untitled


European	Journal	of	Chemistry	5	(4)	(2014)	671‐675	

	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2014	Eurjchem	Publishing	‐	Printed	in	the	USA	

http://dx.doi.org/10.5155/eurjchem.5.4.671‐675.1071	

	
	

	

	

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

	 	 	

Synthesis	of	2‐aryl	substituted	2,3‐dihydroquinazoline‐4(1H)‐ones		
under	solvent	free	conditions	using	ionic	liquid	as	a	mild	and	efficient	catalyst	

Obaiah	Obaiah,	Nandeesh	Nagalingaiah	Kebbahalli,	Raghavendra	Manchigaiah	Goravanahalli,	
Pavankumar	Siddalingaiah	Chottanahalli,	Rangappa	Subbegowda	Kanchugarakoppal,		
and	Mantelingu	Kempegowda	*	

Department	of	Studies	in	Chemistry,	University	of	Mysore,	Manasagangotri,	Mysore,	570006,	India	

*Corresponding	author	at:	Department	of	Studies	in	Chemistry,	University	of	Mysore,	Manasagangotri,	Mysore,	570006,	India.		
Tel.:	+91.821.2412191.	Fax:	+91.821.2412191.	E‐mail	address:	kmantelingu@yahoo.com	(M.	Kempegowda).	

	
	

	 	

	 	 	
COMMUNICATION	INFORMATION	 	 ABSTRACT

	
DOI:	10.5155/eurjchem.5.4.671‐675.1071	

Received:	10	April	2014	
Received	in	revised	form:	14	May	2014	
Accepted:	13	June	2014	
Online:	31	December	2014	

KEYWORDS	

	 A	simple,	green	and	environmentally	benign	procedure	has	been	developed	for	the	synthesis
of	 2,3‐dihydroquinazoline‐4(1H)‐ones	 in	 basic	 ionic	 liquid	 via	 the	 cyclocondensation	 of	 2‐
amino	benzamide	with	an	aldehyde.	This	offers	several	advantages	such	as	high	yields,	simple
procedure,	low	cost,	short	reaction	times,	mild	and	solvent	free	condition.	

Aldehyde		
Ionic	liquid	
Anthranilamide		
Choline	chloride	
Solvent	free	condition	
2,3‐Dihydroquinazoline	4(1H)‐ones	

	
1.	Introduction	
	

2,3‐Dihydroquinazolin‐4(1H)‐one	 derivatives	 are	
important	 heterocyclic	 compounds.	 These	 are	 widely	 used	 in	
biological	and	pharmaceutical	activities	[1].	The	quinazolinones	
display	 wide	 range	 of	 biological	 activities	 such	 as	 antitumor	
[2,3],	 antidefibrillatory	 [4],	 antidepressant	 [5],	 analgesic	 [6],	
diuretic	 [7],	 antihistamine	 [8],	 vasodilating	 [9],	 antihyperten‐
sive	 [10],	 CNS	 stimulant	 [11],	 tranquilizing	 [12]	 and	
antianxietic	 [13].	 Some	 representative	 drug	 molecules	 having	
quinazoline	 skeleton	 are	 shown	 in	 Figure	 1.	 These	 quinazo‐
linones	also	act	as	plant	growth	regulators	[14].	

	

 
	

Figure	1.	Some	marketed	drugs	with	quinazolinone	skeleton.
	
As	 a	 consequence,	 in	 recent	 years	 these	 2,3‐dihydro	

quinazolin‐4(1H)‐ones	 have	 become	 attractive	 targets	 in	

synthetic	 chemistry.	 Development	 of	 novel	 synthetic	
methodologies	 to	 facilitate	 preparation	 of	 desired	 molecules	
has	become	an	 intense	area	of	research.	 In	 this	regard,	efforts	
have	 been	 made	 constantly	 to	 introduce	 new	 methodologies	
that	 are	 efficient	 and	more	 compatible	with	 the	 environment.	
Consequently	enormous	number	of	synthetic	methods	has	been	
developed	for	the	construction	of	quinazoline	alkaloids	[15,16].	
Among	 these,	 condensation	 of	 2‐aminobezamide	with	 aldehy‐
des	is	one	of	the	simple	and	direct	methods	for	the	synthesis	of	
2,3‐dihydroquinazolin‐4(1H)‐ones.	 The	 classical	 methods	 for	
the	synthesis	of	2,3‐dihydroquinazolin‐4(1H)‐ones	are	associa‐
ted	with	various	acid	catalysts	such	as	PTSA/NaHSO3,	TiCl4/Zn,	
CuCl2,	 ionic	 liquid,	 TFA,	 ammonium	 chloride	 and	 chiral	
phosphoric	 acid	 [17,18].	 Although	 these	 methods	 are	 very	
useful	 for	 the	 synthesis	 of	 2,3‐dihydroquinazolin‐4(1H)‐ones	
but	 the	 reactions	 involved	 have	 major	 limitations	 such	 as	
expensive	 reagents,	 lengthy	 reaction	 times,	 high	 temperature	
requirement	 and	also	 tedious	work‐up	procedures.	Therefore,	
the	development	of	novel	method	to	overcome	the	 limitations	
for	 the	 synthesis	 of	 quinazolin‐4(1H)‐ones	 is	 of	 great	
importance	 because	 of	 their	 biological	 and	 pharmaceutical	
importance.		

	



672	 Obaiah	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	671‐675	
	

	

NH2

O

NH2

+

O H

R
N
H

NH

O

RR = Cl, Br, F, OH, OMe, ActOxy, CN, NO2, CF3

Basic Ionic liquid

RT

 
Scheme	1	

	
	
Over	the	past	decade	utility	of	ionic	liquids	in	catalysis	and	

as	 neoteric	 solvent	 for	 various	 synthetic	 processes	 has	 been	
well	recognized	by	the	chemists	all	over	the	world.	Due	to	their	
chemical	 properties,	 such	 as	 recyclability,	 negligible	 vapor	
pressure,	 ability	 to	 dissolve	 wide	 range	 of	 substrates	 and	
catalysts,	 thermal	stability.	 Ionic	 liquids	have	been	considered	
as	 viable	 alternatives	 to	 the	 conventional	 volatile	 organic	
solvents	 [19‐23].	 Protic	 and	 Bronsted	 basic	 liquids,	 in	
particular,	 have	 received	 increasing	attention	 for	 carrying	out	
organic	 transformations	 as	 they	 can	 replace	 volatile	 organic	
solvents	 as	 well	 as	 highly	 acidic	 catalytic	 systems	 [24‐25].	
Hence	 uses	 of	 ionic	 liquids	 have	 been	 found	 advantageous	 as	
they	usually	involve	in	simple	reaction	processes	as	compared	
to	most	of	the	traditional	methods	[23].	
	
2.	Experimental	
	
2.1.	Materials	and	methods	
	

Works	 relating	 to	 analytical	 thin	 layer	 chromatography	
were	 performed	 using	 E.	 Merck	 silica	 gel	 60F254	 aluminum	
plates	and	were	visualized	with	UV	light.	The	following	mobile	
phases	 employed	 for	 TLC	 were	 chloroform,	 methanol	 and	
hexane,	and	ethyl	acetate	 in	different	 ratios.	The	 instrumental	
techniques	 adopted	 for	 the	 characterization	 of	 the	 newly	
synthesized	 compounds	 include	 1H	 and	 13C	 NMR	 and	 mass	
spectroscopy.	 1H	 and	 13C	 NMR	 spectra	 were	 recorded	 on	 a	
Bruker	 WM	 (400	 and	 300	 MHz)	 spectrometer	 in	 CDCl3	 or	
DMSO‐d6	 solution	 using	 tetramethylsilane	 (TMS)	 as	 internal	
standard.	 Chemical	 shifts	 were	 recorded	 in	 ppm	 relative	 to	
TMS.	 Mass	 and	 purity	 were	 recorded	 on	 LC–MSD‐Trap‐XCT	
(Agilent	technologies	Inc).	
	
2.2.	Synthesis	

	
Mixture	 of	 choline	 chloride	 (2	 g,	 0.0143	 mmol)	 and	 urea	

(1.72	 g,	 0.0286	 mmol)	 was	 heated	 for	 100‐200	 °C,	 and	 at	
certain	 temperature	 it	 formed	 into	 liquid.	 To	 this	 reaction	
mixture	 2‐amino	 benzamide	 (0.2	 g,	 0.00147	 mmol)	 and	 4‐
formylphenyl	 acetate	 (0.241	 g,	 0.00147	 mmol)	 were	 added	
(Scheme	 1).	 The	 mixture	 was	 stirred	 for	 3	 h.	 Reaction	
completion	was	confirmed	by	TLC.	 It	was	extracted	with	ethyl	
acetate.	 The	 combined	 organic	 layer	was	washed	with	water,	
and	saturated	brine	solution	followed	by	using	over	anhydrous	
Na2SO4.	 The	 combined	 organic	 layer	 was	 evaporated	 under	
vacuum	pressure	and	the	resulting	crude	product	was	purified	
by	 column	 chromatography	 with	 ethyl	 acetate	 in	 hexane	 as	
eluent	which	afforded	the	desired	product.	The	products	were	
identified	 by	 1H	 NMR,	 13C	 NMR	 and	 LC/MS,	 showed	 good	
agreement	with	the	assigned	structures.	

4‐(4‐Oxo‐1,2,3,4‐tetrahydroquinazolin‐2‐yl)phenyl	 acetate	
(Table	1,	Entry	1):	Color:	White	solid.	Yield:	80%.	1H	NMR	(300	
MHz,	DMSO‐d6,	δ,	ppm):	8.27	(s,	1H,	NH),	7.58‐7.61	(d,	1H,	 J	=	
7.6	 Hz,	 Ar‐H),7.49‐7.52	 (d,	 2H,	 J	=	 8.4	 Hz,	 Ar‐H),	 7.20‐7.25	 (t,	
2H,	 J	=	7.3	Hz,	Ar‐H),	7.11‐7.14	(d,	2H,	J	=	8.4	Hz,	Ar‐H),	6.71‐
6.74	(d,	1H,	J	=	8.1	Hz,	Ar‐H),	6.64‐6.69	(t,	1H,	J	=	7.5	Hz,	CH‐NH‐
),	5.76	(s,	1H,	NH),	2.27	(s,	3H,	CH3‐CO‐O‐).	 13C	NMR	(75	MHz,	
DMSO‐d6,	 δ,	 ppm):	 169.61,	 164.00,	 150.99,	 148.25,	 239.53,	
133.80,	129.66,	128.51,	127.82,	126.32,	122.18,	117.65,	115.36,	
114.80,	66.58,	21.28.	MS	(m/z):	283.20	[M++	H].	Anal.	calcd.	for	

C16H14N2O3:	C,	68.07;	H,	5.00;	N,	9.92.	Found:	C,	68.02;	H,	4.98;	
N,	9.87%.	

2‐(2,	 4‐Dimethylphenyl)‐2,	 3‐dihydroquinazolin‐4(1H)‐one	
(Table	1,	Entry	2):	Color:	White	solid.	Yield:	80%.	1H	NMR	(300	
MHz,	DMSO‐d6,	δ,	ppm):	7.99	(s,	1H,	NH),	7.61‐7.64	(d,	1H,	 J	=	
10.28	Hz,	Ar‐H),	7.40‐7.43	(d,	1H,	J	=	10.64	Hz,	Ar‐H),	7.20‐7.23	
(t,	1H,	J	=	10.14	Hz,	Ar‐H),	7.01‐7.04	(s,	2H,	Ar‐H),	6.65‐6.79	(	m,	
3H,	CH‐NH	+	Ar‐H),	5.93	(s,	1H,	NH),	2.37	(s,	3H,	Ar‐CH3),	2.26	
(s,	 3H,	Ar‐CH3).	 13C	NMR	 (75	MHz,	DMSO‐d6,	 δ,	 ppm):	 164.52,	
149.01,	138.10,	136.35,	135.57,	133.60,	131.71,	129.66,	128.25,	
127.87,	126.86,	117.59,	114.91,	64.51,	21.01,	19.16.	MS	(m/z):	
253.30	[M++	H].		Anal.	calcd.	for	C16H16N2O:	C,	76.16;	H,	6.39;	N,	
11.10.	Found:	C,	76.12;	H,	6.38;	N,	11.12%.	

2‐(4‐Methoxyphenyl)‐2,	 3‐dihydroquinazolin‐4(1H)‐one	
(Table	1,	Entry	3):	Color:	White	solid.	Yield:	81%.	1H	NMR	(300	
MHz,	DMSO‐d6,	δ,	ppm):	8.16	(s,	1H,	NH),	7.57‐7.60	(d,	1H,	 J	=	
7.72	Hz,	Ar‐H),	7.38‐7.41	(d,	2H,	J	=	8.67	Hz,	Ar‐H),	7.19‐7.24	(t,	
1H,	 J	=	7.83	Hz,	Ar‐H),	6.98	(s,	1H,	Ar‐H),	6.91‐6.94	(d,	2H,	 J	=	
8.7	Hz,	Ar‐H),	6.70‐6.73	(d,	1H,	J	=	7.95	Hz,	Ar‐H),	6.63‐6.68	(t,	
1H,	J	=	7.23	Hz,	CH‐NH),	5.68	(s,	1H,	NH),	3.73	(s,	3H,	CH3‐O‐).	
13C	NMR	 (75	MHz,	DMSO‐d6,	 δ,	 ppm):	 164.13,	 159.89,	 148.46,	
133.94,	128.65,	127.79,	117.52,	115.46,	114.86,	114.09,	66.75,	
55.63.	MS	(m/z):	255.28	[M++	H].	Anal.	calcd.	for	C15H14N2O2:	C,	
70.85;	H,	5.55;	N,	11.02.	Found:	C,	70.80;	H,	5.53;	N,	11.00%.	

2‐(3,	 4‐Dimethoxyphenyl)‐2,	 3‐dihydroquinazolin‐4(1H)‐one	
(Table	1,	Entry	4):	Color:	White	solid.	Yield:	82%.	1H	NMR	(300	
MHz,	DMSO‐d6,	δ,	ppm):	8.06	 (s,	1H	NH),	7.60‐7.62	 (d,	1H,	 J	 =	
7.71	Hz,	Ar‐H),	7.15‐7.26	(m,	3H,	Ar‐H),	6.83	(s,	1H,	Ar‐H),	6.65‐
6.73	 (	m,	 3H,	 CH‐NH,	 Ar‐H),	 5.99	 (s,	 1H,	NH),	 3.80	 (s,	 3H	Ph‐
OCH3),	 3.70	 (s,	 3H,	 Ph‐OCH3).	 13C	 NMR	 (75	MHz,	 DMSO‐d6,	 δ,	
ppm):	164.75,	153.20,	146.69,	145.49,	134.54,	134.18,	128.60,	
121.62,	 119.53,	 117.02,	 116.72,	 115.08,	 114.70,	 61.44,	 56.17.	
MS	(m/z):	285.11	[M++	H].	Anal.	calcd.	for	C16H16N2O3:	C,	67.59;	
H,	5.67;	N,	9.85.	Found:	C,	67.56;	H,	5.68;	N,	9.82%.	

2‐(4‐Fluorophenyl)‐2,	3‐dihydroquinazolin‐4(1H)‐one	 (Table	
1,	Entry	5):	Color:	White	solid.	Yield:	88%.	1H	NMR	(300	MHz,	
DMSO‐d6,	 δ,	ppm):	8.26	 (s,	1H,	NH),	7.58‐7.60	 (d,	 1H,	 J	 =	 7.47	
Hz,	 Ar‐H),	 7.49‐7.54	 (m,	 2H,	 Ar‐H),	 7.17‐7.25	 (m,	 3H,	 Ar‐H),	
7.08	(s,	1H,	Ar‐H),	6.71‐6.74	(d,	1H,	J	=	8.04	Hz,	Ar‐H),	6.64‐6.69	
(t,	1H,	J	=	7.41	Hz,	CH‐NH),	5.75	(s,	1H,	NH).	13C	NMR	(75	MHz,	
DMSO‐d6,	 δ,	 ppm):	 163.79,	 161.36,	 148.27,	 138.25,	 133.83,	
129.50,	 127.83,	 117.72,	 115.43,	 115.41,	 114.91,	 66.39.	 MS	
(m/z):	243.24	[M++	H].		Anal.	calcd.	for	C14H11FN2O:	C,	69.41;	H,	
4.58;	N,	11.56.	Found:	C,	69.40;	H,	4.58;	N,	11.53%.	

2‐(4‐Chlorophenyl)‐2,	3‐dihydroquinazolin‐4(1H)‐one	(Table	
1,	Entry	6):	Color:	White	solid.	Yield:	87%.	1H	NMR	(300	MHz,	
DMSO‐d6,	 δ,	ppm):	8.32	 (s,	1H,	NH),	7.58‐7.60	 (d,	 2H,	 J	 =	 7.68	
Hz,	Ar‐H),	7.42‐7.51	(m,	3H,	Ar‐H),	7.20‐7.25	(t,	1H,	J	=	7.23	Hz,	
Ar‐H),	7.12	 (s,	 1H,	 Ar‐H),	6.71‐6.74	 (d,	1H,	 J	 =	 8.10	Hz,	Ar‐H),	
6.64‐6.69	(t,	1H,	J	=	7.53	Hz,	CH‐NH),	5.75	(s,	1H,	NH).	13C	NMR	
(75	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 163.79,	 161.36,	 148.27,	 138.27,	
138.24,	133.83,	129.55,	129.46,	127.83,	117.72,	115.45,	111.41,	
114.91,	 66.39.	 MS	 (m/z):	 259.70	 [M++	 H].	 Anal.	 calcd.	 for	
C14H11ClN2O:C,	65.00;	H,	4.29;	N,	10.83.	Found:	C,	65.02;	H,	4.26;	
N,	10.82%.	

4‐(4‐Oxo‐1,	2,	3,	4‐tetrahydroquinazolin‐2‐yl)benzonitrile	
(Table	1,	Entry	7):	Color:	White	solid.	Yield:	90%.	1H	NMR	(300	
MHz,	DMSO‐d6,	δ,	ppm):	8.47	(s,	1H,	NH),	7.85‐7.87	(d,	2H,	 J	=	
8.4	Hz,	Ar‐H),	7.64‐7.66	 (d,	2H,	 J	 =	8.4	Hz,	Ar‐H),	7.58‐7.60	 (t,	
1H,	J	=	7.6	Hz,	Ar‐H),	7.23‐7.28	(m,	2H,	Ar‐H),	6.74‐6.76	(d,	1H,				



Obaiah	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	671‐675	 673	
 

	
Table	1.	Synthesis	of	2,3‐dihydroquinazolin‐4(1H)‐ones.	
Entry	 R1	 R2	 Product	a,b	 Reaction	time	(h)	 Yield	(%)	
1	

	 	

4 80	

2	

	
	

4 80	

3	

	
	

4	 81	

4	

	
	

4	 82	

5	

	 	

3	 88	

6	

	 	

3	 87	

7	

	 	

3 90	

8	

	 	

3 90	

9	

	 	

3 88	

10	
	

	
	

	

5	 80	

11	

	 	

5 81	

12	

	 	

5	 83	

13	

	 	

5 85	

14	

	

	

5 85	

a	Reaction	condition:	Choline	chloride	(1	mmol),	urea	(2	mmol),	2‐amino	benzamide	(1	mmol),	aldehyde	(1	mmol)	at	room	temperature.	
b	Isolated	yield.	
	
	
	



674	 Obaiah	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	671‐675	
	
	

 
	

Scheme	2	
	
	
J	=	8.0	Hz,	Ar‐H),	6.66‐6.69	 (t,	1H,	 J	=	7.2	Hz,	CH‐NH),	5.84	(s,	
1H,	NH).	13C	NMR	(75	MHz,	DMSO‐d6,	δ,	ppm):	163.30,	147.34,	
147.31,	133.53,	132.39,	127.67,	127.37,	118.64,	117.40,	114.88,	
114.49,	 111.04,	 65.50.	MS	 (m/z):	 250.26	 [M++	H].	 Anal.	 calcd.	
for	C15H11N3O:	 C,	 72.28;	H,	 4.45;	N,	 16.86;	 Found:	 C,	 72.27;	H,	
4.40;	N,	16.84%.	

2‐(6‐(Trifluoromethyl)pyridin‐3‐yl)‐2,	 3‐dihydroquinazolin‐
4(1H)‐one	(Table	1,	Entry	8):	Color:	White	solid.	Yield:	90%.	1H	
NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	8.86	(s,	1H,	Ar‐H),	8.50	(s,	
1H,	NH),	8.14‐8.16	(d,	1H,	J	=	7.2	Hz,	Ar‐H),	7.95‐7.97	(d,	1H,	J	=	
8.0	Hz,	Ar‐H	),	7.61‐7.63	(d,	1H,	J	=	7.2	Hz,	Ar‐H),	7.26‐7.30	(m,	
2H,	Ar‐H),	6.76‐6.78	(d,	1H,	J	=	8.0	Hz,	Ar‐H),	6.70‐6.74	(t,	1H,	J	
=	7.2	Hz,	CH‐NH‐),	5.98	(s,	1H,	NH).	13C	NMR	(75	MHz,	DMSO‐d6,	
δ,	 ppm):	 163.38,	 149.02,	 147.33,	 146.17,	 140.84,	 136.76,	
133.63,	127.44,	122.92,	120.20,	117.77,	115.00,	114.64,	63.99.	
MS	 (m/z):	 294.24	 [M++	 H].	 	 Anal.	 calcd.	 for	 C14H10F3N3O:	 C,	
57.34;	H,	3.44;	N,	14.33.	Found:	C,	57.34;	H,	3.42;	N,	14.32%.	

2‐(4‐Nitrophenyl)‐2,	 3‐dihydroquinazolin‐4(1H)‐one	 (Table	
1,	Entry	9):	Color:	Yellow	solid.	Yield:	88%.	1H	NMR	(300	MHz,	
DMSO‐d6,	 δ,	ppm):	8.50	 (s,	1H,	NH),	8.22‐8.35	 (d,	2H,	 J	 =	8.61	
Hz,	Ar‐H),	7.71‐7.74	(d,	2H,	J	=	8.5	Hz,	Ar‐H),	7.58‐7.60	(d,	1H,	J	
=	7.62	Hz,	Ar‐H),	7.22‐7.27	(t,	2H,	J	=	7.95	Hz,	Ar‐H),	6.73‐6.76	
(d,	1H,	J	=	8.07	Hz,	Ar‐H),	6.64‐6.69	(t,	1H,	J	=	7.47	Hz,	CH‐NH‐),	
5.87	(s,	1H,	NH).	13C	NMR	(75	MHz,	DMSO‐d6,	δ,	ppm):	163.72,	
149.78,	147.89,	147.89,	147.68,	143.00,	128.48,	127.86,	124.02,	
117.91,	115.37,	115.00,	67.75.	MS	(m/z):	270.08	[M++	H].	Anal.	
calcd.	 for	 C14H11N3O3,	 C,	 62.45;	 H,	 4.12;	 N,	 15.61.	 Found:	 C,	
62.43;	H,	4.10;	N,	15.60%.	

2‐(3‐Bromo‐5‐methoxyphenyl)‐2,	 3‐dihydroquinazolin‐
4(1H)‐one	 (Table	1,	 Entry	10):	Color:	White	 solid.	 Yield:	 80%.	
1H	NMR	 (300	MHz,	DMSO‐d6,	 δ,	 ppm):	 8.11	 (s,	 1H,	NH),	 7.62‐
7.64	(d,	1H,	J	=	7.56	Hz,	Ar‐H),7.49‐7.52	(d,	1H,	J	=	8.72	Hz,	Ar‐
H),	7.45	(s,	1H,	Ar‐H),	7.23‐7.27	(t,	1H,	J	=	7.04	Hz,	Ar‐H),	7.03‐
7.05	(d,	1H,	J	=	8.72	Hz,	Ar‐H),	6.88	(s,	1H,	Ar‐H),	6.76‐6.78	(d,	
1H,	 J	=	8.08	Hz,	Ar‐H),	6.67‐6.71	(t,	1H,	 J	=	7.36	Hz,	CH‐NH‐)	 ,	
5.98	 (s,	 1H,	 NH),	 3.83	 (s,	 3H,	 Ar‐OCH3).	 13C	 NMR	 (75	 MHz,	
DMSO‐d6,	 δ,	 ppm):	 164.07,	 156.24,	 148.11,	 133.86,	 132.58,	
131.84,	129.91,	131.84,	129.91,	127.78,	117.76,	115.01,	114.97,	
114.13,	112.08,	61.19,	56.41.	MS	(m/z):	334.17	[M++	H].	 	Anal.	
calcd.	 for	 C15H13BrN2O2:	 C,	 54.07;	 H,	 3.93;	 N,	 8.41.	 Found:	 C,	
54.06;	H,	3.92;	N,	8.40%.	

2‐(3‐Chloro‐2‐hydroxyphenyl)‐2,	3‐dihydroquinazolin‐4(1H)‐
one	(Table	1,	Entry	11):	Color:	White	solid.	Yield:	81%.	1H	NMR	
(300	MHz,	DMSO‐d6,	δ,	ppm):	8.02	(s,	1H,	NH),	7.59‐7.62	(d,	1H,	
J	=	7.74	Hz,	Ar‐H),7.29‐7.33	(m,	2H,	Ar‐H),	7.19‐7.24	(t,	1H,	J	=	
7.63	Hz,	Ar‐H),	6.81‐6.86	(t,	1H,	J	=	7.8	Hz,	Ar‐H),	6.73‐6.76	(d,	
2H,	 J	=	8.04	Hz,	Ar‐H)	 ,	6.64‐6.69	(t,	1H,	 J	 =	7.17	Hz,	CH‐NH‐),	
6.06	(s,	1H,	NH).	13C	NMR	(75	MHz,	DMSO‐d6,	δ,	ppm):	164.28,	
150.87,	148.32,	133.74,	130.88,	129.92,	127.79,	126.62,	121.63,	
120.50,	117.76,	115.09,	62.22.	MS	(m/z):	275.05	[M++	H].	Anal.	
calcd.	 for	 C14H11ClN2O2:	 C,	 61.21;	 H,	 4.04;	 N,	 10.20.	 Found:	 C,	
61.20;	H,	4.02;	N,	10.20%.	

2‐(2‐Chloro‐6‐hydroxy‐4‐methoxyphenyl)‐2,	 3‐dihydroquina	
zolin‐4(1H)‐one	 (Table	 1,	 Entry	 12):	 Color:	White	 solid.	 Yield:	
83%.	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	9.40	(s,	1H,	Ph‐OH),	
8.01	(s,	1H,	NH),	7.61‐7.63	(d,	1H,	J	=	7.6	Hz,	Ar‐H),	7.22‐7.25	(t,	
1H,	J	=	7.2	Hz,	Ar‐H),	6.91	(s,	1H,	Ar‐H),	6.80	(s,	1H,	Ar‐H),	6.75‐
6.77	(d,	2H,	J	=	8.08	Hz,	Ar‐H),	6.66‐6.70	(t,	1H,	J	=	7.48	Hz,	CH‐
NH‐),	6.01	(s,	1H,	NH),	3.83	(s,	3H,	Ph‐OCH3).	13C	NMR	(75	MHz,	
DMSO‐d6,	 δ,	 ppm):	 164.17,	 148.92,	 148.25,	 143.17,	 133.78,	

129.44,	127.78,	122.68,	118.81,	117.70,	115.70,	115.01,	112.38,	
61.33,	 56.83.	 MS	 (m/z):	 305.72	 [M++	 H].	 Anal.	 calcd.	 for	
C15H13ClN2O3:	C,	59.12;	H,	4.30;	N,	9.19.	Found:	C,	59.10;	H,	4.29;	
N,	9.17%.	

2‐(Benzo[d][1,3]dioxol‐5‐yl)‐2,	 3‐dihydroquinazolin‐4(1H)‐
one	(Table	1,	Entry	13):	Color:	White	solid.	Yield:	85%.	1H	NMR	
(300	MHz,	DMSO‐d6,	δ,	ppm):	8.20	(s,	1H,	NH),	7.57‐7.59	(d,	1H,	
J	=	7.71	Hz,	Ar‐H),	7.19‐7.25	(t,	1H,	J	=	7.5	Hz,	Ar‐H),	6.87‐7.02	
(m,	4H,	Ar‐H),	6.71‐6.73	(d,	1H,	 J	=	8.1	Hz,	Ar‐H),	6.65‐6.68	(t,	
1H,	 J	 =	 7.23	Hz,	 CH‐NH‐),	 5.99	 (s,	 2H,	 Ph‐O‐CH2),	 5.65	 (s,	 1H,	
NH).	 	 13C	 NMR	 (75	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 164.02,	 148.27,	
147.75,	136.03,	133.73,	127.78,	120.87,	117.59,	115.42	114.87,	
108.30,	107.61,	101.56,	66.73.	MS	(m/z):	269.26	[M++	H].	Anal.	
calcd.	 for	 C15H12N2O3:	 C,	 67.16;	 H,	 4.51;	 N,	 10.44.	 Found:	 C,	
67.14;	H,	4.51;	N,	10.42%.	

2‐(Thiophen‐2‐yl)‐2,	 3‐dihydroquinazolin‐4(1H)‐one	 (Table	
1,	Entry	14):	Color:	White	solid.	Yield:	85%.	1H	NMR	(300	MHz,	
DMSO‐d6,	 δ,	ppm):	8.43	 (s,	1H,	NH),	7.59‐7.61	 (d,	 1H,	 J	 =	 7.62	
Hz,	Ar‐H),	7.42‐744	(d,	1H,	J	=	4.98	Hz,	Ar‐H),	7.22‐7.27	(t,	2H,	J	
=	6.9	Hz,	Ar‐H),	7.10‐7.11	(d,	1H,	J	=	3.18	Hz,	Ar‐H),	6.94‐6.97	(t,	
1H,	 J	 =	 84.27	Hz,	 Ar‐H),	 6.73‐6.76	 (d,	 1H,	 J	 =	 8.13	Hz,	 Ar‐H)	 ,	
6.66‐6.71	(t,	1H,	J	=	7.38	Hz,	CH‐NH‐)	6.00	(s,	1H,	NH).	13C	NMR	
(75	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 147.68,	 146.90,	 133.81,	 127.76,	
126.90,	 126.32,	 126.13,	 117.96,	 115.36,	 63.01.	 MS	 (m/z):	
231.20.[M++	H].	Anal.	calcd.	for	C12H10N2OS:	C,	62.59;	H,	4.38;	N,	
12.16.	Found:	C,	62.57;	H,	4.38;	N,	12.17%.	
	
3.	Results	and	discussion		
	

In	continuation	numbers	of	our	efforts	in	the	development	
of	novel,	environ‐friendly	and	synthetic	methodologies	[26‐33],	
we	 report	 here	 a	 mild	 and	 efficient	 one‐pot	 protocol	 for	 the	
synthesis	 of	 2,3‐dihydroquinazolin‐4(1H)‐one	 derivatives	 by	
two	component	reactions	catalysed	by	 ionic	 liquid	under	mild	
condition	 (Scheme	 1).	 The	 reaction	when	 tried	with	 different	
aldehydes,	diverse	functional	groups	played	significant	roles	in	
achieving	 the	 product	 yield.	 Aldehydes	 with	 electron	
withdrawing	 group	 react	 with	 2‐amino	 benzaldehyde	 giving	
better	 yield	 (Table	 1	 entries	 5‐9).	 Whereas,	 aldehydes	 with	
electron	releasing	and	both	electron	releasing	and	withdrawing	
give	moderate	yields	(Table	1	entries	1‐4	and	10‐14).	A	mixture	
of	 2‐amino	 benzamide	 (1	 mmol)	 and	 aromatic	 aldehyde	 (1	
mmol)	in	ionic	liquid	was	stirred	at	room	temperature	for	3‐4	h	
without	an	inert	atmosphere.	When	the	reaction	was	complete	
the	 product	 was	 purified	 by	 column	 chromatography.	 The	
scope	 of	 the	 reaction	 was	 examined	 with	 various	 aromatic	
aldehydes	and	the	results	are	summarized	in	Table	1.	

A	 possible	 mechanism	 of	 the	 basic	 ionic	 liquid	 catalysed	
reaction	 of	 2‐amino	 benzamide	 and	 aldehydes	 is	 proposed	 in	
Scheme	2.	2‐Amino	benzamide	1	condensation	of	the	aromatic	
aldehyde	 2	with	 ionic	 liquid	 gives	 imine	 3	 which	 undergoes	
cyclisation	to	afford	dihydroquinazoline	product	4.	
	
4.	Conclusion	
	

In	 summary,	 we	 have	 developed	 a	 direct	 and	 efficient	
method	 for	 the	 preparation	 of	 2,3‐dihydroquinazolin‐4(1H)‐
ones	using	basic	ionic	liquid	via	cyclocondensation	of	2‐amino	
benzamide	with	an	aldehyde.	The	simplicity	of	 the	procedure,	
easy	 work	 up,	 excellent	 yields,	 short	 reaction	 times,	 easy	



Obaiah	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	671‐675	 675	
 

handling	 and	 use	 of	 ecofriendly,	 non‐volatile,	 less	 expensive	
reagents	are	the	advantages	claimed	by	this	method.		
	
Acknowledgements	
	

The	authors	are	grateful	to	University	Grants	Commission,	
Government	 of	 India	 for	 financial	 support	 to	 Kempegowda	
Mantelingu	 for	 the	 project	 vide	 No.	 F.	 No.	 39‐710‐2011	
(SR/dated	12‐01‐2010).	
	
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