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YUTILOV et al.
effected under mild conditions. The ease of this
transformation was explained in terms of the double
effect of the benzene (or pyridine) and imidazole rings
on the C4 N5 bond. The general character of the
process opens new possibilities for synthesizing sub-
stituted histamine and histidine derivatives.
of hydrogen was absorbed). The catalyst was filtered
off, the filtrate was evaporated under reduced pressure
(water-jet pump), and the residue was recrystallized
from appropriate solvent (Table 2).
REFERENCES
1. Stocker, F.B., Fordice, M.W., Larson, J.K., and
Thorstenson, J.H., J. Org. Chem., 1966, vol. 31,
no. 7, pp. 2380 2383.
EXPERIMENTAL
The 1H NMR spectra were recorded on Gemini-200
(200 MHz) and Tesla BS-467C (80 MHz) spectrom-
eters using CD3OD, DMF-d7, CDCl3, or CF3COOH
as solvent and HMDS as internal reference. The purity
of the products was checked by TLC on Silufol
UV-254 plates using alcohol as eluent; spots were
visualized with UV light or iodine vapor.
Initial spinaceamines Ia, Ic, Id, Ig, and Ii were
synthesized by the procedure reported in [1]; com-
pounds Ih and Ij were obtained as described in [2].
Spinacines IIa and IIj were synthesized according
to [1, 2, 6, 7, 16].
4-Arylspinaceamines Ib, Ie, and If. To a solution
of 10 mmol of histamine dihydrochloride in 10 ml
of water we added 25 mmol of sodium hydroxide in
2 3 ml of water and a solution of 10 mmol of approp-
riate benzaldehyde in 25 50 ml of methanol. The
mixture was heated for 12 h on a boiling water bath,
methanol was distilled off, the residue was cooled,
and the product was filtered off and recrystallized
from alcohol or aqueous alcohol (Table 1).
2. Vitali, T., Mossini, F., and Bertassini, G., Farmaco,
Ed. Sci., 1967, vol. 22, no. 10, pp. 821 845.
3. Emmett, J.C., Durant, G.J., Ganellin, C.R., Koe, A.,
and Turner, J.L., J. Med. Chem., 1982, vol. 25,
no. 1, pp. 1168 1174.
4. Yutilov, Yu.M., Abramyants, M.G., and Smo-
lyar, N.N., Russ. J. Org. Chem., 1995, vol. 31,
no. 10, pp. 1429 1430.
5. Aldrich Library of NMR Spectra, 2nd ed., vol. 2, C,
p. 486.
6. Heyl, D., Harris, S.A., and Folkers, K., J. Am. Chem.
Soc., 1948, vol. 70, no. 10, pp. 3429 3431.
7. Casella, L. and Gullotti, M., J. Am. Chem. Soc.,
1981, vol. 103, no. 21, pp. 6338 6347.
8. Black, J.W., Duncan, W.A.M., Durant, C.J.,
Ganellin, C.R., and Parsons, E.M., Nature, 1972,
vol. 239, no. 4, pp. 385 390.
9. Grechishkin, L.L., Gol’dfarb, V.L., Gavrov-
skaya, L.K., and Brovtsina, N.B., Farmakol. Toksi-
kol., 1973, no. 3, pp. 197 203.
4-Arylspinacines IIb IIi and IIk. To a sus-
pension of 20 mmol of L-histidine in 10 ml of water
we added a solution of 60 mmol of KOH in 10 ml
of water, and a solution of 20 mmol of substituted
benzaldehyde in a mixture of 25 ml of water and
25 ml of methanol was then added. The mixture was
heated for 12 h at a bath temperature of 90 C, cooled,
carefully neutralized with hydrochloric acid, and
evaporated to dryness. The residue was ground in
isopropyl alcohol, and the precipitate was filtered
off, dried, and recrystallized from appropriate alcohol
(Table 1).
5-Benzylhistamines IIIa IIIj and 5-benzylhisti-
dines IVa IVk. A solution of 20 mmol of 4-phenyl-
(or pyridyl)spinaceamine Ia Ij or spinacine IIa IIk
in 20 ml of methanol and 20 ml of glacial acetic acid
was hydrogenated at room temperature and hydrogen
pressure equal to atmospheric over 0.5 g of 25% Pd/C.
The reaction time was 3 5 h (until a required amount
10. Shlevkov, B.A., Agafonova, N.A., and Pryanishni-
kov, A.S., Med. Pom., 1995, no. 4, pp. 44 46.
11. Gushchin, I.S., Terapevt. Arkhiv, 1997, no. 10,
pp. 27 34.
12. Uspenskii, V.I., Gistamin (Histamine), Moscow:
Gos. Izd. Med. Lit., 1963.
13. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Khar’kov: Torsing, 1998, vol. 1, p. 273.
14. Comprehensive Organic Chemistry, Barton, D. and
Ollis, W.D., Eds., Oxford: Pergamon Press, 1979,
vol. 5. Translated under the title Obshchaya organi-
cheskaya khimiya, Moscow: Khimiya, 1986, vol. 10,
p. 382.
15. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Khar’kov: Torsing, 1998, vol. 2, p. 130.
16. Cain, M., Guzman, F., Cook, J.M., Rice, K.C., and
Skolnick, Ph., Heterocycles, 1982, vol. 19, no. 6,
pp. 1003 1007.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001