SYNTHESIS OF 2-(4-CHLOROBENZYLAMINO)-1-(4-NITROPHENYL)ETHANOL
2377
The synthesis of compounds IV–VI was carried out
by refluxing in anhydrous toluene (or benzene) in the
presence of triethylamine, the acceptor of the formed
hydrogen bromide.
2-(4-Chlorobenzylamino)-1-(4-nitrophenyl)ethanol
(I). A solution of 8.25 g of p-nitrophenyloxirane and
7.22 g of 4-chlorobenzylamine in 60 ml of 2-propanol
was refluxed with stirring for 6 h. From the obtained
solution light yellow crystals precipitated on cooling.
The crystals were filtered off and washed with 2-
propanol. After recrystallization from 2-propanol 9.3 g
(63%) of the product was obtained with mp 127–128оС.
The obtained 2-(4-chlorobenzyl)[(2-hydroxy-2-(4-
nitrophenyl)ethyl)-amino]-N-(2,6-dihalo-4-nitrophenyl)-
acetamides IV–VI are high-melting white crystalline
compounds soluble in dimethylformamide and hot
alcohol. The IR spectra of IV–VI contain a strong
absorption band of carbonyl group in the region of
1690–1675 cm–1 and bands of nitro group at 1515 and
1340 cm–1.
[N-(4-Chlorobenzyl)-N-(4-nitrophenyloxyethyl)]-
β-D-glucopyranosylamine (II). A mixture of 1.53 g
of 2-(4-chlorobenzylamino)-1-(4-nitrophenyl)ethanol
and 0.9 g of D-glycose in 10 ml of absolute ethanol
was stirred at heating with a reflux condenser at 70оС
for 15 h. The solvent excess was distilled off. The oily
residue obtained was washed several times with
acetonitrile and dried in a desiccator over P2O5 for
several days. The finally obtained semi-glass-like mass
was ground with hexane. Yield 2.19 g (90%). For
additional purification compound II was subjected to
column chromatography on silica gel, eluent 2-
propanol. Light-yellow crystalline powder was
obtained, mp 82–85°С.
1
Their Н NMR spectra alongside the signals of
aromatic and aliphatic protons corresponding to the
structure of compound I that appear in the above
described regions contain the signals of methylene
protons at the amide carbonyl group СН2СОN in the
region centered at 3.37 ppm as a doublet of doublets
with J = 16.8 Hz, and a narrow singlet of the protons
of aromatic 2,6-dihalo-4-nitrophenyl ring in the
relatively weak field, at 8.40–8.60 ppm. Amide proton
is present as a singlet at 9.95 ppm.
1-(4-Aminophenyl)-2-(4-chlorobenzylamino)etha-
nol (III). To a suspension of 0.92 g of I in 30 ml of
50% ethanol at stirring was poured 7 ml of
concentrated hydrochloric acid, then 2.27 g of
anhydrous SnCl2 was added in three portions, and the
mixture was heated under reflux at 80°C for 15 h. Then
the solution was treated with excess 25% aqueous
ammonia, and the precipitated product and tin
hydroxide were filtered off. To the precipitate was
added 200 ml of concentrated alkali solution, and it
was left standing for 24 h to dissolve the tin hydroxide.
The residual solid was filtered off, washed with a
solution of alkali and water, and dried in air. After
two-fold recrystallization from a mixture benzene–
hexane (1:1) we obtained 0.61 g (74%) of amorphous
powder with mp 78–80°С.
Biological screening of compound V for anti-
bacterial and antifungal activity revealed its moderate
activity as compared with the reference substances,
gentamycine and nystatin.
Thus, on the basis of the synthesized by us via p-
nitrophenyloxirane ring cleavage 2-(4-chlorobenzyl-
amino)-1-(4-nitrophenyl)ethanol further chemical
modification of the latter was carried out by
glycosylation, reduction and nucleophilic substitution
reactions aimed at the preparation of new structures
containing pharmacalogically active functional groups.
Among the synthesized compounds compound V was
revealed with moderately expressed antibacterial and
antifungal activity.
EXPERIMENTAL
IR spectra were registered on
a
Fourier
{4-Chlorobenzyl-[2-hydroxy-2-(4-nitrophenyl)-
ethyl]amino}-N-(2,6-dichloro-4-nitrophenyl)acet-
amide (IV). A suspension of 0.32 g of N-(2,6-di-
chloro-4-nitrophenyl)bromoacetamide and 0.3 g of 2-
(4-chlorobenzylamino)-1-(4-nitrophenyl)ethanol in 7 ml
of anhydrous toluene with 0.4 g of triethylamine was
refluxed for 5 h. The precipitate of triethylamine
hydrobromide and product IV was filtered off, washed
several times with benzene and then with water to
remove triethylamine hydrochlorde. The residual
slightly yellowish crystalline solid was dried. 0.36 g
spectrometer AVATAR-320 of Nicolet Company, from
1
KBr pellets. Н NMR spectra were registered on a
Bruker DRX500 spectrometer with operating
frequency 500 МHz from solutions in DMSO-d6 with
internal reference TMS. The melting points were
measured on a Boёtius instument. The reaction
progress and the purity of the obtained compounds
were monitored by TLC on Sorbfil plates in the system
2-propanol–benzene–ammonia in the ratio 10:5:2. The
plates were developed in iodine vapor.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 12 2008
Kulakov
