One-pot three-component synthesis of 6-bromoquinolines and 6-iodoquinolines

Article abstract of DOI:10.1002/jccs.201000086

Three-component one-pot synthesis of some novel 6-bromoquinolines 5a-5h involving the treatment of 2-aminobenzophenone, α-methylene carbonyl compounds, and tetrabutyl-ammonium tribromide was achieved, and this reaction was extended to the preparation of 6

Full text of DOI:10.1002/jccs.201000086

616
Journal of the Chinese Chemical Society, 2010, 57, 616-621
Communication
One-Pot Three-Component Synthesis of 6-Bromoquinolines and
6-Iodoquinolines
Li-Qiang Wu* (
Wei-Wei Ma (
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China
), Xiao Wang (
),
) and Fu-Lin Yan (
)
Three-component one-pot synthesis of some novel 6-bromoquinolines 5a-5h involving the treatment
of 2-aminobenzophenone, a-methylene carbonyl compounds, and tetrabutyl-ammonium tribromide was
achieved, and this reaction was extended to the preparation of 6-iodoquinolines 6a-6e by a three-compo-
nent reaction 2-aminobenzophenone, a-methylene carbonyl compounds, and benzyltrimethylammonium
dichloroiodate in the presence of ZnCl2.
Keywords: 6-Bromoquinolines; 6-Iodoquinolines; Friedlander reation; Tetrabutylammonium
tribromide; Benzyltrimethylammonium dichloroiodate; Heterocycle; Multicomponent
reaction.
INTRODUCTION
15,9j dodecyl phosphoric acid,9k ionic liquids,10 micro-
wave,11 urea,12 poly(N-bromo-N-ethylbenzene-1,3-disul-
fonamide),13 and KOtBu14 have been shown to be effective
for the synthesis of quinolines.
Quinoline and its derivatives are important interme-
diates in organic synthesis and exhibit various physiologi-
cal properties and pharmacological activities, such as
antiparasitic,1 antitubercular,2 antibacterial,3 antifilarial,3
HIV inhibiting,4 HMG-CoA reductase inhibiting.5 In addi-
tion to medicinal applications, quinoline derivatives are
found to undergo hierarchical self-assembly into a variety
of nano-structures and meso-structures with enhanced
electronic and photonic functions.6 In addition, quinolines
have been employed in the study of bioorganic and bio-
organo-metallic processes.7 Considering the significant ap-
plications in the fields of medicinal, bioorganic, industrial
and synthetic organic chemistry, there has been tremendous
interest in developing efficient methods for the synthesis
of quinolines, such as the Combes, Pfitzinger, Skraup and
Friedlander methods.8 Among them, the Friedlander an-
nulation is still one of the most simple and straightforward
approaches for the synthesis of polysubstituted quinolines.
This method involves the acid or base catalyzed or thermal
condensation between a 2-aminoaryl ketone and another
carbonyl compound possessing an a-reactive methylene
group followed by cyclodehydration. Recently, Lewis ac-
ids, such as Ag3PW12O40,9a SnCl2,9b FeCl3,9c Mg(ClO4)2,9d
Nd(NO3)3,9e Y(OTf)3,9f NiCl2,9g and others effective agents
and methods, such as I2/CAN,9h NaHSO4–SiO2,9i Amberlyst
In continuation of our efforts to synthesis of bromo-
heterocyclic compounds using tetrabutylammonium tribro-
mide (TBATB),15 herein, we wish to report a modification
of the Friedlander reaction for the synthesis of 6-bromo-
quinolines, which involves the formation in situ of the 2-
amino-5-bromobenzophenone using TBATB as brominat-
ing agent. This latter reagent also serves as an in situ gener-
ator of HBr, which acts as a catalyst for the subsequent
Friedlander condensation. During our study, we also ob-
served the formation of 6-iodoquinolines in excellent
yields by a three-component reaction 2-aminobenzophe-
none, a-methylene carbonyl compounds, and benzyltri-
methyl ammonium dichloroiodate in the presence of ZnCl2
(Scheme I).
RESULTS AND DISCUSSION
Previously, TABAB was used as a brominating agent.
This solid reagent is considerably safe and convenient, and
has a fine selectivity. It is well known that the bromination
of amines having electron withdrawing groups in the aro-
matic ring with a calculated amount of TABAB can give the
desired p-bromo-substituted products.16 Thus, it is con-
* Corresponding author. E-mail: wliq870@163.com

Synthesis of 6-Bromoquinoline and 6-Iodoquinolines
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 617
one; cyclic ketones such as cyclopentanone and cyclohex-
anone; acyclic ketones including 2-pentanone and 2-oe-
nanthone efficiently reacted with 2-aminobenzophenone
and TBATB to produce the corresponding 6-bromoquino-
lines (Table 1).
Scheme I
Encouraged by these results, we hoped that the pres-
ent protocol could safely be extended to the condensation
reaction of 2-aminobenzophenone, a-methylene carbonyl
compounds, and benzyltrimethylammonium dichloroio-
date in same condition. Unfortunately, 6-iodoquinolines
were obtained in low yields. BTMA ICl2 is insoluble in
CH3CN or AcOH at room temperature, but the addition of
ZnCl2 increases its solubility, allowing the iodination of ar-
omatic amines to proceed smothly under mild conditions.17
In addition, we also noticed the introduction of ZnCl2 could
promote the subsequent Friedlander condensation in the re-
action, which is demonstrated by Scheme III. Therefore,
we executed the reaction in AcOH in the presence of ZnCl2.
6-Iodoquinolines were obtained in excellent yields (Table
2).
ceivable that the reaction involves the following two steps:
(1) the 2-amino-5-bromobenzophenone is initially formed
in situ using TBATB as brominating agent; (2) TBATB
serves as an in situ generator of HBr, which acts as a cata-
lyst for the the subsequent Friedlander condensation in the
second step (see Scheme II).
Scheme II
Scheme III
In a typical example, to a stirred solution of the 2-
aminobenzophenone (1 mmol) and methyl acetoacetate (1
mmol) in CH3CN (10 mL) at room temperature in a 50-mL
reactor, TBATB (1 mmol) was added in a single portion.
The vessel was sealed immediately and stirred at room tem-
perature for 10 h. After completion of the reaction (TLC),
the mixture was filtered and then poured into 50 mL satu-
rated NaHCO3 solution, extracted with 50 mL diethyl ether,
dried over sodium sulfate, and the solvent was evaporated
under reduced pressure. The residue was subjected to col-
umn chromatography over silica gel using EtOAc (8%) in
hexane to obtain pure methyl 6-bromo-2-methyl-4-phenyl-
quinoline-3-carboxylate 5a, in 83% yield, mp 118-119 °C
(Table 1, entry 1).
In summary, we have developed a simple and effi-
cient methodology to synthesize 6-bromoquinolines using
TBATB as a selective brominating agent and an efficient
generator of HBr in Friedlander reaction. In addition, a
novel and highly efficient method for the synthesis of 6-
iodoquinolines from 2-aminobenzophenone, a-methylene
carbonyl compounds, and benzyltrimethylammonium di-
chloroiodate in the presence of ZnCl2 has been also devel-
oped. The methods are associated with the benefits derived
from multicomponent reactions. We feel that this economi-
cally viable procedure will find practical utility for the
one-pot synthesis of 6-bromoquinolines and 6-iodoquino-
lines.
EXPERIMENTAL
Similarly, various 1,3-diketones such as 2,4-pentane-
dione, 5,5-dimethylcyclohexandione, 2H-indene-1,3-di-
one, 1,3-cyclohexanedione, 2-hydroxynaphthalene-1,4-di-
NMR spectra were determined on Bruker AV-400
spectrometer at room temperature using TMS as internal

618 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Wu et al.
a
Table 2. Synthesis of 6-iodoquinolines using BTMA ICl2
Time Yield
Entry
Ketone 2
6-Iodoquinolines 6
(h)
(%)
O
O
O
OMe
N
a
08
88
I
OMe
O
O
O
b
c
10
08
8
82
81
91
I
N
O
O
I
O
N
O
O
d
I
O
N
O
O
e
10
76
I
O
N
O
f
10
12
12
12
75
74
70
78
I
N
O
g
h
i
I
N
O
I
N
O
I
N
a 2-aminobenzophenone: a-methylene carbonyl compounds:
BTMA ICl2: ZnCl2 = 1:1:1:1; reactions executed in a sealed
vessel at room temperature.
standard, coupling constants (J) were measured in Hz; Ele-
mental analysis were performed by a Vario-III elemental

Synthesis of 6-Bromoquinoline and 6-Iodoquinolines
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 619
analyzer; Melting points were determined on a XT-4 binoc-
ular microscope and were uncorrected; Commercially
available reagents were used throughout without further
purification unless otherwise stated.
7-Bromo-3,3-dimethyl-9-phenyl-3,4-dihydroacridin-
1(2H)-one (5d)
1
Pallide-flavens solid; m.p. 207-208 °C. H NMR
(CDCl3, 400 MHz) d: 7.94 (d, J = 8.8 Hz, 1H), 7.83 (dd, J =
2.0, 9.2 Hz, 1H), 7.61 (d, J = 2.0, 1H), 7.53 (m, 3H), 7.19-
7.16 (m, 2H), 3.26 (s, 2H), 2.58 (m, 2H), 1.17 (s, 6H). 13
General Procedure for the synthesis of 6-bromo-
quinolines
C
To a stirred solution of the 2-aminobenzophenone (1
mmol) and a-methylene carbonyl compounds (1 mmol) in
CH3CN (10 mL) at room temperature in a 50-mL reactor,
TBATB (1 mmol) was added in a single portion. The vessel
was sealed immediately and stirred at room temperature for
10-15 h. After completion of the reaction (TLC), the mix-
ture was filtered and then poured into 50 mL saturated
NaHCO3 solution, extracted with 50 mL diethyl ether,
dried over sodium sulfate, and the solvent was evaporated
under reduced pressure. The residue was subjected to col-
umn chromatography over silica gel using EtOAc (8%) in
hexane to obtain pure 6-bromoquinolines.
NMR (CDCl3, 100 MHz) d: 197.7, 161.6, 150.0, 147.6,
136.7, 135.0, 130.3, 130.1, 128.7, 128.3, 128.0, 127.9,
123.3, 120.6, 54.2, 48.3, 32.2, 28.3. Anal. calcd for
C21H18BrNO: C 66.33, H 4.77, N 3.68; found: C 66.45, H
4.62, N 3.62.
8-Bromo-10-phenyl-11H-indeno[1,2-b]quinolin-11-one
(5e)
1
Pallide-flavens solid; m.p. 250-251 °C. H NMR
(CDCl3, 400 MHz) d: 8.12 (d, J = 7.6 Hz, 1H), 8.02 (dd, J =
3.2, 6.0 Hz, 1H), 7.83 (m, 2H), 7.73-7.69 (m, 2H), 7.61 (t, J
= 6.0 Hz, 3H), 7.52 (t, J = 14.8 Hz, 1H), 7.44 (m, 2H). 13
C
NMR (CDCl3, 100 MHz) d: 162.3, 149.0; 147.0, 143.0,
137.4, 135.5, 135.0, 132.1, 131.8, 131.4, 130.6, 129.3,
129.2, 129.1, 128.4, 124.0, 123.3, 121.7, 121.2. Anal.
calcd for C22H12BrNO: C 68.41, H 3.13, N 3.63; found: C
68.52, H 3.06, N 3.75.
Methyl 6-bromo-2-methyl-4-phenylquinoline-3-car-
boxylate (5a)
White solid; m.p. 118-119 °C. 1H NMR (CDCl3, 400
MHz) d: 7.94 (d, J = 8.8 Hz, 1H), 7.80-7.72 (m, 2H), 7.51
(m, 3H), 7.35 (m, 2H), 3.58 (s, 3H), 2.76 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d: 168.6, 155.0, 146.3, 145.4, 134.9,
133.7, 130.7, 129.1, 128.8, 128.5, 128.4, 128.0, 126.3,
120.5, 52.2, 23.8. Anal. calcd for C18H14BrNO2: C 60.69, H
3.96, N 3.93; found: C 60.50, H 4.04, N 3.89.
2-Bromo-12-phenylbenzo[b]acridine-6,11-dione (5f)
Yellow solid; m.p. 317-318 °C. 1H NMR (CDCl3, 400
MHz) d: 8.46 (dd, J = 1.2, 7.6 Hz, 1H), 8.39 (d, J = 9.2 Hz,
1H), 8.18 (m, 1H), 7.99 (dd, J = 2.0, 9.2 Hz, 1H), 7.85-7.81
(m, 2H), 7.73 (d, J = 2.0 Hz, 1H), 7.64 (t, J = 6.0 Hz, 3H),
7.28 (m, 2H). 13C NMR (CDCl3, 100 MHz) d: 182.4, 181.6,
151.9, 148.5, 147.9, 136.3, 136.2, 134.8, 134.7, 134.3,
133.5, 133.0, 130.9, 130.1, 128.6, 128.4, 127.8, 127.7,
127.6, 124.6, 124.5. Anal. calcd for C23H12BrNO2: C
66.69, H 2.92, N 3.38; found: C 66.75, H 3.06, N 3.24.
2-Bromo-9-phenyl-5,6,7,8-tetrahydroacridine (5g)
White solid, m.p. 102-103 °C. 1H NMR (CDCl3, 400
MHz) d: 7.89 (d, J = 8.8 Hz, 1H), 7.70 (dd, J = 2.4, 9.2 Hz,
1H), 7.57-7.46 (m, 4H), 7.22 (d, J = 7.2 Hz, 2H), 3.19-3.16
(m, 2H), 2.61-2.58 (m, 2H), 2.00-1.94 (m, 2H), 1.82-1.76
(m, 2H). 13C NMR (CDCl3, 100 MHz) d: 159.6, 145.6,
144.8, 136.3, 131.8, 130.2, 129.4, 129.0, 128.8, 128.0,
127.9, 127.8, 119.4, 34.2, 28.1, 22.9, 22.8. Anal. calcd for
C19H16BrN: C 67.47, H 4.77, N 4.14; found: C 67.31, H
4.82, N 4.05.
1-(6-Bromo-2-methyl-4-phenylquinolin-3-yl)ethanone
(5b)
White solid; m.p. 157-158 °C. 1H NMR (CDCl3, 400
MHz) d: 7.94 (d, J = 9.2 Hz, 1H), 7.80-7.74 (m, 2H), 7.54
(m, 3H), 7.34 (m, 2H), 2.67 (s, 3H), 1.99 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d: 154.1, 146.1, 143.0, 135.4, 134.4,
133.6, 130.6, 129.9, 129.2, 129.0, 128.2, 126.3, 120.6,
31.8, 23.9. Anal. calcd for C18H14BrNO2: C 63.55, H 4.15,
N 4.12; found: C 63.42, H 4.20, N 4.18.
7-Bromo-9-phenyl-3,4-dihydroacridin-1(2H)-one (5c)
1
Pallide-flavens solid; m.p. 195-196 °C. H NMR
(CDCl3, 400 MHz) d: 7.93 (d, J = 8.8 Hz, 1H), 7.83 (dd, J =
2.0, 8.8 Hz, 1H), 7.60 (d, J = 2.0, 1H), 7.53 (m, 3H), 7.17
(m, 2H), 3.76-3.34 (m, 2H), 2.73-2.70 (m, 2H), 2.29-2.24
(m, 2H). 13C NMR (CDCl3, 100 MHz) d: 197.7, 162.7,
150.4, 147.2, 136.8, 135.1, 130.3, 130.1, 128.7, 128.3,
127.9, 124.4, 120.6, 40.6, 34.6, 21.2. Anal. calcd for
C19H14BrNO: C 64.79, H 4.01, N 3.98; found: C 64.85, H
3.96, N 4.10.
7-Bromo-9-phenyl-2,3-dihydro-1H-cyclopenta[b]quino-
line (5h)
White solid; m.p. 118-119 °C. 1H NMR (CDCl3, 400
MHz) d: 7.93 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 1.6 Hz, 1H),

620 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Wu et al.
7.70-7.67 (m, 1H), 7.56-7.47 (m, 3H), 7.35 (m, 2H), 3.24-
3.20 (m, 2H), 2.92-2.89 (m, 2H), 2.21-2.13 (m, 2H). 13C
NMR (CDCl3, 100 MHz) d: 168.0, 146.6, 141.8, 135.9,
134.7, 131.6, 130.5, 129.2, 128.7, 128.3, 127.8, 127.5,
119.5, 35.2, 30.4, 23.4. Anal. calcd for C18H14BrN: C
66.68, H 4.35, N 4.32; found: C 66.74, H 4.50, N 4.20.
6-Bromo-3-ethyl-2-methyl-4-phenylquinoline (5i)
White solid, m.p. 155-156 °C. 1H NMR (CDCl3, 400
MHz) d: 7.89 (d, J = 8.8 Hz, 1H), 7.67 (dd, J = 2.4, 8.8 Hz,
1H), 7.56-7.48 (m, 3H), 7.36 (d, J = 2.0 Hz, 1H), 7.24 (m,
2H), 2.81 (s, 3H), 2.62-2.56 (m, 2H), 1.07-1.04 (m, 3H).
13C NMR (CDCl3, 100 MHz) d: 159.0, 145.4, 144.6, 136.6,
134.4, 131.7, 130.2, 129.2, 128.6, 128.4, 128.2, 128.0,
119.5, 23.8, 23.5, 14.4. Anal. calcd for C18H16BrN: C
66.27, H 4.94, N 4.29; found: C 66.41, H 5.05, N 4.19.
6-Bromo-3-butyl-2-methyl-4-phenylquinoline (5j)
White solid; m.p. 141-142 °C. 1H NMR (CDCl3, 400
MHz) d: 7.89 (d, J = 8.8 Hz, 1H), 7.67 (dd, J = 2.4, 8.8 Hz,
1H), 7.55-7.50 (m, 3H), 7.38 (d, J = 2.0 Hz, 1H), 7.23 (m,
2H), 2.80 (s, 3H), 2.55-2.51 (m, 2H), 1.40-1.38 (m, 2H),
1.26-1.22 (m, 2H), 0.79-0.76 (m, 3H). 13C NMR (CDCl3,
100 MHz) d: 159.1, 145.6, 144.6, 136.6, 133.3, 131.6,
130.2, 129.2, 128.5, 128.4, 128.2, 128.0, 119.4, 32.2, 30.0,
23.9, 22.9, 13.5. Anal. calcd for C20H20BrN: C 67.80, H
5.69, N 3.95; found: C 67.87, H 5.56, N 4.02.
C18H14INO2: C 53.62, H 3.50, N 3.47; found: C 53.48, H
3.55, N 3.59.
1-(6-Iodo-2-methyl-4-phenylquinolin-3-yl)ethanone
(6b)
White solid, m.p. 155-156 °C; 1H NMR (CDCl3, 400
MHz) d: 7.98-7.93 (m, 2H), 7.80 (d, J = 8.8 Hz, 1H), 7.54-
7.50 (m, 3H), 7.34 (m, 2H), 3.58 (s, 3H), 2.75 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) d: 168.57, 155.22, 146.68,
145.18, 139.05, 135.11, 134.84, 130.59, 129.13, 128.81,
128.49, 127.86, 126.82, 92.23, 52.28, 23.84; Anal. calcd
for C18H14INO: C 55.83, H 3.64, N 3.62; found: C 55.78, H
3.58, N 3.70.
7-Iodo-9-phenyl-3,4-dihydroacridin-1(2H)-one (6c)
White solid, m.p. 189-190 °C; 1H NMR (CDCl3, 400
MHz) d: 8.00 (dd, J = 2.0, 9.2 Hz, 1H), 7.81-7.78 (m, 2H),
7.54-7.50 (m, 3H), 7.17 (m, 2H), 3.37-3.34 (m, 2H),
2.73-2.70 (m, 2H), 2.29-2.06 (m, 2H); 13C NMR (CDCl3,
100 MHz) d: 162.82, 150.15, 147.53, 140.34, 136.73,
136.70, 130.18, 129.20, 128.31, 127.98, 40.57, 34.58,
21.21; Anal. calcd for C19H14INO: C 57.16, H 3.53, N 3.51;
found: C 57.26, H 3.49, N 3.48.
7-Iodo-3,3-dimethyl-9-phenyl-3,4-dihydroacridin-
1(2H)-one (6d)
White solid, m.p. 218-219 °C; 1H NMR (CDCl3, 400
MHz) d: 8.00 (dd, J = 2.0, 8.8 Hz, 1H), 7.83-7.78 (m, 2H),
7.56-7.51 (m, 3H), 7.17 (m, 2H), 3.25 (s, 2H), 2.58 (s, 2H),
1.16 (s, 6H); 13C NMR (CDCl3, 100 MHz) d: 161.74,
149.78, 147.88, 140.29, 136.78, 136.65, 130.18, 129.15,
128.33, 128.00, 127.90, 123.13, 92.24, 54.15, 48.34,
32.22, 28.31; Anal. calcd for C21H18INO2: C 59.03, H 4.25,
N 3.28; found: C 59.01, H 4.32, N 3.32.
General procedure for the preparation of 6-iodo-
quinolines
To a stirred solution of the 2-aminobenzophenone (1
mmol, a-methylene carbonyl compounds (1 mmol), and
ZnCl2 (1 mmol) in AcOH (10 mL) at room temperature in a
50-mL reactor, BTMA ICl2 (1 mmol) was added in a single
portion. The vessel was sealed immediately and stirred at
room temperature for 8-12 h. After completion of the reac-
tion (TLC), the mixture was filtered and then poured into
50 mL saturated NaHCO3 solution, extracted with 50 mL
diethyl ether, dried over sodium sulfate, and the solvent
was evaporated under reduced pressure. The residue was
subjected to column chromatography over silica gel using
EtOAc (8%) in hexane to obtain pure 6-iodoquinolines.
Methyl 6-iodo-2-methyl-4-phenylquinoline-3-car-
boxylate (6a)
White solid, m.p. 129-130 °C; 1H NMR (CDCl3, 400
MHz) d: 7.97-7.95 (m, 2H), 7.79 (d, J = 9.2 Hz, 1H), 7.51
(m, 3H), 7.34 (m, 2H), 2.67 (s, 3H), 1.99 (s, 3H); 13C NMR
(CDCl3, 100 MHz) d: 205.20, 154.24, 146.43, 142.47,
138.82, 135.29, 134.75, 134.37, 130.58, 129.93, 129.22,
128.93, 126.79, 92.33, 31.81, 23.93; Anal. calcd for
8-Iodo-10-phenyl-11H-indeno[1,2-b]quinolin-11-one
(6e)
Yellow solid, m.p. 258-259 °C; 1H NMR (CDCl3, 400
MHz) d: 8.13 (d, J = 7.6 Hz, 1H), 8.03-7.99 (m, 2H), 7.88
(d, J = 8.8 Hz, 1H), 7.74-7.69 (m, 2H), 7.61 (m, 3H),
7.54-7.50 (m, 1H), 7.43 (m, 2H), 13C NMR (CDCl3, 100
MHz) d: 189.75, 162.31, 149.40, 146.76, 142.95, 140.35,
137.51, 137.06, 135.42, 132.07, 131.82, 131.40, 129.45,
129.34, 129.27, 129.13, 128.34, 123.93, 123.16, 121.76,
92.83; Anal. calcd for C22H12INO2: C 60.99, H 2.79, N
3.23; found: C 61.06, H 2.68, N 3.32.
7-Iodo-9-phenyl-2,3-dihydro-1H-cyclopenta[b]quino-
line (6f)
White solid, m.p. 156-157 °C; 1H NMR (CDCl3, 400
MHz) d: 7.97 (d, J = 1.6 Hz, 1H), 7.86 (dd, J = 1.6, 8.8 Hz,
1H), 7.79 (d, J = 8.8 Hz, 1H), 7.57-7.47 (m, 3H), 7.35-7.32

Synthesis of 6-Bromoquinoline and 6-Iodoquinolines
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 621
3. Srivastava, S. K.; Chauhan, P. M. S.; Bhaduri, A. P.; Fatima,
N.; Chatterjee, R. J. Med. Chem. 2000, 43, 2275.
4. Kirsch, R.; Kleim, J. P.; Ries, G.; Rosenstock, B.; Roesner,
M.; Winkler, I. DE Patent 19,613,591, 1997.
(m, 2H), 3.23-3.19 (m, 2H), 2.91-2.88 (m, 2H), 2.20-2.13
(m, 2H); 13C NMR (CDCl3, 100 MHz) d: 168.07, 147.00,
141.54, 136.90, 135.97, 134.45, 134.33, 130.61, 129.14,
128.68, 128.24, 128.07, 91.05, 35.18, 30.36, 23.35; Anal.
calcd for C18H14IN: C 58.24, H 3.80, N 3.77; found: C
58.31, H 3.75, N 3.82.
5. Suzuki, M.; Iwasaki, H.; Fujikawa, Y.; Kitahara, M.;
Sakashita, M.; Sakoda, R. Bioorg. Med. Chem. 2001, 9,
2727.
2-Iodo-9-phenyl-5,6,7,8-tetrahydroacridine (6g)
6. (a) Agarwal, A. K.; Jenekhe, S. A. Macromolecules 1991,
24, 6806. (b) Zhang, X.; Shetty, A. S.; Jenekhe, S. A.
Macromolecules 1999, 32, 7422. (c) Zhang, X.; Shetty, A.
S.; Jenekhe, S. A. Macromolecules 2000, 33, 2069. (d)
Jenekhe, S. A.; Lu, L.; Alam, M. M. Macromolecules 2001,
34, 7315.
White solid, m.p. 146-147 °C; 1H NMR (CDCl3, 400
MHz) d: 7.84 (dd, J = 2.0, 9.2 Hz, 1H), 7.74 (d, J = 8.8 Hz,
1H), 7.67 (d, J = 1.6 Hz, 1H), 7.57-7.48 (m, 3H), 7.22 (m,
2H), 3.19-3.16 (m, 2H), 2.60-2.57 (m, 2H), 2.00-1.94 (m,
2H), 1.82-1.76 (m, 2H); 13C NMR (CDCl3, 100 MHz) d:
159.79, 145.30, 137.03, 136.26, 134.47, 130.22, 129.23,
129.00, 128.76, 128.44, 128.01; Anal. calcd for C19H16IN:
C 59.24, H 4.19, N 3.64; found: C 58.98, H 4.25, N 3.60.
3-Ethyl-6-iodo-2-methyl-4-phenylquinoline (6h)
White solid, m.p. 186-187 °C; 1H NMR (CDCl3, 400
MHz) d: 7.85 (dd, J = 2.0, 8.8 Hz, 1H), 7.76 (d, J = 8.8 Hz,
1H), 7.58-7.49 (m, 4H), 7.24 (m, 2H), 2.81 (s, 3H), 2.58
(m, 2H), 1.07-1.04 (m, 3H); 13C NMR (CDCl3, 100 MHz)
d: 159.19, 145.27, 144.87, 137.05, 136.51, 134.88, 134.28,
130.15, 129.17, 128.99, 128.55, 128.02, 91.21, 23.73,
23.46, 14.40; Anal. calcd for C18H16IN: C 57.92, H 4.32, N
3.75; found: C 58.01, H 4.37, N 3.69.
7. (a) Saito, I.; Sando, S.; Nakatani, K. Bioorg. Med. Chem.
2001, 9, 2381. (b) He, C.; Lippard, S. J. J. Am. Chem. Soc.
2001, 40, 1414.
8. (a) Combes, A. Bull. Soc. Chim. Fr. 1888, 49, 89. (b)
Buu-Hoi, N. P.; Nuong, N. D.; Jacquhnos, P. J. Org. Chem.
1953, 18, 1209. (c) Skraup, Z. H. Ber. Dtsch. Chem. Ges.
1880, 13, 2086. (d) Friedlander, P. Ber. Dtsch. Chem. Ges.
1882, 15, 2572.
9. (a) Yadav, J. S.; Reddy, B. V. S.; Sreedhar, P.; Rao, R. S.;
Nagaiah, K. Synthesis 2004, 14, 2381. (b) Arumugam, P.;
Karthikeyan, G.; Atchudan, R.; Murlidharan, D.; Perumal, P.
T. Chem. Lett. 2005, 34, 314. (c) Wu, J.; Zhang, L.; Diao, T.
N. Synlett 2005, 2653. (d) Varala, R.; Enugala, R.; Adapa, S.
R. Synthesis 2006, 3825. (e) De, S. K.; Gibbs, R. A. Tetrahe-
dron Lett. 2005, 46, 1647. (f) Dabiri, M.; Baghbanzadeh, M.;
Arzroomchilar, E. Heterocycles 2008, 75, 397. (g) Wu, J.;
Xia, H. G.; Gao, K. Org. Biomol. Chem. 2006, 4, 26. (h)
Likhar, P. R.; Subhas, M. S.; Roy, S.; Kantam, M. L.; Sridhar,
B.; Seth, R. K.; Biswas, S. Org. Biomol. Chem. 2009, 7, 85.
(i) Dabiri, M.; Azimi, S. C.; Bazgir, A. Monatsh. Chem.
2007, 138, 659. (j) Das, B.; Damodar, K.; Chowdhury, N.;
Kumar, R. A. J. Mol. Catal. A Chem. 2007, 274, 148. (k)
Ghassamipour, S.; Sardarian, A. R. Tetrahedron Lett. 2009,
50, 514.
3-Butyl-6-iodo-2-methyl-4-phenylquinoline (6i)
White solid, m.p. 125-126 °C; 1H NMR (CDCl3, 400
MHz) d: 7.85 (dd, J = 1.6, 8.8 Hz, 1H), 7.72 (d, J = 8.8 Hz,
1H), 7.59 (d, J = 1.6 Hz, 1H), 7.56-7.48 (m, 3H), 7.24-7.21
(m, 2H), 2.81 (s, 3H), 2.55-2.51 (m, 2H), 1.39 (m, 2H),
1.25-1.22 (m, 2H), 0.79-0.75 (m, 3H); 13C NMR (CDCl3,
100 MHz) d: 259.25, 137.11, 136.45, 134.89, 133.26,
129.98, 129.22, 128.96, 128.51, 128.04, 91.26, 32.14,
29.97, 23.76, 22.91, 13.51; Anal. calcd for C20H20IN: C
59.86, H 5.02, N 3.49; found: C 59.90, H 5.11, N 3.52.
10. Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.;
Srinivasan, K. V. J. Org. Chem. 2003, 68, 9371.
11. Szatmari, I.; Fulop, F. Synthesis 2009, 5, 775.
12. Qi, C.; Zheng, Q.; Hua, R. Tetrahedron 2009, 65, 1316.
13. Ghorbani-Vaghei, R.; Akbari-Dadamahaleh, S. Tetrahedron
Lett. 2009, 50, 1055.
ACKNOWLEDGEMENTS
We are pleased to acknowledge the financial support
from Xinxiang Medical University.
14. Mierde, H. V.; Voort, P. V. D.; Verpoort, F. Tetrahedron Lett.
2009, 50, 201.
Received April 26, 2010.
15. Wu, L.-Q.; Yang, C.-G.; Wu, Y.-F.; Yang, L.-M. J. Chin.
Chem. Soc. 2009, 56, 606.
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