Synthesis and spectroscopic characterization of some new biological active azo-pyrazoline derivatives

Article abstract of DOI:10.1155/2012/525940

A number of 3-[4-(benzyloxy)-3-(2-Chlorophenylazo)-phenyl]-5- (substituted-phenyl)-1- substituted-2-pyrazolines( 4a-j) and (5a-j) have been synthesized by diazotization of 2-chloroaniline and its coupling reaction with 4-hydroxy acetophenone, followed by benzyloxation of the hydroxyl group to give the substrate [4-benzyloxy-3-(2-chlorophenylazo)- acetophenone (1)].The prepared starting material (1) has been reacted with different substituted benzaldehydes to give a new series of chalcone derivatives 1-[(4- benzyloxy)-3-(2-chloro- phenylazo) -phenyl]-3- (substituted phenyl)-2-propen-1-one (3a-j) , in high yields and in a few minutes, and the later compounds were treated with hydrazine hydrate according to Michael addition reaction to afford a new biolological active target compounds (4a-j) and (5a-j). Furthermore, The structures of the newly synthesized compounds were confirmed by FT-IR, ¹³C-NMR, ¹³C-DEPT & ¹H-NMR spectral data. The chalcone and pyrazoline derivatives were evaluated for their anti bacterial activity against Escherichia coli as gram negative and Staphylococcus aureus as gram positive, the results showed significant activity against both types of bacteria.

Full text of DOI:10.1155/2012/525940

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(3), 1613-1622
Synthesis and Spectroscopic Characterization of
Some New Biological Active Azo–Pyrazoline
Derivatives
FAROUQ E. HAWAIZ AND MOHAMMAD K. SAMAD
Department of Chemistry, College of Education/Scientific Depts.,
University of Salahaddin, Hawler, Kurdistan Region, Iraq
emamfarouq@yahoo.com
Received 09 November 2011; Accepted 15 January 2012
Abstract A number of 3-[4-(benzyloxy)-3-(2-Chlorophenylazo)-phenyl]-5-
(substituted-phenyl)-1- substituted-2-pyrazolines( 4a-j) and (5a-j) have been
synthesized by diazotization of 2-chloroaniline and its coupling reaction
with 4-hydroxy acetophenone, followed by benzyloxation of the hydroxyl
group to give the substrate [4-benzyloxy-3-(2-chlorophenylazo)-
acetophenone (1)].The prepared starting material (1) has been reacted with
different substituted benzaldehydes to give a new series of chalcone
derivatives
1-[(4-
benzyloxy)-3-(2-chloro-phenylazo)
-phenyl]-3-
(substituted phenyl)-2-propen-1-one (3a-j) , in high yields and in a few
minutes, and the later compounds were treated with hydrazine hydrate
according to Michael addition reaction to afford a new biolological active
target compounds (4a-j) and (5a-j). Furthermore, The structures of the newly
synthesized compounds were confirmed by FT-IR, 13C-NMR,13C-DEPT
&1H-NMR spectral data. The chalcone and pyrazoline derivatives were
evaluated for their anti bacterial activity against Escherichia coli as gram
negative and Staphylococcus aureus as gram positive, the results showed
significant activity against both types of bacteria.
Keywords : diazotization , benzyloxation ,Chalcone , Pyrazoline, Anti-bacterial activity.
Introduction
Azo-coupling is one of the most important reactions for combining aromatic rings [1]and
preparing azobenzene derivatives containing active functional groups as a precursor for
[3]
further synthesis to give different organic molecules such as : azo-amide[2] , azo-imine
and azo- chalcone [4]. Azo compounds are important as synthetic dyes[5,6] and cosmetics
[7]. Chalcones and azo-chalcones are useful precursor for the synthesis of different
heterocyclic compounds like pyrimidines [8], thiazepines
and
[9]
anti-malarial
[13], anti-bacterial [14] , anti-oxidative[15] , anti-fungal [16], anti-leishmanial [17], anti- tumour

6161 Farouq E. Hawaiz
[18], central nervous system [19], anti-histaminic [20]. Herein , we have described the
synthesis of some new azo-pyrazoline compounds derived from 2-chloro aniline and p-
hydroxy acetophenone with evaluation their anti bacterial studies.
Experimental
Melting points were determined using an Electrothermal melting point apparatus , IR
spectra were recorded on a Bio-rad Merlin FT-IR spectroscopy Mod FTS 3000, using KBr
disc. 1H-NMR and C13-NMR and 13C-DEPT-135 spectra were recorded on a
Bruker(300MHz) with TMS as internal reference in( Jordon) :
1-Preparation of 3-(2-chlorophenylazo)-4-hydroxyacetophenone (1)[21]
The pure compound prepared according to the procedure[21] as yellow crystals, of 3-(2-
chlorophenyl-azo)-4-hydroxyacetophenone (1). (C14H11ClO2N2), m.p. (148-150Co), yield
of (10.86gm, 99%). IR (cm-1)str. 3431 (OH), 1679 (C=O), 1607 (C=C), 1557 (-N=N-),
1
1276 (C-O), H-NMR (ppm): 2.68 (s , 3H , H1-CH3);; 7.12 (d , 1H , H5`) ; 7.41(d , 1H ,
H11 ) ; 7.49 (d , 1H , H12) ; 7.63 (d , 1H , H13) ; 7.98 (d , 1H , H10) ; 8.06 (d , 1H , H4) ; 8.64
(s , 1H , H8) 12.25 (s , 1H , OH).
2-Preparation of 3-(2-chlorophenylazo)-4-benzyloxyacetophen-one (2) [22]
A mixture of 3-(2-chlorophenylazo)-4-hydroxy acetophenone (15gm, 0.0546 mol), benzyl
bromide (14.02gm, 0.082 mol) and anhydrous K2CO3 (15.1gm, 0.109 mol) in ethanol (200
ml - 96%) was refluxed with stirring for 6hrs. The cooled solution poured into water, solid
materials immediately was obtained. The product was filtered off, washed several times
with cold water, dried and recrystallized with a mixture (1:2) xylene: ethanol to obtain
yellow-orange crystals of 3-(2-chlorophenylazo)- 4-benzyloxy acetophenone (2).
(C21H17ClO2N2), m.p. (133-134Co), yield (11.9 gm, 59%). IR (cm-1) str, 1673 (C=O), 1598
(C=C), 1532 (-N=N-), 1271 (C-O), 1H-NMR (ppm) :2.61 (s , 3H , H1-CH3); 5.39 (s , 2H ,
H15) ; 7.16 (d , 1H , H5) 7.35-7.51 (m , 5H , H17, 18, 19, 20, 21) ; 7.62 (d , 1H , H11) ; 7.71 (d ,
1H , H12) ; 7.82 (d , 1H , H13) ; 7.91 (d , 1H , H10) ; 8.04 (d , 1H , H4) ; 8.45 (s , 1H , H8).
13C-NMR : C1: 26.38 ; C15: 71.28 ; C5: 116.91 ; C8 : 119.06 ; C10,: 126.13 ; C11:127.90 ;
C17,21:128.48 ; C14:129.22; C19: 129.59; C18, 20: 130.48 ; C13: 131.08; C12:131.52 ; C3:
132.83; C4: 133.49; C7: 135.39; C16: 136.13; C9: 142.14; C6:159.84; C2: 196.7. Dept-135 :
C1: 26.38 ; C15: 71.28 ; C5: 116.91 ; C8 : 119.06 ; C10,: 126.13 ; C11:127.90 ; C17,21:128.48
;C19: 129.59; C18, 20: 130.48 ; C13: 131.08; C12:131.52 ; C4: 133.49.
3- Synthesis of chalcones (3 a-j)[23]:-
The prepared 3-(2-chlorophenylazo)-4-benzyloxyacetophenone (0.91 gm, 0.0025 mol)
was dissolved in 20ml of 96% ethanol, and added to the solution of an appropriate
substituted benzaldehydes (0.0025 mol) in 96% ethanol (20 ml) and (2.5 ml) of 4%
ethanolic sodium hydroxide. The mixture was stirred at room temperature for (1-5 min.)
until the formation of pale yellow crystals of chalcone, and then kept the solution
overnight at room temperature. The solid crystals were separated by suction filteration,
washed with ethanol and water to neutralize, dried and purified by recrystallization fromꢀ ꢀ
(1ꢀ:ꢀ2)ꢀxylene : ethanolthe results wereꢀꢀillustratedꢀꢀinꢀꢀtableꢀ(1)

Farouq E. Hawaiz
6161
Table 1. Melting points and yields for the prepared chalcones (3a-j).
Prod.
3 a
3 b
3 c
3 d
3 e
3 f
3 g
3 h
3 i
R
H
2-F
2-Cl
4-Cl
Molecular formula
C28H21ClN2O2
M.P. / 0C
103-105
122-124
128-130
138-140
161-163
151-152
157-158
104-106
130-131
140-142
% Yield
85
C28H20ClFN2O2
C28H20Cl2 N2O2
C28H20Cl2 N2O2
C28H20ClF N2O2
C28H20ClBrN2O2
C29H23ClN2O2
C29H23Cl N2O3
C35H27Cl N2O3
C35H26Cl2N2O3
86
93
75
97
86
60
75
76
4-F
4-Br
4-CH3
4-OCH3
3-O-CH2-C6H5
3-(4-Cl-C6H4-
CH2O)
3 j
84
3e: 1H-NMR ;5.48 (s 2H -O-CH2-C22), 7.12 ( d 2H Ar-H-C3,5), 7.15 (d 1H Ar-H-C12), 7.19-
7.56 ( m 7H Ar-H-C2,6,24,25,26,27,28 and 1H CH-Cα ), 7.69 ( d 2H Ar-H-C17,20), 7.91 ( d 1H Ar-
H-C11), 7.97 ( d 2H Ar-H-C18,19). 8.18 (d 1H CH-β-C7), 8.4 (s 1H Ar-H-C15). 13C-NMR,
71.38:O-CH2C22,
114.81:C12, 116.27:C3,5, 118.03:CHαC8, 118.44:C17, 121.28:C15,
127.07: C18 , 128.18: C24,28 , 128.71: C26 , 130.30: C2,6 , 130.42: C25,27 , 130.73: C20
,
131.21: C21 , 131.90: C19, 133.03 : C11, 135.49:C10, 136.20: C1, 142.27: C14 143.28: CHβ
C7, 149.07:C23 159.69 :C16, 162.39: C4 , 165.72 : C13, 188.36: C=O C9; 13C- DEPT -
71.38:O-CH2C22,
114.81:C12, 116.27:C3,5, 118.03:CHαC8, 118.44:C17, 121.28:C15,
127.07: C18 , 128.18: C24,28 , 128.71: C26 , 130.30: C2,6 , 130.42: C25,27 , 130.73: C20
131.90: C19, 133.03 : C11, 143.28: CHβ C7.
,
Table 2. Reaction times, melting points and yields for the prepared pyrazolines (4a-j).
Prod.
R
Molecular
formula
Time/hrs.
M.P./0C
%Yield
4 a
4 b
4 c
4 d
4 e
4 f
4 g
4 h
4 i
H
2-F
2-Cl
4-Cl
4-F
C28H23ClN4O
C28H22ClFN4O
C28H22ClFN4O
C28H22Cl2 N4O
C28H22ClF N4O
C28H22ClBrN4O
C29H25ClN4O
C29H25Cl N4O2
C35H29Cl N4O2
C35H28Cl2N4O2
1.25
0.75
0.5
0.75
0.75
1
0.5
1
1
95-97
113-114
143-144
116-118
137-139
90-92
107-109
66-68
115-116
95-97
78
83
98
84
77
71
61
79
81
86
4-Br
4-CH3
4-OCH3
3-O-CH2-C6H5
3-(4-Cl-C6H4-
CH2O)
4 j
1
3g: 1H-NMR; 2.41 (s 3H -CH3-C29 ), 5.45 (s 2H -O-CH2-C22 ) 7.12-7.9 (m 15H Ar-H-
C2,3,5,6,11,12,17,18,19,20,24,25,26,27,28 and 1H CH-Cα ), 8.19 (d 1H CH-β-C7), 8.41 (s 1H Ar-H-
C15); 21.57:-CH3 , 13C-NMR 71.33 :O-CH2C22, 114.73: C12, 118.04: CHαC8, 118.43 :C17,
120.54 :C15 126.04: C2,6 , 127.07 :C18 , 127.36 :C24,28 , 128.16: C26 , 128,87: C21 , 128.92:
C25,27 , 129.73: C3,5 , 130.73: C20 , 131.45: C10 , 131.87: C19 , 132.20: C1, 133.06: C11 , ,

6161 Farouq E. Hawaiz
136.2: C4 , 141.08: C14 , 142.25: C23
188.54 :C=O C9; 13C- DEPT
,
144.75: CHβ C7 , 149.08: C16, 159.58: C13 ,
3j: 1H-NMR; 5.09 (s 2H -O-CH2-C22), 5.45 (s 2H -O-CH2-C29), 7.04 (d 1H Ar-H-C12),
7.23-7.83 ( m 18H Ar-H-C2,3,4,6,11,17,18,19,20,24,25,26,27,28,31,32,34,35 and 1H CH-Cα), 8.18 (d 1H
CH-β-C7), 8.45 (s 1H Ar-H-C15); 69.32 :O-CH2C22, 13C-NMR , 71.38 :O-CH2C29, , 114.07
:C6 , 114.82 :C4, 117.29 :C12, 118.02 : C2 118.51 : CHαC8,121.75: C17, 121.94: C15
127.08 : C18 ,127.39: C24,26,28 , 128.18:C25,27 128.72: C31,35 , 128.82: C32,34 , 130.06 :C20
,
,
130.73: C3, 131.22: C10 , 131.92: C19, 1133.06 :C11,133.89: C21 , 135.21: C33, 135.51: C1,
136.17: C14,136.43: C23, 142.26: C30 ,144.29: CHβ C7, 149.02 :C16,158.91 :C5, 159.71:
C13, 188.43: C=O C9; 13C- DEPT
4- Synthesis of pyrazolines 3-[4-(benzyloxy)-3-(2-chlorophenylazo)-phenyl]-5-
(substituted-phenyl)-1-substituted-2-pyrazolines( 4a-j) and (5a-j)[24]
:
A mixture of chalcone derivative (0.5mmoles), hydrazine hydrate (2.5mmoles) or
phenylhydrazine (1mmoles) and sodium hydroxide (5ml, 0.4%) in ethanol (15ml ) was
refluxed with stirring for appropriate time until complete the reaction, which was
monitored by either change of the color or the formation of ppt. The ppt. was isolated by
suction filteration, washed with ethanol and water to neutralize, dried and purified by
recrystallization from (1:2) xylene: ethanol. The physical properties and yields are
summarized in table-2 .
4e: 1H-NMR ;3.06 (dd 1H CH2-Ha-C8), 3.52 (dd 1H CH2-Hb-C8), 4.93 (dd 1H CH-Hx-
C7), 5.43(S 2H -O-CH2-C22), 5.95 br.s 1H N-H), 7.01-7.93 (m 16H Ar-H); 13C-NMR
;41.5:CH2 C8 , 63.79: CH C7, 71.66: O-CH2 C22, 115.38: C12,115.5: C3,5, 115.79:C17,
118.05: C15, 126.27: C10, 127.10: C18
, 127.30: C24,28, 127.99: C26 , 128.10: C2,6,
128.61:C25,27, 130.24:C20, 130.61:C19 ,131.56:C11, 138.69:C21 , 138.42 :C1 ,142.61:C14,
149.18:C23, 150.56: C16 , 157.05:C9 , 160.69:C13 , 163.95 : C4; 13C- DEPT; -41.5:CH2
C8 , 63.79: CH C7, 71.66: O-CH2 C22, 115.38: C12,115.5 :C3,5, 115.79:C17, 118.05: C15,
127.10: C18
, 127.30: C24,28, 127.99: C26 , 128.10: C2,6, 128.61:C25,27, 130.24:C20,
130.61:C19 ,131.56:C11.
1
4g: H-NMR ;2.30 (s 3H CH3-C29), 3.09 (dd 1H CH2-Ha-C8), 3.58 (dd 1H CH2-Hb-C8),
5.25 (dd 1H CH-Hx-C7), 5.39 (s 2H -O-CH2-C22), 5.92 (br.s 1H N-H), 6.89-7.95 ( m 16 H
Ar-H); 13C-NMR ;21.52:CH3 C29 ,41.45:CH C8, 63.3: CH C7, 71.43: O-CH2 C22,
114.89: C12, 118.58: C17, 119.54: C15 ,125.76: C10, 126.16: C18, 126.93: C2,6,
127.11:C24,28
,
127.23: C26,128.56: C25,27, 129.09: C3,5,129.95: C20, 130.45:C19,
131.65:C11,132.92: C21 ,136.87: C4, 138.18: C14, 140.23:C1, 144.24:C23, 149.69:C16
,
152.02:C9 , 161.38:C13 . 13C- DEPT; -21.52:CH3 C29 ,41.45:CH C8, 63.3: CH C7, 71.43:
O-CH2 C22, 114.89: C12, 118.58: C17, 119.54: C15, 126.16: C18, 126.93: C2,6,
127.11:C24,28
131.65:C11.
,
127.23: C26 ,128.56: C25,27, 129.09: C3,5,129.95: C20 ,130.45:C19,
4j: 1H-NMR; 3.05 (dd 1H CH2-Ha-C8), 3.55 dd 1H CH2-Hb-C8), 4.95 dd 1H CH-Hx-C7),
5.03 (d 2H, 1H -O-CH2-C29), 5.40 (d 2H, 1H -O-CH2-C22 ), 6.00 (br.s 1H N-H), 6.88-
8.04 (m 20H Ar-H41.5:CH2 C8 , 13C-NMR; 64.27: CH C7, 69.19:O-CH2 C22, 71.65:O-
CH2 C29, 112.64: C4 ,114.15: C6 , 115.38:C12, 115.67: C2, 118.06: C17,119.19:C15,
126.35:C10, 127.12: C18,
127.31: C24,28, 128: C26, 128.62:C25,27, 128.75:C31,35
,128.79:C32,34 , 130.24:C20, 129.97:C3, 130.63 :C19 ,131.57:C11, 133.75 :C21, 135.26:C33,
135.39:C14
136.72:C30 142.61:C23,144.576:C1 ,149.19:C16 ,150.52:C9, 153.03:C13,
158.97:C5; 13C- DEPT; -41.5:CH2 C8 , -64.27: CH C7, -69.19:O-CH2 C22, -71.65:O-CH2
C29, 112.64: C4 ,114.15: C6, 115.38:C12, 115.67: C2, 118.06: C17,119.19:C15, 127.12: C18 ,
127.31: C24,28, 128: C26, 128.62:C25,27, 128.75:C31,35 ,128.79:C32,34, 130.24:C20, 129.97:C3,
130.63 :C19 ,131.57:C11.

Synthesis and Spectroscopic Characterization of Some New Biological 6161
Table 3. Reaction times, melting points and yields for the prepared pyrazolines (5a-j).
Prod.
R
Molecular
formula
Time/hrs.
M.P./0C %Yield
5 a
5 b
5 c
5 d
5 e
5 f
5g
5 h
5 i
5 j
H
2-F
2-Cl
4-Cl
4-F
4-Br
4-CH3
4-OCH3
C34H28ClN4O
C34H22ClFN4O
1.5
2
1.25
2
1.5
1.25
3
1
2
2
155-156
184-186
183-184
180-182
189-191
140-141
189-190
95-96
46
45
60
46
48
50
62
44
68
52
C34H22ClFN4O
C34H22Cl2 N4O
C34H22ClF N4O
C34H22ClBrN4O
C35H25ClN4O
C35H25Cl N4O2
C41H33Cl N4O2
C41H32Cl2N4O2
3-O-CH2-C6H5
3-(4-Cl-C6H4-
CH2O)
125-126
148-149
1
5e: H-NMR ;3.09 (dd 1H CH2-Ha-C8), 3.82 (dd 1H CH2-Hb-C8), 5.22 (dd 1H CH-Hx-
C7), 5.36 (S 2H -O-CH2-C22), 7.01-7.97 (m 21H Ar-H); 13C-NMR 43.04:CH2 C8 , 63.89:
CH C7, 71.65: O-CH2 C22, 113.32: C30,34 ,114.91: C12,115.76 :C3,5, 118.04:C17, 119.18:
C15, 126.13: C10, 127.10: C18 , 127.49: C24,28, 127.60: C26 , 127.98:C25,27, 128.58: C2,6,
128.90:C20, 130.13:C31,33 ,130.57:C19 ,131.59:C11, 136.59 :C21 , 138.19 :C1 ,142.58:C14,
144.67:C23, 146.09:C29 , 149.13: C16 , 156.88:C9 , 160.46:C13 , 163.71 : C4; 13C- DEPT;
-43.04:CH2 C8 , 63.89: CH C7, - 71.65: O-CH2 C22, 113.32: C30,34 ,114.91: C12,115.76
:C3,5, 118.04:C17, 119.18: C15, 127.10: C18 , 127.49: C24,28, 127.60: C26 , 127.98:C25,27
,
128.58: C2,6, 128.90:C20, 130.13:C31,33 ,130.57:C19 ,131.59:C11.
1
5g: H-NMR ;2.35 (s 3H CH3-C29), 3.15 (dd 1H CH2-Ha-C8), 3.85 (dd 1H CH2-Hb-C8),
5.25 (dd 1H CH-Hx-C7), 5.41 (s 2H -O-CH2-C22), 6.80-7.99 ( m 21H Ar-H); 13C-NMR
;21.11:CH3 C29 ,43.68:CH C8, 64.43: CH C7, 71.73: O-CH2 C22, 113.35: C31,35, 114.94:
C12, 115.83: C33, 118.08: C17, 118.99: C15 ,125.84: C10, 126.04: C18, 127.13: C2,6,
127.31:C24,28
,
127.99: C26 ,128.62: C25,27
,
128.89: C3,5,129.82: C20 ,130.14:
C32,34,130.63:C19,
131.54:C11,135.12: C21 ,136.56: C4, 137.11: C14, 139.45:C1,
142.54:C23, 144.76: C30, 146.09:C16 , 149.12:C9 , 156.68:C13 . 13C- DEPT; 21.11:CH3 C29,
-43.68:CH2 C8, 64.43: CH C7, -71.73: O-CH2 C22, 113.35: C31,35, 114.94: C12, 115.83:
C33, 118.08: C17, 118.99: C15 , 126.04: C18, 127.13: C2,6, 127.31:C24,28 , 127.99: C26,
128.62: C25,27, 128.89: C3,5,129.82: C20 ,130.14: C32,34,130.63:C19, 131.54:C11.
5j: 1H-NMR ; 3.15 (dd 1H CH2-Ha-C8), 3.87 dd 1H CH2-Hb-C8), 4.96 (d 2H, 1H -O-
CH2-C29), 5.41(dd 1H CH-Hx-C7), 5.90 (d 2H, 1H -O-CH2-C22 ), 6.84-8.09 (m 25H Ar-
H); 13C-NMR ; 43.56:CH2 C8 , 64.56: CH C7, 69.16:O-CH2 C22, 71.69:O-CH2 C29,
112.11: C4 , 113.31: C37,41 , 114.05: C6 , 114.94:C12, 118.09: C2, 118.67: C17,119.13:C15,
126.25:C10, 127.12: C18
, 127.34: C24,28, 128:01 C26 , 128.63:C25,27, 128.70:C31,35,
128.89:C32,34 , 130.93:C20, 130.15:C3, 130.63 :C19 ,131.58:C11, 133.72 :C21, 135.21:C33,
135.26:C14 , 136.70:C30 142.66:C23, 144.39:C1 ,144.87: C36 ,146.07:C16 ,149.21:C9,
15.92:C13, 159.20:C5;13C- DEPT; -43.56:CH2 C8 ,-64.56: CH C7,- 69.16:O-CH2 C22, -
71.69:O-CH2 C29, 112.11: C4 , 113.31: C37,41 , 114.05: C6 , 114.94:C12, 118.09: C2,
118.67: C17,119.13:C15, 127.12: C18
,
127.34: C24,28, 128:01 C26 , 128.63:C25,27,
128.70:C31,35 ,128.89:C32,34 , 130.93:C20, 130.15:C3, 130.63 :C19 ,131.58:C11.

6161 Farouq E. Hawaiz
O
O
Cl
Cl
2
3
HO
14 Cl
13
8
1
HCl
NaNO2
NH2
9
12
N
N
Cl
4
N
N
7
0o
C
NaOH
10
5
11
6
HO
1
CH2Br
K2CO3, EtOH
reflux 6 hrs.
O
O
O
7
2
H
2
5
14
Cl
13
11
8
7
21
Cl
10
1
1
20
19
15
14
9
3
3
8
4
12
N
N
N
N
9
10
R
4
16
17
5
6
6
12
21
18
26
R
13
O
NaOH
EtOH
28
O
20
19
27
15
16
3a-j
23
22
NH2NH2.H2Oor PhNHNH2
17
4
18
2
24
25
NaOH
EtOH
reflux
3
6
20
2
1
21
Cl
R1
5
19
18
8
16
15
9
N
10
11
7
14
N
17
27
28
23
N
N
26
R2
(R2: H, Ph)
13
O
12
22
25
24
(4,5 a-j)
R1=H, 2-F, 2-Cl, 4-Cl, 4-F, 4-Br, 4-CH3, 4-OCH3, 3-C6H5OCH2, 3-(4-Cl-C6H4OCH2)
Scheme (1)
Results and Discussion
The synthesis of two new series of the target molecules 2-pyrazoline containing
benzyloxy and azo-linkage side-chain is outlines in scheme (1). The skeleton of the
synthesized compounds were confirmed by physical properties and spectroscopic
methods like FT-IR, 1H-NMR, 13C-NMR and 13C-DEPT-135. The IR spectrum of
compound (1) showed a broad band at (3431) cm-1 attributed to (OH) group[30], a
characteristic N=N band was assigned at (1557) cm-1 [31],two strong bands at 1679cm-1 and
1607cm-1 referring to carbonyl and carbon-carbon double bonds. The 1H-NMR spectrum
of compound (1) shows a singlet at (2.68) ppm for three protons of CH3 attached to the
carbonyl group, multiplet at (7.12- 8.06) and a singlet at (8.64) ppm for seven protons of
the two phenyl rings and a distinct singlet signal at (12.25) ppm assigned to the hydroxyl
13
group. C-NMR shows twelve singlet signals corresponding to twelve types of carbon in
different chemical shifts. The IR spectrum of compound (2) shows the disappearance of a
broad band at (3431 ) cm-1 for hydroxyl group of 4-hydroxyacetophenone[25], and shifting
the absorption band of carbonyl group from 1679 cm-1 to 1673 cm-1, is considered as a
good evidence to benzyloxation processes, two strong bands at (2927 and 2873) cm-1
equivalent to the (-CH2-) group of 4-benzyloxy substrate. The1H-NMR spectrum of
compound (2) shows two singlet signals at (2.61 and 5.39) ppm belongs to the three
protons of (-CH3) attached to the carbonyl group and two protons of (-O-CH2-)
respectively, a multiplet signals at (7.16- 8.04) ppm, and a singlet signal at (8.45) ppm
attributed to the twelve protons of aromatic rings. The 13C-NMR spectrum showed three
singlets at (26.38, 71.28 and 196.70) ppm belongs to the carbon atom of (-CH3, -O-CH2-,
and carbonyl) with fourteen signals for fourteen carbons in aromatic regions. The 13C-
DEPT-135 of compound (2) showed upward signal at δ (26.34) for tri-protonated carbon
atom of (-CH3) group and a downward signal at (71.34) corresponding to the di-
protonated carbon atom (-O-CH2-) group with disappearance of non protonated carbon
atoms . The FT-IR spectra of all chalcones (3a-j) showed the characteristic peaks of
particular carbonyl functional groups[26] in the region of (1661 - 1653) cm-1 , the lowering

Synthesis and Spectroscopic Characterization of Some New Biological 6161
of normal (C=O) frequency from( 1673) cm-1 indicates the presence of (C=C) conjugated
to carbonyl group (conjugated enones) [27], table-4.
Table-4: Assignment of characteristic frequencies (cm-1) of IR spectra for the prepared
chalcones (3a-j) and pyrazolines (4 a-j), (5a-j) .
Chalcones (3 a-j)
Pyrazolines (4 a-j)
Pyrazolines
(5 a-j)
Prod.
R
C=O
C=C
C=N
N-H
C=N
A
B
C
D
E
F
G
H
I
H
2-F
1659
1605
1605
3296
1597
1598
1597
1598
1597
1595
1597
1597
1598
1597
1602
1659
1661
1661
1659
1661
1653
1660
1605
1604
1604
1595
1604
1602
1594
1600
1595
1603
1606
1606
1604
1594
1603
1606
1602
1600
3342
3346
3309
3326
3335
3334
3302
3326
3312
2-Cl
4-Cl
4-F
4-Br
4-CH3
4-OCH3
3-OCH2C6H5
J
3-(4-Cl- C6H4- 1660
CH2O)
Table-5: Anti-bacterial activity of some prepared chalcones and pyrazolines with inhibition
zone diameters in (mm) scale against S-aureus and E-coli bio-organisms.
Product no.
E.coli G (-ve)
S-aureus G(+ve)
2
6
8
25
25
25
zero
25
25
zero
25
25
zero
25
25
3 a
4 a
5 a
3 e
4 e
5 e
3 f
4 f
5 f
3 j
4 j
11
25
9
12
18
8
12
18
10
14
16
5 j
zero
1
The H-NMR spectra of chalcones , show characteristic doublet signals for α, β- protons at
(8.18) ppm [28], this deshielding refers to the effect of resonance of the phenyl rings that
bonded to β- carbon atom, but the (CHα) completely emerged with aromatic protons, it is

6161 Farouq E. Hawaiz
hard to distinguish it at a certain number. The 13C-NMR spectra assignment of carbon atoms
presented in chalcones moiety, show the characteristic peak is that related to the β-C atom
nearly around (143 - 145) ppm which is more deshielded than that of α-C atom
approximately at (118) ppm by the mesomeric action of carbonyl group [29]. The 13C-DEPT-
135 appeared a characteristic downward signal approximately at (71) ppm corresponding to
the di-protonated carbon (C22) atom of the (-O-CH2-) group, and two characteristic mono-
protonated carbon, at (118 and143-145) ppm belongs to (Cα and Cβ) atoms respectively, and
the other peaks return to Ar-C atoms. In the IR spectra of pyrazolines (4 a-j) table-4, fig.(1)
exhibited a characteristic band at (3296-3346) cm-1 due to N-H stretching[30], also
pyrazolines (5a-j) appeared strong band at (1594-1606) cm-1 for C=N stretching vibration ,
beside the appearance of above bands, the most important evidence for the formation of 2-
pyrazoline is the disappearance of carbonyl group band at (1653-1661) cm-1special for the
chalcone moiety. The 1H-NMR spectra of pyrazolines showed characteristic signals
corresponding to proton of C8 and C7 of 2-pyrazoline ring; they form a typical ABX system
confirming the nonequivalence of protons at C8 [31]. It causes to appearance of three doublet
to doublet (dd) signals approximately at (3, 3.5 and 4.7) for each compound, fig. (2) .
Figure 1: IR spectrum of compound (4j).
Figure 2: 1H-NMR spectrum of compound (4j).
The 13C-NMR spectra of pyrazolines, showed three signals approximately at, (41.5 ,
63.79 and 71.66) belongs to (C8 , C7 and C22 ) for pyrazoline carbon and O-CH2 groups
respectively, and the other peaks between (112 and 164) ppm approximately attributed to

Synthesis and Spectroscopic Characterization of Some New Biological 6166
aromatic carbon atoms fig(3) . The 13C-DEPT-135 of pyrazolines exhibited tree
downward signals at (40 , 64 and 71) ppm approximately indicated to the di-protonated
carbon atoms of pyrazoline ring and two -OCH2- group respectively, also the appearance
of other upward signals corresponding to mono-protonated carbon atoms, Fig.(4)
Antibacterial Activity:
The synthesized compounds were screened for antimicrobial activity against two types of
bacteria Escherichia coli (gram negative ) and Staphylococcus aureus (gram positive ) by
using the cup-plate agar diffusion method with KBr disc of compounds .The prepared
discs were placed on the surface of the cultured media with each of the two bacteria's and
incubated for 24 hours at 37oC and the results were monitored by measuring the zones of
inhibition in mm .The screening results are listed in table (5) and they show that most of
the prepared compounds are sensitive against both types of test organisms in different
activities.
Figure 3: 13C-NMR spectrum of compound (4j).
Figure 4: 13C-Dept spectrum of compound (4j).
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