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European	Journal	of	Chemistry	5	(2)	(2014)	227‐232	

	

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.5.2.227‐232.967	

	
	

	

	

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

	 	 	

Catalyst	free,	one‐pot,	facile	synthesis	of	novel	pyrazolo‐1,4‐dihydropyridine	
derivative	form	pyranopyrazoles	

Harvinder	Singh	Sohal	a,*,	Arun	Goyal	a,	Rajshree	Khare	a,	Kishanpal	Singh	b	and	Rajeev	Sharma	c	

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

*Corresponding	author	at:	Department	of	Chemistry,	Maharishi	Markandeshwar	University,	Mullana,	133207,	Haryana,	India.		
Tel.:	+91.988.8857705.	Fax:	+91.1731.274375.	E‐mail	address:	luckysohal.singh@gmail.com	(H.S.	Sohal).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.5.2.227‐232.967	

Received:	11	November	2013	
Received	in	revised	form:	26	December	2013	
Accepted:	28	December	2013	
Online:	30	June	2014	

KEYWORDS	

	 One	 pot	 synthesis	 of	 pyrazolo‐1,4‐dihydropyridine	 derivatives	 from	 pyranopyrazoles	 using
acidic	solvent	system	is	described.	The	targeted	molecules	were	obtained	in	good	to	excellent
yield	without	 the	use	of	expensive	catalysts,	 toxic	solvents	and	chromatographic	separation.
The	 generality	 and	 functional	 tolerance	 of	 this	 convergent	 and	 environmentally	 benign
method	is	demonstrated.	

Catalyst	free	
Excellent	yield	
Acidic	medium	
Pyranopyrazoles	
One	pot	synthesis	
Pyrazolo‐1,4‐dihydropyridine	

	
1.	Introduction	
	

Hantzsch	 condensation	 discovered	 1,4‐dihydropyridines	
(1,4‐DHP’s)	 in	 1882	 [1].	 The	 1,4‐DHP’s	 has	 attracted	 more	
attention,	 thanks	 to	 its	 presence	 in	 the	 coenzyme,	diphospho‐
pyridine	 nucleotide	 (DPNH)	 [2]	 and	 recognition	 as	 bio‐active	
material.	 Many	 derivatives	 are	 commercialized	 in	 the	market	
[3‐7].	 Fused	 1,4‐DHPs	 have	 also	 been	 able	 to	 make	 their	
presence	felt	largely	due	to	ability	to	perform	biological	as	well	
as	pharmacological	functions.	1,4‐DHPs	are	an	important	class	
of	 Ca2+	 channel	 blockers	 and	 are	 also	 known	 to	 be	 effective	
cardiovascular	agents	for	the	treatment	of	hypertension.	Apart	
from	these	activities,	DHPs	are	 found	 to	be	as	platelet‐activity	
factor	 antagonists	 [8],	 calcium	 antagonists	 [9],	 anti‐
hypertensives	 [10],	 cerebral	 antischemic	 activity	 in	 the	
treatment	of	Alzheimer’s	disease	and	chemosensitizer	acting	in	
tumor	 therapy.	 Although	 the	 synthesis	 of	 pyrazolo‐1,4‐
dihydropyridines	 using	 expensive	 starting	 material	 like	 3‐
methyl‐4,5‐dihydro‐1H‐pyrazol‐5‐amine	or	3‐methyl‐1‐phenyl‐
4,5‐dihydro‐1H‐pyrazol‐5‐amine,	has	considerably	contributed	
to	the	development	of	new	pyrazolo‐1,4‐DHPs	[11‐15],	yet,	the	
achieved	 molecule	 remains	 beyond	 the	 reach	 of	 most	
manufacturers,	 as	 it	 involves	 the	 usage	 of	 expensive	 starting	
material.	The	molecule	also	does	not	remain	confined	to	the	use	

of	generally	used	methodologies	and	 therefore,	additional	and	
exquisite	methodologies	need	to	be	brought	into	use	[14].		

Therefore,	 recognizing	 the	 development	 of	 a	 clean,	 green	
and	efficient	procedure	as	the	need	of	the	hour,	and	persisting	
with	our	work	on	heterocyclics	[16‐18]	and	in	continuation	of	
our	previous	work	 (Scheme	1),	we	have	been	able	 to	produce	
some	pyrazolo‐1,4‐DHPs	from	easily	available	pyranopyrazoles	
(Figure	1)	[16].	The	present	protocol	is	simpler	as,	use	of	harsh	
reaction	condition	scheme	 is	not	a	pre‐requisite	 to	 it	 (Scheme	
2).	
	
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	 and	
13C	NMR	spectra	were	recorded	in	DMSO‐d6	on	a	Bruker	Avance	
II	 400	MHz	 spectrometer;	 chemical	 shifts	 (δ)	 are	 reported	 in	
ppm	relative	 to	TMS	as	 internal	standard.	The	mass	spectrum	
and	IR	spectra	were	recorded	at	LC‐MS	Spectrometer	Model	Q‐
ToF	 Micro	 Waters	 and	 Perkin‐Elmer	 Spectrum	 II	 infrared	
spectrophotometer,	respectively.		



228	 Sohal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	227‐232	
	

	

 
	

Scheme	1
	
	

 
	

Scheme 2
	
	

 
	

Figure	1.	Synthesis	of	pyranopyrazoles	using	glycerol	as	green	solvent.	
	
	
Elemental	 analyses	 (C,	 H,	 and	N)	were	 performed	 using	 a	

Thermo	Scientific	elemental	analyzer.	
	
2.2.	Synthesis	
	

Pyranopyrazoles	 (1a‐n)	 are	 prepared	 by	 using	 the	 given	
literature	 procedure	 [16].	 In	 a	 conical	 flask,	 hydrazine	
hydrate/phenyl	 hydrazine	 (10	 mmol),	 ethylacetoacetate	 (10	
mmol),	 aromatic	 aldehyde	 (10	mmol)	 and	malononitrile	were	
added	successively	 in	 glycerol	 (20	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	to	afford	
compound	1a‐n.	

6‐Hydroxy‐3‐methyl‐4‐phenyl‐4,7‐dihydro‐1H‐pyrazolo[3,4‐
b]pyridine‐5‐carbonitrile	(2a):	In	a	conical	flask	pyranopyrazole	
(1	mmol)	was	 taken	 in	 the	mixture	 of	 acetic	 acid	 (3	mL)	 and	
sulphuric	acid	(0.1	mL)	and	reflux	at	110	°C	for	the	stipulated	
time	 Table	 1.	 After	 the	 completion	 of	 reaction	 (vide	 TLC),	
reaction	 mixture	 was	 cooled	 to	 room	 temperature,	 solid	
separated	out.	Filtered	and	dried,	recrystallized	from	ethanol	to	
afford	compound	2a	(Entry	1,	Table	2).	Yield:	88%.	M.p.:	>300	
oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3532	 (O‐H	 Str.),	 3460	 (N‐H	 Str.),	
3390	(N‐H	Str.),	2206	(C≡N	Str.).	1H	NMR	(400	MHz,	DMSO‐
d6,	δ,	ppm):	1.78	(s,	3H,	CH3),	4.53	(s,	1H,	CH),	7.11‐7.81	(m,	5H,	
Ar‐H),	9.82	(s,	1H,	OH),	12.14	(s,	1H,	NH),	13.15	(s,	1H,	NH).	13C	
NMR	(100	MHz,	DMSO‐d6,	δ,	ppm):	160.2,	156.9,	148.1,	139.5,	
135.4,	122.1,	120.1,	114.1,	96.7,	77.9,	56.6,	52.6,	34.3,	9.7.	MS	
(EI,	m/z	(%)):	253	(M+,	12).	Anal.	calcd.	for	C14H12N4O:	C,	66.65;	
H,	4.79;	N,	22.21.	Found:	C,	66.61;	H,	4.78;	N,	22.19%.	

Similarly,	 other	 pyranopyrazoles	 1b‐n	 were	 reacted	 to	
afford	various	pyrazolo‐1,4‐dihydropyridines	derivatives	2b‐n	
(Table	2).	Data	obtained	using	advanced	spectral	techniques	for	
some	selected	compounds	have	been	summarized.	

6‐Hydroxy‐3‐methyl‐4‐(4‐chlorophenyl)‐4,7‐dihydro‐1H‐
pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2b):	 Yield:	 84%.	 M.p.:	
>300	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3540	 (O‐H	 Str.),	 3510	 (N‐H	
Str.),	 3442	(N‐H	 Str.),	 2264	(C≡N	 Str.).	 1H	NMR	 (400	MHz,	
DMSO‐d6,	δ,	ppm):	1.73	(s,	3H,	CH3),	4.51	(s,	1H,	CH),	6.91‐7.45	
(m,	4H,	Ar‐H),	9.85	(s,	1H,	OH),	12.01	(s,	1H,	NH),	13.11	(s,	1H,	
NH).	13C	NMR	(100	MHz,	DMSO‐d6,	δ,	ppm):162.1,	153.3,	149.7,	
144.2,	136.7,	133.0,	125.3,	120.9,	118.6,	98.3,	77.5,	 53.2,	35.7,	
9.7.	MS	(EI,	m/z	(%)):	288	(M+,	10).	Anal.	calcd.	for	C14H11ClN4O:	
C,	58.65;	H,	3.87;	N,	19.54.	Found:	C,	58.63;	H,	3.84;	N,	19.53%.	

6‐Hydroxy‐3‐methyl‐4‐(2‐nitrophenyl)‐4,7‐dihydro‐1H‐
pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2e):	 Yield:	 85%.	 M.p.:	
>300	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3572	 (O‐H	 Str.),	 3520	 (N‐H	
Str.),	 3450	(N‐H	 Str.),	 2340	(C≡N	 Str.).	 1H	NMR	 (400	MHz,	
DMSO‐d6,	δ,	ppm):	1.79	(s,	3H,	CH3),	4.76	(s,	1H,	CH),	7.60‐8.06	
(m,	4H,	Ar‐H),	10.01	(s,	1H,	OH),	12.19	(s,	1H,	NH),	13.21	(s,	1H,	
NH).	13C	NMR	(100	MHz,	DMSO‐d6,	δ,	ppm):161.0,	154.7,	147.8,	
146.5,	135.6,	134.0,	129.6,	121.7,	120.3,	96.3,	78.5,	 56.4,	39.5,	
9.7.	MS	(EI,	m/z	(%)):	298	(M+,	13).	Anal.	calcd.	for	C4H11N5O3:	
C,	56.56;	H,	3.73;	N,	23.56.	Found:	C,	56.53;	H,	3.69;	N,	23.54%.	

6‐Hydroxy‐3‐methyl‐4‐(4‐methoxyphenyl)‐4,7‐dihydro‐1H‐
pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2f):	 Yield:	 81%.	 M.p.:	
290‐292	oC.	FT‐IR	(KBr,	ν,	cm‐1):	3510	(O‐H	Str.),	3490	(N‐H	
Str.),	 3460	(N‐H	 Str.),	 2252	(C≡N	 Str.).	 1H	NMR	 (400	MHz,	
DMSO‐d6,	δ,	ppm):	1.72	(s,	3H,	CH3),	3.68(s,	3H,	OCH3),	4.47	(s,	
1H,	CH),	7.21‐7.80	(m,	4H,	Ar‐H),	9.92	(s,	1H,	OH),	12.08	(s,	1H,	
NH),	13.06	(s,	1H,	NH).		



Sohal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	227‐232	 229	
 

	
Table	1.Effect	of	temperature	on	the	synthesis	of	compound	2a.	
Entry	 Compound	 Temperature	(oC)	 Time	(h)	 Yield	a	(%)	
1	 2a	 70 9 20	
2	 2a	 80 7 52	
3	 2a	 90 4 70	
4	 2a	 100 3 79	
5	 2a	 110	 2	 88	
6	 2a	 120	b	 2	 87	
7	 2a	 130 b 2 82	
a	Yield	refer	to	combined	amounts	of	different	crops.	
b	Reaction	were	carried	out	in	silicon	oil	bath	with	the	use	of	cold	water	in	condenser.	

	
	
13C	NMR	(100	MHz,	DMSO‐d6,	 δ,	ppm):160.5,	157.9,	154.7,	

136.1,	 135.4,	 128.3,	 120.7,	 113.4,	 97.6,	 78.5,	 57.9,	 54.7,	 39.5,	
35.6,	 9.7.	 MS	 (EI,	 m/z	 (%)):	 283	 (M+,	 09).	 Anal.	 calcd.	 for	
C15H14N4O2:	C,	63.82;	H,	5.00;	N,	11.34.	Found:	C,	63.79;	H,	4.98;	
N,	11.33%.	

6‐Hydroxy‐3‐methyl‐4‐(4‐methylphenyl)‐4,7‐dihydro‐1H‐
pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2g):	 Yield:	 82%.	 M.p.:	
>300	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3501	 (O‐H	 Str.),	 3489	 (N‐H	
Str.),	 3472	(N‐H	 Str.),	 2199	(C≡N	 Str.).	 1H	NMR	 (400	MHz,	
DMSO‐d6,	 δ,	ppm):	1.75	 (s,	3H,	CH3),	2.21	 (s,	3H,	CH3)	4.46	 (s,	
1H,	CH),	7.01‐7.42	(m,	4H,	Ar‐H),	9.72	(s,	1H,	OH),	11.98	(s,	1H,	
NH),	12.95	(s,	1H,	NH).	13C	NMR	(100	MHz,	DMSO‐d6,	δ,	ppm):	
159.0,	156.4,	150.2,	133.7,	130.8,	124.1,	123.0,	116.5,	95.2,	78.6,	
56.4,	51.2,	40.2,	24.3,	9.7.	MS	(EI,	m/z	(%)):	267	(M+,	10).	Anal.	
calcd.	for	C15H14N4O:	C,	67.65;	H,	5.30;	N,	21.04.	Found:	C,	67.63;	
H,	5.28;	N,	21.01%.	

6‐Hydroxy‐3‐methyl‐1,4‐diphenyl‐4,7‐dihydro‐1H‐pyrazolo	
[3,4‐b]pyridine‐5‐carbonitrile	 (2h):	 Yield:	 85%.	 M.p.:	 228‐230	
oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3490	 (O‐H	 Str.),	 3430	 (N‐H	 Str.),	
2221	(C≡N	Str.).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	1.90	(s,	
3H,	CH3),	4.57	 (s,	1H,	CH),	7.21‐7.48	 (m,	10H,	Ar‐H),	10.07	 (s,	
1H,	 OH),	 13.25	 (s,	 1H,	 NH).	 13C	 NMR	 (100	 MHz,	 DMSO‐d6,	 δ,	
ppm):	 159.2,	 144.2,	 143.3,	 141.2,	 138.8,	 135.1,	 128.6,	 123.4,	
120.5,	113.4,	95.5,	77.5,	74.1,	58.2,	40.6,	39.3,	38.1,	36.6,	33.6,	
12.4.	MS	(EI,	m/z	(%)):	329	(M+,	13).	Anal.	calcd.	for	C20H16N4O:	
C,	73.15;	H,	4.91;	N,	17.06.	Found:	C,	73.12;	H,	4.89;	N,	17.04%.		

6‐Hydroxy‐3‐methyl‐4‐(4‐chlorophenyl)‐1‐phenyl‐4,7‐
dihydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2i):	 Yield:	
82%.	M.p.:	 250‐252	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3499	(O‐H	Str.),	
3434	(N‐H	Str.),	2230	(C≡N	Str.).	1H	NMR	(400	MHz,	DMSO‐
d6,	δ,	ppm):	1.81	(s,	3H,	CH3),	4.49	(s,	1H,	CH),	7.10‐7.62	(m,	9H,	
Ar‐H),	10.02	(s,	1H,	OH),	13.29	(s,	1H,	NH).	13C	NMR	(100	MHz,	
DMSO‐d6,	 δ,	 ppm):159.3,	 147.2,	 144.7,	 142.2,	 138.2,	 137.1,	
129.7,	 126.4,	 122.6,	 116.4,	 97.4,	 79.7,	 78.1,	 59.0,	 41.3,	 39.7,	
39.1,	 38.4,	 35.6,	 12.6.	 MS	 (EI,	m/z	 (%)):	 363	 (M+,	 10).	 Anal.	
calcd.	 for	 C20H15ClN4O:	 C,	 66.21;	 H,	 4.17;	 N,	 15.44.	 Found:	 C,	
66.19;	H,	4.16;	N,	15.41%.	

6‐Hydroxy‐3‐methyl‐4‐(2‐chlorophenyl)‐1‐phenyl‐4,7‐
dihydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2j):	 Yield:	
81%.	M.p.:	 220‐222	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3498	(O‐H	Str.),	
3480	(N‐H	Str.),	2229	(C≡N	Str.).	1H	NMR	(400	MHz,	DMSO‐
d6,	δ,	ppm):	1.87	(s,	3H,	CH3),	4.51	(s,	1H,	CH),	7.11‐7.69	(m,	9H,	
Ar‐H),	10.06	(s,	1H,	OH),	13.27	(s,	1H,	NH).	13C	NMR	(100	MHz,	
DMSO‐d6,	 δ,	 ppm):159.3,	 147.5,	 144.1,	 143.0,	 138.2,	 136.9,	
129.7,	 125.8,	 124.0,	 118.4,	 96.9,	 78.9,	 77.5,	 58.9,	 45.3,	 40.7,	
39.9,	 38.1,	 36.5,	 12.6.	 MS	 (EI,	m/z	 (%)):	 363	 (M+,	 09).	 Anal.	
calcd.	 for	 C20H15ClN4O:	 C,	 66.21;	 H,	 4.17;	 N,	 15.44.	 Found:	 C,	
66.20;	H,	4.15;	N,	15.42%.	

6‐Hydroxy‐3‐methyl‐4‐(4‐nitrophenyl)‐1‐phenyl‐4,7‐dihydro‐
1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2k):	 Yield:	 88%.	
M.p.:	 292‐294	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3560	(O‐H	Str.),	 3499	
(N‐H	Str.),	2290	(C≡N	Str.).	 1H	NMR	(400	MHz,	DMSO‐d6,	δ,	
ppm):	1.74	(s,	3H,	CH3),	4.90	(s,	1H,	CH),	7.37‐8.41	(m,	9H,	Ar‐
H),	 10.21	 (s,	 1H,	 OH),	 13.36	 (s,	 1H,	 NH).	 13C	 NMR	 (100	MHz,	
DMSO‐d6,	 δ,	 ppm):159.6,	 147.9,	 145.7,	 145.0,	 143.9,	 137.4,	
134.4,	129.9,	129.0,	125.9,	122.1,	119.9,	 97.4,	78.3,	57.2,	40.1,	
39.3,	 38.9,	 36.4,	 12.8.	 MS	 (EI,	m/z	 (%)):	 374	 (M+,	 12).	 Anal.	

calcd.	 for	 C20H15N5O3:	 C,	 64.34;	 H,	 4.05;	 N,	 18.76.	 Found:	 C,	
64.33;	H,	4.04;	N,	18.76%.	

6‐Hydroxy‐3‐methyl‐4‐(2‐nitrophenyl)‐1‐phenyl‐4,7‐dihydro‐
1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	(2l):	Yield:	83%.	M.p.:	
286‐288	oC.	FT‐IR	(KBr,	ν,	cm‐1):	3559	(O‐H	Str.),	3440	(N‐H	
Str.),	2263	(C≡N	Str.).	 1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	
1.80	 (s,	 3H,	 CH3),	 4.87	 (s,	 1H,	 CH),	 7.32‐8.11	 (m,	 9H,	 Ar‐H),	
10.20	(s,	1H,	OH),	13.27	(s,	1H,	NH).	13C	NMR	(100	MHz,	DMSO‐
d6,	 δ,	 ppm):159.6,	 147.8,	 145.5,	 144.8,	 143.5,	 136.9,	 134.0,	
130.2,	 129.1,	 124.6,	 121.9,	 119.7,	 98.0,	 78.1,	 55.1,	 41.2,	 39.0,	
37.9,	36.0,	12.7.	MS	(EI,	m/z	(%)):	374	(M+,	14).	Anal.	calcd.	for	
C20H15N5O3:	C,	64.34;	H,	4.05;	N,	18.76.	Found:	C,	64.31;	H,	4.00;	
N,	18.75%.	

6‐Hydroxy‐3‐methyl‐4‐(4‐methoxyphenyl)‐1‐phenyl‐4,7‐
dihydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2m):	 Yield:	
81%.	M.p.:	 265‐267	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3520	(O‐H	Str.),	
3425	(N‐H	Str.),	2219	(C≡N	Str.).	1H	NMR	(400	MHz,	DMSO‐
d6,	 δ,	 ppm):	 1.81	 (s,	 3H,	 CH3),	 3.71	 (s,	 3H,	OCH3),	 4.56	 (s,	 1H,	
CH),	 6.91‐7.93	 (m,	 9H,	 Ar‐H),	 10.18	 (s,	 1H,	 OH),	 13.17	 (s,	 1H,	
NH).	13C	NMR	(100	MHz,	DMSO‐d6,	δ,	ppm):159.1,	158.1,	145.2,	
143.7,	137.6,	135.3,	128.9,	125.7,	119.8,	113.5,	99.4,	98.5,	78.5,	
58.8,	54.8,	40.2,	39.8,	39.1,	38.2,	30.5,	12.5.	MS	 (EI,	m/z	 (%)):	
359	 (M+,	 08).	Anal.	 calcd.	 for	C21H18N4O2:	 C,	 70.38;	H,	 5.06;	N,	
15.63.	Found:	C,	70.35;	H,	5.05;	N,	15.61%.	

6‐Hydroxy‐3‐methyl‐4‐(4‐methylphenyl)‐1‐phenyl‐4,7‐
dihydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile	 (2n):	 Yield:	
80%.	M.p.:287‐288	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3506	 (O‐H	 Str.),	
3419	(N‐H	Str.),	2209	(C≡N	Str.).	1H	NMR	(400	MHz,	DMSO‐
d6,	δ,	ppm):	1.79	(s,	3H,	CH3),	2.61(s,	3H,	CH3),	4.53	(s,	1H,	CH),	
7.41‐8.24	(m,	9H,	Ar‐H),	10.09	(s,	1H,	OH),	12.99	(s,	1H,	NH).	13C	
NMR	 (100	MHz,	 DMSO‐d6,	 δ,	 ppm):159.2,	 145.2,	 143.7,	 140.2,	
137.5,	136.0,	128.8,	127.4,	125.6,	119.8,	98.4,	78.7,	 78.3,	58.9,	
40.2,	 39.8,	 39.4,	 38.9,	 36.6,	 20.6,	 12.5.	MS	 (EI,	m/z	 (%)):	 343	
(M+,	11).	Anal.	calcd.	for	C21H18N4O:	C,	73.67;	H,	5.30;	N,	16.36.	
Found:	C,	73.66;	H,	5.28;	N,	16.36%.	
	
3.	Result	and	discussion		
	

Reactions	 of	 pyranopyrazole	 1a	 with	 the	 mixture	 acetic	
acid	 and	 sulphuric	 acid	 were	 carried	 out	 at	 different	
temperatures	 (70‐130	 °C).	 It	was	 observed	 that	 110	 °C	 is	 the	
optimal	 temperature	 for	 the	 synthesis	 of	 pyrazolo‐1,4‐
dihydropyridines.	 Further,	 rise	 in	 temperature	 results	 in	 the	
decomposition	of	the	reaction	mixture	(Table	1).	

The	structure	of	the	compound	2a	was	confirmed	with	the	
use	of	spectral	 techniques.	 In	 IR	spectrum	absorption	at	3532	
cm‐1	 represents	 the	 O‐H	 stretching,	 absorption	 at	 3460	 and	
3390	 cm‐1	 for	 two	N‐H	 stretching,	 a	 sharp	 absorption	peak	 at	
2206	cm‐1	represent	C≡N	stretching.	In	1H	NMR	spectra	peaks	
two	 singletat	 13.15	 and	 12.14	 ppm	 are	 observed	 for	 two	 NH	
protons,	 a	 singlet	 for	 9.82	 ppm	 for	 OH	 proton,	 peaks	 for	 five	
aromatic	protons	are	observed	at	7.11‐7.81	ppm,	singlet	at	4.53	
ppm	for	–CH	proton	and	a	singlet	for–CH3	group	is	observed	at	
1.78	 ppm.	 Spectral	 data	 of	 compound	 2a	 fully	 supports	 the	
structure	 assigned	 to	 it.Similarly,	 other	 pyrazolo‐1,4‐
dihydropyridine	 derivatives2b‐n	 have	 been	 synthesised	 from	
pyranopyrazoles	 1b‐nin	 the	 mixture	 of	 acetic	 acid	 and	
sulphuric	acid.	The	results	are	summarized	in	Table	2.	



230	 Sohal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	227‐232	
	

	
Table	2.	Synthesis	of	pyrazolo‐1,4‐dihydropyridines	from	pyranopyrazoles.	
S.	No.	 Entry	of	

reactant	
Reactant	 Melting	point	of	

reactant	(oC)
Entry	of	
product

Product	 Melting	point	of	
product	(oC)	

Yield	a	

1	 1a	

O

N

N

H3C

H

CN

NH2

	

243‐245 2a >300	 88

2	 1b	

	

233‐235	 2b	 >300	 84	

3	 1c	

	

246‐248 2c >300	 82

4	 1d	

	

249‐252 2d >300	 90

5	 1e	

	

210‐212	 2e	 >300	 85	

6	 1f	

	

208‐210	 2f	 290‐292	 81	

7	 1g	

	

240‐242 2g >300	 82

8	 1h	

	

169‐170 2h 228‐230	 85

a	Yield	refer	to	combined	amounts	of	different	crops.	
	



Sohal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	227‐232	 231	
 

Table	2.	(Continued).	
S.	No.	 Entry	of	

reactant	
Reactant	 Melting	point	of	

reactant	(oC)
Entry	of	
product

Product	 Melting	point	of	
product	(oC)	

Yield	a	

9	 1i	

	

175‐176 2i 250‐252	 82

10	 1j	

	

143‐145 2j 220‐222	 81

11	 1k	

	

195‐197 2k 292‐294	 88

12	 1l	

	

199‐200	 2l	 286‐288	 83	

13	 1m	

	

175‐177	 2m	 265‐267	 81	

14	 1n	

	

176‐177 2n 287‐288	 80

a	Yield	refer	to	combined	amounts	of	different	crops.	
	

	
Reactions	 proceed	 smoothly	 with	 pyranopyrazoles	

carrying	 electron	 withdrawing	 as	 well	 as	 electron	 donating	
substituent’s	(Table	2).	Efficacy	of	this	method	is	fairly	general	
and	affords	the	resultant	products	 in	excellent	yield	(80‐90%)	
and	products	are	obtained	by	simple	work	up.	

Attempt	 have	 been	 made	 to	 explain	 the	 plausible	
mechanism	 of	 the	 pyrazolo‐1,4‐dihydropyridine	 molecules	
(Scheme	3).	In	the	acidic	medium	opening	of	pyran	ring	1	occur	
via	 addition	 of	 H+	 ion	 to	 give	 compound	 4	 which	 upon	
tautomerism	 produced	 5,	 as	 C‐C	 single	 bond	 rotation	 is	
possible	 in	 structure	5,	 on	 rotating	 produced	6.	 As	we	 know	
C=0	bond	 length	 is	 smaller	 than	C‐NH2,	 then	 the	 closing	 from	
NH2	 terminal	 is	occurred	 to	yield	7.	Further	 in	acidic	medium	
the	 keto	 form	 8	 is	 converted	 into	 more	 stable	 enol	 form	 2	
supported	 by	 the	 presence	 of	 absorption	 peak	 around	 	 3550	

cm‐1	 in	 IR	 and	 peak	 at	 around	 δ	 10	 ppm	 in	 1H	 NMR	
spectroscopy	shows	 the	presence	of	OH	group	and	absence	of	
peak	1650‐1750	cm‐1	confirm	that	enol	form	exist.		
	
4.	Conclusion	
	

The	 present	 procedure	 is	 an	 effective	 method	 for	
production	 of	 pyrazolo‐1,4‐dihydropyridine,	 from	 easily	
obtainable	 initiating	 materials,	 in	 a	 single	 step	 with	 inherent	
flexibility	and	diversity.	This	method	was	efficacious	to	reduce	
labor,	cost,	waste	production	and	also	devoid	of	harsh	reaction	
conditions.	 The	 target	 compounds	 were	 obtained	 in	 an	
acceptable	yield	with	simple	 recrystallization	as	a	purification	
step.	

	



232	 Sohal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	227‐232	
	

	 	

 
	

Scheme	3
	
	

Acknowledgements	
	

The	 authors	 thank	 Maharishi	 Markandeshwar	 University,	
Mullana,	Haryana,	India	for	the	financial	support	and	Harvinder	
Singh	Sohal	and	Arun	Goyal	also	thank	Mr.	Vikas	Pahwa	for	the	
liberal	support.	
	
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