Some cyclization reactions of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one: Preparation and computational analysis of non symmetrical zwitterionic biscyanines

Article abstract of DOI:10.1039/c1ob06622f

Regioselective nucleophilic addition of bisnucleophiles 1,2-benzenediamine, 2-amino-benzenethiol, and N-phenyl-1,2-benzenediamine to 1,3-diphenylbenzo[e] [1,2,4]triazin-7(1H)-one (1) at C6 followed by intramolecular cyclocondensation at the C7 carbonyl af

Full text of DOI:10.1039/c1ob06622f

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Some cyclization reactions of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one:
preparation and computational analysis of non symmetrical zwitterionic
biscyanines†
Theodosia A. Ioannou, Panayiotis A. Koutentis,* Harry Krassos, Georgia Loizou and Daniele Lo Re
Received 22nd September 2011, Accepted 3rd November 2011
DOI: 10.1039/c1ob06622f
Regioselective nucleophilic addition of bisnucleophiles 1,2-benzenediamine, 2-amino-benzenethiol, and
N-phenyl-1,2-benzenediamine to 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) at C6 followed by
intramolecular cyclocondensation at the C7 carbonyl afforded highly coloured tetracenes
1,3-diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-4-ium 4-methylbenzenesulfonate (12),
1,3-diphenyl-1H-[1,2,4]triazino[6,5-b]phenothiazine (14) and 1,3,11-triphenyl-1,6-dihydro-[1,2,4]-
triazino[5,6-b]phenazin-11-ium 4-methylbenzenesulfonate (15), respectively. Neutralization of the latter
with alkali gave the free base 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16).
Furthermore, the benzotriazinone 1 reacts with dimethyl malonate to give 6-(methoxycarbonyl)-7-oxo-
1,3-diphenyl-7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-ide (17) in 74% yield, while with S4N4 [5,6-c]-
thiadiazolo-7-oxo-1,3-diphenyl-1,2,4-benzotriazine (22) was formed in 15% yield. The free bases 16 and
17 display negative solvatochromism, which supports charge separated ground states similar to those of
zwitterionic biscyanines, and DFT calculations at the UB3LYP/6-31G(d) level afford DEST values of
-13.6 and -18.7 kcal mol-1, respectively that strongly favour the singlet ground state. All ring systems
described are new and fully characterized.
at the C8 position,4 however, direct condensations on the car-
1. Introduction
bonyl at C7 using primary amines or active methylenes failed.
1,3-Diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) is a potentially
Nevertheless, the ylidenemalononitrile 4 could be prepared in
useful heterocyclic scaffold that is highly coloured (lmax 544 nm),
and supports a quinonimine moiety. It was originally prepared
in low yield (1–5%) by Neugebauer et al.,1 preventing an in
depth study of its potentially rich chemistry. However, by treating
amidrazone 2 with KMnO4,2 or benzotriazinyl radical 3 with
MnO2,3 the benzotriazinone 1 can be prepared in high yields of 82
and 84%, respectively (Scheme 1).
low yield using either tetracyanoethene (TCNE) or tetracya-
noethylene oxide (TCNEO).4 Furthermore, oxidative and non-
oxidative silver-mediated palladium catalysed cyclizations at C8
afford the triazafluoranthenone 55 that is structurally similar to
the canthinone alkaloids6,7 (Scheme 2).
Scheme 1
Some chemistry of the benzotriazinone 1 has recently been
reported:4,5 benzotriazinone 1 undergoes nucleophilic addition re-
gioselectively at C6, and electrophilic substitution regio-selectively
Scheme 2
Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678
Nicosia, Cyprus. E-mail: koutenti@ucy.ac.cy
Tentatively, the failure to perform condensation chemistry at
the C7 carbonyl was attributed to the strong contribution of a
zwitterionic resonance form (Scheme 3).4
† Electronic supplementary information (ESI) available: 1H and 13C
NMR spectra for all new compounds and computational parameters for
compounds 16–18. See DOI: 10.1039/c1ob06622f
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while the red coloured 1,3-diphenyl-6-[2-(phenylamino)phenyl-
amino]-benzo[e][1,2,4]triazin-7(1H)-one (10) (lmax 430 nm)
was isolated from the reaction mixture of benzotriazinone 1
and N-phenylbenzene-1,2-diamine in a more moderate yield
(51%) (Table 1, entry 2). The reaction of benzotriazinone
1 with 2-aminobenzenethiol gave the brown coloured 6-(2-
aminothiophenyl)-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one
(11) (lmax 520 nm) in 99% yield (Table 1, entry 3).
Subsequent treatment of substituted benzotriazinones 9–11
withTsOH·H2O (1equiv.) inEtOH heated at reflux for 10 or 20 min
gave the expected cyclization products either as the tosylates
or, when treated with aqueous alkali, as the free bases. In the
absence of an alkali work up the reaction of benzotriazinone 9
with TsOH·H2O gave 1,3-diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-
b]phenazin-4-ium 4-methylbenzenesulfonate (12) that readily pre-
cipitated from the reaction mixture on cooling and was isolated
by filtration as deep blue needles (lmax 560 nm) in 78% yield.
Alkali (10% NaOH) treatment of this reaction mixture gave the
free base 1,3-diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazine
(13), giving correct elemental analysis, however, 1H and 13C NMR
spectroscopy in either CDCl3, DMSO-d6 or TFA-d1, failed to give
good spectra owing to poor solubility.
Scheme 3
In this paper we report a regioselective nucleophilic addition
of bisnucleophiles at C6 and their subsequent intramolecular
cyclocondensation at C7 to afford new fused heterocycles, two of
which support zwitterionic motifs. Furthermore, we demonstrate
a successful cycloaddition reaction across the C5–C6 double bond.
2. Results and discussion
Reactions with primary anilines
Intermolecular condensations of anilines or active methylenes
with benzotriazinone 1 failed to give the desired C7 condensation
products.4 Interestingly we had previously encountered similar dif-
ficulties in performing intermolecular condensation reactions with
3,5-dichloro-4H-1,2,6-thiadiazin-4-one 68 but found that reacting
the thiadiazinone with bisnucleophiles like 1,2-benzenediamine
(ortho-phenylenediamine) afforded the monochloro-monoamino-
thiadiazinone 7 which readily underwent intramolecular cyclo-
condensation to give the deep purple coloured quinazoline 8
(Scheme 4).9 In light of benzotriazinone’s regioselective nucle-
ophilic addition at C64 a similar strategy could also lead to in-
tramolecular condensations at the benzotriazinone’s C7 carbonyl.
Similar treatment of 6-(2-aminothiophenyl)-1,3-diphenyl-
benzo[e][1,2,4]triazin-7(1H)-one (11) with TsOH·H2O (1 equiv.),
followed by a basic work-up (10% NaOH) gave 1,3-diphenyl-
1H-[1,2,4]triazino[6,5-b]phenothiazine (14) as green needles (lmax
674 nm) in 82% yield (Scheme 5).
Scheme 5
Scheme 4
Ethanol solutions of benzotriazinone 1 were treated with a range
of bisnucleophiles (1,2-benzenediamine, N-phenylbenzene-
1,2-diamine and 2-aminobenzenethiol) and N-ethyl-N-isopropyl-
propan-2-amine (Hu¨nig’s base) (1.1 equiv.) and heated
to reflux. In the first three cases the expected C6 substituted
benzotriazinones 9–11 were obtained as highly coloured com-
pounds.The reaction of 1,2-benzenediamine gave the orange col-
oured 6-(2-amino-phenylamino)-1,3-diphenylbenzo[e][1,2,4]tri-
azin-7(1H)-one (9) (lmax 431 nm) in 75% yield (Table 1, entry 1),
On other hand, the reaction of 1,3-diphenyl-6-[2-(phenyl-
amino)phenylamino]benzo[e]-[1,2,4]triazin-7(1H)-one (10) with
TsOH·H2O (1 equiv.) in EtOH heated at ca. 78 ◦C for 10 min
gave 1,3,11-triphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-
11-ium 4-methylbenzenesulfonate (15) as blue needles (lmax
1
620 nm) in 99% yield. Elemental analysis and H NMR spec-
troscopy indicated that this compound co-crystallized with EtOH
in a ratio of compound : EtOH (2 : 1). By treating the reaction mix-
ture with a 10% solution of KOH, the free base 1,3,11-triphenyl-
1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16) could be iso-
lated as blue needles (lmax 635 nm) in 87% yield (Scheme 6).
Interestingly, this compound showed negative solvatochromism10
(Fig. 1) typical of zwitterionic biscyanines.11–18
Table 1 Reaction of benzotriazinone 1 with bisnucleophiles (2 equiv.)
and i-Pr2NEt (1.1 equiv.) in EtOH at ca. 78 ◦
C
A number of zwitterionic biscyanines have been reported in
the recent literature and all have been symmetrical,11–18 as such
this compound is a rare example of a non symmetrical biscyanine.
DFT studies [UB3LYP/6-31G(d)] indicated the molecule strongly
preferred the singlet over the possible triplet ground state (DEST
-13.6 kcal mol-1). The HOMO and LUMO are similar to those
reported for other zwitterionic biscyanines (Fig. 2) and a plot of
electrostatic surface potentials (ESP) supports the molecule being
charge separated as a biscyanine (Fig. 3).
Entry
R1
X
Time (h)
Yield (%)
1
2
3
H
Ph
H
NH
NH
SH
25
48
22
9 (75)
10 (51)
11 (99)
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Fig. 3 The electrostatic potential (ESP) mapped on the electron density
surface of 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide
(16) [DFT UB3LYP/6-31G(d)].
Scheme 6
Table 2 NICS (0) and NICS (1) values for rings A, B, C and D
calculated at the B3LYP/6-31G* level for the singlet ground state of the
[1,2,4]triazino[5,6-b]phenazine 16
A
B
C
D
NICS (0)
NICS (1)
-7.1
-8.3
4.8
0.3
-0.8
-3.5
8.7
3.4
Fig. 4 Compound numbering and selected bond lengths (pm).
aromaticity (HOMA)20 value for ring C (HOMA = 0.47) that is
based only on geometric parameters and indicated a low level
p-orbital overlap within ring C as expected for a zwitterion
biscyanine. HOMA is defined as a normalized sum of squared
deviations of bond lengths from the optimal value assumed for a
fully aromatic system and a fully aromatic system has a HOMA =
1 and a non-aromatic HOMA = 0.
Fig. 1 Correlation between solvent polarity ET(30)19 and the maxi-
mum p–p* absorption of 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]-
phenazin-11-ium-6-ide (16) (n = 8; r2 = 0.94; slope = -1.59).
The UV–vis spectrum of monoprotonated 1,3,11-triphenyl-
1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-11-ium 4-methylben-
zenesulfonate (15) (H+/EtOH, lmax 613 nm) showed a blue shift
of the low energy p–p* transitions (~10 nm) when compared to
the free base 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-
11-ium-6-ide (16) (EtOH, lmax 624 nm) (Fig. 5). Similar blue
shifts have been observed on mono and bis protonation of
zwitterionic quinoxalino[2,3-b]phenazines11,12 and we found that
careful addition of (37%) HCl to an EtOH solution of the free base
16 gave the monoprotonated species, which showed a very similar
UV–vis spectra (H+/EtOH, lmax 613 nm) to the p-toluenesulfonate
salt 15. Addition of an excess (69–72%) perchloric acid gave no
bisprotonation since the same UV–vis spectrum was recorded
[H+/EtOH, lmax 613 nm). The failure to bisprotonate in perchloric
acid differed from that of the quinoxalino[2,3-b]phenazines,11,12
indicating that the triazino system was by comparison less basic.
Fig.
2
HOMO (-4.35 eV) and LUMO (-2.25 eV) orbitals
of 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16)
[DFT UB3LYP/6-31G(d)].
Furthermore, bond length analysis of the DFT [UB3LYP/6-
31G(d)] computed ground state structure showed that the two
proposed cyanine fragments were separated by relatively long C–
C bonds (C5a–C11a, 146.6 and C4a–C12a, 145.9 pm) typical
of zwitterionic biscyanines (Fig. 4).11–18 Nucleus independent
chemical shift (NICS) values of the individual rings that comprise
the [1,2,4]triazino[5,6-b]phenazine 16 supported the central ben-
zene (ring C) being markedly less aromatic than the peripheral
arene [NICS (1) (ring A) -8.3 vs. NICS (1) (ring C) -3.5]
(Table 2).
Reactions with active methylenes
Our earlier work4 attempts to condense malononitrile with the
benzotriazinone 1 led to complex highly coloured reaction mix-
tures, from which no stable product could be isolated. Similar com-
plex reaction mixtures were obtained with another active methy-
lene ethyl 2-cyanoacetate, however, the reaction of benzotriazinone
1 with dimethyl malonate (1.04 equiv.) in the presence of Hu¨nig’s
However, since negative NICS (1) values are indicative of
aromaticity we also calculated the harmonic oscillator model of
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gave a correct elemental analysis for the formula C23H15N3O4,
which supported a molecular parent ion of m/z 397 Da (100%)
from EI mass spectrometry. FTIR spectroscopy indicated the
presence of a methyl ester group with a moderately strong carbonyl
stretch at n(C O) 1761 cm-1 and this was also supported by
1H and 13C NMR spectroscopy which showed the presence of
a single methoxy group at dH 3.92 ppm and dC 51.7 ppm.
Furthermore, NMR spectroscopy indicated the absence of the
H6 benzotriazinone hydrogen and the presence of at least 10
quaternary C signals. The data was in agreement with the proposed
fused furanone structure.
As such this compound was potentially an additional rare ex-
ample of a non symmetrical biscyanine. DFT studies [UB3LYP/6-
31G(d)] indicated the molecule strongly preferred the singlet
over the possible triplet ground state (DEST -18.7 kcal mol-1).
The HOMO and LUMO are similar to those reported for other
zwitterionic biscyanines (Fig. 7), however, the plot of electrostatic
surface potential (ESP) (Fig. 8) suggests considerable positive
charge is located at the triazine and that considerable negative
charge is located near the furanone.
Fig.
5
A comparison of the absorption spectra of the free
base 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16)
(lmax 624 nm) and the monoprotonated 1,3,11-triphenyl-1,6-dihydro-
[1,2,4]triazino[5,6-b]phenazin-11-ium 4-methylbenzenesulfonate (15)
(lmax 613 nm) in ethanol.
base (1 equiv.) gave 6-(methoxycarbonyl)-7-oxo-1,3-diphenyl-
7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-ide (17) in 74% yield
(Scheme 7).
Scheme 7
Fig. 7 HOMO (-6.61 eV) and LUMO (-3.36 eV) orbitals of 6-(methoxy-
carbonyl)-7-oxo-1,3-diphenyl-7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-
ide (17) [DFT UB3LYP/6-31G(d)].
6-(Methoxycarbonyl)-7-oxo-1,3-diphenyl-7H-benzofuro[5,6-e]
[1,2,4]triazin-1-ium-4-ide (17) is deep blue green in solution (lmax
629 nm) suggesting a high degree of conjugation and displayed
negative solvatochromism10 typical of a charge separated ground
state (Fig. 6).19 The compound crystallized as green needles and
Fig. 8 The electrostatic surface potential (ESP) mapped on the electron
density surface of 6-(methoxycarbonyl)-7-oxo-1,3-diphenyl-7H-benzofuro
[5,6-e][1,2,4]triazin-1-ium-4-ide (17) [DFT UB3LYP/6-31G(d)].
In light of the ESP data, the zwitterionic biscyanine motif may
not account fully for the structure of this zwitterion. An analysis
of the bond lengths and NICS values of the DFT [UB3LYP/6-
31G(d)] computed ground state structure showed somewhat
Fig.
6
Correlation between solvent polarity ET(30)19 and the
maximium p–p* absorption of 6-(methoxycarbonyl)-7-oxo-1,3-diphenyl-
7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-ide (17) (n = 8; r2 = 0.93; slope =
-2.42).
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Table 3 NICS (0) and NICS (1) values for rings A, B, and C calculated at
the B3LYP/6-31G* level for the singlet ground state of the benzofuro[5,6-
e][1,2,4]triazin-7(4H)-one 17
A
B
C
NICS (0)
NICS (1)
-5.2
-5.0
-6.1
-8.0
-3.3
-6.7
conflicting information: the two C–C bonds that separated the
possible cyanine fragments were separated by relatively long
C–C bonds (C5a–C8a, 145.4 and C4a–C9a, 147.0 pm) typical
of zwitterionic biscyanines.11–18 However, NICS values of the
individual rings that comprise the tricycle supported the central
benzene (ring B) being markedly aromatic [NICS (1) (ring B)
-8.0] and in contrast to the [1,2,4]triazino[5,6-b]phenazine 16
which had a non-aromatic triazine ring [Fig. 4, Table 2, NICS
(1) (ring D) +3.4] the NICS (1) value of the triazine ring of
the benzofuro[5,6-e][1,2,4]triazin-7(4H)-one 17 was clearly of
opposite sign and mildly aromatic [NICS (1) (ring C) -6.7] (Fig. 9,
Table 3).
Fig. 10 Dipole moments of 5,7-diphenylquinoxalino[2,3-b]phenazine
18, the [1,2,4]triazino[5,6-b]phenazine 16 and the benzofuro
[5,6-e][1,2,4]triazin-7(4H)-one 17 expressed as vectors orientated to
an imaginary y-axis to enable direct comparison. Charges are fitted to
the ESP calculated at the B3LYP/6-31G(d) level and constrained to
reproduce the dipole moment.21,22
contribution of a charge separated non-biscyanine resonance form
in compound 17 (cf. structure 17a) and only a minor one in
compound 16, in line with the calculated electrostatic surface
potentials (Fig. 3 and 8).
Fig. 9 Compound numbering and selected bond lengths (pm).
Interestingly, the reaction between dimethyl malonate and the
benzotriazinone 1 to give the benzofuro[5,6-e][1,2,4]triazin-7(4H)-
one 17 could occur via two different pathways: (Path A) the
dimethyl malonate could regioselectively add to the benzotriazi-
none at C6 to give intermediate 19 and subsequent intramolecular
cyclization could occur via the benzotriazinone carbonyl, which
was expected to be strongly nucleophilic owing to the strong con-
tribution of the benzotriazinone’s zwitterionic resonance forms; or
(Path B) the reverse could occur, with the dimethyl malonate react-
ing first with the carbonyl to give intermediate 20 followed by an
intramolecular cyclization onto the benzotriazinone C6 position
(Scheme 9).
As before, we calculated the HOMA20 value for the central arene
(HOMA, ring B = 0.48) which was similar to that determined for
the equivalent central arene in the [1,2,4]triazino[5,6-b]phenazine
16 (HOMA, ring C = 0.47) and supported a low level p-orbital
overlap within ring C as expected for a zwitterion biscyanine. In
light of this we propose that the benzofuro[5,6-e][1,2,4]triazin-
7(4H)-one 17 is probably best represented by the biscyanine motif
but that there may very well be a significant contribution of
resonance structure 17a (Scheme 8).
At this stage we are unable to differentiate between these two
mechanistic possibilities and this cyclization is now under further
investigation.
This new fused heterocycle has structural similarities with
benthocyanins 21 (Scheme 10) that act as inhibitors of lipid per-
oxidation in rat microsomes23 and also showed inhibitory effects
on rat erythrocyte hemolysis;24 as such the benzofurotriazine 17
and related compounds could also show promising biological
properties.
Scheme 8
As a final consideration of the nature of the charge separation
in compounds 17 we calculated and compared the dipoles
(magnitude and vector) for both zwitterions 16 and 17 from the
computational structures (Fig. 10).
Reaction of benzotriazinone 1 with S4N4
Perfectly symmetrical zwitterionic biscyanines such as the
5,7-diphenylquinoxalino[2,3-b]phenazine 1811,12 are expected to
have a dipole moment that lines up with the y-axis (Fig. 10),
and contributions of non-biscyanine charge separated resonance
forms such as that depicted in structure 17a should lead to
the dipole moment deviating from the y-axis. As can be seen,
the calculated dipole moments of both structures 16 and 17
(Fig. 10) deviate from the y-axis, the former showing only a
minor deviation, and the latter showing a considerable devia-
tion. This adds further support for there being a reasonable
To check if the double bond between C5 and C6 on the
benzotriazinone 1 was susceptible to cycloaddition reactions,
benzotriazinone 1 was reacted with various enophiles: the reaction
with phenyl azide gave only complex mixtures, while N,N¢-
bis(trimethylsilyl)sulfur diimide in DMF at ca. 100 ◦C for 12 h gave
only 6-aminobenzotriazinone and unreacted starting material (by
TLC). Fortunately, the reaction of benzotriazinone 1 with S4N4
(5 equiv.) in DMF at reflux 1 h gave the cyclized [5,6-c]thiadiazolo-
7-oxo-1,3-diphenyl-1,2,4-benzotriazine (22) (15%) together with
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Scheme 9
3. Conclusions
1,3-Diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) reacts with bis-
nucleophiles, 1,2-benzenediamine, 2-aminobenzenethiol and
N-phenyl-1,2-benzenediamine, regioselectively at C6 and
these adducts on treatment with TsOH·H2O undergo
intramolecular cyclocondensation at the C7 carbonyl to
afford highly coloured tetracenes 1,3-diphenyl-1,6-dihydro-
[1,2,4]triazino[5,6-b]phenazin-4-ium 4-methylbenzenesulfonate
(12), 1,3-diphenyl-1H-[1,2,4]triazino[6,5-b]phenothiazine (14) and
1,3,11-triphenyl-1,6-dihydro[1,2,4]triazino-[5,6-b]phenazin-11-
ium 4-methylbenzenesulfonate (15), respectively. Neutralization
of the latter with alkali gave the free base 1,3,11-triphenyl-
1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16). A similar
cyclo-condensation reaction occurred between dimethyl malonate
and benzotriazinone 1 affording 6-(methoxycarbonyl)-7-oxo-
1,3-diphenyl-7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-ide (17)
in 74% yield. Finally, an intermolecular cycloaddition across
the C5–C6 bond of benzotriazinone 1 with S4N4 gave [5,6-
c]thiadiazolo-7-oxo-1,3-diphenyl-1,2,4-benzotriazine (22) in
15% yield. The free bases 16 and 17 are zwitterions and DFT
calculations at the UB3LYP/6-31G(d) level afford DEST values of
-13.6 and -18.7 kcal mol-1, respectively that strongly favour the
singlet ground state.
Scheme 10
6-amino-1,2,4-benzotriazinone 23 in 48% yield (Scheme 11). The
alternative use of PhCl or xylene as solvents gave very complex
reactions, while with PhMe only starting material was recovered
from the reaction.
Scheme 11
Compound 22 was brown in solution (lmax 541 nm), tentatively
indicating the extensive conjugation of the starting quinonimine
had been maintained, and was isolated as brown needles that gave
a correct elemental analysis for the formula C19H11N5OS, which
supported a molecular parent ion of m/z 357 Da (47%) from
4. Experimental
4.1. Computational procedure
EI mass spectrometry. H and 13C NMR spectroscopy indicated
1
the absence of the H5 and H6 benzotriazinone hydrogens and
the replacement of two aromatic CH for two quaternary C
assignments supporting functionalization at the C5 and C6 carbon
positions. The data was in agreement with the proposed fused
1,2,5-thiadiazole structure.
The mechanism of the reaction of S4N4 with activated double
and triple bonds is based on the reagent’s ability to cyclo-add
and subsequently fragment to give thermodynamically stable het-
eroarenes such as 1,2,5-thiadiazoles.25,26 Rees and Daley27,28 have
conducted extensive studies on these reactions. It is known29 that in
the reactions with S4N4, elemental sulfur and ammonia are nearly
always formed as side products and the presence of the latter could
explain the formation of the 6-aminobenzotriazinone 23, which
can be prepared directly from ammonia and benzotriazinone 1.4
The geometries of the singlet and triplet states of molecules 16–
18 were fully optimized, and analytical second derivatives were
computed using vibrational analysis to confirm each stationary
point to be a minimum by yielding zero imaginary frequencies
at the UB3LYP/6-31G(d) level of theory. The possibility of
internal instability in the singlet wave function was investigated
using stability calculations. All the energies were corrected after
zero-point energies (ZPE) were scaled by 0.981.30 All the above
computations were performed using the Gaussian 03 suite of
programs.31
Nucleus independent chemical shifts (NICS) were evaluated by
using the gauge invariant atomic orbital32 (GIAO) approach, at the
B3LYP/6-31G* level. The NICS probes (bq’s) were placed above
˚
the geometric centers of the systems at each ring at distances 0.0 A
1344 | Org. Biomol. Chem., 2012, 10, 1339–1348
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˚
(i.e., at the center of the molecular plane) and 1.0 A perpendicular
to the molecular plane.
mg, 75%) as orange needles, mp 278–282 ◦C (from PhCl); Rf 0.23
(t-BuOMe); (found: C, 74.0, H, 4.6; N, 17.2. C25H19N5O requires
C, 74.1; H, 4.7; N, 17.3%); lmax(DCM)/nm 229 (log e 3.46), 277 inf
(3.52), 300 (3.53), 330 inf (3.28), 431 (3.10); nmax/cm-1 3194m (Ar
NH), 1631m, 1568m, 1542s, 1516m, 1489s, 1473m, 1455m, 1448m,
1393m, 1379m, 1313m, 1299m, 1272m, 990m, 766m, 747s; dH(300
MHz, TFA-d1) NH and NH2 exchanged 8.18 (2H, d, J 7.7), 7.77–
7.62 (9H, m), 7.57–7.52 (1H, m), 7.45 (2H, dd, J 7.5, 7.5), 7.18
(2H, dd, J 5.5, 5.1); dC(75 MHz; TFA-d1) 160.9 (C O), 159.4 (s),
152.7 (s), 150.1 (s), 142.2 (s), 138.3 (s), 138.2 (s), 135.1 (d), 134.4
(d), 133.8 (d), 132.8 (d), 131.9 (d), 131.5 (s), 130.8 (d), 130.2 (d),
129.5 (d), 127.1 (s), 127.0 (d), 126.5 (d), 101.8 (d), 100.5 (d); m/z
(EI) 406 (M++1, 12%), 405 (M+, 39), 388 (100), 300 (11), 180 (13),
104 (7), 77 (36), 65 (12), 51 (10).
HOMA20 values for an all carbon system were calculated using
eqn (1), where 257.7 is the normalization value, n = number of
C–C bonds, dopt = the optimized bond length (138.8 pm)20 and di =
the computed bond length from DFT calculations performed at
the UB3LYP/6-31G(d) level of theory.
n
(1)
HOMA = 1−257.7/n
(dopt −di )2,
∑
i
Dipole moments of [1,2,4]triazino[5,6-b]phenazine 16 and
benzofuro[5,6-e][1,2,4]triazin-7(4H)-one 17 and 5,7-diphenyl-
quinoxalino[2,3-b]phenazine 18 are expressed as vectors, after
ESP calculation on G03 at B3LYP/6-31G(d) level of theory to
produce charges fit to the electrostatic potential at points selected
according to the Merz-Singh-Kollman scheme21,22 and constrain
them to reproduce the dipole moment [pop = (MK, dipole)]. The
dipole moment vectors are visualized using GaussView 5.
4.3.2. 1,3-Diphenyl-6-[2-(phenylamino)phenylamino]benzo[e]-
[1,2,4]triazin-7(1H)-one (10). To a stirred solution of 1,3-
diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) (100 mg, 0.33 mmol)
in EtOH (4 ml), at ca. 20 ◦C, protected with a CaCl2 drying
tube, N-phenylbenzene-1,2-diamine (123 mg, 0.67 mmol) and
Hu¨nig’s base (64.7 ml, 0.37 mmol) were added and the reaction
mixture was refluxed for 48 h until no starting material remained
(TLC). The reaction mixture was then diluted (DCM, 25 ml) and
washed (5% HCl, 25 ml) to remove unreacted amine. The organic
layer was separated, dried (Na2SO4) and adsorbed onto silica.
Chromatography (t-BuOMe–DCM–hexane, 1 : 6 : 3) gave the title
compound 10 (58.8 mg, 51%) as red needles, mp 243–245 ◦C
(from PhH), Rf 0.80 (t-BuOMe); (found C, 77.4; H, 4.6; N, 14.4.
C31H23N5O requires C, 77.3; H, 4.8; N, 14.5%); lmax(DCM)/nm
234 (log e 3.39), 289 (3.62), 345 inf (3.06), 430 (3.22), 465 inf (3.20);
4.2. General methods and materials
Solvents: DMF was azeotropically distilled with PhH then distilled
under vacuum from anhydrous MgSO4 and stored over 4 A
˚
molecular sieves. Reactions were protected by CaCl2 drying
tubes. Decomposition points (decomp.) and mp >250 ◦C were
determined using a TA Instruments DSC Q1000 with samples
hermetically sealed in alumini◦um pans under an argon atmo-
sphere, using heating rates of 5 C min-1. 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 chromatographic separations using silica gel 60 (less than
0.063 mm).33 Melting points were determined using a hotstage
microscope apparatus. Solvents used for recrystallization are
indicated after the melting point. Inflections in the UV spectra are
identified by the abbreviation “inf”. FTIR spectra were recorded
using a Ge ATR accessory and strong, medium and weak peaks
are represented by s, m and w respectively. 1H 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.
n
max/cm-1 3200m (N–H), 3065w (Ar CH), 1589m, 1568m, 1549m,
1541m, 1514m, 1487s, 1456m, 1447m, 1396m, 1377m, 1315m,
1290m, 1277m, 989m, 745m, 714m; dH(300 MHz, CDCl3) 8.30
(1H, br s, NH), 8.26–8.22 (2H, m), 7.62–7.54 (5H, m), 7.48–7.40
(5H, m), 7.29–7.23 (3H, m), 7.08–7.02 (3H, m), 6.98–6.93 (2H,
m), 6.19 (1H, s), 5.94 (1H, br s, NH); dC(75 MHz, CDCl3) one Ar
C missing 173.4 (C O), 153.1 (s), 152.6 (s), 150.1 (s), 142.5 (s),
141.8 (s), 138.9 (s), 136.2 (s), 135.2 (s), 130.3 (d), 130.2 (d), 130.1
(d), 129.5 (d), 128.7 (d), 127.7 (d), 127.1 (d), 126.1 (d), 125.4 (d),
122.0 (d), 121.5 (d), 119.3 (d), 118.1 (d), 98.7 (d), 94.6 (d); m/z
(EI) 482 (M++1, 6%), 481 (M+, 15), 464 (100), 389 (9), 207 (9), 180
(7), 167 (6), 77 (25), 51 (6).
4.3.3. 6 - (2 - Aminothiophenyl) - 1,3 - diphenylbenzo[e][1,2,4]-
triazin-7(1H)-one (11). To
a
stirred solution of 1,3-
diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) (107.2 mg, 0.36
mmol) in EtOH (4 ml), Hu¨nig’s base (69 ml, 0.39 mmol) and
2-aminothiophenol (89.8 mg, 0.72 mmol) were added and the
mixture was heated at reflux for 22 h. The reaction mixture
was then allowed to cool to ca. 20 ◦C and the precipitate was
filtered and recrystallized to afford the title compound 11 (149.1
mg, 99%) as brown needles, mp >300 ◦C (from PhCl), Rf
0.34 (t-BuOMe–hexane, 3 : 1); (found: C, 71.2; H, 4.2; N, 13.2.
C25H18N4OS requires C, 71.1; H, 4.3; N, 13.3%); lmax(DCM)/nm
234 (log e 3.52), 271 inf (3.43), 323 (3.53), 413 (3.15), 520 (2.73),
566 inf (2.68), 602 inf (2.49); nmax/cm-1 3335w (Ar NH), 3201w
(Ar NH), 3057w (Ar CH), 1588s, 1576s, 1554m, 1524s, 1511s,
1497s, 1492m, 1483m, 1452m, 1372m, 1314s, 1197m, 1142m,
1004s, 864m, 845m, 838m, 821m, 815m, 778m, 750s, 728m; dH(300
MHz, TFA-d1) NH2 exchanged 8.32 (2H, d, J 8.0), 7.94–7.67 (9H,
4.3. Substitution at benzotriazinone C-6 position
4.3.1. 6 - (2 - Aminophenylamino) - 1,3 - diphenylbenzo[e][1,2,4]-
triazin-7(1H)-one (9). To a stirred solution of 1,3-diphenyl-
benzo[e][1,2,4]triazin-7(1H)-one (1) (214 mg, 0.72 mmol) in EtOH
(8 ml), Hu¨nig’s base (136 mL, 0.79 mmol) and phenylenediamine
(155.5 mg, 1.44 mmol) were added and the reaction mixture
was heated at reflux for ◦25 h. The reaction mixture was then
allowed to cool to ca. 20 C and the precipitate was filtered and
washed with cold hexane to afford the title compound 9 (216.4
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m), 7.56–7.43 (3H, m), 7.40 (1H, s), 7.31 (1H, s); dC(75 MHz,
TFA-d1) 164.1 (s), 163.0 (s), 152.3 (s), 151.3 (s), 142.2 (s), 140.6
(d), 138.2 (s), 135.8 (d), 135.2 (d), 134.7 (d), 134.3 (d), 133.6 (s),
132.8 (s), 132.0 (d), 130.7 (d), 129.7 (d), 127.4 (d), 126.5 (d), 126.2
(d), 122.7 (s), 99.6 (d); m/z (EI) 422 (M+, 22%), 420 (M+-2, 39),
405 (33), 389 (60), 299 (35), 271 (21), 211 (10), 168 (17), 125 (74),
97 (14), 93 (25), 84 (22), 77 (100), 65 (18), 63 (25), 56 (26), 51 (37).
requires C, 74.2; H, 4.0; N, 13.9%); lmax(DCM)/nm 245 (log e
3.42), 304 (3.52), 315 inf (3.49), 349 inf (3.18), 399 inf (2.80),
463 inf (2.89), 488 (2.58), 517 (3.15), 674 (2.52), 623 inf (2.56);
n
max/cm-1 3065w (Ar CH), 1591m, 1518s, 1493m, 1476m, 1452s,
1310m, 972m, 862m, 847m, 781m; dH(300 MHz, TFA-d1) 7.96
(2H, d, J 8.8), 7.82 (1H, br s), 7.73–7.61 (5H, m), 7.53–7.47 (3H,
m), 7.43–7.32 (2H, m), 7.26–7.20 (2H, m), 6.70 (1H, br s); dC(75
MHz, TFA-d1) 154.1 (s), 153.8 (s), 146.9 (s), 143.9 (s), 143.3 (s),
141.2 (s), 135.7 (d), 135.1 (d), 134.3 (d), 133.6 (s), 132.2 (d), 131.0
(d), 130.8 (d), 128.7 (s), 128.5 (d), 127.9 (d), 125.8 (d), 122.0 (s),
122.0 (d), 115.2 (d), 96.8 (d); m/z (EI) 405 (M++1, 39%), 404 (M+,
100), 196 (25), 77 (23), 51 (11).
4.4. Intramolecular cyclocondensation reactions
4.4.1. 1,3-Diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-
4-ium 4-methylbenzenesulfonate (12). To a stirred solution of
6-(2-aminophenylamino) - 1,3 - diphenylbenzo[e] - [1,2,4]triazin-
7(1H)-one (9) (150 mg, 0.37 mmol) in EtOH (5 ml), TsOH·H2O
was added (70.0 mg, 0.37 mmol) and the mixture heated at reflux
for 10 min. The volatiles were removed in vacuo and the residue
crystallized to afford the title compound 12 (160.9 mg, 78%) as
blue needles, mp >300 ◦C (from DCM–MeOH, 1 : 2), Rf 0.31
(t-BuOMe); (found: C, 68.8; H, 4.4; N, 12.4. C32H25N5O3S requires
C, 68.7; H, 4.5; N, 12.5%); lmax(DCM)/nm 229 (log e 3.45), 242
inf (3.40), 297 (3.72), 560 (3.43), 620 inf (3.09); nmax/cm-1 3063w
(Ar CH), 1524s, 1504s, 1493m, 1391m, 1333m, 1151s, 1123m,
1030m, 1007s, 872m, 854m, 797m; dH(300 MHz, TFA-d1) NH
exchanged 7.77 (2H, d, J 7.7), 7.65–7.43 (12H, m), 7.39–7.31 (3H,
m), 7.17 (2H, d, J 7.9), 6.46 (1H, s, H-12), 3.00 (3H, s, CH3);
dC(75 MHz, TFA-d1) 151.1 (C O), 146.2 (s), 146.0 (s), 145.3 (s),
144.6 (s), 142.8 (s), 141.1 (s), 138.4 (s), 135.4 (d), 134.4 (d), 133.7
(d), 132.5 (d), 132.2 (d), 131.5 (s), 131.0 (d), 130.9 (d), 129.6 (s),
128.0 (s), 128.0 (d), 127.2 (d), 126.0 (d), 120.6 (d), 119.8 (d), 99.5
(d), 95.5 (d), 21.2 (CH3); m/z (EI) 388 (M++1, 34%), 387 (M+,
100), 310 (7), 296 (7), 283 (13), 128 (9), 77 (16).
4.4.4. 1,3,11-Triphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phe-
nazin-11-ium 4-methylbenzenesulfonate (15). To
a
stirred
solution of 6-[2-(N-phenylamino)anilino]-1,3-diphenyl-
benzo[e][1,2,4]triazin-7(1H)-one (10) (54.7 mg, 0.11 mmol)
in EtOH (3 ml), TsOH·H2O (19.5 mg, 0.11 mmol) was added and
the mixture heated at reflux for 15 min. The reaction mixture was
cooled to 0 ◦C and then filtered to give the title compound 15 (69.0
◦
mg, 99%) as blue needles, mp 245–248 C (from EtOH), Rf 0.57
(t-BuOMe); (found: C, 71.0, H, 4.8, N, 10.6. C38H29N5O3S·1/2
EtOH requires C, 71.1; H, 4.9; N, 10.6%); lmax(DCM)/nm 308
(log e 3.77), 320 inf (3.67), 401 (2.61), 534 inf (3.17), 574 (3.50),
620.1 (3.59); lmax(EtOH)/nm 305 (log e 4.11), 428 (3.06), 530
inf (3.50), 569 (3.80), 613 (3.86); nmax/cm-1 3414w (NH), 3061w
(Ar CH), 1514s, 1499m, 1468m, 1393m, 1161m, 1121m, 1034m,
1007m; dH(300 MHz, CDCl3) 13.09 (1H, s, NH), 8.06 (2H, d, J
7.1), 7.86 (2H, d, J 8.0), 7.62 (2H, dd, J 7.5, 7.5), 7.52–7.34 (12H,
m), 7.14 (2H, d, J 7.9), 7.07 (1H, s), 6.75 (1H, dd, J 7.2, 7.2),
6.55 (1H, dd, J 7.5, 7.5), 6.07 (1H, d, J 8.1), 5.31 (1H, s, H-12),
3.71 (1H, q, J 7.0, CH3CH2OH), 2.32 (3H, s, CH3), 1.23 (1.5H,
t, CH3CH2OH); dC(75 MHz; CDCl3) one Ar C missing 159.3 (s),
154.4 (s), 145.4 (s), 144.3 (s), 143.5 (s), 140.3 (s), 139.6 (s), 138.8
(s), 135.8 (s), 133.7 (s), 131.8 (d), 131.5 (d), 130.9 (d), 130.6 (d),
130.4 (s), 130.0 (d), 128.9 (d), 128.6 (d), 128.1 (d), 127.6 (d), 127.5
(d), 126.4 (d), 125.8 (d), 125.2 (d), 118.5 (d), 116.5 (d), 102.9 (d),
92.3 (d), 21.6 (CH3); m/z (EI) 464 (M++1, 33%), 463 (M+, 100),
386 (8), 372 (8), 255 (23), 231 (8), 178 (6), 128 (11), 77 (22).
4.4.2. 1,3-Diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phena-
zine (13). To a stirred solution of 6-(2-aminophenylamino)-
1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (9) (55.3 mg, 0.136
mmol) in EtOH (4 ml), TsOH·H2O was added (26.0 mg, 0.137
mmol) and the mixture heated at reflux for 10 min, then cooled
◦
to ca. 20 C and poured into iced water (20 ml). The precipitate
that formed (44.3 mg) was filtered, dissolved in DCM (20 ml)
and washed with NaOH 10% (15 ml). The organic layer was
dried (Na2SO4), filtered and concentrated in vacuo to give the
title compound 13 (22.8 mg, 43%) as blue needles, mp >300 ◦C
(from PhH); (found: C, 77.4; H, 4.4; N, 18.0. C25H17N5 requires
C, 77.5; H, 4.4; N, 18.1%); lmax(DCM)/nm 253 (log e 3.92), 290
(3.97), 514 (3.60), 612 inf (2.87) nmax/cm-1 1569m, 1516m, 1490m,
1449s, 1332m, 1321m, 890m, 772m, 753m; m/z (EI) 388 (M++1,
4.4.5. 1,3,11-Triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-
ium-6-ide (16). To
a stirred solution of 6-[2-(N-phenyl-
amino)anilino]-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (10)
(64 mg, 0.12 mmol) in EtOH (3 ml), TsOH·H2O (22.8 mg; 0.12
mmol) was added and the mixture heated at reflux for 20 min.
On cooling to ca. 20 ◦C the reaction mixture was then diluted
(DCM, 30 ml) and washed (10% KOH, 15 ml). The organic
layer was separated, dried (Na2SO4) and evaporated in vacuo. The
residue obtained was triturated (DCM–MeOH 1 : 3) to give the
title compound 16 (55.1 mg; 87%) as blue needles, mp >300 ◦C
(from PhH), Rf 0.30 (t-BuOMe); (found: C, 80.3, H, 4.4, N, 15.0.
C31H21N5 requires C, 80.3; H, 4.6; N, 15.1%); lmax(CCl4)/nm 407
(2.31), 426 (log e 2.40), 480 (2.18), 513 (2.18), 564 inf (2.26), 607
(2.39), 657 (2.37); lmax(PhMe)/nm 307 (log e 2.86), 316 (2.78),
403 (2.33), 426 (2.43), 478 (2.22), 510 (2.23), 556 inf (2.28), 601
(2.43), 650 (2.40); lmax(1,4-dioxane)/nm 307 (log e 3.44), 313 inf
(3.37), 403 inf (2.80), 426 (2.92), 477 (2.63), 508 (2.67), 550 inf
(2.76), 593 (2.98), 643 (2.95); lmax(CHCl3)/nm 306 (log e 3.70),
406 inf (3.02), 427 (3.13), 477 (2.81), 508 (2.80), 550 inf (3.02),
591 (3.29), 637 (3.29); lmax(DCM)/nm 307 (log e 3.97), 404 inf
25%), 387 (M+, 100), 103 (19), 77 (C6H5 , 42), 71 (14), 69 (17), 57
+
(18), 55 (19), 51 (15).
4.4.3. 1,3 - Diphenyl - 1H - [1,2,4]triazino[6,5 - b]phenothiazine
(14). To a solution of 6-(2-aminophenylthio)-1,3-diphenyl-
benzo[e][1,2,4]triazin-7(1H)-one (11) (155.5 mg, 0.37 mmol) in
EtOH (9 ml) TsOH·H2O (72.0 mg, 0.38 mmol) was added and the
mixture was heated at reflux for 20 min then cooled to ca. 20 ◦C
and poured into iced water (20 ml). The precipitate that formed
was filtered, dissolved in DCM (25 ml) and washed with NaOH
10% (20 ml). The organic layer was dried (Na2SO4), filtered and
concentrated in vacuo to give the title compound 14 (121.3 mg,
82%) as green needles, mp 256–260 ◦C (from PhCl), Rf 0.84 (t-
BuOMe–hexane, 3 : 1); (found: C, 74.3; H, 4.1; N, 14.0. C25H16N4S
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(3.27), 426 (3.39), 477 (3.09), 506 (3.12), 548 inf (3.29), 590 (3.55),
635 (3.55); lmax(MeCN)/nm 304 (log e 3.51), 402 inf (2.83), 425
(2.93), 476 (2.68), 505 (2.74), 541 inf (2.85), 584 (3.09), 628 (3.08);
material was consumed (by TLC). The mixture was allowed to
cool to ca. 20 ◦C, diluted with DCM and washed with H2O. The
organic layer was separated, dried and loaded on silica. Dry flash
chromatography (ether–DCM, 1 : 1) gave the title compound 22 (7
mg, 15%) as brown crystals, mp 285–290 ◦C (from PhCl); (found:
C, 63.9; H, 3.1; N, 19.7. C19H11N5OS requires C, 63.9; H, 3.1;
N, 19.6%); lmax(DCM)/nm 271 (log e 3.69), 309 (3.81), 407 (3.39),
541 (2.73); nmax/cm-1 1619s (C O), 1601m, 1589m, 1573m, 1520s,
1505s, 1489m, 1464m, 1454m, 1438m, 1412m, 1354m, 1250m,
1239s, 1160m, 1153m, 904m, 855m, 833s, 826s, 796m, 790m, 782s,
770s; dH(300 MHz; CDCl3) 8.42–8.32 (2H, m), 7.70–7.57 (5H, m),
7.57–7.48 (3H, m), 6.25 (1H, s, H-5); dC(75 MHz; CDCl3) 173.1
(C O), 157.8 (s), 152.7 (s), 150.8 (s), 150.0 (s), 141.2 (s), 139.8 (s),
132.9 (s), 131.2 (d), 130.5 (d), 130.4 (d), 128.9 (d), 127.0 (d), 124.9
(d), 98.3 (d); m/z (EI) 358 (M++1, 15%), 357 (M+, 47), 340 (13),
l
max(EtOH)/nm 303 (log e 3.48), 406 (2.79), 427 (2.86), 476 (2.60),
541 inf (2.82), 583 (3.09), 624 (3.10); lmax(MeOH)/nm 302 (log e
3.43), 404 (2.72), 426 (2.78), 475 (2.59), 537 inf (2.81), 574 (3.07),
615 (3.09); lmax(H+/EtOH)/nm 305 (log e 3.88), 368 (2.75), 527
inf (3.29), 567 (3.61), 613 (3.67); nmax/cm-1 3049w, 1514s, 1393m;
dH(300 MHz; TFA-d1) 7.27 (2H, d, J 7.4), 7.07–7.01 (5H, m), 6.97–
6.84 (7H, m), 6.79–6.76 (3H, m), 6.71–6.68 (2H, m), 6.20 (1H, d, J
7.9), 5.17 (1H, s, H-12); dC(75 MHz; TFA-d1) 151.8 (s), 146.3 (s),
145.1 (s), 144.5 (s), 144.4 (s), 140.8 (s), 136.0 (s), 135.9 (d), 134.7
(s), 134.4 (d), 133.8 (d), 133.6 (d), 133.5 (d), 132.4 (d), 131.8 (d),
131.0 (d), 129.8 (s), 128.0 (d), 127.7 (s), 127.7 (d), 125.6 (d), 121.1
(d), 119.7 (d), 99.2 (d), 96.7 (d); m/z (EI) 464 (M++1, 32%), 463
(M+, 100), 255 (24), 232 (12), 178 (7), 77 (36).
+
226 (24), 174 (13), 142 (19), 103 (29), 86 (14), 77 (C6H5 , 100), 63
(14), 51 (55). Further elution (ether) gave the orange 6-amino-1,3-
4.4.6. 6 - (Methoxycarbonyl) - 7 - oxo - 1,3 - diphenyl-7H-benzo-
furo[5,6-e][1,2,4]triazin-1-ium-4-ide (17). To a stirred solution
of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) (50 mg, 0.167
mmol) in MeOH (1.5 ml), dimethyl malonate (20 ml, 0.174 mmol)
and Hu¨nig’s base (28 ml, 0.167) were added. The mixture was
refluxed for 6 h. TLC (t-BuOMe–hexane, 3 : 1) showed the absence
of the starting material and the presence of a new less polar green
product. Dry flash chromatography (t-BuOMe–hexane, 2 : 1) of
the residue gave the title compound 17 (49 mg, 74%) as green
needles, mp 272–268 ◦C (DCM–MeOH, 1 : 3), Rf 0.29 (t-BuOMe–
hexane, 3 : 1); (found: C, 69.5; H, 3.7; N, 10.6. C23H15N3O4 requires
C, 69.5; H, 3.8; N, 10.6%); lmax(CCl4)/nm 282 (log e 3.20), 297 inf
(3.09), 357 (2.98), 376 (2.94), 432 (2.44), 457 (2.47), 554 inf (2.40),
600 (2.51), 651 (2.52), 732 inf (2.37); lmax(PhMe)/nm 358 (log e
3.24), 374 (3.23), 429 (2.66), 457 (2.74), 550 inf (2.62), 592 inf
(2.80), 645 (2.88), 711 inf (2.74); lmax(1,4-dioxane)/nm 280 (log
e 3.45), 297 inf (3.33), 353 (3.27), 368 (3.27), 419 inf (2.65), 449
(2.74), 580 inf (2.81), 628 (2.88), 688 inf (2.75); lmax(CHCl3)/nm
280 (log e 3.44), 298 inf (3.33), 354 (3.27), 366 (3.27), 427 inf (2.69),
453 (2.80), 585 (2.80), 635 (2.86), 698 inf (2.74); lmax(DCM)/nm
279 (log e 3.40), 298 inf (3.29), 353 (3.22), 364 (3.21), 429 inf
(2.64), 452 (2.74), 586 inf (2.75), 629 (2.81), 686 inf (2.69);
diphenylbenzo[e][1,2,4]triazin-7-(1H)–one (23) (20 mg, 48%) mp
◦
279–282 C (lit.,4 279–282 ◦C) (from PhH), Rf 0.21 (t-BuOMe–
hexane, 3 : 1); (found: C, 72.7; H, 4.4; N, 17.9. C19H14N4O requires
C, 72.6; H, 4.5; N, 17.8%); lmax(DCM)/nm 274 (log e 3.49), 302
inf (3.46), 312 (3.48), 332 inf (3.29), 401 inf (3.25), 417 (3.30), 504
(2.60); nmax/cm-1 3416w (Ar NH), 1581m, 1566m, 1555s, 1541s,
1491m, 824m; dH(300 MHz; TFA-d1) NH peak missing 8.09 (2H,
d, J 7.6), 7.78–7.64 (7H, m), 7.58–7.48 (3H, m); m/z (EI) 315
(M++1, 23%), 314 (M+, 100), 286 (12), 104 (13), 77 (100), 51 (61)
identical to an authentic sample.
Acknowledgements
The authors wish to thank Dr Antreas Afantitis (Novamechanics
Ltd, Nicosia) for generating the pictures of the dipole mo-
ment (Fig. 10) using GaussView 5, the University of Cyprus
(Medium Sized Grant), the Cyprus Research Promotion Foun-
dation [Grant Nos NEAYPODOMH/NEKYP/0308/02 and
YCEIA/bIOR/0308(bIE)/13] and the following organizations in
Cyprus for generous donations of chemicals and glassware: the
State General Laboratory, the Agricultural Research Institute,
the Ministry of Agriculture and Biotronics Ltd. Furthermore, we
thank the A. G. Leventis Foundation for helping to establish the
NMR facility in the University of Cyprus.
l
max(MeCN)/nm 275 (log e 3.42), 295 inf (3.34), 352 (3.29), 444
(2.82), 606 (2.89); lmax(EtOH)/nm 277 (log e 3.42), 295 inf (3.32),
351 (3.27), 444 (2.83), 600 (2.86); lmax(MeOH)/nm 257 inf (log e
3.50), 276 (3.58), 295 inf (3.47), 348 (3.44), 443 (3.01), 594 (3.03);
n
max/cm-1 3065w, 1761m, 1468s, 1421s, 1396m, 1261m, 1217m,
References
1144m, 982m, 781m; dH(300 MHz, CDCl3) 8.44 (2H, dd, J 7.8,
1.6), 8.09 (1H, s), 7.80–7.75 (3H, m), 7.71–7.68 (2H, m), 7.58–7.51
(3H, m), 6.92 (1H, s, H-9), 3.92 (OCH3); dC(75 MHz, CDCl3) one
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