A splendid method for synthesis of 2-(benzothiazole)-3-phenyl acrylonitrile derivatives catalysed by piperdine

Article abstract of DOI:10.4314/bcse.v26i3.17

A simple and efficient method is developed for the synthesis of 2-(benzothiazol-2-yl)-3- (substituted phenyl)acrylonitrile from 2-(benzothiazole-2-yl)-3-oxopentanedinitrile and aromatic aldehydes in the presence of a catalytic amount of piperdine into ethanol at reflux. Advantage of this procedure is relatively good yields (81-86%) with short reaction times (1.5-3 h), under moderate reaction conditions and simple workup procedure, plus easy preparation and handling of the catalyst.

Full text of DOI:10.4314/bcse.v26i3.17

Bull. Chem. Soc. Ethiop. 2012, 26(3), 467-471.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v26i3.17
ISSN 1011-3924
 2012 Chemical Society of Ethiopia
SHORT COMMUNICATION
A SPLENDID METHOD FOR SYNTHESIS OF 2-(BENZOTHIAZOLE)-3-PHENYL
ACRYLONITRILE DERIVATIVES CATALYSED BY PIPERDINE
Suresh Maddila and Sreekanth B. Jonnalagadda*
School of Chemistry and Physics, University of KwaZulu-Natal, West Ville Campus, Chiltern
Hills, Private Bag 54001, Durban-4000, South Africa
(Received September 16, 2011; revised June 5, 2012)
ABSTRACT. A simple and efficient method is developed for the synthesis of 2-(benzothiazol-2-yl)-3-
(substituted phenyl)acrylonitrile from 2-(benzothiazole-2-yl)-3-oxopentanedinitrile and aromatic aldehydes in the
presence of a catalytic amount of piperdine into ethanol at reflux. Advantage of this procedure is relatively good
yields (81-86%) with short reaction times (1.5-3 h), under moderate reaction conditions and simple workup
procedure, plus easy preparation and handling of the catalyst.
KEYWORDS: 2-(Benzothiazole)-3-phenylacrylonitrile, One-pot synthesis, 2-(Benzo-thiazole-2-yl)-3-
oxopentanedinitrile, Aromatic aldehydes, Piperdine
INTRODUCTION
Benzothiazole, a heterocyclic aromatic moiety with electron rich sulfur and nitrogen atoms,
which is used as a pharmacological agent due its well known immunomodulatory,
immunosuppressive, antitumor, and antiviral properties [1]. The benzothiazole skeleton
constitutes an important template for a wide variety of biologically active compounds. This
molecule and its derivatives are known to be powerful antitumour agents [2, 3], calmodulin
antagonists [4], neurotransmission blocker [5], and neuroprotective agent [6]. Benzothiazole
type compounds attracted considerable attention in anticancer drug development [7, 8].
Modified benzothiazole derivatives with additional functional groups can likely improve the
biological potential of these compounds. 2-Aryl substituted benzothiazoles are studied as
antimicrobial [9], antifungal agents [10] as well as imaging agents for β-amyloid [11],
inhibition of enzymes such as cyclooxygenase [12], acetylcholine esterase [13] and plant growth
regulation [14].
In view of importance of benzothiazole and their derivatives, many methods have been
reported for the synthesis of benzothiazole, such as palladium-catalyzed Suzuki biaryl coupling
of 2-bromobenzothiazole with arylboronic acids [15], coupling of benzothiazoles with aryl
bromides [16] and the reaction between thiophenols and aromatic nitriles [17]. In the recent
past, the reactions catalyzed by silica gel [18], iodine [19] and Backer’s yeast [20] have also
been reported for the synthesis of benzothiazole derivatives. However, many of these methods
are associated with disadvantages such as long reaction time, drastic reaction conditions,
expensive reagents, low yields and tedious work-up procedures. The disadvantage is that the
catalyst is destroyed during the work-up procedure and cannot be recovered or reused [17-19].
Therefore, it is paramount to find a simple, inexpensive procedure for the synthesis of
benzothiazoles, with provision of recoverable and reusable catalyst. Earlier we have reported a
simple and one step method for synthesis of wide range of pyrimidine derivatives [21].
In this article we communicate the prospect to synthesize 2-(benzothiazol-2-yl)-3-
(substituted phenyl)acrylonitrile derivatives by the reaction 2-(benzothiazole-2-yl)-3-
oxopentanedinitrile with aromatic aldehydes, using piperdine as a catalyst (Scheme 1). Here, an
__________
*Corresponding author. E-mail: jonnalagaddas@ukzn.ac.za

468
Suresh Maddila and Sreekanth B. Jonnalagadda
efficient and simple method for the synthesis of target compounds is described. To the best of
our knowledge, using piperdine as a catalyst, the synthesis of benzothiazoles has not been
reported yet.
EXPERIMENTAL
All reagents were synthesis grade and were used without further purification. Melting points
were determined on a Fisher–Johns melting point apparatus were uncorrected. Crude products
were purified by column chromatography on silica gel of 60–120 mesh. IR spectra were
obtained on a Perkin Elmer BX serried FT-IR 5000 spectrometer using KBr pellet. The NMR
1
spectra were recorded on a Bruker 400 MHz spectrometer for H NMR. The chemical shifts
were reported as ppm down field using TMS as an internal standard. LCMS Mass spectra were
recorded on a MASPEC low resolution mass spectrometer operating at 70 eV.
General
procedure
for
the
preparation
of 2-(benzothiazol-2-yl)-3-(substituted
phenyl)acrylonitrile. To a solution of 2-(benzothiazole-2-yl)-3-oxopentanedinitrile 1 (1 mmol)
and aromatic aldehydes 2 (1 mmol) in ethanol (10 mL) was added a few drops of catalytic
piperdine and the reaction mixture was refluxed for 2-3 hours. After completion of the reaction
as indicated by TLC, The precipitate was filtered and washed with 50% EtOH (2×10 mL). The
crude product was purified by recrystallization from ethonal (solid products) or by
chromatography using silica gel and mixtures of hexane/ethyl acetate of increasing polarity.
1
2-(Benzothiazol-2-yl)-3-phenylacrylonitrile (3a). M.p. 154–155 °C; H NMR: δ 5.71 (s, 1H,
CH), 6.34 (s, 1H, ═CH), 7.28–8.20 (m, 9H, Ar–H); IR (KBr, cm–1): 2231 (CN), 1720 (C═O),
1625 (C=N), 1586 (C═C), 762 (C-S); MS (70 eV, EI): m/z (%): 263 (M+1); anal. calcd for
C16H10N2S: C, 73.26; H, 3.84; N, 10.68. Found: C, 73.33; H, 3.78; N, 10.59.
1
2-(Benzothiazol-2-yl)-3-(4-methylphenyl)acrylonitrile (3b). M.p. 159-161 °C; H NMR: δ 2.48
(s, 3H, CH3), 5.68 (s, 1H, CH), 6.31 (s, 1H, ═CH), 7.20–8.15 (m, 8H, Ar–H); IR (KBr, cm–1):
2236 (CN), 1722 (C═O), 1628 (C=N), 1590 (C═C), 769 (C-S); MS (70 eV, EI): m/z (%): 276
(M+); anal. calcd for C17H12N2S: C, 73.88; H, 4.38; N, 10.14. Found: C, 73.81; H, 4.43; N,
10.19.
2-(Benzothiazol-2-yl)-3-(4-ethylphenyl)acrylonitrile (3c). M.p. 188-190 °C; 1H NMR: δ 1.18 (t,
3H, Ar–CH2–CH3), 2.52 (q, 2H, –CH2), 5.72 (s, 1H, CH), 6.35 (s, 1H, ═CH), 6.90–8.10 (m, 8H,
Ar–H); IR (KBr, cm–1): 2233 (CN), 1718 (C═O), 1623 (C=N), 1585 (C═C), 760 (C-S); MS (70
eV, EI): m/z (%): 290 (M+); anal. calcd for C18H14N2S: C, 74.45; H, 4.86; N, 9.65. Found: C,
74.49; H, 4.92; N, 9.72.
1
2-(Benzothiazol-2-yl)-3-(4-chlorophenyl)acrylonitrile (3d). M.p. 235–237 °C; H NMR: δ 5.75
(s, 1H, CH), 6.38 (s, 1H, ═CH), 7.45–8.12 (m, 8H, Ar-H); IR (KBr, cm–1): 2212 (CN), 1694
(C═O), 1610 (C=N), 1538 (C═C), 776 (C–Cl), 760 (C-S); MS (70 eV, EI): m/z (%): 297
(M+1); anal. calcd for C16H9ClN2S: C, 64.75; H, 3.06; N, 9.44. Found: C, 64.81; H, 3.12; N,
9.37.
1
2-(Benzothiazol-2-yl)-3-(4-bromophenyl)acrylonitrile (3e). M.p. 210–211 °C; H NMR: δ 5.78
(s, 1H, CH), 6.43 (s, 1H, ═CH), 7.58–8.13 (m, 8H, Ar–H); IR (KBr, cm–1): 2219 (CN), 1714
(C═O), 1616 (C=N), 1538 (C═C), 774 (C-S); MS (70 eV, EI): m/z (%): 341 (M+2); anal. calcd
for C16H9 BrN2S: C, 56.32; H, 2.66; N, 8.21. Found: C, 56.39; H, 2.71; N, 8.29.
2-(Benzothiazol-2-yl)-3-(4-methoxyphenyl)acrylonitrile (3f). M.p. 194–196 °C; 1H NMR: δ 3.73
(s, 3H, OCH3), 5.74 (s, 1H, CH), 6.40 (s, 1H, ═CH), 6.90–8.20 (m, 8H, Ar–H); IR (KBr, cm–1):
Bull. Chem. Soc. Ethiop. 2012, 26(3)

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469
2225 (CN), 1738 (C═O), 1618 (C=N), 1532 (C═C), 1221 (C–O–C), 761 (C-S); MS (70 eV,
EI): m/z (%): 293 (M+1); anal. calcd for C17H22N2OS: C, 69.84; H, 4.14; N, 9.58. Found: C,
69.77; H, 4.23; N, 9.42.
2-(Benzothiazol-2-yl)-3-(4-(dimethylamino)phenyl)acrylonitrile (3g). M.p. 201–203 °C; 1H
NMR: δ 3.01 (s, 6H, N(CH3)2), 5.73 (s, 1H, CH), 6.38 (s, 1H, ═CH), 6.68–8.16 (m, 8H, Ar–H);
IR (KBr, cm–1): 2219 (CN), 1679 (C═O), 1623 (C=N), 1528 (C═C), 1340 (N(CH3)2), 764 (C-
S); MS (70 eV, EI): m/z (%): 306 (M+1); anal. calcd for C18H15N3S: C, 70.78; H, 4.95; N, 13.76.
Found: C, 70.91; H, 5.03; N, 13.87.
1
2-(Benzothiazol-2-yl)-3-(2,4-dichlorophenyl)acrylonitrile (3h). Mp 149–151 °C; H NMR: δ
5.78 (s, 1H, CH), 6.51 (s, 1H, ═CH), 7.28–8.09 (m, 8H, Ar–H); IR (KBr, cm–1): 2218 (CN),
1682 (C═O), 1637 (C=N), 1545 (C═C), 748 (C-S); MS (70 eV, EI): m/z (%): 331 (M+2); anal.
calcd for C16H8Cl2N2OS: C, 58.02; H, 2.43; N, 8.46. Found: C, 58.19; H, 2.39; N, 8.53.
1
2-(Benzothiazol-2-yl)-3-(2,4,6-trimethylphenyl)acrylonitrile (3i). M.p. 157–159 °C; H NMR: δ
2.36 (s, 3H, Ar–CH3), 2.52 (s, 6H, Ar–CH3), 5.70 (s, 1H, CH), 6.36 (s, 1H, ═CH), 6.90–8.24
(m, 6H, Ar–H); IR (KBr, cm–1): 2208 (CN), 1650 (C═O), 1606 (C=N), 1548 (C═C), 758 (C-S);
MS (70 eV, EI): m/z (%): 304 (M+); anal. calcd for C19H16N2S: C, 74.97; H, 5.30; N, 9.20.
Found: C, 75.07; H, 5.38; N, 9.14.
1
2-(Benzothiazol-2-yl)-3-(4-isopropylphenyl)acrylonitrile (3j). M.p. 181–183 °C; H NMR: δ
1.16 (d, 6H, CH(CH3)2), 2.93 (q, 1H, CH), 5.72 (s, 1H, CH), 6.41 (s, 1H, ═CH), 7.18–8.15 (m,
8H, Ar–H); IR (KBr, cm–1): 2200 (CN), 1690 (C═O), 1600 (C=N), 1533 (C═C), 762 (C-S); MS
(70 eV, EI): m/z (%): 304 (M+); anal. calcd for C19H16N2S: C, 74.97; H, 5.30; N, 9.20. Found: C,
75.07; H, 5.38; N, 9.14.
1
2-(Benzothiazol-2-yl)-3-(4-tert-butylphenyl)acrylonitrile (3k). M.p. 171–172 °C; H NMR: δ
1.28 (s, 9H, 3CH3), 5.70 (s, 1H, CH), 6.40 (s, 1H, ═CH), 7.20–8.22 (m, 8H, Ar–H); IR (KBr,
cm–1): 2237 (CN), 1691 (C═O), 1618 (C=N), 1539 (C═C), 763 (C-S); MS (70 eV, EI): m/z (%):
319 (M+1); anal. calcd for C20H18N2S: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.53; H, 5.79; N,
8.94.
RESULTS AND DISCUSSION
CHO
N
N
CN
CN
CN
CH
Piperdine
S
S
+
EtOH, reflux
O
R
2
1
R
3
Scheme 1. The synthetic route of 2-(benzothiazole)-3-phenylacrylonitrile.
The synthesis of 2-(benzothiazol-2-yl)-3-(substituted phenyl)acrylonitrile derivatives (3a-k) was
achieved through the versatile and efficient synthetic route outlined in Scheme 1. All the
synthesised compounds were obtained in good to high yields. Products were purified and
characterized by various spectroscopic techniques. The IR spectra of compounds (3a-k) showed
characteristic absorption bands at 2237–2200 cm–1, 1738–1682 cm–1, 1637–1600, 1590–1528
and 774–748 cm–1 corresponding to the C≡Nstr, C═Ostr, C═Nstr, C═Cstr and C–Sstr functions in
1
the structures. Similarly the H NMR spectra showed peaks due to in the range of δ 5.68–5.78
Bull. Chem. Soc. Ethiop. 2012, 26(3)

470
Suresh Maddila and Sreekanth B. Jonnalagadda
for –CH, δ 6.31–6.51 for ═CH, and δ 6.68–8.24 for Ar–H. The mass spectrum of all the
compounds showed molecular ion peak at M+, M+H, at M+2H corresponding to its molecular
1
formula, which confirmed its chemical structure. The IR, H NMR, LCMS mass spectra and
elemental analysis showed the structure of various novel 2-(benzothiazol-2-yl)-3-(substituted
phenyl)acrylonitrile derivatives (3a–k).
CONCLUSIONS
In conclusion, we have developed a novel and efficient method for the synthesis of 2-
(benzothiazole)-3-phenylacrylonitrile by treatment of 2-(benzothiazole-2-yl)-3-oxopentane-
dinitrile with aromatic aldehydes using piperdine as an effective catalyst. The noteworthy
advantages of this procedure are good yields (81-86%), short reaction times (1.5-3 h), moderate
reaction conditions, simple workup procedure and finally easy preparation and handling of the
catalyst. This methodology may find wide applications in organic synthesis for preparation of
the 2-(benzothiazole)-3-phenylacrylonitrile.
ACKNOWLEDGEMENTS
The authors are thankful to the University of KwaZulu-Natal, Durban, South Africa for the
facilities, financial support and encouragement.
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