Chemistry of substituted quinolines: Thieno[2,3-b] and thiopyrano[2,3-b] quinolines

Article abstract of DOI:10.1080/10426500601088846

The reaction of 3-formyl-2-chloroquinolines with thioglycolic acid afforded a mixture of uncyclized [(3-formylquinolin-2-yl)thio]acetic acid in a 60-70% yield and cyclized thieno[2,3-b]quinoline-2-carboxylic acids in a 30-40% yield, respectively. The uncyclized compounds on refluxing with POCl3 in various alcoholic media gave [(3-formylquinolin-2-yl)thio]acetates. Further cyclization was achieved by refluxing them with dimethylformamide (DMF) to produce thieno[2,3-b]quinoline derivatives. On the other hand, the reaction of 3-formyl-2-mercaptoquinolines with chloroacetyl chloride in DMF gave 3-chloro-2H-thiopyrano[2,3-b]quinolin-2-ones. The structures of all the newly synthesized compounds were characterized on the basis of elemental analysis, IR, 1H NMR, and mass spectral data.

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Phosphorus, Sulfur, and Silicon
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Chemistry of Substituted
Quinolines: Thieno[2,3- b ] and
Thiopyrano[2,3- b ]quinolines
Balaji M. Kiran a , Belalakatte P. Nandeshwarappa a
Vijayavittala P. Vaidya a & Kittappa M. Mahadevan a
,
a Department of Post Graduate Studies and Research
in Chemistry , Kuvempu University , Shankaraghatta,
Karnataka, India
Published online: 19 Apr 2007.
To cite this article: Balaji M. Kiran , Belalakatte P. Nandeshwarappa , Vijayavittala
P. Vaidya & Kittappa M. Mahadevan (2007) Chemistry of Substituted Quinolines:
Thieno[2,3- b ] and Thiopyrano[2,3- b ]quinolines, Phosphorus, Sulfur, and Silicon and
the Related Elements, 182:5, 969-980, DOI: 10.1080/10426500601088846
To link to this article: http://dx.doi.org/10.1080/10426500601088846
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Phosphorus, Sulfur, and Silicon, 182:969–980, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500601088846
Chemistry of Substituted Quinolines: Thieno[2,3-b] and
Thiopyrano[2,3-b]quinolines
Balaji M. Kiran
Belalakatte P. Nandeshwarappa
Vijayavittala P. Vaidya
Kittappa M. Mahadevan
Department of Post Graduate Studies and Research in Chemistry,
Kuvempu University, Shankaraghatta, Karnataka, India
The reaction of 3-formyl-2-chloroquinolines with thioglycolic acid afforded a mix-
ture of uncyclized [(3-formylquinolin-2-yl)thio]acetic acid in a 60–70% yield and
cyclized thieno[2,3-b]quinoline-2-carboxylic acids in a 30–40% yield, respectively.
The uncyclized compounds on refluxing with POCl in various alcoholic media
3
gave [(3-formylquinolin-2-yl)thio]acetates. Further cyclization was achieved by re-
fluxing them with dimethylformamide (DMF) to produce thieno[2,3-b]quinoline
derivatives. On the other hand, the reaction of 3-formyl-2-mercaptoquinolines with
chloroacetyl chloride in DMF gave 3-chloro-2H-thiopyrano[2,3-b]quinolin-2-ones.
The structures of all the newly synthesized compounds were characterized on the
1
basis of elemental analysis, IR, H NMR, and mass spectral data.
Keywords 3-formyl-2-chloroquinolines; 3-formyl-2-mercaptoquinolines; 3-formyl-
(quinolin-2-yl)thio acetic acids; methyl thieno[2,3-b]quinoline-2-carboxylates; thieno[2,3-
b]quinolines; thiopyrano[2,3-b]quinolines
INTRODUCTION
Five- and six-membered heterocyclic compounds containing one or
two heteroatoms fused to a quinoline ring in a linear fashion are
found in natural products as well as in synthetic compounds of bio-
logical interest.1 They are known to exhibit antiallergenic properties2
and antifungal,3 hypocholesterolemic, hypolemic,4 antibacterial,5 and
Received July 23, 2006; accepted October 6, 2006.
The authors are thankful to the Chairman, Department of PG Studies and Research
in Chemistry, School of Chemical Sciences, Kuvempu University, for providing laboratory
facilities. The authors are also thankful to the Convenor, NMR Research Center, Indian
Institute of Science, Bangalore, for spectral data.
Address correspondence to Kittappa M. Mahadevan, Department of Post Graduate
Studies and Research in Chemistry, Kuvempu University, Shankaraghatta, Karnataka,
577451 India. E-mail: mady kmm@yahoo.co.uk
969

970
B. M. Kiran et al.
antiviral activity.6 Numerous thieno[2,3-b]quinoline derivatives are
well documented for their pharmacological properties exhibiting
antibacterial,7−9 antifungal,9 antianaphylactic,10 antiarrhythmic, and
anti-inflammatory activity.11,12
The synthesis of novel derivatives of quinolines by a convenient
method remains an important synthetic task. Many synthetic meth-
ods have been developed for the synthesis of thieno quinolines,13−20
and because of their great importance, this remains an active research.
In continuation of our research program,21−23 which is directed toward
the synthesis of potentially bioactive molecules via a simple and prac-
tical approach, herein we report the rapid, cost-effective, and efficient
method for the synthesis of sulfur-bearing quinoline derivatives. The
key intermediate 3-formyl-2-chloroquinolines and 3-formyl-2-mercapto
quinolines were prepared from an earlier reported method.23,24
RESULTS AND DISCUSSION
Novel condensed heterocycles like thieno[2,3-b]quinolines and
thiopyrano[2,3-b]quinolines can be convceivably obtained by two
pathways (Scheme 1). From one pathway, i.e., the reaction of 3-formyl-
2-chloroquinolines 1a–d with thioglycolic acid in the presence of
sodium hydroxide in absolute ethanol, two compounds were obtained.
They are [(3-formylquinolin-2-yl)thio]acetic acids 3a–d with a 60–70%
yield and thieno[2,3-b]quinoline-2-carboxylic acids 4a–d with 30–40%
SCHEME 1 General synthetic procedure of [(3-formylquinolin-2-yl)thio]acetic
acids, thieno[2,3-b], and thiopyrano[2,3-b]quinoline derivatives 3a–d, 4a–d,
and 5a–d.

Chemistry of Substituted Quinolines
971
yield. Formation of these two products was confirmed by TLC analysis,
and they were separated by column chromatography.
Our mechanistic investigations using spectral studies gave proof
of cyclized and uncyclized products. A signal that corresponds to
S CH2 that appeared at 4.25 δ in 1H NMR of 3a revealed the forma-
tion of an uncyclized product (>60% column yield is presented). Further,
we investigated the other product 4a (>30%) and found that the signal
due to S CH2 group was absent in the 1H NMR spectrum. This re-
sult prompted us to confirm the subsequent cyclization of 3a. Further,
the structure assigned was confirmed by its mass spectrum. It gave
a molecular ion peak at m/z 247 for 3a and 229 for 4a. Similarly, the
spectral details of all other compounds are given in the Experimental
section.
The cyclization of thieno[2,3-b]quinoline-2-carboxylic acid deriva-
tives 4a–d prompted us to cyclize [(3-formylquinolin-2-yl)-thio]acetic
acid derivatives 3a–d by converting them into different car-
boxylic esters derivatives 6a–l. Thus, 3-formylquinolin-2-yl-thioacetic
acid 3a on refluxing with POCl3 in excess of methanol affords
SCHEME 2 General synthetic procedure of thieno[2,3-b]quinoline-2-
carboxylates 7a–d, 8a–d, and 9a–d.

972
B. M. Kiran et al.
methyl(3-formylquinolin-2-yl)thioacetate 6a. This on stirring with
DMF underwent smooth cyclization at r.t. to produce methyl thieno[2,3-
b]quinoline-2-carboxylate 7a. In a similar fashion compound 3b–d, on
refluxing with ethanol and isopropyl alcohol, gave 6b–l. These deriva-
tives upon stirring with DMF resulted in the formation of 7b–d, 8a–d,
and 9a–d, respectively.
In the 1H NMR spectrum of 7a, the signals corresponding to CHO
proton and the signal due to S CH2 group, which was present in 6a,
were found to be absent, whereas other signals remained at the same
position in 1H NMR spectrum; this confirms the formation of the thieno
ring nucleus. In the IR spectrum, absence of a band at 1640–1644 cm−1
corresponds to the CHO group, and reappearance of band at 1735 cm−1
further confirms the ring cyclization. In the mass spectrum of 7a, pres-
ence of the molecular ion peak at m/z 243 confirms the correct structure.
In another pathway, we observed a very interesting result in the
reaction of 3-formyl-2-mercaptoquinolines 2a–d with chloroacetylchlo-
ride in DMF media. Here compound 2a–d underwent cyclization to
give thiopyrano[2,3-b]quinoline derivatives 5a–d in a single step under
a reflux condition. The 1H NMR spectrum of compound 5a exhibited a
multiplet at 7.53–9.87 δ integrating six aromatic protons corresponding
to the quinoline[2,3-b]thiopyrano ring nucleus. The IR spectrum of 5a
exhibited absorption bands at 1620–1625 cm−1attributed to thiopy-
rano ring carbonyl group. This confirms the one-pot condensation of
3-formyl-2-mercaptoquinoline 2a with chloroacetyl chloride to build
thiopyrano nucleus. Further, a cyclized structure was confirmed by
recording mass spectra of the compounds 5a, which gave a molecular
ion peak at m/z 247.
EXPERIMENTAL
IR spectra were recorded on a Perkin Elmer 157 infrared spectropho-
1
tometer. The H NMR spectra (300 MHz) were recorded on a Bruker
Supercon FT NMR instrument using TMS as an internal standard and
mass spectra on a Jeol JMS-D 300 mass spectrometer operating at 70
eV. Melting points were determined in open capillaries and are uncor-
rected. The purity of the compounds was checked by TLC and were
further purified by column chromatography.
Preparation of [(3-formylquinolin-2-yl)thio]acetic Acid (3a)
Part A
A mixture of 2a (1.8 g, 0.01 mol), chloroacetic acid (1.4 g, 0.015 mol),
and K2CO3 (2.7 g, 0.04 mol) in dry acetone (50 mL) was refluxed on a

Chemistry of Substituted Quinolines
973
water bath for about 4–5 h. By using TLC technique, the progress of
the reaction was monitored. After completion of the reaction, the reac-
tion mixture was filtered; the solvent was evaporated under reduced
pressure and dried. The solid 3a obtained was purified by column chro-
matography (1.7 g, 72%). Similarly, the same procedure was followed
for the synthesis of 3b–d (65–72%).
Part B
A mixture of 1a (1.91 g, 0.01 mol), thioglycolic acid (9.21 g, 0.01 mol),
and sodium hydroxide (1.20 g, 0.03 mol) was dissolved in ethanol (30
mL). The mixture was refluxed on a water bath for 4 h. The progress
of the reaction was monitored by TLC. The reaction mixture was then
poured into water and neutralized with dil HCl. The solid 3a obtained
was filtered, dried, and purified by column chromatography (1.60 g,
70%). Similarly, compounds 3b–d were prepared in a 65–70% yield.
[(3-Formylquinolin-2-yl)thio]acetic Acid (3a)
1
Yield: 1.78 g, 72%; m.p. 156–157◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 4.25 (2H, s, S CH2 ), 7.59–9.58 (5H,
m, Ar H), 10.31 (1H, s, CHO) 11.6 (1H, s, OH); [M+]: 247. Calcd. (%)
for C10H11NO3S: C, 58.29; H, 3.67; N, 5.66; S, 12.97. Found: C, 58.23;
H, 3.59; N, 5.57; S, 12.86.
[(3-Formyl-6-methylquinolin-2-yl)thio]acetic Acid (3b)
1
Yield: 1.69 g, 65%; mp. 161–163◦C; IR (KBr) ν (cm−1): 1681; H NMR
(300 MHz, DMSO-d6) δ (ppm): 2.55 (3H, s, CH3), 4.26 (2H, s, S CH2 ),
7.58–9.56 (4H, m, Ar H), 10.30 (1H, s, CHO), 11.7 (1H, s, OH); [M+]:
261. Calcd. (%) for C13H11NO3S: C, 59.76; H, 4.24; N, 5.36; S, 12.27.
Found: C, 59.68; H, 4.16; N, 5.28; S, 12.23.
[(7-Chloro-6-fluoro-3-formylquinolin-2-yl)thio]acetic Acid (3c)
1
Yield: 1.88 g, 63%; mp. 164–165◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 4.25 (2H, s, S CH2 ), 7.57–9.53 (4H,
m, Ar H), 10.30 (1H, s, CHO), 11.6 (1H, s, OH); [M+]: 299. Calcd. (%)
for C12H7ClFNO3S: C, 48.09; H, 2.35; N, 4.67; S, 10.70. Found: C, 48.01;
H, 2.29; N, 4.56; S, 10.61.
[(6-Chloro-3-formylquinolin-2-yl)thio]acetic Acid (3d)
1
Yield: 1.97 g, 70%; mp. 168–169◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 4.27 (2H, s, S CH2 ), 7.54–9.58 (4H,

974
B. M. Kiran et al.
m, Ar H), 10.32 (1H, s, CHO), 11.6 (1H, s, OH); [M+]: 281. Calcd. (%)
for C12H8ClNO3S: C, 51.16; H, 2.86; N, 4.97; S, 11.38. Found: C, 51.32;
H, 2.75; N, 4.86; S, 11.25.
Preparation of 3-chloro-2H-thiopyrano[2,3-b]quinolin-2-one
A mixture of 3-formyl-2-mercaptoquinoline 2a (1.80 g, 0.01 mol) and
chloroacetyl chloride (1.68 g, 0.015 mol) in DMF (30 mL) was heated on
a water bath for 1 h. After completion of reaction, the reaction mixture
was poured into ice-cold water and stirred well, and the solid thus ob-
tained was filtered, dried, and recrystallized from ethyl acetate to give
5a (1.97 g, 80%). The same procedure was adopted for the synthesis of
5b–d, and the obtained yield was found to be 70–82%.
3-Chloro-2H-thiopyrano[2,3-b]quinolin-2-one (5a)
1
Yield: 1.98 g, 80%; mp. 213–215◦C; IR (KBr) ν (cm−1): 1620; H NMR
(300 MHz, DMSO-d6)δ (ppm): 7.53–9.87 (6H, m, Ar H), [M+]: 247.
Calcd. (%) for C12H6ClNOS: C, 58.19; H, 2.44; N, 5.65; S, 12.95. Found:
C, 58.76; H, 2.31; N, 5.65; S, 12.63.
3-Chloro-7-methyl-2H-thiopyrano[2,3-b]quinolin-2-one (5b)
1
Yield: 1.98 g, 76%; mp. 223–225◦C; IR (KBr) ν (cm−1): 1622; H NMR
(300 MHz, DMSO-d6) δ (ppm): 2.57 (3H, s, CH3), 7.54–9.83 (5H, m,
Ar H); [M+]: 261. Calcd. (%) for C13H9NO2S: C, 59.66; H, 3.08; N, 5.35;
S, 12.25. Found: C, 59.56; H, 3.16; N, 5.26; S, 12.17.
3,8-Dichloro-7-fluoro-2H-thiopyrano[2,3-b]quinolin-2-one (5c)
1
Yield: 2.16 g, 72%; mp. 203–205◦C; IR (KBr) ν (cm−1): 1623; H NMR
(300 MHz, DMSO-d6) δ (ppm): 7.57–9.86 (4H, m, Ar H); [M+]: 300.
Calcd. (%) for C12H4Cl2FNOS: C, 48.02; H, 1.34; N, 4.67; S, 10.68. Found:
C, 48.08; H, 1.39; N, 4.58; S, 10.58.
3,7-Dichloro-2H-thiopyrano[2,3-b]quinolin-2-one (5d)
1
Yield: 2.20 g, 78%; mp. 211–213◦C; IR (KBr) ν (cm−1): 1621; H NMR
(300 MHz, DMSO-d6)δ (ppm): 7.60–9.82 (5H, m, Ar H); [M+]: 282.
Calcd. (%) for C12H5Cl2NOS: C, 51.08; H, 1.79; N, 4.96; S, 11.37. Found:
C, 51.04; H, 1.67; N, 4.89; S, 11.28.

Chemistry of Substituted Quinolines
975
Preparation of [(3-Formylquinolin-2-yl)thio]acetate (6a)
A mixture of 3a (2.4 g, 0.01 mol) and methanol (50 mL) in the presence
of POCl3 (15 mL) was heated on a water bath for 2 h. Completion of the
reaction was monitored by TLC. Excess of POCl3 was distilled off under
reduced pressure; the residue obtained was washed with water, filtered,
and dried. The crude product was purified by column chromatography
and gave (1.99 g, 82%) 6a. In a similar way, 6b–l were prepared in a
73–82% yield.
[(3-Formylquinolin-2-yl)thio]acetate (6a)
Yield: 2.14 g, 82%; mp. 170–172◦C; IR (KBr) ν (cm−1): 1682; 1H
NMR (300 MHz, DMSO-d6) δ (ppm): 3.85 (3H, s, OCH3), 4.23 (2H, s,
S CH2 ), 7.62–9.63 (5H, m, Ar H), 10.33 (1H, s, CHO); [M+]: 261.
Calcd. (%) for C13H11NO3S: C, 59.76; H, 4.24; N, 5.36; S, 12.27. Found:
C, 59.67; H, 4.23; N, 5.28; S, 12.12.
[(3-Formyl-6-methylquinolin-2-yl)thio]acetate (6b)
1
Yield: 2.00 g, 73%; mp. 168–169◦C; IR (KBr) ν (cm−1): 1683; H NMR
(300 MHz, DMSO-d6) δ (ppm): 2.55 (3H, s, CH3), 3.83 (3H, s, OCH3),
4.24 (2H, s, SCH2 ), 7.64–9.61 (4H, m, Ar H), 10.33 (1H, s, CHO);
[M+]: 275. Calcd. (%) for C14H13NO3S: C, 61.07; H, 4.76; N, 5.09; S,
11.65. Found: C, 61.04; H, 4.62; N, 5.02; S, 11.58.
[(7-Chloro-6-fluoro-3-formylquinolin-2-yl)thio]acetate (6c)
Yield: 2.13 g, 68%; mp. 175–178◦C; IR (KBr) ν (cm−1): 1680; 1H
NMR (300 MHz, DMSO-d6) δ (ppm): 3.82 (3H, s, OCH3), 4.26 (2H, s,
S CH2 ), 7.62–9.64 (3H, m, Ar H), 10.31 (1H, s, CHO); [M+]: 313.
Calcd. (%) for C12H7ClFNO3S: C, 49.77; H, 2.89; N, 4.46; S, 10.22. Found:
C, 49.68; H, 2.78; N, 437; S, 10.14.
[(6-Chloro-3-formylquinolin-2-yl)thio]acetate (6d)
Yield: 2.06 g, 71%; mp. 180–182◦C; IR (KBr) ν (cm−1): 1684; 1H
NMR (300 MHz, DMSO-d6) δ (ppm): 3.84 (3H, s, OCH3), 4.25 (2H, s,
S CH2 ), 7.64–9.61 (4H, m, Ar H), 10.30 (1H, s, CHO); [M+]: 295.
Calcd. (%) for C13H10ClNO3S: C, 52.80; H, 3.41; N, 4.74; S, 10.84. Found:
C, 52.71; H, 3.32; N, 4.64; S, 10.73.

976
B. M. Kiran et al.
Ethyl[(3-formylquinolin-2-yl)thio]acetate (6e)
1
Yield: 2.06 g, 75%; mp. 174–175◦C; IR (KBr) ν (cm−1): 1683; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.32 (3H, t, CH3), 4.33 (2H, q, OCH2),
4.21 (2H, s, S CH2 ), 7.63–9.61 (5H, m, Ar H), 10.32 (1H, s, CHO);
[M+]: 275. Calcd. (%) for C14H13NO3S: C, 61.07; H, 4.76; N, 5.09; S,
11.65. Found: C, 62.17; H, 4.65; N, 5.13; S, 11.41.
Ethyl [(3-formyl-6-methylquinolin-2-yl)thio]acetate (6f)
1
Yield: 1.99 g, 69%; mp. 183–185◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.31 (3H, t, CH3), 2.56 (3H, s, CH3), 4.22
(2H, s, S CH2 ), 4.32 (2H, q, OCH2), 7.61–9.64 (4H, m, Ar H), 10.31
(1H, s, CHO); [M+]; 289. Calcd. (%) for C15H15NO3S: C, 62.26; H, 5.23;
N, 4.84; S, 11.08. Found: C, 62.18; H, 5.19; N, 4.74; S, 11.02.
Ethyl [(7-chloro-6-fluoro-3-formylquinolin-2-yl)thio]acetate
(6g)
1
Yield: 2.29 g, 70%; mp. 190–192◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.32 (3H, t, CH3), 4.31 (2H, q, OCH2),
4.20 (2H, s, S CH2 ), 7.63–9.60 (3H, m, Ar H), 10.33 (1H, s, CHO);
[M+], 327. Calcd. (%) for C14H11ClFNO3S: C, 51.30; H, 3.38; N, 4.27; S,
9.78. Found: C, 51.21; H, 3.27; N, 4.18; S, 9.67.
Ethyl [(6-chloro-3-formylquinolin-2-yl)thio]acetate (6h)
1
Yield: 2.21 g, 70%; mp. 195–197◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.30 (3H, t, CH3), 2.55 (3H, s, CH3), 4.22
(2H, s, S CH2 ), 4.30 (2H, q, OCH2), 7.60–9.63 (4H, m, Ar H), 10.31
(1H, s, CHO); [M+]: 309. Calcd. (%) for C14H12ClNO3S: C, 54.28; H, 3.90;
N, 4.52; S, 10.35. Found: C, 54.17; H, 3.79; N, 4.41; S, 10.24.
Isopropyl [(3-formylquinolin-2-yl)thio]acetate (6i)
1
Yield: 2.22 g, 77%; mp. 188–189◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.45 (6H, d, 2CH3), 3.55 (1H, h, CH ),
4.21 (2H, s, S CH2 ), 7.61–9.60 (5H, m, Ar H), 10.30 (1H, s, CHO);
[M+]: 289. Calcd. (%) for C15H15N3OS: C, 62.26; H, 5.23; N, 4.84; S,
11.08. Found: C, 62.17; H, 5.16; N, 4.73; S, 11.02.

Chemistry of Substituted Quinolines
977
Isopropyl [(3-formyl-6-methylquinolin-2-yl)thio]acetate (6j)
1
Yield: 2.12 g, 70%; mp. 176–178◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.43 (6H, d, 2CH3), 3.54 (1H, h, CH ),
4.20 (2H, s, S CH2 ), 7.63-9.62 (4H, m, Ar H), 10.31 (1H, s, CHO);
[M+]; 303. Calcd. (%) for C16H17NO3S: C, 63.34; H, 5.65; N, 4.62; S,
10.57. Found: C, 63.25; H, 5.53; N, 4.53; S, 10.46.
Isopropyl [(7-chloro-6-fluoro-3-formylquinolin-2-yl)thio]
acetate (6k)
1
Yield: 2.52 g, 74%; mp. 185–186◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.40 (6H, d, 2CH3), 3.52 (1H, h, CH ),
4.22 (2H, s, S CH2 ), 7.60-9.63 (3H, m, Ar H), 10.30 (1H, s, CHO);
[M+]; 341. Calcd. (%) for C15H13ClFNO3S: C, 52.71; H, 3.83; N, 4.10; S,
9.38. Found: C, 52.64; H, 3.71; N, 4.25, S, 9.50.
Isopropyl [(6-chloro-3-formylquinolin-2-yl)thio]acetate (6l)
1
Yield: 2.46 g, 76%; mp.197–198◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.41 (6H, d, 2CH3), 3.52 (1H, h, CH ),
4.22 (2H, s, S CH2 ), 7.60–9.63 (4H, m, Ar H), 10.30 (1H, s, CHO);
[M+]; 323. Calcd. (%) for C15H14ClNO3S: C, 55.64; H, 4.36; N, 4.33; S,
9.90. Found: C, 55.53; H, 4.27; N, 4.24; S, 9.79.
Preparation of methyl thieno[2,3-b]quinoline-2-carboxylate
(7a)
A mixture of 6a (2.61 g, 0.01 mol), and DMF (30 mL) was stirred for 4 h.
After the completion of the reaction (monitored by TLC), excess DMF
was distilled off under reduced pressure. Then the reaction mixture was
poured into crushed ice; the solid thus obtained was filtered and dried.
The crude product was purified by column chromatography to provide
2.05 g (85%) of pure 7a. In a similar way, 7b–d, 8a–d, and 9a–d were
prepared in a 70–85% yield.
Methyl thieno[2,3-b]quinoline-2-carboxylate (7a)
1
Yield: 1.90 g, 85%, mp. 282–283◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 3.86 (3H, s, OCH3), 7.62–9.67 (6H, m,
Ar H), [M+]; 243. Calcd. (%) for C13H9NO2S: C, 64.18; H, 3.73; N, 5.76;
S, 13.18. Found: C, 64.26; H, 3.67; N, 63; S, 13.26.

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B. M. Kiran et al.
Methyl 6-methylthieno[2,3-b]quinoline-2-carboxylate (7b)
1
Yield: 1.81 g, 76%; mp. 274–275◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 2.55 (3H, s, CH3), 3.84 (3H, s, OCH3),
7.61–9.65 (5H, m, Ar H); [M+]: 257. Calcd. (%) for C14H11NO2S: C,
65.35; H, 4.31; N, 5.44; S, 12.46. Found: C, 65.26; H, 4.20; N, 5.33; S,
12.35.
Methyl 7-chloro-6-fluorothieno[2,3-b]quinoline-2-carboxylate
(7c)
1
Yield: 1.93 g, 70%; mp. 186–189◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 3.81 (3H, s, OCH3), 7.63–9.62 (4H, m,
Ar H); [M+]: 295. Calcd. (%) for C13H7ClFNO2S: C, 52.80; H, 2.39; N,
4.74; S, 10.84. Found: C, 52.80; H, 2.39; N, 4.74; S, 10.84.
Methyl 6-chlorothieno[2,3-b]quinoline-2-carboxylate (7d)
1
Yield: 1.86 g, 72%, mp. 294–295◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 3.82 (3H, s, OCH3), 7.62–9.65 (5H, m,
Ar H); [M+]: 277. Calcd. (%) for C13H8ClNO2S: C, 56.22; H, 2.90; N,
5.04; S, 11.55. Found: C, 56.32; H, 2.79; N, 5.01; S, 11.47.
Ethyl thieno[2,3-b]quinoline-2-carboxylate (8a)
1
Yield: 1.95 g, 82%; mp. 269–270◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.32 (3H, t, CH3), 4.33 (2H, q, OCH2),
7.61–9.68 (6H, m, Ar H); [M+]: 257. Calcd. (%) for C14H11NO2S: C,
65.35; H, 4.31; N, 5.44; S, 12.46. Found: C, 65.27; H, 4.23; N, 5.36; S,
12.38.
Ethyl 6-methylthieno[2,3-b]quinoline-2-carboxylate (8b)
1
Yield: 1.86 g, 74%; mp. 284–285◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.32 (3H, t, CH3), 2.55 (3H, s, CH3), 4.33
(2H, q, OCH2), 7.61–9.65 (5H, m, Ar H); [M+]: 271. Calcd. (%) for
C15H13NO2S: C, 66.40; H, 4.83; N, 5.16; S, 11.82. Found: C, 66.32; H,
4.73; N, 5.26; S, 11.74.

Chemistry of Substituted Quinolines
979
Ethyl 7-chloro-6-fluorothieno[2,3-b]quinoline-2-carboxylate
(8c)
1
Yield: 2.00 g, 69%; mp. 270–272◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6)δ (ppm): 1.32 (3H, t, CH3), 4.33 (2H, q, OCH2),
7.61–9.65 (4H, m, Ar H); [M+]: 309. Calcd. (%) for C14H9ClFNO2S: C,
54.29; H, 2.93; N, 4.52; S, 10.35. Found: C, 54.17; H, 2.82; N, 4.41; S,
10.46.
Ethyl 6-chlorothieno[2,3-b]quinoline-2-carboxylate (8d)
1
Yield: 1.88 g, 69%; mp. 291–293◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.32 (3H, t, CH3), 4.33 (2H, q, OCH2),
7.61–9.65 (5H, m, Ar H); [M+]: 291. Calcd. (%) for C14H10ClNO2S: C,
57.63; H, 3.45; N, 4.80; S, 10.99. Found: C, 57.52; H, 3.36; N, 4.71; S,
10.84.
Isopropyl thieno[2,3-b]quinoline-2-carboxylate (9a)
1
Yield: 2.01 g, 80%; mp. 257–258◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.45 (6H, d, 2CH3), 3.55 (1H, h, CH ),
7.62–9.64 (6H, m, Ar H); [M+]: 271. Calcd. (%) for C15H13NO2S: C,
66.40; H, 4.83; N, 5.16; S, 11.82. Found: C, 66.33; H, 4.74; N, 5.26; S,
11.73.
Isopropyl 6-methylthieno[2,3-b]quinoline-2-carboxylate (9b)
1
Yield: 2.02 g, 76%; mp. 268–269◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.45 (6H, d, 2CH3), 2.55 (3H, h, Ar CH3)
3.55 (1H, s, CH ), 7.63–9.64 (5H, m, Ar H); [M+]: 285. Calcd. (%) for
C16H15NO2S: C, 67.34; H, 5.30; N, 4.91; S, 11.24. Found: C, 67.24; H,
5.21; N, 4.82; S, 11.16.
Isopropyl 6-chloro-7-fluorothieno[2,3-b]quinoline-2-
carboxylate (9c)
1
Yield: 2.01 g, 66%; mp. 259–261◦C; IR (KBr) ν (cm−1): 1682; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.45 (6H, d, 2CH3), 3.55 (1H, h, CH ),
7.63–9.64 (4H, m, Ar H); [M+]: 323. Calcd. (%) for C15H11ClFNO2S: C,
55.64; H, 3.42; N, 4.33; S, 9.90. Found: C, 55.55; H, 3.31; N, 4.21; S, 9.79.

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Isopropyl 7-chlorothieno[2,3-b]quinoline-2-carboxylate (9d)
1
Yield: 2.00 g, 70%; mp. 241–245◦C; IR (KBr) ν (cm−1): 1680; H NMR
(300 MHz, DMSO-d6) δ (ppm): 1.46 (6H, d, 2CH3), 3.57 (1H, h, CH ),
7.61–9.67 (5H, m, Ar H); [M+]: 305. Calcd. (%) for C15H12ClNO2S: C,
58.92; H, 3.96; N, 4.58; S, 10.49. Found: C, 58.81; H, 3.86; N, 4.48; S,
10.38.
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