The yields of final products 1–3 were 36–75% and depended not so much on the electron-donating properties of the
alkaloid moiety in the amide as on the conformational rigidity of the rings in the starting alkaloids that prevented the β-C atom
of the double bond from being shielded. Compound 2 was obtained in the highest yield. This was explained by the conformational
rigidity of the cytisine rings compared with the conformational flexibility of anabasine and D-pseudoephedrine.
Products 1–3 were powdery and oily compounds that were soluble in EtOH and CHCl with heating. Their structures
3
and compositions were proved using IR and PMR spectroscopy and elemental analysis.
–1
IR spectra of 1–3 contained absorption bands at 780–730 cm (C–Sh), 1060–1040, 1160–1120, 1270–1250 (S–C–S,
N=C–S, N–N), and 1460–1390 (N=C) that were identified as absorption bands of the thiadaizole ring [8, 9]. Other functional
groups of 1–3 appeared in characteristic regions of the spectrum at 1695–1624 (C=O), 1480–1440 (–CH –), and 705–680
2
(C–S–) [10].
EXPERIMENTAL
The course of reactions and purity of 1–3 were monitored using TLC on Silufol UV-254 standard plates with elution
by propan-2-ol:NH OH:H O (7:2:1) and detection by iodine vapor. Elemental analyses of all compounds agreed with those
4
2
calculated. Melting points were determined on a Boetius apparatus. IR spectra in KBr disks were recorded on an Avatar-320
spectrometer; PMR spectra in DMSO-d , on a Bruker AC-300 spectrometer at operating frequency 300 MHz relative to TMS
6
internal standard.
2,5-Bis(1-(anabasin-1-yl)propan-1-on-3-thio)-1,3,4-thiadiazole (1). A solution of anabasine (1.62 g, 0.01 mol) in
benzene was cooled, stirred vigorously in the presence of triethylamine (1.01 g, 0.01 mol), treated dropwise with acryloylchloride
(0.91 g, 0.01 mol) over an hour, and stirred at room temperature for 2 h. The resulting precipitate of triethylammonium
hydrochloride was filtered off. The filtrate was cooled, stirred, treated dropwise with a solution of 1,3,4-thiadiazol-2,5-
dithiol (0.75 g, 0.005 mol) in anhydrous EtOH over an hour, and stirred at room temperature for 2 h. The resulting precipitate
was filtered off to afford a white powdery compound (1.3 g, 44%), mp 89–90°C (EtOH), R 0.82, C H N O S . PMR
f
28 34 6 2 3
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.81 (4H, m, H-9,9′), 2.08 (4H, m, H-8,8′), 2.50 (4H, m, H-10,10′), 2.81
6
(4H, t, J
= 6.0, H-14,14′), 3.27 (2H, m, H-7,7′), 3.32 (4H, t, J
= 6.0, H-15,15′), 3.71 (4H, m, H-11,11′), 7.15 (2H, q,
14,15
15,14
H-3,3′), 7.58 (2H, q, H-4,4′), 8.31 (2H, d, H-6,6′), 8.50 (2H, d, H-2,2′).
2,5-Bis(1-(cytisin-1-yl)propan-1-on-3-thio)-1,3,4-thiadiazole (2) was synthesized analogously to 1 from cytisine
(1.9 g, 0.01 mol) to afford a white powdery compound (2.4 g, 75%), mp 121–122°C (EtOH), R 0.53, C H N O S . PMR
f
30 34 6 4 3
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.92 (4H, m, H-8,8′), 2.81 (4H, t, J
= 6.0, H-14,14′), 2.90 (4H, m,
6
14,15
H-11,11′), 2.98 (2H, m, H-9,9′), 3.10 (2H, m, H-7,7′), 3.30 (4H, t, J
= 6.0, H-15,15′), 3.36 (4H, m, H-13,13′), 3.80 (2H, m,
15,14
H -10,10′), 4.36 (2H, m, H -10,10′), 5.98 (2H, dd, H-5,5′), 6.33 (2H, dd, H-3,3′), 7.23 (2H, dd, H-4,4′).
ax
eq
2,5-Bis(1-(D-pseudoephedrin-1-yl)propan-1-on-3-thio)-1,3,4-thiadiazole (3) was synthesized analogously to 1
from D-pseudoephedrine (1.65 g, 0.01 mol) to afford an oily compound that was purified by column chromatography over
silica gel with elution by benzene:EtOH (2:1), R 0.78, C H N O S . PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz):
f
28 36
4
4 3
6
0.98 (6H, d, 2CH–CH ), 2.48 (2H, m, 2CH–N), 2.65 (6H, s, 2N–CH ), 2.80 (4H, t, J = 6.0, H-14,14′), 3.40 (4H, t,
3
3
14,15
J
= 6.0, H-15,15′), 4.68 (2H, d, CH–OH), 5.35 (2H, s, 2OH), 6.28, 7.34 (10H, m, 2ArH).
15,14
REFERENCES
1.
2.
B. B. Umarov, M. M. Ishankhodzhaeva, K. Sh. Khusenov, N. A. Parpiev, S. A. Talipov, and B. T. Ibragimov,
Zh. Org. Khim., 35, 624 (1999).
L. Labanauskas, V. Kal′tsas, E. Udrenaite, V. Buchinskaite, A. Brukshtus, and I. Susvilo, in: Materials of the First
International Conference “Chemistry and Biological Activity of Nitrogenous Heterocycles and Alkaloids”
[in Russian], 2, Moscow, 2001, p. 181.
3.
4.
T. M. Salimov, M. A. Kukaniev, I. T. Sattorov, and D. M. Osimov, Khim.-farm. Zh., 39, 2829 (2005).
W. Houbin, J. Shukui, M. Shufen, and Q. Zhaohai, J. China Agr. Univ., 9, 63 (2004); Ref. Zh. Khim., 19Zh304
(2004).
847