One-pot synthesis of sulfonyl-1H-1,2,3-triazolyl-thiomorpholine 1,1-dioxide derivatives and evaluation of their biological activity

Article abstract of DOI:10.1080/10426507.2020.1854257

A one-pot procedure for the synthesis of novel 1,2,3-triazole derivatives (5a–5l) in good yields (63 to 77%) using different sulfonic acids and 4-(prop-2-yn-1-yl)thiomorpholine 1,1-dioxide through the in situ generated sulfonyl azides was developed. The structures of the newly synthesized compounds were confirmed by ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The newly synthesized compounds were screened for in?vitro antibacterial activity and free radical scavenging activity in terms of hydrogen donating or radical scavenging ability by the DPPH method. Among all, the compound N-(4-((4-((1,1-dioxidothiomorpholino) methyl)-1H-1,2,3-triazol-1-yl)sulfonyl)phenyl) acetamide (5l) was found to exhibit potent activity as compared to the standard drugs.

Full text of DOI:10.1080/10426507.2020.1854257

Phosphorus, Sulfur, and Silicon and the Related Elements
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One-pot synthesis of sulfonyl-1H-1,2,3-triazolyl-
thiomorpholine 1,1-dioxide derivatives and
evaluation of their biological activity
Rakesh Sreerama , Narasimha Swamy T. , Ravinder M. , Vasudeva Reddy N. &
Sirassu Narsimha
To cite this article: Rakesh Sreerama , Narasimha Swamy T. , Ravinder M. , Vasudeva Reddy N.
&
Sirassu Narsimha (2020): One-pot synthesis of sulfonyl-1H-1,2,3-triazolyl-thiomorpholine 1,1-
dioxide derivatives and evaluation of their biological activity, Phosphorus, Sulfur, and Silicon and
the Related Elements, DOI: 10.1080/10426507.2020.1854257
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2020.1854257
One-pot synthesis of sulfonyl-1H-1,2,3-triazolyl-thiomorpholine 1,1-dioxide
derivatives and evaluation of their biological activity
a
a
a
b
a
Rakesh Sreerama , Narasimha Swamy T. , Ravinder M. , Vasudeva Reddy N. , and Sirassu Narsimha
a
b
Department of Chemistry, Chaitanya Deemed to be University, Warangal, Telangana, India; Department of Chemistry, Kakatiya University,
Warangal, Telangana, India
ABSTRACT
ARTICLE HISTORY
A one-pot procedure for the synthesis of novel 1,2,3-triazole derivatives (5a–5l) in good yields (63
to 77%) using different sulfonic acids and 4-(prop-2-yn-1-yl)thiomorpholine 1,1-dioxide through
the in situ generated sulfonyl azides was developed. The structures of the newly synthesized com-
pounds were confirmed by H NMR, C NMR, mass spectrometry, and elemental analysis. The
newly synthesized compounds were screened for in vitro antibacterial activity and free radical
scavenging activity in terms of hydrogen donating or radical scavenging ability by the DPPH
method. Among all, the compound N-(4-((4-((1,1-dioxidothiomorpholino) methyl)-1H-1,2,3-triazol-1-
yl)sulfonyl)phenyl) acetamide (5l) was found to exhibit potent activity as compared to the stand-
ard drugs.
Received 10 September 2020
Accepted 18 November 2020
1
13
KEYWORDS
1
,2,3-triazole; thiomorpho-
line; sulfonyl azides;
antibacterial activity;
antioxidant activity
GRAPHICAL ABSTRACT
Introduction
synthesize a large variety of novel chemotherapeutic
[
4]
agents. As well, the 1,2,3-triazoles and their derivatives are
of great importance because of their wide applications in
medical, pharmaceutical, biochemical, and material scien-
An increased resistance of pathogenic microorganisms
toward the currently existing antibiotic drugs is a major
concern to public health organizations around the world.
Bacteria are microscopic unicellular organisms and most of
them are harmless to humans and some strains are even
[
5]
ces. On the other hand, the sulfonylazides are resourceful
reagents for a plethora of organic transformations which
[
6]
[
1]
drives welloutside the usually employed diazo as well as
beneficial. However, various types of bacteria are patho-
[
7]
[
2]
azide transfer reactions. They have also been utilized as
genic and can cause serious infectious diseases. Therefore,
the treatment of microbial infections caused by microbio-
logically resistant pathogens becomes an important public
health concern. This has resulted in a significant need for
the development of new and more powerful antimicrobial
agents with a wide range of inhibitory activity, effectiveness,
and low toxicity. Thus, an effective approach to the develop-
ment of new antimicrobial agents with new mechanisms of
valuable reagents in the synthesis of a-diazocarbonyl
[
8]
[9]
reagents, the olefins hydroazidation and aziridation, the
[
10]
[
3]
radical amination,
reactions.
Consequently, several methodologies have been developed
and metal-promoted coupling
[
11]
[
12]
for the synthesis of sulfonylazides.
However, to the best of
our knowledge, no report was available about the use of in situ
action and structural modification is required to improve generated sulfonylazides to sulfonyl-1H-1,2,3-triazoles in the
their target selectivity and effectiveness.
literature. In view of the sustainable chemical synthesis, herein,
The high therapeutic properties of the sulfonyl group we synthesized some new biologically active sulfonyl-1H-1,2,3-
containing drugs have encouraged medicinal chemists to triazolyl-thiomorpholine 1,1-dioxide derivatives (5a–5l) using
CONTACT Sirassu Narsimha
narsimha.s88@gmail.com
Department of Chemistry, Chaitanya Deemed to be University, Warangal, Telangana 506 001, India
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2020.1854257.
ß 2020 Taylor & Francis Group, LLC

2
R. SREERAMA ET AL.
Scheme 1. One pot synthesis of sulfonyl-1H-1,2,3-triazolyl-thiomorpholine 1,1-dioxide.
a
Scheme 2. Synthesis of 1,2,3-triazole derivatives 5a-5l.
The isolated yields are given as percentages.
a
[
13]
the applications of previously developed Sharpless
Batool methodologies (Scheme 1).
and presence of THF at room temperature was found as suitable
reaction condition for the synthesis of desired 4-((1-(phenyl-
[
14]
sulfonyl)-1H-1,2,3-triazol-4-yl)methyl)thiomorpholine
1,1-
dioxide (5c) in good yield. Replacing the THF by other sol-
Results and discussion
vents such as CH Cl , CHCl , CH CN, and 1,4-dioxane
2
2
3
3
decreased product yields (Table 1, entries 5–8).
Using the above optimized conditions, we then extended
,2,3-triazole derivatives were synthesized in a one-pot reac- our approach to synthesize several sulfonyl-1,2,3-trazoles
The synthetic procedure adopted to obtain the targeted
compounds is shown in Scheme 2. The 1,4-disubstituted-
1
tion, starting from sulfonic acid, 4-(prop-2-yn-1-yl)thiomor- and the results are shown in Scheme 2. It has been found
pholine 1,1-dioxide and sodium azide via an in situ that all the sulfonic acid used in the present approach were
generated sulfonylazide. 4-(Prop-2-yn-1-yl)thiomorpholine compatible to give the targeted sulfonyl-1,2,3-traizoles in
1
,1-dioxide (3) was synthesized by using previously reported good yields.
[
5 ]
method. g One pot synthesis of 1,2,3-triazole was first
The structures of the newly synthesized compounds
1
13
tested on 4-(Prop-2-yn-1-yl)thiomorpholine 1,1-dioxide (3) (5a–5l) were confirmed by H NMR, C NMR, ESI-MS,
and phenylsulfonic acid (4c) as model substrates in order to and elemental (CHN) analysis data. All the spectral and ana-
find optimal reaction conditions (Table 1). Our initial inves- lytical data of the synthesized compounds were in full agree-
tigation began with the [3 þ 2] cycloaddition of in situ gen- ment with the proposed structures and also discussed for a
1
erated phenylsulfonylazide from phenylsulfonic acid (4c), representative compound 5a. From the H-NMR spectrum,
alkyne (3), PPh /TCCA/NaN , CuI, and solvent. After sev- the presence of the signals that appeared at d 7.70 (s, 1H,
3
3
eral trials (Table 1, entries 1–4), the combination of 10 mol% triazole), d 3.96 (s, 2H, N-CH -triazole), d 3.32 (s, 3H,
2
of CuI and 4/1.5/2.5 molar ratio of PPh /TCCA/NaN in the CH ), d 3.24–3.16 (m, 4H, 2SO -CH ), d 2.99–2.91 (m, 4H,
3
3
3
2
2

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
a
Table 1. Investigation of the reaction conditions for the synthesis of 1,2,3-triazole .
3 3
PPh /TCCA/NaN
molar ratio
b
Entry
Solvent
% Yield
1
2
3
4
5
6
7
8
a
2/1/2
3/1/2.5
4/1.5/2.5
5/2/3
4/1.5/2.5
4/1.5/2.5
4/1.5/2.5
4/1.5/2.5
THF
THF
THF
THF
16
35
72
74
54
58
61
63
CH
CHCl
CH CN
2
Cl
2
3
3
1,4-dioxane
b
Reactions were performed with 4c (2 mmol), 3 (2 mmol), CuI (10 mol%) and solvent (15 mL) for 8h. Isolated yield
2
N-CH ) confirmed the presence of required protons. From Antioxidant activity
2
1
3
the C-NMR, the presence of carbon signals at 131.35,
All the synthesized compounds 5a–5l were screened for free
1
4
29.55 ppm (2C, triazole), 52.11 ppm (2C, 2SO -CH ),
2 2
9.08 ppm (N-CH -tri), 48.68 ppm (2C, 2N-CH ),40.07 ppm
radical scavenging activity in terms of hydrogen donating or
2
2
radical scavenging ability by 2,2-diphenyl-1- picrylhydrazyl
(SO -CH ) confirmed the presence of characteristic carbon
[16]
2
3
(DPPH) method.
Methanol (95%), DPPH solution, and
signals. The IR spectrum of a representative compound 5a
showed absorption bands in the region 3143, 1597, 1503,
standard compounds (Troloxand ascorbic acid) were used as
blank, control, and reference, respectively.
The examination of free radical scavenging ability of the
synthesized compounds 5a–5l results showed that compounds
ꢀ
1
and 13,811,371 cm , which were recognized to ¼ C-H,
C ¼ N, C ¼ C, and (SO ) stretching vibrations. The presence
2
of [M þ H] ion peak at m/z 295 in ESI-Mass spectra and the
(5j, 5k, and 5l) have exhibited excellent antioxidant activity
elemental analysis (CHN) data (C, 32.57; H, 4.71; N, 18.95)
with IC50 values ranging from 6.38 ± 0.16 to 9.38 ± 0.52 mM.
These results on comparison with the standard Trolox with
IC50 value of 11.73 ± 0.89 mM found to be active by ꢁ1.84 fold
for N-(4-((4-((1,1-dioxidothiomorpholino)methyl)-1H-1,2,3-
triazol-1-yl) sulfonyl)phenyl)acetamide (5l), 1.44 fold for 4-
confirmed the molecular formula (C H N O S ) of com-
pound 5a.
8
14 4 4 2
Antibacterial activity
((1-((2-nitrophenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)methyl)th-
iomorpholine 1,1-dioxide (5j), and 1.25 fold for 4-((4-((1,1-
dioxidothiomorpholino)methyl)-1H-1,2,3-triazol-1-yl)sulfonyl)
benzonitrile (5k). The compounds 5g and 5h have shown good
scavenging ability with IC50 values 17.84 ± 0.66 and
19.41 ± 0.59 mM, respectively. Remaining compounds have
shown moderate to weak scavenging ability/capacity with IC50
values ranging from 23.13 ± 0.93 to 68.44± 1.09 mM. It is to
point out that all the potent analogues which contain electron-
withdrawing substituents like amido, cyano, chloro, and nitro-
phenyl sulfonyl groups on the triazole ring exhibited good to
excellent antioxidant activity. The results of the antibacterial
and antioxidant activities are presented in Table S1
All the synthesized compounds were screened for their
in vitro antibacterial activity against gram-positive (Gþ)
bacterial strains was evaluated by the standard broth micro-
dilution technique by using streptomycin as positive con-
[
15]
trol.
The minimum inhibitory concentrations (MICs) for
all the synthesized compounds were reported in lg/mL. The
results of the antibacterial activity screening revealed that
compound N-(4-((4-((1,1-dioxidothiomorpholino)methyl)-
1
H-1,2,3-triazol-1-yl)sulfonyl)phenyl)acetamide (5l) showed
excellent inhibition against all the tested bacterial strains
with MICs ranging from 1.56 ± 0.23 to 6.25 ± 0.52 lg/mL,
respectively. Similarly, compound 4-((1-(mesitylsulfonyl)-
(Supplemental materials).
1
H-1,2,3-triazol-4-yl)methyl)thiomorpholine 1,1-dioxide (5e)
showed excellent inhibition against B. subtilis and S. aureus
with MIC values 3.12 ± 0.54 and 6.25 ± 0.38 lg/mL, and good
inhibition against S. epidermidis with MIC value
Conclusion
In conclusion, we extended the applications of Sharpless and
Batool Akhlaghinia methodologies for the synthesis of sul-
fonyl-1H-1,2,3-triazolyl-thiomorpholine 1,1-dioxide deriva-
tives in one-pot using 4-(prop-2-yn-1-yl)thiomorpholine 1,1-
1
2.5 ± 0.56 lg/mL, respectively. Compound 4-((1-((2-nitro-
phenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)methyl)thiomorpholine
,1-dioxide (5j) has shown good inhibition against all the
1
tested bacterial strains with MICs ranging from 6.25 ± 0.39 dioxide and commercially available sulfonic acids via an in
to 12.5 ± 0.83 lg/mL, while the rest of the compounds have situ generated sulfonylazides. All the compounds screened
shown modest activity against all the tested strains with for their in vitro antibacterial activity against three gram-
MIC values ranging from 12.5 ± 0.29 to 50 ± 1.38 lg/mL.
positive bacterial strains and compounds 5l, 5e, and 5j

4
R. SREERAMA ET AL.
showed a potent antibacterial activity against the bacterial acetate–hexane, 2:3) to afford the pure desired 1,2,3-triazole
strains. In addition, the compounds 5j, 5k, and 5l have derivatives in good yields.
shown very good antioxidant activity when compared with
the standard drug. These results suggest that the synthesized
compounds might be useful for the optimization and devel-
opment of new antibacterial agents for the treatment of bac-
terial infections.
4
-((1-(Methylsulfonyl)-1H-1,2,3-triazol-4-yl)methyl)thiomor-
pholine 1,1-dioxide (5a)
Pale yellow solid; Mp: 127–129 C; H-NMR (400 MHz,
CDCl ) d: 7.70 (s, 1H, triazole), 3.96 (s, 2H, N-CH ), 3.32
ꢂ
1
3
2
(
4
1
s, 3H, CH ), 3.24–3.16 (m, 4H, 2SO -CH ), 2.99–2.91 (m,
Experimental
3
2
2
13
H, 2N-CH2).
C-NMR (100 MHz, CDCl ) d: 131.35,
3
All the reactants were purchased from the Aldrich Chemical
Company. All the reagents and solvents were purchased from
SD Fine Chemicals limited and used without further purifica-
tion. Thin-layer chromatography (TLC) was performed using
Merck silica gel 60F254 precoated plates (0.25 mm), and silica
gel (particle size 60–120 mesh) was used for column chroma-
29.55, 52.11(2C, SO -CH ), 49.08 (C, N-CH ), 48.68 (2C,
2
2
2
ꢀ1
N-CH ), 40.07 (C, SO -CH ); IR (KBr, cm ) ꢀ: 3143 (C-H,
2
2
3
triazole), 1597 (C ¼ N), 1503 (C ¼ C), 1381, 1371 (SO ),
2
1
281, 1116, 1081 (SO ); MS (ESI) m/z: 295 [M þ H]; Anal.
2
Calcd for C H N O S : C, 32.64; H, 4.79; N, 19.03. Found:
C, 32.57; H, 4.71; N, 18.95.
8
14 4 4 2
1
13
tography. H and C NMR spectra were recorded on a
1
13
Bruker (operating at 400 MHz for H and 100 MHz for C).
Mass spectra were recorded on a Jeol JMC-300 spectrometer
4
-((1-(Ethylsulfonyl)-1H-1,2,3-triazol-4-yl)methyl)thiomor-
pholine 1,1-dioxide (5 b)
Pale yellow solid; Mp: 130–132 C; H-NMR (400 MHz,
(ESI, 70eV). IR spectra were recorded on a Perkin Elmer BX
series FT-IR spectrometer in KBr pellets. Elemental analyses
were performed on Carlo Erba 106 and PerkinElmer model
ꢂ
1
CDCl ) d: 7.75 (s, 1H, triazole), 3.97 (s, 2H, N-CH -tri),
2
40 analyzers. Melting points were determined using a Cintex
3
2
apparatus and are uncorrected. The Supplemental materials 3.36 (q, 3H, J ¼ 2.2 Hz CH
), 3.24 (t, 4H, J ¼ 4.0 Hz, 2SO
-
2
3
1
13
contains sample H and C NMR and mass spectra of the CH
), 2.95 (t, 4H, J ¼ 4.0 Hz, 2N-CH
), 1.62 (t, 3H,
2
2
1
3
products 5 (Figures S1–S35).
J ¼ 4.0 Hz, CH
28.31, 52.13 (2 C, SO -CH ), 49.34 (C, N-CH ), 48.23(2 C,
3
). C-NMR (100 MHz, CDCl ) d: 133.35,
3
1
2
2
2
N-CH ), 41.01(C, SO -CH ), 10.85 (C, C-CH ); MS (ESI) m/
2
2
2
3
Synthesis of 4-(prop-2-yn-1-yl)thiomorpholine 1,1-
dioxide (3)
z: 309 [M þ H]; Anal. Calcd for C H N O S : C, 35.05; H,
[
5g]
9
16
4
4 2
5
.23; N, 18.17. Found: C, 35.01; H, 5.29; N, 18.12.
To a stirred solution of 4-(prop-2-yn-1-yl)thiomorpholine (3g,
0
.021 mol) in dichloromethane (50 mL) was added m-CPBA
ꢂ
(10.9g, 0.0638 mol) at 0 C. The reaction mixture was stirred at
4
-((1-(Phenylsulfonyl)-1H-1,2,3-triazol-4-yl)methyl)thiomor-
room temperature for 6 h. After completion of the reaction, the
solvent was removed under reduced pressure to afford the crude
compound. The crude product was partitioned between ethyl
pholine 1,1-dioxide (5c)
Yellow solid; Mp: 148–150 C; H-NMR (400 MHz, CDCl )
ꢂ
1
3
d: 8.02 (s, 1H, triazole), 7.72 (d, 2H, J ¼ 8.0 Hz, Ar-H), 7.58-
acetate and aqueous NaHCO solution. Then, the organic layer
3
7
.48 (m, 1H, Ar-H), 7.40–7.33 (m, 2H, Ar-H), 3.96 (s, 2H,
was separated, washed with brine, dried over anhydrous
Na SO and evaporated under reduced pressure to afford 71%
N-CH -tri), 3.23 (t, 4H, J ¼ 4.0 Hz, 2SO -CH ), 2.95 (t, 4H,
2
2
2
2
4
13
J ¼ 4.0 Hz, 2N-CH ). C-NMR (100 MHz, CDCl ) d:138.65,
2
3
of 4-(prop-2-yn-1-yl)thiomorpholine 1,1-dioxide (3).
1
4
36.86, 135.05, 129.57, 128.65, 127.90, 52.61 (2C, SO -CH ),
2 2
9.53 (C, N-CH ), 48.61 (2C, N-CH ); MS (ESI) m/z: 357
2
2
General procedure for the synthesis of sulfonyl-1H-1,2,3- [M þ H]; Anal. Calcd for C13
H N O S : C, 43.81; H, 4.52;
16 4 4 2
N, 15.72. Found: C, 43.77; H, 4.48; N, 15.66.
triazolyl-thiomorpholine 1,1-dioxide derivatives (5a-5l)
To a 50 mL round bottom flask, trichloroisocyanuric acid
(
TCCA) (1.5 mmol) and PPh3 (4 mmol) in THF (15 mL)
ꢂ
4-((1-Tosyl-1H-1,2,3-triazol-4-yl)methyl)thiomorpholine 1,1-
dioxide (5d)
were added and allowed to stir at 0–5 C for 15 min. Then,
the sulfonic acid (4) (2 mmol), and NaN (2.5 mmol) were
introduced into the resulting solution and stirring was con-
tinued at room temperature for 30–45 min. Later, the 4-
3
ꢂ
1
Yellow solid; Mp: 154–156 C; H-NMR (400 MHz, CDCl )
3
d: 7.99 (s, 1H, triazole), 7.82 (d, 2H, J ¼ 8.0 Hz, Ar-H),
7
.56–7.47 (m, 2H, Ar-H), 3.97 (s, 2H, N-CH ), 3.21–3.10
2
(prop-2-yn-1-yl)thiomorpholine 1,1-dioxide (3) (2 mmol)
(
3
m, 4H, 2SO -CH ), 2.94–2.82 (m, 4H, 2N-CH ), 2.41 (s,
2 2 2
H, Ar-CH ). C-NMR (100 MHz, CDCl ) d: 141.63, 137.56,
3 3
and CuI (10 mmol%) and the resulting reaction mixture was
stirred at room temperature for further 8 to 10 h. After the
completion as shown by TLC, the reaction mixture was
13
1
36.35, 133.65, 132.68, 128.70, 52.70 (2C, SO -CH ),
2
2
carefully poured into ice water (30 mL). The resulting solid 49.43(C, N-CH ), 48.98(2C, N-CH
2
), 21.61 (2C, Ar-CH
);
3
2
was filtered, washed with excess of water and dried under MS (ESI) m/z: 371 [M þ H]; Anal. Calcd for C14
H N O S :
18 4 4 2
reduced pressure. Finally, the crude product obtained was C, 45.39; H, 4.90; N, 15.12. Found: C, 45.43; H, 4.95;
purified by column chromatography (eluent ethyl N, 15.07.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
1
3
4
-((1-(Mesitylsulfonyl)-1H-1,2,3-triazol-4-yl)methyl)thiomor-
pholine 1,1-dioxide (5e)
White solid; Mp: 181–183 C; H-NMR (400 MHz, CDCl ) CH ), 48.61 (2C, N-CH ); MS (ESI) m/z: 402 [M þ H]; Anal.
C-NMR (100 MHz, CDCl ) d: 147.02, 142.84, 135.91,
3
130.04, 127.23, 123.02, 52.21 (2C, SO -CH ), 49.23 (C, N-
2
2
ꢂ
1
3
2
2
d: 7.86 (s, 1H, triazole), 7.04 (s, 2H, Ar-H), 3.91 (s, 2H, N- Calcd for C H N O S : C, 38.90; H, 3.77; N, 17.45. Found:
13
15 5 6 2
CH ), 3.22 (t, 4H, J ¼ 4.0 Hz, 2SO -CH ), 2.95 (t, 4H,
2
2
2
C, 38.85; H, 3.72; N, 17.52.
J ¼ 4.0 Hz, 2N-CH ), 2.65 (s, 6H, 2Ar-CH ), 2.32 (s, 3H, Ar-
2
3
1
3
CH ). C-NMR (100 MHz, CDCl ) d: 142.80, 137.50, 134.88,
3
3
1
31.86, 130.03, 127.29, 52.55 (2C, SO -CH ), 49.53 (C, N- 4-((1-((2-Nitrophenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)methyl)
2 2
CH ), 48.33 (2C, N-CH ), 22.29 (2C, Ar-CH ), 21.69 (C, Ar- thiomorpholine 1,1-dioxide (5j)
2
2
3
ꢂ
1
CH ); MS (ESI) m/z: 399 [M þ H]; Anal. Calcd for Yellow solid; Mp: 175–177 C; H-NMR (400 MHz, CDCl
)
3
3
C H N O S : C, 48.22; H, 5.56; N, 14.06. Found: C, 48.30; d: 8.40–8.31 (m, 1H, Ar-H), 8.21–8.17 (m, 1H, Ar-H), 8.15
1
6
22
4
4 2
H, 5.59; N, 14.00.
(s, 1H, triazole), 7.99–7.85 (m, 3H), 3.99 (s, 2H, N–CH2),
.38–3.26 (m, 4H, 2SO -CH ), 3.00–2.87 (m, 4H, 2N-
3
2
2
13
CH ). C-NMR (100 MHz, CDCl ) d: 148.78, 138.24, 134.79,
2
3
4
-((1-((4-Methoxyphenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)me-
1
4
34.62, 131.99, 130.22, 127.69, 125.08, 52.51 (2C, SO -CH ),
2 2
thyl)thiomorpholine 1,1-dioxide (5f)
Pale red solid; Mp: 163–165 C; H-NMR (400 MHz, CDCl )
ꢂ
1
9.28 (C, N-CH ), 48.79 (2C, N-CH ); MS (ESI) m/z: 402
2
2
3
[
M þ H]; Anal. Calcd for C H N O S : C, 38.90; H, 3.77;
13
15 5 6 2
d: 8.06 (s, 1H, triazole), 7.85 (d, 2H, J ¼ 8.0 Hz, Ar-H), 7.09
N, 17.45. Found: C, 38.82; H, 3.79; N, 17.50.
(
d, 2H, J ¼ 8.0 Hz, Ar-H), 3.98 (s, 2H, N-CH -tri), 3.84 (s,
2
3
4
1
H, O-CH ), 3.19 (t, 4H, J ¼ 4.0 Hz, 2SO -CH ), 2.90 (m,
3
2
2
13
H, J ¼ 4.0 Hz, 2 N-CH ). C-NMR (100 MHz, CDCl ) d:
2
3
4
1
-((4-((1,1-Dioxidothiomorpholino)methyl)-1H-1,2,3-triazol-
-yl)sulfonyl)benzonitrile (5k)
63.42, 136.67, 131.63, 131.27, 130.03, 118.47, 57.00 (C, O-
CH ), 52.07 (2C, SO -CH ), 49.34 (C, N-CH ), 48.98 (2C,
ꢂ
1
3
2
2
2
Pale red solid; Mp: 166–168 C; H-NMR (400 MHz, CDCl )
3
N-CH ); MS (ESI) m/z: 387 [M þ H]; Anal. Calcd for
2
d: 8.11–8.03 (m, 3H, Ar-H & triazole), 7.86–7.80 (m, 2H,
Ar-H), 3.99 (s, 2H, N–CH ), 3.29–3.24 (m, 4H, 2SO -CH ),
C H N O S : C, 43.51; H, 4.69; N, 14.50. Found: C, 43.58;
1
4
18
4
5 2
2
2
2
H, 4.63; N, 14.44.
13
2
.98–2.89 (m, 4H, 2N-CH ). C-NMR (100 MHz, CDCl ) d:
2 3
1
45.01, 135.31, 132.33, 128.25, 126.69, 119.98, 118.01, 52.33
-CH ), 49.65 (C, N-CH ), 48.92 (2C, N-CH ); MS
4
-((1-((4-Chlorophenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)me-
(2C, SO
2
2
2
2
thyl)thiomorpholine 1,1-dioxide (5g)
Pale yellow solid; Mp: 159–161 C; H-NMR (400 MHz, 44.08; H, 3.96; N, 18.36. Found: C, 44.11; H, 3.89; N, 18.32.
(ESI) m/z: 382 [M þ H]; Anal. Calcd for C H N O S : C,
14
15 5 4 2
ꢂ
1
CDCl ) d: 8.12 (s, 1H, triazole), 7.93 (d, 2H, J ¼ 8.8 Hz, Ar-
3
H),7.53 (d, 2H, J ¼ 8.8 Hz, Ar-H), 3.97 (s, 2H, N-CH -tri),
2
N-(4-((4-((1,1-dioxidothiomorpholino)methyl)-1H-1,2,3-tria-
3
2
1
.26 (t, 4H, J ¼ 4.0 Hz, 2SO -CH ), 2.95 (t, 4H, J ¼ 4.0 Hz,
2
2
13
zol-1-yl)sulfonyl)phenyl) acetamide (5l)
N-CH ). C-NMR (100 MHz, CDCl ) d: 142.66, 138.47,
2
3
ꢂ
1
Pale yellow solid; Mp: 199–201 C; H-NMR (400 MHz,
CDCl ) d: 8.07 (s, 1H, triazole), 7.92–7.83 (m, 2H, Ar-
36.40, 134.56, 130.04, 129.94, 52.58 (2C, SO -CH ), 49.49
2
2
(
C, N-CH ), 48.61 (2C, N-CH ); MS (ESI) m/z: 391
3
2
2
[
3
M þ H]; Anal. Calcd for C H ClN O S : C, 39.95; H, H),7.79–7.70 (m, 2H, Ar-H),7.60 (br, 1H, NH), 3.99 (s, 2H,
1
3
15
4 4 2
.87; N, 14.33. Found: C, 39.90; H, 3.82; N, 14.27.
N–CH
2
), 3.25 (t, 4H, J ¼ 4.0 Hz, 2SO
-CH ), 2.98–2.89 (t,
2 2
1
3
4
(
H, J ¼ 4.0 Hz, 2N-CH ), 2.29 (s, 3H, CH ). C-NMR
2
3
100 MHz, CDCl ) d: 169.42, 147.54, 136.03, 135.93, 130.01,
3
4
-((1-((4-Bromophenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)me-
1
4
26.97, 120.29, 52.51 (2C, SO -CH ), 49.43 (C, N-CH ),
2 2 2
thyl)thiomorpholine 1,1-dioxide (5h)
Yellow solid; Mp: 168–170 C; H-NMR (400 MHz, CDCl )
d: 8.00 (s, 1H, triazole), 7.85–7.78 (m, 2H, Ar-H), 7.69–7.61
8.98 (2C, N-CH ), 23.36(C, CO-CH ); MS (ESI) m/z: 414
ꢂ
1
2
3
3
[
M þ H]; Anal. Calcd for C H N O S : C, 43.57; H, 4.63;
15
19 5 5 2
N, 16.94. Found: C, 43.65; H, 4.58; N, 16.88.
(
2
m, 2H, Ar-H), 3.97 (s, 2H, N-CH ), 3.25 (t, 4H, J ¼ 4.0 Hz,
2
13
SO -CH ), 2.97 (t, 4H, J ¼ 4.0 Hz, 2N-CH ). C-NMR
2
2
2
(100 MHz, CDCl ) d: 142.22, 138.28, 136.23, 134.50, 130.17,
3
Acknowledgments
1
28.27, 52.18 (2C, SO -CH ), 49.69 (C, N-CH ), 48.13 (2C,
2 2 2
The authors are thankful to the head, Department of Bio-Technology,
Chaitanya Deemed to be University, Warangal for providing data of
biological activity.
N-CH ); MS (ESI) m/z: 434 [M þ H] & 436 [M þ 3H]; Anal.
2
Calcd for C H BrN O S : C, 35.87; H, 3.47; N, 12.87.
1
3
15
4
4 2
Found: C, 35.81; H, 3.42; N, 12.82.
Disclosure statement
4
-((1-((4-Nitrophenyl)sulfonyl)-1H-1,2,3-triazol-4-yl)methyl)
thiomorpholine 1,1-dioxide (5i)
Yellow solid; Mp: 177–179 C; H-NMR (400 MHz, CDCl )
No potential conflict of interest was reported by the authors.
ꢂ
1
3
d: 8.48 (d, 2H, J ¼ 8.0 Hz, Ar-H), 8.28 (d, 2H, J ¼ 8.0 Hz, Ar-
ORCID
H), 8.16 (s, 1H, triazole),4.02 (s, 2H, N-CH -tri), 3.33 (t,
2
4
H, J ¼ 4.0 Hz, 2SO -CH ), 3.00 (t, 4H, J ¼ 4.0 Hz, 2N-CH ). Sirassu Narsimha
http://orcid.org/0000-0002-1844-2937
2
2
2

6
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Efficient, Inexpensive, and Shelf-Stable Diazo Transfer Reagent:
imidazole-1-Sulfonyl Azide Hydrochloride. Org. Lett. 2007, 9,
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