Tetracycle formation from the reaction of acetophenones with 1-aminoanthraquinone, and further annulation of pyridine and diazepine rings

Article abstract of DOI:10.1071/CH03136

Acetophenones (H, o-, m-, p-Cl, o-aza) react with aminoanthraquinone in pyridine containing solid sodium hydroxide to form 6-(arylcarbonyl)methyl-2-aryl-7H-naphtho[1,2,3-de]quinolin-7-ones (with the 4-(arylcarbonyl)methyl isomer as minor product). Preformed 7H-benzo[e]perimidin-7-one with acetophenone underwent the second part of this process, i.e. nucleophilic substitution to form 6-phenacyl-7H-benzo-[e]perimidin-7-one. Further reactions are described, including cyclization with ammonium acetate/acetic acid to 2,7-diphenyl-1,6-diazabenzo[e]pyrene and 7-phenyl-1,3,8-triazabenzo[e]pyrene, respectively, and with hydrazine hydrate to 3,8-diphenyl-4H-[1,2]diazepino[3,4-4′,3′ : 4,5-f]naphtho[1,2,3-de]quinoline and 3-phenyl-4H-benzo[e][1,2]diazepino[3,4,5-gh]perimidine.

Full text of DOI:10.1071/CH03136

CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2003, 56, 1219–1224
Tetracycle Formation from the Reaction of Acetophenones with
1-Aminoanthraquinone, and Further Annulation of Pyridine and
Diazepine Rings
Leslie W. DeadyA,B and Clare L. SmithA
A
Chemistry Department, La Trobe University, Victoria 3086, Australia.
B Author to whom correspondence should be addressed (L.Deady@latrobe.edu.au).
Acetophenones (H, o-, m-, p-Cl, o-aza) react with aminoanthraquinone in pyridine containing solid
sodium hydroxide to form 6-(arylcarbonyl)methyl-2-aryl-7H-naphtho[1,2,3-de]quinolin-7-ones (with the 4-
(arylcarbonyl)methyl isomer as minor product). Preformed 7H-benzo[e]perimidin-7-one with acetophenone
underwent the second part of this process, i.e. nucleophilic substitution to form 6-phenacyl-7H-benzo-
[e]perimidin-7-one. Further reactions are described, including cyclization with ammonium acetate/acetic
acid to 2,7-diphenyl-1,6-diazabenzo[e]pyrene and 7-phenyl-1,3,8-triazabenzo[e]pyrene, respectively, and with
hydrazine hydrate to 3,8-diphenyl-4H-[1,2]diazepino[3,4-4ꢀ,3ꢀ : 4,5-f]naphtho[1,2,3-de]quinoline and 3-phenyl-
4H-benzo[e][1,2]diazepino[3,4,5-gh]perimidine.
Manuscript received: 26 May 2003.
Final version: 1 August 2003.
O
O
O
Introduction
The reaction of aminoanthraquinone with acetone in dilute
sodium hydroxide is the standard method of preparation
of 2-methyl-7H-naphtho[1,2,3-de]quinolin-7-one (1), Dia-
gram 1.[1] We have previously used this chemistry as a key
part of the synthesis of the 11-carboxamide (2), a potent
antitumour agent.[2] As part of a study of structure–activity
effects in compounds related to (2), we were interested in
preparing 2-aryl analogues. In the first instance, this required
investigation of the reaction of 1-aminoanthraquinone with
acetophenone. The 1-aminoanthraquinone/acetone reaction
is a form of Friedlander condensation, and an attempt by
us at acid-catalyzed reaction (acetic acid/sulfuric acid—the
Fehnel modification[3]) resulted only in efficient acetylation
oftheaminogroup, whilereactionwithacetaldehydeinacetic
acid reportedly gave (3) and products from further cycliza-
tion onto position 2.[4] Thus, we targeted basic conditions for
the acetophenone work. The use of other simple ketones in
the base-catalyzed conditions does not appear to have been
reported, which was an additional reason for studying the
acetophenone reaction. The reaction turned out to be more
complicated than anticipated but the products were, in turn,
useful precursors to some new polycyclic systems.
O
1
N
CO
NH
N
HN
H
O
3
(CH ) N
CH
CH
3
3 2
3
(1)
(2)
(3)
Diagram 1.
problem.This was overcome by the use of pyridine and, in the
presence of added solid sodium hydroxide, a slow reaction
occurred at room temperature (reflux conditions resulted in
a complex product mixture). The solution turned green, and
when this was acidified after three days a good recovery of a
solid product was obtained (Scheme 1). This was established
to be a 10 : 1 mixture of the 7H-naphtho[1,2,3-de]quinolin-7-
ones (4a) and its 4-isomer (5a), as discussed below. The same
result was obtained from a reaction carried out in a nitrogen
atmosphere.
This reaction occurred only in the presence of an excess
of acetophenone (five-fold was routinely used) and there
was no evidence for the target (3a). This suggests that under
these conditions, nucleophilic substitution in the tetracyclic
compound is more rapid than its formation. Displacement
of ring hydrogens by O- and N-nucleophiles have been
reported for 7H-benzo[e]perimidine[5] and the ‘deaza’ ana-
logue, benzanthrone[6]; 4- and 6-substituted products were
found. Grignard nucleophiles reacted with benzanthrone at
the 6-position.[7]
Results and Discussion
The standard basic conditions and several others were tried
for reaction with acetophenone but, with one exception, with-
out success; solubility of the reagents seemed to be a major
© CSIRO 2003
10.1071/CH03136
0004-9425/03/121219

1220
L. W. Deady and C. L. Smith
Ph
O
z
N
N
O
O
O
O
CH
N
3
6
(ii)
(i)
4
(4a)
N
NH
X
N
2
Ph
Ph
(i)
Y
z
O
O
(8)
(10) X ꢁ CH, Y ꢁ Ph
(11) X ꢁ N, Y ꢁ H
(4)
ꢀ 4-isomer (5) as minor product
X
N
Scheme 1. Reagents and conditions: (i) ArCOCH3, pyridine, NaOH
(solid), 20◦C, 3 d; (ii) N2H4 · H2O, pyridine, reflux 3 h. Z = H (Xa),
p-Cl (Xb), m-Cl (Xc), o-Cl (Xd), o-aza (Xe).
(ii)
Ph
N
Y
(4a) X ꢁ CH, Y ꢁ Ph
(7a) X ꢁ N, Y ꢁ H
O
O
O
O
CH
N
Ar
(ii)
3
X
N
(i)
Y
(7a)
(12) X ꢁ CH, Y ꢁ Ph
(13) X ꢁ N, Y ꢁ H
N
N
N
N
N
(6)
(7)
(9)
Scheme 3. Reagents and conditions: (i) N2H4 · H2O, 2-propanol/
Scheme 2. Reagents and conditions: (i) ArCOCH3, pyridine, NaOH
(solid), 20◦C, 3 d; (ii) N2H4 · H2O, pyridine, reflux 3 h.Ar = C6H5 (7a),
p-MeC6H4 (7b).
AcOH, reflux; (ii) NH4OAc, AcOH, reflux 15 min.
the precursor (4a), which aided spectroscopic study (below).
The diaza (7a) likewise gave mainly (9) (63%; Scheme 2).
The ready formation of (4) and (7), each with two car-
bonyl groups in close proximity, suggested that novel ring
systems would be accessible by suitable annulation through
these groups. As a first example, reaction with hydrazine
hydrate in acetic acid/2-propanol followed a different course
to that described above and led to formation of the diazepino
ring containing compounds (10) (from (4a)) and (11) (from
(7a); Scheme 3).
These conditions were reported to give diazepine com-
pounds from 1,5-diketones.[9] Formulation as (10) and (11)
was made from the characteristic doublets for the non-
equivalent methylene protons in the 1H NMR spectra,
previously noted for similar compounds.[10]
In a second extension, reaction of (4a) with ammonium
acetate in boiling acetic acid for 15 min gave a readily isolable
solid in 64% yield, which was assigned structure (12) primar-
ily from microanalytical and 1H NMR data (Scheme 3). The
loss of oxygen relative to (4a), and presence of two aromatic
singlets in the proton spectrum were consistent with the pen-
tacycle structure shown and there is precedent for formation
of a six-membered aromatic ring from a 1,5-diketone under
theseconditions.[11] Inthesamemanner, (7a)gave(13)(78%)
under these conditions (Scheme 3).
A range of substituted acetophenones was then subjected
to this reaction. With the exception of p-nitro, those car-
rying withdrawing substituents (o-, m-, p-Cl, o-aza) were
successful (yields about 80%), with isomer ratios varying
from only 6-product (o-Cl) through 7–8 : 1 (m- and p-Cl) to
3 : 2 (o-aza); acetophenones with donor p-methyl- and
p-methoxy-substituents failed to react. The isomer ratios
1
were calculated from H NMR spectra, where there was a
small but characteristic difference in the chemical shift of the
methylene protons, with the 6-isomer consistently downfield.
In order to get another perspective on the nucleo-
philic reactivity of this type of tetracyclic system, 7H-
benzo[e]perimidin-7-one (6) was prepared[8] and subjected
to the same reaction conditions. Only the 6-substituted
isomer (7a) was detected and was isolated in 78% yield
(Scheme 2). Interestingly, p-methylacetophenone (unreac-
tive with 1-aminoanthraquinone) readily gave the analogous
product (7b), and these reactions were complete within 19 h.
When compared with the >60 h required for the formation of
(4) from 1-aminoanthraquinone, these results provide further
support that in the latter case, formation of the tetracycle is
the slow step.
Further Chemistry
Structure Assignment
Solubility problems with the chloro substituted (4b)–(4d)
made it difficult to get spectrocsopic data, so most fur-
ther work was confined to (4a). Reaction with an excess of
hydrazine hydrate in boiling pyridine gave deacylation as the
major process and the methyl compound (8) was isolated in
63% yield (Scheme 1).This compound was more soluble than
The assignments of the gross structures of (4) and (7) were
made from NMR and electrospray MS (positive mode) spec-
tral data and microanalysis, and the 6-position location of
the sidechain was proved by their conversion into (12) and
(13), respectively. NMR spectra were consistent with these

Tetracycle Formation from Acetophenones with 1-Aminoanthraquinone
1221
assignments, though low solubility of (4) and complex carbon
spectra meant complete assignments were not obtained for
all compounds. However, the methyl substituted compound
(8), for example, was more soluble than (4a) and the HMBC
spectrum showed 3JCH coupling between C-7 and only one
H, namely H-8, in accord with a substituent at position 6.
The diaza analogue (7) of (4a) and the methyl derivative (9)
were chloroform soluble and a range of 2D NMR experiments
allowed full assignment of protons and carbons.
Only in the case of p-chloroacetophenone was the minor
isomer (5b) able to be separated.The COSY spectrum showed
one example of coupling between two doublets, consistent
with the substituent being at position 4.
isolate a product from this solution failed, for example addi-
tion of hexane gave a black insoluble residue with a poor 1H
NMR spectrum, but which contained a peak at δ 5.2 again,
suggesting some regeneration of the starting ketone.
Compound (7a) was then reacted with acetic anhydride in
pyridine at room temperature and a dark green solid sepa-
rated in good yield when this mixture was added to ice. The
1H and 13C NMR spectra in chloroform revealed a clean sam-
ple of the enol acetate (14b), but attempts to recrystallize or
separate this also led to decomposition, which was somewhat
surprising since the enol acetate of deoxybenzoin is a stable
solid.[12] Loss of the acetyl group was also a facile process
in the mass spectrometer. Interestingly, a chloroform solu-
tion of (7a) was a non-fluorescent brown-green colour; red
fluorescence only developed (slowly) when TFA was added.
The identity of the red fluorescent species has not been estab-
lished; because TFA would also protonate the aza group in
these conditions (see (12) below), it may be a protonated form
of (14a) with the CF3 group being an essential component.
By contrast, addition of the base 1,8-diazabicyclo[5.4.0]-
undec-7-ene(DBU)toachloroformsolutionof(7a)produced
an instant blue-green solution (only very weakly fluorescent),
inwhichthe methyleneprotonsignalof(7a)wasagain absent.
The species formed is probably the enolate anion, where con-
jugation is possible between the two oxygen groups, namely
the chromophore fits the definition of an oxonol. Compound
(7a) was reformed when the solution was acidified. The same
colour changes were noted with (4a).
Absorbance and Fluorescence Behaviour
The yellow (4a) was only slightly soluble in chloroform but
the addition of a drop of trifluoroacetic acid (TFA) to a solu-
tion in an NMR tube gave complete solubility. However, over
3–5 h the solution developed a bright red fluorescence and
the 1H NMR spectrum also changed, with the methylene peak
disappearing and a new one proton singlet appearing in the
aromatic region. This was shown to be general for (4) and
(7a) and was consistent with formation of the corresponding
enol trifluoroacetate (14a), Diagram 2. However, attempts to
Ph
O
OCOZ
Unlike (4) and (7), the pentacycles (12) and (13) were
themselves fluorescent (the former more so) and showed
different behaviour with TFA, which is explicable in terms
of a fast, reversible protonation. Thus, the yellow (12) on
addition of TFA immediately gave a different spectrum with
an increase in green fluorescence intensity. This change was
reversed when base was added.
N
N
(14a) Z = CF3
(14b) Z = CH3
Diagram 2.
Spectral data for these various species are listed inTable 1.
Table 1. Absorbance and fluorescence data
Compound
Conditions
Absorbance
λmax [nm] (ε[M−1cm−1])
Fluorescence
λem [nm]
λex [nm]
Quantum yield
0.10A
(4a)
(7a)
CHCl3
CHCl3/TFA
CHCl3/DBU
367 (24 500)
443 (26 300)
578 (32 700)
627 (52 500)
420
552
CHCl3
368 (28 800)
386 (26 900)
494 (41 500)
687 (20 000)
606 sh
CHCl3/TFA
CHCl3/DBU
500
650
650
561
772
737
0.02A
0.07B
0.02B
639 (46 400)
(12)
(13)
CHCl3
387 (16 000)
408 (22 400)
442 (24 600)
380
420
420
443
473
0.48C
0.98B
CHCl3/TFA
CHCl3
387 (88 900)
404 (92 400)
425D (53 000)
CHCl3/TFA
420
492
0.60B
A Reference: fluorescein.
quinine sulfate.
B Reference: 3,3ꢀ-diethylthiadicarbocyanine iodide.
C Reference:
D Very broad band 380–470 nm.

1222
L. W. Deady and C. L. Smith
Conclusions
2-(4-Chlorophenyl)-6-[2-(4-chlorophenyl)-2-oxoethyl]-7H-
naphtho[1,2,3-de]quinolin-7-one (4b)
The base-catalyzed reactions of 1-aminoanthraquinone and
7H-benzo[e]perimidin-7-one with acetophenone have led to
phenacyl substituted tetracyclic compounds, which are useful
precursors of some novel polycyclic systems with interesting
fluorescence properties.
and 2-(4-Chlorophenyl)-4-[2-(4-chlorophenyl)-2-oxoethyl]-
7H-naphtho[1,2,3-de]quinolin-7-one (5b)
These were prepared as for (4a)/(5a).The crude solid, (0.87 g from 1.74 g
of p-chloroacetophenone) contained the two isomers in a ratio of 7 : 1.
Recrystallizationfromtoluene(hotfiltrationremovedtheinsoluble(5b))
gave (4b) as a light brown solid (0.71 g, 64%), mp 246–247◦C (Found:
C 73.1, H 3.4, N 2.6. C30H17Cl2NO2 requires C 72.9, H 3.5, N 2.8%).
δH ([D6]DMSO) 5.12 (2H, s, CH2), 7.66–7.69 (5H, m), 7.92 (1H, t,
J 7.0), 7.96 (1H, d, J 8.5), 8.12–8.19 (3H, m), 8.46 (1H, d, J 8.6), 8.55
(2H, d, J 8.2), 8.99 (1H, d, J 7.0), 9.17 (1H, s). ES-MS (positive mode)
m/z 494 (100%), 496 (74%), both (M + 1).
Experimental
NMR spectra were recorded on a Bruker AM-300 spectrometer operat-
ing at 300.13 (1H) and 75.47 MHz (13C) and chemical shifts are reported
as δ values (ppm), relative to tetramethylsilane. Standard PENDANT
(polarization enhancement during attached nucleus testing), DEPT (dis-
tortionless enhancement by polarization transfer), COSY (correlation
spectroscopy), HMQC (heteronuclear multiple quantum coupling), and
HMBC (heteronuclear multiple bond coupling) experiments were used
in the assignments of NMR spectra. Electrospray mass spectra (ES-MS)
were obtained on Perkin–Elmer Sciex API-300 and VG Bio-Q triple
quadrupole mass spectrometers. EI and LSI mode high-resolution mass
spectra were obtained by Dr N. Davies, University of Tasmania. Micro-
analyses were carried out at the Campbell Microanalytical Laboratory,
University of Otago, New Zealand.
Recrystallization of (5b) from chloroform gave a fawn solid (7%),
mp 208–210◦C (Found: C 70.1, H 3.5, N 2.7. C30H17Cl2NO2 · H2O
requires C 70.3, H 3.7, N 2.7%). δH ([D6]DMSO) 5.09 (2H, s, CH2),
7.64–7.70(5H, m), 7.90(1H, t, J 7.8), 7.93(1H, d, J 8.5), 8.10–8.17(3H,
m), 8.42 (1H, d, J 8.5), 8.53 (2H, d, J 8.5), 8.95 (1H, d, J 8.1), 9.12 (1H,
s). ES-MS (positive mode) m/z 494 (100%), 496 (80%), both (M + 1).
2-(3-Chlorophenyl)-6-[2-(3-chlorophenyl)-2-oxoethyl]-7H-
naphtho[1,2,3-de]quinolin-7-one (4c)
and 2-(3-Chlorophenyl)-4-[2-(3-chlorophenyl)-2-oxoethyl]-
7H-naphtho[1,2,3-de]quinolin-7-one (5c)
These were prepared as for (4a)/(5a).The crude solid, (0.48 g from 0.69 g
of m-chloroacetophenone) contained the two isomers in a ratio of 8 : 1.
Recrystallization from methyl ethyl ketone gave (4c) (0.36 g, 75%)
as a light brown solid, mp 218–220◦C (Found: C 72.3, H 3.3, N 2.9.
C30H17Cl2NO2 requires C 72.9, H 3.5, N 2.8%). δH ([D6]DMSO) 5.24
(2H, s, CH2), 7.75 (1H, t, J 8.2), 7.66–7.80 (3H, m), 7.89–8.15 (7H, m),
8.44 (1H, d, J 7.6), 8.57 (1H, d, J 7.8), 8.68 (1H, d, J 9.1), 8.87 (1H, s).
The minor isomer (5c) was not isolated.
Absorbance and Fluorescence Measurements
Stocks of the derivatives were prepared in chloroform at a concentra-
tion of 0.1 mg mL−1, except for (7a) (1 mg mL−1). Absorption spectra
were recorded on a Cary 1E UV-Visible spectrometer using 1 nm data
intervals, 0.5 nm slit bands, and 0.2 s integration times. Fluorescence
spectra were determined on a Perkin–Elmer LS-50B luminescence spec-
trometer containing a red sensitive R928 photomultiplier using 5 nm
excitation and emission slit widths and 0.5 nm data intervals. Emission
spectra were recorded using excitation wavelengths across the absorp-
tion band and were corrected for the wavelength-dependent artefacts of
the instrument using correction factors supplied by the manufacturer.
All spectrometric measurements were performed in chloroform at room
temperature. QuantumyieldsΦwerecalculatedfromcorrectedemission
spectra, Equation (1), using 3,3ꢀ-diethylthiadicarbocyanine iodide in
ethanol (Φr 0.33[13]), fluorescein in 1% sodium hydroxide (Φr 0.92[14]),
and quinine sulfate in 1% sulfuric acid (Φr 0.55[14]) as the references:
2-(2-Chlorophenyl)-6-[2-(2-chlorophenyl)-2-oxoethyl]-7H-
naphtho[1,2,3-de]quinolin-7-one (4d)
This was prepared as for (4a)/(5a), and the other isomer was not detected.
The crude solid, (0.33 g from 0.69 g of o-chloroacetophenone) was
recrystallized from toluene to give (4d) as a light brown solid (0.26 g,
59%), mp 121–123◦C (Found: C 72.4, H 3.4, N 3.0. C30H17Cl2NO2
requires C 72.9, H 3.5, N 2.8%). δH ([D6]DMSO) 5.07 (2H, s, CH2),
7.53–7.59 (5H, m), 7.66–7.90 (4H, m), 8.04 (1H, d, J 8.6), 8.10–8.13,
(1H, m), 8.29 (1H, dd, J 8.1, 1.2), 8.49 (1H, d, J 8.5), 8.77 (1H, d, J 8.2),
8.89 (1H, s).
ꢀ
ꢁ
Areasn2s 1 − 10−Abs
r
ꢀ
ꢁ
Φs = Φr
(1)
Arearn2r 1 − 10−Abs
s
6-(2-Oxo-2-(pyridin-2-yl)ethyl)-2-(pyridin-2-yl)-7H-
naphtho[1,2,3-de]quinolin-7-one (4e)
and 4-(2-Oxo-2-(pyridin-2-yl)ethyl)-2-(pyridin-2-yl)-7H-
naphtho[1,2,3-de]quinolin-7-one (5e)
where n is the refractive index of the solvent, Abs is the absorbance
of the sample at the excitation wavelength, Area is the integrated area
under the emission spectrum, and subscripts r and s refer to the reference
and sample, respectively.
These were prepared as for (4a)/(5a).The crude solid, (0.98 g from 1.64 g
of 2-acetylpyridine) contained the two isomers in a ratio of 3 : 2. Recrys-
tallization failed to produce a separation; chloroform/light petroleum
(bp 90–120◦C) gave a dark brown sample (0.83 g, 72%), mp 73–81◦C
(Found: C 77.3, H 4.2, N 9.5. C28H17N3O2 · 0.5H2O requires C 77.1, H
4.2, N 9.6%). δH ([D6]DMSO) 5.30 (2H, s, CH2 (5e)), 5.33 (2H, s, CH2
(4e)), 7.46–9.0 (complex pattern), 9.38 (1H, s, (5e)), 9.51 (1H, s, (4e)).
6-(2-Oxo-2-phenylethyl)-2-phenyl-7H-naphtho-
[1,2,3-de]quinolin-7-one (4a)
A mixture of acetophenone (0.70 g, 2.92 mmol), 1-aminoanthraquinone
(0.13 g, 0.58 mmol), and sodium hydroxide pellets (1.0 g) in pyridine
(10 mL) was stirred at room temperature for 3 d. The dark green mix-
ture that formed was poured onto water (100 mL) and neutralized with
concentrated hydrochloric acid (2 mL). The precipitate that formed was
collected by filtration (0.23 g) and was predominantly a mixture of (4a)
and (5a) (about 10 : 1 from integration of the 1H NMR CH2 signals at
5.16 and 5.11 ppm, respectively). Recrystallization from methyl ethyl
ketone gave (4a) as a golden brown solid (0.18 g, 72%), mp 187–189◦C
(Found: C 84.5, H 4.6, N 3.4. C30H19NO2 requires C 84.7, H 4.5, N
3.3%). δH ([D6]DMSO) 5.16 (2H, s, CH2), 7.59–7.76 (7H, m), 7.92
(1H, t, J 7.5), 7.98 (1H, d, J 8.6), 8.14 (2H, d, J 7.6), 8.20 (1H, d, J
8.3), 8.48 (1H, d, J 8.3), 8.54 (2H, d, J 7.5), 9.00 (1H, d, J 8.0), 9.18
(1H, s). ES-MS (positive mode) m/z 426 (M + 1).
6-(2-Oxo-2-phenylethyl)-7H-benzo[e]perimidin-7-one (7a)
Amixtureofacetophenone(0.52 g, 4.31 mmol), 7H-benzo[e]perimidin-
7-one (6)[8] (0.20 g, 0.86 mmol), and sodium hydroxide pellets (2.0 g)
in pyridine (20 mL) was treated as for the preparation of (4a)/(5a). The
precipitate that formed (0.25 g, 78%) contained none of the 4-isomer.
Recrystallization from acetone gave (7a) as a brown solid, mp 117–
119◦C (Found: C 78.5, H 4.1, N 7.7. C23H14N2O2 requires C 78.8, H
4.0, N 8.0%). δH (CDCl3) 5.15 (2H, s, CH2), 7.55 (2H, t, J 7.5, H-3ꢀ,5ꢀ),
7.63–7.74 (2H, m, H-4ꢀ,9), 7.83 (1H, t, J 7.7, H-10), 7.94 (1H, d, J 8.9,
H-5), 8.15 (2H, d, J 7.6, H-2ꢀ,6ꢀ), 8.29 (1H, d, J 8.1, H-8), 8.46 (1H, d,
J 8.8, H-4), 8.90 (1H, d, J 7.9, H-11), 9.53 (1H, s, H-2). δC (CDCl3) 46.0
(CH2-α), 120.4 (C-11c), 125.4 (CH-11), 125.7 (C-6a), 127.8 (CH-8),
The minor isomer, (5a), was not purified.

Tetracycle Formation from Acetophenones with 1-Aminoanthraquinone
1223
127.9 (CH-2ꢀ,6ꢀ), 128.4 (CH-3ꢀ,5ꢀ), 132.6 and 133.0 (CH-4ꢀ,4,9), 133.4
(C-11a), 133.7 (CH-10), 136.8 (C-1ꢀ), 139.8 (CH-5), 142.3 (C-6), 147.9
(C-3a), 154.6 (CH-2), 157.2 (C-11b), 182.7 (C-7), 195.4 (CH2CO).
δH (CDCl3 + CF3CO2H) 7.80–7.92 (3H, m), 8.41–8.52 (4H, m),
8.85∗ (1H, d, J 9.2), 9.09∗ (1H, d, J 9.2), 9.20 (1H, s), 9.27 (1H, d,
J 7.5), 9.65 (1H, d, J 8.1), 10.23 (1H, s).
dark orange mixture was then concentrated to approximately half its
volume and the yellow solid was filtered off to yield the product (0.07 g,
70%), m.p 241–243◦C after recrystallization from benzene/hexane
(3 : 1) (Found: C 85.6, H 4.6, N 9.6. C30H19N3 requires C 85.5, H 4.5,
N 10.0%). δH ([D6]DMSO) 2.41 (1H, d, J 12.4, CH2-Hα), 5.06 (1H,
d, J 12.4 CH2-Hβ), 7.50–7.59 (6H, m), 7.74–7.77 (2H, m), 8.12–8.19
(3H, m), 8.42–8.47 (3H, m), 8.61–8.64 (1H, m), 8.89–8.92 (1H, m),
9.09 (1H, s). δC ([D6]DMSO, 80◦C) 34.5 (CH2), 112.6 (CH), 119.8,
(C), 121.2 (C), 124.3 (CH), 125.0 (CH), 127.4 (CH), 128.2 (CH), 128.5
(CH), 128.6 (CH), 129.30 (CH), 129.35 (CH), 129.39 (CH), 129.9 (CH),
132.3 (C), 134.0 (C), 134.4 (CH), 134.5 (C), 136.2 (C), 138.7 (C), 145.9
(C), 146.2 (C), 146.9 (C), 156.7 (C).
δH (CDCl3 + DBU) 7.24–7.28 (3H, m), 7.43∗ (1H, d, J 9.7), 7.55–
7.58 (2H, m), 8.05–8.08 (2H, m), 8.55–8.58 (1H, m), 8.85–8.88 (1H,
m), 8.96 (1H, s), 9.30 (1H, s), 9.79∗ (1H, d, J 9.7). δC (CDCl3 + DBU)
108.2 (C), 122.8 (C), 123.9 (CH), 126.3 (CH), 127.4 (2 × CH), 127.7
(2 × CH), 129.2 (CH), 129.28 (CH), 129.34 (CH), 130.8 (CH), 132.5
(C), 135.7 (C), 137.7 (CH), 144.8 (C), 146.9 (C), 147.6 (C), 149.2 (C),
150.0 (CH), 162.6 (CH), 177.2 (C), 187.9 (C).
3-Phenyl-4H-benzo[e][1,2]diazepino[3,4,5-gh]perimidine (11)
6-(2-Oxo-2-p-tolylethyl)-7H-benzo[e]perimidin-7-one (7b)
A mixture of (7a) (0.10 g, 0.43 mmol) and hydrazine monohydrate
(0.022 g, 0.43 mmol) in 2-propanol (5 mL) and acetic acid (0.5 mL) was
stirred and heated at reflux for 2 h. The dark brown solution was then
concentrated to approximately half its volume and the brown solid that
separated was filtered off to yield the product (0.07 g, 47%), m.p 229–
230◦C (from acetonitrile/chloroform (20 : 1)) (Found: C 79.6, H 3.9, N
16.4. C23H14N4 requires C 79.7, H 4.1, N 16.2%). δH ([D6]DMSO)
2.32 (1H, d, J 12.7, CH2-Hα), 5.12 (1H, d, J 12.7, CH2-Hβ), 7.45–7.48
(3H, m), 7.71 (1H, t, J 7.3), 7.80 (1H, t, J 7.3), 8.15–8.17 (2H, m),
8.29–8.35 (2H, m), 8.59 (1H, d, J 7.7), 8.74 (1H, d, J 7.7), 9.45 (1H, s).
δC ([D6]DMSO]) 35.0 (CH2), 117.4 (C), 121.9 (C), 125.1 (CH), 125.4
(CH), 129.3 (2 × CH) 129.5 (2 × CH) 130.4 (CH), 130.6 (C), 131.0
(CH), 132.7 (CH), 133.6 (CH), 134.1 (C), 134.6 (C), 134.9 (CH), 136.3
(C), 146.1 (C), 146.4 (C), 149.1 (C), 155.9 (C), 156.0 (CH).
A
mixture of p-methylacetophenone (0.28 g, 2.16 mmol), 7H-
benzo[e]perimidin-7-one (6)[7] (0.10 g, 0.45 mmol), and sodium
hydroxide pellets (1.0 g) in pyridine (10 mL) was treated as for the
preparation of (4a)/(5a) to yield a single isomer, as a black solid (0.08 g,
50%), mp 185–187◦C (from ethanol). δH (CDCl3) 2.46 (3H, s, CH3),
5.14 (2H, s, CH2), 7.34 (2H, d, J 8.0), 7.73 (1H, t, J 7.6), 7.83 (1H, t,
J 7.5), 7.95 (1H, d, J 7.8), 8.04 (2H, d, J 8.0), 8.30 (1H, d, J 7.8), 8.49
(1H, br d, J 8.7), 8.92 (1H, d, J 7.8), 9.54 (1H, br s). δC ([D6]DMSO)
21.4 (CH3), 46.2 (CH2), 120.4 (C), 125.2 (CH), 125.7 (C), 127.7 (CH),
128.1(2 × CH), 129.1(2 × CH), 132.4(C), 133.6(CH), 133.8(C), 134.4
(CH), 139.6 (CH), 141.6 (C), 143.8 (CH), 148.0 (C), 154.8 (C), 156.6
(C), 182.7 (C), 195.1 (C). ES-MS (positive mode) m/z 365.4 (M + 1).
6-Methyl-2-phenylnaphtho[1,2,3-de]quinolin-7-one (8)
2,7-Diphenyl-1,6-diazabenzo[e]pyrene (12)
Hydrazine monohydrate (0.28 g, 5.65 mmol) was added to a stirred solu-
tion of (4a) (0.40 g, 0.94 mmol) in pyridine (20 mL). The mixture was
refluxed for 3 h, cooled, and the dark brown solution obtained was
poured onto water (approx. 200 mL) and neutralized with concentrated
hydrochloric acid. The dark green solid which separated was filtered
off, washed with water, and recrystallized from ethanol, to yield the
dark green product (0.19 g, 63%). mp 164–166◦C. HRMS (EI), Found:
321.1144. C23H15NO requires 321.1154 (M+). δH (CDCl3) 3.04 (3H,
s, CH3), 7.53–7.61 (4H, m), 7.68 (1H, t, J 7.6, H-9), 7.75–7.81 (2H,
m), 8.26 (2H, d, J 7.0), 8.42 (1H, d, J 8.0, H-11), 8.49 (1H, d, J 7.9,
H-8), 8.63 (1H, s, H-1). δC (CDCl3) 24.5 (CH3), 114.6 (CH), 123.0
(C), 123.5 (CH), 124.6 (C), 128.1 (CH), 128.3 (CH), 129.1 (CH), 130.6
(CH), 131.0 (CH), 132.4 (C), 133.1 (C), 133.2 (CH), 133.6 (C), 136.3
(CH), 136.8 (C), 144.3 (C), 146.2 (C), 156.0 (C), 183.6 (C).
A mixture of (4a) (0.15 g, 0.35 mmol) and ammonium acetate (0.18 g,
2.30 mmol) in acetic acid (10 mL) was stirred and heated at reflux for
15 min. A dark red-brown solution formed and a brown precipitate soon
separated out. This was filtered from the cooled mixture, washed with
water, dried, and recrystallized from toluene to give (12) as a yellow solid
(0.09 g, 64%). mp 289–290◦C (Found: C 88.5, H 4.3, N 7.0. C30H18N2
requires C 88.7, H 4.5, N 6.8%). δH (CDCl3/CF3CO2H) 7.71–7.79 (6H,
m), 8.10–8.15 (4H, m), 8.27–8.36 (2H, m), 8.83 (1H, s), 8.85 (1H, d,
J 7.0), 9.13 (1H, d, J 8.4), 9.20 (1H, d, J 9.7), 9.38 (1H, s), 9.68 (1H,
d, J 7.8). δC (CDCl3/CF3CO2H) 116.4 (C), 118.2 (CH), 123.5 (CH),
124.4 (C), 125.6 (CH), 127.0 (CH), 128.4 (2 × CH), 128.7 (2 × CH),
129.0 (C), 129.3 (CH), 129.76 (2 × CH), 129.83 (C), 129.9 (C), 130.2
(2 × CH), 133.3 (CH), 133.9 (CH), 134.85 (CH), 134.94 (CH), 135.3
(CH), 140.2 (C), 140.5 (C), 142.0 (C), 142.4 (C), 152.0 (C), 153.7 (C).
6-Methyl-7H-benzo[e]perimidin-7-one (9)
7-Phenyl-1,3,8-triazabenzo[e]pyrene (13)
Compound (7a) was reacted with hydrazine monohydrate in pyridine
as for (8) and the crude product was a black solid (0.27 g from 0.25 g
(7a)). This was dissolved in chloroform and eluted through a short col-
umn of neutral alumina with chloroform. The first green coloured band
gave (9) (0.11 g, 63%), mp 78–80◦C after recrystallization from ethanol.
HRMS (EI), Found: 246.0785. C16H10N2O requires 246.0794 (M+).
δH (CDCl3) 3.02 (3H, s, CH3), 7.72–7.83 (2H, m, H-9,10), 7.88 (1H, d,
J 8.6, H-5), 8.22 (1H, d, J 8.7, H-4), 8.38 (1H, d, J 7.8, H-8), 8.87 (1H, d,
J 7.5, H-11), 9.48 (1H, s, H-2). δC (CDCl3) 23.7 (CH3), 119.8 (C-11c),
124.3 (C-6a), 124.7 (CH-11), 127.2 (CH-8), 131.9 (CH-9), 133.1 (CH-
10), 133.4 (C-11a), 133.6 (CH-4), 138.5 (CH-5), 145.8 (C-6), 148.0
(C-3a), 154.7 (CH-2), 155.0 (C-11b), 182.6 (C-7).
A mixture of (7a) (0.10 g, 0.29 mmol) and ammonium acetate (0.14 g,
1.86 mmol) in acetic acid (5 mL) was stirred and heated at reflux for
15 min to give a dark red-brown solution. This was cooled to room tem-
perature and poured onto water (approx. 20 mL). The brown precipitate
that formed was isolated by filtration, washed with water, dried, and
recrystallized from ethanol/light petroleum (bp 90–120◦C) (5 : 1), to
yield the product as a brown solid (0.07 g, 78%). mp 91–93◦C (Found:
C 80.1, H 4.0, N 12.4. C23H13N3 · 0.75H2O requires C 80.1, H 4.2, N
12.2%). δH (CDCl3) 7.60–7.69 (3H, m), 8.13 (1H, t, J 7.2), 8.29 (1H,
t, J 7.2), 8.48 (2H, d, J 7.0), 8.76 (1H, s), 8.84 (1H, d, J 9.5), 9.08
(1H, d, J 9.2), 9.55 (1H, d, J 8.5), 9.74 (1H, d, J 7.8), 9.87 (1H, s).
δC (CDCl3) 114.2 (C), 114.6 (C), 116.3 (CH), 125.1 (2 × CH), 127.4
(2 × CH), 128.9 (2 × CH), 129.5 (CH), 129.8 (CH), 130.3 (CH), 131.7
(CH), 134.9 (C), 135.1 (CH), 138.8 (C), 146.0 (C), 151.1 (C), 153.1 (C),
154.9 (C), 155.2 (CH).
The second, black band gave a black semi-solid (0.09 g). This was
repeatedly extracted with boiling light petroleum (bp 90–120◦C) until
the extract was colourless, and evaporation of solvent from the combined
extracts gave (13) (0.07 g; data below).
3,8-Diphenyl-4H-[1,2]diazepino[3,4-4ꢀ,3ꢀ :4,5-f]naphtho-
[1,2,3-de]quinoline (10)
6-(2-Acetoxy-2-phenylethenyl)-7-oxo-7H- benzo[e]perimidine (14)
To a stirring solution of (7a) (0.10 g, 0.29 mmol) in pyridine (5 mL) was
added acetic anhydride (4 mL) in one portion. The dark green solution
was stirred at room temperature for 3 h then poured onto water (approx.
50 mL) and the green precipitate that formed was filtered off, washed
A mixture of (4a) (0.10 g, 0.24 mmol) and hydrazine monohydrate
(0.012 g, 0.24 mmol) in 2-propanol (5 mL) and acetic acid (2 mL) was
stirred and heated at reflux for 4 h. Solid was present throughout. The
∗ H-4 and H-5 from coupling in COSY spectrum.

1224
L. W. Deady and C. L. Smith
with water, and dried to yield (14) (0.08 g, 73%). This was dissolved in
chloroform, and addition of hexane gave a sample, mp 68–71◦C, which
contained only trace impurities (from 1H NMR analysis). (HR-MS
(LSI) Found: 393.1240. C25H17N2O3 requires 393.1240 [M + H]+). δH
(CDCl3) 2.16 (3H, s, CH3), 7.39–7.47 (4H, m), 7.66–7.85 (4H, m), 8.05
(1H, s), 8.26 (2H, s) (showed as a close AB quartet in some samples),
8.41 (1H, d, J 7.0), 8.90 (1H, d, J 7.0), 9.50 (1H, s). δC (CDCl3) 20.5
(CH3), 116.6 (CH), 120.3 (C), 124.0 (C), 124.9 (CH), 125.1 (2 × CH),
127.5 (CH), 127.9 (C), 128.5 (2 × CH), 129.1 (CH), 132.1 (CH), 133.46
(CH), 133.54 (CH), 133.65 (CH), 134.6 (C), 135.9 (CH), 139.3 (C),
148.7 (C), 148.9 (C), 155.3 (C), 155.9 (C), 167.9 (C), 182.5 (C).
[2] X. Bu, L. W. Deady, G. J. Finlay, B. C. Baguley, W. A. Denny,
J. Med. Chem. 2001, 44, 2004.
[3] E. A. Fehnel, J. Org. Chem. 1966, 31, 2899.
[4] E. P. Fokin, I. V. Fomicheva, J. Org. Chem. (U. S. S. R.) 1970,
6, 1288.
[5] M. V. Kazankov, O. A. Zotova, Russ. J. Org. Chem. 1994, 30,
992.
[6] (a) W. Bradley, J. Chem. Soc. 1937, 1091. (b) W. Bradley
J. Chem. Soc. 1948, 1175.
[7] C. F. H. Allen, S. C. Overbaugh, J. Am. Chem. Soc. 1935, 57,
740.
[8] L. B. Krasnova, S. I. Popov, N. S. Dokunikin, J. Org. Chem.
(U. S. S. R.) 1973, 9, 1523.
Acknowledgments
[9] W. A. Mosher, J. E. Innes, J. Heterocycl. Chem. 1970, 7, 1083.
[10] M. S. Shvartsberg, I. D. Ivanchikova, S. F. Vasilevsky,
Tetrahedron Lett. 1994, 35, 2077.
[11] A. N. Grinev, A. A. Druzhinina, I. K. Sorokina, Chem.
Heterocycl. Cpds 1976, 12, 1048.
[12] R. D. Bach, R. A. Woodward, T. J. Anderson, M. D. Glick,
J. Org. Chem. 1982, 47, 3707.
[13] N. J. L. Roth, A. C. Craig, J. Phys. Chem. 1974, 78, 1154.
[14] Practical Fluorescence 2nd ed. (Ed. G. G. Guilbault) 1990,
p. 15 (Marcel Dekker: New York, NY).
We thank Dr N. Klonis for his expert assistance in obtaining
the fluorescence data, and Dr G. Neumann and MrT. Polyzos
for recording ES-MS. C.L.S. is grateful for the award of an
APRA.
References
[1] U. T. Nabar, V. R. Kanetkar, S. V. Sunthankar, Indian J. Chem.
1983, 22B, 812.