Studies in benzonaphthyridines: Synthesis of benzoimidazonaphthyridines

Article abstract of DOI:10.1071/CH00127

Benzoimidazonaphthyridines were synthesized and quaternary salts of benzonaphthyridine were studied using cyclization reactions. Structural confirmation of the cyclized products was done by nuclear magnetic resonance (NMR), mass spectroscopy and elemental

Full text of DOI:10.1071/CH00127

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Short Communications
Aust. J. Chem., 2001, 54, 105–106
Studies in Benzonaphthyridines: Synthesis of
Benzoimidazonaphthyridines
Barbara BachowskaA,B and Teresa ZujewskaA
AInstitute of Chemistry, Pedagogical University, PL 42–201 Czestochowa, Poland.
BAuthor to whom correspondence should be addressed (e-mail: (b.bachowska@wsp.czest.pl).
Manuscript received: 9 October 2000.
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Quaternary salts of azaaromatics have been intensively
In the present work we describe the cyclization reactions
studied for both theoretical and practical points of view,[1–2]
e.g. they are useful in solar energy conversion and
storage,[3–8] and therefore the chemistry of N-substituted
benzonaphthyridines is of interest.
of 5-phenacylbenzo[c]-1,5-, 6-phenacylbenzo[h]-1,6-, and
6-phenacylbenzo[f]-1,7-naphthyridinium bromides (4)–(6)
with ammonium acetate.
The starting materials (4)–(6) were prepared from
benzo[c]-1,5-, benzo[h]-1,6- and benzo[f]-1,7-naphthy-
ridines by reaction with phenacyl bromide.[15]
We have observed that the reactions of (4)–(6) with
ammonium acetate in the presence of the oxidant ferric
chloride in acetic acid led to cyclization products (7)–(9),
namely 2-phenylbenzo[c]imidazo[1,2-a]-1,5-naphthyridine
(7), 2-phenylbenzo[h]imidazo[2,1-f]-1,6-, naphthyridine (8),
are 2-phenylbenzo[f]imidazo[1,2-h]-1,7-naphthyridine (9)
(see Scheme 2).
In our former work concerning the properties of
quaternary benzonaphthyridinium salts, 1,3-dipolar
cycloaddition reactions of benzo[c]-1,5-, benzo[h]-1,6-, and
benzo[f]-1,7-naphthyridine phenacylides, ethoxycarbonyl-
methylides and dichloromethylides (1)–(3) have been
investigated.[9–14]
Earlier Toja et al.[16] reported a similar procedure for
isoquinolinium phenacyl bromides. Their products,
arylimidazo[2,1-a]isoquinolines, were shown to exhibit
pregnancy-terminating activity in both hamsters and rats.
Accordingly we anticipate similar interesting applications
Tetracyclic cycloadducts: substituted benzopyrrolo-,
benzopyrroline-,
or
benzopyrrolidine-naphthyridines,
resulted from our synthetic work (see Scheme 1).
© CSIRO 2001
10.1071/CH00127
0004-9425/01/020105

106
B. Bachowska et al.
All synthesized products were obtained as small pale-grey crystals.
Their melting points (m.p.), yields, elemental analyses, H NMR and
mass spectroscopic data are shown below.
for our imidazole analogues. The imidazole derivatives (7)–
(9) complete the series of fused, four-ring cyclic derivatives
of benzonaphthyridines which we obtained previously.[9–14]
The structures of the compounds obtained were
1
Compound (7): m.p. 189–190°C; yield 48% (Found: C, 81.1; H, 4.2;
N, 14.0 C20H13N3 requires C, 81.3; H, 4.4; N, 14.2%). 1H NMR δ 9.21,
s, 1H, H 3; 8.62, dd, J12,11 7.35, J12,10 1.21 Hz, 1H, H 12; 8.51, dd, J7,6
4.54, J7,5 1.53 Hz, 1H, H 7; 8.22, dd, J9,10 7.45, J9,11 1.68 Hz, 1H, H 9;
8.01–8.12, m, 2H, H 2Ј,6Ј; 7.78, dd, J6,7 4.54, J6,5 8.38 Hz, 1H, H 6; 7.66,
dd, J10,9 7.45, J10,11 7.15 Hz, 1H, H 10; 7.46–7.61, m, 3H, H 3Ј,5Ј,11;
7.38, dd, J4Ј,3Ј = J4Ј,5Ј 7.09, J4Ј,2Ј = J4,6 1.23 Hz, 1H, H4Ј; 7.23, dd, J5,6
8.38, J5,7 1.53 Hz, 1H, H 5. Mass spectrum: m/z 295 (M+, 100%).
Compound (8): m.p. 195–196.5°C; yield 41% (Found: C, 81.0; H,
4.3; N, 14.1. C20H13N3 requires C, 81.3; H, 4.4; N, 14.2%). 1H NMR δ
9.08, s, 1H, H 3; 8.72, dd, J10,11 4.93, J10,12 1.48 Hz, 1H, H 10; 7.94–
8.10, m, 5H, H 2Ј,6Ј,11,8,12; 7.79, dd, J6,5 7.78, J6,7 7.28 Hz, 1H, H 6;
7.51, dd, J3Ј,2Ј = J5Ј,6Ј 7.81, J3Ј,4Ј = J5Ј,4Ј 7.08 Hz, 2H, H 3Ј,5Ј; 7.42, dd,
J7,8 7.94, J7,6 7.28 Hz, 1H, H 7; 7.32, dd, J4Ј,3Ј = J4Ј,5Ј 7.08, J4Ј,2Ј = J4Ј,6Ј
1.21 Hz, 1H, H 4Ј; 7.21, dd, J5,6 7.78, J5,7 1.23 Hz, 1H, H 5. Mass
spectrum: m/z 295 (M+, 100%).
Compound (9): m.p. 185–186°C; yield 38% (Found: C, 81.1; H, 4.5;
N, 14.4. C20H13N3 requires C, 81.3; H, 4.4; N, 14.2%). 1H NMR δ 8.96,
dd, J11,10 5.13, J11,9 1.2 Hz, 1H, H 11; 8.24, dd, J8,7 7.82, J8,6 1.56 Hz,
1H, H 8; 8.12, s, 1H, H 3; 8.06, dd, J2Ј,3Ј = J6Ј,5Ј 7.91, J2Ј,4Ј = J4Ј,6Ј 1.25
Hz, 2H, H 2Ј,6Ј; 7.89, dd, J6,5 7.85, J6,7 7.34 Hz, 1H, H 6; 7.73, dd, J9,10
8.10, J9,11 1.2 Hz, 1H, H 9; 7.62, dd, J10,9 8.10, J10,11 5.13 Hz, 1H, H 10;
7.51–7.58, m, 3H, H 7,3Ј,5Ј; 7.37, dd, J4Ј,3Ј = J4Ј,5Ј 7.12, J4Ј,2Ј = J4Ј,6Ј 1.25
Hz, 1H, H 4Ј; 7.24, dd, J5,6 7.85, J5,7 1.27 Hz, 1H, H 5. Mass spectrum:
m/z 295 (M+, 100%).
1
confirmed by H nuclear magnetic resonance (NMR) and
mass spectroscopic data, as well as by elemental analysis.
The 1H NMR spectra of the cyclized products (7)–(9)
showed 13 aromatic protons, including five protons from the
phenyl group, and were compared with those of
cycloadducts
obtained
from
the
reaction
of
benzonaphthyridinium N-phenacylides (1a)–(3a) and
respective dipolarophiles. In the 1H NMR spectrum of (7) the
H 12 signal is shifted downfield strongly, compared with that
of the respective benzopyrrolonaphthyridine; this
observation is probaby due to the influence of the additional
nitrogen in the imidazole ring. However, no significant
influence of the nitrogen on the chemical shift of H 12 in the
1H NMR spectrum of (8) was observed. The singlets of H 3
at δ 9.21 in the spectrum of (7), at δ 9.08 in the spectrum of
(8), and at δ 8.12 in the spectrum of (9) are very
characteristic.
These results illustrate the interesting reactivity of
quaternary benzonaphthyridinium salts, especially that
reactions of cyclization can readily lead to novel tetracyclic,
fused heterocycles. The biological activity of (7)–(9) will be
investigated.
References
´
´
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determined on a Boëtius apparatus and are uncorrected. Thin-layer
chromatography was performed on 60F254 silica gel (Merck) precoated
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General Procedure for Synthesis of (7)–(9)
[10] B. Bachowska, W. Sliwa, Acta Chim. Hung. 1988, 125, 491.
A mixture of (4), (5) or (6) (2 g, 5.3 mmol), ammonium acetate (2.7
g, 36.3 mmol), anhydrous ferric chloride (3 g, 18.4 mmol) in acetic acid
(15 cm3) was heated in an autoclave at 150°C for 6 h. After cooling to
room temperature, the precipitated solid was filtered, washed with
acetic acid (10 cm3), water, and then taken up with methylene chloride
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(7), (8), and (9), respectively.
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