Synthesis and pharmacological activity of some derivatives of benzalbisurea and 1-(?-ureidobenzyl)-2-naphthols
Abstract Generated abstract
This study describes the synthesis and preliminary pharmacological evaluation of substituted benzalbisureas and 1-alpha-ureidobenzyl-2-naphthols in a search for anticonvulsant agents. Benzalbisureas were prepared by acid-catalyzed condensation of substituted benzaldehydes with urea, and selected products were further condensed with beta-naphthol to give three isolable naphthol derivatives. The compounds were characterized by melting points and nitrogen analysis, with reported yields for the benzalbisurea series. Pharmacological testing indicated that all synthesized compounds were inactive as anticonvulsants.
Full Text
SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF SOME DERIVATIVES OF BENZALBISUREA AND 1-($\alpha$-UREIDOBENZYL)-2-NAPHTHOLS
A. G. PECHENKIN, L. I. BUGAEVA, E. V. MAST, T. V. MIKHAILOVA
(Presented by the scientific-methodological seminar of the organic departments of KhTF)
In the search for anticonvulsant agents, we synthesized and tested for physiological activity certain derivatives of benzalbisurea (I) and 1-($\alpha$-ureidobenzyl)-2-naphthols (II). Benzalbisureas were obtained by the previously described method [1] according to the following scheme:
\[ \mathrm{ \underset{x}{Ar{-}CHO} + 2NH_2CONH_2 \longrightarrow \underset{x}{Ar{-}CH(NHCONH_2)_2} + H_2O } \]
\[ x = \mathrm{H;\ p{-}Cl;\ p{-}Br;\ o,p{-}OCH_3;\ o,m,p{-}NO_2.} \]
All the compounds are white crystalline substances, insoluble in water and in organic solvents. The characteristics of the benzalbisureas obtained are given in Table 1.
1-($\alpha$-Ureidobenzyl)-2-naphthols were obtained by condensation of $\beta$-naphthol with benzalbisureas [2, 3].
\[ \mathrm{ \underset{x}{Ar{-}CH(NHCONH_2)_2} + \beta\text{-naphthol} \longrightarrow \underset{x}{Ar{-}CH(NHCONH_2){-}C_{10}H_6OH} } \]
\[ x = \mathrm{H;\ m,p{-}NO_2.} \]
In the condensation reaction with $\beta$-naphthol, all the above-mentioned benzalbisureas were used. However, only the 3 products indicated in the reaction scheme were isolated in pure form. The remaining products could not be purified.
Experimental Part
- 0.1 g-mole of urea was dissolved in 50 ml of absolute alcohol containing several drops of hydrochloric acid; with stirring, 0.05 mole of benzaldehyde was added to the solution and the mixture was left to stand at room temperature for 0.5–3 hours. The precipitate was filtered off and washed with ether and methanol to remove benzaldehyde, then with water until a negative reaction for urea was obtained.
Table 1
\[ \mathrm{R{-}CH}\left< \begin{array}{l} \mathrm{NHCONH_2}\\ \mathrm{NHCONH_2} \end{array} \right. \]
| R | \(T_{\mathrm{m}}\) | Nitrogen, % (calc.) | Nitrogen, % (found) | Yield, % |
|---|---|---|---|---|
| \(o\text{-}\mathrm{NO_2{-}C_6H_4{-}}\) | 205—200 | 27,67 | 26,93 | 86,0 |
| \(p\text{-}\mathrm{NO_2{-}C_6H_4{-}}\) | 172—174 | 27,67 | 26,90 | 50,0 |
| \(m\text{-}\mathrm{NO_2{-}C_6H_4{-}}\) | 172—174 | 27,67 | 27,10 | 27,2 |
| \(p\text{-}\mathrm{Cl{-}C_6H_4{-}}\) | 201—204 | 23,10 | 22,90 | 77,0 |
| \(p\text{-}\mathrm{OCH_3{-}C_6H_4{-}}\) | 225—226 | 23,53 | 22,00 | 40,0 |
| \(o\text{-}\mathrm{OCH_3{-}C_6H_4{-}}\) | 230—232 | 23,53 | 23,00 | 42,0 |
| \(p\text{-}\mathrm{Br{-}C_6H_4{-}}\) | 236—238 | 19,51 | 19,28 | 70,4 |
| \(\mathrm{C_6H_5{-}}\) | 221—225 | 26,92 | 27,20 | 80,0 |
They were dried in air, the melting point was determined, and they were analyzed for nitrogen.
- \(0.05\) g-mol of \(\beta\)-naphthol and \(0.05\) g-mol of benzalbisurea were boiled for 2 hours in 25 ml of absolute alcohol with several drops of concentrated hydrochloric acid. After cooling, the mixture was poured into water; the precipitate that separated was filtered off and recrystallized from alcohol with water (1:1).
1-(\(\alpha\)-Ureidobenzyl)-2-naphthol — white crystalline powder, \(T_{\mathrm{m}}\) — 182—184°C, \(N_{\mathrm{calc}}\) 9—62%, \(N_{\mathrm{found}}\) 9—73%.
1-(\(\alpha\)-Ureido-\(m\)-nitrobenzyl)-2-naphthol — yellow crystalline powder, \(T_{\mathrm{m}}\) — 188—190°C, \(N_{\mathrm{calc}}\) — 12,46%, \(N_{\mathrm{found}}\) — 12,58%.
1-(\(\alpha\)-Ureido-\(p\)-nitrobenzyl)-2-naphthol — yellow crystalline powder, \(T_{\mathrm{m}}\) — 155—156°C, \(N_{\mathrm{calc}}\) — 12,46%, \(N_{\mathrm{found}}\) — 12,61%.
All the compounds proved inactive as anticonvulsants.
REFERENCES
-
V. P. Mamaev, Dissertation for the degree of Doctor of Chemical Sciences. Novosibirsk, 1968.
-
V. F. Sedova, L. D. Dikanskaya, V. P. Mamaev. Izv. SO AN SSSR, chem. ser. No. 3, 98, 1966.
-
V. P. Mamaev, V. M. Ignat'ev. Izv. AN SSSR, vol. 6, 1107, 1965.