A new route for the synthesis of functionalized benzothiadiazine 1,1-dioxide derivatives via intramolecular C–H activation reactions of N,N′,N′′-trisubstituted guanidines and benzenesulfonylchloride

Article abstract of DOI:10.1080/17415993.2018.1499743

In this study, a simple and appropriate procedure for the synthesis of functionalized benzothiadiazine 1,1-dioxide with good yields via the Cu-catalyzed intramolecular C–H activation reaction from benzenesulfonylchloride and N,N′,N′′-trisubstitutedguanidines, generated by copper(II) oxide-catalyzed hydroamination of carbodiimides, is reported.

Full text of DOI:10.1080/17415993.2018.1499743

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
A new route for the synthesis of functionalized
benzothiadiazine 1,1-dioxide derivatives
via intramolecular C–H activation reactions
of N,N′,N′′-trisubstituted guanidines and
benzenesulfonylchloride
Maryam Nazari, Manijeh Nematpour, Elham Rezaee, Mehdi Jahani & Sayyed
Abbas Tabatabai
To cite this article: Maryam Nazari, Manijeh Nematpour, Elham Rezaee, Mehdi Jahani & Sayyed
Abbas Tabatabai (2018): A new route for the synthesis of functionalized benzothiadiazine 1,1-
dioxide derivatives via intramolecular C–H activation reactions of N,N′,N′′-trisubstituted guanidines
and benzenesulfonylchloride, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2018.1499743
To link to this article: https://doi.org/10.1080/17415993.2018.1499743
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2018.1499743
A new route for the synthesis of functionalized
benzothiadiazine 1,1-dioxide derivatives via intramolecular
ꢀ
ꢀꢀ
C–H activation reactions of N,N ,N -trisubstituted guanidines
and benzenesulfonylchloride
a
a
a
b
Maryam Nazari , Manijeh Nematpour , Elham Rezaee , Mehdi Jahani and Sayyed
a
Abbas Tabatabai
a
Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Iran; Department of Chemistry, Sharif University of Technology, Tehran, Iran
b
ABSTRACT
ARTICLE HISTORY
Received 11 April 2018
Accepted 7 July 2018
In this study, a simple and appropriate procedure for the synthesis
of functionalized benzothiadiazine 1,1-dioxide with good yields via
the Cu-catalyzed intramolecular C–H activation reaction from ben-
zenesulfonylchloride and N,N ,N -trisubstitutedguanidines, gener-
ated by copper(II) oxide-catalyzed hydroamination of carbodiimides,
is reported.
KEYWORDS
ꢀ
ꢀꢀ
C–H activation;
copper-catalyzed;
benzothiadiazine
1
,1-dioxide;
benzenesulfonylchloride; N;
n’-dicyclohexylcarbodiimide;
primary amine
1. Introduction
1
,2,4-Benzothiadiazine-1,1-dioxides are a class of heterocycles with various pharmacolog-
ical effects which are described as follow: diuretic, anti-hypertensive agents, HCV NS5B
polymerase inhibitors [1], potent angiotensin-II receptor antagonists [2], NMDA receptor-
channel complex antagonists [3], α and 5-HT receptor ligands [4] and mitochondrial
1
1A
ATP-sensitive potassium channels openers [5]. These derivatives are also featured as anti-
diabetes agents due to aldose reductase inhibition and antioxidant activity (Figure 1(A)),
anti-cancer and anti-tubercular agents, [6,7] alkaline phosphatase inhibitors, [8] anti-HIV
CONTACT Sayyed Abbas Tabatabai
sa_tabatabai@sbmu.ac.ir
Supplemental data for this article can be accessed here. https://doi.org/10.1080/17415993.2018.1499743
2018 Informa UK Limited, trading as Taylor & Francis Group
©

2
M. NAZARI ET AL.
Figure 1. Examples of benzothiadiazine 1,1-dioxide derivatives as aldose reductase inhibitor (anti-
diabetes) (A), non-nucleoside reverse transcriptase inhibitor (anti-HIV) (B) and potent anti-tubercular
agent (C, D)
agents due to non-nucleoside reverse transcriptase inhibition [9] (Figure 1(B)), AMPA
receptor modulators [10] and potent anti-tubercular compounds (Figure 1(C, D)).
In the literature, there are a number of classical methods for the synthesis of ben-
zothiadiazine 1,1-dioxide which have some disadvantages, like use of hazardous organic
solvents, strongly acidic conditions, expensive moisture sensitive catalysts and tedious
work-up conditions [11–19]. Since benzothiadiazine 1,1-dioxide core has some numerous
applications and there is no efficient method for synthesis of these compounds, develop-
ment of proper and simple protocols for the synthesis of functionalized benzothiadiazine
1
,1-dioxide derivatives is so substantial.
In recent years, direct activation of unreactive C–H bonds using transition-metal
catalysis and intramolecular heterofunctionalization of C–H bonds based on atom- and
step-economic principles have been so considerable and applied for synthesis various
heterocycles especially those containing nitrogen [20–22]. In our pervious study, this
methodology, using copper-catalyzed [23–25] C–H activation reactions, was applied to
generate new heterocycles compounds [26]. According to the importance of the benzoth-
iadiazine 1,1-dioxide scaffold and in continuous our research on copper-catalyzed C–H
Scheme 1. Synthesis of various benzothiadiazine 1,1-dioxide derivatives by Cu-catalyzed intramolecu-
ꢀ
ꢀꢀ
lar C–H activation reactions of N,N ,N -trisubstitutedguanidines and benzenesulfonylchlorides.

JOURNAL OF SULFUR CHEMISTRY
3
activation reaction, a novel and one-pot protocol for the synthesis of some benzothiadi-
ꢀ
ꢀꢀ
azine 1,1-dioxide from benzenesulfonylchloride 4 and N,N ,N -trisubstituted guanidines
3
[27] is described (see Scheme 1).
2. Results and discussion
Initially, we examined various copper catalysts, including copper (I) bromide, copper (I)
iodide, copper (II) sulfate, copper (II) acetate, and copper (II) oxide, for the synthesis of
ꢀ
ꢀꢀ
N,N ,N -trisubstituted guanidines from aniline and carbodiimides. Only the copper (II)
oxide gave the best results. We therefore optimized the reaction conditions for hydroam-
ination of carbodiimides by using copper (II) oxide as a catalyst for the model reaction
ꢀ
of aniline (2a) with N,N -dicyclohexylcarbodiimide (1a; DCC). A brief screening of sol-
vents including acetonitrile, toluene, THF and DMF in the presence of 10 mol% of catalyst
under reflux showed that acetonitrile was found as the best solvent for this reaction
(
Table 1).
As part of our current studies on the development of new applications of Cu-catalyzed
C–H activation reaction in organic synthesis, we used the optimized condition to pre-
pare highly functionalized benzothiadiazine 1,1-dioxide from benzenesulfonylchlorides
ꢀ
ꢀꢀ
and the N,N ,N -trisubstitutedguanidines prepared by the copper(II) oxide-catalyzed
hydroamination of dialkylcarbodiimides.
To investigate the scope of this transformation, we examined the reactions of a wide
range of anilines containing various electron-withdrawing and electron-donating groups
to give arylguanidines 3. The reaction of these compounds with benzenesulfonyl chlorides
in the presence of several catalysts including CuI, CuCl, CuBr, Cu O, and CuO were inves-
2
tigated with CuI giving the best result. Among the solvents and bases screened, MeCN and
Cs CO proved to be the best (see Table 2).
2
3
ꢀ
Table 1. Optimization of the conditions for the hydroamination of N,N -dicyclohexylcarbodiimide with
0 mol% of copper salt as the catalyst.
1
Entry
Catalyst
CuI
CuI
CuBr
CuBr
CuO
CuO
Cu(OAc)2
Cu(OAc)2
CuSO4
CuSO4
Solvent
Yield (%)a
1
2
3
4
MeCN
THF
MeCN
toluene
MeCN
DMF
MeCN
DMF
THF
MeCN
22
27
35
32
80
71
66
62
59
51
b
5
6
7
8
9
1
0
a
Reaction time 3 h
b
5
mol% catalyst, reaction time was 7 h

4
M. NAZARI ET AL.
Table 2. Optimization of reaction conditions for the formation of product 5a.
Entry
Catalyst
Solvent
Base
Yield (%)a
1b
2
3
4
5
6
7
8
9
CuI
CuI
CuI
CuI
CuCl
CuCl
CuBr
CuBr
Cu2O
Cu2O
CuO
CuO
MeCN
Acetone
DMF
THF
THF
Acetone
MeCN
THF
MeCN
Acetone
THF
Cs2CO3
K2CO3
Cs2CO3
KOt-Bu
K2CO3
NaOH
KOt-Bu
NaOH
KOt-Bu
Cs2CO3
K2CO3
Cs2CO3
80
63
61
70
42
33
46
39
30
21
14
18
1
1
1
a
0
1
2
MeCN
Reaction time 5 h.
b
5
mol% catalyst, reaction time was 10 h.
Table 3. Synthesis of various benzothiadiazine 1,1-dioxide derivatives
Compound
R1
R2
R3
Yield 5 (%)
5
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
i
Ph
Ph
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Cl
Me
OMe
H
80
78
73
83
81
76
79
85
88
4-Br-C6H4
4-Me-C6H4
Ph
H
4-Cl-C6H4
Cyclohexyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
OMe
Me
NO2
NO2
Ph
4-NO2-C6H4
Bn
Thus, the optimized reaction conditions were as follows: 10 mol % of CuI as the cata-
lyst, 1.5 mmol of Cs CO as the base and 20 mol % of L-proline as the ligand, 1.5 mmol
2
3
of the benzenesulfonylchloride, 1.0 mmol of aniline and 1.0 mmol of dialkylcarbodiimides
in MeCN at room temperature to give the corresponding benzothiadiazine 1,1-dioxide
derivatives (5a–i) with good yields (see Table 3).
The structures of compounds 5a–i were assigned by H-NMR, 13C-NMR, mass and
1
1
IR spectral data. The H-NMR spectrum of 5a exhibited two doublets for methyl groups
(
δ = 1.21 and 1.28 ppm) along with characteristic multiplets for the phenyl protons. The
1
3
C-NMR spectrum of 5a displayed 15 signals in agreement with the proposed structure
Obviously there is an overlap of two signals for different C atoms). The NMR spectra
(
of other compounds were alike to those of 5a, except for the substituents, which showed
characteristic signals in the appropriate regions of the spectra. The mass spectrum of 5a
3
5
(
for the Cl isotope) displayed the molecular ion peak at m/z = 391.
A possible reaction mechanism is shown in Scheme 2. It is proposed that N,N ,N -
trisubstitutedguanidines 3, generated by copper(II) oxide-catalyzed hydroamination
ꢀ
ꢀꢀ

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 2. Possible formation mechanism of compounds 5.
of carbodiimides 1, undergoes nucleophilic substitution reaction by benzenesulfonyl
chlorides 4 to give N-isopropyl-N-(N-isopropyl-N’-phenylcarbamimidoyl)benzenesul
fonamide 6. Reaction of CuI with L-proline produced afive-membered chelate A. Oxida-
tive addition of the chelated Cu (I) with compound 6 in the presence of the base Cs CO
2
3
led to the formation of intermediate B stabilized by the guanidine nitrogen atom coordi-
nated to Cu. Reductive elimination of B afforded the product 5 by leaving the chelate A
and catalyst.
3. Conclusion
In conclusion, a novel protocol, one-pot synthesis of various benzothiadiazine 1,1-dioxide
derivatives via a three-component, intramolecular C–H activation reactions of benzene-
ꢀ
ꢀꢀ
sulfonyl chlorides and N,N ,N -trisubstitutedguanidines catalyzed by copper (I) iodide in
MeCN at room temperatureis described. Generally, available starting materials-catalyst,
under mild conditions and ease of purification procedure with high yield make this
reaction a suitable method for the synthesis of various benzothiadiazine 1,1-dioxide
derivatives.
4. Experimental
4.1. General
Melting points were measured on an Electrothermal 9100 apparatus. Elemental analyses C,
H, N were performed using a Heraeus CHN-O-Rapid analyzer. IR spectra were registered
on a Shimadzu IR-460 spectrometer. Mass spectra were received applying FINNIGAN-
1
MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. H-NMR
1
3
and C-NMR spectra were afforded at 500.1 and 125.7 MHz, respectively, on a BRUKER

6
M. NAZARI ET AL.
DRX500-AVANCE FT-NMR instrument with CDCl as solvent. The reagents and solvents
3
used in this work were obtained from Fluka and were used without further purification.
4
.2. General procedure for preparation of compounds 5
A mixture of CuO (0.10 mmol), aniline 2 (1.0 mmol) and dialkylcarbodiimides 1
(
(
1.0 mmol) in MeCN was refluxed for 3 h. Then, a mixture of benzenesulfonylchloride 4
1.5 mmol), CuI (0.10 mmol), Cs CO (1.5 mmol) and 0.2 mmol of L-proline as the ligand
2
3
in MeCN (2 mL) was slowly added to the first solution and the reaction mixture was stirred
at r.t. for 5 h. After completion of the reaction [TLC (AcOEt/ hexane 1:4) monitoring], the
mixture was diluted with CH Cl (3 mL) and aqueous NH Cl solution (3 mL), stirred for
2
2
4
1
0 min. The resulting solid was isolated by filtration and washed with ethanol.
4.2.1. 6-Chloro-2,4-diisopropyl-3-(phenylimino)-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5a)
White powder; yield: 0.31 g (80%); mp: 295–297°C. IR (KBr) (νmax, cm−1): 1634, 1372,
1
3
1
(
184, 750. H-NMR (500 MHz, CDCl ): δ = 1.21 (d, J = 6.8 Hz, 6 H, 2 Me), 1.28
3
H
3
d, J = 6.8 Hz, 6 H, 2 Me), 3.15–3.18 (m, 1 H, Isopropyl CH), 3.19–3.21 (m, 1 H, Iso-
3
propyl CH), 7.25–7.32 (m, 3 H, Ar), 7.43 (s, 1 H, Ar), 7.44 (d, J = 8.1 Hz, 1 H, Ar), 7.57
3
3
13
(
C
1
(
9
t, J = 7.8 Hz, 2 H, Ar), 8.00 (d, J = 8.1 Hz, 1 H, Ar). C-NMR (125.7 MHz, CDCl ):
3
δ = 21.9 (2 Me), 22.1 (2 Me), 52.4 (Isopropyl CH), 52.5 (Isopropyl CH), 122.5 (2 CH),
27.4 (2 CH), 128.7 (CH), 129.2 (CH), 130.1 (2 CH), 135.7 (C), 140.0 (C), 144.8 (C), 152.5
+
35
C), 167.6 (C). MS: m/z (%) = 391 (M ; Cl isotope, 2), 348 (19), 314 (18), 305 (100),
1 (51), 77 (67). Anal. Calc. for C H ClN O S: C, 58.23; H, 5.66; N, 10.72%. Found: C,
19 22 3 2
5
8.20; H, 5.63; N, 10.70%.
4.2.2. 2,4-Diisopropyl-6-methyl-3-(phenylimino)-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5b)
White powder; yield: 0.29 g (78%); mp: 236–238°C. IR (KBr) (νmax, cm−1): 1672, 1342,
1
3
1
(
(
158, 762. H-NMR (500 MHz, CDCl ): δ = 1.25 (d, J = 6.9 Hz, 6 H, 2 Me), 1.41
3
H
3
d, J = 6.9 Hz, 6 H, 2 Me), 2.47 (s, 3 H, Me), 3.19–3.20 (m, 1 H, Isopropyl CH), 3.21–3.24
3
m, 1 H, Isopropyl CH), 7.28–7.33 (m, 3 H, Ar), 7.40 (d, J = 7.8 Hz, 2 H, Ar), 7.45 (s, 1 H,
3
3
13
Ar), 7.48 (d, J = 8.1 Hz, 1 H, Ar), 7.91 (d, J = 8.1 Hz, 1 H, Ar). C-NMR (125.7 MHz,
CDCl ): δ = 21.8 (2 Me), 22.3 (2 Me), 30.0 (Me), 52.4 (Isopropyl CH), 52.5 (Isopropyl
3
C
CH), 127.4 (2 CH), 128.7 (2 CH), 129.2 (CH), 130.6 (C), 132.5 (2 CH), 132.5 (CH), 142.1
+
(
(
C), 147.3 (C), 152.3 (C), 167.6 (C). MS: m/z (%) = 371 (M , 2), 328 (24), 294 (44), 282
100), 91 (72), 77 (20). Anal. Calc. for C H N O S: C, 64.66; H, 6.78; N, 11.31%. Found:
20 25 3 2
C, 64.63; H, 6.72; N, 11.37%.
4
.2.3. 3-((4-Bromophenyl)imino)-2,4-diisopropyl-6-methoxy-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5c)
White powder; yield: 0.34 g (73%); mp: 260–262°C. IR (KBr) (νmax, cm−1): 1672, 1382,
1
3
1
153, 782. H-NMR (500 MHz, CDCl ):): δ = 1.24 (d, J = 6.9 Hz, 6 H, 2 Me), 1.38
3
H
3
(
d, J = 6.9 Hz, 6 H, 2 Me), 3.18–3.20 (m, 1 H, Isopropyl CH), 3.21–3.23 (m, 1 H, Iso-
3
propyl CH), 3.63 (s, 3 H, OMe), 7.26–7.32 (m, 3 H, Ar), 7.42 (d, J = 7.7 Hz, 1 H, Ar), 7.43
3
13
(s, 1 H, Ar), 7.45 (d, J = 8.1 Hz, 2 H, Ar). C-NMR (125.7 MHz, CDCl ): δ = 21.9 (2
3
C

JOURNAL OF SULFUR CHEMISTRY
7
Me), 22.3 (2 Me), 52.9 (Isopropyl CH), 53.0 (Isopropyl CH), 56.7 (OMe), 127.5 (2 CH),
1
28.7 (CH), 129.3 (CH), 132.4 (CH), 133.1 (2 CH), 139.0 (C), 142.9 (C), 147.5 (C), 148.6
+
(
C), 152.5 (C), 167.6 (C). MS: m/z (%) = 466 (M , 4), 422 (13), 310 (24), 154 (100), 90
(
61). Anal. Calc. for C H BrN O S: C, 51.50; H, 5.19; N, 9.01%. Found: C, 51.53; H,
20 24 3 3
5
.14; N, 9.09%.
4.2.4. 2,4-Diisopropyl-3-(p-tolylimino)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine
1
,1-dioxide (5d)
White powder; yield: 0.31 g (83%); mp: 250–252°C. IR (KBr) (νmax, cm−1): 1652, 1350,
1
3
1
143, 752. H-NMR (500 MHz, CDCl ): δ = 1.25 (d, J = 6.9 Hz, 6 H, 2 Me), 1.31
3
H
3
(
d, J = 6.9 Hz, 6 H, 2 Me), 2.47 (s, 3 H, Me), 3.00–3.07 (m, 1 H, Isopropyl CH),
3
.08–3.12 (m, 1 H, Isopropyl CH), 7.16–7.25 (m, 3 H, Ar), 7.29–7.35 (m, 3 H, Ar), 7.48
3
3
13
(
d, J = 8.0 Hz, 1 H, Ar), 7.91 (d, J = 8.0 Hz, 1 H, Ar). C-NMR (125.7 MHz, CDCl3):
δ = 22.3 (2 Me), 22.4 (2 Me), 30.3 (Me), 57.3 (Isopropyl CH), 57.4 (Isopropyl CH), 126.2
C
(
(
CH), 127.5 (2 CH), 128.7 (CH), 129.2 (C), 129.9 (2 CH), 130.5 (2 CH), 147.5 (C), 149.6
C), 152.1 (C), 167.7 (C). MS: m/z (%) = 371 (M , 2), 285 (29), 280 (44), 266 (28), 91 (100).
+
Anal. Calc. for C H N O S: C, 64.66; H, 6.78; N, 11.31%. Found: C, 64.62; H, 6.71; N,
2
0
25
3
2
1
1.24%.
4.2.5. 2,4-Diisopropyl-3-(phenylimino)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine
1
,1-dioxide (5e)
Cream powder; yield: 0.29 g (81%); mp: 242–244°C. IR (KBr) (νmax, cm−1): 1660, 1372,
1
3
1
151, 711. H-NMR (500 MHz, CDCl ): δ = 1.24 (d, J = 6.8 Hz, 6 H, 2 Me), 1.26
3
H
3
(
d, J = 6.8 Hz, 6 H, 2 Me), 3.05–3.17 (m, 1 H, Isopropyl CH), 3.20–3.23 (m, 1 H, Iso-
3 3
propyl CH), 7.15–7.23 (m, 3 H, Ar), 7.35 (d, J = 7.7 Hz, 2 H, Ar), 7.60 (t, J = 8.1 Hz, 2
3
3
13
H, Ar), 7.73 (t, J = 8.1 Hz, 1 H, Ar), 8.03 (d, J = 7.7 Hz, 1 H, Ar). C-NMR (125.7 MHz,
CDCl ): δ = 22.3 (4 Me), 57.7 (Isopropyl CH), 57.8 (Isopropyl CH), 126.3 (CH), 127.5
3
C
(
(
CH), 128.7 (2 CH), 129.2 (CH), 130.5 (2 CH), 130.6 (2 CH), 147.5 (C), 149.6 (C), 151.5
+
C), 167.6 (C). MS: m/z (%) = 357 (M , 8), 280 (29), 271 (42), 268 (32), 77 (100). Anal.
Calc. for C H N O S: C, 63.84; H, 6.49; N, 11.75%. Found: C, 63.81; H, 6.44; N, 11.79%.
1
9
23
3
2
4.2.6. 3-((4-Chlorophenyl)imino)-2,4-dicyclohexyl-6-methoxy-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5f)
Cream powder; yield: 0.38 g (76%); mp: 271–273°C. IR (KBr) (νmax, cm−1): 1651, 1361,
1
1
2
1
122, 714. H-NMR (500 MHz, CDCl ): δ = 0.91–0.94 (m, 6 H, 3 CH ), 1.19–1.22 (m,
3
H
2
H, CH ), 1.23–1.25 (m, 4 H, 2 CH ), 1.36–1.38 (m, 2 H, CH ), 1.48–1.51 (m, 2 H, CH ),
.80–2.00 (m, 2 H, CH ), 2.01–2.10 (m, 2 H, CH ), 3.68–3.69 (m, 1 H, CH), 3.69–3.71
2
2
2
2
2
2
3
(
(
m, 1 H, CH), 3.74 (s, 3 H, OMe), 7.58 (d, J = 8.3 Hz, 2 H, Ar), 7.60 (s, 1 H, Ar), 7.69
3 3 3
d, J = 8.0 Hz, 1 H, Ar), 7.85 (d, J = 8.0 Hz, 1 H, Ar), 7.99 (d, J = 8.3 Hz, 2 H, Ar).
1
3
C-NMR (125.7 MHz, CDCl ): δ = 20.7 (2 CH ), 22.0 (4 CH ), 22.1 (4 CH ), 52.4
3
C
2
2
2
(
(
(
CH), 52.5 (CH), 56.7 (OMe), 127.3 (2 CH), 130.1 (CH), 131.5 (CH), 132.6 (2 CH), 133.0
CH), 135.6 (C), 139.0 (C), 142.2 (C), 144.7 (C), 152.2 (C), 166.1 (C). MS: m/z (%) = 502
+
35
M ; Cl isotope, 2), 390 (32), 378 (23), 125 (35), 111 (100), 91 (29). Anal. Calc. for
C H ClN O S: C, 62.20; H, 6.42; N, 8.37%. Found: C, 62.23; H, 6.40; N, 8.32%.
2
6
32
3
3

8
M. NAZARI ET AL.
4.2.7. 2,4-Dicyclohexyl-6-methyl-3-(phenylimino)-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5 g)
Cream powder; yield: 0.36 g (79%); mp: 290–292°C. IR (KBr) (νmax, cm−1): 1635, 1323,
1
1
117, 790. H-NMR (500 MHz, CDCl ): δ = 0.97–1.00 (m, 6 H, 3 CH ), 1.24–1.56 (m, 6
3
H
2
H, 3 CH ), 1.93–1.98 (m, 2 H, CH ), 2.13–2.15 (m, 2 H, CH ), 2.47 (s, 3 H, Me), 2.47–2.50
2
2
2
(
m, 4 H, 2 CH ), 3.48–3.49 (m, 1 H, CH), 3.53–3.55 (m, 1 H, CH), 7.14–7.21 (m, 3 H, Ar),
2
3
3
7
.31 (d, J = 8.2 Hz, 2 H, Ar), 7.36 (s, 1 H, Ar), 7.40 (d, J = 8.0 Hz, 1 H, Ar), 7.91 (d,
3
13
J = 8.0 Hz, 1 H, Ar). C-NMR (125.7 MHz, CDCl ): δ = 20.8 (2 CH ), 22.2 (4 CH ),
3
C
2
2
2
2.3 (4 CH ), 30.7 (Me), 58.6 (CH), 58.9 (CH), 126.2 (CH), 127.5 (CH), 130.5 (2 CH), 130.6
2
(
2 CH), 131.3 (CH), 132.0 (CH), 137.0 (C), 141.6 (C), 149.6 (C), 149.7 (C), 167.8 (C). MS:
+
m/z (%) = 451 (M , 3), 374 (32), 368 (21), 362 (44), 92 (100), 77 (57). Anal. Calc. for
C H N O S: C, 69.15; H, 7.36; N, 9.30%. Found: C, 69.12; H, 7.33; N, 9.22%.
2
6
33
3
2
4.2.8. 2,4-Dicyclohexyl-6-nitro-3-((4-nitrophenyl)imino)-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5 h)
Yellow powder; yield: 0.45 g (85%); mp: 299–301°C. IR (KBr) (νmax, cm−1): 1675, 1547,
1
1
(
315, 1140, 743. H-NMR (500 MHz, CDCl ): δ = 1.29–1.33 (m, 6 H, 3 CH ), 1.34–1.40
3
H
2
m, 6 H, 3 CH ), 1.45–1.48 (m, 4 H, 2 CH ),1.69–1.71 (m, 4 H, 2 CH ), 3.40–3.42 (m, 1 H,
2 2 2
3
CH), 3.44–3.69 (m, 1 H, CH), 7.48–7.50 (m, 3 H, Ar), 7.64 (d, J = 8.1 Hz, 1 H, Ar), 7.74
3
3
13
(
d, J = 8.2 Hz, 2 H, Ar), 8.06 (d, J = 8.1 Hz, 1 H, Ar). C-NMR (125.7 MHz, CDCl ):
3
δ = 24.2 (2 CH ), 24.6 (2 CH ), 25.4 (4 CH ), 25.5 (2 CH ), 53.6 (CH), 54.5 (CH), 127.4
C
2
2
2
2
(
2 CH), 128.7 (2 CH), 129.2 (CH), 130.1 (CH), 132.5 (CH), 135.7 (C), 144.8 (C), 145.0 (C),
+
1
1
5
49.0 (C), 150.3 (C), 163.8 (C). MS: m/z (%) = 527 (M , 9), 444 (21), 405 (22), 391 (80),
22 (100). Anal. Calc. for C H N O S: C, 56.91; H, 5.54; N, 13.27%. Found: C, 56.97; H,
2
5
29
5
6
.52; N, 13.24%.
4.2.9. 3-(Benzylimino)-2,4-dicyclohexyl-6-nitro-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine 1,1-dioxide (5i)
Yellow powder; yield: 0.41 g (88%); mp: 295–297°C. IR (KBr) (νmax, cm−1): 1667, 1557,
1
1
(
337, 1114, 734. H-NMR (500 MHz, CDCl ): δ = 1.30–1.32 (m, 6 H, 3 CH ), 1.33–1.36
3
H
2
m, 6 H, 3 CH ), 1.69–1.71 (m, 4 H, 2 CH ), 1.87–1.90 (m, 4 H, 2 CH ), 3.40–3.43 (m,
2 2 2
1
H, CH), 3.54–3.70 (m, 1 H, CH), 4.23 (s, 2 H, CH ), 7.25–7.35 (m, 5 H, Ar), 7.41
2
3
3
3
(
t, J = 7.8 Hz, 1 H, Ar), 7.50 (d, J = 8.2 Hz, 1 H, Ar), 7.93 (d, J = 8.2 Hz, 1 H, Ar).
1
3
C-NMR (125.7 MHz, CDCl ): δ = 24.3 (2 CH ), 24.6 (2 CH ), 25.3 (4 CH ), 27.2 (2
3
C
2
2
2
CH ), 44.4 (CH ), 53.6 (CH), 56.0 (CH), 124.6 (CH), 127.5 (2 CH), 128.7 (CH), 129.2
2
2
(
CH), 130.6 (CH), 132.5 (2 CH), 134.2 (C), 142.3 (C), 146.6 (C), 150.0 (C), 162.6 (C). MS:
+
m/z (%) = 496 (M , 9), 405 (23), 393 (30), 291 (28), 105 (56), 91 (100), 77 (87). Anal. Calc.
for C H N O S: C, 62.88; H, 6.49; N, 11.28%. Found: C, 62.84; H, 6.52; N, 11.24%.
2
6
32
4
4
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by the Research Council of Shahid Beheshti University of Medical Sciences.

JOURNAL OF SULFUR CHEMISTRY
9
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