Synthesis of 4,7-phenanthroline derivatives by condensation of arylmethylene(6-quinolyl)amines with hydroxy- and nitro-substituted acetophenone

Article abstract of DOI:10.1023/A:1026321422453

Condensation of arylmethylene(6-quinolyl)amines with hydroxy- and nitro-substituted acetophenones was used to synthesize 1,3-diary1-4,7- phenanthrolines containing hydroxy and nitro groups in the phenyl rings.

Full text of DOI:10.1023/A:1026321422453

Russian Journal of General Chemistry, Vol. 73, No. 6, 2003, pp. 964 967. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 6, 2003,
pp. 1018 1021.
Original Russian Text Copyright
2003 by Gusak, Kozlov.
Synthesis of 4,7-Phenanthroline Derivatives by Condensation
of Arylmethylene(6-quinolyl)amines with Hydroxy-
and Nitro-substituted Acetophenone
K. N. Gusak and N. G. Kozlov
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Received July 9, 2001
Abstract Condensation of arylmethylene(6-quinolyl)amines with hydroxy- and nitro-substituted aceto-
phenones was used to synthesize 1,3-diaryl-4,7-phenanthrolines containing hydroxy and nitro groups in the
phenyl rings.
Functional substituents, such as hydroxy and nitro
groups, in heterocyclic compounds extend the syn-
thetic potential and diversify the physiological activity
of the latter [1, 2].
nitro group is hard to introduce into the azaaromatic
ring by electrophilic substitution. The information
concerning 4,7-phenanthrolines bearing both hydroxy
and nitro substituents is lacking.
Earlier we showed that azomethines of the 6-amino-
quinoline series react with acetophenone to give
1-phenyl-3-aryl-4,7-phenanthrolines [6].
Some information on the synthesis of hydroxy-
substituted 4,7-phenanthrolines is available in the
literature [3, 4]. These compounds are generally
synthesized by Conrad Limpach and Knorr reactions,
starting from 6-quinolylamine or p-phenylenediamine
and esters of -oxo- and -dicarboxylic acids. Nitro-
substituted 4,7-phenanthrolines obtained by nitration
of 4,7-phenanthroline are scarcely studied [5], since
Aiming at introducing two different functional
substituents into the 4,7-phenanthroline molecule, in
the present work we have studied for the first time the
reactions of (m- and p-nitrophenylmethylene)(6-quino-
lyl)amines (Ia, Ib) with p-hydroxyacetophenone (IIa)
R
R
R
O
O
NH
N
+
CH3
R
N
N
Ia Ig
IIa IIc
A
R
R
O
R
R
+
N
N
IIIa IIIi
IVa IVe
R = 3-NO2 (Ia, IIIa, IVc), 4-NO2 (Ib, IIIb), 2-OH (Ic, IIIc, IIId), 4-OH (Id, IIIe, IIIf, IVd), 2-OH,5-NO2 (Ie, IIIg IIIi,
IVe), 2,4-(OH)2 (If, IVa), 3,4-(OH)2 (Ig, IVb); R = 4-OH (IIa, IIIa, IIIb, IIIg, IVc), 3-NO2 (IIb, IIIc, IIIe, IIIh, IVe),
4-NO2 (IIc, IIId, IIIf, IIIi, IVd).
1070-3632/03/7306-0964$25.00 2003 MAIK Nauka/Interperiodica

SYNTHESIS OF 4,7-PHENANTHROLINE DERIVATIVES BY CONDENSATION
965
Table 1. Yields, melting points, and elemental analyses of 1,3-diaryl-4,7-phenanthrolines IIIa IIIi
Found, %
H
Calculated, %
Comp.
no.
Yield, %
mp,
C
Formula
C
N
C
H
N
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
40
42
29
24
21
31
32
30
33
364 365
326 327
321 322
325 326
319 320
322 323
349 350
340 341
337 338
73.31
73.19
73.26
73.09
73.24
73.39
70.22
65.49
65.58
3.88
3.74
3.65
3.74
3.59
3.96
3.64
3.01
3.23
10.34
10.53
10.74
10.93
10.81
10.57
10.33
12.64
12.56
C24H15N3O3
C24H15N3O3
C24H15N3O3
C24H15N3O3
C24H15N3O3
C24H15N3O3
C24H15N3O4
C24H14N4O5
C24H14N4O5
73.28
73.28
73.28
73.28
73.28
73.28
70.42
65.75
65.75
3.82
3.82
3.82
3.82
3.82
3.82
3.67
3.20
3.20
10.70
10.70
10.70
10.70
10.70
10.70
10.27
12.79
12.79
and the reactions of (o- and p-hydroxyphenylmethy-
lene)(6-quinolyl)amines (Ic, Id) with m- and p-nitro-
acetophenones (IIb, IIc). Ketones IIa IIc were also
reacted with (2-hydroxy-5-nitrophenylmethylene)(6-
quinolyl)amine (Ie). By varying substituents in the
aldehyde moiety of Schiff base and in the phenyl
nucleus of acetophenone we expected to prepare 4,7-
phenanthrolines with desired groups.
It should be noted that in 1-butanol, too, we could
not always avoid chalcone formation. These com-
pounds in minor amounts were isolated together with
target 4,7-phenanthrolines IIIa, IIIf, IIIh, whereas
the reactions of (dihydroxyphenylmethylene)(6-quino-
lyl)amines If, Ig with p-nitroacetophenone (IIb) gave
compounds IVa, IVb as single products. m-Nitro-
acetophenone (IIc) failed to react with hydroxy-sub-
stituted azomethines If, Ig. In the reaction mixture
we found nothing more than more 6-quinolylamine
formed by hydrolysis of the latter.
The condensations were performed by refluxing
equimolar amounts of azomethine and acetophenone
in 1-butanol in the presence of catalytic amounts of
concentrated HCl.
It is known [6] that electron-donor substituents in
the aldehyde moiety of azomethine molecule weaken
polarization of the C=N bond and make it less active
toward CH acids. When two electron-donor hydroxy
groups are present in the aldehyde moiety of the
azomethine molecule, it prefers hydrolysis to form
enones IVa, IVb. The C=N bond in azomethines Ic,
Id containing one hydroxy group is weaker de-
activated toward CH acids. (Hydroxyphenylmethy-
lene)(6-quinolyl)amines Ic, Id react with aceto-
phenones, giving more 4,7-phenanthrolines IIIc IIIf
than enones but in lower yields than phenanthrolines
IIIa, IIIb in the reactions of acetophenone IIa with
azomethines Ia, Ib containing the electron-acceptor
nitro group.
According to our previous findings [6], the 4,7-
phenantholine nucleus is formed via intermediacy of
aminoketone A which, in its turn, is formed by addi-
tion of the CH acid to the azomethine C=N bond,
yielding a new C=C bond.
We failed to isolate intermediate aminoketones in
the condensations of azomethines Ia Ie with hydroxy-
and nitro-substituted acetophenones IIa IIc. Under
the mentioned conditions, the reactions gave 1,3-di-
aryl-4,7-phenanthrolines IIIa IIIi containing hydroxy
and nitro groups in the phenyl rings. Under milder
conditions (refluxing in ethanol) in the absence of
catalysts, no reaction was observed between azo-
methines and acetophenones, and in the presence of
HCl, hydroxynitro-substituted chalcones IVa IVe
were obtained. , -Unsaturated ketones IVa IVe can
be formed, on the one hand, by aldol condensation of
acetophenone with the aromatic aldehyde formed by
hydrolysis of the starting azomethine and, on the other,
by hydramine cleavage of intermediate aminoketone
A. In 1-butanol, apparently, both hydrolysis and
cleavage of aminoketones are suppressed, and the
condensation results in preferential formation of 4,7-
phenanthrolines.
Substituents in the phenyl ring of acetophenone
only slightly affect the condesation results. Both
hydroxy- and nitro-substituted acetophenones with
the same azomethine Ie give roughly equal yields of
4,7-phenanthrolines IIIg IIIi.
1,3-Diaryl-4,7-phenanthrolines IIIa IIIi are yellow
high-melting crystals. Their characteristics are listed
in Table 1.
The IR spectra of 4,7-phenanthrolines IIIa IIIi
contain strong characteristic stretching vibration bands
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003

966
GUSAK, KOZLOV
Table 2. 1H NMR spectra of 1,3-diaryl-4,7-phenanthroline IIIa, IIIb, IIId, and IIIf, , ppm (J, Hz)
H9, d.d
(3J 8.2,
4J 2.8)
Phenyl protons (3J 8.0 8.4)
Comp.
no.
H5, d
H6, d
H8, d
H10, d
H2, s
(3J 8.8) (3J 8.8) (3J 4.8)
(3J 8.2)
acetophenone
aldehyde
IIIa
IIIb
IIId
IIIf
8.70
8.61
8.75
8.54
9.10
9.11
9.08
9.12
9.0
9.37
9.37
9.36
9.36
8.18
8.16
8.14
8.10
9.31
9.28
8.93
8.92
7.40 d, 7.60 d 8.08 t, 8.60 d, 8.75 d, 9.13 s
7.41 d, 7.66 d 8.43 d, 8.67 d
8.00 d, 8.70 d 7.40 m, 7.82 t, 8.24 d
8.20 d, 8.70 d 7.36 d, 7.98 d
9.01
9.01
8.99
1
of the nitro groups at 1545 1530 and 1365 1355 cm . compounds IIId, IIIf containing nitrophenyl substi-
The CH stretching vibration bands of the aromatic
tuents in the 1 position of the phenanthroline nucleus,
the H10 signal is upfield from the respective signal of
hydroxyphenyl-substituted analogs IIIa, IIIb. The H10
proton locating over the the phenyl ring plane, in
compounds IIId, IIIf appears to fall into the shielding
cone of the nitro group, which shifts this proton signal
upfield. The same effect was earlier observed in the
spectra of nitrobenzylidene derivatives of 4-aza-
fluorene [10].
1
rings appear at 3060 3030 cm . The bands at 720
1
715 and 855 850 cm are indifferent to substituent
effects and belong to out-of-plane deformation vibra-
tions of two neighboring CH bonds [6].
A characteristic feature of the mass spectra of 4,7-
phenanthrolines IIIa IIIi is that they contain little
fragment ions. The base peaks are formed by mole-
cular ions (M+). Low- and medium-intensity peaks are
also present (5 25%) at m/z 271 and 300, assignable
to [M RC6H4]+ or, for compounds IIIg IIIi (R =
EXPERIMENTAL
2-OH,5-NO2), [M
RC6H3]+ ions.
The IR spectra were measured on a UR-20 instru-
ment in KBr. The mass spectra were obtained on a
Varian Mat-311 spectrometer with direct inlet, ioniz-
ing energy of 70 eV, vaporization temperature 150
200 C, and ion source temperature 200 C. The UV
The electronic absorption spectra of phenanthro-
lines IIIa IIIi show three bands in the UV range
(224 263, 287 313, and 343 370 nm), which are
interpreted as Clar , p, and bands [7]. Compared
with the spectrim of 1,3-diphenyl-4,7-phenanthroline
[8], in the spectra of compounds IIIa IIIi we observe
leveled intensities of the and p bands, and, except
for o-hydroxyphenyl-substituted phenanthrolines IIIc,
IIId, smoothened vibrational structure of the band.
In the spectra of compounds IIIc, IIId, the band is
shifted bathochromically and enhanced, like in the
spectra of analogous compounds of the benzo[f]quino-
line series [9].
4
spectra were measured in ethanol (c 10 M) on a
Specord UV-Vis spectrophotometer. The 1H NMR
spectra were obtained on a Bruker WM-360 spectro-
meter (360 MHz) in CF3COOD, internal reference
TMS. The melting points were measured on a Kofler
hot stage.
Arylmethylene(6-quinolyl)amines Ia Ig were ob-
tained by the procedure in [11].
1,3-Diaryl-4,7-phenanthrolines IIIa IIIi. A mix-
ture of 5 mmol of azomethine Ia Ie, 5 mmol of hydr-
oxy- or nitro-substituted acetophenone IIa IIc, 20 ml
of 1-butanol, and 6 8 drops of conc. HCl was heated
under reflux for 2 3 h. The precipitate that formed
(with compounds IIIb, IIIc, the solvent was eva-
porated by 1/3) was filtered off, treated with ethanolic
NH4OH (1:1) and water, and dried. Phenanthrolines
IIIb, IIIf were recrystallized from nitrobenzene.
1
The H NMR spectra of compounds IIIa, IIIb,
IIId, IIIf (Table 2) were assigned based on the spec-
tral data for 1-phenyl-3-aryl-4,7-phenanthrolines,
reported in [6]. Because of the poor solubility of
hydroxynitro derivatives IIIa, IIIb, IIId, IIIf in
organic solvens, the spectra of these compounds were
measured in CF3COOD. In this connection, compared
with the spectra of analogs measured in CDCl3 [6], all
signals in the spectra of hydroxynitro-substituted 4,7-
phenanthrolines IIIa, IIIb, IIIg, IIIf exhibit a slight
downfield shift induced by the positive charge of the
phenanthroline nitrogen atoms, developed as a result
of deuteration. The anisotropic effects of hydroxy and
nitro groups extend to protons of the phenyl rings
bearing these groups. At the same time, the spectra of
1,3-Diarylpropenones IVa IVe were obtained as
described for compounds IIIa IIIi. Enones IVc IVe
were isolated by evaporation of the mother liquors
after separation of the precipitates of phenanthrolines
IIIa, IIIf, IIIh. Propenones IVa, IVb were recrystal-
lized from ethanol benzene, 1:3, and compounds
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003

SYNTHESIS OF 4,7-PHENANTHROLINE DERIVATIVES BY CONDENSATION
967
IVc IVe, from nitrobenzene. Compound IVa: yield
42%, mp 81 82 C. IR spectrum, , cm : 1700 (CO),
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1
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 6 2003