Facile Synthesis of N-(Benzyl-1H-1,2,3-Triazol-5-yl) Methyl)-4-(6-Methoxybenzo [d] Thiazol-2-yl)-2-Nitrobenzamides via Click Chemistry

Article abstract of DOI:10.1002/jhet.2647

A series of novel N-((l-benzyl-lH-l,2,3-triazol-5-yl) methyl)-4-(6-methoxy benzo[d]thiazol-2-yl)-2-nitrobenzamide derivatives were prepared from 4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitro-N-(prop-2-ynyl) benzamide with benzyl azides by using click reaction (copper-catalyzed Huisgen 1,3-dipolar cycloaddition reaction) in the presence of CuSO₄.5H₂O and sodium ascaorbate. All the newly synthesized compounds were evaluated further in vitro antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtillis), Gram-negative bacteria (Echerichia coli and Pseudomonas aeuroginosa), and fungi (Aspergillus niger and Aspergillusfumigatus) strains. The new compounds were characterized based on spectroscopic evidence. Among them compounds 10a, 10h, and 10i were showed promising activity when compared with standard drugs Ciprofloxacin and Miconazole.

Full text of DOI:10.1002/jhet.2647

Month 2016
Facile Synthesis of N-(Benzyl-1H-1,2,3-Triazol-5-yl) Methyl)-4-
1
(6-Methoxybenzo [d] Thiazol-2-yl)-2-Nitrobenzamides via Click Chemistry
a
a
b
*
Bharath Yarlagadda, Nagaraj Devunuri, and V. Basaveswara Rao Mandava
aChemistry Division, Department Science and Humanities, Vignan’s Foundation for Science Technology and Research
University (VFSTR) University, Vadlamudi, Guntur, Andhra Pradesh 522 213, India
bDepartment of Chemistry, Krishna University, Nuzvid, Andhra Pradesh 521 201, India
*
E-mail: vbrmandava@yahoo.com
Additional Supporting Information may be found in the online version of this article.
Received December 6, 2015
DOI 10.1002/jhet.2647
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel N-((l-benzyl-lH-l,2,3-triazol-5-yl) methyl)-4-(6-methoxy benzo[d]thiazol-2-yl)-2-
nitrobenzamide derivatives were prepared from 4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitro-N-(prop-2-ynyl)
benzamide with benzyl azides by using click reaction (copper-catalyzed Huisgen 1,3-dipolar cycloaddition
reaction) in the presence of CuSO4.5H2O and sodium ascaorbate. All the newly synthesized compounds
were evaluated further in vitro antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus
and Bacillus subtillis), Gram-negative bacteria (Echerichia coli and Pseudomonas aeuroginosa), and fungi
(Aspergillus niger and Aspergillusfumigatus) strains. The new compounds were characterized based on spec-
troscopic evidence. Among them compounds 10a, 10h, and 10i were showed promising activity when com-
pared with standard drugs Ciprofloxacin and Miconazole.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
Additionally, the [3+ 2] cycloaddition is also well known
as Husigen cycloaddition of alkynes to azides to form 1, 4
-disubstituted [1,2,3]-trizoles. These copper (I) catalyzed
[3 + 2] reactions comply fully with the sense of click chem-
istry. Hence, azide–alkyne cycloaddition has put a focus on
as a prototype click chemistry reaction. It is important to the
existence that click reactions achieve their required character-
istics by having a high thermodynamic driving force, usually
greater than 20kcal molÀ1. Such processes proceed rapidly
to completion and also tend to be highly selective for a single
product. We recognize the convenient of inter-molecular
azide-alkyne [3 +2] cycloaddition in order to construct
N-((l-benzyl-lH-l,2,3-triazol-5-yl) methyl)-4-(6-methoxybenzo
[d]thiazol-2-yl)-2-nitrobenzamides. Herein, we describe the
click chemistry and approach for the constructed by copper cat-
alyzed azide–alkyne cycloaddition reaction and their biological
activity studies of N-((l-benzyl-lH-l, 2, 3-triazol-5-yl) methyl)-
4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamides.
Benzothiazole scaffold derivatives consist of fused bicy-
clic ring systems. Benzothiazoles are an important class of
potential organic molecules in medicinal chemistry be-
cause of their extensive range of activity such as neuron
protective [1,2], anti-convulsive [3,4], anti-glutamate [5],
anti-malarial [6], anthelmintic [7], anti-tubercular [8], anal-
gesic, anti-inflammatory [9], antimicrobial [10–14], and
anti-cancer effect [15–17]. In this context, promising bio-
logical profile molecules that are synthetically accessible
have attracted the attention of medicinal organic chemists.
Consequently, design and synthesis of new benzothiazole
scaffold derivatives are attracted as potential chemothera-
peutics. Azide–alkyne [3 + 2] cycloaddition [18] illustrates
that it bring about many of the necessitous. It is well
known that many of the simple mono substituted alkynes
and organic azides are accessible commercially. Many
others can effortlessly be synthesized [18] with an extensive
range of functional groups, those cycloaddition reactions
selectively gives 1,2,3-triazoles. In fact, a Cu (I) catalyzed
alternative that follows a divergent mechanism and insensi-
tive to oxygen and water. These click reactions proceed un-
der mild conditions and not required any protecting groups.
RESULTS AND DISCUSIONS
The synthetic methodology was adopted from the reac-
tion of 4-methyl benzoic acid 1 that reacted with nitrating
© 2016 Wiley Periodicals, Inc.

B. Yarlagadda, N. Devunuri, and V. B. R. Mandava
Vol 9999
mixture afforded to 4-methyl-3 nitro benzoic acid 2.
4-Methyl-3 nitro benzoic acid 2 treated with thionylchloride
followed by p-anisidine in the presence of triethyl amine at
0°C afforded pale yellow crystals of N-(4- methoxyphenyl)-
4-methyl-3-nitrobenzothioamide 3 with 90% yield. Then
compound 3 was converted to N-(4- methoxyphenyl)-4-
methyl-3-nitrobenzothioamide 4 by reacting with Lawesson’s
reagent in dry toluene under reflux condition with 75% yield. Fi-
nally, 6-methoxy-2-(4-methyl-3-nitrophenyl) benzo[d]thiazole
5 were achieved by intra-molecular free-radical cyclization of
N-(4- methoxyphenyl)-4-methyl-3-nitrobenzothioamide 4 by
using Dess–Martin per iodine in CH2Cl2 at room temperature.
The product is light yellow solid in 85% yield (Scheme 1).
Compound 5 upon treatment with freshly prepared tetra
butyl ammonium permanganate (TBAP) in dry pyridine at
room temperature afforded, 6-methoxy-2-(4-methyl-3-
nitrophenyl) benzo[d] thiazole [19–21] (6), as light yellow
solid in 88% yield. Nitro acid 6 was converted to its acid
chloride [25], 7 with thionylchloride, which was condensed
with propargyl amine in the presence of triethyl amine to
obtain nitro amide as brownish solid [21] 8 in 85% yields.
Compound 8 and benzyl azides 9a–j in the presence of
0.5mol% CuSO4.5H2O and 10 mol% sodium ascaorbate
afforded the triazole. The reaction is regioselective only in
the presence of Cu (I) or Cu (II) salts as a catalyst, because
Cu (I) as a catalyst strongly activates the terminal acety-
lenes toward 1,3-dipole in azide to give the desired 1,4-
disubstituted [1,2,3]-triazole derivatives 10a-j in good
yields (85–87%) via click Chemistry [1 g]. Structures were
confirmed by utilizing spectral data and elemental analysis.
We observed that electron-donating methoxy (ÀOCH3)
and benzoxyl (ÀOBn) substituted compounds showed
more antibacterial active compared with other substituted
N-((l-benzyl-lH-l,2,3-triazol-5-yl)methyl)-4-(6-methoxybenzo
[d]thiazol-2-yl)-2-nitrobenzamides(10a-j). All the synthesized
compounds were in good agreement with the proposed
structure. The physical characterization data are given in
Table 1 and Scheme 2.
Antimicrobial activity. In view of developing new class
of antimicrobial agents, synthesized novel compounds were
screened for their in vitro antimicrobial activities to
determine zone of inhibition at 100 μg/mL against two
Gram-positive bacteria (Staphylococcus aureus [MTCC 096],
Bacillus subtilis [MTCC 441]) and two Gram-negative bacteria
(Escherichia coli [MTCC 443], Pseudomonas aeruginosa
[MTCC 424]), as well as two fungi (Aspergillusniger [MTCC
282], Aspergillus fumigates [MTCC 343]), strains using cup
plate method [22,23] where inoculated Muller–Hilton agar for
bacteria and Sabouraud dextrose agar for fungi was poured
onto the sterilized petri dishes (25–30 mL each petri dish).
The poured material was allowed to set (30min), and
thereafter, the ‘cups’ (6-mm diameter) was made by punching
into the agar surface with a sterile cork borer and scooping
out the punched part of the agar. Into these cups, the test
compound solution (0.1 mL) was added with the help of a
micro pipette. The plates were incubated at 37° C for 14 h for
bacteria and 30h for fungi, and the results were noted. The
test solution was prepared by DMSO as solvent. Clinically
antimicrobial drugs Ciprofloxacin and Miconazole were
used as the positive control, and DMSO was used for blank.
The results of antimicrobial screening are summarized in
Table 2. Revealed that all the synthesized compounds,
10a–j could effectively, to some extent, inhibit the growth
of all tested strains in vitro. In antibacterial studies, all the
compounds tested were found less active towards B.subtilis,
as compared with other three strains of bacteria. Most of
the compounds showed moderate to good activity against
S.aureus. In general, 10a, 10 h, and 10i have shown good
Scheme 1. Synthetic schemes of 6-methoxy-2-(4-methyl-3-nitrophenyl)-l,3-benzothiazole and reagents and conditions: (a) Conc. HNO3, Conc. H2SO4
(1:2), CH2C12, 0°C – R. T, 5 h, 84% (b) (i) SOC12, cat. DMF, CH2C12 (ii)P-Anisidine, Et3N, THF, 0 °C- R.T,90% (c) Lawesson’s reagent, toluene, 95°C,75%
(d) DMP, CH2C12, R. T, 20 min, 85%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
N-(Benzyl-1H-1,2,3-Triazol-5-yl) Methyl)-4-(6-Methoxybenzo [d] Thiazol-2-yl)-2-
Nitrobenzamides
Table 1
Physical characterization data of compounds 10a–j.
S. no.
Compound no.
Molecular formula (10a–j)
Time (h)
Yield (%)
mp (°C)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
10a
10b
10c
10d
10e
10f
10 g
10 h
10i
C
25H20N6O4S
12.0
11.4
12.0
11.5
11.3
11.3
12.0
12.0
10.0
11.0
87
85
85
83
83
85
87
85
84
85
205.4–206.6
210–212
196–197
C25H18N6O6S
C22H20N6O6 S
C33H28N6O6 S
C33H28N6O6S
C25 H19ClN6O4 S
C29 H28N6O4S
C29H22N6O4S
C28H26N6O7S
C26H19F3N6O4 S
181–182
169.9–170.8
187.8–188.7
184.3–185.6
193–194
182.8–184.2
196.4–197.5
10j
Scheme 2. Synthetic schemes of N-((l-benzyl-lH-l,2,3-triazol-5-yl) methyl)-4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamides (10a-j) and their re-
agents and conditions: (a) TBAP, dry pyridine, R.T, 88%; (b) SOCl2, cat. DMF, CH2Cl2, R.T, 85%; (c) Propargyl amine, Et3N, dry THF, 0°C – R.T,85%
(d) 0.5 mol% CuSO4.5H2O, 10 mol% Sodium ascorbate, t-BuOH:H2O, R.T, 12 h, (85–95)%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Yarlagadda, N. Devunuri, and V. B. R. Mandava
Vol 9999
Table 2
Antimicrobial activity of title compounds 10a–j.
Zones of inhibition in mm
Anti-bacterial activity (100 μg/mL)
Antifungal activity (100 μg/mL)
Fungi
Gram-positive bacteria
Gram-negative bacteria
Staphylococcus
aureus
Bacillus
subtilis
Escherichia
Pseudomonas
aeruginosa
Aspergillus
Niger
Aspergillus
fumigates
Compound
coli
10a
10b
10c
10d
10e
10f
10 g
10 h
17
13
15
13
13
14
13
16
17
14
20
—
14
12
11
11
10
11
11
10
13
11
21
—
12
15
16
12
10
10
12
14
16
13
22
—
13
12
12
10
11
13
12
14
14
14
20
—
10
10
11
12
11
13
13
14
14
13
—
29
17
18
17
18
18
19
18
18
18
18
—
22
10i
10j
Ciprofloxacin
Miconazole
antibacterial activity against S.aureus. Compunds 10b, 10c,
and 10i have shown moderate activity against E.coli. Out of
two strains of fungi, these compounds were found to be less
active against Aspergillusniger whereas showed moderate to
good activity against A.fumigatus. Compounds, 10a, 10b,
10c, 10d, 10e, 10f, 10g, 10h, 10i, and 10j possessed good
antifungal activity against A.fumigates.
The standard drug for bacteria is Ciprofloxacin and the
standard drug for fungi is Miconazole Zone of Inhibition
(internal diameter: 6 mm). All the compounds were
screened at 100 μg/mL concentration.
spectra were recorded on Perkin-Elmer 683 series
spectrometer (Waltham, MA, USA) with KBr optics, and
1H NMR (400MHz) were recorded on Bruker Avance
400 spectrometer (Billerica, MA, USA) using TMS as
internal standard (chemical shifts in ppm). Mass spectra
were recorded on a VG micro mass 70–70H (Ringoes,
NJ) instrument. CHN analysis was carried out using
Vario Micro Cube Elementar instrument (Donaustraße 7,
Hanau, Germany).
General procedure for the synthesis of N-((l-benzyl-lH-l,
2, 3-triazol-5-yl) methyl)-4-(6-methoxybenzo[d]thiazol-2-yl)-2-
nitrobenzamides (10a–j). Here, we describe the synthesis
of 10a as a model synthesis, and corresponding spectral
data are provided later. Water and tertiary alcohol in the
ratio 1:1 (50mL) were added to the round bottom flask
containing compounds 8a, (5g, 27.2mmol) possessing
triple bond and freshly prepared benzyl azides (4.68g,
35.1mmol) (9a) and stirred for 5–10min. To this reaction,
mixtures were added 0.5mol% CuSO4.5H2O (0.339g,
1.36mmol.) and 10mol% sodium ascorbate (2.155g,
0.40mmol) simultaneously. Reaction was continued for
12 h at room temperature till the completion of the
reaction. After the completion of the reaction (monitored
by Thin Layer Chromatography (TLC)), tertiary alcohol
was removed under pressure, and the aqueous layer was
extracted with ethyl acetate (3 × 50 mL). The combined
organic layer was washed with brine solution and dried
over Na2SO4. The organic layer was separated and
removed in vacuo under reduced pressure. The resulting
material was purified by column chromatography to
afford colorless compound 10a (4.35g) in 87% as a white
solid. mp 205.4-206.6°C; IR (Neat): 3319, 3139, 2923,
1641, 1603, 1539, 1459, 1360, 1292, 1265, 1230, 1124,
CONCLUSIONS
In conclusion, we accomplished the synthesis of the pro-
posed structure of novel N-((l-benzyl-lH-l, 2, 3-triazol5-yl)
methyl)-4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamides
following by in situ inter-molecular 1, 3-dipolar cycloaddition
reaction between easily affordable azides and alkynes with
good yields and high purity. The synthesized compounds
were screened for the antimicrobial activity study by cup-plate
method. Some of the compounds shown strong antimicrobial
activity at low concentrations, and hence, further design and
synthesis of compounds in this direction are in progress. This
study can provide a road map to design and synthesis of
Benzothiazole scaffold based antimicrobial active compounds.
EXPERIMENTAL
General. Melting points were determined using Buchi
510 instrument (New Castle, DE, USA). infrared (IR)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
N-(Benzyl-1H-1,2,3-Triazol-5-yl) Methyl)-4-(6-Methoxybenzo [d] Thiazol-2-yl)-2-
Nitrobenzamides
1060, 1026cmÀ1; H NMR (DMSO-d6, 400MHz); δ 9.20
(brs, 1H, NH), 8.58 (s, 1H, Ar-H), 8.21–8.36 (d, 1H,
J=7.8Hz Ar-H), 7.84–8.05 (m, 2H, Ar-H), 7.65–7.80 (d,
1H, J=7.9Hz),7.54 (s, 1H, Ar-H), 7.25–7.43 (s, 5H, Ar–
H),7.05–7.20 (d, 1H, Ar–H), 5.58 (s, 2H, CH2), 4.51–4.65
(d, 2H, N–CH2), 3.91 (s, 3H, OCH3); 13C NMR (DMSO-
d6, 100.6 MHz): δ 164.09, 159.77, 150.99, 146.80,
146.24, 143.42, 135.33, 134.20, 134.03, 132.19, 129.69,
128.83, 127.47, 126.96, 126.60, 122.73, 121.59, 120.46,
115.20, 102.90, 54.44, 52.23, 34.01; ESI-MS: m/z [M
+Na]+ = 523.116 (Calcd M + =500.127), Elemental Anal.
Calcd for C25H20N6O4S: C, 59.99; H, 4.03; N, 16.79; S,
6.41; found: C, 59.90; H, 4.07; N, 16.83; S, 6.42.
835, 780, 736, 697, 556 cmÀ1 1H NMR (DMSO-d6,
;
1
400MHz) δ 9.31 (t,1H, J= 5.8Hz, NH), 8.58 (d, 1H,
J=1.5Hz, ArH), 8.29–8.45 (dd, 1H, J1=1.5Hz, J2=7.9Hz,
Ar–H), 7.71–7.83 (m, 2H, Ar–H), 7.27–7.48 (m, 5H, Ar–H),
7.15–7.23 (dd, 1H, J1=2.5Hz, J2=8.9Hz, Ar–H),
6.97–7.08 (m, 2H, Ar–H), 6.82–6.91 (m, 1H, Ar–H), 5.51
(s, 2H, CH2), 5.06 (s, 2H, O–CH2), 4.51 (d, 2H, J=5.47Hz,
NCH2), 3.87 (s, 3H, OCH3), 3.76 (s, 3H, OCH3); 13C NMR
(DMSO-d6, 100.6MHz): δ 164.58, 161.22, 157.97, 149.04,
147.62, 147.57, 147.54, 144.16, 136.47, 134.86, 133.06,
131.07, 130.24, 128.56, 128.24, 127.67, 127.58, 123.86,
122.75, 121.54, 120.43, 116.58, 113.55, 112.26, 104.77,
69.80, 55.71, 55.47, 52.57, 34.80; ESI-MS: m/z [M+ H]
+ = 637.188 (Calcd M+ =636.179), Elemental Anal. Calcd
for C33H28N6O6 S: C, 62.25; H, 4.43; N, 13.20; S, 5.04,
found: C, 62.15; H, 4.48; N, 13.24; S, 5.05.
Similar experimental procedure of 10a was employed
for all the remaining derivatives, 10bÀ10j with yields
between 83% and 87%.
N-((l-(Benzo[d][l,3]dioxol-5-yl)-lH-l,2,3-triazol-5-yl)methyl)-
4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamide (10b).
Compound 10b is a colorless solid yielded in 85% (3.90g).
mp 210–212°C; IR (Neat): 3271, 3144, 3098, 2920, 2851,
1639, 1605, 1545, 1505, 1466, 1356, 1299, 1249, 1179,
1035cmÀ1; 1H NMR (DMSO-d6, 400MHz); δ 9.43 (broad
singlet, 1H, NH), 8.49–8.78 (m, 1H, Ar-H), 8.41 (s, 1H,
ArH), 7.64–8.19 (m, 3H, Ar–H), 6.67–7.6 (m, 4H, Ar–H),
6.18 (s, 2H, O–CH2–O), 4.64 (s, 2H, N–CH2), 3.91 (s, 3H,
OCH3); 13C NMR (DMSO-d6, 100.6MHz): δ 164.67,
161.06, 157.94, 147.52, 144.85, 134.96, 130.93, 130.28,
123.79, 121.44, 116.45, 113.48, 108.40, 104.55, 101.92,
101.70, 55.61, 28.86; ESI-MS: m/z [M+H]+ =531.094
(Calcd M+ =530.101), Elemental Anal Calcd for
C25H18N6O6S: C, 56.60; H, 3.42; N, 15.84; S, 6.04, found:
C, 56.70; H, 3.37; N, 12.84; S, 6.02.
N-(l-(3-(benzyloxy)-4-methoxybenzyl)-lH-l,2,3-triazol-4-yl)
methyl)-4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamide (10e).
Compound 10e is a colorless solid yielded in 83% (3.60 g). m
p 169.9–70.8°C;IR (Neat): 3335, 3068, 2923, 1647, 1603,
1538, 1516, 1461, 1431, 1356, 1261, 1232, 1162, 1139,
1
1055, 1021, cmÀ1; H NMR (DMSO-d6, 400MHz): δ 9.33
(t, 1H, J=5.1Hz, NH), 8.56 (s, 1H, Ar–H), 8.33 (d, 1H,
J=8.3Hz, Ar–H), 7.92–8.14 (m, 2H, Ar–H), 7.66–7.87
(m, 2H, Ar–H), 7.27–7.55 (m, 5H, Ar–H), 7.08–7.25
(m, 2H, ArH), 6.85–7.03 (m, 2H, Ar–H), 5.50 (s, 2H, CH2),
5.03 (s, 2H, O–CH2), 4.52 (d, 2H, J=4.9Hz, N–CH2), 3.85
(s, 3H, OCH3), 3.74 (s, 3H, OCH3); 13C NMR (DMSO-d6,
100.6MHz): δ 164.61, 161.18, 157.97, 149.01, 147.70,
147.62, 147.53, 144.19, 136.72, 136.47, 134.87, 133.05,
131.04, 130.24, 128.23, 128.13, 128.06, 127.80, 123.86,
122.75, 121.52, 121.01, 116.55, 113.71, 112.06, 104.72,
69.95, 55.69, 55.50,52.58, 34.83; ESI-MS: m/z [M
+H]+ = 637.188 (Calcd M+ = 636.179),Elemental Anal. Calcd
for C33H28N6O6S: C, 62.25; H, 4.43; N, 13.20; S, 5.04,
found: C, 62.15; H, 4.48; N, 13.24; S, 5.05.
Ethyl 2-(5-((4-(6-methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamido)
methyl)-lH-l,2,3-triazol-l-yl) acetate (10c). Compound 10c is
a colorless solid yielded in 85% (3.70 g). mp 196–197°C;
IR (Neat): 3445, 3243, 3092, 2924, 2853, 1739, 1638,
1535, 1465, 1353, 1222, 1056, 1020 cmÀ1
;
1H NMR
N-((l-(3-chIorobenzyl)-lH-l,2,3-triazol-4-yl)methyl)-4-(6-
fluorobenzo[d]thiazol-2-yl)-2-nitrobenzamide (10f). Compound
10f is a colorless solid yielded in 85% (4.12g). mp 187.8–
188.7°C; IR (Neat): 3424, 3271, 3076, 2933, 1636, 1606,
1555, 1529, 1475, 1436, 1348, 1320, 1269, 1213, 1169,
(DMSO-d6, 400 MHz) δ 9.38 (brs, 1H, NH), 8.58 (s, 1H,
Ar–H), 8.28–8.43 (m, 1H, Ar–H), 7.93–8.14(m, 2H, Ar–H),
7.69–7.83 (m, 2H, Ar–H), 7.06–7.27 (m, 1H, Ar–H), 5.40
(s, 2H, CH 2), 4.47–4.65 (d, 2H, N–CH2), 4.09–4.27
(q, 2H, O–CH2), 3.87 (s, 3H, CH 3), 1.23 (t, 3H, CH3);
13C NMR (DMSO-d6, 100.6 MHz): δ 167.15, 164.75,
161.29, 158.04, 147.68, 147.58, 144.14, 136.54, 134.95,
133.11, 131.17, 130.31, 124.38, 123.93, 121.60, 116.64,
108.41, 61.43, 55.77, 50.32, 34.79, 13.90; ESI-MS: m/z
[M + H]+ = 497.123 (Calcd M+ =496.117), Elemental
Anal. Calcd for C22H20N6O6 S: C, 53.22; H, 4.06; N,
16.93; S, 6.46, found: C, 53.12; H, 4.11; N, 16.96; S, 6.48.
N-((l-(4-(benzyloxy)-3-methoxybenzyl)-lH-l,2,3-triazol-4-yl)
methyl)-4-(6methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamide (10d).
Compound 10d is a colorless solid yielded in 83% (3.51g).
mp 181–182°C; IR (Neat): 3422, 2924, 1642, 1602, 1537,
1459, 1428, 1381, 1353, 1263, 1228, 1161, 1138, 1023,
;
1125, 1060, 1028, 908 cmÀ1 1H NMR (DMSO-d6,
400MHz):δ 9.33 (t, 1H, J=5.4Hz, NH), 8.54 (d, 1H,
J=1.7Hz, Ar-H), 8.32–8.42 (dd, 1H, J1=1.7Hz, J2=7.9Hz,
Ar–H), 8.13 (s, 1H, Ar–H), 8.01 (d, 1H, J= 8.9Hz, ArH),
7.72–7.83 (m, 2H, Ar–H), 7.35–7.47 (m, 3H, Ar–H),
7.14–7.32 (m, 2H, Ar–H), 5.64 (s, 2H, CH2), 4.52 (d, 2H,
J = 5.5 Hz, N–CH2), 3.86(s, 3H, OCH3); 13C NMR
(DMSO-d6, 100.6 MHz): δ 164.63, 161.19, 157.96,
147.63, 147.51, 144.32, 138.34, 136.47, 134.87, 133.17,
133.06, 130.50, 130.24, 127.96, 127.68, 126.48, 123.85,
123.28, 121.52, 116.53, 104.74, 55.70, 51.90, 34.80;
ESI-MS: m/z [M + H]+ = 535.095 (Calcd M+ = 534.088),
Elemental Anal. Calcd for C25 H19ClN6O4 S: C, 56.13;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Yarlagadda, N. Devunuri, and V. B. R. Mandava
Vol 9999
H, 3.58; N, 15.71; S, 5.99, found: C, 56.03; H, 3.63; N,
15.73; S, 6.00.
122.98, 123.91, 130.28, 131.14, 131.34,133.11, 134.90,
136.52, 137.18, 144.29, 147.57, 147.65, 152.93, 158.00,
161.24, 164.69; ESI-MS: m/z [M+H]+ =591.166 (Calcd
M+ =590.158), Elemental Anal. Calcd for C28H26N6O7S:
C, 56.94; H, 4.44; N, 14.23; S, 5.43, found: C, 56.84; H,
4.49; N, 14.26; S, 5.45.
N-((l-(3-tert-butylbenzyl)-lH-l,2,3-triazol-4-yl)methyl)-4-(6-
methoxybenzo[d]thiazol-2-yl)-2-nitrobenzamide (10g). Compound
10g is a colorless solid yielded in 87% (4.20 g). mp 184.3–
185.6 °C; IR (Neat): 3424, 3136, 3065, 2961, 1733, 1658,
1602, 1538, 1462, 1433, 1352, 1304, 1262, 1226, 1125,
N-(6-methoxybenzo[d]thiazol-2-yl)-2-nitro-N-((l-(4-(trifluoromethyl)
benzyl)-lH-l,2,3-triazol-4-yl)methyl benzamide (10j). Compound
10j is a colorless solid yielded in 85% (3.60g). mp 196.4–
197.5°C; IR (Neat): 3271, 3072, 2943, 1631, 1603, 1559,
1530, 1480, 1461, 1434, 1353, 1328, 1262, 1225, 1166,
1
1056, 1024 cmÀ1; H NMR (DMSO-d6, 400 MHz): δ 9.32
(t, 1H, J=5.4 Hz, NH), 8.50–8.69 (d, 1H, .J=1.3Hz,
Ar–H), 8.29–8.47 (m, 1H, Ar–H), 8.07 (s, 1H, Ar–H),
8.01 (d, 1H, J=9.1Hz, Ar–H), 7.70–7.89 (m, 2H, Ar–H),
7.32–7.50 (d, 2H, J= 8.3 Hz, Ar–H), 7.24–7.31 (d, 2H,
J=8.3Hz, Ar–H), 7.15–7.22 I (dd, 1H, .A=2.45Hz,
J2 =9.1Hz, Ar-H), 5.57 (s, 2H, CH2), 4.52 (d, 2H, J=5.3Hz,
NCH2), 3.86 (s, 3H, OCH3), 1.24 (s, 9H, Me); 13C NMR
(DMSO-d6, 100.6 MHz): δ 164.61, 161.20, 157.97, 150.46,
147.64, 147.56, 144.21, 136.48, 134.87, 133.01, 131.06,
130.27, 127.63, 125.35, 123.86, 122.95, 121.52, 116.57,
104.74, 59.63, 55.71, 52.41, 34.15, 30.91; ESI-MS: m/z [M
+H]+ = 557.121 (Calcd M+ =556.189), Elemental Anal. Calcd
for C29 H28N6O4S: C, 62.57; H, 5.07; N, 15.10; S, 5.76,
found: C, 62.47; H, 5.10; N, 15.12; S, 5.77.
;
1122, 1064, 1021, 993 cmÀ1 1H NMR (DMSO-d6,
400MHz):δ 3.87 (s, 3H, OCH3), 4.54 (d, 2H, J=5.8Hz,
N–CH2), 5.74 (s, 2H, CH2), 7.07–7.24 (m, 1H, Ar–H),
7.51 (d, 2H, J=8.3Hz, Ar–H), 7.60–7.84 (m, 4H, Ar–H),
7.89–8.06 (m, 1H, Ar–H), 8.07–8.18 (m, 1H, Ar–H),
8.25–8.42 (m, 1H, Ar–H), 8.47–8.65 (s, 1H, Ar–H), 9.32
(t, 1H, J= 4.95 Hz, Ar–H); 13C NMR (DMSO-d6, 100.6 MHz):
δ 34.74, 52.00, 55.57, 104.51, 116.40, 121.39, 123.33, 123.73,
125.31,125.35, 128.30, 130.12, 130.91, 133.04, 134.89,
136.38, 140.41, 144.28, 147.42, 147.62, 157.91, 164.60;
ESI-MS: m/z [M+H]+ =569.121(Calcd: M+ =568.114),
Elemental Anal. Calcd for C26H19F3N6O4 S: C, 54.93; H,
3.37; N, 14.78; S, 5.64 found: C, 54.83; H, 3.42; N, 14.79;
S, 5.65.
N-(6-fluorobenzo[d]thiazol-2-yl)-N-((l-(naphthalen-2-ylmethyl)-
lH-l,2,3-triazol-4-yl) methyl)-2-nitrobenzamide (10h). Compound
10h is a colorless solid yielded in 85% (3.50 g). mp 193–
194°C; IR (Neat): 3265, 3062, 2932, 1644, 1601, 1533,
1
1469, 1430, 1351, 1260, 1223, 1165, 1053, 1026 cmÀ1; H
REFERENCES AND NOTES
NMR (DMSO-d6, 400MHz): δ 9.30 (t, 1H, J= 5.4Hz, NH),
8.56 (d, 1H, J=1.7Hz, Ar–H), 8.30–8.38 (dd, 1H,
J1=1.7Hz, J2=8.1Hz, Ar–H), 8.23 (d, 1H, J=7.9Hz, Ar–
H), 7.89–8.09 (m, 4H, Ar–H), 7.69–7.81 (m, 2H, Ar–H),
7.38–7.66 (m, 4H, Ar–H), 7.14–7.23 (m, 1H, Ar–H), 6.11
(s, 2H, CH2), 4.50 (d, 2H, J=5.4Hz, N–CH2), 3.86 (s, 3H,
OCH3); 13C NMR (DMSO-d6, 100.6 MHz): δ 164.65,
161.19, 157.99, 147.64, 147.52, 144.21, 136.48, 134.87,
133.25, 133.06, 131.48, 131.07, 130.55, 130.23, 128.54,
128.90, 127.06, 126.67, 126.05, 125.43, 123.87, 123.22,
121.52, 116.57, 104.72, 55.71, 50.68, 34.83; ESI-MS: m/z
[M + H]+ =551.150 (Calcd M+ = 550.142), Elemental Anal.
Calcd for C29H22N6O4S: C, 63.26; H, 4.03; N, 15.26; S,
5.82, found: C, 63.16; H, 4.08; N, 15.29; S, 5.84.
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