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European	Journal	of	Chemistry	8	(4)	(2017)	344‐348	

	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2017	Atlanta	Publishing	House	LLC	‐	All	rights	reserved	‐	Printed	in	the	USA	

http://dx.doi.org/10.5155/eurjchem.8.4.344-348.1630 

	
	

	

	

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

	 	 	

Synthesis	and	antioxidant	study	of	new	hydrazones	derived	from	
bisdemethoxycurcumin	pyrazole	

Tahseen	Abdul	Qader	Alsalim	1,*,	Hussain	Ali	Mzban	1	and	Einas	Nasir	Abood	2	

1	Chemistry	Department,	College	of	Education	for	Pure	Sciences,	University	of	Basrah,	Basrah,	16001,	Iraq	
2	Center	of	Polymer	Research,	University	of	Basrah,	Basrah,	16001,	Iraq	

*	Corresponding	author	at:	Chemistry	Department,	College	of	Education	for	Pure	Sciences,	University	of	Basrah,	Basrah,	16001,	Iraq.		
Tel.:	+964.780.1360990.	Fax:	+964.443.3274766.	E‐mail	address:	tahseenalsalim@yahoo.com	(T.A.Q.	Alsalim).	

	
	

	 	

	 	 	

ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI: 10.5155/eurjchem.8.4.344-348.1630	

Received:	14	July	2017	
Received	in	revised	form:	05	September	2017		
Accepted:	10	September	2017	
Published	online:	31	December	2017	
Printed:	31	December	2017

 

	 The	 antioxidant	 activity	 of	 new	 hydrazones	 derived	 from	 bisdemethoxycurcumin	 pyrazole
was	 investigated.	 The	 study	 was	 divided	 into	 two	 main	 parts:	 The	 first	 one	 includes	 the
synthesis	 and	 characterization	 of	 the	 target	 compounds	 from	 bisdemethoxycurcumin
(BDMC),	while	the	second	step	is	devoted	to	the	investigation	of	their	antioxidant	activities.
In	the	 first	step	of	synthesis,	 the	curcumin‐pyrazole	 (2)	was	synthesized	by	 the	reaction	of
BDMC	 with	 hydrazine	 hydrate.	 Later,	 the	 obtained	 product	 treated	 with	 ethyl	 2‐
chloroacetate	to	produce	curcumine	ester	(3),	then	the	product	was	converted	to	hydrazide
(4)	 by	 the	 reaction	 of	 curcumin	 ester	 (3)	 with	 hydrazine	 hydrate.	 Finally,	 curcumine
hydrazones	 (5a‐f)	 were	 synthesized	 from	 the	 reaction	 of	 hydrazide	 (4)	 with	 substituted
aromatic	aldehydes.	All	compounds	were	characterized	with	the	aid	of	suitable	spectroscopic
techniques.	 The	 antioxidant	 activity	 of	 the	 prepared	 compounds	 was	 studied	 against	 the
stable	 radical	 α,α‐diphenyl‐β‐picrylhydrazyl.	 The	 study	 showed	 that	 only	 the	phenolic	OH‐
containing	compounds	(2,	5b	and	5f)	have	antioxidant	activity.	

KEYWORDS	
Pyrazole	
Hydrazone	
Curcuminoids	
Antioxidant	activity	
Bisdemethoxycurcumin		
α,α‐Diphenyl‐β‐picrylhydrazyl	

Cite	this: Eur.	J.	Chem.	2017,	8(4),	344‐348

	
1.	Introduction	
	

Curcumine	is	a	pigment	isolated	from	Turmeric	(Curcuma	
Longa	 L)	 rhizome	 [1].	The	pigment	contains	 three	 isomers	of	
curcuminoids	(Figure	1)	with	curcumine	as	 the	major	 isomer	
with	 abundance	 of	 about	 77%,	 while	 demethoxycurcumine	
(DMC)	 and	 bisdemethoxycurcumine	 constitute	 about	 17	 and	
3%,	respectively	[2‐4].	

Turmeric	has	been	used	as	a	colour	of	food	and	flavouring	
[5,6]	 as	 well	 as	 a	 traditional	 medicine.	 Curcuminoids	 have	 a	
large	 variety	 of	 activities	 such	 as	 antioxidant	 to	 the	 reactive	
oxygen	species	(ROS)	[7‐9],	anti‐viral	[10],	anti‐bacterial	[11],	
diminishing	the	blood	cholesterol	level	[12],	the	ability	to	treat	
Alzheimer’s	 disease	 [13],	 the	 inhibition	 of	 a	 wide	 types	 of	
tumour	 cells,	 such	 as	 lung	 cancer,	 bladder	 cancer,	 prostate	
cancer,	breast	cancer	and	leukaemia	cancer	[14‐17].	Curcumin	
has	 no	 toxicity	 and	 is	 extremely	 safe	 at	 high	 dose.	 Also,	
curcumine	 binds	 with	 metals,	 albumin	 and	 other	 molecules	
such	as	p‐glycoprotein	 (p‐gp)	 [18].	These	properties	 give	 the	
curcuminoids	 a	 medical	 potency.	 But,	 their	 activities	 are	
limited	due	to	their	limited	solubility	in	water	and	their	short	
half‐life,	 therefore,	 the	 researcher	 dream	 is	 to	 synthesize	 a	
super	 curcumin	 by	 the	 modification	 of	 the	 structure	 of	
curcumin	to	increase	the	activity	[19,20].	

In	 the	 present	 study,	 BDMC	 pyrazole‐hydrazone	
derivatives	 were	 prepared	 and	 characterized	 by	 various	
spectroscopic	techniques,	then	evaluated	for	their	antioxidant	
activity.	
	

	
	

	
	

	
	

Figure	1. Structures	of	curcuminoids.	
	



Alsalim	et	al.	/	European	Journal	of	Chemistry	8	(4)	(2017)	344‐348	 345	
 

	

	
	

Scheme	1

	

	
	

Scheme	2	
	
	

2.	Experimental	
	
2.1.	Instrumentation	
	

IR	 spectra	 were	 recorded	 using	 Shimadzu	 FT‐IR	
spectrophotometer	in	the	region	4000‐400	cm‐1	in	KBr	pellets.	
The	mass	spectra	were	scanned	by	the	EI	 technique	at	70	eV	
with	 an	 Agilent	 Technologies	 5975	 Cs	 spectrometer.	 The	
experimental	values	of	1H	and	13C	NMR	spectra	for	the	studied	
compounds	were	scanned	on	a	Bruker	500	MHz	spectrometer	
operating	at	500	MHz	for	proton	observation	and	125	MHz	for	
carbon	observation	using	TMS	as	the	internal	standard.	DMSO‐
d6	was	used	 as	 solvent.	Elemental	 analysis	 (CHNS)	measured	
by	 using	 elementar	 Vario	 MICRO.	 UV‐Visible	 spectra	 were	
measured	using	a	PG‐instrument	T80+	spectrophotometer. 
	
2.2.	Synthesis	
	

BDMC	 pyrazole‐hydrazone	 was	 synthesized	 from	 BDMC	
pyrazole	in	four	steps	(Scheme	1	and	2).	
	
2.2.1.	Synthesis	of	BDMC,	1,7‐bis(4‐hydroxyphenyl)hepta‐
1,6‐diene‐3,5‐dione	(1)	
	

Acetylacetone	 (5	 g,	 0.046	 mol)	 and	 boric	 oxide	 (2.4	 g,	
0.034	 mol)	 was	 stirred	 for	 1	 hour.	 A	 mixture	 of	 p‐hydroxy	
benzaldehyde	 (11.2	 g,	 0.092	 mol)	 in	 dry	 dimethylacetamide	
(DMA)	(70	mL),	heated	 in	water	bath	at	80	 °C,	and	 trimethyl	

borate	 (10	 g,	 0.092	mol)	was	 added	 to	 the	 previousmixture.	
The	 reaction	 was	 stirred	 for	 5	 min	 followed	 by	 a	 dropwise	
addition	of	a	solution	of	n‐butylamine	(1.5	g,	0.02	mol)	in	DMA	
over	a	period	of	1	h.	The	mixture	was	stirred	 for	 further	3	h.	
The	solution	was	set	aside	overnight.	Acetic	acid	(5	N,	120	mL)	
at	80	°C	was	then	added,	and	the	mixture	stirred	for	1	h.	The	
mixture	 cooled	 and	 the	 solid	 product	 was	 collected	 by	
filtration,	 and	 then	 washed	 by	 hot	 water	 twice,	 dried	 then	
recrystallized	from	ethanol.	Color:	Yellow	needles.	Yield:	56%.	
M.p.:	221‐223	°C.	FT‐IR	(KBr,	ν,	cm‐1):	3217	(OH),	3039	(H‐Ar),	
1622	 (C=O),	 1600	 (C=C),	 1562,	 1512	 (C‐C),	 1448	 (C‐O‐H),	
1240,	1141	(C‐O).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	5.87	
(s,	2H,	vinylic‐H),	6.81	(d,	2H,	J	=	16.2	Hz,	CH=C),	7.09	(d,	4H,	J	
=	7.8	Hz,	Ar‐H),	7.20	(d,	4H,	 J	=	8.4	Hz,	Ar‐H),	7.82	(d,	2H,	 J	=	
16.2	Hz,	CH=C),	9.93	(s,	2H,	OH).	
	
2.2.2.	Synthesis	of4,4'‐((1H‐pyrazole‐3,5‐diyl)bis(ethene‐2,	
1‐diyl))diphenol	(2)	
	

BDMC	(2	g,	6.24	mmol)	was	dissolved	 in	20	mL	of	glacial	
acetic	acid	for	which	1	g	of	hydrazine	monohydrate	was	added.	
The	 mixture	 heated	 under	 reflux	 for	 20	 h,	 then	 cooled	 and	
poured	 into	 ice	 water.	 The	 product	 collect	 by	 filtration	 and	
dried	then	recrystallized	from	n‐hexane:ethylacetate	(v:v,	7:3).	
Color:	White	powder.	Yield:	74%.	M.p.:	273‐275	°C.	FT‐IR	(KBr,	
ν,	 cm‐1):	 3280	 (OH),	 3022(C‐H	 Ar),	 1647	 (C=N),	 1604	 (C=O),	
1554,	1512	 (C‐C),	 1448	 (C‐O‐H),	 1240,	 1008	 (C‐O),	823	 (1,4‐
disubstituted	ring).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	6.68	



346	 Alsalim	et	al.	/	European	Journal	of	Chemistry	8	(4)	(2017)	344‐348	
	
(s,	1H,	CH‐pyrazole	ring),	6.82	(d,	2H,	J	=	16.2	Hz,	CH=C),	6.95	
(d,	4H,	J	=	7.8	Hz,	Ar‐H),	7.10	(d,	4H,	J	=	8.4	Hz,	Ar‐H),	7.40	(d,	
2H,	 J	=	16.2	Hz,	CH=C),	9.65	 (2H,	 s,	OH).	 13C	NMR	 (125	MHz,	
DMSO‐d6,	δ,	ppm):	99.6,	112.9,	116.1,	116.9,	118.6,	128.1,	130,	
142.6,	151.9,	152.1.	
	
2.2.3.	Synthesis	of	1,1'‐((((1H‐pyrazole‐3,5‐diyl)bis(ethene‐
2,1‐diyl))bis(4,1‐phenylene))bis(oxy))bis(butan‐2‐one)	(3)	
	

In	 a	 round	 bottomed	 flask	 was	 added	 20mL	 acetone,	
compound	2	(2	g,	6.6	mmol)	and	potassium	carbonate	(1.84	g,	
13.2	mmol),	then	ethyl	2‐chloro	acetate	(1.6	g,	13.2	mmol)	was	
added.	The	mixture	was	heated	under	reflux	with	stirring	 for	
18	 h,	 cooled	 then	 poured	 into	 ice	 water,	 the	 solid	 product	
filtered	and	recrystallized	 from	hexane:ethylacetate	(v:v,	4:6).	
Color:	White	powder.	Yield:	57.6%.	M.p.:	71‐72	°C.	FT‐IR	(KBr,	
ν,	 cm‐1):	 3307	 (NH),	 3037	 (C‐H,	 Ar),	 2923	 (C‐H,	 aliph),	 1665	
(C=O),	1660	(C=N),	1604	(C=C),	1531,	1508	(C‐O),	1242,	1060	
(C‐O),	823	(1,4‐disubstituted	ring).	1H	NMR	(500	MHz,	DMSO‐
d6,	δ,	ppm):	1.21	(t,	6H,	CH2CH3),	3.96	(q,	4H,	CH2CH3),	4.17	(s,	
4H,	OCH2),	6.40	(s,	1H,	CH‐pyrazole	ring),	6.92	(d,	2H,	J	=	16.2	
Hz,	CH=C),	7.11	(d,	4H,	J	=	7.8	Hz,	Ar‐H),	7.51	(d,	4H,	J	=	8.4	Hz,	
Ar‐H),	 7.59	 (d,	 2H,	 J	 =	 16.2	 Hz,	 CH=C).	 13C	 NMR	 (125	 MHz,	
DMSO‐d6,	δ,	ppm):	14.5,	61.1,	65.1,	99.5,	115.2,	113,	130,	128,	
129,	141.6,	150.2,	158.1,	157.8.	
	
2.2.4.	Synthesis	of2,2'‐((((1H‐pyrazole‐3,5‐diyl)bis(ethene‐
2,1‐diyl))bis(4,1‐phenylene))bis	(oxy))di(acetohydrazide)	
(4)	
	

The	mixture	of	a	solution	of	compound	3	(2	g,	4.2	mmol)	in	
20	 mL	 ethanol	 and	 0.5	 g	 of	 hydrazine	 hydrate	 was	 heated	
under	reflux	with	stirring	for	3	h.	The	mixture	then	cooled	and	
poured	 into	 ice	water	 (100	mL),	 to	 get	 a	white	 solid	product	
which	then	dried	and	recrystallized	from	ethanol:DMF	mixture	
(8:2,	v:v).	Color:	White	powder.	Yield:	67%.	M.p.:	238‐239	°C.	
FT‐IR	 (KBr,	 ν,	 cm‐1):	 3307,	3237	 (NH2),	 3034	 (C‐H,	Ar),	 2931	
(C‐H,	aliph),	1678	(C=O),	1664	(C=N),	1600	(C=C),	1531,	1508	
(C‐O),	1242,	1060	(C‐C),	823	(1,4‐disubstituted	ring).	1H	NMR	
(500	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 4.22	 (s,	 4H,	 NH2),	 4.40	 (s,	
4H,OCH2),	6.50	(s,	1H,	CH‐pyrazole	ring),	7.01	(d,	2H,	J	=	16.2	
Hz,	CH=C),	7.05	(d,	4H,	J	=	7.8	Hz,	Ar‐H),	7.56	(d,	4H,	J	=	8.4	Hz,	
Ar‐H),	7.61	(d,	2H,	J	=	16.2	Hz,	CH=C),	9.42	(s,	2H,	NH‐C=O).	13C	
NMR	 (125	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 66.7,	 99.4,	 111.0,	 111.2,	
115.4,	 127.9,	 128.2,	 129.1,	 130.2,	 141.6,	 149.1,	 150.3,	 157.0,	
166.9,	 167.8.	 MS	 (EI,	 m/z):	 448.4	 [M]+.	 Anal.	 calcd.	 for	
C23H24N6O4:	 C,	 61.60;	 H,	 5.39;	 N,	 18.74.	 Found:	 C,	 61.09;	 H,	
5.48;	N,	18.21%.	
	
2.2.5.	Synthesis	of	compounds	5a‐h	
	

To	a	clear	solution	of	compound	4	 (1	g,	2.23	mmol)	in	10	
mL	 DMF,	 the	 appropriate	 aldehyde	 (4.46	 mmol)	 was	 added	
with	few	drops	of	AcOH.	The	mixture	was	heated	under	reflux	
with	stirring	for	3‐7	h,	then	cooled	and	the	solid	product	was	
collected	 by	 filtration,	 dried	 and	 recrystallized	 from	
chloroform:ethylacetate	(v:v	,7:3).	 	

2,	2'‐((((1H‐Pyrazole‐3,	5‐diyl)	bis(ethene‐2,	1‐diyl))	bis(4,	1‐
phenylene))	 bis(oxy))	 bis(N'‐(4‐methylbenzylidene)acetohydra	
zide)	(5a):	Color:	White	powder.	Yield:	51%.	M.p.:	148‐150	°C.	
FT‐IR	 (KBr,	 ν,	 cm‐1):	 3309	 (N‐H),	 3037	 (C‐H,	 Ar),	 2945	 (C‐H,	
alipha),	1674	(C=O),	1663	(C=N),	1601	(C=C),	1531,	1508	(C‐
O),	1443	(CH2,	bend),	1241,	1062	(C‐C),	823	(1,4‐disubstituted	
ring).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	1.22	(s,	6H,	CH3),	
4.19	(s,	4H,	CH2O),	6.51	(s,	1H,	CH‐pyrazole	ring),	6.91	(d,	2H,	J	
=	 16.2	 Hz,	 CH=C),	 7.08‐7.66	 (m,	 16H,	 Ar‐H),	 7.95	 (d,	 2H,	 J	 =	
16.2	 Hz,	 CH=C),	 8.30	 (s,	 2H,	 CH=N),	 9.64	 (s,	 2H,	 NHCO).	 13C	
NMR	 (125	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 21.5,	 65.3,	 115.3,	 121.3,	
127.5,	 128.5,	 129.9,	 131.7,	 140.2,	 140.5,	 144.5,	 148.4,	 158.7,	
164.4,	168.8.	MS	 (EI,	m/z):	 656.3	 [M]+.	Anal.	 calcd.	 for	C39H36	

N6O4:	 C,	 71.76;	H,	 5.56;	N,	 12.87.	 Found:	 C,	 71.29,	H,	 5.48,	N,	
12.21%.	

2,	2'‐((((1H‐Pyrazole‐3,	5‐diyl)	bis(ethene‐2,	1‐diyl))	bis(4,	1‐
phenylene))bis(oxy))	 bis(N'‐(4‐hydroxybenzylidene)acetohydra	
zide)	(5b):	Color:	White	powder.	Yield:	56%.	M.p.:	176‐179	°C.	
FT‐IR	 (KBr,	 ν,	 cm‐1):	 3203	 (N‐H),	 3062	 (C‐H,	 Ar),	 2949	 (C‐H,	
alipha),	 1681	 (C=O),	 1670(C=N),	 1604	 (C=C),	 1541,	 1508	 (C‐
O),	1438	(CH2,	bend),	1274,	1076	(C‐C),	837	(1,4‐disubstituted	
ring).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	4.17	(s,	4H,	CH2O),	
6.50	(s,	1H,	CH‐pyrazol	ring),	6.91	(d,	2H,	 J	=	16.2	Hz,	CH=C),	
6.90‐7.60	 (m,	 16H,	 Ar‐H),	 7.92	 (d,	 2H,	 J	 =	 16.2	 Hz,	 olefinic	
proton),	8.23	(s,	2H,	CH=N)	9.41	(s,	2H,NHCO),	9.91	(s,	2H,OH).	
13C	 NMR	 (125	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 65.1,	 116.0,	 125.4,	
125.5,	 127.5,	 127.8,	 128.3,	 128.8,	 129.1,	 129.3,	 144.6,	 148.7,	
151.7,	162.7,	168.5,	169.0.	Anal.	calcd.	for	C37H32N6O6:	C,	67.67;	
H,	4.91;	N,	12.80.Found:	C,	67.19;	H,	4.48;	N,	12.27%.		

2,	2'‐((((1H‐Pyrazole‐3,	5‐diyl)	bis(ethene‐2,	1‐diyl))	bis(4,	1‐
phenylene))bis(oxy))bis(N'‐(3‐phenylallylidene)acetohydrazide)	
(5c):	Color:	White	powder.	Yield:	48%.	M.p.:	170‐173	°C.	FT‐IR	
(KBr,	ν,	cm‐1):	3264	(N‐H),	3042	(C‐H,	Ar),	2978	(C‐H,	alipha),	
1686	(C=O),	1673	(C=N),	1602	(C=C),	1583	(C‐O),	1435	(CH2,	
bend),	1270,	1083	(C‐C),	827	(1,4‐disubstituted	ring).	1H	NMR	
(500	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 4.66	 (s,	 4H,CH2O),	 6.53	 (s,	
1H,CH‐pyrazole	ring),	7.01	(d,	2H,	J	=	16.2	Hz,	CH=C),	7.00‐7.83	
(m,	22H,	Ar‐H	and	CH=C),	7.92	(d,	2H,	J	=	16.2	Hz,	CH=C),	8.31	
(s,	2H,	CH=N),	9.43	(s,	2H,	NHCO).	Anal.	calcd.	for	C41H36N6O4:	
C,	72.76;	H,	5.36;	N,	12.42.	Found:	C,	72.09;	H,	5.31;	N,	12.67%.	

2,	2'‐((((1H‐Pyrazole‐3,	5‐diyl)	bis(ethene‐2,	1‐diyl))	bis(4,	1‐
phenylene))bis(oxy))	 bis(N'‐(4‐methoxybenzylidene)acetohydra	
zide)	 (5d):	Color:	White	powder.	 Yield:	52.7%.	M.p.:	 128‐130	
°C.	FT‐IR	(KBr,	ν,	cm‐1):	3207	(N‐H),	3035	(C‐H,	Ar),	2953	(C‐H,	
alipha),	1683	(C=O),	1639	(C=N),	1604	(C=C),	1573,	1508	(C‐
O),	 1456	 (CH2,	 bend),	 1251,	 1170,	 1076	 (C‐C),	 829	 (1,4‐
disubstituted	ring).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	3.80	
(s,	6H,	OCH3),	4.36	(s,	4H,	CH2O),6.53	(s,	1H,	CH‐pyrazole	ring),	
6.91	(d,	2H,	J	=	16.2	Hz,	CH=C),	6.94‐7.71	(m,	16H,	Ar‐H),	7.98	
(d,	 2H,	 J	 =	 16.2	 Hz,	 CH=C),	 8.28	 (s,	 2H,	 CH=N),	 9.33	 (s,	 2H,	
NHCO).	Anal.	calcd.	for	C39H36N6O6:	C,	68.41;	H,	5.30;	N,	12.27.	
Found:	C,	68.09;	H	5.08;	N,	12.21%.	MS	(EI,	m/z):	684.5	[M]+.	

2,	2'‐((((1H‐pyrazole‐3,	5‐diyl)	bis(ethene‐2,	1‐diyl))	bis(4,	1‐
phenylene))	 bis(oxy))	 bis(N'‐(phenanthren‐9‐ylmethylene)aceto	
hydrazide)	(5e):	Color:	Pale	yellow	powder.	Yield:	66.2	%.	M.p.:	
169‐172	°C.	FT‐IR	(KBr,	ν,	 cm‐1):	3217	(N‐H),	3015	(C‐H,	Ar),	
1683	(C=O),	1647	(C=N),	1604	(C=C),	1529,	1508	(C‐O),	1450	
(CH2,	bend),	1230,	1074	(C‐C),	819	(1,4‐disubstituted	ring).	1H	
NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	4.78	(s,	4H,	CH2O),	5.68	(s,	
1H,	 CH‐pyrazole	 ring),	 6.96‐8.11	 (m,	 30H,	 Ar‐H	 and	 CH=C),	
8.32	 (s,	 2H,	 CH=N),	 9.03	 (s,	 2H,	 NHCO).	 13C	 NMR	 (125	MHz,	
DMSO‐d6,	 δ,	 ppm):	 67.2,	 115.3,	 123.4,	 124.0,	 125.5,	 127.6,	
128.5,	 128.7,	 129.8,	 130.2,	 130.7,	 130.9,	 144.8,	 148.7,	 162.7,	
168.9.	Anal.	 calcd.	 for	C53H40N6O4:	C,	 77.17;	H,	4.89;	N,	10.19.	
Found:	C,	77.09;	H,	4.48;	N,	10.53%.	

2,	2'‐((((1H‐Pyrazole‐3,	5‐diyl)	bis(ethene‐2,	1‐diyl))	bis(4,	1‐
phenylene))	 bis(oxy))	 bis(N'‐(4‐hydroxy‐3‐methoxybenzylidene)	
acetohydrazide)	 (5f):	Color:	White	powder.	Yield:	45	%.	M.p.:	
168‐171	°C.	FT‐IR	(KBr,	ν,	 cm‐1):	3217	(N‐H),	3039	(C‐H,	Ar),	
2902	(C‐H,	alipha),	1683	(C=O),	1654	(C=N),	1602	(C=C),	1558,	
1508	 (C‐O),	 1456	 (CH2,	 bend),	 1284	 (C‐C),	 821	 (1,4‐
disubstituted	ring).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	3.82	
(s,	6H,	OCH3),	4.10	(s,	4H,CH2O),6.46	(s,	1H,	CH‐pyrazole	ring),	
6.83	 (d,	 2H,	 J	=	16.2	Hz,	 CH=C),	6.91‐7.61	 (m,	16H,	Ar‐H	 and	
CH=C),	 8.22	 (s,	 2H,	 CH=N),	 9.50	 (s,	 2H,NHCO),	 10.27	 (s,	 2H,	
OH).	13C	NMR	(125	MHz,	DMSO‐d6,	δ,	ppm):	56.0,	65.2,	109.5,	
115.9,	 121.7,	 122.6,	 125.9,	 128.4,	 144.7,	 148.5,	 149.6,	 162.7,	
169.0.	 Anal.	 calcd.	 forC39H36N6O8:	 C,	 65.35;	 H,	 5.06;	 N,	 11.73.	
Found:	C,	65.09;	H,	5.48;	N,	11.22%.	
	
2.3.	α,α‐Diphenyl‐β‐picrylhydra	(DPPH)	radical	scavenging	
assay	
	

	



Alsalim	et	al.	/	European	Journal	of	Chemistry	8	(4)	(2017)	344‐348	 347	
 

	
Table	1.	In‐vitro	antioxidant	activities	of	compounds	2,	5b,	5d,	5e	and	5f.	
Compounds	 Percentage	of	inhibition	 IC50	

μmol/L	25	μmol/L	 50	μmol/L 100 μmol/L 200 μmol/L 
2	 23	 39	 63 91 80.32	
5b	 30	 41	 64 95.4 78.79	
5d	 15.4	 26	 39 63 84.54	
5e	 20	 29	 48 75 83.75	
5f	 21	 39	 63 94 82.96	
	

	
The	 antioxidant	 activity	 of	 the	 synthesized	 curcuminoids	

(2,	 5b,	 5d,	 5e	 and5f)	 was	 determined	 by	 the	 ability	 to	
scavenge	 the	 stable	 DPPH	 free	 radical	 according	 to	 Blois	
method	[21].	Briefly	1mL	of	various	concentration	25,	50,	100	
and	200	μmol/L	of	each	compounds	in	ethanol	solution	mixed	
with	 1	 mL	 of	 200	 μmol/L	 DPPH	 at	 room	 temperature.	 The	
absorbance	was	 read	 at	 517	 nm	 after	 60	min.	 The	 colour	 of	
DPPH	changed	 from	violet	 to	 yellow	or	 colourless	due	 to	 the	
curse	 of	 the	 reaction.	 The	 percentage	 of	 inhibition	 was	
calculated	by	the	following	equation	[22].	
	

	
%	Inhibition	percentage	 	 	 	100

	
Ac As
As


   	 	 (1)	

	
Ac	 =	 Control	 absorbance,	 the	 absorbance	 of	 DPPH	 without	
sample.	
As	=	Sample	absorbance,	the	absorbance	of	DPPH	with	sample.	

The	 IC50	 was	 calculated	 by	 using	 XY	 scattered	 plot,	 the	
liner	 curve	 was	 obtained	 by	 plotting	 inhibitor	 percentage	 of	
radical	versus	concentrations	of	compounds.	IC50	it	is	mean	the	
value	of	the	concentration	of	inhibitor	able	to	scavenging	50%	
DPPH	radical.	
	
3.	Results	and	discussion		
	
3.1.	Spectroscopic	identification	
	

The	 compounds	 prepared	 according	 to	 Scheme	 1	 and	 2,	
and	 their	 proposed	 structures	were	 confirmed	 by	 the	 aid	 of	
spectroscopic	techniques	such	as,	FT‐IR,	1H	and	13C	NMR,	Mass	
spectra	 as	 well	 as	 the	 elemental	 analysis.	 The	 elemental	
analysis	showed	acceptable	differences	between	the	measured	
and	the	calculated	percentages	of	the	elements	which	supports	
the	 validity	 of	 the	 proposed	 structures	 of	 the	 prepared	
compounds.	

The	FT‐IR	spectra	of	the	prepared	compounds	exhibited	all	
the	 expected	 bands.	 Comparing	 the	 IR	 spectra	 of	BDMC	with	
compound	 2,	 shows	 a	 new	 band	 at	 ν	 1647	 cm‐1	 which	 is	
attributed	to	the	C=N	in	pyrazole	ring	[23],	while	IR	spectrum	
of	 BDMC	has	 a	 band	 at	 1622	 cm‐1	 attributed	 to	 the	 carbonyl	
group	 of	 the	 central	 chelated	 ring.	 The	 IR	 spectrum	 of	
compound	3	showed	new	band	at	1685	cm‐1	which	is	assigned	
to	the	ester	carbonyl	group.	Meanwhile,	when	this	compound	
converted	 to	 hydrazide	 (compound	 B),	 a	 new	 band	 was	
appeared	1678	cm‐1.	All	IR	spectra	of	compounds	5a‐5f	show	a	
strong	band	at	the	range	1670‐1639	cm‐1	which	is	assigned	to	
the	 azomethan	 (N=CH)	 group	 as	 well	 as	 bands	 at	 the	 range	
1683‐1674	 cm‐1	 which	 are	 attributed	 to	 the	 N=C	 stretching	
vibration	 in	 the	pyrazole	 ring.	That	 is	 in	addition	 to	bands	at	
1604‐1601	cm‐1	which	are	assigned	to	the	stretching	vibration	
of	the	C=C	group.	

The	 1H	 and	 13C	NMR	spectra	 in	DMSO‐d6	 confirmed	 their	
proposed	 structures.	 BDMC	 characterized	 by	 four	 main	
signals;	 avinylic	proton	at	δ	5.87	ppm,	 the	 two	signals	of	 the	
olefinic	 protons	 at	 δ	 6.81	 and	 7.82	 ppm,	 the	 signals	 of	 the	
aromatic	proton	appear	at	δ	7.20‐7.09	ppm	and	the	singlet	of	
the	 phenolic	 proton	 at	 δ	 9.93	 ppm.	 Curcuminpyrazole	
(compound	2)	shows	a	new	signal	at	δ	6.68	ppm	attributed	to	
the	CH	proton	of	 the	pyrazole	 ring	 [22].	The	phenolic	proton	
disappears	in	the	spectrum	of	compound	3	accompanied	with	
the	appearance	of	new	signal	due	to	CH2O	at	δ	4.17	ppm,	and	

two	 signals	 of	 the	 ester	 group	 (CO‐CH2CH3)	 at	 δ	 1.21	 ppm	
(CH3)	and	at	δ	3.96	ppm	(CH2).	The	spectrum	of	compound	4	
shows	two	singlets	at	δ	9.42	and	4.22	ppm,	due	to	the	protons	
of	 NH	 and	 NH2,	 respectively.	 The	 1H	 NMR	 spectra	 of	
compounds	5a‐f	 show	a	singlet	due	to	 the	azomethan	proton	
within	the	range	δ	8.22	and	8.33	ppm	[24].	They	also	display	a	
singlet	near	δ	9.39	ppm	attributed	to	the	NH‐C=O	proton.	The	
13C	NMR	spectra	of	compounds	5a‐f	display	signals	of	carbon	
skeleton	of	compounds,	the	spectra	were	characterized	by	six	
kind	of	signals,	the	aliphatic,	the	vinylic	signals	of	pyrazol	ring,	
the	 aromatic	 signals,	 the	 azomethan	 signal,	 the	 C=N	 of	
pyrazole	 ring	 signal	 and	 the	 signal	 of	 C=O.	 The	Mass	 spectra	
(EI),	 supported	 the	 proposed	 formulae	 of	 the	 prepared	
compounds	
	
3.2.	Antioxidant	activity	assay	
	

The	 in‐vitro	 free	 radical	 inhibition	 activity	 of	 the	
synthesized	 compounds	 was	 investigated	 by	 the	 DPPH	
method.	 The	 result	 of	 IC50	 and	 the	 percentage	 of	 inhibition	
activity	 are	 gathered	 in	 Table	 1.	 The	 value	 of	 scavenging	
activity	 of	 the	 synthesized	 compounds	 (2,	5b,	5d,	5e,	5f)	 at	
concentration	 25‐200	 μmol/L	 were	 determined	 by	 the	
decrease	of	DPPH	absorbance	at	517	nm	with	the	time	(Table	
1	and	Figure	2).		

	

0

10

20

30

40

50

60

70

80

90

100

2 5b 5d 5e 5f

23

30

15
20 21

39 41

26
29

39

63 64

39

48

63

91
95

63

75

94

In
h

ib
it

io
n

 (
%

)

Compounds

25 μmol /L 50 μmol /L

100 μmol /L 200 μmol /L

	
	
Figure	2.	DPPH	free	radical	scavenging	activity	of	compounds	2,	5b,	5d,	5e	
and	5f	at	concentrations	25‐200	µmol/L	showing	percentage	of	inhibition.	

	
Compound	 2	 showed	 inhibition	 activity	 of	 23%	 at	 25	

μmol/L,	 39%	at	 50	μmol/L,	 63%	at	 100	μmol/L	 and	91%	at	
200	μmol/L.	Compounds	5b	and	5f	showed	high	inhibition	of	
95.4%	 and	 94%	 at	 200	 μmol/L,	 respectively.	 On	 the	 other	
hand	 compounds	 5d	 and	 5e	 were	 not	 so	 active	 and	 their	
percentages	 of	 inhibition	 are63.4	 and	 75%	 at	 200	 μmol/L,	
respectively.		

The	 reduction	 of	 DPPH	 indicates	 the	 activity	 of	 the	
synthesized	 compounds	 against	 the	 free	 radical	 of	 DPPH	
according	to	the	following	equations.	
	

DPPH˙+	RH	→	DPPH‐H	+	R˙		 	 	 (1)	
	
DPPH˙+	R˙	→	DPPH‐R		 	 	 	 (2)	
	



348	 Alsalim	et	al.	/	European	Journal	of	Chemistry	8	(4)	(2017)	344‐348	
	

The	 high	 activity	 of	 the	 compounds	5b,	5f	 and	2	 can	 be	
attributed	 to	 the	 phenolic	 OH	 group	 [24].	 Therefore,	 the	
scavenge	of	radical	activity	of	compounds	2,	5b,	5d,	5eand	5f	
is	 in	 the	 order:	 5b	 >	 5f	 >	 2	 >	 5e	 >	 5d,	 and	 the	 IC50	 of	 the	
scavenge	activity	at	the	range	78.79‐83.75	μmol/L.	
	
4.	Conclusion	
	

In	this	study,	bisdemethoxycurcumin	pyrazole	derivatives	
were	 prepared	 by	 four	 steps	 and	 characterized	 by	 FT‐IR,	 1H	
NMR,	 13C	 NMR,	 Mass	 spectra	 and	 elemental	 analysis	
techniques.	The	antioxidant	activities	of	some	compounds	are	
also	 studied	 by	 using	 DPPH	 as	 a	 source	 of	 radical.	 The	 high	
activity	 of	 compounds	 can	 be	 attributed	 to	 the	 phenolic	 ‐OH	
group.	
	
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