Synthesis, characterization and antimicrobial evaluation of (E)-N'-[(1-(2-methoxy-6-pentadecylbenzyl)-1H-1,2,3-triazol-4-yl]-methylene)benzohydrazide derivatives

Article abstract of DOI:10.14233/ajchem.2016.19310

Anacardic acid (pentadecyl salicylic acid) is a phenolic constituent present in cashew nut shell liquid (Anacardium occidentale L.) and exhibits antimicrobial properties. The present paper describes the synthesis, characterization and antimicrobial evaluation of hydrazone derivatives of anacardic acid (9a-l) linked with 1,2,3-triazole ring. All the newly synthesized compounds were determined by 1H NMR, mass and IR spectroscopy. Compounds 9d, 9e, 9h, 9i and 9j exhibited strong antifungal activity against the tested fungal strains viz., A. Niger and C. albicans.

Full text of DOI:10.14233/ajchem.2016.19310

Asian Journal of Chemistry; Vol. 28, No. 1 (2016), 175-180
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19310
Synthesis, Characterization and Antimicrobial Evaluation of
(E)-N'-[(1-(2-methoxy-6-pentadecylbenzyl)-1H-1,2,3-triazol-4-yl]-
methylene)benzohydrazide Derivatives
1
3
3
N. RAMBABU1,2,*, P.K. DUBEY , B. RAM and B. BALRAM
1Department of Chemistry, Jawaharlal Nehru Technological University, Hyderabad-500 072, India
2Syngene International Ltd, Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Banglore-560 099, India
3Green Evolution Laboratories, Wangapally Village, Nalgonda-500 085, India
*Corresponding author: E-mail: rambabun2013@gmail.com
Received: 30 April 2015;
Accepted: 22 June 2015;
Published online: 5 October 2015;
AJC-17569
Anacardic acid (pentadecyl salicylic acid) is a phenolic constituent present in cashew nut shell liquid (Anacardium occidentale L.) and
exhibits antimicrobial properties. The present paper describes the synthesis, characterization and antimicrobial evaluation of hydrazone
derivatives of anacardic acid (9a-l) linked with 1,2,3-triazole ring. All the newly synthesized compounds were determined by 1H NMR,
mass and IR spectroscopy. Compounds 9d, 9e, 9h, 9i and 9j exhibited strong antifungal activity against the tested fungal strains viz., A.
niger and C. albicans.
Keywords: Anacardic acid, Antibacterial, Antifungal, Hydrazone, 1,2,3-Triazole.
expression of nuclear factor-kB regulated gene products
leading to potentiation of apoptosis [27] inhibitor of the HAT
activity of recombinant Plasmodium falciparum GCN5 [28]
and as modulators of histone acetyltransferases [29]. Cooper
et al. [30] reported the antibacterial activities of anacardic acid
derivatives and Dekker et al. [31,32] reported the anacardic
acid derived salicylates as inhibitors or activatiors of lipoxy-
genases.
Resistance to antibacterial agents is a major problem since
last three decades [33,34]. This emerging resistance has
resulted in the development of a wide variety of antibiotics. In
addition, primary and opportunistic fungal infections continue
to increase rapidly because of the increased number of immune
compromised patients (AIDS, cancer and transplants). Several
reviews have appeared illustrating the problems encountered
by today’s infectious disease clinicians [29]. The present paper
describes herein the synthesis, characterization and antimicrobial
evaluation of hydrazone derivatives of anacardic acid (9a-l)
linked with 1,2,3-triazole ring.
INTRODUCTION
The triazole nucleus is one of the most significant and
well known azole which is widespread and important feature
of a variety of natural products and medicinal agents [1].
Triazole derivatives are known to exhibit various pharmacolo-
gical properties such as antiviral [2], antimicrobial [3,4], anti-
convulsant [5], anticancer [6,7], antitubercular [8], antiinfla-
matory and analgesic [9].
Hydrazones are of great interest to researchers because
of their diverse biological and clinical applications. They have
been reported to exhibit antimicrobial, anticonvulsant,
analgesic, anti-inflammatory, antiplatelet, antitubercular and
antitumor activities [10-12].
Anacardic acid (pentadecyl salicylic acid) is a phenolic
constituent present in cashew nut shell liquid (CNSL);
(Anacardium occidentale L.) and exhibits antimicrobial
properties [13-19], soybean lipoxygenase-1 inhibitory activity
[20,21]. Reddy et al. [22] reported the synthesis of benzamide
derivatives of anacardic acid. Furthermore, the following
anacardic analogs viz., dihydropyridine analogues [23], sildenafil
analogues [24], isonicotinoylhydrazones for antimycobacterial
activity [25], as calcium channel blockers, were appeared to
possess prominent medicinal importance. Furthermore,
anacardic acid exhibited, various activities like, is a specific
activator of kinase activity ofAurora KinaseA [26], suppresses
EXPERIMENTAL
The uncorrected melting points of compounds were taken
in an open capillary in a paraffin bath. All reagents used were
commercial and laboratory grade, melting points were deter-
mined in open capillaries and are uncorrected. IR spectra were
recorded on potassium bromide disks on a Perkin-Elmer 383

176 Rambabu et al.
Asian J. Chem.
spectrophotometer. 1H NMR spectra were obtained on Varian
400 MHz instrument with TMS as internal Standard and
chemical shifts are expressed in ppm solvent used in CDCl3 &
DMSO-d6 and mass spectrum on a Hewelett Packard mass
spectrometer operating at 70 ev, purity of the compounds were
checked by TLC, which is performed with E. Merck pre coated
silica gel plates (60 F-254) with iodine as a developing agent.
Acme, India silica gel, 60-120 mesh for column chroma-
tography is used. All compounds were purified by column
chromatography using ethylacetate in hexane.
3367, 3004, 2924, 2853, 2781, 1689, 1596, 1577, 1472, 1457,
1438, 1409, 1377, 1268, 1180, 1169, 1119, 1080, 823, 788,
650, 474, 466, 418; 1HNMR (400 MHz, CDCl3) δ: 7.20 (t, J =
8.0 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H),
4.75 (d, J = 6.4 Hz, 2H), 3.87 (s, 3H), 2.68 (t, J = 6.4 Hz, 2H),
2.37 (t, J = 6.4 Hz, 1H), 1.53-1.58 (m, 2H), 1.27 (brs, 24H),
0.89 (t, J = 7.2 Hz, 3H, D2O exchangeable OH); 13C NMR
(100 MHz, CDCl3) δ: 14.0, 22.6, 29.3, 29.4, 29.5, 29.6, 29.6,
31.8, 32.1, 33.1, 55.3, 57.3, 108.0, 122.2, 126.8, 128.4, 142.6,
158.2; ESIMS: m/z 349 (M+H)+.
Synthesis of 2-hydroxy-6-pentadecylbenzoic acid (2):
An ethanolic solution (50 mL) of anacardic acid ene mixture
(1) (10 g, 29.16 mmol) was hydrogenated in a 1 L Parr-apparatus
at 50 psi of H2 pressure in presence of 10 % Pd/C (1 g, 10 %)
for 2 h. The reaction mixture was filtered through celite and
the filtrate concentrated under reduced pressure to obtain 2,
which was recrystallized in petroleum ether to obtain the pure
2-hydroxy-6-pentadecylbenzoic acid 2. White solid; Yield: 7
g, 68.8 %; m.p.: 85-86 °C; IR (KBr, νmax, cm-1): 3002, 2918,
2851, 1655, 1450, 1246, 1214; 1H NMR (400 MHz, CDCl3)
δ: 11.02 (brs, 1H), 7.37 (t, J = 8.0 Hz, 1H), 6.88 (d, J = 8.4 Hz,
1H), 6.78 (d, J = 7.6 Hz, 1H), 2.98 (t, J = 8.0 Hz, 2H), 1.57-
1.63 (m, 2H), 1.27 (brs, 24H), 0.89 (t, J = 6.8 Hz, 3H); ESIMS:
m/z 349 (M+H)+.
Synthesis of 2-(bromomethyl)-1-methoxy-3-pentadecyl-
benzene (5): To a stirred solution of triphenyl phosphine (4.86
mmol) in dichloromethane (25 mL) was added tribromoiso-
cyanuric acid (1.7 mmol). After 15 min, (2-methoxy-6-penta-
decylphenyl)methanol (4) (2.43 mmol) was added and the
suspension was stirred at room temperature for 3 h. The comp-
letion of the reaction was monitored by TLC. The cyanuric
acid was filtered off and organic layer was washed with water
(3 × 25 mL), the organic layer was separated, dried over
Na2SO4 and evaporated under reduced pressure to obtain 2-
(bromomethyl)-1-methoxy-3-pentadecylbenzene (5) as a
reddish yellow syrupy liquid. IR (KBr, νmax, cm-1): 3418, 3020,
2949, 2919, 2849, 2717, 1841, 1683, 1593, 1583, 1509, 1468,
1456, 1437, 1421, 1400, 1385, 1349, 1317, 1279, 1234, 1198,
1160, 1135, 1092, 1031, 1010, 982, 873, 809, 774, 734, 721,
652, 567, 540; 1HNMR (400 MHz, DMSO-d6) δ: 7.22 (d, J =
8.0 Hz, 1H), 6.84 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H),
4.62 (s, 2H), 3.84 (s, 3H), 2.63 (t, J = 7.6 Hz, 2H), 1.60-1.54
(m, 2H), 1.30-1.18 (m, 24 H), 0.88 (t, J = 5.6 Hz, 3 H); ESIMS:
m/z 331.4 (M-HBr)+.
Synthesis of 2-(azidomethyl)-1-methoxy-3-pentadecyl-
benzene (6): To a stirred solution of compound 5 (1g, 2.43
mmol) in DMF was added sodium azide (165 mg, 2.55 mol)
and heated to 90 °C for 1 h. After completion of the reaction
(monitored by TLC), the reaction mixture was cooled to room
temperature and diluted with water (10 mL) followed by ethyl
acetate (10 mL). The organic layer was separated, washed with
water followed by brine solution, dried over Na2SO4, filtered
and concentrated under reduced pressure to give pale yellow
syrupy liquid. Yield: 0.8 g, 90 %. IR (KBr, νmax, cm-1): 3444,
2950, 2915, 2849, 2092, 1652, 1599, 1586, 1466, 1437, 1315,
1266, 1186, 1114, 1090, 1054, 864, 829, 783, 768, 754, 721,
669, 564, 493; 1HNMR (400 MHz, CDCl3) δ: 7.22 (d, J = 8.0
Hz, 1H), 6.83 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H),
4.41 (s, 2H), 3.84 (s, 3H), 2.63 (t, J = 7.6 Hz, 2H), 1.60-1.54
(m, 2H), 1.30-1.18 (m, 24 H), 0.88 (t, J = 5.6 Hz, 3 H); ESIMS:
m/z 345.9 (M-N3)+.
Synthesis of methyl 2-methoxy-6-pentadecylbenzoate
(3): To a solution of 2-hydroxy-6-pentadecylbenzoic acid (2)
(5 g, 14.34 mmol) in dry CH3CN (200 mL) was added dimethyl
sulphate (5.44 mL, 57.36 mmol) followed by anhydrous K2CO3
(10.2 g, 71.70 mmol) and refluxed for 24 h.After the completion
of the reaction, the reaction mixture was diluted with isopropyl
acetate (150 mL) and water (200 mL). The organic layer was
washed with water followed by brine solution (75 mL), dried
over Na2SO4, filtered and concentrated to obtain methyl 2-
methoxy-6-pentadecylbenzoate (3). Pale yellow solid; Yield:
18.5 g, 85.6 %; m.p.: 36-37 °C; IR (KBr, νmax, cm-1): 3004,
1
2921, 2852, 1732, 1589, 1460, 1266, 1105; H NMR (400
MHz, CDCl3) δ: 7.25 (t, J = 8.0 Hz, 1H), 6.82 (d, J = 8.0 Hz,
1H), 6.75 (d, J = 8.4 Hz, 1H), 3.90 (s, 3H), 3.81 (s, 3H), 2.53
(t, J = 8.0 Hz, 2H), 1.53-1.60 (m, 2H), 1.25 (brs, 24H), 0.88
(t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 14.0, 22.6,
29.3, 29.3, 29.4, 29.5, 29.6, 29.6, 31.1, 31.8, 33.4, 52.0, 55.8,
108.3, 121.4, 123.4, 130.1, 141.3, 156.2, 168.8; ESIMS: m/z
377 (M+H)+.
Synthesis of (2-methoxy-6-pentadecylphenyl)methanol
(4): A stirred suspension of sodium borohydride (6 eq) and
methyl 2-methoxy-6-pentadecylbenzoate (3) (4 g, 10.62 mmol)
in anhydrous THF (30 mL) was heated under reflux for 20
min. To the above reaction contents, methanol (30 mL) was
added slowly over a period of 30 min. The reaction was further
refluxed for 1 h. The completion of the reaction was monitored
by TLC. The reaction mixture was cooled to room temperature
and quenched with a saturated solution of NH4Cl (25 mL) for
1.5 h and diluted with isopropyl acetate. The organic layer
was separated and the aqueous phase extracted with isopropyl
acetate (2 × 25 mL). The organic extracts were combined and
dried over Na2SO4 and concentrated under low pressure to
give (2-methoxy-6-pentadecylphenyl)methanol (4). Off white
solid; Yield: 3 g, 81 %; m.p.: 60-62 °C; IR (KBr, νmax, cm-1):
Synthesis of 1-(2-methoxy-6-pentadecylbenzyl)-1H-
1,2,3-triazole-4-carbaldehyde (7): To a stirred solution of 2-
(azidomethyl)-1-methoxy-3-pentadecylbenzene (6) (0.8 g,
2.14 mmol) in acetonitrile (4 mL) was added propynaldehyde
diethyl acetal (2.33 mmol) followed by CuI (10 mol %) and
heated to reflux for 3 h. The reaction mixture was cooled to
room temperature and added 2 N HCl (5 mL) and heated to
80 °C for 12 h. After completion of the reaction (monitored
by TLC), the reaction mixture was cooled to room temperature
and diluted with water, the precipitated yellow solids were
filtered and dried to obtain 1-(2-methoxy-6-pentadecylbenzyl)-

Vol. 28, No. 1 (2016) Synthesis of (E)-N'-[(1-(2-methoxy-6-pentadecylbenzyl)-1H-1,2,3-triazol-4-yl]methylene)benzohydrazide Derivatives 177
1H-1,2,3-triazole-4-carbaldehyde (7). IR (KBr, νmax, cm-1):
3428, 3144, 3109, 2952, 2918, 2851, 1704, 1650, 1598, 1589,
1531, 1472, 1458, 1433, 1350, 1328, 1268, 1244, 1172, 1160,
1116, 1103, 1079, 1058, 1038, 1016, 836, 815, 801, 758, 685,
1367, 1351, 1328, 1300, 1276, 1267, 1236, 1180, 1164, 1154,
1102, 1082, 1072, 1056, 967, 949, 917, 858, 835, 812, 789,
761, 715, 701, 662, 635, 623, 565, 515; 1H NMR (400 MHz,
DMSO-d6): δ 11.66 (s, 1H), 10.12 (s, 1H), 8.47 (s, 1H), 8.11
(s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H), 6.93
(t, J = 8.4 Hz, 2H), 6.85 (t, J = 7.2 Hz, 2H), 5.62 (s, 2H), 3.83
(s, 3H), 2.71 (brs, 2H), 1.36 (brs, 2H), 1.19 (brs, 24 H), 0.84
(brs, 3H); ESI-MS: m/z, 562.1 (M+H)+.
1
642, 573; H NMR (400 MHz, DMSO-d6) δ: 10.02 (s, 1H),
8.82 (s, 1H), 7.32 (d, J = 7.6 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H),
6.92 (d, J = 8.0 Hz, 1H), 5.61 (s, 2H), 3.80 (s, 3H), 2.78 (t, J =
7.6 Hz, 2H), 1.42-1.38 (m, 2H), 1.30-1.18 (m, 24 H), 0.82 (t,
J = 5.6 Hz, 3 H); ESIMS: m/z 428.1 (M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-3,4,5-trimethoxybenzohydrazide
(9e): White solid; m.p.: 120-122 °C; IR (KBr, νmax, cm-1): 3440,
3260, 3108, 3090, 3065, 3002, 2922, 2851, 1649, 1614, 1583,
1556, 1525, 1503, 1470, 1461, 1437, 1413, 1376, 1363, 1335,
1268, 1235, 1183, 1133, 1088, 1063, 1002, 974, 849, 835,
General procedure for the preparation of hydrazone
derivatives (9a-l): To a stirred solution of AA-1,2,3-triazole
aldehyde 7 (0.117 mmol) in ethanol was added corresponding
benzohydrazides (8a-l) (0.122 mmol) and refluxed for 30 min.
The reaction mixture was cooled to room temperature, filtered
the precipitated solids and washed with petroleum ether, to
obtain triazole hydrazide-hydrazone derivatives (9a-m) in
quantitative yields.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]benzohydrazide (9a): White solid;
m.p.: 112-113 °C; IR (KBr, νmax, cm-1): 3437, 3260, 3158, 3065,
3014, 2993, 2919, 2869, 2850, 1655, 1616, 1601, 1584, 1565,
1536, 1469, 1435, 1368, 1290, 1277, 1267, 1236, 1181, 1155,
1084, 1055, 957, 911, 823, 795, 716, 693, 681, 654, 572; 1H
NMR (400 MHz, DMSO-d6): δ 11.82 (s, 1H), 8.50 (s, 1H),
8.16 (s, 1H), 7.87 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 7.2 Hz, 2H),
7.52 (d, J = 7.2 Hz, 2H), 7.31 (t, J = 8.0 Hz, 1H), 6.93 (d, J =
8.4 Hz, 1H), 6.86 (d, J = 7.2 Hz, 1H), 5.61 (s, 2H), 3.83 (s,
3H), 2.72 (brs, 2H), 1.36 (brs, 2H), 1.20 (brs, 24 H), 0.84 (brs,
3H); ESI-MS: m/z, 546.1 (M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-4-methoxybenzohydrazide (9b):
White solid; m.p.: 118-119 °C; IR (KBr, νmax, cm-1): 3443,
3252, 3167, 3012, 2954, 2917, 2850, 1648, 1608, 1586, 1561,
1533, 1509, 1472, 1439, 1373, 1361, 1328, 1293, 1267, 1260,
1228, 1185, 1153, 1121, 1110, 1082, 1072, 1060, 1046, 1027,
963, 954, 912, 842, 814, 765, 719, 687, 658, 626, 618, 503;
1H NMR (400 MHz, DMSO-d6): δ 11.69 (s, 1H), 8.50 (s, 1H),
8.13 (s, 1H), 7.86 (d, J = 9.2 Hz, 2H), 7.31 (s, 1H), 6.86 (d,
J = 7.2 Hz, 1H), 5.62 (s, 2H), 3.82 (s, 3H), 3.79 (s, 3H), 2.72
(brs, 2H), 1.36 (brs, 2H), 1.19 (brs, 24 H), 0.84 (brs, 3H);
ESI-MS: m/z, 576.1 (M+H)+.
1
809, 768, 756, 736, 714, 694, 654, 591, 564; H NMR (400
MHz, DMSO-d6): δ 11.66 (s, 1H), 8.52 (s, 1H), 8.19 (s, 1H),
7.31 (t, J = 8.4 Hz, 1H), 7.20 (s, 2H), 6.93 (d, J = 8.8 Hz, 1H),
6.86 (d, J = 7.2 Hz, 1H), 5.61 (s, 2H), 3.85 (s, 3H), 3.83 (s,
3H), 3.72 (s, 3H), 2.72 (brs, 2H), 1.37 (brs, 2H), 1.20 (brs, 24
H), 0.84 (t, J = 5.6 Hz, 3H); ESI-MS: m/z, 636.1 (M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-2,5-dichlorobenzohydrazide (9f):
White solid; m.p.: 122-123 °C; IR (KBr, νmax, cm-1): 3444,
3244, 3062, 2955, 2919, 2850, 1667, 1616, 1585, 1561, 1530,
1465, 1437, 1377, 1364, 1290, 1260, 1239, 1162, 1135, 1099,
1085, 1062, 977, 964, 934, 882, 829, 794, 780, 764, 719, 691,
666, 657, 599, 569, 547; 1H NMR (400 MHz, DMSO-d6): δ
12.08 (* 11.96, s, 1H), 8.30 (* 8.09, s, 1H), 8.19 (* 7.78, s,
1H), 7.69 (s, 1H), 7.61 (s, 1H), 7.54 (s, 1H), 7.33-7.25 (m,
1H), 6.94-6.82 (m, 2H), 5.61 (* 5.50, s, 2H), 3.83 (* 3.73, s,
3H), 2.74-2.67 (m, 2H), 1.36 (brs, 2H), 1.22 (brs, 24 H), 0.84
(t, J = 5.6 Hz, 3H); ESI-MS: m/z, 614.0 (M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-3,5-dichlorobenzohydrazide (9g):
White solid; m.p.: 133-134 °C; IR (KBr, νmax, cm-1): 3432,
3236, 3178, 3115, 3076, 3020, 2994, 2953, 2920, 2849, 1661,
1583, 1566, 1534, 1469, 1434, 1417, 1375, 1360, 1348, 1327,
1298, 1286, 1270, 1261, 1240, 1229, 1170, 1114, 1098, 1084,
1075, 1045, 951, 945, 897, 866, 829, 817, 805, 771, 757, 748,
1
720, 712, 670, 655, 638, 566; H NMR (400 MHz, DMSO-
d6): δ 11.90 (s, 1H), 8.50 (s, 1H), 8.18 (s, 1H), 7.92 (s, 2H),
7.84 (d, J = 7.2 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.56 (t, J =
8.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H),
6.86 (d, J = 7.2 Hz, 1H), 5.61 (s, 2H), 3.83 (s, 3H), 2.72 (brs,
2H), 1.35 (brs, 2H), 1.18 (brs, 24 H), 0.84 (t, J = 5.6 Hz, 3H);
ESI-MS: m/z, 614.0 (M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-4-chlorobenzohydrazide (9c):
White solid; m.p.: 99-101 °C; IR (KBr, νmax, cm-1): 3417, 3253,
3167, 3072, 3012, 2991, 2952, 2920, 2870, 2850, 1653, 1616,
1590, 1563, 1536, 1484, 1467, 1434, 1367, 1297, 1265, 1237,
1180, 1155, 1094, 1085, 1065, 1053, 1013, 962, 910, 853,
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-3-nitrobenzohydrazide (9h): White
solid; m.p.: 86-88 °C; IR (KBr, νmax, cm-1): 3436, 3233, 3170,
3074, 3044, 3015, 2954, 2920, 2870, 2851, 1665, 1655, 1619,
1586, 1567, 1531, 1470, 1439, 1353, 1328, 1298, 1266, 1227,
1159, 1122, 1081, 1060, 1046, 959, 912, 861, 823, 817, 764,
1
823, 771, 757, 720, 703, 690, 666, 656, 623, 571, 534; H
NMR (400 MHz, DMSO-d6): δ 11.88 (s, 1H), 8.50 (s, 1H),
8.17 (s, 1H), 7.90 (d, J = 7.2 Hz, 2H), 7.60 (d, J = 7.6 Hz, 2H),
7.31 (s, 1H), 6.93 (d, J = 6.4 Hz, 1H), 6.85 (d, J = 7.2 Hz, 1H),
5.61 (s, 2H), 3.83 (s, 3H), 2.72 (brs, 2H), 1.35 (brs, 2H), 1.18
(brs, 24 H), 0.84 (t, J = 5.6 Hz, 3H); ESI-MS: m/z, 580.0
(M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-4-hydroxybenzohydrazide (9d):
White solid; m.p.: 126-128 °C; IR (KBr, νmax, cm-1): 3252,
3220, 3162, 3130, 3074, 3019, 2949, 2916, 2850, 2682, 2616,
1698, 1650, 1612, 1588, 1576, 1541, 1512, 1472, 1443, 1379,
1
731, 719, 687, 672, 661, 650, 565; H NMR (400 MHz,
DMSO-d6): δ 12.14 (s, 1H), 8.72 (s, 1H), 8.53 (s, 1H), 8.44
(d, J = 6.8 Hz, 1H), 8.34 (d, J = 6.0 Hz, 1H), 8.22 (s, 1H), 7.85
(s, 1H), 7.31 (s, 1H), 6.94 (d, J = 7.6 Hz, 1H), 6.86 (d, J = 6.4
Hz, 1H), 5.61 (s, 2H), 3.84 (s, 3H), 2.72 (brs, 2H), 1.35 (brs,
2H), 1.18 (brs, 24 H), 0.84 (brs, 3H); ESI-MS: m/z, 591.1
(M+H)+.

178 Rambabu et al.
Asian J. Chem.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-4-fluorobenzohydrazide (9i): White
solid; m.p.: 128-129 °C; IR (KBr, νmax, cm-1): 3432, 3255, 3166,
3074, 3015, 2991, 2950, 2920, 2869, 2850, 1655, 1616, 1602,
1586, 1565, 1537, 1506, 1469, 1435, 1366, 1307, 1288, 1275,
1265, 1234, 1179, 1159, 1099, 1085, 1066, 1053, 957, 912,
857, 826, 812, 771, 763, 720, 690, 662, 656, 625, 612, 571;
1H NMR (400 MHz, DMSO-d6): δ 11.84 (s, 1H), 8.50 (s, 1H),
8.16 (s, 1H), 7.96 (s, 2H), 7.36-7.31 (m, 4H), 6.93 (d, J = 7.6
Hz, 1H), 6.86 (d, J = 4.0 Hz, 1H), 5.61 (s, 2H), 3.83 (s, 3H),
2.72 (brs, 2H), 1.35 (brs, 2H), 1.19 (brs, 24 H), 0.84 (brs, 3H);
ESI-MS: m/z, 564.0 (M+H)+.
antifungal substances, respectively under similar conditions
for comparison. Dimethyl sulphoxide (1 %, DMSO) was used
as control. The minimum inhibitory concentration (MIC) value
was determined at a concentration of 25 µg/mL using dimethyl
sulfoxide (DMSO) as solvent against bacteria as well as fungal
strains. The culture strains of bacteria were maintained on
nutrient agar slant at 37 0.5 °C for 24 h. The antibacterial
activity was evaluated using nutrient agar plate seeded with
0.1 mL of respective bacterial culture strain suspension
prepared in sterile saline (0.85 %) of 105 cfu/mL dilutions.
The wells of 6 mm diameter were filled with 0.1 mL of target
compound dilution ranging from 25 to 1000 µg/mL separately
for each bacterial strain. All the plates were incubated at 37
0.5 °C for 24 h.
For antifungal activity, all the culture strains of fungi main-
tained on potato dextrose agar (PDA) slant at 27 0.2 °C for
24-48 h, till sporulation. Spore of strains were transferred in
to 5 mL of sterile distilled water containing 1 % Tween-80
(to suspend the spore properly). The spores were counted by
haemocytometer (106 CFU/mL). Sterile PDA plate was
prepared containing 2 % agar; 0.1 mL of each fungal spore
suspension was spread on each plate and incubated at 27
0.2 °C for 12 h. After incubation well prepared using sterile
cork borer and each agar well was filled with 0.1 mL compound
solution of concentrations 25 to 1000 µg/mL separately to get
minimum inhibitory concentration value of hydrazone
derivatives 9a-l. The plates were kept in refrigerator for 20 min
for diffusion and then incubated at 27 0.2 °C for 24-28 h.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-2,5-difluorobenzohydrazide (9j):
White solid; m.p.: 94-96 °C; IR (KBr, νmax, cm-1): 3303, 3114,
3090, 3066, 3009, 2950, 2916, 2848, 1667, 1586, 1561, 1534,
1488, 1471, 1441, 1425, 1366, 1307, 1285, 1270, 1246, 1229,
1182, 1135, 1124, 1111, 1083, 1057, 1036, 964, 901, 860,
1
827, 814, 776, 763, 752, 719, 690, 655, 603, 579, 540; H
NMR (400 MHz, DMSO-d6): δ 12.05 (* 11.89, s, 1H), 8.36 (*
8.10, s, 1H), 8.19 (* 7.83, s, 1H), 7.51-7.42 (m, 2H), 7.33-
7.25 (m, 2H), 6.99-6.82 (m, 2H), 5.61 (* 5.51, s, 2H), 3.83 (*
3.74, s, 3H), 2.74-2.67 (m, 2H), 1.35 (brs, 2H), 1.24 (brs, 24
H), 0.84 (t, J = 5.6 Hz, 3H); ESI-MS: m/z, 582.1 (M+H)+.
(E)-N’-[{1-(2-Methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-3-chlorobenzohydrazide (9k):
White solid; m.p.: 134-135 °C; IR (KBr, νmax, cm-1): 3441,
3208, 3072, 3051, 2953, 2920, 2869, 2850, 1654, 1615, 1586,
1561, 1532, 1469, 1436, 1365, 1307, 1289, 1266, 1231, 1172,
1115, 1084, 1072, 1049, 946, 889, 823, 805, 759, 737, 721,
RESULTS AND DISCUSSION
1
The synthesis of (E)-N’-[{1-(2-methoxy-6-pentadecyl-
benzyl)-1H-1,2,3-triazol-4-yl}methylene]benzohydrazide
derivatives (9a-l) is illustrated in Scheme-I. Anacardic acid
(2) was obtained by hydrogenation of anacardic ene mixture
(1) according to the literature procedure [36-40]. Methylation
of anacardic acid (2) was carried out using dimethyl sulphate
in presence of potassium carbonate in acetonitrile to obtain
methylated derivative (3) of ancardic acid. Reduction of
compound 3 with NaBH4 in presence of THF:MeOH [41]
resulted in (2-methoxy-6-pentadecylphenyl)methanol (4).
Bromination of carbinol 4 was carried out using tribromo-
isocyanuric acid in presence of triphenyl phosphine [42] in
dichloro-methane to afford 2-(bromomethyl)-1-methoxy-3-
pentadecyl-benzene (5). Bromide 5 was reacted with sodium
azide in DMF at 90 °C to obtain azide 6. Reaction of azide 6
with propynaldehyde diethal acetal in presence of CuI in
acetonitrile at 3 h followed by the deprotection of acetal group
in acidic medium (2 N HCl) resulted in the formation of the
key intermediate 1-(2-methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazole-4-carbaldehyde (7). Condensation of the triazole
aldehyde 7 with different benzohydrazide 8a-l in ethanol at
reflux for 30 min resulted in the formation of (E)-N’-[{1-(2-
methoxy-6-pentadecylbenzyl)-1H-1,2,3-triazol-4-yl}-
methylene]benzohydrazide derivatives (9a-l) in quantitative
yields. All the synthesized hydrazone derivatives (9a-l) was
689, 683, 655; H NMR (400 MHz, DMSO-d6): δ 11.96 (s,
1H), 8.48 (s, 1H), 8.20 (s, 1H), 7.88 (d, J = 8.0 Hz, 2H), 7.31
(t, J = 8.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 6.4 Hz,
1H), 5.61 (s, 2H), 3.82 (s, 3H), 2.71 (brs, 2H), 1.37 (brs, 2H),
1.18 (brs, 24 H), 0.84 (brs, 3H); ESI-MS: m/z, 580.0 (M+H)+.
(E)-N’-[{1-(2-methoxy-6-pentadecylbenzyl)-1H-1,2,3-
triazol-4-yl}methylene]-4-(methylsulfonyl)benzohydrazide
(9l): White solid; m.p.: 131-132 °C; IR (KBr, νmax, cm-1): 3434,
3279, 3245, 3064, 3038, 3009, 2953, 2918, 2850, 1655, 1585,
1559, 1529, 1505, 1471, 1439, 1395, 1361, 1316, 1298, 1283,
1267, 1233, 1155, 1146, 1087, 1060, 1047, 964, 908, 855,
1
821, 786, 763, 752, 720, 688, 670, 565, 553, 521, 463; H
NMR (400 MHz, DMSO-d6): δ 12.04 (s, 1H), 8.20 (s, 1H),
8.09 (d, J = 4.8 Hz, 4H), 7.31 (t, J = 7.2 Hz, 1H), 6.93 (d, J =
8.8 Hz, 1H), 6.86 (d, J = 7.2 Hz, 1H), 5.61 (s, 2H), 3.83 (s,
3H), 3.82 (s, 3H), 2.72 (brs, 2H), 1.37 (brs, 2H), 1.20 (brs, 24
H), 0.84 (t, J = 5.6 Hz, 3H); ESI-MS: m/z, 624.1 (M+H)+.
Antimicrobial screening
Antibacterial and antifungal assay: The antimicrobial
activities of the synthesized triazole linked hydrazone derivatives
of anacardic acid (9a-l) were determined by agar diffusion
method [35]. The compounds were evaluated for antimicrobial
activity against bacteria viz. Escherichia coli (MTCC 443),
Pseudomonas auriginosa (MTCC 424), Staphylococus aureus
(MTCC 96), Streptococcus pyogenes (MTCC 442) and anti-
fungal activity against fungi viz. Aspergillus niger (MTCC
282), Candida albicans (MTCC 227). The antibiotic ampicillin
and greseofulvin are used as reference antibacterial and
1
characterized by H NMR, mass and IR spectroscopic tech-
niques. Mass spectral data of all the hydrazone derivatives
(9a-l) and its associated intermediates are in agreement with
the desired molecular formulae exhibiting (M+H) peaks. As a

Vol. 28, No. 1 (2016) Synthesis of (E)-N'-[(1-(2-methoxy-6-pentadecylbenzyl)-1H-1,2,3-triazol-4-yl]methylene)benzohydrazide Derivatives 179
OH
O
OH
O
a
OH
b
OH
1
2
O
O
O
OMe
c
OH
d
3
4
O
O
e
f
Br
N3
6
5
O
NH2
N
H
H
N
R
O
CHO
O
R
N
8a-l
O
N
N
N
N
N
g
N
7
9a-l
9a. R = H
9i. R = 4-F
9j. R = 2,5-F
9k. R = 3-Cl
9l. R = 4-SO2Me
9e. R = 3,4,5-OMe
9f. R = 2,5-Cl
9g. R = 3,5-Cl
9h. R = 3-NO2
9b. R = 4-OMe
9c. R = 4-Cl
9d. R = 4-OH
Experimental conditions: a) 10 % Pd-C, EtOH, H2, 50 psi, 2 h; b) Dimethyl sulphate, K2CO3, CH3CN, reflux, 24 h;
c) NaBH4, THF:Methanol, reflux, 1 h; d) Tribromoisocyanuric acid, TPP, dichloromethane, r.t., 3 h; e) NaN3, DMF, 90 °C, 1 h;
f) i. propynaldehyde diethyl acetal, CuI, acetonitrile, reflux, 3 h, ii. 2N HCl, 80 °C, 12 h; g) Benzohydrazide 8a-l, ethanol, 30 min
Scheme-I: Synthesis of novel triazole-hydrazone derivatives of anacardic acid 9a-l
general representative example for hydrazone derivatives, the
1H NMR assignment of (E)-N’-[{1-(2-methoxy-6-pentadecyl-
benzyl)-1H-1,2,3-triazol-4-yl}methylene]-3,4,5-trimethoxy-
benzohydrazide (9f) is exemplified here: the protons signals
at 0.84 ppm (triplet, 3H), 1.30-1.18 ppm (multiplet, 24H),
1.37 ppm (brs, 2H) and 2.72 ppm (brs, 2H) resonating in the
aliphatic region corresponds to the side chain of the anacardic
acid moiety. The protons of the methoxy groups of 9f appeared
in the expected region. The characteristic methylene proton
of 9f appeared as singlet at 5.61 ppm. The characteristic proton
signals resonating at 11.61ppm, 8.52 ppm and 8.19 ppm as
singlets corresponds to -CONH-, -N=CH-and triazole ring
respectively. In the aromatic region, the protons resonating at
7.20 ppm as singlet corresponds to the 3,4,5-trimethoxy phenyl
ring while the protons resonating at 7.31, 6.93 and 6.86 ppm
as triplet and doublets represents the aromatic ring protons of
anacardic acid. The IR spectra of the compounds 9a-l indicated
the following characteristic peaks: A strong characteristic
bands in the region 1667-1649 cm-1 are due to the C=O stret-
ching vibrations of amide functional group. The multiple peaks
in the region 1614-1437 cm-1 are due to C=N and aromatic
ring stretching vibrations. The peaks in the regions 1335-1235
cm-1 are due to (C-N) stretching vibrations. The N-H stretching
vibrations of the compounds gave rise to broad bands in the
region 3443-3418 cm-1. The N=N stretching absorption for
triazole compounds appeared nearly around 1400 cm-1 which
was assigned within the same absorption region of the C=C
stretching for all compounds.
Antibacterial and antifungal: The results of in vitro
antibacterial and antifungal activities are summarized in Table-1.
Compounds 9d, 9e, 9h, 9i and 9j exhibited excellent antifungal
activity against the tested fungal strains viz., A. niger and C.
albicans. Compounds 9c, 9f and 9g showed good activity and
are lower than that of greseoflavin. The remaining compounds
in the series showed moderate fungal activity.
On the basis of zone of inhibition (ZI) with reference to
the standard drug ampicillin, the antibacterial activity of the
compounds 9a-l is measured as good, moderate and weak
activity. In case of Gram-positive bacteria compounds 9c, 9e,
9g, 9h and 9j exhibited good antibacterial activity (ZI: 9-12
mm), compounds 9a, 9d and 9f showed moderate antibacterial
activity (ZI: 6-8 mm), whereas compounds 9b, 9i, 9k and 9l
showed weak to nil antibacterial activity (ZI: 0-4 mm). Similar
trends of antibacterial activity were observed in case of Gram-
negative bacterial strain. Considering the results obtained from
antifungal and antibacterial tests together, it is noteworthy to
mention that tested compounds are more active towards fungi
than bacteria.

180 Rambabu et al.
Asian J. Chem.
TABLE-1
ANTIMICROBIAL ACTIVITY OF HYDRAZONE DERIVATIVES (9a-l)
Zone of inhibition (mm)
Gram-positivee bacteria
Gram-negative bacteria
Fungi
Compound No.
S. aureus
S. pyogenes
E. coli
P. aeruginosa
A. niger
C. albicans
MTCC 96
MTCC 442
MTCC 443
MTCC 424
MTCC 282
MTCC 227
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
6
4
9
8
10
7
10
11
3
11
–
7
3
9
8
9
7
5
11
9
13
10
12
14
6
8
6
12
9
13
9
13
14
6
16
13
17
26
27
19
20
25
24
26
12
14
–
15
12
18
24
23
19
20
24
22
24
12
15
–
7
11
11
3
12
–
11
6
4
11
5
6
9k
9l
SD*
SD**
–
13
–
14
15
15
23
21
SD*: Standard drug: Ampicillin (conc. 25 µg/mL-1) was used as a standard drug for antibacterial activity.
SD**: Greseofulvin (conc. 25 µg/mL) was used as a standard drug for antifungal activity.
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Conclusion
The present paper describes the synthesis, characterization
and antimicrobial evaluation of (E)-N’-[{1-(2-methoxy-6-
pentadecylbenzyl)-1H-1,2,3-triazol-4-yl}methylene]benzo-
hydrazide derivatives 9a-l derived from commercially available
cashew nut shell liquid (Anacardium occidentale L.). The
results of in vitro antibacterial and antifungal activities revealed
that tested compounds are more active towards fungi than
bacteria.
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