Efficient route to benzo[4,5]imidazo[2,1-a]phthalazines

Article abstract of DOI:10.1016/j.tet.2006.07.089

Benzo[4,5]imidazo[2,1-a]phthalazines have been obtained from various o-nitrophenylhydrazines through different 2-(2-nitrophenyl)-1,2-dihydro-1-phthalazinones as intermediates using an elaborated advanced procedure. An activated chlorine atom in 2-nitrophe

Full text of DOI:10.1016/j.tet.2006.07.089

Tetrahedron 62 (2006) 10018–10030
Efficient route to benzo[4,5]imidazo[2,1-a]phthalazines
*
Viktor A. Kuznetsov, Kirill M. Shubin, Andrej A. Schipalkin and Mikhail L. Petrov
Saint-Petersburg State Institute of Technology (Technical University), Department of Organic Chemistry, Moskovsky pr. 26,
Saint-Petersburg 190013, Russia
Received 19 January 2006; revised 10 July 2006; accepted 27 July 2006
Available online 1 September 2006
Abstract—Benzo[4,5]imidazo[2,1-a]phthalazines have been obtained from various o-nitrophenylhydrazines through different 2-(2-nitro-
phenyl)-1,2-dihydro-1-phthalazinones as intermediates using an elaborated advanced procedure. An activated chlorine atom in 2-nitrophenyl
moiety of the latter is able to undergo nucleophilic substitution for secondary alicyclic amines yielding novel substituted phthalazinones. Their
one-pot reduction and cyclodehydration yield a series of novel substituted benzo[4,5]imidazo[2,1-a]phthalazines.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Later BIPHs have been also obtained2 from o-aminophenol
(Scheme 3). Substituted BIPH possess slight antihyper-
tensive and antiinflammatory activities;2 however, neither
further investigations have been performed.
Benzo[4,5]imidazo[2,1-a]phthalazine (BIPH) formerly de-
scribed in 1937 by Rowe et al.1 is a tetracyclic aza-hetero-
cycle isoelectronic to aromatic hydrocarbon viz. chrysene.
Three derivatives of this heterocycle including that of unsub-
stituted BIPH have been obtained (Scheme 1).
2. Results and discussion
In our preliminary communication3 we have briefly de-
scribed the synthesis of several newly substituted BIPH. In
the present work we would like to present their syntheses
more comprehensively.
Diazotized benzene substituted o-nitroanilines have been
transformed into the salts of 2-naphthol-1-sulfonic acid. A
series of transformations involving a scission of naphthalene
cycle and formation of phthalazine cycle result in formation
of 3-(2-nitrophenyl)-substituted phthalazinium-1-olate.
The latter have been reduced with aqueous sodium sulfide
followed by rearrangement and subsequent cyclization on
treating with dilute HCl at 180 ꢀC in a sealed tube.
We have worked out more general but rather brief synthetic
route yielding BIPHs by incorporating various substituents
in heterocyclic moiety. We have found it attractive to use
o-nitrophenylhydrazines for synthesis of phthalazine cycle.
In order to make this scheme more practicable we have to
solve several problems as follows:
The structure of BIPHs has been proved by direct syn-
thesis using alternative route (Scheme 2).1 For two sub-
sequent cyclizations have been used the same conditions:
aqueous sodium sulfide, then dilute HCl at 180 ꢀC in a sealed
tube.
1. To elaborate a general procedure of cyclization of
2-acylbenzoic acids with 2-nitrophenylhydrazines yield-
ing 2-nitrophenyl substituted phthalazin-1-ones;
CH3
O2N
H3C
N
N
OH
N
N+
N
R
SO3-
N+
N
O
R
O2N
R
R = H, Me, Cl
Scheme 1.
Keywords: Nucleophilic substitution; Phthalazinone; Cyclodehydration; Benzimidazole.
* Corresponding author. Tel./fax: +7 812 316 3377; e-mail: kir101@orgchem.spb.ru
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.089

V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
10019
2
R
R2
NO2
H2N
HN
SnCl2
O
H
N
N+
H2N
O2N
N
Na2S
COOH
N
Cl
R1
R1
R1
R1
COOH
O2N
O2N
R2
N
R2
O
R2
N
N
N
N
N
N
R1 = H, CH3, Cl
R2 = H, CH3
Na2S
HCl
180 °C
R1
R1
O
H2N
O2N
R1
Scheme 2.
Ar
Ar
N
HO
Ar
Cl
N
N
N
N
H N
2
PPA
N
N
OH
K2CO3
HN
Ar = C6H5, 4-CH3(C6H5), 4-Cl(C6H5), 3,4-Cl2(C6H5)
Scheme 3.
2. To perform nucleophilic substitution of chlorine atom in
2-nitro-5-chlorophenyl moiety of phthalazin-1-one with
alkylamines;
3. To work out a procedure of reduction of o-nitro group
into amino group;
available are much more limited. These hydrazines are
usually obtained by reduction of diazonium derivatives of
the relative anilines or by substitution of halogen atom in
activated arylhalogenides with hydrazine hydrate. 2-Nitro-
5-chlorophenylhydrazine 1a is easily available by the
reaction of hydrazine with 3,4-dinitrochlorobenzene.4,5 Its
subsequent condensation with o-acylbenzoic acid 2 and
subsequent cyclization of the reaction product may yield
phthalazinone 3 incorporating chlorine atom in para-posi-
tion to nitro group. This chlorine atom is activated enough
to undergo the second nucleophilic substitution thus making
it possible to introduce a wide range of new substituents.
4. To select conditions for cyclization of 2-aminophenyl-
phthalazinones yielding BIPH.
The outlined scheme is shown in Scheme 4.
As to the initial compounds many of the acylbenzoic acids
are readily available. A number of 2-nitrophenylhydrazines
3
R
R3
R3
O
O
R1
R1
H2N
HN
N
R1
R2
N
N
H2 / cat.
OH
2a-i
R2
R2
N
THF
H2SO4
EtOH
O2N
O
O
H2N
O2N
3a-i
1a-c
4a-e
6a-c
R3
Fe
PPA
PPA
H
CH3
C6H5
4-CH3(C6H4)
2a
2b
2c
2d
2e
2f
R3
N
N
N
4-Cl(C6H4)
4-C2H5(C6H4)
3,4-(CH3)2(C6H3)
2,4-(CH3)2(C6H3)
2,5-(CH3)2(C6H3)
R1
2g
2h
2i
R2
5a-i
7a-c
Scheme 4.

10020
V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
Formerly interaction of nitrophenylhydrazines with o-acyl-
benzoic acids has drawn a little attention.6–9 In the literature
there are only limited examples of ring formation involving
o-nitrosubstituted phenylhydrazines, which are especially
difficult for cyclizations.1,8,10 Experimental procedures
used by Rowe et al.1 for synthesis of 2-(2-nitrophenyl)-1-
phthalazinones and subsequent reduction of nitro group
are inconvenient and hardly scalable.
products the almost pure BIPHs have been isolated by water
dilution of the reaction mixture with its subsequent neutral-
ization to pH 7.0. Analytically pure products have been
obtained on their recrystallization from suitable solvent.
We have succeeded in overcoming the problem of poor sol-
ubility of the initial aniline 4 in THF as well as that of sim-
plifying the synthesis of the BIPHs by carrying it out without
isolation of reduction intermediates. To start this transforma-
tion we have tried to use PPA as a solvent. However, we
haven’t succeeded in promoting catalytic reduction in these
conditions. Due to high viscosity of PPA even at elevated
temperatures we couldn’t achieve satisfactory stirring of
the reaction mixture. In order to make the synthesis more
convenient and fast we have used chemical reduction with
iron powder–PPA mixture. To our knowledge formerly this
combination hasn’t been ever used for reduction of nitro
groups.
To our knowledge hydrazine 1a has never been involved into
reaction with acylbenzoic acids. We have tried to perform
this reaction with acid 2 under ordinary conditions but
only intermediate hydrazones were isolated. In searching for
appropriate conditions we have found that a relatively good
yield may be achieved by boiling reagents in ethanol–
sulfuric acid mixture (2:1 by volume). This mixture is boil-
ing in the range from 100 to 120 ꢀC, which happens to be
optimal for cyclization. However, on more prolonged
boiling side reactions lowering the yield of phthalazine 3
(Table 1) become pronounced.
As would be expected the reaction under consideration
occurs as two-stage one-pot synthesis yielding BIPH 5.
The substances obtained proved to be identical with that of
obtained from two-stage synthesis.
Nitro groups of several phthalazines from this series have
beencatalyticallyreducedintorelativeanilines4a–e(Table1)
by gaseoushydrogen in THF solution. The reductionhas been
performed fast and with quantative yields on using Raney
nickel or palladium on carbon. Under these conditions the
solubility of the substituted phenylenediamine 4 has been
noticeably decreased on the enhancement of the molecular
mass of the substituent in position 4 causing their crystalliza-
tion from the reaction mixture and catalyst’s deactivation.
The validity of synthetic route elaborated has been tested by
synthesis of BIPH 7 starting from 2-nitrophenylhydrazine 1b
and 2,4-dinitrophenylhydrazine 1c. The latter has been
used for synthesis of phthalazinones 6a–c (Scheme 4) in
the ethanol–sulfuric acid mixture with increased proportion
of the acid. These phthalazinones especially that of 6b
possess the minor solubility from all the series involved.
Thus we couldn’t hydrogenate them in THF solution. In spite
of their moderate solubility in hot PPA we have obtained
BIPH 7 with high yields. In the case of phthalazinone 6b
both the nitro groups are reduced yielding BIPH with amino
group in 10 position making it possible to extend the range of
substituted BIPH through its reactions.
In the next stage (Scheme 4) we have used polyphosphoric
acid (PPA) as highly efficient dehydrating agent lacking
side reactions unlike sulfuric acid. Moreover at high temper-
atures PPA is an effective solvent for organic compounds
especially for those nitrogen incorporating. A short-term
heating of aniline 4 in PPA solution leads to cyclization of
o-amino group with carbonyl group yielding BIPHs 5a–i.
This reaction is similar to a well-known scheme of synthesis
of benzimidazoles using N-acyl-o-phenylenediamines.11
The chlorine atom in the side benzene ring of the compound
3 is activated enough for nucleophilic substitution with
dialkylamines (Scheme 5).
Under optimal conditions (100–130 ꢀC) only selective de-
hydration (as observed by TLC), with formation of BIPHs
5a–i, occurs with high yield. As we don’t observe any side
It was found that highly basic amines like morpholine,
pyrrolidine, piperidine, and piperazine may easily react with
Table 1
No.
R1
R2
R3
Yield,a %
No.
R1
R2
R3
Yield, %
3a
3b
3c
3d
3e
3f
3g
3h
3i
4a
4b
4c
4d
4e
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
C6H5
4-CH3(C6H4)
4-Cl(C6H4)
4-C2H5(C6H4)
3,4-(CH3)2(C6H3)
2,4-(CH3)2(C6H3)
2,5-(CH3)2(C6H3)
CH3
47
70
58
60
53
35
37
38
47
65
69
83
79
83
5a
5b
5c
5d
5e
5f
5g
5h
5i
6a
6b
6c
7a
7b
7c
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
H
H
H
H
H
H
NO2
H
H
H
CH3
C6H5
4-CH3(C6H4)
4-Cl(C6H4)
4-C2H5(C6H4)
3,4-(CH3)2(C6H3)
2,4-(CH3)2(C6H3)
2,5-(CH3)2(C6H3)
CH3
nab/68c
61/58
64/69
na/55
52/50
68/62
70/85
na/33
na/66
60
C6H5
H
H
H
H
CH3
54
55
63
58
4-Cl(C6H4)
4-C2H5(C6H4)
3,4-(CH3)2(C6H3)
4-Cl(C6H4)
CH3
CH3
NH2
H
H
4-Cl(C6H4)
57
a
Isolated yields.
Yield from aniline 4.
Yield from nitrophthalazinone 3.
b
c

V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
10021
X
R
O
R
CH3
Cl
N
N
HN
N
N
N
N
H2 / cat.
THF
N
N
O
O2N
3a-i
O2N
8a-q
O
9a, X=O (71%)
9b, X=CH2 (79%)
H2N
PPA
Fe
PPA
R
N
N
N
N
10a-q
Scheme 5.
phthalazine 3 yielding substituted dialkylaminophenyl-
phthalazinone 8. This reaction allows introduction of substit-
uents, which are difficult to adopt through o-aminophenol or
o-nitroaniline route. The conversion easily occurs on boiling
of phthalazine 3 in an excess of alicyclic amine with fast
formation of dialkylamino substituted phthalazinone 8 with
high yields (Table 2).
Table 3
R
9-Substituent
Morpholine Pyrrolidine Piperidine Piperazine
(%)
(%)
(%)
(%)
CH3
C6H5
10a (69a)
10e (56)
10h (50)
10k (85)
10b (59)
10f (46)
10i (73)
10l (73)
10c (45)
10g (58)
10j (58)
10m (64) 10n (63)
10o (66)
10p (66)
10d (81)
4-CH3(C6H4)
4-Cl(C6H4)
4-C2H5(C6H4)
3,4-(CH3)2(C6H3)
2,5-(CH3)2(C6H3)
Several dialkylamino derivatives (8) have been hydroge-
nated yielding the relative aniline 9. On hydrogenation in
THF it was found that dialkylamino aniline 9 is much poorly
soluble than the relative chlorine derivative 4. An adequate
yield has been obtained for phthalazinones 9a,b (Scheme 5).
Subsequent cyclization in PPA gives rise to BIPHs 10a,c
with 75% and 87% yields, respectively.
10q (57)
a
Isolated yields.
point is high enough which makes this solvent advantageous
in comparison with aqueous hydrochloric acid. Also above
mentioned pyrrolidine derivatives are more stable in reaction
conditions and less inclined to the thermal decomposition.
Due to rather high water concentration in such an acid
some phthalazinones especially those of chlorine substituted
3 could not be dissolved completely. In these cases tempera-
ture of the reaction mixture has been enhanced to relative
melting point level, this temperature being much lower
than that of pure substances and reduction process has been
carried out in two-phase medium. This results in an enhance-
ment of duration of synthesis and in consumption of iron
powder but practically doesn’t influence the yields.
Dialkylaminophthalazinone 8 has been also directly trans-
formed into BIPHs 10 using iron powder in PPA (Scheme 5,
Table 3). Samples 10a and 10c obtained by two step and one
step procedures have proved to be identical. As would be
expected the solubility of derivative 8 in PPA was substan-
tially higherthanthatof chlorinederivative4; thusthesynthe-
sis may be performed at lower temperature. This is important
as some derivatives for instance those of incorporating pyr-
rolidine moiety happen to be extremely sensitive even to a
small rise of temperature and decompose yielding unidenti-
fied UV-luminescent products soluble only in acidic water.
Further investigations have shown that PPA may be easily
substituted withcommercial 85% phosphoric acid. Itsboiling
3. Conclusion
Thus we have elaborated three-stage procedure of synthesis
of substituted benzo[4,5]imidazo[2,1-a]phthalazines. Sub-
stituents in 5 and 9 positions may be varied in a wide range
and amino group may be introduced in 10 position. Nucleo-
philic substitution of chlorine atom with secondary alicyclic
amines in the side benzene ring of phthalazine 3 makes it
possible to generate dialkylaminophthalazinone 8 formerly
unknown. The latter may be transformed into benzo[4,5]imi-
dazo[2,1-a]phthalazine 10 using one-stage or two-stage pro-
cedures. The most common use of this method making it
possible to vary substituents in 5 and 9 positions has been
demonstrated. All the steps of BIPH synthesis are reliable,
with high yields and have simple laboratory implementation.
Table 2
R
Nucleophile
Morpholine Pyrrolidine Piperidine Piperazine
(%)
(%)
(%)
(%)
CH3
C6H5
8a (71a)
8e (68)
8h (56)
8k (77)
8b (79)
8f (78)
8i (82)
8l (87)
8c (74)
8g (81)
8j (76)
8m (85)
8o (63)
8p (80)
8q (66)
8d (72)
4-CH3(C6H4)
4-Cl(C6H4)
4-C2H5(C6H4)
3,4-(CH3)2(C6H3)
2,5-(CH3)2(C6H3)
8n (86)
a
Isolated yields.

10022
V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
4. Experimental
C15H10ClN3O3 (315.72). Requires, %: C 57.07, H 3.19,
N 13.31.
4.1. General
4.2.3. 2-(2-Nitro-5-chlorophenyl)-4-phenyl-1,2-dihydro-
1-phthalazinone 3c. Mixture of 2-benzoylbenzoic acid 2c
(13.6 g) and 2-nitro-5-chlorophenylhydrazine 1a (10.7 g)
was refluxed for 1 h. After recrystallization from chloro-
form–ethanol 12.4 g (58%) of phthalazinone 3c were
obtained as pale yellow crystals, mp 137–139 ꢀC. nmax
(KBr): 1672, 1599, 1587, 1536, 1472, 1348, 1326, 1137,
739, 692 cmꢁ1. dH (DMSO): 8.42 (1H, m, H1), 8.19 (1H,
d, J¼8.8 Hz, H11), 8.04–7.92 (3H, m, H3, 4, 8), 7.84–7.75
(2H, m, H4, 10), 7.69–7.53 (5H, m, C6H5). dC (DMSO):
157.66, 147.95, 143.40, 138.24, 135.38, 133.97, 133.85,
132.13, 129.26, 129.07, 128.48, 128.23, 127.17, 126.91,
126.12. Found, %: C 63.51, H 3.23, N 11.35. C20H12ClN3O3
(377.79). Requires, %: C 63.59, H 3.20, N 11.12.
Melting points were measured on Boetius apparatus and are
uncorrected. Infra-red spectra were recorded in KBr tablets
on Shimadzu FTIR 8400S instrument. MS spectra were
1
taken on Kratos MS 890. NMR H spectra were obtained
at 400 MHz and 13C at 100 MHz in CDCl3 or DMSO-d6
solution on Bruker WM 400 spectrometer. Numeration of
locations in phthalazines 3, 4, 6, 8, and 9 is given in accor-
dance with their appearance in BIPH 5, 7, and 10, as shown
in Figure 1.
4
1
5
5
4
1
N6
N
3
2
N6
N
3
2
8
9
7
7
8
10
4.2.4. 4-(4-Methylphenyl)-2-(2-nitro-5-chlorophenyl)-
1,2-dihydro-1-phthalazinone 3d. Mixture of 2-(4-methyl-
benzoyl)benzoic acid 2d (14.4 g) and 2-nitro-5-chloro-
phenylhydrazine 1a (10.7 g) was refluxed for 1 h. After
recrystallization from chloroform–ethanol 13.4 g (60%) of
phthalazinone 3d were obtained as pale yellow crystals, mp
184–186 ꢀC. dH (DMSO): 8.42 (1H, m, H1), 8.17 (1H, d,
J¼8.7 Hz, H11), 7.97 (1H, d, J¼1.9 Hz, H8), 8.01–7.90
(2H, m, H2, 3), 7.81 (1H, m, H4), 7.77 (1H, dd, J¼8.7 and
1.9 Hz, H10), 7.52 (2H, d, J¼7.9 Hz, CH–C(Ar)–CH), 7.36
(2H, d, J¼7.9 Hz, CH–C(Me)–CH), 2.43 (3H, s, CH3). dC
(DMSO): 157.64, 147.97, 143.35, 138.78, 138.22, 135.37,
133.92, 132.03, 131.02, 129.20, 128.95, 128.82, 128.56,
127.15, 126.91, 126.05, 20.71. Found, %: C 64.24, H 3.48,
N 10.92. C21H14ClN3O3 (391.82). Requires, %: C 64.38,
H 3.60, N 10.72.
9
N
12
11
O
12
O2N
10
11
Figure 1. Numeration of locations in phthalazinones and BIPHs.
4.2. Synthesis of nitrophthalazinones 3 and 6 by
cyclization of o-acylbenzoic acid 2
General method. 2-Acylbenzoic acid (0.060 mol) and appro-
priate hydrazine (0.057 mol) were refluxed in ethanol–sulfu-
ric acid mixture (80–40 ml) for a given time. The mixture
was poured on 300 g of crushed ice and the product precip-
itated was filtered off. The residue was treated with 5% aque-
ous NaOH, filtered off, washed with water to neutral pH, and
recrystallized from an appropriate solvent.
4.2.5. 2-(2-Nitro-5-chlorophenyl)-4-(4-chlorophenyl)-
1,2-dihydro-1-phthalazinone 3e. Mixture of 2-(4-chloro-
benzoyl)benzoic acid 2e (15.6 g) and 2-nitro-5-chloro-
phenylhydrazine 1a (10.7 g) was refluxed for 1 h. After
recrystallization from chloroform–ethanol 12.4 g (53%)
phthalazinone 3e were obtained as pale yellow crystals, mp
190–192 ꢀC. dH (DMSO): 8.42 (1H, m, H1), 8.18 (1H, d,
J¼8.8 Hz, H11), 8.04–7.94 (3H, m, H2, 3, 8), 7.83–7.75 (2H,
m, H4, 10), 7.69 (2H, d, J¼7.9 Hz, CH–C(Cl)–CH), 7.61
(2H, d, J¼7.9 Hz, CH–C(Ar)–CH). dC (DMSO): 157.62,
146.87, 143.31, 138.32, 135.24, 134.55, 134.06, 132.56,
132.19, 130.79, 129.23, 129.07, 128.44, 128.25, 127.11,
126.97, 126.64, 126.06. Found, %: C 58.24, H 2.70, N
10.40. C20H11Cl2N3O3 (412.23). Requires, %: C 58.27, H
2.69, N 10.19.
4.2.1. 2-(2-Nitro-5-chlorophenyl)-1,2-dihydro-1-phthala-
zinone 3a. Mixture of 2-formylbenzoic acid 2a (9.0 g) and
2-nitro-5-chlorophenylhydrazine 1a (10.7 g) was refluxed
for 1 h. On recrystallization from chloroform–ethanol
7.7 g (45%) of phthalazinone 3a were obtained as pale
yellow crystals, mp 175–177 ꢀC. nmax (KBr): 1663, 1595,
1525, 1343, 752 cmꢁ1. dH (DMSO): 8.58 (1H, s, H5), 8.31
(1H, d, J¼7.6 Hz, H1), 8.16 (1H, d, J¼8.8 Hz, H11), 8.05–
7.97 (2H, m, H3, 4), 7.91 (1H, m, H2), 7.84 (1H, d,
J¼2.1 Hz, H8), 7.75 (1H, dd, J¼8.8 and 2.1 Hz, H10). dC
(DMSO): 158.04, 143.43, 139.87, 138.29, 135.43, 134.17,
132.40, 129.31, 129.23, 129.11, 127.16, 126.73, 126.20.
Found, %: C 55.59, H 2.53, N 14.15. C14H8ClN3O3
(301.69). Requires, %: C 55.74, H 2.67, N 13.93.
4.2.2. 4-Methyl-2-(2-nitro-5-chlorophenyl)-1,2-dihydro-
1-phthalazinone 3b. Mixture of 2-acetylbenzoic acid 2b
(9.8 g) and 2-nitro-5-chlorophenylhydrazine 1a (10.7 g)
was refluxed for 1 h. After recrystallization from chloro-
form–ethanol 12.6 g (70%) of phthalazinone 3b were
obtained as pale yellow crystals, mp 168–170 ꢀC. nmax
(KBr): 1670, 1604, 1527, 1350, 1334, 1326, 1172, 1142,
773, 753, 690 cmꢁ1. dH (CDCl3): 8.48 (1H, d, J¼7.8 Hz, H1),
8.04 (1H, d, J¼8.6 Hz, H11), 7.94–7.78 (3H, m, H2, 3, 4),
7.70 (1H, s, H8), 7.52 (1H, d, J¼8.6 Hz, H10), 2.64 (3H,
s, CH3). dC (DMSO): 157.87, 145.25, 143.34, 138.14,
135.39, 133.95, 131.97, 129.16, 128.82, 126.55, 125.98,
125.66, 18.29. Found, %: C 57.10, H 3.12, N 13.49.
4.2.6. 2-(2-Nitro-5-chlorophenyl)-4-(4-ethylphenyl)-1,2-
dihydro-1-phthalazinone 3f. Mixture of 2-(4-ethyl-
benzoyl)benzoic acid 2f (15.2 g) and 2-nitro-5-chloro-
phenylhydrazine 1a (10.7 g) was refluxed for 1.5 h. After
recrystallization from chloroform–ethanol 8.1 g (35%) of
phthalazinone 3f were obtained as pale yellow crystals, mp
218–220 ꢀC. dH (DMSO): 8.41 (1H, m, H1), 8.21 (1H, d,
J¼8.6 Hz, H11), 8.11–7.96 (3H, m, H2,
8), 7.88–7.79
3,
(2H, m, H4, 10), 7.57 (2H, d, J¼7.4 Hz, CH–C(Ar)–CH),
7.42 (2H, d, J¼7.4 Hz, CH–C(Alk)–CH), 2.69 (2H, q,
J¼7.4 Hz, CH2), 1.24 (3H, t, J¼7.4 Hz, CH3). Found, %:
C 65.00, H 3.87, N 10.57. C22H16ClN3O3 (405.84). Re-
quires, %: C 65.11, H 3.97, N 10.35.

V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
10023
4.2.7. 4-(3,4-Dimethylphenyl)-2-(2-nitro-5-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 3g. Mixture of
2-(3,4-dimethylbenzoyl)benzoic acid 2g (15.2 g) and
2-nitro-5-chlorophenylhydrazine 1a (10.7 g) was refluxed
for 1.5 h. After recrystallization from chloroform–ethanol
8.6 g (37%) of phthalazinone 3g were obtained as pale
yellow crystals, mp 238–240 ꢀC. dH (DMSO): 8.39 (1H,
m, H1), 8.20 (1H, d, J¼8.8 Hz, H11), 8.10–7.94 (3H, m,
2,4-dinitrophenylhydrazine 1c (11.4 g) in the mixture of
40 ml of ethanol and 40 ml of sulfuric acid were refluxed
for 1.5 h. After recrystallization from DMF 9.9 g (54%) of
phthalazinone 6b were obtained as pale yellow crystals,
mp 244–246 ꢀC (lit. mp 2489). nmax (KBr): 3073, 1671,
1608, 1540, 1530, 1350, 1337, 773 cmꢁ1. dH (DMSO):
8.81 (1H, d, J¼1.8 Hz, H11), 8.72 (1H, dd, J¼8.9 and
1.8 Hz, H9), 8.36 (1H, d, J¼7.5 Hz, H1), 8.09 (1H, d,
J¼8.9 Hz, H8), 8.06–8.00 (2H, m, H3, 4), 7.94 (1H, m, H2),
2.66 (3H, s, CH3). dC (DMSO): 158.09, 146.43, 146.11,
144.29, 138.47, 134.65, 132.65, 130.84, 129.20, 128.38,
126.63, 126.25, 126.25, 120.19, 18.50. Found, %: C 55.05,
H 3.00, N 17.34. C15H10N4O5 (326.27). Requires, %: C
55.22, H 3.09, N 17.17.
H
2, 3, 8), 7.87–7.78 (2H, m, H4, 10), 7.44–7.30 (3H, m,
(CH3)2–C6H3), 2.31 (6H, s, 2CH3). Found, %: C 64.97,
H 3.81, N 10.56. C22H16ClN3O3 (405.84). Requires, %:
C 65.11, H 3.97, N 10.35.
4.2.8. 4-(2,4-Dimethylphenyl)-2-(2-nitro-5-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 3h. Mixture of
2-(2,4-dimethylbenzoyl)benzoic acid 2h (15.2 g) and
2-nitro-5-chlorophenylhydrazine 1a (10.7 g) was refluxed
for 1.5 h. After recrystallization from chloroform–ethanol
8.8 g (38%) of phthalazinone 3h were obtained as pale
yellow crystals, mp 204–206 ꢀC. dH (DMSO): 8.40 (1H,
m, H1), 8.21 (1H, d, J¼8.8 Hz, H11), 8.04 (1H, d,
J¼2.0 Hz, H8), 8.01–7.92 (2H, m, H2, 3), 7.83 (1H, dd,
J¼8.8 and 2.0 Hz, H10), 7.32 (1H, m, H4), 7.25–7.14 (3H,
m, (CH3)2–C6H3), 2.37 (3H, s, 20-CH3), 2.09 (3H, s,
40-CH3). dC (DMSO): 157.79, 148.28, 143.48, 138.46,
138.14, 136.13, 135.50, 134.04, 132.14, 130.72, 130.37,
129.40, 129.29, 129.14, 126.97, 126.71, 126.18, 20.66,
18.96. Found, %: C 65.10, H 3.89, N 10.52. C22H16ClN3O3
(405.84). Requires, %: C 65.11, H 3.97, N 10.35.
4.2.12. 2-(2-Nitrophenyl)-4-(4-chlorophenyl)-1,2-dihy-
dro-1-phthalazinone 6c. 2-(4-Chlorobenzoyl)benzoic acid
2e (15.6 g) and 2-nitrophenylhydrazine 1b (8.7 g) in the
mixture of 40 ml of ethanol and 40 ml of sulfuric acid
were refluxed for 1 h. After recrystallization from ethanol
6.0 g (55%) of phthalazinone 6c were obtained as pale
yellow crystals, mp 167–169 ꢀC. dH (DMSO): 8.43 (1H,
m, H1), 8.09 (1H, dd, J¼8.0 and 1.2 Hz, H11), 7.76 (10H,
3, 4, 8, 9,
m, H2,
10, p-Cl–C6H4). dC (DMSO): 157.72,
146.54, 144.77, 134.51, 134.17, 134.00, 133.82, 132.78,
132.19, 130.87, 129.44, 129.17, 128.47, 128.32, 127.33,
127.05, 126.62, 124.37. Found, %: C 63.41, H 3.29,
N 11.33. C20H12ClN3O3 (377.79). Requires, %: C 63.59,
H 3.20, N 11.12.
4.2.9. 4-(2,5-Dimethylphenyl)-2-(2-nitro-5-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 3i. Mixture of
2-(2,5-dimethylbenzoyl)benzoic acid 2i (15.2 g) and
2-nitro-5-chlorophenylhydrazine 1a (10.7 g) was refluxed
for 1.5 h. After recrystallization from chloroform–ethanol
10.9 g (47%) of phthalazinone 3i were obtained as pale
yellow crystals, mp 205–207 ꢀC. dH (DMSO): 8.42 (1H,
m, H1), 8.15 (1H, d, J¼8.9 Hz, H11), 7.93–7.86 (2H,
m, H2, 3), 7.83 (1H, d, J¼2.2 Hz, H8), 7.77 (1H, dd,
J¼8.9 and 2.2 Hz, H10), 7.37 (1H, m, H4), 7.24–7.12
(3H, m, (CH3)2–C6H3), 2.38 (3H, s, 20-CH3), 2.13 (3H,
s, 50-CH3). Found, %: C 65.07, H 3.91, N 10.54.
C22H16ClN3O3 (405.84). Requires, %: C 65.11, H 3.97,
N 10.35.
4.3. Synthesis of nitrophthalazinone 8 by nucleophilic
substitution in 2-(2-nitro-5-chlorophenyl)phthalazinone 3
General method. A solution of phthalazinone 3 (0.010 mol)
in 10 ml of alicyclic amine was refluxing for 1.5 h. Reaction
mixture was poured in 100 ml of hot water. The residual oil,
which solidified upon cooling, was grinded and filtered off.
On washing with hot water the residue was dried and
recrystallized from an appropriate solvent.
4.3.1. 4-Methyl-2-(2-nitro-5-morpholinophenyl)-1,2-
dihydro-1-phthalazinone 8a. From phthalazinone 3b
(3.16 g) and morpholine after recrystallization from chloro-
form–methanol 2.63 g (71%) of product 8a were obtained as
yellow crystals, mp 200–202 ꢀC. nmax (KBr): 1653, 1601,
1506, 1317, 1244, 1101 cmꢁ1. dH (DMSO): 8.31 (1H, d,
J¼7.8 Hz, H1), 8.10 (1H, d, J¼10.0 Hz, H11), 8.00–7.95
(2H, m, H3, 4), 7.90 (1H, m, H2), 7.12–7.03 (2H, m, H8, 10),
3.75 (4H, m, CH2OCH2), 3.43 (4H, m, CH2NCH2), 2.60
(3H, s, CH3). dC (DMSO): 158.08, 154.18, 143.77, 137.43,
134.13, 133.48, 131.50, 129.27, 126.89, 126.28, 125.33,
113.45, 111.87, 65.51, 46.33, 18.27. Found, %: C 62.00,
H 4.74, N 15.51. C19H18N4O4 (366.38). Requires, %:
C 62.29, H 4.95, N 15.29.
4.2.10. 4-Methyl-2-(2-nitrophenyl)-1,2-dihydro-1-phtha-
lazinone 6a. 2-Acetylbenzoic acid 2b (9.8 g) and 2-nitro-
phenylhydrazine 1b (8.8 g) in the mixture of 40 ml of
ethanol and 40 ml of sulfuric acid were refluxed for 1.5 h.
After recrystallization from chloroform–ethanol 9.6 g
(60%) of phthalazinone 6a were obtained as pale yellow
crystals, mp 195–197 ꢀC (lit. mp 203–204 ꢀC8). nmax
(KBr): 1668, 1533, 1356, 1340, 1175, 777, 687 cmꢁ1. dH
(DMSO): 8.32 (1O, d, J¼7.5 Hz, H1), 8.10 (1H, d,
J¼7.9 Hz, H11), 8.02–7.62 (6H, m, H2, 3, 4, 8, 9, 10), 2.62
(3H, s, CH3). dC (DMSO): 157.95, 144.81, 144.74, 134.25,
133.74, 131.84, 129.33, 129.19, 128.88, 126.58, 126.47,
125.53, 124.18, 18.35. Found, %: C 63.81, H 3.82,
N 15.14. C15H11N3O3 (281.27). Requires, %: C 64.05,
H 3.94, N 14.94.
4.3.2. 4-Methyl-2-(2-nitro-5-pyrrolidinophenyl)-1,2-
dihydro-1-phthalazinone 8b. From phthalazinone 3b
(3.16 g) and pyrrolidine after recrystallization from chloro-
form–methanol 2.81 g (79%) of product 8b were obtained
as yellow crystals, mp 235–237 ꢀC. dH (CDCl3): 8.51 (1H,
d, J¼7.2 Hz, H1), 8.22 (1H, d, J¼10.0 Hz, H11), 7.91–7.74
(3H, m, H2, 3, 4), 6.59–6.51 (2H, m, H8, 10), 3.42 (4H, m,
CH2NCH2), 2.62 (3H, s, CH3), 2.06 (4H, m, CH2CH2). dC
4.2.11. 2-(2,4-Dinitrophenyl)-4-methyl-1,2-dihydro-1-
phthalazinone 6b. 2-Acetylbenzoic acid 2b (9.9 g) and

10024
V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
(DMSO): 158.09, 151.25, 143.56, 137.93, 133.46, 131.95,
131.54, 129.34, 127.34, 127.03, 126.23, 125.41, 111.70,
110.23, 47.55, 24.73, 18.33. Found, %: C 64.89, H 5.11, N
16.18. C19H18N4O3 (350.38). Requires, %: C 65.13, H
5.18, N 15.99.
crystals, mp 235–237 ꢀC. dH (DMSO): 8.41 (1H, m, H1),
8.09 (1H, d, J¼9.5 Hz, H11), 8.01–7.89 (2H, m, H2, 3),
7.79 (1H, m, H4), 7.67–7.51 (5H, m, C6H5), 7.11 (1H, d,
J¼2.4 Hz, H8), 7.02 (1H, dd, J¼9.5 and 2.4 Hz, H10), 3.49
(4H, s, CH2NCH2), 1.63 (6H, s, CH2CH2CH2). Found, %:
C 70.29, H 4.96, N 13.32. C25H22N4O3 (426.48). Requires,
%: C 70.41, H 5.20, N 13.14.
4.3.3. 4-Methyl-2-(2-nitro-5-piperidinophenyl)-1,2-di-
hydro-1-phthalazinone 8c. From phthalazinone 3b (3.16 g)
and piperidine after recrystallization from chloroform–
methanol 2.70 g (74%) of product 8c were obtained as
yellow crystals, mp 202–204 ꢀC. dH (CDCl3): 8.50 (1H, d,
J¼7.3 Hz, H1), 8.16 (1H, d, J¼10.0 Hz, H11), 7.92–7.74
(3H, m, H2, 3, 4), 6.88–6.79 (2H, m, H8, 10), 3.43 (4H, m,
CH2NCH2), 2.62 (3H, s, CH3), 1.67 (6H, m, CH2CH2CH2).
Found, %: C 65.77, H 5.32, N 15.60. C20H20N4O3 (364.41).
Requires, %: C 65.92, H 5.53, N 15.37.
4.3.8. 4-(4-Methylphenyl)-2-(2-nitro-5-morpholino-
phenyl)-1,2-dihydro-1-phthalazinone 8h. From phthalazi-
none 3d (3.92 g) and morpholine after recrystallization from
chloroform–methanol 2.48 g (56%) of product 8h were
obtained as yellow crystals, mp 240–242 ꢀC. dH (DMSO):
8.40 (1H, m, H1), 8.12 (1H, d, J¼9.2 Hz, H11), 7.98–7.87
(2H, m, H2, 3), 7.81 (1H, m, H4), 7.35 (2H, d, J¼7.7 Hz,
CH–C(Alk)–CH), 7.32 (2H, d, J¼7.7 Hz, CH–C(Ar)–CH),
7.15 (1H, d, J¼2.1 Hz, H8), 7.08 (1H, dd, J¼9.2 and
2.1 Hz, H10), 3.73 (4H, m, CH2OCH2), 3.41 (4H, m,
CH2NCH2), 2.42 (3H, s, CH3). Found, %: C 67.62, H 4.75,
N 12.85. C25H22N4O4 (442.48). Requires, %: C 67.86, H
5.01, N 12.66.
4.3.4. 4-Methyl-2-(2-nitro-5-piperazinophenyl)-1,2-
dihydro-1-phthalazinone 8d. From phthalazinone 3b
(3.16 g) and piperazine after recrystallization from chloro-
form–ethanol 2.63 g (72%) of the product 8d were obtained
as yellow crystals, mp 187–189 ꢀS. dH (DMSO): 8.31 (1H, d,
J¼7.5 Hz, H1), 8.08 (1H, d, J¼9.0 Hz, H11), 8.00–7.93
(2H, m, H3, 4), 7.88 (1H, m, H2), 7.08–6.97 (2H, m, H8, 10),
3.39 (4H, m, CH2–N(Ar)–CH2), 2.85 (4H, m, CH2–NH–
CH2), 2.59 (3H, s, CH3). Found, %: C 62.40, H 5.14,
N 19.39. C19H19N5O3 (365.39). Requires, %: C 62.46,
H 5.24, N 19.17.
4.3.9. 4-(4-Methylphenyl)-2-(2-nitro-5-pyrrolidino-
phenyl)-1,2-dihydro-1-phthalazinone 8i. From phthalazi-
none 3d (3.92 g) and pyrrolidine after recrystallization
from chloroform–ethanol 3.49 g (82%) of product 8i were
obtained as yellow crystals, mp>260 ꢀC. dH (DMSO): 8.39
(1H, m, H1), 8.12 (1H, d, J¼8.8 Hz, H11), 7.99–7.87
(2H, m, H2, 3), 7.82 (1H, m, H4), 7.50 (2H, d, J¼7.2 Hz,
CH–C(Ar)–CH), 7.35 (2H, d, J¼7.2 Hz, CH–C(Alk)–CH),
6.75–6.62 (2H, m, H8, 10), 3.41 (4H, s, CH2NCH2), 2.42
(3H, s, CH3), 2.02 (4H, s, CH2CH2). Found, %: C 70.31,
H 5.17, N 13.29. C25H22N4O3 (426.48). Requires, %:
C 70.41, H 5.20, N 13.14.
4.3.5. 2-(2-Nitro-5-morpholinophenyl)-4-phenyl-1,2-di-
hydro-1-phthalazinone 8e. From phthalazinone 3c (3.78 g)
and morpholine after recrystallization from chloroform–
methanol 2.91 g (68%) of product 8e were obtained as yellow
crystals, mp 240–242 ꢀC. nmax (KBr): 1653, 1601, 1582,
1491, 1325, 1244 cmꢁ1. dH (DMSO): 8.41 (1H, m, H1),
8.13 (1H, d, J¼9.2 Hz, H11), 8.02–7.89 (2H, m, H2, 3), 7.80
(1H, m, H4), 7.67–7.50 (5H, m, C6H5), 7.19 (1H, d,
J¼2.1 Hz, H8), 7.10 (1H, dd, J¼9.2 and 2.1 Hz, H10), 3.74
(4H, m, CH2OCH2), 3.43 (4H, m, CH2NCH2). dC (DMSO):
157.78, 154.23, 146.65, 137.38, 134.23, 134.09, 133.52,
131.68, 129.12, 128.89, 128.56, 128.18, 127.59, 126.99,
126.67, 126.54, 113.44, 112.08, 65.53, 46.35. Found, %:
C 67.09, H 4.66, N 13.30. C24H20N4O4 (428.45). Requires,
%: C 67.28, H 4.71, N 13.08.
4.3.10. 4-(4-Methylphenyl)-2-(2-nitro-5-piperidino-
phenyl)-1,2-dihydro-1-phthalazinone 8j. From phthalazi-
none 3d (3.92 g) and piperidine after recrystallization from
chloroform–ethanol 3.34 g (76%) of product 8j were
obtained as yellow crystals, mp 161–163 ꢀC. dH (DMSO):
8.40 (1H, m, H1), 8.09 (1H, d, J¼9.3 Hz, H11), 7.99–7.88
(2H, m, H2, 3), 7.81 (1H, m, H4), 7.51 (2H, d, J¼7.6 Hz,
CH–C(Ar)–CH), 7.35 (2H, d, J¼7.6 Hz, CH–C(Alk)–CH),
7.11 (1H, d, J¼2.3 Hz, H8), 7.04 (1H, dd, J¼9.3 and
2.3 Hz, H10), 3.49 (4H, s, CH2NCH2), 2.42 (3H, s, CH3),
1.63 (6H, s, CH2CH2CH2). Found, %: C 70.78, H 5.25,
N 12.93. C26H24N4O3 (440.51). Requires, %: C 70.89,
H 5.49, N 12.72.
4.3.6. 2-(2-Nitro-5-pyrrolidinophenyl)-4-phenyl-1,2-di-
hydro-1-phthalazinone 8f. From phthalazinone 3c (3.78 g)
and pyrrolidine after recrystallization from chloroform–
ethanol 3.25 g (78%) of product 8f were obtained as yellow
crystals, mp 211–213 ꢀC. dH (DMSO): 8.40 (1H, m, H1), 8.14
(1H, d, J¼9.2 Hz, H11), 8.04–7.91(2H, m, H2, 3), 7.80(1H, m,
H4), 7.67–7.51 (5H, m, C6H5), 6.83 (1H, s, H8), 6.71 (1H, d,
J¼9.2 Hz, H10), 3.40 (4H, m, CH2NCH2), 1.98 (4H, m,
CH2CH2). dC (DMSO): 157.86, 151.23, 146.47, 137.83,
134.28, 133.51, 131.88, 131.67, 129.12, 128.90, 128.57,
128.20, 127.65, 127.43, 126.62, 126.48, 111.71, 110.37,
47.59, 24.75. Found, %: C 69.67, H 4.75, N 13.73.
C24H20N4O3 (412.45). Requires, %:C 69.89, H 4.89, N 13.58.
4.3.11. 2-(2-Nitro-5-morpholinophenyl)-4-(4-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 8k. From phthalazi-
none 3e (4.12 g) and morpholine after recrystallization from
chloroform–methanol 3.57 g (77%) of product 8k were
obtained as yellow crystals, mp 230–232 ꢀC. dH (DMSO):
8.41 (1H, m, H1), 8.13 (1H, d, J¼9.3 Hz, H11), 8.02–7.90
(2H, m, H2, 3), 7.79 (1H, m, H4), 7.67 (2H, d, J¼8.7 Hz,
CH–C(Cl)–CH), 7.59 (2H, d, J¼8.7 Hz, CH–C(Ar)–CH),
7.19 (1H, d, J¼2.1 Hz, H8), 7.09 (1H, dd, J¼9.3 and
2.1 Hz, H10), 3.74 (4H, m, CH2OCH2), 3.43 (4H, m,
CH2NCH2). dC (DMSO): 157.83, 154.29, 145.65, 137.32,
134.35, 134.04, 133.70, 132.94, 131.90, 130.95, 128.44,
127.56, 127.07, 126.85, 126.40, 113.45, 112.11, 65.57,
46.35. Found, %: C 62.19, H 4.25, N 12.31. C24H19ClN4O4
(462.90). Requires, %: C 62.27, H 4.14, N 12.10.
4.3.7. 2-(2-Nitro-5-piperidinophenyl)-4-phenyl-1,2-dihy-
dro-1-phthalazinone 8g. From phthalazinone 3c (3.78 g)
and piperidine after recrystallization from chloroform–
ethanol 3.45 g (81%) of product 8g were obtained as yellow

V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
10025
4.3.12. 2-(2-Nitro-5-pyrrolidinophenyl)-4-(4-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 8l. From phthalazi-
none 3e (4.12 g) and pyrrolidine after recrystallization
from chloroform–ethanol 3.89 g (87%) of product 8l were
obtained as yellow crystals, mp 265–267 ꢀC. dH (DMSO):
8.40 (1H, m, H1), 8.10 (1H, d, J¼9.1 Hz, H11), 8.01–7.89
(2H, m, H2, 3), 7.78 (1H, m, H4), 7.66 (2H, d, J¼8.5 Hz,
CH–C(Cl)–CH), 7.58 (2H, d, J¼8.5 Hz, CH–C(Ar)–CH),
6.74 (1H, d, J¼2.5 Hz, H8), 6.70 (1H, dd, J¼9.1 and
2.5 Hz, H10), 3.39 (4H, m, CH2NCH2), 2.00 (4H, m,
CH2CH2). dC (DMSO): 157.83, 151.30, 145.40, 137.75,
134.24, 133.69, 133.07, 131.88, 130.97, 128.42, 127.67,
127.53, 126.82, 126.37, 111.68, 110.50, 47.70, 24.84.
Found, %: C 64.56, H 4.27, N 12.73. C24H19ClN4O3
(446.90). Requires, %: C 64.50, H 4.29, N 12.54.
(3H, m, H2, 3, 4), 7.41–7.23 (3H, m, (CH3)2–C6H3), 7.08–
6.95 (2H, m, H8, 10), 3.50 (4H, s, CH2NCH2), 2.34 (6H, s,
2CH3), 1.67 (6H, s, CH2CH2CH2). Found, %: C 71.25, H
5.61, N 12.55. C27H26N4O3 (454.53). Requires, %: C
71.35, H 5.77, N 12.33.
4.3.17. 4-(2,5-Dimethylphenyl)-2-(2-nitro-5-piperidino-
phenyl)-1,2-dihydro-1-phthalazinone 8q. From phthalazi-
none 3i (4.06 g) and piperidine after recrystallization from
chloroform–methanol 3.00 g (66%) of product 8q were
obtained as yellow crystals, mp 205–207 ꢀC. dH (DMSO):
8.41 (1H, m, H1), 8.09 (1H, d, J¼9.0 Hz, H11), 7.93–7.80
(2H, m, H2, 3), 7.35 (1H, m, H4), 7.25–7.12 (3H, m,
(CH3)2–C6H3), 7.05–6.95 (2H, m, H8, 10), 3.49 (4H, s,
CH2NCH2), 2.37 (3H, s, 20-CH3), 2.13 (3H, s, 50-CH3),
1.67 (6H, s, CH2CH2CH2). Found, %: C 71.02, H 5.76, N
12.53. C27H26N4O3 (454.53). Requires, %: C 71.35, H
5.77, N 12.33.
4.3.13. 2-(2-Nitro-5-piperidinophenyl)-4-(4-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 8m. From phthala-
zinone 3e (4.12 g) and piperidine after recrystallization
from chloroform–methanol 3.92 g (85%) of product 8m
were obtained as yellow crystals, mp 221–223 ꢀC. dH
(DMSO): 8.41 (1H, m, H1), 8.08 (1H, d, J¼9.2 Hz, H11),
8.01–7.88 (2H, m, H2, 3), 7.78 (1H, m, H4), 7.66 (2H, d,
J¼8.5 Hz, CH–C(Cl)–CH), 7.58 (2H, d, J¼8.5 Hz, CH–
C(Ar)–CH), 7.10 (1H, d, J¼2.2 Hz, H8), 7.03 (1H, dd,
J¼9.2 and 2.2 Hz, H10), 3.49 (4H, s, CH2NCH2), 1.62
(6H, s, CH2CH2CH2). Found, %: C 65.08, H 4.61, N
12.35. C25H21ClN4O3 (460.92). Requires, %: C 65.15, H
4.59, N 12.16.
4.4. Aminophthalazinones 4 and 9
General method for nitro group catalytic reduction. Solution
of 0.004 mol of nitrophthalazinone in 40 ml of THF was
hydrogenated over 100 mg of 5% palladium charcoal with
shaking at room temperature and atmospheric pressure. On
absorption of the calculated volume of hydrogen the catalyst
powder was filtered off and the solution was concentrated
under reduced pressure to 10 ml volume. The product was
precipitated by dilution with light petroleum ether to total
volume of 100 ml. The product was filtered off, washed
with petroleum ether, and air-dried. As recrystallization of
amines 4, 9 leads to accumulation of impurities they are
described as being isolated from the reaction mixture.
4.3.14. 2-(2-Nitro-5-piperazinophenyl)-4-(4-chloro-
phenyl)-1,2-dihydro-1-phthalazinone 8n. From phthalazi-
none 3e (4.12 g) and piperazine after recrystallization from
chloroform–ethanol 3.97 g (86%) of product 8n were
obtained as yellow crystals, mp 225–227 ꢀC. dH (DMSO):
8.40 (1H, m, H1), 8.11 (1H, d, J¼9.4 Hz, H11), 7.96 (2H,
m, H2, 3), 7.78 (1H, m, H4), 7.65 (4H, m, p-Cl–C6H4), 7.14
(1H, d, J¼2.2 Hz, H8), 7.06 (1H, dd, J¼9.4 and 2.2 Hz,
H10), 3.41 (4H, m, CH2–N(Ar)–CH2), 3.34 (1H, s, NH),
2.85 (4H, m, CH2–NH–CH2). Found, %: C 62.46, H 4.47,
N 15.35. C24H20ClN5O3 (461.91). Requires, %: C 62.41, H
4.36, N 15.16.
4.4.1. 2-(2-Amino-5-chlorophenyl)-4-methyl-1,2-di-
hydro-1-phthalazinone 4a. From of nitrophthalazinone
3b (1.24 g) was obtained 0.74 g (65%) of aminophthalazi-
none 4a as greenish-yellow crystals, mp 195–196 ꢀC. nmax
(KBr): 3422, 3341, 1656, 1632, 1589, 1499, 1345, 771,
695 cmꢁ1. dH (CDCl3): 8.51 (1H, d, J¼7.2 Hz, H1), 7.93–
3,
7.75 (3H, m, H2,
4), 7.30 (1H, s, H8), 7.16 (1H, d,
J¼8.4 Hz, H10), 6.79 (1H, d, J¼8.4 Hz, H11), 3.92 (2H, s,
NH2), 2.63 (3H, s, CH3). dH (DMSO): 157.86, 144.26,
143.04, 133.09, 131.21, 129.37, 128.23, 127.80, 127.75,
127.62, 126.37, 125.14, 118.66, 117.22, 18.39. Found, %:
C 63.10, H 4.22, N 14.94. C15H12ClN3O (285.74). Requires,
%: C 63.05, H 4.23, N 14.71.
4.3.15. 2-(2-Nitro-5-piperidinophenyl)-4-(4-ethyl-
phenyl)-1,2-dihydro-1-phthalazinone 8o. From phthalazi-
none 3f (4.06 g) and piperidine after recrystallization from
chloroform–methanol 2.87 g (63%) of product 8o were
obtained as yellow crystals, mp 222–224 ꢀC. dH (DMSO):
8.40 (1H, m, H1), 8.08 (1H, d, J¼10.2 Hz, H11), 7.97–7.87
(2H, m, H2, 3), 7.83 (1H, m, H4), 7.53 (2H, d, J¼7.8 Hz,
CH–C(Ar)–CH), 7.36 (2H, d, J¼7.8 Hz, CH–C(Alk)–CH),
7.07–6.98 (2H, m, H8, 10), 3.50 (4H, s, CH2NCH2), 2.73
(2H, q, J¼7.6 Hz, CH2), 1.66 (6H, s, CH2CH2CH2), 1.29
(3H, t, J¼7.6 Hz, CH3). Found, %: C 71.13, H 5.59, N
12.51. C27H26N4O3 (454.53). Requires, %: C 71.35, H
5.77, N 12.33.
4.4.2. 2-(2-Amino-5-chlorophenyl)-4-phenyl-1,2-di-
hydro-1-phthalazinone 4b. From nitrophthalazinone 3c
(1.51 g) was obtained 0.96 g (69%) of aminophthalazinone
4b as colorless crystal, mp 185–187 ꢀC. nmax (KBr): 3400,
3327, 1647, 1492, 1334, 789, 698 cmꢁ1. dH (CDCl3): 8.60
(1H, m, H1), 7.90–7.77 (3H, m, H2, 3, 4), 7.68–7.48 (5H,
m, C6H5), 7.39 (1H, d, J¼2.3 Hz, H8), 7.17 (1H, dd, J¼8.7
and 2.3 Hz, H10), 6.77 (1H, d, J¼8.7 Hz, H11), 3.98 (2H, s,
NH2). dH (DMSO): 157.72, 147.24, 143.26, 134.57,
133.00, 131.24, 129.18, 128.81, 128.70, 128.45, 128.07,
127.68, 127.48, 126.67, 126.36, 118.47, 117.15. Found, %:
C 69.01, H 4.00, N 12.29. C20H14ClN3O (347.81). Requires,
%: C 69.07, H 4.06, N 12.08.
4.3.16. 4-(3,4-Dimethylphenyl)-2-(2-nitro-5-piperidino-
phenyl)-1,2-dihydro-1-phthalazinone 8p. From phthalazi-
none 3g (4.06 g) and piperidine after recrystallization from
chloroform–methanol 3.64 g (80%) of product 8p were
obtained as yellow crystals, mp 238–240 ꢀC. dH (DMSO):
8.39 (1H, m, H1), 8.10 (1H, d, J¼8.9 Hz, H11), 7.97–7.78
4.4.3. 2-(2-Amino-5-chlorophenyl)-4-(4-chlorophenyl)-
1,2-dihydro-1-phthalazinone 4c. From nitrophthalazinone

10026
V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
3e (1.65 g) was obtained 1.27 g (83%) of aminophthalazi-
none 4c as colorless crystal, mp 193–195 ꢀC. dH (DMSO):
8.46 (1H, m, H1), 7.98–7.86 (2H, m, H2, 3), 7.75 (1H, m,
H4), 7.66 (2H, d, J¼8.4 Hz, CH–C(Cl)–CH), 7.54 (2H, d,
J¼8.4 Hz, CH–C(Ar)–CH), 7.37 (1H, d, J¼1.9 Hz, H8),
7.32 (1H, dd, J¼8.7 and 1.9 Hz, H10), 7.18 (1H, d,
J¼8.7 Hz, H11), 5.74 (2H, s, NH2). Found, %: C 62.89, H
3.39, N 11.20. C20H13Cl2N3O (382.25). Requires, %: C
62.84, H 3.43, N 10.99.
of PPAwas heated to 130 ꢀC and stirred for 10 min. On cool-
ing it was diluted with water to 70 ml volume, neutralized
with aqueous NaOH, and extracted with chloroform
(3ꢂ30 ml). Combined extracts were dried over Na2SO4,
filtered off, and evaporated. The residue was recrystallized
from an appropriate solvent.
Method B. BIPH preparation from nitrophthalazinones.
Mixture of 0.004 mol of nitrophthalazinone in 50 ml of
85% phosphoric acid was heated to 100 ꢀC. Iron powder
was added in small portions (to avoid foaming) with efficient
stirring. After consumption of all the starting material (TLC
control) the temperature was raised to 140 ꢀC and the reac-
tion mixture was stirred for 15 min. On cooling it was diluted
with water to 400 ml, neutralized with aqueous NaOH, and
extracted with chloroform (3ꢂ50 ml). Combined extracts
were dried over Na2SO4, filtered off, and evaporated. The
residue was recrystallized from an appropriate solvent.
4.4.4. 2-(2-Amino-5-chlorophenyl)-4-(4-ethylphenyl)-
1,2-dihydro-1-phthalazinone 4d. From nitrophthalazinone
3f (1.62 g) was obtained 1.19 g (79%) of aminophthalazi-
none 4d as colorless crystal, mp 168–170 ꢀS. dH (DMSO):
8.40 (1H, m, H1), 8.01–7.85 (2H, m, H2, 3), 7.75 (1H, m,
H4), 7.58–7.34 (4H, m, p-Et–C6H4), 7.22 (1H, d,
J¼1.9 Hz, H8), 7.16 (1H, dd, J¼8.7 and 1.9 Hz, H10), 6.84
(1H, d, J¼8.7 Hz, H11), 5.36 (2H, s, NH2), 2.65 (2H, q,
J¼7.5 Hz, CH2), 1.23 (3H, t, J¼7.5 Hz, CH3). Found, %:
C 70.24, H 4.77, N 11.41. C22H18ClN3O (375.86). Requires,
%: C 70.30, H 4.83, N 11.18.
4.5.1. 9-Chlorobenzo[4,5]imidazo[2,1-a]phthalazine 5a.
Method B. From 1.21 g of nitrophthalazinone 3a and 1.8 g
of iron powder after recrystallization from 80% aqueous
ethanol 0.69 g (68%) of the product 5a were obtained as
colorless crystals, mp 180–182 ꢀC. nmax (KBr): 1450, 1342,
1308, 1086, 762 cmꢁ1. dH (DMSO): 8.93 (1H, s, H5), 8.62
(1H, d, J¼7.8 Hz, H1), 8.14 (1H, d, J¼7.6 Hz, H4), 8.06–
7.87 (3H, m, H2, 3, 8), 7.83 (1H, d, J¼8.6 Hz, H11), 7.43
(1H, dd, J¼8.6 and 1.9 Hz, H10). dC (DMSO): 144.30,
141.42, 140.14, 132.93, 131.27, 130.72, 128.25, 127.24,
124.72, 124.52, 124.20, 123.05, 120.62, 110.38. Found, %:
C 66.17, H 3.20, N 16.75. C14H8ClN3 (253.69). Requires,
%: C 66.28, H 3.18, N 16.56.
4.4.5. 2-(2-Amino-5-chlorophenyl)-4-(3,4-dimethyl-
phenyl)-1,2-dihydro-1-phthalazinone 4e. From nitro-
phthalazinone 3h (1.62 g) was obtained 1.25 g (83%) of
aminophthalazinone 4e as colorless crystal, mp 190–
192 ꢀS. dH (DMSO): 8.39 (1H, m, H1), 8.01–7.85 (2H, m,
H
2, 3), 7.75 (1H, m, H4), 7.39–7.30 (3H, m, (CH3)2–C6H3),
7.22 (1H, d, J¼2.1 Hz, H8), 7.15 (1H, dd, J¼8.7 and
2.1 Hz, H10), 6.81 (1H, d, J¼8.7 Hz, H11), 5.35 (2H, s,
NH2), 2.31 (6H, s, 2CH3). Found, %: C 70.24, H 4.77, N
11.41. C22H18ClN3O (375.86). Requires, %: C 70.30, H
4.83, N 11.18.
4.5.2. 9-Chloro-5-methylbenzo[4,5]imidazo[2,1-a]phtha-
lazine 5b. Method A. From aminophthalazinone 4a
(1.14 g) after recrystallization from 80% aqueous ethanol
0.65 g (61%) of the product 5b were obtained as colorless
crystals, mp 180–181 ꢀC. nmax (KBr): 1616, 1520, 1450,
1346, 1331, 1272, 806, 768 cmꢁ1. dH (DMSO): 8.56 (1H,
d, J¼7.6 Hz, H1), 7.97–7.66 (5H, m, H2, 3, 4, 8, 11), 7.30
(1H, d, J¼8.4 Hz, H10), 2.69 (3H, s, CH3). dC (DMSO):
151.01, 141.98, 140.26, 133.17, 131.46, 131.32, 127.14,
124.83, 124.62, 124.46, 123.64, 120.95, 110.52, 19.49.
Found, %: C 67.50, H 3.51, N 15.66. C15H10ClN3
(267.72). Requires, %: C 67.30, H 3.77, N 15.70.
4.4.6. 2-(2-Amino-5-morpholinophenyl)-4-methyl-1,2-
dihydro-1-phthalazinone 9a. From nitrophthalazinone 8a
(1.46 g) was obtained 0.96 g (71%) of aminophthalazinone
9a as colorless crystal, mp 155–157 ꢀC. nmax (KBr): 3395,
3302, 1663, 1508, 1329, 1115, 768 cmꢁ1. dH (DMSO):
8.38 (1H, d, J¼7.4 Hz, H1), 7.98–7.90 (2H, m, H3, 4), 7.86
(1H, m, H2), 6.91–6.65 (3H, m, H8, 10, 11), 4.29 (2H, s,
NH2), 3.73 (4H, m, CH2OCH2), 2.96 (4H, m, CH2NCH2),
2.60 (3H, s, CH3). dH (DMSO): 157.80, 143.86, 142.81,
137.31, 133.10, 131.26, 129.32, 128.39, 127.77, 126.45,
125.15, 117.85, 117.35, 116.07, 66.16, 50.28, 18.48. Found,
%: C 67.56, H 5.90, N 16.86. C19H20N4O2 (336.40).
Requires, %: C 67.84, H 5.99, N 16.65.
Method B. From nitrophthalazinone 3b (1.26 g) and 1.3 g
of iron powder after recrystallization from ethanol were
obtained 0.62 g (58%) of product 5b.
4.4.7. 2-(2-Amino-5-piperidinophenyl)-4-methyl-1,2-
dihydro-1-phthalazinone 9b. From nitrophthalazinone 8c
(1.46 g) was obtained 1.06 g (79%) of aminophthalazinone
9b as colorless crystal, mp 95–97 ꢀC. dH (DMSO): 8.36
(1H, d, J¼7.3 Hz, H1), 7.99–7.91 (2H, m, H3, 4), 7.87 (1H,
m, H2), 6.88–6.67 (3H, m, H8, 10, 11), 4.34 (2H, s, NH2),
2.95 (4H, m, CH2NCH2), 2.59 (3H, s, CH3), 1.64 (4H, m,
CH2–CH2–CH2), 1.51 (2H, m, CH2–CH2–CH2). Found, %:
C 71.78, H 6.39, N 16.89. C20H22N4O (334.42). Requires,
%: C 71.83, H 6.63, N 16.75.
4.5.3. 9-Chloro-5-phenylbenzo[4,5]imidazo[2,1-a]phtha-
lazine 5c. Method A. From aminophthalazinone 4b
(1.39 g) after recrystallization from chloroform–ethanol
0.84 g (64%) of product 5c were obtained as colorless crys-
tals, mp 223–225 ꢀC. nmax (KBr): 1449, 1359, 1344, 1273,
772, 710, 690 cmꢁ1. dH (DMSO): 8.66 (1H, d, J¼7.8 Hz,
H1), 8.00–7.75 (5H, m, H2, 3, 4, 8, 11), 7.75–7.56 (5H, m,
C6H5), 7.40 (1H, d, J¼8.6 Hz, H10). dC (DMSO): 153.11,
141.66, 140.59, 134.54, 133.12, 131.69, 131.09, 129.78,
129.66, 128.60, 128.28, 127.48, 125.30, 125.14, 123.94,
120.96, 110.78. Found, %: C 72.70, H 3.43, N 12.87.
C20H12ClN3 (329.79). Requires, %: C 72.84, H 3.67,
N 12.74.
4.5. Benzo[4,5]imidazo[2,1-a]phthalazines
Method A. BIPH preparation from aminophthalazinones.
The mixture of 0.004 mol of aminophthalazinone and 15 g

V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
10027
Method B. From 1.51 g nitrophthalazinone 3c and 1.5 g of
iron powder after recrystallization from dichloromethane–
methanol were obtained 0.91 g (69%) of product 5c.
131.84, 131.46, 130.36, 129.14, 128.04, 127.93, 125.75,
124.72, 124.46, 121.74, 111.39, 20.18, 20.09. Found, %: C
73.63, H 4.34, N 11.94. C22H16ClN3 (357.85). Requires, %:
C 73.84, H 4.51, N 11.74.
4.5.4. 9-Chloro-5-(4-methylphenyl)benzo[4,5]imi-
dazo[2,1-a]phthalazine 5d. Method B. From nitrophthalazi-
none 3d (1.57 g) and of 1.6 g of iron powder after
recrystallization from chloroform–ethanol 0.76 g (55%) of
product 5d were obtained as yellow crystals, mp 241–
243 ꢀC. dH (DMSO): 8.72 (1H, d, J¼7.8 Hz, H1), 8.13–7.86
(5H, m, H2, 3, 4, 8, 11), 7.68 (2H, d, J¼7.5 Hz, CH–C(Ar)–
CH), 7.52 (1H, m, H10), 7.46 (2H, d, J¼7.5 Hz, CH–
C(Alk)–CH), 2.49 (3H, s, CH3). dC (CDCl3): 153.05,
141.62, 140.33, 139.47, 132.22, 131.65, 131.58, 130.12,
129.36, 129.00, 128.14, 125.39, 125.18, 124.12, 123.78,
120.27, 110.98, 21.02. Found, %: C 73.12, H 3.91, N 12.41.
C21H14ClN3 (343.82). Requires, %: C 73.36, H 4.10, N 12.22.
Method B. From nitrophthalazinone 3g (1.62 g) and 2.4 g
of iron powder after recrystallization from ethanol were
obtained 1.22 g (85%) of product 5g.
4.5.8. 9-Chloro-5-(2,4-dimethylphenyl)benzo[4,5]imi-
dazo[2,1-a]phthalazine 5h. Method B. From nitrophthala-
zinone 3h (1.62 g) and 2.4 g of iron powder after
recrystallization from ethanol 0.47 g (33%) of product 5h
were obtained as colorless crystals, mp 142–144 ꢀC. dH
(DMSO): 8.69 (1H, d, J¼7.9 Hz, H1), 8.05–7.89 (3H, m,
H
2, 3, 8), 7.84 (1H, d, J¼8.8 Hz, H11), 7.73 (1H, m, H3 or 2),
7.50 (1H, d, J¼8.0 Hz, H4), 7.40 (1H, dd, J¼8.8 and
1.8 Hz, H10), 7.33–7.13 (3H, m, (CH3)2–C6H3), 2.45 (3H,
s, 20-CH3), 2.14 (3H, s, 40-CH3). dC (DMSO): 153.00,
141.29, 140.30, 138.63, 136.16, 132.62, 131.46, 130.89,
130.77, 130.59, 129.52, 127.70, 127.35, 126.19, 124.96,
124.72, 124.42, 123.68, 120.57, 110.58, 20.86, 19.31. Found,
%: C 73.84, H 4.42, N 11.89. C22H16ClN3 (357.85).
Requires, %: C 73.84, H 4.51, N 11.74.
4.5.5. 9-Chloro-5-(4-chlorophenyl)benzo[4,5]imi-
dazo[2,1-a]phthalazine 5e. Method A. From aminophthala-
zinone 4c (1.53 g) after recrystallization from chloroform–
ethanol 0.76 g (52%) of product 5e were obtained as color-
less crystals, mp 235–237 ꢀC. dH (DMSO): 8.67 (1H, d,
J¼7.7 Hz, H1), 8.06–7.95 (2H, m, ArH), 7.90–7.81 (3H,
m, ArH), 7.77 (2H, d, J¼7.9 Hz, CH–C(Cl)–CH), 7.66
(2H, d, J¼7.9 Hz, CH–C(Ar)–CH), 7.44 (1H, dd, J¼8.5
and 1.6 Hz, H10). dC (DMSO): 151.78, 141.38, 140.14,
135.22, 132.78, 132.55, 131.37, 130.89, 130.50, 128.45,
127.75, 127.70, 125.03, 123.64, 123.50, 120.25, 110.63.
Found, %: C 65.77, H 2.85, N 11.76. C20H11Cl2N3
(364.24). Requires, %: C 65.95, H 3.04, N 11.54.
4.5.9. 9-Chloro-5-(2,5-dimethylphenyl)benzo[4,5]imi-
dazo[2,1-a]phthalazine 5i. Method B. From nitrophthal-
azinone 3i (1.62 g) and 2.4 g of iron powder after
recrystallization from ethanol 0.95 g (66%) of product 5i
were obtained as colorless crystals, mp 160–162 ꢀC. dH
(DMSO): 8.71 (1H, d, J¼8.0 Hz, H1), 8.02 (1H, d,
J¼1.8 Hz, H8), 8.00 (1H, m, H2 or 3), 7.84 (1H, d, J¼
8.5 Hz, H11), 7.78 (1H, m, H3 or 2), 7.53 (1H, d, J¼8.0 Hz,
H4), 7.44 (1H, dd, J¼8.5 and 1.8 Hz, H10), 7.32–7.19
(3H, m, (CH3)2–C6H3), 2.40 (3H, s, 20-CH3), 2.11 (3H, s,
50-CH3). dC (DMSO): 154.31, 142.58, 141.23, 135.91,
134.55, 134.32, 134.20, 132.40, 132.31, 131.14, 131.06,
128.91, 128.08, 125.92, 125.61, 125.22, 124.55, 121.84,
111.61, 21.31, 19.74. Found, %: C 73.76, H 4.35, N 11.93.
C22H16ClN3 (357.85). Requires, %: C 73.84, H 4.51,
N 11.74.
Method B. From nitrophthalazinone 3e (1.65 g) and 2.5 g of
iron powder after recrystallization from chloroform–ethanol
were obtained 0.73 g (50%) of product 5e.
4.5.6. 9-Chloro-5-(4-ethylphenyl)benzo[4,5]imidazo[2,1-
a]phthalazine 5f. Method A. From aminophthalazinone 4d
(1.50 g) after recrystallization from chloroform–ethanol
0.97 g (68%) of product 5f were obtained as colorless crys-
tals, mp 195–197 ꢀC. dH (DMSO): 8.68 (1H, d, J¼7.8 Hz,
3, 4, 8,
H1), 8.02–7.72 (5H, m, H2,
11), 7.64 (2H, d,
J¼7.8 Hz, CH–C(Ar)–CH), 7.46–7.36 (3H, m, H10, CH–
C(Alk)–CH), 2.80 (2H, q, J¼7.4 Hz, CH2), 1.35 (3H, t,
J¼7.4 Hz, CH3). dC (DMSO): 152.70, 145.23, 141.25,
140.31, 132.52, 131.74, 131.44, 130.46, 129.49, 127.96,
127.67, 127.30, 125.19, 124.76, 123.77, 120.52, 110.49,
28.18, 15.29. Found, %: C 73.76, H 4.37, N 11.97.
C22H16ClN3 (357.85). Requires, %: C 73.84, H 4.51, N 11.74.
4.5.10. 5-Methylbenzo[4,5]imidazo[2,1-a]phthalazine 7a.
Method B. From nitrophthalazinone 6a (1.12 g) and 1.6 g of
iron powder after recrystallization from 80% aqueous meth-
anol 0.59 g (63%) of product 7a were obtained as colorless
crystals, mp 159–161 ꢀC (lit. mp 163 ꢀC1). nmax (KBr):
1522, 1450, 1348, 1334, 1240, 743 cmꢁ1. dH (CDCl3):
8.68 (1H, d, J¼7.4 Hz, H1), 7.99 (1H, d, J¼7.2, H4), 7.97–
7.84 (2H, m, H8, 11), 7.81 (1H, d, J¼7.6 Hz, H2), 7.68 (1H,
m, H3), 7.52–7.35 (2H, m, H9, 10), 2.79 (3H, s, CH3). dC
(DMSO): 149.64, 141.42, 140.64, 132.44, 130.77, 130.47,
126.44, 124.50, 124.22, 124.04, 123.31, 122.16, 119.29,
110.51, 19.19. Found, %: C 77.35, H 4.59, N 18.20.
C15H11N3 (233.28). Requires, %: C 77.23, H 4.75, N 18.01.
Method B. From nitrophthalazinone 3f (1.62 g) and 2.4 g
of iron powder after recrystallization from ethanol were
obtained 0.89 g (62%) of product 5f.
4.5.7. 9-Chloro-5-(3,4-dimethylphenyl)benzo[4,5]imi-
dazo[2,1-a]phthalazine 5g. Method A. From aminophthala-
zinone 4e (1.50 g) after recrystallization from chloroform–
ethanol 1.00 g (70%) of product 5g were obtained as colorless
crystals, mp 203–205 ꢀC. dH (DMSO): 8.66 (1H, d, J¼7.8 Hz,
H1), 7.99 (1H, d, J¼1.8 Hz, H8), 7.97–7.72 (4H, m, H2, 3, 4, 11),
7.41 (1H, dd, J¼8.5 and 1.8 Hz, H10), 7.49–7.29 (3H, m,
(CH3)2–C6H3), 2.39 (6H, s, 2CH3). dC (DMSO): 153.93,
142.36, 141.23, 138.82, 137.42, 133.75, 132.76, 132.31,
4.5.11. 10-Amino-5-methylbenzo[4,5]imidazo[2,1-a]-
phthalazine 7b. Method B. From nitrophthalazinone 6b
(1.30 g) and 1.9 g of iron powder after recrystallization
from chloroform–ethanol 0.56 g (58%) of product 7b were
obtained as colorless crystals, mp >270 ꢀC (dec). nmax
(KBr): 3395, 3311, 3184, 1627, 1519, 1443, 1349, 1162,
762, 689 cmꢁ1. dH (DMSO): 8.55 (1H, d, J¼7.7 Hz, H1),

10028
V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
8.05 (1H, d, J¼7.7 Hz, H4), 7.89 (1H, m, H2 or 3), 7.76 (1H,
m, H3 or 2), 7.67 (1H, d, J¼8.6 Hz, H8), 6.96 (1H, s, H11),
6.78 (1H, d, J¼8.6 Hz, H9), 4.33 (2H, s, NH2), 2.82 (3H,
s, CH3). dC (DMSO): 148.34, 146.18, 143.07, 140.08,
132.08, 129.72, 126.21, 124.40, 123.81, 123.66, 122.94,
112.83, 110.49, 101.33, 19.10. Found, %: C 72.48, H 4.61,
N 22.32. C15H12N4 (248.29). Requires, %: C 72.56, H 4.87,
N 22.57.
139.90, 135.57, 131.64, 131.52, 129.07, 125.39, 125.05,
123.78, 123.02, 119.29, 117.38, 96.45, 51.61, 25.54,
23.80, 19.03. Found, %: C 75.45, H 6.16, N 17.87.
C20H20N4 (316.41). Requires, %: C 75.92, H 6.37, N 17.71.
Method B. From nitrophthalazinone 8c (1.34 g) and 1.3 g
of iron powder after recrystallization from ethanol were
obtained 0.57 g (45%) of product 10c.
4.5.12. 5-(4-Shlorophenyl)benzo[4,5]imidazo[2,1-a]-
phthalazine 7c. Method B. From nitrophthalazinone 6c
(1.51 g) and 1.5 g of iron powder after recrystallization
from chloroform–ethanol 0.75 g (57%) of product 7c were
obtained as yellow crystals, mp 217–219 ꢀC. dH (DMSO):
8.74 (1H, d, J¼7.9 Hz, H1), 8.06–7.37 (11H, m, ArH). dC
(DMSO): 152.43, 142.71, 141.60, 135.45, 134.43, 134.03,
132.57, 131.90, 129.60, 128.91, 126.04, 125.70, 124.58,
123.69, 120.55, 111.81. Found, %: C 72.81, H 3.47, N
12.94. C20H12ClN3 (329.79). Requires, %: C 72.84, H
3.67, N 12.74.
4.5.16. 5-Methyl-9-piperazinobenzo[4,5]imidazo[2,1-a]-
phthalazine 10d. Method B. From nitrophthalazinone 8d
(1.46 g) and 1.5 g of iron powder after recrystallization
from chloroform–ethanol 1.02 g (81%) of product 10d
were obtained as yellow crystals, mp 262–264 ꢀC. dH
(CDCl3): 8.68 (1H, d, J¼7.8 Hz, H1), 7.92 (1H, d,
J¼7.8 Hz, H4), 7.89–7.64 (3H, m, H2, 3, 11), 7.49 (1H, d,
J¼1.8 Hz, H8), 7.22 (1H, dd, J¼9.0 and 1.8 Hz, H10), 3.26
(4H, m, CH2NCH2), 3.08 (4H, m, CH2NHCH2), 2.84 (3H,
s, CH3), 1.75 (1H, s, NH). dC (CDCl3): 149.10, 148.79,
140.53, 136.25, 132.08, 131.90, 129.56, 125.83, 125.51,
124.30, 123.52, 119.82, 117.03, 96.62, 51.71, 46.10,
19.42. Found, %: C 71.33, H 5.90, N 22.25. C19H19N5
(317.40). Requires, %: C 71.90, H 6.03, N 22.06.
4.5.13. 5-Methyl-9-morpholinobenzo[4,5]imidazo[2,1-a]-
phthalazine 10a. Method A. From aminophthalazinone 9a
(1.34 g) after recrystallization from 80% aqueous ethanol
0.95 g (75%) of product 10a were obtained as colorless crys-
tals, mp 199–201 ꢀC. nmax (KBr): 1613, 1494, 1448, 1218,
4.5.17. 9-Morpholino-5-phenylbenzo[4,5]imidazo[2,1-a]-
phthalazine 10e. Method B. From nitrophthalazinone 8e
(1.71 g) and 1.7 g of iron powder after recrystallization
from toluene–petroleum ether 1.16 g (76%) of product 10e
were obtained as yellow crystals, mp 223–225 ꢀC. nmax
(KBr): 1612, 1495, 1447, 1220, 1122, 960, 908, 771,
766 cmꢁ1. dH (CDCl3): 8.71 (1H, d, J¼7.9 Hz, H1),
7.89ꢁ7.46 (10H, m, H2, 3, 4, 8, 11, C6H5), 7.19 (1H, dd,
J¼9.0 and 1.8 Hz, H10), 3.85 (4H, m, CH2OCH2), 3.21
(4H, m, CH2NCH2). dC (CDCl3): 152.31, 148.13, 140.25,
136.53, 134.95, 132.12, 131.99, 129.63, 129.40, 129.26,
128.38, 128.00, 125.93, 123.62, 123.43, 119.92, 116.58,
96.59, 66.67, 50.41. Found, %: C 75.59, H 5.33, N 14.91.
C24H20N4O (380.45). Requires, %: C 75.77, H 5.30, N 14.73.
1126, 908 cmꢁ1. dH (DMSO): 8.52 (1H, d, J¼7.5 Hz, H1),
3,
8.11–7.74 (3H, m, H2,
4), 7.68 (1H, dd, J¼9.0 and
2.0 Hz, H11), 7.34 (1H, s, H8), 7.17 (1H, d, J¼9.0 Hz,
H10), 3.82 (4H, s, CH2OCH2), 3.22 (4H, m, CH2NCH2),
2.80 (3H, s, CH3). dC (DMSO): 151.31, 148.46, 139.28,
133.30, 132.59, 131.29, 131.09, 127.19, 124.41, 123.53,
118.51, 116.87, 95.75, 66.22, 49.77, 19.48. Found, %: C
71.61, H 5.58, N 17.77. C19H18N4O (318.38). Requires,
%: C 71.68, H 5.70, N 17.60.
Method B. From nitrophthalazinone 8a (1.47 g) and 1.5 g
of iron powder after recrystallization from ethanol were
obtained 0.88 g (69%) of product 10a.
4.5.18. 5-Phenyl-9-pyrrolidinobenzo[4,5]imidazo[2,1-a]-
phthalazine 10f. Method B. From nitrophthalazinone 8f
(1.65 g) and 1.7 g of iron powder after recrystallization
from chloroform–ethanol 0.91 g (62%) of product 10f
were obtained as yellow crystals, mp >270 ꢀC. dH
(CDCl3): 8.81 (1H, d, J¼8.1 Hz, H1), 7.93–7.49 (9H, m,
dd, J¼8.6 and 1.8 Hz, H10), 3.40 (4H, m, CH2NCH2), 2.05
(4H, m, CH2CH2). dC (CDCl3): 151.95, 145.20, 139.02,
135.24, 133.79, 132.74, 132.10, 129.71, 129.71, 129.23,
128.98, 128.43, 128.43, 128.01, 126.25, 123.49, 123.30,
119.84, 112.51, 91.02, 48.17, 25.34. Found, %: C 78.77, H
5.22, N 15.50. C24H20N4 (364.45). Requires, %: C 79.10,
H 5.53, N 15.37.
4.5.14. 5-Methyl-9-pyrrolidinobenzo[4,5]imidazo[2,1-a]-
phthalazine 10b. Method B. From nitrophthalazinone 8b
(1.40 g) and 1.4 g of iron powder after recrystallization
from ethanol 0.72 g (59%) of product 10b were obtained
as yellow crystals, mp 250–252 ꢀC. dH (DMSO): 8.52 (1H,
d, J¼7.6 Hz, H1), 8.13 (1H, d, J¼7.6 Hz, H4), 7.96 (1H,
m, H2 or 3), 7.82 (1H, m, H3 or 2), 7.71 (1H, d, J¼8.3 Hz,
H11), 6.92–6.81 (2H, m, H8, 10), 3.33 (4H, s, CH2NCH2),
2.82 (3H, s, CH3) 2.02 (4H, m, CH2CH2). dC (CDCl3):
148.40, 144.89, 139.09, 133.43, 132.34, 131.69, 128.78,
125.47, 123.84, 123.00, 119.62, 111.95, 90.48, 47.97,
25.13, 19.19. Found, %: C 75.02, H 5.75, N 18.70.
C19H18N4 (302.38). Requires, %: C 75.47, H 6.00, N 18.53.
H
2, 3, 4, 11, C6H5), 7.11 (1H, d, J¼1.8 Hz, H8), 6.94 (1H,
4.5.15. 5-Methyl-9-piperidinobenzo[4,5]imidazo[2,1-a]-
phthalazine 10c. Method A. From aminophthalazinone 9b
(1.34 g) after recrystallization from 80% aqueous ethanol
1.10 g (87%) of product 10c were obtained as colorless crys-
tals, mp 175–177 ꢀC. dH (CDCl3): 8.58 (1H, d, J¼8.1 Hz,
H1), 7.85–7.52 (4H, m, H2, 3, 4, 11), 7.41 (1H, d, J¼1.9 Hz,
H8), 7.18 (1H, dd, J¼8.9 and 1.9 Hz, H10), 3.22 (4H, m,
CH2NCH2), 2.72 (3H, s, CH3), 1.76 (4H, m, CH2CH2CH2),
1.58 (2H, m, CH2CH2CH2). dC (CDCl3): 148.96, 148.61,
4.5.19. 5-Phenyl-9-piperidinobenzo[4,5]imidazo[2,1-a]-
phthalazine 10g. Method B. From nitrophthalazinone 8g
(1.70 g) and 1.7 g of iron powder after recrystallization
from chloroform–ethanol 0.98 g (65%) of product 10g
were obtained as yellow crystals, mp 230–232 ꢀC. dH
(CDCl3): 8.76 (1H, d, J¼8.3 Hz, H1), 7.90–7.52 (10H, m,
H
2, 3, 4, 8, 11, C6H5), 7.26 (1H, dd, J¼8.0 and 2.1 Hz, H10),
3.24 (4H, m, CH2NCH2), 1.74 (4H, m, CH2CH2CH2), 1.58
(2H, m, CH2CH2CH2). dC (CDCl3): 152.24, 149.39,

V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
10029
140.07, 136.24, 135.16, 132.16, 129.74, 129.28, 128.46,
128.06, 126.10, 123.65, 123.49, 119.75, 117.99, 97.05,
51.88, 25.83, 24.12. Found, %: C 78.83, H 5.71, N 14.94.
C25H22N4 (378.48). Requires, %: C 79.34, H 5.86, N 14.80.
7.89–7.73 (3H, m, H2, 4, 11), 7.67 (2H, d, J¼7.7 Hz, CH–
C(Cl)–CH), 7.62–7.45 (3H, m, H3, CH–C(Ar)–CH), 7.46
(1H, d, J¼1.8 Hz, H8), 7.20 (1H, dd, J¼8.9 and 1.8 Hz,
H10), 3.88 (4H, m, CH2OCH2), 3.23 (4H, m, CH2NCH2).
dC (CDCl3): 151.21, 148.30, 140.17, 136.56, 135.60,
133.44, 132.37, 131.95, 131.06, 129.56, 128.74, 127.66,
125.98, 123.62, 123.36, 120.03, 116.75, 96.52, 66.75,
50.45. Found, %: C 69.45, H 4.42, N 13.71. C24H19ClN4O
(414.90). Requires, %: C 69.48, H 4.62, N 13.50.
4.5.20. 5-(4-Methylphenyl)-9-morpholinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10h. Method B. From nitro-
phthalazinone 8h (1.77 g) and 1.8 g of iron powder after
recrystallization from chloroform–ethanol 0.79 g (50%)
of product 10h were obtained as yellow crystals, mp
188–190 ꢀC. dH (CDCl3): 8.73 (1H, d, J¼7.9 Hz, H1),
4.5.24. 5-(4-Chlorophenyl)-9-pyrrolidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10l. Method B. From nitro-
phthalazinone 8l (1.79 g) and 1.8 g of iron powder after
recrystallization from chloroform–ethanol 1.16 g (73%)
of product 10l were obtained as yellow crystals, mp
234–236 ꢀC. dH (CDCl3): 8.72 (1H, d, J¼8.0 Hz, H1),
7.89–7.75 (3H, m, H2 or 3, 4, 11), 7.70 (2H, d, J¼7.4 Hz,
CH–C(Cl)–CH), 7.65–7.52 (3H, m, H3, CH–C(Ar)–CH),
7.06 (1H, s, H8), 6.90 (1H, d, J¼8.6 Hz, H10), 3.39 (4H,
m, CH2NCH2), 2.04 (4H, m, CH2CH2). dC (CDCl3):
150.71, 145.24, 138.90, 135.46, 133.90, 133.74, 132.72,
132.19, 131.12, 129.02, 128.73, 127.59, 126.34, 123.41,
123.16, 119.98, 112.58, 90.89, 48.16, 25.34. Found, %:
C 72.15, H 4.62, N 14.22. C24H19ClN4 (398.90). Requires,
%: C 72.27, H 4.80, N 14.05.
7.92–7.78 (3H, m, H2 or 3, 4, 11), 7.67–7.55 (3H, m, H3 or 2
,
CH–C(Ar)–CH), 7.51 (1H, d, J¼1.9 Hz, H8), 7.37 (2H, d,
J¼7.6 Hz, CH–C(Alk)–CH), 7.20 (1H, dd, J¼8.8 and
1.9 Hz, H10), 3.88 (4H, m, CH2OCH2), 3.22 (4H, m,
CH2NCH2), 2.46 (3H, s, CH3). dC (CDCl3): 152.56,
148.23, 140.45, 139.45, 136.65, 132.19, 129.60, 129.51,
129.15, 128.21, 126.05, 123.89, 123.58, 120.00, 116.70,
96.79, 66.80, 50.58, 21.24. Found, %: C 76.02, H 5.35, N
14.42. C25H22N4O (394.48). Requires, %: C 76.12, H 5.62,
N 14.20.
4.5.21. 5-(4-Methylphenyl)-9-pyrrolidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10i. Method B. From nitro-
phthalazinone 8i (1.70 g) and 1.7 g of iron powder after
recrystallization from chloroform–ethanol 1.10 g (73%) of
product 10i were obtained as yellow crystals, mp 238–
240 ꢀC. dH (CDCl3): 8.74 (1H, d, J¼8.0 Hz, H1), 7.92–
4.5.25. 5-(4-Chlorophenyl)-9-piperidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10m. Method B. From nitro-
phthalazinone 8m (1.84 g) and 1.8 g of iron powder after
recrystallization from chloroform–ethanol 1.06 g (64%) of
product 10m were obtained as yellow crystals, mp 160–
162 ꢀC. dH (CDCl3): 8.73 (1H, d, J¼7.8 Hz, H1), 7.90–7.75
(3H, m, H2 or 3, 4, 11), 7.72–7.60 (3H, m, H3 or 2, CH–C(Cl)–
CH), 7.51 (2H, d, J¼7.7 Hz, CH–C(Ar)–CH), 7.41 (1H, d,
J¼1.8 Hz, H8), 7.31 (1H, dd, J¼8.8 Hz, H10), 3.23 (4H, m,
CH2NCH2), 1.75 (4H, m, CH2CH2CH2), 1.59 (2H, m,
CH2CH2CH2). dC (CDCl3): 151.04, 149.52, 139.90, 136.19,
135.53, 133.62, 132.31, 132.06, 131.11, 129.40, 128.72,
127.61, 126.14, 123.62, 123.36, 119.80, 118.05, 96.89,
51.81, 25.84, 24.08. Found, %: C 72.65, H 5.01, N 13.75.
C25H21ClN4 (412.93). Requires, %: C 72.72, H 5.13, N 13.57.
7.78 (3H, m, H2 or 3, 4, 11), 7.70–7.55 (3H, m, H3 or 2
,
CH–C(Ar)–CH), 7.39 (2H, d, J¼7.5 Hz, CH–C(Alk)–CH),
7.11 (1H, d, J¼1.8 Hz, H8), 6.90 (1H, dd, J¼8.8 and
1.8 Hz, H10), 3.40 (4H, m, CH2NCH2), 2.49 (3H, s, CH3),
2.05 (4H, m, CH2CH2). dC (CDCl3): 151.08, 144.14,
138.24, 137.85, 132.35, 131.62, 131.25, 130.99, 128.56,
128.05, 127.95, 126.99, 125.00, 122.56, 122.32, 118.60,
111.45, 90.00, 47.06, 24.24, 20.13. Found, %: C 79.04, H
5.52, N 14.93. C25H22N4 (378.48). Requires, %: C 79.34,
H 5.86, N 14.80.
4.5.22. 5-(4-Methylphenyl)-9-piperidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10j. Method B. From nitro-
phthalazinone 8j (1.76 g) and 1.8 g of iron powder after
recrystallization from chloroform–ethanol 0.91 g (58%) of
product 10j were obtained as yellow crystals, mp 205–
207 ꢀC. nmax (KBr): 2935, 2851, 1666, 1601, 1501, 1327,
1103 cmꢁ1. dH (CDCl3): 8.75 (1H, d, J¼7.9 Hz, H1), 7.95–
4.5.26. 5-(4-Chlorophenyl)-9-piperazinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10n. Method B. From nitro-
phthalazinone 8n (1.84 g) and 1.8 g of iron powder after
recrystallization from ethanol 1.04 g (63%) of product
10n were obtained as yellow crystals, mp 216–218 ꢀC.
dH (CDCl3): 8.72 (1H, d, J¼7.9, H1), 7.91–7.76 (3H, m,
7.78 (3H, m, H2 or 3, 4, 11), 7.68–7.58 (3H, m, H3 or 2
,
CH–C(Ar)–CH), 7.61 (1H, d, J¼1.9 Hz, H8), 7.39 (2H, d,
J¼7.6 Hz, CH–C(Alk)–CH), 7.27 (1H, dd, J¼7.9 and
1.9 Hz, H10), 3.24 (4H, m, CH2NCH2), 2.49 (3H, s, CH3),
1.76 (4H, m, CH2CH2CH2), 1.60 (2H, m, CH2CH2CH2).
dC (CDCl3): 152.32, 149.36, 140.14, 139.34, 136.26,
132.31, 132.10, 129.63, 129.28, 129.12, 128.14, 126.15,
123.81, 123.48, 119.72, 117.97, 97.11, 51.91, 25.88,
24.13, 21.24. Found, %: C 79.33, H 5.74, N 14.41.
C26H24N4 (392.51). Requires, %: C 79.56, H 6.16, N 14.27.
H
2 or 3, 4, 11), 7.72–7.61 (3H, m, H3 or 2, CH–C(Cl)–CH),
7.56 (2H, d, J¼8.5 Hz, CH–C(Ar)–CH), 7.48 (1H, d,
J¼2.0 Hz, H8), 7.25 (1H, dd, J¼8.6 and 2.0 Hz, H10),
3.22 (4H, m, CH2NCH2), 3.07 (4H, m, CH2NHCH2), 1.71
(1H, s, NH). dC (CDCl3): 151.14, 148.96, 140.10, 136.46,
135.60, 133.55, 132.37, 132.04, 131.09, 129.53, 128.76,
127.69, 126.09, 123.67, 123.38, 119.95, 117.31, 96.74,
51.59, 46.07. Found, %: C 69.40, H 4.87, N 17.08.
C24H20ClN5 (413.91). Requires, %: C 69.64, H 4.87,
N 16.92.
4.5.23. 5-(4-Chlorophenyl)-9-morpholino-benzo[4,5]-
imidazo[2,1-a]phthalazine 10k. Method B. From nitro-
phthalazinone 8k (1.85 g) and 1.9 g of iron powder after
recrystallization from chloroform–ethanol 1.41 g (85%)
of product 10k were obtained as yellow crystals, mp
220–222 ꢀC. dH (CDCl3): 8.71 (1H, d, J¼7.7 Hz, H1),
4.5.27. 5-(4-Ethylphenyl)-9-piperidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10o. Method B. From nitro-
phthalazinone 8o (1.82 g) and 1.8 g of iron powder after
recrystallization from ethanol 1.07 g (66%) of product 10o

10030
V. A. Kuznetsov et al. / Tetrahedron 62 (2006) 10018–10030
were obtained as yellow crystals, mp 185–187 ꢀC. dH
(DMSO): 8.65 (1H, d, J¼7.7 Hz, H1), 7.91 (1H, m, H2 or 3),
7.82 (1H, d, J¼7.2 Hz, H4), 7.69 (1H, d, J¼9.0 Hz, H11),
7.68 (1H, m, H3 or 2), 7.62 (2H, d, J¼7.5 Hz, CH–C(Ar)–
CH), 7.45–7.36 (3H, m, H8, CH–C(Alk)–CH), 7.18 (1H,
dd, J¼9.0 and 1.8 Hz, H10), 3.21 (4H, m, CH2NCH2), 2.77
(2H, q, J¼7.5 Hz, CH2), 1.74 (4H, m, CH2CH2CH2), 1.60
(2H, m, CH2CH2CH2), 1.34 (3H, t, CH3). dC (DMSO):
151.80, 144.92, 139.42, 136.05, 132.13, 131.52, 129.52,
127.79, 127.60, 125.67, 123.29, 119.43, 117.42, 97.04,
51.64, 28.19, 25.23, 23.60, 15.36. Found, %: C 79.55,
H 6.01, N 13.92. C27H26N4 (406.54). Requires, C 79.77,
H 6.45, N 13.78.
dH (DMSO): 8.63 (1H, d, J¼7.8 Hz, H1), 7.92 (1H, m,
H
3 or 2), 7.71 (1H, d, J¼9.2 Hz, H11), 7.68 (1H, m, H2 or 3),
7.43 (1H, d, J¼8.2 Hz, H4), 7.39 (1H, d, J¼2.0 Hz, H8),
7.31–7.20 (3H, m, (CH3)2–C6H3), 7.19 (1H, dd, J¼9.2 and
2.0 Hz, H10), 3.21 (4H, m, CH2NCH2), 2.40 (3H, s,
20-CH3), 2.11 (3H, s, 50-CH3), 1.72 (4H, m, CH2CH2CH2),
1.58 (2H, m, CH2CH2CH2). dC (DMSO): 153.24, 149.87,
140.34, 136.47, 135.85, 135.02, 134.24, 133.87, 133.72,
132.70, 131.12, 131.03, 130.84, 128.71, 126.27, 124.63,
123.96, 120.66, 118.18, 96.79, 51.76, 26.27, 24.72, 21.24,
19.65. Found, %: C 79.41, H 6.09, N 13.99. C27H26N4
(406.54). Requires, C 79.77, H 6.45, N 13.78.
References and notes
4.5.28. 5-(3,4-Dimethylphenyl)-9-piperidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10p. Method B. From nitro-
phthalazinone 8p (1.82 g) and 1.8 g of iron powder after
recrystallization from ethanol 1.07 g (66%) of product 10p
were obtained as yellow crystals, mp 162–164 ꢀC. dH
(DMSO): 8.60 (1H, d, J¼7.8 Hz, H1), 7.90 (1H, m, H2 or 3),
1. Rowe, F. M.; Adams, D. A. W.; Peters, A. T.; Gillam, J. M.
J. Chem. Soc. 1937, 90–109.
2. Razvi, M.; Ramalingam, T. Indian J. Chem., Sect. B 1992, 31B,
788–789.
3. Shubin, K. M.; Kuznetsov, V. A.; Galishev, V. A. Tetrahedron
Lett. 2004, 45, 1407–1408.
7.83 (1H, d, J¼8.1 Hz, H4), 7.69 (1H, d, J¼8.8 Hz, H11),
7.68 (1H, m, H3
2), 7.49–7.28 (4H, m, H8, (CH3)2–
or
C6H3), 7.18 (1H, dd, J¼8.8 and 2.0 Hz, H10), 3.20 (4H, m,
CH2NCH2), 2.39 (6H, s, 2CH3), 1.71 (4H, m, CH2CH2CH2),
1.59 (2H, m, CH2CH2CH2). dC (DMSO): 152.91, 149.65,
140.25, 138.47, 137.30, 136.56, 133.40, 133.21, 132.60,
131.42, 130.68, 130.26, 128.94, 127.97, 126.37, 124.13,
123.86, 120.56, 118.14, 96.93, 51.84, 26.28, 24.64, 20.14,
20.02. Found, %: C 79.62, H 5.91, N 13.95. C27H26N4
(406.54). Requires, C 79.77, H 6.45, N 13.78.
4. Mangini, A.; Deliddo, C. Gazz. Chim. Ital. 1933, 63, 612–629.
5. Lindley, J. M.; McRobbie, I. M.; Meth-Cohn, O.; Suschitzki, H.
J. Chem. Soc., Perkin Trans. 1 1980, 982–994.
6. Yakovlev, S. V.; Pavlova, L. A. J. Org. Chem. USSR (Engl.
Transl.) 1988, 24, 2195–2197.
7. Runti, C.; Galimberti, S. Ann. Chim. (Rome) 1957, 47, 250–
259.
8. Morgan, D. O.; Ollis, W. D.; Stanforth, S. P. Tetrahedron 2000,
56, 5523–5534.
4.5.29. 5-(2,5-Dimethylphenyl)-9-piperidinobenzo[4,5]-
imidazo[2,1-a]phthalazine 10q. Method B. From nitro-
phthalazinone 8q (1.82 g) and 1.8 g of iron powder after
recrystallization from ethanol 0.82 g (57%) of product
10q were obtained as yellow crystals, mp 220–222 ꢀC.
9. Rowe, F. M.; Osborn, W. J. Chem. Soc. 1947, 829–837.
10. Rowe, F. M.; Heath, G. M.; Patel, C. V. J. Chem. Soc. 1936,
311–315.
11. Grimmett, M. R. Imidazole and Benzimidazole Synthesis;
Academic: London, 1997; 265 p.