One-pot stereoselective synthesis of alkyl (Z)-2-[4-oxo-3-phenyl-2- (phenylimino)-1,3-thiazolan-5-yliden]acetates from acetylenic esters and N, N′ -diphenylthiourea

Article abstract of DOI:10.1080/10426500802111488

N, N′-diphenylthiourea reacts with dialkyl acetylenedicarboxylates in acetone to form 1:1 adducts, which undergo a cyclization reaction to produce alkyl (Z)-2-[4-oxo-3-phenyl-2-(phenylimino)-1,3-thiazolan-5-yliden]acetates in fairly good yields. NMR spect

Full text of DOI:10.1080/10426500802111488

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One-Pot Stereoselective
Synthesis of Alkyl (Z)-2-
[4-Oxo-3-phenyl-2-
(phenylimino)-1,3-thiazolan-5-
yliden]acetates from
Acetylenic Esters and N, N′ -
Diphenylthiourea
Monireh Heshmati Gonbari a , Ali Ramazani a & Ali
Souldozi a
a Chemistry Department, Zanjan University, Zanjan,
Iran
Version of record first published: 04 Feb 2009.
To cite this article: Monireh Heshmati Gonbari, Ali Ramazani & Ali Souldozi (2009):
One-Pot Stereoselective Synthesis of Alkyl (Z)-2-[4-Oxo-3-phenyl-2-(phenylimino)-1,3-
thiazolan-5-yliden]acetates from Acetylenic Esters and N, N′ -Diphenylthiourea,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:2, 309-314
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Phosphorus, Sulfur, and Silicon, 184:309–314, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802111488
One-Pot Stereoselective Synthesis of Alkyl (Z)-2-[4-Oxo-
3-phenyl-2-(phenylimino)-1,3-thiazolan-5-yliden]acetates
from Acetylenic Esters and N, Nꢀ-Diphenylthiourea
Monireh Heshmati Gonbari, Ali Ramazani,
and Ali Souldozi
Chemistry Department, Zanjan University, Zanjan, Iran
N, Nꢀ-diphenylthiourea reacts with dialkyl acetylenedicarboxylates in acetone to
form 1:1 adducts, which undergo a cyclization reaction to produce alkyl (Z)-2-[4-
oxo-3-phenyl-2-(phenylimino)-1,3-thiazolan-5-yliden]acetates in fairly good yields.
NMR spectra indicated that the reaction is completely stereoselective.
Keywords Acetylenic ester; Michael addition; N, Nꢀ-diphenylthiourea; stereoselectivity;
1,3-thiazolan
INTRODUCTION
For several years, acetylenic esters have been attracting the atten-
tion of organic chemists.1–13 Acetylenic esters are reactive systems and
take part in many chemical syntheses.1–13 The compounds act almost
as Michael acceptors in organic reactions.1–13 In recent years, there
has been increased interest in the applications of acetylenic esters in
multicomponent synthesis.1–13 Because of the atom economy, conver-
gent character, and simplicity of one-pot procedures, multicomponent
condensation reactions (MCRs) have an advantageous position among
other reactions.1,14 The discovery and development of novel MCRs are
receiving growing interest from industrial chemistry research groups,
and MCRs represent a new challenge for organic chemists and to the ba-
sic understanding of organic chemistry itself.1,14 Owing to these charac-
teristics and our interest in the synthesis of heterocycles,13–16 we were
prompted to synthesize alkyl (Z)-2-[4-oxo-3-phenyl-2-(phenylimino)-
1,3-thiazolan-5-yliden]acetates (5) from N, Nꢀ-diphenylthiourea (1) and
Received 8 March 2008; accepted 8 April 2008.
This work was supported by the Zanjan University.
Address correspondence to Ali Ramazani, Chemistry Departmeny Zanjan University,
PO Box 45195-313, Zanjan, Iran. E-mail: aliramazani@gmail.com
309

310
M. H. Gonbari et al.
SCHEME 1
dialkyl acetylenedicarboxylates (2) in acetone in fairly good yields
(Scheme 1).
BIOLOGICAL AND INDUSTRIAL IMPORTANCE OF THIAZOLAN
DERIVATIVES
Thiazolan17–19 skeletons are important compounds due to their broad
range of biological activities.20–34 It is well known that thiazolyl deriva-
tives possess anti-inflammatory properties.20–25 Today’s requirements
demand novel medicinal remedies possessing different degrees of se-
lectivity and specificity depending on their purpose. The process of
inflammation often becomes chronic, and the human organism needs
drug therapy support in periods of acute attacks. Therefore, an in-
crease of the variety of specific and selective anti-inflammatory reme-
dies is an important task, especially due to its positive influence on
the chronic sick rate decrease. Some anticancer drugs, such as blenox-
ane, bleomycine, and tiazofurin, that contain thiazolyl moiety in their
structure, are known as antineoplastics.26 In addition, several thia-
zolyl derivatives were found to be potent antitumor agents.26–28 Since
arachidic acid (AA) metabolism results in the generation of mutagens
that damage DNA and induce mutations, members of arachidic acid en-
zymes, especially the lipoxygenase pathway, have been reported to play
a significant role in carcinogenesis. Inhibitors of AA metabolism can
reverse the production of these metabolites resulting in recruitment

One-Pot Synthesis from Acetylenic Esters
311
of apoptotic cell clearance.29 Thiazole derivatives have attracted a
great deal of interest owing to their antibacterial, antifungal, anti-
inflammatory, and antiviral activities.30 They are also useful as anti-
allergic, anthelmintic agents and as sedative hypnotics.30 It is also
well known that the thiazole moiety can be important for significant
biological activity.33,34 In addition to being used in the pharmaceutical
industry,30–32 they also find wide applications in the dye and photo-
graphic industry.30
RESULTS AND DISCUSSION
The compound (5) may result from an initial Michael addition reaction
of N, Nꢀ-diphenylthiourea 1 to the acetylenic ester 2 and concomitant
intramolecular protontransfer of the 1:1 adduct 3, followed by attack of
the imine nitrogen on the carbonyl group of ester to form product 5, in
acetone in fairly good yields (Scheme 1). TLC indicated that the reac-
tion was completed after 15 min. The reaction proceeds smoothly and
cleanly under the reaction conditions. The mechanism of the reaction
has not been established experimentally. However, a possible explana-
tion is proposed in Scheme 1. The formulas of the products 5a–b were
1
deduced from their IR, H NMR, and 13C NMR spectra (See Experi-
mental section). In this reaction, only one stereoisomer was observed,
and therefore the reaction is completely stereoselective. Based on our
previous reports in the areas of syntheses and structures (NMR data
and single crystal X-ray structure determination)4,13,16 of electron-poor
alkenes and comparison of the structural data with the structural data
of the compounds 5, we have concluded that the stereochemistry of the
compounds 5 are Z (for example, for the Z stereoisomers, =CH of alkene
showed distinct resonances at δ = 6.90–7.20 ppm and for E stereoiso-
1
mers, at δ = 5.80–6.60 ppm in their H NMR spectra).4,13,16 The IR
spectrum of 5a showed strong adsorptions at 3062 (CH, aromatic), 2954
(CH, aliphatic), 1731 (C O, ester), 1646 (C N, imine), 1608 (C C), and
1192 (C-O, ester) cm−1 indicating the presence of mentioned groups in
the formula. The 1H NMR spectrum of 5a compound exhibited four sig-
nals readily recognized as arising from one OMe groups (δ = 3.82 ppm,
s), CH (δ = 7.00 ppm, s) and aromatic moieties (δ = 7.1–7.6 ppm, m and
δ = 6.95 ppm, d, 3JHH = 8.0 Hz). The 1H decoupled 13C NMR spectrum
of 5a showed 14 distinct resonances in agreement with the 5a formula.
Partial assignment of these resonances is given in the spectral anal-
1
ysis section (see Experimental section). The H and 13C NMR spectra
of compound 5b are similar to those of 5a, except for the ester group,

312
M. H. Gonbari et al.
which exhibits characteristic signals with appropriate chemical shifts
(see Spectral Analysis section).3,4
CONCLUSION
In summary, we have developed
a new and efficient, one-
pot stereoselective method for preparing of alkyl (Z)-2-[4-oxo-3-
phenyl-2-(phenylimino)-1,3-thiazolan-5-yliden]acetates (5) from N, Nꢀ-
diphenylthiourea (1) and dialkyl acetylenedicarboxylates (2) in acetone
in fairly good yields (Scheme 1). We believe the reported method offers a
simple and efficient route for the preparation of the thiazoles 5 (Scheme
1). Its ease of work-up and fairly good yields make it a useful addition
to modern synthetic methodologies.3,4 Other aspects of this process are
under investigation.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus
and are uncorrected. IR spectra were recorded on a Mattson 1000 FT-IR
spectrometer. 1H and 13C NMR spectra were measured with a BRUKER
Spectrospin spectrometer at 250 and 62.5 MHz, respectively.
General Procedure for the Preparation of Alkyl (Z)-2-[4-oxo-3-
phenyl-2-(phenylimino)-1,3-thiazolan-5-yliden]acetates
(5a–b)
To a magnetically stirred solution of N, Nꢀ-diphenylthiourea 1 (0.23 g,
1.0 mmol) in acetone (5 mL) was added dropwise a mixture of 2 (0.13
mL, 1.0 mmol) in acetone (2 mL) at –10◦C over 15 min. The mixture
was then stirred at –10◦C for 15 min and then allowed to warm up to
room temperature. The solvent was removed under reduced pressure,
and products were recrystallized in ethanol (95%). The crystals of 5
were collected by simple filtration and dried at room temperature. The
characterization data of the compounds (5a–b) are given below:
Selected Data for Methyl (Z)-2-[4-oxo-3-phenyl-2-
(phenylimino)-1,3-thiazolan-5-yliden]acetate (5a)
Light yellow crystals, m. p. 117.5–118.5, yield 83%. IR (KBr)
(vmax, cm−1): 3062, 2954, 1731, 1646, 1608, 1500, 1377, 1323, 1192, 769,
1
700, and 585. H NMR (CDCl3) δH: 3.82 (3 H, s, OCH3); 6.95 (2 H, d,
3JHH = 8.0 Hz, arom.); 7.00 (1 H, s, CH); 7.1–7.6 (8 H, m, arom.). 13
C
NMR (CDCl3) δC: 52.57 (OCH3), 116.49 (=CH); 120.90, 127.85, 129.30,

One-Pot Synthesis from Acetylenic Esters
313
and 129.34 (8 CH, ortho and meta, arom.); 125.25 and 129.18 (2 CH,
para, arom.); 133.98 and 147.32 (2 C, ipso, arom.); 141.42 (=CS); 151.57
(C N); 164.56 and 166.36 (2 C O).
Selected Data for Ethyl (Z)-2-[4-oxo-3-phenyl-2-(phenylimino)-
1,3-thiazolan-5-yliden]acetate (5b)
Light yellow crystals, m. p. 87.5–88.5, yield 64%. IR (KBr)
(vmax, cm−1): 3060, 2923, 1723, 1646, 1377, 1315, 1200, 769, 700, and
1
3
585. H NMR (CDCl3)δH: 1.34 (3 H, t, JHH = 7.1 Hz, CH3); 4.28 (2 H,
3
3
q, JHH = 7.1 Hz, OCH2); 6.96 (2 H, d, JHH = 7.5 Hz, arom.); 6.99 (1
H, s, =CH); 7.1–7.6 (8 H, m, arom.). 13C NMR (CDCl3) δC: 14.14 (CH3);
61.78 (OCH2); 116.95 (=CH); 120.90, 127.85, 129.28, and 129.35 (8 CH,
ortho and meta, arom.); 125.21 and 129.17 (2 CH, para, arom.); 133.97
and 147.34 (2 C, ipso, arom.); 141.13 (=CS); 151.77 (C N); 164.63 and
165.98 (2 C O).
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