SYNTHESIS OF BENZO[4,5]IMIDAZO[2,1-a]PHTHALAZINES
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2.63 s (CH3), 7.52 d (H4'), 7.75 s (H6'), 7.787.99 m (H5,
H6, H7), 8.02 d (H3'), 8.44 d (H8). Found, %: C 56.96,
57.18; H 3.29, 3.41; N 13.17, 13.42. C15H10ClN3O3.
Calculated, %: C 57.07; H 3.19; N 13.31.
intramolecular dehydration (procedure a) where the
phthalazine fragment acted as a cyclic amide. We
simplified the synthesis by developing a direct procedure
of converting compound III into tetracyclic system V.
This method consists in reduction of nitro compounds III
with metallic iron in PPAat heating, and the arising amine
IV is converted into benzoimidazophthalazine (V) by
increasing the reaction mixture temperature to 130140°C
(procedure b). By this method we succeeded in prepara-
tion of compounds Va, b unpossible to obtain by method
a because of low solubility of nitro compounds IIIa, b
and the corresponding amines. Compounds Vc, d were
synthesized by procedure b in higher yields.
2-(2-Nitro-5-chlorophenyl)-4-phenyl-1,2-di-
hydro-1-phthalazinone (IIId). From 13.6 g of 2-benzo-
yl-benzoic acid (Ib) and 10.7 g of 2-nitro-5-chloro-
phenylhydrazine (IIc) after recrystallization from a
mixture chloroform ethanol we obtained 13.7 g (64%)
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phthalazinone IIId, mp 137139°C. H NMR spectrum
(DMSO), d, ppm: 7.527.86 m (H4', H6', 4-phenyl), 7.87
8.01 m (H5, H6, H7), 8.19 d (H3'), 8.41 t (H8). Found, %:
C 63.47, 63.68; H 3.15, 3.44; N 11.03, 11.37.
C20H12ClN3O3. Calculated, %: C 63.59; H 3.20; N 11.12.
The synthetic procedures we developed are a lot
simpler than the previous one [2] and also make it possible
to synthesize a wide range of benzoimidazophthalazine
derivatives in a good yield.
2-(2-Amino-5-chlorophenyl)-4-methyl-1,2-
dihydro-1-phthalazinone (IVa). A solution of 1.9 g
(0.006 mol) of 2-(2-nitro-5-chlorophenyl)-4-methyl-1,2-
dihydro-1-phthalazinone (IIIc) in 20 ml of THF was
subjected to hydrogenation by gaseous hydrogen at
atmospheric pressure with constant stirring in the presence
of 0.16 g of a catalyst (5% Pd on carbon). After
consumption of 370 ml of hydrogen within 6 h the reaction
mixture was filtered from the catalyst and evaporated to
a volume of 10 ml. Then the residue was diluted with
petroleum ether (fraction of bp 4070°C) to 100 ml. The
precipitated reaction product was chromatographically
pure and was used without additional purification. We
obtained 0.7 g (54%) of aminophthalazinone IVa, mp 182
4-Methyl-2-(2-nitrophenyl)-1,2-dihydro-1-
phthalazinone (IIIa). Asolution of 9.8 g (0.060 mol) of
2-acetylbenzoic acid (Ia) and 8.8 g (0.057 mol) of
o-nitrophenylhydrazine (IIa) in a mixture of 80 ml of
ethanol and 40 ml of concn. sulfuric acid was boiled for
1.5 h, then it was poured on 300 g of crushed ice, and the
separated precipitate was filtered off. On recrystallization
from a mixture chloroformethanol we obtained 9.6 g
(60%) of phthalazinone IIIa, mp 195197°C. 1H NMR
spectrum (DMSO), d, ppm: 2.61 s (CH3), 7.617.78 m
(H4', H5'), 7.828.01 m (H5, H6, H7, H6'),* 8.08 d (H3'),
8.37 d (H8). Found, %: C 63.93, 64.21; H 4.02, 4.13;
N 14.76, 15.01. C15H11N3O3. Calculated, %: C 64.05;
H 3.94; N 14.94.
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184°C. H (DMSO), d, ppm: 2.59 s (CH3), 5.04 s (NH2),
6.81 d (H3'), 7.077.15 m (H4', H6'), 7.807.98 m (H5,
H6, H7), 8.37 d (H8). Found, %: C 62.87, 62.99; H 4.24,
4.41; N 14.56, 14.74. C15H12ClN3O.Calculated,%:C 63.05;
H 4.23; N 14.71.
2-(2,4-Dinitrophenyl)-4-methyl-1,2-dihydro-1-
phthalazinone (IIIb). Likewise from 9.9 g of compound
Ia and 11.4 g of 2,4-dinitrophenylhydrazine IIb after
recrystallization from DMF we obtained 9.9 g (54%) of
phthalazinone IIIb, mp 244246°C. 1H NMR spectrum
(DMSO), d, ppm: 2.64 s (CH3), 7.838.18 m (H5, H6,
H7, H6'), 8.37 d (H8), 8.70 d (H5'), 8.80 s (H3'). Found, %:
C 55.13, 55.31; H 3.04, 3.29; N 17.19, 17.41. C15H10N4O5.
Calculated, %: C 55.22; H 3.09; N 17.17.
2-(2-Amino-5-chlorophenyl)-4-phenyl-1,2-
dihydro-1-phthalazinone (IVb). Likewise from 2.3 g
of 2-(2-nitro-5-chlorophenyl)-4-phenyl-1,2-dihydro-1-
phthalazinone (IIId) we obtained 1.9 g (93%) of
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aminophthalazinone IVa, mp 185187°C. H NMR
spectrum (CDCl3), d, ppm: 3.99 s (NH2), 6.80 d (H3'),
7.17 d (H4'), 7.40 d (H6'), 7.457.58 m (H2, H4, H6
4-phenyl), 7.597.65 m (H3, H5 4-phenyl), 7.767.86 m
(H5, H6, H7), 8.61 t (H8). Found, %: C 69.13, 69.24;
H 3.98, 4.17; N 12.22, 12.37. C20H14ClN3O. Calculated,
%: C 69.07; H 4.06; N 12.08.
4-Methyl-2-(2-nitro-5-chlorophenyl)-1,2-
dihydro-1-phthalazinone (IIIc). From 9.8 g of com-
pound Ia and 10.7 g of 2-nitro-5-chlorophenyl-hydrazine
IIc after recrystallization from a mixture chloroform
ethanol we obtained 13.5 g (75%) of phthalazinone IIIc,
5-Methylbenzo[4,5]imidazo[2,1-a]phthalazine
(Va). Procedure b. To a solution of 1.25 g (0.005 mol) of
4-methyl-2-(2-nitrophenyl)-1,2-dihydro-1-phthalazinone
(IIIa) in 20 g of PPA heated to 100°C was added by
portions at stirring 1.25 g of iron powder. After all iron
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mp 168170°C. H NMR spectrum (CDCl3), d, ppm:
* Here and hereinafter the protons of aryl substituent in position
2 are marked with a dash.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 40 No. 11 2004