Ultrasonic assisted synthesis of naphthalene substituted Schiff base derivatives and their antioxidant activity studies

Article abstract of DOI:10.1002/jccs.201190091

New Schiff base derivatives, 2,2′-[naphthalene-2,7-diylbis(oxy)] bis[N′-substituted acetohydrazide] (4a-m) were synthesized by the acid catalyzed condensation of aryl/hetero aromatic aldehydes with 2,2′- [naphthalene-2,7-diylbis(oxy)]diacetohydrazide (3)

Full text of DOI:10.1002/jccs.201190091

Journal of the Chinese Chemical Society, 2011, 58, 583-589
583
Communication
Ultrasonic Assisted Synthesis of Naphthalene Substituted Schiff Base
Derivatives and Their Antioxidant Activity Studies
K. Venkatesan, V. S. V. Satyanarayana and A. Sivakumar*
Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632014, India
Received May 22, 2011; Accepted July 18, 2011; Published Online August 5, 2011
New Schiff base derivatives, 2,2¢-[naphthalene-2,7-diylbis(oxy)]bis[N¢-substituted acetohydrazide]
(4a-m) were synthesized by the acid catalyzed condensation of aryl/hetero aromatic aldehydes with 2,2¢-
[naphthalene-2,7-diylbis(oxy)]diacetohydrazide (3) under reflux temperature and ultrasonic irradiation.
These Schiff base derivatives were confirmed through spectral characterization using IR, 1H NMR, 13
C
NMR and mass spectra. All the synthesized compounds were screened for their antioxidant activity using
DPPH free radical scavenging method.
Keywords: 2,2¢-[Naphthalene-2,7-diylbis(oxy)]diacetohydrazide; Schiff base; Ultrasonic irradia-
tion; Spectral characterization; Antioxidant activity.
INTRODUCTION
Compounds containing azomethine group (–C=N–)
is more convenient and easily controllable. A large number
of organic reactions can be carried out under milder condi-
tions in shorter reaction times providing higher yields un-
der ultrasound irradiation.23 Many homogeneous and het-
erogeneous reactions can be conducted smoothly by soni-
cation to improve yields with increased selectivity.
Hence, in this paper, we are reporting the synthesis of
Schiff base derivatives containing naphthalene analogues
by the reaction of 2,2¢-[naphthalene-2,7-diylbis(oxy)]di-
acetohydrazide (3) with different substituted aryl/hetero ar-
omatic aldehydes using conventional and ultrasonic meth-
ods and their characterization through spectral data such as
IR, 1H NMR, 13C NMR and mass spectra. Their antioxidant
activity was also evaluated.
in the structure are known as Schiff bases, which are usu-
ally synthesized by the condensation of primary amines
and active carbonyl groups. Schiff bases are important
class of compounds in medicinal and pharmaceutical field.
They show biological applications including antibacte-
rial1-6 antifungal2,6 antitumor activity7,8 antioxidant9,10 anti-
inflammatory11 antihypertensive12 anti-HIV13 antifilarial14
anticonvulsant15 herbicidal, insecticidal, schistosomicidal
and anthelmintic16 activities. These are used as protective
agents in natural rubber.17 Schiff bases and their complexes
have a variety of applications in biological, clinical and an-
alytical fields.18 Recently there has been a considerable in-
terest in the chemistry of hydrazine and hydrazone com-
pounds because of their potential pharmacological applica-
tions.19 The remarkable reactivity of acid hydrazides
(R–CONHNH2)20 and the biological activity associated
with their corresponding hydrazones attributed to the pres-
ence of the active pharmacophore (-CONH-N=CH-). Hence
many hydrazone compounds containing this active moiety
showed good anticancer bioactivities.21
RESULTS AND DISCUSSION
Chemistry
Diethyl 2,2¢-[naphthalene-2,7-diylbis(oxy)]diacetate
(2) was synthesized by the reaction of 2,7-dihydroxy naph-
thalene 1 with ethyl chloroacetate in the presence of anhy-
drous K2CO3 and dry DMF at 80 ºC for 16 hours in 82%
yield (Scheme I).24 The IR spectrum of compound 2 shows
an absorption band at 1760 cm-1 indicates the presence of
Ultrasound irradiation has been considered as a clean
and useful protocol in organic synthesis in the last three de-
cades.22 Compared with traditional methods, this technique
1
carbonyl group. The H NMR of compound 2 showed a
* Corresponding author. E-mail: profaskumar09@gmail.com

584 J. Chin. Chem. Soc., Vol. 58, No. 5, 2011
Scheme I Synthetic protocol of compounds 4a-m
Venkatesan et al.
Table 1. Physical data of compounds 4a-m
triplet at d 1.32 ppm and a quatret at d 4.31 ppm showing
the presence of CH3 and COOCH2 groups respectively,
which indicates the acetate formation. By refluxing diethyl
2,2¢-[naphthalene-2,7-diylbis(oxy)]diacetate (2) with hy-
drazine hydrate in ethanol for 6 hours yielded 2,2¢-[naph-
thalene-2,7-diylbis(oxy)]diacetohydrazide (3). The pri-
mary amine (NH2) and secondary amine (NH) signals de-
rived from hydrazide (–NH-NH2) of compound 3 were ap-
peared at 3311 & 3206 cm-1 in IR spectrum and as singlets
at d 4.58 & 9.41 ppm in 1H NMR spectrum. This indicates
the formation of acetohydrazide (3) from acetate (2). The
condensation of compound (3) with different substituted
aromatic aldehydes in chloroform/methanol (1:1) mixture
and DMSO under reflux temperature and ultrasonic irradi-
ation respectively to give corresponding Schiff bases (4a-
m) in good yields. The 1H NMR spectra of compound (4a)
displayed two doublets due to methylene protons at d 5.25
& 4.77 ppm and the NH group resonating as triplet at d
11.61 ppm. The peaks of naphthalene aromatic and phenyl
group protons appeared in the range of 7.05-7.83 ppm. The
signals belonging to -N=CH protons were observed as dou-
blets at d 8.03 & 8.34 ppm, the disappearance of NH2 signal
of compound 3 in compound 4a indicates the function-
alization of hydrazide to hydrazone with benzaldehyde.
The structures of all the new Schiff base derivatives (4a-m)
were confirmed by the spectral characterization using FT-
IR, 1H NMR, 13C NMR and mass spectra. Yields of all the
synthesized products were compared with respective reac-
tion time in presence of reflux temperature and ultrasonic
irradiation and are given in Table 1.
Entry
R
Time (min)a Yield (%)b M.P. (°C)
4a
4b
4c
4d
4e
4f
Phenyl
4-ClPh
180/6
210/8
210/6
240/10
240/10
240/10
240/6
210/8
210/8
240/12
210/6
240/12
210/6
83/82
80/82
80/77
76/78
77/76
75/75
77/75
76/79
75/77
79/75
80/79
73/71
78/75
199-201
236-238
189-191
230-232
220-222
169-171
251-253
210-212
216-218
227-229
218-220
221-223
162-164
4-CH3OPh
2,4-ClPh
4-N(CH3)2Ph
4-OEt,3-CH3OPh
3-NO2Ph
4g
4h
4i
3-OEt,4-OHPh
4-OH,3-CH3OPh
3-CH3Ph
4j
4k
4l
4-EtOPh
Cinnamyl
4m
2-Thiophenyl
a At reflux temperature/ultrasonic irradiation.
b Isolated yields.
DPPH, a stable free radical with a characteristic ab-
sorption at 517 nm, was used to study the radical scaveng-
ing effects of all the synthesized Schiff base derivatives. As
antioxidants donate protons to these radicals, the absorp-
tion decreases. The decrease in absorption is taken as a
measure of the extent of radical scavenging.
The antioxidant studies revealed that compound 4h
and 4i with hydroxyl substitution on benzylidene ring
showed good free radical scavenging activity (62.24%,
88.97% and 52.24%, 81.38%, respectively), comparable to
that of BHT (Butylated hydroxyl toluene) (100%), fol-
lowed by 4e with N(CH3)2 substitution on benzylidene ring
which showed minimum activity (8.45% and 12.24%) at
100 mg/mL towards different incubation time. Free radical
scavenging capacities of the synthesized compounds 4e,
4h, 4i and BHT at 100 µg/mL concentration after half an
hour (Fig. 1) and one hour of (Fig. 2) incubation time in
dark at room temperature, measured by DPPH assay.
ANTIOXIDANT ACTIVITY
All the synthesized compounds (4a-m) were sub-
jected to their possible antioxidant activity using DPPH
free radical scavenging assay method.

Ultrasound Assisted Synthesis of Schiff Base Derivatives
J. Chin. Chem. Soc., Vol. 58, No. 5, 2011 585
The remaining compounds have not showed radical
scavenging activity against 1,1-diphenyl-2-picrylhydrazyl
(DPPH) under the same reaction conditions. Fig. 3 repre-
sents the comparison of antioxidant activity of compounds
4e, 4h, 4i and BHT using DPPH radical scavenging method
after 30 minutes and 1 hour of incubation at 100 mg/mL
concentration.
DPPH free radical scavenging method.
EXPERIMENTAL
General
The melting points were determined by open capillar-
ies and are uncorrected. Infrared (IR) spectra were re-
corded at room temperature from 4000 cm-1 to 400 cm-1
with KBr pellets at a resolution of 4 cm-1, using Avatar 330
In summary we have synthesized a series of new
naphthalene substituted Schiff base derivatives 4a-m on
treatment of 2,2¢-[naphthalene-2,7-diylbis(oxy)]diaceto-
hydrazide (3) with substituted aliphatic/aromatic alde-
hydes in the presence of acid catalyst under reflux tempera-
ture and ultrasonic irradiation. The characterization of all
these new Schiff base derivatives was carried out through
IR, 1H NMR, 13C NMR and mass spectra. Antioxidant ac-
tivity of the synthesized compounds was studied using
1
equipped with DTGS detector. H NMR and 13C NMR
spectra were recorded on a Bruker AV-500 MHz, spectrom-
eter in DMSO-d6, CDCl3 using TMS as an internal standard
and the values are expressed in ppm. Mass spectra were ob-
tained by using HRMS. Sonication was performed in a
SONICS, Vibra Cell, VC 130, ultrasonic processor equipped
with a 3 mm wide and 140 mm long probe, which was im-
mersed directly into the reaction mixture. The operating
frequency was 20 kHz and the output power was 0-130
Watt through manual adjustment. All reagents were pur-
chased from Aldrich, Sd fine and Qualigens and used with-
out further purification.
Procedure for the preparation of compound diethyl
2,2¢-[naphthalene-2,7-diylbis(oxy)]diacetate (2)
To a solution of 2,7-dihyroxy naphthalene (1) (1.0
molar equiv) in dry DMF, anhydrous potassium carbonate
(2.0 molar equiv) and ethyl chloroacetate (2.0 molar equiv)
were added. The resultant mixture was stirred at 80 °C for
16 h, cooled and then poured into a large amount of water.
The solid separated was filtered and washed with excess of
water. The crude product was purified by recrystallization
from ethanol. Yield of the product was 81-82% [lit. yield
40%].25 mp. 92-94 ºC; IR (KBr) nmax: 3258, 2917, 1760,
Fig. 1. Antioxidant activity of compounds 4e, 4h and
4i and BHT using DPPH free radical scaveng-
ing method after 30 min. of incubation.
Fig. 3. Comparsion of antioxidant activity of com-
pounds 4e, 4h and 4i and BHT using DPPH free
radical scavenging method after 30 min. and 1
hr of incubation.
Fig. 2. Antioxidant activity of compounds 4e, 4h and
4i and BHT using DPPH free radical scaveng-
ing method after 1 hr of incubation.

586 J. Chin. Chem. Soc., Vol. 58, No. 5, 2011
Venkatesan et al.
Table 2. Antioxidant activity of compounds 4a-m using DPPH radical scavenging method
After 30 min. incubation* After 1 hr. incubation*
% Antioxidant
% Antioxidant
Compound
Absorbance
Compound
Absorbance
activity
activity
4e
0.531
0.219
0.277
0.580
8.45
62.24
52.24
4e
4h
4i
0.509
0.064
0.108
12.24
88.97
81.38
4h
4i
Control**
* BHT was used as a standard antioxidant. ** DPPH in DMSO.
1654, 1628, 1518, 1384, 1204, 1173, 1076, 1024 cm-1; 1H
NMR (500 MHz, CDCl3, ppm), dH = 7.71 (d, 2H, J = 9.0
Hz, C-4,5 ArH of naphthalene ring), 7.12 (dd, 2H, J = 2.5 &
9.0 Hz, C-3,6 ArH of naphthalene ring), 6.99 (d, 2H, J = 2.5
Hz, C-1,8 ArH of naphthalene ring), 4.73 (s, 4H, OCH2),
4.31 (q, 4H, J = 7.25 Hz, COOCH2), 1.33 (t, 6H, J = 7.25
Hz, CH3); 13C NMR (125.757 MHz, CDCl3, ppm), dC =
168.84, 156.51, 135.36, 129.47, 125.26, 116.48, 106.74,
65.51, 61.43, 14.17; HRMS (EI): m/z [M+] calcd. for
C18H20O6: 332.1260; found: 332.1254.
bis(oxy)]diacetohydrazide 3 (0.01 mole) in chloroform/
methanol (1:1) mixture (30 mL), aryl/hetero aromatic alde-
hyde (0.02 mole) and 1 mL of glacial acetic acid was re-
fluxed for 4-5 hours. The mixture was allowed to cool; the
solid separated was filtered, washed with excess of metha-
nol and then dried at room temperature.
Method B:
A mixture of compound 2,2¢-[naphthalene-2,7-diyl-
bis(oxy)]diacetohydrazide 3 (0.01 mole) in DMSO (30
mL), aryl/hetero aromatic aldehyde (0.02 mole) and 1 mL
of glacial acetic acid was subjected to ultrasonic irradiation
using ultrasonic processor equipped with a 3 mm wide and
140 mm long probe, which was immersed directly into the
reaction mixture varying periods as shown in Table 1. The
operating frequency was 16 kHz and the output power was
104 Watts through manual adjustment. The mixture was al-
lowed to cool and poured into ice cold water (30 mL). The
solid separated was filtered, washed with excess of metha-
nol and then dried at room temperature.
Procedure for the preparation of compound 2,2¢-
[naphthalene-2,7-diylbis(oxy)]diacetohydrazide (3)
Compound 2 (0.01 mole) in ethanol (20 mL) was
stirred at room temperature for 20 min. To this mixture
hydrazine hydrate (0.03 mole) was added and stirred at
room temperature for 15 min. The resultant mixture was
refluxed for 6 hours and the separated solid was filtered us-
ing a sintered glass funnel. The residue was dried and then
desiccated to afford a crystalline powder. The powder was
recrystallized from chloroform/methanol and gave half
white solid. Yield of the product was 88-90%. mp. 232-234
ºC; IR (KBr) nmax: 3311, 3206, 3029, 2923, 1699, 1622,
1471, 1385, 1212, 1174, 1060 cm-1; 1H NMR (500 MHz,
DMSO-d6, ppm), dH = 9.41 (s, 2H, NH), 7.76 (d, 2H, J = 9.0
Hz, C-4,5 ArH of naphthalene ring), 7.04-7.16 (m, 4H,
C-1,3,6,8 ArH of naphthalene ring), 4.86 & 4.96 (2s, 4H,
OCH2), 4.58 (s, 4H, NH2); 13C NMR (125.757 MHz,
DMSO-d6, ppm), dC = 169.15, 167.03, 156.76, 156.54,
135.72, 129.68, 129.54, 124.81, 116.84, 116.76, 107.13,
107.01, 66.72, 65.17; HRMS (EI): m/z [M+] calcd. for
C14H16N4O4: 304.1172; found: 304.1169.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-benzylidene-
acetohydrazide] (4a)
mp. 199-201 ºC; IR (KBr) nmax: 3432, 3091, 2925,
1691, 1629, 1399, 1259, 1070 cm-1; 1H NMR (500 MHz,
DMSO-d6, ppm), dH = 11.61 (t, 2H, J = 8.25 Hz, NH), 8.34
(d, 1H, J = 22.0 Hz, N=CH), 8.03 (d, 1H, J = 10.5 Hz,
N=CH), 7.69-7.83 (m, 6H, o-ArH of bezylidene ring &
C-4,5 ArH of naphthalene ring), 7.41-7.53 (m, 6H, m,p-
ArH of bezylidene ring), 7.05-7.26 (m, 4H, C-1,8 & C-3,6
ArH of naphthalene ring), 5.25 (d, 2H, J = 11.0 Hz, OCH2),
4.77 (d, 2H, J = 13.0 Hz, OCH2); 13C NMR (125.757 MHz,
DMSO-d6, ppm), dC = 169.36, 164.64, 157.24, 157.15,
156.81, 156.70, 148.47, 144.34, 144.26, 135.94, 135.85,
134.46, 130.64, 130.38, 129.57, 129.51, 129.41, 129.39,
129.29, 129.24, 128.83, 127.60, 127.42, 124.74, 124.55,
116.79, 116.55, 107.17, 106.99, 106.91, 67.07, 65.25;
HRMS (EI): m/z [M+] calcd. for C28H24N4O4: 480.1798;
General procedure for the preparation of compound
2,2¢-[naphthalene-2,7-diylbis(oxy)]bis[N¢-substituted
acetohydrazide] (4a-m)
Method A:
A mixture of compound 2,2¢-[naphthalene-2,7-diyl-

Ultrasound Assisted Synthesis of Schiff Base Derivatives
J. Chin. Chem. Soc., Vol. 58, No. 5, 2011 587
found: 480.1784.
7.54 (m, 4H, o-ArH of bezylidene ring), 7.03-7.25 (m, 4H,
C-1,8 & C-3,6 ArH of naphthalene ring), 6.70-6.77 (m, 4H,
m-ArH of bezylidene ring), 5.19 (d, 2H, J = 12.0 Hz,
OCH2), 4.71 (d, 2H, J = 14.5 Hz, OCH2), 2.98 (q, 12H, J =
19.0 Hz, CH3); 13C NMR (125.757 MHz, DMSO-d6, ppm),
dC = 168.74, 168.72, 163.91, 160.26, 157.29, 157.21,
156.86, 156.74, 152.05, 151.89, 151.84, 149.31, 145.18,
145.08, 135.97, 135.86, 129.95, 129.64, 129.53, 129.48,
129.37, 128.94, 128.68, 124.69, 124.50, 121.82, 116.76,
116.48, 112.24, 112.16, 107.15, 106.94, 67.13, 65.27;
HRMS (EI): m/z [M+] calcd. for C32H34N6O4: 566.2642;
found: 566.2640.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(4-chloroben-
zylidene)acetohydrazide] (4b)
mp. 236-238 ºC; IR (KBr) nmax: 3428, 3091, 2979,
1689, 1630, 1514, 1402, 1308, 1206, 1178 , 1088 cm-1; 1H
NMR (500 MHz, DMSO-d6, ppm), dH = 11.67 (d, 2H, J =
12.0 Hz, NH), 8.33 (d, 1H, J = 14.0 Hz, N=CH), 8.02 (d,
1H, J = 9.5 Hz, N=CH), 7.70-7.71 (m, 6H, o-ArH of bez-
ylidene ring & C-4,5 ArH of naphthalene ring), 7.47-7.60
(m, 4H, m-ArH of bezylidene ring), 7.04-7.24 (m, 4H,
C-1,8 & C-3,6 ArH of naphthalene ring), 5.24 (d, 2H, J =
11.5 Hz, OCH2), 4.77 (d, 2H, J = 12.0 Hz, OCH2); HRMS
(EI): m/z [M+] calcd. for C28H22Cl2N4O4: 548.1018; found:
548.1015.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(4-ethoxy-3-
methoxybenzylidene)acetohydrazide] (4f)
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(4-methoxy-
benzylidene)acetohydrazide] (4c)
mp. 169-171 ºC; IR (KBr) nmax: 3442, 3061, 2927,
1679, 1634, 1513, 1466, 1391, 1266, 1139, 1080 cm-1; 1H
NMR (500 MHz, DMSO-d6, ppm), dH = 11.48 (q, 2H, J =
16.0 Hz, NH), 8.26 (s, 1H, N=CH), 7.94 (d, 1H, J = 12.0
Hz, N=CH), 7.74-7.82 (m, 2H, C-4,5 ArH of naphthalene
ring), 7.29-7.34 (m, 2H, o¢-ArH of bezylidene ring), 7.04-
7.23 (m, 6H, C-1,3,6,8 ArH of naphthalene ring & o-ArH
of bezylidene ring), 6.95-7.00 (m, 2H, m-ArH of bezyli-
dene ring), 5.24 (d, 2H, J = 14.0 Hz, OCH2), 4.74 (d, 2H, J
= 15.0 Hz, OCH2), 4.01-4.07 (m, 4H, OCH2 of ethoxy
group), 3.78 (t, 6H, J = 5.0 & 10.5 Hz, OCH3), 1.33 (q, 6H,
J = 6.75 Hz, CH3); HRMS (EI): m/z [M+] calcd. for
C34H36N4O8: 628.2533; found: 628.0453.
mp. 189-191 ºC; IR (KBr) nmax: 3424, 3059, 2913,
1678, 1605, 1540, 1509, 1445, 1384, 1253, 1170, 1084
cm-1; 1H NMR (500 MHz, DMSO-d6, ppm), dH = 11.46 (t,
2H, J = 12.75 Hz, NH), 8.29 (s, 1H, N=CH), 7.97 (d, 1H, J
= 10.5 Hz, N=CH), 7.74-7.82 (m, 2H, C-4,5 ArH of naph-
thalene ring), 7.62-7.68 (m, 4H, o-ArH of bezylidene ring),
7.04-7.25 (m, 4H, C-1,8 & C-3,6 ArH of naphthalene ring),
6.97-7.01 (m, 4H, m-ArH of bezylidene ring), 5.21 (d, 2H,
J = 12.0 Hz, OCH2), 4.74 (d, 2H, J = 13.5 Hz, OCH2); 3.79
(d, 6H, J = 8.5 Hz, OCH3); HRMS (EI): m/z [M+] calcd. for
C30H28N4O6: 540.2009; found: 540.2004.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(2,4-dichloro-
benzylidene)acetohydrazide] (4d)
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(3-nitroben-
zylidene)acetohydrazide] (4g)
mp. 230-232 ºC; IR (KBr) nmax: 3432, 3091, 2925,
1691, 1629, 1399, 1259, 1070 cm-1; 1H NMR (500 MHz,
DMSO-d6, ppm), dH = 11.83 & 11.92 (2d, 2H, J = 9.0 & 9.5
Hz, NH), 8.36 & 8.71 (d & s, 1H, J = 10.0 Hz, N=CH), 7.96
& 8.05 (d & t, 1H, J = 8.5 & 9.0 Hz, N=CH), 7.70-7.83 (m,
4H, o-ArH of bezylidene ring & C-4,5 ArH of naphthalene
ring), 7.44-7.52 (m, 2H, m-ArH of bezylidene ring), 7.05-
7.26 (m, 6H, C-1,8 & C-3,6 ArH of naphthalene ring and
m¢-ArH of bezylidene ring), 5.26 (d, 2H, J = 12.0 Hz,
OCH2), 4.79 (d, 2H, J = 12.0 Hz, OCH2); HRMS (EI): m/z
[M+] calcd. for C28H20Cl4N4O4: 618.0209; found: 618.0209.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(4-(dimethyl-
amino)benzylidene)acetohydrazide] (4e)
mp. 251-253 ºC; IR (KBr) nmax: 3429, 3190, 3043,
2920, 1676, 1628, 1385, 1255, 1169, 1067 cm-1; 1H NMR
(500 MHz, DMSO-d6, ppm), dH = 11.85 (t, 2H, J = 16.0 Hz,
NH), 8.46-8.51 (split peak, 2H, N=CH), 8.12-8.24 (m, 6H,
o & p-ArH of bezylidene ring), 7.67-7.82 (m, 4H, m-ArH
of bezylidene ring & C-4,5 ArH of naphthalene ring),
7.06-7.23 (m, 4H, C-1,8 & C-3,6 ArH of naphthalene ring),
5.30 (d, 2H, J = 12.5 Hz, OCH2), 4.80 (d, 2H, J = 12.5 Hz,
OCH2); HRMS (EI): m/z [M+] calcd. for C28H22N6O8:
570.1499; found: 570.1495.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(3-ethoxy-4-
hydroxybenzylidene)acetohydrazide] (4h)
mp. 210-212 ºC; IR (KBr) nmax: 3369, 3070, 2989,
1668, 1598, 1511, 1438, 1394, 1284, 1167, 1070 cm-1; 1H
NMR (500 MHz, DMSO-d6, ppm), dH = 11.42 (t, 2H, J =
16.5 Hz, NH), 9.48 (d, 1H, J = 3.0 Hz, OH), 9.41 (d, 1H, J =
11.0 Hz, OH), 8.21 (s, 1H, N=CH), 7.89 (d, 2H, J = 11.0
Hz, N=CH), 7.74-7.80 (m, 2H, C-4,5 ArH of naphthalene
mp. 220-222 ºC; IR (KBr) nmax: 3443, 2926, 1664,
1604, 1520, 1368, 1213, 1169, 1068 cm-1; 1H NMR (500
MHz, DMSO-d6, ppm), dH = 11.30 (split peak, 2H, NH),
8.19 (s, 1H, N=CH), 7.90 (d, 1H, J = 11.5 Hz, N=CH),
7.64-7.81 (m, 2H, C-4,5 ArH of naphthalene ring), 7.49-

588 J. Chin. Chem. Soc., Vol. 58, No. 5, 2011
Venkatesan et al.
ring), 7.05-7.28 (m, 8H, o-ArH of bezylidene ring and
C-1,8 & C-3,6 ArH of naphthalene ring), 6.81-6.85 (q, 2H,
J = 8.25 Hz, m ArH of bezylidene ring), 5.21 (d, 2H, J =
13.0 Hz, OCH2), 4.73 (d, 2H, J = 13.5 Hz, OCH2), 4.00-
4.05 (m, 4H, OCH2 of ethoxy), 1.28-1.36 (m, 6H, CH3);
HRMS (EI): m/z [M+] calcd. for C32H32N4O8: 600.2220;
found: 600.2219.
found: 568.2320.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(3-phenyl-
allylidene)acetohydrazide] (4l)
mp. 221-223 ºC; IR (KBr) nmax: 3450, 3053, 2922,
1701, 1623, 1526, 1374, 1206, 1060 cm-1; 1H NMR (500
MHz, DMSO-d6, ppm), dH = 11.51 (t, 2H, J = 11.0 Hz,
NH), 8.13 (d, 1H, J = 4.0 Hz, N=CH), 7.75-7.87 (m, 3H,
C-4,5 ArH of naphthalene ring and N=CH), 7.59-7.62 (m,
4H, o-ArH of bezylidene ring), 7.28-7.41 (m, 6H, m,p-ArH
of bezylidene ring), 7.05-7.24 (m, 8H, C-1,8 & C-3,6 ArH
of naphthalene ring & CH=CH), 5.14 (d, 2H, J = 9.0 Hz,
OCH2), 4.75 (d, 2H, J = 10.0 Hz, OCH2); 13C NMR
(125.757 MHz, DMSO-d6, ppm), dC = 168.99, 164.48,
157.17, 157.11, 150.36, 146.87, 146.79, 139.80, 139.48,
139.41, 136.30, 129.56, 129.41, 129.30, 127.58, 127.52,
125.91, 125.46, 116.74, 116.54, 107.12, 106.87, 106.81,
67.02, 65.13; HRMS (EI): m/z [M+] calcd. for C32H28N4O4:
532.2111; found: 532.2109.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(4-hydroxy-3-
methoxybenzylidene)acetohydrazide] (4i)
mp. 216-218 ºC; IR (KBr) nmax: 3445, 3048, 2993,
2432, 1661, 1606, 1513, 1437, 1291, 1163, 1077, 1027
cm-1; 1H NMR (500 MHz, DMSO-d6, ppm), dH = 11.42 (t,
2H, J = 17.5 Hz, NH), 9.51 (split peak, 2H, OH), 8.23 (s,
1H, N=CH), 7.91 (d, 1H, J = 9.5 Hz, N=CH), 7.74-7.80 (m,
2H, C-4,5 ArH of naphthalene ring), 7.04-7.23 (m, 8H,
o,o¢-ArH of bezylidene ring & C-1,8 & C-3,6 ArH of naph-
thalene ring), 6.82 (t, 2H, J = 8.5 & 8.5 Hz, m¢-ArH of
bezylidene ring), 5.23 (d, 2H, J = 13.0 Hz, OCH2), 4.74 (d,
2H, J = 13.5 Hz, OCH2), 3.79 (split peak, 6H, OCH3);
HRMS (EI): m/z [M+] calcd. for C30H28N4O8: 572.1907;
found: 572.1905.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(thiophen-2-
ylmethylene)acetohydrazide] (4m)
mp. 162-164 ºC; IR (KBr) nmax: 3431, 3105, 2928,
1686, 1631, 1425, 1266, 1170, 1073 cm-1; 1H NMR (500
MHz, DMSO-d6, ppm), dH = 11.57 (q, 2H, J = 14.5 Hz,
NH), 8.57 (s, 1H, N=CH), 8.21 (d, 1H, J = 11.0 Hz,
N=CH), 7.74-7.82 (m, 2H, C-4,5 ArH of naphthalene ring),
7.61-7.67 (m, 2H, C-5 ArH of thiophene ring), 7.44-7.46
(m, 2H, C-3 ArH of thiophene ring), 7.03-7.25 (m, 6H,
C-1,8 & C-3,6 ArH of naphthalene ring & C-4 ArH of
thiophene ring), 5.14 (d, 2H, J = 10.5 Hz, OCH2), 4.75 (d,
2H, J = 12.5 Hz, OCH2); 13C NMR (125.757 MHz, DMSO-
d6, ppm), dC = 168.98, 164.47, 157.20, 156.77, 156.66,
143.63, 139.48, 139.42, 139.29, 139.10, 135.81, 131.60,
131.01, 130.95, 129.66, 129.56, 129.42, 129.05, 129.00,
128.33, 124.75, 116.74, 116.56, 107.24, 107.18, 106.92,
106.86, 67.08, 65.02; HRMS (EI): m/z [M+] calcd. for
C24H20N4O4S2: 492.0926; found: 492.1065.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(3-methylben-
zylidene)acetohydrazide] (4j)
mp. 227-229 ºC; IR (KBr) nmax: 3417, 3262, 3070,
2989, 1668, 1598, 1438, 1394, 1284, 1167, 1080 cm-1; 1H
NMR (500 MHz, DMSO-d6, ppm), dH = 11.58 (d, 2H, J =
15.0 Hz, NH), 8.30 (s, 1H, N=CH), 7.99 (d, 1H, J = 12.5
Hz, N=CH), 7.75-7.82 (m, 2H, C-4,5 ArH of naphthalene
ring), 7.46-7.55 (m, 4H, o-ArH of bezylidene ring), 7.04-
7.34 (m, 8H, m,p-ArH of benzylidene ring and C-1,8 &
C-3,6 ArH of naphthalene ring), 5.24 (d, 2H, J = 12.5 Hz,
OCH2), 4.76 (d, 2H, J = 14.0 Hz, OCH2), 2.33 (t, 6H, J =
7.75 Hz, CH3); HRMS (EI): m/z [M+] calcd. for C30H28N4O4:
508.2111; found: 508.2108.
2,2¢-[Naphthalene-2,7-diylbis(oxy)]bis[N¢-(4-ethoxyben-
zylidene)acetohydrazide] (4k)
mp. 218-220 ºC; IR (KBr) nmax: 3421, 3069, 2927,
1676, 1606, 1511, 1392, 1253, 1170, 1070 cm-1; 1H NMR
(500 MHz, DMSO-d6, ppm), dH = 11.47 (q, 2H, J = 11.25
Hz, NH), 8.28 (s, 1H, N=CH), 7.96 (d, 1H, J = 10.5 Hz,
N=CH), 7.74-7.82 (m, 2H, C-4,5 ArH of naphthalene ring),
7.61-7.67 (m, 4H, o-ArH of bezylidene ring), 7.04-7.25 (m,
4H, C-1,8 & C-3,6 ArH of naphthalene ring), 6.94-6.99 (m,
4H, m-ArH of bezylidene ring), 5.21 (d, 2H, J = 12.0 Hz,
OCH2), 4.74 (d, 2H, J = 13.5 Hz, OCH2), 4.02-4.079 (m,
4H, OCH2 of ethoxy group), 1.32-1.35 (m, 6H, CH3);
HRMS (EI): m/z [M+] calcd. for C32H32N4O6: 568.2322;
Assay of DPPH free radical scavenging activity
The radical-scavenging activity of compounds 4a-m
was evaluated and compared to that of butylated hydroxy
toulene (BHT) by using the DPPH radical scavenging as-
say.26 This assay is based on the measurements of the scav-
enging ability of compounds towards the stable radical
2,2-diphenyl-1-picrylhydrazyl (DPPH×). The disappear-
ance of this commercially available radical is measured
spectrophotometrically at 517 nm in a dimethyl sulphoxide
(DMSO) solution using a UV/Vis-spectrophotometer (Model
UV-1700(E) 23 OCE, Shimadzu, Japan) under thermo-

Ultrasound Assisted Synthesis of Schiff Base Derivatives
J. Chin. Chem. Soc., Vol. 58, No. 5, 2011 589
A. Eur. J. Med. Chem. 1996, 31, 989.
stated conditions at 25 ºC. 3.0 mL of a freshly prepared
DPPH solution of 6.02 ´ 10-5 M in DMSO was placed in a
test tube and 100 µL of a DMSO solution of each test com-
pound was added. After that solution was kept at room tem-
perature for 30 min in dark and the absorbance was mea-
sured at 517 nm. The control contained all the reaction re-
agents except the synthetic compound or positive control
substance. The experiment was carried out in triplicate.
The DPPH scavenging activity was expressed as the inhibi-
tion of free radical DPPH in percent (I %) as described by
Tepe et al,27 and the values are listed in Table 2.
9. Valentina, P.; Ilango, K.; Deepthi, M.; Harusha, P.; Pavani,
G. J. Pharm. Sci. & Res. 2009, 1, 74.
10. Satyanarayana, V. S. V.; Madhumita, R.; Sivakumar, A.
Asian J. Chem. 2011, 23, 1212.
11. Satyanarayana, V. S. V.; Madhumita, R.; Sivakumar, A. A. J.
Chem. 2011, 23, 1295.
12. Haviv, F.; Ratajczyk, J. D.; Denet, R. W.; Kerdesky, F. A.;
Walters, R. L.; Schmidt, S. P.; Holms, J. H.; Young, P. R.;
Carter, G. W. J. Med. Chem. 1988, 31, 1719.
13. Patt, W. C.; Hamilton, H. W.; Taylor, M. D.; Ryan, M. J.;
Taylor, D. G.; Connolly, C. J.; Doherty, A. M.; Klutchko, S.
R.; Sircar, I. J. Med. Chem. 1992, 35, 2562.
14. Bell, F. W.; Cantrell, A. S.; Hoegberg, M.; Jaskunas, S. R.;
Johansson, N. G.; Jordan, C. L.; Kinnick, M. D.; Lind, P.;
Morin, J. M. J. Med. Chem. 1995, 38, 4929.
Inhibition (%) = [(control OD – sample OD)/control
OD] ´ 100.
15. Kumar, Y.; Green, R.; Wise, D. S.; Wotring, L. L.; Townsend,
L. B. J. Med. Chem. 1993, 36, 3849.
ACKNOWLEDGEMENTS
16. Medime, E.; Capan, G. II Farmaco 1994, 49, 449.
17. Metzger, J. V. Comprehensive Heterocyclic Chemistry;
Pergamon; New York; 1984; p 328.
Authors gratefully acknowledge the management of
VIT University, Vellore for encouraging and providing
necessary facilities for carrying out this work.
18. George, R. S.; Joseph, R.; George, K. E. Int. J. Polym. Mat-
ter. 1993, 23, 17.
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