Synthesis and fungicidal activity of bioactive 4,4′-bis[4″-(N-benzylidinylamine)-3″-mercapto-1″,2″,4″-triazole-5″-yl methoxy]dibenzyl

Article abstract of DOI:10.14233/ajchem.2017.20097

The reaction of 4,4′-diamino dibenzyl (I) with sodium nitrite and HCl at 0-5°C followed by hydrolysis gave 4,4′-dihydroxy dibenzyl (II), which on reaction with chloroacetic acid in presence of sodium carbonate yielded 4,4′-ethylenebisphenoxyacetic acid (I

Full text of DOI:10.14233/ajchem.2017.20097

Asian Journal of Chemistry; Vol. 29, No. 1 (2017), 19-21
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2017.20097
Synthesis and Fungicidal Activity of Bioactive
4,4'-bis[4"-(N-Benzylidinylamine)-3"-mercapto-1",2",4"-triazole-5"-yl methoxy]dibenzyl
2
SMRITI DWIVEDI1,* and PRAVIN K. SINGH
1Department of Chemistry, Galgotia College of Engineering and Technology, Greater Noida-201 306, India
2Food Analysis and Research Lab, Centre of Food Technology, University of Allahabad, Allahabad-211 002, India
*Corresponding author: E-mail: smriti96@rediffmail.com
Received: 24 May 2016;
Accepted: 16 August 2016;
Published online: 29 October 2016;
AJC-18090
The reaction of 4,4'-diamino dibenzyl (I) with sodium nitrite and HCl at 0-5 °C followed by hydrolysis gave 4,4'-dihydroxy dibenzyl (II),
which on reaction with chloroacetic acid in presence of sodium carbonate yielded 4,4'-ethylenebisphenoxyacetic acid (III). Nucleophilic
substitution of compound III with hydrazine hydrate gave 4,4'-bis(methoxycarbohydrazide)dibenzyl (IV) which on condensation with
CS2 and KOH gave 4'4-bis-[(3"-mercapto-1",2",4"-oxadiazole-5"-yl)methoxy]dibenzyl (V). Compound V further condensed with hydrazine
hydrate and yielded 4’4-bis[4"-amino-3"-mercapto-1",2",4"-triazole-5"yl methoxy]dibenzyl (VI). It on condensation with different carbonyl
compounds gave 4,4’-bis[4"-(N-benzylidinylamine)-3"-mercapto-1",2",4"-triazole-5"yl methoxy]dibenzyl (VIIa-h). Compounds (VIIa-h)
were evaluated in vitro for their fungi toxicities against Aspergillus niger and Fusarium oxysporum.
Keywords: Dibenzyl, Triazole, Fungitoxicities, Aspergillus niger, Fusarium oxysporum.
continuation of our research [6-13] work we synthesized new
dibenzyl incorporating 1,2,4-triazole moieties.
INTRODUCTION
Presently fungicides play an important role to boost up
the production of agricultural crops, industrial production,
prolonging the utility of manufactured products and controlling
the various human and fungal diseases. In view of this, one
may very well understand the importance of fungitoxic
chemicals in agriculture as well as in industry. Literature survey
on bryophytes have shown that bryophytes as well as extract
of the chemical constituent of bryophytes are not damaged by
fungi. The reason why bryophytes are not affected by fungus
is the presence of structural variants of dibenzyls viz., lunularic
acid and lunularin and bis dibenzyl viz. plagiochin, marchatia,
etc. It has been found that natural as well as synthetic dibenzyls
both show antifungal activity [1]. Dibenzyl are the important
natural products and have attracted considerable interests
due to their biological activities [2]. The occurrence of the
dibenzyls in nature in limited amount in rather inaccessible
plant species has increased the need for good synthetic
methods.
EXPERIMENTAL
All melting points were taken in open capillary tubes and
are uncorrected. 1H NMR were recorded by using DMSO-d6
on a Bruker DRX-300 (300 MHz FT NMR) spectrometer using
TMS as internal reference.
4,4'-Dihydroxy dibenzyl (II): A mixture of cooled solution
of 4,4'-diamino dibenzyl (I) [13] (0.1 mol) in 2 mol of concen-
trated hydrochloric acid and 23 mL of water was added drop-
wise with stirring in a solution of 0.3 mol of sodium nitrite in
water. The solution was stirred for 20 min. The cold solution
was added drop-wise to the top of a tube through which a
vigorous stream of steam was passed. The resulting mixture,
collected at the bottom of the tube, was heated to boiling,
cooled and filtered with suction. The synthesized compound
agreed well with the analytical data already reported in the
literature [14].
Nitrogen heterocyclic compounds containing 1,2,4-triazole
nucleus [3,4], hydrazine and benzylidene derivatives [5] posses
various biological activities. 4,4’-dihydroxy dibenzyl (3)
incorporating 1,2,4-triazole moieties have been relatively less
studied. Prompted by these observation we undertook the
synthesis of some dibenzyl having 1,2,4-triazole moieties. In
4,4'-Ethylenebisphenoxyacetic acid (III): To a solution
of 0.03 mol of 4,4'-dihydroxy dibenzyl (II) in dry acetone (25
mL), anhydrous K2CO3 (10 g) and chloroacetic acid (0.03 mol)
was added and refluxed on a water bath with stirring for 12-
13 h under reduced pressure. The product (III) was filtered,
dried and crystallized from ethanol, (yield 65 %), m.p. 260 °C;

20 Dwivedi et al.
Asian J. Chem.
νmax 1680 cm-1 (C=O), 1030 cm-1 (-C-O-C-). m.f.: C18H18O6;
m/z 330; 1H NMR (δ, ppm) 2.5 (2H, s, COOH), 2.82 (4H, s,
acyclicCH2-CH2), 4.94 (4H, s, OCH2),7.1-7.9 (8H, m, ArH).
4,4'-Bis(methoxycarbohydrazide)dibenzyl (IV): A
mixture of 4,4'-ethylenebisphenoxyacetic acid (III) (0.05 mol)
and hydrazine hydrate (0.06 mol) in absolute ethanol (25 mL)
was refluxed on a steam-bath. After refluxing for 4 h excess
of ethanol distilled, the solid mass thus obtained are filtered,
dried and recrystallized from ethanol (59 %), m.p. 100 °C;
νmax 3300-3100 (NH-NH), 1650 (CONH), 1055-1256 cm-1
(-C-O-C-). m.f.: C18H22N4O4; m/z 358; 1H NMR (δ, ppm): 2.81
(4H, s, acyclicCH2-CH2), 4.65-5.25 (4H, s, NH2), 4.94 (4H, s,
OCH2), 7.1-7.9 (8H, m, ArH), 8.1 (2H, s, NHCO).
4,4'-Bis[3"-mercapto-1",2",4"-oxadiazole)-5"-yl
methoxy]dibenzyl (V): To a solution of 4,4'-bis(methoxy-
carbohydrazide)dibenzyl (IV) (0.01 mol) in ethanol (20 mL),
KOH (O.5 g) in water (5 mL) and CS2 (0.03 mol) were added.
The reaction mixture was refluxed till evolution of H2S ceased.
Thereafter, it was cooled, diluted with cold water (30 mL) and
acidified with glacial acetic acid. The solid separated was
washed with water and crystallized from ethanol (70 %), m.p.
120 °C. νmax 1525 (C=N), 1050 and 1260 (-C-O-C-). m.f.:
C20H18N4O4S2; m/z 442; 1H NMR (δ, ppm): 2.50 (2H, s, SH),
2.81, (4H, s, acyclicCH2-CH2), 4.94 (4H, s, OCH2), 7.1-7.9
(8H, m, ArH).
benzaldehyde (0.01 mol) was refluxed for 20 min. The reaction
mixture was then cooled, diluted with water and the resulting
solid was washed with water and crystallized from ethanol
(70 %), m.p. 65 °C. νmax 2565 (SH), 1670-1680 (C=N), 1600-
1500 (C=C). Similarly compounds VIIa-h were synthesized
from VI by a similar procedure (Scheme-I).
VIIa: m.f.: C34H30N8O2S2; m.p.: 65 °C; m/z 646; 1H NMR
(δ, ppm): 2.50 (2H, s, SH), 2.82, (4H, s, acyclicCH2-CH2),
3.34 (4H, s, Ar-OCH2), 5.06 (2H, s, N=CH), 7.1-7.9 (18H, m,
ArH)
VIIb: m.f.: C34H30N8O4S2; m.p.: 105 °C; m/z 678; 1H NMR
(δ, ppm): 2.50 (2H, s, SH), 2.82, (4H, s, acyclicCH2-CH2), 3.34
(4H, s, Ar-OCH2), 5.06 (2H, s, N=CHAr), 7.12-7.83 (16H, m,
ArH), 12.01 (2H, s, ArOH)
VIIc: m.f.: C36H34N8O4S2; m.p.: 167 °C; m/z 706; 1H NMR
(δ, ppm): 2.50 (s, 2H, SH), 2.82, (4H, s, acyclicCH2-CH2),
3.34 (s, 4H, Ar-OCH2), 4.85 (s, 4H, OCH3), 5.09 (2H,
N=CHAr), 7.12-7.83 (16H, m, ArH), 12.01 (2H, s, ArOH).
VIId: m.f.: C34H28N8O2S2Cl2; m.p.: 205 °C; m/z 714; 1H
NMR (δ, ppm): 2.50 (2H, s, SH), 2.82, (4H, s, acyclicCH2-
CH2), 3.34 (4H, s, Ar-OCH2), 5.05 (2H, s, N=CHAr), 7.17-
7.63 (16H, m, ArH)
VIIe: m.f.: C38H38N8O6S2; m.p.: 180 °C; m/z 766; 1H NMR
(δ, ppm): 2.50 (2H, s, SH), 2.82, (4H, s, acyclicCH2-CH2),
3.34 (s, 4H, Ar-OCH2), 3.39 (6H, s, OCH3), 3.95 (6H, S,
OCH3), 5.06 (2H, s, N=CHAr) 7.21-7.63 (14H, m, ArH)
VIIf: m.f.: C36H34N8O6S2; m.p.: 135 °C; m/z 738; 1H NMR
(δ, ppm): 2.50 (2H, s, SH), 2.82, (4H, s, acyclicCH2-CH2),
3.34 (4H, s, Ar-OCH2) 3.95 (6H, S, OCH3), 5.06 (2H, s,
N=CHAr), 7.12-7.83 (14H, m, ArH), 11.69 (2H, s, ArOH).
VIIg: m.f.: C34H28N10O3S2; m.p.: 190 °C; m/z 640; 1H NMR
(δ, ppm): 2.50 (2H, s, SH), 2.82, (4H, s, acyclicCH2-CH2),
3.34 (4H, s,Ar-OCH2), 5.06 (2H, s, N=CHAr), 7.12-7.83 (16H,
m, ArH)
4,4'-Bis[4"-(N-benzylidinylamino)-3"-mercapto-
1",2",4"-triazol-5"-ylmethoxy]dibenzyl (VI): A mixture of
compound V (0.01 mol) and hydrazine hydrate (0.01 mol) in
dry pyridine (15 mL) was refluxed for 2 h. The reaction mixture
was then neutralized with dil. HCl under cooling. The solid
(VI) obtained was crystallized from DMF (72 %), m.p.146 °C;
ν
max 3225 (NH2), 2575 (SH), 1570 (C=N), 1045 and 1250 (-C-
O-C-). m.f.: C20H22N8O2S2; m/z 470; 1H NMR (δ, ppm): 2.50
(2H, s, SH), 2.81 (4H, s, acyclicCH2-CH2), 4.94 (4H, s, OCH2),
5.72 (4H, s, NH2), 7.1-7.9 (8H, m, ArH), CO).
VIIh: m.f.: C34H30N8O4S2; m.p.: 220 °C; m/z 678; 1H NMR
(δ, ppm): 2.82, (4H, s, acyclicCH2-CH2), 2.50 (2H, s, SH),
3.34 (s, 4H, s, Ar-OCH2) 5.06 (2H, s, N=CHAr), 7.12-7.83
(14H, m, ArH), 11.69 (2H, s, ArOH).
4,4'-Bis[4"-(N-benzylidinylamino)-3"-mercapto-
1",2",4"-triazol-5"-ylmethoxy]dibenzyl (VIIa-h): A solution
of compound VI (0.01 mol) in glacial acetic acid (20 mL) and
O
O
(i)
(ii)
(iii)
H2N
HO
HO
C
H2C O
III
H2NHN
C
H2C O
2
2
2
2
I
II
IV
N
N
N
N
(iv)
vi)
2
(v)
H2CO
HS
H2CO
HS
N
O
2
NH2
V I
V
R
C6H5
Compd.
VIIa
N
N
Scheme condition:
(i)
NaNO2/HCl,0.0 to -50 C
(ii) Cl-CH2COOH, K2CO2/dry acetone
(iii) NH2NH2·H2O
(iv) CS2/KOH
2-OHC6H4
4CH3OC6H4
4ClC6H4
3,4-(CH3O)C6H3
4-OH-3-CH3O·C6H3
4NO2C6H4
VIIb
VIIc
VIIe
VIIe
VIIf
a
b ∆
H+/
H2CO
HS
N
2
N=CHR
VIIa-h
(v) NH2NH2·H2O
(vi) R-CH=O
VIIg
VIIh
4OH-C6H4
Scheme-I

Vol. 29, No. 1 (2017) Synthesis of Bioactive 4,4'-bis[4"-(N-Benzylidinylamine)-3"-mercapto-1",2",4"-triazole-5"-yl methoxy]dibenzyl 21
RESULTS AND DISCUSSION
ACKNOWLEDGEMENTS
The refluxing of 4,4'-ethylenebisphenol(4,4'-dihydroxy
dibenzyl) in dry acetone with chloroacetic acid and potassium
carbonate gave 4,4'-ethylenebisphenoxyacetic acid (III)
which on refluxing with hydrazine hydrate yielded 4,4'-bis-
(methoxycarbohydrazide)dibenzyl IV. Compound IV on treat-
ment with CS2 and KOH gave 4,4’-bis[3"-mercapto-1",2",4"-
oxadiazole)-5"-yl methoxy]dibenzyl (V), which is again
treated with hydrazine hydrate gave 4,4"-bis(4"amino-3"-
mercapto-1",2",4"-triazole-5"-yl methoxy) dibenzyl (VI).
Compound VI on cyclocondensation with different aromatic
aldehyde gave 4,4’-bis[4"-(N-benzylidinylamino)-3"-mercapto-
1",2",4"-triazol-5"-ylmethoxy]dibenzyl (VIIa-h).
Compounds V, VI and VIIa-h were screened for their
antifungal activity against Fusarium oxysporum and Aspergillus
niger at 10, 100 and 1000 ppm concentration by Agar plate
technique [15]. A commercial fungicide dithane M-45 was
also tested under similar condition for comparing the results.
Among the tested compoundsVIIc,VIId andVIIe were found
to be most active against both the test fungus (Table-1).
TheauthorsaregratefultoTheHead, DepartmentofChemistry,
University of Allahabad, Allahabad, India for providing the
laboratory facilities and RSIC, CDRI, Lucknow, India for
conducting the spectral analysis.
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TABLE-1
ANTIFUNGAL SCREENING RESULTS OF
COMPOUNDS VIII, IX AND Xa-e
Aspergillus niger
Fusarium oxysporum
Compd.
1000
100
10
1000
100
10
ppm
47
64
78
73
100
93
89
68
ppm
ppm
ppm
51
61
67
69
100
87
83
70
ppm
ppm
15
20
27
12
51
32
22
18
28
30
14. C.R. Fuson and H.O. House, J. Am. Chem. Soc., 75, 1325 (1953).
15. J.G. Horsfall, Bot. Rev., 11, 357 (1945).
V
VI
32
50
52
47
67
61
72
44
50
47
13
24
32
21
53
38
29
12
23
20
29
33
50
34
74
69
64
49
52
48
VIIa
VIIb
VIIc
VIId
VIIe
VIIf
VIIg
VIIh
72
63
74
65