphenylquinoline (4o) Yield 69%;
1
brown solid. H NMR (CDCl3, 300 MHz) δ: 8.47 (d,
J＝8.16 Hz, 1H), 8.23 (d, J＝6.42 Hz, 2H), 7.95 (s, 1H),
7.88 (d, J＝7.14 Hz, 1H), 7.79 (dd, J＝7.50, 7.80 Hz,
1H), 7.56－7.43 (m, 8H); 13C NMR (CDCl3, 75.0 MHz)
δ: 158.0, 149.5, 148.4, 147.1, 138.8, 138.2, 135.1, 130.2,
129.0, 128.9, 128.7, 127.8, 127.7, 127.4, 123.5, 117.8,
103.2; HRMS (EI) calcd for C21H14N2O2 (M＋) 326.1055,
found 326.1050.
Scopes of this reaction
Under the optimum reaction conditions, the scopes
of YCl3-catalyzed reaction were investigated, and the
results were summarized in Table 2. Despite of the aro-
matic aldehydes having electron-donating or electron-
withdrawing groups, the reaction proceeded smoothly
generating the desired quinoline derivatives in moderate
to good yields (Table 2, Entries 1－3 and 5). Reaction
of the aldehydes having electron-withdrawing substitu-
ent such as 4-nitrobenzaldehyde, aniline and phenyla-
cetylene gave a moderate yield of the product 4e (Table
2, Entry 5). However, the high yields of products with
the aldehydes having electron-rich substituents may be
due to the enhancement of the coordination ability of
aldehydes to the Lewis acid (YCl3), which may assist
the subsequent addition of amine group to the carbonyl
group. For the sterically hindered substrates such as
2-CH3OC6H4CHO, 2,4-Cl2C6H3CHO and 2,4,6-(CH3)3-
C6H2CHO, the products 4f－4h were obtained in mod-
erate yields (Table 2, Entries 6－8). Additionally, the
application of aliphatic aldehyde for this reaction also
gave the desired product (Table 2, Entry 9) in a compa-
rable result to the literature.[15]
2,4-Diphenylbenzo[h]quinoline (4p)[30]
Yield
1
90%; white solid. H NMR (CDCl3, 300 MHz) δ: 9.59
(d, J＝7.71 Hz, 1H), 8.42 (d, J＝7.26 Hz, 2H), 7.98 (s,
1H), 7.91 (d, J＝7.92 Hz, 1H), 7.83－7.72 (m, 4H),
7.58－7.49 (m, 8H); 13C NMR (CDCl3, 75.0 MHz) δ:
154.9, 149.1, 146.7, 139.7, 138.9, 133.6, 132.6, 129.7,
129.3, 128.9, 128.6, 128.3, 128.2, 127.6, 127.5, 127.3,
126.9, 125.3, 123.4, 122.9, 119.5; MS (EI) calcd for
C25H117N (M＋) 331.1, found 332.2.
2-Phenyl-4-(p-tolyl)quinoline (4q)[31] Yield 87%;
1
yellow oil. H NMR (CDCl3, 300 MHz) δ: 8.28－8.20
(m, 3H), 7.95 (d, J＝8.34 Hz, 1H), 7.83 (s, 1H), 7.77－
7.74 (m, 1H), 7.57－7.47 (m, 6H), 7.38 (d, J＝7.77 Hz,
2H), 2.50 (s, 3H); 13C NMR (CDCl3, 75.0 MHz) δ:
156.9, 149.3, 148.9, 139.8, 138.4, 135.5, 130.2, 129.6,
129.4, 128.9, 127.7, 126.3, 125.9, 125.8, 119.4, 21.4;
MS (EI) calcd for C22H17N (M＋) 295.1, found 296.2.
Chin. J. Chem. 2013, 31, 465—471
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
467

Zhang et al.
Table 1 Screening the optimized reaction conditions for the synthesis of 2,4-diphenylquinoline under YCl3-catalyzed conditiona
FULL PAPER
CHO
NH2
YCl3
+
+
MW, Solvent-free
N
1a
2a
3a
4a
Entry
1d
2d
3d
4
Ratiob
Cat./%
10
10
10
10
10
10
10
10
10
10
10
10
0
Time
Solvent
Toluene
Toluene
－
T/℃
Yieldc/%
26
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1
1∶1∶1.3
1∶1∶1.5
1∶1∶2.0
1∶1∶1.5
24 h
r.t.
24 h
Reflux
130
38
24h
45
10 min
10 min
10 min
10 min
10 min
10 min
12 min
8 min
6 min
10 min
8 min
8 min
8 min
8 min
8 min
8 min
－
130 (MW, 500W)
150 (MW, 500W)
180 (MW, 500W)
180 (MW, 600W)
180 (MW, 700W)
180 (MW, 800W)
180 (MW, 700W)
180 (MW, 700W)
180 (MW, 700W)
180 (MW, 500W)
180 (MW, 700W)
180 (MW, 700W)
180 (MW, 700W)
180 (MW, 700W)
180 (MW, 700W)
180 (MW, 700W)
58
5
－
65
6
－
73
7
－
73
8
－
79
9
－
80
10
11
12
13
14
15
16
17
18
19e
－
80
－
79
－
60
－
trace
72
8
－
15
10
10
10
10
－
79
－
84
－
92
－
93
－
90
a
b
Reaction conditions: benzaldehyde (1.0 mmol), aniline (1.0 mmol), solvent (10 mL). Mole ratio (benzaldehyde∶aniline∶
phenylacetylene). c Isolated yield. d Performed under conventional thermal conditions. e Catalyzed by 10 mol% YCl3•6H2O.
Then, the scopes of amines were examined for this
reaction (Table 2, Entries 10－16). It is found that aro-
matic amines containing either an electron-donating
group or an electron-withdrawing group proceeded
smoothly for this reaction to give the corresponding
quinolines in moderate to good yields (Table 2, Entries
10－15). It is worth noticed that a bulky 1-naphthamine
was also suitable for this reaction and smoothly gener-
ated the desired product 4p in 90% yield (Table 2, Entry
16). Substituted phenylacetylene was also suitable for
this transformation with isolation of the expected prod-
uct 4q in 89 % yield (Table 2, Entry 17).
In comparison with results obtained with other cata-
lysts,[14,15] our reactions show the advantages of wide
range of aromatic amines and phenylacetylenes and
aromatic or aliphatic aldehydes producing the products
in good to excellent yields within a short reaction time
(8 min).
3, most of the rare-earth metal chlorides exhibited well
to high catalytic activities for this reaction. The absence
of rare-earth metal chlorides led to only trace amount of
the product.
Proposed mechanism of the reaction
Based on these experimental results, a tentative
mechanism was proposed as shown in Scheme 1. The
coordination of aldehyde to RECl3 with subsequent
condensation with amine leads to the formation of the
imine, which undergoes nucleophilic attack by phenyla-
cetylene to give a propargylamine intermediate A. In-
termediate A further undergoes intramolecular cycliza-
tion to give intermediate B, which undergoes isomeriza-
tion and further oxidation to give the quinoline prod-
uct.[16a]
Recycle of the catalyst
The facts that rare-earth metal chlorides are not very
sensitive to water and air and are stable at high tem-
perature, the recycle of catalyst was tested. Although
there are many reports about the recyclization of rare-
Effect of rare-earth metals
Results indicated that rare-earth metals have a little
effect on the activity of this reaction. As shown in Table
468
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 465—471

Rare-Earth Metal Chlorides Catalyzed One-pot Syntheses of Quinolines
Table 2 Synthesis of quinoline derivatives by YCl3-catalyzed three-component reaction of aldehydes, alkynes, and aminesa
R3
NH2
10 mol% YCl3
R1 CHO
+
+
MW, 180 οC, 8 min
Solvent-free
N
R1
R2
R2
R3
1
3
4
2
Entry
R1
R2
R3
H
H
H
H
H
H
H
H
Product
4a
Yieldb/%
92
1
2
3
4
5
6
7
8
C6H5
H
H
H
H
H
H
H
H
4-CH3OC6H4
4-CH3C6H4
4-ClC6H4
4b
91
4c
89
4d
82
4-O2NC6H4
2-CH3OC6H4
2,4-Cl2C6H3
4e
61
4f
79
4g
74
2,4,6-(CH3)3C6H2
4h
78
9
H
H
4i
50
10
11
12
13
14
15
16
17
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-CH3
H
H
4j
93
91
83
73
63
69
90
89
4-CH3O
4-Br
4k
4l
H
2-CH3
4-O2N
3-O2N
2-Naphthyl
H
H
4m
4n
4o
4p
4q
H
H
H
4-CH3
a Aldehyde (1.0 mmol); amine (1.0 mmol); alkyne (1.5 mmol), MW irradiation (700 W). b Isolated yield.
Scheme 1 Proposed mechanism for the formation of quinoline derivatives
Chin. J. Chem. 2013, 31, 465—471
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
469

Zhang et al.
FULL PAPER
Table 3 Catalytic activities of rare earth metal chloridesa
2009, 17, 4441; (c) Welsch, M. E.; Snyder, S. A.; Stockwell, B. R. Curr.
Opin. Chem. Biol. 2010, 14, 347.
RE
No
Y La Ce Pr Nd Sm Eu Gd Dy Tm Yb
[2] (a) Kim, J. I.; Shin, I.-S.; Lee, J.-K. J. Am. Chem. Soc. 2005, 127, 1614;
(b) Thompson, M. E.; Ma, B.; Djurovich, P. US 20050164031A1, 2005.
[3] (a) Sheng, R.; Wang, P.; Gao, Y.; Wu, Y.; Liu, W.; Ma, J.; Li, H.; Wu, S.
Org. Lett. 2008, 10, 5015; (b) Jung, H. S.; Kwon, P. S.; Lee, J. W.; Kim,
J. I.; Hong, C. S.; Kim, J. W.; Yan, S.; Lee, J. Y.; Lee, J. H.; Joo, T.; Kim,
J. S. J. Am. Chem. Soc. 2009, 131, 2008; (c) Laras, Y.; Hugues, V.;
Chandrasekaran, Y.; Blanchard-Desce, M.; Acher, F. C.; Pietrancosta, N.
J. Org. Chem. 2012, 77, 8294.
Yield/% trace 92 80 82 87 89 90 83 83 86 88 89
a Reaction of benzaldehyde (1.0 mmol), aniline (1.0 mmol) with
phenylacetylene (1.5 mmol) catalyzed by 10 mol% RECl3 at 180
℃ for 8 min under MW irradiation (700 W) and solvent-free
conditions.
earth triflates RE(OTf)3,[32,16a] few studies have been
performed on the recyclization of rare-earth metal chlo-
rides. After the crude reaction product was extracted
with diethyl ether (3×10 mL), the remaining rare-earth
metal chloride was directly used as a catalyst for the
reaction of benzaldehyde, aniline and phenylacetylene
(1∶1∶1.5) under the above indicated conditions. As
shown in Figure 1, the catalyst can be recycled for six
times with only a slight decrease of the catalytical per-
formance attributed to the slight loss of the amount of
RECl3 during separation of the reaction products.
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Figure 1 Results of six consecutive cycles of the catalyst.
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Conclusions
In summary, we have developed a facile one-pot
synthesis of the substituted quinolines from readily
available simple starting materials of aldehydes, alkynes,
and amines under solvent-free and microwave irradia-
tion conditions. This reaction features a short reaction
time, broad scope of substrates, solvent-free conditions,
readily available and recyclable catalysts, and easy
operation, which may have a potential application in the
synthesis of quinoline derivatives.
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Acknowledgement
[14] Xiao, F.; Chen, Y.; Liu, Y.; Wang, J. Tetrahedron 2008, 64, 2755.
[15] Cao, K.; Zhang, F.-M.; Tu, Y.-Q.; Zhuo, X.-T.; Fan, C.-A. Chem. Eur. J.
2009, 15, 6332.
The work was supported by the National Natural
Science Foundation of China (21172004, 21172003 and
21072004), the National Basic Research Program of
China (2012CB821604), and grants from the Ministry
of Education (20103424110001).
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