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European	Journal	of	Chemistry	4	(2)	(2013)	121‐123	

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

DOI:10.5155/eurjchem.4.2.121‐123.740	

	
	

	

	

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

	 	 	

Synthesis	and	spectral	characterization	of	some	heterocyclic		
nitrogen	compounds	

Mamdouh	Adly	Hassan	a,	Maghrabi	Ali	Seleem	b,	Ahmed	Mohamed	Mosallem	Younes	b,		
Mohamed	Mobark	Taha	b	and	Abou‐Bakr	Haredi	Abdel‐Monsef	b,	*	

a	Pharmaceutical	Chemistry	Department,	Faculty	of	Pharmacy,	Sinai	University,	Arish,	45518,	Egypt	
b	Chemistry	Department,	Faculty	of	Science,	South	Valley	University,	Qena,	83523,	Egypt	

*Corresponding	author	at:	Chemistry	Department,	Faculty	of	Science,	South	Valley	University,	Qena,	83523,	Egypt.		
Tel.:	+20.96.5211281;	fax:	+20.96.5211279.	E‐mail	address:	bakooos2004@yahoo.com	(A.H.	Abdel‐Monsef).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	
Received:	04	February	2013	
Accepted:	16	February	2013	
Online:	30	June	2013	

KEYWORDS	

	 Quinazolines	 and	 pyrimidines	 are	 most	 important	 class	 of	 compounds	 and	 have	 received
much	attention	from	both	synthetic	and	medicinal	chemists,	because	of	 the	diverse	range	of
their	 pharmacological	 properties.	 Owing	 to	 their	 versatile	 chemotherapeutic	 importance,	 a
number	 of	 quinazolin‐2,4‐dione	 derivatives	 were	 synthesized	 using	 appropriate	 synthetic
routes	and	characterized	by	IR,	1H	NMR,	MS,	and	elemental	analysis.	

Arylidine	
Hydrazide	
Pyrimidines	
Carbon	disulphide	
Quinazolin‐2,4‐dione	
Glycine	ethyl	ester	hydrochloride	

	
1.	Introduction	
	

It	 is	 well	 known	 that	 the	 quinazolines	 and	 pyrimidines	
derivatives	are	compounds	with	high	biological	activities.	As	an	
important	 class	 of	 electron‐rich	 N‐containing	 heterocycles,	
pyrimidines	 are	 widely	 present	 in	 biologically	 active	
compounds	 and	 have	 also	 versatile	 synthetic	 applications.	
Many	 derivatives	 of	 pyrimidines	 showed	 antifungal	 [1],	
antibacterial	 [2],	 anti‐inflammatory	 [3]	 anticonvulsant	 [4‐6].	
Pyrimidines	[7]	encourage	the	authors	to	gather	these	moieties	
hoping	 to	 produce	 valuable	 new	 compounds	 of	 expected	
antibacterial	 and	 antifungal	 activity.	 We	 report	 here	 the	
synthesis	 of	 novel	 quinazolin‐2,4‐dione	 derivatives	 starting	
from	 (2,4‐dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	
hydrazide	 (3).	 All	 the	 synthesized	 compounds	 have	 been	
supported	by	their	spectral	data.	
	
2.	Experimental	
	
2.1.	Instrumentation	
	

Melting	 points	 were	 uncorrected	 and	 determined	 on	 an	
electric	melting	point	apparatus	(Kofler).	The	IR	spectra	(KBr)	
were	recorded	on	a	Shimadzu	408	spectrometer.	The	1H	NMR	
spectra	 were	 recorded	 using	 300	 MHz	 Varian	 EM	 390	
spectrometer;	chemical	shifts	are	reported	in	ppm	with	TMS	as	
an	 internal	standard	and	are	given	 in	δ	units.	Electron	 impact	
mass	 spectra	 were	 obtained	 at	 70	 eV	 with	 Shimadzu	 GC‐MS	
(QP‐2010	 plus).	 Elemental	 analyses	 were	 carried	 out	 at	 the	
Microanalysis	 Unit	 at	 Cairo	 University.	 The	 purity	 of	 the	
compounds	was	detected	by	TLC.	
	
	

2.2.	Synthesis	
	
2.2.1.	(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	acid	
ethyl	ester	(2)	
	

A	 mixture	 of	 N‐phenylsulphonyloxyphthalimide	 (1)	 (5	 g,	
0.016	mol)	and	glycine	ethyl	ester	hydrochloride	(2.99	g,	0.02	
mol)	 in	 pyridine	 (20	 mL)	 was	 refluxed	 for	 9	 hours.	 After	
cooling;	 the	 reaction	 mixture	 was	 acidified	 with	 cold	 dilute	
hydrochloric	 acid	 (1:1),	 and	 the	 solid	 formed	was	 filtered	 off	
and	dried.	The	target	product	was	crystallized	from	benzene	to	
give	 compound	 2	 as	 a	 gray	 crystal	 (Scheme	 1).	 Yield:	 3.7	 g,	
90%.	M.p.:	206‐208	 oC.	FT‐IR	 (KBr,	 ν,	 cm‐1):	3380	 (NH),	1719,	
1671	(C=O’	s).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	1.1	(t,	3H,	
CH3),	4.1	(q,	2H,	CH2),	4.6	(s,	2H,	N‐CH2),	7.2‐7.9	(m,	4H,	arom.),	
11.6	(s,	1H,	NH).	MS	(m/z,	%):	248	(31.1	%)	(M+).	Anal.	calcd.	
for	C12H12N2O4:	C,	58.06;	H,	4.87;	N,	11.28.	Found:	C,	58.25;	H,	
4.89;	N,	11.35%.	
		
2.2.2.	(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	acid	
hydrazide	(3)	
	

To	a	 solution	of	compound	2	 (2.5	g,	0.01	mol)	 in	absolute	
ethanol	 (30	 mL),	 5	 mL	 of	 hydrazine	 hydrate	 was	 added;	 the	
reaction	 mixture	 was	 refluxed	 for	 8	 hours.	 The	 reaction	
mixture	 was	 allowed	 to	 cool	 and	 the	 separated	 product	 was	
filtered	 and	 dried.	 Crystallization	 of	 the	 crude	 product	 with	
ethanol	and	acetic	acid,	afforded	compound	3	as	a	white	crystal	
(Scheme	1).	Yield	1.6	g,	62	%.	M.p.:	>300.	FT‐IR	(KBr,	ν,	cm‐1):	
3296	 (NH),	 3196	 (NH2),	 1714,	 1665	 (C=O’	 s).	 1H	 NMR	 (300	
MHz,	DMSO‐d6,	δ,	ppm):	4.5	 (s,	2H,	CH2),	4.2	 (s,	2H,	NH2),	7.1‐
7.9	(m,	4H,	arom.),	9.2	(s,	1H,	NH),	11.5	(s,	1H,	NH).		

	



122	 Hassan	et	al.	/	European	Journal	of	Chemistry	4	(2)	(2013)	121‐123	
	

	

	

Scheme	1	
	
	

	
	

Scheme	2
	

	
MS	(m/z,	%):	234	(20.1	%)	(M+).	Anal.	calcd.	for	C10H10N4O3:	

C,	51.28;	H,	4.30;	N,	23.92.	Found:	C,	51.49;	H,	4.31;	N,	23.98%.	
	
2.2.3.	3‐(5‐Thioxo‐[1,3,4]oxadiazolidin‐2‐ylidenemethyl)‐1H‐
quinazoline‐2,4‐dione	(4)	
	

To	a	solution	of	compound	3	(0.5	g,	0.002	mol)	in	pyridine	
(20	mL),	 1	mL	 of	 carbon	 disulphide	 was	 added;	 the	 reaction	
mixture	was	refluxed	for	10	hours	or	until	the	hydrogen	sulfide	
has	 been	 evolved.	 After	 cooling;	 the	 reaction	 mixture	 was	
acidified	with	cold	dilute	hydrochloric	acid	(1:1),	and	the	solid	
formed	was	filtered	off	and	dried.	The	product	was	crystallized	
from	 acetic	 acid	 to	 give	 compound	 4,	 as	 a	 yellowish	 white	
crystal	(Scheme	2).	Yield	0.3	g,	60	%.	M.p.:	274	oC.	1H	NMR	(300	
MHz,	 DMSO‐d6,	 δ,	 ppm):	 4.6	 (s,	 1H,	 Olifinic	 CH),	 5.1	 (s,	 1H,	
NH(4)),	7.2‐7.9	(m,	4H,	arom.),	10.2	(s,	1H,	NHCS),	11.5	(s,	1H,	
NH).	 Anal.	 calcd.	 for	 C11H8N4O3S:	 C,47.82;	 H,2.92;	 N,	 20.28;	 S,	
11.61.	Found:	C,	48.02;	H,	2.94;	N,	20.35;	S,	11.59%. 
	
2.2.4.	3‐(4‐Amino‐5‐mercapto‐4H‐[1,2,4]triazol‐3‐ylmethyl)‐
1H‐quinazoline‐2,4‐dione	(5)	
	

To	 a	 solution	 of	 (2,4‐dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐
yl)‐acetic	 acid	 hydrazide	 (3)	 (1	 g,	 0.004	 mol)	 in	 absolute	
ethanol	(30	mL),	potassium	hydroxide	(0.45	g,	0.008	mol)	and	
carbon	disulfide	(3	mL)	were	added,	respectively.	The	mixture	
was	stirred	for	8	hours	in	ice	bath.	The	yellow	formed	salt	was	
filtered	off	and	dried.	Then	the	solid	was	dissolved	in	distilled	
water	 (50	mL)	and	hydrazine	hydrate	 (0.1	mol)	was	added	 to	
this	 solution	 with	 reflux	 for	 10	 hours,	 after	 that	 the	 mixture	
was	 neutralized	 with	 diluted	 acetic	 acid	 to	 form	 white	
precipitate	which	collected	by	filtration.	The	resulting	product	
was	recrystallized	from	ethanol	to	give	compound	5	as	a	white	
crystal	(Scheme	2).	Yield	0.8	g,	66%.	M.p.:	282	oC.	FT‐IR	(KBr,	ν,	
cm‐1):	 3304	 (NH),	 3203,	 3169	 (NH2),	 1715,	 1660	 (C=O’	 s).	 1H	
NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	5.1	(s,	2H,	NH2),	5.7	(s,	2H,	
CH2),	7.2‐7.9	(m,	4H,	arom.),	11.6	(s,	1H,	NH),	13.5	(s,	1H,	SH).	
Anal.	calcd.	for	C11H10N6O2S:	C,	45.51;	H,	3.47;	N,	28.95;	S,	11.04.	
Found:	C,	45.80;	H,	3.49;	N,	29.02;	S,	11.24%. 

2.2.5.	General	procedures	for	synthesis	of	arylidines	(6a‐d)	
	

(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	
hydrazide	3	(0.45	g,	0.002	mol)	was	heated	under	reflux	for	10‐
12	 hours	 with	 the	 appropriate	 aromatic	 aldehydes	 namely	
benzaldehyde,	 p‐nitrobenzaldehyde,	 2‐furaldehyde	 and	
thiophenecarbaldehyde	 (0.003	 mol)	 in	 absolute	 ethanol	 (20	
mL)	and	 in	presence	of	piperidine	as	a	 catalyst.	After	 cooling;	
the	 reaction	 mixture	 was	 filtered	 off	 and	 crystallized	 from	
appropriate	 solvent	 to	 give	 the	 arylidine	 derivatives	 6a‐d,	
respectively	(Scheme	3).	

(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	
benzylidene	 hydrazide	 (6a):	 White	 crystal.	 Yield:	 0.3	 g,	 55%.	
M.p.:	 >	 300	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3258	 (NH),	 3102	 (CH	
aliphatic),	1722,	1693	(C=O’	s).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	
ppm):	5.0	(s,	2H,	CH2),	7.2‐8.2	(m,	9H,	arom.),	8.01	(s,	1H,	CH),	
11.54	(s,	1H,	NH),	11.65	(s,	1H,	NH).	MS	(m/z,	%):	322	(2.4	%).	
Anal.	calcd.	for	C17H14N4O3:	C,	63.35;	H,	4.38;	N,	17.39.	Found:	C,	
63.53;	H,	4.41;	N,	17.45%.	

(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	 (4‐
nitrobenzylidene)‐hydrazide	 (6b):	 White	 crystal .Yield	 0.34	 g,	
56%.	M.p.:	>	300	oC.	FT‐IR	(KBr,	ν,	cm‐1):	3206	(NH),	3183	(CH	
aliphatic),	1715,	1694	(C=O’	s).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	
ppm):	5.0	 (s,	 2H,	CH2),	7.2‐8.3	 (m,	8H,	 arom.),	 8.0	 (s,	 1H,	CH),	
11.6	 (s,	 1H,	NH),	 12.0	 (s,	 1H,	NH).	MS	 (m/z,	%):	 367	 (3.0	%).	
Anal.	 calcd.	 for	C17H13N5O5:	C,55.58;	H,3.56;	N,19.04.	Found:	C,	
55.60;	H,	3.58;	N,	19.02%.	

(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	
(furan‐2‐ylmethylene)‐hydrazide	 (6c):	Yellow	crystal.	Yield:	0.4	
g,	 72%.	M.p.:	 >	 300	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3383	 (NH),	 3009	
(CH	aliphatic),	1739,	1638	(C=O’	s).	1H	NMR	(300	MHz,	DMSO‐
d6,	δ,	ppm):	4.9	(s,	2H,	CH2),	6.6	(dd,	1H,	HX),	6.8	(dd,	1H,	HM),	
7.7	 (dd,	 1H,	 HA),	 7.2‐7.9	 (m,	 4H,	 arom.),	 8.09	 (s,	 1H,	 CH=N),	
11.59	(s,	1H,	NH),	11.67	(s,	1H,	NH).	Anal.	calcd.	for	C15H12N4O4:	
C,	57.68;	H,	3.85;	N,	17.93.	Found:	C,	57.60;	H,	3.86;	N,	17.91%.	

(2,4‐Dioxo‐1,4‐dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	
(thiophen‐2‐ylmethylene)‐hydrazide	 (6d):	 Yellow	 crystal.	 Yield:	
0.39	 g,	 75%.	M.p.:	 >	 300	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3201	 (NH),	
2924,	2852	(CH	aliphatics),	1740,	1659	(C=O’	s).		



Hassan	et	al.	/	European	Journal	of	Chemistry	4	(2)	(2013)	121‐123	 123	
 

	

	
	

Scheme	3
	
	
	

3

N
H

N

O

O

O

H
N

NH2
Ar ..

C

S

S

+

Ar =

base Ar

O

N

H

NH C

S

S -

Ar

O

N NH

C

S

S
- -

Ar

O

N N

C

SH

S
-

H

O

NH

H
N

Ar

S

- H2S

	
	

Scheme	4
	
	
1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	4.9	(s,	2H,	CH2),	7.1	

(dd,	1H,	HX),	7.5	(dd,	1H,	HM),	7.8	(dd,	1H,	HA),	7.2‐7.9	(m,	4H,	
arom.),	 8.4	 (s,	 1H,	 CH=N.),	 11.5	 (s,	 1H,	 NH),	 11.7	 (s,	 1H,	NH).	
Anal.	calcd.	for	C15H12N4O3S:	C,	54.86;	H,	3.67;	N,	17.05,	S,	9.76.	
Found:	C,	54.98;	H,	3.80;	N,	17.11,	S,	9.74%. 
	
2.2.6.	3‐(4‐Acetyl‐5‐phenyl‐4,5‐dihydro‐[1,3,4]oxadiazol‐2‐
ylmethyl)‐1H‐quinazoline‐2,4‐dione	(7a)	
	

A	solution	of	compound	6a	(0.4	g,	0.0012	mol.)	with	acetic	
anhydride	(20	mL)	was	heated	under	reflux	for	12	hours.	After	
cooling;	 the	 reaction	mixture	 was	 poured	 into	 crushed	 ice	 to	
give	 white	 precipitate	 which	 collected	 by	 filtration	 then	
crystallized	 from	 ethanol	 to	 give	 compound	 7a	 as	 a	 white	
crystal	 (Scheme	 3). Yield:	 0.42	 g,	 70%.	 M.p.:	 >	 300	 oC.	 FT‐IR	
(KBr,	 ν,	 cm‐1):	 3198	 (NH),	 1740,	 1637	 (C=O’	 s).	 1H	NMR	 (300	
MHz,	DMSO‐d6,	δ,	ppm):	2.  1 (s,	3H,	CH3),	4.8	(s,	2H,	CH2),	7.0	(s,	
1H,	CH),	7.1‐7.9	(m,	9H,	arom.),	11.5	(s,	1H,	NH).	Anal.	calcd.	for	
C19H16N4O4:	C,	62.62;	H,	4.40;	N,	15.37.	Found:	C,	62.64;	H,	4.42;	
N,	15.42%.	
	
3.	Results	and	discussion	
	

In	 this	 study,	 our	 target	 was	 to	 synthesize	 novel	
quinazolindiones	 derivatives	 which	 based	 on	 the	 reaction	
between	 glycine	 ethyl	 ester	 hydrochloride	 and	 N‐
phenylsulphonyloxyphtahlimide	via	 Lossen	 rearrangement	 [8‐
9]	giving	quinazoline‐2,4‐dione	derivatives.	In	the	course	of	the	
present	 work,	 we	 found,	 reacting	 of	 N‐phenylsulphonyl	
oxyphthalimide	 (1)	 with	 glycine	 ethyl	 ester	 hydrochloride	 in	
pyridine	 under	 reflux	 for	 9	 hours	 afford	 (2,4‐dioxo‐1,4‐
dihydro‐2H‐quinazolin‐3‐yl)‐acetic	 acid	 ethyl	 ester	 (2),	 which	
then	converted	to	starting	material	(2,4‐dioxo‐1,4‐dihydro‐2H‐
quinazolin‐3‐yl)‐acetic	 acid	 hydrazide	 (3)	 in	 a	 good	 yield	
through	 its	 reaction	 with	 hydrazine	 hydrate	 in	 absolute	
ethanol.	 The	 synthetic	 procedures	 to	 obtain	 the	 target	
compounds	are	depicted	in	Scheme	1.		

Scheme	2	outlines	the	synthetic	pathway	used	to	obtain	3‐
(5‐thioxo‐[1,3,4]oxadiazolidin‐2‐ylidenemethyl)‐1H‐quinazoli‐
ne‐2,4‐dione	(4)	which	prepared	by	treatment	of	compound	3	
with	with	carbon	disulphide	in	pyridine	under	reflux	for	9	hrs.	
as	 given	 mechanism	 in	 Scheme	 4.	 Also,	 we	 can	 obtain	 3‐(4‐

amino‐5‐mercapto‐4H‐[1,2,4]triazol‐3‐ylmethyl)‐1H‐quinazoli‐
ne‐2,4‐dione	 (5)	 by	 reaction	 of	 hydrazide	 (3)	 with	 carbon	
disulphide	 and	 ethanolic	 potassium	 hydroxide	 followed	 by	
treatment	the	resulted	intermediate	with	hydrazine	hydrate	in	
distilled	water.	

Scheme	 3	 outlines	 our	 strategies	 for	 the	 synthesis	 of	
arylidines	(6a‐d)	which	produced	by	reaction	of	hydrazide	(3)	
with	 some	 aromatic	 aldehydes	 like	 benzaldehyde,	 p‐
nitrobenzaldehyde,	 furan	 aldehyde	 and	 thiophenealdehyde,	
respectively,	 in	 ethanol.	 Also,	 we	 can	 use	 compound	 6a	 to	
synthesis	 oxadiazole	 ring	 attached	 to	 quinazoline	 moiety	 by	
treatment	of	compound	6a	with	acetic	anhydride	under	reflux	
for	 12	 hrs.	 afford	 3‐(4‐acetyl‐5‐phenyl‐4,5‐dihydro‐[1,3,4]oxa	
diazol‐2‐ylmethyl)‐1H‐quinazoline‐2,4‐dione	(7a).	
	
4.	Conclusion	
	 	

In	 conclusion,	 an	 efficient	 synthesis	 of	 tetrachloro	
quinazolindione	derivatives	has	been	developed.	
	
Acknowledgment	
	

The	 authors	 are	 grateful	 to	 Mr.	 Ibrahim	 M.	 A.	 Ismael,	
Central	Lab.	of	South	Valley	University	 for	his	help	 in	analysis	
of	some	samples.		
	
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