Synthesis of 2-aryl and coumarin substituted benzothiazole derivatives

Article abstract of DOI:10.1002/jhet.5570430535

A facile and effective method for the synthesis of some benzothiazole derivatives is described. The method involves the action of aryl aldehyde and o-aminothiophenol in acetic acid resulting into in situ formation of the thiol substituted Schiffs base and

Full text of DOI:10.1002/jhet.5570430535

Sep-Oct 2006
1367
Synthesis of 2-Aryl and Coumarin Substituted
Benzothiazole Derivatives
Rajesh S. Kenny and Uday C. Mashelkar*
Organic Research Laboratory, Patkar-Varde College of Science, Goregaon (W), Mumbai 400062, India.
Received October 31, 2005
R1
R1
R2
R3
O
O
R2
R3
O
O
NH2
SH
CH3COOH
+
R4
R4
N
S
O
H
A facile and effective method for the synthesis of some benzothiazole derivatives is described. The method
involves the action of aryl aldehyde and o-aminothiophenol in acetic acid resulting into in situ formation of
the thiol substituted Schiff’s base and its cyclization to 2-aryl benzothiazole upon prolonged heating.
J. Heterocyclic Chem., 43, 1367 (2006).
Benzothiazoles are heterocyclic compounds with
which acts as a solvent and catalyst (Scheme 1). The 2-
aminothiophenol is first condensed with an aldehyde to
give a thiol substituted Schiff’s base which then cyclizes
upon prolonged heating to give the benzothiazole
derivative. The various substituted 2H-1-benzo/naphtha-
pyran-2-ones-4-aldehydes (11-16) as depicted in Scheme 2
required for the synthesis has been prepared as per the
method reported earlier and also some of them developed
in our laboratory [24a-d]. These 2H-1-benzo/naphthopyran-
2-ones-4-aldehydes (11-16) where reacted with o-amino-
thiophenol in refluxing acetic acid to give 4-(2-benzo-
thiazolyl)-2H-1-benzo/naphthopyran-2-ones (17-22).
multiple applications and they have been known from long
ago to be biologically active, [1-3] their varied biological
features are still of great scientific interest nowadays. They
are widely found in bioorganic and medicinal chemistry
with applications in drug discovery and have a very
intensive antitumor [4-6], antiviral [7], anti-HIV [8],
microbiological activity [9-10], for treatment of auto-
immune and inflammatory diseases [11], in the prevention
of solid organ transplant rejection epilepsy [12-14], amyo-
trophic lateral sclerosis [15] and analgesia [16].
Several research efforts towards the synthesis of
substituted benzothiazoles have been used. The methods
involve the oxidative cyclization of 2-thiobenzanilides to
corresponding benzothiazoles. Hexacyanoferrate [17] and
organic ammonium tribromide (OATB) [18] are some of
the oxidizing agents of choice. In most of the cases the
Schiff’s base formed by heating the o-aminothiophenol
and an aldehyde in appropriate solvent is isolated,
followed by its oxidation to desired benzothiazole using
FeCl3 [19]. One more reagent, scandium triflate [20]
which acts as an acid catalyst for cyclization and
oxidation step is widely used. Microwave mediated one-
pot synthesis of 2-arylbenzothiazoles from 2-aminothio-
phenol with aromatic aldehydes in an ionic liquid medium
has been studied [21]. Literature survey has revealed the
synthesis of benzoxazole and benzimidazole substituted
on the 4-position of 2H-1-benzopyran-2-ones, but hardly
any report on the synthesis of such 4-substituted
benzothiazole has been cited [22].
Scheme 1
NH2
Ar
CH3COOH
+
N
S
H
O
SH
Ar
1, 6 :- Ar = Ph
2, 7 :- Ar = 4-MePh
3, 8 :- Ar = 4-MeOPh
4, 9 :- Ar = 4-ClPh
5, 10:- Ar = 2-C4H3S
Scheme 2
R1
R1
R2
R3
O
O
R2
R3
O
O
NH2
CH3COOH
+
SH
R4
R4
N
S
O
H
We in this paper have reported our finding on the
synthesis of 2-arylbenzothiazole from 2-aminothiophenol
and aryl aldehydes in high yields. For the synthesis of 2-
arylbenzothiazoles (6-10)[23], the aryl aldehyde (1-5) and
o-aminothiophenol were refluxed for 5 hours in acetic acid
11, 17 :- R1, R3, R4 = H, R2 = Me
12, 18 :- R1, R2, R4 = H, R3 = Me
13, 19 :- R1-R2 = benzo, R3, R4 = H
14, 20 :- R2, R4 = H, R1, R3 = Me
15, 21 :- R1, R4 = H, R2, R3 = Me
16, 22 :- R1, R3, R4 = H, R2 = OAc

1368
R. S. Kenny and U. C. Mashelkar
Vol 43
EXERIMENTAL
2-(2-Thiophenyl)benzo[d]thiazole (10).
The compound was obtained as colourless crystals from
ethanol/water, (Yield = 65%, mp = 97-98 °C, lit.[23] ] mp = 98
°C), ir (KBr): 1450, 1356, 1262, 1146, 850 and 729 cm-1; 1H nmr
(CDCl3): ꢀ = 7.05-7.13 (m, 2H), 7.28 (d, J = 7.8 Hz, 1H), 7.40 (t,
J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.83 (d, J = 7.2 Hz,
1H), 8.05 (d, J = 7.2 Hz, 1H).
1H nmr(400 Mz) spectra were measured on Varian Mercury
400 AS (30° C) instrument using TMS as an internal standard.
The ir spectra were recorded in KBr, on a Shimadzu FTIR-4200
spectrophotometer. Melting points are uncorrected and measured
on a Büchi apparatus. The (un)substituted benzaldehydes
required were purchased from Lancester Chemical company.
Anal. Calcd. for C11H7NS2: C, 60.80; H, 3.25; N, 6.45; S,
29.51. Found: C, 60.98; H, 3.11; N, 6.60; S, 29.72.
General Procedure for One-pot Syntheses of 2-Phenylbenzo[d]-
thiazole (6).
4-(2-Benzothiazolyl)-7-methyl-2H-1-benzopyran-2-one (17).
Benzaldehyde 1 (0.583 g, 5.5 mmol) and o-aminothiophenol
(0.625 g, 5 mmol) were taken in 7 ml of acetic acid and heated
to reflux for 5 h. Reaction mixture was cooled to room
temperature and decomposed over ice water mixture. The solid
that separated was collected by filration, dried and crystallized
from ethanol/water with some decolorizing carbon to obtain
pure crystalline product 6, 0.8 g (yield = 76 %, mp = 113-14 °C,
lit.[23] mp = 114 °C).
For the synthesis of various coumarin substituted benzothia-
zoles 17-22, the coumarin-4-carboxaldehyde 11-16 and o-
aminothiophenol was refluxed in acetic acid as per the procedure
given above. The spectroscopic data for (un)substituted 2-
phenylbenzo[d]thiazole (6-10) and 4-(2-benzothiazolyl)-2H-1-
benzo/naphthopyran-2-ones (17-22) are given below.
The compound was obtained as colourless crystals from
ethanol, (Yield = 76%, mp = 162-63), ms: m/z = 293, 294 (M+,
M+1); ir (KBr): 2923, 1726, 1622, 1481, 1382, 1267, 1188, 1110,
879, 817 and 723 cm-1; 1H nmr (CDCl3): ꢀ = 2.50 (s, 3H), 6.83
(s, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 7.54 (t, J = 7.4
Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 8.22
(d, J = 8.0 Hz, 1H), 8.55 (d, J = 8.0 Hz, 1H).
Anal. Calcd. for C17H11NO2S: C, 69.61; H, 3.78; N, 4.77; S,
10.93. Found: C, 69.49; H, 3.83; N, 4.62; S, 10.85.
4-(2-Benzothiazolyl)-6-methyl-2H-1-benzopyran-2-one (18).
The compound was obtained as colourless crystals from
ethanol, (Yield = 80%, mp = 153-55), ir (KBr): 3064, 2920,
1728, 1564, 1483, 1423, 1315, 1261, 1178, 1107, 952, 858 and
727 cm-1; 1H nmr (CDCl3): ꢀ = 2.45 (s, 3H), 6.85 (s, 1H), 7.34
(d, J = 8.5 Hz, 1H), 7.42 (d, J = 8.5 Hz, 1H), 7.54 (t, J = 7.7 Hz,
1H), 7.62 (t, J = 7.7 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 8.25 (d, J
= 8.2 Hz, 1H), 8.38 (s, 1H).
2-Phenylbenzo[d]thiazole (6).
The compound was obtained as colourless crystals from
ethanol/water, (Yield = 76%, mp = 113-14 °C, lit.[23] mp = 114
°C), ir (KBr): 1478, 1362, 1252, 1125, 883 and 750 cm-1; 1H nmr
(CDCl3): ꢀ = 7.09-7.20 (m, 3H), 7.25-7.33 (m, 3H) 7.58 (t, J =
7.4 Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 8.03 (d, J = 7.5 Hz, 1H).
Anal. Calcd. for C13H9NS: C, 73.90; H, 4.29; N, 6.63; S,
15.18; Found: C, 73.69; H, 4.42; N, 6.51; S, 15.35.
Anal. Calcd. for C17H11NO2S: C, 69.61; H, 3.78; N, 4.77; S,
10.93. Found: C, 69.52; H, 3.68; N, 4.64; S, 10.80.
4-(2-Benzothiazolyl)-2H-1-naphtho[1,2-b]pyran-2-one (19).
The compound was obtained as pale yellow crystals from
ethanol, (Yield = 86%, mp = 149-50), ir (KBr): 3060, 1732,
1631, 1589, 1554, 1481, 1375, 1267, 1151, 1020, 925, 852 and
750 cm-1; 1H nmr (CDCl3): 6.97 (s, 1H), 7.56 (t, J = 8.0 Hz, 1H),
7.63 (t, J = 8.0 Hz, 1H), 7.68 (t, J = 7.7 Hz, 2H), 7.76 (d, J = 8.0
Hz, 1H), 7.91 (dd, 1H), 8.03 (d, J = 8.0 Hz, 1H), 8.26 (d, J = 8.0
Hz, 1H), 8.63 (dd, 2H).
2-(4-Methylphenyl)benzo[d]thiazole (7).
The compound was obtained as pale yellow crystals from
ethanol/water, (Yield = 80%, mp = 82-83 °C, lit.[23] mp = 83 °C), ir
(KBr): 1475, 1365, 1241, 1130, 892 and 745 cm-1; 1H nmr (CDCl3):
ꢀ = 2.42 (s, 3H), 7.16 (d, J = 8.2 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1H),
7.48 (t, J = 7.4 Hz, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.98-8.05 (m, 3H).
Anal. Calcd. for C14H11NS: C, 74.63; H, 4.92; N, 6.22; S,
14.23. Found: C, 74.45; H, 4.79; N, 6.34; S, 14.32.
Anal. Calcd. for C20H11NO2S: C, 72.93; H, 3.37; N, 4.25; S,
9.73. Found: C, 72.82; H, 3.48; N, 4.11; S, 9.60.
4-(2-Benzothiazolyl)-6,8-dimethyl-2H-1-benzopyran-2-one (20).
2-(4-Methoxyphenyl)benzo[d]thiazole (8).
The compound was obtained as colourless crystals from
ethanol, (Yield = 82%, mp = 173-75), ir (KBr): 3068, 2920,
1720, 1602, 1568, 1483, 1458, 1388, 1261, 1172, 1018, 954, 856
The compound was obtained as pale yellow crystals from ethanol,
(Yield = 83%, mp = 201-02°C, lit.[23] mp = 202 °C), ir (KBr):
1476, 1368, 1262, 1142, 889 and 744 cm-1; 1H nmr (CDCl3): ꢀ =
3.86 (s, 3H), 6.98 (d, J = 8.2 Hz, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.44
(t, J = 7.5 Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 8.02-8.09 (m, 3H).
Anal. Calcd. for C14H11NOS: C, 69.68; H, 4.59; N, 5.80; S,
13.29. Found: C, 69.91; H, 4.47; N, 5.65; S, 13.42.
1
and 761cm-1; H nmr (CDCl3): ꢀ = 2.41 (s, 3H), 2.45 (s, 3H),
6.83 (s, 1H), 7.29 (s, 1H), 7.54 (t, J = 7.8 Hz, 1H), 7.61 (t, J =
7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 8.15 (s, 1H), 8.24 (d, J =
7.8 Hz, 1H).
Anal. Calcd. for C18H13NO2S: C, 70.34; H, 4.26; N, 4.56; S,
10.43. Found: C, 70.23; H, 4.12; N, 4.39; S, 10.33.
2-(4-Chlorophenyl)benzo[d]thiazole (9).
4-(2-Benzothiazolyl)-6,7-dimethyl-2H-1-benzopyran-2-one (21).
The compound was obtained as colourless crystals from ethanol,
(Yield = 65%, mp = 115-16°C, lit.[23] mp = 116 °C), ir (KBr): 1470,
1375, 1245, 1133, 876 and 716 cm-1;1H nmr (CDCl3): ꢀ = 7.10 (d, J =
8.3 Hz, 2H), 7.32 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.5 Hz, 1H), 7.81 (d,
J = 7.2 Hz, 1H), 7.95 (d, J = 8.3 Hz, 2H), 8.10 (d, J = 7.2 Hz, 1H).
Anal. Calcd. for C13H8ClNS: C, 63.54; H, 3.28; Cl, 14.43; N, 5.70;
S, 13.05. Found: C, 63.37; H, 3.15; Cl, 14.60; N, 5.49; S, 13.14.
The compound was obtained as colourless crystals from
ethanol, (Yield = 77%, mp = 194-96), ir (KBr): 3060, 1724, 1622,
1587, 1485, 1454, 1369, 1271, 1222, 1161, 1085, 850 and 754
cm-1; 1H nmr (CDCl3): ꢀ = 2.31 (s, 3H), 2.38 (s, 3H), 6.79 (s, 1H),
7.20 (s, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 8.00
(d, J = 7.8 Hz, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.33 (s, 1H).

Sep-Oct 2006
Synthesis of 2-Aryl and Coumarin Substituted Benzothiazole Derivatives
1369
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The compound was obtained as colourless crystals from
ethanol, (Yield = 70%, mp = 179-80), ir (KBr): 3070, 1735,
1616, 1558, 1481, 1379, 1315, 1265, 1202, 1010, 854 and 759
cm-1; 1H nmr (CDCl3): ꢀ = 2.38 (s, 3H), 6.87 (s, 1H), 7.15 (d, J =
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9.50. Found: C, 64.15; H, 3.20; N, 4.01; S, 9.67.
Acknowledgements.
The authors thank Dr. Deepak Manohar Rane, Mumbai for
technical assistance.
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