Synthesis of amino and hydroxy derivatives of 4,7-phenanthroline

Article abstract of DOI:10.1023/B:RUGC.0000039094.36299.03

Nitro-, dinitro-, and hydroxynitrophenyl-substituted 4,7-phenanthrolines were reduced with tin(II) chloride in a mixture of acetic and nitric acids to obtain amino, diamino, and hydroxy derivatives of 4,7-phenanthroline. When heated with aromatic aldehydes, the products form azomethines of the 4,7-phenanthroline series.

Full text of DOI:10.1023/B:RUGC.0000039094.36299.03

Russian Journal of General Chemistry, Vol. 74, No. 5, 2004, pp. 776 780. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 5, 2004,
pp. 844 848.
Original Russian Text Copyright
2004 by Gusak, Kozlov, Tereshko.
Synthesis of Amino and Hydroxy Derivatives
of 4,7-Phenanthroline
K. N. Gusak, N. G. Kozlov, and A. B. Tereshko
Institute of Physical Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Received April 15, 2002
Abstract Nitro-, dinitro-, and hydroxynitrophenyl-substituted 4,7-phenanthrolines were reduced with tin(II)
chloride in a mixture of acetic and nitric acids to obtain amino, diamino, and hydroxy derivatives of
4,7-phenanthroline. When heated with aromatic aldehydes, the products form azomethines of the 4,7-phen-
anthroline series.
Amino and hydroxy groups deserve special atten-
tion among functional substituents in heterocyclic
compounds. Amino- and hydroxy-substituted hetero-
cycles are interesting by their biological activity [1, 2]
and as starting materials for synthesis of diverse and
practically promising compounds, such as sulfamides,
acetylamines, azomethines, esters, and azo dyes.
varying substituents in the aldehyde moiety of the
Schiff base and in the phenyl ring of the acetophenone
one can obtain 4,7-phenanthrolines with desired
substituents. In this way, by reacting (p-dialkylamino-
phenyl)methylene- and o- and p-hydroxyphenylme-
thylene-6-quinolylamines with acetophenone, as well
as by reacting azomethines of the 6-aminoquinoline
series with p-hydroxyacetophenone we synthesized
p-dialkylaminophenyl- and hydroxyphenyl-substituted
4,7-phenanthrolines. However, this approach fails to
provide 4,7-phenanthroline with a free amino group.
The amino-substituted benzaldehyde required to
prepare the corresponding Schiff base forms a
polymer that does not react with 6-quinolylamine.
The synthesis of 4,7-phenanthrolines containing
hydroxy groups has been reported in [3, 4]. These
compounds are most commonly obtained by Conrad
Limpach and Knorr reactions, starting from
6-quinolylamine or p-phenylenediamine and esters of
-oxo- and -dicarboxylis acids. Amino derivatives of
4,7-phenanthroline are less accessible. Mlochowski
and Skrowarczewska managed to nitrate 4,7-phen-
anthroline to obtain 5-nitro-4,7-phenanthroline [5],
but did not reduce the latter. 5-Amino-4,7-phenanthro-
line [6] was prepared by substitution of the halogen
in 5-chloro- or 5-bromo-4,7-phenanthrolines under
the action of concentrated ammonia in the presence
of copper(II) acetate, and 5,6-diamino-4,7-phenanthro-
line [7], by a multistep procedure involving nitration
of p-toluenesulfonyl derivative of 5-amino-4,7-
phenanthroline, hydrolysis of the sulfamide group,
and reduction of the 6-NO2 group. Later on 5,6-di-
amino-3,8-dimethyl-4,7-phenanthroline was obtained
by amination of 3,8-dimethyl-5-nitro-4,7-phenanthro-
line with hydroxylamine in the presence of alkali, but
the product contained an admixture of 6-amino-5-nitro-
4,7-phenanthroline [8]. No 4,7-phenanthrolines
containing both amino and hydroxy groups have so
far been reported.
p-Aminoacetophenone, too, fails to undergo the
catalytic condensation. The catalyst (conc. HCl) is
primarily consumed for protonation of the amino
group, thus decreasing the nucleophilic activity of the
carbonyl group, its ability to protonation, and, as a
consequence, CH-acidity of the methylketone.
Aiming at preparing previously unknown com-
pounds of the 4,7-phenanthroline series, containing
both an amino and a hydroxy groups in one molecule,
we reduced nitro-, dinitro-, and hydroxynitro-sub-
stituted 4,7-phenanthrolines obtained by condensation
of arylmethylene-6-quinolylamines, with aceto-
phenone, m-nitro-, p-nitro-, and p-hydroxyaceto-
phenone and 2-acetylquinoline.
The reduction of nitro groups was accomplished
by heating at 100 C over the course of 2 3 h of a
mixture of phenanthroline Ia Im, tin(II) chloride,
glacial acetis acid, and conc. HCl and resulted in
preparation of amino-, diamino-, and hydroamino-
phenyl-substituted 1,3-diphenyl-4,7-phenanthrolines
IIa IIl, as well as 3-(3-aminophenyl)-1-(2-quinolyl)-
Earlier [9, 10] we showed that acid-catalyzed reac-
tion of azomethines of the 6-aminoquinoline series
with acetophenone and substituted acetophenones
gives rise to 1,3-diaryl-4,7-phenanthrolines. By
1070-3632/04/7405-0776 2004 MAIK Nauka/Interperiodica

SYNTHESIS OF AMINO AND HYDROXY DERIVATIVES OF 4,7-PHENANTHROLINE
777
R
R
R
O
N
N
+
R
N
Ia Im
SnCl2
R = C6H4NO2
R = 3-NO2, 4-NO2
H2N
3
6
3
4
4
2
1
2
1
NH2
R
2
5
5
R
1
3
6
10
N
N
9
8
5
N
N
6
IIc IIj
IIa, IIb, IIk IIm
R
R
N
N
R
R
N
N
N
N
IIId
IIIa IIIc, IIIe
R = C6H5 (Ia, Ib, IIa, IIb, IIIa, IIIb), 3-NO2C6H4 (Ic If), 4-NO2C6H4 (Ig Ij), 4-HOC6H4 (Ik, Il, IIk, IIl, IIIe),
2-quinolyl (Im, IIm), 4-C6H5CH=NC6H4 (IIIc), 2-OH (IIId); R = 3-NO2 (Ia, Ic, Ig, Ik, Im), 4-NO2 (Ib, Id, Ih, Il), 2-OH
(Ie, Ii, IIe, IIi, IIId, IIIe), 4-OH (If, Ij, IIf, IIj), 3-NH2 (IIc, IIg), 4-NH2 (IId, IIh), 4-Br (IIIa), 4-Cl (IIIb), H (IIIc);
positions of amino groups and azomethine bonds in phenyl rings: 3 (IIa, IIc IIf, IIk, IIm, IIIb, IIId), 4 (IIb, IIh IIj, IIl,
IIIa, IIIc, IIId).
4,7-phenanthroline (IIm). Characteristics of com-
pounds IIa IIm are given in the table.
The UV spectra of amino-4,7-phenanthrolines IIa
IIm (see table) in band positions (Clar -, -, and
-bands [11]) are similar to those of 1,3-diaryl-4,7-
phenanthrolines [12]. The presence in the phenyl ring
of a meta-amino group not conjugated with the
phenanthroline nucleus has almost no effect on band
positions and intensities, whereas a para-amino group
in the phenyl ring strongly enhances the long-wave
-band, as is the case with p-dialkylaminophenyl-
substituted 4,7-phenanthrolines [12].
The IR spectra of compounds IIa IIm lack stretch-
ing vibration bands of nitro groups at 1540 1510 and
1
1350 1340 cm , characteristic of the starting nitro
1
derivatives Ia Im. Band at 3420 3210 cm appear,
assignable to stretching vibrations of amino groups.
The mass spectra of aminophenanthrolines IIa IIm
show a base molecular ion peak and a number of low-
1
intensity fragment ions [M
C6H5NH2]+, [M
In the H NMR spectra of compounds IIa IIm,
C6H5OH]+, and [M
HCN]+. There are double-
amino protons appear as broadened singlets at 5.30
5.75 ppm. The para-hydroxy group of the phenyl ring
gives a singlet at 9.50 9.80 ppm, and the ortho-
hydroxy group, a singlet at 13.10 14.15 ppm. Phenan-
charged molecular [M]2+ and fragment [M HCN]2+
ion peaks, which is characteristic of fused hetero-
aromatic compounds.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 5 2004

778
GUSAK et al.
Yields, melting points, UV spectra, and elemental analyses of 4,7-phenanthroline derivatives IIa IIm and IIIa IIIe
Found, %
H
Calculated, %
mp, C
UV spectrum, max, nm (log )
Formula
C
N
C
H
N
IIa
IIb
IIc
36 222 223 237 (4.56), 291 (4.57), 358 (3.83)
82.91 4.88 11.79 C24H17N3
83.00 4.90 12.10
83.00 4.90 12.10
79.56 4.97 15.47
37 243 244 235 (4.56), 261 (4.47), 292 (4.46), 345 (4.48) 82.79 4.91 11.94 C24H17N3
49 284 285 236 (4.52), 259 (4.46), 290 (4.56), 337 (3.90), 79.58 4.63 15.21 C24H18N4
357 (3.81)
IId
IIe
IIf
IIg
IIh
IIi
58 290 291 239 (4.50), 291 4.49), 348 (4.45)
47 271 272 238 (4.41), 292 (4.46), 353 (4.11)
42 279 280 237 (4.49), 293 (4.47), 356 (3.97)
56 287 288 243 (4.52), 291 (4.45), 349 sh (3.90)
47 264 265 243 (4.60), 291 (4.43), 340 (4.52)
79.37 4.81 15.11 C24H18N4
79.41 4.73 11.38 C24H17N3O 79.34 4.68 11.57
79.17 4.59 11.46 C24H17N3O 79.34 4.68 11.57
79.24 4.75 15.31 C24H18N4
79.55 4.83 15.41 C24H18N4
79.56 4.97 15.47
79.56 4.97 15.47
79.56 4.97 15.47
36 268 270 234 (4.35), 258 (4.40), 293 (4.43), 339 (4.21), 79.48 4.73 11.46 C24H17N3O 79.34 4.68 11.57
352 sh (4.08)
IIj
IIk
IIl
45 297 298 239 (4.43), 260 (4.39), 292 (4.40), 347 (4.49) 79.31 4.55 11.37 C24H17N3O 79.34 4.68 11.57
44 291 293 238 (4.41), 290 (4.39), 351 sh (3.79)
79.19 4.60 11.43 C24H17N3O 79.34 4.68 11.57
79.22 4.59 11.19 C24H17N3O 79.34 4.68 11.57
49 289 290 240 (4.47), 259 (4.45), 291 (4.48)
IIm 34 209 210 238 (4.51), 292 (4.50), 353 sh (3.82)
81.37 4.26 13.84 C27H18N4
81.41 4.52 14.07
IIIaa 72 248 249 231 (4.52), 262 (4.45), 293 (4.47), 344 (4.43), 72.32 3.57 7.84 C31H20BrN3 72.37 3.89 8.17
363 sh (4.40)
IIIbb 64 185 186 232 (4.38), 264 (4.52), 291 (4.66), 358 sh (3.94) 79.14 4.09 8.74 C31H20ClN3 79.23 4.26 8.95
IIIc 69 357 359 232 (4.49), 289 (4.38), 334 (4.37)
89.58 4.66 10.33 C38H26N4
84.76 4.83 10.41
IIId 77 299 300 237 (4.59), 292 (4.48), 341 (4.40), 357 sh (4.09) 79.69 4.49 8.64 C31H21N3O2 79.66 4.50 8.99
IIIe 79 249 250 238 (4.67), 264 (4.60), 289 (4.58), 352 sh (3.78) 79.41 4.23 8.75 C31H21N3O2 79.66 4.50 8.99
a
Found Br, %: 15.24. Calculated Br, %: 15.56. b Found Cl, %: 7.22. Calculated Cl, %: 7.56.
throline proton signals (7.20 8.90 ppm) are at posi-
tions expected from the spectra of 1,3-diaryl-4,7-
phenanthrolines [9]. The anisotropic effect of the
hydroxy and amino groups extends mostly to protons
of the phenyl rings (6.35 8.10 ppm) bearing these
groups. In the spectra of phenanthrolines IIc IIj
amino-substituted in the phenanthroline 1-Ph ring, we
observe a downfield shift of the signal of H10 which
comes under the cone of phenyl ring current forces.
Probably, amino substitution in the phenyl ring
disturbes its acoplanarity, thus attenuating its shield-
ing effect. If there is an ortho-hydroxy substituent in
the phenanthroline 3-Ph ring, the signal of the H2
proton closest to this phenyl group shifts downfield
(8.07 8.10 ppm).
actants in alcoholic toluene (toluene is added in view
of the poor solubility of aminophenanthrolines in
alcohols). The reactions with amines IIa and IIb give
azomethines IIIa and IIIb, while diamine IIh
provides bisazomethine IIIc. Aminohydroxy-sub-
stituted phenanthrolines IIi and IIk react with sali-
cylaldehyde to form bisphenol azomethines of the
4,7-phenanthroline series IIId and IIIe. The yields of
condensation peroducts IIIa IIIe (see table) suggest a
fairly high reactivity of the amino groups toward
aldehydes.
The IR spectra of compounds IIIa IIIe lack bands
1
at 3420 3210 cm , characteristic of NH2 stretching
vibrations. A band characteristic of N=CH stretching
1
vibrations appears at 1635 1630 cm . The mass
spectra contain molecular ion peaks [M]+ (I 50 70%).
Peaks of [M C6H4R ]+, [M CH C6H4R ]+, and
[M HCN]+ fragment ions and [M]2+, [M HCN]2+,
To assess the reactivity of the amino groups in
4,7-phenanthrolines, we have studied condensation of
compounds IIa, IIb, IIh, IIi, and IIk with aromatic
aldehydes. Since the amino group in 1,3-diaryl-4,7-
phenanthrolines is a constituent part of the aniline
moiety, to react compounds IIa, IIb, IIh, IIi, and IIk
with aldehydes requires the same conditions as to
condense the latter with aniline, i.e. to heat the re-
and [M CH
C6H4R ]2+ double-charged ions are
also present.
The UV spectra of azomethines IIIa IIIe (see
table) are similar to those of the starting amines IIa,
IIb, IIh, IIi, and IIk in terms of band positions and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 5 2004

SYNTHESIS OF AMINO AND HYDROXY DERIVATIVES OF 4,7-PHENANTHROLINE
779
relative intensities. The spectra of phenanthrolines
IIIb and IIIe with the azomethine bond in the meta
position of the phenyl ring show an additional band at
264 nm, that partially overlaps with the p-band (291
293 nm) of the phenanthroline nucleus. This band
(264 nm) can be assigned to the , * transition in the
ArCH=N group [13] that is not conjugated with the
phenanthroline nucleus and acts as an independent
chromophore. In p-arylmethyleneamino-substituted
phenanthrolines, the azomethine moiety is incor-
porated into the common conjugation system.
1-(3-Nitrophenyl)-3-(4-nitrophenyl)-4,7-
phenanthroline (Id) and 1-(4-nitrophenyl)-3-(3-
nitrophenyl)-4,7-phenanthroline (Ig) were prepared
in a similar way from the corresponding azomethine
(3- or 4- nitrophenylmethylene-6-quinolylamine) and
3- or 4- nitroacetophenone. Compound Id, yield 39%,
1
mp 298 299 C. IR spectrum, , cm : 1530, 1355
(NO2). Mass spectrum, m/z (Ire1l, %): 422 [M]+ (100),
392 (8), 376 (10), 300 (29). H NMR spectrum, ,
ppm: 7.10 d.d (H9), 7.80 s (H2), 7.88 d (H10), 8.26 d,
8.30 m (H5,6), 8.88 d.d (H8), 7.59 m, 8.20 s, 8.36 d,
8.46 d (8Harom). Found, %: C 68.21; H 3.36; N 12.93.
C24H14N4O4. Calculated, %: C 8.25; H 3.32; N 13.26.
Compound Ig, yield 44%, mp 301 302 C. IR
1
The H NMR spectra of azomethines IIIa IIIe lack
amino proton sinals. The azomethine proton appears
as a singlet at 9.10 9.15 ppm. In the group of aro-
matic proton signals (6.35 8.90 ppm), additional
aldehyde proton signals appear. Arylmethylene sub-
stitution in the phenanthroline 1-Ph ring enhances
shielding of H10 and shifts its signal upfiled (7.90
7.95 ppm) with respect to the same proton signal in
the starting amino derivatives IIg IIj (8.10
8.15 ppm).
1
spectrum, , cm : 1535, 1362 (NO2). Mass spectrum,
1
m/z (Irel, %): 422 [M]+, 300 (18). H NMR spectrum,
, ppm: 7.11 d.d (H9), 7.86 s (H2), 7.79 d (H10),
8.29 m (H5,6), 8.87 d.d (H8), 7.49 m, 8.08 d, 8.18 s,
8.38 d (8Harom). Found, %: C 67.96; H 3.19; N 13.23.
C24H14N4O4. Calculated, %: C 68.25; H 3.32; N
13.26.
3-(3-Aminophenyl)-1-phenyl-4,7-phenanthroline
(IIa). A hot solution of 7 g of SnCl2 2H2O in 40 ml
of conc. HCl was added with stirring to a suspension
of 1.6 g of 3-(3-nitrophenyl)-1-phenyl-4,7-phenanthro-
line (Ia) in 40 ml of glacial acetic acid. The mixture
was heated for 2h at 100 C, cooled, and neutralized
with 20% aqueous NaOH. The precipitate that formed
was filtered off and dried. Compound IIa was ex-
tracted with toluene in a Soxhlet apparatus.
EXPERIMENTAL
The mass spectra were recorded on a Varian MAT-
311 with direct inlet, ionizing energy 70 eV. The IR
spectra were measured on a Nicolet Protege-460
Fourier spectrometer. The 1H NMR spectra were ob-
tained on a Tesla BS-567 spectrometer (100 MHz) in
DMSO-d6, internal reference TMS. The UV spectra
were obtained on a Specord UV-Vis spectrophoto-
4
meter for ethanol solutions (c 10 M). The melting
Aminophenanthrolines IIb IIm were prepared in a
similar way. With compounds IIc, IId, IIg, and IIh,
the reaction mixture was heated for 3 h. With com-
pounds IIb IId, IIi, and IIk, after heating, a pre-
cipitate formed and was filtered off, washed with
glacial acetic acid, and neutralized; further workup
points were measured on a Kofler hot stage.
Nitro-substituted 1,3-diphenyl-4,7-phenanthrolines
Ia, Ib, and Ih were prepared as described in [9],
hydroxynitrophenanthrolines Ie, If, and Ii Il, as
described in [10], and 1-(2-quinolyl)-3-(3-nitrophenyl)- was performed as described above. Hydroxyamine IIi
4,7-phenanthroline (Im), as described in [14].
was recrystallized from toluene and its isomer IIk,
from DMF.
1,3-Bis(3-nitrophenyl)-4,7-phenanthroline (Ic).
A mixture of 1.4 g of 3-nitrophenylmethylene-
1H NMR spectrum of diaminophenanthroline IIh, ,
6-quinolylamine, 0.8
g
of 3-nitroacetophenone,
ppm (J, Hz): 5.45 s (NH2), 5.60 s (NH2), 6.65 d (H3 ,5
,
3
3
20 ml of 1-butanol, and 0.5 ml of conc. HCl was
refluxed for 2 h. The precipitate that formed was
filtered off, treated with aqueous NH4OH, and
recrystallized for ethanol toluene (1:1). Yield
3J 8.0), 6.72 d (H3 ,5 , J 7.8), 7.12 d (H2 ,6 , J 8.0),
7.22 d (H9, 3J 8.2, J 4.1), 7.76 s (H2), 8.04 d (H2 ,6
,
4
3J 7.8), 8.11 m (H5,6,10), 8.80 d.d (H8, J 4.1, J 1.8).
3
4
0.75 g (36%), mp 294 295 C. IR spectrum,
,
3-[4(4-Bromobenzylidene)aminophenyl]-1-
phenyl-4,7-phenanthroline (IIIa). A solution of
0.5 g of p-bromobenzaldehyde in 20 ml of ethanol
was added to a solution of 0.9 g of 3-(4-amino-
phenyl)-1-phenyl-4,7-phenanthroline (IIb) in 30 ml of
toluene. The mixture was refluxed for 10 min. The
1
cm : 1530, 1350 (NO2). Mass spectrum, m/z (Irel,
%): 422 [M]+ (100), 392 (10), 376 (11), 300 (20), 278
1
(18). H NMR spectrum, , ppm: 7.13 d.d (H9), 7.83 s
(H2), 7.90 d (H10), 8.30 m (H5,6), 8.85 d.d (H8), 7.47
7.60 m, 8.35 s, 8.44 m (8Harom). Found, %: C 68.10;
H 3.19; N 13.08. C24H14N4O4. Calculated, %: C 68.25; precipitate that formed was filtered off and recrystal-
H 3.32; N 13.26. lized from ethanol toluene (2:1).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 5 2004

780
GUSAK et al.
Azomethines IIIb IIIe were synthesized in a
6. Sykes, W.O., J. Chem. Soc., 1953, no. 11, p. 3543.
similar way. Compounds IIIb, IIIc, and IIIe were
isolated after removal of the solvent and purified by
recrystallization from 2-propanol (IIIb, IIIc) or
7. Case, F.N., J. Heterocycl. Chem., 1967, vol. 4, no. 1,
p. 157.
8. Savosin, I.V. and Shaburov, V.V., Zh. Org. Khim.,
1
toluene (IIId, IIIe). H NMR spectrum of compound
1987, vol. 23, no. 11, p. 2476.
IIId, , ppm (J, Hz): 6.95 7.80 m (12Harom), 7.92 d
3
3
9. Kozlov, N.S., Gusak, K.N., Serzhanina, V.A., and
Krot, N.A., Khim. Geterotsikl. Soedin., 1985, no. 10,
p. 1398.
(H10, J 7.9), 8.24 8.40 m (4Harom), 8.90 d.d (H8, J
4
4.8, J 2.1), 9.15 s (CH=N), 13.0 s (OH), 14.15 s
(OH).
10. Gusak, K.N. and Kozlov, N.G., Zh. Obshch. Khim.,
2003, vol. 73, no. 6, p. 1018.
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