Synthesis and antimicrobial of some new substituted tetrazolomethylbenzo[d] -[1,2,3]triazole derivatives using 1H-benzo[d][1,2,3]triazole as starting material

Article abstract of DOI:10.1007/s11164-013-1059-6

A series of tetrazolomethylbenzo[d][1,2,3]triazole derivatives (2-14) have been synthesized and evaluated as antimicrobial agents from 1H-benzo[d][1,2,3] triazole (1) as starting material. The reaction of benzotriazole 1 with chloroacetonitrile afforded 2-(1H-benzo[d][1,2,3]-triazol-1-yl)acetonitrile 2, which was reacted with sodium azide to give tetrazole derivative 3. Esterification of benzotriazole 1 with ethyl bromoacetate in the presence of anhydrous potassium carbonate afforded ester 4, which was treated with hydrazine hydrate to afford the corresponding hydrazide 5. Reaction of 3 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide afforded the nitro-glycoside derivative 6, which was deacetylated using methanolic ammonia to deprotected nitroglycoside 7. The hydrazide 5 was reacted with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-benzenetetracarboxylic dianhydride in refluxing glacial acetic acid to give the corresponding imides 8 and 9, respectively. Also, the hydrazide 5 was reacted with carbon disulphide in ethanol to give potassium salt 10, which was reacted with hydrazine hydrate to afford aminotriazole derivative 11. The latter compound was reacted with carbon disulphide to afford thiadiazole derivative 12, which was treated with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide to give the thioglycoside derivative 13. Deacetylation of the thioglycoside 13 using methanolic ammonia solution at room temperature afforded the deprotected thioglycoside 14. The antimicrobial screening of some synthesized compounds showed that many of these compounds have good antimicrobial activities comparable to streptomycin and fusidic acid as reference drugs.

Full text of DOI:10.1007/s11164-013-1059-6

Res Chem Intermed
DOI 10.1007/s11164-013-1059-6
Synthesis and antimicrobial of some new substituted
tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives
using 1H-benzo[d][1,2,3]triazole as starting material
Omar M. Ali
Elsayed E. Mostafa
•
Abd El-Galil E. Amr
•
Received: 4 January 2013 / Accepted: 15 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract A series of tetrazolomethylbenzo[d][1,2,3]triazole derivatives (2–14)
have been synthesized and evaluated as antimicrobial agents from 1H-benzo[d]
[
1,2,3]triazole (1) as starting material. The reaction of benzotriazole 1 with chloro-
acetonitrile afforded 2-(1H-benzo[d][1,2,3]-triazol-1-yl)acetonitrile 2, which was
reacted with sodium azide to give tetrazole derivative 3. Esterification of benzotri-
azole 1 with ethyl bromoacetate in the presence of anhydrous potassium carbonate
afforded ester 4, which was treated with hydrazine hydrate to afford the corre-
sponding hydrazide 5. Reaction of 3 with 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl
bromide afforded the nitro-glycoside derivative 6, which was deacetylated using
methanolic ammonia to deprotected nitroglycoside 7. The hydrazide 5 was reacted
with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-benzenetetracarboxylic dian-
hydride in refluxing glacial acetic acid to give the corresponding imides 8 and 9,
respectively. Also, the hydrazide 5 was reacted with carbon disulphide in ethanol to
give potassium salt 10, which was reacted with hydrazine hydrate to afford amino-
triazole derivative 11. The latter compound was reacted with carbon disulphide to
O. M. Ali
Department of Chemistry, Faculty of Medical and Applied Science, Taif University, Turabah,
Taif, Saudi Arabia
O. M. Ali
Department of Chemistry, Faculty of Science, El-Menoufia University, Shebin El-Kom, Egypt
A. E.-G. E. Amr (&)
Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair,
College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
e-mail: aamr1963@yahoo.com
A. E.-G. E. Amr
Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, Egypt
E. E. Mostafa
Department of Microbial Chemistry, National Research Center, Cairo, Egypt
123

O. M. Ali et al.
afford thiadiazole derivative 12, which was treated with 2,3,4,6-tetra-O-acetyl-a-D-
glucopyranosyl bromide to give the thioglycoside derivative 13. Deacetylation of the
thioglycoside 13 using methanolic ammonia solution at room temperature afforded
the deprotected thioglycoside 14. The antimicrobial screening of some synthesized
compounds showed that many of these compounds have good antimicrobial activities
comparable to streptomycin and fusidic acid as reference drugs.
Keywords 1H-Benzo[d][1,2,3]triazole ꢀ Tetrazolomethylbenzo[d][1,2,3]triazole ꢀ
Sugar ꢀ Antimicrobial agents
Introduction
The heterocyclic group is of great importance in treating biological systems. Anti-
inflammatory, analgesic and antipyretic activities are observed in some heterocyclic
derivatives [1–5]. Some of synthetic compounds have exhibited a range of biological
activities, such as antitumor, antifilarial, antibiotic, antibacterial, antifungal, and anti-
inflammatory [6–9]. Also, heterocyclic derivatives have been reported to possess
diverse biological activities, such as antibacterial [10–16] and anti-inflammatory
[
17–19] activities. In addition, several substituted pyridines and their derivatives were
reported to exhibit significant antimicrobial [20], anti-inflammatory [21], and
anticancer activities [22]. In continuation of our interest in the heterocyclic chemistry
and disubstituted pyridine derivatives [23–26], we report here on the synthesis of
a new series of some substituted tetrazolomethylbenzo[d][1,2,3]triazole derivatives
as antimicrobial agents.
Results and discussion
2
-(1H-Benzo[d][1,2,3]triazol-1-yl)acetonitrile 2 was synthesized by the reaction of
benzotriazole 1 with chloroacetonitrile in the presence of anhydrous potassium
carbonate in DMF at room temperature. When, compound 2 reacted with sodium
azide in DMF in the presence of ammonium chloride at reflux temperature, it
afforded 1((1H-tetrazol-5-yl)methyl)-1H-benzo[d][1,2,3] triazole 3. The IR spectra
of 3 showed the presence of a characteristic absorption band corresponding to the
-
1
NH group in the region 3220 cm and the disappearance of the CN group present
in compound 2. On the other hand, esterification of benzotriazole 1 with ethyl
bromoacetate in the presence of anhydrous potassium carbonate in DMF at room
temperature afforded ethyl 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetate 4, which was
treated with hydrazine hydrate to afford the corresponding hydrazide 5 (Scheme 1).
The IR spectrum of 4 showed the presence of a characteristic absorption band
-
1
corresponding to the carbonyl group in the region 1747 cm and the disappearance
of the NH group present in benzotriazole 1. The IR spectrum of 5 showed the
presence of a characteristic absorption band corresponding to the NH group in
-
1
-1
the region 3746 cm and the NH group in the region 3328 and 3424 cm , and
2
-
1
the amide group in the region 1696 cm
.
1
23

Synthesis tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives
Reaction of 3 with 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide in dry
acetone at room temperature afforded the nitro-glycoside derivative 6, which was
deacetylated using methanolic ammonia solution at room temperature to the
corresponding deprotected nitroglycoside 7 (Scheme 2). The IR spectrum of 6
-
1
showed the characteristic absorption bands at 1745 cm corresponding to the
1
carbonyl group. Its H NMR spectrum revealed the presence of the O-acetyl-methyl
groups at d 2.02–2.20 ppm, the signals of the sugar protons were at d
4
at 3390 cm corresponding to the hydroxyl groups.
.07–6.20 ppm. The IR spectrum of 7 showed the characteristic absorption bands
-
1
Treatment of hydrazide 5 with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-
benzenetetracarboxylic dianhydride in refluxing glacial acetic acid afforded the corre-
sponding imide derivatives 8and 9, respectively (Scheme 3). The IR spectrum of 8showed
-
1
the characteristic absorption bands at 3166 cm corresponding to the NH group, at
-1
-
1
1
748 cm corresponding to the carbonyl group, and at 1613 cm corresponding to the
amide group. Also, the IR spectrum of 9 showed the characteristic absorption bands at
-
1
-1
455 cm corresponding to the NH group, at 1699 cm corresponding to the carbonyl
3
group, and at 1654 cm corresponding to the amide group.
-1
Finally, treatment of hydrazide 5 with carbon disulphide in ethanol in the presence
of potassium hydroxide at water bath temperature, afforded potassium salt 10, which
was reacted with hydrazine hydrate in water at refluxed temperature with stirring to
afford the corresponding aminotriazole derivative 11. The latter compound 11 was
reacted with carbon disulphide in ethanol in the presence of potassium hydroxide
at refluxed temperature to give 3-((1H-benzo[d][1,2,3] triazole-1-yl)methyl-[1,2,4]
N
BrCH COOC H /
ClCH CN/
2
2
2 5
N
K CO / DMF, r.t
K CO , DMF, r.t
2
3
2
3
N
H
1
N
N
N
N
N
N
O
CH CN
4
2
2
O
NH NH .H O/
2
2
2
NaN , NH Cl/
3
4
EtOH, reflux
DMF , reflux
N
N
N
N
N
O
N
N
N
N
NH
2
N
H
N
H
5
3
Scheme 1 Synthetic pathway for compounds 2–5
123

O. M. Ali et al.
N
N
AcO
N
N
N
O
N
N
OAc
OAc
N
N
Br
AcO
N
N
AcO
N
O
N
OAc
OAc
KOH/acetone/r.t.
N
H
3
6
AcO
eOH
3/
M
H
N
N
r.t
N
N
N
N
OH
N
O
N
OH
OH
7
HO
Scheme 2 Synthetic pathway for compounds 6 and 7
Cl
O
N
N
Cl
N
O
Cl
Cl
O
O
N
N
O
Cl
Cl
N
Acetic acid
reflux
HN
N
O
Cl
5
O
HN
NH
2
Cl
8
O
O
O
O
O
Acetic acid
reflux
O
N
N
N
N
N
N
O
O
O
O
HN
N
N
NH
O
O
9
Scheme 3 Synthetic pathway for compounds 8 and 9
triazolo[3,4-b][1,3,4]thiadiazole-6-thiol 12, which was treated with 2,3,4,6-tetra-O-
acetyl-a-D-glucopyranosyl bromide to give the thioglycoside derivative 13. Deacet-
ylation of the thioglycoside 13 using methanolic ammonia solution at room
1
23

Synthesis tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives
temperature afforded the deprotected thioglycoside 14 (Scheme 4). The IR spectrum
-1
of 13 showed the characteristic absorption bands at 1741 cm corresponding to the
1
carbonyl group. Its H NMR spectrum revealed the presence of the O-acetyl-methyl
groups at d 2.06–2.24 ppm and the signals of the sugar protons at d 4.11–6.23 ppm.
The IR spectrum of 14 showed the characteristic absorption bands at 3,405 cm
corresponding to the hydroxyl groups.
-1
Antimicrobial activity
The antimicrobial activities of the synthesized compounds 2–14 were determined by
the agar diffusion method as recommended by the national committee for clinical
laboratory standards (NCCLS) [27]. The compounds 2–14 were evaluated for
antimicrobial activity against bacteria, i.e. Streptomyces sp., Bacillus subtilis,
Streptococcus lactis, Escherichia coli, and Pseudomonas sp. and antifungal activity
against various fungi, i.e. (Aspergillus niger, and Penicillium sp.) and yeast
(
Candida albicans and Rhodotorula ingeniosa).
The concentrations of the tested compounds (10 lg/mL) were used according to
modified Kirby–Bauer’s disk diffusion method [28]. The sterile discs were
impregnated with 10 lg/disc of the tested compound. Each tested compound was
performed in triplicate. The solvent DMSO was used as a negative control and
streptomycin/fusidic acid were used as standard calculated average diameters (for
triplicates) of the zone of inhibition (in mm) for tested samples with that produced
by the standard drugs.
Some of the synthesized compounds exhibited potent antibacterial and antifungal
bioactivity compared with standard drug used. The other tested compounds were
found to exhibit a moderate of low antibacterial activity (Table 1). On the other
hand, when different concentrations of the compound that exhibited a moderate
antibacterial activity (6, 12, 13) were used, this compound exhibit very good
antibacterial activity at higher concentration (39 and 49) (Table 2), while the
different concentrations of compounds (3 and 7) exhibited a very good antifungal
activity (29 and 39) (Table 3).
Experimental
Melting points were measured with a B u¨ chi apparatus and are uncorrected. TLC was
performed on plastic plates Silica Gel 60 F254 (layer thickness 0.2 mm; Merck). IR
spectra (KBr) were recorded on Bruker-Vector22 instrument (Bruker, Bremen,
1
Germany). H NMR spectra were recorded on Varian Gemini spectrometer at
3
00 MHz and 200 MHz with TMS as internal standard. Chemical shifts were reported
in d scale (ppm) relative to TMS as a standard, and the coupling constants (J values)
are given in Hz. The progress of the reactions was monitored by TLC using aluminium
silica gel plates 60 F245. EI-mass spectra were measured on HP D5988 A 1,000 MHz
spectrometer (Hewlett–Packard, Palo Alto, CA, USA). Elemental analyses were
carried out at the Microanalytical center of Cairo University. Compounds 2 and 3 have
been synthesized according to the reported procedures [29].
123

O. M. Ali et al.
N
N
N
N
N
CS / KOH
2
N
O
O
S
EtOH
SK
NH
NH2
N
H
10
HN
5
NH NH / H O
2
2
2
reflux / stirring
N
N
N
N
CS / KOH
2
N
N
EtOH / reflux
N
N
N
N
N
N
SH
S
12
N
11
NH2
SH
OAc
TEA/DMF/r.t.
O
AcO
AcO
Br
OAc
N
N
N
N
N
N
N
N
N
N
NH / MeOH
3
N
N
N
r.t
OH
OAc
S
S
N
O
O
HO
AcO
AcO
S
S
HO
OH
OAc
1
4
13
Scheme 4 Synthetic pathway for compounds 10–14
2
-(1H-Benzo[d][1,2,3]triazol-1-yl)acetonitrile (2)
To a solution of benzotriazole 1 (5.59 g, 0.05 mol) and anhydrous potassium
carbonate (7 g, 0.05 mol) in dimethylformamide (20 mL), chloroacetonitrile (3.8 g,
0.05 mol) was added dropwise. The reaction mixture was stirred overnight at room
temperature, and then poured onto water. The obtained crude product was extracted
1
23

Synthesis tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives
Table 1 Antimicrobial activities of the newly compounds
Comp. No.
Inhibition zone (mm)
Bacteria strains
Str. sp.
Fungi strains
Gram-
Gram?
A.n.
Pen. sp.
Cand. alb.
R.i.
B.s.
S.l.
E.c.
P. sp.
2
3
6
7
8
9
13
11
17
14
21
14
7
12
12
16
15
23
15
8
10
12
15
13
23
13
10
20
18
12
21
–
9
13
17
11
22
12
9
11
11
16
11
21
14
8
19
14
13
14
19
12
11
21
13
19
–
20
13
12
15
20
13
12
21
12
18
–
19
16
11
14
19
11
11
22
11
19
–
19
15
12
13
21
12
10
21
12
17
–
11
12
13
14
20
18
10
21
–
21
16
11
22
–
19
17
13
22
–
20
16
13
21
–
Streptomycin
Fusidic acid
17
17
18
18
B.s. Bacillus subtilis, S.l. Streptococcus lactis, E.c. Escherichia coli, P. sp. Pseudomonas sp., Str. sp.
Streptomyces sp., A.n. Aspergillus niger, Pen. sp. Penicillium sp. Cand. alb Candida albicans, R.i.
Rhodotorula ingeniosa
Table 2 Effect of different
concentrations of the selected
compounds 6, 12 and 13
Comp. No.
Conc.
Str. sp.
Bacteria strains
Gram-
Gram?
B. s
S. l
E.c
P. sp.
6
19
16
19
22
23
20
22
23
24
16
20
22
22
17
20
22
24
20
23
25
25
18
20
22
23
16
19
21
23
21
22
24
26
16
19
21
23
15
18
20
22
20
22
25
25
18
21
23
23
17
20
22
23
19
22
24
24
17
20
24
24
29
39
49
1
2
3
19
29
39
49
1
19
29
39
49
9
= 10 lg
Species abbreviations as in
Table 1
from the reaction mixture by ethyl acetate, dried over anhydrous potassium
carbonate, and evaporated under reduced pressure. The obtained residue was
triturated with diethyl ether, filtered off, dried, and crystallized from ethanol to give
123

O. M. Ali et al.
Table 3 Effect of different
concentrations of selected
compounds 3 and 7
Comp. No
Conc.
Fungi strains
A.n
Pen. sp.
Cand. alb.
R.i
3
19
14
15
18
20
14
16
18
20
13
15
17
19
15
16
19
19
16
18
20
20
14
17
20
20
15
17
20
21
13
16
20
20
29
39
49
7
19
29
39
49
9
= 10 lg
Species abbreviations as in
Table 1
compound 2 as colorless crystals. Yield 7.5 g (94 %), m.p. = 86–88 °C; MS,
?
m/z (%): 158 [M , 100] corresponding to the molecular formula C H N . Anal.
8
6 4
Calcd. For C H N (158.16): C, 60.75; H, 3.82; N, 35.42. Found: C, 60.70; H,
8
6 4
3
1
.78; N, 35.37.
((1H-Tetrazol-5-yl)methyl)-1H-benzo[d][1,2,3]triazole (3)
A mixture of compound 2 (2.2 g, 0.01 mol), sodium azide (0.91 g, 0.014 mol) and
ammonium chloride (0.75 g, 0.014 mol) in dimethylformamide (7 mL) was heated
under reflux for 1 h. The reaction mixture was evaporated under reduced pressure,
the obtained residue was solidified with water (20 mL) and the resulting
precipitate (first portion) was collected by filtration. The filtrate was acidified
with dilute hydrochloric acid to pH *2, after cooling; the obtained solid (second
portion) was filtered off, washed with water, and dried. The two portions were
combined and crystallized from methanol to give compound 3 as white powder.
-
1
Yield 2.5 g (92.5 %); m.p. = 180–182 °C; IR (KBr) cm ; 3220 (NH). MS,
?
m/z (%): 201 [M , 12] corresponding to the molecular formula C H N . Anal.
8
7 7
Calcd. For C H N (201.18): C, 47.76; H, 3.51; N, 48.73. Found: C, 47.71; H,
8
7 7
3
.48; N, 48.68.
Ethyl 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetate (4)
To a stirred solution of compound 1 (1.19 g, 0.01 mol) and anhydrous potassium
carbonate (1.4 g, 0.01 mol) in dimethylformamide (8 mL), ethyl bromoacetate
(
2.2 g, 0.01 mol) was added dropwise at room temperature. The reaction mixture
was continued at the same condition for 24 h, then poured into ice water. The
obtained precipitate was filtered off, washed with water, dried, and crystallized from
ethanol to afford the corresponding compound 4 as white powder. Yield 1.98 g
-
1
?
(
96 %); m.p. = 242–244 °C. IR (KBr, cm ): 1747 (C=O); MS, m/z (%): 205 [M ,
] corresponding the molecular formula C H N O . Anal. Calcd. For C H N O
205.21): C, 58.53; H, 5.40; N, 20.48. Found: C, 58.45; H, 5.35; N, 20.42.
8
1
0
11
3
2
10 11 3 2
(
1
23

Synthesis tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives
2
-(1H-Benzo[d][1,2,3]triazol-1-yl)acetohydrazide (5)
A mixture of the ester 4 (2.05 g, 0.01 mol) and hydrazine hydrate (1.5 g, 0.03 mol)
in absolute ethanol (15 mL) was refluxed for 5 h. The reaction mixture was diluted
with cold water (5 mL); the obtained precipitate was filtered off, washed with water,
dried, and crystallized from ethanol to afford the corresponding hydrazide 5 as
-
1
white crystals. Yield 1.9 g (57 %), m.p. = 186–188 °C; IR (KBr, cm ): 3746
?
(
corresponding to the molecular formula C H N O. Anal. Calcd. For C H N O
NH), 3424 and 3328 (NH ), 1696 (C=O); MS, m/z (%): 191 [M , 15]
2
8
9
5
8 9 5
(
191.18): C, 50.26; H, 4.74; N, 36.63. Found: C, 50.20; H, 4.69; N, 36.58.
2
-(5-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl-1H-tetrazol-1-yl)-6-
acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (6)
(
To a solution of compound 3 (2.01 g, 0.01 mol) in aqueous potassium hydroxide
0.56 g, 0.01 mol in distilled water (2 mL)], a solution of 2,3,4,6-tetra-O-acetyl-a-
[
D-glucopyranosyl bromide (4.25 g, 0.01 mol) in acetone (20 mL) was added. The
reaction mixture was stirred at room temperature for 7 days. The solvent was
evaporated under reduced pressure at 40 °C and the residue was washed with
distilled water to remove potassium bromide formed. The product was dried, and
crystallized from ethanol to obtain compound 6 as white powder. Yield 3.35 g
-
1
1
(
70.82 %), m.p. = 98–100 °C. IR (KBr, cm ): 1745 (C=O). H NMR (DMSO-d ):
6
d = 2.02–2.20 (s, 12H, 4-COCH ), 4.07–4.19 (m, 2H, H-5}), 5.04 (m, 1H, H-4‘),
3
5
.07 (m, 1H, H-5‘), 5.20 (m, 1H, H-2‘), 5.37 (s, 2H, CH CN), 5.52 (m, 1H, H-3‘),
2
?
.20 (m, 1H, H-1‘), 7.09–8.13 (m, 4H, Ar–H) ppm; MS, m/z (%): 531 [M , 6]
6
corresponding to the molecular formula C H N O . Anal. Calcd. For C H N O
22 25 7 9
2
2
25
7
9
(
531.47): C, 49.72; H, 4.74; N, 18.45. Found: C, 49.66; H, 4.70; N, 18.38.
2
-(5-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-1H-tetrazol-1-yl)-tetrahydro-6-
hydroxymethyl)-2H-pyran-3,4,5-triol (7)
(
A solution of compound 6 (0.47 g, 0.001 mol) in methanolic ammonia was stirred at
room temperature for 4 days. The reaction mixture was evaporated under reduced
pressure, the obtained residue was extracted with ethyl acetate, dried over
anhydrous sodium sulphate, and evaporated to dryness to give compound 7 as an
-
1
oily product in pure form. Yield 0.18 g (50 %); IR (KBr, cm ): 3390 (broad band,
OH). Anal. Calcd. For C H N O (353.32): C, 46.28; H, 4.72; N, 26.99. Found: C,
1
4 17 7 5
4
6.23; H, 4.66; N, 26.93.
2
-(1H-Benzo[d][1,2,3]triazol-1-yl)-N-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-
-yl)acetamide (8)
2
To a suspension of the benzotriazole hydrazide 5 (0.19 g, 1 mmol) and 2,3,4,
5
7
-tetrachlorophthalic anhydride (1 mmol) in acetic acid (50 mL) was refluxed for
h. The solid was collected by filtration by filtration, washed with acetic acid,
and crystallized from methanol to give compound 8 as white powder.
123

O. M. Ali et al.
-
1
Yield = 0.32 g (69.7 %), m.p. [ 300. IR (KBr) cm : 3166 (NH), 1748 (C=O),
?
613 (amide); MS, m/z (%): 459 [M , 4] corresponding to the molecular formula
1
C H Cl N O . Anal. Calcd. For C H Cl N O (459.07): C, 41.86; H, 1.54; Cl,
1
6
7
4
5
3
16
7
4 5 3
3
0.89; N, 15.26. Found: C, 41.80; H, 1.50; Cl, 30.84; N, 15.22.
0
N,N -(1,3,5,7-tetraoxopyrrolo[3,4,f]isoindole-2,6(1H,3H,5H,7H)-diyl)bis(2-(1H-
benzo[d]-[1,2,3]triazol-1-yl)acetamide) (9)
To a suspension of the benzotriazole hydrazide 5 (0.19 g, 1 mmol) and 1,2,4,5-
benzenetetracarboxylic dianhydride (2 mmol) in acetic acid (50 mL) was refluxed
for 7 h. The solid was collected by filtration by filtration, washed with acetic acid
and crystallized from methanol to give compound 9 as gray powder. Yield = 0.38 g
-
1
(
m/z (%): 564 [M , 12] corresponding to the molecular formula C H N O . Anal.
67.3 %), m.p. [ 300; IR (KBr, cm ): 3455 (NH), 1699 (C=O), 1654 (amide); MS,
?
2
6 16 10 6
Calcd. For C H N O (4564.46): C, 55.32; H, 2.86; N, 24.81. Found: C, 55.26;
6 16 10 6
2
H, 2.80; N, 24.76.
Potassium 2-(2-(1H-benzo[d][1,2,3]triazol-1-yl)acetyl)hydrazinecarbodithioate
10)
(
A solution of potassium hydroxide (0.57 g, 0.01 mol), benzotriazol hydrazide 5
(
(
1.91 g, 0.01 mol) and carbon disulphide (1.52, 0.02 mol) in absolute ethanol
20 mL) was heated on a water bath for 15 h. The reaction mixture was evaporated
under reduced pressure to give a gum material 10 in pure form. Yield = 2 g
(
65.5 %), Anal. Calcd. For C H KN OS (305.42): C, 35.39; H, 2.64; N, 22.93; S,
9 8 5 2
2
1.00. Found: C, 35.35; H, 2.60; N, 22.87; S, 20.95.
5
-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-4-amino-4H-1,2,4-triazol-3-thiol
11)
(
To suspension of (3.05 g, 0.01 mol) potassium salt 10 in water (1 mL), hydrazine
hydrate (0.02 mol) was added. The reaction mixture was refluxed with stirring for
about 6 h, until the evaluation of hydrogen sulphide, diluted with water (30 mL) and
acidified with HCl. The formed solid was filtered off, washed with cold water,
and crystallized from ethanol to give compound 11. Yield = 1.8 g, (72 %),
?
m.p. = 228–230 °C; MS, m/z (%): 247 [M , 24] corresponding to the molecular
formula C H N S. Anal. Calcd. For C H N S (247.27): C, 43.71; H, 3.67; N, 39.65;
S, 12.97. Found: C, 43.65; H, 3.60; N, 39.60; S, 12.92.
9
9
7
9 9 7
3-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)[1,2,4]tiazolo[3,4-b][1,3,4]thia
diazaole-6-thiol (12)
To a mixture of compound 11 (2.47 g, 0.01 mol) and potassium hydroxide (0.57 g,
0
.01 mol) in ethanol (30 mL), carbon disulphide (1.52 g, 0.02 mol) was added. The
reaction mixture was refluxed for 40 h, then evaporated under reduced pressure, and
the obtained residue was dissolved in 10 % KOH. The solution was acidified with
1
23

Synthesis tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives
dil. HCl to pH 3, the obtained solid was filtered off, washed with water, dried,
and crystallized from methanol to give compound 12 as a pale-brown powder,
?
Yield = 1.8 g (62.2 %), m.p. = 190–192 °C; MS, m/z (%): 289 [M , 65]
corresponding to the molecular formula C H N S . Anal. Calcd. For C H N S
10 7 7 2
1
0
7
7
2
(289.33): C, 41.51; H, 2.44; N, 33.89; S, 22.16. Found: C, 41.44; H, 2.40; N, 33.83;
S, 22.12.
2
-(3-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)[1,2,4]triazolo[3,4,b]
1,3,4]thiadiazol-6-ylthio)-6-acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl
[
triacetate (13)
To a solution of compound 12 (2.89 g, 0.01 mol) in DMF (10 mL), triethylamine
(
1 mL) and 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide (4.25 g, 0.01 mol)
were added. The reaction mixture was stirred at room temperature for 7 days, then
poured onto ice water. The obtained solid was filtered off, washed with water, dried,
and crystallized from methanol to obtain compound 13 as a page powder.
-
1
1
Yield = 3.5 g (56.5 %), m.p. = 114–116 °C; IR (KBr) cm : 1741 (C=O); H
NMR (DMSO-d ): d = 2.06–2.24(s, 12H, 4-Ac), 4.11–4.23 (m, 2H, H-5}), 5.04 (m,
6
1
H, H-4‘), 5.08 (m, 1H, H-5‘), 5.11 (m, 1H, H-2‘), 5.24 (s, 2H, CH CN), 5.40 (m,
2
1
H, H-1‘), 6.23 (m, 1H, H-3‘), 7.54–8.13(m, 4H, Ar–H) ppm; MS, m/z (%): 620
?
M ?1, 5] corresponding the molecular formula C H N O S . Anal. Calcd. For
[
C H N O S (619.62): C, 46.52; H, 4.07; N, 15.82; S, 10.35. Found: C, 46.45; H,
2
4 25 7 9 2
2
4 25 7 9 2
4
.00; N, 15.76; S, 10.30.
2
-(3-((1H-Benzo[d][1,2,3]triazol-1-yl)methyl)-[1,2,4]triazolo[3,4-b]
[
1,3,4]thiadiazol-6-ylthio)-tetrahydro-6-(hydroxymethyl)-2H-Pyran-3,4,5-triol
14)
(
A solution of compound 13 (0.619 g, 0.001 mol) in methanolic ammonia solution
15 mL) was stirred at room temperature for 4 days. The reaction mixture was
evaporated under reduced pressure to dryness to give compound 14 as an oily
(
-
1
material in pure form. Yield = 0.25 g (55.5 %); IR (KBr) cm : 3405 (broad band,
?
OH); MS, m/z (%): 451 [M , 24] corresponding to the molecular formula
C H N O S . Anal. Calcd. For C H N O S (451.48): C, 42.56; H, 3.80; N,
16 17 7 5 2
1
6
17
7
5
2
2
1.72; S, 14.20. Found: C, 42.50; H, 3.75; N, 21.68; S, 14.15.
Acknowledgment The authors extend their appreciation to the Deanship of Scientific Research at King
Saud University for funding the work through the research group project No. RGP-VPP-0172.
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