Microwave-assisted syntheses of 2-phenylbenzothiazoles

Article abstract of DOI:10.1080/00397910802517822

A new and easy synthetic route to 2-phenylbenzothiazoles has been achieved by direct thiation of benzoyl derivatives of aniline, various substituted anilines, and 1-naphthylamine under microwave irradiation. The oxidative cyclization using elemental sulfur in the presence of a catalytic amount of iodine is inexpensive and worked well for a number of anilides. Copyright Taylor & Francis Group, LLC.

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Microwave-Assisted Syntheses
of 2-Phenylbenzothiazoles
Sudhir Pal a , Gopal Patra a & Sankar Bhunia a
a Chemistry Department, Midnapore College,
Midnapore, India
Published online: 04 Mar 2009.
To cite this article: Sudhir Pal , Gopal Patra & Sankar Bhunia (2009) Microwave-
Assisted Syntheses of 2-Phenylbenzothiazoles, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:7,
1196-1203
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Synthetic Communications1, 39: 1196–1203, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802517822
Microwave-Assisted Syntheses of
2-Phenylbenzothiazoles
Sudhir Pal, Gopal Patra, and Sankar Bhunia
Chemistry Department, Midnapore College, Midnapore, India
Abstract: A new and easy synthetic route to 2-phenylbenzothiazoles has been
achieved by direct thiation of benzoyl derivatives of aniline, various substituted
anilines, and 1-naphthylamine under microwave irradiation. The oxidative cycli-
zation using elemental sulfur in the presence of a catalytic amount of iodine is
inexpensive and worked well for a number of anilides.
Keywords: Anilides, benzothiazoles, microwave, oxidative cyclization, thiation
INTRODUCTION
Compounds with benzothiazole skeletons are of paramount interest
because of their antitumor,[1] anticancer,[2] and antibacterial[3] activities.
These also exhibit nonlinear optical[4] and luminescent[5]=fluorescent[6]
properties and are therefore being used in designing sensor molecules
of specific interest, so a large number of citations are appearing in recent
times that deal with the syntheses of benzothiazoles. All these methods
employed either the thiol function[7] at the ortho-position of the aniline
moieties of the starting materials or initiated cyclization of appropriate
thiobenzanilides.[8] We are searching for new methods to prepare sensor
molecules that have this heterocyclic ring system and found a new and
easy method of preparing 2-phenylbenzothiazole from benzanilide by
direct thiation under microwave heating conditions. We then tested the
generality of the procedure by taking benzoates of various aromatic
Received August 18, 2008.
Address correspondence to Sudhir Pal, Chemistry Department, Midnapore
College, 721101, Midnapore, India. E-mail: sudhirpal08@gmail.com
1196

Syntheses of 2-Phenylbenzothiazoles
1197
Figure 1. Syntheses of substituted benzothiazoles.
amines with unsubstituted ortho-positions. In this communication, we
report the results of this simple technique.
RESULTS AND DISCUSSION
The benzoate of 1-napthylamine, aniline, or appropriately substituted
aniline (Figs. 1 and 2) is intimately mixed with sulfur and a catalytic
amount of iodine and then subjected to microwave irradiation in a
domestic microwave oven. We followed microwave irradiation, as the
rates of reactions are faster than conventional heating methods. The reac-
tions were carried out in solvent and under solvent-free conditions. The
products were isolated in moderate to good yields. The best result with
respect to yield and time was found using dimethylformamide (DMF)
as solvent. Again some additives were used during the reactions, espe-
cially to improve the yield. Addition of a small amount of formic acid
gave encouraging results though the reaction in formic acid as solvent
was unsuccessful.
Figure 2. Synthesis of 2-phenyl-naphtho[1,2-d]thiazole.

1198
S. Pal, G. Patra, and S. Bhunia
Benzanilide I gave an excellent yield of 2-phenylbenzothiazole 1.
Benzoates of 1-naphthyl amine IX and 4-toluidine II afforded only 9
and 2 respectively as sole products in good yields. 4-Anisidine benzoate
III also yielded a single product, but it was the corresponding demethy-
lated compound (viz., 6-hydroxy-2-phenylbenzothiazole 3) rather
than the expected 6-methoxy compound. Compound IV, obtained from
3-toluidine, furnished 5-methyl-2-phenylbenzothiazole 4a as the major
product and 7-methyl isomer 4b as a minor product as expected.
3-Anisidine benzoate VII also gave two products, namely 5- and 7-
methoxy-2-phenylbenzothiazoles 7a and 7b, but yields are rather low.
3-Chloroaniline benzoate V, however, gave a very good yield of 5-
chloro-2-phenylbenzothiazole 5 as the only isolable product. Benzoates
of anilines with strong electron-withdrawing substituent (e.g., nitro
group) failed to yield any product. Benzoate of 4-aminobenzoic acid
VI, however, furnished expected product 6-carboxy-2-phenylbenzothia-
zole 6 in moderate yield. Reaction of the benzoate of 4-bromoaniline VIII
yielded 2-phenylbenzothiazole 8a in major amount (i.e., bromine is
eliminated during the reaction). The normally expected 6-bromo-2-
phenylbenzothiazole was obtained in a very small amount. The details
of reaction conditions and yield of products are presented in Table 1.
Table 1. Specific reaction conditions and yields
Conditions
Reactants MW Time (min) Solvent (additive) Product (s)a Yield (%)
I
240 W
15
15
15
15
15
10
20
Neat
DMF
DMSO
1
1
40
58
55
80
58
52
32
25
62
54
24
18
47
11
30
47
1
DMF (þHCOOH)
DMF (þHCOOH)
DMF (þHCOOH)
DMF (þHCOOH)
1
II
240 W
240 W
160 W
2
III
IV
3
4a,
4b
5
V
320 W
320 W
240 W
15
100
10
DMF (þHCOOH)
DMF (þHCOOH)
DMF (þHCOOH)
VI
VII
6
7a,
7b
8a,
8b
9
VIII
240 W
12
DMF (þHCOOH)
10
10
DMF
DMF (þHCOOH)
IX
240 W
9
aAll the products have been characterized by IH NMR, 13C NMR, IR and mass
spectral studies.

Syntheses of 2-Phenylbenzothiazoles
1199
Scheme 1. Proposed mechanistic routes.
It may be mentioned that imine, obtained from the condensation of
benzaldehyde with aniline, has also been reported to undergo this sort of
oxidative cyclization with sulfur to furnish benzothiazole on heating, but
we found that the result is far from satisfactory. Moreover, imines are not
quite stable compounds. In contrast, benzoates are stable and can be
easily prepared, and the procedure worked well for the syntheses of quite
a number of substituted 2-phenylbenzothiazoles.
Two mechanisms could be probable as shown in Scheme 1: (i) it may
involve [4 þ 2] cycloaddition of the iminol intermediate tautomer T of the
benzoate, or (ii) it may proceed via the electrophilic attack of sulfur at
C-2 of the benzoate in line with the mechanism of the Willgerodt–Kindler
reaction.
EXPERIMENTAL
Preparation of the Benzoates
The respective aniline was benzoylated following the standard procedure
of the Schotten–Baumen reaction and then recrystallized from the appro-
priate solvent. The purity of the samples was checked by melting points
reported in the literature.
Preparation of the Benzothiazoles
As a general procedure, the reactants (viz., benzoate of the particular
aniline and sulfur in the molar ratio of 1:1.2, along with 10 mol% iodine)
were intimately mixed together in a mortar and then subjected to

1200
S. Pal, G. Patra, and S. Bhunia
Table 2. Physical and spectral data of 2-phenylbenzothiazoles
Melting
point (ꢀC)
Compound
Spectral data
2-Phenylbenzothiazole (1)
and (8a)
120
Mass: m=z 211 (Mþ, base peak),
109 (10%).
1H NMR (300 MHz): d 8.05–8.07, 3H;
7.86 1H, d (J ¼ 8 Hz); 7.44–7.59, 4H,
and 7.35, 1H, t (J ¼ 8 Hz).
13C NMR (125 MHz): d 168.11, 154.22,
135.13, 131.0, 129.06, 127.62,
127.49, 126.36, 125.23, 123.3,
and 121.66.
6-Methyl-2-
phenylbenzothiazole (2)
130
Mass, m=z 225 (Mþ).
1H NMR (300 MHz): d 8.07–8.08, 2H;
7.96, 1H, d (J ¼ 8.4 Hz); 7.68, 1H, s;
7.47–7.50, 3H; 7.30, 1H,
d (J ¼ 8.4 Hz), and 2.51, 3H, s.
13C NMR (125 MHz): d 167.18,
152.76,135.64, 135.56, 134.2, 131.05,
129.32, 128.25, 127.85, 123.22,
121.71, and 21.98.
6-Hydroxy-2-
phenylbenzothiazole (3)
168
Mass, m=z 227 (M þ , base peak),
197 (7%).
IR, nmax3451 cmꢁ1 (br).
1H NMR (200 MHz): d 8.85, 1H, s;
8.20, 2H; 7.97, 1H, d (J ¼ 8.8 Hz);
7.73, 1H; 7.60–7.70, 2H; 7.50, 1H,
d (J ¼ 2.5 Hz); 7.06, 1H, dd (J ¼ 8.8
& 2.5 Hz).
13C NMR (125 MHz): d 163.54, 155.20,
147.10, 135.70, 133.17, 129.76, 128.34,
126.38, 122.87, 115.58, and 106.04.
Mass, m=z 225 (Mþ).
5-Methyl-2-
phenylbenzothiazole (4a)
140
1H NMR (200 MHz): d 8.02–8.15, 2H;
7.88, 1H, s (fine splitting, J ¼ 1 Hz);
7.78, 1H, d (J ¼ 8.2 Hz); 7.45–7.60,
3H; 7.21, d with fine splitting
(J ¼ 8.2 & 1 Hz),
1H; 2.55, 3H, s.
13C NMR (125 MHz): d 168.18, 154.62,
136.42, 133.85, 132.10, 130.86,
129.01, 127.54, 126.85, 123.32,
121.12, and 21.54
(Continued )

Syntheses of 2-Phenylbenzothiazoles
1201
Table 2. Continued
Melting
point (ꢀC)
Compound
Spectral data
7-Methyl-2-
phenylbenzothiazole (4b)
131
Mass, m=z 225 (Mþ, 30%),
211 (base peak).
1H NMR (200 MHz): d 7.83–7.90, 3H;
7.43–7.60, 3H; 7.20–7.40, 1H;
6.95, 1H, d (J ¼ 7.5 Hz); and
2.36, 3H, s.
13C NMR (125 MHz): 165.95,
138.85, 137.90, 134.99, 131.63,
128.75, 128.59, 127.06, 125.30,
121.07, 117.51, and 21.40.
Mass, m=z 245 (Mþ, base peak),
247 (Mþ þ 2, 33%).
5-Chloro-2-
phenylbenzothiazole (5)
118
13C NMR (125 MHz): 169.95, 155.07,
133.38, 133.34, 132.38, 131.37,
129.13, 127.66, 125.69, 123.10,
and 122.33.
6-Carboxy-2-
phenylbenzothiazole (6)
123
139
Mass, m=z 255 (Mþ).
IR, nmax 3305 cmꢁ1 (br.), 1702 cmꢁ1
.
1H NMR (300 MHz): d 10.26, 1H, br.s;
8.12–8.15, 3H; 7.60–7.63; 2H, and
7.30–7.41, 3H.
5-Methoxy-2-
phenylbenzothiazole (7a)
Mass, m=z 241 (Mþ).
1H NMR (500 MHz): d 8.11–8.13, 2H;
7.35, 1H, d (J ¼ 9 Hz); 7.57, 1H,
d (J ¼ 1.7 Hz); 7.47–7.49, 3H;
7.03, 1H, dd (J ¼ 9 & 1.7 Hz)
and 3.90, 3H, s.
4,5-Benzo-2-
110
Mass, m=z 261 (Mþ).
phenylbenzothiazole (or
2-phenylnaphtho
[1,2-d ]thiazole) (9)
1H NMR (200 MHz): d 9.00,
1H, d (J ¼ 8 Hz); 8.23–8.25,
2H; 7.91–7.98, 2H; 7.83, 1H,
d (J ¼ 8 Hz); 7.71, 1H, t (J ¼ 8 Hz);
7.61, 1H, t (J ¼ 8 Hz); and
7.50–7.56, 3H.
13C NMR (125 MHz): d 167.08,
150.50, 134.06, 132.11, 131.72,
130.61, 129.06, 128.85, 128.10,
127.37, 126.97, 126.16, 125.94,
124.08, and 8.99.

1202
S. Pal, G. Patra, and S. Bhunia
microwave heating in an open vessel with or without solvent. The
reactions were carried out in a domestic microwave oven (model
23SC1: IFB). The power and time was gradually increased. The reaction
was monitored from time to time by thin-layer chromatography (TLC).
After completion, the reaction mixture was extracted with ether, dried,
and chromatographed over silical gel (Merck, 60–120 mesh).
Physical and Spectral Data of Some of the Benzothiazoles
IR spectra (Shimadzu spectrophotometer) were recorded in KBr discs.
1
All the products are soluble in chloroform, and so their H and 13C
NMR spectra (Brucker instruments) were recorded in CDCl3 using tetra-
methysilane (TMS) as an internal standard. The data are presented in
Table 2.
In conclusion, we have established a direct thiation of benzoyl
derivatives of anilines as an easy route to 2-phenylbenzothiazoles. The
method could be extended to the syntheses of 2-arylbenzothiazoles,
that is, similar products with substituent(s) at the phenyl ring at the
2-position. We are exploring this possibility currently.
ACKNOWLEDGMENTS
The authors acknowledge the financial assistance of UGC in the form of
minor research project. The help of Prof. A. Sarkar, Prof. D. Mal,
Bimalendu Roy, Dr. Subrata K. Pal, and Kaushik Chandra in collecting
spectra of products and of Dr. Kumaresh Ghosh for discussions in the
course of the work is thankfully acknowledged.
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