A facile synthesis of annulated thiatriazine dioxides

Article abstract of DOI:10.1055/s-0029-1218840

The reactions of five-, six-, seven-, and eight-membered cyclic imido ethers with one equivalent of sulfamide lead to the corresponding sulfamoylamidines in 70-80% yields. Sulfamoylamidines undergo condensations with aliphatic and aromatic aldehydes as well as aliphatic ketones to give thiatriazine dioxides in 50-95% yields. The NMR spectroscopic studies reveal ring-chain tautomerism of some thiatriazine dioxides in solution. The ratio between the tautomers depends on the temperature, solvent polarity, and electronic properties of the substituents of the pendant aryl rings. Thiatriazine dioxides are readily alkylated and acylated at position 2. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1218840

2588
PAPER
A Facile Synthesis of Annulated Thiatriazine Dioxides
F
acile Synthesis of
l
A
nnul
e
ated Thiatr
x
iazine
D
ioxi
a
Konstantin G. Nazarenko,e Andrey A. Tolmacheva,f
a
ChemBioCenter, Taras Shevchenko Kiev National University, 62 Volodymyrska St., Kiev 01033, Ukraine
Taras Shevchenko Chernigiv State Pedagogical University, 53 Getman Polubotok St., Chernigiv 14013, Ukraine
The Institute of High Technologies, Taras Shevchenko Kiev National University, 62 Volodymyrska St., Kiev 01033, Ukraine
STC ‘Institute for Single Crystals’, National Academy of Sciences of Ukraine, 60 Lenina Ave., Kharkiv 61001, Ukraine
b
c
d
e
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska St., Kiev 02094, Ukraine
Enamine Ltd., 23 Alexander Matrosov St., Kiev 01103, Ukraine
f
Fax +380(44)5373253; E-mail: shivan1@yandex.ru
Received 1 March 2010; revised 21 April 2010
R3
N
R3
R3
N
Abstract: The reactions of five-, six-, seven-, and eight-membered
cyclic imido ethers with one equivalent of sulfamide lead to the cor-
responding sulfamoylamidines in 70–80% yields. Sulfamoyl-
amidines undergo condensations with aliphatic and aromatic
aldehydes as well as aliphatic ketones to give thiatriazine dioxides
in 50–95% yields. The NMR spectroscopic studies reveal ring-
chain tautomerism of some thiatriazine dioxides in solution. The ra-
tio between the tautomers depends on the temperature, solvent po-
larity, and electronic properties of the substituents of the pendant
aryl rings. Thiatriazine dioxides are readily alkylated and acylated
at position 2.
R2
HN
R1
NH
R2
NH
R2
R1CHO
+
NH2
NH2
N
N
S
S
S
O
O
O
O
O
O
A
B
C
R3
R3
R2
N
R2
NH
X = H, Alk
OX
Key words: imido ethers, sulfamide, sulfamoylamidines, thiatria-
zine dioxides, tautomerism
D
O
E
NH2
O
H2N
NH2
H2N
S
S
O
O
O
F
F
Some functionalized thiatriazine dioxides of type A
(Scheme 1) are efficient anticholesteremic agents,1 gastric
secretion inhibitors,2 herbicides,3 and H2-antagonists.4
These compounds are synthesized through the condensa-
tion of sulfonamides with formaldehyde and primary
amines,5 the reaction of 5-aminotetrazole with chlorosul-
fonyl isocyanate in the presence of a tertiary amine,6 con-
densation of sulfonylamide with phthalaldehyde,7 the
rearrangement of thiatriazole dioxides,8 and oxidation of
thiatriazine oxides.9 Thiatriazine dioxides are also synthe-
sized starting from carboimidates.10 These methods have
technological drawbacks that hamper combinatorial syn-
thesis of drug-like thiatriazine dioxides for systematic
QASAR studies. Among these drawbacks are low multi-
step reaction procedures, long reaction times, low yields
of target compounds, and the necessity to use highly reac-
tive reagents such as chlorosulfonylamides, chlorosulfo-
nyl isocyanate, and sodium amide.
Scheme 1 Retrosynthetic analysis of thiatriazine dioxides
five-, six-, seven-, and eight-membered nitrogen-contain-
ing heterocycles.
Readily available cyclic imido ethers 111 reacted with one
equivalent of sulfamide in isopropyl alcohol (reflux, 3 h)
to give sulfamoylamidines 2 in 70–95% yield after simple
recrystallization from water (Scheme 2). Under similar
conditions the corresponding cyclic lactams did not react
with sulfamide, apparently due to their lower reactivity.
The reaction of compounds 2 and 1 (i-PrOH, reflux, 10 h)
afforded bisamidines 3 in 80–93% yield. Compounds 2
were also synthesized through the reaction of sulfamide
with two equivalents of the corresponding imino ether 1.
(CH2)n
NH
(CH2)n
NH
(CH2)n
NH
(CH2)n
N
SO2(NH2)2
1
Retrosynthetic analysis revealed that molecules A
(Scheme 1) contain three fragments that could be connect-
ed via two condensation reactions. Theoretically interme-
diate B could be synthesized through the reaction of
amides D or imido ethers E with sulfamide F.
N
N
N
SO2
SO2NH2
2a–d
OMe
1a–d
3a,c,d
n = 1 a ; n = 2 b ; n = 3 c; n = 4 d
Herein we report a facile and versatile synthetic method-
ology for the annulation of the triazine dioxide ring to
Scheme 2 Reaction of cyclic imido ethers with sulfamide
All attempts to synthesize compounds 2 from the corre-
sponding cyclic amides and sulfamide failed (D + F in
Scheme 1) most probably due to the lower reactivity of
the amides compared to the imido ethers.
SYNTHESIS 2010, No. 15, pp 2588–2598
Advanced online publication: 25.06.2010
DOI: 10.1055/s-0029-1218840; Art ID: P03210SS
x
x.
x
x
.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

PAPER
Facile Synthesis of Annulated Thiatriazine Dioxides
2589
Table 1 Yields of Thiatriazines 4–7
Compounds 2 readily reacted with aromatic and aliphatic
aldehydes and ketones (i-PrOH, reflux, 6 h) to give thia-
triazine dioxides 4–7 in 50–95% yield (Table 1). The re-
action of acetals of aliphatic aldehydes also resulted in the
corresponding thiatriazine sulfoxides in preparative
yields. Compounds 4–7 crystallized from the reaction
mixture and they were additionally purified by recrystal-
lization from alcohols or acetonitrile.
R1
R2
(CH2)n
R1R2C=O
i-PrOH
reflux
(CH2)n
NH
N
NH
O
N
S
N
SO2NH2
O
2
Product
4a
4b
4c
4–7
n
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
R1
H
R2
H
H
H
H
H
H
H
H
H
H
H
Yield (%)
74
61
79
70
81
79
94
59
56
86
64
84
67
74
77
79
91
51
59
61
58
71
77
75
90
49
67
70
71
77
80
89
61
68
Compounds 4 and 6 readily reacted with methyl iodide,
bromoacetophenone, benzoyl chloride, and acetic anhy-
dride (see the experimental section) to give derivatives 8
(Table 2) in 77–81% yield. Compounds 8 were purified
by simple crystallization.
Me
Ph
4d
4e
3-MeC6H4
Table 2 Yields of Thiatriazine 8a
4-ClC6H4
4-OHCC6H4
4-O2NC6H4
4-Me2NC6H4
4-MeOC6H4
4-HO2CC6H4
4-HOC6H4
Me
R1
R2
(CH2)n
N
R1
R2
(CH2)n
N
4f
N
R3
NH
O
4g
4h
4i
N
N
S
S
O
O
O
4, 6
8
4j
Product
8a
n
1
3
1
1
R1
R2
H
H
H
H
R3
Yield (%)
4k
4l
4-MeC6H4
4-FC6H4
Ph
Me
78
81
71
77
Me
8b
CH2Bz
Bz
4m
4n
5a
5b
5c
Et
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
8c
4-FC6H4
Ph
8d
Ph
Ac
a For reagents and conditions, see the experimental section.
4-ClC6H4
4-O2NC6H4
4-Me2NC6H4
4-MeOC6H4
H
The composition and structure of compounds 2–8 were
1
proved by LC-MS, elemental analysis, H, 13C, NOESY
5d
5e
NMR spectroscopy, and single crystal X-ray crystallogra-
phy.
6a
6b
6c
Molecular structures of compounds 2a–d are shown in
Figure 1. The N2–C1 bond in 2a–d is N1–C1 bond is
shortened compared to the mean values for the Csp2=N2
(1.313 Å)12 and the Csp2–N3 (1.339 Å) bonds respective-
CH2Cl
2-pyridyl
Ph
6d
6e
4-ClC6H4
4-O2NC6H4
4-Me2NC6H4
4-MeOC6H4
2-MeC6H4
4-FC6H4
Ph
6f
6g
6h
6i
6j
7a
7b
7c
4-ClC6H4
4-O2NC6H4
4-Me2NC6H4
4-MeOC6H4
7d
7e
Figure 1 Molecular structures and numbering schemes of com-
pounds (a) 2a, (b) 2b, (c) 2c, and (d) 2d
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

2590
A. N. Khodachenko et al.
PAPER
ly. Such a redistribution of the electron density allows ratio depends on the temperature, electronic effects of the
considering the structure of 2a–d as a superposition of substituents, and the size of the azaheterocycle. This can
neutral and zwitterionic resonance structures N and ZI be explained by equilibrium between isomers X and Y
(Scheme 3, top).
which interconvert slowly on the NMR timescale. The
NOESY experiments revealed that the NH and methine
CH protons of form Y emerge as a broadened triplet and
a sharp singlet, respectively. Form Y was further charac-
terized by H7–H10, H7–H10¢ NOESY correlations and
the absence of NOE between H7 and H6 (Figure 3). In
form X the methine proton H2 gives NOE to the NH pro-
ton H1 and two diastereotopic methylene protons H5 and
H5¢. No exchange cross peaks were observed between the
signals of X and Y indicating that the equilibrium is slow
(CH2)n
(CH2)n
N–
SO2NH2
N
N+
H
a
N
H
SO2NH2
ZI
N
(CH2)n
N+ N–
SO2
(CH2)n
1
on the human timescale. Variable temperature H NMR
measurements revealed considerable increase of [Y]/[X]
in dimethyl sulfoxide-d6 by three to four times upon rais-
ing the temperature from 303 K to 360 K. This indicates
the higher entropy of open form X compared to cyclic
form Y. Although nonlinearity of the DG vs. T plots pre-
vented reliable estimation of DH and DS of the equilibri-
um it is possible to make conclusion that the trans-
formation of X to Y is an endothermic, entropy-driven
process.
N
N
R1
R2
R1
R2
b
SO2
N
N
H
H
ZI
N
Scheme 3 Resonance structures of (a) 2a–d and (b) 4l, 5a, 5b, and
6i
Molecular structures of compounds 4l, 5a, 5b, and 6i are
shown in Figure 2. Analysis of the bond lengths within the
fragment N1–C1–N2 revealed that these molecules can
also be described as the superpositions of neutral and
zwitterionic forms (Scheme 3, bottom).
Figure 3 1H NMR spectra (298 K, 500 MHz) compound 6g in
DMSO-d6. NOE: H1–H2, H2–H4, H2–H5, H2–H5¢, H6–H9, H7–
H10, H3–H4, H8–H9.
The data listed in Table 3 indicate that form Y is stabilized
by p-electron-donor functional groups in the phenyl ring.
In a simplistic way, this can be explained by stabilization
of form Y through the resonance of neutral N and zwitter-
ionic ZI structures. Apparently such p-electron-donor
groups as OMe, and NMe2 should stabilize the zwitterion-
ic form favoring structure Y.
Figure 2 Molecular structures and numbering schemes of com-
pound (a) 4l, (b) 5a, (c) 5b, and (d) 6i
1
The H NMR spectra of compounds 4–7 bearing p-elec-
tron-donor functional groups in the para-position of the
aryl ring measured in dimethyl sulfoxide-d6 and deutero-
chloroform contain two sets of signals (Figure 3) whose
Form Y is more stable in the case of the larger azahetero-
cycles [DDG (5a–7a) = 1.0 kcal/mol, DDG (4i–6h) = 2.3
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

PAPER
Facile Synthesis of Annulated Thiatriazine Dioxides
2591
kcal/mol, DDG (4h–7e) = DDG (5b–7b) = 1.15 kcal/mol]. In conclusion the reaction of readily available sulfon-
This can be explained by the larger entropy loss for larger amides 2 with various aromatic aliphatic aldehydes fur-
azaheterocycles in the cyclization.
nishes annulated drug-like thiatriazine dioxides 4–7
bearing various functional groups and, thus, can be used
for systematic quantitative structure–activity relation-
ships. There is no doubt that wide scope, high yield, and
simple synthesis and purification protocol makes this syn-
thetic approach applicable in combinatorial synthesis of
functionalized thiatriazine dioxides. Compounds 4–7
bearing p-electron-donor functional groups in the pendant
aromatic rings exist in dimethyl sulfoxide-d6 and deutero-
chloroform as mixtures of cyclic and open tautomers that
interconvert slowly on the NMR timescale. The position
of this equilibrium depends on the M-effect of the func-
tional group in the aromatic ring, temperature, polarity of
solvent, and the size of the azaheterocycle. It is likely that
this equilibrium may be used as a motif for rational design
of covalent self-assembling systems.13
It should be noted that in dimethyl sulfoxide-d6 the equi-
librium constants are considerably lower than in deutero-
chloroform (see Table 3). Most probably this can be
explained by stabilization of form X through hydrogen
bonding between the sulfonamide fragment and mole-
cules of dimethyl sulfoxide-d6.
Table 3 Equilibrium Constants and DG Values for Equilibrium be-
tween X and Y
(CH2)n
(CH2)n
K
NH
R
N
N
N
NH
N
S
R
S
O
O
O
O
X
Y
All commercially available starting materials were used without ad-
ditional purification. All solvents were purified by standard meth-
ods. All procedures were carried out under an open atmosphere with
no precautions taken to exclude ambient moisture. Melting points
(CH2)n
NH
(CH2)n
NH
N–
S
O
N
N
S
O
N
1
are uncorrected. H NMR spectra were recorded on 400 MHz and
500 MHz spectrometers with TMS as internal standard. 13C NMR
(125 MHz) spectra and NMR experiments were recorded on a 500
MHz spectrometer with TMS as internal standard. LC/MS spectra
were recorded using chromatography/mass spectrometric system
that consists of HPLC unit equipped with diode-matrix and mass-
selective detector. Ionization method is chemical ionization under
atmospheric pressure (APCI). Ionization mode is simultaneous
scanning of positive and negative ions in the mass range of 80–1000
m/z. According to HPLC-MS and 1H NMR spectra data all the syn-
thesized compounds have purity >95%.
O
O
X+
X
N
ZI
Compd
CDCl3
K
DMSO-d6
DG (kcal/mol) K
DG (kcal/mol)
>2.7
4c
4e
4h
4i
<0.01
<0.01
0.75
0.10
0.15
0.25
15.70
0.90
0.70
0.85
>100
4.60
0.90
1.70
0.40
>100
5.25
>2.7
>2.7
0.17
<0.01
<0.01
0.09
>2.7
Compounds 2a–d; General Procedure
1.42
A soln of freshly distilled imido ether 1 (0.3 mol) in i-PrOH (50 mL)
was added dropwise to a stirred and refluxed soln of sulfamide (0.36
mol) in i-PrOH (300 mL). The mixture was stirred at reflux for 3 h.
Upon cooling to r.t. a precipitate formed that was filtered off and
washed with i-PrOH (2 × 20 mL). The crude product was recrystal-
lized (H2O) and dried.
1.36
<0.01
<0.01
<0.01
0.41
>2.7
5a
5b
5d
5e
6d
6e
6g
6h
7a
7b
7c
7d
7e
1.12
>2.7
0.82
>2.7
–1.63
0.06
0.53
N-(Pyrrolidin-2-ylidene)sulfamide (2a)
White solid; yield: 78%; mp 200–201 °C.
0.03
2.07
1H NMR (500 MHz, DMSO-d6): d = 8.25 (s, 1 H, NH), 6.28 (s, 2 H,
NH2), 3.38–3.35 (m, 2 H, CH2), 2.63 (s, 2 H, CH2), 1.98–1.92 (m, 2
H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 170.9, 45.5, 31.6, 20.9.
MS (APCI): m/z = 164.0 [M + H]+.
0.21
<0.01
<0.01
3.76
>2.7
0.10
>2.7
<–2.7
–0.90
0.06
–0.78
2.07
0.03
Anal. Calcd for C4H9N3O2S: C, 29.44; H, 5.56; N, 25.75; S, 19.65.
Found: C, 29.27; H, 5.49; N, 25.82; S, 19.58.
<0.01
<0.01
<0.01
0.75
>2.7
–0.31
0.54
>2.7
N-(Piperidin-2-ylidene)sulfamide (2b)
White solid; yield: 72%; mp 187–188 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.10 (s, 1 H, NH), 6.30 (s, 2 H,
NH2), 3.33 (s, 2 H, CH2), 2.44 (s, 2 H, CH2), 1.65 (s, 4 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 164.4, 42.0, 29.5, 21.6, 19.6.
MS (APCI): m/z = 178.0 [M + H]+.
>2.7
<–2.7
–1.00
0.17
0.05
1.77
Anal. Calcd for C5H11N3O2S: C, 33.89; H, 6.26; N, 23.71; S, 18.09.
Found: C, 33.78; H, 6.23; N, 23.74; S, 18.02.
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

2592
A. N. Khodachenko et al.
PAPER
N-(Azepan-2-ylidene)sulfamide (2c)
White solid; yield: 74%; mp 147–148 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.95 (s, 1 H, NH), 6.47 (s, 2 H,
NH2), 3.40–3.16 (m, 2 H, CH2), 2.55–2.31 (m, 2 H, CH2), 1.74–1.35
(m, 6 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 170.3, 43.4, 35.3, 29.7, 29.1,
24.1.
MS (APCI): m/z = 192.0 [M + H]+.
Compounds 4a and 6a; General Procedure
Paraformaldehyde (5.7 mmol) was added to a soln of sulfamoylami-
dine 2 (5.2 mmol) in i-PrOH (25 mL). The mixture was stirred at 50
°C for 16 h. The precipitate formed was filtered and the residue
washed with H2O (2 × 2 mL) and dried to give 4a or 6a as a white
solid.
3,4,7,8-Tetrahydro-6H-pyrrolo[2,1-c][1,2,4,6]thiatriazine 2,2-
Dioxide (4a)
White solid; yield: 74%; mp 178–179 °C (i-PrOH).
1H NMR (500 MHz, DMSO-d6): d = 6.93 (t, 3J = 8.5 Hz, 1 H, NH),
4.63 (d, 3J = 8.5 Hz, 2 H, CH2), 3.52 (t, 3J = 7.0 Hz, 2 H, CH2), 2.60
(t, 3J = 7.5 Hz, 2 H, CH2), 2.05–1.93 (m, 2 H, CH2).
Anal. Calcd for C6H13N3O2S: C, 37.68; H, 6.85; N, 21.97; S, 16.77.
Found: C, 37.73; H, 6.81; N, 21.95; S, 16.65.
N-(Azocan-2-ylidene]sulfamide (2d)
13C NMR (125 MHz, DMSO-d6): d = 167.9, 57.5, 50.9, 33.4, 19.0.
MS (APCI): m/z = 176.0 [M + H]+.
White solid; yield: 81%; mp 158–159 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.74 (s, 1 H, NH), 6.40 (s, 2 H,
NH2), 3.38 (s, 2 H, CH2), 2.40 (s, 2 H, CH2), 1.75–1.36 (m, 8 H,
CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.3, 42.3, 32.0, 31.2, 29.2,
25.4, 24.0.
Anal. Calcd for C5H9N3O2S: C, 34.28; H, 5.18; N, 23.98; S, 18.30.
Found: C, 34.10; H, 5.12; N, 23.90; S, 18.22.
3,4,7,8,9,10-Hexahydro-6H-[1,2,4,6]thiatriazino[4,3-a]azepine
2,2-Dioxide (6a)
White solid; yield: 61%; mp 165–166 °C (i-PrOH).
MS (APCI): m/z = 206.0 [M + H]+.
Anal. Calcd for C7H15N3O2S: C, 40.96; H, 7.37; N, 20.47; S, 15.62.
Found: C, 40.78; H, 7.33; N, 20.51; S, 15.54.
1H NMR (500 MHz, DMSO-d6): d = 7.18 (dd, 3J = 9.0, 8.5 Hz, 1 H,
3
NH), 4.64 (d, J = 9.0 Hz, 2 H, CH2), 3.51–3.89 (m, 2 H, CH2),
2.46–2.38 (m, 2 H, CH2), 1.75–1.50 (m, 8 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 167.6, 62.3, 51.0, 37.4, 29.0,
27.3, 24.2.
Compounds 3a,c,d; General Procedure
A soln of sulfamide (10 mmol) and imido ether 1 (40 mmol) in
i-PrOH (30 mL) was stirred at reflux for 10 h. The mixture was
cooled to r.t. and the precipitate was filtered off, washed with
i-PrOH (2 × 2 mL) and H2O and dried in vacuo to give 3 as a white
solid. Analytical samples of compounds 3 were additionally puri-
fied by recrystallization (H2O).
MS (APCI): m/z = 204.0 [M + H]+.
Anal. Calcd for C7H13N3O2S: C, 41.36; H, 6.45; N, 20.67; S, 15.78.
Found: C, 41.22; H, 6.37; N, 20.50; S, 15.83.
N,N¢-Bis(pyrrolidin-2-ylidene)sulfamide (3a)
White solid; yield: 93%, mp 248–249 °C.
4-Methyl-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-c][1,2,4,6]thia-
triazine 2,2-Dioxide (4b)
A soln of 2a (1 g, 5.2 mmol) and acetaldehyde (0.44 mL, 7.8 mmol)
in i-PrOH (30 mL) was refluxed for 4 h. The mixture was reduced
to 20 mL and cooled to r.t. The crude product was recrystallized
(MeCN) to give 4b as a white solid; yield: 0.69 g (61%); mp 128–
129 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.23 (s, 2 H, NH), 3.38–3.26
(m, 4 H, CH2), 2.65–2.56 (m, 4 H, CH2), 1.98–1.93 (m, 4 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 170.9, 45.5, 31.6, 20.9.
MS (APCI): m/z = 231.0 [M + H]+.
3
1H NMR (500 MHz, DMSO-d6): d = 6.97 (d, J = 11.0 Hz, 1 H,
Anal. Calcd for C8H14N4O2S: C, 41.72; H, 6.13; N, 24.33; S, 13.92.
Found: C, 41.63; H, 6.18; N, 24.20; S, 13.87.
NH), 4.92–5.01 (m, 1 H, CH), 3.61–3.51 (m, 2 H, CH2), 2.65–2.56
(m, 2 H, CH2), 1.98–1.87 (m, 2 H, CH2), 1.43 (d, 3J = 5.2 Hz, 3 H,
CH3).
N,N¢-Bis(azepan-2-ylidene)sulfamide (3c)
White solid; yield: 86%; mp 132–133 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.14 (s, 2 H, NH), 3.37–3.31
(m, 4 H, CH2), 2.55–2.47 (m, 4 H, CH2), 1.73–1.40 (m, 12 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 170.7, 43.6, 35.0, 29.8, 29.2,
24.2.
MS (APCI): m/z = 287.0 [M + H]+.
13C NMR (125 MHz, DMSO-d6): d = 167.7, 64.7, 49.0, 33.4, 18.2,
18.0.
MS (APCI): m/z = 190.0 [M + H]+.
Anal. Calcd for C6H11N3O2S: C, 38.08; H, 5.86; N, 22.21; S, 16.94.
Found: C, 37.88; H, 5.82; N, 22.15; S, 16.87.
2H-1,2,4,6-Thiatriazine 1,1-Dioxides 4c–k, 5a–e, 6c–i, 7a–e;
General Procedure
Anal. Calcd for C12H22N4O2S: C, 50.33; H, 7.74; N, 19.56; S, 11.20.
Found: C, 50.27; H, 7.63; N, 19.48; S, 11.24.
TsOH (10 mg) was added to a mixture of powdered 2 (6.1 mmol)
and excess of the corresponding benzaldehyde (9.2 mmol) in i-PrOH
(30 mL). The mixture was stirred at reflux for 8 h. Upon cooling a
solid was formed, which was filtered off and washed with H2O (3 ×
5 mL) and i-PrOH (2 × 2 mL). The crude product was recrystallized.
N,N¢-Bis(azocan-2-ylidene)sulfamide (3d)
White solid; yield: 80%; mp 179–180 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.91 (s, 2 H, NH), 3.47–3.37
(m, 4 H, CH2), 2.48–2.37 (m, 4 H, CH2), 1.76–1.64 (m, 4 H, CH2),
1.59–1.37 (m, 12 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 169.4, 42.2, 31.9, 31.2, 29.4,
25.5, 24.4.
4-Phenyl-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-c][1,2,4,6]thia-
triazine 2,2-Dioxide (4c)
White solid; yield: 79%; mp 192–193 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 7.56–7.54 (m, 2 H, ArH),
7.44–7.42 (m, 3 H, ArH), 7.33 (d, 3J = 13.5 Hz, 1 H, NH), 5.86 (d,
3J = 13.5 Hz, 1 H, CH), 3.28–3.20 (m, 1 H, CH2), 3.04–2.95 (m, 1
H, CH2), 2.80–2.70 (m, 1 H, CH2), 2.67–2.56 (m, 1 H, CH2), 1.95–
1.80 (m, 2 H, CH2).
MS (APCI): m/z = 315.2 [M + H]+.
Anal. Calcd for C14H26N4O2S: C, 53.47; H, 8.33; N, 17.82; S, 10.20.
Found: C, 53.36; H, 8.27; N, 17.85; S, 10.17.
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

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Facile Synthesis of Annulated Thiatriazine Dioxides
2593
1H NMR (500 MHz, CDCl3): d = 7.58–7.42 (m, 5 H, ArH), 5.91 (d,
3J = 12.0 Hz, 1 H, NH), 5.26 (d, 3J = 11.5 Hz, 1 H, CH), 3.22–3.18
(m, 2 H, CH2), 3.00–2.84 (m, 1 H, CH2), 2.77–2.60 (m, 1 H, CH2),
2.05–1.89 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.5, 134.5, 130.0, 129.2,
128.5, 71.0, 50.4, 32.5, 18.0.
Anal. Calcd for C13H18N4O2S: C, 53.04; H, 6.16; N, 19.03; S, 10.89.
Found: C, 52.94; H, 6.11; N, 18.98; S, 10.82.
4-(4-Methoxyphenyl)-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (4i)
White solid; yield: 56%; mp 200–201 °C (i-PrOH).
1H NMR (500 MHz, DMSO-d6): d = 7.50 (d, J = 6.4 Hz, 2 H, ArH),
7.30 (d, J = 8.8 Hz, 1 H, NH), 6.97 (d, J = 6.4 Hz, 2 H, ArH), 5.79
(d, J = 8.8 Hz, 1 H, CH), 3.77 (s, 3 H, OCH3), 3.24–3.16 (m, 1 H,
CH2), 3.00–2.92 (m, 1 H, CH2), 2.77–2.68 (m, 1 H, CH2), 2.66–2.56
(m, 1 H, CH2), 1.94–1.77 (m, 2 H, CH2).
1H NMR (500 MHz, CDCl3): d = 7.42 (d, J = 6.8 Hz, 2 H, ArH),
6.99 (d, J = 6.8 Hz, 2 H, ArH), 5.86 (d, J = 7.6 Hz, 1 H, NH), 4.96
(d, J = 8.8 Hz, 1 H, CH), 3.85 (s, 3 H, OCH3), 3.19 (t, J = 7.1 Hz, 1
H, CH2), 3.00–2.86 (m, 1 H, CH2), 2.76–2.63 (m, 2 H, CH2), 2.04–
1.90 (m, 2 H, CH2).
MS (APCI): m/z = 252.0 [M + H]+.
Anal. Calcd for C11H13N3O2S: C, 52.57; H, 5.21; N, 16.72; S, 12.76.
Found: C, 52.38; H, 5.25; N, 16.77; S, 12.69.
4-(3-Methylphenyl)-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (4d)
White solid; yield: 70%; mp 171–172 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 7.44–7.20 (m, 5 H, ArH, NH),
5.82 (d,3J = 11.0 Hz, 1 H, CH), 3.30–3.20 (m, 1 H, CH2), 3.09–2.99
(m, 1 H, CH2), 2.83–2.71 (m, 1 H, CH2), 2.72–2.57 (m, 1 H, CH2),
2.34 (s, 3 H, CH3), 1.99–1.83 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.3, 160.5, 129.9, 125.7,
114.5, 70.6, 55.7, 49.9, 33.7, 17.7.
MS (APCI): m/z = 282.2 [M + H]+.
13C NMR (125 MHz, DMSO-d6): d = 168.4, 138.5, 134.4, 130.6,
129.1, 129.0, 125.5, 71.0, 50.3, 33.7, 21.5, 18.2.
Anal. Calcd for C12H15N3O3S: C, 51.23; H, 5.37; N, 14.94; S, 11.40.
Found: C, 51.27; H, 5.31; N, 14.86; S, 11.34.
MS (APCI): m/z = 266.2 [M + H]+.
Anal. Calcd for C12H15N3O2S: C, 54.32; H, 5.70; N, 15.84; S, 12.09.
Found: C, 54.21; H, 5.65; N, 15.78; S, 12.14.
4-(2,2-Dioxido-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazin-4-yl)benzoic Acid (4j)
White solid; yield: 86%; mp 257–258 °C.
4-(4-Chlorophenyl)-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (4e)
White solid; yield: 81%; mp 210–211 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 7.59–7.45 (m, 4 H, ArH), 7.39
(d, J = 8.0 Hz, 1 H, NH), 5.91 (d, J = 8.0 Hz, 1 H, CH), 3.30–3.23
(m, 1 H, CH2), 3.11–3.03 (m, 1 H, CH2), 2.80–2.70 (m, 1 H, CH2),
2.68–2.59 (m, 1 H, CH2), 1.97–1.84 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.5, 134.5, 133.4, 130.3,
129.1, 70.1, 50.5, 33.7, 18.3.
MS (APCI): m/z = 286.0 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 13.13 (s, 1 H, COOH), 7.98 (d,
3
3J = 8.5 Hz, 2 H, ArH), 7.65 (d, J = 8.0 Hz, 2 H, ArH), 7.48 (d,
3J = 10.0 Hz, 1 H, NH), 6.00 (d, 3J = 10.0 Hz, 1 H, CH), 3.35–3.27
(m, 1 H, CH2), 3.19–3.09 (m, 1 H, CH2), 2.85–2.74 (m, 1 H, CH2),
2.73–2.61 (m, 1 H, CH2), 2.02–1.89 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.6, 167.3, 139.4, 132.1,
130.0, 128.6, 70.3, 50.7, 33.7, 18.4.
MS (APCI): m/z = 296.2 [M + H]+.
Anal. Calcd for C12H13N3O4S: C, 48.80; H, 4.44; N, 14.23; S, 10.86.
Found: C, 48.68; H, 4.38; N, 14.19; S, 10.82.
Anal. Calcd for C11H12ClN3O2S: C, 46.24; H, 4.23; Cl, 12.41; N,
14.71; S, 11.22. Found: C, 46.08; H, 4.27; Cl, 12.33; N, 14.60; S,
11.25.
4-(2,2-Dioxido-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazin-4-yl)phenol (4k)
White solid; yield: 64%; mp 202–203 °C (i-PrOH).
4-(4-Nitrophenyl)-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (4g)
White solid; yield: 94%; mp 258–259 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 8.25 (d, J = 8.8 Hz, 2 H, ArH),
7.75 (d, J = 8.4 Hz, 2 H, ArH), 7.60 (d, J = 8.8 Hz, 1 H, NH), 6.12
(d, J = 8.8 Hz, 1 H, CH), 3.43–3.32 (m, 1 H, CH2), 3.29–3.16 (m, 1
H, CH2), 2.87–2.63 (m, 2 H, CH2), 2.09–1.88 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.8, 148.3, 142.5, 129.6,
124.0, 69.7, 51.1, 33.0, 18.7.
MS (APCI): m/z = 297.0 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 9.73 (s, 1 H, OH), 7.38 (d,
3
3J = 8.5 Hz, 2 H, ArH), 7.19 (d, J = 11.0 Hz, 1 H, NH), 6.79 (d,
3J = 8.5 Hz, 2 H, ArH), 5.74 (d, 3J = 11.0 Hz, 1 H, CH), 3.25–3.15
(m, 1 H, CH2), 3.03–2.93 (m, 1 H, CH2), 2.78–2.68 (m, 1 H, CH2),
2.67–2.56 (m, 1 H, CH2), 1.97–1.79 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.3, 158.8, 129.9, 124.7,
115.8, 70.8, 50.1, 33.7, 18.1.
MS (APCI): m/z = 268.2 [M + H]+.
Anal. Calcd for C11H13N3O3S: C, 49.43; H, 4.90; N, 15.72; S, 12.00.
Found: C, 49.25; H, 4.91; N, 15.68; S, 11.89.
Anal. Calcd for C11H12N4O4S: C, 44.59; H, 4.08; N, 18.91; S, 10.82.
Found: C, 44.70; H, 4.02; N, 18.80; S, 10.73.
4-(4-Methylphenyl)-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (4n)
White solid; yield: 74%; mp 164–165 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 8.02 (d,3J = 10.5 Hz, 1 H, NH),
7.87 (d, 3J = 9.0 Hz, 2 H, ArH), 7.57 (d, 3J = 9.0 Hz, 2 H, ArH), 5.55
(d, 3J = 10.5 Hz, 1 H, CH), 3.25–3.15 (m, 1 H, CH2), 3.00–2.87 (m,
1 H, CH2), 2.80–2.74 (m, 1 H, CH2), 2.68–2.60 (m, 1 H, CH2), 2.45
(s, 3 H, CH3), 1.97–1.78 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 167.6, 138.9, 134.9, 131.3,
129.8, 128.3, 125.0, 70.5, 51.6, 32.9, 20.6, 19.4.
MS (APCI): m/z = 266.2 [M + H]+.
4-[4-(Dimethylamino)phenyl]-3,4,7,8-tetrahydro-6H-pyrro-
lo[2,1-c][1,2,4,6]thiatriazine 2,2-Dioxide (4h)
Yellow solid; yield: 59%; mp 195–196 °C (MeCN).
1H NMR (500 MHz, DMSO-d6): d = 7.36 (d, J = 6.8 Hz, 2 H, ArH),
7.12 (d, J = 9.2 Hz, 1 H, NH), 6.70 (d, J = 6.8 Hz, 2 H, ArH), 5.68
(d, J = 8.8 Hz, 1 H, CH), 3.21–3.14 (m, 1 H, CH2), 3.00–2.93 (m, 1
H, CH2), 2.90 [s, 6 H, N(CH3)2], 2.80–2.67 (m, 1 H, CH2), 2.66–
2.56 (m, 1 H, CH2), 1.93–1.75 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.6, 151.2, 129.3, 121.2,
111.9, 71.3, 50.1, 33.8, 21.4, 18.0.
MS (APCI): m/z = 295.2 [M + H]+.
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

2594
A. N. Khodachenko et al.
PAPER
Anal. Calcd for C12H15N3O2S: C, 54.32; H, 5.70; N, 15.84; S, 12.09.
Found: C, 54.39; H, 5.73; N, 15.76; S, 12.01.
1H NMR (500 MHz, DMSO-d6): d = 7.50 (d, J = 7.6 Hz, 1 H, NH),
7.39 (d, J = 6.4 Hz, 2 H, ArH), 6.94 (d, J = 6.8 Hz, 2 H, ArH), 5.74
(d, J = 7.6 Hz, 1 H, CH), 3.76 (s, 3 H, OCH3), 3.07–2.96 (m, 1 H,
CH2), 2.88–2.77 (m, 1 H, CH2), 2.57–2.47 (m, 1 H, CH2), 2.44–2.35
(m, 1 H, CH2), 1.75–1.62 (m, 4 H, CH2).
4-Phenyl-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4,6]thia-
triazine 2,2-Dioxide (5a)
White solid; yield: 77%; mp 178–179 °C (i-PrOH).
13C NMR (125 MHz, DMSO-d6): d = 163.3, 160.0, 129.6, 127.5,
1H NMR (500 MHz, DMSO-d6): d = 7.60 (d, J = 7.2 Hz, 1 H, NH),
7.47–7.33 (m, 5 H, ArH), 5.79 (d, J = 7.6 Hz, 1 H, CH), 3.11–3.02
(m, 1 H, CH2), 2.94–2.81 (m, 1 H, CH2), 2.60– 2.51 (m, 1 H, CH2),
2.45–2.36 (m, 1 H, CH2), 1.79–1.61 (m, 4 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 162.8, 134.7, 133.8, 130.0,
128.8, 73.4, 48.0, 32.6, 22.4, 19.1.
114.8, 74.1, 56.2, 47.7, 33.0, 22.8, 18.9.
MS (APCI): m/z = 196.0 [M + H]+.
Anal. Calcd for C13H17N3O3S: C, 52.86; H, 5.80; N, 14.23; S, 10.86.
Found: C, 52.71; H, 5.86; N, 14.31; S, 10.72.
4-Pyridin-3-yl-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6c)
MS (APCI): m/z = 266.0 [M + H]+.
White solid; yield: 71%; mp 173–174 °C (i-PrOH).
Anal. Calcd for C12H15N3O2S: C, 54.32; H, 5.70; N, 15.84; S, 12.09.
Found: C, 54.21; H, 5.68; N, 15.79; S, 12.02.
1H NMR (500 MHz, DMSO-d6): d = 8.58–8.45 (m, 2 H, ArH), 7.83
(d, 3J = 7.0 Hz, 1 H, ArH), 7.74 (d, 3J = 7.0 Hz, 1 H, CH), 7.43–7.33
(m, 1 H, ArH), 6.00 (d, 3J = 6.5 Hz, 1 H, NH), 3.71–3.58 (m, 1 H,
CH2), 3.22–3.10 (m, 1 H, CH2), 2.94–2.80 (m, 1 H, CH2), 2.42–2.31
(m, 1 H, CH2), 1.92–1.72 (m, 2 H, CH2), 1.66–1.42 (m, 4 H, CH2).
4-(4-Chlorophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (5b)
White solid; yield: 79%; mp 208–209 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 7.68 (d, J = 8.8 Hz, 1 H, NH),
7.50–7.39 (m, 4 H, ArH), 5.82 (d, J = 8.8 Hz, 1 H, CH), 3.17–3.07
(m, 1 H, CH2), 2.99–2.89 (m, 1 H, CH2), 2.62–2.51 (m, 1 H, CH2),
2.46–2.36 (m, 1 H, CH2), 1.84–1.58 (m, 4 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 163.1, 135.4, 129.3, 129.0,
128.2, 74.2, 47.9, 32.6, 22.7, 19.0.
13C NMR (125 MHz, DMSO-d6): d = 168.1, 149.8, 149.2, 135.7,
132.4, 123.6, 72.6, 51.1, 37.9, 28.9, 27.4, 24.4.
MS (APCI): m/z = 281.2 [M + H]+.
Anal. Calcd for C12H16N4O2S: C, 51.41; H, 5.75; N, 19.98; S, 11.44.
Found: C, 51.27; H, 5.69; N, 19.91; S, 11.42.
MS (APCI): m/z = 300.2 [M + H]+.
4-Phenyl-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thiatriazino[4,3-
a]azepine 2,2-Dioxide (6d)
White solid; yield: 77%; mp 174–175 °C (i-PrOH).
1H NMR (500 MHz, DMSO-d6): d = 7.64 (d, J = 6.8 Hz, 1 H, NH),
7.44–7.31 (m, 5 H, ArH), 5.84 (d, J = 7.2 Hz, 1 H, CH), 3.51–3.43
(m, 1 H, CH2), 3.19–3.10 (m, 1 H, CH2), 2.79–2.70 (m, 1 H, CH2),
2.46–2.37 (m, 1 H, CH2), 1.87–1.38 (m, 6 H, CH2).
Anal. Calcd for C12H14ClN3O2S: C, 48.08; H, 4.71; Cl, 11.83; N,
14.02; S, 10.70. Found: C, 47.98; H, 4.67; N, 14.10; S, 10.63.
4-(4-Nitrophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (5c)
White solid; yield: 91%; mp 229–230 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.22 (d, J = 6.8 Hz, 2 H, ArH),
7.54 (d, J = 6.0 Hz, 1 H, NH), 7.63 (d, J = 6.8 Hz, 2 H, ArH), 5.98
(d, J = 6.4 Hz, 1 H, CH), 3.27–3.20 (m, 1 H, CH2), 3.10–3.03 (m, 1
H, CH2), 2.65–2.56 (m, 1 H, CH2), 2.47–2.39 (m, 1 H, CH2), 1.91–
1.63 (m, 4 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 162.4, 148.0, 143.6, 129.3,
123.8, 73.0, 48.6, 32.5, 22.3, 19.0.
13C NMR (125 MHz, DMSO-d6): d = 168.5, 135.9, 129.1, 128.7,
128.2, 74.5, 50.4, 38.0, 28.9, 27.0, 24.4.
MS (APCI): m/z = 280.0 [M + H]+.
Anal. Calcd for C13H17N3O2S: C, 55.89; H, 6.13; N, 15.04; S, 11.48.
Found: C, 55.80; H, 6.20; N, 14.89; S, 11.49.
4-(4-Chlorophenyl)-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6e)
MS (APCI): m/z = 311.0 [M + H]+.
White solid; yield: 75%; mp 183–184 °C (MeCN).
Anal. Calcd for C12H14N4O4S: C, 46.44; H, 4.55; N, 18.05; S, 10.33.
Found: C, 46.50; H, 4.52; N, 17.96; S, 10.41.
1H NMR (500 MHz, DMSO-d6): d = 7.73 (d, J = 8.0 Hz, 1 H, NH),
7.48–7.33 (m, 4 H, ArH), 5.89 (d, J = 8.0 Hz, 1 H, CH), 3.65–3.48
(m, 1 H, CH2), 3.20–3.06 (m, 1 H, CH2), 2.87–2.73 (m, 1 H, CH2),
2.45–2.29 (m, 1 H, CH2), 1.90–1.36 (m, 6 H, CH2).
4-[4-(Dimethylamino)phenyl]-3,4,6,7,8,9-hexahydropyrido[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (5d)
Yellow solid; yield: 51%; mp 223–224 °C (MeCN).
13C NMR (125 MHz, DMSO-d6): d = 168.0, 135.8, 133.5, 130.0,
1H NMR (500 MHz, DMSO-d6): d = 7.74 (d, J = 7.2 Hz, 1 H, NH),
7.29 (d, J = 6.8 Hz, 2 H, ArH), 6.69 (d, J = 6.8 Hz, 2 H, ArH), 5.66
(d, J = 8.4 Hz, 1 H, CH), 3.15–3.05 (m, 1 H, CH2), 2.90 [s, 6 H,
N(CH3)2], 2.83–2.74 (m, 1 H, CH2), 2.60–2.51 (m, 1 H, CH2), 2.43–
2.35 (m, 1 H, CH2), 1.70–1.61 (m, 4 H, CH2).
128.6, 73.7, 50.9, 37.9, 28.7, 27.4, 24.1.
MS (APCI): m/z = 314.0 [M + H]+.
Anal. Calcd for C13H16ClN3O2S: C, 49.76; H, 5.14; N, 13.39; S,
10.22. Found: C, 49.58; H, 5.11; N, 13.42; S, 10.16.
13C NMR (125 MHz, DMSO-d6): d = 163.1, 151.5, 133.7, 129.5,
4-(4-Nitrophenyl)-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6f)
White solid; yield: 90%; mp 239–240 °C.
112.1, 74.0, 46.9, 33.8, 23.3, 19.0.
MS (APCI): m/z = 309.0 [M + H]+.
Anal. Calcd for C14H20N4O2S: C, 54.52; H, 6.54; N, 18.17; S, 10.40.
Found: C, 54.32; H, 6.55; N, 18.20; S, 10.31.
1H NMR (500 MHz, DMSO-d6): d = 8.20 (d, J = 8.8 Hz, 2 H, ArH),
7.93 (d, J = 7.2 Hz, 1 H, NH), 7.60 (d, J = 8.8 Hz, 2 H, ArH), 6.10
(d, J = 7.2 Hz, 1 H, CH), 3.76–3.67 (m, 1 H, CH2), 3.20–3.10 (m, 1
H, CH2), 2.95–2.85 (m, 1 H, CH2), 2.41–2.30 (m, 1 H, CH2), 1.96–
1.40 (m, 6 H, CH2).
4-(4-Methoxyphenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (5e)
White solid; yield: 59%; mp 162–163 °C (i-PrOH).
13C NMR (125 MHz, DMSO-d6): d = 168.0, 147.7, 144.6, 129.3,
123.5, 73.8, 51.1, 37.7, 29.0, 27.4, 24.1.
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

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Facile Synthesis of Annulated Thiatriazine Dioxides
2595
MS (APCI): m/z = 325.0 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 7.74 (d, J = 7.2 Hz, 1 H, NH),
7.50–7.33 (m, 5 H, ArH), 5.85 (d, J = 7.2 Hz, 1 H, CH), 3.90–3.79
(m, 1 H, CH2), 2.99–2.87 (m, 1 H, CH2), 2.85–2.70 (m, 1 H, CH2),
2.32–2.21 (m, 1 H, CH2), 1.97–1.21 (m, 8 H, CH2).
Anal. Calcd for C13H16N4O4S: C, 48.14; H, 4.97; N, 17.27; S, 9.89.
Found: C, 48.2; H, 5.01; N, 17.21; S, 9.84.
4-[4-(Dimethylamino)phenyl]-3,4,7,8,9,10-hexahydro-6H-
[1,2,4,6]thiatriazino[4,3-a]azepine 2,2-Dioxide (6g)
Yellow solid; yield: 49%; mp 200–201 °C (MeCN).
1H NMR (500 MHz, CDCl3): d = 8.81 (s, 1 H, CH), 8.43 (br t, 1 H,
NH), 7.77 (d, J = 6.8 Hz, 2 H, ArH), 6.67 (d, J = 6.8 Hz, 2 H, ArH),
3.45–3.34 (m, 2 H, CH2), 3.09 [s, 6 H, N(CH3)2], 2.64–2.51 (m, 2 H,
CH2), 1.84–1.67 (m, 6 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.1, 135.8, 129.3, 128.9,
128.1, 72.2, 46.9, 35.2, 30.0, 28.7, 25.6, 23.6.
MS (APCI): m/z = 294.0 [M + H]+.
Anal. Calcd for C14H19N3O2S: C, 57.31; H, 6.53; N, 14.32; S, 10.93.
Found: C, 57.18; H, 6.48; N, 14.41; S, 10.86.
4-(4-Chlorophenyl)-3,4,6,7,8,9,10,11-octahydro[1,2,4,6]thiatri-
azino[4,3-a]azocine 2,2-Dioxide (7b)
White solid; yield: 80%; mp 205–206 °C (EtOH).
13C NMR (125 MHz, DMSO-d6): d = 166.9, 151.1, 133.2, 129.5,
112.0, 74.8, 43.9, 38.3, 30.0, 29.1, 24.2.
MS (APCI): m/z = 323.2 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 7.85 (d, J = 6.4 Hz, 1 H, NH),
7.43 (s, 4 H, ArH), 5.89 (d, J = 6.4 Hz, 1 H, CH), 3.88 (t, J = 10.8
Hz, 1 H, CH2), 2.94 (d, J = 12.0 Hz, 1 H, CH2), 2.82 (t, J = 9.6 Hz,
1 H, CH2), 2.30–2.19 (m, 1 H, CH2), 1.94–1.25 (m, 8 H, CH2).
Anal. Calcd for C15H22N4O2S: C, 55.88; H, 6.88; N, 17.38; S, 9.95.
Found: C, 55.71; H, 6.82; N, 17.26; S, 9.90.
4-(4-Methoxyphenyl)-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6h)
13C NMR (125 MHz, DMSO-d6): d = 167.5, 135.2, 133.7, 129.9,
128.7, 71.3, 47.5, 35.0, 29.9, 29.0, 25.4, 24.3.
White solid; yield: 67%; mp 162–163 °C (i-PrOH).
MS (APCI): m/z = 328.0 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 7.53 (d, J = 7.6 Hz, 1 H, NH),
7.36 (d, J = 6.4 Hz, 2 H, ArH), 6.92 (d, J = 6.8 Hz, 2 H, ArH), 5.78
(d, J = 7.2 Hz, 1 H, CH), 3.75 (s, 3 H, OCH3), 3.42–3.32 (m, 1 H,
CH2), 3.20–3.09 (m, 1 H, CH2), 2.74–2.62 (m, 1 H, CH2), 2.50–2.40
(m, 1 H, CH2), 1.81–1.33 (m, 6 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.0, 160.0, 129.8, 127.4,
114.1, 74.3, 55.7, 49.9, 38.0, 28.8, 27.3, 24.7.
Anal. Calcd for C14H18ClN3O2S: C, 51.29; H, 5.53; Cl, 10.81; N,
12.82; S, 9.78. Found: C, 51.16; H, 5.49; Cl, 10.73; N, 12.73; S,
9.71.
4-(4-Nitrophenyl)-3,4,6,7,8,9,10,11-octahydro[1,2,4,6]thia-
triazino[4,3-a]azocine 2,2-Dioxide (7c)
White solid; yield: 89%; mp 189–190 °C.
MS (APCI): m/z = 310.2 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 8.21 (d, J = 6.8 Hz, 2 H, ArH),
8.08 (d, J = 6.0 Hz, 1 H, NH), 7.62 (d, J = 6.8 Hz, 2 H, ArH), 6.08
(d, J = 6.0 Hz, 1 H, CH), 3.98 (t, J = 10.8 Hz, 1 H, CH2), 3.00 (d,
J = 12.4 Hz, 1 H, CH2), 2.90 (t, J = 10.0 Hz, 1 H, CH2), 2.24 (d,
J = 10.0 Hz, 1 H, CH2), 1.96–1.34 (m, 8 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 167.1, 148.0, 144.2, 128.8,
123.7, 70.8, 48.2, 34.9, 29.9, 29.1, 25.5, 24.5.
Anal. Calcd for C14H19N3O3S: C, 54.35; H, 6.19; N, 13.58; S, 10.36.
Found: C, 54.21; H, 6.11; N, 13.53; S, 10.32.
4-(2-Methylphenyl)-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6i)
White solid; yield: 70%; mp 192–193 °C (MeCN).
1H NMR (500 MHz, DMSO-d6): d = 7.62 (d, 3J = 8.0 Hz, 1 H, NH),
7.28–7.13 (m, 4 H, ArH), 5.88 (d, 3J = 8.0 Hz, 1 H, CH), 3.57–3.47
(m, 1 H, CH2), 3.16–3.06 (m, 1 H, CH2), 2.92–2.80 (m, 1 H, CH2),
2.45–2.38 (m, 1 H, CH2), 2.36 (s, 3 H, CH3), 1.94–1.75 (m, 2 H,
CH2), 1.68–1.45 (m, 4 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.1, 136.8, 133.7, 131.0,
128.8, 127.4, 125.8, 72.3, 50.94, 38.0, 29.0, 27.5, 24.5, 19.1.
MS (APCI): m/z = 339.2 [M + H]+.
Anal. Calcd for C14H18N4O4S: C, 49.69; H, 5.36; N, 16.56; S, 9.48.
Found: C, 49.51; H, 5.32; N, 16.50; S, 9.35.
4-[4-(Dimethylamino)phenyl]-3,4,6,7,8,9,10,11-octahy-
dro[1,2,4,6]thiatriazino[4,3-a]azocine 2,2-Dioxide (7d)
Yellow solid; yield: 61%; mp 214–215 °C (MeCN).
MS (APCI): m/z = 294.2 [M + H]+.
1H NMR (500 MHz, CDCl3): d = 8.82 (s, 1 H, CH), 8.20 (br t, 1 H,
NH), 7.75 (d, J = 6.8 Hz, 2 H, ArH), 6.67 (d, J = 6.8 Hz, 2 H, ArH),
3.54–3.43 (m, 2 H, CH2), 3.09 [s, 6 H, N(CH3)2], 2.50 (t, J = 5.2 Hz,
2 H, CH2), 1.89–1.58 (m, 8 H, CH2).
Anal. Calcd for C14H19N3O2S: C, 57.31; H, 6.53; N, 14.32; S, 10.93.
Found: C, 57.17; H, 6.46; N, 14.25; S, 10.88.
4-(4-Fluorophenyl)-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6j)
13C NMR (125 MHz, DMSO-d6): d = 168.6, 133.0, 129.2, 112.5,
112.0, 72.5, 42.3, 31.9, 29.2, 25.5, 24.4.
White solid; yield: 71%; mp 170–171 °C (EtOH).
MS (APCI): m/z = 337.0 [M + H]+.
3
1H NMR (500 MHz, DMSO-d6): d = 7.67 (d, J = 8.0 Hz, 1 H),
Anal. Calcd for C16H24N4O2S: C, 57.12; H, 7.19; N, 16.65; S, 9.53.
Found: C, 57.1; H, 7.15; N, 16.72; S, 9.48.
7.48–7.39 (m, 2 H), 7.19 (t, 3J = 9.0 Hz, 2 H), 5.88 (d, 3J = 8.5 Hz,
1 H), 3.56–3.44 (m, 1 H), 3.20–3.08 (m, 1 H), 2.82–2.71 (m, 1 H),
2.44–2.36 (m, 1 H), 1.86–1.66 (m, 2 H), 1.63–1.41 (m, 4 H).
4-(4-Methoxyphenyl)-3,4,6,7,8,9,10,11-octahydro[1,2,4,6]thia-
triazino[4,3-a]azocine 2,2-Dioxide (7e)
White solid; yield: 68%; mp 163–164 °C (MeCN).
13C NMR (125 MHz, DMSO-d6): d = 168.1, 161.6, 132.6, 130.4,
115.5, 73.8, 50.6, 28.9, 27.3, 24.4.
MS (ESI): m/z = 298.2 [M + H]+.
1H NMR (500 MHz, DMSO-d6): d = 7.62 (d, J = 7.6 Hz, 1 H, NH),
7.43 (d, J = 6.8 Hz, 2 H, ArH), 6.94 (d, J = 6.8 Hz, 2 H, ArH), 5.79
(d, J = 8.0 Hz, 1 H, CH), 3.76 (s, 3 H, OCH3), 2.92 (d, J = 11.2 Hz,
1 H, CH2), 2.74 (t, J = 8.8 Hz, 1 H, CH2), 2.33–2.21 (m, 1 H, CH2),
1.95–1.81 (m, 1 H, CH2), 1.79–1.14 (m, 8 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.0, 159.8, 129.2, 127.5,
114.3, 72.2, 55.8, 35.3, 30.4, 29.1, 26.0, 24.9.
Anal. Calcd for C13H16FN3O2S: C, 52.51; H, 5.42; N, 14.13; S,
10.78. Found: C, 52.37; H, 5.36; N, 14.08; S, 10.69.
4-Phenyl-3,4,6,7,8,9,10,11-octahydro[1,2,4,6]thiatriazino[4,3-
a]azocine 2,2-Dioxide (7a)
White solid; yield: 77%; mp 154–155 °C (EtOH).
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

2596
A. N. Khodachenko et al.
PAPER
MS (APCI): m/z = 324.0 [M + H]+.
Anal. Calcd for C7H13N3O2S: C, 41.36; H, 6.45; N, 20.67; S, 15.78.
Found: C, 41.17; H, 6.38; N, 20.60; S, 15.71.
Anal. Calcd for C15H21N3O3S: C, 55.71; H, 6.54; N, 12.99; S, 9.91.
Found: C, 55.53; H, 6.51; N, 12.87; S, 9.90.
4,4-Diethyl-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-c][1,2,4,6]thia-
triazine 2,2-Dioxide (4m)
White solid; yield: 67%; mp 143–144 °C.
1H NMR (500 MHz, DMSO-d6): d = 6.84 (s, 1 H, NH), 3.58–3.48
(m, 2 H, CH2), 2.66–2.56 (m, 2 H, CH2), 2.01–1.74 (m, 6 H, CH3),
0.92–0.82 (m, 6 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 166.8, 77.2, 48.5, 33.6, 28.5,
18.2, 7.8.
MS (APCI): m/z = 232.0 [M + H]+.
4-(2,2-Dioxido-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazin-4-yl)benzaldehyde (4f)
Compound 2a (1.5g, 9.2 mmol) was added in 0.1-g portions over 2
h to a stirred and refluxed soln of terephthalaldehyde (6.2 g, 46
mmol). The suspension was stirred under reflux for 2 h. The pre-
cipitate was filtered off and recrystallized (AcOH) to give a white
solid; yield: 79%; mp 212–213 °C.
1H NMR (500 MHz, DMSO-d6): d = 10.04 (s, 1 H, COH), 9.95 (d,
3
3J = 7.5 Hz, 2 H, ArH), 7.78 (d, J = 7.5 Hz, 2 H, ArH), 7.30 (d,
3J = 10.5 Hz, 1 H, NH), 5.96 (d, 3J = 11.0 Hz, 1 H, CH), 3.42–3.27
(m, 1 H, CH2), 3.20–3.07 (m, 1 H, CH2), 2.89–2.75 (m, 1 H, CH2),
2.75–2.63 (m, 1 H, CH2), 2.11–1.92 (m, 2 H, CH2).
Anal. Calcd for C9H17N3O2S: C, 46.73; H, 7.41; N, 18.17; S, 13.86.
Found: C, 46.60; H, 7.45; N, 18.13; S, 13.75.
Compounds 8a and 8b; General Procedure
1H NMR (500 MHz, CDCl3): d = 10.11 (s, 1 H, COH), 8.04 (d,
3J = 7.5 Hz, 2 H, ArH), 7.72 (d, 3J = 7.5 Hz, 2 H, ArH), 6.01 (br d,
1 H, NH), 5.15 (br d, 1 H, CH), 3.35–3.20 (m, 2 H, CH2), 3.04–2.91
(m, 1 H, CH2), 2.86–2.73 (m, 1 H, CH2), 2.15–2.00 (m, 2 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 193.3, 168.7, 141.2, 137.1,
130.1, 129.1, 70.3, 50.8, 33.7, 18.5.
MeI (for 8a) or bromoacetophenone (for 8b) (4.5 mmol) was added
to a mixture of KOH (4.5 mmol) and a soln of the corresponding
thiatriazine dioxide (3.77 mmol) in DMF (20 mL). The resulting
mixture was stirred at 40 °C for 6 h. H2O (100 mL) was added with
stirring and the mixture was allowed to stand for several hours. The
precipitate was filtered off, washed with H2O (2 × 20 mL) and dried
in vacuo.
MS (APCI): m/z = 280.2 [M + H]+.
Anal. Calcd for C12H13N3O3S: C, 51.60; H, 4.69; N, 15.04; S, 11.48.
Found: C, 51.48; H, 4.60; N, 14.98; S, 11.42.
3-Methyl-4-(4-methylphenyl)-3,4,7,8-tetrahydro-6H-pyrro-
lo[2,1-c][1,2,4,6]thiatriazine 2,2-Dioxide (8a)
White solid; yield: 78%; mp 155–156 °C (EtOH).
4-(Chloromethyl)-3,4,7,8,9,10-hexahydro-6H-[1,2,4,6]thia-
triazino[4,3-a]azepine 2,2-Dioxide (6b)
3
1H NMR (500 MHz, DMSO-d6): d = 7.30 (d, J = 8.0 Hz, 2 H,
ArH), 7.24 (d, 3J = 8.0 Hz, 2 H, ArH), 5.83 (s, 1 H, CH), 3.43–3.33
(m, 1 H, CH2), 3.30–3.20 (m, 1 H, CH2), 2.85–2.75 (m, 1 H, CH2),
2.79–2.69 (m, 1 H, CH2), 2.57 (s, 3 H, CH3), 2.34 (s, 3 H, CH3),
2.07–1.96 (m, 2 H, CH2).
The mixture of chloroacetaldehyde (5.4 mmol) and a soln of 2c (1
g, 5.2 mmol) in 0.1 M HCl (20 mL) was stirred at r.t. for 10 h. The
cooled mixture (ice bath) was neutralized with Et3N (0.35 mL) and
extracted with CH2Cl2 (2 × 30 mL). The organic layer was washed
with H2O (2 × 30 mL) and dried (anhyd Na2SO4). The solvent was
removed under reduced pressure and the white solid obtained was
dried in vacuo; yield: 0.76 g (58%); mp 182–183 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.65 (d, 3J = 6.5 Hz, 1 H, NH),
4.85–4.70 (m, 1 H, CH2), 4.07 (dd, 2J = 12.0 Hz, 3J = 10.5 Hz, 1 H,
CH), 3.87–3.73 (m, 1 H, CH2), 3.69–3.49 (m, 2 H, CH2), 2.64–2.53
(m, 1 H, CH2), 2.44–2.30 (m, 1 H, CH2), 1.81–1.44 (m, 6 H, CH2).
13C NMR (125 MHz, DMSO-d6): d = 168.1, 139.2, 131.8, 129.6,
128.4, 76.7, 51.7, 35.4, 33.5, 21.3, 18.1.
MS (APCI): m/z = 280.0 [M + H]+.
Anal. Calcd for C13H17N3O2S: C, 55.89; H, 6.13; N, 15.04; S, 11.48.
Found: C, 55.70; H, 6.05; N, 15.11; S, 11.47.
2-[4-(4-Fluorophenyl)-2,2-dioxido-7,8,9,10-tetrahydro-6H-
[1,2,4,6]thiatriazino[4,3-a]azepin-3(4H)-yl]-1-phenylethanone
(8b)
13C NMR (125 MHz, DMSO-d6): d = 167.0, 73.3, 51.2, 41.5, 37.8,
28.7, 27.9, 24.2.
White solid; yield: 81%; mp 194–195 °C (AcOH).
MS (APCI): m/z = 252.2 [M + H]+.
3
1H NMR (500 MHz, DMSO-d6): d = 8.09 (d, J = 7.5 Hz, 2 H,
Anal. Calcd for C8H14ClN3O2S: C, 38.17; H, 5.61; Cl, 14.08; N,
16.69; S, 12.74. Found: C, 38.01; H, 5.57; Cl, 14.03; N, 16.67; S,
12.81.
ArH), 7.80–7.48 (m, 5 H, ArH), 7.31–7.13 (m, 2 H, ArH), 6.16 (s,
1 H, CH), 5.02 (d, 2J = 18.5 Hz, 1 H, CH2), 4.75 (d, 2J = 18.5 Hz, 1
H, CH2), 3.90–3.72 (m, 1 H, CH2), 3.23–3.08 (m, 1 H, CH2), 3.07–
2.91 (m, 1 H, CH2), 2.47–2.34 (m, 1 H, CH2), 2.04–1.50 (m, 6 H,
CH2).
Compounds 4l, 4m; General Procedure
TsOH (10 mg) was added to a soln of sulfamoylamidine 2 (6.1
mmol) in the corresponding ketone (30 mL) and the mixture was
stirred at reflux for 24 h. The volume of the mixture was reduced to
10 mL, the precipitate was filtered off and washed with correspond-
ing ketone (2 × 3 mL) and dried in vacuo.
13C NMR (125 MHz, DMSO-d6): d = 194.6, 168.0, 163.4, 161.5,
135.4, 134.2, 133.5, 129.3, 128.5, 115.1, 79.5, 57.4, 52.5, 37.9,
29.3, 27.3, 24.5.
MS (APCI): m/z = 417.2 [M + H]+.
Anal. Calcd for C21H22FN3O3S: C, 60.71; H, 5.34; N, 10.11; S, 7.72.
Found: C, 60.53; H, 5.38; N, 10.08; S, 7.68.
4,4-Dimethyl-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-c][1,2,4,6]thia-
triazine 2,2-Dioxide (4l)
White solid; yield: 84%; mp 227–228 °C.
3-Benzoyl-4-phenyl-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (8c)
1H NMR (500 MHz, DMSO-d6): d = 7.02 (s, 1 H, NH), 3.60–3.51
(m, 2 H, CH2), 2.64–2.53 (m, 2 H, CH2), 1.94–1.84 (m, 2 H, CH2),
1.48 (s, 6 H, CH3).
13C NMR (125 MHz, DMSO-d6): d = 166.2, 71.7, 48.1, 33.7, 25.9,
17.7.
BzCl (0.48 mL, 4.15 mmol) was added dropwise to a suspension of
4c (1 g, 3.77 mmol) in anhyd pyridine (20 mL) at 0 °C with stirring.
The mixture was warmed to r.t. and stirred for a further 6 h. H2O
(100mL) was added and the mixture was left to stand for 3 h. The
precipitated formed was filtered off, washed with H2O (2 × 5 mL)
and recrystallized (AcOH) to give 8c as a white solid; yield: 1 g
(71%); mp 206–207 °C.
MS (APCI): m/z = 204.0 [M + H]+.
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

PAPER
Facile Synthesis of Annulated Thiatriazine Dioxides
2597
3
1H NMR (500 MHz, DMSO-d6): d = 7.72 (d, J = 7.0 Hz, 2 H,
ArH), 7.68–7.58 (m, 1 H, ArH), 7.57–7.33 (m, 7 H, ArH), 7.21 (s,
1 H, CH), 3.91–3.79 (m, 1 H, CH2), 3.76–3.66 (m, 1 H, CH2), 3.06–
2.93 (m, 1 H, CH2), 2.92–2.81 (m, 1 H, CH2), 2.35–2.12 (m, 2 H,
CH2).
13C NMR (125 MHz, DMSO-d6): d = 169.0, 167.8, 135.5, 129.5,
129.0, 127.3, 68.1, 52.4, 33.3, 25.6, 19.2.
MS (APCI): m/z = 294.2 [M + H]+.
Anal. Calcd for C13H15N3O3S: C, 53.23; H, 5.15; N, 14.32; S, 10.93.
Found: C, 53.08; H, 5.11; N, 14.28; S, 10.97.
13C NMR (125 MHz, DMSO-d6): d = 171.1, 168.1, 135.7, 135.2,
133.3, 129.5, 129.3, 129.1, 128.7, 126.9, 69.6, 52.6, 33.3, 19.3.
X-ray diffraction study. All crystallographic experiments were car-
ried out on the «Xcalibur-3» diffractometer (graphite monochro-
mated MoKa radiation, CCD detector, w-scanning) at 273 K. The
structures were solved by direct method using SHELXTL pack-
age.14 Structures were refined within anisotropic approximation for
non-hydrogen atoms. The restrictions on the bond lengths (Csp3–
Csp3 1.54 Å, Csp3–N 1.49 Å, Csp3–NH 1.46 Å, CAr–CAr 1.38 Å) in
the disordered fragment were applied in the refinement of structures
5a and 5b. The position of the hydrogen atoms were located from
the electron density map and were calculated geometrically for the
disordered fragments in 5a and 5b and were refined by ‘riding’
model with Uiso = 1.2 Ueq of non-hydrogen atom bonded with given
hydrogen atom in 5a and 5b. The position of the hydrogen atoms in
other structures were located from the electron density map and re-
fined in isotropic approximation. The crystallographic data and ex-
perimental parameters are listed in Table 4.
MS (APCI): m/z = 356.2 [M + H]+.
Anal. Calcd for C18H17N3O3S: C, 60.83; H, 4.82; N, 11.82; S, 9.02.
Found: C, 60.72; H, 4.80; N, 11.85; S, 8.98.
3-Acetyl-4-phenyl-3,4,7,8-tetrahydro-6H-pyrrolo[2,1-
c][1,2,4,6]thiatriazine 2,2-Dioxide (8d)
Anhyd Et3N (0.56 mL, 4 mmol) was added to a soln of 4c (1 g, 3.77
mmol) in Ac2O (10 mL). The mixture was stirred at 80 °C for 4 h.
Solvent was removed under reduced pressure and the residue was
recrystallized (i-PrOH) to give 8d as a brown solid; yield: 1 g
(77%); mp 145–146 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.46–7.32 (m, 5 H, ArH), 7.29
(s, 1 H, CH), 3.84–3.73 (m, 1 H, CH2), 3.54–3.43 (m, 1 H, CH2),
3.02–2.91 (m, 1 H, CH2), 2.88–2.78 (m, 1 H, CH2), 2.43 (s, 3 H,
CH2), 2.22–2.05 (m, 2 H, CH2).
Table 4 Crystallographic Data for Compounds 2a–d, 4n, 5a,b, 6k
Parameter
a (Å)
2a
2b
2c
10.6994(2) 7.7446(2)
5.4982(1) 7.6854(2)
14.8152(3) 8.4094(3)
2d
4n
5a
5b
13.9509(4) 10.451(1)
5.9620(2) 8.5089(7)
16.3475(5) 16.829(1)
6k
5.1160(1)
10.1523(2)
13.7515(4)
5.1992(9)
14.811(2)
10.288(1)
8.9699(4)
7.9729(4)
9.5150(4)
9.8652(5)
b (Å)
c (Å)
13.0615(5) 14.7804(7)
72.166(4)
a (°)
b (°)
98.286(2)
97.45(1)
92.039(2)
105.893(3)
94.025(4)
89.852(4)
74.490(4)
1267.9(1)
560
92.496(3)
108.020(8)
g (°)
V (Å3)
706.79(3)
344
785.6(2)
376
870.99(3)
408
481.40(2)
220
931.80(7)
432
1358.42(7) 1423.2(2)
624 624
monoclinic monoclinic
F(000)
crystal system
space group
Z
monoclinic
P21/c
4
monoclinic
P21/c
4
monoclinic monoclinic
monoclinic triclinic
P21/c
4
P21
P21/c
4
P-1
P21/c
4
P21/n
4
2
4
m (mm–1)
Dcalcd (g/cm3)
2 qmax (°)
measured refln
independent refln
Rint
0.400
1.534
50
0.367
1.498
50
0.337
1.459
60
0.310
1.416
60
0.320
1.449
60
0.253
1.390
50
0.436
1.466
60
0.233
1.369
50
4110
4789
2568
0.017
2368
8272
2531
0.016
2041
17049
4400
0.027
2368
8905
2712
0.029
1783
10124
4433
0.020
2848
14899
3962
0.024
2471
8158
2490
0.015
2065
1231
0.018
1009
reflections with
F > 4s(F)
parameters
127
100
161
178
171
360
194
257
R1
0.027
0.071
0.964
730855
0.071
0.191
1.069
730856
0.028
0.080
0.953
730857
0.022
0.052
0.989
730858
0.041
0.109
0.898
730862
0.047
0.128
0.970
730859
0.041
0.107
0.886
730860
0.029
0.082
1.085
730861
wR2
S
CCDC number
Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York

2598
A. N. Khodachenko et al.
PAPER
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Acknowledgment
The authors acknowledge Mr. V. V. Polovinko (Enamine Ltd.) for
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Synthesis 2010, No. 15, 2588–2598 © Thieme Stuttgart · New York