352
POPOV et al.
a positive test for primary amino group was obtained.
Table 1 contains yields, melting or boiling points,
and elemental analyses of Schiff bases IIIa IIIr
and IVi IVn.
The dipolar character of the double C N bond
in Schiff bases makes them highly reactive toward
nucleophiles [4, 5]. Such nucleophilic reagents as
acetamide (VIIa), benzamide (VIIb), and benzanilide
(VIIc) with Schiff bases III form addition products
at both C N bonds (Scheme 4).
The reactions were carried out at a molar reactant
ratio of 1:2 in toluene under reflux. Products VIIIa
VIIIi were obtained in 50 90% yield.
According to the results of computational predic-
tion, the ArCH N moiety determines a probable
spectrum of pharmacological activity of the Schiff
bases prepared in this work. Their biological activity
should strongly depend on the nature and position
of substituent in the aromatic ring. Schiff bases III
are likely to exhibit antibacterial (antiseptic and tuber-
culostatic) and fungicide activity, and compounds V,
VI, and VIII should possess antitumor, neuroleptic,
cardiotonic, analgetic, and fungicide properties. All
the synthesized compounds were registered at the
All-Russian Scientific Center for Biologically Active
Substances (Kupavna).
Some bis-condensation products III were reduced
with lithium aluminum hydride in tetrahydrofuran to
obtain the corresponding diamines V (Scheme 2). The
reduction of Schiff base IIIl was accompanied by
transformation of the aromatic nitro group into amino.
Using sodium tetrahydridoborate as a more selective
reducing agent, we succeeded in conserving the nitro
group in the substrate [2]. The yields, melting or
boiling points, and elemental analyses of compounds
V are given in Table 2.
Scheme 2.
Diamines V are readily converted into the corre-
sponding dihydrochlorides VI by treatment with
hydrogen chloride in anhydrous solvents at 0 to 5 C
(Scheme 3).
EXPERIMENTAL
The IR spectra were recorded on a Specord M-82
instrument from samples dispersed in mineral oil or
Scheme 3.
1
prepared as thin film. The H NMR spectra were
obtained on a Tesla BS-487 spectrometer at 100 MHz
using HMDS as internal reference. GLC was per-
formed on a Tsvet-100 chromatograph equipped with
a flame-ionization detector and a 1-m column packed
with 5% of DS-550 on Chromaton (0.25 0.45 mm);
injector temperature 470 C; oven temperature prog-
ramming from 100 to 250 C at 40 deg/min; carrier
gas flow rate 30 ml/min; sample volume 1 l.
Scheme 4.
1,4-Bis(benzylideneaminomethyl)cyclohexane
(IIIa). A reactor was charged with 1.5 g (14.2 mmol)
of benzaldehyde, and 1 g (7.1 mmol) of 1,4-bis-
(aminomethyl)cyclohexane was added with stirring.
The mixture was heated for 30 min at 60 C under
reduced pressure (40 60 mm) with simultaneous
removal of water. The product was purified by
vacuum distillation. Yield 2.2 g (98%), bp 178
180 C (4 mm).
1,3-Bis[2-(m-phenoxybenzylideneamino)ethyl]-
adamantane (IIIm). A mixture of 1 g (4.5 mmol) of
1,3-bis(2-aminoethyl)adamantane and 1.78 g (9 mmol)
of m-phenoxybenzaldehyde in 10 ml of ethanol was
heated for 1.5 2 h at 60 C. After cooling, crystalline
product IIIm was filtered off. Yield 2.4 g (92%),
colorless crystals, mp 86 88 C.
VII, R2 = H, R3 = Me (a); R2 = H; R3 = Ph (b); R2 = R3 =
Ph (c); VIII, R1 = m-C6H4F, R2 = H, R3 = Ph (a); R1 =
m-C6H4F, R2 = R3 = Ph (b); R1 = m-C6H4F, R2 = H,
R3 = Me (c); R1 = p-C6H4NO2, R2 = H, R3 = Ph (d); R1 =
p-C6H4NO2, R2 = R3 = Ph (e); R1 = p-C6H4NO2, R2 = H,
R3 = Me (f); R1 = m-PhOC6H4, R2 = H, R3 = Ph (g);
R1 = m-PhOC6H4, R2 = R3 = Ph (h); R1 = m-PhOC6H4,
R2 = H, R3 = Me (i).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002
Popov
