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European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	

	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2015	Atlanta	Publishing	House	LLC	‐	All	rights	reserved	‐	Printed	in	the	USA	

http://dx.doi.org/10.5155/eurjchem.6.2.98‐106.1161	

	
	

	

	

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

	 	 	

Synthesis,	reactions	and	antimicrobial	activity	of	benzothiazoles	

Eman	Mostafa	Abbas	1,*,	Marwa	Saied	Salem	2,	Asmaa	Fathy	Kassem	1,	
Sherein	Ismail	Abd	El‐Moez	3	and	Mohamed	Youssef	El‐Kady	2	

1	Department	of	Chemistry,	Natural	and	Microbial	Products,	National	Research	Center,	Dokki,	Giza,	12622,	Egypt	
2	Synthetic	Organic	Chemistry	Laboratory,	Chemistry	Department,	Faculty	of	Science,	Ain	Shams	University,	Abbasiya,	Cairo,	11566,	Egypt	
3	Microbiology	and	Immunology	Department,	Veterinary	Division,	National	Research	Center,	Dokki,	Giza,	12622,	Egypt	

*	Corresponding	author	at:	Department	of	Chemistry,	Natural	and	Microbial	Products,	National	Research	Center,	Dokki,	Giza,	12622,	Egypt.		
Tel.:	+2.012.23502762.	Fax:	+2.37161666.	E‐mail	address:	eman_m69@yahoo.com	(E.M.	Abbas).	

	
	

	 	

	 	 	

ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.6.2.98‐106.1161	

Received:	23	September	2014	
Received	in	revised	form:	16	December	2014	
Accepted:	11	January	2015	
Published	online:	30	June	2015	
Printed:	30	June	2015	

	 Benzothiazoles	 have	 been	 proven	 to	 be	 potent	 antimicrobial	 agents.	 In	 this	 study,	 3‐(5,6‐
dimethoxy‐2‐oxo‐1,3‐benzothiazol‐3(2H)‐yl)propanohydrazide	has	been	utilized	as	a	scaffold
for	 synthesis	 of	 pyrrole,	 indolylidene,	 pyrazoles,	 mercaptotriazole,	 oxadiazole,	 triazole	 and
oxothiazolidine	derivatives.	Structures	of	the	synthesized	compounds	were	elucidated	on	the
basis	of	elemental	analyses	and	spectral	data.	All	the	synthesized	compounds	were	screened
for	their	antimicrobial	activity.	

KEYWORDS	
Pyrrole	
Schiff's	base	
Benzothiazole	
Thioglycolic	acid	
Mercaptotriazole	
Antimicrobial	activity	

Cite	this:	Eur.	J.	Chem.	2015,	6(2),	98‐106	

	
1.	Introduction	
	

Despite	 numerous	 attempts	 to	 develop	 new	 structural	
prototype	 in	 the	 search	 for	 more	 effective	 antimicrobials,	
benzothiazoles	still	remain	as	one	of	the	most	versatile	class	of	
compounds	 against	 microbes	 [1‐7]	 and	 therefore,	 they	 are	
useful	substructures	for	further	molecular	exploration.	Benzo‐
thiazole	derivatives	have	attracted	continuing	interest	because	
of	their	various	biological	activities	viz	antitumor	[8‐13],	anti‐
tubercular	 [14],	 antimalarial	 [15],	 anticonvulsant	 [16],	
anthelmintic	 [17],	 analgesic	 [18],	 anti‐inflammatory	 [19]	 and	
antidiabetic	 [20].	 Recently	 benzothiazole	 derivatives	 have	
been	 evaluated	 as	 potential	 amyloidal‐binding	 diagnostic	
agents	 in	 neurodegenerative	 disease	 [21,22]	 and	 as	 selective	
fatty	acid	amide	hydrolase	inhibitors	[23].	The	above	observa‐
tions	 encouraged	 us	 to	 synthesize	 a	 novel	 series	 of	 benzo‐
thiazole	derivatives	and	evaluated	their	antimicrobial	activity.	
	
2.	Experimental		
	
2.1.	Instrumentation	
	

All	melting	points	were	determined	on	an	electrothermal	
Gallenkamp	 apparatus.	 The	 IR	 spectra	 were	 measured	 on	 a	

Pye‐Unicam	 SP300	 instrument	 in	 potassium	 bromide	 discs.	
The	 1	H	NMR	spectra	were	recorded	on	Varian	Mercury	VXR‐
300	 MHz	 spectrometer	 (300	 or	 400	 MHz)	 and	 the	 chemical	
shifts		(ppm)	down	field	from	tetramethylsilane	(TMS)	as	an	
internal	standard.	The	mass	spectra	were	recorded	on	a	GCMS‐
Q1000‐EX	Shimadzu	and	GCMS	5988‐A	HP	spectrometers,	the	
ionizing	 voltage	was	 70	 eV.	 Elemental	 analyses	were	 carried	
out	 by	 the	 Microanalytical	 Center	 of	 Cairo	 University,	 Giza,	
Egypt.	 TLC	 was	 run	 on	 silica	 gel	 G	 coated	 plates	 and	 iodine	
vapor	as	visualizing	agent.	
	
2.2.	Synthesis	
	

Solvents	 were	 generally	 distilled	 and	 dried	 by	 standard	
literature	procedures	prior	to	use.	
	
2.2.1.	Synthesis	of	3‐(5,6‐dimethoxy‐2‐oxobenzothiozol‐3‐
yl)‐propionic	acid	ethyl	ester	(2)	
	

A	mixture	 of	 compound	1	 (2.1	 g,	 0.01	mol),	 ethyl	 bromo	
propanoate	 (1.6	 mL,	 0.01	 mol)	 and	 anhydrous	 potassium	
carbonate	 (0.76	 g,	 0.01	 mol)	 in	 50	 mL	 dry	 acetone	 was	
refluxed	for	10	h.	The	reaction	mixture	was	cooled	and	poured	
onto	ice/cold	water;	the	solid	that	separated	out	was	filtered,	



Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	 99	
 

dried	 and	 recrystallized	 from	 ethanol	 to	 give	 compound	 2	
(Scheme	1).	Color:	Pale	yellow	crystals.	Yield:	80%.	M.p.:	83‐85	
°C.	FT‐IR	(KBr,	ν,	cm‐1):	1719,	1671	(C=O).	1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):	1.19	(t,	3H,	CH2CH3),	2.76	(t,	2H,	CH2),	3.86	
(s,	3H,	OCH3),	3.92	(s,	3H,	OCH3),	4.11	(q,	2H,	CH2CH3),	4.21	(t,	
2H,	 ‐N‐CH2),	 6.74	 (s,	 1H,	 Ar‐H),	 6.77(s,	 1H,	 Ar‐H).	 MS	 (m/z	
(%)):	311	(M+,	100),	296	(40),	266	(5),	211	(5),	196	(15),	180	
(25),	101	(10),	85	(10),	55	(20).	Anal.	calcd.	for	C14H17NO5S:	C,	
54.01;	H,	 5.50;	N,	 4.50;	 S,	 10.30.	 Found:	 C,	 54.08;	H,	 5.57;	N,	
4.49;	S,	10.35%.	
	
2.2.2.	Synthesis	of	3‐(5,6‐dimethoxy‐2‐oxobenzo[d]thiazol‐
3(2H)‐yl)	propanohydrazide	(3)	
	

A	 mixture	 of	 compound	 2	 (3.11	 g,	 0.01	 mol)	 hydrazine	
hydrate	 (98%)	 (2	mL,	0.04	mol)	and	30	mL	absolute	 ethanol	
was	 refluxed	 for	 6	 h.	 The	 reaction	 mixture	 was	 cooled;	 the	
formed	precipitate	was	filtered,	dried	and	recrystallized	from	
acetic	acid	to	give	compound	3	(Scheme	1).	Color:	White	solid.	
Yield:	80%.	M.p.:	192‐194	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3444,	3346,	
3215(NH,	NH2),	1674,	1612	(C=O).	1H	NMR	(400	MHz,	DMSO‐
d6,	 δ,	ppm):	2.38	(t,	2H,	CH2),	3.78,	 (s,	3H,	OCH3),	3.79	(s,	3H,	
OCH3),	3.80	(t,	2H,	‐N‐CH2),	4.09	(s,	2H,	NH2,	exchangeable	by	
D2O),	 7.01	 (s,	 1H,	 Ar‐H),	 7.29	 (s,	 1H,	 Ar‐H),	 9.09	 (s,	 1H,	 NH,	
exchangeable	by	D2O).	MS	(m/z	(%)):	297	(M+,	100),	266	(65),	
224	(60),	196	(50),	180	(15),	87	(10),	55	(50).	Anal.	calcd.	for	
C12H15N3O4S:	 C,	 48.47;	 H,	 5.08;	 N,	 14.13;	 S,	 10.78.	 Found:	 C,	
48.33;	H,	5.37;	N,	14.19;	S,	10.80%.	
	
2.2.3.	Synthesis	of	N‐(3,4‐dichloro‐2,5‐dioxo‐2H‐pyrrol‐1	
(5H)‐yl)‐3‐(5,6‐dimethoxy‐2‐oxobenzo[d]thiazol‐3‐(2H)‐
yl)propanamide	(4)	
	

A	 mixture	 of	 compound	 3	 (0.6	 g,	 0.002	 mol)	 and	
dichloromaleic	 anhydride	 (0.33	 g,	 0.002	mol)	 in	 5	mL	 acetic	
acid	was	refluxed	for	8	h.	The	formed	precipitate	was	filtered,	
dried	and	recrystallized	 from	acetic	acid	 to	give	compound	4	
(Scheme	1).	Color:	Orange	crystals.	Yield:	60%.	M.p.:	226‐228	
°C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3187	 (NH),	 1749,	 1708,	 1661,	 1612	
(C=O).	MS	 (m/z	 (%)):	447	 ([M+2]+,	 17),	 446	 ([M+1]+,	5),	445	
([M]+,	 19),	 430	 (6),	 283	 (7),	 266	 (9),	 196	 (31),	 211	 (22),	 87	
(35).	Anal.	calcd.	for	C16H13Cl2		N3O6S:	C,	43.06;	H,	2.94;	N,	9.42;	
S,	7.19.	Found:	C,	43.33;	H,	2.89;	N,	9.40;	S,	7.20	%.	
	
2.2.4.	Synthesis	of	3‐(5,6‐dimethoxy‐2‐oxobenzothiazol‐3‐
yl)‐propionic	acid	(2‐oxo‐1,2‐dihydro‐indol‐3‐ylidene)	
hydrazide	(5)	
	

To	a	solution	of	compound	3	(0.6	g,	0.002	mol)	in	DMF	(10	
mL)	was	added	isatin(0.3	g,	0.002	mol)	refluxed	for	4	h,	left	to	
cool	 then	 poured	 onto	 crushed	 ice.	 The	 product	 formed	was	
filtered	off	and	recrystallized	from	ethanol	to	give	compound	5	
(Scheme	1).	Color:	Pale	yellow	crystals.	Yield:	80%.	M.p.:	198‐
200	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3450,	 3214	 (NH),	 1669,	 1618,	
1590	(CO).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	3.29	(t,	2H,	
CH2),	3.68,	(s,	3H,	OCH3),	3.75	(s,	3H,	OCH3),	4.23(t,	2H,	N‐CH2),	
6.86	(d,	1H,	Ar‐H),	6.88	(t,	1H,	Ar‐H),	7.11	(s,	2H,	Ar‐H),	7.21(d,	
1H,	Ar‐H),	7.30	(t,	1H,	Ar‐H),	11.22(s,	1H,	NH	exchangeable	by	
D2O),	12.49	 (s,	1H,	NH,	exchangeable	by	D2O).	MS	(m/z	 (%)):	
427([M++1],	10),	426	([M+],	34),	417	(4),	377	(6),	356	(7),	300	
(5),	266	(12),	224	(35),	210	(13)	196	(34),	132	(35),	104	(51),	
77	 (53),	 55	 (100).	 Anal.	 calcd.	 for	 C20H18N4O5S:	 C,	 56.33;	 H,	
4.25;	 N,	 13.14;	 S,	 7.52.	 Found:	 C,	 56.39;	 H,	 4.08;	 N,	 13.23;	 S,	
7.46%.	
	
2.2.5.	Synthesis	of	3‐(3‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐3‐
oxopropyl)‐5,6‐dimethoxybenzo[d]thiazol‐2(3H)‐one	(6)	
	

Refluxing	a	mixture	of	compound	3	(0.6	g,	0.002	mol),	with	
acetyl	acetone	(2	mL,	0.002	mol)	in	15	mL	acetic	acid	for	8	h.	
The	 formed	 precipitate	 after	 cooling	 was	 filtered,	 dried	 and	
recrystallized	 from	 methanol:ethyl	 acetate	 (1:1,	 v:v)	 to	 give	

compound	6	 (Scheme	 1).	 Color:	White	 crystals.	 Yield:	 65	%.	
M.p.:	 189‐191	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1684,	 1610	 (C=O).	 1H	
NMR	(400	MHz,	DMSO‐d6,	 δ,	ppm):	2.21	 (s,	3H,	CH3),	2.33	 (s,	
3H,	 CH3),	 3.51	 (t,	 2H,	 CH2),	 3.86,	 (s,	 3H,	 OCH3),3.90	 (s,	 3H,	
OCH3),	 4.36	 (t,	 2H,	 CH2),	 5.97	 (s,	 1H,	 CH),	 6.77	 (s,	 1H,	 Ar‐H),	
6.96	 (s,	 1H,	 Ar‐H).	 13C	 NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	
14.18,	 14.43	 (2	 CH3),	 33.17,	 39.87	 (2	 CH2),	 56.54	 (2	 OCH3),	
97.33	 (=CH),	 98.42,	 108.16,	 112.29,	 130.31,	 143.52,	 146.87	
(Ar‐C),	 169.77	 (C=O),	 171.59	 (C=N),	 172.43	 (C=O).	 MS	 (m/z	
(%)):	 363	 ([M+2]+,	 4),	 361([M+],	 20),	 360([M+‐1],	 10),	 236	
(12),	 211	 (29),	 151	 (43),	 97	 (69),	 55	 (100).	 Anal.	 calcd.	 for	
C17H19N3O4S:	 C,	 56.50;	 H,	 5.30,	 N,	 11.63;	 S,	 8.87.	 Found:	 C,	
56.71;	H,	5.28,	N,	11.68;	S,	8.90%.	
	
2.2.6.	Synthesis	of	ethyl	5‐amino‐1‐(3‐(5,6‐dimethoxy‐2‐
oxobenzo[d]thiazol‐3(2H)‐yl)propanoyl)‐1H‐pyrazole‐4‐
carboxylate	(7)	
	

A	 mixture	 of	 compound	 3	 (0.6	 g,	 0.002	 mol)	 and	 ethyl	
(ethoxymethylene)	 cyano‐acetate	 (0.34	 g,	 0.002	 mol)	 in	
absolute	ethanol	(20	mL)	was	heated	under	reflux	for	8h.	After	
cooling,	 the	 product	 was	 collected	 by	 filtration	 then	
recrystallized	 from	 ethanol	 to	 give	 compound	7	 (Scheme	 1).	
Color:	White	crystals.	Yield:	74%.	M.p.:	172‐174	°C.	FT‐IR	(KBr,	
ν,	 cm‐1):	 3469,	3357	 (NH2),	1734,	1679,	1613	 (C=O).	 1H	NMR	
(400	MHz,	DMSO‐d6,	δ,	ppm):	1.21(t,	3H,	CH2‐CH3),	2.60	(t,	2H,	
CH2),	3.70,	(s,	3H,	OCH3),	3.77	(s,	3H,	OCH3),	3.78	(q,	2H,	CH2‐
CH3),	 4.17	 (t,	 2H,	 CH2),	 7.00	 (s,	 1H,	 Ar‐H),	 7.29	 (s,	 1H,	 Ar‐H),	
7.71	(s,	1H,	N=CH),	9.97	(s,	2H,	NH2,	exchangeable	by	D2O).	MS	
(m/z	 (%)):	 420	 ([M+],	 40),	 375	 (5),	 353	 (15),	 307	 (10),	 266	
(60),	 237	 (35),	 224	 (50),	 211	 (45),	 196	 (40),	 109	 (25),	 55	
(100).	Anal.	calcd.	for	C18H20N4O6S:	C,	51.42;	H,	4.79;	N,	13.33;	
S,	7.63.	Found:	C,	51.47;	H,	4.68;	N,	13.45;	S,	7.42%.	
	
2.2.7.	Synthesis	of	ethyl	N'‐(3‐(5,6‐dimethoxy‐2‐oxobenzo[d]	
thiazol‐3(2H)‐yl)propanoyl)formohydrazonate	(9)	
	

A	 mixture	 of	 compound	 3	 (0.6	 g,	 0.002	 mol)	 and	
triethylorthoformate	(5	mL)	was	heated	under	reflux	for	12	h.	
After	 cooling,	 the	 solvent	 was	 evaporated	 under	 reduced	
pressure	 and	 the	 solid	 product	 obtained	was	 filtered	 off	 and	
recrystallized	 from	 ethanol	 to	 give	 compound	9	 (Scheme	 1).	
Color:	White	crystals.	Yield:	55%.	M.p.:	135‐137	°C.	FT‐IR	(KBr,	
ν,	 cm‐1):	 3210	 (NH),	 1682,	 1612	 (C=O).	 1H	 NMR	 (400	 MHz,	
DMSO‐d6,	 δ,	 ppm):	 1.29	 (t,	 3H,	 CH2‐CH3),	 2.81(t,	 2H,	 CH2),	
3.77(s,	3H,	OCH3),3.78	(s,	3H,	OCH3),	4.12	(t,	2H,	N‐CH2),	4.15	
(q,	2H,	CH2‐CH3),	7.01	(s,	1H,	Ar‐H),	7.27	(s,	1H,	Ar‐H),	8.09	(s,	
1H,	N=CH),	10.59	 (s,	1H,	NH,	exchangeable	by	D2O).	MS	 (m/z	
(%)):	353([M+],	100),	307	(45),	292	(15),	266	(15),	211	(30),	
196	 (35),	 97	 (25),	 55	 (50).	 Anal.	 calcd.	 for	 C15H19N3O5S:	 C,	
50.98;	H,	 5.42;	N,	 11.89;	 S,	 9.07.	 Found:	 C,	 50.88;	H,	 5.49;	N,	
11.83;	S,	9.23%.	
	
2.2.8.	Synthesis	of	3‐(2‐(5‐mercapto‐1H‐1,2,4‐triazol‐3‐yl)	
ethyl)‐5,6‐dimethoxybenzo[d]thiazol‐2(3H)‐one	(10)	
	

A	 mixture	 of	 compound	 3	 (0.6	 g,	 0.002	 mol)	 and	
ammonium	thiocyanate	 (0.15	g,	0.002	mol)	was	 fused	at	200	
°C	 for	30	min.	The	 solid	mass	was	 triturated	with	hot	water,	
left	 to	cool	and	acidified	with	concentrated	hydrochloric	acid.	
The	 formed	 precipitate	 was	 filtered	 and	 recrystallized	 from	
ethanol	 to	 give	 compound	10	 (Scheme	2).	 Color:	 Pale	 yellow	
crystals.	 Yield:	 77%.	 M.p.:	 208‐210	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	
3171,	(NH),	1646	(C=O).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
2.87	(t,	2H,	CH2),	3.73	(s,	3H,	OCH3),	3.79	(s,	3H,	OCH3),	4.18	(t,	
2H,	N‐CH2),	6.91	(s,	1H,	Ar‐H),	7.26	(s,	1H,	Ar‐H),	7.28	(s,	1H,	
NH,	exchangeable	by	D2O),	11.19	 (s,	1H,	 SH,	exchangeable	by	
D2O).	MS	(m/z	(%)):	339	([M++1],	21),	338	([M+],	58),	323(13),	
311(15),	291(16),	146	(14),	224	(15),	211	(71),	196	(100),	180	
(51),	128	(74),	55	(72).	Anal.	calcd.	for	C13H14N4O3S2:	C,	46.14;	
H,	4.17;	N,	16.56;	S,	18.95.	Found:	C,	46.18;	H,	4.09;	N,	16.39;	S,	
18.82%.	



100	 Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	
	
	

S

H
NH3CO

H3CO

O

Br

S

NH3CO

H3CO

O

COOC2H5

S

NH3CO

H3CO

O

CONHNH2

N2H4.H2O

1

2

3

O

Cl

Cl

O

O

S

NH3CO

H3CO

O

NH
O N

O

O

Cl

Cl

4

S

NH3CO

H3CO

O

NH

O

N
CHOC2H5

9

S

NH3CO

H3CO

O

N
N

O
CH3

H3C

6

EtO

H CN

COOEt S

NH3CO

H3CO

O

N

O

N

H2N

COOEt

7

5

EtO

O

O O

S

NH3CO

H3CO

O

O

N
N

8

S

N
H3CO

H3CO
O

NH
O

N

NH
O

N
H

O

O

CH(OC2H5)3

 
	

Scheme	1
	
	
2.2.9.	Synthesis	of	1‐(3‐(5,6‐dimethoxy‐2‐oxobenzo[d]thia	
zol‐3‐(2H)‐yl)propanoyl)‐4‐methylthio‐semicarbazide	(11)	
	

A	mixture	 of	 compound	3	 (0.6	 g,	 0.002	mol)	 and	methyl	
isothiocyanate	(0.15	g,	0.002	mol)	in	10	mL	DMF	was	refluxed	
for	6	h.	After	cooling	pouring	onto	ice/cold	water,	acidified	by	
hydrochloric	 acid,	 the	 formed	 precipitate	 was	 filtered	 dried	
and	 recrystallized	 from	 methanol	 to	 give	 compound	 11	
(Scheme	2).	Color:	White	 crystals.	Yield:	70	%.	M.p.:	192‐194	
°C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3395,	 3329,	 3199	 (NH),	 1650,	 1610	
(C=O),	1249	(C=S).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.47	
(t,	2H,	CH2),	2.82	(d,	3H,	CH3),	3.71,	(s,	3H,	OCH3),	3.79	(s,	3H,	
OCH3),	4.13	(t,	2H,	N‐CH2),	7.02	(s,	1H,	Ar‐H),	7.31	(s,	1H,	Ar‐
H),	 7.78	 (s,	 1H,	 NH,	 exchangeable	 by	 D2O),	 9.17	 (s,	 1H,	 NH,	
exchangeable	by	D2O),	9.80	(s,	1H,	NH,	exchangeable	by	D2O).	
MS	(m/z	(%)):	371	[(M++1],	61),	370	([M+],	80),	351	(74),	338	
(61),	 318	 (95),	 296	 (77),	 279	 (70),	 257	 (78),	 232	 (78),	 198	
(74),	167	(86),	73	(100),	51	(70).	Anal.	calcd.	for	C14H18N4O4S2:	
C,	45.39;	H,	4.90;	N,	15.12;	S,	17.31.	Found:	C,	45.42;	H,	4.87;	N,	
15.18;	S,	17.16%.	

2.2.10.	Synthesis	of	5,6‐dimethoxy‐3‐(2‐(5‐thioxo‐4,5‐
dihydro‐1,3,4‐oxadiazol‐2‐yl)ethyl)benzo[d]thiazol‐2(3H)‐
one	(12)	
	

A	mixture	 of	 compound	3	 (0.6	 g,	 0.002	mol)	 and	 carbon	
disulfide	 (6	 mL)	 in	 pyridine	 (10	 mL)	 and	 DMF	 (5	 mL)	 was	
heated	under	 reflux	 on	water	 bath	 for	 8	 h.	 After	 cooling,	 the	
solvent	was	 evaporated	 under	 reduced	 pressure	 and	 residue	
was	triturated	with	an	ice‐	water	mixture	and	neutralized	with	
diluted	HCl.	The	solid	precipitate	 formed	was	 filtered	off	 and	
recrystallized	 from	 ethanol	 to	 afford	 compound	 12	 (Scheme	
2).	 Color:	 Pale	 yellow	 crystals.	 Yield:	 99%.	M.p.:	 110‐112	 °C.	
FT‐IR	 (KBr,	 ν,	 cm‐1):	 3152	 (NH),	 1658	 (C=O),	 1208	 (C=S).	 1H	
NMR	 (400	MHz,	DMSO‐d6,	 δ,	 ppm):	3.34	 (t,	 2H,	CH2),	 3.77	 (s,	
3H,	OCH3),	3.80	(s,	3H,	OCH3),	4.27	(t,	2H,	N‐CH2),	6.97	(s,	1H,	
Ar‐H),	 7.29	 (s,	 1H,	 Ar‐H),	 14.30	 (s,	 1H,	 NH.	 exchangeable	 by	
D2O).	 13C	NMR	 (400	MHz,	DMSO‐d6,	 δ,	 ppm):	 16.84,	 23.80	 (2	
CH2),	 56.65	 (2	 OCH3),	 97.31,	 107.37,	 111.65,	 127.91,	 130.23,	
142.25	(Ar‐C),	155.07	(C=N),	164.18	(C=S),	169.83(C=O).		

	



Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	 101	
 

	

 
	

Scheme	2
	
	
MS	(m/z	(%)):	339	([M+],	100),	324	(5),	283	(15),	264	(10),	

224	(20),	211	(40),	196	(65),	180	(25),	143	(15),	108	(10),	55	
(15).	Anal.	calcd.	for	C13H13N3O4S2	:	C,	46.01;	H,	3.86;	N,	12.38;	
S,	18.90.	Found:	C,	45.08;	H,	3.62;	N,	12.29;	S,	18.93%.	
	
2.2.11.	Synthesis	of	3‐(2‐(4‐amino‐5‐thioxo‐4,5‐dihydro‐1H‐
1,2,4‐triazol‐3‐yl)ethyl)‐5,6‐dimethoxybenzo[d]thiazol‐2	
(3H)‐one	(13)	
	

A	mixture	of	the	oxadiazolinethione	12	(0.34	g,	0.001	mol)	
and	hydrazine	hydrate	(3	mL)	in	absolute	ethanol	(20	mL)	was	
heated	 under	 refluxed	 6	 h.	 After	 cooling,	 the	 solvent	 was	
removed	 in	 vacuum	 and	 the	 residue	 obtained	was	 triturated	
with	 water.	 The	 solid	 product	 formed	 was	 filtered	 off	 and	
recrystallized	 from	 ethanol	 to	 afford	 compound	 13	 (Scheme	
2).	 Color:	White	 crystals.	 Yield:	 80%.	M.p.:	 150‐152	 °C.	 FT‐IR	
(KBr,	ν,	cm‐1):	3194,	2952	(NH,	NH2),	1646	(C=O),	1203	(C=S).	
1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):2.97	(t,	2H,	CH2),	3.77	(s,	
3H,	OCH3),	3.79	(s,	3H,	OCH3),	4.18	(t,	2H,	N‐CH2),	5.15	(s,	1H,	
NH	 exchangeable	 by	D2O),	 6.00	 (s,	 2H,	NH2,	 exchangeable	 by	
D2O),	6.98	(s,	1H,	Ar‐H),	7.30	(s,	1H,	Ar‐H).	MS	(m/z	(%)):	353	
([M+],	 10),	 297	 (25),	 282	 (5),	 266	 (25),	 224	 (30),	 211	 (100),	
196	(70),	168	(20),	140	(20),	108	(25),	57	(55).	Anal.	calcd.	for	
C13H15N5O3S2:	 C,	 44.18;	 H,	 4.28;	 N,	 19.82;	 S,	 18.15.	 Found:	 C,	
44.30;	H,	4.19;	N,	19.86;	S,	18.09%.	
	
2.2.12.	Synthesis	of	5,6‐dimethoxy‐3‐(2‐(5‐((2‐morpholino	
ethyl)thio)‐1,3,4‐oxadiazol‐2‐yl)ethyl)benzo[d]thiazol‐
2(3H)‐one	(14)	
	

A	mixture	of	the	oxadiazolethione	12	 (0.68	g,	0.002	mol),	
sodium	 acetate	 (0.38	 g,	 0.002	 mol)	 and	 4‐(2‐chloroethyl)	

morpholine	hydrochloride	 (0.37	 g,	 0.002	mol)	 in	 ethanol	 (30	
mL)	 was	 heated	 under	 reflux	 for	 6	 h.	 The	 solvent	 was	
evaporated	 and	 the	 residue	 was	 triturated	 with	 water.	 The	
solid	 product	 formed	 was	 collected	 by	 filtration	 and	
recrystallized	 from	 ethanol	 to	 give	 afford	 compound	 14	
(Scheme	2).	Color:	Bright	gray	crystals.	Yield:	80%.	M.p.:	85‐87	
°C.	FT‐IR	(KBr,	ν,	cm‐1):	1662	(C=O).	1H	NMR	(400	MHz,	DMSO‐
d6,	δ,	ppm):	1.66	(t,	4H,	OCH2),	2.54	(t,	4H,	N‐CH2),	2.56	(t,	2H,	
CH2),	3.19	(t,	2H,	S‐CH2‐CH2‐N),	3.23	(t,	2H,	S‐CH2‐CH2‐N),	3.70	
(s,	3H,	OCH3),	3.78	 (s,	3H,	OCH3),	 4.28	 (t,	2H,	N‐CH2),	6.96	 (s,	
1H,	 Ar‐H),	 7.29	 (s,	 1H,	 Ar‐H).	MS	 (m/z	 (%)):	 453([M+1]+,	 4),	
452	([M]+,	5),	450	(3),	430	(3),	414	(4),	392	(6),	375	(5),	351	
(4),	339	(12),	288	(5),	255	(5),	211	(6),	196	(8),	113	(36),	100	
(100),	85	(16),	70	(12),	55	(16).	Anal.	calcd.	for	C19H24N4O5S2:	
C,	50.43;	H,	5.35;	N,	12.38;	S,	14.17.	Found:	C,	50.30;	H,	5.27;	N,	
12.43;	S,	14.22%.	
	
2.2.13.	General	procedure	for	preparation	of	Schiff's	base	
compounds	15a‐h	
	

To	a	solution	of	compound	3	(0.6	g,	0.002	mol)	in	absolute	
ethanol	 (20	 mL)	 containing	 glacial	 acetic	 acid	 (5	 mL)	 was	
added	 different	 aromatic	 aldehydes	 (0.01	 mol)	 the	 reaction	
mixture	 was	 refluxed	 for	 5	 h.	 Then	 cooled,	 poured	 onto	
crushed	 ice.	 The	 product	 was	 filtered	 off	 and	 recrystallized	
from	acetic	acid	to	give	15a‐h	(Scheme	3).	

3‐(5,6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐propionic	 acid	
(4‐fluoro‐benzylidene)‐hydrazide	 (15a):	 Color:	 Pale	 white	
crystals.	 Yield:	 85%.	 M.p.:	 180‐183	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	
3141	(NH),	1606	(C=N),	1711,	1672	(C=O).		

	
	



102	 Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	
	

	

 
	

Scheme	3
	
	
1H	 NMR	 (400	MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.31	 (t,	 2H,	 CH2),	

3.68,	 (s,	3H,	OCH3),	3.78	(s,	3H,	OCH3),	4.23	(t,	2H,	CH2),	7.05	
(d,	1H,	Ar‐H),	7.06	(d,	1H,	Ar‐H),	7.13	(s,	1H,	Ar‐H),	7.20	(d,	1H,	
Ar‐H),	7.27	(d,	1H,	Ar‐H),	7.52	(s,	1H,	Ar‐H),	7.87	(s,	1H,	N=CH),	
11.38(s,	 1H,	 NH,	 exchangeable	 by	 D2O.).	 MS	 (m/z	 (%)):	 404	
([M++1],	15),	403	([M+],	69),	266	(13),	244	(27),	211	(84),	196	
(57),	 193	 (49),	 168	 (14),	 150	 (8),	 55	 (100).	 Anal.	 calcd.	 for	
C19H18FN3O4S:	 C,	 56.57;	 H,	 4.50;	 N,	 10.42;	 S,	 7.95.	 Found;	 C,	
56.49;	H,	4.31;	N,	10.49;	S,	7.36%.	

3‐(5,6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐propionic	 acid	
(2‐chloro‐benzylidene)‐hydrazide	 (15b):	 Color:	White	 crystals.	
Yield:	80	%.	M.p.:	120‐122	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3184	(NH),	
1598	 (C=N),	 1669	 (C=O).	 1H	 NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	
ppm):2.97	(t,	2H,	CH2),	3.77	(s,	3H,	OCH3),	3.80	(s,	3H,	OCH3),	
4.22	(t,	2H,	N‐CH2),6.99	(d,	1H,	Ar‐H),	7.01	(s,	1H,	Ar‐H),	7.08	
(m,	1H,	Ar‐H),	7.22	 (m,	1H,	Ar‐H),	7.39	 (d,	1H,	Ar‐H),	8.21	(s,	
1H,	Ar‐H),	8.92	(s,	1H,	N=CH),	11.47	(s,	1H,	NH,	exchangeable	
by	D2O).	MS	(m/z	 (%)):	421	([M+1]+,	21),	419	([M]+,	55),	266	
(18),	224	(30),	211	(97),	196	(62),	168	(15),	137	(28),	89	(30),	
55	 (100).	 Anal.	 calcd.	 for	 C19H18ClN3O4S:	 C,	 54.35;	H,	 4.32;	N,	
10.01;	S,	7.64.	Found:	C,	54.40;	H,	4.29;	N,	10.13;	S,	7.36%.	

3‐(5,6‐Dimehoxy‐2‐oxo‐benzothiazole‐3‐yl)‐propionic	 acid	
(1,4‐diphenyl‐1H‐pyrazol‐3‐ylmethylene)‐hydrazide	 (15c):	
Color:	Pale	white	crystals.	Yield:	80	%.	M.p.:	205‐207	°C.	FT‐IR	
(KBr,	 ν,	 cm‐1):	 3127	 (NH),	 1599(C=N),	 1680	 (C=O).	 1H	 NMR	
(400	 MHz,	 DMSO‐d6,	 δ,	 ppm):2.86	 (t,	 2H,	 CH2),	 3.76	 (s,	 3H,	
OCH3),3.79	(s,	3H,	OCH3),	4.18	(t,	2H,	N‐CH2),	7.03	(s,	1H,	Ar‐
H),	7.25	(s,	1H,	Ar‐H),	7.32	(m,	3H,	Ar‐H),	7.47	(m,	3H,	Ar‐H),	
7.59	(d,	2H,	Ar‐H),	7.86	(d,	2H,	Ar‐H),	8.01	(s,	1H,	Ar‐H),	8.90	
(s,	 1H,	 N=CH),	 11.21	 (s,	 1H,	 NH,	 exchangeable	 by	 D2O).	 MS	
(m/z	(%)):	527	([M]+,	15),	526	([M‐1]+,	15),	428	(15),	317	(11),	
282	(28),	245	(55),	196	(47),	147	(18),	77	(100),	55	(81).	Anal.	
calcd.	 for	 C28H25	 N5O4S:	 C,	 63.74;	 H,	 4.78;	 N,	 13.27;	 S,	 6.08.	
Found:C,	63.80;	H,	4.61;	N,	13.42;	S,	6.10%.	

3‐(5,6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐propionic	 acid	
(2‐nitro‐benzylidene)‐hydrazide	 (15d):	 Color:	 Yellow	 crystals.	

Yield:	85	%.	M.p.:	237‐239	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3274	(NH),	
1651	(C=N),	1697(C=O).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
3.26	(t,	2H,	CH2),	3.69	(s,	3H,	OCH3),	3.78	(s,	3H,	OCH3),	4.23(t,	
2H,	N‐CH2),	7.06	 (d,	1H,	Ar‐H),	7.07(s,	1H,	Ar‐H),	7.12	 (s,	 1H,	
Ar‐H),	7.57	(t,	1H,	Ar‐H),7.89	(d,	1H,	Ar‐H),	7.98	(s,	1H,	Ar‐H),	
8.25	 (s,	 1H,	N=CH),	 11.62	 (s,	 1H,	NH,	 exchangeable	 by	D2O.).	
MS	(m/z	(%)):	432	([M++2],	5),	431	([M++1],	8),	430	([M+],	27),	
211	 (23),	 196	 (30),	 77	 (8),	 55	 (100).	 Anal.	 calcd.	 for	 C19H18	

N4O6S:	C,	53.02;	H,	4.22;	N,	13.02;	S,	7.45.	Found:	C,	53.31;	H,	
4.40;	N,	13.11;	S,	7.23%.		

3‐(5,6‐dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐propionic	 acid	
(3‐nitro‐benzylidene)‐hydrazide	 (15e):	 Color:	 White	 solid.	
Yield:	85	%.	M.p.:	238‐240	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3222	(NH),	
1640	 (C=N),	 1710	 (C=O).	 1H	 NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	
ppm):	3.22	(t,	2H,	CH2),	3.69	(s,	3H,	OCH3),	3.81	(s,	3H,	OCH3),	
4.23	(t,	2H,	N‐CH2),	7.16	(s,	1H,	Ar‐H),	7.89	(d,	2H,	Ar‐H),	7.96	
(s,	1H,	Ar‐H),	8.11	(d,	2H,	Ar‐H),	8.23	(s,	1H,	N=CH),	11.69	(s,	
1H,	NH,	exchangeable	by	D2O).	MS	(m/z	(%)):	430	([M+],	0.4),	
419	(7),	266	(5),	224	(3),	211	(11),	196	(9),	180	(8),	118	(20),	
55	 (100).	 Anal.	 calcd.	 for	 C19H18	 N4O6S:	 C,	 53.02;	 H,	 4.22;	 N,	
13.02;	S,	7.45.	Found:	C	53.12;	H,	4.41;	N,	13.11;	S,	7.30%.	

3‐(5,6‐dimethoxy‐2‐oxobenzothiazol‐3‐yl)	 propionic	 acid	
(3,4,5‐trimethoxy‐benzylidene)‐hydrazide	 (15f):	 Color:	 White	
crystals.	 Yield:	 85	 %.	 M.p.:	 189‐191	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐

1):3175	 (NH),	 1595(C=N),	 1682	 (C=O).	 1H	 NMR	 (400	 MHz,	
DMSO‐d6,	δ,	ppm):	3.19	(t,	2H,	CH2),	3.82	(s,	6H,	2OCH3),	3.92	
(s,	 9H,	 3OCH3),	 4.34	 (t,	 2H,	 N‐CH2),	 6.83‐7.64	 (m,	 4H,	 Ar‐H),	
8.03	(s,	1H,	N=CH),	9.53	(s,	1H,	NH,	exchangeable	by	D2O.).	MS	
(m/z	(%)):	476	([M+1]+,	17),	474	([M]+,	35),	429	(5),	302	(15),	
266	(32),	196	(51),	94	(18),	77	(11),	55	(100).	Anal.	calcd.	for	
C22H25	N3O7S:C,	55.57;	H,	5.30;	N,	8.84;	S,	6.74.	Found:	C,	55.47;	
H,	5.29;	N,	8.86;	S,	6.83%.	

3‐(5,6‐dimethoxy‐2‐oxobenzothiazol‐3‐yl)	propionic	acid	(4‐
dimethylamino‐benzylidene)‐hydrazide	 (15g):	 Color:	 White	
crystals.	 Yield:	 80	%.	 M.p.:	 178‐180	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	
3203	 (NH),	 1599	 (C=N),	 1670	 (C=O).	 1H	 NMR	 (400	 MHz,	



Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	 103	
 

DMSO‐d6,	δ,	ppm):	2.89	(s,	6H,	2CH3),	2.91	(t,	2H,	CH2),	3.77	(s,	
3H,	OCH3),	3.79	(s,	3H,	OCH3),	4.20	(t,	2H,	N‐CH2),	6.59	(d,	1H,	
Ar‐H),	6.61	(d,	1H,	Ar‐H),7.05	(s,	1H,	Ar‐H),	7.22	(d,	1H,	Ar‐H),	
7.26	(d,	1H,	Ar‐H),	7.74	(s,	1H,	Ar‐H),	7.90	(s,	1H,	N=CH),	11.08	
(s,	1H,	NH,	exchangeable	by	D2O).	MS	(m/z	(%)):	429	([M+1]+,	
15),	428	([M]+,	54),	427	([M‐1]+,	17),	266	(15),	218	(56),	146	
(100),	132	(29),	55	(94).	Anal.	calcd.	for	C21H24	N4O4S:	C,	58.86;	
H,	5.65;	N,	13.07;	S,	7.48.	Found:	C,	58.63;	H,	5.72;	N,	13.13;	S,	
7.39%.	

3‐(5,	 6‐Dimehoxy‐2‐oxo‐benzothiazol‐3‐yl)‐propionic	 acid	
(5‐methyl‐furan‐2‐ylmethylene)‐hydrazide	 (15h):	 Color:	White	
crystals.	 Yield:	 85%.	 M.p.:	 110‐112	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	
3127	 (NH),	 1596	 (C=N),	 1672	 (C=O).	 1H	 NMR	 (400	 MHz,	
DMSO‐d6,	δ,	ppm):	1.23	(s,	3H,	CH3),	3.15	(t,	2H,	CH2),	3.86	(s,	
3H,	OCH3),	3.89	(s,	3H,	OCH3),	4.31	(t,	2H,	‐N‐CH2),	6.16	(d,	1H,	
=	CH.	furan),	6.59	(s,	1H,	Ar‐H),	6.89	(d,	1H,	=CH.	furan),	7.52	
(s,	 1H,	 Ar‐H),	 8.47	 (s,	 1H,	 N=CH),	 10.24(s,	 1H,	 NH,	
exchangeable	by	D2O.).	MS	(m/z	(%)):	389	([M]+,	80),	311	(15),	
296	(5),	266	(35),	224	(25),	196	(55),	179	(75),	108	(35),	79	
(25),	55	(100).	Anal.	calcd.	for	C18H19	N3O5S	(389.1):	C,	55.52;	
H,	4.92;	N,	10.79;	S,	8.23.	Found:	C,	55.60;	H,	4.98;	N,	10.62;	S,	
8.33%.	
	
2.2.14.	General	method	for	preparation	of	oxathiazolidin	
compound	16a‐e	
	

Thioglycolic	 acid	 (0.01	mol)	was	 added	 to	 a	well	 stirred	
solution	of	Schiff’s	bases	(0.01	mol)	15a‐d	in	dry	benzene	(50	
mL).	 Then	 refluxed	 for	 5	 h	 and	 excess	 of	 solvent	 was	
evaporated	 under	 reduced	 pressure	 and	 the	 residue	 was	
washed	 by	 2%	 NaHCO3,	 then	 treated	 with	 petroleum	 ether.	
The	 solid	 product	 was	 filtered	 off,	 washed	 with	 petroleum	
ether,	 and	 then	 recrystallized	 from	 methanol	 to	 give	
compound	16a‐e,	respectively	(Scheme	3).	

3‐(5,	 6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐N‐(2‐(4‐fluro‐
phenyl)‐4‐oxo‐thiazolidin‐3‐yl)‐propanamide	(16a):	Color:	Pale	
white	 crystals.	 Yield:	 65	%.	 M.p.:	 230‐232	 °C.	 FT‐IR	 (KBr,	 ν,		
cm‐1):	3315	(NH),	1725,	1657,	1611	(C=O).	1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):3.67	(s,	3H,	OCH3),	3.71	(s,	3H,	OCH3),	3.81	
(t,	2H,	CH2),	3.92	(t,	2H,	‐N‐CH2),	4.00	(m,	2H,	‐S‐CH2),	5.50	(s,	
1H,	‐N‐CH),	6.96	(s,	1H,	Ar‐H),	7.12	(d,	2H,	Ar‐H),	7.14	(d,	2H,	
Ar‐H),	 7.32	 (s,	 1H,	 Ar‐H),	 10.20	 (s,	 1H,	 NH,	 exchangeable	 by	
D2O).	MS	(m/z	(%)):	478	([M+1]+,	4),	477	([M]+,	11),	467	([M‐
1]+,	6),	282	(8),	266	(9),	224	(12),	212	(9),	196	(56),	122	(31),	
55	 (100).	 Anal.	 calcd.	 for	 C21H20FN3O5S2:	 C,	 52.82;	H,	 4.22;	N,	
8.80;	S,	13.43.	Found:	C,	52.70;	H,	4.32;	N,	8.73;	S,	13.50%.		

N‐[2‐(4‐Chloro‐phenyl)‐4‐oxo‐thiazolidin‐3‐yl)‐3‐(5,	6‐dimet	
hoxy‐2‐oxo‐benzothiazol‐3‐yl)‐propionamide	(16b):	Color:	Pale	
white	 crystals.	 Yield:	 65	%.	 M.p.:	 140‐142	 °C.	 FT‐IR	 (KBr,	 ν,		
cm‐1):	3237	(NH),	1726,	1671,	1595	(C=O).	1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):	2.52	(t,	2H,CH2),	3.78,(s,	3H,	OCH3),	3.80	(s,	
3H,	OCH3),	3.83	(q,	2H,	‐S‐CH2),	4.07	(t,	2H,	‐N‐CH2),	5.90	(s,	1H,	
‐N‐CH),	6.94	(s,	1H,	Ar‐H),	7.28	(s,	1H,	Ar‐H),	7.32‐7.41(m,	4H,	
Ar‐H),	10.42	(s,	1H,	NH,	exchangeable	by	D2O).	 13C	NMR	(400	
MHz,	 DMSO‐d6,	 δ,	 ppm):	 29.12,	 31.84,	 39.82(3	 CH2),	 56.59,	
56.70	(2	OCH3),	58.88	(‐N‐CH),	97.79,	107.26,	111.71,	128.26,	
130.32,	130.51,	130.67,	132.57,	136.00,	146.24,	149.08	(Ar‐C),	
169.62,	 169.72,	 171.07	 (3C=O).	MS	 (m/z	 (%)):	 493	 ([M]+,	 1),	
411	 (10),	 266	 (13),	 211	 (100),	 196	 (48),	 168	 (17),	 55	 (61).	
Anal.	 calcd.	 for	 C21H20ClN3O5S:	 C,	 51.06;	 H,	 4.08;	 N,	 8.51;	 S,	
12.98.	Found:	C,	51.32;	H,	4.21;	N,	8.10;	S,	12.61%.		

3‐(5,	 6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐N‐[2‐(1,	 4‐di	
phenyl‐1H‐pyrazol‐3‐yl)‐4‐oxo‐thiazolidin‐3‐yl]‐propionamide	
(16c):	Color:	Pale	white	crystals.	Yield:	60	%.	M.p.:	128‐130	°C.	
FT‐IR	 (KBr,	 ν,	 cm‐1):	 3281	 (NH),	 1720,	 1661,	 1597	 (C=O).	 1H	
NMR	 (400	MHz,	DMSO‐d6,	 δ,	 ppm):	 2.46	 (t,	 2H,	 CH2),	 3.62	 (t,	
2H,	‐N‐CH2),	3.68	(s,	3H,	OCH3),	3.69	(s,	3H,	OCH3),	3.72	(q,	2H,	
‐S‐CH2),	5.86	(s,	1H,	‐N‐CH),	7.15‐8.55	(m,	13H,	Ar‐H),	10.37	(s,	
1H,	NH,	exchangeable	by	D2O).	MS	(m/z	(%)):	602	([M+1]+,	3),	
600	 ([M‐1]+,	 2),	 585	 (3),	 524	 (2),	 431	 (3),	 318	 (27),	 277	 (6),	
263	(17),	246	(21),	211	(27),	196	(16),	168	(10),	108	(20),	77	

(95),	55	(100).	Anal.	calcd.	for	C30H27N5O5S2:	C,	59.88;	H,	4.52;	
N,	11.64;	S,	10.66	.Found:	C,	59.79;	H,	4.60;	N,	11.36;	S,	10.81%.	

3‐(5,	 6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐N‐[2‐(2‐nitro‐
phenyl)‐4‐oxo‐thiazolidin‐3‐yl]‐propionamide	 (16d):	 Color:	
Pale	white	crystals.	Yield:	65	%.	M.p.:	237‐239	°C.	FT‐IR	(KBr,	
ν,	 cm‐1):3120	 (NH),	 1722,	 1670,	 1625	 (3	 C=O).	 1H	NMR	 (400	
MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.13	 (t,	 2H,	 CH2),	 3.74(s,	 3H,	 OCH3),	
3.76	 (s,	 3H,	 OCH3),	 3.92	 (q,	 2H,	 ‐S‐CH2),	 4.03	 (t,	 2H,	 ‐N‐CH2),	
5.72	(s,	1H,	‐N‐CH),	6.92	(s,	1H,	Ar‐H),	7.24	(s,	1H,	Ar‐H),	7.63	
(m,	 3H,	 Ar‐H),	 8.14	 (s,	 1H,	 Ar‐H),	 10.30	 (s,	 1H,	 NH,	
exchangeable	 by	 D2O).	 MS	 (m/z	 (%)):	 505	 ([M+1]+,	 2),	 504	
([M]+,	5),	503	([M‐1]+,	3),	282	(3),	223	(24),	211	(22),	196	(13),	
55	 (100).	 Anal.	 calcd.	 for	 C21H20N4O7S2:	 C,	 49.99;	 H,	 4.00;	 N,	
11.10;	S,	12.71.	Found:	C,	49.71;	H,	4.32;	N,	11.36;	S,	12.52%.		

3‐(5,	 6‐Dimethoxy‐2‐oxo‐benzothiazol‐3‐yl)‐N‐[2‐(3‐nitro‐
phenyl)‐4‐oxo‐thiazolidin‐3‐yl]‐propionamide	(16e):	Color:	Pale	
white	crystals.	Yield:	65	%.	M.p.:	198‐200	°C.	FT‐IR	(KBr,	ν,	cm‐

1):3332	 (NH),	 1733,	 1674,	 1600	 (C=O).	 1H	 NMR	 (400	 MHz,	
DMSO‐d6,	δ,	ppm):	3.29	(t,	2H,	CH2),	3.68	(s,	3H,	OCH3),	3.71	(s,	
3H,	OCH3),	4.03	(t,	2H,	‐NCH2),	4.06	(q,	2H,	SCH2),	5.65	(s,	1H,	‐
NCH),	6.14	(s,	1H,	Ar‐H),	7.24	(s,	1H,	Ar‐H),	7.29	(d,	2H,	Ar‐H),	
8.12	(d,	2H,	Ar‐H),	10.30	(s,	1H,	NH,	exchangeable	by	D2O).	MS	
(m/z	 (%)):	 505	 ([M+1]+,	 16),	 504	 ([M]+,	 24),	 498	 (18),	 468	
(13),	 461	 (22),	 435	 (20),	 420	 (29),	 408	 (34),	 303	 (31),	 276	
(25),	212	(26),	195	(23),	132	(59),	91(100),	77	(54),	55	(22).	
Anal.	 calcd.	 for	 C21H20N4O7S2:	 C,	 49.99;	 H,	 4.00;	 N,	 11.10;	 S,	
12.71.	Found:	C,	49.75;	H,	4.09;	N,	11.23;	S,	12.59%.	
	
2.2.15.	Synthesis	of	3‐(5,6‐dimethoxy‐2‐oxo‐benzothiazol‐3‐
yl)‐propionicacid(4‐{[3‐5,6‐dimethoxy‐2‐oxobenzothiazol‐
3‐yl)‐propionyl]‐hydrazonomethyl}‐benzlidene)‐hydrazide	
(17)	
	

To	a	solution	of	compound	3	(0.6	g,	0.002	mol)	in	absolute	
ethanol	 (20	 mL)	 containing	 glacial	 acetic	 acid	 (5	 mL)	 was	
added	 benzene	 1,4	 dicarbaldehyde	 (0.54	 g,	 0.004	 mol).	 The	
reaction	mixture	was	refluxed	for	5	h	then	cooled,	poured	onto	
crushed	ice.	The	product	was	filtered	off	and	crystallized	from	
acetic	 acid	 to	 give	 compound	 17	 (Scheme	 3).	 Color:	 Yellow	
crystals.	 Yield:	 85	%.	 M.p.:	 249‐251	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	
3465,	 3181	 (NH),	 1610,	 1660	 (C=O).	 1H	 NMR	 (400	 MHz,	
DMSO‐d6,	δ,	ppm):	2.97	(t,	4H,	2CH2),	3.69	(s,	3H,	OCH3),	3.77,	
(s,	3H,	OCH3),	3.79	(s,	3H,	OCH3),	3.80	(s,	3H,	OCH3),	4.22	(t,	4H,	
2NCH2),	 7.06‐7.46	 (m,	 8H,	 Ar‐H	 ),	 7.56	 (s,	 1H,N=CH),	 7.85	 (s,	
1H,	N=CH),	11.49	(s,	1H,	NH,	exchangeable	by	D2O	),	11.93	(s,	
1H,	 NH,	 exchangeable	 by	 D2O	 ).	 MS	 (m/z	 (%)):	 693	 ([M++1],	
61),	692	([M+],	66),	691	([M+‐1],	59),	618	(45),	597	(62),	586	
(62),	 519	 (79),	 413	 (100),	 189	 (83),	 96	 (60).	 Anal.	 calcd.	 for	
C32H32N6O8S2:	 C,	 55.48;	 H,	 4.66;	 N,	 12.13;	 S,	 9.26Found:	 C,	
55.51;	H,	4.60;	N,	12.25;	S,	9.32%.	
	
2.3.	Biological	evaluations	
	
2.3.1.	Preparation	of	microbial	suspensions	
	

Antimicrobial	 activities	 were	 tested	 out	 against	 highly	
pathogenic	 reference	 strains	 accused	 of	 causing	 food	
poisoning	 from	 food	 of	 animal	 origin.	 Two	 Gram	 positive	
bacteria	(Methicillin	resistance	Staphylococcus	aureus	 (MRSA),	
Staphylococcus	 aureus	 NCINB	 50080),	 two	 Gram	 negative	
bacteria	 (Escherichia	 coli	O157ATCC	 700728,	Escherichia	 coli	
ATCC	 11775)	 and	 one	 mycotic	 strain	 (Candida	 albicans	
ATCC10231)	 were	 selected	 as	 model	 organisms.	 Agar	 well	
diffusion	 (qualitative	 method)	 and	 minimum	 inhibitory	
concentration	 (MIC)	 (quantitative	method)	were	 used	 in	 this	
study.	Wherein	 a	 suspension	 ofbacterial	 and	mycotic	 strains	
were	freshly	prepared	by	inoculating	fresh	stock	culture	from	
each	strain	into	separate	broth	tubes,	each	containing	7	mL	of	
Muller	 Hinton	 Broth	 for	 bacterial	 strains	 and	 Sabaroud	
Dextrose	broth	 for	mycotic	strain.	The	 inoculated	 tubes	were	
incubated	at	37	and	28	°C	for	24	h,	respectively.	



104	 Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	
	

	
Table	1.	Agar	well	diffusion	method	showing	antimicrobial	activities	of	the	tested	compounds	compared	with	reference	drugs,	results	given	in	mm	*.	
Chemical/Compound	 E.	coli	O157,	ATCC	700728	 E.	coli,	ATCC	11775	 MRSA	 S.	aureus,	NCINB	50080	 C.	albicans,	ATCC10231	
3	 ‐ve	 13 ‐ve 12 11	
4	 11	 12 ‐ve 12 10s	
5	 ‐ve	 10	 ‐ve	 10	 ‐ve	
6	 ‐ve	 10	 ‐ve	 11	 ‐ve	
7	 10‐12s	 10	 ‐ve	 10	 ‐ve	
9	 12	 10	 12	 10	 ‐ve	
10	 13	 11 12 12 10	
11	 10	 10 ‐ve 10 ‐ve	
12	 12	 12 ‐ve 11 ‐ve	
13	 11	 10 ‐ve 10 ‐ve	
14	 11	 12 ‐ve 10 ‐ve	
15a	 12s	 15 ‐ve 14 ‐ve	
15b	 ‐ve	 11 ‐ve 9 10	
15c	 ‐ve	 11	 ‐ve	 11	 ‐ve	
15d	 11s	 9	 ‐ve	 8	 9s	
15e	 11s	 ‐ve ‐ve ‐ve 9s	
15f	 12s	 12	 ‐ve	 12	 ‐ve	
15g	 ‐ve	 9 ‐ve 9 9s	
15h	 11s	 12 ‐ve 12 ‐ve	
16a	 12	 11 12 9 10	
16b	 10s	 10 ‐ve 10 11s	
16c	 10s	 8 ‐ve 9 ‐ve	
16d	 11s	 7 ‐ve 7 ‐ve	
16e	 ‐ve	 9	 ‐ve	 9	 ‐ve	
17	 11	 10 ‐ve ‐ve ‐ve	
Ciprofloxacin,	100	µg/mL	 39	 42 ‐ve 39 ND	
Fluconazole,	100	µg/mL	 ND	 ND ND ND 32	
Control	negative,	DMSO	 ‐ve	 ‐ve ‐ve ‐ve ‐ve	
*	ND	=	not	defined,	‐ve	=	indicates	that	the	tested	compound	did	not	show	any	hindrance	activity	against	the	tested	isolate.	
	

Serial	 dilutions	were	 carried	 out	 for	 each	 strain,	 dilution	
matching	 with	 0.5	 Mc‐Farland	 (about	 1×108	 cells/mL),	 was	
selected	for	screening	of	antimicrobial	activities.	Ciprofloxacin	
100	µg/mL	and	fluconazole	100	µg/mL	were	used	as	reference	
drugs	(Oxoid),	DMSO	was	used	as	control	negative.	
	
2.3.2.	Determination	of	antimicrobial	activity	by	agar	well	
diffusion	method	
	

Muller	 Hinton	 and	 Sabaroud	 Dextrose	 agar	 plates	 were	
prepared	 [24,25].	 Bacterial	 and	 fungal	 strains	matching	with	
0.5	Mc‐Farland	were	spread	onto	the	surface	of	the	agar	plates	
using	 sterile	 cotton	 swabs.	 For	 evaluation	 of	 antibacterial	
activities,	wells	were	 formed	 in	 the	agar	plates	using	pasture	
pipette	and	each	well	was	 filled	with	50	µL	of	 the	compound	
dissolved	in	DMSO	(300	µg	of	the	tested	compound	dissolved	
in	 1	 mL	 DMSO),	 others	 were	 saturated	 with	 50	 µL	 ciproflo‐
xacin	(100	µg/mL)	and	others	50	µL	DMSO	as	control	negative.	
The	 same	 method	 was	 used	 for	 evaluation	 of	 antimycotic	
activities	using	fluconazole	(100	µg/mL).	Then	inoculated	agar	
plates	 and	 left	 for	 1	 h	 at	 25	 °C	 to	 allow	 a	 period	 of	 pre‐
incubation	 diffusion	 in	 order	 to	 minimize	 the	 effects	 of	
variation	 in	 time	 between	 the	 applications	 of	 different	
solutions.	The	plates	were	re‐incubated	at	37	°C	and	28	°C	for	
24	 h	 for	 bacterial	 and	 mycotic	 isolates,	 respectively.	 After	
incubation,	 plates	were	 observed	 for	 antimicrobial	 activities,	
zone	 of	 inhibition	 were	 measured	 in	 mm	 using	 a	 ruler.	 The	
experiment	was	carried	out	 in	duplicate	and	 the	mean	of	 the	
zone	of	inhibition	was	tabulated	in	Table	1.		
	
2.3.3.	Determination	of	Minimum	Inhibitory	concentration	
(MIC)	
	

Microtiter	 dilution	 plate	 quantitative	 method,	 i.e.	 the	
minimum	 inhibitory	 concentration	 (MIC)	 was	 used	 for	
evaluation	 of	 the	 antimicrobial	 activity	 of	 tested	 compounds.	
Determination	 of	 MIC	 of	 extract	 against	 tested	 strains	 was	
achieved	 using	 96‐well	 sterile	 micro	 plates.	 The	 first	 well	
contain	the	concentrated	form	of	the	tested	compound	used	in	
the	agar	disk	diffusion	method	(300	µg	of	the	tested	compound	
dissolved	 in	 1	mL	DMSO),	 then	 two	 fold	 serial	 dilutions	was	
carried	 out	 for	 the	 tested	 compounds,	 reference	 drugs	
(ciprofloxacin	 and	 fluconazole)	 and	 DMSO,	 Then	 wells	 were	

inoculated	 with	 100	 µL	 of	 tested	 isolates	 (0.5	 Mc‐Farland,	
about	1×108	cells/mL)	and	incubated	at	37‐28	°C	for	24	h	for	
bacterial	 and	 fungal	 strains	 respectively.	 After	 incubation,	
plates	were	 examined	 visually	 for	 bacterial	 or	 fungal	 growth	
precipitation.	 The	 experiment	was	 repeated	 three	 times.	 The	
lowest	 concentration	 that	 showed	 complete	 hindrance	 of	
growth	was	taken	as	MIC.	
	
3.	Results	and	discussion	
	
3.1.	Chemistry	
	

The	key	 intermediate	3	was	prepared	by	condensation	of	
5,6‐dimethoxy‐3H‐benzothiazol‐2‐one	 (1)	 with	 ethylbromo	
propanoate	 to	 give	 ethyl	 3‐(5,6‐dimethoxy‐2‐oxobenzo[d]	
thiazol‐3(2H)‐yl)propanoate	 (2)	 which	 was	 condensed	 with	
hydrazine	hydrate	(98%)	in	ethanol	to	give	3‐(5,6‐dimethoxy‐
2‐oxobenzo[d]thiazol‐3(2H)‐yl)	 propanehydrazide	 (3)	 which	
is	 very	 useful	 starting	material	 for	 the	 synthesis	 of	 all	 target	
compounds.	 The	 structures	 of	 compounds	 2	 and	 3	 were	
established	 on	 the	 basis	 of	 elemental	 analyses	 and	 spectral	
data.	 The	 reaction	 of	 compound	 3	 with	 dichloromaleic	
anhydride	in	acetic	acid	gave	the	amide	compound	4	[26].	The	
mass	spectrum	of	compound	4	showed	the	molecular	ion	peak	
M+	at	m/e	445.	Simple	reaction	of	hydrazide	(3)	with	isatin	in	
absolute	ethanol	containing	a	catalytic	amount	of	glacial	acetic	
acid	gave	compound	5	[27].	1H	NMR	spectrum	of	compound	5	
showed	the	appearance	of	two	singlet	signals	representing	the	
proton	 of	 two	NH	 groups	near	 δ	 11.22	 and	12.49	ppm.	Also,	
cyclization	 of	 compound	 3	 with	 acetylacetone	 afforded	 the	
corresponding	 pyrazole	 derivative	 6	 [28].	 Structure	 of	
compound	6	was	assigned	to	the	reaction	product	on	the	basis	
of	 1H	 NMR	 spectrum,	 which	 revealed	 the	 absence	 of	 amino	
group	 and	 exhibited	 signals	 corresponding	 to	 two	 methyl	
groups.	 Furthermore,	 hydrazide	 3	 reacted	 with	 ethyl	
(ethoxymethylene)cyanoacetate	 in	boiling	ethanol	 to	give	 the	
corresponding	pyrazole	derivative	7.	The	1H	NMR	spectrum	of	
compound	 7	 displayed	 the	 characteristic	 triplet	 and	 quartet	
signals	 at	 δ	 1.21	 and	 3.78	 ppm,	 respectively	 assigned	 to	 the	
ethyl	 protons	 and	 D2O	 exchangeable	 singlet	 signal	 at	 δ	 9.97	
ppm	due	to	NH2	protons.		

	
	



Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	 105	
 

	
Table	2.	Minimum	inhibitory	concentration	showing	antimicrobial	activities	of	the	tested	compounds	compared	with	reference	drugs,	results	given	in	mm	*.	
Chemical/Compound	 E.	coli	O157,	ATCC	700728	 E.	coli,	ATCC	11775	 S.	aureus,	NCINB	50080	 C.	albicans,	ATCC10231	
3	 ND 50 100 100	
4	 100	 100 100 ND	
6	 ND ND 100 ND	
9	 100	 100 ND ND	
10	 50	 100	 100	 ND	
12	 100	 100	 100	 ND	
13	 100	 100 ND ND	
14	 100	 100	 ND	 ND	
15a	 ND	 25	 25	 ND	
15b	 ND 100 ND ND	
15c	 ND 100 ND ND	
15f	 ND 100 100 ND	
15h	 ND 100 100 ND	
16a	 100	 100 ND ND	
17	 100	 ND	 ND	 ND	
Ciprofloxacin,	100	µg/mL	 1.56	 0.78 1.56 ND	
Fluconazole,	100	µg/mL	 ND ND ND 3.125	
Control	negative,	DMSO	 ‐ve ‐ve ‐ve ‐ve	
*	ND	=	not	defined;	‐ve	=	indicates	that	the	tested	compound	did	not	show	any	hindrance	activity	against	the	tested	isolate.	

	
When	 compound	 3	 was	 allowed	 to	 react	 with	 triethyl	

orthoformate,	 the	 product	 was	 not	 the	 expected	 oxadiazole	
derivative	 8	 but	 it	 was	 identified	 as	 the	 methylenepropano	
hydrazide	derivative	9	(Scheme	1)	[29].	

Moreover,	 fusion	 of	 hydrazide	 3	 with	 ammonium	
thiocyanate	 gave	 the	 corresponding	mercaptotriazole	 deriva‐
tive	10.	 Furthermore,	 treatment	 of	 hydrazide	3	 with	methyl	
isothiocyanate	gave	4‐methylthiosemicarbazide	derivative	11.	
The	 structure	 of	 compound	 11	 was	 confirmed	 by	 its	 IR	
spectrum,	which	displayed	absorption	bands	at	3329	cm‐1	for	
NH,	1650	cm‐1	due	to	C=O	and	1249	cm‐1	corresponding	to	C=S	
stretch	 vibrations.	 The	 reaction	 of	 compound	3	with	 carbon	
disulfide	 in	boiling	pyridine	and	DMF	gave	the	corresponding	
oxadiazole	 derivative	12	which	was	 converted	 to	 the	 amino‐
triazole	 derivative	 13	 through	 condensation	 with	 hydrazine	
hydrate.	 Also	 alkylation	 of	 compound	 12	 with	 4‐(2‐
chloroethyl)	 morpholine	 hydrochloride	 in	 boiling	 ethanol	 in	
the	presence	of	 fused	sodium	acetate	gave	the	corresponding	
morpholine	derivative	14	(Scheme	2).	

To	get	a	new	series	of	expected	biologically	active	Schiff's	
bases	15a‐h,	 it	was	of	 interest	to	condense	compound	3	with	
different	 aromatic	 and/or	 heterocyclic	 aldehydes	 in	 ethanol	
containing	few	drops	of	glacial	acetic	acid	(Scheme	3).	

The	 structures	 of	 compounds	15a‐h	were	 established	 on	
the	 basis	 of	 elemental	 analyses	 and	 spectral	 data.	 The	 IR	
spectrum	 of	 compound	 15a	 showed	 an	 absorption	 peak	 at	
1606	 cm‐1	 due	 to	 C=N	 stretching	 vibrations,	 its	 1HNMR	
spectrum	displayed	a	singlet	signal	at	δ	7.87	ppm	attributed	to	
‐N=CH	 proton	 and	 a	 multiple	 at	 δ	 7.05‐7.54	 ppm	 for	 Ar‐H	
protons	and	 its	mass	 spectra	 showed	 the	molecular	 ion	peak	
M+	 at	 m/e	 403	 corresponding	 to	 the	 molecular	 formula	
C19H18FN3O4S.	Also	the	reactivity	of	compounds	15a‐e	towards	
other	 reagents	 has	 been	 investigated	 to	 obtain	 new	
biologically	 active	heterocyclic	 systems.	Thus,	 the	 reaction	of	
Schiff's	bases	15a‐e	with	thioglycolic	acid	in	dry	benzene	gave	
the	 thiazolidinones	 16a‐e	 (Scheme	 3)	 [30].	 The	 cyclic	
structures	 were	 readily	 determined	 on	 the	 basis	 of	 1H	 NMR	
spectra,	 which	 clearly	 indicated	 the	 absence	 of	 the	 ylidenic	
proton	 and	 the	 appearance	 of	 new	 singlet	 signals	 at	 δ	 5.60‐
5.90	ppm	assigned	to	azomethine	proton.	It	was	of	interest	to	
react	 hydrazide	3	with	 benzene‐1,4‐dicarbaldehyde	 to	 afford	
the	bis‐benzothiazole	17.	 1H	NMR	spectrum	of	 the	compound	
confirmed	the	proposed	structure	by	revealing	an	increase	 in	
the	integration	of	the	aromatic	protons	relative	to	hydrazide	3.	
	
3.2.	Biological	activities	
	

All	 the	 newly	 synthesized	 compounds	 3‐15h	 were	
screened	 for	 their	 antimicrobial	 activity	 determined	 by	 agar	
diffusion	method	[24,25]	for	determination	of	the	preliminary	
antibacterial	 and	 antifungal	 activity	 and	 the	 results	 were	

recorded	for	each	tested	compound	as	the	average	diameter	of	
inhibition	zones	(IZ)	of	bacterial	or	 fungal	growth	around	the	
discs	 in	 mm	 (Table	 1).	 In	 addition,	 the	 minimum	 inhibitory	
concentrations	 (MIC)	 were	 recorded	 for	 compounds	 that	
showed	promising	growth	inhibition	using	the	two‐fold	serial	
dilution	method	 [31,32].	The	MIC	 (µg/mL)	values	against	 the	
tested	bacterial	and	fungal	isolates	were	recorded	in	Table	2.	

The	 potentiality	 of	 the	 synthesized	 compounds	 as	
antimicrobials	 was	 appraised	 for	 their	 antimicrobial	 studies	
against	two	strains	of	Gram	positive	bacteria	(S.	aureus	NCINB	
50080,	MRSA),	 and	 two	strains	of	Gram	negative	bacteria	 (E.	
coli	 ATCC	 11775,	E.	 coli	 O157ATCC	 700728)	 using	 ciproflox‐
acin	 as	 a	 standard	 drug	 (100	 μg/mL).	 They	 were	 also	
evaluated	 for	 their	 in	 vitro	 antifungal	 activity	 against	 the	
mycotic	strain	(C.	albicans	ATCC10231)	using	fluconazole	as	a	
standard	antifungal	drug	(100	μg/mL).	

According	to	 the	data	of	Table	1	and	2,	 it	 is	clear	 that	six	
compounds	15a,	3,	4,	10,	15f	and	15h	were	 found	 the	most	
potent,	 they	 showed	 moderate	 activity	 against	 E.	 coli	 ATCC	
11775	 and	 S.	 Aureus	NCINB	 50080	 strains	 compared	 to	 the	
reference	 standard	 ciprofloxacin	 (Figure	 1).	 DMSO	 was	 also	
taken	 in	 a	 control	 experiment	which	 showed	no	 effect	 in	 the	
experiment.	

	

	
Figure	1. Antibacterial	 activity	 of	 the	 bioactive	 compounds	 against E.	 coli
ATCC	 11775	 and	 S.	 Aureus	 NCINB	 50080	 strains	 determined	 by	 zone	 of	
inhibition	and	MIC.	

	
The	Schiff	base	15a	containing	4‐fluro	substituted	phenyl	

ring	was	found	the	most	potent	against	E.	coli	ATCC	11775	and	
S.	Aureus	NCINB	50080	strains	with	zone	of	inhibition	15	and	
14	mm,	 respectively,	 and	MIC	 equals	 25	µg/mL.	 It	was	more	
potent	than	the	parent	hydrazide	3	(zone	of	inhibition	13	and	
12	mm	and	MIC	equals	50	and	100	µg/mL,	 respectively)	and	
the	 two	 Schiff's	 bases	 15f	 and	 15h	 containing	 trimethoxy	
substituted	phenyl	and	5‐meethylfuryl	functionalities,	respect‐



106	 Abbas	et	al.	/	European	Journal	of	Chemistry	6	(2)	(2015)	98‐106	
	
tively	(zone	of	 inhibition	12	mm	and	MIC	equals	100	µg/mL).	
Furthermore,	 the	 dichloropyrrol	 dione	 compound	 4	 and	 the	
mercaptotriazole	 derivative	 10	 displayed	 equal	 antibacterial	
activity	(zone	of	inhibition	12	mm,	11	and	12	mm,	respectively	
and	MIC	equals	100	µg/mL).	

Moreover,	 four	 compounds;	 mercaptotriazole	 10	 and	 its	
oxadiazole	bioisoster	12	(zone	of	inhibition	13	mm,	11mm	and	
12	 mm,	 and	 MIC	 equals	 50,	 100	 µg/mL	 and	 100	 µg/mL,	
respectively)	as	well	as	the	hydrazone	9	(zone	of	inhibition	12	
mm,10	 mm	 and	 MIC	 equals	 100	 µg/mL)	 and	 the	 4‐fluoro	
substituted	thiazolidinone	16a	 (zone	of	 inhibition	12	mm,	11	
mm	 and	 MIC	 equals	 100	 µg/mL)	 were	 the	 most	 potent	
antibacterial	 compounds	 tested	 against	 Gram	 negative	
bacterial	 strains;	 E.	 coli	 ATCC	 11775	 and	 E.	 coli	 O157	 ATCC	
700728	(Figure	2).	

	

	
Figure	2.	 Antibacterial	 activity	 of	 the	 bioactive	 compounds	 against E.	 coli
ATCC	11775	and	E.	coli	O157	ATCC	700728	strains	determined	by	zone	of	
inhibition	and	MIC.	

	
It	 is	 obvious	 from	 the	analysis	 activity	 results	 that	 the	4‐

flourophenyl	 substituted	 compounds	 have	 considerable	
activity	 against	 both	 tested	 Gram	 positive	 (S.	 Aureus	 NCINB	
50080)	 and	 Gram	 negative	 (E.	 coli	 ATCC	 11775	 and	 E.	 coli	
O157	 ATCC	 700728)	 bacterial	 strains.	 This	 observation	 is	
supported	 by	 the	 antibacterial	 activity	 shown	by	 compounds	
15a	 and	 16a.	 On	 the	 other	 hand,	 all	 the	 tested	 compounds	
showed	negative	hindrance	activities	against	tested	Methicillin	
Resistance	Staph	aureus.	

Further,	 these	 compounds	3‐15h	 were	 also	 screened	 for	
their	 antifungal	 activity	 against	 C.	 Albicans	 ATCC1023.	
Fluconazole	 was	 taken	 as	 a	 standard	 drug	 throughout	 the	
experiment.	 Only	 compound	 3	 showed	 hindrance	 effect	
against	C.	Albicans	ATCC10231	with	zone	of	inhibition	11	mm	
and	MIC	equals	100	µg/mL.	
	
4.	Conclusion	
	

In	conclusion,	we	report	 the	synthesis	of	new	derivatives	
of	 pyrrole,	 indolylidene,	 pyrazoles,	 mercaptotriazole,	 oxadia‐
zole,	triazole	and	oxothiazolidine	incorporated	with	the	benzo‐
thiazole	 unit	 via	 reaction	 of	 3‐(5,6‐dimethoxy‐2‐oxobenzo[d]	
thiazol‐3(2H)‐yl)propanohydrazide	 (3)	 with	 different	 rea‐
gents.	 The	 structures	 of	 the	 newly	 synthesized	 compounds	
were	established	on	the	basis	of	spectral	data	(IR,	1H	NMR,	13C	
NMR,	Mass)	 and	 elemental	 analyses.	 Also	 some	 of	 the	 newly	
synthesized	 compounds	 were	 evaluated	 for	 antimicrobial	
activity	and	the	results	showed	that	some	compounds	showed	
good	activity	against	the	tested	microorganisms.	
	
Acknowledgements	
	

The	authors	thank	ALLAH	for	giving	them	the	potential	to	
achieve	this	work.	Also,	we	would	like	to	express	our	thanks	to	
Microbiology	 and	 Immunology	 Department,	 Veterinary	

Division,	National	Research	Center	and	Microanalytical	Center	
of	Cairo	University.	
	
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