Synthesis of fused derivatives of 4,7-phenanthroline by condensation of 6-aminoquinoline with aromatic aldehydes and dimedone

Article abstract of DOI:10.1023/A:1013483424111

8-Aryl-11,11-dimethyl-7,8,9,10,11,12-hexahydrobenzo[a]phenanthrolin-9-ones were obtained by condensation of 6-aminoquinoline with aromatic aldehydes and dimedone.

Full text of DOI:10.1023/A:1013483424111

Russian Journal of Organic Chemistry, Vol. 37, No. 10, 2001, pp. 1495 1502. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 10, 2001,
pp. 1564 1571.
Original Russian Text Copyright
2001 by Gusak, Tereshko, Kozlov.
Synthesis of Fused Derivatives of 4,7-Phenanthroline
by Condensation of 6-Aminoquinoline with Aromatic Aldehydes
and Dimedone
K. N. Gusak, A. B. Tereshko, and N. G. Kozlov
Institute of Physical Organic Chemistry, Belarussian Academy of Sciences, Minsk, 220072 Belarus
Received December 27, 2000
Abstract 8-Aryl-11,11-dimethyl-7,8,9,10,11,12-hexahydrobenzo[a]phenanthrolin-9-ones were obtained by
condensation of 6-aminoquinoline with aromatic aldehydes and dimedone.
Compounds of 4,7-phenanthroline series possess
high and versatile biological activity. Proceeding
from 4,7-phenanthroline-5,6-dione were developed
very efficient bactericidal pharmaceuticals Entobex
and Mexaform [1]. Among the derivatives of
4,7-phenanthroline were found compounds of anti-
allergic and antitumor activity, enzymes inhibitors,
and fungicides [2 6]. The main trend in the building
up of 4,7-phenanthroline skeleton is a construction of
additional pyridine ring on the carbocyclic core of
6-aminoquinoline. It was formerly shown [7] that in
reaction with 6-aminoquinoline with aromatic
aldehydes and 1,3-cyclohexanedione the building up
of the pyridine cycle was accompanied with fusion of
cyclohexanone ring affording 8-aryl-7,8,9,10,11,12-
hexahydrobenzo[a]phenanthrolin-9-ones. These com-
pounds because of the presence in the molecule of
partly hydrogenated pyridine and benzene rings are
interesting as analogs of ergoalkaloids whose main
structural fragment is azaphenanthrene skeleton [8].
diones, is considered in detail in [7, 9, 10]. The reac-
tion proceeds through intermediate formation of
2-[(aryl)(6-quinolylamino)methyl]-5,5-dimethyl-1,3-
cyclohexanedione (A) and its cyclization product,
hydroxyketone (B) (route a). Neither aminodiketone
(A) nor cyclic alcohol (B) were isolated in the reac-
tion under study. Apparently due to high reactivity of
carbonyl group and of methylene group located
between them intermediate (A) quickly transforms
into aminoalcohol (B) that is stabilized by water
elimination to afford benzo[a]-4,7-phenanthrolines
LII C.
To confirm the assumed three-component con-
densation route we synthesized azomethines of
6-aminoquinoline series III LI by reaction of
6-aminoquinoline with aromatic aldehydes, isolated
them as individual compounds, and brought them into
reaction with diketone I under conditions used in
one-pot condensation of the latter with amine II
and aromatic aldehydes. The target compounds,
phenanthrolines LII C, formed in approximately
same yield as in the three-component condensation.
In order to prepare new compounds of this class
were brought into reaction dimedone (I), 6-amino-
quinoline (II), and aromatic aldehydes. The reaction
was carried out by boiling in 1-butanol of equimolar
reagents amounts with no catalyst.
The substituent in the aromatic ring of aldehyde R
affects to a certain degree the yield of the target reac-
tion products LII C (Table 1). The presence in the
phenyl ring of the aldehyde of a hydroxy group in
meta- and para-position, of halogen atom, nitro,
alkoxy, alkoxycarbonyl group activates aldehyde
molecule by I-effect or by I- and M-effect during
its reaction with amine II. In the next stage these
groups activate the azomethine molecule during con-
densation with diketone I. Therefore the yield of
It was shown before [7] that three-component
condensation of diketone I, amine II, and aromatic
aldehyde can take either of two routes. The most
probable for the majority of aldehydes is a primary
reaction with amine II providing azomethines III LI
that further undergo condensation with dimedone (I)
yielding fused derivatives of 4,7-phenanthroline,
8-aryl-11,11-dimethyl-7,8,9,10,11,12-hexahydro-
benzo[a]phenanthrolin-9-ones (LII C).
compounds
LVII LXIII,
LXVII LXXXII,
LXXXVII XCI is higher than that of alkyl- and
alkylamino-substituted phenanthrolines LIII LVI,
LXXXIII LXXXV. The increased yield of reaction
The mechanism of reaction between Schiff,s bases
and CH-acids, in particular, with the cyclic 1,3-
1070-4280/01/3710-1495$25.00 2001 MAIK Nauka/Interperiodica

1496
GUSAK et al.
R = H (III, LII, CI), 4-MeC6H4 (IV, LIII), 2-MeC6H4 (V, LIV), 4-EtC6H4 (VI, LV), 4-(i-Pr)C6H4 (VII, LVI),
4-FC6H4 (VIII, LVII), 2-FC6H4 (IX, LVIII), 4-ClC6H4 (X, LIX), 2-ClC6H4 (XI, LX), 4-BrC6H4 (XII, LXI),
3-BrC6H4 (XIII, LXII), 2,3-Cl2C6H3 (XIV, LXIII), 2,4-Cl2C6H3 (XV, LXIV), 2,3-Cl2C6H3 (XVI, LXV), 2-Cl,
6-FC6H3 (XVII, LXVI), 4-HOC6H4 (XVIII, LXVII), 3-HOC6H4 (XIX, LXVIII), 3,4-(HO)2C6H3 (XX, LXIX),
4-MeOC6H4 (XXI, LXX), 2-MeOC6H4 (XXII, LXXI), 4-EtOC6H4 (XXIII, LXXII), 4-PrOC6H4 (XXIV, LXXIII),
2,4-(MeO)2C6H3 (XXV, LXXIV), 2,5-(MeO)2C6H3 (XXVI, LXXV), 3,4-(MeO)2C6H3 (XXVII, LXXVI),
3,4,5-(MeO)3C6H2 (XXVIII, LXXVII), 4-HO, 3,5-(MeO)2C6H2 (XXIX, LXXVIII), 3-EtO, 4-HOC6H3 (XXX,
LXXIX), 2-MeO, 5-BrC6H3 (XXXI, LXXX), 4-MeO2CC6H4 (XXXII, LXXXI), 3-MeO, 4-MeO2CC6H3 (XXXIII,
LXXXII), 4-Me2NC6H4 (XXXIV, LXXXIII), 4-Et2NC6H4 (XXXV, LXXXIV), 4-(CH2CH2Cl)2NC6H4 (XXXVI,
LXXXV), 3,4-CH2O2C6H3 (XXXVII, LXXXVI), 4-NO2C6H4 (XXXVIII, LXXXVII), 3-NO2C6H4 (XXXIX,
LXXXVIII), 2-NO2C6H4(XL, LXXXIX), 4-PhC6H4(XLI, XC), -
3-MeO, 4-PhCH2OC6H3
(XLIII, XCII), 2-CF3C6H4 (XLIV, XCIII), cyclohexen-4-yl (XLV, XCIV), 4-MeSC6H4 (XLVI, XCV), 2-thienyl
4 PhCH2OC6H4(XLII, XCI),
(XLVII, XCVI), 3-methyl-2-thienyl (XLVIII, XCVII), 2-pyridyl (XLIX, XCVIII), 3-pyridyl
1-naphthyl (LI, C), 6-OH (CII), 7,8-benzo (CIII).
(L, XCIX),
products XCVI XCIX is caused by the replacement
of the phenyl ring by pyridine or thiophene one. In
this case the increase in polarization and reactivity of
C=O and C=N bonds in the molecules of aldehyde
and azomethine is due to the I-effect of the nitrogen
or sulfur atom of the heterocyclic ring.
scheme are not shown the enol and enolate-anion
forms present in the proton-acceptor solvent, alcohol
[10]).
The replacement of the phenyl ring in the
azomethine molecule by naphthyl results in reduced
yield of reaction product C due to steric hindrances
from the bulky substituent. The considerably smaller
yields of phenanthrolines LXV, LXVI are caused
apparently by steric hindrances from two ortho-sub-
stituents.
We believe that the observed yield reduction for
phenanthrolines LXXXIII LXXXV is due to de-
celeration of the reaction at the stage of Schiff,s base
XXXIV XXXVI condensation with diketone I caused
by stabilization of a protonated form of the azo-
methine through mesomeric transformations as it is
known for para-dialkylamino-substituted benzal-
anilines and benzal-2-naphthylamines [10, 11].
The condensation of salicylaldehyde, resorcyl-
aldehyde, and also of 2-hydroxy-1-naphthalenecarb-
aldehyde with diketone I and amine II does not afford
the expected 4,7-phenanthroline derivatives. The
reaction provides products that do not contain nitro-
The quaternization of azomethine is provided by a
proton cleaved from diketone I (for brevity on the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

SYNTHESIS OF FUSED DERIVATIVES OF 4,7-PHENANTHROLINE
1497
Table 1. Yields, melting points, and elemental analyses of aryl(heteryl)methylene-6-aminoquinolines V, XIV, XVI,
XXII XXIV, XXVI, XXX, XXXI, XXXIII, XLIII XLIX, LI and 8-aryl-11,11-dimethyl-7,8,9,10,11,12-
hexahydrobenzo[a]-4,7-phenanthrolin-9-ones LII C
Found, %a
H
Calculated, %b
H
Compd.
no.
Yield, %
mp,
C
Formula
C
N
C
N
V
XIV
XVI
78
75
69
76
82
79
74
81
78
83
80
84
75
83
77
72
68
76
65
55
59
58
51
73
75
69
72
68
69
83
58
48
30
78
71
66
70
78
66
78
81
80
69
78
75
44 45
82.90
63.51
63.80
77.53
77.96
78.51
74.09
73.62
59.77
71.29
78.17
5.74
3.18
3.07
5.36
5.53
6.24
5.56
5.36
3.67
4.83
5.25
11.69
9.26
9.11
10.54
9.87
9.27
9.31
9.23
8.03
8.45
7.73
9.26
11.63
9.34
11.53
10.92
18.15
9.76
7.69
7.81
7.33
7.29
7.04
7.36
7.19
6.88
7.14
6.28
6.11
6.71
6.29
6.39
7.01
7.63
7.42
7.12
7.33
7.08
6.87
6.94
6.41
6.67
6.84
5.97
6.73
C17H14N2
82.92
63.79
63.79
77.86
78.26
78.62
73.93
73.93
59.82
71.25
78.26
5.69
3.32
3.32
5.34
5.80
6.21
5.48
5.48
3.81
5.00
5.43
12.07
9.30
9.30
10.69
10.14
9.66
9.59
9.59
8.21
8.75
7.61
9.33
11.91
9.59
11.76
11.11
18.03
9.93
7.91
7.61
7.61
7.33
7.07
7.53
7.53
7.21
7.21
6.47
6.47
6.62
6.62
6.62
6.89
7.57
7.57
7.25
7.29
7.29
7.04
6.80
6.76
6.76
6.76
6.31
6.51
43 144
115 116
140 141
92 93
73 75
88 89
144 145
118 119
121 122
153 154
71 72
48 49
114 115
88 89
C16H10Cl2N2
C16H10Cl2N2
C17H14N2O
C18H16N2O
C19H18N2O
C18H16N2O2
C18H16N2O2
C17H13BrN2O
C19H16N2O3
C24H20N2O2
C17H11F3N2
C16H15N2
XXII
XXIII
XXIV
XXVI
XXX
XXXI
XXXIII
XLIII
XLIV
XLV
XLVI
XLVII
XLVIII
XLIX
LI
LII
LIII
LIV
LV
LVI
LVII
LVIII
LIX
LX
81.49
74.12
70.51
71.28
76.94
84.89
81.12
81.43
81.64
81.73
81.59
6.41
5.29
4.26
4.53
4.70
4.71
6.23
6.28
6.50
6.90
7.28
81.70
73.97
70.59
71.43
77.25
85.11
81.36
81.52
81.52
81.68
81.82
6.38
5.48
4.20
4.76
4.72
4.96
6.21
6.52
6.52
6.81
7.07
C18H16N2S
C14H10N2S
C15H12N2S
C15H11N3
62 63
51 52
43 44
C20H14N2
321 322
319 320
329 330
310 311
319 320
307 308
308 309
314 315
340 341
320 321
323 324
345 346
335 336
287 288
294 295
334 335
342 343
322 324
310 311
299 300
305 306
248 249
323 324
309 310
265 266
263 264
273 274
C24H22N2O
C25H24N2O
C25H24N2O
C26H26N2O
C27H28N2O
C24H21FN2O
C24H21FN2O
C24H21ClN2O
C24H21ClN2O
C24H21BrN2O
C24H21BrN2O
C24H20Cl2N2O
C24H20Cl2N2O
C24H20Cl2N2O
C24H20ClFN2O
C24H22N2O2
C24H22N2O2
C24H22N2O3
C25H24N2O2
C25H24N2O2
C26H26N2O2
C27H28N2O2
C26H26N2O3
C26H26N2O3
C26H26N2O3
C27H28N2O4
C26H26N2O4
73.92
74.01
66.47
66.32
67.75
68.10
67.93
5.29
5.52
4.79
4.69
4.52
4.84
4.59
74.13
74.13
66.51
66.51
68.09
68.09
68.09
5.41
5.41
4.85
4.85
4.73
4.73
4.73
LXI
LXII
LXIII
LXIV
LXV
LXVI
LXVII
LXVIII
LXIX
LXX
LXXI
LXXII
LXXIII
LXXIV
LXXV
LXXVI
LXXVII
LXXVIII
77.92
78.01
74.59
77.76
78.08
78.24
78.41
75.51
75.30
75.10
73.00
72.46
6.04
6.11
5.73
6.14
6.31
6.59
6.52
6.39
6.44
6.16
6.39
5.91
77.84
77.84
74.61
78.13
78.13
78.39
78.64
75.36
75.36
75.36
72.97
72.56
5.95
5.95
5.70
6.25
6.25
6.53
6.80
6.28
6.28
6.28
6.31
6.05
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1498
GUSAK et al.
Table 1 (Contd.)
Found, %a
Calculated, %b
H
Compd.
no.
Yield, %
mp,
C
Formula
C
H
N
C
N
LXXIX
LXXX
LXXXI
LXXXII
LXXXIII
LXXXIV
LXXXV
LXXXVI
LXXXVII
LXXXVIII
LXXXIX
XC
XCI
XCII
XCIII
XCIV
XCV
XCVI
XCVII
XCVIII
XCIX
82
81
82
78
39
34
40
59
75
74
70
71
72
64
68
65
65
72
78
71
78
52
318 319
335 336
311 312
282 283
299 300
294 295
276 277
321 322
344 345
304 305
305 306
306 308
283 284
254 255
314 315
272 273
307 308
333 334
328 329
292 293
322 323
320 321
75.13
64.58
75.46
73.18
78.63
78.74
67.68
75.40
71.93
72.16
72.04
83.59
83.77
78.21
6.22
5.23
5.80
6.01
6.82
7.19
5.94
5.31
5.06
5.21
5.29
5.94
6.39
6.03
6.59
5.77
6.84
C26H26N2O3
C25H24BrN2O2
C26H24N2O3
C27H26N2O4
C26H27N3O
C28H31N3O
C28H29Cl2N3O
C25H22N2O3
C24H21N3O3
C24H21N3O3
C24H21N3O3
C30H26N2O
C31H28N2O
C32H30N2O3
C25H21FN2O
C24H25N2O
C25H24N2OS
C22H20N2OS
C23H22N2OS
C23H21N3O
C23H21N3O
C28H24N2O
75.36
64.66
75.73
73.30
78.59
79.06
68.02
75.38
72.18
72.18
72.18
83.72
83.78
78.37
6.28
5.17
5.83
5.88
6.80
7.29
5.87
5.53
5.26
5.26
5.26
6.05
6.31
6.12
6.76
6.03
6.80
6.33
10.58
9.88
8.50
7.04
10.53
10.53
10.53
6.51
6.31
5.71
7.29
7.84
7.00
7.78
7.49
11.83
11.83
6.93
5.97
10.36
10.01
8.33
7.11
10.24
10.64
10.31
6.50
5.98
5.76
7.03
7.65
6.69
7.54
80.44
74.83
73.20
74.00
77.55
77.80
82.78
7.07
6.02
5.61
5.92
5.90
5.83
6.00
80.67
75.00
73.33
73.80
77.75
77.75
83.17
7.00
6.00
5.56
5.88
5.92
5.92
5.94
7.31
11.65
11.84
6.64
C
a
Found, %: Br 23.09 (XXXI), 18.22 (LXI), 18.50 (LXII), 17.19 (LXXX); Cl 23.22 (XIV), 23.19 (XVI), 8.93 (LIX), 8.86 (LX),
16.53 (LXIII), 16.34 (LXIV), 16.80 (LXV), 14.28 (LXXXV); S 10.52 (XLVI), 13.12 (XLII), 12.58 (XLVIII), 7.78 (XCV),
8.63 (XCVI), 8.24 (XCVII).
Calculated, %: Br 23.46 (XXXI), 18.48 (LXI, LXII), 17.24 (LXXX); Cl 23.59 (XIV, XVI), 9.14 (LIX, LX), 16.78
(LXIII LXV), 14.37 (LXXXV); S 10.96 (XLVI), 13.45 (XLVII), 12.70 (XLVIII), 8.00 (XCV), 8.89 (XCVI), 8.56 (XCVII).
b
gen, 2,5-dioxo-1-cyclohexyl derivatives of tetra-
hydroxanthene CI CIII.
aromatic aldehydes and amine II. Thus with dime-
done the second condensation route is limited to
aldehydes containing ortho- or para-hydroxy group.
The latter provided efficient transformation of bis-
diketone (C) into partially hydrogenated xanthene
derivatives.
Obviously the three-component condensation with
the above aldehydes takes the route b where the
molecule of the aromatic aldehyde reacts with two
dimedone (I) molecules yielding intermediate com-
pound C followed by dehydration of the latter with
participation of hydroxy group attached to benzene or
naphthalene ring that affords exclusively tetrahydr-
oxanthenes CI CIII.
Synthesized fused derivatives of 4,7-phenanthro-
line LII C are colorless or yellow high-melting
crystalline compounds. In their IR spectra appear
characteristic absorption bands of stretching vibra-
tions of NH and CO groups at 3290 3210 and 1620
Demethylated analogs of xanthenes CI, CII were
previously obtained by condensation of 6-amino-
quinoline with salicylaldehyde, resorcylaldehyde, and
1,3-cyclohexadiene. With this diketone and the other
aldehydes were isolated intermediate bisdiketones (B)
that at heating with excess amine II afforded deriv-
atives of 4,7-phenanthroline. We failed to obtain
bisdiketones (C) in reaction of dimedone (I) with
1
1585 cm respectively. The shift of the bands to
lower frequencies is due to an intramolecular hydro-
gen bond [12], and also to conjugation of the
carbonyl group with the quinoline ring. The stretch-
ing vibrations of alkyl groups and cycloaliphatic C H
1
bonds are observed in the region 2960 2870 cm , of
1
aromatic C H bonds at 3060 3030 cm . In the IR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1
Table 2. H NMR spectrum of 8-aryl-l 1,1 I-dimethyl -7,8,9,10,ll,12-hexahydrobenzo[a]4,7-phenanthroline-9-enes (LII C), , ppma
Compd.
no.
H1, d
H2, d.d
H3, d
H5, H6, 2d H8, s H10, m H12, d.d
Aromatic protons (J, Hz)
NH, s
Me, s
3J 4.6 Hz) (3J 8.2, 4J 2.8 Hz) (3J 8.2 Hz) (3J 8.6 Hz)
(2J16.0 Hz)
LII
LIII
LIV
LV
LVI
LVII
LVIII
LIX
LX
8.29
8.28
8.33
8.30
8.32
8.32
8.29
8.33
8.30
8.29
8.31
8.28
8.29
8.30
8.29
8.31
8.33
8.32
8.29
8.31
8.27
8.32
8.27
8.30
8.39
8.37
8.36
8.31
8.28
8.29
8.27
8.30
7.33
7.30
7.31
7.32
7.30
7.34
7.30
7.31
7.33
7.29
7.30
7.30
7.31
7.28
7.34
7.36
7.31
7.39
7.30
7.32
7.30
7.29
7.30
7.31
7.39
7.35
7.33
7.28
7.30
7.30
7.26
7.31
8.61
8.60
8.59
8.61
8.58
8.64
8.62
8.59
8.64
8.60
8.58
8.61
8.59
8.62
8.66
8.67
8.64
8.67
8.65
8.64
8.60
8.66
8.59
8.60
8.65
8.61
8.62
8.60
8.63
8.69
8.60
8.57
7.49, 7.80 5.75 2.47
7.50, 7.81 5.73 2.46
7.51, 7.80 5.79 2.48
7.50, 7.82 5.76 2.43
7.49, 7.77 5.81 2.45
7.51, 7.88 5.80 2.43
7.49, 7.80 5.77 2.48
7.50, 7.79 5.73 2.50
7.48, 7.81 5.78 2.47
7.51, 7.78 5.75 2.51
7.50, 7.79 5.69 2.50
7.52, 7.79 5.74 2.46
7.49, 7.80 5.78 2.49
7.50, 7.83 5.75 2.53
7.51, 7.80 5.59 2.52
7.49, 7.84 5.61 2.50
7.50, 7.86 5.74 2.47
7.51, 7.87 5.63 2.51
7.49, 7.81 5.79 2.52
7.50, 7.77 5.78 2.48
7.46, 7.75 5.76 2.50
7.51, 7.87 5.74 2.50
7.48, 7.79 5.70 2.46
7.49, 7.81 5.73 2.49
7.51, 7.85 5.72 2.50
7.50, 7.82 5.75 2.48
7.48, 7.81 5.71 2.46
7.49, 7.80 5.66 2.49
7.50, 7.76 5.70 2.51
7.49, 7.80 5.78 2.48
7.48, 7.77 5.76 2.49
7.49, 7.78 5.73 2.50
2.10
2.10
2.13
2.12
2.11
2.10
2.08
2.10
2.09
2.10
2.12
2.11
2.10
2.12
2.11
2.12
2.10
2.13
2.11
2.10
2.11
2.15
2.10
2.12
2.14
2.12
2.13
2.12
2.10
2.07
2.11
2.10
6.94-7.10 m
9.50 0.88, 1.11
9.51 0.90, 1.10
9.49 0.89, 1.11
9.52 0.92, 1.12
9.53 0.91, 1.10
9.80 0.89, 1.03
9.51 0.89, 1.10
9.56 0.90, 1.11
9.53 0.91, 1.10
9.60 0.90, 1.12
9.61 0.89, 1.09
9.52 0.90, 1.10
9.50 0.91, 1.13
9.58 0.88, 1.11
9.63 0.89, 1.07
9.74 0.87, 1.02
9.71 0.90, 1.09
9.63 0.91, 1.06
9.63 0.90, 1.08
9.59 0.89, 1.10
9.60 0.88, 1.10
9.76 0.86, 1.09
9.57 0.91, 1.10
9.56 0.89, 1.10
9.51 0.92, 1.12
9.55 0.95, 1.08
9.49 0.97, 1.11
9.50 0.94, 1.10
9.47 0.91, 1.09
9.54 0.90, 1.10
9.66 0.87, 1.08
9.70 0.88, 1.11
6.86 d, 7.12 d (3J 8.2)
6.95-7.11 m
6.90 d, 7.11 d (3J 8.0)
6.94 d, 7.10 d (3J 8.5)
6.91 t (3J 8.9), 7.18 m
6.99 m (3J 8.8), 7.19-7.28 m
7.14 d, 7.22 d (SJ
6.98-7.17 m
8.2)
LXI
LXII
7.11 d, 7.39 d (3J 7.9)
7.00 s, 7.11-7.28 m
7.08-7.21 m
LXIII
LXIV
LXV
LXVI
LXVII
LXVIII
LXIX
LXX
LXXI
LXXII
LXXIII
LXXIV
LXXV
LXXVI
LXXVII
LXXVIII
LXXIX
LXXX
LXXXI
LXXXII
LXXXIII
7.02-7.11 m, 7.14 s
7.06-7.19 m
6.66-6.94 m
6.48 d, 6.99 d (3J 8.8)
6.42 d (V 4.0), 6.50-7.00 m
6.48 s, 6.50 s
6.60 d, 7.07 d (3J 8.1)
6.72-7.04 m
6.69 d, 7.10 d (3J 8.0)
6.68 d, 7.12 d (3J 7.9)
6.31-6.49 m, 7.06 d (3J 8.2)
6.40-6.50 m, 7.00 s
6.60 m, 7.01 s
6.45 s
6.42 s
6.51-6.63 m, 7.00 s
6.64 s, 6.71-6.99 m
7.36 d, 7.71 d (3J 8.1)
7.01 s, 7.11-7.21 m
6.46 d, 6.99 d (3J 8.6)

Table 2. (Contd.)
Compd.
no.
H1, d
H2, d.d
H3, d
H5, H6, 2d H8, s H10, m H12, d.d
Aromatic protons (J, Hz)
NH, s
Me, s
3J 4.6 Hz) (3J 8.2, 4J 2.8 Hz) (3J 8.2 Hz) (3J 8.6 Hz)
(2J16.0 Hz)
LXXXIV
LXXXV
LXXXVI
LXXXVII
LXXXVII
LXXXIX
XC
XCI
XCII
XCIII
XCIV
XCV
XCVI
XCVII
XCVIII
XCIX
8.34
8.30
8.28
8.30
8.29
8.80
8.28
8.29
8.30
8.33
8.37
8.32
8.31
8.30
8.32
8.29
8.36
7.32
7.29
7.27
7.31
7.30
7.25
7.30
7.28
7.28
7.30
7.38
7.39
7.30
7.27
7.29
7.32
7.31
8.64
8.63
8.60
8.64
8.63
8.70
8.62
8.63
8.60
8.61
8.70
8.56
8.58
8.60
8.61
8.60
8.58
7.50, 7.77
7.51, 7.82
7.48, 7.80
7.53, 7.93
7.55, 7.94
7.54, 7.90
7.51, 7.83
7.50, 7.81
7.52, 7.80
7.53, 7.86
7.50, 7.82
7.49, 7.83
7.50, 7.80
7.48, 7.80
7.50, 7.76
7.51, 7.83
7.49, 7.81
5.65
5.74
5.67
5.84
5.89
5.92
5.79
5.78
5.80
5.88
5.49
5.73
6.03
5.76
5.79
5.71
5.77
2.51
2.47
2.49
2.50
2.52
2.51
2.52
2.48
2.50
2.52
2.49
2.49
2.50
2.53
2.50
2.49
2.50
2.12
2.12
2.10
2.09
2.11
2.10
2.13
2.11
2.10
2.09
2.18
2.11
2.14
2.18
2.13
2.11
2.13
6.40 d, 7.00 d (3J 8.5)
6.52 d, 7.03 d (3J 8.6)
6.59 s, 6.78 s
9.69 0.88, 1.10
9.70 0.90, 1.09
9.59 0.89, 1.10
9.72 0.90, 1.12
9.78 0.90, 1.10
9.80 0.80, 1.03
9.59 0.94, 1.11
7.45 d, 8.02 d (3J 8.2)
7.60-7.82 m, 8.10 s
7.10 d, 7.40 m,
7.75 d (3J 8.2) 7.32-7.48 m
6.70 d, 7.12 d (3J 7.8), 7.32 m 9.52 0.95, 1.10
6.76-6.98 m, 7.07 s
7.36-7.47 m, 8.03-8.19 m
9.51 0.94, 1.12
9.73 0.91, 1.11
9.61 0.99, 1.12
9.82 0.88, 1.04
9.61 0.89, 1.10
9.76 0.90, 1.11
9.70 0.91, 1.12
9.72 0.90, 1.10
9.74 0.89, 1.10
7.00 d, 7.19 d (3J 7.9)
6.55 s, 6.70 s, 7.00 s
6.53 d, 6.95 d (3J 7.9)
6.96-7.11 m, 8.49 d (3J 7.8)
6.91-7.06 m, 8.37 s
6.95-7.22 m
C
a
Chemical shifts, , ppm: 2.18, s (Me) (LIV); 1.15 t, 2.50 q (Et) (LV); 1.08 d, 2.70 m (CHMe2) (LVI); 9.00 s (OH) (LXVII); 9.11 s (OH) (LVIII);
8.38 s (OH), 8.47 s (LXIX); 3.80 s (OMe) (LXX); 3.82 s (OMe) (LXXI); 1.20 t, 4.10 q (OEt) (LXXII); 0.94 t, 1.60 q, 3.75 t (OCH2CH2Me)
(LXXIII); 3.62 s (OMe), 3.87 s (OMe) (LXXIV); 3.60 s (OMe), 3.86 s (OMe) (LXXV); 3.14 s (OMe), 3.21 s (OMe) (LXXVI); 3.55 s (OMe),
(LXXVII); 3.66 s [(OMe2)], 7.90 s (OH) (LXXVIII); 1.18 t, 4.13 q (OEt), 8.10 s (OH) (LXXIX); 3.76 s (OMe) (LXXX); 3.76 s (CO2Me) (LXXXI);
3.70 s (OMe), 3.82 s (CO2Me) (LXXXII); 2.72 s (NMe2) (LXXXIII); 0.98 t, 3.15 q (NEt2) (LXXXIV); 3.12 d 4.58 d [N(CH2CH2Cl)2] (LXXXV);
5.84 m (OCH2O) (LXXXVI); 4.90 s (OCH2Ph) (XCI); 3.84 s (OMe), 4.87 s (OCH2Ph) (XCII); 1.16 2.00 m (7H cycloaliph.), 4.80 s (CH=CH)
(XCIV); 2.44 s (Me) (XCVII).

SYNTHESIS OF FUSED DERIVATIVES OF 4,7-PHENANTHROLINE
1501
1
spectra of compounds LXX LXXXII, LXXXVI,
XCI, XCII appear the bands from the C O C frag-
ment in the region 1245 1230 cm , in the spectrum
A characteristic feature of H NMR spectra of
4,7-phenanthrolines LII C consists in a downfield
shift of the signal from the methine proton in the
hydrogenated pyridine ring (H8) as compared to the
usual position of methine proton signals in cyclic
compounds. This shift is due to the effect of the
adjacent nitrogen atom and of an aromatic ring. The
influence of the latter is confirmed by the fact that in
the spectrum of phenanthroline XCIV where instead
of aryl is present a cyclohexenyl substituent the down-
field shift of H8 atom is the least in the phenanthroline
series LII c, and the corresponding chemical shift is
the smallest (5.49 ppm).
1
of compound XCV is observed a strong band of
1
stretching vibrations of C S bond at 1125 cm , and
those of phenanthrolines LXXXI, LXXXII contain
an absorption band of the ester group at 1725
1
1720 cm .
In the mass spectra of benzophenanthrolines LII C
the molecular ion [M]+ peaks are of moderate inten-
sity (12 45%). The most abundant (100%) is the ion
[M R]+ (m/z 277). In the spectra of compounds
LXXIV, LXXXIII, C were registered peaks of ions
[R + H]+ , m/z 138 (26%), 121 (83%), 128 (15%)
respectively evidencing the relative stability of
1,3-dimethoxybenzene, N,N-dimethylaniline, and
naphthalene ions to electron impact. In all the spectra
of phenanthrolines LII C appears a peak of ion with
m/z 193 (18 52%) corresponding to elimination of a
fragment (CH3)2CHCH2CO from ion [M R]+ .
Thus the three-component condensation of
6-aminoquinoline, aromatic aldehyde, and dimedone
can serve as a convenient one-pot preparation method
for synthesis of diverse hard-to-obtain derivatives of
4,7-phenanthroline. The intermediate compounds in
the phenanthrolines synthesis, azomethines of the
6-aminoquinoline series, are of separate interest as
potential biologically active substances and synthons
for preparation of various nitrogen-containing hetero-
cycles.
The electron absorption spectra of compounds
LII C have bands in the UV region with pronounced
vibronic structure. Since in the molecules of benzo-
phenanthrolines LII C the benzene and pyridine
rings are partly hydrogenated, the main chromophore
is the quinoline core conjugated with a carbonyl
EXPERIMENTAL
IR spectra were obtained on UR-20 instrument
from KBr pellets. Mass spectra were registered on
MKh-1320 device with direct samples input, energy
of ionizing electrons 50 eV, evaporation of samples
at 180 200 C. UV spectra of solutions in ethanol (c
10 mol l ) were measured on spectrophotometer
Specord UV-Vis. H NMR spectra were recorded on
spectrometers Bruker AC-300 (300 MHz) or Tesla
BS-567 (100 MHz) at concentration of solutions
2 5 wt% in deuterochloroform for azomethines
III LI and DMSO-d6 for compounds LII C, internal
reference TMS. Melting points were measured on
Koeffler heating block.
group. Therefore the bands with
214 222, 234
max
258, 288 299 nm may be assigned to the 6-amino-
quinoline system [UV spectrum, max, nm (log ):
206 (4.08), 247 (4.35), 279 (3.59)]. A considerable
red shift and greater intensity of the first and third
bands in the spectra of phenanthrolines LII C are
apparently due to the effect of the carbonyl group and
overlapping with the absorption bands of phenyl,
heteroaromatic, or naphthalene substituent R uncon-
jugated with the quinoline core. The bands appearing
in the longwave spectrum region (333 339, 369
381 nm) are probably due to the presence of the
carbonyl group [13]. The substituents in the phenyl
ring of compounds LIII XCIII, XCIV virtually do
not affect the position and intensity of the absorption
bands. It is noteworthy that the UV spectra of com-
pounds LII C are identical to those of the previously
studied demethylated analogs, 8-aryl-7,8,9,10,11,12-
hexahydrobenzo[a]-4,7-phenanthrolin-9-ones [7] that
presumably evidences no steric hindrances to con-
formational lability of cyclohexene and dihydro-
pyridine rings from the of methyl groups; therefore
the presence of the methyl groups does not affect the
electron transitions in the fused quinoline system and
the carbonyl group.
4
1
1
6-Aminoquinoline (II) was prepared along
procedure [14]. Arylmethylene-6-aminoquinolines
III LI were synthesized by boiling amine II and an
appropriate aromatic aldehyde in ethanol or 2-propan-
ol. Preparation procedure and characteristics of azo-
methines III,IV, VI XIII, XV, XVII XXI, XXV,
XXVII XXIX, XXXII, XXXIV XLII, L) were
published elsewhere [14]. The yields and analytical
data on the azomethines obtained for the first time
V, XIV, XVI, XXII XXIV, XXVI, XXX, XXXI,
XXXIII, XLIII XLIX, LI are presented in Table 1.
8-Aryl-11, 11-dimethyl-7,8,9,10,11,12-hexa-
hydro[a]-4, 7-phenanthrolin-9-ones LII C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1502
GUSAK et al.
(a) A solution of 5 mmol of dimedone (I), 5 mmol of
6-aminoquinoline (II), and 5 mmol of an appropriate
aldehyde in 20 ml of 1-butanol was refluxed for 5
6 h. The precipitate separated on cooling was filtered
off and recrystallized from a mixture ethanol benzene
(3: 1). (b) A solution of 5 mmol of dimedone (I) and
5 mmol of azomethine III LI in 20 ml of 1-butanol
was refluxed for 5 h. The reaction products LII C
were isolated as described above. Yield of phenanthro-
lines LII C 40 85%.
REFERENCES
1. Mashkovskii M.D., Lekarstvennye veshchestva
(Drugs), Kharkov: Torsing, 1998, vol. 2, pp. 313 314.
2. Europe 13666, 1980. Chem. Abstr., 1981, vol. 94,
15704x.
3. Hall, C.M., Wright, J.B., Johnson, H.G., and
Taylor, A.J., J. Med. Chem., 1977, vol. 20, no. 10,
pp. 1337 1343.
4. Pushkareva, Z.V., Alekseeva, L.V., Konyu-
khov, V.N., and Darienko, V.P., Abstracts of Papers,
Soveshch. po metodam issled. org. soed. i khim.
protsessov (Meeting on Method of Organic Com-
pounds Investigation),, Frunze, 1964, pp. 26 38.
5. Bicsak, T.A., Rann, L.R., Reiter, A., and Chase, T.,
Arch. Biochem. Biophys., 1982, vol. 216, no. 2,
pp. 605 615.
6. Jastrzebska-Glapa, M., Mlochowski, J. and Sliwa, W.,
Pol. J. Chem., 1979, vol. 53, no. 4, pp. 811 820.
7. Gusak K.N., Tereshko A.B., Kozlov N.G., and
Shakailo, N.I., Zh. Org. Khim., 2000, vol. 70,
no. 11, pp. 1904 1911.
8. Cardellini, M., Cingolani, G.M., Claudi, F., Cristal-
li, G., Gulini, W., and Martelli, S., J. Org. Chem.,
1982, vol. 47, no. 4, pp. 688 692.
9. Kozlov, N.S., 5,6-Benzokhinoliny, Minsk: Nauka i
tekhnika, 1979, pp. 37 40.
10. Kozlov, N.G., Gusak, K.N., and Bezborodov, V.S.,
Zh. Org. Khim., 2000, vol. 36, no. 1, pp. 98 102.
11. Bovykin, B.A., Ranskii, A.P., Zanina, I.A., and
Artyukhova, E.P., Voprosy Khimii i Khimicheskoi
Tekhnologii, 1983, no. 70, pp. 23 26.
12. Neiland, O., Tsiklicheskie -Diketony Cyclic Di-
ketones), Riga: Akad. Nauk Latv. SSR, 1961,
pp. 41 54.
9-[1-(1,3-Dioxocyclohexyl)]-3,3,6,6-tetramethyl-
1,2,3,4-tetrahydroxanthen-1-ones CI CIII were
obtained from dimedone (I), 60 aminoquinoline (II),
and an appropriate aldehyde along procedure a.
Reaction products CI CIII were recrystallized from
ethanol. Compound CI, yield 39%, mp 205 206 C.
1
IR spectrum, , cm : 1620 (C=O), 1255 (C O C),
1
2960 2870 (CH3, CH2). H NMR spectrum, , ppm:
0.96 s (6H, CH3), 1.08 s (3H, CH3), 1.14 s (3H,
CH3), 2.18 2.60 m (8H, CH2), 5.08 s (1H, CH),
7.00 7.20 m (4H arom). Mass spectrum, m/z (Irel, %):
366 [M]+ (58), 281 (100), 227 (80). Found, %: C
75.25; H 7.02. C23H26O4. Calculated, %: C 75.41;
H 7.10. Compound CII, yield 66%, mp 242 243 C.
1
IR spectrum, , cm : 1630 (C=O), 1240 (C O C),
1
2970 2890 (CH3, CH2). H NMR spectrum, , ppm:
0.98 s (6H, CH3), 1.08 s (3H, CH3), 1.16 s (3H,
CH3), 2.20 2.62 m (8H, CH2), 5.00 s (1H, CH),
6.38 6.88 m (3H arom). Mass spectrum, m/z (Irel,
%): 382 [M]+ (20), 298 (25), 242 (50), 227 (100).
Found, %: C 72.02; H 6.88. C23H26O5. Calculated,
%: C 72.25; H 6.81. Compound CIII, yield 48%,
1
mp 244 245 C. IR spectrum, , cm : 1650 (C=O),
1
1240 (C O C), 2950 2820 (CH3, CH2). H NMR
spectrum, , ppm: 0.90 s (6H, CH3), 1.08 s (3H,
CH3), 1.18 s (3H, CH3), 2.10 2.68 m (8H, CH2),
5.62 s (1H, CH), 7.20 8.35 m (6H arom). Mass
spectrum, m/z (Irel, %): 416 [M]+ (50), 332 (45),
277 (100). Found, %: C 77.49; H 6.49. C27H28O4.
Calculated, %: C 77.88; H 6.71.
13. Ctrakov, A.Ya., Gudrinietse, E.Yu., adn Zitsa-
ne, D.R., Khim. Geterotsikl. Soed., 1974, no. 8,
pp. 1011 1030.
14. Gusak, K.N., Tereshko, A.B., and Kozlov, N.G.,
Zh. Org. Khim., 2000, vol. 70, no. 2, pp. 320 326.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001