Synthesis of triazafluoranthenones via silver(I)-mediated nonoxidative and oxidative intramolecular palladium-catalyzed cyclizations

Article abstract of DOI:10.1021/jo200966k

Silver(I) fluoride (AgF)-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 1,3-diphenyl- and 8-iodo-1,3- diphenylbenzo[e][1,2,4]triazin-7(1H)-ones 6a (R = H) and 7a (R = I) afford a new 'alkaloid like' ring system 2-ph

Full text of DOI:10.1021/jo200966k

ARTICLE
pubs.acs.org/joc
Synthesis of Triazafluoranthenones via Silver(I)-Mediated
Nonoxidative and Oxidative Intramolecular Palladium-Catalyzed
Cyclizations
Panayiotis A. Koutentis,* Georgia Loizou, and Daniele Lo Re
Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
S Supporting Information
b
ABSTRACT: Silver(I) fluoride (AgF)-mediated intramolecular
nonoxidative and oxidative palladium-catalyzed cyclizations of
1,3-diphenyl- and 8-iodo-1,3-diphenylbenzo[e][1,2,4]triazin-
7(1H)-ones 6a (R = H) and 7a (R = I) afford a new ‘alkaloid
like’ ring system 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-
6-one 8a (triazafluoranthenone) in 86 and 100% yields, respec-
tively. Furthermore, these cyclization protocols were used to
prepare triazafluoranthenone analogues 8bÀe bearing dialkyla-
mino, methoxy, and phenylsulfanyl substituents at C-5, which
were also independently synthesized from triazafluoranthenone
8a by regioselective nucleophilic addition. Similar AgF-
mediated intramolecular nonoxidative and oxidative palla-
dium-catalyzed cyclizations of 8,10-dihydro-1-iodo-10-phenyl-
phenazin-2(7H)-ones 13 gave the new ‘alkaloid like’ ring system 8H-indolo[1,2,3-mn]phenazin-8-one 14 in 80 and 18% yields,
respectively.
1. INTRODUCTION
Fluoranthene (1) (1,2-benzacenaphthene)1 is an all-carbon
polyarene, found naturally in coal tar2 and as a byproduct of
hydrocarbon combustion processes.3 Several aza analogues of
fluoranthene are natural product alkaloids with cytotoxic activ-
ities such as the monoaza analogue rufescine (2)4 and the diaza
analogues canthin-6-one (3)5 and eupolauridine (4)6 (Figure 1).
We recently reported some chemistry of a potentially useful
heterocyclic scaffold 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-
one (6a, R = H)7 that can be prepared in good yield from 1,4-
dihydro-1,3-diphenylbenzo[1,2,4]triazin-4-yl (5) (Blatter’s
radical).8 We now report the silver-mediated palladium-catalyzed
nonoxidative and oxidative intramolecular cyclization of the
benzotriazinones 6 and 7 to give the first examples of triaza-
fluoranthenes 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-
ones 8aÀe (Scheme 1).
Figure 1. Structure of fluoranthene and selected aza analogues.
Scheme 1
These new triazafluoranthenes support an important quino-
nimine moiety which promises to lead to useful redox-sensitive
biological activity. Several polycyclic quinonimines have inter-
esting anticancer9 and antibiotic activity.10 For example, actino-
mycin D (9), isolated from Streptomyces parvulus,9c is a strong
antitumor agent but has limited use due to side effects such as
myelosuppression and cardiotoxicity; the synthetic 7-(benzyl-
amino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one
(10, BA-TPQ) is active against a variety of human cancer cell
lines.11 In addition, several polycyclic quinonimines such as
endophenazine B (11) [λmax(MeOH) 516 nm (log ε 3.89)],
isolated from Streptomyces anulatus12 and 10-phenylphenazin-
2(10H)-one (12, aposafranone),13 are highly colored. The latter
Received: May 12, 2011
Published: June 03, 2011
r
2011 American Chemical Society
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the use of 8-bromo or 8-chlorobenzotriazinones gave mainly
unreacted starting materials.
In a effort to reduce the need for stoichiometric palladium, the
amine base was replaced by silver(I) fluoride (AgF) that has been
shown to be beneficial in nonoxidative16 and Hiyama coupl-
ings.17 AgF not only acts as a mild fluoride base but has been
implicated in the reoxidation of the Pd(0) to fulfill the catalytic
cycle.17a,18 Because AgF has excellent solubility in acetonitrile the
reactions were re-examined in this solvent, and Pd(Ph3P)2Cl2
was shown to be the most promising palladium source. Further-
more, the use of additional Ph3P (10 mol %) ligand was needed
to help the reactions proceed to completion. As such, when
8-iodobenzotriazinone 7a was reacted with Pd(Ph3P)2Cl2
(10 mol %), AgF (1.5À2.5 equiv), and Ph3P (0.1 equiv) in
MeCN at ca. 100 °C under an aerial oxygen (entries 6, 7, and 9),
the desired triazafluoranthenone 8a was obtained in good yields
(75À91%), although the reactions did require ca. 1 d to come to
completion. The use of less (1.5 equiv) or more (2.5 equiv) AgF
was disadvantageous and led to some protodeiodination to give
benzotriazinone 6a in low yields. Attempts to lower the amount
of palladium to 5 mol % in MeCN were unsuccesful (entry 10);
however, after examining various modifications that included
switching to alternative silver(I) salts (AgOAc and Ag2CO3),
adding inorganic and organic bases to AgF, and introducing
various alternative phosphine ligands, it was shown that switch-
ing the solvent back to DMF was beneficial (entries 11À15). In
fact, in DMF the reaction required no additional phosphine
ligand (entries 12, 14, and 15) and both the palladium catalyst
and AgF loadings could be reduced to 5 mol % and 1.5 equiv,
respectively, to afford the target triazafluoranthenone 8a quanti-
tatively in only 30 min (entry 15). While these optimized
cyclization conditions still failed to work for the 8-bromo- and
8-chlorobenzotriazinones, they did work in most cases well
for several 6-substituted benzotriazinones (entries 16À19):
6-diethylamino-, pyrrolidino-, methoxy-, and phenylthio-substi-
tuted 8-iodobenzotriazinones 7bÀe were readily prepared in two
steps from benzotriazinone 6a via regioselective nucleophilic
addition at C-6 to give the 6-substituted benzotriazinones 6bÀe
followed by iodination using NIS at C-8 with established
protocols.7 C-6 dialkylamino- and methoxy-substituted 8-iodo-
benzotriazinones 7bÀd cyclized faster than the parent system to
give the corresponding substituted triazafluoranthenones 8bÀd
in high yields (83À93%) (entries 16À18); however, the cycliza-
tion of 8-iodo-6-phenylthiobenzotriazione 7e could not be
driven to completion and gave only a moderate yield of cyclized
product 8e (53%) together with recovered starting material 7e
(20%) (entry 19).
Figure 2. Selected natural and synthetic quinonimines.
have been investigated as dyes and incorporated in organic
photovoltaic devices14 (Figure 2).
2. RESULTS AND DISCUSSION
2.1. Nonoxidative Coupling of Benzotriazinones. The
palladium-catalyzed nonoxidative intramolecular cyclization of
benzotriazinones 6, a type of MizorokiÀHeck reaction,15 re-
quired access to the 8-halobenzotriazinones 7 which could be
readily prepared by regioselective halogenation using the corre-
sponding N-halosuccinimide.7 Initially the noncatalytic use of
Pd(OAc)2 (1À2 equiv) was investigated and some useful obser-
vations were quickly made. In the absence of base, ligands, or
cocatalysts, 8-iodobenzotriazinone 7a (R = H) treated with
Pd(OAc)2 (2 equiv) in wet or dry DMF or DMA at 100 °C
for 3À3.5 h under both air and argon atmospheres afforded the
dark brown-colored triazafluoranthenone 8a (R = H) in 65À70%
yields. The use of less Pd(OAc)2 (1À1.5 equiv) or DMSO, or
AcOH as solvent, led to complex reaction mixtures and un-
reacted iodobenzotriazinone 7a. Because the cyclization involved
the loss of HI, the addition of base to the reaction mixture was
examined: Performing the cylization in DMF in the presence of
inorganic bases (MCO3, MHCO3, MOH, and MF where M =
Cs, K, or Na) or trialkylamines Et3N and H€unig’s base led to low
yielding reactions that featured considerable build up of polar
baseline material (by TLC), while the use of either pyridine,
DMAP, or DBU (entries 1À4, Table 1) gave triazafluoranthe-
none 8a in high yields, although the use of DBU together with
prolonged reaction times led to reduced yields. Interestingly,
a pure sample of triazafluoranthenone 8a in either DMF or DMA
at ca. 100 °C under an argon atmosphere was stable over 16 h
but decomposed rapidly in the presence of K2CO3, NaHCO3,
DMAP, Et3N, H€unig’s base, or DBU; however, under these
conditions, triazafluoranthenone 8a was stable to pyridine and
could be recovered unchanged.
2.2. Regioselective Nucleophilic Addition of Triazafluor-
anthenone. The 6-substituted triazafluoranthenones 8bÀe
were also prepared directly from triazafluoranthenone 8a by
regioselective nucleophilic addition. The selectivity observed was
similar to that observed for both benzotriazinone 7a7 and
aposafranone 12;10a however, nucleophilic addition to triaza-
fluoranthenone required more forceful reaction conditions com-
pared to those needed to functionalize benzotriazinone 7a
(Table 2).
With these initial reaction conditions [DMF, 100 °C, pyridine
or DBU as base (1 equiv)] both Pd(Ph3P)4 and Pd(OAc)2
worked well while Pd(Ph3P)2Cl2, (dba)3Pd2, (MeCN)2PdCl2,
and (dppf)PdCl2 DCM did not. The stronger base DBU (pKb ∼
Unlike that for benzotriazinone 7a, nucleophilic addition of
secondary dialkylamines diethylamine and pyrrolidine to triaza-
fluoranthenone 8a could not be achieved using stoichiometric
amounts of amines but required the use of excess amines to give
the 5-diethylamino- and 5-pyrrolidinotriazafluoranthenones 8b
and 8c in 60 and 100% yields, respectively (entries 1 and 2,
3
2) (entries 2 and 4) did give faster reactions compared to the
pyridine base (pKb ∼ 8.9) (entries 1 and 3), and in combination
with Pd(Ph3P)4 (entry 4) the reaction was too fast to work up,
leading to reduced product yields. Attempts to reduce the
quantity of palladium catalyst led to incomplete reactions while
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Table 1. Conversion of 8-Iodobenzotriazinones 7aÀe (0.1 mmol) into Triazafluoranthenones 8aÀe, with Pd Catalyst and
Additives in Solvent (1 mL), under an Air Atmosphere Protected by a CaCl2 Tube, at ca. 100 °C
entry
R
Pd catalyst (mol %)
solvent
base (equiv)
Ph3P (equiv)
time (h)
yields (%)
1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Pd(OAc)2 (100)
Pd(OAc)2 (100)
Pd(Ph3P)4 (100)
Pd(Ph3P)4 (100)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (10)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (5)
Pd(Ph3P)2Cl2 (5)
DMF
DMF
DMF
DMF
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
pyridine (1)
DBU (1)
pyridine (1)
DBU (1)
AgF (1)
À
3
8a (91)
8a (93)
8a (95)
8a (73)
ira
8a (75)b
8a (91)
ira
2
À
0.50
1
3
À
À
0.1
0.1
0.1
À
4
0.13
24
5
6
AgF (1.5)
AgF (2)
24
7
19
8
AgF (2)
24
9
AgF (2.5)
AgF (2)
0.1
0.1
0.1
À
26
8a (82)c
ira
10
11
12
13
14
15
16
17
18
19
24
AgF (2)
2
8a (95)
8a (93)
8a (99)
8a (99)
8a (99)
8b (93)
8c (83)
8d (89)
8e (53)d
AgF (2)
2
AgF (2)
0.1
À
1.50
2
AgF (2)
AgF (1.5)
AgF (1.5)
AgF (1.5)
AgF (1.5)
AgF (1.5)
À
0.50
0.33
0.25
0.33
24
NEt2
À
pyrolidinyl
OMe
À
À
SPh
À
a ir = incomplete reaction. b 1,3-Diphenylbenzotriazinone 6a (6%) recovered. c 1,3-Diphenylbenzotriazinone 6a (3%) recovered. d 8-Iodo-
6-(phenylthio)benzotriazinone 7e (20%) recovered.
Table 2. Regioselective Nucleophilic Addition to Triazafluoranthenone 8a
entry
R
reagent (equiv)
base (equiv)
solvent
EtOH
temp (°C)
time (h)
yields (%)
1
2
3
4
5
6
NEt2
Et2NH (48)
À
20
20
20
60
20
20
22
4
8b (60)
pyrrolidinyl
OMe
pyrrolidine (60)
2N MeONa (1)
2N MeONa (10)
KOH (2)
À
EtOH
8c (100)
a
À
MeOH
5
_
a
OMe
À
MeOH
2
_
a
OH
À
THF/H2O 10:1
0.5
2.5
_
SPh
PhSH (2)
i-Pr2NEt (1.1)
DCM
8e (100)
a No trace of desired product: only intractable polar materials at baseline on TLC.
Table 2). The reaction of triazafluoranthenone 8a with alkoxide
[2 N MeONa (1 or 10 equiv) at 20 to 60 °C] or with hydroxide
[KOH (2 equiv) at 20 °C] gave only intractable polar materials
(baseline on TLC) (entries 3À5). This reactivity differed con-
siderably from the analogous nucleophilic addition of methoxide
or hydroxide to benzotriazinone 7a which worked well.7 While
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Table 3. Oxidative Cyclization of Benzotriazinones 6aÀe (0.1 mmol) into Triazafluoranthenones 8aÀe Using Pd(OAc)2,
Cu(OTf)2, and AgF in DMSO at ca. 100 °C under O2 Atmosphere
entry
R
Pd(OAc)2 (equiv)
Cu(OTf)2 (equiv)
AgF (equiv)
time (h)
yields of 8 (%)
yields of 6 (%)
1
H
H
H
H
H
H
H
H
H
H
H
1.0
À
À
À
2
À
À
À
À
1
4
12a
12.5
7
8a (78)
6a (0)
b
b
2
1.0
3
0.5
8a (40)
8a (45)
6a (31)
6a (54)
4
0.1
5
0.1
2
8
8a (56)
c
6a (42)
c
6
0.1
À
2
2
18
7
7
0.1
2
8a (79)
8a (86)
8a (86)
8a (70)
8a (55)
8b (67)
8c (76)
8d (19)
8e (15)
6a (19)
6a (6)
8
0.1d
0.15d
0.1d
0.1d
0.1d
0.1d
0.1d
0.1d
2
2
7
9
2
2
7
6a (7)
10
11
12
13
14
15
3
2
7
6a (15)
6a (26)
6b (0)
6c (0)
2
3
7
NEt2
2
2
2
pyrrolidinyl
OMe
2
2
2.5
18
14.5
2
2
6d (28)
6e (44)
SPh
2
2
a In air atmosphere. b Decomposition: baseline on TLC. Traces of triazafluoranthenone 8a, mainly starting material recovered. d Pd(OAc)2 freshly
c
recrystallized from AcOH.
the direct regioselective nucleophilic addition of oxygen nucleo-
philes to triazafluoranthenone 8a was not successful, we note that
these compounds were readily accessible via the above alter-
native nonoxidative intramolecular cyclization route (entry 18,
Table 1). Nevertheless, direct addition favored the introduction
of sulfur substituents, because treating the triazafluoranthenone
8a with thiophenol (2 equiv) in the presence of H€unig’s base (1.1
equiv) gave the 5-(phenylthio)triazafluoranthenone 8e in quan-
titative yield (entry 6, Table 2) which could not be prepared
readily via the nonoxidative intramolecular cyclization route
(entry 19, Table 1). These two stratergies were therefore comple-
mentary.
We speculate that the observed differences in the ease of
nucleophilic addition to the two quinonimines, benzotriazinone
6a and triazafluoranthenone 8a, are owed to the ring fusion in the
latter. π-Orbital delocalization of the fused ring’s electron density
could make the quinonimine moiety less electrophilic toward
nucleophiles. Furthermore, the planarity of the arene on triazine
N-1 can assist the withdrawal of electron density from that
nitrogen and thus reduce the zwitterionic resonance contribu-
tion, making the carbonyl more prone to attack by hard nucleo-
philes such as alkoxides.
reduce the palladium loading have included the use of co-oxidants
such as O2,19f Cu(OAc)2,20 and tert-butyl hydroperoxide.21
Oxidative cyclization of benzotriazinones 6 could provide a
shorter route to the triazafluoranthenones 8 and bypass the
above C-8 iodination step. Treatment of the benzotriazinone 6a
with Pd(OAc)2 (1.5 equiv) in AcOH at ca. 100 °C led only to
intractable polar products (baseline on TLC). Interestingly,
these conditions can lead to degradation of related oxygenated
carbazoles22 and treatment of triazafluoranthenone 8a under
similar reaction conditions for 1 d also led to consumption and
degradation of the tetracycle. In the absence of Pd(OAc)2,
however, the triazafluoranthenone 8a was stable in AcOH at
ca. 100 °C. In light of this, the stability of triazafluoranthenone 8a
in the presence of catalytic Pd(OAc)2 (10 mol %) in various
solvents (AcOH, DMF, DMSO, and PhMe) at ca. 100 °C under
aerial oxygen was screened, and DMSO was found to afford the
least decomposition (by TLC). Interestingly, DMSO has been
reported to prevent the precipitation of the Pd(0) before further
reoxidation23 and to act as ligand to support the direct oxidation
of Pd(0) to Pd(II).24 Further optimizations were conducted in
DMSO (Table 3).
Increasing the Pd(OAc)2 to 1 equiv under an O2 atmosphere
led to complete consumption of the starting material in 4 h and
gave triazafluoranthenone 8a in 78% yield (entry 1, Table 3);
however, in an aerial oxygen the reaction was slow, and after 12 h
only an intractable mixture was obtained (baseline on TLC)
(entry 2). The use of less palladium catalyst (0.5 equiv) in the
presence of oxygen failed to consume the benzotriazinone 6a
(entry 3). Similar efforts to catalyze the reaction by using
2.3. Oxidative Coupling of Benzotriazinones. Intramolecu-
lar oxidative cyclizations that involve the formation of a new
CÀC bond have been used for the synthesis of fused heterocycles
such as dibenzofurans and carbazoles.19 Traditionally, the reac-
tion conditions invoked the use of stoichiometric Pd(OAc)2
(1À1.5 equiv), in AcOH, at ca. 100 °C; however, recent efforts to
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Cu(II)(OAc)2 H2O (2.5 equiv), 1,4-benzoquinone, or tert-butyl
hydroperoxide as co-oxidants or by switching the solvent
(dioxane, AcOH, DMF, and DMA) or the palladium sources
Scheme 2
3
[(dppf)PdCl2 DCM, (dba)3Pd2, PdCl2, (MeCN)2PdCl2, PdO,
3
(PhP3)4Pd, or Pd/C 5 wt %] failed to provide better results.
Nevertheless, some success was observed with the use of
Cu(II)(OAc)2 H2O in DMSO in the presence of O2, as such
3
a range of copper salts were examined. Treating benzotriazinone
6a with Pd(OAc)2 (10 mol %) in DMSO at ca. 100 °C with either
CuSO4 or CuCl2 2H2O (2 equiv) in a O2 athmosphere gave
3
after 1 d only a trace of triazafluoranthenone 8a; however, the use
of Cu(OTf)2 (2 equiv) gave the desired product 8a in a 45% yield
with 54% of recovered starting material (entry 4, Table 3). In
light of our successful use of AgF in the nonoxidative coupling
and also because silver(I) salts have been shown to be beneficial
in oxidative couplings,25 we subsequently introduced some AgF
(1 equiv) to the reaction mixture and saw an immediate
improvement, obtaining the triazafluoranthenone 8a in a 56%
yield with 42% of recovered starting material (entry 5). Increas-
ing the amount of AgF (up to 2 equiv) led to improved yields of
triazafluoranthenone 8a (up to 79%, entry 7), although some
benzotriazinone 6a (19%) remained unreacted even after 7 h.
More importantly, in the absence of Cu(OTf)2, the use of AgF
(2 equiv) and palladium catalyst gave only traces of the desired
product after 18 h (entry 6), supporting the need for both Cu and
Ag reagents. Using freshly recrystallized Pd(OAc)2 improved the
consumption of benzotriazinone 6a and raised the yields of
triazafluoranthenone 8a to 86%, leaving only some benzotriazi-
none 6a (6%) unreacted (entry 8). Marginal increases of the
amount of palladium catalyst (entry 9), Cu (entry 10), and Ag
(entry 11) used did not improve these yields and in some cases
were detrimental. With these improved conditions, catalyst
(0.1 equiv), Cu(OTf)2 (2 equiv), AgF (2 equiv), O2 atmosphere,
and 100 °C, a re-examination of the solvents (PhMe, AcOH,
DMF, and DMA) merely confirmed that DMSO was needed
because PhMe and AcOH gave no reaction while DMF and
DMA only gave a trace of triazafluoranthenone 8a.
Again, the optimized conditions [freshly recrystallized Pd(OAc)2
(10 mol %), AgF (2 equiv), and Cu(OTf)2 (2 equiv)] were
screened for 6-substituted benzotriazinone 6bÀe. 6-Diethylami-
no- and 6-pyrrolidinobenzotriazinone 6b and 6c gave the corre-
sponding 5-substituted triazafluoranthenone 8b and 8c in a
67 and 76% yield, respectively, in a shorter reaction time if
compared with the parent system (entries 12 and 13, Table 3).
Unfortunately, the oxidative intramolecular cyclizations of
6-methoxy- and 6-(phenylthio)benzotriazinone 6d and 6e could
not be driven to completion and gave the desired 5-methoxy-
and 5-(phenylthio)triazafluoranthenones 8d and 8e in low yields
(19 and 15%, respectively) (entries 14 and 15).
indolophenazinone 14 in a 80% yield (Scheme 2). The oxidative
cyclization of aposafranone 12 could not, however, be performed
using catalytic palladium, and at best the use of Pd(OAc)2 (1
equiv) in DMSO at ca. 100 °C under an oxygen atmosphere gave
after 1 d the desired cyclized product 14 in only 18% yield.
The indolophenazinone 14 was pink-red in color. Differential
scanning calorimetry (DSC) under an argon atmosphere re-
vealed that an exothermic reaction occurred in the solid state
with onset and peak temperatures of 227 and 229 °C, respec-
tively. As such, no melting point could be recorded. Low
resolution (EI) mass spectrometry (m/z 270 Da, 100%) and
elemental analysis (C, 80.05; H, 3.8; N, 10.3%) supported a
molecular formula of C18H10N2O. The UV/vis spectra showed a
low energy absorption at λmax/nm 495 (log ε 2.91) supporting
extended conjugation. The compound showed a mild pink
fluorescence to the naked eye when in solution.
3. CONCLUSIONS
8-Iodobenzotriazinones 7aÀe undergo palladium-catalyzed
nonoxidative intramolecular coupling in the presence of AgF
to give the 6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-ones 8aÀe
(triazafluorantheones) in moderate to excellent yields while
palladium-catalyzed oxidative intramolecular cyclization of ben-
zotriazinones 6aÀe required a combination of co-oxidants such
as AgF and Cu(OTf)2 in an oxygen atomosphere. Both methods
were used to prepare 8H-indolo[1,2,3-mn]phenazin-8-one (14).
Additionally, triazafluoranthenone 8a was shown to suffer re-
gioselective nucleophilic addition at C-5 by amines and thiols but
gave intractable polar mixtures with oxygen nucleophiles.
4. EXPERIMENTAL SECTION
4.1. General Methods and Materials. Solvents: DCM was
freshly distilled from CaH2 under argon. DMF was azeotropically
distilled with PhH and then distilled under vacum from anhydrous
MgSO4 and stored over 4 Å molecular sieves. Acetonitrile was distilled
over CaH2. Reactions were protected by CaCl2 drying tubes. Decom-
position points (decomp) and mp >250 °C were determined using a TA
Instruments DSC Q1000 with samples hermetically sealed in aluminum
pans under an argon atmosphere, using heating rates of 5 °C/min.
Anhydrous Na2SO4 was used for drying organic extracts, and all volatiles
were removed under reduced pressure. All reaction mixtures and column
eluents were monitored by TLC using commercial glass-backed thin
layer chromatography (TLC) plates (Kieselgel 60 F254). The plates were
observed under UV light at 254 and 365 nm. The technique of dry flash
chromatography was used throughout for all non-TLC scale chromato-
graphic separations using silica gel 60 (less than 0.063 mm). Melting
points were determined using a hotstage microscope apparatus. Solvents
used for recrystallization are indicated after the melting point. Inflections
2.4. Preparation of 8H-Indolo[1,2,3-mn]phenazin-8-one
(14). Because significant structural similarities exist between
the benzotriazinone 6a and 10-phenylphenazin-2(10H)-one 12
(aposafranone) we examined the behavior of the latter in the
above intramolecular cyclizations. The anticipated cyclization
could lead to the new 8H-indolo[1,2,3-mn]phenazin-8-one 14
system (Scheme 2). Regioselective iodination at C-1 occurred
readily upon treating a solution of aposafranone 12 with NIS (2
equiv) at ca. 20 °C. 1-Iodoaposafranone 13 when treated with
Pd(OAc)2 (1.25 equiv) and pyridine (1 equiv) in DMF at 100 °C
readily cyclized to the desired indolophenazinone 14 in a 78%
yield. Similarly, treatment of 1-iodoaposafranone 13 with Pd-
(Ph3P)2Cl2 (5%) and AgF (1.5 equiv) in DMF at 100 °C gave the
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in the UV spectra are identified by the abbreviation “inf”. FTIR spectra
4.2.3. 6-Methoxy-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6d).
To a stirred solution of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one
(6a) (30 mg, 0.1 mmol) in MeOH (2 mL) was added 2 N MeONa
(0.1 mL, 0.2 mmol), and the reaction mixture was heated at reflux for 4 h.
TLC (t-BuOMe) showed the absence of the starting material and the
presence of a new red-purple compound. The mixture was diluted with
DCM (10 mL) and adsorbed onto silica gel. Dry flash chromatography
(t-BuOMe) gave the title compound 6d (11.4 mg, 35%) as red needles,
mp 226À228 °C (from benzene); Rf 0.14 (t-BuOMe); (found: C, 72.7;
H, 4.6; N, 12.5. C20H15N3O2 requires C, 72.9; H, 4.6; N, 12.8%);
λmax(DCM)/nm 246 (log ε 3.29), 312 (3.58), 358 inf (2.92), 381 inf
(2.58), 520 (2.68); νmax/cmÀ1 3063w (Ar CH), 1611 m, 1587 m, 1555s,
1516 m, 1493 m, 1456w, 1439w, 1385w, 1352w, 1315w, 1285 m, 1244s,
1209 m, 1184 m, 1157w, 1134w, 1067w, 1026w, 999w, 980w, 926w, 856
m, 843 m, 820 m, 773 m, 741 m; δH(300 MHz; CDCl3) 8.30À8.27 (2H,
m, Ar H), 7.61À7.55 (5H, m, Ar H), 7.48À7.46 (3H, m, Ar H), 7.00
(1H, s, Ar H), 6.21 (1H, s, Ar H), 4.09 (3H, s, OCH3); δC(75 MHz;
CDCl3) 175.1 (s), 164.1 (s), 155.2 (s), 151.5 (s), 141.5 (s), 135.3 (s),
134.4 (s), 130.6 (d), 130.3 (d), 130.1 (d), 128.9 (d), 126.9 (d), 125.9
(d), 104.3 (d), 97.1 (d), 57.0 (OCH3); m/z (EI) 330 (M+ + 1, 23%), 329
(M+, 91), 300 (100), 286 (10), 283 (5), 271 (4), 195 (3), 180 (5), 168
were recorded using a Ge ATR accessory and strong, medium and weak
1
peaks are represented by s, m, and w respectively. H NMR spectra
were recorded at either 300 or 500 MHz and 13C NMR spectra were
recorded at either 75 and 125 MHz, respectively. DEPT 135 or APT
NMR studies identified quaternary and tertiary carbons, which are
indicated by (s) and (d) notations, respectively. Deuterated solvents
were used for homonuclear lock and the signals are referenced to
the deuterated solvent peaks. Low resolution (EI) mass spectra were
recorded on a GCMS with direct inlet probe. 1,3-Diphenylbenzo[e]-
[1,2,4]-triazin-7(1H)-one (6a),8a 6-hydroxy-1,3-diphenylbenzo[e][1,2,4]-
triazin-7(1H)-one (6f),7 6-(phenylthio)benzo[e][1,2,4]triazin-7(1H)-
one (6e),7 8-iodo-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one
(7a),7 and 10-phenylphenazin-2(10H)-one (12) (aposafranone)13b were
prepared according to literature procedures.
4.2. Preparation of C-6 Substituted Benzotriazinones. 4.2.1.
6-(Diethylamino)-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6b). A
mixture of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6a) (36.2
mg, 0.12 mmol) with diethylamine (0.5 mL, 4.81 mmol) was stirred
to ca. 20 °C for 25 h until no starting material remained (TLC).
The reaction mixture was then diluted (DCM) and washed (5%
HCl) to remove unreacted amine. The organic layer was separated,
dried (Na2SO4), filtered, and adsorbed onto silica. Chromatography
(t-BuOMe/hexane/DCM, 1:3:6) gave the title compound 6b (20.4 mg,
46%) as orange needles, mp >300 °C (from EtOH); Rf 0.30 (t-BuOMe/
hexane, 3:1); (found: C, 74.4; H, 5.9; N, 15.2. C23H22N4O requires C,
74.6; H, 6.0; N, 15.1%); λmax(DCM)/nm 276 inf (log ε 3.55), 301
(3.67), 321 inf (3.49), 351 inf (3.07), 365 inf (2.96), 435 inf (3.49), 453
(3.56); νmax/cmÀ1 2970w, 2928w, 1593w, 1585 m, 1537s, 1504 m, 1493
m, 1481 m, 1449 m, 1408w, 1395w, 1377w, 1352w, 1315 m, 1290w,
1265 m, 1173w, 1152w, 1128w, 1082w, 1069w, 1026w, 1003w, 988 m,
926w, 887w, 837w, 822 m, 779 m, 745w; δH(300 MHz; CDCl3)
8.28À8.24 (2H, m, Ar H), 7.58À7.50 (5H, m, Ar H), 7.48À7.42 (3H,
m, Ar H), 6.70 (1H, s, Ar H), 6.02 (1H, s, Ar H), 3.82 (4H, q, J 6.9,
NCH2), 1.35 (6H, t, J 7.0, CH3); δC(75 MHz; CDCl3) 177.0 (s), 153.5
(s), 152.4 (s), 152.2 (s), 142.2 (s), 135.8 (s), 135.3 (s), 130.3 (d), 130.2
(d), 130.0 (d), 129.0 (d), 127.3 (d), 126.4 (d), 101.6 (d), 98.0 (d), 47.8
(NCH2), 13.6 (CH3); m/z (EI) 371 (M+ + 1, 12%), 370 (M+, 37), 341
(100), 327 (14), 313 (4), 299 (5), 271 (4), 185 (3), 180 (7), 169 (4),
+
(7), 155 (4), 144 (5), 128 (4), 116 (6), 103 (7), 89 (4), 77 (C6H5 , 45),
63 (4), 51 (12).
4.2.5. 6-Methoxy-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6d).
To a stirred solution of 6-hydroxy-1,3-diphenylbenzo[e][1,2,4]triazin-
7(1H)-one (6f)7 (31.5 mg, 0.1 mmol) in MeCN (1 mL) were added
MeI (24 μL, 0.4 mmol) and H€unig’s base (137 μL, 0.8 mmol). The mixture
was stirred at ca. 20 °C for 29 h. TLC (t-BuOMe) showed the absence of the
starting material and the presence of a faster running compound. Dry flash
chromatography (t-BuOMe/MeOH, 9:1) of the residue gave the title
compound 6d (26 mg, 78%) as red needles, identical to that described above.
4.3. C-8 Iodination of C-6 Substituted Benzotriazinones
6bÀd. 4.3.1. 6-(Diethylamino)-8-iodo-1,3-diphenylbenzo[e][1,2,4]-
triazin-7(1H)-one (7b). To a stirred solution of 6-(diethylamino)-1,3-
diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6b) (37 mg, 0.1 mmol) in
DCM (1 mL) was added NIS (22.4 mg, 0.1 mmol), and the mixture was
stirred at ca. 20 °C for 6 h. TLC (t-BuOMe/hexane 3:1) showed the
absence of the starting material and the presence of a new less polar red
compound. The solvent was evaporated in vacuo and the residue
crystallized to give the title compound 7b (36 mg, 73%) as red cubes,
mp 185À187 °C (from DCM/MeOH 1:2); Rf 0.41 (t-BuOMe);
(found: C, 55.6; H, 4.3; N, 11.2. C23H21IN4O requires C, 55.7; H,
4.3; N, 11.3%); λmax(DCM)/nm 246 (log ε 3.28), 310 (3.42), 334
(3.24), 375 inf (2.84), 463 (3.36); νmax/cmÀ1 2972w, 2930w, 1601 m,
1585 m, 1557s, 1528 m, 1487s, 1468 m, 1456 m, 1443 m, 1406 m,
1375w, 1352 m, 1312 m, 1292 m, 1260 m, 1231w, 1192w, 1169w, 1152
m, 1125w, 1080w, 1067w, 1028w, 1001w, 982 m, 912 m, 862w, 824 m,
785w, 768 m; δH(300 MHz, CDCl3) 8.29À8.26 (2H, m, Ar H),
7.55À7.53 (4H, m, Ar H), 7.50À7.44 (4H, m, Ar H), 6.67 (1H, s, Ar
H), 3.77 (4H, q, J 6.9, NCH2), 1.39 (6H, t, J 7.0, CH3); δC(75 MHz,
CDCl3) 173.20 (s), 153.9 (s), 151.9 (s), 150.5 (s), 142.9 (s), 137.5 (s),
135.1 (s), 130.2 (d), 129.2 (d), 129.1 (d), 128.7 (d), 127.2 (d), 127.1
(d), 100.4 (d), 74.1 (s), 47.6 (NCH2), 13.3 (CH3); m/z (EI) 497 (M+ +
1, 19%), 496 (M+, 68), 467 (78), 453 (4), 419 (3), 370 (38), 341 (100),
327 (14), 313 (5), 298 (10), 271 (4), 254 (10), 180 (16), 168 (7), 143
+
144 (4), 118 (8), 103 (20), 91 (5), 77 (C6H5 , 40), 63 (5), 51 (15).
4.2.2. 1,3-Diphenyl-6-(pyrrolidin-1-yl)benzo[e][1,2,4]triazin-7(1H)-one
(6c). Addition of pyrrolidine (0.4 mL, 3.4 mmol) to 1,3-diphenylbenzo-
[e][1,2,4]triazin-7(1H)-one (6a) (30 mg, 0.1 mmol) at ca. 20 °C
resulted a very rapid reaction (1 min) and consumption of starting
material (TLC). The reaction mixture was then diluted with DCM
(15 mL) and washed with 5% HCl (10 mL) to remove unreacted amine.
The organic layer was separated, dried (Na2SO4) and evaporated in
vacuo to afford the title compound 6c (37 mg, 100%) as orange needles,
mp 254À255 °C (from cyclohexane); Rf 0.47 (t-BuOMe); (found: C,
74.9; H, 5.6; N, 15.3. C23H20N4O requires C, 75.0; H, 5.5; N, 15.2%);
λmax(DCM)/nm 230 (log ε 3.24), 277 inf (3.45), 300 (3.56), 317 inf
(3.43), 348 (2.98), 366 inf (2.88), 452 (3.51); νmax/cmÀ1 3067w (Ar
CH), 2947w, 2930w, 1585 m, 1535s, 1493 m, 1483 m, 1449 m, 1406w,
1395 m, 1371 m, 1312 m, 1292 m, 1229w, 1175w, 1132w, 1069w,
1026w, 1003w, 993w, 916 m, 839 m, 814 m, 799w, 772 m; δH(300 MHz;
CDCl3) 8.27À8.24 (2H, m, Ar H), 7.58À7.48 (5H, m, Ar H),
7.46À7.42 (3H, m, Ar H), 6.53 (1H, s, Ar H), 5.99 (1H, s, Ar H),
4.34 (2H, br s, NCH2), 3.53 (2H, br s, NCH2), 1.98 (4H, s, CH2); δC(75
MHz; CDCl3) one Ar CH missing 176.6 (s), 152.5 (s), 152.1 (s), 152.0
(s), 141.9 (s), 135.7 (s), 135.4 (s), 129.7 (d), 129.5 (d), 128.5 (d), 126.8
(d), 126.0 (d), 100.8 (d), 96.7 (d), 51.9 (CH2), 50.9 (CH2), 27.1 (CH2),
23.7 (CH2); m/z (EI) 369 (M+ + 1, 28%), 368 (M+, 100), 339 (9), 325
(10), 313 (51), 299 (16), 285 (4), 236 (4), 184 (8), 160 (7), 132 (4),
+
(4), 127 (8), 118 (9), 104 (13), 89 (5), 77 (C6H5 , 74), 67 (8), 51 (17).
4.3.2. 8-Iodo-1,3-diphenyl-6-(pyrrolidin-1-yl)benzo[e][1,2,4]triazin-
7(1H)-one (7c). To a stirred solution of 1,3-diphenyl-6-(pyrrolidin-1-
yl)benzo[e][1,2,4]triazin-7(1H)-one (6c) (37 mg, 0.1 mmol) in DCM
(1 mL) was added NIS (22.4 mg, 0.1 mmol), and the mixture was stirred
at ca. 20 °C for 7 h. TLC (t-BuOMe/hexane, 3:1) showed the absence of
the starting material and the presence of a new less polar red compound.
The solvent was evaporated in vacuo and the residue crystallized to give
the title compound 7c (32.4 mg, 65%) as red needles, mp >300 °C (from
+
118 (4), 103 (8), 91 (5), 77 (C6H5 , 51), 63 (5), 51 (15).
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DCM/MeOH, 1:2); Rf 0.61 (t-BuOMe/hexane, 3:1); (found: C, 55.7;
H, 4.0; N, 11.3. C23H19IN4O requires C, 55.9; H, 3.9; N, 11.3%);
λmax(DCM)/nm 212 (log ε 4.30), 305 (3.56), 372 inf (3.10), 458
(3.41); νmax/cmÀ1 3065w (Ar CH), 2970w, 2920w, 2853w, 1601 m,
1585 m, 1568s, 1524s, 1489s, 1470 m, 1454 m, 1441s, 1400 m, 1371 m,
1342w, 1302s, 1223w, 1196w, 1171w, 1123w, 1105w, 1088w, 1069w,
1047w, 1026w, 1001w, 991w, 934 m, 874w, 839w, 814 m; δH(300 MHz,
CDCl3) 8.28À8.25 (2H, m, Ar H), 7.57À7.52 (4H, m, Ar H),
7.48À7.42 (4H, m, Ar H), 6.51 (1H, s, Ar H), 4.34 (2H, br s, NCH2),
3.56 (2H, br s, NCH2), 2.02 (4H, br s, CH2); δC(75 MHz, CDCl3)
173.4 (s), 154.0 (s), 152.0 (s), 149.0 (s), 143.1 (s), 137.8 (s), 135.2 (s),
130.2 (d), 129.2 (d), 129.1 (d), 128.7 (d), 127.3 (d), 127.1 (d), 100.3
(d), 73.3 (s), 52.6 (NCH2), 51.2 (NCH2), 29.9 (CH2), 26.9 (CH2); m/z
(EI) 495 (M+ + 1, 13%), 494 (M+, 52), 451 (2), 368 (100), 363 (6), 339
(22), 325 (12), 313 (50), 299 (17), 286 (8), 271 (5), 254 (11), 247 (6),
236 (8), 184 (7), 180 (10), 168 (10), 160 (7), 152 (5), 140 (9), 127 (9),
diphenylbenzo[e][1,2,4]triazin-7(1H)-one (7a) (42.5 mg, 0.1 mmol) in
DMF (1 mL) were added Pd(Ph3P)2Cl2 (3.5 mg, 0.005 mmol, 5 mol %)
and AgF (19 mg, 0.15 mmol), and the mixture was heated at 100 °C for
30 min. TLC (t-BuOMe/hexane, 3:1) showed the presence of a new more
polar compound and the absence of the starting material. The reaction
mixture was diluted with Et2O (5 mL) and washed with H2O (5 mL). The
organic layer was separated, dried (Na2SO4), and evaporated in vacuo. Dry
flash chromatography (t-BuOMe/hexane, 1:2) of the residue gave the title
compound 8a (29.5 mg, 99%) as dark brown colored needles, mp (DSC
onset) 183 °C (decomp) (from cyclohexane); Rf 0.60 (t-BuOMe/hexane,
1:3); (found: C, 76.7; H, 3.8; N, 14.1. C19H11N3O requires C, 76.8; H, 3.7;
N, 14.1%); λmax(DCM)/nm 238 (log ε 3.37), 286 (3.57), 319 inf (3.01),
416 (2.70), 543 (3.46); νmax/cmÀ1 3064w (Ar CH), 1643 m, 1622s, 1572w,
1541 m, 1506 m, 1483 m, 1452 m, 1436 m, 1402w, 1390w, 1364 m, 1330 m,
1314 m, 1299w, 1266w, 1203w, 1173w, 1161w, 1144 m, 1114w, 1095w,
1072 m, 1025w, 1005w, 989w, 976w, 952w, 932w, 903w, 860w, 855w, 828s;
δH(300MHz, CDCl3) 8.55À8.52 (2H, m, Ar H), 8.36(2H, dd, J7.4, 7.4, Ar
H), 7.68 (1H, d, J9.9, Ar H), 7.69À7.55 (5H, m, Ar H), 7.23 (1H, d, J9.8, Ar
H); δC(75 MHz, CDCl3) 178.6 (s), 156.5 (s), 153.9 (s), 146.0 (d), 135.0
(s), 134.2 (s), 131.8 (d), 131.5 (d), 129.3 (d), 129.2 (d), 128.2 (d), 126.6
(s), 126.1 (s), 125.8 (d), 123.3 (d), 113.5 (d), 105.2 (s); m/z (EI) 298
(M+ + 1, 21%), 297 (M+, 100), 268 (11), 242 (2), 168 (4), 140 (10), 113
(7), 88 (6), 77 (6), 63 (4).
+
116 (9), 103 (13), 91 (6), 77 (C6H5 , 98), 63 (7), 51 (24).
4.3.3. 8-Iodo-6-methoxy-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-
one (7d). To a stirred solution of 6-methoxy-1,3-diphenylbenzo[e]-
[1,2,4]triazin-7(1H)-one (6d) (50 mg, 0.15 mmol) in MeOH (3 mL)
was added NIS (34 mg, 0.15 mmol), and the mixture was stirred at ca.
20 °C for 7 h. TLC (t-BuOMe) showed the absence of the starting
material and the presence of a new less polar red compound. The solvent
was evaporated in vacuo and the residue crystallized to give the title
compound 7d (58.1 mg, 84%) as purple needles, mp 227À229 °C (from
DCM/MeOH, 1:2); Rf 0.24 (t-BuOMe/hexane, 3:2); (found: C, 52.6;
H, 2.9; N, 9.1. C20H14IN3O2 requires C, 52.8; H, 3.1; N, 9.2%);
λmax(DCM)/nm 251 (log ε 3.37), 324 (3.45), 371 inf (3.04), 537
(2.70); νmax/cmÀ1 3022w (Ar CH), 2922w, 2853w, 1593s, 1580 m,
1541 m, 1501 m, 1479s, 1454s, 1438 m, 1375w, 1348 m, 1310w, 1285w,
1246s, 1223s, 1188w, 1177 m, 1159w, 1130 m, 1088w, 1072w, 1020w,
1005w, 978w, 903 m, 843 m, 835 m, 785 m, 773 m; δH(300 MHz,
CDCl3) 8.30À8.27 (2H, m, Ar H), 7.58À7.47 (8H, m, Ar H), 6.98 (1H,
s, Ar H), 4.09 (3H, s, OCH3); δC(75 MHz, CDCl3) 172.3 (s), 160.7 (s),
155.8 (s), 151.0 (s), 142.5 (s), 137.0 (s), 133.8 (s), 130.9 (d), 129.6 (d),
129.3 (d), 128.9 (d), 127.0 (d), 127.0 (d), 105.1 (d), 73.3 (s), 57.2
(OCH3); m/z (EI) 456 (M+ + 1, 9%), 455 (M+, 41), 426 (4), 363 (4),
328 (84), 313 (24), 310 (14), 300 (25), 285 (21), 271 (4), 257 (4), 218
(5), 197 (3), 182 (4), 168 (17), 164 (11), 154 (15), 143 (11), 140 (17),
4.4.2. 5-(Diethylamino)-2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carba-
zol-6-one (8b). To a stirred solution of 6-(diethylamino)-8-iodo-1,3-
diphenylbenzo[e][1,2,4]triazin-7(1H)-one (7b) (49.6 mg, 0.1 mmol) in
DMF (1 mL) were added Pd(Ph3P)2Cl2 (3.5 mg, 0.005 mmol, 5 mol %)
and AgF (19 mg, 0.15 mmol), and the mixture was heated at 100 °C for
20 min. TLC (t-BuOMe/hexane, 3:1) showed the presence of a new
more polar compound and the absence of the starting material. The
reaction mixture was diluted with Et2O (5 mL) and washed with H2O
(5 mL). The organic layer was separated, dried (Na2SO4), and evapo-
rated in vacuo. Dry flash chromatography (t-BuOMe/hexane, 1:2) of the
residue gave the title compound 8b (34.3 mg, 93%) as red needles, mp
152À154 °C (from EtOH); Rf 0.62 (t-BuOMe/hexane, 3:1); (found: C,
75.1; H, 5.4; N, 15.2. C23H20N4O requires C, 75.0; H, 5.5; N, 15.2%);
λmax(DCM)/nm 232 (log ε 3.59), 265 (3.61), 276 (3.62), 303 (3.55),
413 (3.17), 438 (3.35), 461 (3.30); νmax/cmÀ1 2967w, 2930w, 2907w,
1643 m, 1626 m, 1570w, 1528 m, 1518s, 1499 m, 1476 m, 1450w,
1431w, 1410w, 1395w, 1360w, 1310w, 1292w, 1283 m, 1258 m, 1248 m,
1169w, 1152w, 1123w, 1094w, 1070w, 1028w, 1009w, 986 m, 943 m,
926w, 831w, 814 m, 793 m, 773 m, 758 m; δH(300 MHz; CDCl3)
8.49À8.46 (2H, m, Ar H), 8.30 (1H, d, J 7.8, Ar H), 8.25 (1H, d, J 8.2),
7.59À7.46 (5H, m, Ar H), 6.44 (1H, s, Ar H), 3.84 (4H, q, J 6.9, NCH2),
1.44 (6H, t, J 7.0, CH3); δC(75 MHz; CDCl3) 174.7 (s), 157.3 (s), 157.2
(s), 152.5 (s), 136.6 (s), 135.2 (s), 130.4 (d), 128.8 (d), 128.0 (d), 127.8
(d), 126.8 (s), 125.7 (s), 124.6 (d), 122.4 (d), 113.2 (d), 104.6 (s), 98.8
(d), 48.2 (NCH2), 13.2 (CH3); m/z (EI) 369 (M+ + 1, 13%), 368 (M+,
47), 339 (100), 325 (14), 297 (8), 269 (3), 193 (2), 165 (4), 151 (4),
+
126 (22), 115 (13), 103 (15), 89 (6), 77 (C6H5 , 100), 63 (10), 51 (33).
4.3.4. 8-Iodo-1,3-diphenyl-6-(phenylthio)benzo[e][1,2,4]triazin-7(1H)-
one (7e). To a stirred solution of 6-(phenylthio)benzo[e][1,2,4]triazin-
7(1H)-one (6e)7 (40.7 mg, 0.1 mmol) in MeOH (1 mL) was added NIS
(22.4 mg, 0.1 mmol), and the mixture was stirred at ca. 20 °C for 18 h. TLC
(t-BuOMe/hexane, 2:1) showed the absence of the starting material and the
presence of a new less polar brown compound. The solvent was evaporated
in vacuo and the residue crystallized to give the title compound 7e (44.6 mg;
84%) as brown needles, mp 218À223 °C (from DCM/MeOH, 1:1); Rf
0.86 (t-BuOMe/hexane, 3:1); (found: C, 56.3; H, 2.9; N, 7.7. C25H16IN3OS
requires C, 56.3; H, 3.0; N, 7.9%); λmax(DCM)/nm 218 (log ε 4.23), 267
(3.34), 350 (3.33), 424 (2.99), 547 (1.41); νmax/cmÀ1 3055w (Ar CH),
2922w, 2849w, 1593 m, 1566w, 1524w, 1501w, 1479s, 1451 m, 1439 m,
1418w, 1364w, 1310w, 1281w, 1254w, 1213w, 1184w, 1136w, 1069w,
1024w, 1011 m, 972w, 947w, 928w, 912w, 883 m, 849w, 829w, 816w, 808w,
783w, 775 m; δH(300 MHz, CDCl3) 8.21À8.17 (2H, m, Ar H), 7.68À7.65
(2H, m, Ar H), 7.59À7.50 (8H, m, Ar H), 7.46À7.41 (3H, m, Ar H), 6.87
(1H, s, ArH);δC(75MHz, CDCl3) twoArCH missing 174.1 (s), 157.5 (s),
152.8 (s), 151.2 (s), 142.4 (s), 137.8 (s), 135.8 (d), 133.6 (s), 130.9 (d),
130.5 (d), 129.7 (d), 129.4 (s), 129.3 (d), 128.9 (d). 127.0 (d), 121.3 (d),
72.2(s);m/z(EI) 534(M+ + 1, 12%), 533 (M+, 33), 406 (96), 378 (5), 328
(16), 275 (12), 247 (6), 197 (7), 169 (10), 148 (4), 145 (6), 121 (12), 109
+
140 (5), 125 (4), 114 (4), 77 (C6H5 , 6), 51 (3).
4.4.3. 2-Phenyl-5-(pyrrolidin-1-yl)-6H-[1,2,4]triazino[5,6,1-jk]carba-
zol-6-one (8c). To a stirred solution of 8-iodo-1,3-diphenyl-6-(pyr-
rolidin-1-yl)benzo[e][1,2,4]triazin-7(1H)-one (7c) (49.4 mg, 0.1 mmol)
in in DMF (1 mL) were added Pd(Ph3P)2Cl2 (3.5 mg, 0.005 mmol,
5 mol %) and AgF (19 mg, 0.15 mmol), and the mixture was heated at
100 °C for 15 min. TLC (t-BuOMe/hexane, 3:1) showed the presence
of a new more polar compound and the absence of the starting material.
The reaction mixture was diluted with Et2O (5 mL) and washed with H2O
(5 mL). The organic layer was separated, dried (Na2SO4), and evaporated
in vacuo. Dry flash chromatography (t-BuOMe/hexane, 1:2) of the residue
gave the title compound 8c (30.2 mg, 83%) as red needles, mp
134À137 °C (from DCM/MeOH, 1:2); Rf 0.71 (t-BuOMe/hexane,
3:1); (found: C, 75.1; H, 5.1; N, 15.2. C23H18N4O requires C, 75.4; H,
5.0; N, 15.3%); λmax(DCM)/nm 231 (log ε 3.38), 267 inf (3.39), 276
+
(9), 103 (7), 93 (7), 89 (8), 77 (C6H5 , 100), 65 (7), 51 (36).
4.4. Nonoxidative Coupling. 4.4.1. 2-Phenyl-6H-[1,2,4]triazino-
[5,6,1-jk]carbazol-6-one (8a). To a stirred solution of 8-iodo-1,3-
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The Journal of Organic Chemistry
ARTICLE
(3.41), 304 (3.30), 371 inf (2.58), 415 inf (3.00) 438 (3.21), 460 (3.06);
νmax/cmÀ1 3049w, 2955w, 2916w, 2870w, 2849w, 1641 m, 1626 m,
1570w, 1510s, 1479w, 1452 m, 1393w, 1368w, 1348w, 1341w, 1321w,
1308w, 1260 m, 1244w, 1229w, 1173w, 1140w, 1105w, 1070w, 1028w,
1007w, 993w, 953w, 937w, 924w, 908w, 858w, 833w, 808w, 785w, 773w;
δH(300 MHz; CDCl3) 8.46À8.43 (2H, m, Ar H), 8.20À8.17 (2H, m, Ar
H), 7.55À7.41 (5H, m, Ar H), 6.17 (1H, s, Ar H), 4.35 (2H, br s, NCH2),
3.52 (2H, br s, NCH2), 2.01 (4H, br s, CH2); δC(75 MHz; CDCl3) 173.8
(s), 156.8 (s), 155.0 (s), 151.9 (s), 136.5 (s), 135.0 (s), 130.2 (d), 128.5
(d), 127.8 (d), 127.4 (d), 126.3 (s), 125.8 (s), 124.3 (d), 122.1 (d), 112.9
(d), 103.7 (s), 97.9 (d), 52.2 (NCH2), 29.8 (CH2); m/z (EI) 367 (M+ + 1,
30%), 366 (M+, 100), 337 (12), 323 (17), 311 (28), 297 (34), 269 (6), 235
(4), 207 (6), 179 (5), 165 (7), 151 (8), 140 (10), 120 (5), 114 (8), 103
113.5 (d), 103.4 (s); m/z (EI) 406 (M+ + 1, 28%), 405 (M+, 100), 388
(56), 376 (5), 328 (4), 302 (12), 274 (11), 245 (4), 202 (9), 197 (11),
182 (4), 168 (8), 153 (5), 137 (5), 125 (8), 114 (7), 103 (4), 77
(C6H5 ,15), 63 (4), 51 (12). Further elution gave unreacted 7e (10.5
mg, 20%).
+
4.5. Regioselective Nucleophilic Addition of Triazafluor-
anthenone. 4.5.1. 5-(Diethylamino)-2-phenyl-6H-[1,2,4]triazino-
[5,6,1-jk]carbazol-6-one (8b). To a stirred solution of 2-phenyl-
6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one (8a) (30 mg, 0.1 mmol)
in EtOH (0.5 mL) was added diethylamine (0.5 mL, 4.8 mmol), and the
mixture was stirred at ca. 20 °C for 22 h. TLC (t-ButOMe/hexane, 2:1)
showed the absence of the starting material and the presence of a more
polar red compound. The solution was diluted with DCM (15 mL) and
washed with 5% HCl (10 mL) to remove unreacted amine. The organic
layer was separated, dried (Na2SO4), evaporated in vacuo, and crystal-
lized to afford the title compound 8b (22.1 mg, 60%) as red needles,
identical to that described above.
4.5.2. 2-Phenyl-5-(pyrrolidin-1-yl)-6H-[1,2,4]triazino[5,6,1-jk]carba-
zol-6-one (8c). To a stirred solution of 2-phenyl-6H-[1,2,4]triazino-
[5,6,1-jk]carbazol-6-one (8a) (30.6 mg; 0.1 mmol) in EtOH (0.5 mL)
was added pyrrolidine (0.5 mL, 6 mmol). The mixture was stirred at ca.
20 °C for 4 h. TLC (t-BuOMe/hexane, 2:1) showed the absence of the
starting material and the presence of a more polar red compound. The
solution was diluted with DCM (15 mL) and washed with 5% HCl
(10 mL) to remove unreacted amine. The organic layer was separated,
dried (Na2SO4), and evaporated in vacuo and the residue crystallized to
afford the title compound 8c (37.6 mg, 100%) as red needles, identical to
that described above.
4.5.3. 2-Phenyl-5-(phenylthio)-6H-[1,2,4]triazino[5,6,1-jk]carbazol-
6-one (8e). To a stirred solution of 2-phenyl-6H-[1,2,4]triazino[5,6,1-
jk]carbazol-6-one (8a) (30 mg, 0.1 mmol) in DCM (2 mL) were added
H€unig’s base (18.8 μL; 0.11 mmol) and thiophenyl (20.6 μL, 0.2 mmol).
The mixture was stirred at ca. 20 °C for 2.5 h. TLC (t-BuOMe/hexane,
3:1) showed the absence of the starting material and the presence of a
new less polar compound. The mixture was diluted with DCM (15 mL)
and washed with 1 M HCl (10 mL) and then with sat. NaHCO3 (1 Â
10 mL). The organic layer was separated, dried (Na2SO4), and
evaporated in vacuo to afford the title compound 8e (40.4 mg, 100%)
as brown needles, identical to that described above.
+
(9), 77 (C6H5 , 12), 69 (5), 51 (8).
4.4.4. 5-Methoxy-2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-
one (8d). To a stirred solution of 8-iodo-6-(methoxy)-1,3-diphenylbe-
nzo[e][1,2,4]triazin-7(1H)-one (7d) (45.5 mg, 0.1 mmol) in DMF
(1 mL) were added Pd(Ph3P)2Cl2 (3.5 mg, 0.005 mmol, 5 mol %) and
AgF (19 mg, 0.15 mmol), and the mixture was heated at 100 °C for
20 min. TLC (t-BuOMe/hexane, 3:1) showed the presence of a new
more polar compound and the absence of the starting material. The
reaction mixture was diluted with Et2O (5 mL) and washed with H2O
(5 mL). The organic layer was separated, dried (Na2SO4), and evapo-
rated in vacuo. Dry flash chromatography (t-BuOMe/hexane, 1:2) of the
residue gave the title compound 8d (29.2 mg, 89%) as orange plates, mp
245À247 °C (from DCM/MeOH, 1:2); Rf 0.36 (t-BuOMe/hexane,
3:1); (found: C, 73.5; H, 4.0; N, 12.5. C20H13N3O2 requires C, 73.4; H,
4.0; N, 12.8%); λmax(DCM)/nm 235 (log ε 3.27), 270 (3.23), 301
(3.54), 343 (2.83), 395 (2.80), 419 (2.74), 515 (2.27); νmax/cmÀ1
3006w (Ar CH), 2988w, 2958w, 2923w, 2854w, 1650w, 1631w, 1542 m,
1509w, 1484w, 1467w, 1453w, 1432w, 1407w, 1390w, 1314w, 1276s,
1260s, 1231 m, 1185w, 1177w, 1150w, 1133w, 1104w, 1075w, 1027w,
1002w, 977w, 936w, 917w, 898w, 867w, 822w, 795w; δH(300 MHz;
CDCl3) 8.52À8.49 (2H, m, Ar H), 8.35 (1H, d, J 8.3, Ar H), 8.27 (1H, d,
J 8.3, Ar H), 7.65À7.50 (5H, m, Ar H), 6.76 (1H, s, Ar H), 4.11 (3H, s,
OCH3); δC(75 MHz; CDCl3) 171.7 (s), 167.1 (s), 156.5 (s), 154.1 (s),
135.3 (s), 134.8 (s), 131.1 (d), 129.0 (d), 128.7 (d), 128.0 (d), 126.3 (s),
125.5 (d), 124.8 (s), 123.2 (d), 113.3 (d), 104.1 (s), 102.4 (d), 57.6
(OCH3); m/z (EI) 328 (M+ + 1, 11%), 327 (M+, 47), 298 (100), 269
(4), 194 (4), 168 (4), 153 (7), 139 (9), 125 (16), 114 (6), 103 (5), 99
+
(10), 77 (C6H5 , 10), 51 (5).
4.6. Oxidative Coupling. 4.6.1. 2-Phenyl-6H-[1,2,4]triazino-
[5,6,1-jk]carbazol-6-one (8a). To a stirred mixture of 1,3-diphenylbe-
nzo[e][1,2,4]triazin-7(1H)-one (6a) (30 mg, 0.1 mmol) in DMSO
(1 mL) were added Pd(OAc)2 (2.3 mg, 0.01 mmol), AgF (25 mg, 0.2
mmol), and Cu(OTf)2 (72 mg, 0.2 mmol), and the solution was heated
at ca. 100 °C under an oxygen atmosphere for 7 h. TLC (t-BuOMe/
hexane 3:1) showed the presence of a less polar red-brown compound.
The reaction mixture was then cooled, diluted with DCM (15 mL), and
washed with water (3 Â 15 mL). The organic layer was dried (Na2SO4)
and concentrated in vacuo. Dry flash chromatography (t-BuOMe/
hexane, 1:2) of the residue gave the title compound 8a (25.6 mg,
86%) as dark brown colored needles, identical to that described above.
4.6.2. 5-(Diethylamino)-2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carba-
zol-6-one (8b). To a stirred solution of 6-(diethylamino)-1,3-
diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6b) (37 mg, 0.1 mmol) in
DMSO (1 mL) were added Pd(OAc)2 (2.3 mg, 0.01 mmol), AgF
(25 mg, 0.2 mmol), and Cu(OTf)2 (72 mg, 0.2 mmol), and the mixture
was heated at ca. 100 °C under an oxygen atmosphere for 2 h. TLC
(t-BuOMe/hexane, 3:1) showed the presence of a less polar red compound.
The reaction mixture was then cooled to ca. 20 °C, diluted with DCM
(15 mL), and washed with water (3 Â 15 mL). The organic layer was dried
(Na2SO4) and concentrated in vacuo. The residue obtained was dry flash
chromatographed (t-BuOMe/hexane, 1:2) to afford the title compound 8b
(24.7 mg, 67%) as red needles, identical to that described above.
4.4.5. 2-Phenyl-5-(phenylthio)-6H-[1,2,4]triazino[5,6,1-jk]carbazol-
6-one (8e). To a stirred solution of 8-iodo-1,3-diphenyl-6-(phenyl-
thio)benzo[e][1,2,4]triazin-7(1H)-one (7e) (53.3 mg, 0.1 mmol) in dry
MeCN (1 mL) were added AgF (25 mg, 0.1 mmol), Ph3P (2.6 mg,
0.01 mmol), and Pd(Ph3P)2Cl2 (7 mg, 0.01 mmol), and the mixture was
stirred at reflux for 24 h. TLC (t-BuOMe/hexane, 3:1) showed the
absence of the starting material and the presence of a less polar product.
Dry flash chromatography (t-BuOMe/hexane, 1:1) of the residue gave
the title compound 8e (21.6 mg, 53%) as brown needles, mp
279À281 °C (from PhMe); Rf 0.87 (t-BuOMe/hexane, 3:1); (found:
C, 73.9; H, 3.6; N, 10.3. C25H15N3OS requires C, 74.1; H, 3.7; N
10.4%); λmax(DCM)/nm 217 (log ε 3.99), 269 (3.34), 284 (3.29), 305
(3.28), 324 (3.14), 387 (1.79), 430 (2.95), 451 (3.02); νmax/cmÀ1
3053w (Ar CH), 1643s, 1624 m, 1612w, 1574w, 1556w, 1539w, 1502s,
1474 m, 1450w, 1441w, 1433w, 1418w, 1400w, 1385w, 1362w, 1329w,
1315w, 1306w, 1294w, 1265w, 1242w, 1173w, 1155w, 1130w, 1107w,
1069w, 1024w, 1013w, 980w, 972w, 947w, 928w, 868w, 847w, 833w,
806w, 797w; δH(300 MHz; CDCl3) 8.44À8.41 (2H, m, Ar H), 8.36
(1H, d, J 7.9, Ar H), 8.30 (1H, d, J 8.3, Ar H), 7.70À7.65 (3H, m, Ar H),
7.63À7.55 (4H, m, Ar H), 7.53À7.50 (3H, m, Ar H), 6.77 (1H, s, Ar H);
δC(75 MHz; CDCl3) two Ar CH missing 173.8 (s), 165.5 (s), 156.8 (s),
151.5 (s), 135.9 (d), 135.3 (s), 134.9 (s), 131.1 (d), 130.6 (d), 129.5 (s),
129.0 (d), 128.0 (d), 126.9 (s), 126.1 (s), 125.5 (d), 123.1 (d), 120.2 (d),
5800
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The Journal of Organic Chemistry
ARTICLE
4.6.3. 2-Phenyl-5-(pyrrolidin-1-yl)-6H-[1,2,4]triazino[5,6,1-jk]carba-
zol-6-one (8c). To a stirred solution of 1,3-diphenyl-6-(pyrrolidin-1-
yl)benzo[e][1,2,4]triazin-7(1H)-one (6c) (36.8 mg, 0.1 mmol) in
DMSO (1 mL) were added Pd(OAc)2 (2.3 mg, 0.01 mmol), AgF
(25 mg, 0.2 mmol), and Cu(OTf)2 (72 mg, 0.2 mmol), and the mixture
was heated at ca. 100 °C under an oxygen atmosphere for 2.5 h. TLC
(t-BuOMe/hexane, 3:1) showed the presence of a less polar red
compound. The reaction mixture was then cooled, diluted with DCM
(15 mL), and washed with water (3 Â 15 mL). The organic layer was
dried (Na2SO4) and concentrated in vacuo, and dry flash chromatog-
raphy (t-BuOMe/hexane, 1:2) gave the title compound 8c (27.8 mg,
76%) as red needles, identical to that described above.
4.6.4. 5-Methoxy-2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-
one (8d). To a stirred solution of 6-methoxybenzo-1,3-diphenyl[e]-
[1,2,4]triazin-7(1H)-one (6d) (31.5 mg, 0.1 mmol) in DMSO (1 mL)
were added Pd(OAc)2 (2.3 mg, 0.01 mmol), AgF (25 mg, 0.2 mmol),
and Cu(OTf)2 (72 mg, 0.2 mmol), and the solution was heated at ca.
100 °C under an oxygen atmosphere for 18 h. TLC (t-BuOMe/hexane,
3:1) showed the presence of a less polar red compound. The reaction
mixture was then cooled to ca. 20 °C, diluted with DCM (15 mL), and
washed with water (3 Â 15 mL). The organic layer was dried (Na2SO4)
and concentrated in vacuo, and dry flash chromatography (t-BuOMe/
hexane, 1:2) gave the title compound 8d (6.0 mg, 19%) as orange plates,
identical to that described above. Further elution gave unreacted 6d
(9.3 mg, 28%).
4.6.5. 2-Phenyl-5-(phenylthio)-6H-[1,2,4]triazino[5,6,1-jk]carbazol-
6-one (8e). To a stirred solution of 1,3-diphenyl-6-(phenylthio)benzo-
[e][1,2,4]triazin-7(1H)-one (6e) (40.7 mg, 0.1 mmol) in DMSO
(1 mL) were added Pd(OAc)2 (2.3 mg, 0.01 mmol), AgF (25 mg,
0.2 mmol), and Cu(OTf)2 (72 mg, 0.2 mmol), and the mixture was
heated at ca. 100 °C under an oxygen atmosphere for 14.5 h. TLC
(t-BuOMe/hexane, 3:1) showed the presence of a less polar brown
compound. The reaction mixture was then cooled to ca. 20 °C, diluted
with DCM (15 mL), and washed with water (3 Â 15 mL). The organic
layer was dried (Na2SO4) and concentrated in vacuo. The residue
obtained was dry flash chromatographed (t-BuOMe/hexane, 1:2) to
afford the title compound 8e (6 mg, 15%), as brown needles, identical to
that described above. Further elution gave unreacted 6e (18 mg, 44%)
4.7. Preparation of 8H-Indolo[1,2,3-mn]phenazin-8-one
(14). 4.7.1. 8,10-Dihydro-1-iodo-10-phenylphenazin-2(7H)-one (13). To
a stirred solution of 10-phenylphenazin-2(10H)-one (12) (50 mg,
0.18 mmol) in dry DCM (2 mL) was added NIS (82.7 mg, 0.37 mmol),
and the mixture was stirred under Ar atmosphere for 1 d. TLC (EtOAc)
showed the absence of the starting material and the presence of a less polar
purple colored product. The solvent was evaporated in vacuo, and dry flash
chromatography (EtOAc) of the residue gave the title compound 13 (73mg,
100%) as red needles mp 221À225 °C (cyclohexane); Rf 0.65 (t-BuOMe/
hexane, 3:1); (found: C, 54.2; H, 2.7; N, 7.0. C18H11IN2O requires C, 54.3;
H, 2.8; N, 7.0%); λmax(DCM)/nm 287 (log ε 3.63), 355 (2.95), 367 (2.93),
538 (2.97); νmax/cmÀ1 3005w (Ar CH), 2990w, 1603w, 1585w, 1518s,
1481 m, 1466w, 1456w, 1393w, 1348w, 1315w, 1300w, 1277 m, 1261w,
1240w, 1213w, 1157w, 1146w, 1099w, 1026w, 1003w, 934w, 921w, 893w,
827 m, 754s; δH(300 MHz, CDCl3) 7.98À7.94 (1H, m, Ar H), 7.63À7.59
(4H, m, Ar H), 7.45À7.37 (4H, m, Ar H), 7.20 (1H, d, J 9.6, Ar H),
6.91À6.87 (1H, m, Ar H); δC(75 MHz, CDCl3) 180.2 (s), 147.6 (s), 138.9
(s), 136.7 (s), 135.1 (d), 134.6 (s), 132.9 (s), 132.4 (d), 131.9 (d), 131.8 (d),
130.6 (d), 130.5 (d), 129.8 (d), 124.8 (d), 116.6 (d), 79.9 (C-1); m/z (EI)
399 (M+ + 1, 4%), 398 (M+, 18), 271 (100), 242 (40), 216 (8), 190 (4), 136
(11), 121 (11), 115 (8), 108 (6), 88 (4), 77 (11), 63 (7), 51 (17).
4.7.2. 8H-Indolo[1,2,3-mn]phenazin-8-one (14) via Stochiometric
Nonoxidative Coupling. To a stirred solution of 8,10-dihydro-1-iodo-
10-phenylphenazin-2(7H)-one (13) (32.4 mg; 0.082 mmol) in dry
DMF (2 mL) were added pyridine (6.5 mg; 0.082 mmol) and Pd(OAc)2
(22.9 mg; 0.102 mmol), and the mixture was stirred under Ar atmosphere
at 100 °C during 40 min. TLC (EtOAc) showed the absence of the
starting material and the presence of a new more polar orange product.
The mixture was filtered on Celite and extracted with EtOAc (5 Â
3 mL). The combined organic extracts were evaporated under reduced
pressure and dry flash chromatography (EtOAc) of the residue gave the
title compound 14 (17.1 mg; 78%) as pink-red needles (DSC onset)
227 °C (decomp) (from cyclohexane); Found: C, 80.1; H, 3.8; N, 10.3.
C18H10N2O requires C, 80.0; H, 3.7; N, 10.4%); λmax (DCM)/nm 230
(log ε 3.39), 241 (3.50), 265 (3.33), 290 (3.35), 298 (3.41), 341 (3.18),
353 (3.18), 495 (2.91); νmax/cmÀ1 3129w, 3065 (Ar CÀC), 1636 m,
1613s, 1603s, 1570w, 1561w, 1543 m, 1512 m, 1487 m, 1466w, 1447w,
1425w, 1406w, 1368w, 1356w, 1327w, 1302w, 1271w, 1241w, 1221w,
1190w, 1158w, 1131w, 1121w, 1090w, 1048w, 1025w, 953w, 835 m,
797w; δH(300 MHz, CDCl3) 8.51À8.46 (2H, m, Ar H), 8.33À8.30
(1H, m, Ar H), 8.26 (1H, dd, J 8.2, 1.5, Ar H), 7.87À7.81 (1H, ddd, J 8.7,
7.3, 1.5, Ar H), 7.66 (1H, ddd, J 8.3, 7.4, 1.2, Ar H), 7.62À7.51 (3H, m,
Ar H), 7.00 (1H, d, J 9.9, Ar H); δC(75 MHz, CDCl3) 180.1 (s), 146.9
(s), 138.8 (d), 138.4 (s), 133.9 (s), 133.2 (d), 132.3 (d), 131.5 (d), 128.8
(s), 128.7 (s), 126.9 (s), 126.3 (d), 125.9 (d), 125.5 (d), 123.3 (d), 115.4
(d), 115.1 (d), 108.4 (s); m/z (EI) 271 (M+ + 1, 20%), 270 (M+, 100),
+
242 (55), (12), 214 (13), 188 (6), 140 (6), 121 (12), 77 (C6H5 , 2).
4.7.3. 8H-Indolo[1,2,3-mn]phenazin-8-one (14) via Catalytic Non-
oxidative Coupling. To a stirred solution of 8,10-dihydro-1-iodo-10-
phenylphenazin-2(7H)-one (13) (39.8 mg, 0.1 mmol) in DMF (1 mL)
were added Pd(Ph3P)2Cl2 (3.5 mg, 0.005 mmol, 5 mol %) and AgF
(19 mg, 0.15 mmol), and the mixture was heated at 100 °C for 2 h. The
reaction mixture was diluted with Et2O (5 mL) and washed with H2O
(5 mL). The organic layer was separated, dried (Na2SO4), and evapo-
rated in vacuo. Dry flash chromatography (EtOAc) of the residue gave
the title compound 14 (21.7 mg, 80%) as pink-red crystals, identical to
that described above.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra for
S
b
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: koutenti@ucy.ac.cy.
’ ACKNOWLEDGMENT
The authors thank the Cyprus Research Promotion Founda-
tion [grant no. YGEIA/BIOS/0308(BIE)/13] and the following
organizations in Cyprus for generous donations of chemicals and
glassware: the State General Laboratory, the Agricultural Re-
search Institute and the Ministry of Agriculture, and the A. G.
Leventis Foundation for helping establish the NMR facility in the
University of Cyprus. Furthermore, we thank Prof. H.-J. Kn€olker
for suggesting the use of freshly recrystallized Pd(OAc)2.
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