One-Pot Synthesis of 2-Aryl-4-methyl-3-nitro-2,3-dihydro-1,5- benzothiazepines

Full text of DOI:10.1134/S1070428010100295

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 10, pp. 1590–1591. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © R.I. Baichurin, N.I. Aboskalova, V.M. Berestovitskaya, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 10,
pp. 1583–1584.
SHORT
COMMUNICATIONS
One-Pot Synthesis of 2-Aryl-4-methyl-3-nitro-2,3-dihydro-
1,5-benzothiazepines
R. I. Baichurin, N. I. Aboskalova, and V. M. Berestovitskaya
Hertzen Russian State Pedagogical University, nab. r. Moiki 48, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
Received April 30, 2010
DOI: 10.1134/S1070428010100295
Wide application in medical practice of compounds
whose molecules contain seven-membered thiazepine
rings (examples are diltiazem which exhibits antian-
ginal, hypotensive, and antiarrhythmic activity and
neuroleptic quetiapine [1, 2]), strongly stimulated
studies aimed at developing new methods of synthesis
of thiazepine derivatives and extending their series.
pines IV–VI separated from the reaction solution, and
their yields attained 98%. Presumably, the process
follows nucleophilic addition pattern with subsequent
heterocyclization of S-adducts.
Compounds IV–VI were isolated as colorless or
yellowish crystalline substances which were diastereo-
isomerically pure. Their structure was confirmed by
spectral methods. The IR spectra of functionally sub-
stituted 1,5-benzothiazepines IV–VI contained strong
absorption bands due to stretching vibrations of uncon-
With the goal of obtaining new nitro-substituted
thiazepine structures we examined reactions of acces-
sible and reactive 4-aryl-3-nitrobut-3-en-2-ones I–III
–
1
jugated nitro group (1560, 1360 cm ), and C=N
[3] with o-aminobenzenethiol. Unlike other α,β-unsat-
–
1
stretching vibrations had a frequency of 1645 cm .
urated ketones which react with o-aminobenzenethiol
under fairly drastic conditions (heating in boiling
methanol for several hours in the presence of acid [4]
or base catalyst [5] or heating in higher-boiling sol-
vents, such as toluene, in the absence of catalyst [6]) to
produce seven-membered heterocycles, reactions of
nitro enones I–III with o-aminobenzenethiol occurred
very readily at 18–20°C in methanol (without a cata-
lyst) and were complete in 10–20 min. Crystalline
1
The H NMR spectra of IV–VI were consistent
with the assumed structure. Compound V displayed in
1
the H NMR spectrum (CDCl ) two clearly defined
3
doublets from H and H at δ 5.45 and 5.25 ppm,
A
B
3
respectively, with a coupling constant J of 11.90 Hz;
AB
protons in the methyl and methoxy groups resonated as
singlets at δ 2.43 and 3.76 ppm, respectively; aromatic
protons appeared as doublets at δ 7.11 and 6.79 ppm
and multiplets at δ 7.57, 7.52, 7.29, and 7.20 ppm. In
2
-aryl-4-methyl-3-nitro-2,3-dihydro-1,5-benzothiaze-
Ar
NO2
Ar
NO2
MeOH, 18–20°C
0–20 min
S
SH
1
Ar
Me
+
S
Me
NO2
OH
O
NH2
N
H
H
O
NH2
Me
I–III
HB
S
Ar
HA
2
4
3
–
H O
2
NO2
Me
N
IV–VI
6 4 2 6 4
I, IV, Ar = Ph; II, V, Ar = 4-MeOC H ; III, VI, Ar = 4-Me NC H .
1
590

ONE-POT SYNTHESIS OF 2-ARYL-4-METHYL-3-NITRO-2,3-DIHYDRO-1,5-...
1591
1
3
the C NMR spectrum of V (recorded with decoupling
light orange crystals, mp 144–146°C (from ethanol).
–
1
from protons), the downfield signal at δ 162.68 ppm
was assigned to the C=N carbon atom (C ), and signals
IR spectrum, ν, cm : 1645 (C=N); 1560, 1360 (NO ).
C
2
4
1
H NMR spectrum (CDCl ), δ, ppm: 2.43 s (3H, CH ),
3
3
2
3
at δ 58.43 and 91.30 ppm were attributed to C and
2.91 s (6H, NCH ), 5.23 d (1H, H , J = 11.90 Hz),
5.46 d (1H, H , J = 11.90 Hz), 6.57 d and 7.03 d
A AB
C
3 B AB
3
1
13
3
C . The assignment of signals in the H and C NMR
spectra was proved by HMQC and HMBC correlation
experiments.
(2H each, C H ); 7.18 t, 7.28 d, 7.50 t, 7.58 d (4H,
6
4
1
3
1
6-H, 7-H, 8-H, 9-H). C–{ H} NMR spectrum
(
CDCl ), δ , ppm: 22.09 (CH ), 40.41 (NCH ), 59.01
3 C 3 3
Initial 4-aryl-3-nitrobut-3-en-2-ones I–III were
synthesized according to the procedures reported in
3], and o-aminobenzenethiol was prepared as de-
scribed in [7].
2
3
(
C ), 91.46 (C ); 112.41, 121.00, 124.44, 126.41,
26.29, 130.67, 135.30, 150.04, 150.70, 150.00
Carom); 162.74 (C=N). Found, %: N 12.01.
C H N O S. Calculated, %: N 12.31.
1
(
[
1
8
19
3
2
4
-Methyl-3-nitro-2-phenyl-2,3-dihydro-1,5-ben-
1
13
The H and C NMR spectra, including HMQC
and HMBC experiments, were recorded on a Jeol
JNM-ECX400A spectrometer at 100.53 ( C) and
zothiazepine (IV). Yield 81%, colorless crystals,
mp 136–137°C (from petroleum ether). IR spectrum, ν,
1
3
–
1
1
cm : 1645 (C=N); 1560, 1360 (NO ). H NMR spec-
2
1
3
99.78 MHz ( H) using the residual solvent signal
(CHCl ) as internal reference. The IR spectra were
measured from solutions in CHCl (c = 0.1–0.001 M)
trum (CDCl ), δ, ppm: 2.44 s (3H, CH ), 5.27 d (1H,
3
3
3
3
3
H , J = 11.90 Hz), 5.52 d (1H, H , J = 11.90 Hz),
.17–7.58 m (9H, Harom). C–{ H} NMR spectrum
B
AB
A
AB
1
3
1
3
7
(
1
1
2
3
on a Shimadzu IR Prestige-21 spectrometer with
Fourier transform. The elemental compositions were
determined on a EuroVector EA 3022 CHN Dual
analyzer.
CDCl ), δ , ppm: 21.99 (CH ), 58.70 (C ), 90.98 (C );
3 C 3
20.50, 124.56, 126.39, 126.60, 129.02, 129.23,
31.04, 135.28, 139.89, 150.09 (Carom); 162.76 (C=N).
Found, %: C 64.61; H 4.91; N 9.15. C H N O S. Cal-
1
6
14
2
2
culated, %: C 64.41; H 4.73; N 9.39.
REFERENCES
2
-(4-Methoxyphenyl)-4-methyl-3-nitro-2,3-dihy-
dro-1,5-benzothiazepine (V). Yield 98%, light yellow
crystals, mp 132–134°C (from ethanol). IR spectrum,
ν, cm : 1645 (C=N); 1560, 1360 (NO ). H NMR spec-
trum (CDCl ), δ, ppm: 2.43 s (3H, CH ), 3.76 s (3H,
OCH ), 5.25 d (1H, H , J = 11.90 Hz), 5.45 d (1H,
H , J = 11.90 Hz), 6.79 d and 7.11 d (2H each,
1. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Novaya Volna, 2007, pp. 72, 433.
–
1
1
2. Registr lekarstvennykh sredstv Rossii. Entsiklopediya
lekarstv (Drug Register of Russia. Encyclopedia of
Drugs), RLS-2002, 2002, pp. 9, 298, 411.
3. Fel’gendler, A.V., Aboskalova, N.I., and Berestovits-
kaya, V.M., Russ. J. Gen. Chem., 2000, vol. 70, p. 1087.
4. Khanna, M.S., Kumar, D., Garg, C.P., and Kapoor, R.P.,
Indian J. Chem., Sect. B., 1995, vol. 34, p. 333.
5. Orlov, V.D., Kolos, N.N., and Ruzhitskaya, N.N., Khim.
Geterotsikl. Soedin., 1983, p. 1638.
2
3
3
3
3
B
AB
3
A
AB
C H ); 7.20 t, 7.29 d, 7.52 t, and 7.57 d (4H, 6-H, 7-H,
6
4
1
3
1
8
-H, 9-H). C–{ H} NMR spectrum (CDCl ), δ ,
3 C
2
ppm: 22.05 (CH ), 55.38 (OCH ), 58.43 (C ), 91.30
3
3
3
(
1
(
C ); 114.49, 120.59, 121.68, 124.54, 126.54, 127.69,
30.93, 132.11, 135.24, 150.00, 159.90 (Carom); 162.68
C=N). Found, %: N 8.80. C H N O S. Calculated,
6
. Gupta, A.K., Singh, V.K., and Pant, U.C., Indian J.
Chem., Sect. B, 1983, vol. 22, p. 1057.
1
7
16
2
3
%
: N 8.53.
-(4-Dimethylaminophenyl)-4-methyl-3-nitro-
,3-dihydro-1,5-benzothiazepine (VI). Yield 98%,
7
. Metody polucheniya khimicheskikh reaktivov i preparatov
(Methods for Preparation of Chemicals), Moscow: IREA,
1964, vol. 9, p. 26.
2
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010