Microwave-assisted synthesis and evaluation of antibacterial activity of 2,2'-(naphthalene-2,7-diylbis(oxy))bis(n'-substituted acetohydrazide) derivatives

Article abstract of DOI:10.4314/bcse.v26i2.9

A series of Schiff base of 2,2'-(naphthalene-2,7-diylbis(oxy))bis(N'- substituted acetohydrazide) (4a-m) derivatives has been synthesized by the acid catalyzed condensation of aryl/hetero aromatic aldehydes with 2,2'-(naphthalene-2,7-diylbis(oxy))diacetoh

Full text of DOI:10.4314/bcse.v26i2.9

Bull. Chem. Soc. Ethiop. 2012, 26(2), 257-265.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v26i2.9
ISSN 1011-3924
 2012 Chemical Society of Ethiopia
MICROWAVE-ASSISTED SYNTHESIS AND EVALUATION OF ANTIBACTERIAL
ACTIVITY OF 2,2'-(NAPHTHALENE-2,7-DIYLBIS(OXY))BIS(N'-SUBSTITUTED
ACETOHYDRAZIDE) DERIVATIVES
K. Venkatesan, V.S.V. Satyanarayana, A. Sivakumar*
Chemistry Division, School of Advanced Sciences, VIT University, Vellore – 632 014, India
(Received September 16, 2011; revised March 9, 2012)
ABSTRACT. A series of Schiff base of 2,2'-(naphthalene-2,7-diylbis(oxy))bis(N'-substituted acetohydrazide)
(4a-m) derivatives has been synthesized by the acid catalyzed condensation of aryl/hetero aromatic aldehydes
with 2,2'-(naphthalene-2,7-diylbis(oxy))diacetohydrazide (3) under microwave irradiation and conventional
method for comparison. The structures of all the newly synthesized compounds have been characterized by IR, 1H
NMR, 13C NMR and Mass spectra. All the synthesized compounds have been screened for their in vitro
antibacterial activity.
KEY WORDS: 2,2'-(Naphthalene-2,7-diylbis(oxy))diacetohydrazide, Schiff base, Microwave irradiation,
Spectral characterization, Antibacterial activity
INTRODUCTION
The chemistry of the carbon-nitrogen double bond plays a vital role in the advancement of
synthetic organic chemistry. Schiff bases are usually synthesized by the condensation of primary
amines with compounds containing active carbonyl groups. Schiff bases are an important class
of compounds in medicine and pharmaceutics. They show biological applications including
antibacterial [1-6], antifungal [3-6], antitumor [7, 8], antioxidant [9, 10], anti-inflammatory
[11], antihypertensive [12], anti-HIV [13], antifilarial [14], anticonvulsant [15], herbicidal,
insecticidal, schistosomicidal and anthelmintic activities [16]. Schiff bases are used as
protective agents in natural rubber [17]. Recently there has been a considerable interest in the
chemistry of hydrazine and hydrazone compounds because of their potential pharmacological
applications [18]. The remarkable reactivity of acid hydrazides R–CONHNH2 [19] and the
biological activity associated with their corresponding hydrazones attributed to the presence of
the active pharmacophore (-CONH-N=CH-). Hence many hydrazone compounds containing this
active moiety are known to exhibit good anticancer bioactivities according to the literature [20].
Some of the Schiff bases complex combinations with metals are used as insecticides,
fungicides, herbicides [21].
Microwave-assisted organic synthesis (MAOS) has been known since 1986 [22]. This “non-
conventional” synthetic method has shown broad applications as a very efficient way to
accelerate the course of many organic reactions, producing high yields and higher selectivity,
lower quantities of side products and consequently, easier work-up procedures and purification
of the products. MAOS is considered as “green” technology, principally since many organic
reactions can be carried out in solvent-free conditions [23]. In recent years, researchers have
applied microwave as a tool in order to reduce reaction time, avoid side products, increase yield
and simplify the course of reaction for combinatorial chemistry [24]. Solvent-free reactions are
of interest not only from an ecological point of view but in many cases they also offer
considerable advantages in terms of yield, selectivity and simplicity.
__________
*Corresponding author. E-mail: svkmr7627@gmail.com

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In many cases reactions that normally require many hours at reflux temperature under
normal synthetic conditions can be completed within several minutes or even seconds in a
microwave oven. Recent simplification of microwave organic reaction enhancement (MORE)
technique has increased safety and practical utility of the microwave oven for their use in
organic laboratories without any modification.
Hence, in this paper, we are reporting eco-friendly synthesis of some new Schiff bases by
condensing 2,2'-(naphthalene-2,7-diylbis(oxy))diacetohydrazide with aryl/hetero aromatic
aldehydes using microwave irradiation technique and the yields are compared with traditional
method and their characterization carried out using IR, 1H NMR,13CNMR and Mass spectra. All
the synthesized compounds have been screened for their antibacterial activity.
EXPERIMENTAL
Screening of antibacterial activity
The newly synthesized Schiff base compounds (4a-m) were screened for their antibacterial
activity against Escherichia coli (ATTC-25922) (E. coli), Staphylococcus aureus (ATTC-
25923) (S. aureus) and Pseudomonas aeruginosa (ATCC-27853) (P. aeruginosa) bacterial
strains by agar well diffusion method in Muller Hinton agar medium. Twenty milliliters of agar
media was poured into each Petri dish and plates were dried by placing in an incubator at 37 °C
for an hour. Using a punch, wells were made on these seeded agar plates and concentrations of
the test compounds in dimethylsulfoxide (DMSO) were added into each labelled well. A control
was also prepared for the plates in the same way using solvent DMSO. All the plates were
incubated at 37 °C for 24 hrs for incubation. The degree of effectiveness was measured by
determining the diameters of the zone of inhibition caused by the compounds. Activity of each
compound was compared with standard drug tetracycline which is available in the market.
General
All reagents were purchased from Aldrich, SD Fine Chemicals and Qualigens and used without
further purification. For the microwave irradiation experiments described below a conventional
(unmodified) household microwave oven equipped with a turntable was used (LG, MG-395
WA, 760 W) and operating at 2450 MHz. The melting points were determined by open
capillaries and are uncorrected. Infrared (IR) spectra were recorded at room temperature from
4000 cm-1 to 400 cm-1 with KBr pellets at a resolution of 4 cm-1, using Avatar 330 equipped with
DTGS detector. 1H NMR and 13C NMR spectra were recorded on a Bruker AV-500 MHz,
spectrometer in DMSO-d6, CDCl3 using TMS as internal standard and the values are expressed
in ppm. Mass spectra were obtained by using HRMS.
Procedure for the preparation of compound diethyl 2,2'-[naphthalene-2,7-diylbis(oxy)]di
acetate (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 it was poured into a large
amount of water. The solid separated was filtered and washed with excess of water. The crude
product was recrystallized from ethanol. Yield of the product was 81-82% [lit. yield 40%] [25].
M.p. 92-94 ºC; IR (KBr) νmax: 3258, 2917, 1760, 1654, 1628, 1518, 1384, 1204, 1173, 1076,
1
1024 cm-1; H NMR (500 MHz, CDCl3, ppm), δH = 7.71 (d, 2H, J = 9.0 Hz , C-4,5 ArH of
naphthalene ring), 7.12 (dd, 2H, J = 2.5 and 9.0 Hz, C-3,6 ArH of naphthalene ring), 6.99 (d,
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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), δC = 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.
Procedure for the preparation of compound 2,2'-[naphthalene-2,7-diylbis(oxy)]diaceto
hydrazide (3)
Compound 2 (0.01 mole) in ethanol (20 mL) were stirred at room temperature for 20 min. To
this mixture hydrazine hydrate (0.03 mol) was added and stirring continued for 15 more min.
The resultant mixture was refluxed for 6 h and the separated solid was filtered using 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%. M.p. 232-234 ºC; IR (KBr) νmax: 3311, 3206, 3029, 2923, 1699, 1622,
1
1471, 1385, 1212, 1174, 1060 cm-1; H NMR (500 MHz, DMSO-d6, ppm), δH = 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 and 4.96 (2s, 4H, OCH2), 4.58 (s, 4H, NH2); 13CNMR (125.757
MHz, DMSO-d6, ppm), δC = 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.
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-diylbis(oxy))diacetohydrazide 3 (0.01
mol) in chloroform/methanol (1:1) mixture (30 mL), aryl/hetero aromatic aldehyde (0.02 mole)
and 1mL of glacial acetic acid was refluxed for 4-5 h. The mixture was allowed to cool; the
solid separated was filtered, washed with excess of methanol and then dried at room
temperature.
Method B. A mixture of 2,2'-(naphthalene-2,7-diylbis(oxy))diacetohydrazide 3 (0.01 mol),
aryl/hetero aromatic aldehyde (0.02 mol) and catalytic amount of glacial acetic acid were taken
in DMSO (2 mL) in a beaker and then the reaction mixture was subjected to microwave
irradiation at an interval of 1 min at 180 W for about 1-2 min; progress of the reaction was
monitored by TLC. After the completion of the reaction, the obtained product was poured into
ice cold water stirred well and the solid separated was filtered, washed with excess of methanol
and then dried at room temperature.
2,2'-[Naphthalene-2,7-diylbis(oxy)]bis[N'-benzylideneacetohydrazide] (4a). M.p. 199-201 ºC;
1
IR (KBr) νmax: 3432, 3091, 2925, 1691, 1629, 1399, 1259, 1070 cm-1; H NMR (500 MHz,
DMSO-d6, ppm), δH = 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 and 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 and
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), δC = 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; found: 480.1784.
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2,2'-[Naphthalene-2,7-diylbis(oxy)]bis[N'-(4-chlorobenzylidene)acetohydrazide] (4b). M.p.
236-238 ºC; IR (KBr) νmax: 3428, 3091, 2979, 1689, 1630, 1514, 1402, 1308, 1206, 1178, 1088
cm-1; 1H NMR (500 MHz, DMSO-d6, ppm), δH = 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 bezylidene
ring and 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 and 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-methoxybenzylidene)acetohydrazide] (4c). M.p.
189-191 ºC; IR (KBr) νmax 3424, 3059, 2913, 1678, 1605, 1540, 1509, 1445, 1384, 1253, 1170,
1084 cm-1; 1H NMR (500 MHz, DMSO-d6, ppm), δH = 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 naphthalene
ring), 7.62-7.68 (m, 4H, o-ArH of bezylidene ring), 7.04-7.25 (m, 4H, C-1,8 and 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 = 8.5Hz, 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-dichlorobenzylidene)acetohydrazide] (4d). M.p.
1
230-232 ºC; IR (KBr) νmax: 3432, 3091, 2925, 1691, 1629, 1399, 1259, 1070 cm-1; H NMR
(500 MHz, DMSO-d6, ppm), δH = 11.83 and 11.92 (2d, 2H, J = 9.0 and 9.5 Hz, NH), 8.36 &
8.71 (d and s, 1H, J = 10.0 Hz, N=CH), 7.96 and 8.05 (d & t, 1H, J = 8.5 and 9.0 Hz, N=CH),
7.70-7.83 (m, 4H, o-ArH of bezylidene ring and 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 and 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-(dimethylamino)benzylidene)acetohydrazide]
(4e). M.p. 220-222 ºC; IR (KBr) νmax: 3443, 2926, 1664, 1604, 1520, 1368, 1213, 1169, 1068
1
cm-1; H NMR (500 MHz, DMSO-d6, ppm), δH = 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),
7.49-7.54 (m, 4H, o-ArH of bezylidene ring), 7.03-7.25 (m, 4H, C-1,8 and 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), δC = 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-ethoxy-3-methoxybenzylidene)acetohydrazide]
(4f). M.p. 169-171 ºC; IR (KBr) νmax: 3442, 3061, 2927, 1679, 1634, 1513, 1466, 1391, 1266,
1
1139, 1080 cm-1; H NMR (500 MHz, DMSO-d6, ppm), δH = 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 and o-ArH of bezylidene ring), 6.95-7.00 (m, 2H, m-ArH of bezylidene
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 and 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.
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2,2'-[Naphthalene-2,7-diylbis(oxy)]bis[N'-(3-nitrobenzylidene)acetohydrazide] (4g). M.p. 251-
1
253 ºC; IR (KBr) νmax: 3429, 3190, 3043, 2920, 1676, 1628, 1385, 1255, 1169, 1067 cm-1; H
NMR (500 MHz,DMSO-d6, ppm), δH = 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- and p-ArH of bezylidene ring), 7.67-7.82 (m, 4H, m-ArH of
bezylidene ring and C-4,5 ArH of naphthalene ring), 7.06-7.23 (m, 4H, C-1,8 and 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-ydroxybenzylidene)acetohydrazide]
(4h). M.p. 210-212 ºC; IR (KBr) νmax: 3369, 3070, 2989, 1668, 1598, 1511, 1438, 1394, 1284,
1
1167, 1070 cm-1; H NMR (500 MHz, DMSO-d6, ppm), δH = 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 ring), 7.05-7.28 (m, 8H, o-
ArH of bezylidene ring and C-1,8 and 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.
2,2'-[Naphthalene-2,7-diylbis(oxy)]bis[N'-(4-hydroxy-3-methoxybenzylidene) acetohydrazide]
(4i). M.p. 216-218 ºC; IR (KBr) νmax: 3445, 3048, 2993, 2432, 1661, 1606, 1513, 1437, 1291,
1
1163, 1077, 1027 cm-1; H NMR (500 MHz, DMSO-d6, ppm), δH = 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 and C-
1,8 and C-3,6 ArH of naphthalene ring), 6.82 (t, 2H, J = 8.5 and 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'-(3-methylbenzylidene)acetohydrazide] (4j). M.p.
227-229 ºC; IR (KBr) νmax: 3417, 3262, 3070, 2989, 1668, 1598, 1438, 1394, 1284, 1167, 1080
1
cm-1; H NMR (500 MHz, DMSO-d6, ppm), δH = 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 and 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-ethoxybenzylidene)acetohydrazide] (4k). M.p.
218-220 ºC; IR (KBr) νmax: 3421, 3069, 2927, 1676, 1606, 1511, 1392, 1253, 1170, 1070 cm-1;
1H NMR (500 MHz, DMSO-d6, ppm), δH = 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 and 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; found: 568.2320.
2,2'-[Naphthalene-2,7-diylbis(oxy)]bis[N'-(3-phenylallylidene)acetohydrazide] (4l). M.p. 221-
1
223 ºC; IR (KBr) νmax: 3450, 3053, 2922, 1701, 1623, 1526, 1374, 1206, 1060 cm-1; H NMR
(500 MHz, DMSO-d6, ppm), δH = 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-
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1,8 and C-3,6 ArH of naphthalene ring and 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), δC = 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'-(thiophen-2-ylmethylene)acetohydrazide] (4m). M.p.
1
162-164 ºC; IR (KBr) νmax: 3431, 3105, 2928, 1686, 1631, 1425, 1266, 1170, 1073 cm-1; H
NMR (500 MHz, DMSO-d6, ppm), δH = 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 and C-3,6 ArH of naphthalene ring and 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, DMSOd6,
ppm), δC = 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.
RESULTS AND DISCUSSION
In the present study, diethyl 2,2'-(naphthalene-2,7-diylbis(oxy))diacetate (2) was synthesized
from 2,7-dihydroxy naphthalene 1 on reacting with ethyl chloroacetate in anhydrous potassium
carbonate and dry DMF at 80ºC for 16 hours resulting in 82% yield (Scheme 1) [25]. The IR
spectrum of compound 2 exhibited absorption frequency at 1760 cm-1 for carbonyl group. In 1H
NMR of compound 2 the characteristic signals of an ester moiety confirm the presence of ester
group in the structure by resonating as quartet and triplet for -CH2 and -CH3 at δ 4.31 ppm and
δ 1.32 ppm respectively, which indicates acetate formation. Treatment of compound 2 with
hydrazine hydrate in ethanol and refluxing for 6 hours resulted in the formation of 2,2'-
(naphthalene-2,7-diylbis(oxy))diacetohydrazide 3. The structure of compound
3 was
confirmed by IR, 1H NMR and Mass spectra. IR spectrum showed the absence of ester
stretching frequency, instead it gave band at 1699 cm-1 for carbonyl group and showed two
sharp bands in the region of 3311 and 3206cm-1 due to -NH and –NH2 groups.
O
O
HO
OH
O
O
K2CO
3
O
O
O
O
dryDMF, 80oC
Cl
1
2
NH NH .H2O
2
2
O
O
O
O
R-CHO
H2N
O
O
NH
2
N
O
O
N
R
R
N
H
N
H
N
H
N
H
H+,MW
3
4a-m
Scheme 1. Synthetic pathway for the preparation of compounds 4a-m.
Bull. Chem. Soc. Ethiop. 2012, 26(2)

2,2'-(Naphthalene-2,7-diylbis(oxy))bis(n'-substituted acetohydrazide) derivatives
263
Table 1. Data of synthesized Schiff base compounds 4a-m.
Reaction time (min)
Yielda (%)
Conventional
Entry
R
M.p. (ºC)
MW
1.0
1.5
1.0
1.5
1.5
1.5
2.0
1.5
1.5
1.5
1.0
2.0
1.5
Conventional
180
210
MW
90
88
87
85
86
83
85
84
83
86
87
82
84
4a
4b
4c
4d
4e
4f
Phenyl
4-ClPh
83
80
80
76
77
75
77
76
75
79
80
73
78
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
210
240
4-N(CH3)2Ph
4-OEt,3-CH3OPh
3-NO2Ph
240
240
4g
4h
4i
240
210
3-OEt,4-OHPh
4-OH,3-CH3OPh
3-CH3Ph
210
240
4j
4k
4l
4-EtOPh
Cinnamyl
2-Thiophenyl
210
240
4m
210
a = Isolated yield; MW = Microwave.
1H NMR spectrum of compound 3 exhibited no peak corresponding to ester, instead it
showed signals at δ 9.41 ppm and δ 4.58 ppm for -NH and -NH2 of hydrazide.
Compound 3 was treated with substituted aromatic aldehyde in presence of catalytic amount
of acetic acid in (1:1) methanol/chloroform mixture and DMSO under reflux temperature and
microwave irradiation to synthesise 2,2'-(naphthalene-2,7-diylbis(oxy))bis(N'-substituted
acetohydrazides 4a-m. The IR spectra of the compound 4a revealed two strong absorption
1
bands at 1629 cm-1 and 1691 cm-1 for C=O and C=N group respectively. The H NMR spectra
of compound (4a) displayed two doublets due to methylene protons at δ 5.25 & 4.77 ppm and
the NH group was resonated as triplet at δ 11.61 ppm. The peaks of naphthalene aromatic and
phenyl group protons appeared between 7.05-7.83 ppm. The signals belonging to -N=CH
protons were observed as doublets at δ 8.03 & 8.34 ppm, the disappearance of NH2 signal of
compound 3 in compound 4a indicates the functionalization of hydrazide to hydrazone. 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. Shorter reaction times were
observed for the formation of compounds 4a-m under microwave irradiation rather than the
reflux temperature. Reaction time for the formation of compound 4a is one minute under
microwave irradiation and 180 minutes under reflux temperature with slightly improved yields,
respectively. Comparative yields of all the synthesized products with respect to reaction time
and reflux temperature as well as microwave irradiation and are given in Table 1.
The newly synthesized Schiff base compounds (4a-m) were screened for their antibacterial
activity against E. coli, S. aureus and P. aeruginosa bacterial strains by agar well diffusion
method in Muller Hinton agar medium. Zone of inhibition was determined for all the newly
synthesized compounds and the results are summarized in Table 2. The synthesized compounds
4h and 4i, having 3-ethoxy-4-hydroxybenzylidene and 3-methoxy-4-hydroxybenzylidene ring as
substitute R showed potent activity against S.aureus, E.coli and P.aeruginosa, whereas the
compounds 4d and 4l, having 3-nitro benzylidene and cinnamyl ring as substitute R showed
least activity against S.aureus, E.coli and P.aeruginosa. The compounds 4a, 4b, 4c, 4f and 4m
showed good activity against E.coli, S.aureus and P.aeruginosa. The compound 4e also showed
good activity against E.coli and moderate activity against S.aureus and P.aeruginosa. The above
results indicate that the compounds containing electron donating groups show good activity than
the compounds containing electron withdrawing groups and the results were depicted in Table
2.
Bull. Chem. Soc. Ethiop. 2012, 26(2)

264
A. Sivakumar et al.
Table 2. Antibacterial activities of the Schiff base compounds 4a-m.
Compound
Antibacterial activitya (MIC, mg/mL)
S. aureus
8 (250)
E. coli
8 (250)
8 (250)
9 (250)
11 (500)
12 (500)
9 (250)
8 (500)
11 (250)
15 (250)
10 (750)
8 (500)
8 (500)
9 (250)
16 (250)
Ps. aeruginosa
9 (500)
8 (250)
4ª
4b
11 (500)
8 (250)
4c
4d
9 (250)
9 (500)
9 (500)
10 (750)
9 (500)
9 (250)
4e
4f
4g
10 (250)
8 (500)
8 (250)
10 (500)
12 (250)
19 (250)
9 (500)
4h
4i
9 (250)
8 (500)
9 (500)
4j
4k
10 (500)
11 (750)
9 (250)
4l
4m
10 (500)
9 (500)
12 (250)
Tetracyclineb
14 (250)
azone of inhibition in mm; bStandard antibacterial drug.
CONCLUSIONS
In this work, the synthesis of naphthalene substituted Schiff base derivatives 4a-m derived from
2,2'-(naphthalene-2,7-diylbis(oxy))diacetohydrazide with aromatic/hetero aldehyde in
3
presence of acid catalyst under conventional heating and by the use of microwave irradiation, is
reported. The advantages of the method employed include simple reaction set-up, high product
yield, short reaction times and use of small amount of solvents or no solvents. The structures of
the synthesized compounds have been confirmed through spectral characterization such as IR,
1H NMR, 13C NMR and mass spectra. From the antibacterial screening carried out, it is
observed that compounds 4a-m exhibited activity which is comparable with activity of standard
drug.
ACKNOWLEDGEMENTS
Authors gratefully acknowledge the management of VIT University, Vellore for encouraging
and providing necessary facilities for carrying out this work.
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