N,N′-(hexane-1,6-diyl)bis(N-((1-aryl/alkyl-1H-1,2,3-triazol-4-yl)methyl)-4-methyl benzenesulfonamide): Synthesis, antibacterial, antioxidant, and DNA-cleavage activities

Article abstract of DOI:10.1080/10426507.2016.1146273

Thirteen novel bis-1,2,3-triazole derivatives were synthesized under copper (I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition of N,N′-(hexane-1,6-diyl)bis(4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide) with different aryl azides and evaluated their bio

Full text of DOI:10.1080/10426507.2016.1146273

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
N,N'-(hexane-1,6-diyl)bis(N-((1-aryl/
alkyl-1H-1,2,3-triazol-4-yl)methyl)-4-methyl
benzenesulfonamide): Synthesis, antibacterial,
antioxidant, and DNA-cleavage activities
Sirassu Narsimha, Kumara Swamy Battula, Lavudya Sudhakar, Nagavelli
Vasudeva Reddy & S.K Althaf Hussain
To cite this article: Sirassu Narsimha, Kumara Swamy Battula, Lavudya Sudhakar, Nagavelli
Vasudeva Reddy & S.K Althaf Hussain (2016): N,N'-(hexane-1,6-diyl)bis(N-((1-aryl/alkyl-1H-1,2,3-
triazol-4-yl)methyl)-4-methyl benzenesulfonamide): Synthesis, antibacterial, antioxidant, and
DNA-cleavage activities, Phosphorus, Sulfur, and Silicon and the Related Elements
To link to this article: http://dx.doi.org/10.1080/10426507.2016.1146273
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Feb 2016.
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Date: 17 February 2016, At: 03:55

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Synthesis of 1,2,3-triazol derivatives of 4-methyl benzenesulfonamide
N,N'-(hexane-1,6-diyl)bis(N-((1-aryl/alkyl-1H-1,2,3-triazol-4-yl)methyl)-4-methyl
benzenesulfonamide): Synthesis, antibacterial, antioxidant, and DNA-cleavage activities
1
1
1
1,*
Sirassu Narsimha , Kumara Swamy Battula , Lavudya Sudhakar , Nagavelli Vasudeva Reddy ,
2
SK Althaf Hussain
1
Department of Chemistry, Kakatiya University, Warangal-506009, T. S, India
2
Department of Biotechnology, Kakatiya University, Warangal-506 009, T. S, India
*
Corresponding author’s E-mail: vasujac3@gmail.com
Abstract
Thirteen novel bis-1,2,3-triazole derivatives were synthesized under copper (I)-catalyzed azide-
alkyne 1, 3-dipolar cycloaddition of N,N'-(hexane-1,6-diyl)bis(4-methyl-N-(prop-2-yn-1-
yl)benzenesulfonamide) with different aryl azides and evaluated their biological activity. All the
1
newly synthesized compounds were confirmed by H-NMR, IR and ESI-MS spectral studies.
The synthesized bis-1, 2, 3-triazoles were evaluated for their antioxidant activity and some of
them found to exhibit good to excellent antioxidant activity (IC50: 11.13 ± 1.5 to 98.98 ± 1.7 M)
in comparison with standard references Trolox (11.73 ± 1.5M) and ascorbic acid (3.34 ± 1.8
M). The bistriazoles also exhibited excellent to moderate anti-bacterial activity (MIC: 2.253 to

1
7
5 µg mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas
aeruginosa when compared with Streptomycin. N,N'-(hexane-1,6-diyl)bis(N-((1-(3,5-
dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl benzenesulfonamide) has completely
cleaved DNA at 100 mg mL concentration and the remaining compounds have partially
cleaved the DNA.
1
1
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Keywords
Bis-1, 4-disubstituted 1, 2, 3-triazoles, antioxidant, antibacterial, DNA-cleavage activity.
2
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INTRODUCTION
The world population had been suffering from infectious disease due to the multi-drug resistant
pathogens against man made antibiotics. Among them, bacterial infections are second most
leading death causing diseases after cardiovascular disease in the world, due to their rapid
1
-3
spread, toxicity and resistance towards the existing antibiotic drugs. The importance of 1, 2, 3-
triazoles in biological systems has attracted great interest due to their medicinal and
pharmacological characteristics. Many compounds containing the 1,2,3-triazole moiety have
4
5, 6
7
found widespread biological activities, which include antimicrobial, anticancer, antioxidant,
8
, 9
10
11
12
13
anti-HIV,
anti-inflammatory,
antiprotozoal,
anticonvulsant,
antihistamine,
and
1
4
antitubercular properties. Such compounds have also been reported as β3-selective adrenergic
1
5
16, 17
18,19
receptor agonists, kinase inhibitors
and other enzyme inhibitors.
The Cu-catalyzed [3+2] cycloaddition reaction using azide-alkyne was discovered individually
by Sharpless and Meldal and led to the fundamental development of the Huisgen thermal
reaction and offers a unique approach for the regio selective synthesis of 1,4-disubstituted 1,2,3-
20, 21
triazoles.
The 1,4-disubstituted 1,2,3-triazoles can also be prepared by one-pot three
component reaction of substituted halides, sodium azide and terminal alkynes in the presence of
2
2-24
a copper catalyst.
Therefore, in continuation of our research towards the synthesis of
25-28
biologically potent 1, 2, 3-triazole derivatives,
we report herein, one-pot three component
and simple two component synthesis of a small library of N,N'-(hexane-1,6-diyl)bis(4-
methylbenzenesulfonamide) linked bis1,4-disubstituted 1,2,3-triazole conjugates and their
antibacterial, antioxidant and DNA cleavage activities.
RESULTS AND DISCUSSION
3
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Chemistry
The target bis-1,2,3-triazoles (5a-h) and (6a-e) were synthesized as outlined in Scheme S1. The
2
9
intermediates 3 and 4 were prepared according to the known reported synthetic route. p-
toluenesulfonyl chloride (1) reacted with hexamethylenediamine(2) to form N, N'- (hexane-1,6-
diyl) bis (4-methyl benzene sulfonamide) (3). Compound 4 was obtained by the reaction of
t
compound 3 with propargyl bromide and BuOK in DMF at room temperature. The treatment of
compound 4 with substituted azides in the presence of a copper (I) catalyst afforded title
compounds (5a-h). Compound 4 was treated with organic halides, sodium azide and CuI in the
presence of THF-H O mixture to obtain the desired compounds (6a-e) in good to excellent
2
yields.
1
All the newly synthesized bis triazoles were well characterized by IR, H NMR, elemental
analysis and mass (ESI-MS) spectral techniques. The IR spectrum of a representative compound

1
5
a showed absorption bands in the region 3137-3076 cm , which were recognized to = C--H
1
stretching vibrations of the triazole ring. The H NMR spectrum of compound 5a showed one
characteristic singlet at 8.01 due to the presence of two triazole protons. A sharp singlet at 
5
.32 confirmed the presence of four protons of two -CH groups attached to the triazole ring. The
2
presence of two sharp singlet peaks at  and 2.39, corresponded to the -OCH and --CH
3
3
protons attached to the aromatic ring. One triplet signal was observed at  3.14, accounted for the
protons of the N-CH - group. Further, all the aromatic protons were observed in the region
2
7
.01--7.68. The presence of two multiplets in the region  1.34-1.13, confirmed the methylene
protons of hexamethylenediamine (-N-CH -(CH2) -CH -N-). The mass spectrum of compound
2
4
2
4
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5
a exhibited two signals at m/z 800.2 and m/z 822.4 corresponding to [M+H] and [M+Na],
which are in agreement with calculated values.
Antioxidant activity
3
0
All the synthesized compounds (5a-h and 6a-e) were screened for in vitro antioxidant activity
and results are presented in Table S 1 (Supplemental Materials). The evaluation of the
antioxidant activity revealed that the most of the tested compounds exhibited moderate to strong
DPPH radical scavenging ability compared with the positive controls Trolox and ascorbic acid.
Among them, the compound bearing 3-(trifluoromethyl)phenyl (5h) and 3,5-dichloro phenyl
(5b) on the triazole ring were found to be more effective and potent DPPH radical scavenging
ability as compared with positive control drug Trolax. Remaining compounds have shown good
to moderate radical scavenging activity with IC values in the range of 28.62 ± 1.890 - 97.18 ±
5
0
2
.051 μM. From the above results it is obvious that compounds bearing electron attracting
groups on the triazole attached phenyl group have found to possess potent radical scavenging
ability.
Antibacterial activity
31
In vitro antibacterial activity was examined using broth dilution method
and results are
presented in Table S 2 (Supplemental Materials). The evaluation of antibacterial data revealed
that the most of the tested compounds exhibited moderate to excellent antibacterial activity.
Among them, compound 5a has exhibited excellent activity against B.Subtilis (MIC = 2.253 g

1
1
mL ) and S.aureus (MIC = 4.587 g mL ). Similarly, compound 5h showed good activity

1
1
against B.Subtilis (MIC = 6.350 g mL ) and P.aeroginosa (MIC = 4.687g mL ). Compound

1
6
c also exhibited good activity against E. coli (MIC = 2.343 g mL ). The remaining
5
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compounds also showed moderate activity against tested microbial strains with MIC ranging

1
from 9.575 to 75 g mL .
DNA cleavage activity
The DNA cleavage activity of the titled compounds (5a-h & 6a-e) was determined using agarose
3
2, 33
gel electrophoresis method
as depicted in Figure S 1. The gel after electrophoresis clearly
revealed that, the plasmid pUC18 having three forms of DNA, whereas in case of standard

1
FeSO (10 mg mL ) complete DNA and partial cleavage was observed. Compared to standard
4

1
FeSO , compound 5g have completely cleaved the DNA at 100 mg mL . The compounds 5b, 5e
4

1
and 6b showed partial cleavage at 100 mg mL .
EXPERIMENTAL
All the solvents and the starting materials were purchased from commercial sources and used
without further purification. Column chromatography was performed on silica gel 60--120 mesh.
Melting points were determined using a Cintex apparatus. Elemental analysis was measured by
means of Perkin Elmer 2400 CHN elemental analyzer. 400 MHz NMR spectrometer was used to
1
acquire H-NMR spectra. Coupling constant (J) values are presented in Hertz and spin multiples
are given as s (singlet), d (doublet), t (triplet), and m (multiplet). Mass spectra were recorded by
using ESI--MS.
Synthesis of N,N'-(hexane-1,6-diyl)bis(4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide)
(4): To a stirred solution of compound 3 (11.8 mmol) in N, N-dimethylformamide (50 mL) was
t
added BuOK (47.16 mmol) at 0°C and the reaction mixture was stirred for 2 h under N
2
atmosphere. After 2 h, propargyl bromide (35.3 mmol) was added drop wise to the reaction mass
and stirred at room temperature for 6h. After completion of the reaction by TLC, the reaction
6
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mixture was poured carefully into ice-cold water (100 mL), The solid was filtered off, washed
with water and dried to afford N,N'-(hexane-1,6-diyl)bis(4-methyl-N-(prop-2-yn-1-
1
yl)benzenesulfonamide). Yield: 68%; mp: 74-76 C; H NMR (400 MHz, CDCl )  7.70 (d, J =
3
8
2
.0 Hz, 4H), 7.43 (d, J = 8.2 Hz, 4H), 4.71 (s, 4H, CH ), 3.08 (t, J = 4.0 Hz, 4H, N-CH -CH -),
2 2 2
.41(s, 6H, Ar-CH ), 2.29 (s, 2H, alkyne-H), 1.33 (m, 4H, N-CH -CH -CH -),1.15 (m, 4H, N-
3
2
2
2
CH -CH -CH -); ESI-MS m/z: 501.7 [M+H] & 523.4 [M+Na]. Anal. Cal for C H N O S : C,
2
2
2
26 32
2
4 2
6
2.37; H, 6.44; N, 5.60; found: C, 62.41; H, 6.47; N, 5.54.
General procedure for 5a-h
To a solution of compound 4 (0.2 g, 0.4 mmol) and arylazide (1.2 mmol) in THF (15mL) was
added copper iodide (20 mol-%). The reaction mixture was stirred at room temperature for 8-10
h and the progress of the reaction was monitored by TLC. After completion of the reaction, the
reaction mixture was diluted with water (15 mL) and the product was extracted with ethyl acetate
(
220 mL). The combined organic layer was dried over anhydrous Na SO . After filtration, the
2
4
solvent was evaporated under vacuum and the crude product obtained was purified by column
chromatography (hexane/ethyl acetate gradient) to afford the pure desired product.
N,N'-(hexane-1,6-diyl)bis(N-((1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl
benzenesulfonamide) (5a): Yield: 68%; mp: 97-99 C; 8 h; IR (KBr): 3137, 1678, 1594, 1489

1 1
cm ; H NMR (400 MHz, CDCl ):  8.01(s, 2H, triazole-H), 7.68 (d, J = 8.0 Hz, 4H, Ar-H),
3
7
4
.61(d, J = 8.0, 4H, Ar-H), 7.41(d, J = 8.2 Hz, 4H, Ar-H), 7.01(d, J = 8.0, 4H, Ar-H), 5.32 (s,
H, N = N-CH ), 3.86 (s, 6H, -OCH ) 3.14 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.39 (s, 6H, Ar-
2
3
2
2
CH ), 1.32-1.28 (m, 4H, N-CH -CH -CH -), 1.18- 1.06 (m, 4H, N-CH -CH -CH -); ESI-MS
3
2
2
2
2
2
2
7
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m/z: 800.2 [M+H], 822.4 [M+Na]. Anal. Cal for C H N O S : C, 60.13; H, 5.80; N, 14.02;
40
46
8
6 2
found: C, 60.10; H, 5.86; N, 14.08.
N,N'-(hexane-1,6-diyl)bis(N-((1-(3,5-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-
methyl benzenesulfonamide) (5b): Yield: 58%; mp: 112-114 C; 10 h; IR (KBr): 3152, 1677,

1 1
1
7
589, 1492 cm ; H NMR (400 MHz, CDCl ):  8.12 (s, 2H, triazole-H), 7.82 (s, 2H, Ar-H),
3
.72 (d, J = 8.0 Hz, 4H, Ar-H), 7.62 (s, 4H, Ar-H), 7.44 (d, J = 8.0 Hz, 4H, Ar-H), 5.36 (s, 4H,
N = N-CH ), 3.17 (t, J = 4.0 Hz, 4H, N-CH -CH -), 2.44 (s, 6H, Ar-CH ), 1.42-1.30 (m, 4H, N-
2
2
2
3
CH -CH -CH -), 1.19-1.10 (m, 4H, N-CH -CH -CH -); ESI-MS m/z: 877.4 [M+H]. Anal. Cal
2
2
2
2
2
2
for C H Cl N O S : C, 52.06; H, 4.37; N, 12.78; found: C, 52.14; H, 4.40; N, 12.80.
3
8
38
4
8
4 2
N,N'-(hexane-1,6-diyl)bis(N-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl
benzenesulfonamide) (5c): Yield: 62%; mp: 107-109 C; 8 h; IR (KBr): 3147, 1680, 1597, 1495

1 1
cm ; H NMR (400 MHz, CDCl ):  8.08 (s, 2H, triazole-H), 7.71 (d, J = 8.2 Hz, 4H, Ar-H),
3
7
.66 (d, J = 7.8 Hz, 4H, Ar-H), 7.59-7.43 (m, 8H, Ar-H), 5.34 (s, 4H, N-CH ), 3.14 (t, J = 4.0
2
Hz, 4H, N-CH -CH -), 2.42 (s, 6H, Ar-CH ), 1.41-1.29 (m, 4H, N-CH -CH -CH -), 1.21- 1.08
2
2
3
2
2
2
(
m, 4H, N-CH -CH -CH -); ESI-MS m/z: 808.3 [M+H]. 830.7 [M+Na]. Anal. Cal for
2 2 2
C H Cl N O S : C, 56.50; H, 4.99; N, 13.87; found: C, 56.45; H, 4.91; N, 13.79;
38
40
2
8
4 2
N,N'-(hexane-1,6-diyl)bis(N-((1-(4-chloro-3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-
yl)methyl)-4-methylbenzenesulfonamide) (5d): Yield: 47%; mp: 128-130 C; 12 h; IR (KBr):

1 1
3
139, 1689, 1593, 1494 cm ; H NMR (400 MHz, CDCl ):  8.10 (s, 2H, triazole-H), 7.74 (d, J
3
=
8.2 Hz, 4H, Ar-H), 7.54 (s, 4H, Ar-H), 7.41(d, J = 8.2 Hz, 4H, Ar-H), 5.33 (s, 4H, N = N-
CH ), 3.88 (s, 6H, -OCH ), 3.84 (s, 6H, -OCH ), 3.18 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.41 (s,
2
3
3
2
2
6
H, Ar-CH ), 1.42- 1.32 (m, 4H, N-CH -CH -CH -), 1.18-1.08 (m, 4H, N-CH -CH -CH -); ESI-
3 2 2 2 2 2 2
8
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MS m/z: 950.7 [M+Na]. Anal. Cal for C H Cl N O S : C, 54.36; H, 5.21; N, 12.08; found: C,
4
2
48
2
8
8 2
5
4.40; H, 5.19; N, 12.13.
N,N'-(hexane-1,6-diyl)bis(N-((1-(4-butylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl
benzenesulfonamide) (5e): Yield: 55%; mp: 83-85 C; 11h; IR (KBr): 3144, 1667, 1594, 1488

1 1
cm ; H NMR (400 MHz, CDCl ):  7.99 (s, 2H, triazole-H), 7.74-7.66 (m, 8H, Ar-H), 7.52-
3
7
.38 (m, 8H, Ar-H), 5.32 (s, 4H, N = N-CH ), 3.11 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.52-2.41
2 2 2
(
m, 10H, Ar-CH & Ar-CH -CH -), 1.60-1.52 (m, 4H, Ar-CH -CH -), 1.34-1.24 (m, 8H, N-CH -
3 2 2 2 2 2
CH -CH - & Ar-CH -CH -CH -CH ), 1.18-1.10 (m, 4H, N-CH -CH -CH -), 0.98 (t, J = 6.0 Hz,
2
2
2
2
2
3
2
2
2
6
H, Ar-CH -CH -CH -CH ); ESI-MS m/z: 852.2 [M+H]. Anal. Cal for C H N O S : C, 64.91;
2 2 2 3 46 58 8 4 2
H, 6.87; N, 13.17; found: C, 64.88; H, 6.79; N, 13.24.
N,N'-(hexane-1,6-diyl)bis(4-methyl-N-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)
benzenesulfonamide) (5f): Yield: 57%; mp: 116-118 C; 11 h; IR (KBr): 3141, 1689, 1594,

1 1
1
493 cm ; H NMR (400 MHz, CDCl ):  8.24 (d, J = 7.8 Hz, 4H, Ar-H), 8.18 (s, 2H, triazole-
3
H), 7.88 (d, J = 7.8 Hz, 4H, Ar-H), 7.72 (d, J = 8.0 Hz, 4H, Ar-H), 7.46 (d, J = 8.2 Hz, 4H, Ar-
H), 5.36 (s, 4H, N = N-CH ), 3.18 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.44 (s, 6H, Ar-CH ), 1.42-
2
2
2
3
1
.30 (m, 4H, N-CH -CH -CH -), 1.22-1.10 (m, 4H, N-CH -CH -CH -); ESI-MS m/z: 852.6
2 2 2 2 2 2
[
M+Na]. Anal. Cal for C H N O S : C, 55.06; H, 4.86; N, 16.90; found: C, 55.12; H, 4.78; N,
38 40 10 8 2
1
6.94.
N,N'-(hexane-1,6-diyl)bis(N-((1-(3,5-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-
methyl benzenesulfonamide) (5g): Yield: 66%; mp: 96-98 C; 10 h; IR (KBr): 3142, 1682,

1 1
1
4
592, 1489 cm ; H NMR (400 MHz, CDCl ):  8.00 (s, 2H, triazole-H), 7.69 (d, J = 8.0 Hz,
3
H, Ar), 7.43 (d, J = 8.2 Hz, 4H, Ar-H),7.35 (s, 4H, Ar), 7.16 (s, 2H, Ar), 5.33 (s, 4H, N = N-
9
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CH ), 3.19-3.08 (m, 4H, N-CH -CH -), 2.40 (s, 6H, Ar-CH ), 2.38 (s, 12H, Ar-CH ), 1.46-1.26
2
2
2
3
3
(
m, 4H, N-CH -CH -CH -), 1.20-1.10 (m, 4H, N-CH -CH -CH -); ESI-MS m/z: 796.4 [M+H].
2 2 2 2 2 2
Anal. Cal for C H N O S : C, 63.45; H, 6.34; N, 14.09; found: C, 63.51; H, 6.39; N, 14.14.
4
2
50
8
4 2
N,N'-(hexane-1,6-diyl)bis(4-methyl-N-((1-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)
methyl)benzenesulfonamide) (5h): Yield: 51%; mp: 124-126 C; 11 h; IR (KBr): 3161, 1678,

1 1
1
7
593, 1496 cm ; H NMR (400 MHz, CDCl ):  8.19 (s, 2H, triazole-H), 8.03 (s, 2H, Ar), 7.83-
3
.75 (m, 6H, Ar-H), 7.72 (d, J = 8.0 Hz, 4H, Ar-H), 7.45 (d, J = 8.2 Hz, 4H, Ar-H), 5.37 (s, 4H,
N = N-CH ), 3.18 (t, 4H, N-CH -CH -), 2.44 (s, 6H, Ar-CH ), 1.42-1.31 (m, 4H, N-CH -CH -
2
2
2
3
2
2
CH -), 1.28-1.12 (m, 4H, N-CH -CH -CH -); ESI-MS m/z: 897.8 [M+Na]. Anal. Cal for
2
2
2
2
C H F N O S : C, 54.91; H, 4.61; N, 12.81; found: C, 54.88; H, 4.58; N, 12.78.
40
40
6
8
4 2
General procedure for 6a-e
To a solution of compound 4 (0.2 g, 0.4 mmol), organic halide (1.0mmol) and sodium azide (1.0
mmol) in THF-H O mixture (15mL) was added copper iodide (20 mol-%). The reaction mixture
2
o
was stirred at 60 C for 8 h and the progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was diluted with water (15 mL) and the product
was extracted with ethyl acetate (220 mL). The combined organic layer was dried over
anhydrous Na SO . After filtration, the solvent was evaporated under vacuum and the crude
2
4
product obtained was purified by column chromatography (hexane / ethyl acetate gradient) to
afford the pure desired product.
N,N'-(hexane-1,6-diyl)bis(N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-4-methylbenzene

1 1
sulfonamide) (6a): Yield: 60%; mp: 80-82 C; 8 h; IR (KBr): 3161, 1671, 1591, 1493 cm ; H
NMR (400 MHz, CDCl ):  7.79 (s, 2H, triazole-H), 7.66 (d, J = 8.0 Hz, 4H, Ar-H), 7.42 (d, J =
3
10
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8
.2 Hz, 4H, Ar-H), 7.40-2-7.28 (m, 4H, Ar-H), 7.20-7.00 (m, 6H, Ar-H), 5.30 (s, 4H, N = N-
CH ), 5.20 (s, 4H, Ar-CH ) 3.09 (t, J = 4.0 Hz, 4H, N-CH -CH -), 2.39 (s, 6H, Ar-CH ), 1.42-
2
2
2
2
3
1
.28 (m, 4H, N-CH -CH -CH -), 1.22-1.10 (m, 4H, N-CH -CH -CH -); ESI-MS m/z: 768.5
2 2 2 2 2 2
[
M+H]. Anal. Cal for C H N O S : C, 62.64; H, 6.05; N, 14.61; found: C, 62.57; H, 6.11; N,
40 46 8 4 2
1
4.54
N,N'-(hexane-1,6-diyl)bis(4-methyl-N-((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)methyl)
benzenesulfonamide) (6b): Yield: 58%; mp: 87-89 C; 8 h; IR (KBr): 3152, 1675, 1594, 1490

1 1
cm ; H NMR (400 MHz, CDCl ):  7.81 (s, 2H, triazole-H), 7.70 (d, J = 8.0 Hz, 4H, Ar), 7.42
3
(d, J = 8.2 Hz, 4H, Ar), 7.37-7.27 (m, 4H, Ar), 7.24-7.17 (m, 4H, Ar), 5.31 (s, 4H, N = N-CH2),
5
.22 (s, 4H, Ar-CH ), 3.11 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.44 (s, 6H, Ar-CH ), 2.24 (s, 6H,
2
2
2
3
Ar-CH ), 1.42-1.28 (m, 4H, N-CH -CH -CH -), 1.21-1.09 (m, 4H, N-CH -CH -CH -); ESI-MS
3
2
2
2
2
2
2
m/z: 796.4 [M+H]. Anal. Cal for C H N O S : C, 63.45; H, 6.34; N, 14.09; found: C, 63.41;
4
2
50
8
4 2
H, 6.27; N, 14.15.
N,N'-(hexane-1,6-diyl)bis(4-methyl-N-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)
benzenesulfonamide) (6c): Yield: 55%; mp: 93-95 C; 8 h; IR (KBr): 3142, 1678, 1590, 1493

1
1
cm ; H NMR (400 MHz, CDCl ):  7.84 (s, 2H, triazole-H), 7.70 (d, J = 8.0 Hz, 4H, Ar-
3
H),7.62 (d, J = 8.2 Hz, 4H, Ar-H), 7.50-7.40 (m, 4H, Ar-H), 7.38-7.18 (m, 4H, Ar-H), 5.31 (s,
4
H, N = N-CH ), 5.22 (s, 4H, Ar-CH ) 3.11 (t, J = 4.0 Hz, 4H, N-CH -CH -), 2.42 (s, 6H, Ar-
2 2 2 2
CH ), 1.40-1.30 (m, 4H, N-CH -CH -CH -), 1.22-1.10 (m, 4H, N-CH -CH -CH -); ESI-MS m/z:
3
2
2
2
2
2
2
8
5
58.3 [M+H]. Anal. Cal for C H N O S : C, 56.06; H, 5.18; N, 16.34; found: C, 56.01; H,
40 44 10 8 2
.22; N, 16.28.
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N,N'-(hexane-1,6-diyl)bis(N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl
benzenesulfonamide) (6d): Yield: 62%; mp: 90-92 C; 8 h; IR (KBr): 3144, 1667, 1592, 1490

1
1
cm ; H NMR (400 MHz, CDCl ):  7.87 (s, 2H, triazole-H), 7.71 (d, J = 8.0 Hz, 4H, Ar-
3
H),7.64 (d, J = 8.2 Hz, 2H, Ar-H), 7.45 (d, J = 8.2 Hz, 2H, Ar-H), 7.36-7.18 (m, 6H, Ar-H),
6
.92(d, J = 7.8 Hz, 2H, Ar-H), 5.33 (s, 4H, N = N-CH ), 5.22 (s, 4H, Ar-CH ), 3.82 (s, 6H, O-
2 2
CH ), 3.11 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.43 (s, 6H, Ar-CH ), 1.42-1.30 (m, 4H, N-CH -
3
2
2
3
2
CH -CH -), 1.22-1.10 (m, 4H,N-CH -CH -CH -); ESI-MS m/z: 828.3 [M+H]. Anal. Cal for
2
2
2
2
2
C H N O S : C, 61.00; H, 6.09; N, 13.55; found: C, 61.05; H, 6.16; N, 13.51.
42
50
8
6 2
N,N'-(hexane-1,6-diyl)bis(4-methyl-N-((1-(3-methylbenzyl)-1H-1,2,3-triazol-4-yl)methyl)
benzenesulfonamide) (6e): Yield: 54%; mp: 86-88 C; 8 h; IR (KBr): 3131, 1672, 1592, 1494

1 1
cm ; H NMR (400 MHz, CDCl ):  7.80 (s, 2H, triazole-H), 7.69 (d, J = 8.0 Hz, 4H, Ar-H),
3
7
.40 (d, J = 8.2 Hz, 4H, Ar-H), 7.38-7.22 (m, 4H, Ar-H), 7.20-7.15 (m, 4H, Ar-H), 5.33 (s, 4H,
N = N-CH ), 5.18 (s, 4H, Ar-CH ), 3.13 (t, J = 4.4 Hz, 4H, N-CH -CH -), 2.42 (s, 6H, Ar-CH ),
2
2
2
2
3
2
.34 (s, 6H, Ar-CH ), 1.41-1.30 (m, 4H, N-CH -CH -CH -),1.18-1.08 (m, 4H,N-CH -CH -CH -
3 2 2 2 2 2 2
)
; ESI-MS m/z: 796.2 [M+H]. Anal. Cal for C H N O S : C, 63.45; H, 6.34; N, 14.09; found:
42 50 8 4 2
C, 63.50; H, 6.37; N, 14.00.
CONCLUSION
In conclusion, we have synthesized novel bis 1,4-disubstituted 1,2,3-triazoles in good yields, and
evaluated their antibacterial, antioxidant and DNA cleavage activities. The compounds 5h and
5
b showed very good antioxidant activity and the compounds 5a, 5h and 6c showed remarkable
antibacterial activity compared to standard drugs. Similarly, compound 5g showed complete
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
1
DNA cleavage at 100 g mL . These results suggest that the synthesized compounds can be
good candidates for future investigations.
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AKNOWLEDGEMENTS
The authors Narsimha and Satheesh are thankful to the council of scientific and industrial
research - University Grant Commission (CSIR-UGC) New Delhi, for the award of senior
research fellowship.
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t
Scheme 1: Synthetic route: i) THF / 10% NaOH; ii) propargyl bromide/ BuOK, DMF, rt, 12 h;
1
iii) ArN / CuI, THF, rt, 8-12 h; iv) Ar CH -Br / NaN , THF-H O, 60 C, 8 h.
3
2
3
2
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