Chemoselective synthesis of thieno[3,2-c][1,8]naphthyridin-4(5H)-ones by tandem cyclization

Article abstract of DOI:10.1002/hc.20234

A number of the thieno[3,2-c][1,8]-naphthyridin-4(5H)-ones are chemoselectively synthesized from 4-(4′-aryloxybut-2′-ynylthio)-1- phenyl-1,8-naphthyridin-2(1H)-ones in 82-90% yield by the formation of sulfoxide, followed by [2,3] and [3,3]sigmatropic rear

Full text of DOI:10.1002/hc.20234

Heteroatom Chemistry
Volume 18, Number 1, 2007
Chemoselective Synthesis of
Thieno[3,2-c][1,8]naphthyridin-4(5H)-ones
by Tandem Cyclization
Krishna C. Majumdar and Rafique-ul-Islam
Department of Chemistry, University of Kalyani, Kalyani 741235, India
Received 23 June 2005; revised 23 January 2006
ported by Majumdar and Thyagaranjan. This pro-
ABSTRACT: A number of the thieno[3,2-c][1,8]-
tocol when applied to selenium analogues [14] pro-
naphthyridin-4(5H)-ones are chemoselectively syn-
ceeded with different results. Recently, we have
thesized from 4-(4ꢀ-aryloxybut-2ꢀ-ynylthio)-1-phenyl-
reported some applications of sulfoxide [15–18] and
1,8-naphthyridin-2(1H)-ones in 82–90% yield by
amine oxide [19–22] rearrangement in heterocyclic
the formation of sulfoxide, followed by [2,3] and
substrates for the synthesis of tricyclic skeleton.
[3,3]sigmatropic rearrangement and an intramolec-
Some fused tricyclic derivatives of naphthyridinones
ꢁ
C
ular Michael addition.
2007 Wiley Periodicals, Inc.
are known to possess a wide spectrum of medicinal
properties [23], and this prompted us to undertake
the study on the synthesis of some tricyclic com-
pounds having 1,8-naphthyridine skeleton. Here we
report the results of our investigation.
Heteroatom Chem 18:87–92, 2007; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20234
INTRODUCTION
RESULTS AND DISCUSSION
1,8-Naphthyridin-2-ones and their derivatives are
known to possess anti-inflammatory, antiallergic,
potent gastric antisecretary, antitumor, and bron-
codilator properties [1–3]. 1-Phenyl-4-hydroxy-1,8-
naphthyridin-2(1H)-one and its derivatives have
been used as antiallergic agent [4]. 2-Oxo-1,8-naph-
thyridin-3-carboxylic acid derivatives possess potent
gastric antisecretary properties and anti-inflammat-
ory activities [5,6]. A series of novel imidazo[4,5-c]
[1,8]naphthyridin-4(5H)-ones exhibited potent bron-
chodilator activity [7]. The construction of the five-
membered heterocyclic ring in benzo(b)-thiophenes
and indoles through sulfoxide [8–10] and amine
oxide [11–13] rearrangement, respectively was re-
The starting materials for this investigation, 4-(4ꢀ-ary-
loxybut-2ꢀ-ynylthio)-1-phenyl-1,8-naphthyridin-2(1H)-
ones 5a–f, were synthesized by the phase-transfer
catalyzed alkylation of 4-mercapto-1-phenyl-1,8-na-
phthyridin-2(1H)-ones 3 with 1-aryloxy-4-chlorobut-
2-ynes 4a–f in 65–75% yield. 4-Mercapto-1-phenyl-
1,8-naphthyridin-2(1H)-one 3 was prepared in situ
from 1-phenyl-4-tosyloxy-1,8-naphthyridin-2(1H)-
one 2, which in turn was prepared from 1-phenyl–
4-hydroxy-1,8-naphthyridin-2(1H)-one 1. 1-Phenyl-
4-hydroxy-1,8-naphthyridin-2(1H)-one 1 was pre-
pared by the procedure described by Sherlock et al.
[4] (Scheme 1).
Compounds 5a–f were all solids and character-
ized from their elemental analyses and spectroscopic
data.
Substrates 5a–f contain a suitably placed alkynyl
segment so as to allow the occurrence of a [2,3]
Correspondence to: Krishna C. Majumdar; e-mail: kcm ku@
yahoo.co.in.
Contract grant sponsor: CSIR, New Delhi.
2007 Wiley Periodicals, Inc.
c
ꢁ
87

88 Majumdar and Islam
SCHEME 1 Reagents and reaction condition: (i) TsCl, Pyri-
dine, Stirr., rt., 30 min. (ii) NaSH, dry EtOH, 0-5◦C, Stirr., 5 h
(iii) Aqueous NaOH, CHCl3, BTEAC, Stirr., 8-10 h.
SCHEME 2 Reagents and reaction condition: (i) m -CPBA,
dichloromethane, 0-5◦C, 30 min (ii) Dichloromethane, reflux,
1 h.
sigmatropic rearrangement in the corresponding
sulfoxides. With this in view, compound 5a was
treated with m-chloroperoxybenzoic acid (m-CPBA)
at 0–5◦C in CH2Cl2 solution over 0.5 h. The formation
of the sulfoxide was indicated by a single spot (TLC
monitoring, Rf = 0.4 in petroleum ether:ethyl acetate
(70:30) % (v/v)) and disappearance of the starting
sulfide. The sulfoxides are quite susceptible to re-
arrangement and rearranges even during the work
up process of the reaction mixture. Therefore, no
attempt was made to isolate the sulfoxide, and the
reaction mixture was directly subjected to thermal
rearrangement without further purification. The re-
action mixture was then refluxed in CH2Cl2 for 1 h
to give a solid, which was characterized from its ele-
mental analysis and spectroscopic data to be 6a. The
1H NMR spectrum of compound 6a displayed a mul-
tiplet at δ 3.78–3.84, indicating the presence of two
SCH2 protons. The ring juncture proton appeared
as one-proton double doublet at δ 5.07–5.11 (J = 7.2,
9.6 Hz). Two one-proton doublets at δ 4.96 (J =
16 Hz) and δ 5.00 (J = 16 Hz) showed the presence of
aryloxy methylene protons adjacent to ketonic car-
bonyl group. The remaining substrates 5b–f were
also similarly subjected to sulfoxide rearrangement
to furnish the products 6b–f (Scheme 2).
tautomerization to 10. Intermediates 10 possess a
nucleophilic SH functionality favorably juxtaposed
to an ꢀ,ꢁ-enone moiety so as to allow an internal
Michael-type addition to produce compounds 6.
Another mode of cyclization of intermediate 10
could have occurred. SH function could have de-
livered its nucleophilic attack to the carbonyl car-
bon of the enone moiety, leading to the allylic alco-
hol 11. SN2ꢀ attack of water or m-chlorobenzoate ion
on 11 might have given to compound 12. However,
we could not obtain this compound 12 in any of the
cases.
This method is found to be general for the
chemoselective synthesis of thieno[3,2-c][1,8]naph-
thyridin-4(5H)-ones in excellent yield. This is a very
mild and direct method for the synthesis of this po-
tentially bioactive polyheterocycles by using sulfox-
ide rearrangement methodology.
EXPERIMENTAL
The formation of products 6 from 5 may be
mechanistically interpreted as depicted in Scheme 3.
Initial [2,3] sigmatropic rearrangement of the sulfox-
ides 7 gives the allenyl intermediates. Occurrence
of [3,3] sigmatropic rearrangement in 8 may gen-
erate the intermediates 9, which may then undergo
Melting points were determined in an open capil-
lary and are uncorrected. IR spectra were recorded
on a Perkin-Elmer L 120-000A spectrometer (νmax
in cm−1) on KBr disks. UV absorption spectra were
recorded in EtOH on a Shimadzu UV-2401PC spec-
trophotometer (λmax in nm). 1H NMR (300, 400, 500,
Heteroatom Chemistry DOI 10.1002/hc

Chemoselective Synthesis of Thieno[3,2-c][1,8]naphthyridin-4(5H)-ones by Tandem Cyclization 89
SCHEME 3 Mechanism of formation of products thieno[3,2-c][1,8]naphthyridin-4(5H )-ones 6a–f from the sulfides 5a–f.
600 MHz) and 13C NMR (75.5, 125.7 MHz) spec-
tra were recorded on a Bruker DPX-300, Vaian-
400 MHz FT NMR, Bruker DPX-500 and Varian-
600 MHz spectrometers in CDCl3 (chemical shifts in
δ) with TMS as internal standard. Elemental analy-
ses and mass spectra were recorded on a Leco 932
CHNS analyzer and on a JEOL JMS-600 instrument,
respectively. 1H NMR and 13C NMR spectra were
recorded at the Indian Institute of Chemical Biol-
ogy, Kolkata and Bose Institute, Kolkata. Silica gel
((60–120 mesh), Spectrochem, India) was used for
chromatographic separation. Silica gel G (E-Merck,
India) was used for TLC. Petroleum ether refers to
the fraction boiling between 60 and 80◦C.
was shaken for about 30 min at room temperature.
The reaction mixture was then poured into crushed
ice and left overnight. The precipitate was filtered,
washed with water, and dried. The solid was recrys-
tallized from methanol to give a white solid 2 (3.71 g,
95%).
Compound 2. Yield 95%, solid, m.p. 206–208◦C;
IR (KBr) νmax: 3057, 1666, 1584, 1440 cm−1; UV
(EtOH), λmax: 222, 328 nm; 1H NMR (400 MHz,
CDCl3): δH 2.48 (s, 3H, CH3), 6.50 (s, 1H, CH),
7.16–7.25 (m, 4H, ArH), 7.40–7.43 (d, 1H, J =
8.4 Hz, ArH), 7.49–7.58 (m, 3H, ArH), 7.91–7.3 (d,
2H, J = 8.4 Hz, ArH), 8.14–8.16 (dd, 1H, J = 1.6, 8
Hz, ArH), 8.46–8.47 (dd, 1H, J = 1.6, 3.6 Hz, ArH).
The 1-aryloxy-4-chlorobut-2-ynes 4a–f were pre-
pared according to the published procedure [24].
General Procedure for the Preparation of
4-Mercapto-1-phenyl-1,8-naphthyridin-2(1H)-
one 3
General Procedure for the Preparation of 1-Phen-
yl-4-tosyloxy-1,8-naphthyridin-2(1H)-one 2
1-Phenyl-4-hydroxy-1,8-naphthyridin-2(1 H )-one
(2.38 g, 10 mmol) was dissolved in dry pyridine
(20 mL) and toluene-4-sulfonyl chloride (1.9 g,
10 mmol) was added to the solution and the mixture
1-Phenyl-4-tosyloxy-1,8-naphthyridin-2(1H)-one
(0.75 g, 2 mmol) was dissolved in dry ethanol
(100 mL) and anhydrous NaOH (0.56 g, 10 mmol)
was added to it at 0–5◦C with constant stirring. The
Heteroatom Chemistry DOI 10.1002/hc

90 Majumdar and Islam
reaction mixture was allowed to attain room tem-
perature and stirred for 5 h. The alcohol was re-
moved under reduced pressure in vacuum. Ice-cold
50% aqueous HCl was added to the reaction mixture
to maintain the pH ∼2. The reaction mixture was ex-
tracted in chloroform (2 × 50 mL); the extract was
washed with water (2 × 25 mL) and dried (Na2SO4).
Organic layer was evaporated under reduced pres-
sure to get the crude product 3 and this crude prod-
uct 3 was used in the subsequent phase-transfer cat-
alyzed reaction without further purification.
8.11–8.13 (d, 1H, J = 7.9 Hz, Ha), 8.45–8.46 (d, 1H,
J = 3.2 Hz, Hc); MS (m/z): 426 (M+). Anal. Calcd for
C26H22N2O2S: C, 73.23; H, 5.16; N, 6.57%. Found: C,
73.01; H, 4.94; N, 6.79%.
Compound 5c. Yield 65%, solid, m.p. 118–
120◦C; IR (KBr) νmax: 2951, 1648, 1579, 1436 cm−1;
UV (EtOH) λmax: 205, 221, 310, 326 nm; 1H NMR (600
MHz, CDCl3): δH 2.26 (s, 6H, CH3), 3.87 (t, 2H, J = 2
Hz, SCH2), 4.68 (t, 2H, J = 2 Hz, OCH2), 6.57–
6.61 (m, 3H, ArH), 6.72 (s, 1H, CH, Hd), 7.15–7.17
(dd, 1H, J = 4.8, 7.8 Hz, Hb), 7.26–7.28 (m, 2H, ArH),
7.48–7.51 (m, 2H, ArH), 7.56–7.58 (m, 1H, ArH),
8.11–8.13 (dd, 1H, J = 1.2, 7.8 Hz, Ha), 8.45–8.46 (dd,
1H, J = 1.8, 4.8 Hz, Hc); MS (m/z): 426 (M+). Anal.
Calcd for C26H22N2O2S: C, 73.23; H, 5.16; N, 6.57%.
Found: C, 73.44; H, 5.01; N, 6.38%.
General Procedure for the Preparation of
4-(4ꢀ-Aryloxybut-2ꢀ-ynylthio)-1-phenyl-1,8-
naphthyridin-2(1H)-one 5a–f
To a mixture of 4-mercapto-1-phenyl-1,8-naphthy-
ridin-2(1H)-one 3 (0.5 g, 2 mmol) and 1-aryloxy-4-
chloro-2-butyne 4a–f (2.4 mmol) was added a solu-
tion of benzyltriethyl ammonium chloride (BTEAC)
in 1% aqueous NaOH (50 mL), and the mixture was
stirred at room temperature for about 8–10 h. The re-
action mixture was then diluted with water (100 mL),
and the organic layer was extracted with chloro-
form (3 × 25 mL). The organic layer was repeatedly
washed with saturated brine and dried (Na2SO4).
The solvent was removed and the viscous mass was
chromatographed over silica gel using petroleum
ether:ethyl acetate (3:1) as eluant to afford the prod-
ucts 5a–f.
Compound 5d. Yield 65%, solid, m.p. 120–
122◦C; IR (KBr) νmax: 2934, 1651, 1581, 1481 cm−1;
UV (EtOH) λmax: 205, 222, 294, 312, 328 nm; 1H NMR
(500 MHz, CDCl3): δH 3.85 (t, 2H, J = 2 Hz, SCH2),
4.79 (t, 2H, J = 2 Hz, OCH2), 6.71 (s, 1H, CH, Hd),
6.97–6.99 (d, 1H, J = 8.2 Hz, C4ꢀ-H), 7.15–7.18 (dd,
2H, J = 3.3, 7.8 Hz, C5ꢀ-H, Hb), 7.25–7.28 (m, 2H,
ArH), 7.34–7.35 (d, 1H, J = 2.3 Hz, C2ꢀ-H), 7.48–7.51
(t, 1H, J = 7.4 Hz, ArH), 7.56–7.59 (t, 2H, J = 7.5 Hz,
ArH), 8.09–8.11 (dd, 1H, J = 1.0, 7.8 Hz, Ha), 8.46–
8.47 (d, 1H, J = 3.3 Hz, Hc); MS (m/z): 470, 468, 466
(M+) Anal. Calcd for C24H16N2O2SCl2: C, 61.67; H,
3.42; N, 5.99%. Found: C, 66.84; H, 3.49; N, 5.73%.
Compound 5a. Yield 70%, solid, m.p. 151–
153◦C; IR (KBr) νmax: 2951, 1651, 1579, 1481, 1402
Compound 5e. Yield 75%, solid, m.p. 155–
157◦C; IR (KBr) νmax: 2938, 1642, 1579, 1432 cm−1;
UV (EtOH) λmax: 221, 269, 277, 311, 326 nm; 1H NMR
(500 MHz, CDCl3): δH 3.86 (t, 2H, J = 2 Hz, SCH2),
4.72 (t, 2H, J = 2 Hz, OCH2), 6.72 (s, 1H, CH, Hd),
6.93–6.96 (m, 3H, ArH), 7.14–7.16 (dd, 1H, J = 4.6,
7.9 Hz, Hb), 7.25–7.29 (m, 4H, ArH), 7.48–7.51 (t, 1H,
J = 7.3 Hz, ArH), 7.56–7.59 (t, 2H, J = 1.5, 7.9 Hz,
ArH), 8.10–8.12 (dd, 1H, J = 1.5, 7.9 Hz, Ha), 8.45–
8.46 (dd, 1H, J = 1.5, 4.6 Hz, Hc); MS (m/z): 398 (M+)
Anal. Calcd for C24H18N2O2S: C, 72.36; H, 4.52; N,
7.03%. Found: C, 72.17; H, 4.39; N, 7.25%.
1
cm−1; UV (EtOH) λmax: 222, 282, 309, 326 nm; H
NMR (600 MHz, CDCl3): δH 3.86 (t, 2H, J = 2 Hz,
SCH2), 4.80 (t, 2H, J = 2 Hz, OCH2), 6.71 (s, 1H,
CH, Hd), 6.89–6.92 (dt, 1H, J = 1.2, 7.8 Hz, C4ꢀ-
H), 7.04–7.05 (dd, 1H, J = 1.8, 7.8 Hz, C5ꢀ-H), 7.15–
7.17 (dd, 1H, J = 4.2, 7.8 Hz, Hb), 7.19–7.22 (dt, 1H,
J = 1.2, 7.8 Hz, C3ꢀ-H), 7.27–7.28 (m, 2H, ArH), 7.34–
7.35 (dd, 1H, J = 1.8, 7.8 Hz, C2ꢀ-H), 7.48–7.51 (m,
1H, ArH), 7.56–7.59 (m, 2H, ArH), 8.10–8.12 (dd, 1H,
J = 1.3, 7.8 Hz, Ha), 8.45–8.46 (dd, 1H, J = 1.2, 4.2
Hz, Hc); MS (m/z): 434, 432 (M+). Anal. Calcd for
C24H17N2O2SCl: C, 66.58; H, 3.93; N, 6.47%. Found:
C, 66.32; H, 4.05; N, 6.67%.
Compound 5f. Yield 65%, solid, m.p. 138–
140◦C; IR (KBr) νmax: 2939, 1666, 1578, 1493 cm−1;
1
Compound 5b. Yield 70%, solid, m.p. 118–
120◦C; IR (KBr) νmax: 2919, 1646, 1580, 1504, 1433
UV (EtOH) λmax: 221, 282, 309, 327 nm; H NMR
(600 MHz, CDCl3): δH 2.22 (s, 3H, CH3), 3.86 (t,
2H, J = 2 Hz, SCH2), 4.73 (t, 2H, J = 2 Hz, –OCH2),
6.73 (s, 1H, CH), 6.85–6.91 (m, 2H, ArH), 7.11–
7.13 (m, 1H, ArH), 7.15–7.17 (dd, 1H, J = 4.6, 7.9 Hz,
Hb) 7.26–7.28 (m, 2H, ArH), 7.48–7.51 (m, 2H, ArH),
7.56–7.59 (m, 2H, ArH), 8.11–8.13 (dd, 1H, J = 1.2,
7.2 Hz, Ha), 8.45–8.46 (dd, 1H, J = 1.2, 4.2 Hz, Hc);
1
cm−1; UV (EtOH) λmax: 222, 282, 308, 326 nm; H
NMR (300 MHz, CDCl3): δH 2.19 (s, 3H, CH3), 2.22
(s, 3H, CH3), 3.86 (t, 2H, J = 2 Hz, SCH2), 4.70 (t,
2H, J = 2 Hz, OCH2), 6.73 (s, 1H, CH, Hd), 6.78–
6.94 (m, 3H, ArH), 7.14–7.18 (dd, 1H, J = 3.2, 7.8 Hz,
Hb), 7.26–7.28 (m, 2H, ArH), 7.47–7.60 (m, 3H, ArH),
Heteroatom Chemistry DOI 10.1002/hc

Chemoselective Synthesis of Thieno[3,2-c][1,8]naphthyridin-4(5H)-ones by Tandem Cyclization 91
MS (m/z) = 412 (M+). Anal. Calcd for C25H20N2O2S:
112.77, 118.59, 126.70, 127.28, 127.49, 128.88,
129.16, 129.67, 130.83, 132.04, 134.96, 136.89,
150.93, 151.13, 154.00, 154.21, 159.30, 205.80; MS
(m/z): 442 (M+). Anal. Calcd for C26H22N2O3S: C,
70.58; H, 4.97; N, 6.33%. Found: C, 70.76; H, 5.06; N,
6.21%.
C, 72.81; H, 4.85; N, 6.79%. Found: C, 72.62; H, 4.97;
N, 6.91%.
General Procedure for the Oxidation and
Rearrangement of 4-(4ꢀ-Aryloxybut-2ꢀ-ynylthio)-
1-phenyl-1,8-naphthyridin-2(1H)-one 5a–f
Compound 6c. Yield 90%, solid, m.p. 212–
214◦C; IR (KBr) νmax: 2914, 1726, 1647, 1597, 1581,
A solution of m-CPBA (0.24 mmol, 0.08 g (50%)) in
dichloromethane (30 mL) was slowly added to a well-
stirred solution of the sulfide 5a–f (0.24 mmol) in
dichloromethane (30 mL) at 0–5◦C over a period of
15 min. The reaction mixture was stirred at room
temperature for an additional 30 min. Then the re-
action mixture was refluxed for 1 h. The resulting so-
lution was then washed with 10% aqueous Na2CO3
(3 × 25 mL), brine (25 mL), and dried (Na2SO4). Re-
moval of dichloromethane furnished the crude prod-
uct, which was purified by column chromatography
over silica gel. Elution of the column with petroleum
ether:ethyl acetate (5:1) mixture gave the pure com-
pound 6a–f.
1
1445 cm−1; UV (EtOH) λmax: 221, 280, 329 nm; H
NMR (300 MHz, CDCl3): δH 2.22 (s, 6H, CH3), 3.63–
3.83 (m, 2H, SCH2), 4.94–4.99 (m, 3H, OCH2, ring
juncture H), 6.51 (s, 2H, ArH), 6.60 (s, 1H, ArH),
7.16–7.25 (m, 3H, ArH), 7.48–7.57 (m, 3H, ArH),
7.81–7.83 (d, 1H, J = 7.5 Hz, Ha), 8.47–8.48 (d, 1H,
J = 2.9 Hz, Hc); MS (m/z): 442 (M+). Anal. Calcd for
C26H22N2O3S: C, 70.58; H, 4.97; N, 6.33%. Found: C,
70.41; H, 4.82; N, 6.55%.
Compound 6d. Yield 90%, solid, m.p. 198–
200◦C; IR (KBr) νmax: 2917, 1724, 1644, 1581, 1483
cm−1; UV (EtOH) λmax: 221, 281, 293, 332 nm;
1H NMR (300 MHz, CDCl3): δH 3.69–3.89 (m, 2H,
SCH2), 4.97–5.11 (m, 3H, OCH2, ring juncture
H), 6.81–6.84 (d, 1H, J = 8.7 Hz, C5ꢀ-H), 7.09–7.36
(m, 4H, ArH), 7.50–7.57 (m, 4H, ArH), 7.82–7.85 (d,
1H, J = 7.4 Hz, Ha), 8.45–8.49 (d, 1H, J = 4.4 Hz,
Hc); MS (m/z): 486, 484, 482 (M+). Anal. Calcd for
C24H16N2O3SCl2: C, 59.62; H, 3.31; N, 5.79%. Found:
C, 59.79; H, 3.42; N, 6.01%.
Compound 6a. Yield 88%, solid, m.p. 196–
198◦C; IR (KBr) νmax: 2951, 1725, 1643, 1582, 1484
1
cm−1; UV (EtOH) λmax: 220 281, 331 nm; H NMR
(500 MHz, CDCl3): δH 3.78–3.84 (m, 2H, SCH2), 4.96
(d, 1H, J = 16 Hz, OCH2), 5.00 (d, 1H, J = 16 Hz,
OCH2), 5.07–5.11 (dd, 1H, J = 7.6, 9.6 Hz, ring junc-
ture H), 6.86–6.88 (d, 1H, J = 8.3 Hz, ArH), 6.90–
6.93 (t, 1H, J = 7.5 Hz, ArH), 7.14–7.25 (m, 4H, ArH),
7.34–7.36 (d, 1H, J = 7.8 Hz, ArH), 7.46–7.49 (t, 1H,
J = 7.4 Hz, ArH), 7.53–7.58 (t, 2H, J = 7.3 Hz, ArH),
7.81–7.83 (dd, 1H, J = 1.2, 7.7 Hz, Ha), 8.47–8.48 (dd,
1H, J = 1.3, 4.5 Hz, Hc); 13C NMR (125 MHz, CDCl3):
35.54, 54.5, 74.01, 113.00, 114.06, 118.83, 122.80,
123.24, 127.50, 128.27, 129.08, 129.35, 129.87,
130.87, 135.19, 137.09, 151.13, 151.37, 153.71,
154.58, 159.55, 204.59; MS (m/z): 450, 448 (M+). Anal.
Calcd for C24H17N2O3SCl: C, 64.21; H, 3.79; N, 6.24%.
Found: C, 64.37; H, 3.64; N, 6.04%.
Compound 6e. Yield 82%, solid, m.p. 216–
218◦C; IR (KBr) νmax: 2914, 1722, 1646, 1582, 1445
1
cm−1; UV (EtOH) λmax: 221, 280, 330 nm; H NMR
(400 MHz, CDCl3): δH 3.65–3.83 (m, 2H, SCH2),
4.96–5.03 (m, 3H, OCH2, ring juncture H), 6.88–
6.90 (d, 1H, J = 8.4 Hz, C5ꢀ-H), 6.94–6.98 (t, 1H,
J = 7.7 Hz, C3ꢀ-H), 7.01–7.03 (d, 1H, J = 8 Hz, C1ꢀ-
H), 7.16–7.31 (m, 4H, ArH), 7.46–7.61 (m, 4H, ArH),
7.81–7.83 (dd, 1H, J = 1.6, 7.6 Hz, Ha), 8.47–8.48 (dd,
1H, J = 1.2, 4.4 Hz, Hc); MS (m/z): 414 (M+). Anal.
Calcd for C24H18N2O3S: C, 69.56; H, 4.34; N, 6.76%.
Found: C, 69.81; H, 4.12; N, 6.59%.
Compound 6b. Yield 85%, solid, m.p. 142–
144◦C; IR (KBr) νmax: 2923, 1731, 1646, 1582, 1503,
1
1441 cm−1; UV (EtOH) λmax: 221, 280, 331 nm; H
NMR (400 MHz, CDCl3): δH 2.24 (s, 6H, CH3) 3.64–
3.80 (m, 2H, SCH2), 4.85 (d, 1H, J = 16 Hz, OCH2),
4.93 (d, 1H, J = 16 Hz, OCH2) 5.01–5.05 (dd, 1H,
J = 7.2, 9.6 Hz, ring juncture H), 6.58–6.60 (d, 1H,
J = 8 Hz, ArH), 6.87–6.89 (d, 1H, J = 8 Hz, ArH), 6.95
(d, 1H, J = 1 Hz, ArH), 7.16–7.19 (dd, 1H, J = 4.8,
7.6 Hz, Hb) 7.24–7.25 (m, 2H, ArH), 7.47–7.55 (m,
3H, ArH), 7.80–7.82 (d, 1H, J = 7.6 Hz, Ha), 8.47–
8.48 (d, 1H, J = 4.8 Hz, Hc); 13C NMR (100 MHz,
CDCl3): 16.45, 20.65, 35.42, 54.03, 73.47, 111.27,
Compound 6f. Yield 85%, solid, m.p. 172–
174◦C; IR (KBr) νmax: 2914, 1723, 1645, 1603, 1580,
1
1445 cm−1; UV (EtOH) λmax: 220, 280, 328 nm; H
NMR (300 MHz, CDCl3): δH 2.28 (s, 3H, CH3), 3.64–
3.83 (m, 2H, SCH2), 4.89–5.07 (m, 3H, OCH2, ring
juncture H), 6.69–6.72 (d, 1H, J = 8.1 Hz, C5ꢀ-H),
6.86–6.90 (t, 1H, J = 7.3, 14.6 Hz, C4ꢀ-H), 7.07–7.23
(m, 5H, ArH), 7.46–7.58 (m, 3H, ArH), 7.81–7.83 (dd,
1H, J = 1.2, 7.5 Hz, Ha), 8.48–8.49 (dd, 1H, J = 1.2,
3.0 Hz, Hc); MS (m/z): 428 (M+). Anal. Calcd for
Heteroatom Chemistry DOI 10.1002/hc

92 Majumdar and Islam
[9] Majumdar, K. C.; Thyagaranjan, B. S. Int J Sulfur
Chem 1972, 2A, 93–103.
C25H20N2O3S: C, 70.09; H, 4.67; N, 6.54%. Found: C,
70.21; H, 4.74; N, 6.72%.
[10] El-Osta, B.; Majumdar, K. C.; Thyagaranjan, B. S. Int
J Heterocycl Chem 1973, 10, 107–109.
[11] Hillard, J. B.; Thyagaranjan, B. S.; Reddy, K. V.;
Majumdar, K. C. Tetrahedron Lett 1974, 1999–2002.
[12] Hillard, J. B.; Reddy, K. V.; Majumdar, K. C.;
Thyagaranjan, B. S. J Heterocycl Chem 1974, 11, 369–
375.
[13] Thyagaranjan, B. S.; Majumdar, K. C. J Heterocycl
Chem 1975, 12, 43–47.
[14] Reich, H. J.; Shah, S. K. J Am Chem Soc 1977, 99,
263–265.
ACKNOWLEDGMENTS
Rafique-ul-Islam is thankful to CSIR (New Delhi) for
a Junior Research Fellowship.We also thank the DST
(New Delhi) for providing UV–Vis spectrophotome-
ter and FT-IR spectrometer under DST-FIST pro-
gram.
[15] Majumdar, K. C.; Chattopadhyay, S. K. J Chem Soc,
Chem Commum 1987, 524–525.
[16] Majumdar, K. C.; Chattopadhyay, S. K.; Khan, A. T. J
Chem Soc, Perkin Trans 1, 1989, 1285–1289.
[17] Majumdar, K. C.; Ghosh, S. K. J Chem Soc, Perkin
Trans 1, 1994, 2889–2894.
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Heteroatom Chemistry DOI 10.1002/hc