A facile and effective synthesis of 4-imino-3-(arylidene)- azetidine-2-thiones via phosphorus pentasulfide

Article abstract of DOI:10.1080/17415993.2014.956213

A new and an efficient synthesis of 4-imino-3-(arylidene)-azetidine-2-thiones is reported. The reaction of arylidenemalononitriles with phosphorus pentasulfide and ethanol affords the title products in good yields. Elemental analysis, infrared, ¹

Full text of DOI:10.1080/17415993.2014.956213

This article was downloaded by: [Dicle University]
On: 12 November 2014, At: 21:55
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
Journal of Sulfur Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gsrp20
A facile and effective synthesis of
4-imino-3-(arylidene)- azetidine-2-
thiones via phosphorus pentasulfide
Ouafa Amiria, El Mostapha Rakiba, Medaghri-Alaoui Abdelouahida,
Maria A.F. Faustinob, Maria G.P.M.S. Nevesb & José A.S. Cavaleirob
a Laboratoire de Chimie Organique et Analytique, Faculté des
Sciences et Techniques, Université Sultan Moulay Slimane, B.P.
523, Béni-Mellal, Morocco
b Department of Chemistry and QOPNA, University of Aveiro,
3810-193 Aveiro, Portugal
Published online: 09 Sep 2014.
To cite this article: Ouafa Amiri, El Mostapha Rakib, Medaghri-Alaoui Abdelouahid, Maria A.F.
Faustino, Maria G.P.M.S. Neves & José A.S. Cavaleiro (2014): A facile and effective synthesis of 4-
imino-3-(arylidene)- azetidine-2-thiones via phosphorus pentasulfide, Journal of Sulfur Chemistry,
DOI: 10.1080/17415993.2014.956213
To link to this article: http://dx.doi.org/10.1080/17415993.2014.956213
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
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. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Sulfur Chemistry, 2014
http://dx.doi.org/10.1080/17415993.2014.956213
A facile and effective synthesis of 4-imino-3-(arylidene)-
azetidine-2-thiones via phosphorus pentasulfide
Ouafa Amiria, El Mostapha Rakiba∗, Medaghri-Alaoui Abdelouahida, Maria A.F. Faustinob,
Maria G.P.M.S. Nevesb and José A.S. Cavaleirob
aLaboratoire de Chimie Organique et Analytique, Faculté des Sciences et Techniques, Université Sultan
b
Moulay Slimane, B.P. 523, Béni-Mellal, Morocco; Department of Chemistry and QOPNA, University of
Aveiro, 3810-193 Aveiro, Portugal
(Received 21 June 2014; accepted 16 August 2014)
A new and an efficient synthesis of 4-imino-3-(arylidene)-azetidine-2-thiones is reported. The reaction
of arylidenemalononitriles with phosphorus pentasulfide and ethanol affords the title products in good
yields. Elemental analysis, infrared, 1H NMR, 13C NMR and mass spectral data elucidated structure of
newly synthesized compounds.
NH
CN
P2S5, EtOH
NH
Reflux
CN
R1
R
3 S
R1
R3
R2
R2
8 examples
50-89%
Keywords: azetidine-2-thione; arylidenemalononitriles; phosphorus pentasulfide; ethanol
1. Introduction
2-Azetidinones, known as β-lactams, serve as synthons for much biologically important
class of organic compounds. 2-Azetidinones and its derivatives display interesting biologi-
cal activities such as antifungal, antimicrobial,[1–4] anti-inflammatory,[5–7] antitubercular,[8,9]
antiplasmodial,[10] antidepressant,[11] antitumoral [12,13] and cholesterol absorption inhibitory
properties.[14–16] 2-Azetidinones are not only useful in medicinal applications, but also used
as intermediates and synthons for the production of several organic compounds.[17] Several
synthetic methods have been developed for the preparation of the β-lactam ring.[18] Prompted
by these observations and as part of our ongoing work on the development of azetidinones
derivatives, herein we report a new method for the synthesis of 4-imino-3-(arylidene)-azetidine-
2-thiones by reaction of arylidenemalononitriles with P2S5 in the presence of ethanol.
∗Corresponding author. Email: elmostapha1@ymail.com
This article makes reference to supplementary material available on the publisher’s website at http://dx.doi.org/10.1080/
17415993.2014.956213.
c
ꢀ 2014 Taylor & Francis

2
O. Amiri et al.
2. Results and discussion
Commercially available phosphorus pentasulfide has been widely employed in organic synthesis
for effecting the conversion of carbonyl compounds to thiocarbonyl compounds under a variety
of conditions such as the use of polar solvents or base catalysts.[19–21] Despite the wide range
of reagents available for the conversion of nitriles to thioamides,[22] little attempts have been
made to use the readily accessible phosphorus pentasulfide. Recently simply phosphorus penta-
sulfide in different solvents, especially in ethanol under refluxing conditions, has been reported
to give thioamides.[23] In this paper, we wish to provide an efficient single-step procedure for
the preparation of 4-imino-3-(arylidene)-azetidine-2-thiones from arylidenemalononitriles with
P2S5 in ethanol.
As shown in Scheme 1, the reaction of arylidenemalononitriles 2a–h with phosphorus
pentasulfide in refluxing ethanol, afforded azetidine-2-thiones 3a–h in good yields. The aryliden-
emalononitriles 2a–h were prepared from the reaction of arylaldehydes 1a–h with malonitrile in
ethanol under reflux in the presence of phosphorus pentoxide as catalyst.
The structures of compounds 3a–h were deduced from their elemental analyses and their
infrared (IR), 1H NMR and 13C NMR spectra.
O
NH
CN
P2S5, EtOH
CH2(CN)2
H
NH
Reflux
R1
CN
P2O5, EtOH
reflux
R
R1
R3
3 S
R1
R3
R2
R2
a R1 = R2 = R3 = H
R2
2
3
b R1 = CH3O, R2 = R3 = H
c R2 = CH3O, R1 = R3 = H
d R3 = NO2, R1 = R2 = H
e R1 = Cl, R2 = R3 = H
f R2 = Br, R1 = R3 = H
g R1 = CH3, R2 = R3 = H
1
h R1 = N(CH3)2, R2 = R3 = H
Scheme 1. Synthesis of 4-imino-3-(arylidene)-azetidine-2-thiones 3a-h.
N
C
Ar
NH
S
P
S
P
CN
HS
OC2H5
+ EtOH
P2S5
Ar
S
OC2H5
OC2H5
CN
OC2H5
A
S
HS
B
OC2H5
P
C2H5O
S
OC2H5
OC2H5
S
P
C2H5O
S
S
P
S
OC2H5
NH
S
HS
OC2H5
P
Ar
C2H5O
P
Ar
NH2
NH
S
Ar
S
OC2H5
C2H5O
C
N
HN
3a-h
CN
C
D
Scheme 2. A plausible mechanism for the synthesis of azetidine-2-thiones 3a–h.

Journal of Sulfur Chemistry
3
1
For example, the H NMR spectrum of 3b exhibited two broad signals at δ = 9.46 and
9.97 ppm, respectively, due to the NH protons and a signal at 8.04 ppm for the vinylic proton.
The two single signals observed at 9.46 and 9.97 ppm disappeared after the addition of a few
drops of D2O to DMSO-d6 solution of compound 3b. These signals are related to NH protons.
A plausible mechanism for the formation of azetidine-2-thiones 3a–h is proposed as shown
in Scheme 2. First, P2S5 reacts with ethanol to furnish the activated intermediate O,O-diethyl
S-hydrogen phosphorodithioate A. Nucleophilic attack on arylidenemalononitriles by A provides
the intermediate B, which reacted with the same active specie of A to afford the thioamide D,
with the elimination of phosphorus oxide-sulfide. Azetidine-2-thiones 3a–h cores were formed
by means of subsequent intramolecular cyclization of D.
3. Conclusions
In summary, with a simple approach, a new series of 4-imino-3-(arylidene)-azetidine-2-thiones
3a–h were synthesized by reaction of arylidenemalononitriles with P2S5 in the presence of
ethanol. This appears to be a new method to prepare new building blocks of possible interest
in medicinal chemistry. Compounds 3a–h can be used as intermediates and synthons for the
construction of several interesting heterocyclic compounds.
4. Experimental
Melting points were determined using a Büchi-Tottoli apparatus. IR spectra were recorded on
a Perkin-Elmer 577 spectrometer using KBr disks; only noteworthy IR absorptions are listed
(cm−1). 1H and 13C NMR spectra were recorded in CDCl3, DMSO-d6 and solution (unless oth-
erwise specified) with TMS as an internal reference using a Bruker AC 300 (1H) or 75 MHz (13C)
instruments. Chemical shifts are given in d parts per million (ppm) downfield from TMS. Mul-
tiplicities of 13C NMR resources were assigned by distortionless enhancement by polarization
transfer (DEPT) experiments. Low-resolution mass spectra (MS) were recorded on a Perkin-
Elmer Sciex API 3000 spectrometer. Column chromatography was carried out on SiO2 (silica
gel 60 Merck 0.063–0.200 mm). Thin-layer chromatography (TLC) was carried out on SiO2 (sil-
ica gel 60, F 254 Merck 0.063–0.200 mm), and the spots were located with UV light. Commercial
reagents were used without further purification unless stated.
4.1. General procedure for the synthesis of 2-(arylidene)malononitriles 2a–h
In a 250 ml round bottom flask, aromatic aldehyde (10 mmol), malononitrile (10 mmol) and phos-
phorus pentoxide (3.54 mmol) were stirred mechanically for 10 min in 25 ml absolute ethanol.
The resulting reaction mixture was heated at reflux using a water bath. The reaction mixture was
poured on the crushed ice after the completion of the reaction monitored by TLC. On stirring, the
separation of desired product takes place. The solid was filtered, washed with petroleum ether,
dried and recrystalized by using ethanol.
4.1.1. 2-(Benzylidene)malononitrile (2a)
Yield: 89%, Mp: 88–90◦C; 1H NMR (DMSO-d6): δ 7.57–7.68 (m, 3H, H-Ar), 7.91–7.95 (m, 2H,
H-Ar), 8.52 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 82.1 (C), 113.7 (CN), 114.6 (CN), 129.9
(2CH), 131.0 (2CH), 131.8 (C), 134.8 (CH), 162.0 (CHvinyl).

4
O. Amiri et al.
4.1.2. 2-(4-Methoxybenzylidene)malononitrile (2b)
1
Yield: 86%, Mp: 110–112◦C; H NMR (DMSO-d6): δ 3.86 (s, 3H, CH3O), 7.14 (d, 2H, J =
9.0 Hz), 7.93 (d, 2H, J = 9.0 Hz), 8.34 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 56.4 (CH3O),
77.3 (C), 114.3 (CN), 115.2 (CN), 115.6 (2CH), 124.6 (C), 133.8 (2CH), 160.9 (CHvinyl), 164.8
=
( CO).
4.1.3. 2-(3-Methoxybenzylidene)malononitrile (2c)
1
Yield: 88%, Mp: 134–136◦C; H NMR (DMSO-d6): δ 3.79 (s, 3H, CH3O), 7.24–7.28 (m, 1H,
H-Ar), 7.49–7.52 (m, 3H, H-Ar)„ 8.48 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 55.9 (CH3O),
82.3 (C), 113.6 (CN), 114.5 (CN), 115.6 (CH), 120.7 (CH), 123.4 (CH), 131.2 (CH), 132.9 (C),
=
159.9 ( CO), 161.8 (CHvinyl).
4.1.4. 2-(2-Nitrobenzylidene)malononitrile (2d)
Yield: 90%, Mp: 124–126◦C; 1H NMR (DMSO-d6): δ 7.87–8.00 (m, 3H, H-Ar), 8.32 (dd, 1H,
J = 8.1 et 1.2 Hz), 8.95 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 87.5 (C), 112.3 (CN), 113.6
(CN), 125.9 (CH), 127.6 (C), 130.9 (CH), 133.8 (CH), 135.5 (CH), 147.3 (C), 161.8 (CHvinyl).
4.1.5. 2-(4-Chlorobenzylidene)malononitrile (2e)
1
Yield: 79%, Mp: 148–150◦C; H NMR (DMSO-d6): δ 7.67 (d, 2H, J = 8.4 Hz), 7.92 (d, 2H,
J = 8.4 Hz), 8.51 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 82.7 (C), 113.5 (CN), 114.5 (CN),
130.2 (2CH), 130.6 (C), 132.6 (2CH), 139.5 (C), 160.6 (CHvinyl).
4.1.6. 2-(3-Bromobenzylidene)malononitrile (2f)
1
Yield: 69%, Mp: 112–114◦C; H NMR (DMSO-d6): δ 7.56 (t, 1H, J = 8.1 Hz), 7.85–7.94 (m,
2H, H-Ar), 8.08 (m, 1H, H-Ar)„ 8.50 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 84.0 (C), 113.2
(CN), 114.3 (CN), 122.8 (C), 129.4 (CH), 132.0 (CH), 133.3 (CH), 133.8 (C), 136.9 (CH), 160.3
(CHvinyl).
4.1.7. 2-(4-Methylbenzylidene)malononitrile (2g)
1
Yield: 68%, Mp: 130–132◦C; H NMR (DMSO-d6): δ 2.39 (s, 3H, CH3), 7.41 (d, 2H, J =
8.1 Hz), 7.84 (d, 2H, J = 8.1 Hz), 8.45 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 21.9 (CH3),
80.4 (C), 113.9 (CN), 114.8 (CN), 129.2 (C), 130.6 (2CH), 131.1 (2CH), 146.1 (C), 161.8
(CHvinyl).
4.1.8. 2-(4-(Dimethylamino)benzylidene)malononitrile (2h)
1
Yield: 96%, Mp: 172–174◦C; H NMR (DMSO-d6): δ 3.08 (s, 3H, N(CH3)2), 6.81 (d, 2H,
J = 9.3 Hz), 7.79 (d, 2H, J = 9.3 Hz), 7.99 (s, 1H, H-vinyl); 13C NMR (DMSO-d6): δ 40.1
(NCH3), 69.1 (C), 112.2 (2CH), 115.9 (CN), 116.7 (CN), 119.2 (C), 134.1 (2CH), 154.8 (C),
159.3 (CHvinyl).

Journal of Sulfur Chemistry
5
4.2. General procedure for the synthesis of 4-Imino-3-(arylidene)-azetidine-2-thiones 3a–h
A solution of phosphorus pentasulfide P2S5 (20 mmol) in ethanol absolute (10 mL) was stirred
for 1 h. Arylidenemalononitrile (10 mmol) was added and the resulting solution was heated to
reflux for 3–6 h. The mixture was then washed with ethyl acetate; the organic phase was dried
over MgSO4 and concentrated in vacuo. Chromatography (EtOAc–hexane 10:90) gave the pure
azetidine-2-thiones in good yield.
4.2.1. 4-Imino-3-(benzylidene)-azetidine-2-thione (3a)
1
Yield:50%, Mp: 135–137◦C; IR (KBr, cm−1): 3310, 3180 (2NH), 1590 (C NH), 1210 (CS); H
=
NMR (DMSO-d6): δ 7.30–7.36 (m, 3H, H-Ar), 7.51–7.55 (m, 2H, H-Ar), 8.06 (s, 1H, H-vinyl),
9.71 (s, 1H, NH), 9.86 (s, 1H, NH); 13C NMR (DMSO-d6): δ 128.5 (CH), 116.7 (C), 119.2 (C),
129.1 (CH), 129.7 (CH), 130.6 (CH), 132.7 (CH), 133.9 (C), 147.2 (CHvinyl), 192.8 (CS); MS:
m/z 189 [M + 1]+. Anal. Calcd for C10H8N2S: C, 63.80; H, 4.28; N, 14.88. Found: C, 63.72; H,
4.36; N, 14.75.
4.2.2. 4-Imino-3-(4-methoxybenzylidene)-azetidine-2-thione (3b)
Yield: 78%, Mp: 191–193◦C; IR (KBr, cm−1): 3300, 3170 (2NH), 1605 (C NH), 1180 (CS);
=
1H NMR (DMSO-d6): δ 3.83 (s, 3H, CH3O), 7.11 (d, 2H, J = 9.0 Hz), 7.94 (d, 2H, J = 9.0 Hz),
8.04 (s, 1H, H-vinyl), 9.46 (s, 1H, NH), 9.97 (s, 1H, NH); 13C NMR (DMSO-d6): δ 56.1 (CH3O),
=
109.5 (C), 115.4 (2CH), 117.3 (C), 124.6 (C), 133.2 (2CH), 147.5 (CHvinyl), 163.1 ( CO), 193.1
(CS); MS: m/z 219 [M + 1]+. Anal. Calcd for C11H10N2OS: C, 60.53; H, 4.62; N, 12.83. Found:
C, 60.65; H, 4.51; N, 12.74.
4.2.3. 4-Imino-3-(3-methoxybenzylidene)-azetidine-2-thione (3c)
Yield: 86%, Mp: 136–138◦C; IR (KBr, cm−1): 3270, 3140 (2NH), 1615 (C NH), 1195 (CS);
=
1H NMR (DMSO-d6): δ 3.79 (s, 3H, CH3O), 7.12–7.16 (m, 1H, H-Ar), 7.46–7.51 (m, 3H, H-
Ar), 8.02 (s, 1H, H-vinyl), 9.61 (s, 1H, NH), 10.10 (s, 1H, NH); 13C NMR (DMSO-d6): δ 55.8
(CH3O), 113.1 (C), 115.3 (CH), 116.7 (C), 118.6 (CH), 123.2+(CH), 130.8 (CH), 133.6 (C), 147.1
=
(CHvinyl), 159.9 ( CO), 192.8 (CS); MS: m/z 219 [M + 1] . Anal. Calcd for C11H10N2OS: C,
60.53; H, 4.62; N, 12.83. Found: C, 60.58; H, 4.56; N, 12.68.
4.2.4. 4-Imino-3-(2-nitrobenzylidene)-azetidine-2-thione (3d)
Yield: 56%, Mp: 109–111◦C; IR (KBr, cm−1): 3280, 3165 (2NH), 1600 (C NH), 1510, 1365
=
(NO2), 1185 (CS); 1H NMR (DMSO-d6): δ 7.77–7.85 (m, 2H, H-Ar), 7.90–7.95 (m, 1H, H-Ar),
8.26 (d, 1H, J = 8.1 Hz), 8.47 (s, 1H, H-vinyl), 9.63 (s, 1H, NH), 10.24 (s, 1H, NH); 13C NMR
(DMSO-d6): δ 55.8 (CH3O), 115.4 (C), 117.1 (C), 125.7 (CH), 129.1 (C), 131.2 (CH), 132.4
+
=
(CH), 135.2 (CH), 146.6 (CHvinyl), 147.6 ( CN), 191.1 (CS); MS: m/z 234 [M + 1] . Anal.
Calcd for C10H7N3O2S: C, 51.49; H, 3.02; N, 18.02. Found: C, 51.62; H, 3.14; N, 17.94.
4.2.5. 4-Imino-3-(4-chlorobenzylidene)-azetidine-2-thione (3e)
1
Yield: 58%, Mp: 185–186◦C; IR (KBr, cm−1): 3320, 3150 (2NH), 1600 (C NH), 1200 (CS); H
=
NMR (DMSO-d6): δ 7.61 (d, 2H, J = 9.3 Hz), 7.92 (d, 2H, J = 9.3 Hz), 8.15 (s, 1H, H-vinyl),
9.00 (s, 1H, NH), 9.50 (s, 1H, NH); 13C NMR (DMSO-d6): δ 107.8 (C), 129.8 (2CH), 131.2 (C),

6
O. Amiri et al.
132.1 (2CH), 137.3 (C), 149.7 (CHvinyl), 160.1 (C), 192.0 (CS); MS: m/z 223 [M + 1]+. Anal.
Calcd for C10H7ClN2S: C, 53.93; H, 3.17; N, 12.58. Found: C, 54.12; H, 3.35; N, 12.46.
4.2.6. 4-Imino-3-(3-bromobenzylidene)-azetidine-2-thione (3f)
1
Yield: 45%, Mp: 173–174◦C; IR (KBr, cm−1): 3275, 3150 (2NH), 1605 (C NH), 1200 (CS); H
=
NMR (DMSO-d6): δ 7.77–7.95 (m, 3H, H-Ar), 8.26 (dd, 1H, J = 8.1 and 1.2 Hz), 8.47 (s, 1H,
H-vinyl), 9.62 (s, 1H, NH), 10.24 (s, 1H, NH); 13C NMR (DMSO-d6): δ 115.4 (C), 117.1 (C),
125.7 (CH), 129.1 (C), 131.2 (CH), 132.4 (CH), 135.2 (CH), 146.7 (CHvinyl), 147.6 (C), 191.1
(CS); MS: m/z 268 [M + 1]+, 270 [M+3]+. Anal. Calcd for C10H7BrN2S: C, 44.96; H, 2.64; N,
10.49. Found: C, 44.84; H, 2.56; N, 10.57.
4.2.7. 4-Imino-3-(4-methylbenzylidene)-azetidine-2-thione (3g)
Yield: 62%, Mp: 168–170◦C; IR (KBr, cm−1): 3280, 3165 (2NH), 1610 (C NH), 1190 (CS);
=
1H NMR (DMSO-d6): δ 2.36 (s, 3H, CH3), 7.35 (d, 2H, J = 8.1 Hz), 7.82 (d, 2H, J = 8.1 Hz),
8.03 (s, 1H, H-vinyl), 9.56 (s, 1H, NH), 10.05 (s, 1H, NH); 13C NMR (DMSO-d6): δ 21.7 (CH3),
111.7 (C), 116.9 (C), 129.6 (C),130.4 (2CH), 130.8 (2CH), 143.4 (C), 147.4 (CHvinyl), 192.9
(CS); MS: m/z 203 [M+1]+. Anal. Calcd for C11H10N2S: C, 65.32; H, 4.98; N, 13.85. Found:
C, 65.45; H, 5.08; N, 13.70.
4.2.8. 4-Imino-3-(4-(dimethylamino)benzylidene)-azetidine-2-thione (3h)
1
Yield: 89%, mp: 236–238◦C; IR (KBr, cm−1): 3285, 3180 (2NH), 1600 (C NH), 1205 (CS); H
=
NMR (DMSO-d6): δ 3.04 (s, 3H, NCH3), 6.80 (d, 2H, J = 9.0 Hz), 7.85 (d, 2H, J = 9.0 Hz),
8.04 (s, 1H, H-vinyl), 9.12 (s, 1H, NH), 9.67 (s, 1H, NH); 13C NMR (DMSO-d6): δ 40.0 (NCH3),
103.8 (C), 112.3 (2CH), 118.5 (C), 118.8 (C), 133.7 (2CH), 153.6 (C), 149.2 (CHvinyl), 193.4
(CS); MS: m/z 232 [M + 1]+. Anal. Calcd for C12H13N3S: C, 62.31; H, 5.66; N, 18.17. Found:
C, 62.48; H, 5.58; N, 18.24.
Acknowledgement
The authors also thank the FCT-Portugal and CNRST-Morocco for the financial assistance to the joint collaborative
project.
Funding
The synthetic work was supported by a grant of the University of Sultan Moulay Slimane, Béni-Mellal and the National
Centre for Scientific and Technical Research (CNRST), Rabat, Morocco.
Supplemental data
Supplemental data for this article can be accessed at 10.1080/17415993.2014.956213.
References
[1] Long B, He C, Yang Y, Xiang J. Synthesis, characterization and antibacterial activities of some new ferocene-
containing penems. Eur J Med Chem. 2010;45:1181–1188.

Journal of Sulfur Chemistry
7
[2] Chavan AA, Pai NR. Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones. Molecules.
2007;12:2467–2477.
[3] Ishwar BK, Mishra SK, Jainey PJ, Shastry CS. Antimicrobial studies of synthesized azetidinone derivatives from
sulfamethoxazole moiety. J Chem Pharm Res. 2011;3:114–118.
[4] Ceric´ H, Šindler-Kulyk M, Kovac´evic´ M, Peric´ M, Živkovic´ A. Azetidinone-isothiazolidinones: stereoselective
synthesis and antibacterial evaluation of new monocyclic beta-lactams. Bioorg Med Chem. 2010;18:3053–3058.
[5] Kumar A, Rajput CS, Bhati SK. Synthesis of 3-[4’-(p-chlorophenyl)-thiazol-2’-yl]-2-[(substituted azetidinone/
thiazolidinone)-aminomethyl]-6-bromoquinazolin-4-ones as anti-inflammatory agent. Bioorg Med Chem.
2007;15:3089–3096.
[6] Smith EM, Sorota S, Kim HM, McKittrick BA, Nechuta TL, Bennett C, Knutson C, Burnett DA, Kieselgof J,
Tan Z, Rindgen D, Bridal T, Zhou X, Jia Y-P, Dong Z, Mullins, D, Zhang X, Priestley T, Correll CC, Tulshian
D, Czarniecki M, Greenlee WJ. T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-
optimization, design and synthesis. Bioorg Med Chem Lett. 2010;20:4602–4606.
[7] Mehta PD, Sengar NPS, Pathak AK. 2-Azetidinone – A new profile of various pharmacological activities. Eur J
Med Chem. 2010;45:5541–5560.
[8] Sharma R, Samadhiya P, Srivastava SD, Srivastava SK. Synthesis and pharmaceutical importance of 2-azetidinone
derivatives of phenothiazine. J Chem Sci. 2012;124:633–637.
[9] Sharma S, Sharma PK, Kumar N, Dudhe R. A review on various heterocyclic moieties and their antitubercular
activity. Biomed Pharmacother. 2011;65:244–251.
[10] Singh P, Sachdeva S, Raj R, Kumar V, Mahajan MP, Nasser S, Vivas L, Gut J, Rosenthal PJ, Feng T-S, Chibale K.
Antiplasmodial and cytotoxicity evaluation of 3-functionalized 2-azetidinone derivatives. Bioorg Med Chem Lett.
2011;21:4561–4563.
[11] Mittal M, Goel RK, Bhargava G, Mahajan, MP. Pass-assisted exploration of antidepressant activity of 1,3,4-
trisubstituted-β-lactam derivatives. Bioorg Med Chem Lett. 2008;18:5347–5349.
[12] O’Boyle NM, Greene LM, Bergin O, Fichet J-B, McCabe T, Lloyd DG, Zisterer DM, Meegan MJ. Synthe-
sis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones. Bioorg Med Chem.
2011;19:2306–2325.
[13] Tripodi F, Pagliarin R, Fumagalli G, Bigi A, Fusi P, Orsini F, Frattini M, Coccetti P. Synthesis and biological eval-
uation of 1,4-diaryl-2-azetidinones as specific anticancer agents: activation of adenosine monophosphate activated
protein kinase and induction of apoptosis. J Med Chem. 2012;55:2112–2124.
[14] Wang Y, Zhang H, Huang W, Kong J, Zhou J, Zhang B. 2-Azetidinone derivatives: design, synthesis and evaluation
of cholesterol absorption inhibitors. Eur J Med Chem. 2009;44:1638–1643.
[15] Okuyama K-I, Momoi Y, Sugimoto K, Okano K, Tokuyama H. Synthetic studies toward haouamine B: construction
of indenotetrahydropyridone skeleton. Synlett. 2011;1:73–76.
[16] D’hooghe M, Mollet K, Dekeukeleire S, De Kimpe N. Stereoselective synthesis of trans-and cis-2-aryl-3-
(hydroxymethyl)aziridines through transformation of 4-aryl-3-chloro-β-lactams and study of their ring opening.
Org Biomol Chem. 2010;8:607–615.
[17] Alcaide B, Almendros P, Luna A, Rosario Torres M. Divergent reactivity of 2-azetidinone-tethered allenols with
electrophilic reagents: controlled ring expansion versus spirocyclization. Adv Synth Catal. 2010;352:621–626.
[18] Fu N, Tidwell, TT. Preparation of β-lactams by [2+2] cycloaddition of ketenes and imines. Tetrahedron.
2008;64:10465–10496.
[19] (a) Lagiakos HR, Walker A, Aguilar M-I, Perlmutter P. Thionation of amides using a solid-supported P2S5 reagent
under microwave irradiation. Tetrahedron Lett. 2011;52:5131–5132.
[20] Polshettiwar V, Kaushik MP. Alumina encapsulated phosphorus pentasulfide (P4S10/Al2O3) mediated efficient
thionation of long chain amides. Tetrahedron Lett. 2006;47:2315–2317 (and references cited therein).
[21] Sudalai A, Kanagasabapathy S, Benicewicz BC. Phosphorus pentasulfide: a mild and versatile catalyst/reagent for
the preparation of dithiocarboxylic esters. Org Lett. 2000;2:3213–3216.
[22] Goswami S, Maity AC, Das NK. Advanced reagent for thionation: rapid synthesis of primary thioamides from
nitriles at room temperature. J Sulfur Chem. 2007;28:233–237.
[23] Kaboudin B, Elhamifar D. Phosphorus pentasulfide: a mild and versatile reagent for the preparation of thioamides
from nitriles. Synthesis. 2006; 2:224–226.