Lithium triflate (LiOTf): A highly efficient and reusable catalytic system for the synthesis of diversified quinolines under neat conditions

Article abstract of DOI:10.1007/s00706-012-0906-2

A series of diverse polyfunctionalized quinolines were easily prepared in excellent yields via a Friedlander reaction of o-aminoaryl ketone or o-aminoaryl aldehyde with α-methylene ketones using lithium triflate as an expeditious catalyst under solvent free conditions. The protocol provides a practical and straightforward approach toward highly functionalized quinoline derivatives in excellent yields. The catalyst is easily recoverable and less sensitive to moisture, which makes this protocol more advantageous.

Full text of DOI:10.1007/s00706-012-0906-2

Monatsh Chem (2013) 144:695–701
DOI 10.1007/s00706-012-0906-2
ORIGINAL PAPER
Lithium triflate (LiOTf): a highly efficient and reusable catalytic
system for the synthesis of diversified quinolines under neat
conditions
•
Amol B. Atar Someshwer D. Dindulkar
•
Yeon Tae Jeong
Received: 2 August 2012 / Accepted: 16 December 2012 / Published online: 26 February 2013
Ó Springer-Verlag Wien 2013
Abstract A series of diverse polyfunctionalized quino-
lines were easily prepared in excellent yields via a
Friedlander reaction of o-aminoaryl ketone or o-aminoaryl
aldehyde with a-methylene ketones using lithium triflate as
an expeditious catalyst under solvent free conditions. The
protocol provides a practical and straightforward approach
toward highly functionalized quinoline derivatives in
excellent yields. The catalyst is easily recoverable and less
sensitive to moisture, which makes this protocol more
advantageous.
quinolines have been employed in the study of bioorganic
and bioorganometallic processes [6]. Quinoline was first
extracted from coal tar in 1834 by Friedlieb Ferdinand
Runge [7]. Coal tar remains the principal source of com-
mercial quinoline. Many methods have been developed for
the construction of quinoline building blocks, which
include the classical Skraup, Doebner-von Miller, and
Friedlander reactions [8–11].
The best-known method for quinolines and related
polyheterocycles is the Friedlander quinoline synthesis
[12]. The Friedlander quinoline synthesis involves the
reaction between 2-aminoaryl aldehydes or ketones and
carbonyl compounds containing active methylene ketone
functionality under acidic or basic conditions. The reaction
can be promoted by acid or base catalysis or by heating.
However, under basic or thermal conditions sometimes
the reaction between 2-aminobenzophenone and simple
ketones or b-keto esters fails [11]. But recently Elena
Perez-Mayoral and co-workers reported methylaminopro-
pyl (MAP) as a basic catalyst for the Friedlander reaction
[13]. Very recently, catalysts such as ZnCl2, FeCl3,
Sc(OTf)3, Amberlite-15, CAN, [Hbim]BF4, PEG-sup-
ported sulfonic acid, I2, and LaCl3 have been shown to be
effective for the synthesis of quinoline [9, 14–21].
Although these methods insure good results in many
instances, there is still a great demand for rapid and envi-
ronment-friendly catalytic reaction conditions. Although
few of the reported methodologies have been reported
using a homogeneous Lewis acid catalyst, most of them
suffer from one or more drawbacks such as an expensive
catalyst, toxic acidic waste after reaction work up, pro-
longed reaction times, and low yields. We focused our
initial investigation to find out the best environment-
friendly catalytic system for this precious one-pot Fried-
lander reaction.
Keywords Quinolines Á Lithium triflate Á
Homogenous catalysis Á Friedlander synthesis Á
Solvent free
Introduction
The quinoline nucleus exists in numerous natural com-
pounds (cincona alkaloids) and its related precursor is
pharmacologically displaying a broad range of biological
activity [1]. The biological activities of quinoline com-
pounds have been discovered in the form of antiasthmatic,
antibacterial, anti-inflammatory, and antihypertensive
properties [2–5]. Quinoline drugs like chloroquine, pri-
maquine, and quinacrine act as antimalarial compounds
(Fig. 1). An extension of the medicinal applications,
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-012-0906-2) contains supplementary
material, which is available to authorized users.
A. B. Atar Á S. D. Dindulkar Á Y. T. Jeong (&)
Department of Image Science and Engineering,
Pukyong National University, Busan 608-737, Korea
e-mail: ytjeong@pknu.ac.kr
123

696
A. B. Atar et al.
R1
R1
R2
R3
R2
R3
NEt2
NH2
HN
HN
Li(OTf)
O
R
R
80 °C, neat
O
NH2
N
Cl
N
O
N
1
2
3
Chloroquine
Primaquine
O
O
O
Cl
O
Ph
NH2
H
NEt2
O
NH2
NH2
HN
N
1a
1b
1c
O
Scheme 1
Cl
Quinacrine
Fig. 1 The antimalarial compounds
Table 1 Reaction of 2-amino-4,5-(methylenedioxy)acetophenone
and ethyl acetoacetate in the presence of various catalysts
Entry
Catalyst (10 mol %)
Time/h
Yielda/%
Among the triflate Lewis acid catalysts, lanthanide tri-
flates are triflate salts of the lanthanide family which are
widely used in organic chemistry as Lewis acid catalysts.
The catalysts act similarly to aluminium chloride or ferric
chloride, but are stable in water, which makes it possible to
use water as a solvent instead of organic solvents. Lan-
thanide triflates consist of a lanthanide metal ion and three
triflate ions. Chemically triflate is a contraction of tri-
fluoromethanesulfonate, its molecular formula is CF3SO3
(OTf). Being a superacid, triflic acid and its conjugate base
ions are very stable. The metal triflate complex is strongly
electrophilic, thus it acts as a strong Lewis acid. So LiOTf
Lewis acids are used to catalyse a wide variety of reactions.
Recently, lithium triflate has emerged as a highly effi-
cient, mild, neutral Lewis acid and reusable catalyst for a
variety of organic transformations such as aminolysis,
glycosylation, dithioacetalization, tetrahydropyranylation
of alcohols/phenols, acetylation of alcohols, and diacety-
lation of aldehydes [22–24]. Remarkable properties like
low toxicity, air/water compatibility, operational simplic-
ity, and selectivity in reaction by suppressing side reactions
in conventional strong acid sensitive substrates makes for a
more valuable and advantageous catalyst in synthetic
organic chemistry [25, 26].
1
2
3
4
5
6
7
8
9
–
4
Trace
50
AlCl3
3
Cu(OTf)2ÁSiO2
ThiamineÁHCl
ZnCl2ÁSiO2
Cu–Sn (200 mesh, 100 mg)
TiO2ÁSiO2
2
72
1.5
2
75
85
3
40
4
60
MnCl2
3.5
0.5
65
LiOTf
96
Reaction conditions: 2-aminoaryl aldehydes or ketones (1 mmol),
carbonyl compounds containing an active methylene (1 mmol); cat-
alyst (10 mol %) at 80 °C
a
Isolated yields
can promote the synthesis of quinolines in an excellent
yield for the Friedlander reaction.
Results and discussion
In the present work, we report an efficient and environ-
mentally benign protocol for the synthesis of quinolines by
using 2-aminoaryl aldehydes or ketones and carbonyl
compounds containing an active methylene functionality in
the presence of a catalytic amount of lithium triflate under
solvent-free conditions at 80 °C (Scheme 1). Compared
with conventional organic solvents, a solvent free condition
was found to be a more effective reaction condition
recently [30].
So, in the course of our ongoing efforts in the devel-
opment of newer environmentally benign methodology for
the synthesis of useful precursors in the field of biology,
industry, and key intermediates for multistep syntheses, we
have been especially interested in exploring the potential
green catalytic system for the synthesis of medicinally
valuable moieties [27–29]. So herein we wish to report a
tandem synthesis of 1,2,3-trisubstituted quinolines from
o-aminoaryl ketone or o-aminoaryl aldehyde and a-meth-
ylene ketones using LiOTf as expeditious reusable catalyst
in an excellent yield (Scheme 1). After a series of studies,
we concluded that the catalytic amount of lithium triflate
In the optimization of the best catalytic system, the
reaction of 2-amino-4,5-(methylenedioxy)acetophenone
and ethyl acetoacetate in the presence of different catalysts
was considered as the model reaction (Table 1). In order to
establish the real effectiveness of the catalyst for the syn-
thesis of ethyl 6,8-dimethyl[1,3]dioxolo[4,5-g]quinoline-
7-carboxylate, a test reaction was performed without
123

Lithium triflate (LiOTf): highly efficient and reusable catalytic system
697
Table 2 Optimization of the LiOTf catalyzed reaction of 2-amino-
4,5-(methylenedioxy)acetophenone and ethyl acetoacetate
Table 3 Recyclability of LiOTf
Entry
Reaction cycle
Yielda/%
Entry
LiOTf/mol %
Temp/°C
Time/h
Yielda/%
1
2
3
4
a
1st (fresh run)
2nd cycle
3rd cycle
97
95
92
90
1
2
3
4
5
6
7
8
5
10
10
10
10
10
20
30
80
RT
40
2
80
64
78
85
96
90
92
90
4
4th cycle
3
60
2
Isolated yields
80
0.5
0.5
0.5
0.5
120
80
The reusability of the LiOTf catalyst is one of the most
important benefits and makes it useful for commercial
applications as well. Thus the recovery and reusability of the
catalyst were investigated. The recyclability of the catalyst in
the reaction of 2-amino-4,5-(methylenedioxy)acetophenone
and ethyl acetoacetate was checked (Table 3, entries 1–4).
The catalyst was recovered after completion of the first fresh
run, thereactionmixturecooled toroom temperatureandthen
water was added. The catalyst was dissolved in water and
product was precipitated out. The precipitated crude product
was separated by simple filtration and LiOTf was recovered
by evaporating the aqueous layer under reduced pressure, the
resulting solid LiOTf residue was again precipitated out in
acetonitrile to give the corresponding pure LiOTf (95 %
catalyst was recovered). The recovered LiOTf was dried at
90–100 °C for 12 h and tested in up to three more reaction
cycles. Thesamecatalyst wasreusedforsubsequentreactions
(three runs) with fresh substrates under the same conditions.
The catalyst showed excellent recyclability in all these
reactions (Table 3), as the reaction times and yield remained
almost the same without having the loss of catalytic activity.
To explore the scope of this methodology, reactions of
several carbonyl compounds containing active methylene
functionality with 2-aminoaryl aldehydes or ketones in the
presence of 10 mol % of LiOTf were conducted. The
results are summarized in Table 4.
80
Reaction conditions: 2-aminoaryl aldehydes or ketones (1 mmol),
carbonyl compounds containing an active methylene (1 mmol); cat-
alyst LiOTf
a
Isolated yields
catalyst. It was observed that only trace amounts of product
were observed even after a long reaction time (Table 1,
entry 1). The common Lewis acids such as Cu(OTf)2ÁSiO2,
Cu–Sn alloy (200 mesh), TiO2ÁSiO2, thiamineÁHCl, CuCl2,
AlCl3, and MnCl2 give the desired product only in mod-
erate yield after a long reaction time (Table 1, entries 2–8).
We found that lithium triflate can efficiently catalyze this
reaction and can afford the desired products in high yields
in a relatively shorter time (Table 1, entry 9).
Careful analysis of Table 1 shows that among the
screened different Lewis acid catalysts, ZnCl2ÁSiO2 give a
good yield as compared to other acid catalysts (Table 1,
entry 5). Although Cu(OTf)2ÁSiO2 (Table 1, entry 3) and
thiamineÁHCl (Table 1, entry 4) exhibited good catalytic
activity, they required more time for the completion of the
reaction. It is obvious that LiOTf demonstrated superior
catalytic activity and was the best catalyst system among
those examined (Table 1, entry 9).
Once we found LiOTf as the best catalyst for this sys-
tem, the optimization of catalyst loading and temperature
was done (Table 2, entries 3–7). Consequently, the opti-
mum 10 mol % loading of LiOTf provided the maximum
yield in minimum time (Table 2, entry 5), but while
loading of the high amount of catalyst, the reaction pro-
ceeded quite slowly with lower yield (Table 2, entries 7, 8),
on the other hand, a decrease in yield was observed by
lowering the amount of catalyst (Table 2, entry 1). Once
we found 10 mol % catalyst is the optimal amount for this
reaction, the effect of various temperatures was carried out.
We observed that the reaction proceeded with higher yield
in a short time at 80 °C under neat condition (Table 2,
entry 5). However, by increasing temperature from 100 to
120 °C, there was no significant improvement in the yield
of the reaction and neitherdoes it reduce the time. On the
contrary, there were slight decreases in yield that were
observed with elevated temperature (Table 2, entry 6).
A variety of a-methylene ketones like various substi-
tuted acetoacetates, dimedone, as well as cyclohexanone
reacted smoothly with 2-aminoaryl aldehydes or ketones
under optimized conditions. Cyclic ketones like dimedone
and cyclohexanone were reacted with o-aminoaryl ketones/
aldehydes in the same reaction conditions to afford the
corresponding tricyclic quinolines in good yields (Table 4,
compounds 3e, 3f, 3k, 3l, 3u, and 3v). Careful analysis of
Table 4 shows that the reaction of 2-aminoaryl aldehydes
and a-methylene ketones gives the corresponding product
in shorter time as compared to 2-aminoaryl ketones.
A possible mechanism of this one pot reaction has been
postulated on the basis of previously reported literature
[19]. Initially a keto–enol intermediate is formed from the
a-methylene compound, which further reacts with o-am-
inoaryl ketones/aldehydes to get an aldol type intermediate.
Subsequent dehydration of the formed aldol intermediate
123

698
A. B. Atar et al.
Table 4 Synthesis of quinoline
derivatives via LiOTf-catalyzed
Friedlander annulations
Comp.
Ketones
Time /min Yielda /% M.p. /°C
Reported
m.p. /°C
1
20
20
30
25
97
95
92
88
146–148
128–129
119–120
96–97
–
–
–
–
3a
3b
1a
1a
1a
1a
3cb
3db
35
42
85
84
166–168
140–141
–
–
3e
3f
1a
1a
10
10
15
20
98
94
90
82
84–85
138–139
96–97
–
–
–
–
3g
3h
3ib
3jb
1b
1b
1b
1b
Reaction conditions:
2-aminoaryl aldehydes or
ketones (1 mmol), carbonyl
compounds containing an active
methylene (1 mmol); catalyst
LiOTf (10 mol %)
122–123
a
Isolated yields
15
93
152–153
–
3k
1b
b
Products were purified using
column chromatography
leads to an, a,b-unsaturated compound. Finally, intramo-
lecular dehydratative cyclization of the, a,b-unsaturated
compound proceeds by nucleophilic attack of nitrogen to
the carbonyl group to get the final target quinoline
(Scheme 2). All new compounds were completely char-
acterized by their spectral properties such as 1H, 13C NMR,
and HRMS.
Conclusion
In summary, we have described an efficient and environ-
mentally benign protocol for the synthesis of quinolines via
Friedlander condensation of 2-aminoaryl ketones/alde-
hydes with diversified a-methylene ketones using lithium
triflate as a recyclable catalyst. To the best of our
Scheme 2
TfOLi
O
O
R1
TfOLi
O
R3
OH
R2
R3
R1
NH2
R1
LiOTf
R
OH
R
R
NH2
NH2
R2
R1
N
R1
R1
R1
R3
HO
R3
R3
R2
R3
OH
R2
LiOTf
O
-H2O
-H2O
-LiOTf
H
O
R
R
R
N
H
NH2
R2
R2
NH2
R
Product
123

Lithium triflate (LiOTf): highly efficient and reusable catalytic system
699
1H), 6.10 (s, 2H), 3.98 (s, 3H), 2.61 (s, 3H), 2.53 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): d = 171.06, 153.29,
152.01, 148.96, 146.78, 141.35, 127.29, 123.39, 106.85,
102.87, 100.70, 53.46, 24.51, 17.30 ppm; HRMS (ESI):
m/z calcd for C14H13NO4 259.0845, found 259.0847.
knowledge, this is the first report on the synthesis of
quinolines using lithium triflate as a catalyst via the
Friedlander reaction. The main advantages of this present
methodology are the simple work-up, easy recovery of
catalyst, no need for anhydrous conditions, no base or any
additional activator required, and the residue was crystal-
lized from ethanol to give the pure product without further
purification.
Benzyl 6,8-dimethyl[1,3]dioxolo[4,5-g]quinoline-7-carbox-
ylate (3c, C20H17NO4)
Rf = 0.36 (hexane/ethyl acetate 7:3); m.p.: 119–120 °C;
1H NMR (400 MHz, CDCl3): d = 7.46 (d, J = 8.0 Hz,
2H), 7.42–7.34 (m, 3H), 7.28 (s, 1H), 7.19 (s, 1H), 6.09 (s,
2H), 5.42 (s, 2H), 2.57 (s, 3H), 2.48 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3): d = 170.40, 152.01, 148.95, 146.80,
141.36, 136.29, 129.85, 129.78, 106.87, 102.88, 100.67,
68.52, 62.16, 42.92, 24.50, 17.23 ppm; HRMS (ESI): m/z
calcd for C20H17NO4 335.1158, found 335.1160.
Experimental
Chemicals were purchased from Aldrich and Alfa Aesar
chemical companies. The NMR spectra were recorded in
CDCl3 on a Jeol JNM ECP 400 NMR instrument using
TMS as an internal standard. The HRMS was recorded on a
Jeol JMS-700 mass spectrometer. Melting points were
taken in open capillaries on an Electrothermal-9100
instrument (Japan).
Ethyl 6-(chloromethyl)-8-methyl[1,3]dioxolo[4,5-g]quino-
line-7-carboxylate (3d, C15H14ClNO4)
1
Rf = 0.38 (hexane/ethyl acetate 7:3); m.p.: 96–97 °C; H
NMR (400 MHz, CDCl3): d = 7.33 (s, 1H), 7.25 (s, 1H),
6.13 (s, 2H), 4.87 (s, 2H), 4.52–4.47 (m, 2H), 2.60 (s, 3H),
1.45 (t, J = 8.0 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 169.32, 152.40, 151.85, 150.04, 146.46,
143.22, 126.34, 124.99, 107.30, 103.13, 100.75, 62.99,
47.26, 47.26, 17.35, 15.16 ppm; HRMS (ESI): m/z calcd
for C15H14NO4 307.0611, found 307.0608.
General experimental procedure
To a mixture of 2-aminoaryl ketone/aldehyde (1 mmol)
and a-methylene ketone (1 mmol) was added LiOTf
(10 mol %). The resulting reaction mixture was stirred at
80 °C for a certain period as indicated in Table 4 under
conventional heating. After completion of the reaction
(monitored by TLC), the residue was diluted with 10 cm3
water. The mixture was filtered and washed with water.
The catalyst LiOTf was dissolved in water. The LiOTf was
recovered by evaporating the aqueous layer under reduced
pressure, the resulting solid LiOTf residue was again pre-
cipitated out in acetonitrile to give the corresponding pure
LiOTf. The solid crude product was easily purified by
washing with hexane or recrystallized from ethanol; in
some exceptional cases the product was subjected to col-
umn chromatography over silica gel using EtOAc (7 %) in
hexane to get pure product 3.
7,8-Dihydro-7,7,10-trimethyl[1,3]dioxolo[4,5-b]acridin-
9(6H)-one (3e, C17H17NO3)
Rf = 0.35 (hexane/ethyl acetate 7:3); m.p.: 166–168 °C;
1H NMR (400 MHz, CDCl3): d = 7.41 (s, 1H), 7.27 (s,
1H), 6.12 (s, 2H), 3.10 (s, 2H), 2.94 (s, 3H), 2.61 (s, 2H),
1.12 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3):
d = 201.60, 160.51, 153.10, 149.07, 148.53, 148.46,
125.38, 123.90, 106.52, 103.04, 101.72, 55.38, 49.30,
33.21, 29.28, 17.30 ppm; HRMS (ESI): m/z calcd for
C17H17NO3 283.1208, found 283.1206.
6,7,8,9-Tetrahydro-10-methyl[1,3]dioxolo[4,5-b]acridine
(3f, C15H15NO2)
Ethyl 6,8-dimethyl[1,3]dioxolo[4,5-g]quinoline-7-carbox-
ylate (3a, C15H15NO4)
Rf = 0.38 (hexane/ethyl acetate 7:3); m.p.: 140–141 °C; 1H
NMR (400 MHz, CDCl3): d = 7.24 (s, 1H), 7.17 (s, 1H),
6.03 (s, 2H), 3.02 (s, 2H), 2.80 (s, 2H), 2.40 (s, 4H), 1.88 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): d = 157.02,
150.35, 148.08, 145.04, 141.25, 127.93, 124.41, 106.38,
102.35, 100.06, 35.10, 27.93, 24.30, 23.87, 14.95 ppm;
HRMS (ESI): m/z calcd for C15H15NO2 241.1103, found
241.1105.
Rf = 0.37 (hexane/ethyl acetate 7:3); m.p.: 146–148 °C;
1H NMR (400 MHz, CDCl3): d = 7.29 (s, 1H), 7.22 (s,
1H), 6.10 (s, 2H), 4.49–4.43 (m, 2H), 2.63 (s, 3H), 2.54 (s,
3H), 1.43 (t, J = 6 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 170.58, 153.24, 151.96, 148.95, 146.73,
141.15, 127.59, 123.47, 106.87, 102.87, 100.70, 62.62,
24.49, 17.20, 15.31 ppm; HRMS (ESI): m/z calcd for
C15H15NO4 273.2839, found 273.2837.
Ethyl 6-chloro-2-methylquinoline-3-carboxylate
(3g, C13H12ClNO2)
Methyl 6,8-dimethyl[1,3]dioxolo[4,5-g]quinoline-7-carbox-
ylate (3b, C14H13NO4)
1
Rf = 0.26 (hexane/ethyl acetate 7:3); m.p.: 84–85 °C; H
Rf = 0.38 (hexane/ethyl acetate 7:3); m.p.: 128–129 °C;
1H NMR (400 MHz, CDCl3): d = 7.29 (s, 1H), 7.22 (s,
NMR (400 MHz, CDCl3): d = 8.62 (s, 1H), 7.96 (d,
J = 8.0 Hz, 1H), 7.83 (d, J = 2.2 Hz, 1H), 7.69 (dd,
123

700
A. B. Atar et al.
J = 2.2 Hz, 9.2 Hz, 1H), 4.45–4.42 (m, 2H), 2.97 (s, 3H),
1.45 (t, J = 8.0 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 167.23, 159.83, 147.99, 139.78, 133.45,
133.23, 131.26, 127.96, 127.40, 125.88, 62.62, 26.66,
15.34 ppm; HRMS (ESI): m/z calcd for C13H12ClNO2
249.0557, found 249.0559.
2-Chloro-5,6,7,8-tetrahydroacridine (3l, C13H12ClN)
1
Rf = 0.27 (hexane/ethyl acetate 7:3); m.p.: 86–87 °C; H
NMR (400 MHz, CDCl3): d = 7.88 (d, J = 9.2 Hz, 1H),
7.64 (d, J = 12.1 Hz, 2H), 7.51 (dd, J = 2.0 Hz, 9.0 Hz,
1H), 3.09 (t, J = 6.6 Hz, 2H), 2.94 (t, J = 6.2 Hz, 2H),
1.99–1.95 (m, 2H), 1.89–1.85 (m, 2H) ppm; 13C NMR
(100 MHz, CDCl3): d = 160.74, 145.94, 134.94, 133.04,
132.06, 130.94, 130.34, 128.76, 126.49, 34.52, 30.26,
24.10, 23.77 ppm; HRMS (ESI): m/z calcd for C13H12ClN
217.0658, found 217.0656.
Methyl 6-chloro-2-methylquinoline-3-carboxylate
(3h, C12H10ClNO2)
Rf = 0.25 (hexane/ethyl acetate 7:3); m.p.: 138–139 °C;
1H NMR (400 MHz, CDCl3): d = 8.63 (s, 1H), 7.96 (d,
J = 8.0 Hz, 1H), 7.82 (d, J = 4.0 Hz, 1H), 7.70 (dd,
J = 4.0 Hz, 8.0 Hz, 1H), 3.98 (s, 3H), 2.97 (s, 3H) ppm;
13C NMR (100 MHz, CDCl3): d = 167.62, 159.87, 148.06,
139.94, 133.56, 133.29, 131.28, 127.98, 127.37, 125.47,
53.54, 26.66 ppm; HRMS (ESI): m/z calcd for C12H10
ClNO2 235.04, found 235.04.
t-Butyl 6-chloro-2-methylquinoline-3-carboxylate
(3m, C15H16ClNO2)
1
Rf = 0.28 (hexane/ethyl acetate 7:3); m.p.: 98–99 °C; H
NMR (400 MHz, CDCl3): d = 8.51 (s, 1H), 7.95 (d,
J = 9.2 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.68 (dd,
J = 2.4 Hz, 8.9 Hz, 1H), 2.94 (s, 3H), 1.65 (s, 9H) ppm;
13C NMR (100 MHz, CDCl3): d = 166.71, 159.50, 147.75,
139.31, 133.15, 133.09, 131.18, 127.89, 127.70, 127.51,
83.49, 29.28, 26.70 ppm; HRMS (ESI): m/z calcd for
C15H16ClNO2 277.0807, found 277.0809.
Benzyl 6-chloro-2-methylquinoline-3-carboxylate
(3i, C18H14ClNO2)
1
Rf = 0.28 (hexane/ethyl acetate 7:3); m.p.: 96–97 °C; H
NMR (400 MHz, CDCl3): d = 8.63 (s, 1H), 7.94 (d,
J = 9.2 Hz, 1H), 7.79 (d, J = 2.2 Hz, 1H), 7.67 (dd,
J = 2.2 Hz, 8.8 Hz, 1H), 7.49–7.35 (m, 5H), 5.41 (s, 2H),
2.96 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): d =
166.95, 159.92, 140.01, 136.57, 133.60, 133.28, 131.27,
129.82, 129.65, 129.56, 128.02, 127.35, 125.44, 68.42,
26.75 ppm; HRMS (ESI): m/z calcd for C18H14ClNO2
311.0713, found 311.0710.
Ethyl 6-chloro-2-(trifluoromethyl)quinoline-3-carboxylate
(3n, C13H9ClF3NO2)
1
Rf = 0.28 (hexane/ethyl acetate 7:3); m.p.: 99–100 °C; H
NMR (400 MHz, CDCl3): d = 8.59 (s, 1H), 8.19 (d,
J = 9.2 Hz, 1H), 7.95 (d, J = 2.2 Hz, 1H), 7.83 (dd,
J = 2.2 Hz, 9.2 Hz, 1H), 4.51–4.45 (m, 2H), 1.44 (t,
J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 166.22, 146.29, 140.08, 134.44, 132.73, 129.88,
128.44, 127.78, 63.74, 14.98 ppm; HRMS (ESI): m/z calcd
for C13H9ClF3NO2 303.0274, found 303.0275.
Ethyl 6-chloro-2-(chloromethyl)quinoline-3-carboxylate
(3j, C13H11Cl2NO2)
Rf = 0.27 (hexane/ethyl acetate 7:3); m.p.: 122–123 °C;
1H NMR (400 MHz, CDCl3): d = 8.71 (s, 1H), 8.05 (d,
J = 8.8 Hz, 1H), 7.89 (d, J = 2.2 Hz, 1H), 7.75 (dd,
J = 2.2 Hz, 9.2 Hz, 1H), 5.24 (s, 2H), 4.52–4.46 (m, 2H),
1.47 (t, J = 7.1 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 166.34, 156.97, 147.65, 140.83, 134.78,
133.94, 131.95, 128.29, 128.00, 125.15, 63.11, 47.39,
15.20 ppm; HRMS (ESI): m/z calcd for C13H11Cl2NO2
283.0167, found 283.0169.
Isopropyl 6-chloro-2-methylquinoline-3-carboxylate
(3o, C14H14ClNO2)
1
Rf = 0.27 (hexane/ethyl acetate 7:3); m.p.: 96–97 °C; H
NMR (400 MHz, CDCl3): d = 8.58 (s, 1H), 7.95 (d,
J = 9.2 Hz, 1H), 7.83 (d, J = 2.2 Hz, 1H), 7.68 (dd,
J = 2.4 Hz, 8.3 Hz, 1H), 5.34–5.24 (m, 1H), 2.96 (s, 3H),
1.43 (d, J = 6.2 Hz, 4H) ppm; 13C NMR (100 MHz,
CDCl3): d = 166.82, 159.71, 147.89, 139.58, 133.33,
133.16, 131.20, 127.93, 127.41, 126.37, 70.32, 26.66,
22.98 ppm; HRMS (ESI): m/z calcd for C14H14ClNO2
263.0713, found 263.0711.
7-Chloro-3,4-dihydro-3,3-dimethylacridin-1(2H)-one
(3k, C15H14ClNO)
Rf = 0.29 (hexane/ethyl acetate 7:3); m.p.: 152–153 °C;
1H NMR (400 MHz, CDCl3): d = 8.72 (s, 1H), 7.98 (d,
J = 8.8 Hz, 1H), 7.90 (d, J = 2.2 Hz, 1H), 7.72 (dd,
J = 2.2 Hz, 8.8 Hz, 1H), 3.18 (s, 2H), 2.66 (s, 2H), 1.15 (s,
6H) ppm; 13C NMR (100 MHz, CDCl3): d = 198.61,
162.12, 149.35, 136.48, 132.95, 134.01, 131.26, 129.07,
128.38, 126.89, 53.45, 48.14, 33.76, 29.39 ppm; HRMS
(ESI): m/z calcd for C15H14ClNO 259.0764, found
259.0766.
Ethyl 6-chloro-2-propylquinoline-3-carboxylate
(3p, C15H16ClNO2)
1
Rf = 0.28 (hexane/ethyl acetate 7:3); m.p.: 72–73 °C; H
NMR (400 MHz, CDCl3): d = 8.57 (s, 1H), 7.98 (d,
J = 9.2 Hz 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.69 (dd,
J = 2.2 Hz, 9.1 Hz, 1H), 4.47–4.41 (m, 2H), 3.27 (t,
J = 7.9 Hz, 2H), 1.85-1.75 (m, 2H), 1.45 (t, J = 7.0 Hz,
3H), 1.04 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz,
123

Lithium triflate (LiOTf): highly efficient and reusable catalytic system
701
11. Marco-Contelles J, Perez-Mayoral E, Samadi A, do Carmo
Carreiras M, Soriano E (2009) Chem Rev 109:2652
12. Li AH, Beard DJ, Coate H, Honda A, Kadablbajoo M, Kleinberg
A, Laufer R, Mulvihill KM, Nigro A, Rastogi P, Siu MW, Steinig
AG, Wang T, Zwerner D, Crew AP, Mulvihill MJ (2010)
Synthesis 10:1629
CDCl3): d = 167.51, 163.24, 148.00, 139.77, 133.28,
133.18, 131.42, 127.88, 127.31, 126.01, 62.66, 40.68,
40.68, 24.31, 15.30 ppm; HRMS (ESI): m/z calcd for
C15H16ClNO2 277.0870, found 277.0872.
Ethyl 6-chloro-2-(4-nitrophenyl)quinoline-3-carboxylate
(3q, C18H13ClN2O4)
´
13. Domınguez-Fernandez F, Lopez-Sanz J, Perez-Mayoral E, Bek
D, Martın-Aranda RM, Lopez-Peinado AJ, Cejka J (2009)
´
´
´
ˇ
´
´
ChemCatChem 1:241
Rf = 0.27 (hexane/ethyl acetate 7:3); m.p.: 150–151 °C;
1H NMR (400 MHz, CDCl3): d = 8.69 (s, 1H), 8.34 (d,
J = 8.0 Hz, 2H), 8.12 (d, J = 12.0 Hz, 1H), 7.95 (s, 1H),
7.79 (t, J = 8.0 Hz, 3H), 4.26–4.23 (m, 2H), 1.17 (t,
J = 8.0 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 167.45, 157.32, 148.94, 147.79, 147.74, 139.95,
134.99, 134.16, 132.24, 130.74, 127.97, 127.84, 126.48,
124.37, 63.05, 14.88 ppm; HRMS (ESI): m/z calcd for
C18H13ClN2O4 356.0564, found 356.0566.
14. Wang J, Fan X, Zhang X, Han L (2004) Can J Chem 82:1192
15. Yadav JS, Reddy BVS, Sreedhar P, Rao RS, Nagaiah K (2004)
Synthesis 14:2381
16. Das B, Damodar K, Chowdhury N, Kumar RA (2007) J Mol
Catal 274:148
17. Sridharan V, Ribelles P, Ramos MT, Menendez JC (2009) J Org
Chem 74:5715
18. Palimkar SS, Siddiqui SA, Daniel T, Lahoti RJ, Srinivasan KV
(2003) J Org Chem 68:9371
19. Zhang X-L, Wang Q-Y, Sheng S-R, Wang Q, Liu XL (2009)
Synth Commun 39:3293
20. Wu J, Xia H-G, Gao K (2006) Org Biomol Chem 4:126
21. Chen Y, Huang J, Hwang T-L, Li TJ, Cui S, Chan J, Bio M
(2012) Tetrahedron Lett 53:3237
Acknowledgments This research work was supported by the Sec-
ond Phase of Brain Korea (BK21) Program.
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