Convenient approach for the one-pot, three-component synthesis of triheterocyclic 4 H-pyrimido[2,1-b]benzothiazole derivatives using TBAHS

Article abstract of DOI:10.1080/00397911.2011.592624

An efficient and convenient synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives has been achieved by a one-pot, three-component condensation reaction of 2-aminobenzothiazole (1) with substituted benzaldehydes (2a-f) and -dicarbonyl derivatives (3a-e) in presence of 30mol% of tetrabutylammonium hydrogen sulfate (TBAHS) in good to excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.592624

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Convenient Approach for the One-
Pot, Three-Component Synthesis of
Triheterocyclic 4H-Pyrimido[2,1-
b]benzothiazole Derivatives Using TBAHS
Lingaiah Nagarapu a , Hanmant K. Gaikwad a , Jyothsna Devi Palem a
, Ramineni Venkatesh a , Rajashaker Bantu a & B. Sridhar a
a Organic Chemistry Division II, Indian Institute of Chemical
Technology, Hyderabad, India
Accepted author version posted online: 01 Feb 2012. Version of
record first published: 05 Sep 2012
To cite this article: Lingaiah Nagarapu, Hanmant K. Gaikwad, Jyothsna Devi Palem, Ramineni
Venkatesh, Rajashaker Bantu & B. Sridhar (2013): Convenient Approach for the One-Pot, Three-
Component Synthesis of Triheterocyclic 4H-Pyrimido[2,1-b]benzothiazole Derivatives Using TBAHS,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:1, 93-104
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Synthetic Communications1, 43: 93–104, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.592624
CONVENIENT APPROACH FOR THE ONE-POT,
THREE-COMPONENT SYNTHESIS OF
TRIHETEROCYCLIC 4H-PYRIMIDO[2,1-b]
BENZOTHIAZOLE DERIVATIVES USING TBAHS
Lingaiah Nagarapu, Hanmant K. Gaikwad, Jyothsna Devi
Palem, Ramineni Venkatesh, Rajashaker Bantu, and B. Sridhar
Organic Chemistry Division II, Indian Institute of Chemical Technology,
Hyderabad, India
GRAPHICAL ABSTRACT
Abstract An efficient and convenient synthesis of 4H-pyrimido[2,1-b]benzothiazole deriva-
tives has been achieved by a one-pot, three-component condensation reaction of 2-amino-
benzothiazole (1) with substituted benzaldehydes (2a–f) and b-dicarbonyl derivatives
(3a–e) in presence of 30 mol% of tetrabutylammonium hydrogen sulfate (TBAHS) in good
to excellent yields.
Keywords Multicomponent condensation; pyrimidobenzothaizole; tetrabutylammonium
hydrogen sulfate (TBAHS)
INTRODUCTION
Multicomponent condensation reactions have a wide range of applicability in
the field of synthetic organic chemistry and they constitute an especially attractive
synthetic strategy because they provide easy and rapid access to large libraries of
organic compounds with diverse substitution patterns. Because these are one-pot
reactions, they are easier to carry out than multistep syntheses, and these products
are formed in a single step. Diversity can be achieved simply by varying each compo-
nent.[1] In the past few years, combinatorial methods using multicomponent reac-
tions have been closely examined as fast and convenient solutions for the synthesis
of diverse classes of compounds.[2] Recently, this strategy became important in drug
Received February 11, 2011.
Address correspondence to Lingaiah Nagarapu, Organic Chemistry Division II, Indian Institude of
Chemical Technology, Uppal Road, Hyderabad 500607, India. E-mail: lnagarapuiict@yahoo.com,
nagarapu@iict.res.in
93

94
L. NAGARAPU ET AL.
Scheme 1. Biginelli condensation reaction.
discovery in the context of synthesis of biologically active compounds. This method
increases the efficiency of the reactions and decrease the number of laboratory opera-
tions along with solvents and chemicals used. It also reduces reaction time and
facilitates the yield of products more than the normal multistep methods.[3]
Bicyclic 3,4-dihydropyrimidin-2(1H)-ones such as 4H-pyrimido[2,1-b]
benzothiazoles, thiazdopyrimidines, and imidazopyrimidines, which have potent
vasorelaxant activity, these are prepared in two steps by Atwal modification of the
Biginelli reaction[4] and a single step in ionic liquids.[5] Biginelli condensation reac-
tion[6] is a three-component condensation of an aldehyde, a urea or thiourea, and
b-carbonyl compound under acidic conditions in ethanol (Scheme 1). In connection
to our interest in multicomponent reactions and Biginelli-like compounds, we estab-
lished simple synthesis of 4H-pyrimido[2,1-b]benzothiazoles ring systems by a
one-pot, three-component condensation of aldehydes, b-dicarbonyls, and 2-amino-
benzothiazole instead of urea or thiourea.
Compounds having benzothiazole moiety possess a wide variety of biological
activities such as anticonvulsant,[7] antitumor,[8] anti-inflammatory,[9] and antituber-
cular[10] activities, and also act as chemo sensitizers in chemotherapy and
neuroprotectant-cerebral antischemic agents.[11]
Acidic tetrabutylammonium hydrogen sulfate (TBAHS) acts as
a
phase-transfer catalyst and performs many organic transformations under mild con-
ditions. It has been used for dehydration and cyclization steps in the Hantzsch reac-
tion, and it is easy to handle, inexpensive, and thermally stable.[12]
As part of our current studies on the development of new routes to heterocyclic
systems,[13] we now report an efficient and clean synthetic route to 4H-pyrimido[2,1-
b]benzothiazole derivatives (4a–j) utilizing 30 mol% of TBAHS as a catalyst by the
condensation reaction of 2-aminobenzothiazole (1) with substituted benzaldehyde
(2a–f) and b-dicarbonyl derivatives (3a–e) in ethylene glycol (Scheme 2).
Scheme 2. Multicomponent condensation reaction of 2-aminobenzothiazole (1), benzaldehyde (2), and
ethyl acetoacetate (3).

4H-PYRIMIDO[2,1-b]BENZOTHIAZOLE DERIVATIVES
95
Table 1. Three-component reaction of 1, 2, and 3 under different conditions and catalyst
Entry
Catalyst
Cat. (mol %)
Solvent
Time (h)
Yield (%)a
1
2
—
—
—
—
—
30
30
20
30
30
10
30
50
30
PEG
n-Butanol
Glycerol
12
12
12
12
12
18
12
12
2
Nrb
Nrb
Nrb
15
3
—
FeCl3
4
Ethylene glycol
Ethylene glycol
Ethylene glycol
n-Butanol
5
p-TSA
TBAB
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
Nrb
53
6
7
Nrb
32
8
Glycerol
9
Ethylene glycol
Ethylene glycol
Ethylene glycol
Diethylene glycol
71
83
10
11
12
2
1
81
76
2
aIsolated yields obtained after column chromatography.
bNo reaction.
RESULTS AND DISCUSSION
Initially, a model reaction was examined using 2-aminobenzothiazole (1), ben-
zaldehyde (2), and ethyl acetoacetate (3) in the presence of TBAHS (30 mol %) in
ethylene glycol as solvent (Scheme 2). After 2 h, 83% of 4H-pyrimido[2,1-b]ben-
zothiazole (4) product was isolated. When the amount of TBAHS was increased
to 100 mol%, the yield was slightly decreased from 83% to 71%. Several other cata-
lysts have been tested, and it was found that FeCl3 and tetrabutylammonium bro-
mide (TBAB) offered poor yields, and the reaction did not proceed in the forward
direction in para-tolunesulfonic acid (p-TSA). Subsequently, we investigated the
effect of different solvents on the reaction and yields of the product (Table 1). The
use of ethylene glycol resulted in better yields than n-butanol, glycerol, polyethylene-
glycol (PEG), and diethylene glycol (Table 1). We chose the optimized conditions as
in entry 10, Table 1, for further investigation.
With optimized conditions in hand, the scope of reaction was explored with
different starting materials, and several derivatives of 4a–j were synthesized in good
to excellent yields (Scheme 3). The compounds 4a–e were obtained by using various
b-dicarbonyl derivatives 3a–e (Table 2), and compounds 4f–j were obtained by using
substituted benzaldehyde 2a–f (Table 3) with greater yields. The structures of the
Scheme 3. Multicomponent condensation reaction of 2-aminobenzothiazole (1), substituted benzaldehyde
(2a–f), and b-dicarbonyl derivatives (3a–e).

96
L. NAGARAPU ET AL.
Scheme 4. Plausible mechanism for the formation of 4H-pyrimido[2,1-b]benzothiazole tricylic ring.
products 4a–j were established from their spectral data, infrared (IR), 1H NMR, 13
C
NMR, and mass spectroscopic analyses. The formation of compound 4a was evident
from the appearance of [M þ H]þ peak at m=z 351 in mass spectrum (ESI)þ and the
appearance of characteristic methine proton as singlet at d 6.36 in 1H NMR. To further
conform the structure by x-ray analysis (crystal data for 4a: yellow crystals,
˚
C20H18N2O2S, M ¼ 350.42, monoclinic, space group P21=n, a ¼ 10.543(13) A,
3
b ¼ 9.720(12) A, c ¼ 17.36(2) A, b ¼ 95.26(2) , V ¼ 1772(4) A , dcalc ¼ 1.314 Mg mꢁ3).
ꢀ
˚
˚
˚
Data were collected at room temperature using a Bruker Smart Apex CCD diffract-
˚
ometer with graphite monochromated MoKa radiation (k ¼ 0.71073 A) with x-scan
method.[14] Preliminary lattice parameters and orientation matrices were obtained from
four sets of frames. Unit cell dimensions were determined using 5371 reflections in the
rangeof2.36< h < 27.79ꢀ for compound 4a, asAJ53. Integrationandscalingofintensity
datawereaccomplishedusingtheSAINT[14] program. The structure was solvedby direct
methods using SHELXS97,[15] and refinement was carried out by the full-matrix least-
squares technique using SHELXL97.[15] All hydrogen atoms were positioned geometri-
cally and were treated as riding on their parent carbon atoms, with C-H distance of
˚
0.93–0.98 A, with Uiso(H) ¼ 1.2Ueq (C) or 1.5Ueq(C). The highest unassigned peak is
˚
located 0.49 A from atom H19A. The structure was refined with R1 ¼ 0.0594,
wR2¼ 0.1737 for 2759 reflections with I > 2r(I). The structure is shown in Fig. 1.
In summary, we have developed a convenient approach for the synthesis of
4H-pyrimido[2,1-b]benzothiazole derivatives with excellent yields and short reaction
times which involves the use of inexpensive catalyst TBAHS. Furthermore, the
present procedure is readily amenable to parallel synthesis and generation of
combinatorial pyrimidobenzothiazole libraries.
EXPERIMENTAL
All commercial reagents and solvents were used as received without further
purification unless specified, and reaction solvents were distilled. The reactions were
monitored, and Rf values were determined using analytical thin-layer chromato-
graphy (TLC) with Merck silica-gel 60 F254 precoated plates (0.25 mm thick). Spots
on the TLC plates were visualized using ultraviolet light (254 nm). Flash column

4H-PYRIMIDO[2,1-b]BENZOTHIAZOLE DERIVATIVES
97
Table 2. Three-component condensation reaction of 2-aminobenzothiazole (1) and benzaldehyde (2a)
with various b-dicarbonyls (3a–e)a
Entry
b-Dicarboyls 3a–e
Product 4a–e
Time (h)
Yields (%)b
Mp (ꢀC)
177–179
1
1.0
83
2
1.0
78
146–148
3
4
5
1.5
2.0
2.0
75
72
68
138–140
216–218
205–207
aReaction conditions: 1 (1 mmol), 2a (2 mmol), 3a–e (2 mmol), TBAHS (30 mol %), 120 ꢀC, and ethylene
glycol (5 mL).
bIsolated yields obtained after column chromatography.
chromatography was performed with Merck silica gel 60 (100–200 mesh). Melting
1
points were determined in capillaries and are uncorrected. H NMR spectra were
recorded on Bruker DRX-300, Varian 400 and Varian-500 NMR spectrometers.
13C NMR spectra were recorded on a Bruker DRX-300 instrument. Proton chemical
shifts are reported in ppm (d) relative to internal tetramethylsilane (TMS, d) 0.00 or
with the solvent reference relative to TMS employed as the internal standard
(CDCl3, d 7.26 ppm), and multiplicities of NMR signals are designated as s (singlet),

98
L. NAGARAPU ET AL.
Table 3. Three-component condensation reaction of 2-aminobenzothiazole (1), and ethyl acetoacetate
(3a) with substituted benzaldehyde (2b-f)a
Entry
Aldehyde 2b–f
Product 4a–e
Time (h)
Yields (%)
Mp (ꢀC)
1
1.5
79
125–127
2
2.0
72
156–158
3
4
5
2.0
1.5
2.0
78
74
79
141–144
Yellow oil
133–135
aReaction conditions: 1 (1 mmol), 2b–f (2 mmol), 3a (2 mmol), TBAHS (30 mol %), 120 ꢀC, and ethylene
glycol (5 mL).
bIsolated yields obtained after column chromatography.
d (doublet), t (triplet), q (quartet), br (broad), m (multiplet, for unresolved lines), etc.
Infrared (IR) spectra were recorded on a Perkin Elmer Fourier transform (FT)–IR
400 spectrometer; data are reported in wave numbers (cmꢁ1). Mass spectra were
recorded on Agilent Technologies 1100 Series (Agilent Chemistation Software).

4H-PYRIMIDO[2,1-b]BENZOTHIAZOLE DERIVATIVES
99
Figure 1. X-ray crystal structure AJ53. Displacement ellipsoids are drawn at 30% probability level and H
atoms are shown as small spheres of arbitrary radii. (Figure is provided in color online.)
General Experimental Procedure for the Preparation of
Compounds 4a–j
2-Aminobezothiazole (1 mmol), benzaldehyde (2.0 mmol), and ethyl acetoace-
tate (2.0 mmol) in ethylene glycol (5 mL) were mixed in a flask, and TBAHS
(30 mol%) was added at room temperature. The resulting mixture was heated at
120 ꢀC for 1–2 h, and completion of the reaction was monitored by TLC (ethyl acet-
ate–hexane 3:7). After completion of the reaction, the reaction mixture was allowed
to cool, diluted with water, and extracted with ethyl acetate and then it was purified
by column chromatography.
Ethyl-2-methyl-4-(phenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4a)
Yield: 83%, mp 177–179 ꢀC. IR: nmax 2932, 1672, 1587, 1509, 1371, 1240, 1096,
1
745, 699, 635 cmꢁ1. H NMR (400 MHz, CDCl3): d 1.29 (t, J ¼ 7.08 Hz, 3H, CH3),
2.41 (s, 3H, CH3), 4.16 (q, J ¼ 6.88 Hz, 2H, OCH2), 6.36 (s, 1H, CH), 7.04–7.13
(m, 2H, Ar-H), 7.16–7.27 (m, 4H, Ar-H), 7.36–7.44 (m, 3H, Ar-H); 13C NMR
(75 MHz, CDCl3): d 14.25, 23.57, 57.65, 61.13, 102.92, 111.73, 122.03, 123.83,
126.50, 128.24, 128.51, 128.63, 137.77, 141.24, 147.24, 154.66, 155.62,163.61,
166.47; MS (ESI)þ: m=z ¼ 351 [M þ H]þ. Anal. calcd. for C20H18N2O2S: C, 68.55;
H, 8.18; N, 7.99; O, 9.13; S, 9.15. Found: C, 68.41; H, 8.07. Crystallographic data
has been deposited for compound 4a as AJ53 with the Cambridge Crystallographic
Data Centre [CCDC No. 812211]. Copies of the data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge

100
L. NAGARAPU ET AL.
Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK;
fax: þ44(0) 1223 336 033; e-mail: deposit@ccdc.cam.ac.uk].
Methyl-2-methyl-4-(phenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4b)
Yield: 78%, mp 146–148 ꢀC. IR: nmax 2930, 1672, 1583, 1505, 1239, 1098, 749,
696, 632 cmꢁ1 1H NMR (300 MHz, CDCl3): d 2.40 (s, 3H, CH3), 3.70 (s, 3H,
.
OCH3), 6.35 (s, 1H, CH), 7.04 (d, J ¼ 8.30 Hz, 1H, Ar-H), 7.11 (d, J ¼ 7.55 Hz,
1H, Ar-H), 7.15–7.26 (m, 4H, Ar-H), 7.34–7.43 (m, 3H, Ar-H); 13C NMR
(75 MHz, CDCl3): d 23.63, 51.01, 57.64, 102.80, 111.65, 122.64, 123.85, 126.54,
126.95, 128.60, 137.94, 141.31, 154.92, 163.45, 166.90; MS (ESI)þ: m=z ¼ 337
[M þ H]þ. Anal. calcd. for C19H16N2O2S: C, 67.84; H, 4.79; N, 8.33; O, 9.51; S,
9.53. Found: C, 67.36; H, 4.68.
2-Methyl-4-(phenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-ethanone (4c)
Yield: 75%, mp 138–140 ꢀC. IR: nmax 2928, 1650, 1587, 1515, 1086, 786, 732,
648 cmꢁ1. 1H NMR (300 MHz, CDCl3): d 2.37 (s, 3H, CH3), 2.42 (s, 3H, CH3), 6.53
(s, 1H, CH), 7.09–7.17 (m, 3H, Ar-H), 7.19–7.25 (m, 3H, Ar-H), 7.36 (d, J ¼ 7.54 Hz,
Hz, 2H, Ar-H), 7.45 (d, J ¼ 7.54 Hz, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d 25.14,
31.84, 56.93, 111.95, 114.15, 122.10, 124.00, 126.99, 128.66, 128.53, 138.06, 141.16,
154.17, 195.20; MS (ESI)þ: m=z ¼ 321 [M þ H]þ. Anal. calcd. for C19H16N2OS: C,
71.22; H, 5.03; N, 8.74; O, 4.99; S, 10.01. Found: C, 71.08; H, 4.95.
12-Phenyl-2,3,4,12-tetrahydro-1H-benzo[4,5][1,3]thiazolo[2,3-
b]quinazolin-1(2H)-one (4d)
Yield: 72%, mp 216–218 ꢀC. IR: nmax 2938, 2883, 1658, 1619, 1579, 1487, 1176,
1
959, 832, 743, 615 cmꢁ1. H NMR (300 MHz, CDCl3): d 1.92–2.08 (m, 2H, CH2),
2.26–2.39 (m, 2H,CH2), 2.51–2.64 (m, 2H, CH2), 6.49 (s, 1H, CH), 7.06–7.11 (m,
2H, Ar-H), 7.13–7.27 (m, 4H, Ar-H), 7.37 (d, J ¼ 6.79 Hz, 2H, Ar-H), 7.48 (d,
J ¼ 7.54 Hz, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d 27.00, 31.43, 36.43, 55.76,
112.15, 122.03, 124.12, 126.25, 126.72, 126.81, 127.94, 128.22, 128.53, 140.75,
160.24, 163.71, 195.57. MS (ESI)þ: m=z ¼ 333 [M þ H]þ. Anal. calcd. for
C20H16N2OS: C, 72.26; H, 4.85; N, 8.43; O, 4.81; S, 9.65. Found: C, 72.18; H, 4.62.
3,3-Dimethyl-12-phenyl-2,3,4,12-tetrahydro-1H-
benzo[4,5][1,3]thiazolo[2,3-b]quinazolin-1(2h)-one (4e)
Yield: 68%, mp 205–207. IR: nmax 2930, 2874, 1658, 1612, 1472, 1267, 1129,
1
986, 824, 738, 616 cmꢁ1. H-NMR (300 MHz,CDCl3): d 0.93 (s, 3H, CH3), 1.09 (s,
3H, CH3), 2.20 (d, J ¼ 7.55 Hz, 2H, CH2), 2.44 (s, 2H, CH2), 6.45 (s, 1H, CH),
7.10 (d, J ¼ 8.39 Hz, 1H, Ar-H), 7.13–7.18 (m, 2H, Ar-H), 7.20–7.27 (m, 3H,
Ar-H), 7.38 (d, J ¼ 7.55 Hz, 2H, Ar-H), 7.47 (d, J ¼ 6.79 Hz, 1H, Ar-H);13C NMR
(75 MHz, CDCl3): d 27.22, 32.55, 45.23, 50.79, 56.03, 110.31, 112.23, 122.06,

4H-PYRIMIDO[2,1-b]BENZOTHIAZOLE DERIVATIVES
101
124.16, 126.81, 128.09, 128.58, 138.24, 140.54, 158.46, 165.56; 195.32; MS (ESI)þ: m=
z ¼ 361 [M þ H]þ. Anal. calcd. for C22H20N2OS: C, 73.30; H, 5.59; N, 7.77; O, 4.44;
S, 8.90. Found: C, 73.14; H, 5.39.
Ethyl-2-methyl-4-(2-chlorophenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4f)
Yield: 79%, mp 125–127 ꢀC. IR: nmax 2936, 1680, 1594, 1516, 1382, 1183, 974,
825, 689 cmꢁ1. 1H NMR (300 MHz, CDCl3): d 1.24 (t, J ¼ 7.17 Hz, 3H, CH3), 2.44 (s,
3H, CH3), 4.15 (q, J ¼ 7.17 Hz, 2H, OCH2), 6.74 (s, 1H, CH), 7.08–7.16 (m, 2H,
Ar-H), 7.19–7.28 (m, 2H, Ar-H), 7.39 (d, J ¼ 7.55 Hz, 1H, Ar-H), 7.46 (d,
J ¼ 8.30 Hz, 2H, Ar-H), 7.62 (d, J ¼ 7.55 Hz, 1H, Ar-H); 13C NMR (75 MHz,
CDCl3): d 14.36, 23.60, 54.42, 59.94, 102.74, 111.64, 121.93, 123.24, 123.98,
126.69, 128.03, 129.40, 129.61, 130.40, 131.41, 138.20, 139.54, 155.26, 163.15,
166.18; MS (ESI)þ: m=z ¼ 386 [M þ H]þ. Anal. calcd. for C20H17ClN2O2S: C,
62.41; H, 4.45; Cl, 9.21; N, 7.28; O, 8.31; S, 8.33. Found: C, 62.38; H, 4.40.
Ethyl-2-methyl-4-(4-nitrophenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4g)
Yield: 72%, mp 156–157 ꢀC. IR: nmax 2924, 1674, 1550, 1333, 1246, 1198, 1096,
1
983, 836, 699 cmꢁ1. H NMR (500 MHz, CDCl3): d 1.30 (t, J ¼ 7.29 Hz, 3H, CH3),
2.43 (s, 3H, CH3), 4.19 (q, J ¼ 7.29 Hz, 2H, OCH2), 6.61 (s, 1H, CH), 7.01 (d,
J ¼ 8.20 Hz, 1H, Ar-H), 7.16 (t, J ¼ 7.74 Hz, 1H, Ar-H), 7.24 (t, J ¼ 7.74 Hz, 1H,
Ar-H), 7.48 (d, J ¼ 8.20 Hz, 1H, Ar-H), 7.59 (d, J ¼ 8.20 Hz, 2H, Ar-H), 8.12 (d,
J ¼ 8.20 Hz, 2H, Ar-H); 13C NMR (75 MHz, CDCl3): d 14.34, 23.90, 57.03, 60.37,
102.01, 111.88, 122.42, 123.74, 123.97, 124.37, 126.80, 127.95, 137.43, 147.86,
155.78, 163.52, 166.25; MS (ESI)þ: m=z ¼ 396 [M þ H]þ. Anal. calcd. for
C20H17N3O4S: C, 60.75; H, 4.33; N, 10.63; O, 16.18; S, 8.11. Found: C, 60.52; H, 4.21.
Ethyl-2-methyl-4-(4-methoxyphenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4h)
Yield: 78%, mp 141–144 ꢀC. IR: nmax 2910, 1680, 1587, 1471, 1256, 1209, 1092,
986, 839, 742, 630 cmꢁ1
.
1H-NMR (300 MHz, CDCl3): d 1.29 (t, J ¼ 7.17 Hz,
3H,CH3), 2.43 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 4.19 (q, J ¼ 7.17 Hz, 2H, OCH2),
6.36 (s, 1H, CH), 7.04–7.13 (m, 1H, Ar-H), 7.19–7.30 (m, 3H, Ar-H), 7.38–7.57
(m, 3H, Ar-H), 8.12 (d, J ¼ 6.71 Hz, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d
23.0, 57.51, 59.98, 60.57, 65.57, 102.39, 111.75, 120.71, 122.04, 123.91, 126.94,
128.02, 128.41, 129.61, 132.53, 140.97, 154.77, 163.48, 166.27; MS (ESI)þ:
m=z ¼ 381 [M þ H]þ. Anal. calcd. for C21H20N2O3S: C, 66.29; H, 5.30; N, 7.36; O,
12.62; S, 8.43. Found: C, 66.11; H, 5.23.
Ethyl-2-methyl-4-(3-chlorophenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4i)
Yield: 74%, yellow oil. IR: nmax 2938, 1674, 1568, 1509, 1328, 1240, 1199, 986,
1
838, 756, 697 cmꢁ1. H NMR (300 MHz, CDCl3): d 1.31 (t, J ¼ 7.17 Hz, 3H, CH3),

102
L. NAGARAPU ET AL.
2.43 (s, 3H, CH3), 4.17 (q, J ¼ 7.17 Hz, 2H, OCH2), 6.34 (s, 1H, CH), 7.04
(d, J ¼ 8.30 Hz, 1H, Ar-H), 7.11–7.27 (m, 4H, Ar-H), 7.37–7.52 (m, 3H, Ar-H);
13C NMR (75 MHz, CDCl3): d 14.23, 23.41, 57.21, 60.14, 102.40, 111.54, 122.18,
124.11, 125.20, 126.61, 127.21, 128.48, 129.88, 132.48, 134.40, 143.02, 154.81,
163.30, 166.14. MS (ESI)þ: m=z ¼ 386 [M þ H]þ. Anal. calcd. for C20H17ClN2O2S:
C, 62.41; H, 4.45; Cl, 9.21; N, 7.28; O, 8.31; S, 8.33. Found: C, 62.28; H, 4.39.
Ethyl-2-methyl-4-(2,4-dichlorophenyl)-4H-pyrimido[2,1-
b][1,3]benzothiazole-3-carboxylate (4j)
Yield: 79%, mp 133–135 ꢀC. IR: nmax 2940, 1683, 1581, 1503, 1389, 1239, 1198,
1
976, 822, 742, 650 cmꢁ1. H NMR (300 MHz, CDCl3): d 1.26 (t, J ¼ 7.17 Hz, 3H,
CH3), 2.44 (s, 3H, CH3), 4.16 (q, J ¼ 7.17 Hz, 2H, OCH2), 6.70 (s, 1H, CH), 7.13
(d, J ¼ 7.55 Hz, 1H, Ar-H), 7.16–7.19 (m, 1H, Ar-H), 7.22 (d, J ¼ 7.55 Hz, 1H,
Ar-H), 7.28–7.31 (m, 1H, Ar-H), 7.39–7.44 (m, 2H, Ar-H), 7.56 (d, J ¼ 9.06 Hz,
1H, Ar-H);13C NMR (75 MHz, CDCl3): d 14.85, 24.12, 54.44, 60.53, 102.86,
111.91, 122.53, 124.63, 127.22, 128.93, 129.55, 135.11, 138.62, 138.41, 156.00,163.76,
166.51. MS (ESI)þ: m=z ¼ 419 [M þ H]þ. Anal. calcd. for C20H16Cl2N2O2S: C, 57.29;
H, 3.85; Cl, 16.91; N, 6.68; O, 7.63; S, 7.65. Found: C, 57.04; H, 3.71.
ACKNOWLEDGMENTS
The authors are thankful to the director, IICT, and head, Organic Chemistry
Division II, Indian Institude of Chemical Technology, for their constant encourage-
ment and support. Hanmant K. Gaikwad thanks the University Grants
Commission, New Delhi, for the award of a research fellowship.
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