Novel, mild, and highly efficient method for the synthesis of 2-arylbenzothiazoles by the oxidation of 2-arylbenzothiazolines with silicon lewis acids

Article abstract of DOI:10.1080/00397910903531896

Oxidation of structurally diverse 2-arylbenzothiazolines to give the corresponding 2-arylbenzothiazoles has been carried out in benzene using dimethyldichlorosilane and trimethylchlorosilane. Short reaction times, mild reaction conditions, easy and quick isolation of the products, and excellent yields are the main advantages of this procedure. Copyright

Full text of DOI:10.1080/00397910903531896

This article was downloaded by: [Pennsylvania State University]
On: 19 May 2012, At: 00:13
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Novel, Mild, and Highly Efficient
Method for the Synthesis of 2-
Arylbenzothiazoles by the Oxidation
of 2-Arylbenzothiazolines with Silicon
Lewis Acids
Sonika a , Meenakshi a & Rajesh Malhotra a
a Department of Chemistry, Guru Jambheshwar University of Science
and Technology, Hisar, Haryana, India
Available online: 14 Dec 2010
To cite this article: Sonika, Meenakshi & Rajesh Malhotra (2010): Novel, Mild, and Highly Efficient
Method for the Synthesis of 2-Arylbenzothiazoles by the Oxidation of 2-Arylbenzothiazolines with
Silicon Lewis Acids, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:1, 136-146
To link to this article: http://dx.doi.org/10.1080/00397910903531896
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,

demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 136–146, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531896
NOVEL, MILD, AND HIGHLY EFFICIENT METHOD FOR
THE SYNTHESIS OF 2-ARYLBENZOTHIAZOLES BY THE
OXIDATION OF 2-ARYLBENZOTHIAZOLINES WITH
SILICON LEWIS ACIDS
Sonika, Meenakshi, and Rajesh Malhotra
Department of Chemistry, Guru Jambheshwar University of Science and
Technology, Hisar, Haryana, India
Oxidation of structurally diverse 2-arylbenzothiazolines to give the corresponding 2-aryl-
benzothiazoles has been carried out in benzene using dimethyldichlorosilane and trimethyl-
chlorosilane. Short reaction times, mild reaction conditions, easy and quick isolation of the
products, and excellent yields are the main advantages of this procedure.
Keywords: Benzothaizoles;
trimethylchlorosilane
benzothiazolines;
dimethyldichlorosilane;
silicon
Lewis
acids;
INTRODUCTION
Benzothiazoles are a very important group of heterocyclic compounds that
have many applications in both pharmaceutical and industrial research. They are
widely used in bioorganic and medicinal chemistry with applications in drug dis-
covery.[1] They have also found potent utility as imaging agents for b-amyloid[2]
and as luminescent=fluorescent agents.[3]
There are three major routes to synthesize benzothiazoles (Scheme 1). The meth-
odology developed following strategy A involves the reaction of 2-aminothiophenol
with aldehydes,[4] carboxylic acids,[5] and esters[6] using a number of oxidants=cata-
lysts. Strategy B includes cyclization of thioanilides or halothioanilides promoted
by various reagents.[7] Benzothiazoles have been also prepared by the oxidative
cyclization of thiophenolic Schiff’s bases=benzothiazolines (strategy C) using various
oxidants such as pyridinium chlorochromate[8] and recently via electrooxidation.[9]
However, most of these synthetic approaches suffer from drawbacks such as
harsh reaction conditions (strong acids, high temperatures), tedious workup, possi-
bility of side reactions, and generation of acidic=metallic wastes. Therefore, there is a
need to overcome these limitations by developing an efficient and convenient meth-
odology for the synthesis of benzothiazoles.
Received September 20, 2009.
Address correspondence to Sonika, Department of Chemistry, Guru Jambheshwar University of
Science and Technology, Hisar-125001, Haryana, India. E-mail: sc_ic2001@yahoo.co.in
136

SYNTHESIS OF 2-ARYLBENZOTHIAZOLES
137
Scheme 1. Synthetic routes to 2-arylbenzothiazoles.
Among various synthetic applications of organosilicon compounds, the trans-
formations utilizing derivatives containing leaving groups at the silicon atom have
become especially widespread. Tetravalent triorganosilanes, such as trimethylsilyl
chloride, iodide, and triflate, are the standard silylating agents employed for
functional-group manipulations in organic synthesis. The Lewis acidity of silicon
compounds is attributed mainly to the intrinsic capability of silicon to extend its
valence shell, giving rise to five- and six-coordinate intermediates. The latter might
dissociate, depending on the strength of the silicon–leaving group bond. Formally,
these tetravalent reagents might be understood as silylium ion precursors.
The use of silicon Lewis acids (SLAs) is advantageous over traditional
metal-centered activators because they are not prone to aggregation and are compat-
ible with many synthetically valuable C-nucleophiles, such as cuprates, allyl organo-
metallic reagents, and silyl enol ethers. Morever, the reactivity of SLAs can be
controlled by varying the steric volume of alkyl substituents. The tendency of silicon
to form five- and six-coordinate intermediates is further enhanced upon insertion of
two or more electron-withdrawing substituents (i.e., of the type R2SiX2 or RSiX3).[10]
RESULTS AND DISCUSSION
It is expected that the reaction of 2-aminothiophenol with several typical alde-
hydes leads to the corresponding Schiff bases. The actual products are 2-substituted
benzothiazolines. However, several metal ions induce rearrangement of these ben-
zothiazolines to yield the corresponding Schiff base–metal complexes. These Schiff
bases derived from 2-substituted benzothiazolines act as bidentate ligands and form

138
SONIKA, MEENAKSHI, AND R. MALHOTRA
Scheme 2. Reaction of 2-substituted benzothiazolines with metal ions.
five-membered N, S-bonded chelate rings. Many researchers have paid attention to
reactions classified as ‘‘metal ion–induced rearrangement’’ (Scheme 2).[11]
However, when we carried out the reaction of benzothiazoline with
dimethyldichlosilane=trimethylchlorosilane (DMSCl=TMSCl) (1.1 eq) in dry ben-
zene, we obtained the corresponding benzothiazoles in excellent yields and purities
in short reaction times. Purity of products was further confirmed by thin-layer chro-
matography (TLC) on silica (fluorescence); under ultravoilet light, benzothiazoles
fluoresced bright blue, whereas the benzothiazoline gave quenched spots. Not even
a trace of the addition complex was observed in this reaction, as reported pre-
viously.[12] To explore the generality and scope of this process, diversified benzothia-
zolines were studied in the synthesis of benzothiazoles (Scheme 3, Table 1).
We extended our methodology to the oxidation of benzothiazolines of formyl
pyrazoles (3), which, on treatment with DMSCl or TMSCl, afforded the correspond-
ing 2-pyrazolylbenzothiazoles (4) in 90–95% yields. There were no steric hindrances
due to the presence of bulky groups (Scheme 4, Table 1).
No significant substituent effect was observed on the yields of the products.
The reaction was carried out at different temperatures to evaluate the effect of reac-
tion temperature. At room temperature, the reaction rate was slow (30–40 min),
and it increased with temperature. At 45–50 ꢀC, the reaction rate was maximum
(5–10 min), and further increase in temperature did not show any enhancement.
Praveen et al.[8] assigned a Schiff base structure to the condensation products
of 2-aminothiophenol and various benzaldehydes. However, these compounds have
thiazoline structure rather than the Schiff base structure.
The oxidation of benzothiazoline was supported by the disappearance of
1
N-H stretch peaks in the infrared (IR) spectra. Also, in the H NMR spectra of
Scheme 3. Synthesis of 2-aryl=heteroarylbenzothiazoles.

SYNTHESIS OF 2-ARYLBENZOTHIAZOLES
139
Table 1. Synthesis of 2-arylbenzothiazoles by the oxidation of corresponding benzothiazolines with
DMSCl and TMSCl
S. no.
Ar
Product
DMSCl yield (%)
TMSCl yield (%)
Ref.
1
2
C6H5
2a
2b
2c
2d
2e
4a
4b
4c
4d
4e
4f
92
93
90
85
86
91
87
95
93
92
94
89
90
92
95
88
90
92
85
94
90
93
93
92
6
4c
4c
4c
6
4-Cl-C6H4
2-Cl-C6H4
2-thienyl
3
4
5
2-pyridyl
C6H5
6
—
—
8
7
4-CH3-C6H4
4-OCH3-C6H4
2-OCH3-C6H4
4-Cl-C6H4
4-Br-C6H4
4-F-C6H4
8
9
—
8
10
11
12
8
—
4g
Note. All the products were characterized by IR, NMR, and comparison of melting points with those
reported in the literature.
benzothiazoles, the broad singlet at d 4.3 due to the NH proton and the singlet at d
6.3 due to the C2-H proton disappear. In the case of benzothiazolines of formyl
pyrazoles, the pyrazolyl-H, which resonated as a singlet at d 8.2–8.3, showed a sig-
nificant downfield shift after oxidation and appeared as a singlet at d 8.6.
Benzothiazoles have been also prepared from 2-aminothiophenol and aldehydes
in dimethyformamide (DMF) using TMSCl (2 mol) as a promoter and water-acceptor
agent, followed by oxidation with air oxygen.[4a] To exclude the role of air oxygen, we
carried out a set of reactions under nitrogen with both DMSCl and TMSCl in dry ben-
zene, and again we got the same oxidized products. This clearly establishes that in our
case the oxidation is being carried out by the DMSCl and TMSCl and not by air oxygen.
A mechanistic rationale for this reaction (as shown in Scheme 5) can be given.
Initially, the benzothiazoline reacts with TMSCl by the associative mechanism to
form a five-coordinate intermediate (5). The presence of alkyl groups at the silicon
atom makes 5 much less stable for both electronic and stertic reasons, leading to
the ionization of a chloride and formation of salt 6. The complexes 5 and 6 are likely
to be short-lived intermediates, which either very rapidly revert to the starting
compounds or undergo oxidation to give the benzothiazole. In this case, the equilib-
rium is shifted to right, probably because of the formation of thermodynamically
more stable benzothiazoles.
Scheme 4. Synthesis of 2-pyrazolylbenzothiazoles.

140
SONIKA, MEENAKSHI, AND R. MALHOTRA
Scheme 5. Proposed mechanism for the SLA-mediated oxidation.
In conclusion, DMSCl and TMSCl have been employed as a novel, mild, and
very efficient reagent for the convenient preparation of benzothiazoles from ben-
zothiazolines. The methodology is applicable to a wide variety of structurally diverse
substrates and delivers the target products in good yields, excellent homogeneity,
and often analytically pure form.
EXPERIMENTAL
Melting points were uncorrected and determined in open capillaries. Fourier
transform (FT)—IR spectra were obtained as KBr pellets with a Perkin-Elmer Spec-
1
trum RX1 instrument. H NMR and 13C NMR spectra were recorded on Bruker
Avance II 400-MHz and 100-MHz NMR spectrometers, respectively, in CDCl3 with
tetramethysilane (TMS) as an internal standard. Elemental analyses were carried out
on a Perkin-Elmer 2400 instrument. Mass spectra were recorded on a Thermo
Finnigan LCQ Advantage MAX instrment. Analytical TLC was performed on pre-
coated plastic sheets of silica gel G=UV-254 of 0.2 mm thickness (Macherey-Nagel,
Germany). All the solvents used were dried by conventional methods. Diphenyldi-
chlorosilane and triphenylchlorosilane were obtained through Aldrich and used as
such without any further purification.
Synthesis of 2-Aryl/Heteroarylbenzothiazolines (1a–e)
2-Phenylbenzothiazoline (1a),[11a] 2-(4-chlorophenyl)-benzothiazoline (1b),[11a]
2-(2-chlorophenyl)-benzothiazoline (1c),[11b] 2-(2-thienyl)-benzothiazoline (1d),[13]
and 2-(2-pyridyl)-benzothiazoline (1e)[14] were prepared by literature methods.

SYNTHESIS OF 2-ARYLBENZOTHIAZOLES
141
Synthesis of Benzothiazolines of Formyl Pyrazoles (3a–f): General
Procedure
4-Formyl pyrazoles were prepared in two steps. The first was the reaction
between acetophenone derivatives and phenylhydrazine. The hydrazone derivatives
were treated with the Vilsmeier–Haack reagent (DMF–POCl3), leading to the corre-
sponding 4-carboxaldehyde functionalized pyrazole heterocyclic ring in mild operat-
ing conditions. Three equivalents of this reagent, instead of two as described by Kira
et al.,[15] were necessary to obtain the aldehydes in good yields.
Equimolar quantities of 2-aminothiophenol (4.0 mmol, 0.50 g) and the appro-
priate 4-formyl pyrazoles (4.0 mmol) were heated together for 5–10 min at 50–60 ꢀC,
the reaction mixture was cooled and triturated with hexane, and the solid was col-
lected and recrystallized with methanol.
Synthesis of 2-Arylbenzothiazoles (2a–e and 3a–f): General
Procedure
DMSCl=TMSCl (1.1 mmol) was added dropwise to a stirred solution of 2-aryl-
benzothiazolines (1.0 mmol) in 5 mL of dry benzene at room temperature. The reac-
tion mixture was warmed to 40–45 ꢀC. The product separated immediately; however,
the stirring was continued for an additional 5–10 min to ensure the completion of the
reaction. After completion of the reaction, the solvent was removed in vacuo to
afford the crude product, which was triturated with dry cyclohexane and recrystal-
lized with methanol.
Spectral and Analytical Data
2-(1,3-Diphenyl-1-H-pyrazol-4-yl)benzothiazoline (3a). White solid; mp
130 ꢀC; Rf ¼ 0.43 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1): 3350, 3051,
2916, 1598, 1580, 1543, 1503, 1459, 1447, 1396, 1351, 1223, 1121, 1064, 1012, 956,
744. 1H NMR (400 MHz, CDCl3): d 4.33 (bs, 1H, NH), 6.51 (s, 1H, C2-H),
0
6.64–6.66 (dd, 1H, J ¼ 7.68 & 0.60 Hz, C4 -H), 6.76–6.80 (dt, 1H, J ¼ 7.52 &
1.04 Hz, C6-H), 6.92–6.96 (dt, 1H, J ¼ 7.68 & 1.20 Hz, C5-H), 7.06–7.08 (dd, 1H,
0
00
J ¼ 7.56 & 0.96 Hz, C7-H), 7.23–7.29 (m, 1H, C4 -H), 7.35–7.50 (m, 5H, C3 -H,
00
00
0
0
0
0
00
00
C4 -H, C5 -H, C3 -H & C5 -H), 7.70–7.80 (m, 4H, C2 -H, C6 -H, C2 -H & C6 -H),
8.28 (s, 1H, pyrazolyl-H). Anal. calcd. for C22H17N3S: C, 74.34; H, 4.82; N, 11.82;
S, 9.02%. Found: C, 74.00; H, 4.23; N, 11.99; S, 8.58%. ESI-MS [M þ H]þ ¼ 356.26;
calcd. for C22H17N3S ¼ 355.11.
2-(1-Phenyl-3-p-tolyl-1-H-pyrazol-4-yl)benzothiazoline (3b). White solid;
mp 134 ꢀC; Rf ¼ 0.42 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1): 3310, 3143,
3066, 2920, 2859, 1596, 1581, 1541, 1500, 1469, 1455, 1408, 1363, 1333, 1221,
1
1058, 960, 826, 735. H NMR (400 MHz, CDCl3) d 2.40 (s, 3H, CH3), 4.39 (bs,
1H, NH), 6.54 (s, 1H, C2-H), 6.67–6.69 (m, 1H, C4-H), 6.77–6.81 (dt, 1H, J ¼ 7.52
& 1.02 Hz, C6-H), 6.93–6.97 (dt, 1H, J ¼ 7.60 & 1.16 Hz, C5-H), 7.08–7.10 (dd,
0
00
00
1H, J ¼ 7.92 & 0.80 Hz, C7-H), 7.25–7.29 (m, 3H, C4 -H, C3 -H & C5 -H),
0
0
00
00
7.41–7.45 (m, 2H, C3 -H & C5 -H), 7.60–7.62 (d, 2H, J ¼ 8.04 Hz, C2 -H & C6 -H),
0
0
7.71–7.73 (m, 2H, C2 -H & C6 -H), 8.29 (s, 1H, pyrazolyl-H). Anal. calcd. for

142
SONIKA, MEENAKSHI, AND R. MALHOTRA
C23H19N3S: C, 74.77; H, 5.18; N, 11.37; S, 8.68%. Found: C, 74.24; H, 5.35; N,
11.03; S, 8.36%. ESI-MS [M þ H]þ ¼ 370.25; calcd. for C23H19N3S ¼ 369.13.
2-[3-(4-Methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]benzothiazoline (3c).
White solid; mp 113–114 ꢀC; Rf ¼ 0.30 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1):
3307, 3141, 3050, 3003, 2931, 2871, 2837, 1611, 1595, 1583, 1540, 1528, 1503, 1471,
1455, 1244, 1174, 1060, 840, 735. 1H NMR (400 MHz, CDCl3): d 3.82 (s, 3H,
OCH3), 4.35 (bs, 1H, NH), 6.48 (s, 1H, C2-H), 6.64–6.66 (dd, 1H, J ¼ 7.72 &
0.64 Hz, C4-H), 6.76–6.80 (dt, 1H, J ¼ 7.56 & 1.04 Hz, C6-H), 6.91–6.95 (dt, 1H,
00
00
J ¼ 7.60 & 1.20 Hz, C5-H), 6.96–6.99 (m, 2H, C3 -H & C5 -H), 7.06–7.08 (dd, 1H,
0
0
J ¼ 7.56 & 1.04 Hz, C7-H), 7.23–7.27 (m, 1H, C4 -H), 7.39–7.43 (m, 2H, C3 -H &
0
00
00
0
0
C5 -H), 7.62–7.66 (m, 2H, C2 -H & C6 -H), 7.68–7.70 (m, 2H, C2 -H & C6 -H), 8.24
(s, 1H, pyrazolyl-H). Anal. calcd. for C23H19N3OS: C, 71.66; H, 4.97; N, 10.90; S,
8.32%. Found: C, 71.28; H, 4.49; N, 11.18; S, 8.09%. ESI-MS [M þ H]þ ¼ 386.24;
calcd. for C23H19N3OS ¼ 385.12.
2-[3-(2-Methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]benzothiazoline (3d).
Pale yellow solid; mp 128–130 ꢀC; Rf ¼ 0.38 (AcOEt=petroleum ether 10%). IR
(KBr, cmꢁ1): 3320, 3130, 3050, 2925, 1594, 1580, 1547, 1505, 1475, 1450, 1400,
1
1360, 1323, 1220, 1060, 950, 830, 738. H NMR (400 MHz, CDCl3): d 3.85 (s, 3H,
OCH3), 4.51 (bs, 1H, NH), 6.17 (s, 1H, C2-H), 6.55–6.57 (m, 1H, C4-H),
6.70–6.74 (dt, 1H, J ¼ 7.60 & 0.92 Hz, C6-H), 6.87–6.91 (dt, 1H, J ¼ 7.60 &
00
1.12 Hz, C5-H), 6.96–6.98 (d, 1H, J ¼ 8.28 Hz, C3 -H), 7.03–7.07 (m, 2H, C7-H &
00
0
00
0
0
C5 -H), 7.21–7.25 (m, 1H, C4 -H), 7.34–7.40 (m, 3H, C4 -H, C3 -H & C5 -H),
00
0
0
7.50–7.52 (dd, 1H, J ¼ 7.48 & 1.68 Hz, C6 -H), 7.66–7.68 (m, 2H, C2 -H & C6 -H),
8.20 (s, 1H, pyrazolyl-H). Anal. calcd. for C23H19N3OS: C, 71.66; H, 4.97; N,
10.90; S, 8.32%. Found: C, 71.30; H, 5.10; N, 10.78; S, 8.49%. ESI-MS
[M þ H]þ ¼ 386.22; calcd. for C23H19N3OS ¼ 385.12.
2-[3-(4-Chloro-phenyl)-1-phenyl-1H-pyrazol-4-yl]benzothiazoline (3e).
White solid; mp 124–125 ꢀC; Rf ¼ 0.36 (AcOEt=petroleum ether 10%). IR (KBr,
cmꢁ1): 3322, 3051, 2923, 1599, 1575, 1558, 1541, 1503, 1466, 1409, 1396, 1211,
1
1093, 1062, 1007, 831, 743. H NMR (400 MHz, CDCl3): d 4.35 (bs, 1H, NH),
6.50 (s, 1H, C2-H), 6.68–6.70 (dd, 1H, J ¼ 7.32 & 0.62 Hz, C4-H), 6.79–6.83 (dt,
1H, J ¼ 7.52 & 1.00 Hz, C6-H), 6.94–6.98 (dt, 1H, J ¼ 7.60 & 1.20 Hz, C5-H),
0
7.08–7.10 (dd, 1H, J ¼ 7.60 & 0.96 Hz, C7-H), 7.27–7.31 (m, 1H, C4 -H), 7.40–7.49
00
(m, 4H, C3 -H, C5 -H, C3 -H & C5 -H), 7.66–7.73 (m, 4H, C2 -H, C6 -H, C2 -H &
00
0
0
0
0
00
00
C6 -H), 8.28 (s, 1H, pyrazolyl-H). Anal. calcd. for C22H16ClN3S: C, 67.77; H,
4.14; N, 10.78; S, 8.22%. Found: C, 67.40; H, 4.31; N, 10.93; S, 8.08%. ESI-MS
[M þ H]þ ¼ 390.21; calcd. for C22H16ClN3S ¼ 389.08.
2-[3-(4-Bromo-phenyl)-1-phenyl-1H-pyrazol-4-yl]benzothiazoline (3f).
White solid; mp 195–196 ꢀC; Rf ¼ 0.40 (AcOEt=petroleum ether 10%). IR (KBr,
cmꢁ1): 3293, 3111, 3050, 2924, 1597, 1576, 1533, 1505, 1473, 1398, 1360, 1308,
1
1277, 1200, 1117, 1065, 831, 738. H NMR (400 MHz, CDCl3): d 4.29 (bs, 1H,
NH), 6.49 (s, 1H, C2-H), 6.68–6.70 (m, 1H, C4-H), 6.79–6.83 (m, 1H, C6-H),
0
6.94–6.98 (m, 1H, C5-H), 7.08–7.10 (m, 1H, C7-H), 7.24–7.31 (m, 1H, C4 -H),
0
0
0
0
00
00
7.36–7.46 (m, 2H, C3 -H & C5 -H), 7.56–7.71 (m, 6H, C2 -H, C6 -H, C2 -H, C3 -H,
00
00
C5 -H & C6 -H), 8.28 (s, 1H, pyrazolyl-H). Anal. calcd. for C22H16BrN3S: C,

SYNTHESIS OF 2-ARYLBENZOTHIAZOLES
143
60.83; H, 3.71; N, 9.67; S, 7.38%. Found: C, 60.96; H, 3.58; N, 9.791; S, 7.49%.
ESI-MS [M þ H]þ ¼ 434.17; calcd. for C22H16BrN3S ¼ 433.02.
2-[3-(4-Fluoro-phenyl)-1-phenyl-1H-pyrazol-4-yl]benzothiazoline (3g).
White solid; mp 129 ꢀC; Rf ¼ 0.33 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1):
1
3310, 3045, 3305, 1603, 1570, 1500, 1475, 1357, 1268, 1110, 836, 740. H NMR
(400 MHz, CDCl3): d 4.29 (bs, 1H, NH), 6.48 (s, 1H, C2-H), 6.67–6.69 (d, 1H,
J ¼ 7.64 Hz, C4-H), 6.78–6.82 (dt, 1H, J ¼ 7.60 & 0.88 Hz, C6-H), 6.93–6.97 (dt,
1H, J ¼ 7.64 & 1.00 Hz, C5-H), 7.07–7.09 (dd, 1H, J ¼ 7.60 & 0.64 Hz, C7-H),
00
00
0
7.11–7.18 (m, 2H, C3 -H & C5 -H), 7.26–7.30 (m, 1H, C4 -H), 7.36–7.45 (m, 2H,
0
0
0
0
00
00
C3 -H & C5 -H), 7.68–7.71 (m, 4H, C2 -H, C6 -H, C2 -H & C6 -H), 8.27 (s, 1H,
pyrazolyl-H). Anal. calcd. for C22H16FN3S: C, 70.76; H, 4.32; N, 11.25; S, 8.59%.
Found: C, 70.90; H, 4.20; N, 11.37; S, 8.72%. ESI-MS [M þ H]þ ¼ 374.24; calcd.
for C22H16FN3S ¼ 373.10.
2-(1,3-Diphenyl-1H-pyrazol-4-yl)benzothiazole (4a). Yellow solid; mp
139–140 ꢀC; Rf ¼ 0.47 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1): 3029, 2923,
1596, 1584, 1544, 1527, 1506, 1448, 1355, 1246, 1065, 962, 930, 752. 1H NMR
0
(400 MHz, CDCl3): d 7.30–7.36 (m, 2H, C4 -H & C6-H), 7.44–7.51 (m, 6H, C5-H,
0
C3 -H, C5 -H, C3 -H, C4 -H & C5 -H), 7.75–7.77 (m, 3H, C4-H, C2 -H & C6 -H),
0
00
00
00
00
00
0
0
7.82–7.84 (d, 2H, J ¼ 8.00 Hz, C2 -H & C6 -H), 8.00–8.02 (d, 1H, J ¼ 8.12 Hz, C7-
H), 8.64 (s, 1H, pyrazolyl-H). 13C NMR (100 MHz, CDCl3): d 117.36 (C4-pyrazolyl),
0
119.30 (C2 & C6 ), 121.32 (C4), 122.53 (C7), 124.79 (C5), 126.13 (C6), 127.22 (C4 ),
0
0
00
00
00
00
128.19 (C5-pyrazolyl), 128.41 (C2 & C6 ), 129.06 (C4 ), 129.53 (C3 & C5 ), 129.6
00
0
0
00
0
(C3 & C5 ), 131.93 (C1 ), 134.96 (C7a), 139.34 (C1 ), 152.12 (C4a), 153.14 (C2),
160.04 (C3-pyrazolyl). Anal. calcd. for C22H15N3S: C, 74.76; H, 4.28; N, 11.82; S,
9.07%. Found: C, 74.70; H, 4.41; N, 11.99; S, 8.99%. ESI-MS [M þ H]þ ¼ 354.27;
calcd. for C22H15N3S ¼ 353.10.
2-(1-Phenyl-3-p-tolyl-1H-pyrazol-4-yl)benzothiazole (4b). White solid;
mp 182–183 ꢀC; Rf ¼ 0.36 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1): 3030,
2936, 2846, 1620, 1605, 1593, 1550, 1522, 1478, 1440, 1305, 1237, 1160, 1012, 950,
1
0
745. H NMR (400 MHz, CDCl3): d 2.44 (s, 3H, CH3), 7.24–7.35 (m, 4H, C4 -H,
00
C6-H, C3 -H & C5 -H), 7.43–7.50 (m, 3H, C5-H, C3 -H & C5 -H), 7.62–7.64 (d,
00
0
0
00
00
2H, J ¼ 7.72 Hz, C2 -H & C6 -H), 7.75–7.77 (d, 1H, J ¼ 7.92 Hz, C4-H), 7.81–7.83
0
0
(d, 2H, J ¼ 7.92 Hz, C2 -H & C6 -H), 8.00–8.02 (d, 1H, J ¼ 8.08 Hz, C7-H), 8.64 (s,
1H, pyrazolyl-H). 13C NMR (100 MHz, CDCl3): d 21.45 (C4-CH3), 117.36 (C4-pyr-
0
azolyl), 119.30 (C2 & C6 ), 121.32 (C4), 122.52 (C7), 124.74 (C5), 126.10 (C6), 127.15
0
0
(C4 ), 128.11 (C5-pyrazolyl), 129.00 (C1 ), 129.15 (C2 & C6 ), 129.52 (C3 & C5 ),
00
00
00
0
0
00
00
00
0
129.54 (C3 & C5 ), 135.01 (C7a), 139.02 (C4 ), 139.42 (C1 ), 152.24 (C4a), 153.17
(C2), 160.23 (C3-pyrazolyl). Anal. calcd. for C23H17N3S: C, 75.18; H, 4.66; N,
11.44; S, 8.73%. Found: C, 75.98; H, 4.39; N, 10.95; S, 8.22%. ESI-MS
[M þ H]þ ¼ 368.30; calcd. for C23H17N3S ¼ 367.11.
2-[3-(4-Methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl)]benzothiazole (4c).
White solid; mp 168–169 ꢀC (lit.[8] mp 167–169 ꢀC); Rf ¼ 0.34 (AcOEt=petroleum
ether 10%). IR (KBr, cmꢁ1): 3024, 2963, 2930, 2835, 1610, 1598, 1583, 1547, 1515,
1
1475, 1456, 1293, 1248, 1177, 1023, 963, 840, 750. H NMR (400 MHz, CDCl3): d
00
00
0
3.87 (s, 3H, OCH3), 6.99–7.02 (m, 2H, C3 -H & C5 -H), 7.30–7.35 (m, 2H, C4 -H

144
SONIKA, MEENAKSHI, AND R. MALHOTRA
0
& C6-H), 7.43–7.50 (m, 3H, C5-H, C3 -H & C5 -H), 7.66–7.68 (m, 2H, C2 -H & C6 -
0
00
00
0
0
H), 7.76–7.78 (m, 1H, C4-H), 7.81–7.83 (m, 2H, C2 -H & C6 -H), 8.00–8.02 (d, 1H,
J ¼ 8.00 Hz, C7-H), 8.66 (s, 1H, pyrazolyl-H). 13C NMR (100 MHz, CDCl3): d
00
00
0
0
55.29 (C4-OCH3), 113.89 (C3 & C5 ), 117.24 (C4-pyrazolyl), 119.25 (C2 & C6 ),
00
121.32 (C4), 122.46 (C7), 124.21 (C1 ), 124.75 (C5), 126.12 (C6), 127.13 (C4 ),
0
0
128.08 (C5-pyrazolyl), 129.51 (C3 & C5 ), 130.97 (C2 & C6 ), 134.90 (C7a), 139.37
0
00
00
0
00
(C1 ), 151.99 (C4a), 153.07 (C2), 160.27 (C3-pyrazolyl), 160.39 (C4 ). Anal. calcd.
for C23H17N3OS: C, 72.04; H, 4.47; N, 10.96; S, 8.36%. Found: C, 71.78; H, 4.39;
N, 11.08; S, 8.22%. ESI-MS [M þ H]þ ¼ 384.28; calcd. for C23H17N3OS ¼ 383.11.
2-[3-(2-Methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl)]benzothiazole (4d).
White solid; mp 173–174 ꢀC; Rf ¼ 0.40 (AcOEt=petroleum ether 10%). IR (KBr,
cmꢁ1): 3020, 2970, 2933, 2840, 1608, 1595, 1575, 1540, 1480, 1450, 1290, 1170,
1
1030, 960, 845, 760. H NMR (400 MHz, CDCl3): d 3.63 (s, 3H, OCH3), 7.00–7.02
00
00
(d, 1H, J ¼ 8.44 Hz, C3 -H), 7.10–7.14 (t, 1H, J ¼ 7.28 Hz, C5 -H), 7.24–7.34 (m,
0
2H, C4 -H & C6-H), 7.41–7.52 (m, 5H, C5-H, C4 -H, C6 -H, C3 -H & C5 -H),
00
00
0
0
0
0
7.71–7.73 (d, 1H, J ¼ 7.84 Hz, C4-H), 7.82–7.84 (d, 2H, J ¼ 7.80 Hz, C2 -H & C6 -
H), 7.97–7.98 (d, 1H, J ¼ 8.04 Hz, C7-H), 8.77 (s, 1H, pyrazolyl-H).13C NMR
00
(100 MHz, CDCl3): d 55.35 (C2-OCH3), 111.14 (C3 ), 118.91 (C4-pyrazolyl), 119.27
0
(C2 & C6 ), 120.88 (C5 ), 121.16 (C1 ), 121.28 (C4), 122.21 (C7), 124.40 (C5),
0
00
00
0
125.96 (C6), 127.01 (C4 ), 127.02 (C5-pyrazolyl), 129.45 (C3 & C5 ), 130.99 (C6 ),
0
0
00
00
0
00
131.83 (C4 ), 134.85 (C7a), 139.45 (C1 ), 149.63 (C4a), 152.89 (C2), 158.11 (C4 ),
160.65 (C3-pyrazolyl). Anal. calcd. for C23H17N3OS: C, 72.04; H, 4.47; N, 10.96;
S, 8.36%. Found: C, 71.80; H, 4.67; N, 10.67; S, 8.19%. ESI-MS [M þ H]þ ¼ 384.27;
calcd. for C23H17N3OS ¼ 383.11.
2-[3-(4-Chloro-phenyl)-1-phenyl-1H-pyrazol-4-yl)]benzothiazole
(4e).
White solid; mp 205–206 ꢀC (lit.[8] mp 205–207 ꢀC); Rf ¼ 0.41 (AcOEt=petroleum
ether 10%). IR (KBr, cmꢁ1): 3060, 2922, 2848, 1598, 1540, 1522, 1506, 1269, 1247,
1
1091, 1012, 962, 931, 831, 754. H NMR (400 MHz, CDCl3): d 7.34–7.38 (m, 2H,
0
C4 -H & C6-H), 7.43–7.52 (m, 5H, C5-H, C3 -H, C5 -H, C3 -H & C5 -H), 7.72–7.75
00
00
0
0
00
00
0
0
(m, 2H, C2 -H & C6 -H), 7.79–7.83 (m, 3H, C4-H, C2 -H & C6 -H), 8.01–8.03 (d,
1H, J ¼ 8.12 Hz, C7-H), 8.63 (s, 1H, pyrazolyl-H).13C NMR (100 MHz, CDCl3): d
0
117.18 (C4-pyrazolyl), 119.33 (C2 & C6 ), 121.35 (C4), 122.67 (C7), 125.00 (C5),
0
0
126.20 (C6), 127.39 (C4 ), 128.56 (C5-pyrazolyl), 128.62 (C2 & C6 ), 129.59 (C3
00
00
0
&
0
C5 ), 130.45 (C1 ), 130.89 (C3 & C5 ), 134.88 (C7a), 135.11 (C4 ), 139.23 (C1 ),
00
00
00
00
0
0
150.79 (C4a), 153.19 (C2 ), 159.64 (C3-pyrazolyl). Anal. calcd. for C22H14ClN3S: C,
68.12; H, 3.64; N, 10.83; S, 8.27%. Found: C, 68.00; H, 3.41; N, 11.16; S, 8.01%.
ESI-MS [M þ H]þ ¼ 388.25; calcd. for C22H14ClN3S ¼ 387.06.
2-[3-(4-Bromo-phenyl)-1-phenyl-1H-pyrazol-4-yl)]benzothiazole
(4f).
White solid; mp 210–211 ꢀC (lit.[8] mp 210–214 ꢀC); Rf ¼ 0.42 (AcOEt=petroleum
ether 10%). IR (KBr, cmꢁ1): 3052, 2924, 2854, 1597, 1550, 1517, 1481, 1247, 1071,
1
0
960, 829, 753. H NMR (400 MHz, CDCl3): d 7.34–7.38 (m, 2H, C4 -H & C6-H),
0
0
00
7.46–7.52 (m, 3H, C5-H, C3 -H & C5 -H), 7.59–7.61 (d, 2H, J ¼ 8.40 Hz, C2 -H &
00
00
00
C6 -H), 7.67–7.69 (d, 2H, J ¼ 8.40 Hz, C3 -H & C5 -H), 7.80–7.82 (d, 3H,
0
0
J ¼ 7.60 Hz, C4-H, C2 -H & C6 -H), 8.01–8.03 (d, 1H, J ¼ 8.00 Hz, C7-H), 8.59 (s,
1H, pyrazolyl-H).13C NMR (100 MHz, CDCl3): d 117.22 (C4-pyrazolyl), 119.37

SYNTHESIS OF 2-ARYLBENZOTHIAZOLES
145
0
(C2 & C6 ), 121.41 (C4), 122.74 (C7), 123.44 (C4 ), 125.06 (C5), 126.31 (C6), 127.45
0
00
0
(C4 ), 128.61 (C5-pyrazolyl), 129.65 (C3 & C5 ), 130.96 (C1 ), 131.20 (C2 & C6 ),
0
0
00
00
00
00
00
00
131.62 (C3 & C5 ), 134.93 (C7a), 139.27 (C1 ), 150.82 (C4a), 153.28 (C2), 159.65
(C3-pyrazolyl). Anal. calcd. for C22H14BrN3S: C, 61.12; H, 3.26; N, 9.72; S,
7.42%. Found: C, 60.46; H, 3.48; N, 9.31; S, 7.60%. ESI-MS [M þ H]þ ¼ 432.17;
calcd. for C22H14BrN3S ¼ 431.01.
2-[3-(4-Fluoro-phenyl)-1-phenyl-1H-pyrazol-4-yl)]benzothiazole
(4g).
White solid; mp 160 ꢀC; Rf ¼ 0.37 (AcOEt=petroleum ether 10%). IR (KBr, cmꢁ1):
1
3040, 2934, 1610, 1555, 1527, 1512, 1487, 1257, 1078, 1019, 970, 750. H NMR
00
00
0
(400 MHz, CDCl3): d 7.13–7.18 (m, 2H, C3 -H & C5 -H), 7.32–7.37 (m, 2H, C4 -H
0
& C6-H), 7.44–7.51 (m, 3H, C5-H, C3 -H & C5 -H), 7.73–7.82 (m, 5H, C4-H, C2 -H,
0
00
00
0
0
C6 -H, C2 -H & C6 -H), 7.99–8.01 (d, 1H, J ¼ 8.12 Hz, C7-H), 8.60 (s, 1H,
pyrazolyl-H). 13C NMR (100 MHz, CDCl3): d 115.34 & 115.56 (C3 & C5 ), 117.2
00
00
0
(C4-pyrazolyl), 119.33 (C2 & C6 ), 121.34 (C4), 122.64 (C7), 124.94 (C5), 126.23
0
0
(C6), 127.34 (C4 ), 128.00 & 128.04 (C1 ), 128.37 (C5-pyrazolyl), 129.58 (C3 & C5 ),
00
0
0
00
131.47 & 131.55 (C2 & C6 ), 134.88 (C7a), 139.29 (C1 ), 151.07 (C4a), 153.23 (C2),
00
0
00
159.77 (C3-pyrazolyl), 162.19 & 164.66 (C4 ). Anal. calcd. for C22H14FN3S: C,
71.14; H, 3.80; N, 11.31; S, 8.63%. Found: C, 70.60; H, 3.66; N, 11.68; S, 8.46%.
ESI-MS [M þ H]þ ¼ 372.26; calcd. for C22H14FN3S ¼ 371.09.
ACKNOWLEDGMENT
The authors are grateful to the Sophisticated Analytical Instrumentation
Facility (SAIF), Panjab University, Chandigarh, India, for providing the NMR
facility and elemental analysis.
REFERENCES
1. Rana, A.; Siddiqui, N.; Khan, S. A. Benzothiazoles: A new profile of biological activities.
Indian J. Pharm. Sci. 2007, 69, 10–17 and references therein.
2. Alagille, D.; Baldwin, R. M.; Tamagnan, G. D. One-step synthesis of 2-arylbenzothiazole
(‘‘BTA’’) and -benzoxazole precursors for in vivo imaging of b-amyloid plaques. Tetra-
hedron Lett. 2005, 46, 1349–1351.
3. Chen, L.; Yang, C.; Li, S.; Qin, J. Synthesis and electronic absorption and fluorescence of
2-arylbenzothiazole. Spectrochim. Acta Mol. Biomol. Spectros. 2007, 68, 317–322.
4. (a) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Tolmachev, A. A. Synthesis of
fused imidazoles and benzothiazoles from (hetero)aromatic ortho-diamines or ortho-
aminothiophenol and aldehydes promoted by chlorotrimethylsilane. Synthesis
2006, 3715–3726; (b) Pratap, U. R.; Mali, J. R.; Jawale, D. V.; Mane, R. A. Bakers’
yeast–catalyzed synthesis of benzothiazoles in an organic medium. Tetrahedron Lett.
2009, 50, 1352–1354; (c) Al-Qualaf, F.; Mekheimer, R. A.; Sadek, K. U. Cerium(IV)
ammonium nitrate (CAN)–catalyzed one-pot synthesis of 2-arylbenzothiazoles. Molecules
2008, 13, 2908–2914.
5. Gupta, S. D.; Singh, H. P.; Moorthy, N. S. H. N. Iodine-catalyzed, one-pot, solid-phase
synthesis of benzothiazole derivatives. Synth. Commun. 2007, 37, 4327–4329.
6. Matshushita, H.; Lee, S. H.; Joung, M.; Clapham, B.; Janda, K. D. Smart cleavage reac-
tions: The synthesis of benzimidazoles and benzothiazoles from polymer-bound esters.
Tetrahedron Lett. 2004, 45, 313–316.

146
SONIKA, MEENAKSHI, AND R. MALHOTRA
7. (a) Downer-Riley, N. K.; Jackson, Y. A. Iodine-mediated cyclisation of thiobenzamides to
produce benzothiazoles and benzoxazoles. Tetrahedron 2007, 63, 10276–10281; (b) Bose,
D. S.; Idrees, M.; Srikanth, B. Synthesis of 2-arylbenzothiazoles by DDQ-promoted
cyclization of thioformanilides: A solution-phase strategy for library synthesis. Synthesis
2007, 819–813.
8. Praveen, C.; Kumar, K. H.; Muralidharan, D.; Perumal, P. T. Oxidative cyclization of
thiophenolic and phenolic Schiff’s bases promoted by PCC: A new oxidant for 2-substi-
tuted benzothiazoles and benzoxazoles. Tetrahedron 2008, 64, 2369–2374.
9. Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.; Komata, M.; Tomozawa, K.; Chiba,
T. Electro-oxidative cyclization of benzylideneaminothiophenols to the corresponding
2-arylbenzothiazoles. Heterocycles 2008, 75, 35–42.
10. (a) Dilman, A. D.; Loffe, S. L. Carbonꢁcarbon bond-forming reactions mediated by sili-
con Lewis acids. Chem. Rev. 2003, 103, 733–772; (b) Rendler, S.; Oestritch, M. Hyperva-
lent silicon as a reactive site in selective bond-forming processes. Synthesis 2005, 1727–
1747; (c) Orito, Y.; Nakajima, M. Lewis base-catalyzed asymmetric reactions involving
hypervalent silicate intermediates. Synthesis 2006, 1391–1401.
11. (a) Kawamoto, T.; Nishiwaki, M.; Tsunekawa, Y.; Nozaki, K.; Konno, T. Synthesis and
characterization of luminescent zinc(II) and cadmium(II) complexes with N,S-chelating
Schiff base ligands. Inorg. Chem. 2008, 47, 3095–3104; (b) Kawamoto, T. Activation of
C–H and C–Cl bonds in the reactions of 2-substituted benzothiazolines with
[RhCl(PPh3)3]. Inorg. Chim. Acta 2000, 300–302, 512–516; (c) Mahajan, K.; Swami, M.;
Singh, R. V. Microwave synthesis, spectral studies, antimicrobial approach, and coordi-
nation behavior of antimony(III) and bismuth(III) compounds with benzothiazoline.
Russ. J. Coord. Chem. 2009, 35, 179–185.
12. Singh, K.; Tandon, J. P. Synthesis and spectral studies of methylsilicon(IV) chloride com-
plexes with biologically active heterocyclic benzothiazoline. Indian J. Chem. 1991, 30A,
283–285.
13. Emerson, W. S.; Patrick, T. M. The preparation of 2-thiophenealdehyde and some of its
derivatives. J. Org. Chem. 1949, 14, 790–797.
14. Palmerr, P. G.; Trigg, B.; Warrington, J. V. Benzothiazolines as antituberculosis agents. J.
Med. Chem. 1971, 14, 248–251.
15. Kira, M. A.; Abdel-Raeman, M. O.; Gadalla, K. Z. The Vilsmeier–Haack reaction, III:
Cyclization of hydrazones to pyrazoles. Tetrahedron Lett. 1969, 10, 109–110.