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European	Journal	of	Chemistry	4	(4)	(2013)	422‐424	

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

DOI:10.5155/eurjchem.4.4.422‐424.857	

	
	

	

	

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

	 	 	

Indion	190	resin:	Reusable	catalyst	for	the	synthesis	of	quinoxalines	and	
pyrido‐pyrazines	at	ambient	temperature	

Gangadhar	Asaram	Meshram	*,	Shruti	Shashank	Deshpande,		
Vipul	Amratlal	Vala	and	Pramod	Arun	Wagh	

Department	of	Chemistry,	University	of	Mumbai,	Vidyanagri,	Kalina,	Santacruz	(E),	Mumbai‐400098,	India	

*Corresponding	author	at:	Department	of	Chemistry,	University	of	Mumbai,	Vidyanagri,	Kalina,	Santacruz	(E),	Mumbai‐400098,	India.	
Tel.:	+91.986.9504996;	fax:	+91.022.26528547.	E‐mail	address:	meshramga@chem.mu.ac.in	(G.A.	Meshram).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	
Received:	15	June	2013	
Received	in	revised	form:	19	July	2013	
Accepted:	22	July	2013	
Online:	31	December	2013	

KEYWORDS	

	 An	efficient	method	for	synthesis	of	quinoxalines	and	substituted	pyrido‐pyrazines	has	been
developed	 from	 different	 1,2‐dicarbonyl	 compounds	 and	 substituted	 1,2‐diamines	 using
Indion	190	resin	as	a	solid	acid	catalyst.	Ambient	reaction	conditions,	high	product	yield	and
reusability	 of	 the	 catalyst	 with	 minimal	 loading	 are	 the	 salient	 features	 of	 the	 present
protocol.	

1,2‐Diamines		
1,2‐Dicarbonyls		
Indion	190	resin	
Solid	acid	catalyst	
Quinoxaline	derivatives	
Substituted	pyrido‐pyrazines	

	
1.	Introduction	
	

Quinoxaline	 is	a	privileged	ring	 system	and	 its	derivatives	
represent	 an	 important	 class	 of	 nitrogen	 containing	
heterocycles	 as	 they	 constitute	 useful	 dyes	 and	 intermediates	
in	 organic	 synthesis	 [1].	 As	 depicted	 in	 literature,	 pyrido[2,3‐
b]pyrazines	 and	 pyrido[3,4‐b]pyrazines	 are	 exhibiting	
promising	biological	properties	and	are	used	for	the	treatment	
of	 malignant	 tumors	 and	 other	 diseases	 related	 to	 cell	
proliferations.	 Functionalized	 quinoxalines	 exhibit	 broad	
biological	activities	and	have	been	evaluated	as	anticancer	[2],	
antiviral	 [3],	 antibacterial	 [4],	 and	 kinase	 inhibition	 agents	
[5,6].	 In	 addition	 to	 their	 therapeutic	properties,	 quinoxalines	
have	 also	 found	 applications	 as	 dyes	 [7],	 organic	 semicon‐
ductors	 [8]	 and	 chemically	 controllable	 switches	 [9].	 Conse‐
quently,	 there	 has	 been	 tremendous	 interest	 in	 developing	
efficient	synthetic	strategies	for	preparing	quinoxalines	due	to	
their	 widespread	 applications	 in	 the	 fields	 of	 medicinal,	
industrial	 and	 synthetic	 organic	 chemistry.	 Commonly	
employed	method	involves	condensation	of	an	aryl‐1,2‐diamine	
with	a	1,2‐dicarbonyl	 in	refluxing	ethanol	or	acetic	acid	 for	2‐
12	 h	 yielding	 34‐85%	 of	 product	 [10].	 Several	 improved	
methods	 reported	 in	 the	 literature	 for	 the	 synthesis	 of	
quinoxalines	include	microwave	synthesis	[11],	the	use	of	PEG‐
400	 [12],	 RuCl‐(PPh3)3‐TEMPO	 [13],	 CAN	 [14],	 CuSO4.5H2O	
[15],	 SA/MeOH	 [16],	 montmorillonite	 K‐10	 [17],	 InCl3	 [18],	
Zn/proline	[19],	Ga(OTf)3	[20],	HClO4‐SiO2	[21],	‐cyclodextrins	
in	water	[22],	FeMAP	[23],	TiO2‐P25	[24],	ZnO‐beta	zeolite	[25],	
silica‐supported	antimony(III)	chloride	[26]	as	catalysts.	

Indion	 190	 resin,	 a	 macroporous	 strongly	 acidic	 cation	
exchanger	with	styrene	DVB	matrix,	is	used	as	a	heterogeneous	
catalyst	 in	modern	organic	 synthesis	 [27,28].	 It	 is	 a	 sulphonic	
acid	resin	with	an	exchange	capacity	of	4.7	meq/g.	Particle	size	

of	 the	 catalyst	 ranges	 from	 0.42	 to	 1.20	 mm	 and	 maximum	
operating	 temperature	 is	 150	 °C.	 Venturing	 towards	 the	
development	of	efficient	and	environmentally	benign	synthetic	
strategies,	 we	 have	 investigated	 the	 synthesis	 of	 substituted	
quinoxalines	 and	 pyrido‐pyrazines	 by	 condensation	 of	 1,2‐
diamines	and	1,2‐diketones	using	Indion‐190	resin,	an	efficient	
reusable	catalyst,	at	room	temperature	(Scheme	1).	
	
2.	Experimental	

	
2.1.	Instrumentation	

	
The	 reactions	 and	 purity	 of	 quinoxalines	were	monitored	

by	 thin	 layer	 chromatography	 (TLC)	using	 glass	plates	 coated	
with	silica	gel.	The	isolated	products	(5d,	6a‐d	and	7a‐c)	were	
purified	 by	 column	 chromatography	 whereas	 (5a‐c)	 were	
purified	by	recrystallization.	1H	NMR	and	13C	NMR	spectra	were	
recorded	 on	 Bruker	 Avance	 Spectrospin	 300	 MHz.	 All	 NMR	
samples	were	run	in	CDCl3	and	chemical	shifts	are	expressed	as	
δ	relative	to	internal	TMS.	IR	spectra	were	obtained	on	Perkin	
Elmer	 FT‐IR	 spectrophotometer	 spectrum	 2000	 using	
potassium	 bromide	 pellets.	 	 Mass	 spectra	 were	 obtained	 on	
Thermo‐Finnigm	Discovery‐Max	GC‐MS.	All	 the	melting	points	
were	determined	in	an	open	capillary	tube	using	Expo	Hi	Tech.	
melting	point	apparatus.	
	
2.2.	Typical	procedure		

	
To	a	mixture	of	1,2‐diamine	(1)	(1	mmol)	and	benzil	(2)	or	

ninhydrin	 (3)	or	acenaphthenequinone	 (4)	 (1	mmol)	 in	AcOH	
(5	mL),	Indion	190	resin	(20%/w)	with	respect	to	1,2‐diamine	
was	 added	 and	 the	mixture	was	 stirred	at	 room	 temperature.	
The	 progress	 of	 reaction	 was	 monitored	 using	 thin	 layer	
chromatography.		



Meshram	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	422‐424	 423	
 

	

	

Scheme	1	
	
	
After	 completion	 of	 reaction,	 catalyst	 was	 filtered	 and	

solvent	was	distilled	out.	The	reaction	mass	was	poured	in	ice	
cold	 water	 and	 filtered	 to	 afford	 crude	 product.	 The	 isolated	
products	 (5a‐5c)	were	purified	by	 recrystallization	with	95%	
ethanol	whereas	(5d,	6a‐d	and	7a‐c)	were	purified	by	column	
chromatography.	
	
3.	Results	and	discussion		

	
Initially,	 a	 model	 condensation	 reaction	 between	 1,2‐

phenylenediamine	and	benzil	was	subjected	to	varying	reaction	
conditions.	 In	order	 to	determine	the	optimum	conditions,	we	
first	 examined	 the	 effective	 catalyst	 concentration	 (Table	 1)	
followed	by	the	influence	of	solvent	(Table	2).	We	also	analyzed	
the	 reusability	 of	 the	 sulphonic	 acid	 resin	 catalyst	 (Figure	 1).	
For	 a	 typical	 experiment,	 1,2‐phenylenediamine	 and	 benzil	
were	stirred	in	AcOH	(5	mL)	at	room	temperature	in	presence	
of	 Indion	 190	 resin	 (20	%/w).	Reaction	was	 completed	 in	 10	
min	 to	 afford	 2,3‐diphenyl	 quinoxaline	 (Table	 3,	 Entry	 5a,	
97%).	Encouraged	by	the	outstanding	results	obtained	from	the	
present	protocol	and	to	check	its	further	versatility	and	scope,	
we	 have	 employed	 various	 1,2‐diamines	 and	 1,2‐dicarbonyls,	
the	results	of	which	are	summarized	in	Table	3.	
	
Table	1.	Optimization	of	the	amount	of	Indion	190	resin	a.	
Entry	 Catalyst	concentration	(%/w)	 Yield	(%)	b
1	 10	 81
2	 20	 97	
3	 30	 92	
4	 40	 92	
5	 50	 92
6	 60	 64
a	Reaction	condition:	1,2‐phenylenediamine	(1	mmol),	benzil	(1	mmol),	room	
temperature	and	AcOH	(5	mL).	
b	Isolated	yield.	
	
3.1.	Optimization	of	catalyst	
	

Catalyst	 concentration	 plays	 a	 vital	 role	 in	 synthesis	 of	
quinoxalines.	 Application	 of	 20%/w	 of	 Indion	 190	 resin	 gave	
excellent	 yield	 of	 2,3‐diphenyl‐quinoxaline	 (Table	 1).	 At	 a	
higher	 amount	 of	 catalyst,	 the	 yield	 of	 the	 corresponding	
product	decreases	may	be	due	to	increase	in	the	acidity	of	the	
reaction	medium.	

	
Table	2.	Effect	of	solvents	a.	
Entry Solvent Time	(min)	 Yield	(%)	b
1 MeOH 30 94	
2	 EtOH	 75	 85	
3	 MeCN	 75	 83	
4 MeOH:H2O(1:1) 120	 90	
5 EtOH:H2O(1:1) 120	 88	
6 MeCN:H2O(1:1) 160	 86	
7 AcOH	c 10 97	
a	 Reaction	 condition:	 1,2‐phenylenediamine	 (1	 mmol),	 benzil	 (1	 mmol),	
catalyst	Indion	190	resin	(20%	w/w),	room	temperature	and	solvent	(5	mL).	
b	Isolated	yield.	
c	 Glacial	 acetic	 acid	 AR	 grade	with	 less	 than	 0.98	%	moisture	 content	was	
used.	
	
Table	3.	Synthesis	of	quinoxalines	and	pyrido‐pyrazines	a.	
Entry R X Product Time	(min)	 Yield	(%)	b
1	 H		 C	 5a	 10	 97	
2	 NO2		 C	 5b	 15	 92	
3	 CH3	 C	 5c	 10	 94	
4 Br N 5d 20	 90
5 H C 6a 20	 92
6 NO2 C 6b 35	 83
7 CH3 C 6c 30	 89
8 Br N 6d 25	 84
9 H C 7a 25	 93
10 NO2 C 7b 25	 87
11	 Br	 N	 7c	 30	 85	
a	 Reaction	 condition:	 1,2‐diammines	 (1	 mmol),	 1,2‐diketones	 (1	 mmol),	
catalyst:	 Indion	 190	 resin	 (20%	 w/w),	 solvent:	 AcOH	 (5	 mL),	 room	
temperature.		
b	Isolated	yield.	
	
3.2	Effect	of	solvent	on	preparation	of	quinoxaline	
	

In	 order	 to	 elucidate	 the	 role	 of	 the	 solvents,	 various	
solvents	were	used	to	evaluate	the	scope	and	limitations	of	the	
reaction.	Solvent	optimization	study	revealed	that,	glacial	acetic	
acid	was	the	most	conducive	solvent	favoring	quinoxaline	ring	
formation	(Table	2).		
	
3.3.	Recycling	of	Indion‐190	resin	
	

The	 reusability	 of	 the	 catalyst	 is	 important	 for	 the	 large‐
scale	operation	and	from	an	industrial	point	of	view.	Therefore,	
the	recovery	and	reusability	of	Indion	190	resin	was	examined.	
The	 catalyst	 was	 separated	 and	 reused	 after	 washing	 with	
ethanol	 and	drying	at	110	 .	 Figure	1	 illustrates,	 the	 catalyst	



424	 Meshram	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	422‐424	
	
can	be	used	 four	 times	with	consistent	 yield.	 The	 color	of	 the	
catalyst	remains	the	same	even	after	the	four	cycles.	

In	 the	 present	 synthesis,	 the	 activation	 of	 the	 carbonyl	
oxygen	 by	 the	 acidic	 proton	 of	 Indion	 190	 resin	 followed	 by	
cyclocondensation	 with	 aryl	 diamine	 and	 subsequent	 loss	 of	
water	molecule	 results	 in	 the	 product	 formation.	 A	 variety	 of	
quinoxalines	 and	 pyrido‐pyrazines	 (Table	 3)	 have	 been	
synthesized	in	good	yields	ranging	from	97	to	83%	irrespective	
of	the	complexities	and	different	substituted	functionalities.	All	
the	 synthesized	 products	 are	 known	 and	 reported	 in	 the	
literature	[11,29,30].	

	

	
	

Figure	1.	Recyclability	of	the	catalyst.	
	

4.	Conclusion	
	

In	conclusion,	commercially	available	 Indion‐190	resin,	an	
inexpensive,	non‐toxic	and	highly	reusable	catalyst	provides	an	
environmentally	 benign	 route	 for	 easy	 access	 to	 a	 variety	 of	
quinoxaline	 and	 pyrido‐pyrazine	 derivatives.	 An	 efficient	 and	
highly	reusable	catalytic	system,	mild	reaction	conditions,	and	
short	 reaction	 time	with	high	product	 yield	make	 the	present	
protocol	more	attractive	for	practical	purposes.	
	
Acknowledgements	
	

This	 work	 was	 supported	 by	 Departmental	 Research	
Fellowship	provided	by	Department	of	Chemistry,	University	of	
Mumbai.	
	
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