Reactions of 4,5-dihydro-1,4-benzothiazepin-3(2H)-one 1,1-dioxide and 1,5-dihydro-4,1-benzothiazepin-2(3H)-one 4,4-dioxide derivatives with vilsmeier reagent and DMFDMA

Article abstract of DOI:10.1002/jhet.1906

The regioselectivity of the interaction between isomeric 4,5-dihydro-1,4-benzothiazepin-3(2H)-one 1,1-dioxide and 1,5-dihydro-4,1- benzothiazepin-2(3H)-one 4,4-dioxide derivatives with the Vilsmeier reagent and DMFDMA (N,N-dimethylformamide dimethylacetal

Full text of DOI:10.1002/jhet.1906

Month 2014 Reactions of 4,5-Dihydro-1,4-Benzothiazepin-3(2H)-one 1,1-Dioxide and
1,5-Dihydro-4,1-Benzothiazepin-2(3H)-one 4,4-Dioxide Derivatives with
Vilsmeier Reagent and DMFDMA
a
a
a
b
b,c
*
Taras M. Tarasiuk, Tatyana A. Volovnenko, Kirill S. Popov, Volodymyr V. Medviediev, Oleg V. Shishkin, and
Yulian M. Volovenkoa
aDepartment of Organic Chemistry, Taras Shevchenko Kyiv National University, Kyiv 01033, Ukraine
bSSI “Institute for Single Crystals” National Academy of Science of Ukraine, 60 Lenina ave., Kharkiv 61001, Ukraine
cDepartment of Inorganic Chemistry, V. N. Karazin Kharkiv National University, 4 Svobody sq, Kharkiv 61122, Ukraine
*
E-mail: taras88ximik@ukr.net
Received September 4, 2012
DOI 10.1002/jhet.1906
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
The regioselectivity of the interaction between isomeric 4,5-dihydro-1,4-benzothiazepin-3(2H)-one
1,1-dioxide and 1,5-dihydro-4,1-benzothiazepin-2(3H)-one 4,4-dioxide derivatives with the Vilsmeier
reagent and DMFDMA (N,N-dimethylformamide dimethylacetal) has been investigated. The structures
1
of synthesized compounds are confirmed by H, 13C NMR, elemental analysis, and X-ray data.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
A review of the literature shows that 2,3-dihydro-
1,5-benzothiazepin-4(5H)-ones I and 3,4-dihydro-1,
4-benzothiazepin-5(2H)-ones II are well studied, while
isomeric 4,5-dihydro-1,4-benzothiazepin-3(2H)-ones III
and 1,5-dihydro-4,1-benzothiazepin-2(3H)-ones IV have
been less well studied.
We proposed earlier two alternative methods for the
synthesis of 4,5-dihydro-1,4-benzothiazepin-3(2H)-one deriva-
tives [18,19]. The synthesis of 1,5-dihydro-4,1-benzothiazepin-
2(3H)-one has been described in 1965 [20]. Substituted
benzothiazepinones have attracted the attention of chemists
because of their reactivity. The carboxamide group is one
of the functional groups possessing synthetic potential, and
widely-used. Electron withdrawing groups are known to
cause high activity of adjacent methylene groups in reactions
with electrophilic agents. Introduction of a carbonyl group or
its analogues opens new possibilities for the synthesis and
modifications of different heterocyclic systems.
In recent years, a number of compounds that show high
levels of biological activity were found among benzothiazepine
derivatives. Both 1,5- and 1,4-benzothiazepines have
generated great interest [1–3]. For example, diltiazem [4]
(cis-(+)-[2-(2-dimethylaminoethyl)-5-(4-methoxyphenyl)-3-
oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9,11-trien-4-yl]
ethanoate) – a well-known drug (calcium channel blocker)
used in the treatment of hypertension, angina pectoris,
and some types of arrhythmia. This compound has a
1,5-benzothiazepine scaffold I (Fig. 1). Some 2,3-dihydro-
1,5-benzothiazepin-4(5H)-one I derivatives are used in the
treatment of cardiovascular diseases [5], including bradykinin
agonists [6], growth hormone secretagogues (GHSs) [7], and
Ca antagonists [8]. N-alkyl-3,4-dihydro-1,4-benzothiazepin-5
(2H)-one II derivatives are known to show properties of
Ca antagonists [9] and antitumoral agents [10]. Substituted
4,5-dihydro-1,4-benzothiazepin-3(2H)-ones III can be
used in the treatment of seizures, neurological disorders
such as epilepsy [11,12]and as neuroprotective agents to
protect against conditions such as stroke [12]. Among
1,5-dihydro-4,1-benzothiazepin-2(3H)-ones IV, there are
squalene synthase inhibitors [13], antidepressants [14,15],
and anticonvulsants [16,17].
The Vilsmeier reagent is the most commonly used formy-
lating agent. Several reviews have been written [21–23] during
decades of existence of the Vilsmeier reaction. The interest to
usage of DMFDMA has increased in the last years [24].
Comparison of Vilsmeier reagent and DMFDMA has not been
reported. The aim of this work was to compare interaction of
the above mentioned formylating agents with some sulfones.
© 2013 HeteroCorporation

T. M. Tarasiuk, T. A. Volovnenko, K. S. Popov, V. V. Medviediev, O. V. Shishkin, and Y. M. Volovenko Vol 000
Figure 1. Some of possible isomers of benzothiazepinones.
RESULTS AND DISCUSSION
There are two activated methylene group, which can be
attacked by electrophiles, in both isomeric 4,5-dihydro-
1,4-benzothiazepin-3(2H)-one 1,1-dioxides V and 1,
5-dihydro-4,1-benzothiazepin-2(3H)-one 4,4-dioxides VI
(Fig. 2). We predicted that different chemical environment
of these groups causes the CH2 between SO2 and CO to be
more reactive to electrophilic agents. In addition to that, each
individual case has some specific peculiarities, caused by
chemical nature of substrates and electrophiles.
We have developed two methods for the synthesis
4-methyl-7-nitro-4,5-dihydro-1,4-benzothiazepin-3(2H)-one.
Oxidation of this compound leads to corresponding
sulfone 1 [19]. We expected to obtain dimethylaminomethylene
derivative using DMFDMA and chloroaldehyde as the
Vilsmeier reagent. But treatment of sulfone 1 with Vilsmeier
reagent and DMFDMA was found to afford compound
2 (Scheme 1).
The structure of compound 2 is confirmed by X-ray
diffraction data (Fig. 3). Moreover, there are characteristic
signals in 1H NMR spectrum of compound 2: singlet = CH-
at 7.36 ppm and two singlets of methyl groups at 2.93 and
3.24 ppm, that confirm the presence of the dimethylamino-
methylene group. Compound 2 exists in crystal phase as
E-isomer ( the S1-C10-C11-N3 torsion angle is À179.5(3)ꢀ).
The exocyclic C=C double bond also is significantly twisted
(the C9-C10-C11-N3 torsion angle is À15.1(5)ꢀ). Probably,
Figure 3. Molecular structure of compound 2 according to results of X-ray
diffraction study.
this is caused by significant steric repulsion between
dimethylamino group and atoms of ring (shortened intramo-
lecular contact C12-H12A. . .C9 2.56 Å, van der Waals radii
sum [25] is 2.87Å). The seven-membered ring adopts a dis-
torted half-chair conformation with deviation of the N1, C9
and C10 atoms from mean plane of remaining atoms of ring
by 0.840(5) Å, 0.453(6) Å and À0.586(5) Å, respectively.
It was interesting to investigate the reaction of 7-nitro-4,
5-dihydro-1,4-benzothiazepin-3(2H)-one 1,1-dioxide 6
with formylating agents. The long time we could not
obtain the desired compounds 5, 6, according to described
methods [18,19] due to difficulties in synthesis of (2-chloro-
5-nitrobenzyl)amine 4. In spite of the apparent simplicity of
structure of amine 4, the synthesis of this compound has
not been described. After many attempts, the synthesis of
compound 4 has been carried out: commercially available
2-chloro-5-nitrobenzamide 3 has been reduced by in situ
generated borane from BF3ÁOEt2 and NaBH4 (Scheme 2).
Compound 5 has been obtained by described method [18]
in 82 % yield. Treatment of 7-nitro-4,5-dihydro-1,
4-benzothiazepin-3(2H)-one 5 with peracetic acid led to
corresponding sulfone 6 in 85 % yield.
Characteristic signals in 1H NMR spectra of compounds
5 and 6 are singlets at 3.93 and 4.85 ppm (2-CH2), doublets
at 4.50 and 4.80 ppm (5-CH2) and triplets at 8.18 and
8.67 ppm (NH) correspondingly.
Figure 2. Possible directions to formylating agent attack.
Scheme 2
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Reactions of 4,5-Dihydro-1,4-Benzothiazepin-3(2H)-one 1,1-Dioxide and 1,5-Dihydro-4,
1-Benzothiazepin-2(3H)-one 4,4-Dioxide Derivatives with Vilsmeier Reagent and DMFDMA
Reaction of sulfone 6 and DMFDMA afforded the expected
product 7 similarly to dimethylaminomethylene derivative 2
(Scheme 3). The H NMR spectrum of compound 7 is
The seven-membered ring adopts a distorted half-chair
conformation with deviation of the N1, C9 and C10 atoms
from mean plane of remaining atoms of ring by À0.628(2)
Å, 0.102(2) Å and 0.879(2) Å, respectively.
The next step of this work was the investigation of inter-
action of isomeric sulfone 9 [20] with formylating agents.
An interesting fact has been observed, that treatment
of compounds 9 with Vilsmeier reagent did not led to
dimethylaminomethylene derivative (Scheme 4). Instead
of that we obtained mixture of undesirable side products.
Possibly, ring opening took place.
1
characterized by the signals of the aromatic protons and
also the regular chemical shift of the protons on C-5 at
4.64 as doublet (J = 4.8 Hz), the signal on NH is found at
8.22 ppm as triplets (J = 4.8 Hz). There are also singlets
of methyl groups at 2.94 and 3.23 ppm and singlet of
1
=CH- at 8.22. The triplet of NH is exchangeable in H
NMR spectrum recorded with addition D2O, and doublet
of 5-CH2 becomes singlet.
Treatment of sulfone 6 with the Vilsmeier reagent led
to introduction of dimethylaminomethylene group and
formylation of nitrogen in position 4 (Scheme 3).
There is a characteristic singlet for the formyl group at
Performing the reaction of sulfone 9 with 2 equivalents of
DMFDMA in toluene allowed us to obtain compound 10 in
63 % yield. DMFDMA is known to have the properties
of formylating and alkylating agents [24]. In our case we
observed both of mentioned properties.
1
8.91 ppm, which is present in the H NMR spectrum in
addition of D2O. Signals of other groups of compound
8 are shifted to low field in comparison with compounds
7: singlet = СН- at 7.76 ppm, singlets of methyl groups
at 2.97 and 3.38 ppm and singlet of 5-CH2. Finally, the
structure of compound 8 was established by X-ray diffraction
study (Fig. 4).
Compound 8 exists in crystal phase as the E-isomer
(the S1-C10-C11-N3 torsion angle is 172.4(1)ꢀ). Exocyclic
C=C double bond is significantly twisted (the C9-C10-C11-
N3 torsion angle is À19.2(2)ꢀ). Again, this is probably
caused by steric repulsion between dimethylamino group
and atoms of ring (shortened intramolecular contact C12-
H12A...C9 2.74 Å, van der Waals radii sum [25] is 2.87 Å).
The structure of compound 10 is confirmed by X-ray
diffraction study (Fig. 5) and NMR spectra. There are charac-
teristic signals in 1H NMR: wide singlet (6H) of N(CH3)2 at
2.82ppm, singlets of methyl, methylene and =CH- groups at
3.35, 4.34 and 6.64 ppm correspondingly.
Compound 10 exists in crystal phase as the E-isomer
(the S1-C8-C10-N2 torsion angle is 176.5(2)ꢀ). Twisting of
exocyclic C=C double bond is considerably smaller than in
molecules 2, 8 (the C9-C8-C10-N2 torsion angle is À9.6(3)ꢀ)
despite of stronger steric repulsion between dimethylamino
group and atoms of ring (shortened intramolecular contact
Scheme 4
Scheme 3
Figure 4. Molecular structure of compound 8 according to results of X-
Figure 5. Molecular structure of compound 10 according to results of X-
ray diffraction study.
ray diffraction study.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

T. M. Tarasiuk, T. A. Volovnenko, K. S. Popov, V. V. Medviediev, O. V. Shishkin, and Y. M. Volovenko Vol 000
Table 1
C13-H13A...C9 2.49 Å, van der Waals radii sum [25] is
Crystallographic data, parameters of experiments and structure refinement
2.87 Å). The seven-membered ring adopts a boat conformation
with deviation of the S1, C8 and C9 atoms from mean
of structures of compounds 2, 8, 10.
plane of remaining atoms of ring by 1.532(3) Å, 2.070(2)
2
8
10
Å and 1.071(3) Å, respectively.
Crystal data:
Empirical formula C13H15N3O5S C13H13N3O6S C13H16N2O3S
In summary, we have compared reactivity of 4,5-dihydro-1,
4-benzothiazepin-3(2H)-one 1,1-dioxides V and 1,5-dihydro-
4,1-benzothiazepin-2(3H)-one 4,4-dioxides VI in reactions
with formylating agents. We observed the introduction of
dimethylaminomethylene groups in positions between SO2
and CO, as was predicted. But each case has own specificity.
It has been shown that the nature of the aromatic ring influ-
ences on reactions of the NH groups. When the molecule con-
tains an anilide NH, we observed alkylation by DMFDMA.
When the NH is the part of aliphatic amide we saw that
DMFDMA did not alkylate the NH, but the Vilsmeier reagent
leads to N-formylation. We have shown that DMFDMA and
the Vilsmeier reagent are useful for introduction of a carbonyl
group and its analogues. It should be noted that DMFDMA
are more convenient in some syntheses.
Crystal system
Space group
a, Å
monoclinic
P21/c
15.1599(17)
6.7385(8)
monoclinic
P21/c
8.4101(2)
8.5343(2)
monoclinic
P21/n
7.7711(4)
12.5922(7)
13.9856(6)
96.167(5)
1360.64(12)
4
b, Å
c, Å
14.8507(16) 20.1471(5)
ꢀ
b,
105.238(12)
1463.7(3)
4
95.756(2)
1438.75(6)
4
V, Å3
Z
Dc, g/sm-3
m(MoKa), mm-1
T, K
1.476
0.249
293
1.567
0.262
293
1.369
0.243
293
F(000)
680
704
592
Data collection:
Independent
Reflelections
Rint
3538
4595
4395
0.0769
57.7
0.0169
64.1
0.0381
64.1
2θmax
Refinement:
Parameters
Reflections with
F > 4s(F)
R1 [F2 > 2s(F2)
wR2 (all data)
S (goodness-of-fit)
CCDC dep.
Numbers
202
2029
210
3805
175
2690
EXPERIMENTAL
0.0673
0.1795
1.02
0.0372
0.1085
1.06
0.0468
0.1324
1.01
X-ray diffraction study of compound 2, 8 and 10.
Crystallographic data and parameters of experiments are listed in
Table 1. Intensities of reflections were measured on an automatic
«Xcalibur 3» diffractometer (graphite monochromated MoKa
radiation, CCD-detector o scaning). All structures were solved by
direct method using SHELX97 package [26]. Positions of the
hydrogen atoms were located from electron density difference
maps and refined by “riding” model with Uiso = nUeq of carrier
non-hydrogen atom (n= 1.5 for methyl group and n = 1.2 for other
hydrogen atoms). Full-matrix least-squares refinement against
F2 was performed for non-hydrogen atoms using anisotropic
approximation. Final atomic coordinates, geometrical
parameters and crystallographic data have been deposited with
the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK (fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk). These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/products/csd/request/.
All commercially available chemicals were purchased from
Aldrich (St. Louis, MO, USA) and Merck (Darmstadt, Germany).
NMR spectra of DMSO-d6 solutions with TMS as internal
standard were recorded on a Varian Mercury 400 spectrometer.
Elemental analyses were determined on a vario MICRO cube
elemental analyzer. Melting points were measured with a small
Boetius apparatus equipped with a VEB Analytic RNMK apparatus.
Purity of the compounds synthesized was monitored by TLC on
Silufol UV-254 plates with 9:1 chloroform–methanol as eluent.
General procedure for the reaction of sulfones with
Vilsmeier reagent. To magnetically stirred dry DMF (14mL)
at 0 ꢀC was added dropwise phosphorus oxychloride (8.3 mL,
40mmol). After 30minutes at 0 ꢀC the solution of corresponding
sulfone (10mmol) in dry DMF (6 mL) was added. The mixture
obtained was stirred for 6 hours at 60–70ꢀC. The solution was
poured onto crushed ice (150g) and the resulting solid was
filtered, washed with water and dried.
885596
885594
885595
General procedure for the reaction of sulfones with
DMFDMA. A mixture of DMFDMA (0.27 mL, 20 mmol)
and corresponding sulfone (10 mmol) in dry toluene (50 mL)
was heated at reflux for 3 hours. The resulting solution was
concentrated in vacuo. To the residue i-PrOH (10 ml) was
added. The precipitate was filtered, washed and dried.
(2E)-2-[(Dimethylamino)methylene]-4-methyl-7-nitro-4,5-dihydro-
1,4-benzothiazepin-3(2H)-one 1,1-dioxide (2). This compound
1
was obtained as pale yellow solid (dioxane); mp 243–245 ꢀC; H
nmr (DMSO-d6): d 2.93 (s, 3H, CH3), 2.99 (s, 3H, NCH3), 3.24
(s, 3H, CH3), 4.91 (s, 2H, CH2), 7.36 (s, 1H, CH), 8.10 (d, 1H,
H9, J = 8.4 Hz), 8.34 (d, 1H, H8, J = 8.4 Hz), 8.41 (s, 1H, H6); 13C
nmr (DMSO-d6): d 35.10, 47.14, 53.05, 67.03, 96.69, 124.83,
125.24, 126.70, 136.93, 148.79, 150.24, 151.19, 165.25. Anal.
calcd. for C13H15N3O5S: C, 47.99; H, 4.65; N, 12.92. Found: C,
48.01; H, 4.66; N, 12.90.
2-Chloro-5-nitrobenzylamine hydrochloride (4).
To a
magnetically stirred suspension of amide 2-chloro-5-nitrobenzoic
acid 1 (20.0g, 0.1 mol) and sodium borohydride (15.2g, 0.4mol)
in dry THF (300 mL) at 20ꢀC was added dropwise boron
trifluoride etherate (50.8mL, 0.4 mol). The resultant mixture was
stirred at 50ꢀC for 24hours, concentrated in vacuo. Then water
(250ml) was added. Aqueous solution was extracted with
CH2Cl2. The extract was washed with brine, dried over MgSO4
and evaporated in vacuo. To residue was added i-PrOH (15 mL)
and calculated amount of hydrochloric acid. The precipitate
was collected by filtration, washed Et2O, and dried to give
2-chloro-5-nitrobenzylamine hydrochloride 2 (13.8 g, 62 %). White
solid; mp >300 ꢀC; 1H nmr (DMSO-d6): d 4.21 (s, 2H, CH2), 7.75
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Reactions of 4,5-Dihydro-1,4-Benzothiazepin-3(2H)-one 1,1-Dioxide and 1,5-Dihydro-4,
1-Benzothiazepin-2(3H)-one 4,4-Dioxide Derivatives with Vilsmeier Reagent and DMFDMA
(d, 1H, H3, J = 8.8 Hz), 8.22 (dd, 1H, H4, J = 2.4, 8.8 Hz), 8.59
(d, 1H, H6, J = 2.4 Hz), 8.7-9.0 (br s, 3H, N+H3); 13C nmr
(DMSO-d6): d 39.66, 125.15, 125.74, 131.21, 134.53, 140.28,
146.52. Anal. calcd. for C7H8Cl2N2O2: C, 37.69; H, 3.62; N,
12.56. Found: C, 37.70; H, 3.62; N, 12.53.
(3E)-3-[(Dimethylamino)methylene]-1-methyl-1,5-dihydro-
4,1-benzothiazepin-2(3H)-one 4,4-dioxide (10). This compound
1
was obtained as pale yellow solid (toluene, 63%); mp 196ꢀC; H
nmr (DMSO-d6): d 2.81 (s, 6H, 2CH3), 3.34 (s, 3H, NCH3), 4.39
(s, 2H, CH2), 6.64 (s, 1H, CH), 7.25-7.44 (m, 4H, C6H4); 13C nmr
(DMSO-d6): d 36.05, 36.06, 39.59, 57.90, 99.24, 124.54, 127.26,
128.47, 130.13, 130.89, 144.46, 146.04, 162.96. Anal. calcd. for
C13H16N2O3S: C, 55.70; H, 5.75; N, 9.99. Found: C, 55.70;
H, 5.77; N, 10.01.
7-Nitro-4,5-dihydro-1,4-benzothiazepin-3(2H)-one (5). To
a stirred solution of 2-chloro-5-nitrobenzylamine hydrochloride
2 (11.15 g, 0.05 mol) and triethylamine (20.9mL, 0.15 mol) in
25mL DMSO was added methyl thioglycolate (4.5 mL, 0.05 mol).
After being stirred at 60ꢀC for 5 h, the reaction mixture was
cooled to room temperature, quenched with water (250mL), and
then stirring was continued 30 min. The precipitate was filtered
off, washed by acetone and dried to give 8.51 g (76%) of
7-nitro-4,5-dihydro-1,4-benzothiazepin-3(2H)-one 5. Pale yellow
solid; mp 263–265 ꢀC; 1H nmr (DMSO-d6): d 3.93 (s, 2H, 2-CH2),
4.50 (d, 2H, 5-CH2, J = 6.4 Hz), 7.33 (d, 1H, H9, J = 8.8Hz), 7.96
(dd, 1H, H8, J = 2.0, 8.8 Hz), 8.59 (d, 1H, H6, J = 2.0 Hz), 8.18
(t, 1H, NH, J = 6.4 Hz); 13C nmr (DMSO-d6): d 32.04, 44.76,
123.24, 125.26, 128.56, 135.38, 144.55, 146.06, 169.71. Anal.
calcd. for C9H8N2O3S: C, 48.21; H, 3.60; N, 12.49. Found: C,
48.20; H, 3.62; N, 12.50.
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7-Nitro-4,5-dihydro-1,4-benzothiazepin-3(2H)-one 1,1-dioxide
(6). A mixture of 3 (6.72g, 0.03 mol) and 30% H2O2 (18 mL)
in 200 ml acetic acid was stirred at 40ꢀC for 3 days. The resultant
reaction mixture was concentrated in vacuo. MeOH 25mL was
added to residue, precipitate was collected by filtration, washed
MeOH, dried. The pure product was obtained by crystallization
1
from AcOH. White solid; mp 296–298 ꢀC; H nmr (DMSO-d6):
d 4.80 (d, 2H, 5-CH2, J = 5.6Hz), 4.85 (s, 2H, 2-CH2), 8.16
(d, 1H, H9, J = 8.4Hz), 8.35-8.38 (m, 2H, H6, H8), 8.67 (t, 1H,
NH, J =5.6 Hz); 13C nmr (DMSO-d6): d 44.09, 59.51, 124.05,
124.76, 127.68, 138.15, 148.26, 149.23, 163.31. Anal. calcd. for
C9H8N2O5S: C, 42.19; H, 3.15; N, 10.93. Found: C, 42.21; H,
3.13; N, 10.95.
(2E)-2-[(Dimethylamino)methylene]-7-nitro-4,5-dihydro-1,
4-benzothiazepin-3(2H)-one 1,1-dioxide (7).
This compound
1
was obtained as pale yellow solid (dioxane); mp 277–278 ꢀC; H
nmr (DMSO-d6): d 2.94 (s, 3H, CH3), 3.23 (s, 3H, CH3), 4.64
(d, 2H, CH2, J = 4.8Hz), 7.39 (s, 1H, CH), 8.09 (d, 1H, H9,
J = 8 Hz), 8.22 (t, 1H, NH, J = 4.8Hz), 8.28-8.30 (m, 2H, H6, H8);
13C nmr (DMSO-d6): d 41.15, 45.20, 47.20, 96.93, 124.33,
124.71, 126.74, 138.35, 148.95, 150.36, 151.75, 167.18. Anal.
calcd. for C12H13N3O5S: C, 46.30; H, 4.21; N, 13.50. Found: C,
46.33; H, 4.20; N, 13.49.
(2E)-2-[(Dimethylamino)methylene]-7-nitro-3-oxo-2,3-dihydro-
1,4-benzothiazepine-4(5H)-carbaldehyde 1,1-dioxide (8). This
compound was obtained as pale yellow solid (dioxane);
mp 257–258 ꢀC; 1H nmr (DMSO-d6): d 2.97 (s, 3H, CH3), 3.38
(s, 3H, CH3), 5.20 (s, 2H, CH2), 7.76 (s, 1H, CH), 8.14 (d, 1H,
H9, J = 7.6 Hz), 8.34 (d, 1H, H8, J = 7.6 Hz), 8.50 (s, 1H, H6),
8.91 (s, 1H, CHO); 13C nmr (DMSO-d6): d 41.95, 44.44,
47.82, 96.84, 124.40, 125.06, 125.93, 135.18, 148.34, 149.14,
154.98, 161.90, 165.83. Anal. calcd. for C13H13N3O6S: C,
46.01; H, 3.86; N, 12.38. Found: C, 46.00; H, 3.88; N, 12.40.
[25] Zefirov, Y. V.; Zorkiy, P. M. Usp Khim 1989, 58, 713–731.
[26] Sheldrick, G. M. Acta Cryst Section
112–122.
A 2008, 64,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet