Cannizzaro reaction of 2-chloro-3-formylquinolines and its synthetic utility for 2-acetylfuro[2,3-b]quinolines: The alkaloid analogues

Article abstract of DOI:10.1007/s12039-012-0297-2

Cannizzaro reaction of 2-chloro-3-formylquinolines was investigated under two different conditions. Under both conditions, redox and methoxylation proceeded simultaneously and gave 2-methoxy- 3-formylquinolines, 2-methoxyquinolin-3-yl-methanols and 2-meth

Full text of DOI:10.1007/s12039-012-0297-2

c
J. Chem. Sci. Vol. 124, No. 5, September 2012, pp. 1071–1076. ꢀ Indian Academy of Sciences.
Cannizzaro reaction of 2-chloro-3-formylquinolines and its synthetic
utility for 2-acetylfuro[2,3-b]quinolines: The alkaloid analogues
DEVADOSS KARTHIK KUMAR, RAJAKANDHAN SHANKAR and SUBRAMANIAM
PARAMESWARAN RAJENDRAN∗
Department of Chemistry, School of Chemical Sciences, Bharathiar University, Coimbatore 641 046, India
e-mail: dskarthik06@gmail.com; rajendransp@yahoo.com
MS received 3 September 2011; revised 18 November 2011; accepted 19 April 2012
Abstract. Cannizzaro reaction of 2-chloro-3-formylquinolines was investigated under two different con-
ditions. Under both conditions, redox and methoxylation proceeded simultaneously and gave 2-methoxy-
3-formylquinolines, 2-methoxyquinolin-3-yl-methanols and 2-methoxyquinoline-3-carboxylic acids. The
synthesized 2-methoxy-3-formylquinolines were then condensed with acetone in the presence of sulphuric acid
to give 4-(2-methoxy-quinolin-3-yl)-but-3-en-2-ones which in turn were bromocyclized and dehydrobromi-
nated to get 2-acetylfuro[2,3-b]quinolines.
Keywords. Cannizzaro reaction; bromocyclisation; 2-methoxy-3-formylquinolines; furoquinolines;
2-chloro-3-formylquinolines.
1. Introduction
NMR spectra were taken on BRUKER 400 MHz and
500 MHz spectrometer using TMS as an internal ref-
erence. The chemical shifts were expressed in parts
per million (ppm). The mass spectra were determined
on an Autospec EI+ mass spectrometer and HRMS
(ESI) mass spectrometer. Elemental analyses were per-
formed on Vario EL IIICHNS Analyzer and Perkin
Elmer Analyzer.
Natural products bearing furo[2,3-b]quinoline skeleton
and their synthetic analogues play a vital role in drug
development and drug discovery. In recent years, many
synthetic methods have been developed for furo[2,3-
b]quinolines.1–4 The 2-acetylfuro[2,3-b]quinoline alka-
loids (figure 1) have been isolated from the root
bark of Melicope semecarpifolia and the extract of
this plant was used for antiplatelet aggregation acti-
vity.5 Molecules containing furo[2,3-b]quinoline scaf-
fold show a wide range of biological activities which
include vasoconstructive, antidiuretic, antiarrhythmic,
spamolytic, sedative, hypothermal effects,6 antitumour,
antipyretic, antiplatelet and cytotoxic activities.7,8 This
wide range of biological activities has encouraged us
to develop a new route for the synthesis of acetyl
substituted furo[2,3-b]quinolines.
2.2 General Procedure for 2-methoxyquinoline-3-
carbaldehydes 2(a–f), 2-methoxyquinolin-3-yl)-methanols
3(a–f) and 2-methoxyquinoline-3-carboxylic acids 4(a–f)
A solution of compound 1(a–f) (1d, 1.025 g, 0.005 mol)
in KOH (6 g) in methanol (30 mL) was stirred for 24 h
at room temperature or refluxed for 12 h until start-
ing material was disappeared. The mixture was then
poured into crushed ice and neutralized with 4N HCl.
The precipitate was filtered off, dried and column chro-
matographed over silcagel using a mixture of petroleum
ether and ethylacetate as eluent. The solvent (PE: EA)
combination ratio for 2(a–f), 3(a–f) and 4(a–f) were
100:0, 90:10, 80:20, respectively.
2. Experimental
2.1 General
Melting points were determined using a Raga melt-
ing point apparatus and were uncorrected. IR spectra
were recorded on Shimadzu FT IR PC (S) 8201spec-
trometer using KBr pellets and the absorption frequen-
cies are expressed in reciprocal centimetres (cm−1).
2.2a 2-Methoxy-quinoline-3-carbaldehydes 2(a–f): The
spectroscopic data and melting points are consistent
with reported in literature.10–12
2.2b (2-Methoxy-8-methylquinolin-3-yl)-methanol
(3d). mp 101◦C; IR (KBr): 3212 cm−1; 1H NMR
∗For correspondence
1071

1072
D.K. Kumar et al.
1H, C5H), 7.67 (d, 1H, J = 9 Hz, C7H), 8.11(s, 1H,
OCH3
OCH3
H3CO
C4H ); Anal, Calcd for C12H13NO3: C, 65.74; H, 5.98;
N, 6.39. Found: C, 65.58; H, 5.78; N, 6.23.
H3CO
N
O
N
O
O
O
2-Acetylevolitrine
2-Acetylpteleine
2.2g 2, 7-Dimethoxyquinolin-3-yl-methanol (3f). mp
98◦C; IR (KBr): 3230 cm−1; 1H NMR (500 MHz;
DMSO-d6): δ = 3.84 (s, 3H, 7-OCH3), 3.94 (s, 3H, 2-
OCH3), 4.60 (d, 2H, J = 5Hz, CH2OH), 5.29 (t, 1H,
J = 5Hz, OH), 7.12 (s, 1H, C8H), 7.28 (d, 1H, J =
8.2Hz, C5H), 7.38 (d, 1H, J = 8.2Hz, C6H), 8.19 (s, 1H,
C4H); Anal, Calcd for C12H13NO3: C, 65.74; H, 5.98;
N, 6.39. Found: C, 65.90; H, 5.82; N, 6.22.
Figure 1. Acetyl derivative of furoquinoline alkaloids.
(500 MHz; DMSO-d6): δ = 2.65 (s, 3H, CH3), 4.03 (s,
3H, OCH3), 4.60 (d, 2H, J = 5Hz, CH2OH), 5.36 (t,
1H, J = 5Hz, OH), 7.30 (t, 1H, J = 7.4 Hz C6H), 7.49
(d, 1H, J = 7.4 Hz, C7H), 7.72 (d, 1H, J = 7.4 Hz,
C5H), 8.15(s, 1H, C4H); 13C NMR (125 MHz, DMSO-
d6): 17.8, 53.3, 58.3,124.1, 125.3, 125.7, 126.6, 129.4,
134.3, 134.9, 143.9, 158.9. MS (ESI, m/z): 204.13 [M
+H]+. Anal, Calcd for C12H13NO2: C, 70.92; H, 6.45;
N, 6.89. Found: C, 70.73; H, 6.26; N, 6.70.
2.2h 8-Methyl-2-methoxyquinoline-3-carboxylic acid
(4d). mp 186◦C; IR (KBr): 1699, 3116 cm−1; 1H NMR
(500 MHz; DMSO-d6): δ = 2.65 (s, 3H, CH3), 4.06 (s,
3H, OCH3), 7.37 (t, 1H, J = 8 Hz, C6H), 7.64 (d, 1H,
J = 8 Hz, C7H), 7.84 (d, 1H, J = 8 Hz, C5H), 8.15
(s, 1H, C4H); 13C NMR (125 MHz, DMSO-d6) 17.6,
53.7, 117.1, 124, 124.8, 127, 132.1, 134.6, 142.5, 145.9,
158.5, 166.4. Anal, Calcd for C12H11NO3: C, 66.35; H,
5.10; N, 6.45. Found: C, 66.19; H, 5.28; N, 6.24.
2.2c (2-Methoxyquinolin-3-yl)-methanol (3a). mp
109◦C; IR (KBr): 3215 cm−1; H NMR (500 MHz;
1
DMSO-d6): δ = 4.03 (s, 3H, OCH3), 4.62 (d, 2H, J =
5Hz, CH2OH), 5.38 (t, 1H, J = 5Hz, OH), 7.63 (t, 1H,
J = 8.5Hz, C6H), 7.85 (t, 1H, J = 8.5Hz, C7H), 7.96
(d, 1H, J = 8.5Hz, C8H), 8.07 (d, 1H, J = 8.5Hz,
C5H), 8.20 (s, 1H, C4H ); Anal, Calcd for C11H11NO2:
C, 69.83; H, 5.86; N, 7.40. Found: C, 69.62; H, 6.03; N,
7.23.
2.2i 2-Methoxyquinoline-3-carboxylic acid (4a).
1
mp 174◦C; IR (KBr): 1695, 3120 cm−1; H NMR
(500 MHz; DMSO-d6): δ = 4.03 (s, 3H, OCH3), 7.68
(t, 1H, J = 8.6 Hz, C6H), 7.89 (t, 1H, J = 8.6 Hz,
C7H), 8.12 (d, 1H, J = 8.6 Hz C8H), 8.17 (d, 1H,
J = 8.6 Hz, C5H), 8.23 (s, 1H, C4H); Anal, Calcd
for C11H9NO3: C, 65.02; H, 4.46; N, 6.89. Found: C,
65.16; H, 4.32; N, 6.74.
2.2d (2-Methoxy-6-methylquinolin-3-yl)-methanol
(3b). mp 127◦C; IR (KBr): 3222 cm−1; 1H NMR
(500 MHz; DMSO-d6): δ = 2.43 (s, 3H, CH3), 4.01 (s,
3H, 2-OCH3), 4.52 (d, 2H, J = 5Hz, CH2OH), 5.29
(t, 1H, J = 5 Hz, OH), 7.21 (d, 1H, J = 9 Hz, C8H),
7.33 (s, 1H, C5H), 7.64 (d, 1H, J = 9 Hz, C7H), 8.06
(s, 1H, C4H ); Anal, Calcd for C12H13NO2: C, 70.92;
H, 6.45; N, 6.89. Found: C, 70.75; H, 6.25; N, 6.72.
2.2j 2-Methoxy-6-methylquinoline-3-carboxylic acid
(4b). mp 182◦C; IR (KBr): 1702, 3128 cm−1; 1H NMR
(500 MHz; DMSO-d6): δ = 2.44 (s, 3H, CH3), 4.01 (s,
3H, 2-OCH3), 7.22 (d, 1H, J = 8.3 Hz, C8H), 7.34 (s,
1H, C5H), 7.64 (d, 1H, J = 8.3Hz, C7H), 8.04 (s, 1H,
C4H); Anal, Calcd for C12H11NO3: C, 66.35; H, 5.10;
N, 6.45. Found: C, 66.19; H, 5.32; N, 6.59.
2.2e (2-Methoxy-7-methylquinolin-3-yl)-methanol
(3c). mp 112◦C; IR (KBr): 3234 cm−1; 1H NMR
(500 MHz; DMSO-d6): δ = 2.41 (s, 3H, CH3), 3.97 (s,
3H, 2-OCH3), 4.54 (d, 2H, J = 5 Hz, CH2OH), 5.32
(t, 1H, J = 5Hz, OH), 7.15 (s, 1H, C8H), 7.31 (d, 1H,
J = 8.4 Hz, C5H), 7.35 (d, 1H, J = 8.4 Hz, C6H), 8.17
(s, 1H, C4H); Anal, Calcd for C12H13NO2: C, 70.92; H,
6.45; N, 6.89. Found: C, 70.78; H, 6.60; N, 7.05.
2.2k 2-Methoxy-7-methylquinoline-3-carboxylic acid
(4c). mp 203◦C; IR (KBr): 1722, 3133 cm−1; 1H NMR
(500 MHz; DMSO-d6): δ = 2.41 (s, 3H, CH3), 3.98
(s, 3H, 2-OCH3), 7.19 (s, 1H, C8H), 7.35 (d, 1H, J =
8.2Hz, C5H), 7.39 (d, 1H, J = 8.2 Hz, C6H), 8.20 (s,
1H, C4H), Anal, Calcd for C12H11NO3: C, 66.35; H,
5.10; N, 6.45. Found: C, 66.52; H, 5.27; N, 6.28.
2.2f 2, 6-Dimethoxyquinolin-3-yl-methanol (3e). mp
105◦C; IR (KBr): 3227 cm−1; H NMR (500 MHz;
1
DMSO-d6): δ = 3.85 (s, 3H, 6-OCH3), 3.97 (s, 3H, 2-
OCH3), 4.57 (d, 2H, J = 5Hz, CH2OH), 5.33 (t, 1H,
J = 5Hz, OH), 7.24 (d, 1H, J = 9 Hz, C8H), 7.35 (s,
2.2l 2,6-Dimethoxyquinoline-3-carboxylic acid (4e).
1
mp 168◦C; IR (KBr): 1731, 3142 cm−1; H NMR

Cannizzaro rection and 2-acetylfuro[2,3-b]quinolines
1073
(500 MHz; DMSO-d6): δ = 3.87 (s, 3H, 6-OCH3), 3.99 2.3c 4-(2-Methoxy-6-methylquinolin-3-yl)-but-3-en-2-
(s, 3H, 2-OCH3), 7.40 (d, 1H, J = 9 Hz, C8H), 7.46 (s, one (5b): Yield 80%; mp 87◦C; IR (KBr): 1656 cm−1;
1H, C5H), 7.72 (d, 1H, J = 9 Hz, C7H), 8.60 (s, 1H, 1H NMR (500 MHz; DMSO-d6): δ = 2.42 (s, 3H,
C4H), 13.1(s, 1H, COOH); Anal, Calcd for C12H11NO4: CH3), 2.48 (s, 3H, 6-CH3) 4.13 (s, 3H, 2-OCH3), 7.92
C, 61.80; H, 4.75; N, 6.01. Found: C, 61.64; H, 4.58; N, (d, 1H, J = 16.5 Hz, CαH), 7.46 (d, 1H, J = 9 Hz,
6.18.
C8H), 7.49 (s, 1H, C5H), 7.71 (d, 1H, J = 9 Hz, C7H),
7.76 (d, 1H, J = 16.5 Hz, CβH), 8.10 (s, 1H, C4H);
Anal, Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81.
Found: C, 74.50; H, 6.45; N, 5.99.
2.2m 2,7-Dimethoxyquinoline-3-carboxylic acid (4f).
mp 156◦C; IR (KBr): 1737, 3126 cm−1; H NMR
1
(500 MHz; DMSO-d6): δ = 3.85 (s, 3H, 7-OCH3), 3.96
(s, 3H, 2-OCH3), 7.14 (s, 1H, C8H), 7.31 (d, 1H, J =
8.4Hz, C5H), 7.40 (d, 1H, J = 8.4 Hz, C6H), 8.23 (s,
1H, C4H); Anal, Calcd for C12H11NO4: C, 61.80; H,
4.75; N, 6.01. Found: C, 61.97; H, 4.91; N, 5.83.
2.3d 4-(2-Methoxy-7-methylquinolin-3-yl)-but-3-en-2-
one (5c): Yield 82%; mp 79◦C; IR (KBr): 1676 cm−1;
1H NMR (500 MHz; DMSO-d6): δ = 2.35 (s, 3H,
CH3), 2.44 (s, 3H, 7-CH3), 4.05 (s, 3H, 2-OCH3), 6.99
(d, 1H, J = 16.2 Hz, CαH), 7.51 (d, 1H, J = 8.5Hz,
C6H), 7.63 (s, 1H, C8H), 7.65 (d, 1H,J = 8.5Hz, C5H),
7.69 (s, 1H, J = 16.2 Hz, CβH), 8.53 (s, 1H, C4H);
Anal, Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81.
Found: C, 74.82; H, 6.11; N, 5.98.
2.3 General procedure for 4-(2-methoxyquinolin-3-yl)-
but-3-en-2-one 5(a–f)
A mixture of compound 2(a–f) (2d, 1.006 g, 0.005 mol)
and acetone (40 mL) and few drops of sulphuric acid
was refluxed in water bath for 6 h. After completion of
the reaction which was checked by TLC the mixture
was poured into crushed ice. The precipitate was fil-
tered off, dried, and column chromatographed over sili-
ca gel using petroleum ether and ethyl acetate (90:10)
as eluent to give compound 5(a–f).
2.3e 4-(2, 6-Dimethoxyquinolin-3-yl)-but-3-en-2-one
1
(5e): Yield 64%; mp 68◦C; IR (KBr): 1682 cm−1; H
NMR (500 MHz; DMSO-d6): δ = 2.36 (s, 3H, CH3),
3.81 (s, 3H, 6- OCH3), 4.02 (s, 3H, 2-OCH3), 6.12 (d,
1H, J = 16 Hz, CαH), 7.34 (d, 1H, J = 9 Hz, C8H),
7.45 (s, 1H, C5H), 7.72 (d, 1H, J = 16 Hz, CβH), 7.81
(d, 1H, J = 9 Hz, C7H), 8.86 (s, 1H, C4H); Anal, Calcd
for C15H15NO3: C, 70.02; H, 5.88; N, 5.44. Found: C,
69.88; H, 5.72; N, 5.58.
2.3a 4-(8-Methyl-quinolin-3-yl)-but-3-en-2-one (5d):
Yield 86%; mp 83◦C; IR (KBr): 1674 cm−1; H NMR
1
2.3f 4-(2,7-Dimethoxyquinolin-3-yl)-but-3-en-2-one
(5f): Yield: 58%; mp 60◦C; IR (KBr): 1686 cm−1; 1H
NMR (500 MHz; DMSO-d6): δ = 2.41 (s, 3H, CH3),
3.92 (s, 3H, 7-OCH3), 3.98 (s, 3H, 2-OCH3), 7.12
(d, 1H, J = 16.5 Hz, CαH), 7.46 (d, 1H, J = 8 Hz,
C6H), 7.58 (s, 1H, C8H), 7.63 (d, 1H, J = 8 Hz, C5H),
7.72 (d, 1H, J = 16.5 Hz, CβH), 8.68 (s, 1H, C4H);
Anal, Calcd for C15H15NO3: C, 70.02; H, 5.88; N, 5.44.
Found: C, 70.20; H, 5.73; N, 5.28.
(500 MHz; CDCl3): δ = 2.42 (s, 3H, COCH3), 2.69
(s, 3H, CH3), 4.15 (s, 3H, OCH3), 6.95 (d, 1H, J =
16.4 Hz, CαH), 7.27 (t, 1H, J = 8.4 Hz, C6H), 7.50 (d,
1H, J = 8.4 Hz, C5H), 7.57 (d, 1H, J = 8.4Hz, C7H),
7.78 (d, 1H, J = 16.4 Hz, CβH), 8.17 (s, 1H, C4H);
13C NMR (125 MHz, DMSO) 17.8,28.2, 53.3, 119.1,
124.8, 125, 126.6, 130.1, 131.5, 134.6, 136.9, 139.3,
145.3, 158.9, 199.2; MS (ESI, m/z): 242.20 [M+H]+.
Anal, Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81.
Found: C, 74.48; H, 6.42; N, 5.63.
2.4 General procedure for 1-Furo[2,3-b]quinolin-2-yl-
ethanone 6(a–f)
2.3b 4-(2-Methoxyquinolin-3-yl)-but-3-en-2-one (5a):
1
Yield 76%; mp 74◦C; IR (KBr): 1675 cm−1; H NMR
A mixture of compound 5(a–f) (5d, 0.6025 g,
0.0025 mol) and excess of bromine in chloroform
(15 mL) and glacial acetic acid (15 mL) was heated
at 96◦C for 12 h. After completion of the reaction
which was checked by TLC, the excess of bromine
was removed by adding 25% solution of sodium sul-
phite through the dropping funnel. The colourless chlo-
roform layer was separated out, washed with water
(400 MHz; CDCl3): δ = 2.38 (s, 3H, COCH3), 4.09 (s,
3H, OCH3), 7.05 (d, 1H, J = 16 Hz, CαH), 7.46 (t,
1H, J = 8.4 Hz, C6H), 7.70 (t, 1H, J = 8.4 Hz, C7H),
7.73 (d, 1H, J = 16 Hz, CβH), 7.77 (d, 1H, J = 8.4
Hz, C8H), 7.91 (d, 1H, J = 8.4 Hz, C5H), 8.71 (s, 1H,
C4H); Anal, Calcd for C14H13NO2: C, 73.99; H, 5.77;
N, 6.16. Found: C, 73.83; H, 5.92; N, 5.96.

1074
D.K. Kumar et al.
and dried over magnesium sulphate. After a few min- 2.4f 1-(7-Methoxyfuro[2, 3-b]quinolin-2-yl)-ethanone
utes, the magnesium sulphate was removed by filtration. (6f). IR (KBr): 1692 cm−1; 1H NMR (500 MHz;
The solution was evaporated to dryness to give 6(a–f) DMSO-d6): δ = 2.42 (s, 3H, COCH3), ), 3.89 (s, 3H,
which was purified by column chromatography using 7-OCH3), 7.42 (d, 1H, J = 8.6 Hz, C5H), 7.51 (s, 1H,
petroleum ether and ethyl acetate (85:15) as eluent.
J = 8.6 Hz, C8H), 7.82 (d, 1H, J = 8.6 Hz, C6H),
8.08 (s, 1H, C4H), 8.89 (s, 1H, C3H); Anal, Calcd
for C14H11NO3: C, 69.70; H, 4.60; N, 5.81. Found: C,
69.87; H, 4.43; N, 5.99.
2.4a 1-Furo[2,3-b]quinolin-2-yl-ethanone (6a). IR
1
(KBr): 1677 cm−1; H NMR (500 MHz; DMSO-d6):
δ = 2.64 (s, 3H, COCH3), 7.62 (t, 1H, J = 8.5Hz,
C6H), 7.84 (t, 1H, J = 8.5Hz, C7H), 8.05 (d, 1H, J =
8.5Hz, C8H), 8.20 (d, 1H, J = 8.5Hz, C5H), 8.08 (s, 1H,
C4H ), 8.97(s, 1H, C3H); 13C NMR (125 MHz, DMSO-
d6): 26.9, 113.3, 120.2, 125.7, 126.8, 128.4, 129.4, 131,
134.4, 146.7, 152.8, 161.1, 188.8; HRMS (ESI) Calcd
for C13H9NO2, (M + H) 212.0712, Found 212.0711.
3. Results and discussion
Recently we have reported9 the synthesis of 2-
benzoylfuro[2,3-b]quinolines from quinoline-based
chalcones by bromocyclization method. We report here
an extension of this methodology for the synthesis of
2-acetylfuro[2,3-b]quinolines started from 2-methoxy-
3-formylquinolines10–12 which in turn were synthesized
from 2-chloro-3-formylquinolines in single step under
the Cannizzaro reaction conditions.
2.4b 1-(6-Methylfuro[2, 3-b]quinolin-2-yl)-ethanone
(6b). IR (KBr): 1686 cm−1; 1H NMR (500 MHz;
DMSO-d6): δ = 2.46 (s, 3H, COCH3), 2.49 (s, 3H, 6-
CH3), 7.52 (s, 1H, C5H), 7.58 (d, 1H, J = 8.3Hz, C8H),
7.84 (d, 1H, J = 8.3Hz, C7H), 8.03 (s, 1H, C4H), 8.92
(s, 1H, C3H); Anal, Calcd for C14H11NO2: C, 74.65; H,
4.92; N, 6.22. Found: C, 74.79; H, 4.78; N, 6.01.
Cannizzaro reaction is the redox disproportiona-
tive conversion of aldehydes into their corresponding
alcohols and acids. It has been examined in hetero-
cyclic compounds only on few cases and reported to
give expected products.13–17 But we have observed
that in case of 2-chloro-3-formylquinolines, in
addition to redox reaction, methoxylation also pro-
ceeded and gave 2-methoxy-3-formylquinolines
2(a–f), 2-methoxyquinolin-3-yl-methanols 3(a–f)
and 2-methoxyquinoline-3-carboxylic acids 4(a–f)
(scheme 1). We have investigated Cannizarro reaction
of compound 1a with KOH in methanol under two
different conditions and found that, in the condition of
stirring at room temperature (A), compound 2a was
major product and under the condition of reflux (B),
compound 4a was major product. The results of diffe-
rent derivatives are presented in table 1. For separation
of these mixtures 2(a–f), 3(a–f) and 4(a–f) in column
chromatography, we used PE: EA combinations in the
ratio of 100:0, 90:10, and 80:20 as a solvent for elution.
Next, the conversion of 2(a–f) to 6(a–f) was
attempted as shown in scheme 2. Reaction of 2(a–
f) with acetone in the presence of sulphuric acid
afforded 4-(2-methoxy-quinolin-3-yl)-but-3-en-2-ones
5(a–f) with good yields. The synthesized compounds
5(a–f) were identified by spectral analysis. As an exam-
ple, compound 5d showed, two signals of vinylic pro-
tons of α, β unsaturated carbonyl were found at δ=
6.95 ppm for Hα and 7.78 ppm for Hβ with a coupling
constant (J) of 16.4 Hz. The same reaction was also tried
with 2-hydroxy-3-formylquinoline but it was found that
the desired product was not produced.
2.4c 1-(7-Methylfuro[2, 3-b]quinolin-2-yl)-ethanone
(6c). IR (KBr): 1695 cm−1; 1H NMR (500 MHz;
DMSO-d6): δ = 2.46 (s, 3H, COCH3), 2.49 (s, 3H, 7-
CH3), 7.49 (d, 1H, J = 9Hz, C5H), 7.54 (s, 1H, C8H),
7.76 (d, 1H, J = 8.8Hz, C6H), 8.06 (s, 1H, C4H), 8.92
(s, 1H, C3H); Anal, Calcd for C14H11NO2: C, 74.65; H,
4.92; N, 6.22. Found: C, 74.78; H, 4.72; N, 6.36.
2.4d 1-(8-Methylfuro[2,3-b]quinolin-2-yl)-ethanone
(6d). IR (KBr): 1681 cm−1; 1H NMR (500 MHz;
DMSO-d6): δ = 2.52 (s, 3H, COCH3), 2.66 (s, 3H,
8-CH3), 7.46 (d, 1H, J = 8Hz, C5H), 7.52 (t, 1H, J =
8 Hz, C6H), 7.92 (d, 1H, J = 8Hz, C7H), 8.15 (s, 1H,
C4H), 8.90 (s, 1H, C3H); Anal, Calcd for C14H11NO2:
C, 74.65; H, 4.92; N, 6.22. Found: C, 74.44; H, 4.73;
N, 6.40.
2.4e 1-(6-Methoxyfuro[2, 3-b]quinolin-2-yl)-ethanone
(6e). IR (KBr): 1701 cm−1; 1H NMR (500 MHz;
DMSO-d6): δ = 2.44 (s, 3H, COCH3), 3.98 (s, 3H,
6- OCH3), 7.62 (s, 1H, C5H), 7.68 (d, 1H, J = 8.4
Hz, C8H), 7.89 (d, 1H, J = 8.4 Hz, C7H), 8.10 (s, 1H,
C4H), 8.86 (s, 1H, C3H); Anal, Calcd for C14H11NO3:
C, 69.70; H, 4.60; N, 5.81. Found: C, 69.53; H, 4.75; N,
5.66.

Cannizzaro rection and 2-acetylfuro[2,3-b]quinolines
1075
R1
R2
COOH
OCH3
R1
R2
CHO
Cl
R1
R2
CHO
R1
R2
CH2OH
A or B
+
+
N
N
N
OCH3
N
R33a-f
OCH3
R3
R3
R3
1a-f
4a-f
2a-f
a) R1 = R2= R3 = H.
Conditions:
b) R1 = CH3, R2 = R3 = H.
c) R1 = R3 = H, R2 = CH3.
d) R1 = R2 = H, R3 = CH3.
e) R1 = OCH3, R2 = R3 = H.
A) KOH / CH3OH, Stirring, r.t, 24 h.
B) KOH / CH3OH, Reflux, 12 h.
f) R1 = H, R2 = OCH3, R3 = H.
Scheme 1. Cannizzaro reaction of 2-chloro-3-formylquinolines.
Table 1. Cannizzaro reaction of 2-chloro-3-formylquinolines.
Products
Condition A
Condition B
Starting materials
R2
(% of Yield)
Entry
R1
R3
2(a–f)
3(a–f)
4(a–f)
2(a–f)
3(a–f)
4(a–f)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
H
CH3
H
H
OCH3
H
H
H
CH3
H
H
OCH3
H
H
H
CH3
H
H
73
75
70
80
78
72
6
7
7
6
5
8
21
18
23
14
17
20
22
20
16
20
18
19
28
24
25
29
26
32
50
56
59
51
56
49
O
R1
R2
CHO
OCH3
R1
R2
R1
R2
i
ii
N
N
OCH3
N
O
O
R3
R3
R3
5a-f
2a-f
6a-f
i) CH3COCH3 / H2SO4, 6 h, reflux.
ii) Br2, CH3COOH/CHCl3, 12 h, reflux.
a) R1 = R2= R3 = H.
b) R1 = CH3, R2 = R3 = H.
c) R1 = R3 = H, R2 = CH3.
d) R1 = R2 = H, R3 = CH3.
e) R1 = OCH3, R2 = R3 = H.
f) R1 = H, R2 = OCH3, R3 = H.
Scheme 2. Synthesis of 2-acetylfuro[2,3-b] quinolines.
Table 2. Synthesis of 2-acetylfuro[2,3-b]quinolines.
Entry
Product
R1
R2
R3
Condition
Yield (%)
Mp(◦C)
1
2
3
4
5
6
6a
6b
6c
6d
6e
6f
H
CH3
H
H
OCH3
H
H
H
CH3
H
H
OCH3
H
H
H
CH3
H
H
96◦C/ 12 h
96◦C/ 12 h
96◦C/ 12 h
96◦C/ 12 h
96◦C/ 12 h
96◦C/ 12 h
80
82
78
87
74
70
156
174
182
161
142
134

1076
D.K. Kumar et al.
Br
H
Br-Br
O
Br
O
O
O
OH
Br
CH3COOH
Br2
H
5a-f
N
H
N
H
O
N
H
Br
-HBr
Br
-HBr
O
O
N
O
N
O
6a-f
Not isolated
Scheme 3. Proposed mechanism for bromocyclisation.
Furthermore, the cyclisation of synthesized com- References
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The formation of 6a from 5a may be explained as
shown in scheme 3. The methoxy group of compound
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In summary, we have reported an efficient synthesis
of 2-acetyl furo[2,3-b]quinolines through the con-
densation reaction of 2-methoxy-3-formylquinolines
with acetone in the presence of sulphuric acid fol-
lowed by bromocyclisation and dehydrobromination.
The starting materials were prepared from 2-chloro-
3-formylquinolines under the condition of Cannizzaro
reaction. The experimental procedures are also very
simple.
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We thank the NMR Research Centre of Indian Institute
of Science (IISC), Bangalore and Shopisticated Ana-
lytical Instrument Facility, Indian Institute of Technol-
ogy (IIT) Madras for providing spectral and analytical
facilities.