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European	Journal	of	Chemistry	2	(3)	(2011)	311‐313	

	
European	Journal	of	Chemistry	

ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2011	EURJCHEM	
DOI:10.5155/eurjchem.2.3.311‐313.414	

	
	

	

	

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

	 	 	

Synthesis	and	characterization	of	1‐formyl‐3‐phenyl‐5‐aryl‐2‐pyrazolines	

Assia	Sida,*,	Kaddour	Lamaraa,	Mahieddine	Mokhtaria,	Nouara	Ziania	and	Paul	Mossetb	

a	Laboratory	of	Applied	Chemistry	and	Materials	Technology,	Chemistry	Institute,	University	of	Oum	El	Bouaghi,	Rue	de	Constantine,	04000,	Algeria	
b	Université	de	Rennes	1,	Laboratoire	Sciences	Chimiques	de	Rennes,	Centre	National	de	la	Recherche	Scientifique,	Unité		Mixte	de	Recherche	6226,	Avenue	du	
Général	Leclerc,	Rennes	Cedex,	35042,	France	

*Corresponding	author	at:	Laboratory	of	Applied	Chemistry	and	Materials	Technology,	Chemistry	Institute,	University	of	Oum	El	Bouaghi,	Rue	de	Constantine,	
04000,	Algeria.	Tel.:	+213.32421036;	fax:	+213.32424213.	E‐mail	address:	madamesid9@yahoo.fr	(A.	Sid).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	07	March	2011	
Received	in	revised	form:	19	April	2011	
Accepted:	17	May	2011	
Online:	30	September	2011	

KEYWORDS	

	 Reaction	 of	 chalcone	 derivatives	 1‐4 with	 hydrazine	 hydrate	 in	 presence	 of	 formic	 acid
yielded	 2‐pyrazolines	 5‐8.	 Structures	 of	 these	 compounds	 have	 been	 elucidated	 by
spectroscopic	methods;	IR,	UV,	1H	NMR,	13C	NMR.	Their	purities	were	confirmed	by	elemental
analyses.	

Chalcones		
Formic	acid	
Pyrazolines	
Hydrazine	hydrate	
Fluorescence	spectroscopy	
Spectroscopy	

	
1.	Introduction	
	

Numerous	pyrazolines	type	compounds	have	been	found	to	
exhibit	 bioactivities.	 Pyrazolines	 derivatives	 with	 a	 phenyl	
group	 at	 the	5‐position	possess	 good	 film‐forming	properties,	
exhibit	excellent	characteristics	of	blue	photoluminescence	and	
electroluminescence	 [1].	 Pyrazolines	 are	 also	 used	 as	 optical	
brighteners	 and	 whiteners.	 They	 display	 various	 biological	
activities	 such	 as	 antimicrobial	 [2],	 antifungal	 [3],	
antidepressant	[4],	immunosuppressive	[5],	anticonvulsant	[6],	
anti‐tumor	 [7],	 antiamoebic	 [8],	 antibacterial	 [9]	 and	 anti‐
inflammatory	 [10]	 activities.	 Synthesis	 of	 pyrazolines	 by	
reaction	 of	 α,β‐unsaturated	 carbonyl	 compounds	 with	
diazoalkanes	[11]	or	with	hydrazine	hydrate	were	reported	in	
the	 literature	 [12,13].	 N‐substituted	 thiocarbamoyl‐3,5‐
diphenyl‐2‐pyrazoline	 derivatives	 having	 NS	 donor,	 their	
palladium	 π	 complexes	 [14]	 and	 hydroxylphenyl	 pyrazolines	
have	 also	 been	 synthesised	 [15].	 The	 reaction	 of	E‐arylidenes	
with	 diazomethane	 affords	 trans‐pyrazolines	 while	 Z‐
arylidenes	 gave	 cis‐isomers	 [16].	 1,3‐Dipolar	 cycloaddition	 of	
exocyclic	α,β‐unsaturated	ketones	with	diazomethane	has	also	
been	studied	[17‐22].	

The	 present	 paper	 deals	 with	 the	 synthesis	 of	 four	 2‐
pyrazolines	 derivatives	 5‐8	 from	 the	 reaction	 of	 chalcone	
derivatives	 1‐4	 and	 hydrazine	 hydrate	 in	 the	 presence	 of	
formic	 acid	 (Scheme	 1).	 The	 structures	 of	 these	 compounds	
were	established	by	spectroscopic	techniques.	
	
2.	Experimental	
	
2.1.	Instrumentation	
	

Melting	 points	 were	 determined	 with	 a	 (Bransted/‐
Electrothermal)	 apparatus	 and	 are	 uncorrected.	 UV	 spectra	

were	 recorded	 on	 a	 Perkin‐Elmer	 double	 beam	 UV‐visible	
spectrophotometer	(λ‐25)	in	ethanol.	IR	spectra	were	recorded	
in	KBr	pellets	on	a	Perkin‐Elmer	FT‐IR‐01	spectrophotometer.	
1H	and	13C	NMR	spectra	were	obtained	 in	CDCl3	on	an	Avance	
400	 Bruker	 spectrometer	 (400.13	 MHz	 in	 1H)	 using	 TMS	 as	
internal	standard.	

	

 
	

Scheme	1	
	

2.2.	Synthesis	
	
2.2.1.	Synthesis	of	chalcones	
	

In	 a	 round‐bottomed	 flask,	 substituted	benzaldehydes	 (50	
mmol)	and	acetophenone	(50	mmol)	were	dissolved	in	ethanol.	
The	reaction	mixture	was	cooled	in	an	ice	bath	and	a	solution	of	
10	%	sodium	hydroxide	was	added	dropwise.	The	mixture	was	
stirred	for	4	hours.	The	yellow	precipitate	obtained	was	filtered	
and	washed	 by	 HCl	 (0.1	 N)	 then	 crystallised	 from	 ethanol	 or	
ethyl	acetate	to	afford	chalcone	derivatives	2,3,4	except	for	the	
chalcone	 1	 that	 is	 obtained	 as	 yellow	 oil.	 The	 chalcones	 1‐4	



312	 Sid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	311‐313	
	
were	 afforded	with	 excellent	 yields	 (85‐91	%).	 Their	melting	
points	are	111,	102	and	113	°C,	respectively.	
	
2.2.2.	Synthesis	of	pyrazolines	
	

A	 mixture	 of	 chalcone	 (10.0	 mmol),	 hydrazine	 hydrate	
(50.0	mmol)	 and	 formic	 acid	 (40	mL)	were	 refluxed	 for	 24	h.	
The	 resulting	 mixture	 was	 poured	 into	 water	 (100	 mL)	 and	
allowed	 to	 stand.	 The	 precipitate	 that	 has	 formed	 was	
separated	 by	 filtration,	 washed	 with	 cold	 water	 and	 then	
crystallized	from	a	mixture	of	ethanol:toluene	(1:1)	to	yield	2‐
pyrazolines	(Scheme	1).	

1‐Formyl‐3‐phenyl‐5‐(4‐isopropylphenyl)‐2‐pyrazoline	 (5):	
Pale	crystals.	Yield:	76%.	M.p.:	144‐145	°C.	UV/VIS	(λmax,	nm):	
407,	337,	325.	IR	(KBr,	cm‐1):	1662	(C=O),	1636	(C=N),	1224	(C‐
N).	 1H	 NMR	 (400	MHz,	 CDCl3):	 8.96	 (d,	 1H,	 J	 =	 1.0	 Hz,	 CHO),	
7.78‐7.69	(m,	2H	of	Ar	H),	7.48‐7.38	(m,	3H	of	Ar	H),	7.22‐7.14	
(m,	4H,	symmetrical	system,	AA’BB’	system	of	the	p‐substituted	
aromatic),	5.52	(ddd,	1H,	J	=	11.7,	4.8,	1.0	Hz,	CH),	3.78	(dd,	1H,	
J	=	17.7,	11.7	Hz,	CH2),	3.22	(dd,	1H,	J	=	17.7,	4.8	Hz,	CH2),	2.87	
(septet,	 1H,	 J=	 6.9	 Hz,	 CH(CH3)2),	 1.21	 (d,	 6H,	 J	 =	 6.9	 Hz,	
CH(CH3)2.	13C	NMR	(100	MHz,	CDCl3):	160.10	(CH),	155.85	(C),	
148.59	(Ar‐C),	137.94	(Ar‐C),	130.97	(Ar‐C),	130.62	(CH	para	of	
Ar	 H),	 128.81	 (2	 CH	 of	 Ar‐H),	 127.08	 (2	 CH	 of	 p‐C6H4‐i‐Pr),	
126.69	 (2	 CH	 of	 Ar	 H),	 125.62	 (2	 CH	 of	 p‐C6H4‐i‐Pr),	 58.80	
(CH),42.60	 (CH2),	 33.77	 (CH(CH3)2),	 23.92	 (CH(CH3)2),	 23.90	
(CH(CH3)2).	Anal.	Calcd.	for	C19H20N2O:	C,	78.05,	H,	6.89,	N,	9.42;	
found:	C,	78.05,	H,	6.84,	N,	9.42%.	

1‐Formyl‐3‐phenyl‐5‐(4‐methylphenyl)‐2‐pyrazoline	 (6).	
Yellow	 crystals.	 Yield:	 80%.	 M.p.:	 148‐149	 °C.	 UV/VIS	 (λmax,	
nm):	 409,	 335,	 322.	 IR	 (KBr,	 cm‐1):	 1658	 (C=O),	 1630	 (C=N),	
1225	(C‐N).	1H	NMR	(400	MHz,	CDCl3):	8.95	(d,	1H,	 J	=	1.0	Hz,	
CHO),	 7.77‐7.68	 (m,	 2H	 of	 Ar	H),	 7.47‐7.37	 (m,	 3H	 of	 Ar	H),	
7.20‐7.12	(s,	4H	of	the	p‐substituted	aromatic),	5.50	(ddd,	1H,	J	
=	11.7,	4.8,	1.0	Hz,	CH),	3.75	(dd,	1H,	J	=	17.7,	11.7	Hz,	CH2),	3.20	
(dd,	1H,	J	=	17.7,	4.8	Hz,	CH2),	1.20	(s,	3H,	CH3).	13C	NMR	(100	
MHz,	 CDCl3):	 160.30	 (CH),	 155.55	 (C),	 148.32	 (Ar‐C),	 137.35	
(Ar‐C),	130.85	(Ar‐C),	130.60	(CH	para	of	Ar	H),	128.73	(2	CH	of	
Ar	H),	126.90	(2	CH	of	p‐Ar‐Me),	126.69	(2	CH	of	Ar	H),	125.62	
(CH	 of	 p‐Ar‐Me),	 58.79	 (CH),	 42.58	 (CH2),	 23.86	 (CH3).	 Anal.	
Calcd.	for	C17H16N2O:	C,	77.25,	H,	4.60,	N,	9.83;	found:	C,	76.98,	
H,	6.10,	N,	10.72%.	

1‐Formyl‐3‐phenyl‐5‐(4‐chlorophenyl)‐2‐pyrazoline	(7).	Pale	
Yellow	crystals.	Yield:	87%	M.p:	140‐141	°C.	UV/VIS	(λmax,	nm):		
405,	334,	322.	IR	(KBr,	cm‐1):	1660	(C=O),	1632	(C=N),	1135	(C‐
N),	754	(C‐Cl).	1H	NMR	(400	MHz,	CDCl3):	8.94	(d,	1H,	J	=	1.0	Hz,	
CHO),	 7.45‐7.42	 (m,	 2H	 of	 Ar	H),	 7.28‐7.30	 (m,	 3H	 of	 Ar	 H),	
7.18‐7.20	(m,	4H	of	the	p‐C6H4‐Cl),	5.53	(ddd,	1H,	J	=	11.8,	4.8,	
1.0	Hz,	CH),	3.82	(dd,	1H,	J=	18.3,	11.8	Hz,	CH2),	3.21	(dd,	1H,	J	=	
18.3,	 4.8	 Hz,	 CH2).	 13C	 NMR	 (100	 MHz,	 CDCl3):	 160.15	 (CH),	
155.83	(C),	148.48	(Ar‐C),	137.86	(Ar‐C),	130.95	(Ar‐C),	130.59	
(CH	para	 of	Ar	H),	 128.80	 (2	CH	of	Ar	H),	 127.02	 (2	CH	of	p‐
C6H4‐Cl),	 126.59	 (2	 CH	 of	 Ar	 H),	 125.60	 (2	 CH	 of	 p‐C6H4‐Cl),	
57.70	(CH),	42.40	(CH2).	Anal.	Calcd.	for	C16H13N2OCl:	C,	67.49,	
H,	4.60,	N,	9.84;	found:	C,	67.27,	H,	4.52,	N,	9.83%.	

1‐Formyl‐3‐phenyl‐5‐(fluorophenyl)‐2‐pyrazoline	 (8).	 Pale	
crystals.	Yield:	76%.	M.p.:	142‐143	°C.	UV/VIS	(λmax,	nm):	404,	
337,	322.	 IR	(KBr,	cm‐1):	1659	(C=O),	1635	(C=N),	1136	(C‐N).	
1H	NMR	(400	MHz,	CDCl3):	8.93	(d,	1H,	 J	=	1.0	Hz,	CHO),	7.44‐
7.41	(m,	2H	of	Ar‐H),	7.29‐7.27	(m,	3H	of	Ar‐H),	7.18‐7.14	(m,	
4H,	of	p‐C6H4‐F),	5.51	(ddd,	1H,	 J	=	11.9,	4.8,	1.0	Hz,	CH),	3.81	
(dd,	1H,	 J	=	18.4,	11.9	Hz,	CH2),	3.22	 (dd,	1H,	 J	=	18.4,	4.8	Hz,	
CH2).	 13C	 NMR	 (100	 MHz,	 CDCl3):	 159.30	 (CH),	 154.75	 (C),	
147.69	 (Ar‐C),	 138.94	 (Ar‐C),	 130.97	 (C),	 130.62	 (CH	 para	 of	
Ar‐H),	 128.81	 (2	 CH	 of	 p‐C6H4‐F),	 127.05	 (2	 CH	 of	 p‐C6H4‐F),	
126.65	 (2	CH	of	Ar‐H),	125.61	 (2	CH	of	p‐C6H4‐F),	58.79	 (CH),	
41.95	 (CH2).	 Anal.	 Calcd.	 for	 C16	H13N2OF:	 C,	 58.90,	H,	 4.54,	N,	
9.14,	found:	C,	60.42,	H,	4.56,	N,	9.24.	
	
	
	

3.	Results	and	discussion	
	

Formation	 of	 2‐pyrazolines	 by	 the	 reaction	 of	 α,β‐
unsaturated	ketones	and	hydrazine	hydrate	 takes	place	under	
various	reaction	conditions	using	ethanol	[23],	acetic	acid	[24],	
formic	 acid	 [25]	 or	 pyridine	 [26]	 as	 solvent.	 After	 some	
preliminary	 experiments,	 formic	 acid	 was	 found	 to	 be	 a	
convenient	 solvent	 in	 our	 case.	 Chalcone	 derivatives	1‐4	 was	
allowed	 to	 react	with	hydrazine	hydrate	 in	hot	 formic	 acid	 to	
afford	 1‐formyl‐3‐phenyl‐5‐aryl‐2‐pyrazolines	 (5‐8)	 with	
excellent	yields	due	to	the	stability	of	2‐pyrazolines.	Structures	
of	compounds	5‐8	have	been	elucidated	by	UV,	IR,	1H	NMR	and	
13C	 NMR	 (2D,	 J‐mod,	 HSQC)	 measurements.	 Their	 spectra	
showed	 a	 strong	 band	 for	 the	 carbonyl	 group	 at	 (1662‐1658	
cm‐1)	and	a	band	at	(1636‐1630	cm‐1)	for	C=N.	In	the	1H	NMR	
spectra	of	2‐pyrazolines,	the	three	hydrogen	atoms	attached	to	
the	C‐4	and	C‐5	carbon	atoms	of	 the	heterocyclic	ring	gave	an	
ABX	 spin	 system	 and	 a	 doublet	 signal	 at	 around	 8.94	 ppm,	
which	 refers	 to	 the	 presence	 of	 N‐formyl	 group.	 Measured	
chemical	 shift	 and	 coupling	 constant	 values	 prove	 the	 2‐
pyrazoline	structure.	In	the	13C	NMR	spectra	of	new	1‐formyl‐3‐
phenyl‐5‐aryl‐2‐pyrazolines,	the	chemical	shift	values	of	carbon	
atoms	 C‐3	 (154‐156	 ppm),	 C‐4	 (41‐40	 ppm)	 and	 C‐5	 (56‐58	
ppm)	 corroborate	 the	 2‐pyrazoline	 structures	 determined	 by	
1H	NMR	spectroscopic	measurements.	13C	NMR	chemical	shifts	
of	 the	N‐formyl	 group	have	 been	 assigned	 at	 (159‐160	ppm).	
The	electronic	spectra	of	the	pyrazolines	derivatives	(studied	in	
the	 UV	 region)	 in	 ethanol	 showed	 three	 absorption	 bands	 at	
(321‐325	nm),	(334‐337	nm),	(404‐409	nm)	assignable	to	n‐π*,	
π‐π*	 and	n‐σ*	 transitions.	 Substituted	pyrazolines	have	strong	
fluorescence	 in	 different	 solvents.	 They	 also	 give	 excellent	
fluorescence	properties	 in	 solid	 state	 because	 the	 conjugation	
system	 contains	 two	 nitrogen	 atoms	 and	 one	 carbon	 atom	
while	the	other	carbon	atoms	are	sp3	hybridized.	
	
4.	Conclusion	
	

We	 have	 synthesized	 substituted	 3‐phenyl‐5‐aryl‐2‐
pyrazolines	by	the	reaction	of	hydrazine	hydrate	and	chalcones	
bearing	 a	para‐substituted	 group	 in	 their	 benzaldehyde	 rings.	
These	 new	 substances	 allow	 the	 investigation	 of	 the	 possible	
linkage	of	the	2‐pyrazolines	to	various	sites	in	living	organisms	
in	the	course	of	the	investigation	of	their	bioactivities.	The	new	
1‐formyl‐3‐phenyl‐5‐aryl‐2‐pyrazolines	described	in	this	paper	
are	very	stable	compounds,	a	property	which	may	render	them	
especially	useful	substances	in	drug	research.	
	
Acknowledgement	

	
We	 thank	 the	 director	 of	 the	 laboratory	 of	 applied	

chemistry	 and	materials	 technology	 of	 the	University	 of	OUM	
EL	 BOUAGHI	 for	 his	 support	 of	 this	 work.	 We	 gratefully	
acknowledge	 Philippe	 JEHAN	 and	 Muriel	 ESCADEILLAS	 for	
providing	elemental	analysis.	

	
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