untitled


European	Journal	of	Chemistry	4	(4)	(2013)	450‐453	

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

DOI:10.5155/eurjchem.4.4.450‐453.769	

	
	

	

	

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

	 	 	

Glycerol	mediated,	one	pot,	multicomponent	synthesis	of		
dihydropyrano[2,3‐c]pyrazoles	

Harvinder	Singh	Sohal	a,	Arun	Goyal	a,	Rajeev	Sharma	a,	Rajshree	Khare	b	and	Sanjay	Kumar	a,*	

a	Department	of	Chemistry,	Multani	Mal	Modi	College,	Patiala,	147001,	Punjab,	India	
b	Department	of	Chemistry,	Maharishi	Markandeshwar	University,	Mullana,	133207,	Haryana,	India	

*Corresponding	author	at:	Department	of	Chemistry,	Multani	Mal	Modi	College,	Patiala,	147001,	Punjab,	India.		
Tel.:	+91.988.8339791;	fax:	+91.175.2212049.	E‐mail	address:	sanjay2002@gmail.com	(S.	Kumar).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	12	March	2013	
Received	in	revised	form:	13	June	2013	
Accepted:	14	June	2013	
Online:	31	December	2013	

KEYWORDS	

	 Multi	component,	one	pot	synthesis	of	various	dihydropyrano[2,3‐c]pyrazole	derivatives	from
the	 condensation	of	 ethyl	 acetoacetate,	 hydrazine,	 aromatic	 aldehyde	and	malononitrile	has
been	 described	 using	 glycerol,	 as	 environmentally	 benign,	 economical,	 and	 easily	 available
solvent.	The	targeted	molecules	are	obtained	in	excellent	yield	without	use	of	any	additional
catalyst.	

Glycerol	
Aldehydes	
Catalyst	free	
Malononitrile	
Pyrazol‐5‐one	
Dihydropyrano[2,3‐c]pyrazole	

	
1.	Introduction	
	

The	development	of	green	methodologies	with	the	choice	of	
green	 solvents	 and	 solvents	 from	 renewable	 resources	 has	
gained	much	 interest	 in	 recent	years	 [1‐5].	With	 this	concern,	
use	 of	 water	 has	 attracted	 much	 attention	 [6‐11],	 however	
water	 based	 processes	 are	 still	 subject	 to	 limitations	 due	 to	
solubility	 problems	 of	 highly	 hydrophobic	 substrates.	 On	 the	
other	hand,	excellent	solvent	properties	like	low	toxicity	(LD50	
(oral	 rat)	 12600	 mg/kg),	 biodegradability,	 low‐flammability,	
long	 liquid	 range	 (Boiling	 point	 290	 °C),	 low	 vapor	 pressure	
and	solubility	of	polar	organic	compounds	made	the	glycerol	an	
excellent	 option	 to	 use	 as	 solvent	 for	 organic	 synthesis	 [12].	
Further	with	 the	 present	 emphasis	 and	 increasing	 demand	 of	
biodiesel,	 which	 is	 responsible	 for	 the	 excess	 production	 of	
glycerol	 as	 by‐product,	 triggered	 the	 discovery	 of	 processes	
that	use	glycerol	for	the	synthesis	of	value	added	chemicals,	as	
reaction	medium	 and	 for	 other	 applications	 [13‐19].	 Recently	
glycerol	 has	been	used	 for	Heck	 and	 Suzuki	 coupling	 [20‐22],	
Michael	addition	[23],	Fridel‐Crafts	type	addition,	epoxide	ring	
opening	[24],	synthesis	of	xanthenes	[25]	and	very	recently	for	
the	 production	 of	 benzodiazepines	 and	 octahydroacridines	
[26,27].	

In	 addition,	 pyranopyrazoles	 are	 important	 class	 of	
heterocyclic	chemistry.	Compounds	containing	pyranopyrazole	
scaffold	 are	 biological	 active	 and	 have	 applications	 as	
pharmaceutical	 ingredients	 and	 biodegradable	 agrochemicals	
[28‐31].	Pyrano[2,3‐c]pyrazole	derivatives	show	many	bioacti‐
vities	such	as	antimicrobial	 [32],	 insecticidal	 [33],	 anti‐inflam‐
matory	 activities	 [34]	 and	 molluscicidal	 activity	 [35,36].	
Pyrano[2,3‐c]pyrazoles	 are	 known	 have	 application	 in	
screening	kit	for	Chk1	kinase	inhibitor	[37,38]	and	also	used	as	
photoactive	material	[39].	

These	 molecules	 can	 be	 synthesized	 by	 the	 reaction	 of	
pyrazol‐5‐one	 with	 tetracyanoethylene	 [28],	 arylidene	
malononitrile	 using	 catalysts	 like	 TEA	 [29‐31].	 In	 addition	
multi‐component	 procedures	 have	 been	 developed	 using	
catalysts	 like	 DBSA	 [40],	 MgO	 [41],	 imidazole	 [42],	 β‐
cyclodextrin	 [43],	 Ba(OH)2	 [44].	 The	 already	 reported	
procedures	 have	many	 advantages	 over	 one	 another,	 but	 few	
methods	 have	 one	 or	 another	 drawback	 like	 solubility	 of	
reactants,	 tedious	work‐up	procedures	and	hazardous	 regents	
or	 solvents.	 Therefore,	 development	 of	 clean	 and	 efficient	
procedure	 for	 the	 synthesis	 of	 dihydropyrano[2,3‐c]pyrazoles	
is	still	timely.	In	the	present	paper,	we	have	described	a	catalyst	
free,	 one	 pot,	 multicomponent	 protocol	 for	 the	 synthesis	 of	
dihydropyrano[2,3‐c]pyrazoles	 using	 glycerol	 as	 an	
economical,	 easily	 available	 and	 environment	 friendly	 solvent	
(Scheme	1).	
	
2.	Experimental	
	
2.1.	Instrumentation	

	
Materials	 were	 obtained	 from	 commercial	 suppliers	 and	

were	 used	 without	 further	 purifications.	 Melting	 points	 were	
recorded	in	open	end	capillaries	and	are	uncorrected.	1H	NMR	
spectra	were	recorded	in	CDCl3	solution	on	a	Bruker	Avance	II	
400	MHz	spectrometer;	chemical	shifts	(δ)	are	reported	in	ppm	
relative	 to	 TMS	 as	 internal	 standard.	 The	 IR	 spectra	 were	
recorded	at	Perkin‐Elmer	Spectrum	 II	 infra‐red	 spectrophoto‐
meter.	

	
2.2.	Synthesis	

	
2.2.1.	General	procedure	for	synthesis	of	6‐amino‐4‐(aryl)‐3‐
methyl‐1,4‐dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile	
	



Sohal	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	450‐453	 451	
 

	 	

 

Scheme	1	
	
	
In	 a	 conical	 flask,	 hydrazine	 hydrate	 (1	 mmol),	

ethylacetoacetate	 (1	 mmol),	 aldehyde	 (1	 mmol)	 and	
malononitrile	 were	 added	 successively	 in	 glycerol	 (2	 mL).	
Reaction	mixture	was	stirred	at	80	°C.	After	 the	completion	of	
reaction	(monitored	by	TLC),	diluted	the	reaction	mixture	with	
ice	 cold	 water.	 Filtered	 the	 solid	 thus	 obtained	 and	
recrystallized	with	ethanol	(Scheme	1).	

6‐Amino‐5‐cyano‐3‐methyl‐4‐phenyl‐1,4‐dihydropyrano[2,3‐
c]pyrazole	 (5a):	Color:	White	 crystals.	M.p.:	243‐245	 °C.	FT‐IR	
(KBr,	ν,	cm‐1):	3450,	3370,	3116,	2195,	1645,	1610,	1605,	1483,	
1390,	1240,	1022,	860.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	1.80	
(s,	 3H,	 CH3),	 4.62	 (s,	 1H,	 CH),	 6.95	 (s,	 2H,	NH2),	 7.16‐7.45	 (m,	
5H,	 Ar‐H),	 12.16	 (br	 s,	 1H,	 NH).	 Anal.	 calcd.	 for	 C14H12N4O:	 C,	
66.65;	H,	4.79;	N,	22.21.	Found:	C,	66.51;	H,	4.70;	N,	22.07%.	

6‐Amino‐4‐(4‐chlorophenyl)‐3‐methyl‐1,4‐dihydropyrano[2,	
3‐c]pyrazole‐5‐carbonitrile	 (5b):	 Color:	 White	 crystals.	 M.p.:	
233‐235	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3490,	3253,	2930,	2260,	1650,	
1610,	1508,	1399,	1270,	1200,	1050,	750.	 1H	NMR	 (400	MHz,	
CDCl3,	δ,	ppm):	1.78	(s,	3H,	CH3),	4.54	(s,	1H,	CH),	6.59	(s,	2H,	
NH2),	7.1‐7.2	(m,	4H,	Ar‐H),	11.94	(br	s,	1H,	NH).	Anal.	calcd.	for	
C14H11N4ClO:	 C,	 58.65;	 H,	 3.87;	 N,	 19.54.	 Found:	 C,	 58.61;	 H,	
3.80;	N,	19.51%.	

6‐Amino‐3‐methyl‐4‐(3‐nitrophenyl)‐1,4‐dihydropyrano[2,3‐
c]pyrazole‐5‐carbonitrile	 (5f):	Color:	White	 crystals.	M.p.:	218‐
220	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3510,	 3260,	 2945,	 2332,	 1670,	
1620,	 1525,	 1410,	 1283,	 1225,	 1100,	 950,	 850.	 1H	NMR	 (400	
MHz,	CDCl3,	δ,	ppm):	1.83	(s,	3H,	CH3),	4.80	(s,	1H,	CH),	6.84	(s,	
2H,	 NH2),	 7.5‐8.1	 (m,	 4H,	 Ar‐H),	 12.09	 (br	 s,	 1H,	 NH).	 Anal.	
calcd.	 for	 C14H11N5O3:	 C,	 56.56;	 H,	 3.73;	 N,	 23.56.	 Found:	 C,	
56.60;	H,	3.76;	N,	23.51%.	

6‐Amino‐5‐cyano‐4‐(4‐methoxyphenyl)‐3‐methyl‐1,4‐dihydro	
pyrano[2,3‐c]pyrazole	(5h):	Color:	White	crystals.	M.p.:	208‐210	
°C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3481,	 3253,	 2925,	 2191,	 1642,	 1600,	
1492,	 1392,	 1258,	 1172,	 1031,	 870,	 804,	 565.	 1H	 NMR	 (400	
MHz,	CDCl3,	δ,	ppm):	1.75	(s,	3H,	CH3),	3.69	(s,	3H,	OCH3),	4.50	
(s,	1H,	CH),	6.83	(s,	2H,	NH2),	7.04‐7.5	(m,	4H,	Ar‐H),	12.05	(br	
s,	 1H,	 NH).	 Anal.	 calcd.	 for	 C15H14N4O2:	 C,	 63.82;	 H,	 5.00;	 N,	
19.85.	Found:	C,	63.71;	H,	5.15;	N,	19.94%.	

6‐Amino‐3‐methyl‐4‐(4‐methylphenyl)‐1,4‐dihydropyrano[2,	
3‐c]pyrazole‐5‐carbonitrile	 (5j):	 Color:	 White	 crystals.	 M.p.:	
240–242	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3492,	3250,	3150,	2930,	2200,	
1620,	1595,	1508,	1410,	1260,	1180,	1050,	835.	1H	NMR	(400	
MHz,	CDCl3,	δ,	ppm):	1.80	(s,	3H,	CH3),	2.28	(s,	3H,	CH3),	4.50	(s,	
1H,	CH),	6.57	(s,	2H,	NH2),	6.81‐7.10	(m,	4H,	Ar‐H),	11.93	(br	s,	
1H,	NH).	Anal.	calcd.	for	C15H14N4O:	C,	67.65;	H,	5.30;	N,	21.04.	
Found:	C,	68.10;	H,	5.20;	N,	20.01%.	
	
2.2.2.	General	procedure	for	synthesis	of	6‐amino‐4‐(aryl)‐3‐
methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]pyrazole‐5‐
carbonitrile	
	

In	 a	 conical	 flask,	 pheynyl	 hydrazine	 (1	 mmol),	
ethylacetoacetate	(1	mmol),	were	added	in	glycerol	(2	mL)	and	
stirred	 for	 10	 min	 at	 80	 °C.	 Then,	 aldehyde	 (1	 mmol)	 and	
malononitrile	were	added	successively	and	stirred	the	reaction	
mixture	 at	 the	 same	 temperature.	 After	 the	 completion	 of	
reaction	(monitored	by	TLC),	diluted	the	reaction	mixture	with	

ice	 cold	 water.	 Filtered	 the	 solid	 thus	 obtained	 and	
recrystallized	with	ethanol	(Scheme	1).	

6‐Amino‐5‐cyano‐3‐methyl‐1,4‐diphenyl‐1,4‐dihydropyrano	
[2,3‐c]	 pyrazole	 (6a):	 Color:	 White	 crystals.	 M.p.:	 169‐170	 °C.	
FT‐IR	(KBr,	ν,	cm‐1):	3472,	3320,	2195,	1660,	1590,	1264,	1125,	
1027,	753.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	1.93	(s,	3H,	CH3),	
4.62	 (s,	 1H,	 CH),	 6.99	 (s,	 2H,	 NH2),	 7.16‐7.32	 (m,	 10H,	 Ar‐H).	
Anal.	 calcd.	 for	 C20H16N4O:	 C	 73.15,	 H	 4.91,	 N	 17.06;	 Found	 C	
73.19,	H	5.01,	N	17.10%.	

6‐Amino‐4‐(4‐chlorophenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole	 (6b):	 Color:	White	 crystals.	M.p.:	
175‐176	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3468,	3325,	2200,	1662,	1596,	
1390,	 1262,	 1122,	 1016,	 752.	 1H	 NMR	 (400	 MHz,	 CDCl3,	 δ,	
ppm):	1.83	(s,	3H,	CH3),	4.51	(s,	1H,	CH),	6.73	(s,	2H,	NH2),	6.75‐
7.90	(m,	9H,	Ar‐H).	Anal.	calcd.	for	C20H15ClN4O:	C	66.21,	H	4.17,	
N	15.44;	found	C	66.26,	H	4.19,	N	15.52%.	

6‐Amino‐4‐(2‐chlorophenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole	 (6c):	 Color:	White	 crystals.	M.p.:	
143‐145	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3472,	3324,	2194,	1656,	1592,	
1389,	 1264,	 1125,	 1028,	 752.	 1H	 NMR	 (400	 MHz,	 CDCl3,	 δ,	
ppm):	1.90	(s,	3H,	CH3),	4.52	(s,	1H,	CH),	6.62	(s,	2H,	NH2),	6.9‐
7.6	(m,	9H,	Ar‐H).	Anal.	calcd.	for	C20H15ClN4O:	C	66.21,	H	4.17,	
N	15.44;	found	C	66.26,	H	4.22,	N	15.48%.	

6‐Amino‐4‐(4‐nitrophenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole	 (6d):	 Color:	White	 crystals.	M.p.:	
195‐197	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3430,	3340,	2192,	1665,	1596,	
1354,	1124,	832,	754.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	1.80	
(s,	 3H,	CH3),	 4.96	 (s,	 1H,	 CH),	 6.98	 (s,	 2H,	NH2),	 7.32‐8.20	 (m,	
9H,	Ar‐H).	Anal.	calcd.	for	C20H15N5O3:	C	64.34,	H	4.05,	N	18.76;	
found	C	64.40	H	4.08,	N	18.80%.	

6‐Amino‐4‐(3‐nitrophenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole	 (6f):	 Color:	 White	 crystals.	 M.p.:	
191‐193	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3420,	3330,	2194,	1675,	1598,	
1390,	 1264,	 1126,	 1030,	 752.	 1H	 NMR	 (400	 MHz,	 CDCl3,	 δ,	
ppm):	1.82	(s,	3H,	CH3),	4.91	(s,	1H,	CH),	7.40	(s,	2H,	NH2),	7.20‐
8.12	(m,	9H,	Ar‐H).	Anal.	calcd.	for	C20H15N5O3:	C	64.34,	H	4.05,	
N	18.76;	found	C	64.38	H	4.10,	N	18.81%.	

6‐Amino‐4‐(4‐hydroxyphenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐
1,4‐dihydropyrano[2,3‐c]pyrazole	 (6g):	 Color:	 White	 crystals.	
M.p.:	209‐211	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3414,	3314,	2178,	1658,	
1594,	1398,	1258,	1128,	1026,	754.	1H	NMR	(400	MHz,	CDCl3,	δ,	
ppm):	1.78	(s,	3H,	CH3),	4.56	(s,	1H,	CH),	7.12	(s,	2H,	NH2),	6.72‐
7.78	(m,	9H,	Ar‐H),	9.38	(s,	1H,	OH).	Anal.	calcd.	for	C20H16N4O2:	
C	69.76,	H	4.68,	N	16.27;	found	C	69.82,	H	4.72,	N	16.31%.	

6‐Amino‐4‐(4‐methoxyphenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐
1,4‐dihydropyrano[2,3‐c]	 pyrazole	 (6h):	 Color:	 White	 crystals.	
M.p.:	175‐177	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3395,	3322,	2192,	1660,	
1595,	 1394,	 1250,	 1128,	 813.	 1H	 NMR	 (400	 MHz,	 CDCl3,	 δ,	
ppm):	1.81	(s,	3H,	CH3),	3.76	(s,	3H,	OCH3),	4.57	(s,	1H,	CH),	7.2	
(s,	2H,	NH2),	6.8‐8.1	(s,	9H,	Ar‐H).	Anal.	calcd.	for	C21H18N4O2:	C	
70.38,	H	5.06,	N	15.63;	found	C	70.42,	H	5.11,	N	15.68%.	

6‐Amino‐4‐(4‐methylphenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole	 (6j):	Color:	White	 crystals.	 	M.p.:	
140‐142	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3414,	3314,	2178,	1658,	1594,	
1398,	 1258,	 1128,	 1026,	 754.	 1H	 NMR	 (400	 MHz,	 CDCl3,	 δ,	
ppm):	1.81	(s,	3H,	CH3),	2.1	(s,	3H,	CH3),	4.5	(s,	1H,	CH),	6.85	(s,	
2H,	NH2),	 7.1‐8.01	 (m,	9H,	Ar‐H).	Anal.	 calcd.	 for	C21H18N4O:	C	
73.67,	H	5.30,	N	16.36;	found	C	73.71,	H	5.34,	N	16.42%.	



452	 Sohal	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	450‐453	
	

	
Table	1.	Effect	of	solvent	on	the	synthesis	of	compounds	5a	and	6a.	
Product	 Yield,	%	a	

EtOH	 MeOH Glycerol CH3CN	
5a	 87	 88	 93 80	
6a	 86	 87	 92 82	
a	Yield	refers	to	pure	isolated	product.	
	
	

 
	

Scheme	2
	
	
3.	Results	and	discussion		

	
At	first,	reaction	between	hydrazine	1,	ethyl	acetoacetate	2,	

benzaldehyde	3,	and	malononitrile	4,	was	carried	out	as	a	test	
reaction	 in	 different	 solvents	 like	 methanol,	 ethanol,	
acetonitrile	and	glycerol.	Glycerol	as	solvent	provides	the	good	
results	as	compared	to	other	organic	solvents	(Table	1).	

In	a	typical	experimental	procedure,	a	mixture	of	hydrazine	
hydrate	(10	mmol,	0.5	g)	1,	ethyl	acetoacetate	(10	mmol,	1.30	
g)	2,	benzaldehyde	(10	mmol,	1.06	g)	3	and	malononitrile	(10	
mmol,	0.66	g)	4	were	added	in	glycerol	(10	mL)	and	stirred	in	a	
pre‐heated	bath	at	80	°C.	After	the	completion	of	reaction	(vide	
TLC),	 reaction	mixture	 was	 cooled	 to	 room	 temperature	 and	
water	(50	mL)	was	added.	Solid	thus	separated	was	filtered	and	
dried,	 recrystallized	 from	 ethanol	 to	 afford	 5a,	 6‐amino‐5‐
cyano‐3‐methyl‐4‐phenyl‐1,4‐dihydropyrano[2,3‐c]pyrazole,	 in	
93%	 yield,	 colorless	 crystals,	 melting	 point	 243‐245	 °C.	
Structure	 of	 compound	 5a	 is	 confirmed	 by	 advanced	
spectroscopic	 techniques.	 In	 1H	 NMR	 spectrum,	 singlet	 is	
observed	at	δ	12.16	ppm	for	N‐H	proton	and	multiplet	for	five	
aromatic	proton	of	phenyl	ring	is	observed	between	δ	7.16‐7.45	
ppm	and	for	NH2	group,	a	signal	is	observed	at	δ	6.95	ppm	and	
a	singlet	observed	at	δ	1.80	ppm	represented	‐CH3	group.	In	IR	
spectrum,	 N‐H	 stretching	 is	 observed	 at	 3370	 cm‐1	 and	 CN	
stretching	is	observed	at	2195	cm‐1.	

To	 check	 the	 versatility	 of	 this	 process,	 we	 have	 reacted	
hydrazine	 hydrate/phenyl	 hydrazine,	 ethylacetoacetate,	 and	
malononitrile	 with	 different	 aldehydes	 and	 results	 are	
summarized	 in	 Table	 2.	 Reactions	 proceed	 smoothly	 with	
aldehydes	 bearing	 electron	 withdrawing	 as	 well	 as	 electron	
donating	substituents	(Table	2).	This	method	tolerates	various	

functionalities	 like	nitro,	 ether,	 halogen	 etc.	 on	 the	 aldehydes.	
Efficacy	 of	 this	 method	 is	 fairly	 general	 and	 afforded	 the	
resultant	products	in	excellent	yield	and	products	are	obtained	
by	simple	work	up.	

Taking	 into	 account	 the	 reports	 of	 the	 literature	 [32],	we	
have	 proposed	 a	 route	 (Scheme	 2)	 for	 the	 formation	 of	
compound	5	and	6.	In	the	first	step,	condensation	of	hydrazine	
and	 ethylacetoacetate	 take	 place	 to	 form	 7	 and	 Knoevenagal	
condensation	 take	 place	 between	malononitrile	 and	 aldehyde	
to	form	arylidenepropanedinitrile	8,	then	the	Michael	addition	
of	compound	7	to	8	occur	to	form	9.	Then	attack	of	nucleophilic	
oxygen	of	9	on	CN	take	place	to	form	desired	product	5	or	6.	
	
4.	Conclusion	

	
In	conclusion,	the	present	work	provides	an	excellent	route	

for	 the	 production	 of	 6‐amino‐4‐(aryl)‐3‐methyl‐1,4‐
dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile	 and	 6‐amino‐4‐
(aryl)‐3‐methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]pyrazole‐5‐
carbonitrile	without	use	of	any	hazardous	reagent.	In	addition,	
use	of	environmentally	benign,	economical	and	easily	available	
glycerol	 as	 solvent	 proves	 the	 merit	 of	 this	 protocol.	 The	
targeted	 molecules	 are	 obtained	 in	 excellent	 yield	 (86‐93%)	
without	any	side	product.	

	
Acknowledgements	

	
The	 authors	 thank	 University	 Grants	 Commission,	 New	

Delhi,	 India	 for	 the	 financial	 support	 (Sanction	 No.	 F.No.8‐2	
(52)/2011	(MRP/NCRB)).	
	



Sohal	et	al.	/	European	Journal	of	Chemistry	4	(4)	(2013)	450‐453	 453	
 

	
Table	2.	Synthesis	of	1,4‐dihydropyrano[2,3‐c]pyrazole	derivative.	

 

 
	

Sample	no	 Product	a	 R1	 R	 Yield	(%)	b	 Melting	point	(°C)	
1	 5a	 C6H5	 H 93 243‐245	
2	 5b	 4‐Cl	C6H5	 H 92 233‐235	
3	 5c	 2‐Cl	C6H5	 H 90 246‐248	
4	 5d	 4‐NO2C6H5	 H 92 249‐252	
5	 5e	 2‐NO2C6H5	 H	 86	 210‐212	
6	 5f	 3‐NO2C6H5	 H	 90	 218‐220	
7	 5g	 4‐OHC6H5	 H 90 202‐204	
8	 5h	 4‐OMeC6H5	 H	 92	 208‐210	
9	 5i	 C6H5CH=CH	 H	 88	 200‐202	
10	 5j	 4‐MeC6H5	 H 89 240‐242	
11	 6a	 C6H5	 Ph 92 169‐170	
12	 6b	 4‐Cl	C6H5	 Ph 91 175‐176	
13	 6c	 2‐Cl	C6H5	 Ph 88 143‐145	
14	 6d	 4‐NO2C6H5	 Ph 87 195‐197	
15	 6e	 2‐NO2C6H5	 Ph	 89	 199‐200	
16	 6f	 3‐NO2C6H5	 Ph 91 191‐193	
17	 6g	 4‐OHC6H5	 Ph	 90	 209‐211	
18	 6h	 4‐OMeC6H5	 Ph	 92	 175‐177	
19	 6i	 C6H5CH=CH	 Ph	 87	 140‐142	
20	 6j	 4‐CH3C6H4	 Ph 89 176‐177	
a	Products	were	characterized	with	spectral	techniques	and	compared	with	authentic	samples.	
b	Yield	refers	to	pure	isolated	product.	
	
	
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