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European	Journal	of	Chemistry	2	(3)	(2011)	295‐299	

	
European	Journal	of	Chemistry	

ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2011	EURJCHEM	
DOI:10.5155/eurjchem.2.3.295‐299.376	

	
	

	

	

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

	 	 	

Synthesis	of	nitrogen	heterocycles	from		
ethyl	3‐(6‐dibenzothiophen‐2‐yl‐pyridazin‐3‐ylamino)‐3‐oxopropanoate			

Mohamed	Sayed	Behalo*	and	Aly	Abdelmaboud	Aly	

Department	of	Chemistry,	Faculty	of	Science,	Benha	University,	Benha,	13518,	Egypt	

*Corresponding	author	at:	Department	of	Chemistry,	Faculty	of	Science,	Benha	University,	Benha,	13518,	Egypt.	Tel.:	+20101599607;	fax:	+20133222578.		
E‐mail	address:	mohamedbehalo@hotmail.com	(M.S.		Behalo).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	23	December	2010	
Received	in	revised	form:	28	March	2011	
Accepted:	29	March	2011	
Online:	30	September	2011	

KEYWORDS	

	 An	efficient	synthesis	of	nitrogen‐containing	heterocycles	pyrazole,	 triazole,	 	pyridinone	and
pyrimidinone	 derivatives	 from	 ethyl	 3‐(6‐dibenzothiophen‐2‐yl‐pyridazin‐3‐ylamino)‐3‐
oxopropanoate	 (2)	 was	 described.	 The	 structures	 of	 all	 products	 were	 confirmed	 and
characterized	by	the	elemental	analysis	and	spectroscopic	studies	(IR,	MS,	1H	NMR,	13C	NMR).	

Dibenzothiophene	
Pyridazine	
Triazole	
Pyrimidinone  
Pyrazole	
Pyridinone	

	
1.	Introduction	
	

Nitrogen	and	sulfur‐containing	heterocycles	have	received	
a	great	deal	of	interest	in	the	biological	and	medicinal	sciences	
and	this	justifies	continuing	efforts	in	the	development	of	new	
efficient	 and	 mild	 synthetic	 strategies	 for	 their	 synthesis.	
Among	 a	 large	 variety	 of	 nitrogen	 containing	 heterocyclic	
compounds,	 pyridazines	 have	 received	 considerable	 attention	
because	 of	 their	 pharmacological	 properties	 and	 clinical	
applications	 [1‐9].	 For	 example,	 3‐amino‐6‐aryl‐pyridazines	
were	 reported	 to	 possess	 anti‐inflammatory	 and	 analgesic	
properties	 [7].	 Also,	 pyridazine	 derivatives	 possess	 antiviral	
and	anticancer	[10‐12],	antituberculosis	[13],	antihypertensive	
[14,15]	and	antimicrobial	 [16‐19]	activity.	On	 the	other	hand,	
6‐alkoxy‐[1,2,4]triazolo[4,3‐b]pyridazines	 have	 been	 reported	
to	possess	anticonvulsant	properties	[20].	

Based	on	the	reported	observations	and	in	continuation	of	
our	 research	 interest	 for	 the	 synthesis	 of	 biologically	 active	
heterocycles	[21‐24],	 the	aim	of	this	study	is	 to	design	simple	
route	for	the	synthesis	of	pyrazoles,	triazoles,	pyridinones	and	
pyrimidinones	derivatives	attached	to	pyridazine	moiety.	
	
2.	Experimental	
	
2.1.	Synthesis	
	
2.1.1.	Ethyl	3‐(6‐dibenzothiophen‐2‐yl‐pyridazin‐3‐ylamino)‐
3‐oxopropanoate	(2)	
	

A	mixture	 of	 an	 equimolar	 amount	 of	 aminopyridazine	1	
[25]	and	diethylmalonate	(0.01	mol)	was	heated	in	an	oil	bath	
at	 180	 oC	 for	 2	 hours	 then	 left	 to	 cool.	 The	 product	 was	
collected	 and	 purified:	 Yellow,	 Yield:	 80%,	 (Ethanol)	 (Scheme	
1).	M.p.:	 176‐178	 C.	 IR	 (KBr,	 cm‐1):	 3390‐3280	(NH),	 2950,	

2880	 (CH2),	 1730,	 1685	 (CO),	 1630	 (C=N).	 1H	 NMR	 (200	
MHz,	 CDCl3):	 1.32	 (t,	 3H,	 CH3),	 4.31	 (q,	 2H,	 CH2),	 5.40	 (s,	 2H,	
CH2),	8.62	(s,	1H,	NH,	exchangeable),	6.91‐7.96	(m,	9H,	Ar‐H). 
13C	 NMR	 (50	MHz,	 CDCl3):	 17.2	 (CH3),	 54.3	 (CH2	 ester),	 47.1	
(CH2),	 119.2,	 121.3,	 121.8,	 122.6,	 123.1,	 123.7,	 124.2,	 124.6,	
126.3,	 127.6,	 128.1,	 132.5,	 138.3,	 139.1,	 148.7,	 151.1	
(dibenzothiophene	 and	 pyridazine	 carbons),	 172.2,	 175.4	
(2CO).	 MS	 (m/z):	 391	 (M+).	 Anal.	 Calcd.	 for	 C21H17N3O3S:	 C,	
64.43;	H,	4.38;	N,	10.73.	Found:	C,	64.28;	H,	4.25;	N,	10.56	%.	

	

 
	

Scheme	1	
		
2.1.2.	Ethyl	2‐(6‐dibenzothiophen‐2‐yl	–pyridazin‐3‐yl	
carbamoyl)‐3‐phenylacrylate	(3)		
	

Benzaldehyde	(0.01	mol)	was	added	to	a	solution	of	ester	2	
(0.01	 mol)	 in	 dioxan	 (30	 mL)	 containing	 few	 drops	 of	
piperidine.	The	reaction	mixture	was	heated	under	reflux	for	3	
hours	 then	 the	 solvent	 was	 removed.	 The	 remaining	 residue	
was	triturated	with	petroleum	ether	to	give	the	solid	product:	
Yellow,	Yield:	68%	(Butanol)	(Scheme	2).	M.p.:	197‐199	C.	 IR	
(KBr,	 cm‐1):	 3360‐3230	 (NH),	 2940,	 2860	 (CH‐aliphatic)	
1715,	 1670	 (CO),	 1620	 (C=C).	 1H	 NMR	 (200	 MHz,	 CDCl3):	
1.32		(t,	3H,	CH3),		4.20	(q,	2H,	CH2),		6.62	(s,	1H,	C=CH),		8.81	(s,		
	



296	 Behalo	and	Aly	/	European	Journal	of	Chemistry	2	(3)	(2011)	295‐299	
	
	

NH

O O

OC2H5
CHPh

NHC

O

N

NR
Ph

OH

Ar

Ar

3

4a,b

4a R = H, 4b R = C6H5

RNHNH2

2
PhCHO

NHC

O

OO

CHO

OH

Ar

5

NH

O O

OC2H5
N

NH

Ph

Ar

6

NH2NH2

N

N
NPhNHC

HO

O

Ar

7

PhN2Cl

 
	

Scheme	2
		
	
1H,	NH,	 exchangeable),	 6.84‐8.02	 (m,	14H,	ArH).	13C	NMR	 (50	
MHz,	 CDCl3):	 16.4	 (CH3),	 55.6	 (CH2	 ester),	 123.6	 (C=CHPh),	
146.2	(C=CHPh),	125.6,	127.3,	128.2,	135.5	(phenyl	carbons,	in	
addition	 to	 dibenzothiophene	 and	 pyridazine	 carbons).	 MS	
(m/z):	479	(M+).	Anal.	Calcd.	for	C28H21N3O3S:	C,	70.13;	H,	4.41;	
N,	8.76	.	Found:	C,	70.27;	H,	4.52;	N,	8.58	%.	
	
2.1.3.	General	procedure	for	the	synthesis	of	4a,b	
	

A	mixture	of	3	(0.01	mol)	and	hydrazine	hydrate	or	phenyl‐
hydrazine	 (0.01	 mol)	 was	 heated	 in	 ethanol	 (30	 mL)	 under	
reflux	 for	 3	 hours	 then	 left	 to	 cool.	 The	 formed	 solid	 product	
was	collected	by	filtration	and	recrystallized	(Scheme	2).	

N‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐yl)‐3‐hydroxy‐5‐
phenyl‐1H‐pyrazole‐4‐carboxamide	 (4a):	 Yellow,	 Yield:	 81%	
(Ethanol).	M.p.:	 180‐182	 C.	 IR	 (KBr,	 cm‐1):	 3490‐3240	 (OH,	
NH),	 1685	 (CO),	 1650	 (C=N),	 1635	 (C=C).	 1H	 NMR	 (200	
MHz,	CDCl3):	8.52,	9.33	(2s,	2H,	2NH,	exchangeable),	10.24	(s,	
1H,	OH),	 7.02‐7.98	 (m,	 14H,	 Ar‐H).	MS	 (m/z):	 463	(M+).	 Anal.	
Calcd.	 for	 C26H17N5O2S:	 C,	 67.37;	 H,	 3.70;	 N,	 15.11.	 Found:	 C,	
67.20;	H,	3.53;	N,	14.85	%.	

N‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐yl)‐3‐hydroxy‐1,5‐
diphenyl‐1H‐pyrazole‐4‐carboxamide	 (4b):	 Yellow,	 Yield:	 74%	
(Ethanol).	M.p.:	 186‐188	 C.	 IR	 (KBr,	 cm‐1):	 3460‐3255	 (OH,	
NH),	 1685	 (CO),	 1645	 (C=N),	 1622	 (C=C).	 1H	 NMR	 (200	
MHz,	CDCl3):	8.90	(s,	1H,	NH,	exchangeable),	10.28	(s,	1H,	OH),	
7.89‐8.10	(m,	H,	19Ar‐H).	MS	(m/z):	539	(M+).	Anal.	Calcd.	 for	
C32H21N5O2S:	 C,	 71.23;	 H,	 3.92;	 N,	 12.98.	 Found:	 C,	 71.04;	 H,	
3.64;	N,	12.74	%.	
	
2.1.4.	N‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐yl)‐2‐oxo‐2H‐
chromene‐3‐carbox	amide	(5)	
	

The	 same	 procedures	 described	 for	 the	 synthesis	 of	
compound	 3.	 Yellow,	 Yield:	 82	 %	 (Ethanol)	 (Scheme	 2).	 M.p.	
206‐208	 C.	 IR	 (KBr,	 cm‐1):	 3390‐3270	 (NH),	 3020	 (CH‐
aromatic),	1710,	1680	(CO),	1620	(C=C).	1H	NMR	(200	MHz,	
CDCl3):	6.92‐7.88	(m,	14H,	ArH+chromene‐H),	8.93	(s,	1H,	NH,	
exchangeable).	13	C	NMR	(50	MHz,	CDCl3):	120.2,	123.6,	126.1,	
126.9,	 127.5,	 128.6,	 148.3,	 150.2,	 (in	 addition	 to	 dibenzo	
thiophene	 and	 pyridazine	 carbons),	 162.2,	 163.4	 (2CO).	 MS	
(m/z):	449	(M+);	Anal.	Calcd.	for	C26H15N3O3S:	C,	69.48;	H,	3.36;	
N,	9.35.	Found:	C,	69.25;	H,	3.16;	N,	9.18	%.	
	
2.1.5.	Ethyl	3‐(6‐dibenzothiophen‐2‐yl–pyridazin‐3‐
ylamino)‐3‐oxo‐2‐(phenylhyda	zono)propanoate	(6)	
	

A	 cold	 solution	of	 benzene	diazonium	 chloride	 (0.01	mol)	
was	 added	 to	 stirred	 solution	 of	3	 (0.01	mol)	 in	 ethanol	 (30	

mL).	The	reaction	mixture	was	stirred	at	room	temperature	for	
3	hours	and	the	formed	solid	product	was	collected	by	filtration	
and	washed:	 Orange,	 Yield:	 78	%	 (Ethanol)	 (Scheme	 2).	M.p.:	
170‐172	 C.	 IR	 (KBr,	 cm‐1):	 2930,	 2850	(CH‐aliphatic),	 1705,	
1685	(CO),	3360‐3225	(NH).	1H	NMR	(200	MHz,	CDCl3):	1.32	
(t,	 3	H,	CH3),	4.21	 (q,	2H,	CH2),	 6.83‐8.02	 (m,	14H,	ArH),	8.84,	
9.23	 (2s,	 2H,	 2NH,	 exchangeable).	 MS	 (m/z):	 495	 (M+).	 Anal.	
Calcd.	 for	 C27H21N5O3S:	 C,	 65.44;	 H,	 4.27;	 N,	 14.13.	 Found:	 C,	
65.32;	H,	4.07;	N,	13.94	%.	
	
2.1.6.	N‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐yl)‐5‐hydroxy‐
2‐phenyl‐2H‐1,2,3‐triazole‐4‐	carboxamide	(7)	
	

A	mixture	of	hydrazone	6	(0.01	mol)	and	hydrazine	hydrate	
(0.01	mol)	 in	 ethanol	 (30	mL)	was	 heated	 under	 reflux	 for	 4	
hours.	 After	 evaporation	 of	 solvent	 on	 a	 vacuum,	 the	 solid	
product	 was	 recrystallized:	 Yellow,	 Yield	 70	 %	 (Acetone)	
(Scheme	2).	M.p.:	180‐182	C.	IR	(KBr,	cm‐1):	3480‐3255	(OH,	
NH),	 1680	 (CO),	 1630	 (C=N),	 1605	 (C=C).	 1H	 NMR	 (200	
MHz,	 DMSO‐d6):	 6.97‐7.94	 (m,	 14H,	 ArH),	 8.32	 (s,	 1H,	 NH,	
exchangeable),	 9.22	 (s,	1H,	OH,	 exchangeable).	MS	 (m/z):	464	
(M+).	 Anal.	 Calcd.	 for	 C25H16N6O2S:	 C,	 64.64;	H,	 3.47;	N,	 18.09.	
Found:	C,	64.42;	H,	3.3;	N,	17.89	%.	
	
2.1.7.	5‐Acetyl‐N‐(6‐dibenzothiophen‐2‐yl–pyridazin‐3‐yl)‐4‐
hydroxy‐2‐(phenylamino)	thiophene‐3‐carboxamide	(10)		
	

Phenyl	isothiocyanate	(0.01	mol)	was	added	to	a	solution	of	
2	 (0.01	 mol)	 in	 dimethylformamide	 (30	 mL)	 containing	
potassium	 hydroxide	 (0.01	 mol).	 The	 reaction	 mixture	 was	
stirred	 at	 room	 temperature	 overnight.	 Then	 chloroacetone	
(0.01	 mol)	 was	 added	 to	 the	 reaction	 mixture	 and	 all	 was	
stirred	 at	 room	 temperature	 overnight.	 The	 mixture	 was	
poured	into	crushed	ice	and	hydrochloric	acid.	The	precipitated	
solid	 was	 collected	 by	 filtration,	 washed	 and	 dried:	 Yellow,	
Yield:	 62	%	 (Ethanol)	 (Scheme	 3).	M.p.:	 175‐177	 C.	 IR	 (KBr,	
cm‐1):	 3420‐3270	(OH,	NH),	1690,	 1675	(CO),	 1630	(C=C).	
1H	NMR	(200	MHz,	CDCl3):	2.30	(s,	3H,	CH3),	7.06‐7.94	(m,	14H,	
Ar‐H),	8.41,	8.83	(2s,	2H,	2NH,	exchangeable),	10.26	(s,	1H,	OH,	
exchangeable).	 13C	 NMR	 (50	 MHz,	 CDCl3):	 20.4	 (CH3),	 114.5,	
118.2,	127.1,	142.1	(phenyl	carbons),	125.3,	135.2,	148.5,	151.1	
(thiophene	 carbons),	 118.6,	 121.1,	 121.5,	 122.2,	 122.8,	 123.2,	
124.1,	 124.8,	 125.4,	 127.3,	 128.5,	 131.2,	 136.6,	 138.2,	 146.3,	
150.4	(dibenzothiophene	and	pyridazine	carbons),	178.5,	182.2	
(2CO).	 MS	 (m/z):	 536	 (M+).	 Anal.	 Calcd.	 for	 C29H20N4O3S2:	 C,	
64.91;	H,	3.76;	N,	10.44.	Found:	C,	64.80;	H,	3.64;	N,	10.32	%.	
	
	
	



Behalo	and	Aly	/	European	Journal	of	Chemistry	2	(3)	(2011)	295‐299	 297	
 

 
 

	

 
	

Scheme	3	
	
	
2.1.8.	General	procedure	for	the	synthesis	of	11a,b	
	

A	mixture	of	ester	2	(0.01	mol)	and	urea	or	thiourea	(0.01	
mol)	 was	 heated	 in	 ethanol	 (30	 mL)	 containing	 sodium	
ethoxide	under	reflux	for	6	hours	then	left	to	cool.	The	reaction	
mixture	 was	 poured	 into	 cold	 water	 and	 the	 formed	 solid	
product	 was	 collected	 by	 filtration,	 washed,	 dried	 and	
recrystallized	(Scheme	4).	

6‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐ylamino)pyrimidine‐
2,4(3H,5H)‐dione	 (11a):	 Yellow,	 Yield:	 77	 %	 (Butanol).	 M.p.:	
210‐212	C.	 IR	(KBr,	cm‐1):	3440‐3250	(OH,	NH),	1682,	1665	
(CO),	 1610	 (C=N).	 1H	 NMR	 (200	 MHz,	 CDCl3):	 3.21	 (s,	 2H,	
CH2),	 6.84‐8.01	 (m,	 9H,	 Ar‐H),	 8.33,	 9.81	 (2s,	 2H,	 2NH,	
exchangeable).	Anal.	Calcd.	for	C20H13N5O2S:	C,	62.00;	H,	3.38;	N,	
18.08.	Found:	C,	61.82;	H,	3.16;	N,	17.88	%.	

6‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐ylamino)‐2‐thioxo‐
2,3‐dihydropyrimidine‐4(5H)‐one	 (11b):	 Yellow,	 Yield:	 71	 %	
(Butanol).	 M.p.:	 195‐197	 C.	 IR	 (KBr,	 cm‐1):	 3420‐3180	 (OH,	
NH),	1680	(CO),	1625	(C=N).	1H	NMR	(200	MHz,	CDCl3):	2.92	
(s,	 2H,	 CH2),	 7.16‐7.94	 (m,	9H,	Ar‐H),	 8.52,	 9.80	 (2s,	 2H,	 2NH,	
exchangeable).	Anal.	Calcd.	for	C20H13N5OS2:	C,	59.54;	H,	3.25;	N,	
17.36.	Found:	C,	59.19;	H,	3.11;	N,	17.20	%.	
	
2.1.9.	General	procedure	for	the	synthesis	of	pyrimidines	
(12a‐d)	
	

A	 cold	 solution	 of	 aryl	 diazonium	 chloride	 (0.01	 mol)	
namely	 benzene	 diazonium	 chloride	 or	 4‐methxybenzene	
diazonium	 chloride	 was	 added	 to	 stirred	 solution	 of	
pyrimidines	11a,b	 (0.01	mol)	 in	 ethanol	 (30	mL)	 and	 sodium	
acetate.	The	reaction	mixture	was	stirred	at	room	temperature	
for	 3	 hours	 and	 the	 formed	 solid	 product	 was	 collected	 by	
filtration,	washed,	 dried	 and	 crystallized	 from	 proper	 solvent	
(Scheme	4).	

6‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐ylamino)‐5‐
(phenylhydrazono)pyrimidine‐2,4(3H,5H)‐dione	 (12a):	 yellow,	
Yield:	74	%	(Ethanol).	M.p.:	191‐193	C.	 IR	 (KBr,	 cm‐1):	3435‐
3220	(OH,	NH)	1675,	1665	(CO),	1620	(C=N).	1H	NMR	(200	
MHz,	 CDCl3):	 5.32,	 7.21,	 10.41	 (3s,	 3H,	 3NH,	 exchangeable),	
6.74‐7.93	(m,	14H,	Ar‐H).	MS	(m/z):	491	 (M+).	Anal.	Calcd.	 for	
C26H17N7O2S:	 C,	 63.53;	 H,	 3.49;	 N,	 19.95.	 Found:	 C,	 63.40;	 H,	
3.28;	N,	19.71	%.	

6‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐ylamino)‐5‐(4‐
methoxyphenyl)	 hydrazonopyrimidine‐2,4(3H,5H)‐dione	 (12b):	
Yellow,	Yield:	77	%	(Ethanol).	M.p.:	211‐213	C.	IR	(KBr,	cm‐1):	
3460‐3235	(OH,	NH),	1670,	1665	(CO),	1630	(C=N).	1H	NMR	
(200	MHz,	CDCl3):	3.55	 (s,	3H,	OCH3),	7.44,	8.23,	9.82	 (3s,	3H,	
3NH,	 exchangeable)	 6.91‐8.03	 (m,	 13H,	 Ar‐H).	MS	 (m/z):	 521	
(M+).	 Anal.	 Calcd.	 for	 C27H19N7O3S:	 C,	 62.18;	 H,	 3.67;	 N,	 8.80.	
Found:	C,	61.88;	H,	3.50;	N,	8.62	%.	

6‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐ylamino)‐5‐phenyl	
hydrazono‐2‐thioxo‐2,3‐dihydropyrimidine‐4(5H)‐one	 (12c):	
Yellow,	Yield:	69	%	(Ethanol).	M.p.:	217‐219	C.	IR	(KBr,	cm‐1):	
3410‐3210	 (NH)	 1680,	 1668	 (CO),	 1620	 (C=N).	 1H	 NMR	
(200	MHz,	CDCl3):	5.63,	9.28,	9.92	(3s,	3H,	3NH,	exchangeable)	

7.10‐8.04	(m,	14H,	Ar‐H).	MS	(m/z):	507	 (M+).	Anal.	Calcd.	 for	
C27H17N7OS2:	 C,	 61.52;	 H,	 3.38;	 N,	 19.32.	 Found:	 C,	 61.37;	 H,	
3.25;	N,	19.21	%.	

6‐(6‐Dibenzothiophen‐2‐yl–pyridazin‐3‐ylamino)‐5‐(4‐
methoxyphenyl)hydrazono‐2‐thioxo‐2,3‐dihydropyrimidine‐
4(5H)‐one	 (12d):	Yellow,	Yield:	80	%	(Ethanol).	M.p.:	184‐186	
C.	 IR	 (KBr,	 cm‐1):	 3420‐3190	 (OH,	 NH),	 1682,	 1670	 (CO),	
1626	 (C=N).	 1H	 NMR	 (200	 MHz,	 CDCl3):	 3.33	 (s,	 3H,	 OCH3),	
8.33,	 8.94,	 10.40	 (3s,	 3H,	 3NH,	 exchangeable)	 6.83‐7.94	 (m,	
13H,	Ar‐H).	MS	(m/z):	537	(M+).	Anal.	Calcd.	 for	C27H19N7O2S2:	
C,	60.32;	H,	3.56;	N,	18.24.	Found:	C,	60.24;	H,	3.42;	N,	18.11	%.	
	
2.1.10.	General	procedure	for	the	synthesis	of	pyrimidines	
(13a‐d)	
	

A	 mixture	 of	 pyrimidine	 11a,b	 (0.01	 mol)	 and	 aromatic	
aldehydes,	 e.g.	 benzaldehyde	 and	 4‐chlorobenzaldahyde	 (0.01	
mol)	was	heated	 in	 ethanol	 (30	mL)	under	 reflux	 for	 6	hours	
then	 left	 to	 cool.	 The	 solid	product	was	 collected	 by	 filtration	
and	recrystallized	from	proper	solvent	(Scheme	4).	

5‐Benzylidene‐6‐(6‐dibenzothiophen‐2‐yl–pyridazin‐3‐
ylamino)pyrimidine‐2,4	 (3H,5H)‐dione	 (13a):	 Yellow,	 Yield:	 85	
%	(Ethanol).	M.p.:	188‐190	C.	IR	(KBr,	cm‐1):	3415‐3140	(OH,	
NH)	 1675,	 1667	 (CO),	 1620	 (C=N),	 1605	 (C=C).	 1H	 NMR	
(200	 MHz,	 CDCl3):	 8.34,	 10.13	 (2s,	 2H,	 2NH,	 exchangeable),	
6.91‐7.93	(m,	15H,	Ar‐H	and	CH=C).	MS	(m/z):	475	(M+).	Anal.	
Calcd.	 for	 C27H17N5O2S:	 C,	 68.20;	 H,	 3.60;	 N,	 14.73.	 Found:	 C,	
68.03;	H,	3.48;	N,	14.57	%.	

5‐(4‐Chlorobenzylidene)‐6‐(6‐dibenzothiophen‐2‐yl–
pyridazin‐3‐ylamino)pyrimidine‐2,4(3H,5H)‐dione	(13b):	Yellow	
Yield:	87	%	(Ethanol).	M.p.:	167‐169	C.	 IR	 (KBr,	 cm‐1):	3400‐
3175	(OH,	NH),	1681,	1668	(CO),	1625	(C=N),1616	(C=C).	
1H	 NMR	 (200	 MHz,	 CDCl3):	 9.24,	 10.61	 (2s,	 2H,	 2NH,	
exchangeable),	7.10‐8.22	(m,	14H,	Ar‐H	and	CH=C).	Anal.	Calcd.	
for	C27H16ClN5O2S:	C,	63.59;	H,	3.16;	N,	13.73.	Found:	C,	63.43;	
H,	3.06;	N,	13.57	%.	

5‐Benzylidene‐6‐(6‐dibenzothiophen‐2‐yl–pyridazin‐3‐yl	
amino)‐2‐thioxo‐2,3‐dihydropyrimidine‐4(5H)‐one	 (13c):	
Yellow,	Yield:	78	%	(Ethanol).	M.p.:	182‐184	C.	IR	(KBr,	cm‐1):	
3480‐3160	(OH,	NH),	 1680,	 1665	(CO),	 1625	(C=N),	 1612	
(C=C).	 1H	 NMR	 (200	 MHz,	 CDCl3):	 8.51,	 9.87	 (2s,	 2H,	 2NH,	
exchangeable),	6.84‐7.92	(m,	15H,	Ar‐H	and	CH=C).	Anal.	Calcd.	
for	C27H17N5O2S:	C,	65.97;	H,	3.49;	N,	14.25.	Found:	C,	65.75;	H,	
3.33;	N	14.11	%.	

5‐(4‐Chlorobenzylidene)‐6‐(6‐dibenzothiophen‐2‐yl–
pyridazin‐3‐ylamino)‐2‐thioxo‐2,3‐dihydropyrimidine‐4(5H)‐one	
(13d):	yellow,	Yield:	81	%	(Ethanol).	M.p.:	202‐204	C.	IR	(KBr,	
cm‐1):	3455‐3215	(OH,	NH),	1675,	1662	(CO),	1625	(C=N),	
1610	 (C=C).	 1H	 NMR	 (200	MHz,	 CDCl3):	 9.37,	 10.21	 (2s,	 2H,	
2NH,	 exchangeable),	 6.90‐8.11(m,	14H,	Ar‐H	and	CH=C).	Anal.	
Calcd.	 for	C27H16ClN5O2S:	C,	61.65;	H,	3.07;	N,	13.31.	Found:	C,	
61.71;	H,	3.16;	N,	13.19	%.	
	

		
	



298	 Behalo	and	Aly	/	European	Journal	of	Chemistry	2	(3)	(2011)	295‐299	
	
	

 
	

Scheme	4	
		
	
2.1.11.	General	procedure	for	the	synthesis	of	pyridines	
(14a,b)	
	

To	 a	 solution	of	 ester	2	 (0.01	mol)	 in	dimethylformamide	
(30	 mL)	 containing	 triethylamine	 (few	 drops),	 either	
malononitrile	 or	 ethyl	 cyanoacetate	 (0.01	 mol)	 was	 added.	
After	heating	of	 the	 reaction	mixture	 for	6	hours	 and	 cooling,	
the	mixture	was	poured	into	crushed	ice	and	hydrochloric	acid.	
The	 precipitated	 product	 was	 collected	 by	 filtration,	 washed	
and	dried	(Scheme	5).	

Ethyl	 4,6‐diamino‐1‐(6‐dibenzothiophen‐2‐yl‐pyridazin‐3‐
yl)‐2‐oxo‐1,2‐dihydropyridine‐3‐carboxylate	 (14a):	 Yellow,	
Yield:	63	%	(Ethanol).	M.p.:	195‐197	C.	 IR	 (KBr,	 cm‐1):	3390‐
3180	 (NH2),	 3050	 (CH‐aromatic),	 1705,	 1680	 (CO),	 1620	
(C=C).	1H	NMR	(200	MHz,	CDCl3):	1.31	(t,	3H,	CH3),	4.23	(q,	2H,	
CH2),	 6.92‐7.87	 (m,	 9H,	 Ar‐H),	 7.11	 (s,	 1H,	 pyridine	 H),	 8.44,	
8.93	 (2s,	 4H,	 2NH2,	 exchangeable).	MS	 (m/z):	 457	 (M+).	 Anal.	
Calcd.	 for	 C24H19N5O3S:	 C,	 63.01;	 H,	 4.19;	 N,	 15.31.	 Found:	 C,	
62.88;	H,	4.05;	N,	15.15	%.	

Ethyl	 4‐amino‐1‐(6‐dibenzothiophen‐2‐yl‐pyridazin‐3‐yl)‐6‐
hydroxy‐2‐oxo‐1,2‐dihydropyridine‐3‐carboxylate	 (14b):	Yellow,	
Yield:	65	%	 (Ethanol).	M.p.:	186‐188	C.	 IR	 (KBr,	 cm‐1):	3520‐
3310	 (OH,	 NH2),	 3040	 (CH‐aromatic),	 1700,	 1683	 (CO),	
1626	 (C=C).	 1H	 NMR	 (200	 MHz,	 CDCl3):	 1.29	 (t,	 3H,	 CH3),	
4.31(q,	2H,	CH2),	6.98‐7.92	(m,	9H,	Ar‐H),	6.91	(s,	1H,	pyridine	
H),	 6.33	 (s,	 2H,	 NH2,	 exchangeable),	 9.82	 (s,	 1H,	 OH).	 Anal.	
Calcd.	 for	 C24H18N4O4S:	 C,	 62.87;	 H,	 3.96;	 N,	 12.22.	 Found:	 C,	
62.33;	H,	3.85;	N,	12.11	%.	
	
2.1.12.	Ethyl	6‐amino‐5‐cyano‐1‐(6‐dibenzothiophen‐2‐yl‐
pyridazin‐3‐yl)‐2‐oxo‐4‐phenyl‐1,2‐dihydro	pyridine‐3‐
carboxylate	(15)	
	

The	 same	 procedures	 described	 for	 the	 synthesis	 of	
compounds	14a,b.	 Yellow,	 Yield:	 68	%	 (Ethanol)	 (Scheme	 5).	
M.p.:	 201‐203	 C.	 IR	 (KBr,	 cm‐1):	 3385‐3190	 (NH2),	 3040	
(CH‐aromatic),	2220	(C≡N),	1705,	1685	(CO),	1630	(C=C).	
1H	NMR	(200	MHz,	CDCl3):	1.31	(t,	3H,	CH3),	4.32	(q,	2H,	CH2),	
6.80‐7.93	(m,	14H,	Ar‐H),	8.34	(s,	2H,	NH2,	exchangeable).	Anal.	
Calcd.	 for	 C31H21N5O3S:	 C,	 68.49;	 H,	 3.89;	 N,	 12.88.	 Found:	 C,	
68.36;	H,	3.81;	N,	12.73	%.	
	
2.2.	Instrumentation		
	

Melting	 points	 of	 the	 prepared	 products	 are	 uncorrected.	
All	 reactions	 were	 monitored	 by	 thin	 layer	 chromatography	

(TLC)	carried	out	on	0.2	mm	silica	gel	60	F254	(Merck)	plates.	
IR	 spectra	 in	 KBr	 were	 recorded	 using	 a	 Perkin‐Elmer	 298	
spectrophotometer.	 1H‐	 and	 13C	 NMR	 spectra	 were	 obtained	
using	a	Varian	Gemini	 200	MHz	and	50	MHz	 instrument.	 The	
solvent	 used	 for	 NMR	 analysis	 was	 CDCl3,	 unless	 stated	
otherwise.	 Mass	 spectra	 were	 obtained	 using	 a	 Shimadzu	
GCMS‐QP	1000	EX	mass	spectrometer.		
	
3.	Results	and	discussion	
	

Schemes	1‐5	 show	 the	 synthetic	 pathways	 to	prepare	 the	
target	 compounds	 2‐15.	 The	 key	 substrate	 ester	 2	 was	
synthesized	 from	 the	 reaction	 of	 aminopyridazine	 derivative	
[25]	1	 and	 diethyl	malonate	 (Scheme	 1).	 The	 IR	 spectrum	 of	
compound	2	showed	two	strong	absorption	bands	at	1730	and	
1685	 cm‐1	 assigned	 to	 ester	 and	 amide	 carbonyl	 groups	
respectively.	 Another	 band	 was	 revealed	 at	 3380‐3280	 cm‐1	
characterized	for	amide	NH.	1H	NMR	spectrum	displayed	also	a	
triplet	 signal	 at	 1.3	 ppm	 assigned	 for	 CH3	 group,	 a	 quartet	
signal	 at	 4.3	 ppm	 due	 to	 CH2	 and	 signal	 at	 8.8	 ppm	 (D2O	
exchangeable)	 due	 to	 NH	 proton.	 Furthermore,	 13C	 NMR	
spectrum	of	compound	2	displayed	signals	at	172.2	and	175.4	
corresponding	to	two	CO	respectively.	

The	 reactivity	 of	 the	 ester	2	 towards	 some	 reagents	with	
the	aim	of	 the	 synthesis	of	novel	 five	membered	heterocycles	
was	investigated.		

Thus,	the	reaction	of	compound	2	with	aromatic	aldehydes	
viz	 benzaldehyde	 afforded	 ethyl	 2‐(6‐dibenzothiophen‐2‐yl‐
pyridazin‐3‐ylcarbamoyl)‐3‐phenylacrylate	(3).	Cyclization	of	3	
by	 hydrazine	 hydrate	 or	 phenylhydrazine	 to	 pyrazole	
derivatives	 4a,b	 was	 achieved	 by	 refluxing	 in	 ethanol.	 The	
structures	of	 the	products	were	assigned	on	the	basis	of	 their	
spectral	 data	 and	 elemental	 analysis.	 On	 the	 other	 hand,	 the	
reaction	 of	 compound	 2	 with	 salicyldehyde	 furnished	
chromene	 derivative	 5.	 Treatment	 of	 compound	 2	 with	
benzene	diazonium	chloride	afforded	the	hydrazone	derivative	
6,	which	 in	turn	reacted	with	hydrazine	hydrate	 to	give	1,2,3‐
triazole	derivative	7	(Scheme	2).	

On	the	other	hand,	the	reaction	of	compound	2	with	phenyl	
isothiocyanate	 8	 in	 dimethylformamide	 solution	 afforded	 the	
intermediate	9.	Cyclization	of	the	 latter	by	chloroacetone	gave	
thiophene	derivative	10	(Scheme	3).		

Also,	 the	 reactivity	 of	 ester	 2	 for	 the	 synthesis	 of	 six	
membered	 heterocycles	 was	 depicted.	 Thus,	 the	 reaction	 of	
ester	2	with	urea	and/or	thiourea	in	ethanolic	sodium	ethoxide	
solution	afforded	pyrimidinones	11a,b.		



Behalo	and	Aly	/	European	Journal	of	Chemistry	2	(3)	(2011)	295‐299	 299	
 

 
 

	

 
	

Scheme	5
	

	
IR	 spectra	 displayed	 absorption	 band	 at	 3375‐3250	 cm‐1	

corresponding	to	NH	group.	Treatment	of	pyrimidinones	11a,b	
with	 aryl	 diazonium	 chloride	 or	 aromatic	 aldehydes	 result	 in	
the	 formation	 of	 pyrimidinone	12a‐d	 and	13a‐d,	 respectively	
(Scheme	4).	

The	 reaction	 of	 compound	 2	 with	 active	 methylene	
reagents	 viz	 malononitrile	 and	 ethyl	 cyanoacetate	 in	
dimethylformamide	 containing	 triethyl	 amine	 afforded	
pyridinone	 derivatives	 14a,b,	 respectively	 (Scheme	 5).	
Similarly,	 the	 reaction	 of	 2	 with	 α‐cyanocinnamonitrile	
furnished	 ethyl	 6‐amino‐5‐cyano‐1‐(6‐dibenzothiophen‐2‐yl‐
pyridazin‐3‐yl)‐2‐oxo‐4‐phenyl‐1,2‐dihydropyridine‐3‐
carboxylate	(15).	
	
4.	Conclusion		
	

In	the	present	paper	we	describe	the	reaction	of	ethyl	3‐(6‐
dibenzothiophen‐2‐yl‐pyridazin‐3‐ylamino)‐3‐oxopropanoate	
with	various	 reagents	providing	novel	 five	 and	 six	membered	
heterocycle	 derivatives	 attached	 to	 pyridazine	 and	
dibenzothiophene	moieties.	The	structures	of	all	products	were	
confirmed	by	the	elemental	analysis	and	spectroscopic	studies.	
	
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