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European	Journal	of	Chemistry	5	(4)	(2014)	676‐680	

	

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.5.4.676‐680.1110	

	
	

	

	

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

	 	 	

PEG‐400:	An	efficient	and	recyclable	reaction	medium	for	the	synthesis	of	
pyrazolo[1,5‐a]pyrimidines	

Shankaraiah	Guruvaiah	Konda	*	

Department	of	Chemistry,	Karamsibhai	Jethabhai	Somaiya	College	of	Arts,	Commerce	and	Science,	Kopargaon,	423601,	India	

*Corresponding	author	at:	Department	of	Chemistry,	Karamsibhai	Jethabhai	Somaiya	College	of	Arts,	Commerce	and	Science,	Kopargaon,	423601,	India.		
Tel.:	+91.02423.222254.	Fax:	+91.02423.222254.	E‐mail	address:	kondasg@rediffmail.com	(S.G.	Konda).	

	
	

	 	

	 	 	
COMMUNICATION	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.5.4.676‐680.1110	

Received:	20	June	2014	
Received	in	revised	form:	02	August	2014	
Accepted:	09	August	2014	
Online:	31	December	2014	

KEYWORDS	

	 An	 efficient	 and	 convenient	 route	 is	 described	 for	 the	 synthesis	 of	 new	 pyrazolo	 [1,5‐a]
pyrimidine	derivatives	by	the	reaction	of	4‐(4’‐chloro‐phenylazo)‐5‐amino	pyrazole	with	α,β‐
unsaturated	carbonyl	compounds	(chalcones)	using	polyethylene	glycol	(PEG‐400)	as	benign
reaction	 medium.	 The	 advantage	 of	 this	 protocol	 includes	 the	 excellent	 yields,	 operational
simplicity,	 short	 reaction	 times	 and	 avoidance	 of	 volatile	 organic	 solvents	 and	 expensive
catalysts.	

PEG‐400	
Recyclability	
Benign	synthesis	
5‐Amino	pyrazole	
α,β‐Unsaturated	ketones	
Pyrazolo[1,5‐a]pyrimidine	

	
1.	Introduction	
	

In	the	past	few	years,	there	has	been	a	growing	interest	in	
the	chemistry	of	pyrazolo	 [1,5‐a]	pyrimidines,	which	 is	due	 to	
the	 extent	 of	 their	 applications	 in	 pharmacological	 science.	
Indeed	 they	 are	 known	 for	 their	 antitrypanosomal	 [1]	 and	
antichistosomal	[2]	activities,	their	sedative	and	anxiolitic–like	
properties	 [3,4]	and	 they	are	potential	 as	HMG‐CoA	reductase	
inhibitors	[5],	COX‐2‐selective	inhibitors	[6],	AMP	phoshodies‐
tarase	 inhibitors	 [7],	 KDR	 kinase	 inhibitors	 [8]	 and	 selective	
peripheral	 benzodiazepine	 receptor	 ligands	 [9,10].	 These	
interesting	 biological	 properties	 have	 been	 prompt	 us	 to	 the	
development	 of	new	procedures	 for	 the	 synthesis	 of	pyrazolo	
[1,5‐a]	 pyrimidines	 [11,12].	 Classical	 conditions	 for	 the	
synthesis	of	pyrazolo	[1,5‐a]	pyrimidines	involve	refluxing	a	5‐
amino‐4‐aryl‐pyrazole	 with	 a	 commercially	 available	 2‐aryl	
malondialdehyde	 in	ethanol	with	catalytic	acetic	acid	 for	24	h	
to	deliver	pyrazolo	[1,5‐a]	pyrimidines	in	40‐60%	yields	[13].	

Recently,	 liquid	 polymers	 or	 low	 melting	 polymers	 have	
emerged	 as	 alternative	 green	 reaction	 media	 with	 unique	
properties	 such	 as	 thermal	 stability,	 commercial	 availability,	
non‐volatility,	 immiscibility	with	a	number	of	organic	solvents	
and	 recyclability.	 PEGs	 are	 preferred	 over	 other	 polymers	
because	 they	 are	 inexpensive,	 completely	 non‐halogenated,	
easily	 degradable	 and	 of	 low	 toxicity	 [14].	 Many	 organic	
reactions	 have	 been	 carried	 out	 using	 PEGs	 as	 solvent	 or	 co‐

solvent	such	as	Heck	reaction	[15],	asymmetric	dihydroxylation	
[16,17],	 Suzuki	 cross‐coupling	 reaction	 [18],	 oxy‐dehydroge‐
nation	 of	 alcohols	 and	 cyclic	 dienes,	 oxidation	 of	 sulfides,	
Wacker	 reaction	 [19],	 deallylation	 [20]	 and	 partial	 reduction	
reaction	of	alkynes	[21].	The	use	of	PEG	as	a	recyclable	solvent	
system	for	the	metal	mediated	radical	polymerization	of	methyl	
methacrylate	 and	 styrene	 has	 also	 been	 reported	 [22].	 A	
number	of	recent	literatures	have	also	covered	PEG	as	a	green	
reaction	solvent	[23‐26].	

Continuing	 our	 studies	 on	 the	 development	 of	 new,	
selective,	 and	 environmentally	 friendly	 methodologies	 using	
PEG‐400	as	a	solvent	 for	 the	preparation	of	biologically	active	
compounds	 [27‐30],	 herein	 I	 report	 the	 expeditious	 synthesis	
of	novel	pyrazolo	[1,5‐a]	pyrimidine	derivatives	by	the	reaction	
of	 amino	 pyrazole	 with	 novel	 α,β‐unsaturated	 carbonyl	
compounds	 in	 PEG‐400	 as	 green	 reaction	 solvent	 under	mild	
temperature.		
	
2.	Experimental	
	

Melting	 points	 were	 uncorrected	 and	 determined	 in	 an	
open	 capillary	 tube.	 IR	 spectra	 were	 recorded	 on	 FTIR‐
Shimadzu	 spectrometer.	 1H	 NMR	 spectra	 were	 recorded	 in	
DMSO‐d6	 on	 Avance‐300	 MHz	 spectrometer	 using	 TMS	 as	 an	
internal	 standard.	 The	 mass	 spectra	 were	 recorded	 on	 EI‐
Shimadzu‐GC‐MS	spectrometer.	



Konda	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	676‐680	 677	
 

	

 
	

Scheme	1
	
	

 
	

Scheme	2
	
	
Elemental	 analyses	 were	 performed	 on	 a	 Carlo	 Erba	 106	

Perkin‐Elmer	model	240	analyzer.	
	
2.1.	General	procedure	for	the	synthesis	of	chalcones	1(a‐l)	
[31]	
	

An	 equimolar	 mixture	 of	 substituted	 acetophenone	 (1	
mmol),	hetero	aromatic	aldehyde	(1	mmol)	and	KOH	(2	mmol)	
was	 stirred	 in	 PEG‐400	 (15	 mL)	 at	 40	 °C	 for	 1	 hour.	 After	
completion	 of	 the	 reaction	 (monitored	 by	 TLC),	 the	 crude	
mixture	was	 worked	 up	 in	 ice	 cold	 water	 (100	mL).	 Product	
separated	 out	 was	 filtered	 and	 processed	 out.	 The	 PEG	 was	
recycled	 and	 reused	 to	 synthesize	 further	 chalcones	 (Scheme	
1).	
	
2.2.	Typical	procedure	for	the	synthesis	of	pyrazolo	[1,	5‐a]	
pyrimidines	(2a‐l)	
	

A	 mixture	 of	 1b	 (0.322	 g,	 1	 mmol)	 and	 4‐(4’‐chloro‐
phenylazo)‐5‐amino	pyrazole	(0.236	g,	1	mmol)	was	stirred	in	
PEG‐400	 (10	 mL)	 at	 80	 °C	 for	 2	 hours.	 The	 progress	 of	 the	
reaction	was	monitored	by	TLC.	After	completion,	the	reaction	
mixture	 was	 extracted	 with	 ethyl	 acetate	 (2×20	 mL).	 The	
combined	 organic	 layers	 were	 dried	 over	 anhydrous	 Na2SO4,	
and	 the	 solvent	was	 evaporated	 under	 reduced	pressure.	 The	
crude	product	was	 recrystallized	 from	aqueous	DMF	to	afford	
to	 the	 pure	 product	 2b.	 The	 remaining	 mother	 liquor	 was	
recovered	and	recycled	in	subsequent	reactions	(Scheme	2).	

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐butyl‐
4‐chloro‐1H‐imidazol‐5‐yl)pyrazolo[1,	 5‐a]pyrimidin‐5‐yl)‐
4‐chlorophenol	 (2a):	 Color:	 Reddish	 brown.	 Yield:	 90%.	 M.p.:	
112‐114	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1618	 (‐C=N),	 3096	 (‐OH),	
3329	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	0.93	(t,	J	=	
7.5	Hz,	 3H,	 CH3),	 1.31‐136	 (m,	 2H,	 ‐CH2‐),	 1.66‐1.69	 (m,	 2H,	 ‐
CH2‐),	2.76	(t,	J	=	7.2	Hz,	2H,	CH2),	4.01	(bs,	2H,	NH2),	7.02‐7.96	
(m,	 7H,	 Ar‐H),	 8.11(s,	 1H,	 NH),	 8.51	 (s,	 1H,	 6H‐pyrimidine),	
12.36	(s,	1H,	‐OH,	D2O	exchangeable).	13C	NMR	(75	MHz,	DMSO‐
d6,	δ,	ppm):	14,	22,	29,	30,	93,	115,	119,	120,	121,	122,	123,	125,	
126,	127,	128,	129	(2	x	C),	130	(2	x	C),	132,	146,	152,	155,	161,	
163.	MS	 (EI,	m/z	 (%)):	554	 (M+),	 127	 (100%).	Anal.	 calcd.	 for	
C25H21N8OCl3:	 C,	 54.02;	 H,	 3.81;	 N,	 20.16.	 Found:	 C,	 54.11;	 H,	
3.88;	N,	20.12%.		

(3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐7‐(2‐butyl‐4‐chloro‐1H‐
imidazol‐5‐yl)‐5‐(4‐chlorophenyl)pyrazolo[1,	 5‐a]pyrimidin‐
2‐amine	(2b):	Color:	Reddish	brown.	Yield:	92%.	M.p.:	125‐127	
°C.	FT‐IR	(KBr,	ν,	cm‐1):	1619	(‐C=N),	3359	(‐NH2).	1H	NMR	(300	
MHz,	DMSO‐d6,	δ,	ppm):	0.93	(t,	J	=	7.2	Hz,	3H,	CH3),	1.32‐1.36	
(m,	2H,	‐CH2‐),	1.68‐1.72	(m,	2H,	‐CH2‐),	2.74	(t,	J	=	7.2	Hz,	2H,	

CH2),	 4.16	 (bs,	 2H,	NH2),	 7.05‐7.99	 (m,	 8H,	Ar‐H),	 8.16	 (s,	 1H,	
NH),	8.49	(s,	1H,	6H‐pyrimidine).	 13C	NMR	(75	MHz,	DMSO‐d6,	
δ,	ppm):	14,	22,	29,	30,	93,	119,	120,	122,	123,	125,	126,	127	(2	
x	C),	128	(2	x	C),	129	(2	x	C),	130	(2	x	C),	132,	134,	135,	152,	
161,	163.	MS	(EI,	m/z	(%)):	538	(M+),	127	(100%).	Anal.	calcd.	
for	C25H21N8Cl3:	C,	55.64;	H,	3.91;	N,	20.76.	Found:	C,	55.51;	H,	
3.99;	N,	20.61%.	

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐butyl‐
4‐chloro‐1H‐imidazol‐5‐yl)pyrazolo[1,	 5‐a]pyrimidin‐5‐yl)‐4‐
chloro‐6‐iodophenol	 (2c):	Color:	Dark	Brown.	Yield:	86%.	M.p.:	
134‐136	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1616	 (‐C=N),	 3142	 (‐OH),	
3325	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	0.91	(t,	J	=	
7.2	Hz,	 3H,	 CH3),	 1.35‐1.39	 (m,	2H,	 ‐CH2‐),	 1.66‐1.71	 (m,	2H,	 ‐
CH2‐),	2.78	(t,	J	=	7.5	Hz,	2H,	CH2),	4.05	(bs,	2H,	NH2),	7.11‐7.95	
(m,	 6H,	 Ar‐H),	 8.18	 (s,	 1H,	 NH),	 8.48	 (s,	 1H,	 6H‐pyrimidine),	
12.48	 (s,	 1H,	 ‐OH,	 D2O	 exchangeable).	 MS	 (EI,	m/z	 (%)):	 682	
(M+),	 127	 (100%).	 Anal.	 calcd.	 for	 C25H20N8OCl3I:	 C,	 44.04;	 H,	
2.96;	N,	16.44.	Found:	C,	44.11;	H,	2.91;	N,	16.53%.	

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐butyl‐
4‐chloro‐1H‐imidazol‐5‐yl)pyrazolo[1,	 5‐a]pyrimidin‐5‐yl)‐
6‐bromo‐4‐chlorophenol	 (2d):	 Color:	 Brown.	 Yield:	 89%.	M.p.:	
121‐123	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1620	 (‐C=N),	 3126	 (‐OH),	
3338	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	0.91	(t,	J	=7	
.5	Hz,	3H,	CH3),	1.33‐1.38	(m,	2H,	‐CH2‐),	1.65‐1.69	(m,	2H,	‐CH2‐
),	2.71	(t,	J	=	7.2	Hz,	2H,	CH2),	4.12	(bs,	2H,	NH2),	7.11‐7.88	(m,	
6H,	Ar‐H),	8.18	(s,	1H,	NH),	8.46	(s,	1H,	6H‐pyrimidine),	12.51	
(s,	1H,	‐OH,	D2O	exchangeable).	MS	(EI,	m/z	(%)):	634	(M+),	79	
(100).	 Anal.	 calcd.	 for	 C25H20N8OCl3Br:	 C,	 47.31;	 H,	 3.18;	 N,	
17.65.	Found:	C,	47.38;	H,	3.15;	N,	17.73%.		

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐butyl‐
4‐chloro‐1H‐imidazol‐5‐yl)pyrazolo[1,	 5‐a]pyrimidin‐5‐yl)‐
4‐chloro‐5‐methylphenol	 (2e):	 Color:	 Reddish	 brown.	 Yield:	
86%.	M.p.:	138‐140	°C.	FT‐IR	(KBr,	ν,	cm‐1):	1620	(‐C=N),	3068	
(‐OH),	3315	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	0.91	
(t,	 J	=	7.2	Hz,	3H,	CH3),	1.35‐1.38	(m,	2H,	‐CH2‐),	1.66‐1.72	(m,	
2H,	‐CH2‐),	2.21	(s,	3H,	CH3),	2.65	(t,	 J	=	7.2	Hz,	2H,	CH2),	4.11	
(bs,	2H,	NH2),	7.05‐7.98	(m,	6H,	Ar‐H),	8.21	(s,	1H,	NH),	8.46	(s,	
1H,	6H‐pyrimidine),	12.28	 (s,	 1H,	 ‐OH,	D2O	exchangeable).	MS	
(EI,	m/z	(%)):	570	(M+),	43	(100).	Anal.	calcd.	for	C26H23N8OCl3:	
C,	54.80;	H,	4.07;	N,	19.656.	Found:	C,	54.72;	H,	4.13;	N,	19.76%.		

6‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐butyl‐
4‐chloro‐1H‐imidazol‐5‐yl)pyrazolo[1,	 5‐a]pyrimidin‐5‐yl)‐
4‐chloro‐6‐iodo‐5‐methylphenol	 (2f):	 Color:	 Reddish	 brown.	
Yield:	86%.	M.p.:	152‐154	°C.	FT‐IR	(KBr,	ν,	cm‐1):	1622	(‐C=N),	
3088	(‐OH),	3328	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	
0.91	(t,	J	=	7.5	Hz,	3H,	CH3),	1.33‐1.38	(m,	2H,	‐CH2‐),	1.68‐1.72	
(m,	 2H,	 ‐CH2‐),	 2.24	 (s,	 3H,	 CH3),	 2.68	 (t,	 J	 =	 7.2	Hz,	 2H,	 CH2),	
4.18	 (bs,	 2H,	NH2),	 7.05‐7.95	 (m,	 5H,	 Ar‐H),	 8.22	 (s,	 1H,	 NH),	



678	 Konda	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	676‐680	
	
8.51	 (s,	 1H,	 6H‐pyrimidine),	 12.42	 (s,	 1H,	 ‐OH,	 D2O	 exchan‐
geable).	MS	(EI,	m/z	(%)):	695	(M+),	127	(100).	Anal.	calcd.	for	
C26H22N8OCl3I:	 C,	 44.88;	H,	 3.19;	N,	 16.10.	 Found:	 C,	 44.76;	H,	
3.28;	N,	16.18%.		

6‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐butyl‐
4‐chloro‐1H‐imidazol‐5‐yl)pyrazolo[1,	 5‐a]pyrimidin‐5‐yl)‐
6‐bromo‐4‐chloro‐5‐methylphenol	 (2g):	 Color:	 Brown.	 Yield:	
88%.	M.p.:	105‐107	°C.	FT‐IR	(KBr,	ν,	cm‐1):	1618	(‐C=N),	3095	
(‐OH),	3335	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	0.93	
(t,	 J=7.2	 Hz,	 3H,	 CH3),	 1.33‐1.39	 (m,	 2H,	 ‐CH2‐),	 1.68‐1.71	 (m,	
2H,	‐CH2‐),	2.28	(s,	3H,	CH3),	2.71	(t,	J=7.5	Hz,	2H,	CH2),	3.98	(bs,	
2H,	NH2),	7.12‐8.05	(m,	5H,	Ar‐H),	8.24	(s,	1H,	NH),	8.49	(s,	1H,	
6H‐pyrimidine),	12.35	(s,	1H,	 ‐OH,	D2O	exchangeable).	MS	(EI,	
m/z	(%)):	648	(M+),	77	(100).	Anal.	calcd.	for	C26H22N8OCl3Br:	C,	
48.13;	H,	3.42;	N,	17.27.	Found:	C,	48.21;	H,	3.51;	N,	17.38%.		

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐amino‐
4‐(4‐chlorophenyl)thiazol‐5‐yl)pyrazolo[1,	5‐a]pyrimidin‐5‐yl)‐4‐
chlorophenol	(2h):	Color:	Brick	 red.	Yield:	86%.	M.p.:	158‐160	
°C.	FT‐IR	(KBr,	ν,	cm‐1):	1616	(‐C=N),	3092	(‐OH),	3325	(‐NH2).	
1H	NMR	 (300	MHz,	DMSO‐d6,	 δ,	 ppm):	 4.26	 (bs,	 2H,	NH2,	D2O	
exchangeable),	 7.15‐8.21	 (m,	 11H,	 Ar‐H),	 8.32	 (s,	 2H,	 NH2‐
thiazole,	D2O	exchangeable),	8.58	(s,	1H,	6H‐pyrimidine),	11.91	
(s,1H,	OH,	D2O	exchangeable).	Anal.	calcd.	for	C27H17N8OSCl3:	C,	
53.35;	H,	2.82;	N,	18.43.	Found:	C,	53.22;	H,	2.92;	N,	18.38%.		

(3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐7‐(2‐amino‐4‐(4‐
chlorophenyl)thiazol‐5‐yl)‐5‐(4‐chlorophenyl)pyrazolo[1,5‐
a]pyrimidin‐2‐amine	 (2i):	 Color:	 Brick	 red.	 Yield:	 90%.	 M.p.:	
165‐167	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1619	 (‐C=N),	 3096	 (‐OH),	
3338	 (‐NH2).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 4.21	 (bs,	
2H,	NH2,	D2O	exchangeable),	7.11‐8.16	(m,	12H,	Ar‐H),	8.33	(s,	
2H,	 NH2‐thiazole,	 D2O	 exchangeable),	 8.51	 (s,	 1H,	 6H‐
pyrimidine).	MS	(EI,	m/z	(%)):	592	(M+),	43	(100).	Anal.	calcd.	
for	C27H17N8SCl3:	C,	54.79;	H,	2.89;	N,	18.93.	Found:	C,	53.86;	H,	
2.94;	N,	18.86%.		

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐amino‐
4‐(4‐chlorophenyl)thiazol‐5‐yl)pyrazolo[1,	5‐a]pyrimidin‐5‐yl)‐4‐
chloro‐6‐iodophenol	 (2j):	 Color:	 Brick	 red.	 Yield:	 88%.	 M.p.:	
131‐133	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1618	 (‐C=N),	 3111	 (‐OH),	
3335	 (‐NH2).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 4.11	 (bs,	
2H,	NH2,	D2O	exchangeable),	7.15‐8.15	(m,	10H,	Ar‐H),	8.33	(s,	
2H,	 NH2‐thiazole,	 D2O	 exchangeable),	 8.46	 (s,	 1H,	 6H‐
pyrimidine),	 12.25	 (s,	 1H,	OH,	D2O	 exchangeable).	Anal.	 calcd.	
for	C27H16N8OSCl3:	C,	44.19;	H,	2.20;	N,	15.27.	Found:	C,	44.11;	
H,	2.29;	N,	15.34%.		

2‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐amino‐
4‐(4‐chlorophenyl)thiazol‐5‐yl)pyrazolo[1,	5‐a]pyrimidin‐5‐yl)‐6‐
bromo‐4‐chlorophenol	 (2k):	Color:	Brick	 red.	Yield:	90%.	M.p.:	
142‐144	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1618	 (‐C=N),	 3118	 (‐OH),	
3338	 (‐NH2).	 1H	 NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 4.21	 (bs,	
2H,	NH2,	D2O	exchangeable),	7.11‐8.05	(m,	10H,	Ar‐H),	8.34	(s,	
2H,	 NH2‐thiazole,	 D2O	 exchangeable),	 8.51	 (s,	 1H,	 6H‐
pyrimidine),	12.26	(s,	1H,	OH,	D2O	exchangeable).	MS	(EI,	m/z	
(%)):	 686	 (M+),	 79	 (100).	 Anal.	 calcd.	 for	 C27H16N8OSCl3Br:	 C,	
47.22;	H,	2.35;	N,	16.32.	Found:	C,	47.28;	H,	2.31;	N,	16.41%.		

6‐((3E)‐3‐(2‐(4‐chlorophenyl)diazenyl)‐2‐amino‐7‐(2‐amino‐
4‐(4‐chlorophenyl)thiazol‐5‐yl)pyrazolo[1,	5‐a]pyrimidin‐5‐yl)‐4‐
chloro‐5‐methylphenol	 (2l):	 Color:	 Brick	 red.	 Yield:	 88%.	M.p.:	
174‐176	 °C.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 1622	 (‐C=N),	 3098	 (‐OH),	
3335	(‐NH2).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	2.24	(s,	3H,	
CH3),	 4.18	 (bs,	 2H,	NH2,	D2O	 exchangeable),	 7.05‐8.14	 (m,	 9H,	
Ar‐H),	8.32	(s,	2H,	NH2‐thiazole,	D2O	exchangeable),	8.46	(s,	1H,	
6H‐pyrimidine),	 12.38	 (s,	 1H,	 OH,	 D2O	 exchangeable).	 Anal.	
calcd.	for	C28H18N8OSCl3I:	C,	44.97;	H,	2.43;	N,	14.98.	Found:	C,	
44.91;	H,	2.49;	N,	14.89%.		
	
3.	Results	and	discussion	
	

The	 newly	 synthesized	 α,β‐unsaturated	 carbonyl	
compounds	 1a‐l	 were	 prepared	 by	 Claisen‐Schmidt	 conden‐
sation	 method	 [31]	 from	 substituted	 acetophenones	 and	
different	 hetero	 aldehydes	 in	 polyethylene	 glycol	 (PEG‐400)	

under	alkaline	medium	at	40	 °C	 for	 1	hour	 (Scheme	1),	while	
the	4‐(4’‐chloro‐phenylazo)‐5‐amino	pyrazole	was	prepared	in	
two	 steps	 from	 the	 corresponding	 p‐chloroamine	 by	
diazotization	 and	 then	 treatment	with	malononitrile	 followed	
by	reaction	with	hydrazine	hydrate	[32,33].		

The	 initial	 investigation	 was	 concerned	 with	 the	
condensation	 of	 1‐(4‐chlorophenyl)‐3‐(2‐butyl‐4‐chloro‐1H‐
imidazol‐5‐yl)‐2‐propen‐1‐one	with	4‐(4’‐chloro‐phenylazo)‐5‐
amino	 pyrazole	 in	 polyethylene	 glycol	 (PEG‐400)	 as	 reaction	
solvent	 at	 80	 °C	 for	 2	 hours	 to	 formed	 the	 corresponding	
product	 (2b)	 (Scheme	 2).	 We	 choose	 this	 system	 as	 model	
reaction.	 In	 order	 to	 optimize	 the	 reaction	 conditions,	 we	
carried	 out	 the	 above	 reaction	 in	 different	 solvents	 such	 as	
ethanol,	dichloromethane,	acetonitrile,	acetic	acid	and	PEG‐400	
(Table	 1).	 We	 found	 that	 PEG‐400	 as	 an	 efficient	 reaction	
medium	 in	 terms	 of	 reaction	 time	 as	 well	 as	 yield	 (92%).	
Encouraged	 by	 these	 results,	we	 next	 turned	 our	 attention	 to	
different	chalcones	and	5‐amino	pyrazole	 in	PEG‐400	at	80	°C	
to	 afford	 the	 corresponding	 products	 in	 excellent	 yields	
(Scheme	2,	Table	2).		

	
Table	1.	 Solvent	 effect	 on	 the	 reaction	 of	 1‐(4‐chlorophenyl)‐3‐(2‐butyl‐4‐
chloro‐1H‐imidazol‐5‐yl)‐2‐propen‐1‐one	 with	 4‐(4’‐chloro‐phenylazo)‐5‐
amino	pyrazole	at	80	°C.		
Entry	 Solvent	 Time	(h)	 Yield	(%)	
1 EtOH 12	 58	
2 DCM 8 62	
3 CH3CN 9 65	
4 Acetic	acid 10	 68	
5 PEG‐400 2 92	
 

	
In	 addition,	 it	 is	 noticed	 that	 the	 PEG‐400	was	 recovered	

and	 reused	 for	 four	 runs	 without	 loss	 of	 its	 activity.	 To	
determine	 the	 reusability	 of	 the	 solvent,	 the	 reaction	mixture	
was	extracted	with	ethyl	acetate	and	the	PEG	was	isolated	and	
subjected	for	second	run	by	charging	the	same	substrates.	The	
obtained	results	are	shown	in	graphical	representation	(Figure	
1).	

	

	
	

Figure	1.	Recyclability	of	PEG‐400.	
	
	
The	 formation	 of	 products	2a‐l	were	 assumed	 to	 proceed	

through	 the	 Micheal	 type	 addition	 of	 the	 ring	 nitrogen	 in	 5‐
amino	pyrazole	(which	is	more	active)	to	the	activated	double	
bond	 followed	 by	 intra‐molecular	 cyclisation	 [34,35]	 with	
elimination	 of	 water	 and	 dehydrogenation.	 The	 structure	 of	
compounds	 2a‐l	 was	 appropriately	 established	 by	 spectros‐
copic	and	analytical	methods.	The	 IR	spectra	of	 compound	2a	
revealed	 the	 presence	 of	NH2	 at	 3329	 cm‐1	while	 the	 1H	NMR	
data	were	consistent	with	structure	2a	and	exhibits	a	singlet	at	
δ	12.36	ppm	(D2O	exchangeable,	phenolic	‐OH),	multiplate	at	δ	
7.02‐7.96	ppm	(aromatic	protons)	and	a	broad	signal	at	δ	3.98	
ppm	(D2O	exchangeable,	‐NH2	protons).	Also,	mass	spectrum	of	
compound	2a	exhibited	a	molecular	ion	peak	m/z	=	554	[M+].		

	



Konda	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	676‐680	 679	
 

	
Table	2.	Physical	and	analytical	data	of	pyrazolo	[1,5‐a]	pyrimidines	(2a‐l).	
Product	 R1	 R2	 R3	 R4	 Hetero	substitution	 Yield	a,	b	(%)	 M.p.	(°C)	
2a	 OH	 H	 H	 Cl 90	 112‐114

2b	 H	 H	 Cl	 H 92	 125‐127

2c	 OH	 I	 H	 Cl	 86	 134‐136	

2d	 OH	 Br	 H	 Cl	 89	 121‐123	

2e	 OH	 H	 CH3	 Cl 86	 138‐140

2f	 OH	 I	 CH3	 Cl 86	 152‐154

2g	 OH	 Br	 CH3	 Cl 88	 105‐107

2h	 OH	 H	 H	 Cl	 86	 158‐160	

2i	 H	 H	 Cl	 H 90	 165‐167

2j	 OH	 I	 H	 Cl	 88	 131‐133	

2k	 OH	 Br	 H	 Cl 90	 142‐144

2l	 OH	 I	 CH3	 Cl 88	 174‐176

a	Isolated	yield.	
b	Products	are	characterized	by	IR,	1H	NMR	and	Mass	spectroscopy.	
	

It	 is	 noteworthy	 to	 mention	 that	 the	 pyrazolo	 [1,5‐a]	
pyrimidines	 2a‐l	 having	 variety	 of	 substituents	 such	 as	
hydroxy,	 chloro,	 bromo,	 iodo,	 methyl	 were	 prepared	 in	 high	

yields.	 In	 addition,	 the	 remarkable	 feature	 of	 the	 present	
methodology	 include	 the	 introduction	 of	 novel	 heterocyclic	
moiety	in	pyrazolo[1,5‐a]pyrimidines.		



680	 Konda	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	676‐680	
	
4.	Conclusion	
	

In	 summary,	 we	 report	 a	 novel,	 efficient	 and	
environmentally	 benign	 methodology	 for	 the	 synthesis	 of	
pyrazolo	 [1,5‐a]	 pyrimidines	 by	 the	 reaction	 of	 5‐amino	
pyrazoles	 with	 α,β‐unsaturated	 carbonyl	 compounds	 in	 PEG‐
400	is	described.	The	introduction	of	novel	heterocyclic	moiety	
in	 pyrazolo	 [1,5‐a]	 pyrimidines,	 it	 may	 enhance	 biological	
activity	as	well	as	scope	and	applications.	The	advantages	of	the	
present	protocol	are	the	simplicity	of	operation;	the	high	yields	
of	products,	the	recyclability	of	PEG‐400	and	preclusion	of	the	
usage	of	volatile	organic	solvents.	
	
Acknowledgements	
	

Author	 is	 thankful	 to	 University	 Grants	 Commission,	 New	
Delhi	 for	 financial	 support	 under	 Minor	 Research	 Project	 [F.	
No:	47‐306/12(WRO)].	
	
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