Synthesis of N-(3-alkyl-4-phenyl-3H-thiazol-2-ylidene)benzamide derivatives by reaction of phenacyl bromide and aroyl isothiocyanates in the presence of primary amines

Article abstract of DOI:10.3184/174751913X13667104816225

A three-component and one-pot reaction between phenacyl bromide and aroyl isothiocyanates in the presence of primary amines gave N-(3-alkyl-4-phenyl-3H- thiazol-2-ylidene)benzamide derivatives in good yields.

Full text of DOI:10.3184/174751913X13667104816225

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 331
JUNE, 331–332
Synthesis of N-(3-alkyl-4-phenyl-3H-thiazol-2-ylidene)benzamide
derivatives by reaction of phenacyl bromide and aroyl isothiocyanates
in the presence of primary amines
Alireza Hassanabadi*
Department of Chemistry, Zahedan Branch, Islamic Azad University, PO Box 98135-978, Zahedan, Iran
A three-component and one-pot reaction between phenacyl bromide and aroyl isothiocyanates in the presence of
primary amines gave N-(3-alkyl-4-phenyl-3H-thiazol-2-ylidene)benzamide derivatives in good yields.
Keywords: phenacyl bromide, aroyl isothiocyanates, N-(3-alkyl-4-phenyl-3H-thiazol-2-ylidene)benzamides, primary amines
A central objective in synthetic organic chemistry has been to
develop efficient syntheses of biologically active compounds
with potential application in the pharmaceutical or agrochemi-
cal industries. Thiazoles occupy a prominent position among
heterocycles. In nature, the thiazolium ring is the chemically
active centre in the coenzyme derived from vitamin B1 (thia-
min). A large number of thiazoles obtained from microbial and
marine origins exhibit important biological effects such as
antitumor, antifungal, antibiotic, and antiviral activities.1 Syn-
thetic thiazoles have also been shown to exhibit a wide variety
of biological activities,2 while others have found application as
liquid crystals3 and cosmetic sunscreens.4 The classical method
for the synthesis of thiazoles is the Hantzsch process, in which
a α-haloketone is condensed with a thioamide.5 Other methods
have been reported for the synthesis of thiazoles.6–12 As a
part of studies on the development of new routes in organic
synthesis,13–19 I now report an efficient one-pot synthesis of N-
(3-alkyl-4-phenyl-3H-thiazol-2-ylidene)benzamidederivatives
employing readily available starting materials.
these compounds displayed molecular ion peaks at appropriate
m/z values. The H NMR spectrum of 4a in CDCl3 showed
1
two singlets for the methylene (δ = 5.43) and methine (δ =
6.47) protons. Aromatic protons resonate between 7.06 and
7.42 ppm as multiplets. The 13C NMR spectrum of 4a showed
17 signals in agreement with the proposed structure. The IR
spectrum of compound 4a also supported the suggested struc-
ture. A tentative mechanism for this transformation is proposed
in Scheme 2.
It is reasonable to assume that unsymmetrical thiourea 5
results from the initial addition of the primary amines 3 to
aroyl isothiocyanates 1. Thiourea 5 is alkylated by phenacyl
bromide 2 to intermediate 6, which undergoes cyclisation to
generate 7. Dehydration of intermediate 7 affords product 4.
Experimental
All melting points are uncorrected. Elemental analyses were per-
formed using a Heraeus CHN–O–rapid analyser. Mass spectra were
recorded on a Finnigan-MAT 8430 mass spectrometer operating at an
ionisation potential of 70 eV. IR spectra were recorded on a Shimadzu
1
IR-470 spectrometer. H and 13C spectra were recorded on Bruker
Results and discussion
DRX-500 Avance spectrometer in CDCl3 using TMS as the internal
standard. Chemicals were purchased from Fluka (Buchs, Switzerland)
and were used without further purification.
Reaction between aroyl isothiocyanates 1 and phenacyl
bromide 2 in the presence of primary amines 3 gave N-(3-
alkyl-4-phenyl-3H-thiazol-2-ylidene)benzamide derivatives 4
in good yields (Scheme 1).
General procedure
Phenacyl bromide (1 mmol) was added dropwise to a magnetically
stirred solution of primary amines (1 mmol) and aroyl isothiocyanates
(1 mmol) in 15 mL acetonitrile at room temperature. The reaction
The structures of compounds 4a–f were confirmed by IR, 1H
NMR, 13C NMR and mass spectral data. The mass spectra of
Scheme 1 Three-component reaction between aroyl isothiocyanates, primary amines and phenacyl bromide.
* Correspondent. E-mail: ar_hasanabadi@yahoo.com

332 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 2 Suggested mechanism for formation of compound 4.
mixture was then stirred for 24 h. The solvent was removed under
reduced pressure and the residue was purified by silica gel column
chromatography using hexane-ethyl acetate as eluent. The solvent was
removed under reduced pressure to afford the product.
N-(3-Benzyl-4-phenyl-3H-thiazol-2-ylidene)benzamide (4a): Cream
powder, m.p. 145–149 °C, IR (KBr) (νmax cm−1): 1595, 1477, 1353.
Anal. Calcd for C23H18N2OS: C, 74.57; H, 4.90; N, 7.56. Found: C,
74.65; H, 4.83; N, 7.40%. MS (m/z, %): 370 (5). 1H NMR (500 MHz,
CDCl3): δ 5.43 (2H, s, CH2), 6.47 (1H, s, CH), 7.06–7.42 (15H, m,
15CH aromatic) ppm. 13C NMR (125.8 MHz, CDCl3): δ 47.85 (CH2),
106.71 (CH), 123.83 (C), 127.56, 128.32, 128.45, 129.13, 129.78,
130.15, 131.32, 131.87, 132.46, 133.38, 135.25 and 135.32 (aromatic
moiety), 170.28 (C=N), 177.83 (C=O) ppm.
N-(3-Butyl-4-phenyl-3H-thiazol-2-ylidene)4-nitrobenzamide (4f):
Cream powder, m.p. 137–140 °C, IR (KBr) (νmax cm−1): 1600, 1484,
1357. Anal. Calcd for C20H19N3O3S: C, 62.98; H, 5.02; N, 11.02.
Found: C, 63.10; H, 5.15; N, 11.14%. MS (m/z, %): 381 (11). 1H NMR
(500 MHz, CDCl3): δ 0.92 (3H, t, 3JHH = 7.4 Hz, CH3), 1.27–134 (2H,
3
m, CH2), 1.72–176 (2H, m, CH2), 4.28 (2H, t, JHH = 7.4 Hz, CH2),
6.67 (1H, s, CH), 7.56 (2H, d, 3JHH = 8.5 Hz, 2CH), 8.25 (2H, d, 3JHH
= 8.5 Hz, 2CH), 7.07–7.48 (5H, m, 5CH aromatic) ppm. 13C NMR
(125.8 MHz, CDCl3): δ 15.13 (CH3), 20.34 (CH2), 30.85 (CH2), 47.63
(CH2), 108.53 (CH), 124.57 (C), 128.56, 129.88, 130.22, 131.58,
131.85, 132.43, 135.28 and 142.36 (aromatic moiety), 170.39 (C=N),
174.63 (C=O) ppm.
N-(3-Benzyl-4-phenyl-3H-thiazol-2-ylidene)4-chlorobenzamide
(4b): Cream powder, m.p. 153–156 °C, IR (KBr) (νmax cm−1): 1598,
1472, 1350. Anal. Calcd for C23H17ClN2OS: C, 68.22; H, 4.23; N,
6.92. Found: C, 68.10; H, 4.30; N, 6.74%. MS (m/z, %): 404 (3). 1H
NMR (500 MHz, CDCl3): δ 5.56 (2H, s, CH2), 6.54 (1H, s, CH), 7.11
(2H, d, 3JHH = 7.8 Hz, 2CH), 7.48 (2H, d, 3JHH = 7.8 Hz, 2CH), 7.05–
7.44 (10H, m, 10CH aromatic) ppm. 13C NMR (125.8 MHz, CDCl3):
δ 48.06 (CH2), 108.55 (CH), 123.94 (C), 127.48, 128.22, 128.57,
129.28, 129.81, 130.09, 131.57, 131.82, 132.35, 133.32, 135.17 and
142.23 (aromatic moiety), 170.06 (C=N), 178.18 (C=O) ppm.
N-(3-Benzyl-4-phenyl-3H-thiazol-2-ylidene)4-nitrobenzamide (4c):
Cream powder, m.p. 123–126 °C, IR (KBr) (νmax cm−1): 1599, 1483,
1352. Anal. Calcd for C23H17N3O3S: C, 66.49; H, 4.12; N, 10.11.
Found: C, 66.40; H, 4.03; N, 10.23%. MS (m/z, %): 415 (9). 1H NMR
(500 MHz, CDCl3): δ 5.58 (2H, s, CH2), 6.65 (1H, s, CH), 7.54 (2H,
d, 3JHH = 8.5 Hz, 2CH), 8.21 (2H, d, 3JHH = 8.5 Hz, 2CH), 7.07–7.46
(10H, m, 10CH aromatic) ppm. 13C NMR (125.8 MHz, CDCl3):
δ 47.98 (CH2), 107.81 (CH), 124.07 (C), 127.48, 128.22, 128.57,
129.28, 129.81, 130.09, 131.57, 131.82, 132.35, 133.32, 135.17 and
142.23 (aromatic moiety), 170.25 (C=N), 178.26 (C=O) ppm.
N-(3-Butyl-4-phenyl-3H-thiazol-2-ylidene)benzamide (4d): Cream
powder, m.p. 132–135 °C, IR (KBr) (νmax cm−1): 1601, 1478, 1351.
Anal. Calcd for C20H20N2OS: C, 71.40; H, 5.99; N, 8.33. Found: C,
71.50; H, 5.85; N, 8.40%. MS (m/z, %): 336 (7). 1H NMR (500 MHz,
CDCl3): δ 0.82 (3H, t, 3JHH = 7.4 Hz, CH3), 1.23–126 (2H, m, CH2),
1.65–168 (2H, m, CH2), 4.20 (2H, t, 3JHH = 7.4 Hz, CH2), 6.52 (1H, s,
CH), 7.06–7.45 (10H, m, 10CH aromatic) ppm. 13C NMR (125.8
MHz, CDCl3): δ 14.11 (CH3), 20.16 (CH2), 30.54 (CH2), 47.52 (CH2),
107.28 (CH), 124.32 (C), 128.45, 129.72, 130.17, 131.30, 131.74,
132.42, 135.23 and 135.38 (aromatic moiety), 168.35 (C=N), 174.58
(C=O) ppm.
I gratefully acknowledge financial support from the Research
Council of Islamic Azad University of Zahedan of Iran.
Received 1 February 2013; accepted 4 March 2013
Paper 1301764 doi: 10.3184/174751913X13667104816225
Published online: 12 June 2013
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