Synthesis and crystal structure of some novel 2-aroylimino-3-aryl-4-phenyl- 1,3-thiazolines

Article abstract of DOI:10.1080/00397910802026212

An efficient synthesis of some novel 2-aroylimino-3-aryl-4-phenyl-1,3- thiazolines was carried out by base-catalyzed cyclization of 1-aroyl-3-arylthioureas with acetophenone in the presence of bromine. The structures were confirmed by spectroscopic data,

Full text of DOI:10.1080/00397910802026212

This article was downloaded by: [Fordham University]
On: 02 December 2012, At: 06:18
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
Synthesis and Crystal Structure
of Some Novel 2-Aroylimino-3-
aryl-4-phenyl-1,3-thiazolines
Aamer Saeed a , Sabah Zaman a & Michael Bolte b
a Department of Chemistry, Quaid-I-Azam University,
Islamabad, Pakistan
b Institute for Inorganic Chemistry, J. W. Goethe-
Universitat Frankfurt, Frankfurt/Main, Germany
Version of record first published: 18 Aug 2008.
To cite this article: Aamer Saeed, Sabah Zaman & Michael Bolte (2008): Synthesis
and Crystal Structure of Some Novel 2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:13, 2185-2199
To link to this article: http://dx.doi.org/10.1080/00397910802026212
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, 38: 2185–2199, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802026212
Synthesis and Crystal Structure of Some Novel
2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
Aamer Saeed,1 Sabah Zaman1 and Michael Bolte2
1Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan
2Institute for Inorganic Chemistry, J. W. Goethe-Universitat Frankfurt,
Frankfurt=Main, Germany.
Abstract: An efficient synthesis of some novel 2-aroylimino-3-aryl-4-
phenyl-1,3-thiazolines was carried out by base-catalyzed cyclization of 1-aroyl-
3-arylthioureas with acetophenone in the presence of bromine. The structures
were confirmed by spectroscopic data, elemental analyses, and in one case (2t)
by single-crystal X-ray diffraction data.
Keywords: 1-Aroyl-3-arylthioureas; 2-imino-1,3-thiazolines
INTRODUCTION
The majority of pharmaceuticals and biologically active agrochemicals
are heterocyclic in nature. 1,3-Thiazolines are naturally occurring aro-
matic heterocycles with a wide range of pharmacological and synthetic
applications. 2-Imino derivatives of 1,3-thiazolines possess an additional
point of structural diversity in a thiazoline-based pharmacophore (Fig. 1).
Thus, thiazoline derivatives show potent bioactivities ranging from
antitubercular[1] to anti-HIV activities.[2] Iminothiazolines containing a
pyrazine ring show significant antibacterial and antimicrobial activity[3]
and are potent, selective, and less toxic antimicrobial agents.[4]
2-Thiazolylimino-5-arylidene-4-thiazolidinones show marked antibacter-
ial and antimicrobial activity against several Gram-positive and
Gram-negative bacteria, yeasts, and mold;[5] derivatives of rhodanine
show antibacterial, anti-inflammatory, and antiviral activities;[6] and
Address correspondence to Aamer Saeed, Department of Chemistry, Quaid-I-
Azam University 45320, Islamabad, Pakistan. E-mail: aamersaeed@yahoo.com
2185

2186
A. Saeed, S. Zaman, and M. Bolte
Figure 1. 2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines.
bis-thiazoline derivatives show marked anticancer activity against human
cell lines.[7] A 2-imino-1,3-thiazoline derivative KHG22394 significantly
inhibits melanin production in a dose-dependant manner and thus acts
as a skin whitening agent.[8] 4-Phenyl-2-hydrazonothiazolines exhibit
potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity
comparable to that of vitamin E.[9] 3-Alkyl-3H-thiazoline derivative PS-
028 acts as potent and selective GPllb=llla antagonist and has potential as
a versatile template for other b-turn mimics.[10] 2-Acylimino-1,3-thiazo-
lines have been reported to show bleaching herbicidal activity against
upland weeds and selectivity against crops.[11] 2-Phenylimino-1,3-thiaz-
oline-4-acetanilides have shown significant antifungal activity against rice
blast fungus Pyricularia oryzae, and thus can be used as fungicides.[12]
The biological activity of 1,3-thiazolines can be enhanced by coordi-
nation with metallic ions to form complexes that are more active and less
toxic than Cisplatin.[13] Polyacrilonitrile-2-amino-2-thiazoline resin is
useful in separation, preconcentration determination, recovery, and puri-
fication of precious metals.[14] N,N0-Diaryl-2-iminothazoline derivatives
show atropisomerism. The optically pure isomers obtained by resolution
are used as new nonbiaryl ligands for enantioselective metal catalysis.[15,16]
Key synthetic strategies for 2-iminothiazolines consist of the reac-
tion of 1,2-diaza-1,3-butadienes with rhodanine and similar com-
pounds through a sequential conjugate addition[7,17] and treatment of
3-aryl-4-formylsydnone thiosemicarbazones with ethyl 2-chloroaceto-
acetate or phenacyl bromide in ethanol solution containing sodium
acetate and an acetic acid buffer system.[9,18] A general synthetic
route to 2-(N-acylimino)-5-alkyl-3-aryl-1,3-thiazoline consists of action

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2187
of N-propargylanilines with acyl isothiocyanates to yield 2-(N-acylimino)-
1,3-thiazolidine followed by treatment with a base to afford 5-alkyl-1,3-
thiazoline.[11] Treatment of a-bromomethyl ketimines with potassium
thiocyanate in methanol also gives corresponding 2-iminothiazoline deri-
vatives,[19] alkylation of 2-aminothiazoles obtained from condensation of
a-haloketones with thiourea,[20] and synthesis of 2-imino-1,3-thiazolines
from 1-arylmethyl-2-(bromomethyl)aziridines via ring transformation
of 1-arylmethyl-2 (thiocyanomethyl) aziridines.[21]
Taking into consideration the aforementioned biological and syn-
thetic significance of 2-imino-1,3-thiazolines, we designed the synthesis
of some new 2-aroylimino-3-aryl-4-phenyl-1,3-thiazolines (2a–t) starting
from readily available 1-aroyl-3-arylthioureas (1a–t). We envisioned three
points of diversity in our designed target molecule (viz, a substituted N-
aroyl group at C-2, a substituted N-aryl group at C-3, and substitution at
C-4 phenyl) for systematic evaluation of biological activities and estab-
lishment of structure–activity relationship (SAR) in depth. Herein, we
report a facile synthesis of 1,3-thiazolines by cyclization of corresponding
1-toyl-3-aryl thioureas with acetophenone in the presence of bromine and
triethyl amine in high overall yields. All the new compounds 2a–t were
characterized by physical data, elemental analyses, and spectroscopic
data (1H and 13C NMR, gas chromatograph-mass spectrometer (GC-
MS), and Fourier transform infrared (FTIR)), and in the case of 2t by
single-crystal X-ray diffraction data.
RESULTS AND DISCUSSION
Chemistry
The reaction sequence leading to the formation of the desired heterocycle
is outlined in Scheme 1. The requisite 1-(substituted methylbenzoyl)-3-aryl
thioureas were prepared according to the published procedure[22] involving
treatment of methylbenzoyl chlorides with potassium thiocyanate in acet-
one followed by reaction with suitably substituted anilines. The thioureas
were characterized by typical IR absorptions at 3351, 3200 cmꢀ1 for free
and associated NH, at 1667 for carbonyl, and at 1230–1250 for thiocarbo-
nyl groups. The characteristic broad singlets at ca. d 9.0 and 12 for HN(1)
and HN(3) and peaks at 170, 179 for carbonyl and thiocarbonyl were
observed in the 1H and 13CNMR spectra respectively.
The base-catalyzed cyclization of 1-aroyl-3-arylthioureas with aceto-
phenone was achieved in the presence of bromine. Thus triethyl amine
was added to a solution of 1-aroyl-3-arylthioureas in dry dichloro-
methane followed by the treatment with a mixture of acetophenone

2188
A. Saeed, S. Zaman, and M. Bolte
Scheme 1. Synthetic route to 2-aroylimino-3-aryl-4-phenyl-1,3-thiazolines.
and bromine under an inert atmosphere to afford 2-aroylimino-3-aryl-4-
phenyl-1,3-thiazolines.
The physical data show that the melting points of iminothiazolines
are higher as compared to the corresponding thioureas, which may be
attributed to an increase in molecular weight and polarity, which is also
responsible for the decrease in their Rf values. These cyclization reactions
are extremely susceptible to moisture, and yield is greatly affected by the
presence of slight moisture in the solvent or atmosphere. In the IR spec-
tral data of 2-aroylimino-3-aryl-4-phenyl-1,3-thiazolines, the absence of
N-H peaks at 3200–3400 cmꢀ1 and slight shifting of C O absorptions
=
to 1630–1675 cmꢀ1 indicated the formation of a thiazoline ring from
thiourea moiety. Appearance of strong peaks at 1450–1495 cmꢀ1
=
depicted the presence of characteristic C N of iminothiazolines; other
,
peaks include (C-S) at 1260–1295 cmꢀ1, (CꢀH) at 1403–1421 cmꢀ1
(C C-H) at 2924–2953 cmꢀ1, and (CH3) at 2832–2856 cmꢀ1 in addition
=
to aromatic (C C) peaks at 1601–1618 cmꢀ1. The structures were further
=
1
confirmed by H NMR spectra, which shows the disappearance of N-H
peaks and appearance of a 1H characteristic singlet at d 6.5–6.9 due to
C C-H of the thiazoline ring. In 13C NMR, iminothiazoline ring olefinic
=
carbon gave a characteristic peak at d 107.2–107.9. In a typical case,

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2189
Scheme 2. Mechanistic pathway for conversion of thioureas into 2-iminothiazolines.
2-(2-methylbenzoyl)imino-3-(2-methoxyphenyl)-4-phenyl-1,3-thiazoline
(2a), the singlet appeared at d 6.98 and the doublet at 7.92 with J value of
8.4 Hz assigned to ortho protons of the aroyl ring, wheras H-3 appeared
as a triplet at 7.41 with a J-value of 8.4. The multiplet for H-2 and H-4
appeared at d 7.35, and the 4Hs of substituted N-tolyl and 5Hs of phenyl
ring, at C-4, appeared in the region d 7.05–7.30. In the mass spectra of
these compounds, the base peak originates as a result of homolytic
cleavage of C-N bond between carbonyl carbon and nitrogen of imino
group at m=z 119. Other important peaks include those at m=z 313, 277,
91, and 65.
The mechanism of cyclization involves the attack of sulfur of the
mesomeric anion generated by the transfer of more acidic N-1 proton
to base to the a-carbon of the phenacyl bromide formed in situ to
afford the isothiourea intermediate, followed by the attack of anion from
N-3 to the carbonyl group, resulting in intramolecular cyclization and
dehydration (Scheme 2).
X-ray Data Collection, Structure Solution, and Refinement
The molecular structure of 2t was established by single-crystal X-ray
analysis (Fig. 2). The data were collected on a STOE-IPDS-II diffract-
ometer with monochromated Mo-Ka radiation at 173 K. An empirical
absorption correction was performed using the Mulabs option[23] in
Platon[24]
. The structure was solved with direct methods using

2190
A. Saeed, S. Zaman, and M. Bolte
Figure 2. Molecular structure of 2t. Displacement ellipsoids are shown at the
50% probability level.
SHELXS-97[25] and refined with full-matrix least-squares against F2
using SHELXL-97.[26] C26H18N2OS, mw ¼ 406.48 g=mol, monoclinic,
˚
˚
˚
a ¼ 13.1820(9) A, b ¼ 9.6112(6) A, c ¼ 16.9072(10) A, b ¼ 104.355(5),
V ¼ 2075.2(2) A3, T ¼ 173 K, P21=n, Z ¼ 4, l ¼ 0.176 mmꢀ1, 16902
˚
reflections measured, 3881 unique (Rint ¼ 0.0412), final R1 ¼ 0.0457
(all data), final wR2 ¼ 0.1033 (all data).
Full crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as supplemen-
tary publication no. CCDC-658606. Copies of the data can be obtained free
of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [fax: ( þ 44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk]
Bond lengths and angles are in the usual ranges. The thiazole ring is
planar and encloses dihedral angles of 47.9ꢁ with the attached phenyl ring
and 89.6ꢁ with the naphthyl residue.
EXPERIMENTAL
Melting points were recorded using a digital Gallenkamp (Sanyo) model
1
MPD BM 3.5 apparatus and are uncorrected. H NMR spectra were
determined as CDCl3 solutions at 300 MHz using a Bruker AM-300
spectrophotometer. FT-IR spectra were recorded using an FTS 3000

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2191
MX spectrophotometer; mass spectra (EI, 70 eV) were measured on a
GC-MS instrument from Agilent Technologies. Acetone and dichloro-
methane were dried according to standard procedures and distilled before
use. All compounds were purified by thick-layer chromatography using
silica gel from Merck.
Synthesis of 2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines (2a–2t)
Triethylamine (1 mmol) was added to a stirred solution of 1-aroyl-3-
arylthiourea (1 mmol) in dichloromethane (20 mL), followed by dropwise
addition of a solution of bromine (1 mmol) in acetophenone (1 mmol)
under an atmosphere of nitrogen. The reaction was stirred further for
1–2 h and progress of the reaction was monitored by thin-layer chroma-
tography. After the reaction was complete, the mixture was filtered;
the filtrate was concentrated to give crude 2-aroylimino-3-aryl-4-
phenyl-1,3-thiazoline, which was purified either by recrystallization from
95% ethanol or preparative thin-layer chromatography followed by
recrystallization.
Spectroscopic data for compounds 2a–2t
2-(2-Methylbenzoyl)imino-3-(2-methoxyphenyl)-4-phenyl-1,3-
thiazoline (2a)
ꢁ
Yield 63%; mp 205 C; Rfa 0.25; IR (KBr): n=cmꢀ1 1633 (C O), 1561
=
1
(Ar-C C), 1466 (C N), 1267 (C-S), 1158 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.98 (s, 1H, CH C), 7.12–8.43 (m, 13H, 2C6H4, C6H5), 3.65
(s, 3H, OCH3), 2.47 (s, 3H, CH3); 13CNMR (75 MHz, CDCl3): 21.51,
55.68, 107.79, 126.49, 126.75, 128.0, 128.63, 128.71, 128.84, 129.06,
129.12, 129.67, 130.09, 130.18, 132.54, 134.30, 136.3, 137.66, 138.59,
169.54, 174.60. Anal. calcd. for C24H20N2O2S: C, 71.98; H, 5.03; N,
6.99; S, 8.01%. Found: C, 70.66; H, 5.11; N, 7.21; S, 8.11%; GC-MS
(m=z): 400 (M. þ ), 309, 119 (100%), 91, 63.
2-(2-Methylbenzoyl)imino-3-(3-methylphenyl)-4-phenyl-1,3-
thiazoline (2b)
ꢁ
ꢀ1
Yield 54%; mp 185 C; Raf 0.52; IR (KBr): n=cm 1645 (C O), 1557
=
1
(Ar-C C), 1456 (C N), 1248 (C-S), 1159 (C-N); H NMR (300 MHz,
=
=
aPet ether–ethyl acetate 4:1.

2192
A. Saeed, S. Zaman, and M. Bolte
=
CDCl3): d 6.44 (s, 1H, CH C), 7.14–8.25 (m, 13H, 2C6H4, C6H5), 2.46 (s,
3H, CH3), 2.42 (s, 3H, CH3); 13CNMR (75 MHz, CDCl3): 21.40, 107.71,
126.50, 126.75, 128.0, 128.63, 128.77, 128.88, 129.06, 129.12, 129.67,
130.0, 130.18, 132.51, 134.30, 136.3, 137.68, 138.59, 169.58, 174.61. Anal.
calcd. for C24H20N2OS: C, 74.97; H, 5.24; N, 7.29; S, 8.34%. Found: C,
74.55; H, 5.30; N, 7.68; S, 8.26%; GC-MS (m=z): 384 (M. þ ) 293 119
(100%), 91, 63.
2-(2-Methylbenzoyl)imino-3-(2-chlorophenyl)-4-phenyl-1,3-
thiazoline (2c)
ꢁ
ꢀ1
Yield 62%; mp 165 C; Raf 0.49; IR (KBr): n=cm 1657 (C O), 1589
=
(Ar-C C), 1474 (C N), 1298 (C-S), 1157 (C-N); 1HNMR (300MHz,
=
=
=
CDCl3): d 6.48 (s, 1H, CH C), 7.24–8.04 (m, 13H, 2C6H4, C6H5), 2.37 (s,
3H, CH3); 13C NMR (75MHz, CDCl3): 21.44, 107.76, 126.51, 126.75,
128.0, 128.63, 128.77, 128.88, 129.06, 129.12, 129.67, 130.09, 130.18,
132.54, 134.30, 136.3, 137.66, 138.59, 169.56, 174.66. Anal. calcd. for
C23H17N2OSCl: C, 68.22; H, 4.23; N, 6.92; S, 7.92%. Found: C, 68.01; H,
4.33; N, 7.21; S, 7.90%; GC-MS (m=z): 404 (M. þ ), 313.5, 119 (100%), 91, 63.
2-(2-Methylbenzoyl)imino-3-(3-chlorophenyl)-4-phenyl-1,3-
thiazoline (2d)
ꢁ
ꢀ1
Yield 54%; mp. 182 C; Raf 0.49; IR (KBr): n=cm 1654 (C O), 1589 (Ar-
=
1
C C), 1455 (C N), 1279 (C-S), 1161 (C-N); H NMR (300 MHz, CDCl3):
=
=
=
d 6.68 (s, 1H, CH C), 6.98–8.11 (m, 13H, 2C6H4, C6H5), 2.51 (s, 3H, CH3);
13CNMR (75 MHz, CDCl3): 21.44, 107.76, 126.51, 126.75, 128.0, 128.63,
128.77, 128.88, 129.06, 129.12, 129.67, 130.09, 130.18, 132.54, 134.30,
136.3, 137.66, 138.59, 169.56, 174.66. Anal. calcd. for C23H17N2OSCl: C,
68.22; H, 4.23; N, 6.92; S, 7.92%. Found: C, 68.13; H, 4.20; N, 7.13; S,
7.89%. GC-MS (m=z): 404 (M. þ ), 313.5, 119 (100), 91, 63.
2-(3-Methylbenzoyl)imino-3-(2-methylphenyl)-4-phenyl-1,3-
thiazoline (2e)
ꢁ
ꢀ
Yield 61%; mp 172 C; Raf 0.65; IR (KBr): n=cm 1634 (C O), 1598 (Ar-
=
C C), 1476 (C N), 1266 (C-S), 1140 (C-N); 1H NMR (300 MHz,
=
=
=
CDCl3): d 6.74 (s, 1H, CH C), 7.05–8.13 (m, 13H, 2C6H4, C6H5), 2.58
(s, 3H, CH3), 2.44 (s, 3H, CH3); 13CNMR (75 MHz, CDCl3): 21.39,
107.71, 126.56, 126.75, 128.0, 128.63, 128.77, 128.89, 129.06, 129.12,
129.67, 130.09, 130.18, 132.54, 134.30, 136.38, 137.66, 138.59, 169.58,

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2193
174.70. Anal. calcd. for C24H20N2OS: C, 74.97; H, 5.24; N, 7.29; S,
8.34%. Found: C, 74.29; H, 5.35; N, 7.59; S, 8.29%; GC-MS (m=z):
384 (M. þ ), 293, 119 (100%), 91, 63.
2-(3-Methylbenzoyl)imino-3-(3-methylphenyl)-4-phenyl-1,3-
thiazoline (2f)
ꢁ
Yield 60%; mp 192 C; Rfa 0.37; IR (KBr): n=cmꢀ1 1644 (C O), 1595
=
1
(Ar-C C), 1458 (C N), 1263 (C-S), 1138 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.84 (s, 1 H, CH C), 7.00–8.23 (m, 13 H, 2C6H4, C6H5),
2.65 (s, 3 H, CH3), 2.55 (s, 3 H, CH3); 13C NMR (75 MHz, CDCl3):
21.51, 107.73, 126.51, 126.75, 128.20, 128.63, 128.77, 128.08, 129.06,
129.12, 129.67, 130.09, 130.18, 132.54, 134.30, 136.32, 137.66, 138.59,
169.60, 174.76. Anal. calcd. for C24H20N2OS: C, 74.97; H, 5.24; N,
7.29; S, 8.34%. Found: C, 74.54; H, 5.21; N, 7.51; S, 8.25%.
2-(3-Methylbenzoyl)imino-3-(3-chlorophenyl)-4-phenyl-1,3-
thiazoline (2g)
ꢁ
Yield 71%; mp 187 C; Rfa 0.52; IR (KBr): n=cmꢀ1 1646 (C O), 1569
=
1
(Ar-C C), 1489 (C N), 1265 (C-S), 1157 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d ppm 6.73 (s, 1 H, CH C), 7.15–7.99 (m, 13 H, 2C6H4,
C6H5), 2.38 (s, 3 H, CH3); 13C NMR (75 MHz, CDCl3): 21.44, 107.76,
126.51, 126.75, 128.0, 128.63, 128.77, 128.88, 129.06, 129.12, 129.67,
130.09, 130.18, 132.54, 134.30, 136.3, 137.66, 138.59, 169.56, 174.66.
Anal. calcd. for C23H17N2OSCl: C, 68.22; H, 4.23; N, 6.92; S, 7.92%.
Found: C, 68.08; H, 4.30; N, 7.29; S, 7.81%; GC-MS (m=z %): 404
(M. þ ), 313.5, 119 (100%), 91, 63.
2-(3-Methylbenzoyl)imino-3-(4-bromophenyl)-4-phenyl-1,3-
thiazoline (2h)
ꢁ
Yield 69%; mp 150 C; Rfa 0.85; IR (KBr): n=cmꢀ1 1695 (C O), 1561
=
1
(Ar-C C), 1449 (C N), 1234 (C-S), 1159 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d ppm 6.71 (s, 1 H, CH C), 7.12–8.00 (m, 13 H, 2C6H4,
C6H5), 2.39 (s, 3 H, CH3); 13C NMR (75 MHz, CDCl3): 21.65, 107.67,
121.95, 122.36, 128.62, 128.82, 128.89, 129.02, 129.40, 130.17, 130.33,
131.99, 133.87, 136.87, 137.63, 138.53, 142.13, 169.57, 174.67. Anal.
calcd. for C23H17N2OSBr: C, 61.48; H, 3.81; N, 6.23; S, 7.14%. Found:
C, 61.19; H, 3.49; N, 6.99; S, 7.20%; GC-MS (m=z %): 449 (M.þ), 357,
119 (100), 91, 63.

2194
A. Saeed, S. Zaman, and M. Bolte
2-(3-Methylbenzoyl)imino-3-(2-methoxyphenyl)-4-phenyl-1,3-
thiazoline (2i)
ꢁ
Yield 62%; mp 167 C; Rfa 0.38; IR (KBr): n=cmꢀ1 1666 (C O), 1544
=
1
(Ar-C C), 1472 (C N), 1275 (C-S), 1146 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d ppm 6.67 (s, 1 H, CH C), 6.89–7.99 (m, 13 H, 2C6H4,
C6H5), 3.62 (s, 3 H, OCH3), 2.40 (s, 3 H, CH3); 13C NMR (75 MHz,
CDCl3): 21.34, 56.08, 7.71, 126.51, 126.75, 128.09, 128.63, 128.77,
128.76, 129.06, 129.12, 129.67, 130.09, 130.21, 132.54, 134.30, 136.51,
137.66, 138.59, 169.56, 174.66. Anal. calcd.: C, 71.98; H, 5.03; N, 6.99;
S, 8.01%. Found: C, 70.65; H, 5.20; N, 7.35; S, 8.14%; GC-MS m=z
(%): 400 (M. þ ), 309, 119 (100), 91, 63.
2-(3-Methylbenzoyl)imino-3-(2-nitrophenyl)-4-phenyl-1,3-
thiazoline (2j)
ꢁ
Yield 58%; mp 170 C; Rfa 0.26; IR (KBr): n=cmꢀ1 1645 (C O), 1561
=
1
(Ar-C C), 1459 (C N), 1264 (C-S), 1154 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.77 (s, 1 H, CH C), 7.11–8.20 (m, 13 H, 2C6H4, C6H5),
2.45 (s, 3 H, CH3); 13C NMR (75 MHz, CDCl3): 21.34, 56.08, 7.71,
126.51, 126.75, 128.09, 128.63, 128.77, 128.76, 129.06, 129.12, 129.67,
130.09, 130.21, 132.54, 134.30, 136.51, 137.66, 138.59, 169.56, 174.66.
Anal. calcd. for C23H17N3O3S: C, 66.49; H, 4.12; N, 10.11; S, 7.72%.
Found: C, 65.89; H, 4.26; N, 10.67; S, 7.84%; GC-MS m=z (%): 415
(M. þ ), 324, 119 (100), 91, 63.
2-(3-Methylbenzoyl)imino-3-(3-nitrophenyl)-4-phenyl-1,3-
thiazoline (2k)
ꢁ
Yield 56%; mp 191 C; Rfa 0.23; IR (KBr): n=cmꢀ1 1654 (C O), 1567
=
1
(Ar-C C), 1466 (C N), 1285 (C-S), 1155 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.58 (s, 1 H, CH C), 7.12–8.24 (m, 13 H, 2C6H4, C6H5),
2.45 (s, 3 H, CH3); 13C NMR (75 MHz, CDCl3): 21.53, 107.79, 126.51,
126.75, 128.0, 128.63, 128.77, 128.88, 129.06, 129.12, 129.67, 130.09,
130.18, 132.54, 134.30, 135.39, 137.66, 138.60, 169.76, 174.78. Anal.
calcd. for C23H17N3O3S: C, 66.49; H, 4.12; N, 10.11; S, 7.72%. Found:
C, 66.01; H, 4.19; N, 10.50; S, 7.80%.
2-(4-Methylbenzoyl)imino-3,4-diphenyl-1,3-thiazoline (2l)
ꢁ
Yield 64%; mp 168 C; Rfa 0.6; IR (KBr): n=cmꢀ1 1634 (C O), 1607 (Ar-
=
C C), 1459 (C N), 1256 (C-S), 1155 (C-N); 1H NMR (300 MHz,
=
=

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2195
=
CDCl3): d 6.62 (s, 1 H, CH C), 7.14–8.11 (m, 14 H, C6H4, 2C6H5), 2.45
(s, 3 H, CH3); 13C NMR (75 MHz, CDCl3): 21.44, 107.76, 126.51, 126.75,
128.0, 128.63, 128.77, 128.88, 129.06, 129.12, 129.67, 130.09, 130.18,
132.54, 134.30, 136.3, 137.66, 138.59, 169.56, 174.66. Anal. calcd. for
C23H18N2OS: C, 74.57; H, 4.90; N, 7.96; S, 8.66%. Found: C, 74.14;
H, 4.82; N, 8.21; S, 8.61%.
2-(4-Methylbenzoyl)imino-3-(4-bromophenyl)-4-phenyl-1,3-
thiazoline (2m)
ꢁ
Yield 59%; mp 204 C; Rfa0.55; IR (KBr): n=cmꢀ1 1648 (C O), 1598
=
1
(Ar-C C), 1461 (C N), 1258 (C-S), 1154 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.68 (s, 1 H, CH C), 7.35–8.03 (m, 13 H, 2C6H4, C6H5),
2.40 (s, 3 H, CH3); 13C NMR (75 MHz, CDCl3): 21.65, 107.67, 121.95,
122.36, 128.62, 128.82, 128.89, 129.02, 129.40, 130.17, 130.33, 131.99,
133.87, 136.87, 137.63, 138.53, 142.13, 169.57, 174.67. Anal. calcd. for
C23H17N2OSBr: C, 61.48; H, 3.81; N, 6.23; S, 7.14%. Found: C, 61.06;
H, 3.51; N, 6.52; S, 7.16%.
2-(4-Methylbenzoyl)imino-3-(2-methylphenyl)-4-phenyl-1,3-
thiazoline (2n)
ꢁ
Yield 62%; mp 159 C; Rfa 0.55; IR (KBr): n=cmꢀ1 1643 (C O), 1590
=
1
(Ar-C C), 1451 (C N), 1260 (C-S), 1156 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.06 (s, 1 H, CH C), 7.10–8.13 (m, 13 H, 2C6H4, C6H5),
2.47 (s, 3 H, CH3), 2.42 (s, 3 H, CH3); Anal. calcd. for C24H20N2OS: C,
74.97; H, 5.24; N, 7.29; S, 8.34%. Found: C, 74.61; H, 5.29; N, 7.64; S,
8.28%.
2-(4-Methylbenzoyl)imino-3-(2-methoxyphenyl)-4-phenyl-
1,3-thiazoline (2o)
ꢁ
Yield: 61%; mp 206 C; Rfa 0.54; IR (KBr): n=cmꢀ1 1652 (C O), 1597
=
1
(Ar-C C), 1461 (C N), 1249 (C-S), 1157 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.16 (s, 1 H, CH C), 7.11–8.25 (m, 13 H, 2C6H4, C6H5), 3.57 (s,
3H, OCH3), 2.46 (s, 3H, CH3); Anal. calcd. for C24H20N2O2S: C, 71.98;
H, 5.03; N, 6.99; S, 8.01%. Found: C, 71.21; H, 5.12; N, 7.08; S, 8.10%.
2-Benzoylimino-3,4-diphenyl-1,3-thiazoline (2p)
ꢁ
Yield 65%; mp 210 C; Rfa 0.50; IR (KBr): n=cmꢀ1 1633 (C O), 1531
=
1
(Ar-C C), 1450 (C N), 1275 (C-S), 1158 (C-N); H NMR (400 MHz,
=
=

2196
A. Saeed, S. Zaman, and M. Bolte
=
CDCl3): 6.71 (s, 1 H, 1 H, CH C), 7.12 (d, 2 H, J ¼ 8.4 Hz), 7.23 (m, 6H),
7.33 (t, 2 H, J ¼ 7.6 Hz), 7.39 (d, 3 H, J ¼ 7.0 Hz), 8.21 (d, 2 H,
J ¼ 8.4 Hz), 13C NMR (75 MHz, CDCl3): 107.6, 128.1, 128.5,128.6,
128.9, 129.0, 129.4, 130.7, 131.6, 136.8, 137.7, 139.2, 170.0, 174.7. Anal.
calcd. for C22H16N2OS: C, 74.13; H, 4.52; N, 7.86; S, 9.00%. Found:
C, 74.00; H, 4.47; N, 7.99; S, 8.78%; GC-MS (m=z %): 356 (M. þ ),
279, 105 (100), 77, 65.
2-(2-Bromobenzoyl)imino-3-(2,4-dichlorophenyl)-4-phenyl-
1,3-thiazoline (2q)
ꢁ
Yield 68%; mp 181 C; Rfa 0.49; IR (KBr): n=cmꢀ1 1649 (C O), 1542
=
1
(Ar-C C), 1454 (C N), 1256 (C-S), 1150 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.76 (s, 1H, CH C), 7.17–7.85 (m, 12H, C6H3,C6H4, C6H5).
13C NMR (75 MHz, CDCl3): 107.8, 122.3, 128.0, 128.6, 128.8, 129.0,
129.1, 129.7, 130.5, 132.6, 134.4, 137.6, 139.0, 139.4, 170.1, 173.2. Anal.
calcd for C22H13N2OSBrCl2: C, 52.40; H, 2.60; N, 5.56; S, 6.36%. Found:
C, 52.15; H, 2.54; N, 5.83; S, 6.21%; GC-MS m=z (%): 501 (M. þ ), 348,
184 (100).
2-(2-Chlorobenzoyl)imino-3-(2-methoxyphenyl)-4-phenyl-1,3-thiazoline
(2r)
ꢁ
Yield 70%; mp 165 C; Rfa 0.51; IR (KBr): n=cmꢀ1 1640 (C O), 1529
=
1
(Ar-C C), 1453 (C N), 1278 (C-S), 1153 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d ppm 6.72 (s, 1H, CH C), 6.85–7.89 (m, 13H, 2C6H4, C6H5),
3.57 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3): 21.49, 55.98, 107.71,
126.51, 126.75, 128.0, 128.63, 128.77, 128.88, 129.06, 129.12, 129.67,
130.09, 132.54, 134.30, 136.3, 137.66, 138.61, 169.67, 174.69 Anal. calcd.
for C23H17N2O2SCl: C, 65.63; H, 4.07; N, 6.66; S, 7.62%. Found: C,
65.17; H, 4.01; N, 6.97; S, 7.51%.
2-(3-Chlorobenzoyl)imino-3,4-diphenyl-1,3-thiazoline (2s)
ꢁ
Yield 69%; mp 202 C; Rfa 0.53; IR (KBr): n=cmꢀ1 1653 (C O), 1526
=
1
(Ar-C C), 1451 (C N), 1265 (C-S), 1151 (C-N); H NMR (300 MHz,
=
=
=
CDCl3): d 6.76 (s, 1H, CH C), 7.13–8.09 (m, 14H, C6H4, 2C6H5);
13C NMR (75 MHz, CDCl3): 107.70, 126.57, 126.71, 128.0, 128.63,
128.77, 128.88, 129.06, 129.12, 129.67, 130.09, 130.18, 132.54, 134.30,
136.31, 137.66, 138.53, 169.59, 174.79. Anal. calcd. for C22H15N2O2SCl:

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2197
C, 67.60; H, 3.87; N, 7.17; S, 8.20%. Found: C, 67.14; H, 3.76; N, 7.48; S,
8.04%.
2-Benzoylimino-3-a-naphthyl-4-phenyl-1,3-thiazoline (2t)
ꢁ
Yield 72%; mp 194 C; Rfa 0.46; IR (KBr): n=cmꢀ1 1655 (C O), 1560
=
1
(Ar-C C), 1457 (C N), 1255 (C-S), 1154 (C-N); H NMR (300 MHz,
=
=
CDCl3): d 6.84 (s, 1H, CH C), 7.08–7.99 (m, 17H, 2C6H5, C10H7); 13C
=
NMR (75 MHz, CDCl3): 107.22, 122.98, 125.10, 126.57, 126.90, 127.38,
127.79, 128.22, 128.39, 128.48, 128.93, 129.23, 129.66, 130.14, 130.39,
131.36, 134.02, 134.58, 136.60, 169.97, 174.69. Anal. calcd. for
C26H18N2OS: C, 76.82; H, 4.46; N, 6.89; S, 7.89%. Found: C, 75.30;
H, 4.49; N, 7.08; S, 7.46%; GC-MS (m=z %): 406 (M. þ ), 329, 105
(100), 77, 65.
REFERENCES
1. Shehata, I. A.; Elsubbagh, H. I.; Abdelal, A. M.; Elsherbeny, M. A.; Alobaid,
A. A. Synthesis, Antitumor and Anti-HIV-1 testing of certain thieno[2,3-
d]pyrimidine, thieno[2,3-d]imidazo[1,2-c] pyrimidine and thieno[2,3-
d][1,3]thiazine derivatives. Med. Chem. Res. 1996, 6, 148.
2. Venkatachalan, T. K.; Sudbeck, E. A.; Mao, C.; Uckun, F. M. Anti-HIV
activity of aromatic and heterocyclic thiazolyl thiourea compounds Bioorg.
Med.Chem. Lett. 2001, 11, 523.
3. Bonde, C. G.; Gaikwad, N. J. J., Synthesis and preliminary evaluation
of some pyrazine containing thiazolines and thiazolidinones as antimi-
crobial agents. Bioorg. Med. Chem. 2004, 12, 2151.
4. Bondock, S.; Khalifa, W.; Fadda, A. A. Synthesis and antimicrobial evalu-
ation of some new thiazole, thiazolidinone and thiazoline derivatives start-
ing from 1-chloro-3,4-dihydronaphthalene-2-carboxaldehyde. Eur. J. Med.
Chem. 2007, 1–7.
5. Eckhardt, S. Recent progress in the development of anticancer agents. Curr.
Med. Chem. Anti-Cancer Agents 2002, 2, 419.
6. Lee, C. L.; Sim, M. M., Solid-phase combinatorial synthesis of 5-arylalkyli-
dene rhodanine. Tetrahedron Lett. 2000, 41, 5729.
7. Arcadi, A.; Attanasi, O. A.; Giorgi, G.; Filippone, P.; Rossi, E.; Santeusanio,
S. Pyrido[3,4-c]thiazoles through combined palladium-catalysed coupling of
2-substituted-5-acetyl-4-thiazolyltriflates with alkynes=annulation reactions.
Tetrahedron Lett. 2003, 44, 8391.
8. Fahmy, Y. T. H.; Bekhit, A. A. Synthesis of some new bis-thiazoles as poss-
ible anticancer agents. Pharmazie, 2002, 57, 800.
9. Shih, M.-H.; Ke, F.-Y. J. Syntheses and evaluation of antioxidant activity
of sydnonyl substituted thiazolidinone and thiazoline derivatives. Bioorg.
Med. Chem. 2004, 12, 4633.

2198
A. Saeed, S. Zaman, and M. Bolte
10. Manaka, A.; Ishii, T.; Takahashi, K.; Sato, M. 2-Acylimino-3-alkyl-3H-thi-
azoline derivatives: one-pot, three-component condensation synthesis of
novel b-turn mimics. Tetrahedron Lett. 2005, 46, 419.
11. Sanemitsu, Y.; Kawamura, S.; Satoh, J.; Katayama, T.; Hashimoto, S.,
Synthesis and herbicidal activity of 2-acylimino-3-phenyl-1,3-thiazolines—A
new family of bleaching herbicides. J. Pestic. Sci. 2006, 31(3), 305.
12. Bae, S.; Hahnand, H.-G.; Nam, K. D. Solid-Phase synthesis of fungitoxic 2-
Imino-1,3-thiazolines. J. Comb. Chem. 2005, 7, 7.
13. Bolos, C. A.; Papazisis, K. T.; Kortsaris, A. H.; Voyatzi, S.; Zambouli, D.;
Kyziakidis, D. A. Antiproliferative activity of mixed-ligand dien-Cu(II) com-
plexes with thiazole, thiazoline and imidazole derivatives. J. Inorg. Biochem.
2002, 88, 25; Barros-Garcia, F. J.; Bernalte-Garcia, A.; Higes-Rolando, F. J.;
´
Luna-Giles, F.; Maldonado-Rogado, M. A. Vinuelas-Zahınos E., synthesis,
crystal structure, spectroscopic and magnetic properties of copper(II)
complexes with 2-(2-pyridyl)imino-N-(2-thiazolin-2-yl)thiazolidine (PyTT).
J. Inorg. Chim. Acta 2004, 357, 3574.
14. Chen, Y.; Zhao, Y. J. Synthesis and characterization of polyacrylonitrile-2-
amino-2-thiazoline resin and its sorption behavior for noble metal ions.
React. Funct. Poly. 2003, 55, 89.
15. Bouchekara, M.; Djafri, A.; Vanthyne, N.; Roussel, C. Atropisomerism in
some N,N0-diaryl-2-iminothiazoline derivatives: chiral separation and con-
figurational stability, Arkivoc, 2002, 72.
16. Barros-Garcia, F. J.; Bernalte-Garcia, A.; Lozano-Vila, A. M.; Luna-Giles,
F.; Vinuelas-Zahinos, E. Pseudotetrahedral cobalt(II) complexes with thiaz-
oline and thiazine derivative ligands: Synthesis and characterization. Poly-
hedron, 2005, 24, 129.
17. Zhu, X.; Yu, Q.; Cutler, R. G.; Culmsee, C. W.; Holloway, H. W. Novel p53
inactivators with neuroprotective action: Syntheses and pharmacological
evaluation of 2-Imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-Imino-
2,3,4,5,6,7-hexahydrobenzoxazole derivatives. J. Med. Chem. 2002, 45, 5090.
18. A.; Dono, R.; Lingor, P.; Planchamp, V.; Lamballe, F.; Bahr, M.; Kraus,
J-L.; Maina, F. Imino-tetrahydrobenzothiazole derivatives as p53 inhibitors:
Discovery of a highly potent in vivo inhibitor and its action mechanism.
J. Med. Chem. 2006, 49, 3645.
19. Sondhi, S. M.; Bhattacharjee, G.; Jameel, R. K.; Shukla, R.; Raghubir, R.;
Lozach, O.; Meijer, L. Antiinflammatory, analgesic and kinase inhibition
activities of some acridine derivatives. Cent. Eur. J. Chem. 2004, 2, 1.
20. Kimpe, N. D.; Cock, W.; Keppens, M.; Smaele, D. D.; Meszaroz, A., Syn-
thesis of 2-Imino-4-thiazolines, 2-Imino-4-alkoxythiazolidines, Thiazoles
and 4-Imidazolin-2-ones from a-Halomethyl ketimines. J. Heterocyclic
Chem. 1996, 33, 1179.
21. D’hooghe, M.; Waterinekx, A.; Kimpe, N. D. A novel entry toward 2-Imino-
1,3-thiazolidines and 2-Imino-1,3-thiazolines by ring transformation of 2-
(Thiocyanomethyl) aziridines. J. Org. Chem. 2005, 70, 227.
22. Saeed, A.; Parvez, M. The crystal structure of 1-(4-chlorophenyl)-3-(4-
methylbenzoyl)thiourea. Cent. Eur. J. Chem. 2005, 3, 780.

2-Aroylimino-3-aryl-4-phenyl-1,3-thiazolines
2199
23. Blessing, R. H. An empirical correction for absorption anisotropy. Acta
Cryst. 1995, A51, 33–38.
24. Spek, A. L. Single crystal structure validation with the program PLATON.
J. Appl. Cryst. 2003, 36, 7.
25. Sheldrick, G. M. Acta Cryst. 1990, A46, 467–473.
26. Sheldrick, G. M. SHELXL-97: Phase annealing in SHELX90: direct methods
for larger structures, program for the refinement of crystal structures. Uni-
versity of Gottingen, Germany, 1997.