Reductive transformations of schiff bases in the synthesis of functionally substituted heteroaromatic amines

Article abstract of DOI:10.1134/S1070428009070148

Schiff bases synthesized by condensation of 5- and 6-aminoquinolines, 5-amino-2-methylquinoline, nitroanilines, and pyrimidinylaminoanilines with substituted benzaldehydes and pyridinecarbaldehydes were reduced with sodium tetrahydridoborate in acetic aci

Full text of DOI:10.1134/S1070428009070148

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 7, pp. 1070–1078. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © Zh.V. Ignatovich, A.P. Kadutskii, E.V. Koroleva, A.V. Baranovskii, K.N. Gusak, 2009, published in Zhurnal Organicheskoi Khimii,
2009, Vol. 45, No. 7, pp. 1083–1091.
Reductive Transformations of Schiff Bases in the Synthesis
of Functionally Substituted Heteroaromatic Amines
Zh. V. Ignatovicha, A. P. Kadutskiib, E. V. Korolevaa, A. V. Baranovskiic, and K. N. Gusaka
a Institute of New Materials Chemistry, National Academy of Sciences of Belarus,
ul. F. Skoriny 36, Minsk, 220141 Belarus
e-mail: evk@ichnm.basnet.by
b Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
c Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
Received August 5, 2008
Abstract—Schiff bases synthesized by condensation of 5- and 6-aminoquinolines, 5-amino-2-methylquino-
line, nitroanilines, and pyrimidinylaminoanilines with substituted benzaldehydes and pyridinecarbaldehydes
were reduced with sodium tetrahydridoborate in acetic acid to obtain the corresponding N-aryl(hetaryl)benzyl-
amines, N-(pyridylmethyl)anilines, and N-(1,2,3,4-tetrahydroquinolyl)benzylamine derivatives. The reduction
of arylhetarylimines with hydrazine hydrate in the presence of Raney nickel involved only the azomethine C=N
bond, while the nitrogen-containing heteroaromatic ring remained intact. Under analogous conditions, nitro-
substituted Schiff bases and benzyl- and pyridylmethylamines were converted into previously unknown
N-(aminobenzyl)quinolinamines and aryl(pyridyl)methyl-substituted phenylenediamines.
DOI: 10.1134/S1070428009070148
Among a variety of nitrogen-containing hetero-
cyclic compounds, amino derivatives of pyridine,
pyrimidine, and quinoline attract considerable interest
due to their versatile biological activity and wide ap-
plication in medicine [1–6]. We previously showed [7]
that reductive alkylation of p-nitroaniline, 6-amino-
quinoline, and N-(5-amino-2-methylphenyl)-4-(pyri-
din-3-yl)pyrimidin-2-amine with methyl 4-formylben-
zoate leads to the formation of methoxycarbonyl-sub-
stituted N-aryl(hetaryl)benzylamines as key interme-
diates in the synthesis of biomolecules [8].
In the present work we synthesized new function-
alized heteroaromatic amines starting from p-bromo-
benzaldehyde (I), m-nitrobenzaldehyde (II), methyl
4-formylbenzoate (III), pyridine-3-carbaldehyde (IV),
on the one hand, and m-nitroaniline (V), 2-methyl-5-
nitroaniline (VI), quinolin-5-amine (VII), 2-methyl-
quinolin-5-amine (VIII), and N-[4-(pyridin-3-yl)py-
rimidin-2-yl]benzene-1,4-diamine (IX), on the other.
Compound IX is an intermediate in the synthesis of
an analog of antileukemic drug Imatinib [8, 9].
amines involves intermediate formation of Schiff
bases, aldehydes I–IV were brought into condensation
with aromatic and heteroaromatic amines V–IX. The
reactions were carried out by heating equimolar
amounts of the reactants in boiling ethanol over
a period of 10–30 min, and previously unknown Schiff
bases X–XVIII were isolated in 75–96% yield and
were then reduced with sodium tetrahydridoborate in
acetic acid (Scheme 1).
The structure of compounds X–XVIII was con-
firmed by the IR, NMR, and mass spectra. The IR
spectra of X–XVIII contained an absorption band at
1630–1610 cm–1, which is typical of stretching vibra-
tions of C=N bond. The azomethine CH=N proton res-
1
onated in their H NMR spectra in the region δ 8.49–
8.65 ppm; also, signals from protons in the other mo-
lecular fragments were present. The number of signals
in the 13C NMR spectra of Schiff bases X–XVIII was
consistent with their structure; the signals were as-
signed using DEPT pulse sequence. Compounds X–
XVIII displayed molecular ion peaks in the mass
1
Taking into account our previous results [7], ac-
cording to which reductive alkylation of primary
spectra. The H NMR spectra of N-(pyridin-3-ylmeth-
ylidene)anilines XII and XIII were characterized by
1070

REDUCTIVE TRANSFORMATIONS OF SCHIFF BASES
1071
Scheme 1.
NaBH4
R'NH2
V–IX
+
3 AcOH
NaBH(OAc)3
+ 3 H2
NaBH4, AcOH
R'
R'
RCHO
+
R
N
R
N
H
I–IV
X–XVIII
XIX–XXV
I, XIV, XXIII, R = 4-BrC6H4; II, XV, R = 3-O2NC6H4; III, X, XI, XVI–XX, XXIV, XXV, R = 4-MeOCOC6H4;
IV, XII, XIII, XXI, XXII, R = pyridin-3-yl; V, X, XII, XIX, XXI, R′ = 3-O2NC6H4; VI, XI, XIII, XX, XXII, R′ =
2-Me-5-O2NC6H3; VII, XIV–XVI, XXIII, XXIV, R′ = quinolin-5-yl; VIII, XVII, R′ = 2-methylquinolin-5-yl;
5'
6''
6'
4'
3'
5''
4''
N
4'''
2''
IX, XVIII, XXV, R′ =
.
1'
N
5'''
6'''
N
3'''
2'''
2'
H
N
downfield position (δ > 9 ppm) of signal from proton
in position 2 of the pyridine ring due to deshielding by
the C=N bond.
nitrogen atom and facilitates reduction of the pyridine
ring, which occurs together with the reduction of the
azomethine bond even at room temperature. The yield
of amine XXVI was 75% calculated on the initial
NaBH4. Neither reduction of acetic acid salts nor N-al-
kylation of the heterocyclic fragment occurred under
the above conditions.
The reduction of Schiff bases X–XVIII was per-
formed by stirring a mixture of the substrate, NaBH4,
and acetic acid at a ratio of 1:2:6 in benzene at room
temperature over a period of 20 h. Sodium triacetoxy-
hydridoborate generated in that system from NaBH4
and 3 equiv (or excess) acetic acid reduces the pro-
tonated C=N bond in Schiff bases X–XIV, XVI,
and XVIII at room temperature to give the correspond-
ing benzylamines XIX–XXV in 65–82% yield
(Scheme 1). The reduction of 2-methylquinolin-5-
amine derivative XVII was accompanied by hydro-
genation of the pyridine ring with formation of methyl
4-(2-methyl-1,2,3,4-tetrahydroquinolin-5-ylamino-
methyl)benzoate (XXVI) (Scheme 2). According to
published data, the reduction of quinoline with the
system NaBH4–AcOH at elevated temperature (50°C)
gives N-ethyl-1,2,3,4-tetrahydroquinoline as a result of
hydrogenation of the nitrogen-containing ring and
simultaneous alkylation of the nitrogen atom; here, the
alkylating agent is likely to be acetaldehyde generated
by self-reduction of NaBH(OAc)3 [10]. The presence
of a methyl group in position 2 of the quinoline ring in
molecule XVII favors its protonation at the endocyclic
Among Schiff bases XIV–XVI of the 5-amino-
quinoline series, the reduction of only N-(m-nitroben-
zylidene)quinolin-5-amine (XV) with sodium tetrahy-
dridoborate in acetic acid gave N-(m-nitrobenzyl)-
1,2,3,4-tetrahydroquinolin-5-amine (XXVII). Accord-
1
ing to the H NMR data, compound XXVII was
formed as a mixture with quinolin-5-amine A at a ratio
of 2:1 (Scheme 2). Insofar as amines XXVII and A
were difficult to separate, Schiff base XV was reduced
with the use of 6 equiv of NaBH4 to ensure complete
conversion of intermediate product A. In such a way
we succeeded in isolating tetrahydroquinoline XXVII
in 76% yield.
The structure of the reduction products was deter-
1
mined on the basis of their IR, H and 13C NMR, and
mass spectra. Unlike initial Schiff bases X–XVIII, the
IR spectra of amines XIX–XXVII lacked absorption
bands assignable to stretching vibrations of azomethine
C=N bond, but NH absorption bands were present in
Scheme 2.
N
HN
HN
R
R
R
NaBH4, AcOH
X
N
X
N
X
N
H
XV, XVII
A
XXVI, XXVII
XV, XXVII, X = H, R = 3-O2N; XVII, XXVI, X = Me, R = 4-MeOCO.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 7 2009

IGNATOVICH et al.
1072
the region 3450–3360 cm–1. The NH proton resonated
in the H NMR spectra of XIX–XXVII at δ 3.92–
6.80 ppm, and signal from the NCH2 group was locat-
A primary amino group was introduced into mole-
cules of amines XIX–XXII via Zinin reaction, i.e., by
reduction of compounds XIX–XXII with hydrazine
hydrate over Raney nickel, as described in [16] for
aromatic nitro compounds. For this purpose, hydrazine
hydrate was added to a mixture of XIX–XXII and the
catalyst, and the mixture was heated at 50–60°C for
a short time. As a result, we isolated 80–85% of
N-benzyl- and N-(pyridin-3-ylmethyl)benzene-1,3-di-
amines XXVIII–XXXI. The reaction of nitro-substi-
tuted Schiff bases X–XIII with hydrazine hydrate over
Raney nickel was accompanied by reduction of the
azomethine bond, and the products were the same di-
amines (XXVIII–XXXI) as those obtained from nitro-
anilines XIX–XXII (Scheme 3). Under analogous con-
ditions, the reduction of N-(3-nitrobenzylidene)quino-
lin-5-amine (XV) involved the azomethine C=N bond
and the nitro group, while the quinoline ring remained
unchanged, and the product was N-(3-aminobenzyl)-
quinolin-5-amine (XXXII) (Scheme 4).
1
ed at δ 4.41–4.59 ppm. The corresponding carbon
13
signal appeared in the C NMR spectra of XIX–XXV
at δC 48.0–50.0 ppm and was the only signal in that
region in the spectra of most amines, except for com-
pounds XIX, XX, XXIV, and XXV having a methoxy-
carbonyl group or other carbon-containing substituent.
1
The H NMR spectra of tetrahydroquinoline deriva-
tives XXVI and XXVII contained signals in the region
δ 1.63–3.44 ppm due to methylene protons in the
hydrogenated heteroring, and the NH proton in the
heteroring gave a signal at δ 3.80–3.98 ppm. Amines
XXVI and XXVII displayed in the 13C NMR spectra
six and four signals, respectively, in the region
δC 21.5–52.3 ppm. Among these, three signals belong
to the endocyclic methylene groups, and one signal
(δC 46.5–48.0 ppm) originates from the exocyclic
methylene group; the other signals belong to carbon-
containing substituents.
The product structure was confirmed by spectral
methods. The primary amino group in molecules
XXVIII–XXXI gave rise to IR absorption bands in the
region 3460–3380 cm–1, stretching vibrations of the sec-
ondary N–H bonds had a frequency of 3400–3380 cm–1,
and absorption bands in the region 1620–1580 cm–1
were assigned to bending vibrations of the amino
group. In the 1H NMR spectra of compounds XXVIII–
XXXI we observed a singlet from proton in the second-
ary amino group and broadened two-proton singlets
from the primary amino group. The position of these
signals was not characteristic, and it depended on the
structure of particular compound. It should be noted
that signals from aromatic protons in the benzene-
diamine fragment of XXVIII–XXXI were displaced
appreciably upfield (by about 1.5 ppm) relative to the
corresponding signals of the initial nitro derivatives;
the position of signals from the aromatic carbon atoms
in the 13C NMR spectra almost did not change.
Molecules of Schiff bases X–XVIII and the corre-
sponding reduction products XIX–XXVII contain
pharmacophoric heterocyclic fragments, bromine
atom, and reactive imino, amino, nitro, ester, and other
groups. Therefore, these compounds are promising as
potential biologically active substances with a broad
spectrum of activity, as well as intermediate products
for the preparation of new compounds possessing
practically important properties. Among numerous
reactions involving the above groups, of particular
interest are condensations of imines and secondary
amines with CH acids, which could lead to polynuclear
fused heterocycles having pyridine and quinoline frag-
ments [11–14]. Carboxy group is a precursor of amide
bond in biomolecules. Molecules of many medicines
contain a nitro group [15] which can be reduced to
primary amino group responsible for high chemical
and biological potential.
Scheme 3.
HN
R
Y
HN
R
Y
N
R
Y
N
R
Y
N2H4, Raney Ni
N2H4, Raney Ni
O2N
H2N
XXVIII–XXXI, XXXV
H2N
O2N
X–XIII, XXIII
XIX–XXII
B
X, XI, XIX, XX, XXVIII, XXIX, XXXIII, XXXV, R = 4-MeOCOC6H4; XII, XIII, XXI, XXII, XXX, XXXI, R = pyridin-3-yl;
X, XII, XIX, XXI, XXVIII, XXX, XXXIII, XXXV, Y = H; XI, XIII, XX, XXII, XXIX, XXXI, Y = Me; X, XII, XIX, XXI,
Y = 3-O2N; XI, XIII, XX, XXII, Y = 5-O2N; XXXIII, Y = 4-O2N; XXVIII, XXX, Y = 3-H2N; Y = XXIX, XXXI, 5-H2N;
XXXV, Y = 4-H2N.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 7 2009

REDUCTIVE TRANSFORMATIONS OF SCHIFF BASES
1073
Scheme 4.
NO2
NH2
N2H4, Raney Ni
H
N
N
N
N
XV, XXIV
XXXII, XXXVI
XV, 5-CH=N, 3-O2N; XXIV, 6-CH=N, 4-O2N; XXXII, 5-NHCH2, 3-H2N; XXXVI, 6-NHCH2, 4-H2N.
The system hydrazine hydrate–Raney nickel was
also used to reduce methyl 4-(4-nitrophenylimino-
methyl)benzoate (XXXIII) and N-(4-nitrobenzylidene)-
quinolin-6-amine (XXXIV) which are isomeric to
Schiff bases X and XV; the nitro group in molecules
XXXIII and XXXIV is conjugated with the C=N
bond. The reduction products were methyl 4-(4-amino-
phenylaminomethyl)benzoate (XXXV) and
N-(4-aminobenzyl)quinolin-6-amine (XXXVI)
(Schemes 3, 4). Their yields (75 and 70%) were com-
parable with the yields of isomeric compounds
XXVIII and XXXV. These data suggest the absence
of mesomeric effect of nitro group in both amine and
aldehyde fragments on the reaction course. 5- and
6-Aminoquinoline, pyridine, and pyrimidine rings and
carboxy and amide groups remain intact in the reduc-
tion with hydrazine hydrate over Raney nickel, but this
system readily reduces aldehyde group.
It is known that hydrazine hydrate, which is usually
used for selective reduction of nitro group to amino,
also reduces nonactivated C=C bond in dicyclopenta-
diene under analogous conditions [17]. Exocyclic C=N
bond in Schiff bases is readily reduced with hydrogen
generated in situ during aromatization of hydrogenated
pyridine ring in the synthesis of azaphenanthrenes
from Schiff bases [12, 14]. Taking into account high
catalytic activity of Raney nickel, the observed trans-
formation of the C=N bond in the reduction of nitro-
substituted Schiff bases with hydrazine hydrate is quite
explicable. This reaction deserves specific attention as
a one-step procedure for the conversion of nitro imines
into diamines.
With a view to determine the scope of the above
procedure and the effect of nitro group and its position
on the composition of reduction products, we ex-
amined reduction with hydrazine hydrate over Raney
nickel of Schiff bases XVI and XVIII having no nitro
group. We thus obtained the corresponding secondary
amines XXIV and XXV in high yield (85–92%), as in
the reduction of Schiff bases XVI and XVIII with
sodium tetrahydridoborate. No reduction of the hetero-
cyclic fragment was observed. The reaction of Schiff
base XVII with hydrazine hydrate in the presence of
Raney nickel gave benzylamine A (Scheme 2), while
hydrogenated quinoline derivative XXVI was not de-
tected even in trace amount.
It was also interesting to estimate the probability
for decomposition of initial Schiff bases by the action
of strong base under the reduction conditions. Decom-
position products (up to 20%) were detected in Schiff
bases derived from p-nitrobenzaldehyde in which the
nitro group is conjugated with the reaction center. For
example, the reduction of m-nitrophenyl derivative XV
gives up to 15% of quinolin-6-amine. Analogous retro
reaction was observed in some cases with the use of
less active skeletal catalyst. Therefore, the activity of
skeletal catalyst is crucial for decomposition of Schiff
bases by the action of strong base, which is concurrent
to the reduction of the C=N bond.
Monitoring of the reaction progress by TLC
showed formation of intermediate product (obviously,
imino amine B; Scheme 3) in a few minutes after addi-
tion of hydrazine hydrate and the catalyst; the corre-
sponding nitrobenzylamines XIX–XXII (reduction
products of Schiff bases with sodium tetrahydrido-
borate) were absent in the reaction mixture. These
findings indicate that in the reduction with hydrazine
hydrate amino-substituted Schiff base B is formed
initially and that the subsequent hydrogenation of the
C=N bond in the latter yields the final diamine.
We can conclude that variation of reducing agents
in the hydrogenation of functionally substituted Schiff
bases, including those containing a nitro group,
ensures selective synthesis of secondary amines with
conservation of the nitro group, benzylamines of the
quinoline series with partially hydrogenated hetero-
cyclic fragment, and pyridyl-, pyrimidinyl-, and quin-
olyl-substituted diamines having both primary and
secondary amino groups.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 7 2009

IGNATOVICH et al.
H 4.51; N 9.26. C16H14N2O4. Calculated, %: C 64.43;
1074
EXPERIMENTAL
H 4.70; N 9.40.
The IR spectra were measured in KBr on a Nicolet
Protégé-460 spectrometer with Fourier transform. The
1H and 13C NMR spectra were recorded on from solu-
tions in CDCl3 and DMSO-d6 a Bruker Avance-500
spectrometer at 500 and 125 MHz, respectively, using
tetramethylsilane as internal reference. The mass spec-
tra (electron impact, 70 eV) were obtained on
a Hewlett–Packard 5890/5972 GC–MS (HP-5MS cap-
illary column, 30 m×0.25 mm, stationary phase 5% of
phenylmethylsilicone; injector temperature 250°C).
Thin-layer chromatography was performed on Kiesel-
gel 60 F254 plates (Merck) using butanol–ethanol–
NH4OH (8:1:1) and chloroform–methanol (95:5) as
eluents.
3-Nitro-N-(pyridin-3-ylmethylidene)aniline
(XII). Yield 82%, mp 95°C. IR spectrum, ν, cm–1:
3090, 3030, 1725 (C=O), 1623 (C=N), 1518, 1355
1
(NO2). H NMR spectrum (DMSO-d6), δ, ppm: 7.30 t
3
3
(1H, 5′-H, J = 7.4 Hz), 7.44 d.d (1H, 5-H, J = 8.8,
4
4.7 Hz), 7.84 d (1H, 2′-H, J = 2.3 Hz), 8.08 d.d (1H,
3
4
3
4′-H, J = 7.4, J = 2.3 Hz), 8.20 d (1H, 6′-H, J =
7.4 Hz), 8.38 d (1H, 6-H, 3J = 9.0, 4J = 1.6 Hz), 8.49 s
(1H, CH=N), 8.77 d.d (1H, 4-H, 3J = 4.7, 4J = 1.4 Hz),
9.14 d (1H, 2-H, 4J = 1.4 Hz). Mass spectrum: m/z 227
[M]+. Found, %: C 63.27; H 3.89; N 18.36. C12H9N3O2.
Calculated, %: C 63.44; H 3.96; N 18.50.
2-Methyl-5-nitro-N-(pyridin-3-ylmethylidene)-
aniline (XIII). Yield 80%, mp 154–155°C. IR spec-
trum, ν, cm–1: 3065, 3030, 2920, 2850, 1625 (C=N),
1522, 1350 (NO2). H NMR spectrum (DMSO-d6), δ,
ppm: 2.47 s (3H, Me), 7.41 d (1H, 3′-H, J = 8.3 Hz),
N-[4-(Pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-di-
amine (IX) [7], methyl 4-(4-nitrophenyliminomethyl)-
benzoate (XXXIII) [9], and N-(4-nitrophenylmethyli-
dene)quinolin-6-amine (XXXIV) [18] were synthe-
sized by known methods.
1
3
3
4
7.48 d.d (1H, 5-H, J = 9.2, J = 4.8 Hz), 7.84 d (1H,
4
3
4
6′-H, J = 2.3 Hz), 8.04 d.d (1H, 4′-H, J = 8.3, J =
3
4
2.3 Hz), 8.33 d.d (1H, 6-H, J = 9.2, J = 1.8 Hz),
Schiff bases X–XVIII (general procedure). A solu-
tion of equimolar amounts (10 mmol) of aldehyde I–
IV and amine V–IX in 30 ml of ethanol was heated for
10–30 min under reflux. The mixture was cooled, and
the precipitate was filtered off and recrystallized from
ethanol (X–XIV, XVIII) or ethanol–benzene (2:1)
(XV–XVII).
3
4
8.51 s (1H, CH=N), 8.77 d.d (1H, 4-H, J = 4.8, J =
1.6 Hz), 9.10 d (1H, 2-H, 4J = 1.6 Hz). 13C NMR spec-
trum, δC, ppm: 158.70, 152.59, 151.03, 150.90, 146.94,
140.36, 135.28, 131.21, 130.89, 123.88, 120.76,
112.35, 18.18. Found, %: C 64.68; H 4.41; N 17.25.
C13H11N23O2. Calculated, %: C 64.73; H 4.56; N 17.43.
N-(4-Bromophenylmethylidene)quinolin-5-
amine (XIV). Yield 85%, mp 108–109°C. IR spec-
trum, ν, cm–1: 3070, 3055, 1620 (C=N). 1H NMR spec-
Methyl 4-(3-nitrophenyliminomethyl)benzoate
(X). Yield 96%, mp 147–148°C. IR spectrum, ν, cm–1:
3060, 3048, 2940, 2850, 1718 (C=O), 1624 (C=N),
3
trum (CDCl3),, δ, ppm: 7.14 d (1H, 6′-H, J = 7.3 Hz),
1
3
1517, 1350 (NO2). H NMR spectrum (CDCl3), δ,
7.43 d.d (1H, 3′-H, J = 8.3, 4.2 Hz), 7.65 d (2H, 2-H,
6-H, 3J = 7.6 Hz), 7.70 t (1H, 7′-H, 3J = 8.5 Hz), 7.87 d
ppm: 3.95 s (3H, OMe), 7.54 d and 7.57 t (2H, 5′-H,
6′-H, 3J = 8.1 Hz), 7.99 d (2H, 2-H, 6-H, 3J = 8.2 Hz),
3
3
(2H, 3-H, 5-H, J = 7.6 Hz), 8.00 d (1H, 8′-H, J =
8.5 Hz), 8.52 s (1H, CH=N), 8.69 d (1H, 4′-H, J =
3
8.06 s (1H, 2′-H), 8.11 d (1H, 4′-H, J = 8.1 Hz),
8.16 d (2H, 3-H, 5-H, 3J = 8.2 Hz) 8.55 s (1H, CH=N).
13C NMR spectrum (CDCl3), δC, ppm: 166.12, 161.15,
152.34, 148.70, 138.84, 132.81, 129.83, 129.76,
128.74, 127.35, 120.66, 115.09, 52.16. Found, %:
C 63.14; H 4.21; N 9.73. C15H12N2O4. Calculated, %:
C 63.38; H 4.23; N 9.86.
3
5
8.3 Hz), 8.95 d.d (1H, 2′-H, J = 4.2, J = 1.5 Hz).
13C NMR spectrum, δC, ppm: 159.42, 150.62, 148.30,
148.26, 134.66, 132.24, 131.88, 130.08, 129.21,
127.12, 126.10, 123.99, 120.57, 112.67. Found, %:
C 61.57; H 3.39; Br 25.60; N 8.72. C16H11BrN2. Cal-
culated, %: C 61.74; H 3.54; Br 25.72; N 9.00.
Methyl 4-(2-methyl-5-nitrophenyliminomethyl)-
benzoate (XI). Yield 92%, mp 182–183°C. IR spec-
trum, ν, cm–1: 3070, 3030, 2964, 2920, 1725 (C=O),
N-(3-Nitrophenylmethylidene)quinolin-5-amine
(XV). Yield 80%, mp 157–158°C. IR spectrum, ν,
cm–1: 3060, 3040, 1623 (C=N), 1532, 1350 (NO2).
1H NMR spectrum (CDCl3), δ, ppm: 7.16 d (1H, 6′-H,
1
1630 (C=N), 1520, 1355 (NO2). H NMR spectrum
3
3J = 7.3 Hz), 7.42 d.d (1H, 3′-H, J = 8.4, 4.1 Hz),
(CDCl3), δ, ppm: 2.46 s (3H, Me), 3.96 s (3H, OMe),
3
4
7.69 m (2H, 5-H, 7′-H), 8.01 d (1H, 8′-H, 3J = 8.4 Hz),
7.38 d (1H, 3′-H, J = 8.2 Hz), 7.82 d (1H, 6′-H, J =
3
3
3
2.8 Hz), 8.00 d (2H, 2-H, 6-H, J = 8.1 Hz), 8.03 d
(1H, 4′-H, J = 8.2 Hz), 8.18 d (2H, 3-H, 5-H, J =
8.30 d (1H, 6-H, J = 7.6 Hz), 8.34 d (1H, 4-H, J =
3
3
3
8.1 Hz), 8.60 s (1H, CH=N), 8.69 d (1H, 4′-H, J =
8.4 Hz), 8.83 s (1H, 2-H), 8.94 d (1H, 2′-H, J =
3
8.1 Hz), 8.49 s (1H, CH=N). Found, %: C 64.35;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 7 2009

REDUCTIVE TRANSFORMATIONS OF SCHIFF BASES
1075
4.1 Hz). 13C NMR spectrum, δC, ppm: 158.07, 151.04,
148.73, 148.53, 147.75, 137.61, 134.39, 132.40, 129.94,
129.38, 128.11, 125.93, 124.31, 123.54, 121.05, 112.96.
Found, %: C 69.11; H 3.76; N 14.94. C16H11N3O2. Cal-
culated, %: C 69.31; H 3.97; N 15.16.
10 mmol of Schiff base X–XVIII in 30 ml of benzene
was added under stirring at 0°C to a mixture of NaBH4
(20 mmol in the synthesis of compounds XIX–XXVI
or 60 mmol in the synthesis of XXVII), 10 ml of ben-
zene, and glacial acetic acid (60 mmol in the synthesis
of XIX–XXVI or 360 mmol in the synthesis of
XXVII). The mixture was stirred for 2 h without
external cooling and was left to stand for 20 h at room
temperature. The mixture was then treated with 40–
50 ml of 20% aqueous sodium hydroxide, and the or-
ganic phase was separated, washed with water, and dried
over MgSO4. The solvent was distilled off, and the
solid residue was recrystallized from ethanol (XIX–
XXII, XXVI, XXVII) or toluene (XXIII–XXV).
Methyl 4-(quinolin-5-yliminomethyl)benzoate
(XVI). Yield 83%, mp 157–158°C. IR spectrum, ν,
cm–1: 3040, 3005, 2940, 2858, 1716 (C=O), 1623
1
(C=N). H NMR spectrum (CDCl3), δ, ppm: 3.98 s
3
(3H, OMe), 7.18 d (1H, 6′-H, J = 7.4 Hz), 7.45 d.d
3
3
(1H, 3′-H, J = 8.4, 4.2 Hz), 7.72 t (1H, 7′-H, J =
3
7.4 Hz), 8.03 d (1H, 8′-H, J = 7.4 Hz), 8.09 d (2H,
3
3
2-H, 6-H, J = 8.2 Hz), 8.19 d (2H, 3-H, 5-H, J =
3
8.2 Hz), 8.65 s (1H, CH=N), 8.73 d (1H, 4′-H, J =
8.4 Hz), 8.97 d (1H, 2′-H, 3J = 4.2 Hz). 13C NMR spec-
trum, δC, ppm: 167.03, 160.41, 151.46, 149.04, 148.99,
146.49, 140.30, 133.21, 133.10, 130.60, 130.02, 129.42,
128.19, 124.88, 121.47, 113.50, 52.94. Found, %:
C 74.25; H 4.71; N 9.53. C18H14N2O2. Calculated, %:
C 74.48; H 4.83; N 9.66.
Methyl 4-(3-nitrophenylaminomethyl)benzoate
(XIX). Yield 79%, mp 125–126°C. IR spectrum, ν,
cm–1: 3410 (NH), 3080, 3060, 2950, 2900, 1720
(C=O), 1620 (δNH), 1540, 1340 (NO2). 1H NMR spec-
trum (CDCl3), δ, ppm: 3.91 s (3H, OMe), 4.46 d (2H,
3
CH2, J = 5.8 Hz), 4.52 br.s (1H, NH), 6.85 d.d (1H,
3
4
3
6′-H, J = 8.1, J = 2.3 Hz), 7.25 t (1H, 5′-H, J =
Methyl 4-(2-methylquinolin-5-yliminomethyl)-
benzoate (XVII). Yield 78%, mp 169–170°C. IR spec-
trum, ν, cm–1: 3055, 3035, 2950, 2850, 1717 (C=O),
3
8.1 Hz), 7.41 d (2H, 2-H, 6-H, J = 8.1 Hz), 7.43 br.s
3
4
(1H, 2′-H), 7.53 d.d (1H, 4′-H, J = 8.1, J = 1.7 Hz),
8.02 d (2H, 3-H, 5-H, J = 8.1 Hz). 13C NMR spec-
3
1
1623 (C=N). H NMR spectrum (CDCl3), δ, ppm:
trum, δC, ppm: 167.01, 149.60, 148.63, 143.58, 130.39,
130.09, 129.76, 127.35, 118.93, 112.72, 106.93, 52.40,
47.92. Mass spectrum: m/z 286 [M]+. Found, %:
C 62.80; H 4.83; N 9.54. C15H14N2O4. Calculated, %:
C 62.94; H 4.90; N 9.79.
2.77 s (3H, Me), 3.97 s (3H, OMe), 7.11 d (1H, 6′-H,
3
3J = 7.5 Hz), 7.32 d (1H, 3′-H, J = 7.5 Hz), 7.65 d.d
3
3
(1H, 7′-H, J = 7.5, 8.5 Hz), 7.93 d (1H, 8′-H, J =
3
8.5 Hz), 8.08 d (2H, 2-H, 6-H, J = 8.3 Hz), 8.18 d
3
3
(2H, 3-H, 5-H, J = 8.3 Hz), 8.59 d (1H, 4′-H, J =
8.5 Hz), 8.62 s (1H, CH=N). 13C NMR spectrum, δC,
ppm: 166.47, 159.62, 159.54, 148.26, 148.15, 139.79,
132.53, 130.00, 129.39, 128.80, 126.90, 122.44, 121.78,
121.34, 112.20, 52.35, 25.34. Found, %: C 74.82;
H 5.19; N 9.02. C19H16N2O2. Calculated, %: C 75.00;
H 5.26; N 9.21.
Methyl 4-(2-methyl-5-nitrophenylaminomethyl)-
benzoate (XX). Yield 82%, mp 120–121°C. IR spec-
trum, ν, cm–1: 3420 (NH), 3100, 3080, 2930, 2860,
1
1712 (C=O), 1612 (NH), 1530, 1341 (NO2). H NMR
spectrum (CDCl3), δ, ppm: 2.24 s (3H, Me), 3.90 s
3
(3H, OMe), 4.20 t (1H, NH, J = 5.5 Hz), 4.50 d (2H,
3
3
CH2, J = 5.5 Hz), 7.16 d (1H, 3′-H, J = 8.0 Hz),
Methyl 4-{3-[4-(pyridin-3-yl)pyrimidin-2-yl-
amino]phenyliminomethyl}benzoate (XVIII). Yield
80%, mp 174–175°C. IR spectrum, ν, cm–1: 3302
(NH), 3080, 3030, 2940, 2855, 1718 (C=O), 1610
4
7.33 d (1H, 6′-H, J = 1.6 Hz), 7.43 d (2H, 2-H, 6-H,
3J = 8.2 Hz), 7.51 d.d (1H, 4′-H, 3J = 8.0, 4J = 1.6 Hz),
8.01 d (2H, 3-H, 5-H, J = 8.1 Hz). 13C NMR spec-
3
1
trum, δC, ppm: 166.47, 147.46, 145.87, 143.04, 129.98,
129.90, 129.43, 129.31, 129.10, 127.00, 112.21, 103.71,
51.87, 47.43, 17.51. Mass spectrum: m/z 300 [M]+.
Found, %: C 63.76; H 5.20; N 9.17. C16H16N2O4. Cal-
culated, %: C 64.00; H 5.53; N 9.33.
(C=N). H NMR spectrum (CDCl3), δ, ppm: 3.80 s
(3H, OMe), 6.97 d (1H, 5′-H, 3J = 8.0 Hz), 7.21 d (1H,
3
5″-H, J = 5.1 Hz), 7.43 m (2H, 6′-H, 5′′′-H), 7.56 m
(2H, 2′-H, 4′-H), 7.71 s (1H, NH), 7.99 d (2H, 2-H,
3
3
6-H, J = 8.2 Hz), 8.16 d (2H, 3-H, 5-H, J = 8.2 Hz),
8.36 d (1H, 4′′′-H, 3J = 7.9 Hz), 8.54 d (1H, 6″-H, 3J =
5.1 Hz), 8.58 s (1H, CH=N), 8.73 d (1H, 6′′′-H, J =
3-Nitro-N-(pyridin-3-ylmethyl)aniline (XXI).
Yield 80%, mp 143–144°C. IR spectrum, ν, cm–1: 3396
(NH), 3065, 3040, 2920, 2855, 1620 (NH), 1537, 1345
3
4.7 Hz), 9.31 s (1H, 2′′′-H). Found, %: C 70.29;
H 4.56; N 16.83. C24H19N5O2. Calculated, %: C 70.42;
H 4.65; N 17.11.
1
(NO2). H NMR spectrum (CDCl3), δ, ppm: 4.48 d
(2H, CH2, 3J = 5.6 Hz), 5.78 br.s (1H, NH), 6.86 d (1H,
6′-H, 3J = 7.4 Hz), 7.27 t (1H, 5′-H, 3J = 7.4 Hz), 7.43 s
(1H, 2′-H), 7.50 m (2H, 5-H, 4′-H), 7.94 d (1H, 4-H,
Reduction of Schiff bases X–XVIII with sodium
tetrahydridoborate. A solution or suspension of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 7 2009

IGNATOVICH et al.
1076
3
3J = 7.8 Hz), 8.50 d (1H, 6-H, J = 5.3 Hz), 8.64 s
(1H, 2-H). 13C NMR spectrum, δC, ppm: 149.35,
148.16, 146.40, 146.31, 146.08, 137.76, 129.77, 125.03,
118.29, 112.28, 106.76, 44.58. Mass spectrum: m/z 229
[M]+. Found, %: C 62.63; H 4.55; N 18.31. C12H11N3O2.
Calculated, %: C 62.88; H 4.80; N 18.34.
(NH), 3360, 3040, 3010, 2923, 2854, 1716 (C=O),
1600 (NH). 1H NMR spectrum (CDCl3), δ, ppm: 3.92 s
3
(3H, OMe), 4.30 br.s (1H, NH), 4.45 d (2H, CH2, J =
3
5.7 Hz), 6.34 d (1H, 5′-H, J = 8.0 Hz), 6.99 d (1H,
6′-H, 3J = 7.4 Hz), 7.17 m (3H, 2′-H, 4-H, NH), 7.28 d
3
3
(1H, 5″-H, J = 5.2 Hz), 7.42 d.d (1H, 5′′′-H, J = 8.0,
4J = 4.1 Hz), 7.45 d (2H, 2-H, 6-H, 3J = 8.1 Hz), 8.18 d
(2H, 3-H, 5-H, J = 8.1 Hz), 8.34 d (1H, 4′′′-H, J =
8.0 Hz), 8.48 d (1H, 6″-H, J = 5.2 Hz), 8.73 d (1H,
2-Methyl-5-nitro-N-(pyridin-3-ylmethyl)aniline
(XXII). Yield 78%, mp 117–118°C. IR spectrum, ν,
cm–1: 3382 (NH), 3080, 3055, 2940, 2860, 1615 (NH),
1540, 1355 (NO2). H NMR spectrum (CDCl3), δ,
ppm: 2.42 s (3H, Me), 4.39 d (2H, CH2, J = 5.0 Hz),
3
3
3
6′′′-H, 3J = 4.1 Hz), 9.28 s (1H, 2′′′-H). 13C NMR spec-
trum, δC, ppm: 166.68, 162.19, 160.04, 158.61, 151.16,
148.27, 146.26, 144.65, 140.12, 136.66, 134.87, 134.17,
132.49, 129.46, 128.74, 126.84, 125.03, 123.33, 108.72,
107.91, 107.29, 103.39, 51.81, 47.70. Found, %:
C 69.93; H 4.85; N 16.87. C24H21N5O2. Calculated, %:
C 70.07; H 5.11; N 17.03.
1
3
3
5.68 br.s (1H, NH), 7.38 d (1H, 3′-H, J = 8.1 Hz),
3
7.49 d.d (1H, 5-H, J = 8.0, 5.6 Hz), 7.76 d (1H, 6′-H,
4J = 1.9 Hz), 7.96 d.d (1H, 4′-H, 3J = 8.1, 4J = 1.9 Hz),
3
3
8.01 d (1H, 4-H, J = 8.0 Hz), 8.54 d (1H, 6-H, J =
5.6 Hz), 8.61 d (1H, 2-H, 4J = 1.9 Hz). Mass spectrum:
m/z 243 [M]+. Found, %: C 63.99; H 5.23; N 17.04.
C13H13N3O2. Calculated, %: C 64.20; H 5.35; N 17.28.
Methyl 4-(2-methyl-1,2,3,4-tetrahydroquinolin-
5-ylaminomethyl)benzoate (XXVI). Yield 75%,
mp 94–95°C. IR spectrum, ν, cm–1: 3410 (NH), 3396,
3070, 3052, 2925, 2915, 2855, 1718 (C=O), 1610
(NH). 1H NMR spectrum (CDCl3), δ, ppm: 1.20 d (3H,
Me), 1.63 m and 2.01 m (2H, 3′-H), 2.48 m (2H, 4′-H),
3.33 m (1H, 2′-H), 3.80 br.s (1H, NH), 3.91 s (3H,
OMe), 4.41 s (2H, CH2), 3.90 br.s (1H, NH), 5.94 d
(1H, 6′-H, 3J = 8.0 Hz), 6.00 d (1H, 8′-H, 3J = 8.0 Hz),
N-(4-Bromobenzyl)quinolin-5-amine (XXIII).
Yield 84%, mp 164–165°C. IR spectrum, ν, cm–1: 3410
(NH), 3060, 3035, 2942, 2855, 1618 (NH). H NMR
spectrum (DMSO-d6), δ, ppm: 4.46 d (2H, CH2, J =
5.5 Hz), 6.34 d (1H, 6′-H, J = 7.6 Hz), 6.70 br.s (1H,
1
3
3
3
NH), 7.25 d (1H, 7′-H, J = 7.6 Hz), 7.30 d (2H, 2-H,
6-H, 3J = 8.4 Hz), 7.35 d.d (1H, 3′-H, 3J = 8.5, 4.1 Hz),
3
6.84 t (1H, 7′-H, J = 8.0 Hz), 7.43 d (2H, 2-H, 6-H,
3
7.39 d (1H, 8′-H, J = 7.6 Hz), 7.43 d (2H, 3-H, 5-H,
3
3J = 8.2 Hz), 8.00 d (2H, 3-H, 5-H, J = 8.2 Hz).
3
3J = 8.4 Hz), 8.59 d (1H, 4′-H, J = 8.5 Hz), 8.78 d
13C NMR spectrum, δC, ppm: 167.20, 146.14, 145.61,
145.55, 130.12, 129.18, 127.41, 105.58, 105.43, 102.38,
100.45, 52.29, 48.29, 46.51, 30.33, 22.49, 21.54. Found,
%: C 73.40; H 6.97; N 8.78. C19H22N2O2. Calculated,
%: C 73.55; H 7.10; N 9.03.
(1H, 2′-H, J = 4.1 Hz). 13C NMR spectrum, δC, ppm:
3
148.37, 147.79, 142.74, 137.48, 130.09, 129.14, 129.00,
127.67, 119.06, 118.97, 117.78, 115.82, 102.92, 94.70,
45.88. Found, %: C 61.23; H 3.95; Br 25.41; N 8.61.
C16H13BrN2. Calculated, %: C 61.34; H 4.15; Br 25.56;
N 8.95.
N-(3-Nitrobenzyl)-1,2,3,4-tetrahydroquinolin-5-
amine (XXVII). Yield 76%, mp 108–109°C. IR spec-
trum, ν, cm–1: 3440, 3412 (NH), 3055, 3030, 2923,
Methyl 4-(quinolin-5-ylaminomethyl)benzoate
(XXIV). Yield 72%, mp 108–109°C. IR spectrum, ν,
cm–1: 3413 (NH), 3080, 3070, 2936, 2852, 1716
1
2850, 1600 (NH), 1526, 1344 (NO2). H NMR spec-
trum (CDCl3), δ, ppm: 2.04 m (2H, 3′-H), 2.53 m (2H,
4′-H), 3.25 m (2H, 2′-H), 3.98 br.s (1H, NH), 4.47 s
1
(C=O), 1615 (NH). H NMR spectrum (DMSO-d6), δ,
ppm: 3.89 s (3H, OMe), 4.59 d (2H, CH2, 3J = 5.3 Hz),
3
(2H, CH2), 4.92 br.s (1H, NH), 5.88 d (1H, 6′-H, J =
3
3
6.48 d (1H, 6′-H, J = 8.1 Hz), 6.80 br.s (1H, NH),
7.40–7.54 m (5H, 2-H, 6-H, 4′-H, 7′-H, 8′-H), 7.57 t
8.1 Hz), 6.03 d (1H, 8′-H, J = 8.1 Hz), 6.64 t (1H,
7′-H, 3J = 8.1 Hz), 7.49 m (2H, 5-H, 6-H), 8.26 m (2H,
2-H, 4-H). 13C NMR spectrum, δC, ppm: 149.92,
145.33, 142.09, 140.73, 133.05, 129.86, 129.22, 126.82,
121.80, 119.39, 105.43, 99.88, 47.31, 40.89, 22.01,
21.08. Found, %: C 67.69; H 5.73; N 14.58.
C16H17N3O2. Calculated, %: C 67.84; H 6.01; N 14.84.
3
3
(1H, 3′-H, J = 8.4 Hz), 7.97 d (2H, 3-H, 5-H, J =
8.2 Hz), 8.05 d (1H, 2′-H, 3J = 8.8 Hz). 13C NMR spec-
trum, δC, ppm: 167.27, 166.74, 165.70, 165.63, 163.96,
148.91, 143.68, 143.08, 134.54, 132.27, 128.92, 125.90,
118.76, 116.92, 111.14, 104.85, 95.07, 51.04, 46.37.
Found, %: C 73.74; H 5.21; N 9.36. C18H16N2O2. Cal-
culated, %: C 73.97; H 5.48; N 9.58.
Reduction of Schiff bases X–XIII, XV, XVI,
XVIII, XXXIII, and XXXIV and nitro-substituted
amines XIX–XXII with hydrazine hydrate over
Raney nickel (general procedure). Schiff base X–
XIII, XV, XVI, XVIII, XXXIII, or XXXIV or nitro
Methyl 4-{3-[4-(pyridin-3-yl)pyrimidin-2-yl-
amino]phenylaminomethyl}benzoate (XXV). Yield
65%, mp 142–143°C. IR spectrum, ν, cm–1: 3420
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 7 2009

REDUCTIVE TRANSFORMATIONS OF SCHIFF BASES
1077
3
4
amine XIX–XXII, 0.01 mol, was dissolved in 20 ml of
ethanol or ethanol (methanol)–tetrahydrofuran (3:1),
0.06 g of Raney nickel was added, and 0.04 mol of
80% hydrazine hydrate was then added. The mixture
foamed and turned colorless. It was stirred for 25–
45 min at 50–60°C and for 1 h at room temperature,
and filtered through a layer of celite, the filtrate was
evaporated, and the residue was purified by reprecip-
itation from toluene or ethyl acetate with hexane or
by recrystallization from toluene (XXIV, XXV). Crude
4-aminobenzylquinolin-6-amine (XXXVI) was treated
with boiling water to remove quinolin-6-amine and
dried prior to recrystallization. Analytical samples
were obtained through the corresponding hydro-
chlorides.
2.1 Hz), 6.07 d.d (1H, 4′-H, J = 7.8, J = 2.2 Hz),
3
4
6.09 d.d (1H, 6′-H, J = 7.8, J = 2.0 Hz), 6.95 t (1H,
5′-H, 3J = 7.8 Hz), 7.26 d.d (1H, 5-H, 3J = 7.9, 4.8 Hz),
3
3
7.68 d (1H, 6-H, J = 7.9 Hz), 8.51 d.d (1H, 4-H, J =
4
4
4.8, J = 1.6 Hz), 8.60 d (1H, 2-H, J = 1.6 Hz).
13C NMR spectrum, δC, ppm: 148.98, 148.77, 148.52,
147.54, 135.04, 130.13, 123.49, 105.38, 103.91, 99.45,
45.62. Mass spectrum: m/z 199 [M]+. Found, %:
C 72.19; H 6.46; N 20.88. C12H13N3. Calculated, %:
C 72.36; H 6.53; N 21.11.
6-Methyl-N1-(pyridin-3-ylmethyl)benzene-1,3-di-
amine (XXXI). Yield 83% (from XIII), 85% (from
XXII), mp 143–144°C. IR spectrum, ν, cm–1: 3440,
3380 (NH), 3070, 3040, 2942, 2855, 1600, 1580 (NH).
1H NMR spectrum (CDCl3), δ, ppm: 2.44 s (3H, Me),
4.48 s (2H, CH2), 3.78 br.s (3H, NH, NH2), 5.90 t
Methyl 4-(3-aminophenylaminomethyl)benzoate
(XXVIII). Yield 84% (from X), 85% (from XIX);
mp 125–126°C. IR spectrum, ν, cm–1: 3450, 3420,
3380 (NH, NH2), 3065, 3030, 2840, 2435, 1714
4
3
(1H, 2′-H, J = 1.4 Hz), 6.08 d.d (1H, 4′-H, J = 8.0,
1.4 Hz), 6.82 d (1H, 5′-H, J = 8.0 Hz), 7.23 d.d (1H,
5-H, J = 7.6, 4.5 Hz), 7.70 d (1H, 4-H, J = 7.5 Hz),
3
3
3
1
3
4
(C=O), 1609 (NH). H NMR spectrum (CDCl3), δ,
8.50 d.d (1H, 6-H, J = 5.0, J = 1.9 Hz), 8.64 d (1H,
2-H, J = 1.9 Hz). Mass spectrum: m/z 213 [M]+.
4
ppm: 3.75 br.s (2H, NH2), 4.20 s (3H, OMe), 4.44 br.s
(2H, CH2), 5.94 t (1H, 2′-H, 4J = 2.1 Hz), 6.12 d.d and
Found, %: C 72.19; H 6.46; N 20.88. C13H15N3. Calcu-
lated, %: C 72.36; H 6.53; N 21.11.
3
6.15 d.d (1H each, 4′-H, 6′-H, J = 7.8, 2.1 Hz), 7.02 t
3
3
(1H, 5′-H, J = 7.8 Hz), 7.49 d (2H, 2-H, 6-H, J =
8.1 Hz), 8.08 d (2H, 3-H, 5-H, 3J = 8.1 Hz). 13C NMR
spectrum, δC, ppm: 166.21, 148.71, 147.25, 144.72,
129.86, 129.59, 129.05, 126.76, 104.99, 103.72, 99.19,
60.63, 47.64. Found, %: C 70.22; H 6.09; N 10.63.
C15H16N2O2. Calculated, %: C 70.31; H 6.25; N 10.94.
N-(3-Aminobenzyl)quinolin-5-amine (XXXII).
Yield 78% (from XV), mp 108–109°C. IR spectrum, ν,
cm–1: 3458, 3420, 3388 (NH), 3065, 3048, 2942, 2855,
1610, 1592 (NH). 1H NMR spectrum (CDCl3), δ, ppm:
4.22 br.s (2H, NH2), 3.77 br.s (1H, NH), 4.47 s (2H,
CH2), 5.88 d (1H, 6′-H, 3J = 8.1 Hz), 6.03 d (1H, 8′-H,
3J = 8.1 Hz), 7.34 d.d (1H, 3′-H, 3J = 8.4, 4.1 Hz), 7.49 t
(1H, 7′-H, 3J = 8.1 Hz), 7.56 d (1H, 6-H, 3J = 8.4 Hz),
Methyl 4-(5-amino-2-methylphenylaminometh-
yl)benzoate (XXIX). Yield 80% (from XI), 83% (from
XX); mp 120–121°C. IR spectrum, ν, cm–1: 3473,
3445, 3380 (NH, NH2), 3060, 3030, 2920, 2850, 1708
3
3
8.15 d (1H, 8′-H, J = 7.2 Hz), 8.30 d (1H, 6-H, J =
3
7.6 Hz), 8.34 d (1H, 4-H, J = 8.1 Hz), 8.69 d (1H,
1
3
3
4
(C=O), 1620 (NH). H NMR spectrum (CDCl3), δ,
4′-H, J = 8.4 Hz), 8.86 d.d (1H, 2′-H, J = 4.1, J =
1.6 Hz). 13C NMR spectrum, δC, ppm: 161.97, 149.90,
148.73, 146.48, 141.98, 134.69, 129.74, 129.38, 129.28,
119.75, 119.51, 119.28, 117.84, 113.36, 109.72, 29.39.
Mass spectrum: m/z 249 [M]+. Found, %: C 76.98;
H 5.79; N 16.58. C16H15N3. Calculated, %: C 77.11;
H 6.02; N 16.87.
ppm: 2.07 s (3H, Me), 3.88 s (3H, OMe), 3.30 br.s
(2H, NH2), 4.38 s (2H, CH2), 3.48 br.s (1H, NH),
4
3
5.85 d (1H, 6-H, J = 2.2 Hz), 6.02 d.d (1H, 4-H, J =
8.0, 4J = 2.2 Hz), 6.82 d (1H, 3′-H, J = 8.0 Hz), 7.4 d
3
(2H, 2-H, 6-H, 3J = 8.2 Hz), 7.98 d (2H, 3-H, 5-H, 3J =
8.1 Hz). 13C NMR spectrum, δC, ppm: 166.94, 146.46,
145.70, 145.04, 130.70, 129.93, 128.99, 127.03, 112.36,
104.23, 97.97, 52.06, 47.84, 16.65. Mass spectrum:
m/z 270 [M]+. Found, %: C 70.94; H 6.39; N 10.19.
C16H18N2O2. Calculated, %: C 71.11; H 6.67; N 10.37.
Methyl 4-(4-aminophenylaminomethyl)benzoate
(XXXV). Yield 75% (from XXXIII), mp 125–126°C.
IR spectrum, ν, cm–1: 3460, 3410, 3385 (NH), 3080,
1
3055, 2928, 2852, 1600, 1580 (NH). H NMR spec-
N-(Pyridin-3-ylmethyl)benzene-1,3-diamine
(XXX). Yield 80% (from XII), 84% (from XXI);
mp 143–144°C. IR spectrum, ν, cm–1: 3460, 3430,
3390 (NH, NH2), 3065, 3035, 2925, 2845, 1605, 1588
(NH). 1H NMR spectrum (CDCl3), δ, ppm: 4.31 s (2H,
trum (CDCl3), δ, ppm: 3.90 s (3H, OMe), 4.20 br.s
(2H, NH2), 4.33 s (2H, CH2), 4.50 br.s (1H, NH),
3
6.49 d (2H, 2′-H, 6′-H, J = 8.6 Hz), 6.59 d (2H, 3′-H,
5′-H, 3J = 8.6 Hz), 7.43 d (2H, 2-H, 6-H, 3J = 8.3 Hz),
3
7.99 d (2H, 3-H, 5-H, J = 8.3 Hz). 13C NMR spec-
4
CH2), 4.00 br.s (3H, NH, NH2), 5.95 t (1H, 2′-H, J =
trum, δC, ppm: 166.71, 145.16, 140.61, 137.76, 129.58,
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IGNATOVICH et al.
1078
5. Romero, D.L., Busso, M., Tan, C-K., Reusser, F.,
Palmer, A.P.A., So, A.G., Resnick, L., and Tarplay, W.G.,
Proc. Natl. Acad. Sci. USA, 1991, vol. 88, p. 8806.
6. Leopoldo, M., Giorgio, P., Berardi, F., Lacivita, E.,
Colabuto, N.A., Perrone, R., and Tortorella, V., J. Med.
Chem., 2002, vol. 45, p. 5727.
7. Ignatovich, J., Gusak, K., Kozlov, N., Kovalev, V., and
Koroleva, E., Archivoc, 2008, part (ix), p. 51.
8. Szakacs, Z., Beni, S., Vagra, Z., Orfi, L., Keri, G., and
Noszal, B., J. Med. Chem., 2005, vol. 48, p. 249.
9. EPV Patent no. 0564409, 1994; Chem. Abstr., 1994,
vol. 120, no. 107056w.
10. Gribbl, G.W., Chem. Soc. Rev., 1998, vol. 27, p. 395;
Gribbl, G.W. and Heald, P.W., Synthesis, 1975, p. 650.
11. Kadutskii, A.P. and Kozlov, N.G., Synlett, 2006, p. 3349.
12. Gusak, K.N. and Kozlov, N.G., Russ. J. Org. Chem.,
128.15, 126.95, 116.56, 114.25, 51.79, 48.76. Mass
spectrum: m/z 256 [M]+. Found, %: C 70.15; H 6.05;
N 10.84. C15H16N2O2. Calculated, %: C 70.31; H 6.25;
N 10.94.
N-(4-Aminobenzyl)quinolin-6-amine (XXXVI).
Yield 78% (from XXXIV), mp 108–109°C. IR spec-
trum, ν, cm–1: 3455, 3400, 3392 (NH), 3065, 3035,
1
2930, 2848, 1598, 1590 (NH). H NMR spectrum
(CDCl3), δ, ppm: 3.98 br.s (3H, NH, NH2), 4.25 s (2H,
3
CH2), 6.64 d (2H, 3-H, 5-H, J = 8.1 Hz), 7.14 d (2H,
2-H, 6-H), 7.21 d.d and 7.24 d.d (1H each, 3′-H, 4′-H,
3J = 5.7, 3.1 Hz), 7.82–7.87 m (3H, 5′-H, 7′-H, 8′-H),
3
3
8.62 d.d (1H, 2′-H, J = 8.1, J = 1.5 Hz). 13C NMR
spectrum, δC, ppm: 146.94, 146.23, 144.84, 134.07,
133.99, 130.64, 130.32, 130.28, 129.10, 121.77, 121.57,
121.52, 115.46, 107.57, 103.22, 48.09. Found, %:
C 77.03; H 5.81; N 16.63. C16H15N3. Calculated, %:
C 77.11; H 6.02; N 16.87.
2007, vol. 43, p. 706.
13. Kozlov, N.G., Koroleva, E.V., Ignatovich, Zh.V., Gu-
sak, K.N., and Kadutskii, A.P., Russ. J. Org. Chem.,
2007, vol. 43, p. 901.
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