untitled


European	Journal	of	Chemistry	4	(2)	(2013)	98‐101	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2013	EURJCHEM	

DOI:10.5155/eurjchem.4.2.98‐101.714	

	
	

	

	

European	Journal	of	Chemistry	
Journal	homepage:	www.eurjchem.com	

	 	 	

Synthesis	and	antimicrobial	activity	of	some	novel	2‐azetidinones	and		
4‐thiazolidinones	derivatives	

Shivaji	Chavan,	Sainath	Zangade,	Archana	Vibhute	and	Yeshwant	Vibhute	*	

Laboratory	of	Organic	Synthesis,	Department	of	Studies	in	Chemistry,	Yeshwant	Mahavidyalaya,	Nanded‐431602,	India	

*Corresponding	author	at:	Laboratory	of	Organic	Synthesis,	Department	of	Studies	in	Chemistry,	Yeshwant	Mahavidyalaya,	Nanded‐431602,	India.		
Tel.:	+91.9960128307;	fax:	+91.2462253726.	E‐mail	address:	drybv@rediffmail.com	(Y.	Vibhute).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	02	December	2012	
Received	in	revised	form:	08	January	2013	
Accepted:	08	January	2013	
Online:	30	June	2013	

KEYWORDS	

	 Several	 2‐azetidinones	 2a‐e	 and	 4‐thiazolidinones	 3a‐e	 have	 been	 synthesized	 from	 halo‐
substituted	 Schiff	 bases	 using	 conventional	 as	 well	 as	 microwave	 technique.	 The	 newly
synthesized	compounds	were	established	on	the	basis	of	spectroscopic	technique.	Further,	all
compounds	 screened	 for	 antimicrobial	 activity	 against	 Bacillus	 subtilis,	 Escherichia	 coli,
Aspergillus	niger	and	Aspergillus	flavus.	Most	of	the	titled	compounds	show	potent	activity.	

Synthesis	
2‐Azetidinones	
4‐Thiazolidinones	
Microwave	technique	
Antimicrobial	activity	
Halosubstituted	Schiff	bases	

	
1.	Introduction	
	

Literature	 survey	 reveals	 that	 most	 of	 the	 compounds	
having	 thiazolidiones	 and	 azetidinones	 nucleus	 possess	
pharmacological	 action	 [1,2].	 Azetidinones,	 which	 are	 part	 of	
antibiotics	 structures	 are	 known	 to	 exhibit	 interesting	
biological	activities.	A	 large	number	of	3‐chloro	monocyclic	β‐
lactam	 possesses	 powerful	 antibacterial,	 antimicrobial,	 anti‐
inflammatory,	 anticonvulsant	 and	 antitubercular	 activities	 [3‐
5].	They	also	function	as	enzyme	inhibitors	and	are	effective	on	
the	 central	 nervous	 system	 [6‐8].	 4‐Thiazolidinones	 and	 its	
derivatives	are	known	 to	possess	a	verity	of	physiological	viz.	
analgesic	 local	 [9]	 and	 spiral	 [10]	 anesthetic,	 central	 nervous	
system	(CNS)	stimulant	[11],	hypnotics	[12],	antibacterial	[13],	
antifungal	[14],	antitubercular	[15]	and	antioxidant	[16].	

The	 classical	 synthesis	 of	 these	 compounds	 involves	
cycloaddition	 of	monochloroacetyl	 chloride	with	 imine	 (Schiff	
base)	 resulting	 in	 formation	 of	 2‐azetidinone	 (β‐lactam)	 [17].	
Conventional	 synthesis	 of	 4‐thiazolidinones	 involves	 the	
cyclocondensation	 reaction	 between	 Schiff	 base	 and	
mercaptoacetic	acid	[18].	The	one	pot	and	convenient	synthesis	
of	 4‐thiazolidinones	 achieved	 by	 the	 reaction	 of	 enaminones	
with	 ethyl	 2‐bromo	 propionate	 [19].	 As	 part	 of	 our	 interest	
towards	the	development	of	novel	heterocycles	[20‐24],	herein	
we	wish	to	report	 the	synthesis	of	2‐azetidinones	2a‐e	and	4‐
thiazolidinones	 3a‐e	 by	 the	 reaction	 of	 imines	 1a‐e	 with	
chloroacetyl	 chloride	 and	 thioglycolic	 acid	 respectively	 using	
conventional	as	well	as	microwave	technique	(Scheme	1).	
	
2.	Experimental	
	
2.1.	Instrumentation		
	

Melting	points	were	determined	 in	 an	open	 capillary	 tube	
and	 are	 uncorrected.	 IR	 spectra	 were	 recorded	 in	 KBr	 on	 a	

Perkin‐Elmer	spectrometer.	1H	NMR	spectra	were	recorded	on	
a	Gemini	300	MHz	instrument	in	DMSO‐d6	as	solvent	and	TMS	
as	 an	 internal	 standard.	 The	mass	 spectra	 were	 recorded	 on	
Shimadzu	 GC/MS	 spectrometer.	 Elemental	 analyses	 were	
performed	 on	 a	 Perkin‐Elmer	 240	 CHN	 elemental	 analyzer.	 A	
multimode	 LG	 domestic	microwave	 (640	Watt)	 oven	 induced	
reactions	were	carried	out	in	an	open	borosil	glass	vessel	under	
atmospheric	pressure.	
	
2.2.	Synthesis	of	Schiff	bases	(1a‐e)	
	

Compound	1a‐e	 is	 synthesized	according	 to	 given	method	
in	literature	[25].	Equimolar	quantities	of	halogeno	substituted	
benzaldehyde	and	substituted	aromatic	amines	were	dissolved	
in	 methanol	 (15	 mL)	 acetic	 acid	 (0.5	 mL)	 was	 added	 and	
refluxed	 for	 2	 hr.	 After	 completion	 of	 reaction	 (monitored	 on	
TLC),	 the	 reaction	 mixture	 was	 cooled	 and	 poured	 in	 water,	
solid	separated	out.	Solid	was	filtered,	washed	with	water	and	
crystallized	from	ethanol	to	give	corresponding	Schiff	bases	1a‐
e.		
	
2.3.	General	procedure	for	preparation	of	2‐azetidinones	
(2a‐e)	
	
2.3.1.	Conventional	technique		
	

A	 solution	 of	 2‐[(2,6‐dichlorophenylimino)‐methyl]3‐
bromo‐4,5‐dimethoxybenzene	 (0.001	 mole,	 0.463	 mg)	 in	 dry	
dioxane	 (15	 mL)	 was	 added	 to	 well	 stirred	 mixture	 of	
chloroacetyl	 chloride	 (0.002	mole)	 and	 triethyl	 amine	 (0.003	
mole)	in	dry	dioxane	at	0‐5	oC.	The	reaction	mixture	was	stirred	
for	6	hr.	Excess	of	solvent	was	distilled.	The	resultant	solid	was	
poured	 into	 ice‐cold	 water.	 The	 separated	 solid	 was	 filtered	
and	recrystallized	from	alcohol	to	give	2e.	
	



Chavan	et	al.	/	European	Journal	of	Chemistry	4	(2)	(2013)	98‐101	 99	
 

	

N

R

R3

H3CO

H3CO

Br R2

Cl
Cl

O

R

OCH3

OCH3

Br

R2

N

R3

O

Cl

HO
SH

O

N
R

R1

OCH3

OCH3

Br

R2

S

O

R3

R1

R1

2a-e 3a-e

1a-e

Dioxane,

Et3N, 0
oC

MW /

Anhyd. ZnCl2,
Reflux
Dioxane

 
	

Scheme	1
	
Table	1.	Physical	and	analytical	data	2‐azetidinones	derivatives.	

Entry	 R	 R1	 R2	 R3	 M.p.,	oC	
Yield,	%	

Conventional		
technique	

Microwave		
technique	

2a	 I	 H	 I	 NO2	 158 68 84	
2b	 I	 H	 I	 Cl	 215 74 90	
2c	 Cl	 I	 H	 Cl	 162 75 89	
2d	 H	 NO2	 H	 I	 180	 70	 86	
2e	 Cl	 H	 H	 Cl	 178 72 88	
	

	
2.3.2.	Microwave	technique	
	

A	 mixture	 of	 2‐[(2,6‐dichlorophenylimino)‐methyl]3‐
bromo‐4,5‐dimethoxybenzene	 (0.001	 mole,	 0.463	 mg)	 in	 dry	
dioxane	 (15	mL)	 was	 taken	 in	 conical	 flask,	 and	 chloroacetyl	
chloride	 (0.002	 mole)	 and	 triethyl	 amine	 (0.003	 mole)	 were	
added	slowly	at	0‐5	oC.	The	reaction	mixture	was	irritated	in	a	
microwave	 oven	 for	 7	 min	 with	 short	 interval	 of	 20	 sec.	 to	
avoid	the	excessive	evaporation	of	solvent.	The	separated	solid	
was	 filtered	 and	 recrystallized	 from	 ethyl	 alcohol	 to	 give	 2e.	
Some	of	 the	physical	data	of	synthesized	compounds	2a‐e	 are	
given	in	Table	1.	

4‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐chloro‐1‐(3,6‐diiodo‐2‐
nitro‐phenyl)‐azetidin‐2‐one	 (2a):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2937	
(Arom.	C‐H	str.),	1672	(C=O	str.),	1468,	1455	(Arom.	C=C	str.),	
1387	(C‐N	str.).	 1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	2.87	(s,	
1H,	‐CH),	3.83	(s,	3H,	OCH3),	3.89	(s,	3H,	OCH3),	5.03	(s,	1H,	CH‐
Cl),	 7.27‐8.08	 (m,	4H,	ArH).	MS	 (EI,	m/z	 (%)):	693.5	 (M+,	80).	
Anal.	 calcd.	 for	 C17H12O5N2I2BrCl:	 C,	 29.41;	 H,	 1.73.	 Found:	 C,	
29.35;	H,	1.75%.	

4‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐chloro‐1‐(2‐chloro‐3,6‐
diiodo‐phenyl)‐azetidin‐2‐one	 (2b):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2934	
(Arom.	C‐H	str.),	1670	(C=O	str.),	1460,	1438	(Arom.	C=C	str.),	
1390	(C‐N	str.).	 1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	2.85	(s,	
1H,	‐CH),	3.86	(s,	3H,	OCH3),	3.88	(s,	3H,	OCH3),	5.05	(s,	1H,	CH‐
Cl),	 7.35‐8.12	 (m,	 4H,	 ArH).	 MS	 (EI,	m/z	 (%)):	 682	 (M+,	 25).	
Anal.	 calcd.	 for	 C17H12O3I2Cl2NBr:	 C,	 29.91;	 H,	 1.75.	 Found:	 C,	
29.95;	H,	1.73%.	

4‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐chloro‐1‐(2,6‐dichloro‐
4‐iodo‐phenyl)‐azetidin‐2‐one	 (2c):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2937	
(Arom.	C‐H	str.),	1670	(C=O	str.),	1482,	1442	(Arom.	C=C	str.),	
1388	(C‐N	str.).	 1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	2.85	(s,	
1H,	‐CH),	3.86	(s,	3H,	OCH3),	3.90	(s,	3H,	OCH3),	5.07	(s,	1H,	CH‐
Cl),	 7.17‐7.98	 (m,	 4H,	 ArH).	 MS	 (EI,	m/z	 (%)):	 590	 (M+,	 40).	
Anal.	 calcd.	 for	 C17H12O3Cl3IBrN:	 C,	 34.57;	 H,	 2.03.	 Found:	 C,	
34.52;	H,	2.06%.	

4‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐chloro‐1‐(2‐iodo‐3‐
nitro‐phenyl)‐azetidin‐2‐one	 (2d):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2943	

(Arom.		C‐H	str.),	1673	(C=O	str.),	1473,	1432	(Arom.	C=C	str.),	
1392	(C‐N	str.).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	2.87	(s,	
1H,	‐CH),	3.89	(s,	3H,	OCH3),	3.90	(s,	3H,	OCH3),	5.02	(s,	1H,	CH‐
Cl),	 7.13‐8.10	 (m,	 5H,	 ArH).	 MS	 (EI,	m/z	 (%)):	 567	 (M+,	 40).	
Anal.	 calcd.	 for	 C17H13O5N2IBrCl:	 C,	 35.97;	 H,	 2.29.	 Found:	 C,	
35.92;	H,	2.32%.	

3‐Chloro‐1‐(2,6‐dichlorophenyl)‐4‐(3‐bromo‐4,5‐dimehtoxy	
phenyl)‐2‐azetidinone	(2e):	FT‐IR	(KBr,	ν,	cm‐1):	2924	(Arom.	C‐
H	str.),	1670	(C=O	str.),	1470,	1450	(Arom.	C=C	str.),	1390	(C‐N	
str.).	 1H	NMR	 (300	MHz,	DMSO‐d6,	 δ,	 ppm):	 2.85	 (s,	 1H,	 ‐CH),	
3.81	(s,	3H,	OCH3),	3.88	(s,	3H,	OCH3),	5.0	(s,	1H,	CH‐Cl),	7.32‐
7.91	(m,	5H,	ArH).	MS	(EI,	m/z	(%)):	464	(M+,	60).	Anal.	calcd.	
for	C17H13O3Cl3BrN:	C,	43.96;	H,	2.58.	Found:	C,	43.90;	H,	2.60%.	
	
2.4.	General	procedure	for	preparation	of	4‐thiazolidinone	
(3a‐e)	
	
2.4.1.	Conventional	technique		
	

A	 mixture	 of	 2‐[(2,6‐dichlorophenylimino)‐methyl]3‐
bromo‐4,5‐dimethoxybenzene	 (0.001	 mole,	 0.462	 mg)	 in	
dioxane	 (15	 ml)	 containing	 anhydrous	 ZnCl2	 (0.01	 g)	 and	
thioglycolic	 acid	 (0.001	 mole)	 was	 refluxed	 for	 8	 hrs.	 The	
reaction	 mixture	 was	 cooled	 and	 poured	 into	 ice	 cold	 water.	
The	 separated	 solid	 was	 filtered	 and	 recrystallized	 from	
dioxane	to	give	3e.		
	
2.4.2.	Microwave	technique	
	

A	 mixture	 of	 2‐[(2,6‐dichlorophenylimino)‐methyl]3‐
bromo‐4,5‐dimethoxybenzene	 (0.01	 mole,	 0.462	 mg)	 in	
dioxane	 (15	 mL)	 containing	 anhydrous	 ZnCl2	 (0.01	 g)	 and	
thioglycolic	 acid	 (0.001	mole)	 was	 irradiated	 in	 a	microwave	
oven	 for	 8‐10	min.	with	 short	 interval	 of	 20	 sec.	 to	 avoid	 the	
excessive	 evaporation	 of	 solvent.	 The	 separated	 solid	 was	
filtered	and	recrystallized	 from	ethyl	alcohol	 to	give	3e.	 Some	
of	 the	physical	data	of	synthesized	compounds	3a‐e	 are	given	
in	Table	2.	



100	 Chavan	et	al.	/	European	Journal	of	Chemistry	4	(2)	(2013)	98‐101	
	
Table	2.	Physical	and	analytical	data	4‐thiazolidinones	derivatives.	

Entry	 R	 R1	 R2	 R3	 M.p.,	oC	
Yield,	%

Conventional		
technique	

Microwave		
technique

3a	 I	 H	 I	 NO2	 162	 70	 82
3b	 I	 H	 I	 Cl	 178	 65	 88
3c	 Cl	 I	 H	 Cl	 190	 60	 84
3d	 H	 NO2	 H	 I	 128	 58	 75	
3e	 Cl	 H	 H	 Cl	 149	 72	 90	
	

2‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐(3,6‐diiodo‐2‐nitro‐
phenyl)‐thiazolidin‐4‐one	 (3a):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2860	
(Arom.	C‐H	str.),	1779	(C=O	str.),	1578,	1522,	1443	(Arom.	C=C	
str.).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.29	 (s,	 1H,	 CH),	
3.74	(s,	3H,	OCH3),	3.80	(s,	3H,	OCH3),	4.91	(s,	2H	CH2S),	7.20‐
8.48	(m,	4H,	ArH).	MS	(EI,	m/z	(%)):	691	(M+,	72).	Anal.	calcd.	
for	 C17H13O5N2I2BrS:	 C,	 29.52;	 H,	 1.88.	 Found:	 C,	 29.57;	 H,	
1.86%.	

2‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐(2‐chloro‐3,6‐diiodo‐
phenyl)‐thiazolidin‐4‐one	 (3b):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2872	
(Arom.		C‐H	str.),	1782	(C=O	str.),	1583,	1532,	1448	(Arom.	C=C	
str.).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.27	 (s,	 1H,	 CH),	
3.72	(s,	3H,	OCH3),	3.79	(s,	3H,	OCH3),	4.92	(s,	2H	CH2S),	7.08‐
8.30	(m,	4H,	ArH).	MS	(EI,	m/z	(%)):	680.5	(M+,	55).	Anal.	calcd.	
for	 C17H13O3I2BrClSN:	 C,	 29.97;	 H,	 1.91.	 Found:	 C,	 29.92;	 H,	
1.93%.	

2‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐(2,6‐dichloro‐4‐iodo‐
phenyl)‐thiazolidin‐4‐one	 (3c):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2883	
(Arom.	C‐H	str.),	1780	(C=O	str.),	1573,	1555,	1460	(Arom.	C=C	
str.).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.28	 (s,	 1H,	 CH),	
3.75	(s,	3H,	OCH3),	3.81	(s,	3H,	OCH3),	4.90	(s,	2H	CH2S),	7.11‐
8.20	(m,	4H,	ArH).	MS	(EI,	m/z	(%)):	588	(M+,	30).	Anal.	calcd.	
for	 C17H13O3Cl2IBrSN:	 C,	 34.69;	 H,	 2.21.	 Found:	 C,	 34.65;	 H,	
2.24%.	

2‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐(2‐iodo‐4‐nitro‐
phenyl)‐thiazolidin‐4‐one	 (3d):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2887	
(Arom.	C‐H	str.),	1783	(C=O	str.),	1578,	1527,	1458	(Arom.	C=C	
str.).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.25	 (s,	 1H,	 CH),	
3.73	(s,	3H,	OCH3),	3.82	(s,	3H,	OCH3),	4.88	(s,	2H	CH2S),	7.07‐
8.10	(m,	5H,	ArH).	MS	(EI,	m/z	(%)):	565	(M+,	75).	Anal.	calcd.	
for	C17H14O5N2IBrS:	C,	36.10;	H,	2.47.	Found:	C,	36.14;	H,	2.44%.	

2‐(3‐Bromo‐4,5‐dimethoxy‐phenyl)‐3‐(2,6‐dichloro‐phenyl)‐
thiazolidin‐4‐one	 (3e):	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2868	 (C‐H	 str.),	
1776	 (C=O	 str.),	 1589,	 1506,	 1446	 (Arom.	 C‐H	 str.).	 1H	 NMR	
(300	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.30	 (s,	 1H,	 CH),	 3.72	 (s,	 3H,	
OCH3),	3.84	(s,	3H,	OCH3),	4.94	(s,	2H,	CH2S),	7.26‐8.52	(m,	5H,	
Ar‐H).	 MS	 (EI,	 m/z	 (%)):	 462	 (M+,	 60).	 Anal.	 calcd.	 for	
C17H14O3Cl2BrSN:	C,	44.15,	H,	3.03.	Found:	C,	44.19;	H,	3.07%.	
	
2.5.	Antimicrobial	activity	
	

The	 antibacterial	 activities	 of	 the	 synthesized	 compounds	
(2a‐e	 and	 3a‐e)	 were	 determined	 by	 agar	 well	 diffusion	
method	 [24,26].	 The	 compounds	 were	 evaluated	 for	
antibacterial	 activity	 against	 Bacillus	 subtilis	 and	 Escherichia	
coli.	 The	 antifungal	 activity	 was	 assessed	 against	 Aspergillus	
niger	 and	 Aspergillus	 flavus.	 The	 antibiotic	 streptomycin	 (25	
μg/mL)	 and	 fluconazole	 used	 as	 reference	 drug	 for	
antibacterial	 and	 antifungal	 activity,	 respectively.	 Dimethyl	
sulphoxide	(1%,	DMSO)	used	a	control	without	compound.	

The	culture	strains	of	bacteria	were	maintained	on	nutrient	
agar	 slant	 at	 37	 ±	 0.5	 oC	 for	 24	 h	 [24,26].	 The	 antibacterial	
activity	was	evaluated	using	nutrient	agar	plate	seeded	with	0.1	
mL	of	 respective	bacterial	 culture	 strain	 suspension	prepared	
in	sterile	saline	(0.85%)	of	105	CFU/mL	dilutions.	The	wells	of	
6	mm	diameter	were	filled	with	0.1	mL	of	compound	solution	
at	 fixed	 concentration	25	μg/mL	separately	 for	 each	bacterial	
strain.	All	plates	were	incubated	at	37	±	0.5	oC	for	24	h.	Zone	of	
inhibition	were	noted	in	mm,	Table	3.		

For	 antifungal	 activity,	 all	 culture	 strains	 of	 fungi	
maintained	on	potato	dextrose	agar	(PDA)	slant	at	27	±	0.2	oC	
for	 24‐48	 h,	 until	 sporulation	 [24,26].	 Spore	 of	 strains	 were	

transferred	 into	 5	mL	of	 sterile	 distilled	water	 containing	1%	
Tweenty‐80	(to	suspend	the	spore	properly).	The	spores	were	
counted	by	haemocytometer	 (106	CFU/mL).	Sterile	PDA	plate	
was	prepared	containing	2%	agar;	0.1	mL	of	each	fungal	spore	
suspension	was	spread	on	each	plate	and	 incubated	at	27±0.2	
oC	 for	 12	 h.	 After	 incubation	well	 prepared	 using	 sterile	 cork	
borer	and	each	agar	well	was	 filled	with	0.1	mL	of	compound	
solution	at	fixed	concentration	25	μg/mL.	The	plates	were	kept	
in	 refrigerator	 for	 20	min	 for	 diffusion	 and	 then	 incubated	 at	
27±0.2	oC	for	7	days.	After	 incubation,	zone	of	 inhibition	were	
measured	in	mm	along	with	standard,	Table	3.	
	
Table	3.	Antimicrobial	activity	of	2‐azetidinones	and	4‐thiazolidinones.		

Entry	
Zone	of	inhibition	in	mm	

Bacillus	
subtilis

Escherichia	
coli

Aspergillus	
niger	

Aspergillus	
flavus

2a 12 12 ‐	 ‐
2b 24 18 20	 18
2c 22 19 17	 18
2d 11 ‐ 12	 09
2e	 14	 ‐	 07	 ‐	
3a 12 16 11	 13
3b	 29	 17	 12	 12	
3c	 25	 26	 19	 24	
3d	 14	 17	 14	 11	
3e 18 15 14	 13
Streptomycin 26 24 ‐	 ‐
Fluconazole ‐ ‐ 25	 27
	
3.	Result	and	discussion	
	
3.1.	Synthesis	
	

In	view	of	the	importance	of	this	class	of	heterocycles	and	
in	 continuation	 of	 our	 earlier	 investigation,	 reported	 the	
synthesis	 of	 4‐thiazolidinones	 from	 imines	 and	 some	 of	 the	
thiazolidinones	 were	 found	 to	 have	 antibacterial	 action	 [27].	
Therefore	 in	 present	 paper,	 we	 synthesized	 new	 class	 of	 2‐
azetidinones	 and	 4‐thiazolidinones	 by	 cyclocondensation	
reaction	of	imines	1a‐e	(Scheme	1).		

The	 starting	 iodoanilines	 required	 for	 the	 preparation	 of	
imines	 were	 prepared	 by	 iodination	 of	 substituted	 anilines	
using	 molecular	 iodine	 and	 iodic	 acid	 by	 refluxing	 technique	
[28].	 Bromination	 of	 3,4‐dimethoxybenzaldehyde	was	 carried	
out	 using	 Br2/acetic	 acid	 as	 brominating	 agent	 to	 yield	 3‐
bromo‐4,5‐dimethoxybenzaldehyde.	 The	 substituted	 iodo‐
anilines	 and	 3‐bromo‐4,5‐dimethoxybenzaldehyde	 on	
condensation	 in	 presence	 of	 slightly	 acidic	 medium	 to	 yield	
Schiff	bases	1a‐e	[25].		

The	 compounds	 1a‐e	 on	 cyclocondensation	 with	
chloroacetyl	 chloride	 affords	 2‐azetidinones,	 2a‐e,	 and	 with	
thioglycolic	 acid	 affords	 4‐thiazolidinones,	 3a‐e,	 using	 both	
conventional	 as	 well	 as	 microwave	 irradiation	 (MWI)	
technique.	 MWI	 technique	 were	 used	 over	 conventional	
technique	 due	 to	 the	 application	 of	 microwave	 (MW)	
irradiation	as	a	nonconventional	energy	source	for	activation	of	
reactions	 has	 now	 become	 a	 very	 popular	 and	 useful	
technology	 in	 organic	 chemistry	 [29].	Many	 researchers	 have	
described	 accelerated	 organic	 reactions	 towards	 proving	 the	
synthetic	utility	of	MW	irradiation	in	routine	organic	synthesis	
[30].	Thus	MW	technique	has	advantage	 including	easy	work‐
up	procedure,	short	reaction	time,	and	does	not	need	effort	for	
isolation	 of	 products	 giving	 high	 percentage	 yields.	 The	
structures	 of	 newly	 synthesized	 compounds	 2a‐e	 and	 3a‐e	
have	been	confirmed	by	elemental	analysis,	IR,	1H	NMR	and	MS	
spectral	studies.		

In	 1H	 NMR	 spectra	 of	 2‐azetidinones	 obtained	 at	 δ	 value	
2.85	ppm	and	δ	near	5.0	ppm	is	due	to	proton	of	CH‐N	and	CH‐
Cl,	 respectively.	 The	 singlet	 of	 three	 proton	 of	 OCH3	 obtained	
near	 at	 δ	 value	 around	 3.85	 ppm.	 The	 1H	 NMR	 spectra	 of	 4‐
thiazolidinones	show	characteristics	δ	value	at	4.90	ppm	due	to	
two	protons	of	‐CH2S.	The	δ	value	at	3.32	ppm	is	due	to	‐CH	of	
five‐membered	thiazolidinone	ring.	



Chavan	et	al.	/	European	Journal	of	Chemistry	4	(2)	(2013)	98‐101	 101	
 

3.2.	Antimicrobial	activity	
	

The	 results	 of	 antimicrobial	 screening	 data	 are	 given	 in	
Table	3.	 In	comparison	with	reference	drugs,	only	compounds	
3c	 showed	 effective	 activity	 against	 all	 tested	 microbes.	
Compounds	 2b	 and	 3b	 showed	 near	 to	 par	 activity	 against	
Bacillus	 subtilis.	 The	 remaining	 compounds	2b,	2c,	3d	and	3e	
displayed	 moderate	 antimicrobial	 activity	 against	 Escherichia	
coli,	Aspergillus	niger	and	Aspergillus	flavus.	On	the	other	hand	
compound	2a,	2d	and	2e	are	inactive	against	Aspergillus	niger,	
Aspergillus	 flavus	 and	 Escherichia	 coli,	 respectively.	 Results	
show	 that	 presence	 of	 halogen	 with	 methoxy	 substituent	 in	
basic	 2‐azetidinones	 and	 4‐thiazolidinone	 nucleus	 exhibits	
potent	antimicrobial	activity	against	various	pathogens.	
	
4.	Conclusion	
	

In	 summary,	 2‐azetidinones	 and	 4‐thiazolidinones	
derivative	have	been	synthesized	from	halo‐substituted	imines	
using	 conventional	 as	 well	 as	 microwave	 technique.	 Percent	
yields	 of	 the	 products	 obtained	 by	 microwave	 technique	 are	
higher	 than	 conventional	 technique.	 Newly	 synthesized	
derivatives	 2b,	 3b	 and	 3c	 showed	 effective	 antimicrobial	
activity	against	tested	microbes.		
	
Acknowledgements	
	

The	 authors	 gratefully	 acknowledge	 University	 Grant	
Commission	 New	 Delhi	 for	 sanctioning	 major	 research	 grant	
(No.	38‐267/2009).	The	authors	are	also	thankful	to	Principal,	
Yeshwant	 Mahavidyalaya,	 Nanded,	 for	 providing	 laboratory	
facilities	and	Director	 Indian	 Institute	of	Chemical	Technology	
(IICT),	 Hyderabad	 for	 providing	 necessary	 instrumental	
facilities.	
	
References	
	
[1]. Dave,	T.	K.;	Purohit,	D.	H.;	Akbari,	J.	D.;	Joshi,	S.	H.	Indian	J.	Chem.	2007,	

46B,	352‐356.		
[2]. Patel,	 R.	 B.;	 Desai,	 P.	 S.;	 Desai,	 K.	 R.;	 Chikhalia,	 K.	 H.	 Indian	 J.	Chem.	

2006,	45B,	773‐778.		
[3]. Vijay,	 K.	 M.	 M.	 J.;	 Nagaraja,	 T.	 S.;	 Shameer,	 H.;	 Jayachandran,	 E.;	

Sreenivasa,	G.	M.	J.	Pharm.	Sci.	Res.	2009,	1,	83‐92.		
[4]. Udupi,	R.	H.;	Kasinath,	N.;	Bhat,	A.	R.	Indian	J.	Heterocycl.	Chem.	1998,	

17,	221‐224.		
[5]. Singh,	G.	S.;	Mbukwa,	E.;	Pheko,	T.	Arkivoc	2007,	9,	80‐90.		
[6]. Chavan,	A.	A.;	Pai,	N.	R.	Molecules	2007,	12,	2467‐2477.		
[7]. Havaldar,	F.	H.;	Mishra,	S.	J.	Indian	J.	Heterocycl.	Chem.	2004,	13,	197‐

200.		
[8]. Patel,	K.	H.;	Metha,	A.	G.	E‐J.	Chem.	2006,	3,	267‐273.		
[9]. Trautman,	H.	D.;	Longe,	L.	M.	J.	Am.	Chem.	Soc.	1948,	70,	3436‐3439.		
[10]. Surray,	A.	R.	J.	Am.	Chem.	Soc.	1949,	71,	3354‐3356.		
[11]. French,	G.	Chem.	Abstr.	1966,	65,	4439‐4445.		
[12]. Doran,	W.	J.;	Sholen,	H.	A.	J.	Org.	Chem.	1938,	3,	193‐197.		
[13]. Kuçukguzel,	G.;	Kocatepe,	A.;	De	Clercq,	E.;	Sahin,	F.;	Gulluce,	M.	Eur.	J.	

Med.	Chem.	2006,	41,	353‐359.	
[14]. Yadav,	R.;	 Srivastav,	 S.	D.;	 Srivastav,	 S.	 K.	 Indian	 J.	Chem.	2005,	44B,	

1262‐1266.		
[15]. Oza,	H.;	Joshi,	D.	Parekh,	H.	Indian	J.	Chem.	1998,	37B,	822‐824.		
[16]. Saundane,	 A.	 R.;	 Yarlakatti,	 M.;	 Walmik,	 P.;	 Katkar,	 V.	 J.	 Chem.	 Sci.	

2012,	124,	469‐481.		
[17]. Patel,	R.	B.;	Desai,	P.	S.;	Desai,	K.	R.;	Chikhalia,	K.	H.	Indian	J.	Chem.	B	

2006,	45,	773‐778.		
[18]. Solankee,	A.	N.;	Patel,	K.	P.;	Patel,	R.	B.	Pelagia	Res.	Lib.	2012,	3,	117‐

122.		
[19]. Bouzroura,	S.;	Bentarzi,	Y.;	Kaoua,	R.;	Nedjar‐koli,	B.;	Poulain‐Martini,	

S.;	Dunach,	E.	Org.	Commun.	2010,	3,	8‐14.		
[20]. Zangade,	 S.	 B.;	Mokle,	 S.	 S.;	 Shinde,	A.	 T.;	 Vibhute,	 Y.	 B.	Green	Chem.	

Lett.	Rev.	2013,	6,	123‐127.	
[21]. Zangade,	S.;	Shinde,	A.;	Patil,	A.;	Vibhute,	Y.	Eur.	J.	Chem.	2012,	3,	208‐

210.		
[22]. Karamunge,	K.	G.;	Sayed,	M.	A.;	Vibhute,	A.	Y.;	Vibhute,	Y.	B.	 J.	Indian.	

Chem.	Soc.	2011,	88,	443‐446.		
[23]. Zangade,	 S.;	 Mokle,	 S.;	 Chavan,	 S.;	 Vibhute,	 Y.	 Orbital:	 Electronic	 J.	

Chem.	2011,	3,	144‐149.		
[24]. Zangade,	S.	B.;	Shinde,	A.	T.;	Vibhute,	A.	Y.;	Vibhute,	Y.	B.	Pak.	J.	Chem.	

2012,	2(1),	18‐23.		

[25]. Chavan,	 S.	 B.;	 Zangade,	 S.	 B.;	 Vibhute,	A.	 Y.	 Vibhute,	 Y.	 B.	Research	 J.	
Pharm.	Bio.	Chem.	Sci.	2012,	3,	262‐269.	

[26]. Bouzroura,	S.;	Bentarzi,	Y.;	Kaoua,	R.;	Nedjar‐Kolli,	B.;	Poulain‐Martini,	
S.;	Dunach,	E.	Org.	Commun.	2010,	3(1),	8‐14.	

[27]. Pawar,	R.	P.;	Andurkar,	N.	M.;	Vibhute,	Y.	B.	J.	Indian.	Chem.	Soc.	1999,	
76,	271‐272.		

[28]. Shinde,	A.	T.;	Zangade,	S.	B.;	Chavan,	S.	B.;	Vibhute,	A.	Y.;	Nalwar,	Y.	S.;	
Vibhute,	Y.	B.	Synth.	Commun.	2010,	40,	3506‐3513.		

[29]. Varma,	S.	Green	Chem.	1999,	1,	43‐55.		
[30]. Borah,	 R.;	 Kalita,	D.	 J.;	 Sarma	 J.	 C.	 Indian	 J.	Chem.	B	2002,	41,	 1032‐

1038.