SYNTHESIS OF 8-PIPERIDINO-5,6-DIHYDRO-4H-THIAZOLO[5,4-c]AZEPINES
1179
Ia and Ib with piperidine in the presence of HgCl2 to
bind hydrogen sulfide liberated during the process.
By reaction of thiazoloazepinethiones Ia and Ib with
chloroacetonitrile were synthesized 8-amino-5,6-di-
hydro-4H-bis[1,3]thiazolo[3,2-a:5 ,4 -c]azepin-7-ium
chlorides VIa and VIb.
184 [M]+. C7H8N2S2. Calculated, %: C 45.62; H 4.38;
N 15.20; S 34.80. M 184.
5,5-Dimethyl-8-piperidino-5,6-dihydro-4H-thi-
azolo[5,4-c]azepine (Va). Compound Ia, 100 mg,
was dissolved in 2 ml of piperidine, 128 mg of HgCl2
was added, and the mixture was heated for 2 h under
reflux. It was then cooled and filtered, piperidine was
distilled off, the residue was dissolved in benzene, and
the solution was passed through a short column
charged with aluminum oxide, followed by elution
with benzene. The solvent was distilled off from the
eluate, and the residue was dissolved in chloroform
and purified by column chromatography on silica gel
using first chloroform and then chloroform ethanol as
eluent. Yield 77 mg (62%), mp 170 C (from benzene
5,5-Dimethyl-4,5,6,7-tetrahydrobenzothiazol-7-
one (IIIa). Chlorothiazoloazepinone IVa, 4.95 g, was
dissolved in 25 ml of ethanol, 5.2 g of reduced iron
and 12.5 ml of acetic acid were added, and the mix-
ture was heated for 40 h at the boiling point under
stirring. The mixture was cooled and filtered, the
solvent was distilled off from the filtrate, the residue
was dissolved in diethyl ether, and the organic solu-
tion was washed with an aqueous solution of NaHCO3
until neutral reaction and dried over Na2SO4. The
product was purified by column chromatography on
aluminum oxide using chloroform as eluent. Yield
3.62 g (87%). 1H NMR spectrum (DMSO-d6), , ppm:
1.19 s (6H, Me2C), 2.68 s (2H, 6-H), 3.01 s (2H, 4-H),
8.85 s (1H, 2-H). Found, %: C 59.66; H 6.14; N 7.71;
S 17.67. m/z 181 [M]+. C9H11NOS. Calculated, %:
C 59.64; H 6.12; N 7.73; S 17.69. M 181.
1
hexane). H NMR spectrum (DMSO-d6), , ppm (J,
Hz): 1.21 s (6H, Me2C), 1.64 m (6H, CH2, piperidine),
2.65 s (2H, 4-H), 3.40 s (2H, 6-H), 3.47 t (4H, NCH2,
piperidine, J = 6.3). Found, %: C 63.81; H 8.06;
N 1.93; S 12.17. m/z 263 [M]+. C14H21N3S. Calcu-
lated, %: C 63.84; H 8.04; N 1.95; S 12.17. M 263.
8-Piperidino-5,6-dihydro-4H-thiazolo[5,4-c]-
azepine (Vb) was synthesized in a similar way from
compound Ib. Yield 60%, mp 172 C (from benzene
4,5,6,7-Tetrahydrobenzothiazol-7-one (IIIb)
was synthesized in a similar way from compound IVb.
Yield 82%. 1H NMR spectrum (DMSO-d6), , ppm (J,
Hz): 2.06 m (2H, 5-H), 2.81 t (2H, 6-H, J = 6.5),
2.89 t (2H, 4-H, J = 6.2), 8.83 s (1H, 2-H). Found,
%: C 54.85; H 4.63; N 9.42; S 20.90. m/z 153 [M]+.
C7H7NOS. Calculated, %: C 54.88; H 4.61; N 9.41; S
20.93. M 153. Compounds IIIa and IIIb were iso-
lated as oily liquids.
1
hexane). H NMR spectrum (DMSO-d6), , ppm (J,
Hz): 1.64 m (6H, CH2, piperidine), 2.11 m (2H, 5-H),
2.88 t (2H, 4-H, J = 6.2), 3.48 t (4H, NCH2, piperi-
dine, J = 6.3), 3.51 t (2H, 6-H, J = 6.4). Found, %:
C 61.22; H 7.29; N 17.84; S 13.60. m/z 235 [M]+.
C12H17N3S. Calculated, %: C 61.24; H 7.28; N 17.85;
S 13.62. M 235.
5,5-Dimethyl-5,6-dihydro-4H-bis[1,3]thiazolo-
[3,2-a:5 ,4 -c]azepin-7-ium chloride (VIa). A mix-
ture of 143 mg of thiazoloazepinethione Ia (finely
powdered in a mortar) and 3 ml of chloroacetonitrile
was heated for 2 h on a boiling water bath. The mix-
ture was cooled and filtered, the precipitate was
washed on a filter with diethyl ether and mixed with
3 ml of isobutyl alcohol, and the mixture was heated
for 30 min under reflux, cooled, and filtered. The
precipitate was washed on a filter with isobutyl al-
cohol, dried in air, and recrystallized twice from
ethanol. Yield 140.62 mg (73%), mp 284 C (decomp.,
5,5-Dimethyl-5,6,7,8-tetrahydro-4H-thiazolo[5,4-
c]azepine-8-thione (Ia). Compound IIa, 1.96 g, was
dissolved in 20 ml of pyridine, 3.7 g of P4S10 was
added, and the mixture was heated for 9 h under re-
flux. The solvent was distilled off, the residue was
dissolved in chloroform, and the product was purified
by column chromatography on aluminum oxide using
chloroform as eluent. Yield 1.34 g (63%), mp 164C
(from toluene). 1H NMR spectrum (DMSO-d6),
,
ppm (J, Hz): 1.10 s (6H, Me2C), 2.94 s (2H, 4-H),
3.15 d (2H, 6-H, J = 6.7), 8.46 br.s (1H, 7-H), 8.77 s
(1H, 2-H). Found, %: C 50.90; H 5.71; N 13.18; S
30.18. m/z 212 [M]+. C9H12N2S2. Calculated, %: C
50.91; H 5.70; N 13.19; S 30.20. M 212.
from toluene). 1H NMR spectrum (DMSO-d6),
,
ppm: 1.02 s (6H, Me2C), 3.18 s (2H, 4-H), 4.25 s (2H,
6-H), 6.75 s (1H, thiazole), 6.98 br.s (2H, NH2), 9.36
s (1H, thiazole). Found, %: C 45.90; H 4.89; Cl
5,6,7,8-Tetrahydro-4H-thiazolo[5,4-c]azepine-8-
thione (Ib) was synthesized in a similar way from
compound IIb. Yield 61%, mp 167 C (from toluene).
1H NMR spectrum (DMSO-d6), , ppm (J, Hz):
1.97 m (2H, 5-H), 3.09 t (2H, 4-H, J = 6.0), 3.39 m
(2H, 6-H), 8.59 br.s (1H, 7-H), 8.79 s (1H, 2-H).
Found, %: C 45.60; H 4.39; N 15.18; S 34.77. m/z
12.33; N 14.63; S 22.23. m/z 252 [M
C11H13N3S2 HCl. Calculated, %: C 45.91; H 4.87;
Cl 12.35; N 14.61; S 22.26. [M HCl] 252.
HCl]+.
5,6-Dihydro-4H-bis[1,3]thiazolo[3,2-a :5 ,4 -c]-
azepin-7-ium chloride (VIb) was synthesized in a
similar way from thiazoloazepinethione Ib and chlo-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006
Stepanov
