New Schiff's base and 2-azetidinone derivatives of 3-benzo[4,5]imidazo[2,1- b]thiazol-3-yl-chromen-2-one by vilsmeier-haack formylation

Article abstract of DOI:10.1080/00397910902985507

A new Schiff's base and 2-azetidinone derivatives obtained via the corresponding 3-benzo [4,5] imidazo [2,1-b] thiazol-3-yl-chromen-2-one by Vilsmeier-Haack formylation scaffold is described. Our design is aimed at obtaining new triheterocyclic and tetraheterocyclic derivatives.

Full text of DOI:10.1080/00397910902985507

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New Schiff's Base and 2-Azetidinone
Derivatives of 3-Benzo[4,5]imidazo[2,1-
b]thiazol-3-yl-chromen-2-one by
Vilsmeier–Haack Formylation
Harisha R. Seetharamareddy a , Kallappa M. Hosamani a & Rangappa
S. Keri a
a P.G. Department of Studies in Chemistry , Karnatak University ,
Pavate Nagar, Dharwad, India
Published online: 06 Jan 2010.
To cite this article: Harisha R. Seetharamareddy , Kallappa M. Hosamani & Rangappa S. Keri (2010)
New Schiff's Base and 2-Azetidinone Derivatives of 3-Benzo[4,5]imidazo[2,1-b]thiazol-3-yl-chromen-2-
one by Vilsmeier–Haack Formylation, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:3, 450-461, DOI: 10.1080/00397910902985507
To link to this article: http://dx.doi.org/10.1080/00397910902985507
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Synthetic Communications1, 40: 450–461, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902985507
NEW SCHIFF’S BASE AND 2-AZETIDINONE
DERIVATIVES OF 3-BENZO[4,5]IMIDAZO
[2,1-b]THIAZOL-3-YL-CHROMEN-2-ONE
BY VILSMEIER–HAACK FORMYLATION
Harisha R. Seetharamareddy, Kallappa M. Hosamani,
and Rangappa S. Keri
P.G. Department of Studies in Chemistry, Karnatak University, Pavate
Nagar, Dharwad, India
A new Schiff’s base and 2-azetidinone derivatives obtained via the corresponding 3-benzo
[4,5] imidazo [2,1-b] thiazol-3-yl-chromen-2-one by Vilsmeier–Haack formylation scaf-
fold is described. Our design is aimed at obtaining new triheterocyclic and tetraheterocyclic
derivatives.
Keywords: Antitumor agents; azetidin-2-one; DNA; fused ring systems; Schiff’s base; Vilsmeier–Haack
formylation
INTRODUCTION
The majority of DNA intercalating antitumor drugs have a common general
structure consisting of a planar tricyclic and tetracyclic chromophore.[1–3] The con-
densed heterocycles containing thiazole and imidazole ring are effective as antipro-
tozoal,[4] anticonvulsant,[5] antidepressive,[6] anti-HIV,[7] antitrichinellosis,[8] and
hypoglycemic agents.[9] Recently, the gastric antisecretory activity of thiazolo [3,2-a]
benzimidazol-1-oxide (WY-26,769) was reported.[10] Also, some thiazolo [3,2-a]
benzimidazole derivatives have been used for treatment of cancer,[11] neurogenic
pain,[12] and bone diseases.[13] Further synthetic products of many 3-substituted bihe-
terocylic coumarins with thiazoles and fused thiazoles exhibit promising biological
activities.[14,15] A large number of 3-chloromonocyclic 2-azetidinones having substi-
tution at positions 1 and 4 possess a broad spectrum of pharmacological activi-
ties.[16–19] The need for potent, effective b-lactam antibiotics as well as more
effective b-lactamase inhibitors has motivated synthetic organic and medicinal che-
mists to design new functionalized 2-azetidinones. Apart from their clinical use as
antibacterial agents, these compounds have been used as synthons in the preparation
of various heterocyclic compounds of biological significance.[20] On the other
hand, Schiff’s bases exhibit a wide range of biological and controlled therapeutic
Received January 31, 2009.
Address correspondence to Kallappa M. Hosamani, P.G. Department of Studies in Chemistry,
Karnatak University, Pavate Nagar, Dharwad 580 003, India. E-mail: dr_hosamani@yahoo.com
450

VILSMEIER–HAACK FORMYLATION
451
activities.[21–24] These structural observations led to the synthesis of new sub-
stituted Schiff’s base and 2-azetidinone derivatives of 3-benzo[4,5]imidazo[2,1-b]
thiazol-3-yl-chromen-2-one by Vilsmeier–Haack formylation.
RESULTS AND DISCUSSION
The versatile, 3-benzo[4,5]imidazo[2,1-b]thiazol-3-yl-chromen-2-one (1) was
synthesized according a literature method.[10] Next, treatment of compound 1 under
Vilsmeier–Haack formylation afforded 3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]-
imidazo[2,1-b]thiazoles-2-carbaldehyde (2) (Scheme 1). It was characterized by its
elemental analysis and spectral data. Thus, its infrared (IR) spectrum revealed
1715, 1680, and 1660 cmꢀ1 assignable three bands due to two carbonyl (C O)
=
1
and one imine (C N) groups, whereas its H NMR spectrum displayed character-
=
istic signals at 9.17 for aldehyde (s, 1H, CHO) and 7.20–7.72 (m, 8H, Ar-H) and
8.12 (s, 1H, C4) for coumarin.
Compound 2 reacted with substituted anilines in refluxing dry ethanol and in
the presence of a catalytic amount of glacial acetic acid, resulting in the formation
of Schiff’s base derivatives (3a–l) (Scheme 1). The structures of the compounds were
confirmed on the basis of spectral data. For example, the IR spectrum of the isolated
products in each case revealed one band due to carbonyl group in the region
1722–1717 cmꢀ1 and two absorption bands in the region 1630–1522 cmꢀ1 due to
aromatic and aliphatic imine groups. The mass spectra of the same compounds
showed peaks corresponding to their molecular ions.
Furthermore, the reaction of the Schiff’s base derivatives with chloroacetyl
chloride and triethyl amine in 1,4-dioxane gives 2-azetidinone derivatives (4a–l)
(Scheme 2). However, the elemental analysis and spectral data of the reaction
products were comparable with the 2-azetidinone structures. The IR spectrum of
the isolated products revealed in each case the appearance of 2-carbonyl absorption
Scheme 1. Schematic representation of compounds 2 and 3a–l.

452
H. R. SEETHARAMAREDDY ET AL.
Scheme 2. Schematic representation of compounds 4a–l.
bands near 1730–1620 cmꢀ1. In addition, an imine absorption band in the region
1558–1541 cmꢀ1 and their mass spectra revealed a peak corresponding to the
molecular ion.
CONCLUSION
We have disclosed an efficient and reliable general method for the construction
of new triheterocyclic and tetraheterocyclic derivatives of benzimidazole by
Vilsmeier–Haack formylation in good purity with good isolated yields. It is note-
worthy that in vitro and in vivo screening of these newly synthesized compounds
is currently under way and will be reported in due course.
EXPERIMENTAL
Materials and Methods
Melting points are uncorrected. Merck precoated 60 F254 aluminium=silica-gel
sheets were used for thin-layer chromatography (TLC) analyses. IR spectra were
recorded on a Nicolet 5700 Fourier transform (FT)–IR instrument as potassium bro-
1
mide discs. The H and 13C NMR spectras were measured with a Bruker Avanace
300, a 300-MHz instrument, using tetramethylsilane (TMS) internal standard and
dimethylsulfoxide (DMSO-d6). All chemical shifts were reported at d (ppm) values.
Mass spectrometer with ionization energy maintained at 70eV was measured on a
Shimadzu mass spectrometer, and elemental analyses were carried out on a MT-3
analyzer.
Synthesis of Compounds
Synthesis of 3-(2-Oxo-2H-chromen-3-yl)-benzo[4,5]imidazo[2,1-b]thia-
zole-2-carbaldehyde (2). The Vilsmeier reagent was prepared by adding POCl3
(1.58 mL, 0.017 mol) to dimethylformamide (DMF, 20 mL) at 0ꢁC, with stirring.
Then, 3-benzo[4,5]imidazo[2,1-b]thiazole-3-yl-chromen-2-one (3.183 g, 0.01 mol)
was added, and the mixture was further stirred at 90ꢁC for 14–15 h. After cooling
and addition of water, the product was filtered and washed with ice-cold water,
and the crude material was recrystallized from a chloroform=ethanol system
(Scheme 1 and Table 1).

VILSMEIER–HAACK FORMYLATION
453
Table 1. Analytical data of compounds 2 and 3a–l
Compound
R
Mp (ꢁC)
Yield (%)
Mol. formula
Mol. weight
2
—
270–272
287–289
251–253
254–256
237–239
248–250
231–233
219–221
227–229
235–237
224–226
219–221
254–256
76.34
72.10
77.93
76.11
61.25
64.00
68.97
71.03
74.68
66.17
69.48
72.55
78.02
C19H10N2O3S
C25H15N3O2S
346.36
421.47
449.52
449.52
455.92
455.92
466.47
466.47
435.50
435.50
435.50
480.50
451.50
3a
3b
3c
3d
3e
3f
3g
3h
3i
Aniline
3,4-Dimethyl aniline
2,6-Dimethyl aniline
2-Chloroaniline
3-Chloroaniline
3-Nitroaniline
4-Nitroaniline
2-Toluidine
C27H19N3O2S
C27H19N3O2S
C25H14ClN3O2S
C
25H14ClN3O2S
C25H14N4O4S
C25H14N4O4S
C26H17N3O2S
3-Toluidine
4-Toluidine
C
26H17N3O2S
C26H17N3O2S
26H16N4O4S
C26H17N3O3S
3j
3k
3l
3-Nitro-4-toluidine
4-Anisidine
C
IR (KBr): c (cmꢀ1) 1715.0 (ArCHO), 1680.92 (C O of coumarin), 1660.21
=
1
=
(C N); H NMR (DMSO-d6, 300 MHz): d (ppm) 7.20 (s, 1H, Ar-H), 7.26 (s, 3H,
Ar-H), 7.55 (m, 2H, Ar-H), 7.72 (m, 2H, Ar-H), 8.12 (s, 1H, Ar-H), 9.17 (s, 1H,
CHO of aldehyde); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 115.47 (s, C, Ar-C),
=
120.09 (s, C, Ar-C), 125.2 (s, C, Ar-C), 129.4 (s, C, Ar-C), 164.0 (s, C, C O of cou-
=
marin), 180.45 (s, C, C O of Ar-CHO); CIMS: m=z 346.36. Anal. calcd. for
C19H10N2O3S: C, 65.89; H, 2.91; N, 8.09; S, 9.26. Found: C, 65.88; H, 2.89; N,
8.06; S, 9.24.
General Procedure for the Synthesis of Schiff’s Base Derivatives (3a–l)
A mixture of 3-(2-oxo-2H-chromen-3-yl)benzo[4,5]imidazo[2,1-b]thiazole-2-
carbaldehyde (2) (3.463 g, 0.01 mol), substituted anilines (0.01 mol), and catalytic
amount of glacial acetic acid were refluxed in dry ethanol (30 mL) for about 11–
12 h. The solvent was distilled off at reduced pressure, and the solid mass thus
obtained was recrystallized from ethanol (Scheme 1 and Table 1).
3-(2-Phenyliminomethyl-benzo[4,5]imidazo[2,1-b]thiazol-3-yl-chromen-
2-one (3a). IR (KBr): c (cmꢀ1) 1721.0 (C O of coumarin), 1605.4 (C N of benzimi-
=
=
1
=
dazole), 1554.5 (C N of Schiff’s base); H NMR (DMSO-d6, 300 MHz): d (ppm) 7.20
(m, 4H, Ar-H), 7.35 (m, 5H, Ar-H), 7.48 (d, 2H, J ¼ 7.9, Ar-H), 7.68 (s, 3H, Ar-H),
8.11 (s, 1H, Ar-H); 13C NMR (DMSO-d6, 75MHz): d (ppm) 116.47 (s, C, Ar-C),
=
121.10 (s, C, Ar-C), 125.02 (s, C, Ar-C), 129.5 (s, C, Ar-C), 163.0 (s, C, C N of
Schiff’s base); CIMS: m=z 421.47. Anal. calcd. for C25H15N3O2S: C, 71.24; H, 3.59;
N, 9.97; S, 7.61. Found: C, 71.23; H, 3.58; N, 9.94; S, 7.60.
3-{2-[(3,4-Dimethyl-phenylimino)-methyl]-benzo[4,5]imidazo
[2,1-b]
thiazol-3-yl}-chromen-2-one (3b). IR (KBr): c (cmꢀ1) 1721.2 (C O of coumarin),
=
1606.5 (C N of benzimidazole), 1549.5 (C N of Schiff’s base); 1H NMR
(DMSO-d6, 300 MHz): d (ppm) 2.30 (s, 6H, 2CH3), 6.91 (s, 3H, Ar-H), 7.22 (m,
4H, Ar-H), 7.55 (m, 3H, Ar-H), 7.72 (s, 2H, Ar-H), 8.13 (s, 1H, Ar-H); 13C NMR
(DMSO-d6, 75 MHz): d (ppm) 27.43 (s, 2C, 2CH3), 116.47 (s, C, Ar-C), 118.9 (s,
=
=

454
H. R. SEETHARAMAREDDY ET AL.
C, Ar-C), 121.10 (s, C, Ar-C), 125.02 (s, C, Ar-C), 129.5 (s, C, Ar-C), 136.7 (s, C,
=
Ar-C), 164.1 (s, C, C N of Schiff’s base); CIMS: m=z 449.52. Anal. calcd. for
C27H19N3O2S: C, 72.14; H, 4.26; N, 9.35; S, 7.13. Found: C, 72.15; H, 4.25; N,
9.37; S, 7.11.
3-{2-[(2,6-Dimethyl-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]thia-
zol-3-yl}-chromen-2-one (3c). IR (KBr): c (cmꢀ1) 1721.0 (C O of coumarin),
=
1605.8 (C N of benzimidazole), 1533.4 (C N of Schiff’s base); 1H NMR
(DMSO-d6, 300 MHz): d (ppm) 2.30 (m, 6H, 2CH3), 6.91–7.28 (s, 7H, Ar-H),
7.45–7.68 (s, 3H, Ar-H), 7.73 (d, 2H, J ¼ 8.7, Ar-H), 8.11 (s, 1H, Ar-H); 13C
NMR (DMSO-d6, 75 MHz): d (ppm) 25.20 (s, 2C, 2CH3), 118.27 (s, C, Ar-C),
123.17 (s, C, Ar-C), 125.12 (s, C, Ar-C), 131.1 (s, C, Ar-C), 150.7 (s, C, Ar-C),
=
=
=
160.9 (s, C, C N of Schiff’s base); CIMS: m=z 449.52. Anal. calcd. for
C27H19N3O2S: C, 72.14; H, 4.26; N, 9.35; S, 7.13. Found: C, 72.13; H, 4.25; N,
9.33; S, 7.11.
3-{2-[(2-Chloro-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]thiazol-
3-yl}-chromen-2-one (3d). IR (KBr): c (cmꢀ1) 1717.2 (C O of coumarin), 1608.0
=
1
=
=
(C N of benzimidazole), 1562.6 (C N of Schiff’s base), 754.5 (C-Cl); H NMR
(DMSO-d6, 300 MHz): d (ppm) 7.11–7.32 (m, 8H, Ar-H), 7.40–7.68 (s, 3H, Ar-H),
7.69 (d, 2H, J ¼ 8.5, Ar-H), 8.10 (s, 1H, Ar-H); 13C NMR (DMSO-d6, 75 MHz): d
(ppm) 111.94 (s, C, Ar-C), 121.3 (s, C, Ar-C), 126.62 (s, C, Ar-C), 137.1 (s, C,
=
Ar-C), 142.31 (s, C, Ar-C), 148.4 (s, C, Ar-C), 164.9 (s, C, C N of Schiff’s base);
CIMS: m=z 455.92. Anal. calcd. for C25H14ClN3O2S: C, 65.86; H, 3.10; Cl, 7.78;
N, 9.22; S, 7.03. Found: C, 65.87; H, 3.09; Cl, 7.79; N, 9.20; S, 7.01.
3-{2-[(3-Chloro-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]thiazol-
3-yl}-chromen-2-one (3e). IR (KBr): c (cmꢀ1) 1720.6 (C O of coumarin), 1604.9
=
1
=
=
(C N of benzimidazole), 1562.6 (C N of Schiff’s base), 758.0 (C-Cl); H NMR
(DMSO-d6, 300 MHz): d (ppm) 7.10–7.32 (m, 8H, Ar-H), 7.48 (d, 2H, J ¼ 7.7,
Ar-H), 7.51 (s, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.71 (d, 2H, J ¼ 8.6, Ar-H); 13C
NMR (DMSO-d6, 75 MHz): d (ppm) 122.97 (s, C, Ar-C), 128.12 (s, C, Ar-C),
=
140.61 (s, C, Ar-C), 143.81 (s, C, Ar-C), 151.6 (s, C, Ar-C), 158.03 (s, C, C N of
Schiff’s base); CIMS: m=z 455.92. Anal. calcd. for C25H14ClN3O2S: C, 65.86; H,
3.10; Cl, 7.78; N, 9.22; S, 7.03. Found: C, 65.87; H, 3.10; Cl, 7.76; N, 9.21; S, 7.01.
3-{2-[(3-Nitro-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]thiazol-3-
yl}-chromen-2-one (3f). IR (KBr): c (cmꢀ1) 1719.1 (C O of coumarin), 1606.9
=
=
(C N of Schiff’s base), 1522.2 and 1348.2 (NO2 asymmetric and symmetric stretch-
1
ing); H NMR (DMSO-d6, 300 MHz): d (ppm) 7.16–7.31 (m, 4H, Ar-H), 7.40–7.70
(s, 4H, Ar-H), 7.71–7.73 (s, 3H, Ar-H), 8.10–8.12 (s, 3H, Ar-H); 13C NMR
(DMSO-d6, 75 MHz,): d (ppm) 112.4 (s, C, Ar-C), 122.72 (s, C, Ar-C), 128.11 (s,
=
C, Ar-C), 143.35 (s, C, Ar-C), 149.5 (s, C, Ar-C), 160.0 (s, C, C N of Schiff’s base);
CIMS: m=z 466.47. Anal. calcd. for C25H14N4O4S: C, 64.37; H, 3.03; N, 12.01; S,
6.87. Found: C, 64.35; H, 3.04; N, 12.02; S, 6.86.
3-{2-[(4-Nitro-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]thiazol-3-
yl}-chromen-2-one (3g). IR (KBr): c (cmꢀ1) 1718.2 (C O of coumarin), 1630.2
=
=
(C N of Schiff’s base), 1598.5 and 1306.2 (NO2 asymmetric and symmetric

VILSMEIER–HAACK FORMYLATION
455
stretching); 1H NMR (DMSO-d6, 300 MHz): d (ppm) 7.16–7.24 (s, 4H, Ar-H),
7.38–7.55 (m, 5H, Ar-H), 7.70 (d, 2H, J ¼ 8.4, Ar-H), 8.12–8.18 (m, 3H, Ar-H);
13C NMR (DMSO-d6, 75 MHz): d (ppm) 122.20 (s, C, Ar-C), 132.52 (s, C,
=
Ar-C), 141.85 (s, C, Ar-C), 153.1 (s, C, Ar-C), 162.74 (s, C, C N of Schiff’s
base); CIMS: m=z 466.47. Anal. calcd. for C25H14N4O4S: C, 64.37; H, 3.03; N,
12.01; S, 6.87. Found: C, 64.38; H, 3.01; N, 12.02; S, 6.86.
3-[2-(o-Tolylimino-methyl)-benzo[4,5]imidazo[2,1-b]thiazol-3-yl]-chro-
men-2-one (3h). IR (KBr): c (cmꢀ1) 1722.2 (C O of coumarin), 1606.1 (C N of
=
=
1
Schiff’s base); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.30 (s, 3H, CH3), 7.10 (s,
4H, Ar-H), 7.20–7.35 (m, 4H, Ar-H), 7.38–7.56 (s, 3H, Ar-H), 7.71 (d, 2H, J¼ 9.1,
Ar-H), 8.12 (s, 1H, Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 18.34 (s, C,
CH3), 122.0 (s, C, Ar-C), 131.2 (s, C, Ar-C), 143.0 (s, C, Ar-C), 148.7 (s, C, Ar-C),
=
161.04 (s, C, C N of Schiff’s base); CIMS: m=z 435.50. Anal. calcd. for C26H17N3O2S:
C, 71.71; H, 3.93; N, 9.65; S, 7.36. Found: C, 71.70; H, 3.91; N, 9.63; S, 7.34.
3-[2-(m-Tolylimino-methyl)-benzo[4,5]imidazo[2,1-b]thiazol-3-yl]-chro-
men-2-one (3i). IR (KBr): c (cmꢀ1) 1721.6 (C O of coumarin), 1605.8 (C N of
=
=
1
Schiff’s base); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.48 (s, 3H, CH3), 7.12
(s, 4H, Ar-H), 7.18–7.37 (m, 4H, Ar-H), 7.40–7.62 (s, 3H, Ar-H), 7.71 (d, 2H,
J ¼ 8.1, Ar-H), 8.56 (s, 1H, Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 21.74
(s, C, CH3), 121.3 (s, C, Ar-C), 125.2 (s, C, Ar-C), 133.30 (s, C, Ar-C), 145.3 (s,
=
C, Ar-C), 147.75 (s, C, Ar-C), 158.72 (s, C, C N of Schiff’s base); CIMS: m=z
435.50. Anal. calcd. for C26H17N3O2S: C, 71.71; H, 3.93; N, 9.65; S, 7.36. Found:
C, 71.73; H, 3.92; N, 9.64; S, 7.37.
3-[2-(p-Tolylimino-methyl)-benzo[4,5]imidazo[2,1-b]thiazol-3-yl]-chro-
men-2-one (3j). IR (KBr): c (cmꢀ1) 1722.4 (C O of coumarin), 1606.2 (C N of
Schiff’s base); 1H NMR (DMSO-d6, 300 MHz): d (ppm) 2.35 (s, 3H, CH3),
7.11–7.13 (m, 4H, Ar-H), 7.22–7.32 (s, 4H, Ar-H), 7.36–7.44 (m, 3H, Ar-H),
7.68–7.72 (s, 2H, Ar-H), 8.11 (m, 1H, Ar-H); 13C NMR (DMSO-d6, 75 MHz): d
(ppm) 23.14 (s, C, CH3), 117.85 (s, C, Ar-C), 124.92 (s, C, Ar-C), 132.09 (s, C,
=
=
=
Ar-C), 143.13 (s, C, Ar-C), 147.5 (s, C, Ar-C), 164.70 (s, C, C N of Schiff’s base);
CIMS: m=z 435.50. Anal. calcd. for C26H17N3O2S: C, 71.71; H, 3.93; N, 9.65; S, 7.36.
Found: C, 71.73; H, 3.92; N, 9.66; S, 7.35.
3-{2-[(4-Methyl-3-nitro-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]-
thiazol-3-yl}-chromen-2-one (3k). IR (KBr): c (cmꢀ1) 1717.0 (C O of coumarin),
=
=
1605.3 (C N of Schiff’s base), 1524.7 and 1346 (NO2 asymmetric and symmetric
1
stretching); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.31 (s, 3H, CH3), 7.26 (m,
4H, Ar-H), 7.42–7.62 (m, 6H, Ar-H), 7.70 (d, 2H, J ¼ 8.4, Ar-H), 8.12 (s, 1H,
Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 20.18 (s, C, CH3), 117.20 (s, C,
Ar-C), 135.72 (s, C, Ar-C), 142.65 (s, C, Ar-C), 146.7 (s, C, Ar-C), 162.80 (s, C,
=
C N of Schiff’s base); CIMS: m=z 480.50. Anal. calcd. for C26H16N4O4S: C, 64.99;
H, 3.36; N, 11.66; S, 6.67. Found: C, 64.97; H, 3.34; N, 11.65; S, 6.65.
3-{2-[(4-Methoxy-phenylimino)-methyl]-benzo[4,5]imidazo[2,1-b]thiazol-
3-yl}-chromen-2-one (3l). IR (KBr): c (cmꢀ1) 2854 (O-CH3), 1721.5 (C O of cou-
=
1
=
marin), 1605.5 (C N of Schiff’s base); H NMR (DMSO-d6, 300 MHz): d (ppm)

456
H. R. SEETHARAMAREDDY ET AL.
3.62 (s, 1H, OCH3 merged with solvent peak), 6.89–7.28 (s, 8H, Ar-H), 7.35–7.52 (m,
3H, Ar-H), 7.72–8.14 (s, 3H, Ar-H); 13C NMR (DMSO-d6, 75 MHz,): d (ppm) 58.49
(s, C, OCH3), 125.90 (s, C, Ar-C), 131.64 (s, C, Ar-C), 137.02 (s, C, Ar-C), 142.53 (s,
=
C, Ar-C), 143.17 (s, C, Ar-C), 158.22 (s, C, OCH3), 165.00 (s, C, C N of Schiff’s
base); CIMS: m=z 451.50. Anal. calcd. for C26H17N3O3S: C, 69.16; H, 3.80; N,
9.31; S, 7.10. Found: C, 69.17; H, 3.79; N, 9.30; S, 7.09.
General Procedure for the Synthesis of 2-Azetidinone Derivatives
(4a–l). A mixture of 3a–l (0.01 mol) in 1,4-dioxan (20 mL) and chloroacetyl chloride
(1.12 mL, 0.01 mol) with triethyl amine (2.78 mL, 0.02 mL) was placed in a
round-bottom flask. It was refluxed for 17–18 h on a water bath. After completion
of the reaction, the solvent was distilled off at reduced pressure, and the solid mass
thus obtained was recrystallized from ethanol (Scheme 2 and Table 2).
3-Chloro-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]imidazo[2,1-b]thiazol-
2-yl}-1-phenyl-azetidin-2-one (4a). IR (KBr): c (cmꢀ1) 1720 (C O of azetidi-
=
=
none), 1630 (C O of coumarin), 1554.5 (C N of benzimidazole), 810 (C-Cl of
=
1
azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 3.10 (s, 1H, Ar-CH), 3.89
(1H, ArCH-Cl merged with solvent peak), 7.12 (d, 2H, J ¼ 6.8, Ar-H), 7.18–7.32
(m, 7H, Ar-H), 7.45–7.52 (s, 2H, Ar-H), 7.71–7.98 (m, 3H, Ar-H); 13C NMR
(DMSO-d6, 75 MHz): d (ppm) 51.01 (s, C, Ar-C), 62.17 (s, C, ArC-Cl), 116.07 (s,
C, Ar-C), 122.12 (s, C, Ar-C), 125.2 (s, C, Ar-C), 137.44 (s, C, Ar-C), 141.8 (s, C,
=
=
Ar-C), 161.40 (s, C, C O of azetidinone), 164.23 (s, C, C O of coumarin); CIMS:
m=z 497.95. Anal. calcd. for C27H16ClN3O3S: C, 65.12; H, 3.24; Cl, 7.12; N, 8.44;
S, 6.44. Found: C, 65.11; H, 3.23; Cl, 7.11; N, 8.42; S, 6.41.
3-Chloro-1-(3,4-dimethyl-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo-
[4,5]imidazo [2,1-b] thiazol-2-yl}-azetidin-2-one (4b). IR (KBr): c (cmꢀ1) 1715
=
(C O of azetidinone), 1625 (C O of coumarin), 1552.7 (C N of benzimidazole),
=
=
1
818 (C-Cl of azetidinone); H NMR (DMSO-d6, 300 MHz,): d (ppm) 2.30 (s, 6H,
2CH3), 3.11 (s, 1H, Ar-CH), 3.68 (1H, ArCH-Cl merged with solvent peak),
6.89–7.32 (s, 7H, Ar-H), 7.50–7.71 (m, 4H, Ar-H), 8.12 (s, 1H, Ar-H); 13C NMR
(DMSO-d6, 75 MHz): d (ppm) 20.18 (S, 2C, 2CH3), 51.76 (s, C, Ar-C), 63.7 (s, C,
Table 2. Analytical data of compounds 4a–l
Compound
R
Mp (ꢁC)
Yield (%)
Mol. formula
Mol. weight
4a
4b
4c
4d
4e
4f
Aniline
254–256
250–252
234–236
244–246
264–266
253–255
221–223
232–234
224–226
236–238
287–289
276–278
84.90
81.29
78.04
73.73
76.25
77.84
75.31
65.12
69.53
79.06
73.99
74.18
C
27H16ClN3O3S
497.95
526.01
526.01
532.40
532.40
542.95
542.95
511.98
511.98
511.98
556.98
527.98
3,4-Dimethyl aniline
2,6-Dimethyl aniline
2-Chloroaniline
3-Chloroaniline
3-Nitroaniline
4-Nitroaniline
2-Toluidine
C29H20ClN3O3S
29H20ClN3O3S
C27H15Cl2N3O3S
27H15Cl2N3O3S
C
C
C27H15ClN4O5S
C27H15ClN4O5S
C28H18ClN3O3S
4g
4h
4i
3-Toluidine
4-Toluidine
C28H18ClN3O3S
C28H18ClN3O3S
C28H17ClN4O5S
4j
4k
4l
3-Nitro-4-toluidine
4-Anisidine
C
28H18ClN3O4S

VILSMEIER–HAACK FORMYLATION
457
ArC-Cl), 115.22 (s, C, Ar-C), 124.32 (s, C, Ar-C), 127.02 (s, C, Ar-C), 137.55 (s, C,
=
=
Ar-C), 140.0 (s, C, Ar-C), 161.90 (s, C, C O of azetidinone), 163.73 (s, C, C O of
coumarin); CIMS: m=z 526.01. Anal. calcd. for C29H20ClN3O3S: C, 66.22; H, 3.83;
Cl, 6.74; N, 7.99; S, 6.10. Found: C, 66.20; H, 3.82; Cl, 6.72; N, 7.98; S, 6.09.
3-Chloro-1-(2,6-dimethyl-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo-
[4,5]imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4c). IR (KBr): c (cmꢀ1) 1717.0
=
(C O of azetidinone), 1622.0 (C O of coumarin), 1548.7 (C N of benzimidazole),
=
=
1
820 (C-Cl of azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.31 (s, 6H,
2CH3), 3.11 (s, 1H, Ar-CH), 3.82 (1H, ArCH-Cl merged with solvent peak),
6.90–7.24 (m, 7H, Ar-H), 7.52–7.69 (m, 4H, Ar-H), 8.10 (s, 1H, Ar-H); 13C NMR
(DMSO-d6, 75 MHz,): d (ppm) 26.08 (S, 2C, 2CH3), 53.76 (s, C, Ar-C), 61.22 (s,
C, ArC-Cl), 113.0 (s, C, Ar-C), 122.85 (s, C, Ar-C), 129.92 (s, C, Ar-C), 134.05
=
(s, C, Ar-C), 142.2 (s, C, Ar-C), 161.88 (s, C, C O of azetidinone), 162.55 (s, C,
=
C O of coumarin); CIMS: m=z 526.01. Anal. calcd. for C29H20ClN3O3S: C, 66.22;
H, 3.83; Cl, 6.74; N, 7.99; S, 6.10. Found: C, 66.21; H, 3.81; Cl, 6.71; N, 7.98; S, 6.08.
3-Chloro-1-(2-chloro-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]-
imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4d). IR (KBr): c (cmꢀ1) 1720.6
=
=
(C O of azetidinone), 1621.4 (C O of coumarin), 1558.0 (C N of benzimidazole),
=
1
835 (C-Cl of azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 3.18 (s, 1H,
Ar-CH), 3.91 (1H, ArCH-Cl merged with solvent peak), 7.18 (d, 2H, J ¼ 7.1,
Ar-H), 7.10–7.28 (s, 6H, Ar-H), 7.48 (d, 2H, J ¼ 7.3, Ar-H), 7.73–8.10 (s, 3H,
Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 53.78 (s, C, Ar-C), 61.02 (s, C,
ArC-Cl), 115.70 (s, C, Ar-C), 121.45 (s, C, Ar-C), 129.99 (s, C, Ar-C), 137.9 (s, C,
=
=
Ar-C), 141.2 (s, C, Ar-C), 161.0 (s, C, C O of azetidinone), 162.75 (s, C, C O of
coumarin); CIMS: m=z 532.40. Anal. calcd. for C27H15Cl2N3O3S: C, 60.91; H,
2.84; Cl, 13.32; N, 7.89; S, 6.02. Found: C, 60.89; H, 2.82; Cl, 13.31; N, 7.88; S, 6.01.
3-Chloro-1-(3-chloro-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]-
imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4e). IR (KBr): c (cmꢀ1) 1721.2
=
=
=
(C O of azetidinone), 1628.8 (C O of coumarin), 1556.4 (C N of benzimidazole),
1
816 (C-Cl of azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 3.16 (s, 1H,
Ar-CH), 3.80 (1H, ArCH-Cl merged with solvent peak), 6.91–7.28 (m, 8H, Ar-H),
7.54 (d, 2H, J ¼ 7.7, Ar-H), 7.72–8.11 (s, 3H, Ar-H); 13C NMR (DMSO-d6,
75 MHz): d (ppm) 51.18 (s, C, Ar-C), 60.12 (s, C, ArC-Cl), 117.56 (s, C, Ar-C),
123.85 (s, C, Ar-C), 128.79 (s, C, Ar-C), 137.2 (s, C, Ar-C), 141.18 (s, C, Ar-C),
=
=
161.04 (s, C, C O of azetidinone), 162.55 (s, C, C O of coumarin); CIMS: m=z
532.40. Anal. calcd. for C27H15Cl2N3O3S: C, 60.91; H, 2.84; Cl, 13.32; N, 7.89; S,
6.02. Found: C, 60.90; H, 2.83; Cl, 13.30; N, 7.87; S, 6.03.
3-Chloro-1-(3-nitro-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]-
imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4f). IR (KBr): c (cmꢀ1) 1721.0 (C O
=
=
=
of azetidinone), 1628.9 (C O of coumarin), 1556.4 (C N of benzimidazole), 1523.6
and 1346.0 (NO2 asymmetric and symmetric stretching), 812 (C-Cl of azetidinone);
1H NMR (DMSO-d6, 300 MHz,): d (ppm) 3.17 (s, 1H, Ar-CH), 3.68 (1H, ArCH-Cl
merged with solvent peak), 7.22 (d, 2H, J ¼ 6.9, Ar-H), 7.38–7.56 (s, 6H, Ar-H), 7.71
(d, 2H, J ¼ 8.0, Ar-H), 8.11–8.14 (s, 3H, Ar-H); 13C NMR (DMSO-d6, 75 MHz): d
(ppm) 51.11 (s, C, Ar-C), 61.14 (s, C, ArC-Cl), 115.66 (s, C, Ar-C), 122.18 (s, C,

458
H. R. SEETHARAMAREDDY ET AL.
=
Ar-C), 126.49 (s, C, Ar-C), 136.12 (s, C, Ar-C), 141.50 (s, C, Ar-C), 160.0 (s, C, C O
=
of azetidinone), 164.95 (s, C, C O of coumarin); CIMS: m=z 542.95. Anal. calcd. for
C27H15ClN4O5S: C, 59.73; H, 2.78; Cl, 6.53; N, 10.32; S, 5.91. Found: C, 59.72; H,
2.77; Cl, 6.51; N, 10.29; S, 5.90.
3-Chloro-1-(4-nitro-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]-
imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4g). IR (KBr): c (cmꢀ1) 1721.6
=
(C O of azetidinone), 1622.6 (C O of coumarin), 1551.3 (C N of benzimidazole),
=
=
1525.1 and 1344.9 (NO2 asymmetric and symmetric stretching), 830 (C-Cl of azetidi-
1
none); H NMR (DMSO-d6, 300 MHz): d (ppm) 3.12 (s, 1H, Ar-CH), 3.84 (1H,
ArCH-Cl merged with solvent peak), 7.20–7.40 (s, 4H, Ar-H), 7.28 (d, 2H, J ¼ 7.0,
Ar-H), 7.45–7.58 (s, 2H, Ar-H), 7.71–7.74 (s, 2H, Ar-H), 8.12–8.18 (m, 3H, Ar-H);
13C NMR (DMSO-d6, 75MHz): d (ppm) 50.1 (s, C, Ar-C), 61.24 (s, C, ArC-Cl),
116.16 (s, C, Ar-C), 124.78 (s, C, Ar-C), 129.09 (s, C, Ar-C), 139.52 (s, C, Ar-C),
=
=
145.55 (s, C, Ar-C), 161.30 (s, C, C O of azetidinone), 164.70 (s, C, C O of cou-
marin); CIMS: m=z 542.95. Anal. calcd. for C27H15ClN4O5S: C, 59.73; H, 2.78; Cl,
6.53; N, 10.32; S, 5.91. Found: C, 59.71; H, 2.77; Cl, 6.54; N, 10.33; S, 5.90.
3-Chloro-4-{3-(2-oxo-2H-chromen-3-yl)-benzo [4,5] imidazo [2,1-b] thiazol-
2-yl}-1-o-tolyl-azetidin-2-one (4h). IR (KBr): c (cmꢀ1) 1717.2 (C O of azetidi-
=
=
none), 1629.4 (C O of coumarin), 1555.9 (C N of benzimidazole), 814 (C-Cl of
=
1
azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.31 (s, 3H, CH3), 3.16 (s,
1H, Ar-CH), 3.92 (1H, ArCH-Cl merged with solvent peak), 7.11 (d, 2H, J ¼ 6.7,
Ar-H), 7.12–7.26 (m, 6H, Ar-H), 7.41–7.65 (s, 2H, Ar-H), 7.71–8.11 (m, 3H,
Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 21.1 (s, C, CH3), 53.3 (s, C,
Ar-C), 61.41 (s, C, ArC-Cl), 113.11 (s, C, Ar-C), 126.48 (s, C, Ar-C), 127.29 (s, C,
=
Ar-C), 134.05 (s, C, Ar-C), 148.75 (s, C, Ar-C), 161.22 (s, C, C O of azetidinone),
=
163.20 (s, C, C O of coumarin); CIMS: m=z 511.98. Anal. calcd. for
C28H18ClN3O3S: C, 65.69; H, 3.54; Cl, 6.92; N, 8.21; S, 6.26. Found: C, 65.68; H,
3.55; Cl, 6.94; N, 8.21; S, 6.25.
3-Chloro-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]imidazo[2,1-b]thiazol-
2-yl}-1-m-tolyl-azetidin-2-one (4i). IR (KBr): c (cmꢀ1) 1721.8 (C O of azetidi-
=
=
none), 1608.0 (C O of coumarin), 1551.3 (C N of benzimidazole), 838 (C-Cl of
=
1
azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.49 (s, 3H, CH3), 3.13 (s,
1H, Ar-CH), 3.56 (1H, ArCH-Cl merged with solvent peak), 6.91 (d, 2H, J ¼ 6.6,
Ar-H), 7.13–7.48 (s, 6H, Ar-H), 7.54 (d, 2H, J ¼ 8.2, Ar-H), 7.71–8.14 (s, 3H,
Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 32.4 (s, C, CH3), 52.7 (s, C,
Ar-C), 65.60 (s, C, ArC-Cl), 112.61 (s, C, Ar-C), 123.1 (s, C, Ar-C), 133.37 (s, C,
=
Ar-C), 136.75 (s, C, Ar-C), 145.8 (s, C, Ar-C), 163.07 (s, C, C O of azetidinone),
=
163.07 (s, C, C O of coumarin); CIMS: m=z 511.98. Anal. calcd. for
C28H18ClN3O3S: C, 65.69; H, 3.54; Cl, 6.92; N, 8.21; S, 6.26. Found: C, 65.68; H,
3.51; Cl, 6.94; N, 8.20; S, 6.28.
3-Chloro-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]imidazo[2,1-b]thiazol-
2-yl}-1-p-tolyl-azetidin-2-one (4j). IR (KBr): c (cmꢀ1) 1722.2 (C O of azetidi-
=
=
none), 1626.2 (C O of coumarin), 1546.7 (C N of benzimidazole), 822 (C-Cl of
=
1
azetidinone); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.37 (s, 3H, CH3), 3.15 (s,
1H, Ar-CH), 3.68 (1H, ArCH-Cl merged with solvent peak), 7.12 (d, 2H, J ¼ 7.4,

VILSMEIER–HAACK FORMYLATION
459
Ar-H), 7.16 (d, 2H, J ¼ 7.2, Ar-H), 7.24–7.29 (s, 4H, Ar-H), 7.56 (d, 2H, J ¼ 7.9,
Ar-H), 7.74–8.12 (m, 3H, Ar-H); 13C NMR (DMSO-d6, 75 MHz): d (ppm) 32.4 (s,
C, CH3), 53.1 (s, C, Ar-C), 62.40 (s, C, ArC-Cl), 117.87 (s, C, Ar-C), 126.70 (s, C,
=
Ar-C), 133.33 (s, C, Ar-C), 139.15 (s, C, Ar-C), 161.09 (s, C, C O of azetidinone),
=
163.27 (s, C, C O of coumarin); CIMS: m=z 511.98. Anal. calcd. for
C28H18ClN3O3S: C, 65.69; H, 3.54; Cl, 6.92; N, 8.21; S, 6.26. Found: C, 65.68; H,
3.52; Cl, 6.91; N, 8.22; S, 6.24.
3-Chloro-1-(4-methyl-3-nitro-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo-
[4,5]imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4k). IR (KBr): c (cmꢀ1) 1721.0
=
=
=
(C O of azetidinone), 1624.4 (C O of coumarin), 1541.7 (C N of benzimidazole),
1532.1 and 1329.6 (NO2 asymmetric and symmetric stretching), 811 (C-Cl of azetidi-
1
none); H NMR (DMSO-d6, 300 MHz): d (ppm) 2.31 (s, 3H, CH3), 3.14 (s, 1H,
Ar-CH), 3.72 (1H, ArCH-Cl merged with solvent peak), 7.20–7.37 (s, 6H, Ar-H),
7.69 (d, 2H, J ¼ 8.4, Ar-H), 7.72–7.91 (s, 3H, Ar-H), 8.13 (s, 1H, Ar-H); 13C NMR
(DMSO-d6, 75MHz): d (ppm) 22.3 (s, C, CH3), 53.2 (s, C, Ar-C), 64.04 (s, C, ArC-Cl),
115.76 (s, C, Ar-C), 125.67 (s, C, Ar-C), 130.09 (s, C, Ar-C), 135.82 (s, C, Ar-C), 144.35
=
=
(s, C, Ar-C), 162.38 (s, C, C O of azetidinone), 165.27 (s, C, C O of coumarin); CIMS:
m=z 556.98. Anal. calcd. for C28H17ClN4O5S: C, 60.38; H, 3.08; Cl, 6.37; N, 10.06; S,
5.76. Found: C, 60.37; H, 3.09; Cl, 6.38; N, 10.04; S, 5.74.
3-Chloro-1-(4-methoxy-phenyl)-4-{3-(2-oxo-2H-chromen-3-yl)-benzo[4,5]-
imidazo[2,1-b]thiazol-2-yl}-azetidin-2-one (4l). IR (KBr): c (cmꢀ1) 1722.4 (C O
=
=
=
of azetidinone), 1628.1 (C O of coumarin), 1553.7 (C N of benzimidazole), 815
(C-Cl of azetidinone); 1H NMR (DMSO-d6, 300 MHz): d (ppm) 3.14 (s, 1H,
Ar-CH), 3.74 (4H, ArCH-Cl and OCH3 merged with solvent peak), 6.98 (d, 2H,
J ¼ 7.1, Ar-H), 7.11 (d, 2H, J ¼ 7.6, Ar-H), 7.26–7.28 (s, 4H, Ar-H), 7.62 (d, 2H,
J ¼ 8.3, Ar-H), 7.79 (d, 2H, J ¼ 9.2, Ar-H), 8.11 (m, 1H, Ar-H); 13C NMR
(DMSO-d6, 75 MHz): d (ppm) 60.11 (s, C, OCH3), 54.71 (s, C, Ar-C), 61.60 (s, C,
ArC-Cl), 118.22 (s, C, Ar-C), 124.37 (s, C, Ar-C), 136.63 (s, C, Ar-C), 142.85 (s,
=
=
C, Ar-C), 160.19 (s, C, C O of azetidinone), 162.57 (s, C, C O of coumarin); CIMS:
m=z 527.98. Anal. calcd. for C28H18ClN3O4S: C, 63.70; H, 3.44; Cl, 6.71; N, 7.96; S,
6.07. Found: C, 63.69; H, 3.43; Cl, 6.70; N, 7.95; S, 6.05.
ACKNOWLEDGMENTS
This research work is financially supported by the University Grant
Commission (UGC), New Delhi [Ref. No. 33–296=2007 (SR)]. Dr. K. M. Hosamani
is indebted to the British Commonwealth Scholarship Commission, UK [Ref. No.
INCF-2008–68].
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