Redox Active Quinoidal 1,2,4-Benzotriazines

Article abstract of DOI:10.1021/acs.joc.8b01311

Modifying the para-quinonimine 1,3-diphenyl-1,2,4-benzotriazin-7(1H)-one (2a) (E_1/2^-1/0 -1.20 V), by replacing the N1-phenyl by pentafluorophenyl, the C3-phenyl by trifluoromethyl, or the C7 carbonyl by ylidenemalononitrile, led to improved electron affinities as determined by cyclic voltammetry and computational studies. Combining structural changes further improved electron accepting abilities: the most electron deficient analogues (E_1/2^-1/0 ～ -0.65 V) involved combining the ylidenemalononitrile groups at C7 with the trifluoromethyl groups at C3. 1,2,5-Thiadiazolo fusion at C5-C6 did not affect the redox behavior but did enhance the UV-vis absorption profile. During the synthesis of the thiadiazolo analogues, 1,4-thiazino-fused analogues 6 were obtained in low yield, which thermally ring contract to the triazafluoranthenones 7. Compounds are fully characterized, and X-ray data are provided for selected analogues.

Full text of DOI:10.1021/acs.joc.8b01311

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Article
Redox Active Quinoidal 1,2,4-Benzotriazines
Georgia A. Zissimou, Andreas Kourtellaris, Maria Manoli, and Panayiotis A. Koutentis
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01311 • Publication Date (Web): 25 Jun 2018
Downloaded from http://pubs.acs.org on June 27, 2018
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Redox Active Quinoidal 1,2,4ꢀBenzotriazines
Georgia A. Zissimou, Andreas Kourtellaris, Maria Manoli and Panayiotis A. Koutentis*
Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
* Corresponding author; eꢀmail: koutenti@ucy.ac.cy
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GRAPHICAL ABSTRACT
ABSTRACT
ꢀ1/0
Modifying the paraꢀquinonimine 1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7(H)ꢀone (2a) (E1/2 ꢀ1.20 V),
by replacing the N1ꢀphenyl by pentafluorophenyl, the C3ꢀphenyl by trifluoromethyl, or the C7
carbonyl by ylidenemalononitrile led to improved electron affinities as determined by cyclic
voltammetry and computational studies. Combining structural changes further improved electron
accepting abilities: the most electron deficient analogues (E1/2ꢀ1/0 ~ꢀ0.65 V) involved combining the
ylideneꢀmalononitrile groups at C7 with the trifluoromethyl groups at C3. 1,2,5ꢀThiadiazolo fusion
at C5ꢀC6 did not affect the redox behavior but enhanced the UVꢀvis absorption profile. During the
synthesis of the thiadiazolo analogues, 1,4ꢀthiazinoꢀfused analogues (6) were obtained in low yield
which thermally ring contract to the triazafluoranthenones (7). Compounds are fully characterized,
and Xꢀray data are provided for selected analogues.
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1. INTRODUCTION
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Redox activity is important in a wide array of biological processes,1 e.g., cellular respiration2 and
photosynthesis.3 Furthermore, redox active materials have commercial uses e.g., in metallurgy,4 as
anticorrodants,5 antioxidants,6 as components in semiconductors,7 electrochemical sensors,8 fuel
cells,9 for radical polymerisations,10 selfꢀassembled coatings,11 and many other applications.
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Well known redox active organic compounds include acceptors such as fullerene (C60),12 and
tetracyanoquinodimethane (TCNQ),13 2,3ꢀdichloroꢀ5,6ꢀdicyanoꢀ1,4ꢀbenzoquinone (DDQ),14 as well
as donors such as tetrathiafulvalene (TTF),15 ferrocene,16 and stable neutral organic radicals (e.g.,
TEMPO)17 (Figure 1).
Figure 1. Structures of electron poor (top) and rich (bottom) redox active molecules.
The present interest in organic electronics has led to an increased focus on the synthesis, chemistry,
properties and applications of redox active compounds, oligomers and polymers. In particular, the
properties of electroactive small organic molecules based on quinoidal motifs have led to their use
in electronic applications such as organic photovoltaics,18 batteries,19 and spintronic devices.20
Considering the above, and as part of our ongoing studies in rare heteroarenes,21 we began studies
on 1,2,4ꢀbenzotriazinꢀ4ꢀyls (aka Blatter22 radicals 1)23 which are electron rich but stable neutral
organic radicals that have two fully reversible one electron redoxes to give the analogous cation 1+
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and anion 1ꢀ.24 Oxidation of radicals 1 affords the analogous benzotriazinones 2,25 that can also be
prepared by oxidation of Nꢀphenylamidrazones 3 (Scheme 1).23c
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Scheme 1. The Redox Behavior of Benzotriazinyls 1, Preparation and Redox Behavior of
Benzotriazinones 2
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Benzotriazinones are paraꢀquinonimines and thus electron deficient redox active species.
Electrochemical reduction affords the anion radical (2·ꢀ) and dianion (22ꢀ) in succession and both
processes are fully reversible (Scheme 1). Benzotriazinones can be readily functionalized with good
regioselectivity making them potentially useful building blocks for library synthesis.26 Furthermore,
they can also be used to construct πꢀextended Blatter radicals,27 and unusual zwitterionic
biscyanines.28
Like many other paraꢀquinonimines,29 several 1,2,4ꢀbenzotriazinones, show interesting biological
properties such as anticancer activity,30 and as dual inhibitors of βꢀamyloid (Aβ) fibrillization and
acetylꢀ (AChE) and/or butyrylꢀ (BChE) cholinesterase, all valuable targets for the treatment of
Alzheimer’s disease.31 Finally, benzotriazinones have been proposed as potential precursors to
stable anion radicals.32
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Herein, we investigate how structural changes on 1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7(H)ꢀone (2a, R1
= R2 = Ph) affect its electron accepting abilities. Cyclic voltammetry (CV), UVꢀvis spectroscopy
and DFT computational studies were used to investigate the electrochemical window to better
understand the redox behavior of these unusual quinoidal benzotriazines.
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2. RESULTS AND DISCUSSION
From our inꢀhouse compound library, we identified several radicals with suitable electron
withdrawing groups (EWGs) at either N1 or C3: the 1ꢀpentafluorophenylꢀ and 1ꢀ(pyridꢀ2ꢀyl)ꢀ
substituted 3ꢀphenylbenzotriazinones 1b23a and 1c23b with EWGs at the N1 position, and the 3ꢀtriꢀ
fluoromethylꢀ and 3ꢀ(pyridꢀ2ꢀyl)ꢀ substituted 1ꢀphenylbenzotriazinones 1d23b and 1e23b with EWGs
at the C3 position. Radicals 1aꢀe were oxidized using MnO2 (10ꢀ50 equiv) to the corresponding
quinonimines 2aꢀe. Present in our library was also the 1,3ꢀdi(pyridꢀ2ꢀyl)benzotriazinone 2f23b that
has EWGs at both N1 and C3, but this was prepared directly from the leuco benzotriazine 1f
(Scheme 2).
Scheme 2. MnO2ꢀMediated Oxidation of Benzotriazinyls 1aꢀf to Benzotriazinones 2aꢀf
Computational studies (DFT) on the benzotriazinone core [Supporting Information (SI), Section S4]
revealed significant molecular orbital density on the N1 positions in both the frontier molecular
orbitals (FMOs) but a nodal point exists at the C3 position of the LUMO. This suggested that
substitution at N1 and C3 positions will affect the energy of the HOMOs more significantly than
that of the LUMOs. Nevertheless, Xꢀray studies23a,34 of 1,3ꢀdiarylꢀ1,2,4ꢀbenzotriazinyls show that
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while the C3ꢀaryl groups are typically in the plane of the benzotriazine, the N1ꢀaryl groups are
twisted out of the plane owing to steric interactions with the peri C8 hydrogen. As such,
substituents at N1 have a predominantly inductive effect, while those on C3 have a combined
mesomeric and inductive influence on the electrochemistry of the benzotriazinone scaffold.
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CV studies on quinonimines 2aꢀf (Table 1) provided useful information to guide the design of more
electron poor analogues. The replacement of either the N1 or C3 phenyls (σmeta 0.06, σpara ꢀ0.01)33
by pyridꢀ2ꢀyl (σmeta 0.33, σpara 0.17)33 groups led to a similar effect on both redox peaks: the first
redox (E1/2ꢀ1/0) was raised by 0.08 V for the N1 pyridyl 2c and 0.04 V for the C3 pyridyl 2e, while
the second redox (E1/2ꢀ2/ꢀ1) was raised by 0.14 V and 0.11 V for pyridyl analogues 2c and 2e,
respectively. These +ve redox shifts showed that substitution at either site moderated the electron
affinity of the scaffold (Table 1, entries 3 and 5). Furthermore, while replacing both phenyls by
pyridyls (Table 1, entry 6) only led to a 0.08 V +ve shift of the first redox (E1/2ꢀ1/0) very similar to
ꢀ
that seen with the N1 pyridyl 2c, there was a marked increase in the value of the second redox (E1/2
2/ꢀ1) which was raised by 0.18 V, i.e. combining substitution changes improved the electron affinity
of the quinonimine.
CV studies on analogues 2b and 2d, with more strongly electron withdrawing pentafluorophenyl
(σmeta 0.26, σpara 0.27)33 and trifluoromethyl (σmeta 0.43, σpara 0.54)33 groups at N1 and C3,
respectively, showed less ꢀve first redox values 2b (E1/2ꢀ1/0 ꢀ1.04 V) and 2d (E1/2ꢀ1/0 ꢀ0.99 V) than the
pyridyl analogues 2b,e and 2f, but interestingly, their second redox values (E1/2ꢀ2/ꢀ1) were similar
(ꢀ1.70 and ꢀ1.69 V) to the mono pyridyls (ꢀ1.68 V and ꢀ1.71 V) (Table 1, entries 2, 4ꢀ6).
Unfortunately, we were unable to prepare the 1,3ꢀdi(trifluoromethyl)ꢀ, 1,3ꢀdi(pentafluorophenyl)ꢀ,
1ꢀpentafluorophenylꢀ3ꢀtrifluoromethylꢀ or 3ꢀpentafluorophenylꢀ1ꢀtrifluoromethylꢀ substituted
benzotriazinones as either the chemistry to make the precursor radicals failed or the required
reagents were not available. This prevented our ability to examine combinations of these
substituents on the redox behavior. Nevertheless, since the introduction of pentafluorophenyl or
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trifluoromethyl groups led to the least ꢀve redox values, we focused on making further structural
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changes on quinonimines 2b and 2d (Table 1, entries 2 and 4).
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Table 1. Optical, Electrochemical and Theoretical Details of 2aꢀf, 4aꢀc, 5a,b and 10a,b
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Opt
ꢀ1/0
ꢀ2/ꢀ1
TDꢀDFT
entry compd λmax(abs)
Eg
E1/2
[V]
E1/2
[V]
Eg
ELUMO
[eV]c
ꢀ3.60
ꢀ3.76
ꢀ3.68
ꢀ3.81
ꢀ3.64
ꢀ3.68
ꢀ3.95
ꢀ4.09
ꢀ4.14
ꢀ3.70
ꢀ3.90
ꢀ3.95
ꢀ4.16
EHOMO
[eV]d
ꢀ5.43
ꢀ5.72
ꢀ5.54
ꢀ5.66
ꢀ5.48
ꢀ5.53
ꢀ5.43
ꢀ5.59
ꢀ5.72
ꢀ5.54
ꢀ5.77
ꢀ5.44
ꢀ5.66
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.
[nm]
639
611
628
626
635
636
780
730
762
645
636
819
810
[eV]a
1.83
1.96
1.86
1.85
1.84
1.85
1.48
1.50
1.58
1.84
1.87
1.49
1.50
[eV]b
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2.34
2.24
2.41
2.35
2.32
1.95
2.04
2.05
2.16
2.35
1.84
1.96
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ꢀ1.20
ꢀ1.04
ꢀ1.12
ꢀ0.99
ꢀ1.16
ꢀ1.12
ꢀ0.85
ꢀ0.71
ꢀ0.66
ꢀ1.10
ꢀ0.90
ꢀ0.85
ꢀ0.64
ꢀ1.82
ꢀ1.70
ꢀ1.68
ꢀ1.69
ꢀ1.71
ꢀ1.64
ꢀ1.55
ꢀ1.46
ꢀ1.40
ꢀ1.76
ꢀ1.69
ꢀ1.52
ꢀ1.35
2a
2b
2c
2d
2e
2f
4a
4b
4c
5a
5b
10a
10b
a Eg was calculated from the onset of the λmax from UVꢀvis and the BeerꢀLambert equation (E =
Opt
h*C/λ); b EgTDꢀDFT = first excitation energy from TDꢀDFT/UB3LYP 6ꢀ31G(d); ELUMO = ꢀ[E1/2
+
c
ꢀ1/0
4.8] eV; d EHOMO = ELUMO ꢀ EgOpt (eV).
UVꢀvis studies on quinonimines 2aꢀf show broad, structured low energy absorption bands between
400 and 700 nm, centered at ~550 nm (Figure 2). Based on TDꢀDFT calculations (Sect. S4.4, SI)
we attributed these low energy bands to transitions between the frontier molecular orbitals (FMOs)
(i.e. HOMO → LUMO, f 0.06ꢀ0.09). Varying the substitutents at either N1 or C3, had little effect
on the quinonimine’s optical band gaps (EgOpt) which ranged between 1.83ꢀ1.96 eV (Table 1). This
was owed to the substituent effects being similar in sign and magnitude to both the HOMO and
LUMO energy levels (Table S2, SI).
1.2
1.0
1.0
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0.8
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0.6
400
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0.4
0.2
0.0
2a
2b
2c
2d
2e
2f
300
400
500
600
700
800
Wavelength (nm)
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Figure 2. UVꢀvis of quinonimines 2a (black), 2b (red), 2c (blue), 2d (green), 2e (orange) and 2f
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4
(pink) in DCM at ~1.5 × 10ꢀ5 mol·Lꢀ1.
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To increase the electron affinity of quinonimines 2a,b and 2d, we attempted to convert them into
their ylidenemalononitriles 4 (Scheme 3). The ylidenemalononitrile moiety is a powerful electron
withdrawing group.35 This transformation was challenging owing to the strong electron release
from the triazine N1 atom to the C7 carbonyl.26a Prior studies showed that treating benzotriazinone
2a with either tetracyanoethylene (TCNE) or tetracyanoethylene oxide (TCNEO) in PhCl heated at
ca. 140 °C for 18 h afforded the ylidene in low yields (17ꢀ19%).26a Improved yields were obtained
by reꢀoptimizing these reaction conditions: by using TCNEO (1.5 equiv) in anhydrous PhMe,
heated at ca. 110 °C for only 1 h product 4a was isolated in 50% yield. These conditions also
worked to convert the 1ꢀpentafluorophenyl and 3ꢀtrifluoromethyl benzotriazinones 2b and 2d into
ylidenes 4b (40%) and 4c (25%), respectively (Scheme 3).
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Scheme 3. Synthesis of Ylidenemalononitriles 4aꢀc
Ylidenemalononitriles 4aꢀc were isolated as blueꢀgreen needles that dissolved readily in typical
organic solvents. Compared to quinonimines 2 the UVꢀvis spectra showed substantially redꢀshifted,
broad, structured low energy absorptions between 450ꢀ900 nm, centered at ~675 nm (Figure 3).
TDꢀDFT calculations (Sect. S4.4, SI) support that the lowest energy absorptions were owed to
transitions between FMOs (i.e. HOMO → LUMO, f 0.18ꢀ0.19) and that the reduction in the optical
Opt
band gaps (Eg 1.48ꢀ1.58 eV) is owed to a lowering of the LUMO energy level relative to the
HOMO by ~0.24 eV (Table S2, SI).
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0.6
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Wavelength (nm)
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Wavelength (nm)
Figure 3. UVꢀvis of ylidenes 4a (red), 4b (blue), and 4c (green) in DCM at ~1.5 × 10ꢀ5 mol·Lꢀ1.
Computational DFT studies on ylidenes 4aꢀc revealed large dipole moments (ꢀ 5.66ꢀ9.23 D)
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suggesting highly polarized molecules (Sect. S4.3, SI). This was also supported by the C NMR
data (CDCl3, 500 MHz) that revealed upꢀfield signals of δC 65.2 for the ylidenemalononitrile 4a
=C(CN)2 resonance that shifted even further upꢀfield to δC 58.6 in more polar DMSOꢀd6 that can
stabilize more readily the polarized resonance form. Typically, the more upꢀfield the signal for the
malononitrile C2 signal, the more negative charge, i.e. shielding, is associated with that carbon.36
CV studies on ylidenes 4aꢀc showed that replacing the carbonyl by the ylidenemalononitrile group
improved the electron affinities of the molecules (Table 1, entries 7ꢀ9). Both the first (E1/2ꢀ1/0) and
second reduction (E1/2ꢀ2/ꢀ1) peaks were +ve shifted by ~0.34 and ~0.27 V, respectively, compared to
the analogous quinonimines. Combining the C3 trifluoromethyl and C7 ylidenemalononitrile
moieties in compound 4c gave the analogue with the least negative electron affinity: E1/2ꢀ1/0 ꢀ0.66 V
and E1/2ꢀ2/ꢀ1 ꢀ1.40 V (Table 1, entry 9).
Additional structural modifications that we investigated included the introduction of 1,2,5ꢀ
thiadiazole fusion across the C5ꢀC6 benzotriazine bond. 1,2,5ꢀThiadiazoloꢀfused arenes are useful
electron acceptors in a variety of organic electronic applications (e.g., OPV, OFET, OLED etc).37
While there are many routes to building benzothiadiazoles,38 a fast and cheap way to build the ring
system directly onto a quinone scaffold is to use tetrasulfur tetranitride (S4N4).39
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Previously, the reaction of benzotriazinone 2a with S4N4 (5 equiv) in DMF at ca. 153 °C for 1 h,
had given a mixture of the desired thiadiazoloꢀfused benzotriazinone 5a (15%) together with a side
product, 6ꢀaminobenzotriazinone 6a (48%).28 Under these conditions, the reaction of ylideneꢀ
malononitriles 4aꢀc with S4N4 gave only black intractable tars. As such, we prepared the
thiadiazoloꢀfused benzotriazinones 5 first and then converted them into the ylidenemalononitriles
10 (Schemes 4 and 6).
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Scheme 4. Preparation of ThiadiazoloꢀFused Triazafluoranthenones
During this effort, we discovered that reacting 6ꢀaminoꢀ1,3ꢀdiphenylbenzotriazinone 6a with
additional S4N4 (5ꢀ10 equiv) under the same reaction conditions (DMF, ca. 153 °C, 1ꢀ12 h), gave
the desired thiadiazolobenzotriazinone 5a in 30% yield. Considering this, we optimized the yield of
thiadiazolobenzotriazinone 5a. Several solvents (1,4ꢀdioxane, PhH, PhMe, PhCl, 1,2ꢀDCB, DMA
and DMF) were tested in combinations with different equivalents of S4N4 (5ꢀ10 equiv), reaction
scales and mode of addition. By treating a solution of benzotriazinone 2a in DMF at ca. 153 °C
over a 7 h period with five equal portions of S4N4 (total 10 equiv) the desired
thiadiazolobenzotriazinone 5a was isolated in high 80% yield, together with a new less polar [Rf
0.78
(nꢀhexane/DCM/tꢀBuOMe,
30:60:10)]
redꢀcolored
product
2ꢀphenylꢀ7Hꢀ
[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]triazino[1,6,5ꢀmn]ꢀphenothiazinꢀ7ꢀone (7a) (7%) and a small
quantity of 6ꢀaminoꢀ1,3ꢀdiphenylbenzotriazinone 6a (5%) (Scheme 4). The use of additional S4N4
failed to consume the amino analogue. Using these conditions, the reaction of S4N4 with 1ꢀphenylꢀ
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3ꢀ(trifluoromethyl)ꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone 2d gave a mixture of 2ꢀ(trifluoromethyl)ꢀ7Hꢀ
[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]triazino[1,6,5ꢀmn]phenothiazinꢀ7ꢀone (7b) (18%), the desired 6ꢀ
phenylꢀ8ꢀ(trifluoromethyl)ꢀ[1,2,5]thiadiazolo[3',4':5,6]benzo[1,2ꢀe][1,2,4]ꢀtriazinꢀ4(6H)ꢀone (5b)
(49%) and 6ꢀaminoꢀ1ꢀphenylꢀ3ꢀ(trifluoromethyl)benzo[e][1,2,4]triazinꢀ7(1H)ꢀone (6b) (17%)
(Scheme 4). Unfortunately, the reaction of S4N4 with 1ꢀ(perfluorophenyl)ꢀ3ꢀphenylꢀ1,2,4ꢀ
benzotriazinone 2b, gave a complex reaction mixture (TLC) and no products were isolable in
sufficient purity to allow characterization; partly owing to their unstable nature during the workꢀup.
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The structure assignment of the thiazines was supported by elemental analysis, and mass
spectrometry which tentatively indicated the additional sulfur. Furthermore, the loss of the
1
benzotriazine H8 resonance in the H NMR and the appearance of a splitting pattern for the 1ꢀ
phenyl suggesting a 1,2ꢀdisubstituted arene supported the assignment. Thermolysis of the 1,4ꢀ
thiazinoꢀfused systems 7a (R = Ph) and 7b (R = CF3) led to the ring contracted
triazafluoranthenones 8a (98%) and 8b (97%), respectively (Scheme 5). To the best of our
knowledge, there is only one report by Rees et al.40 on the thermal ring contraction of 1,4ꢀthiazines.
Finally, the thiadiazoloꢀfused triazafluoranthenone 8a was also independently prepared in 79%
yield by reacting S4N4 with triazafluoranthenone 9,26b which helped to further support the structure
assignment (Scheme 5).
Scheme 5. Preparation of ThiadiazoloꢀFused Triazafluoranthenones 8a and 8b
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A spectroscopic feature of the 1,4ꢀthiazines was a broad low intensity absorption in the UVꢀvis
spectra that peaked at ~800 nm but extended into the near InfraꢀRed (NIR), beyond the range of our
instrument (Figure 4). TDꢀDFT calculations (Sect. S4.4, SI) attribute this absorption to a weak
HOMO→LUMO transition (f ~0.01) that is accompanied by a redistribution (or charge transfer) of
the FMOs from the electron rich benzothiazine to the electron poor thiadiazolobenzotriazine moiety
(Figure 5). An Electrostatic Surface Potential (ESP) calculation of thiazine 7a showed considerable
electron deficiency (dark blue) at the thiadiazolobenzotriazinone moiety (Figure 6).
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1.2
1.0
1.0
0.5
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600
750
900
Wavelength (nm)
0.4
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7a
7b
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400
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800
1000
Wavelength (nm)
Figure 4. UVꢀvis of thiazines 7a (red) and 7b (blue) in DCM at ~1.5 × 10ꢀ5 mol Lꢀ1.
ELUMO = ꢀ3.914 eV
EHOMO = ꢀ5.281 eV
Figure 5. FMOs of 2ꢀphenylꢀ7Hꢀ[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]triazino[1,6,5ꢀmn]phenothiazinꢀ7ꢀ
one (7a).
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Figure 6. ESP of 2ꢀphenylꢀ7Hꢀ[1,2,5]thiadiazolo[3,4ꢀb]ꢀ[1,2,4]triazino[1,6,5ꢀmn]phenothiazinꢀ7ꢀ
one (7a).
Treating the available thiadiazolobenzotriazinones 5a and 5b with TCNEO (1.5 equiv.) in PhMe at
110 °C for 1 h gave the desired final thiadiazoloꢀfused ylidenemalononitriles 10a (30%) as brown
shiny needles, and 10b (26%) as green metallic plates, respectively.
Scheme 6. Preparation of ThiadiazoloꢀFused Triazafluoranthenones 10a and 10b
Interestingly, while the 2ꢀphenylꢀsubstituted thiadiazolo ylidenemalononitrile 10a had a high
thermal stability (DSC onset 392.6 °C), the trifluoromethyl 10b sublimed at ca. 280ꢀ290 °C (DSC
Opt
onset 288.2 °C). Comparing the UVꢀvis data of the thiadiazoloꢀfused benzotriazines 5a,b (Eg
Opt
Opt
1.84ꢀ1.87 eV) and 10a,b (Eg 1.49ꢀ1.50 eV) with their nonꢀthiadiazoleꢀfused analogues 2 (Eg
Opt
1.83ꢀ1.96 eV) and 4 (Eg 1.48ꢀ1.58 eV), respectively showed that thiadiazolo fusion had little
effect on the their optical band gaps (Table 1). Nevertheless, all the thiadiazoloꢀfused
benzotriazines showed an additional strong absorption band at around 350ꢀ400 nm, leading to
broader absorption properties than their nonꢀfused counterparts (Figure 7).
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10a
10b
300
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Wavelength (nm)
Figure 7. UVꢀvis of thiadiazolo ylidenemalononitriles 10a (red) and 10b (blue) in DCM at ~1.5 ×
10ꢀ5 mol Lꢀ1.
CV studies on the thiadiazoloꢀfused benzotriazinones 5a (R = Ph) and 5b (R = CF3) and
(benzotriazinylidene)malononitriles 10a (R = Ph) and 10b (R = CF3) showed that the ring fusion
only slightly improved the compounds’ electron affinities (Table 1, entries 10ꢀ13). For both
benzotriazinone 2a and ylidenemalononitrile 4a, fusing the 1,2,5ꢀthiadiazole moiety led to a less ꢀve
first reduction potential (E1/2ꢀ1/0) by ~0.09 V, but only in the case of the benzotriazinone 2a was the
second reduction (E1/2ꢀ2/ꢀ1) affected by a small 0.06 V +ve shift. The improvement in the electron
affinity was even less pronounced when the ring fusion was combined with the
ylidenemalononitriles 4a (R = Ph) and 4c (R = CF3) with the trifluoromethylꢀsubstituted
thiadiazoloꢀfused ylideneꢀmalononitrile 10b showing similar reduction potentials to the nonꢀfused
ylidenemalononitrile 4c: (E1/2ꢀ1/0): 4c ꢀ0.66 V vs 10b ꢀ0.64 V and (E1/2ꢀ2/ꢀ1) 4c ꢀ1.40 V vs 10b ꢀ1.35
V (Table 1, entries 9 and 13). The data suggested that these structural changes did not have an
additive effect on the electrochemistry of the benzotriazine core.
Analysis of the FMOs (Table 1) reveals that the ylidenes 4aꢀc (EHOMO ꢀ5.72 to ꢀ5.29 eV; ELUMO
ꢀ
3.95 to ꢀ4.14 eV) and thiadiazoloꢀfused ylidenes 10a,b (EHOMO ꢀ5.44 to ꢀ5.66 eV, ELUMO ꢀ3.95 to ꢀ
4.16 eV), have LUMO energies, comparable to other wellꢀknown and widely used electron
acceptors, such as fullerene derivatives e.g., [6,6]ꢀphenylꢀC71ꢀbutyric acid methyl ester (PC70BM,
EHOMO ꢀ5.90 eV; ELUMO ꢀ3.90 eV),51 and oligothiophene functionalized naphthalene diimides
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(EHOMO ꢀ6.06 to ꢀ5.53 eV; ELUMO ꢀ3.97 to ꢀ4.14 eV),52.that are widely used as electron acceptors in
OPV devices. The similarity between these FMO energy values tentatively supports that ylidenes 4
and 10 could find use in similar energy applications.
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2.1. Crystallography. Single crystal structures of compounds 2b (CCDC 1840980), 2d (CCDC
1840989), 4c (CCDC 1840990) and 10b (CCDC 1840979) were obtained from bulk
recrystallisations enabling a comparison of experimental and computational bond lengths (Table S1,
SI). Furthermore, since benzotriazines 2d, 4c and 10b were all N1ꢀphenyl, C3ꢀtrifluoromethylꢀ
substituted analogues the data enabled a comparative study of the bond lengths based on the
replacement of C=O for C=C(CN)2 and on the effect of thiadiazolo ring fusion on the ylidene.
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In general, bond lengths determined via computational studies [DFT RB3LYP/6ꢀ31G(d)] were
similar to those obtained from the Xꢀray data (σ ~0.01 Å). Bond order analysis supported the
quinoidal structure for all analogues with typical carbonyl bond lengths [d(C=O) ~1.23 Å, bond
orders ~1.9] (cf. cyclohexanone d(C=O) ~1.23 Å).50 The benzotriazine cores deviated slightly from
planarity owing to a very shallow boat conformation for the quinonimine moiety, and the plane
angles between the N1ꢀaryl and triazine rings were 52.0‒63.7° (Xꢀray) and 52.6‒66.7° (DFT).
Interestingly, the ylidenemalononitrile 4c showed reduced bond orders for the exocyclic [d(C=C)
1.399(3) Å, bond order 1.8] and endocyclic [d(C=C) 1.369(3) Å, bond order 1.9] ethenes separating
the N1ꢀphenyl from the ylidenemalononitrile moiety. This suggested a stronger electron release
from the triazine N1 to the ylidenemalononitrile, which was expected. Somewhat surprising, was
that the thiadiazole fusion moderated this electron release to give marginally longer bond orders for
the analogous exocyclic [d(C=C) 1.379(7) Å, bond order 1.9] and endocyclic [d(C=C) 1.379(7) Å, bond
order 1.9] ethenes. The thiadiazole bond lengths [d(NꢀS) ~1.62 Å and d(C=N) ~1.33 Å] were typically
aromatic (bond orders ~1.5), suggesting considerable delocalization (cf. compound 10b, Figure 8).
Benzotriazinone bond length comparisons between the N1ꢀpentafluorophenyl 2b and the C3ꢀ
trifluoromethyl 2d revealed insignificant differences, nevertheless, the N1ꢀpentafluorophenyl was
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significantly more twisted out of the benzotriazinyl plane (66.7°) than the N1ꢀphenyl group of 2d
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(52.9°).
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ꢀ1/0
ESP calculations for the two best electron acceptors the ylidenemalononitriles 4c [E1/2 ꢀ0.66 V
and E1/2ꢀ2/ꢀ1 ꢀ1.40 V (Table 1, entry 9)] and 10b [E1/2ꢀ1/0 ꢀ0.64 V and E1/2ꢀ2/ꢀ1 ꢀ1.35 V (Table 1, entry
13)] (Figure 9) show in deep blue color the regions most deficient in electron density, which are
predominantly over the triazinyl moiety but extend in the latter case over the thiadiazole.
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Figure 8. Xꢀray structure of thiadiazoloꢀfused benzotriazine 10b. (CCDC 1840979). Thermal
ellipsoids are at 50% probability. Crystallographic number showing. Hydrogens removed for
clarity.
Figure 9. ESP for ylidene 4c (left) and thiadiazoloꢀfused benzotriazine 10b (right).
3. CONCLUSION
ꢀ1/0
Structural modifications on 1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7(H)ꢀone (2a) (E1/2
ꢀ1.20 V) gave
compounds with superior electron accepting capabilities. The combination of a C3 trifluoromethyl
and C7 ylidenemalononitrile groups gave analogues 4c and 10b with significantly reduced first
ꢀ1/0
reduction potentials (E1/2 ~ꢀ0.65 V). Furthermore, FMO energies for these analogues are similar
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in value to known electron acceptors such as PC70BM which suggests that they could act as
electron accepting components in electronic devices. The preparation of 1,2,5ꢀthiadiazoloꢀfused
analogues 5a,b using S4N4 also led to unusual 1,4ꢀthiazinoꢀfused sideꢀproducts 7a,b that undergo a
rare ring contraction on thermolysis to give triazafluoranthoneone 8a,b. which were independently
synthesized. Further studies to understand their chemistry and potential applications are underway.
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4. EXPERIMENTAL SECTION
4.1. General Methods and Materials. Dichloromethane (DCM) was dried over CaH2 and toluene
over molecular sieves (4 Å) in a DeanꢀStark apparatus prior to use. 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 (Merck 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 prep scale chromatographic separations using Merck
Silica Gel 60 (less than 0.063 mm).53 Melting and decomposition points were determined using
either a PolyThermꢀA, Wagner & Munz, KoflerꢀHotstage Microscope apparatus or a TA
Instruments DSC Q1000. Differential scanning calorimetry (DSC) was used to determine melting
and decomposition points with samples hermetically sealed in aluminum pans under an argon
atmosphere, using heating rates of 5 °C/min. DSC can often provide thermal decomposition points
which appear as exothermic signals. Typically, the pans are opened after seeing an exothermic
signal to confirm the material has decomposed rather than a chemical transformation to other
isolable product(s). Solvents used for recrystallisation are indicated after the melting point. UVꢀvis
spectra were obtained using a PerkinꢀElmer Lambdaꢀ25 UVꢀvis spectrophotometer and inflections
are identified by the abbreviation ‘inf’. IR spectra were recorded on a Shimadzu FTIRꢀNIR
Prestigeꢀ21 spectrometer with a Pike Miracle Ge ATR accessory and strong, medium and weak
1
13
peaks are represented by s, m and w, respectively. H and C (APT) NMR spectra were recorded
on either a BrukerAvance 500 machine (at 500 and 125 MHz, respectively) or on a Bruker 300
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instrument (at 300 and 75 MHz, respectively). Deuterated solvents were used for homonuclear lock
and the signals are referenced to the deuterated solvent peaks. MALDIꢀTOF MS were conducted on
a Bruker BIFLEX III timeꢀofꢀflight (TOF) mass spectrometer using positive ionization mode. 2,5ꢀ
Dihydroxybenzoic acid (DHB)54 and 2B graphite pencil55 were used as calibrant and/or matrix as
indicated. Elemental analysis was performed on a PerkinElmer 2400 series elemental analyzer by
Stephen Boyer of London Metropolitan University. Tetrasulfur tetranitride (S4N4),56
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tetracyanoethylene
oxide
(TCNEO),57
1ꢀ(perfluorophenyl)ꢀ3ꢀphenylꢀ1,4ꢀdihydroꢀ1,2,4ꢀ
benzotriazinꢀ4ꢀyl (1b),23a 1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2a),23c 3ꢀphenylꢀ1ꢀ(pyridꢀ2ꢀyl)ꢀ
1,2,4ꢀbenzotriazinꢀ7ꢀone (2c),30a 1ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2d),30b 1ꢀ
phenylꢀ3ꢀ(pyridꢀ2ꢀyl)ꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2e),30a 1,3ꢀdi(pyridꢀ2ꢀyl)ꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone
(2f)23b and 2ꢀphenylꢀ6Hꢀ[1,2,4]triazino[5,6,1ꢀjk]carbazolꢀ6ꢀone (9)26b were prepared according to
the literature.
4.2. Cyclic Voltammetry. The concentrations of all studied compounds were 0.001 molꢁLꢀ1 in dry
(over CaH2) HPLC grade DCM (5 mL) containing nꢀBu4NPF6 (0.1 M) as a supporting electrolyte.
A threeꢀelectrode electrochemical cell was employed with glassy carbon (3 mm diameter), Pt wire
and Ag/AgCl (1 M KCl) as working, counter and reference electrodes, respectively. The
ferrocene/ferrocenium (Fc/Fc+) couple was used as an internal reference and all redox couples are
referenced against it (EFc/Fc+ 0.0 V). Scan rate 100 mV·s−1. Temp 20 °C. The calculation of ELUMO
ꢀ1/0
was performed according to the simplified empirical equation: ELUMO = ꢀ[E1/2 + 4.8] eV, where
value “4.8” represents the value of the ferrocene’s EHOMO (ꢀ4.8 eV in vacuo). The HOMO levels
were calculated by incorporating the optical band gap according to the following empirical
Opt
equation: EHOMO = ELUMO ꢀ Eg
.
4.3. XꢀRay Crystallography. Data were collected on an Oxford Di raction Supernova
di ractometer, equipped with a CCD area detector using MoꢀKα radiation (λ = 0.7103 Å) for
compound 4c and CuꢀKα radiation (λ = 1.5418 Å) for compounds 2b, 2d and 10b. A suitable
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crystal was attached to glass fibers using paratoneꢀN oil and transferred to a goniostat where they
were cooled for data collection. Unit cell dimensions were determined and refined by using 3152
(4.06 ≤ θ ≤ 74.14°), 1983 (6.74 ≤ θ ≤ 72.24°), 2189 (3.06 ≤ θ ≤ 28.82°) and 2992 (4.72 ≤ θ ≤
66.99°) reflections for 2b, 2d, 4c and 10b, respectively. Empirical absorption corrections (multiscan
based on symmetryꢀrelated measurements) were applied using CrysAlis RED software.58 The
structures were solved by direct method and refined on F2 using fullꢀmatrix leastꢀsquares using
SHELXL97 or SHELXL2014.59 Software packages used CrysAlis CCD58 for data collection,
CrysAlis RED58 for cell refinement and data reduction, WINGX for geometric calculations,60 and
DIAMOND61 for molecular graphics. The nonꢀH atoms were treated anisotropically. The hydrogen
atoms were placed in calculated, ideal positions and refined as riding on their respective carbon
atoms.
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Crystal refinement data for compound 2b (CCDC 1840980): C19H8F5N3O, M = 389.28, monoclinic,
space group P21/n, a = 12.1586(7) Å, b = 6.2942(4) Å, c = 20.7512(12) Å, α = 90°, β = 95.028(5)°,
γ = 90°, V = 1581.95(16) Å3, Z = 4, T = 100(2) K, ρcalcd = 1.634 g cmꢀ3, 2θmax = 67. Refinement of
253 parameters on 2086 independent reflections out of 3152 measured reflections (Rint = 0.0294)
led to R1 = 0.0585 [I > 2σ(I)], wR2 = 0.2158 (all data), and S = 1.081with the largest difference peak
and hole of 0.369 and ꢀ0.414 eꢀ3, respectively.
Crystal refinement data for compound 2d (CCDC 1840989): C14H8F3N3O, M = 291.23,
orthorhombic, space group P b c a, a = 15.4804(4) Å, b = 7.6884(2) Å, c = 20.7339(6) Å, α = β = γ
= 90°, V = 2467.74(12) Å3, Z = 8, T = 100(2) K, ρcalcd = 1.568 g cmꢀ3, 2θmax = 67. Refinement of
190 parameters on 2198 independent reflections out of 15140 measured reflections (Rint = 0.0340)
led to R1 = 0.0366 [I > 2σ(I)], wR2 = 0.1035 (all data), and S = 1.106 with the largest difference
peak and hole of 0.244 and ꢀ0.280 eꢀ3, respectively.
Crystal refinement data for compound 4c (CCDC 1840990): C17H8F3N5, M = 339.22, triclinic,
space group P ꢁ1, a = 6.7763(9) Å, b = 8.5591(7) Å, c = 13.2125(14) Å, α = 95.469(8)°, β =
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=
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25. Refinement of 226 parameters on 2585 independent reflections out of 4562 measured
reflections (Rint = 0.0305) led to R1 = 0.0485 [I > 2σ(I)], wR2 = 0.1291 (all data), and S = 1.006 with
the largest difference peak and hole of 0.611 and ꢀ0.497 eꢀ3, respectively.
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Crystal refinement data for compound 10b (CCDC 1840979): C17H6F3N7S, M = 397.35,
monoclinic, space group P21/c, a = 9.7769(7) Å, b = 27.140(3) Å, c = 6.6499(7) Å, α = 90°, β =
106.914(9)°, γ = 90°, V = 1688.2(3) Å3, Z = 4, T = 100(2) K, ρcalcd = 1.563 g cmꢀ3, 2θmax = 67.
Refinement of 253 parameters on 2992 independent reflections out of 5880 measured reflections
(Rint = 0.0607) led to R1 = 0.0715 [I > 2σ(I)], wR2 = 0.2159 (all data), and S = 0.940 with the largest
difference peak and hole of 0.541 and ꢀ0.644 eꢀ3, respectively.
4.4. Computational Methods. Restricted polarized density functional theory (RDFT) utilizing the
hybrid B3LYP method was used for all calculations employing the 6ꢀ31G(d) basis set to calculate
all properties.62 The geometries of the close shell singlet 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. All the energies were corrected after zeroꢀpoint
energies (ZPE) were scaled by 0.981 according to the equation: GSETOT = EGS + (ZPE × SF).63 TDꢀ
DFT calculations were performed at the RB3LYP/6ꢀ31G(d) level of theory to calculate the vertical
excitation energy. The latter in combination with the HOMO energy taken from the optimization
calculations provide a more accurate energy for the LUMO orbital according to the equation: ELUMO
= EHOMO + EHOMO LUMO. All the above computations were performed using the Gaussian 03 suite of
ꢀ
programs.64
4.5. Synthesis of 1ꢀ(Perfluorophenyl)ꢀ3ꢀphenylꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2b). To a vigorously
stirred solution of 1ꢀ(perfluorophenyl)ꢀ3ꢀphenylꢀ1,4ꢀdihydroꢀ1,2,4ꢀbenzotriazinꢀ4ꢀyl (1b) (374.3
mg, 1.0 mmol) in dry DCM (10.0 mL) at ca. 20 °C was added MnO2 (869.4 mg, 10.0 mmol). After
1 h the radical X was fully consumed (by TLC) and the reaction was judged complete. The mixture
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was then filtered through Celite®, that was then rinsed with DCM (50 mL). The filtrate and DCM
washings were combined, and the volatiles removed in vacuo. Chromatography (nꢁhexane/tꢀ
BuOMe, 50:50) of the residue afforded the title compound 2b (342.6 mg, 88%) as dark purple
cubes; mp (hotꢀstage) decomp.: 218.9–220.1 °C (PhMe); mp (DSC) decomp. onset: 208.6 °C,
decomp. peak max: 215.3 °C (PhMe); Rf 0.58 (nꢁhexane/tꢀBuOMe, 50:50); Anal. Calcd for
C19H8F5N3O: C, 58.62; H, 2.07; N, 10.79. Found: C, 58.83; H, 2.11; N, 10.85%; λmax(DCM)/nm
278 inf (log ε 4.47), 293 (4.56), 305 inf (4.47), 340 inf (3.86), 485 inf (3.54), 520 (3.63), 562 inf
(3.52), 611 inf (2.94); νmax/cmꢀ1 1624m, 1611m, 1555m, 1518s, 1460m, 1443m, 1327m, 1244m,
1105m, 1069m, 1009m, 991s, 918s, 866m, 785m, 766m, 725m, 700s; δH(500 MHz, CDCl3) 8.21–
8.19 (2H, m), 7.70 (1H, d, J 10.0, Hꢀ5), 7.52–7.48 (3H, m), 7.25 (1H, dd, J 10.0, 2.0, Hꢀ6, overlap
with CDCl3), 5.66 (1H, d, J 1.5, Hꢀ8); δC(125 MHz, CDCl3) one C (s) resonance missing, 182.5 (s,
Cꢀ8), 156.3 (s), 151.3 (s), 143.5 (dm, 1JCF 270.0), 143.1 (dm, 1JCF 258.8), 142.2 (d), 138.4 (dm, 1JCF
246.3) 135.7 (s), 133.0 (d), 131.1 (d), 128.9 (d), 126.8 (d), 115.1 (s), 97.6 (d); m/z (MALDIꢀTOF)
390 (MH+, 47%), 389 (M+, 5), 374 (27), 242 (100).
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4.6. Synthesis of Benzoꢀ1,2,4ꢀtriazinꢀ7ꢀylidenemalononitriles 4aꢀc.
4.6.1. 2ꢁ(1,3ꢁDiphenylbenzo[e][1,2,4]triazinꢁ7(1H)ꢁylidene)malononitrile (4a). To a stirred solution
of 1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2a) (60.0 mg, 0.2 mmol) in toluene (2 mL) at ca. 20 °C
was added TCNEO (43.3 mg, 0.3 mmol) and the reaction mixture was then immersed into a preꢀ
heated (~115 °C) oil bath. The reaction mixture was heated at reflux for 1 h, cooled to ca. 20 °C,
poured over a silica dry flash column and chromatographed (DCM) to afford the title compound 2a
(34.8 mg, 50%) as blue needles; mp (hotꢀstage) not observed; mp (DSC) onset: 320.0 °C, peak max:
320.3 °C (PhMe) (lit.26a 306–311 °C); Rf 0.48 (DCM); λmax(DCM)/nm 258 (log ɛ 4.45), 277 inf
(4.40), 337 (4.47), 359 (4.65), 376 inf (4.69), 418 (4.22), 586 inf (4.05), 644 (4.26), 698 (4.30), 780
(4.05); νmax/cmꢀ1 3061w (aryl CꢀH), 2203s (C≡N), 1612m, 1551m, 1508s, 1489s, 1377s, 1364m,
1341m, 1306s, 1267s, 1188m, 1152m, 1136m, 1003m, 841s, 833m, 781m, 752s; δH(500 MHz,
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CDCl3) 8.26 (2H, d, J 6.5), 7.94 (1H, dd, J 9.5, 1.5, Hꢀ6), 7.70–7.59 (6H, m), 7.52–7.46 (3H, m),
6.59 (1H, d, J 1.5, Hꢀ8); δH(500 MHz, 80 °C, DMSOꢀd6) 8.24‒8.22 (2H, m), 7.92 (1H, d, J 9.5),
7.85‒7.81 (3H, m), 7.78‒7.71 (3H, m), 7.58‒7.57 (3H, m), 6.32 (1H, d, J 1.0, Hꢀ8); δC(125 MHz,
80 °C, DMSOꢀd6) 155.2 (s), 153.0 (s), 152.1 (s), 140.2 (s), 136.5 (d), 135.4 (s), 132.9 (d), 130.6 (d),
130.5 (d), 130.3 (d), 129.7 (d), 128.5 (d), 126.3 (d), 125.3 (s), 115.9 (s, C≡N), 115.8 (s, C≡N), 93.8
(d), 58.6 [s, C(CN)2]; m/z (MALDIꢀTOF) 348 (MH+, 21%), 347 (M+, 100); identical to an authentic
sample.
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4.6.2. 2ꢁ[1ꢁ(Perfluorophenyl)ꢁ3ꢁphenylbenzo[e][1,2,4]triazinꢁ7(1H)ꢁylidene]malononitrile (4b). To
a stirred solution of 1ꢀ(perfluorophenyl)ꢀ3ꢀphenylbenzo[e][1,2,4]triazinꢀ7(1H)ꢀone (2b) (77.8 mg,
0.2 mmol) in toluene (2 mL) at ca. 20 °C was added TCNEO (43.3 mg, 0.3 mmol) and the reaction
mixture was then immersed in a preꢀheated (~115 °C) oil bath. The reaction mixture was heated at
reflux for 1 h, cooled to ca. 20 °C, poured over a silica flash column and chromatographed (DCM)
to afford the title compound 4b (35.0 mg, 40%) as blue needles; mp (hotꢀstage) 277.0–278.1 °C
(PhMe); mp (DSC) onset: 275.4 °C, peak max: 278.8 °C (PhMe); Rf 0.75 (DCM); Anal. Calcd for
C22H8F5N5·1.5 PhMe: C, 67.82; H, 3.50; N, 12.17. Found: C, 67.80; H, 3.37; N, 11.87%;
λmax(DCM)/nm 259 (log ε 4.54), 280 inf (4.50), 334 inf (4.71), 353 (4.82), 370 (4.78), 402 inf
(4.07), 427 inf (3.91), 515 inf (3.89), 563 inf (4.22), 612 (4.37), 661 (4.35), 730 inf (4.04); νmax/cmꢀ1
2207s (C≡N), 1514s, 1389m, 1385m, 1337m, 1331m, 1302m, 1277m, 1179m, 1148m, 1123m,
1074m, 1015m, 995s, 920s, 837s, 785m, 760m, 735m, 721m; δH(500 MHz, CDCl3) 8.18 (2H, dd, J
7.0, 2.0), 7.93 (1H, dd, J 9.5, 2.0, Hꢀ6), 7.57 (1H, d, J 9.5, Hꢀ5), 7.55ꢀ7.48 (3H, m), 7.27‒7.24
(2.6H, m, overlap with CDCl3, PhMe), 7.18‒7.14 (1.8H, m, PhMe), 6.09 (1H, d, J 1.5, Hꢀ8), 2.36
(1.8H, PhMe); δC(125 MHz, CDCl3) one C (s) and one CF resonance missing, 157.3 (s), 154.2 (s),
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152.9 (s), 143.5 (dm, JCF 254.4), 137.9 (s, PhMe), 138.6 (dm, JCF 215.8), 137.8 (d), 133.9 (s),
132.4 (s), 131.7 (d), 131.2 (d), 129.0 (d, PhMe), 129.0 (d), 128.2 (d, PhMe), 127.1 (d), 125.3 (d,
PhMe), 114.8 (s, C≡N), 114.4 (s, C≡N), 90.3 (d), 70.4 [s, C(CN)2], 21.4 (t, PhMe); m/z (MALDIꢀ
TOF) 438 (MH+, 17%), 437 (M+, 100).
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4.6.3. 2ꢁ[1ꢁPhenylꢁ3ꢁ(trifluoromethyl)benzo[e][1,2,4]ꢁtriazinꢁ7(1H)ꢁylidene]malononitrile (4c). To
a stirred solution of 1ꢀphenylꢀ3ꢀ(trifluoromethyl)benzo[e][1,2,4]triazinꢀ7(1H)ꢀone (2d) (58.3 mg,
0.2 mmol) in toluene (2 mL) at ca. 20 °C was added TCNEO (43.3 mg, 0.3 mmol) and the reaction
mixture was then immersed into a preꢀheated (~115 °C) oil bath. The reaction mixture was heated
at reflux for 1 h, cooled to ca. 20 °C, poured over a silica flash column and chromatographed
(DCM) to afford the title compound 4c (17.0 mg, 25%) as greenꢀblue needles; mp (hotꢀstage)
242.2‒245.3 °C (nꢀhexane); mp (DSC) onset: 245.8 °C, peak max: 247.1 °C (nꢁhexane); Rf 0.65
(DCM); Anal. Calcd for C17H8F3N5: C, 60.18; H, 2.38; N, 20.64. Found: C, 60.15; H, 2.28; N,
20.51%; λmax(DCM)/nm 253 (log ɛ 4.12), 309 inf (4.23), 325 (4.32), 342 (4.38), 358 (4.37), 401
(3.84), 569 inf (3.85), 627 (4.03), 682 (4.02), 762 inf (3.73); νmax/cmꢀ1 3103w and 3057w (aryl Cꢀ
H), 2203m (C≡N), 1555m, 1530s, 1493s, 1416s, 1371s, 1352s, 1233s, 1206m, 1190s, 1167s, 1152s,
1134s, 1105s, 995s, 893m, 845s, 829m, 799m, 762s, 716s; δH(500 MHz, CDCl3) 7.95 (1H, dd, J
9.5, 1.0, Hꢀ6), 7.69‒7.62 (3H, m), 7.55‒7.51 (3H, m), 6.56 (1H, d, J 1.5, Hꢀ8); δC(125 MHz,
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CDCl3) 157.9 (s), 153.2 (s), 145.5 (q, JCF 38.8, CCF3), 139.2 (s), 138.7 (d), 134.7 (s), 131.4 (d),
130.7 (d), 130.4 (d), 124.8 (d), 118.8 (q, 1JCF 272.5, CF3), 114.4 (s, C≡N), 114.3 (s, C≡N), 96.4 (d),
70.2 [s, C(CN)2]; m/z (MALDIꢀTOF, pencil matrix) 340 (MH+, 14%), 339 (M+, 100), 301 (11), 242
(19), 128 (95).
4.7. Synthesis of [1,2,5]Thiadiazolobenzo[1,2,4]triazinꢀ7ꢀones 5aꢀb, [1,2,5]Thiadiazoloꢀ
benzo[1,2,4]triazino[1,6,5]phenothiazinꢀ7ꢀones 7aꢀb and 6ꢀAminobenzo[1,2,4]triazinꢀ7ꢀones
6aꢀb.
4.7.1. 6,8ꢁDiphenyl[1,2,5]thiadiazolo[3',4':5,6]benzo[1,2ꢁe][1,2,4]triazinꢁ4(6H)ꢁone (5a). To a
stirred solution of 1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2a) (60.0 mg, 0.2 mmol) in DMF (4 mL)
at ca. 20 °C was added S4N4 (73.7 mg, 0.4 mmol) and the reaction mixture was heated at ca. 153
°C. Over a 5 h period at ca. 153 °C, to the reaction mixture was added an additional four portions of
S4N4 (4 × 73.7 mg). The reaction mixture was heated for a total of 7 h, allowed to cool to ca. 20 °C
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and then extracted with 50:50 H2O/DCM (100 mL). The organic layer was separated, washed with
additional H2O (20 mL), dried (MgSO4), filtered and the volatiles were removed in vacuo.
Chromatography (DCM/Et2O, 95:5) gave 2ꢀphenylꢀ7Hꢀ[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]triazinoꢀ
[1,6,5ꢀmn]phenothiazinꢀ7ꢀone (7a) (5.4 mg, 7%) as pink needles; mp (hotꢀstage) not observed; mp
(DSC) onset: 327.2 °C, peak max: 327.4 °C; decomp. onset: 328.0 °C, decomp. peak max: 329.6 °C
(PhMe); Rf 0.78 (nꢀhexane/DCM/tꢁBuOMe, 30:60:10); Anal. Calcd for C19H9N5OS2: C, 58.90; H,
2.34; N, 18.08. Found: C, 58.95; H, 2.26; N, 18.18%; λmax(DCM)/nm 257 inf (log ε 4.30), 301
(4.55), 320 inf (4.42), 375 inf (3.98), 515 (3.76), 812 (3.10); νmax/cmꢀ1 3067w (aryl CꢀH), 1609s
(C=O), 1582s, 1566s, 1518s, 1497m, 1472m, 1458s, 1433s, 1404s, 1368m, 1348m, 1331s, 1317m,
1275m, 1236s, 1165s, 1121m, 1109m, 945m, 883s, 829s, 777m, 760s, 733s; δH(500 MHz, TFAꢀd)
9.09 (1H, d, J 8.5), 8.58 (2H, d, J 7.5), 8.37 (1H, d, J 7.5), 8.13 (1H, dd, J 7.8, 7.8), 7.99 (1H, dd, J
7.8, 7.8), 7.63‒7.58 (3H, m); δC(125 MHz, TFAꢀd) 175.7 (s), 159.1 (s), 157.6 (s), 155.6 (s), 152.0
(s), 138.2 (d), 137.7 (s), 135.8 (d), 135.4 (d), 135.3 (d), 134.7 (s), 133.7 (s), 131.7 (d), 130.5 (d),
126.0 (s), 123.7 (d), 106.7 (s); m/z (MALDIꢀTOF) 388 (MH+, 100%), 387 (M+, 30), 373 (14), 372
(23), 371 (100). Further elution (DCM/Et2O, 80:20) afforded the title compound 5a (57.4 mg, 80%)
as brown needles; mp (hotꢀstage) not observed; mp (DSC) onset: 313.6 °C, peak max: 314.9 °C
(PhCl) (lit.28 285ꢀ290 °C); Rf 0.34 (DCM/tꢀBuOMe, 90:10); λmax(DCM)/nm 269 (log ɛ 4.01), 309
(4.18), 406 (3.75), 499 inf (2.98), 540 (3.09), 580 (3.04), 636 inf (2.73); νmax/cmꢀ1 3067w (aryl Cꢀ
H), 1612s, 1601s, 1591s, 1574m, 1516s, 1499s, 1466m, 1458m, 1441m, 1406m, 1350m, 1279m,
1236s, 1159m, 1119m, 905m, 831m, 783m, 773s, 746m, 723m; δH(500 MHz, CDCl3) 8.39–8.37
(2H, m), 7.69–7.60 (5H, m), 7.55–7.51 (3H, m), 6.26 (1H, s, Hꢀ8); identical to an authentic sample.
Further elution (DCM/Et2O, 50:50) afforded 6ꢀaminoꢀ1,3ꢀdiphenylꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (6a) as
yellow needles; mp (hotꢀstage) 279‒281 °C (PhH), (lit.26a 279‒282 °C); Rf 0.21 (tꢀBuOMe/nꢀ
hexane, 75:25); δH (500 MHz; TFAꢀd) NH peak missing, 8.09 (2H, d, J 7.6), 7.79‒7.65 (7H, m),
7.58‒7.48 (3H, m); m/z (MALDIꢀTOF) 316 (MH++1, 34%), 315 (MH+, 100), 314 (M+, 4); identical
to an authentic sample.
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4.7.2. 6ꢁPhenylꢁ8ꢁ(trifluoromethyl)[1,2,5]thiadiazolo[3',4':5,6]benzo[1,2ꢁe][1,2,4]triazinꢁ4(6H)ꢁ
one (5b). To a stirred solution of 1ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (2d) (58.3
mg, 0.2 mmol) in DMF (4 mL) at ca. 20 °C was added S4N4 (73.7 mg, 0.4 mmol) and the reaction
mixture was the heated to ca. 153 °C. Over a 5 h period at ca. 153 °C, to the reaction mixture was
added an additional four portions of S4N4 (4 × 73.7 mg). The reaction mixture was heated for a total
of 7 h, allowed to cool to ca. 20 °C and then extracted with 50:50 H2O/DCM (100 mL). The organic
layer was separated, washed with additional H2O (20 mL), dried (MgSO4), filtered and the volatiles
were removed in vacuo. Chromatography (DCM/Et2O, 95:5) gave 2ꢀ(trifluoromethyl)ꢀ7Hꢀ
[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]triazino[1,6,5ꢀmn]phenothiazinꢀ7ꢀone (7b) (13.7 mg, 18%) as red
needles; mp (hotꢀstage) not observed; mp (DSC) onset: 309.7 °C, peak max: 310.8 °C (PhH); Rf
0.83 (nꢀhexane/DCM/tꢀBuOMe, 30:60:10), Rf 0.30 (nꢀhexane/DCM/tꢀBuOMe, 60:30:10); Anal.
Calcd for C14H4F3N5OS2: C, 44.33; H, 1.06; N, 18.46. Found: C, 44.46; H, 0.62; N, 18.82%;
λmax(DCM)/nm 282 (log ɛ 4.62), 336 (4.35), 500 (3.64), 819 (3.18); νmax/cmꢀ1 3055w (aryl CꢀH),
1613s (C=O), 1586s, 1533s, 1491m, 1468s, 1412m, 1385s, 1375m, 1354m, 1335m, 1302m, 1206s,
1153s, 1142s, 1125s, 1115s, 1078m, 1043m, 1038m, 949m, 891s, 868m, 839m, 776s, 768s, 748m,
735s, 718s; δH(500 MHz, TFAꢀd) 8.24 (1H, d, J 9.0), 7.48 (1H, dd, J 6.8, 6.8), 7.36 (1H, br s), 7.16
(1H, d, J 7.5); m/z (MALDIꢀTOF, DHB matrix) 380 (MH+, 21%), 379 (M+, 100). Further elution
(DCM/tꢀBuOMe, 80:20) afforded the title compound 5b (34.3 mg, 49%) as purple needles; mp
(hotꢀstage) 230.2‒232.2 °C (PhH); mp (DSC) onset: 235.1 °C, peak max: 236.0 °C (PhH); Rf 0.64
(DCM/tꢀBuOMe, 90:10); Anal. Calcd for C14H6F3N5OS: C, 48.14; H, 1.73; N, 20.05. Found: C,
48.27; H, 1.75; N, 20.04%; λmax(DCM)/nm 259 (log ɛ 4.35), 298 (4.33), 311 (4.32), 324 (4.21), 372
(3.82), 390 (3.77), 457 inf (3.22), 492 inf (3.39), 526 (3.45), 571 inf (3.33), 624 inf (2.91); νmax/cmꢀ1
3061w (aryl CꢀH), 1626s, 1586m, 1547s, 1491m, 1396s, 1350m, 1240s, 1206s, 1138s, 1115m,
1103s, 1049s, 908s, 858m, 839m, 829s, 791m, 773s; δH(500 MHz, CDCl3) 7.68‒7.61 (3H, m),
7.54‒7.53 (2H, m), 6.19 (1H, s, Hꢀ8); δC(125 MHz, CDCl3) 173.6 (s, C=O), 157.3 (s), 151.9 (s),
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272.5), 100.6 (d); m/z (MALDIꢀTOF) 350 (MH+, 100%). Further elution (DCM/Et2O, 50:50) gave
6ꢀaminoꢀ1ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ1,2,4ꢀbenzotriazinꢀ7ꢀone (6b) (10.5 mg, 17%) as orange
needles; mp (hotꢀstage) not observed (PhH); mp (DSC) onset: 349.4 °C, peak max: 352.1 °C (PhH);
Rf 0.65 (DCM/tꢀBuOMe, 50:50); Anal. Calcd for C14H9F3N4O: C, 54.91; H, 2.96; N, 18.29. Found:
C, 54.84; H, 2.92; N, 18.38%; λmax(DCM)/nm 266 (log ε 3.97), 284 inf (3.81), 323 inf (3.18), 374
inf (3.19), 396 inf (3.56), 416 (3.66), 495 inf (2.68); νmax/cmꢀ1 3381w, 3300w, 3233m and 3196m
(NꢀH), 1578s, 1574s, 1551s, 1505m, 1493m, 1416m, 1393m, 1285s, 1198s, 1155s, 1130s, 1092m,
1063m, 995s, 855m, 830m, 772s, 756m; δH(500 MHz, DMSOꢀd6) 8.62 (1H, br s, NH), 7.80 (1H, br
s, NH), 7.70‒7.64 (5H, m), 6.73 (1H, s, Hꢀ8), 5.64 (1H, s, Hꢀ5); δC(125 MHz, DMSOꢀd6) 173.2 (s,
C=O), 155.3 (s), 151.7 (s), 142.6 (q, 2JCF 35.0), 140.8 (s), 136.3 (s), 130.2 (d), 129.9 (d), 126.1 (d),
119.8 (q, 1JCF 272.5), 98.0 (d), 95.0 (d); m/z (MALDIꢀTOF) 308 (MH++1, 9%), 307 (MH+, 100).
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4.8. Synthesis of 1,2,5ꢀThiadiazoloꢀ1,2,4ꢀtriazinoꢀ1,6,5ꢀcarbazolꢀ7ꢀones (Triazafluoranthenꢀ
ones) 8aꢀb.
4.8.1. 2ꢁPhenylꢁ7Hꢁ[1,2,5]thiadiazolo[3,4ꢁb][1,2,4]triazino[1,6,5ꢁlm]carbazolꢁ7ꢁone (8a).
Method A. A stirred mixture of 2ꢀphenylꢀ7Hꢀ[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]triazino[1,6,5ꢀmn]ꢀ
phenothiazinꢀ7ꢀone (7a) (38.7 mg, 0.1 mmol) and mꢀterphenyl (115.2 mg, 0.5 mmol) under an
argon atmosphere was immersed into a preheated (~270 °C) Wood’s metal bath for 3 h. After 3 h
the thiazinone 7a was fully consumed (by TLC) and the reaction was judged complete. The mixture
was left to cool down to ca. 20 °C, diluted with DCM and poured onto a short silica pad, washed
with DCM to remove remaining mꢀterphenyl and byꢀproducts and then chromatographed (DCM/tꢀ
BuOMe, 80:20) to afford the title compound 8a (34.8 mg, 98%) as maroon needles; mp (hotꢀstage)
not observed; mp (DSC) onset: 304.9 °C, peak max: 307.7 °C (cꢀhexane/PhMe, 90:10); Rf 0.43 (nꢁ
hexane/DCM/tꢀBuOMe, 60:30:10); Rf 0.87 (nꢁhexane/DCM/tꢀBuOMe, 30:60:10); Anal. Calcd for
C19H9N5OS: C, 64.22; H, 2.55; N, 19.71. Found: C, 64.49; H, 2.46; N, 20.04%; λmax(DCM)/nm 247
(log ε 4.19), 273 (4.26), 299 (4.41), 317 (4.22), 378 (3.82), 392 (3.77), 413 (3.67), 466 inf (3.11),
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496 (3.17), 530 (3.13), 572 inf (2.85); νmax/cmꢀ1 1661s, 1649s, 1613m, 1530m, 1503m, 1493m,
1466s, 1449s, 1437m, 1343m, 1335m, 1263m, 1236m, 1161s, 1148m, 1115m, 1017m, 934m,
912m, 847m, 818s, 783m, 770m, 758m, 747s, 743s; δH(500 MHz, 50 °C, CD2Cl2) 8.68ꢀ8.67 (2H,
m), 8.56 (1H, d, J 7.5), 8.48 (1H, d, J 8.0), 7.79 (1H, dd, J 7.5, 7.0), 7.74 (1H, dd, J 8.0, 7.5), 7.65ꢀ
7.63 (3H, m); m/z (MALDIꢀTOF) 356 (MH+, 100%), 355 (M+, 11), 339 (34), 333 (37).
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Method B. To a stirred solution of 2ꢀphenylꢀ6Hꢀ[1,2,4]triazino[5,6,1ꢀjk]carbazolꢀ6ꢀone (9) (59.5
mg, 0.2 mmol) in DMF (4.0 mL) at ca. 20 °C under an argon atmosphere, was added S4N4 (73.7
mg, 0.4 mmol) and the reaction mixture was then immersed into a preheated (~153 °C) Wood’s
metal bath. Additional S4N4 (4 × 73.7 mg) was added portion wise over a period of 5 h. After a total
of 7 h heating, the reaction was allowed to cool to ca. 20 °C and extracted with 50:50 H2O/DCM
(100 mL). The organic layer was separated, washed with additional H2O (20 mL), dried (MgSO4),
filtered and volatiles were removed in vacuo. Chromatography (DCM/tꢀBuOMe, 80:20) gave the
title compound 8a (56.1 mg, 79%) as maroon needles; mp (hotꢀstage) not observed; mp (DSC)
onset: 304.9 °C, peak max: 307.7 °C (cꢀhexane/PhMe, 90:10); Rf 0.87 (nꢁhexane/DCM/tꢀBuOMe,
30:60:10); λmax(DCM)/nm 247 (log ε 4.19), 273 (4.26), 299 (4.41), 317 (4.22), 378 (3.82), 392
(3.77), 413 (3.67), 466 inf (3.11), 496 (3.17), 530 (3.13), 572 inf (2.85); νmax/cmꢀ1 1661s, 1649s,
1613m, 1530m, 1503m, 1493m, 1466s, 1449s, 1437m, 1343m, 1335m, 1321w, 1263m, 1236m,
1161s, 1148m, 1115m, 1017m, 934m, 912m, 847m, 818s, 783m, 770m, 758m, 747s, 743s; m/z
(MALDIꢀTOF) 356 (MH+, 100%), 355 (M+, 11), 339 (34), 333 (37); identical to the one described
above.
4.8.2.
2ꢁ(Trifluoromethyl)ꢁ7Hꢁ[1,2,5]thiadiazolo[3,4ꢁb][1,2,4]triazino[1,6,5ꢁlm]carbazolꢁ7ꢁone
(8b). Method A. A stirred mixture of 2ꢀ(trifluoromethyl)ꢀ7Hꢀ[1,2,5]thiadiazolo[3,4ꢀb][1,2,4]ꢀ
triazino[1,6,5ꢀmn]phenothiazinꢀ7ꢀone (7b) (37.9 mg, 0.1 mmol) and mꢀterphenyl (115.2 mg, 0.5
mmol) under an argon atmosphere was immersed into a preheated (~270 °C) Wood’s metal bath for
3 h. After 3 h the thiazinone 7b was fully consumed (by TLC) and the reaction was judged
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complete. The mixture was left to cool down to ca. 20 °C, diluted with DCM and poured onto a
shortꢀpad of silica, which was washed with DCM to remove remaining mꢀterphenyl and minor byꢀ
products and then chromatographed (DCM/tꢀBuOMe, 80:20) to afford the title compound 8b (33.7
mg, 97%) as maroon needles; mp (hotꢀstage) not observed; mp (DSC) onset: 274.7 °C, peak max:
277.9 °C (cꢀhexane/PhMe, 90:10); Rf 0.89 (nꢁhexane/DCM/tꢀBuOMe, 30:60:10); Anal. Calcd for
C14H4F3N5OS: C, 48.42; H, 1.16; N, 20.17. found: C, 48.29; H, 1.44; N, 20.13%; λmax(DCM)/nm
247 inf (log ε 4.38), 270 (4.55), 295 inf (4.32), 305 (4.39), 317 (4.38), 345 inf (3.81), 366 (4.01),
386 inf (3.97), 407 (4.00), 469 inf (3.24), 499 (3.33), 531 (3.29), 578 inf (2.97); νmax/cmꢀ1 1659s,
1597m, 1530m, 1467m, 1413m, 1379s, 1352m, 1335m, 1306m, 1263m, 1246m, 1204s, 1144s,
1113s, 1103m, 1040s, 941s, 889m, 826s, 777s, 758s, 729s; δH(500 MHz, CDCl3) 8.63 (1H, d, J
8.0), 8.44 (1H, d, J 8.5), 7.86 (1H, ddd, J 8.0, 8.0, 1.0), 7.79 (1H, dd, J 7.8, 7.8, 1.0); δC(125 MHz,
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CDCl3) 170.0 (s, C=O), 161.1 (s), 153.6 (s), 149.2 (s), 148.0 (q, JCF 38.8), 134.7 (s), 130.5 (d),
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128.3 (s), 128.0 (d), 126.1 (s), 123.7 (d), 119.4 (q, JCF 273.8), 113.5 (d), 108.1 (s); m/z (MALDIꢀ
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4.9. Synthesis of 1,2,5ꢀThiadiazoloꢀ1,2,4ꢀbenzotriazinꢀ7ꢀylidenemalononitriles 10aꢀb.
4.9.1.
2ꢁ(6,8ꢁDiphenyl[1,2,5]thiadiazolo[3',4':5,6]benzo[1,2ꢁe][1,2,4]triazinꢁ4(6H)ꢁylidene)ꢁ
malononitrile (10a). To a stirred solution of 6,8ꢀdiphenyl[1,2,5]thiadiazolo[3',4':5,6]benzo[1,2ꢀe]ꢀ
[1,2,4]triazinꢀ4(6H)ꢀone (5a) (71.5 mg, 0.2 mmol) in toluene (2 mL) at ca. 20 °C was added
TCNEO (43.3 mg, 0.3 mmol) and the reaction mixture was then immersed into a preꢀheated (~115
°C) oil bath. The reaction mixture was then heated at reflux for 1 h, cooled to ca. 20 °C, poured
over a silica flash column and chromatographed (DCM) to afford the title compound 10b (24.3 mg,
30%) as brown shiny needles; mp (hotꢀstage) not observed; mp (DSC) onset: 392.6 °C, peak max:
394.6 °C (PhMe), Rf 0.83 (DCM/tꢀBuOMe, 90:10); Anal. Calcd for C22H11N7S: C, 65.17; H, 2.73;
N, 24.18. Found: C, 64.99; H, 2.68; N, 24.15%; λmax(DCM)/nm 279 (log ɛ 4.07), 311 (4.02), 320
(4.01), 352 inf (3.86), 403 (3.46), 477 inf (3.96), 503 (4.08), 583 inf (3.43), 631 (3.47), 687 inf
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(3.40), 772 inf (3.04); νmax/cmꢀ1 3067w (aryl CꢀH), 2205s and 2193m (C≡N), 1530s, 1526s, 1493s,
1460m, 1423m, 1385s, 1358m, 1281s, 1244m, 945m, 910w, 853m, 843m, 743m; δH(500 MHz,
CDCl3) 8.35 (2H, dd, J 8.0, 1.0), 7.73 (2H, dd, J 7.3, 7.3), 7.68–7.64 (3H, m), 7.56–7.51 (3H, m),
6.70 (1H, s, Hꢀ8); δC(125 MHz, DMSOꢀd6) 153.9 (s), 152.4 (s), 150.9 (s), 150.5 (s), 145.0 (s), 140.8
(s), 138.5 (s), 132.7 (s), 131.5 (d), 131.1 (d), 130.5 (d), 129.2 (d), 126.7 (d), 125.6 (d), 116.6 (s,
C≡N), 116.5 (s, C≡N), 93.9 (d), 58.2 [s, C(CN)2]; m/z (MALDIꢀTOF, DHB matrix) 407 (MH++1,
21%), 406 (MH+, 100), 405 (M+, 56).
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4.9.2. 2ꢁ[6ꢁPhenylꢁ8ꢁ(trifluoromethyl)[1,2,5]thiadiazolo[3',4':5,6]benzo[1,2ꢁe][1,2,4]triazinꢁ4(6H)ꢁ
ylidene]malononitrile (10b). To a stirred solution of 6ꢀphenylꢀ8ꢀ(trifluoromethyl)[1,2,5]thiadiazoloꢀ
[3',4':5,6]benzo[1,2ꢀe][1,2,4]triazinꢀ4(6H)ꢀone (5b) (69.9 mg, 0.2 mmol) in toluene (2 mL) at ca. 20
°C was added TCNEO (43.3 mg, 0.3 mmol) and then the reaction mixture was immersed into a preꢀ
heated (~115 °C) oil bath. The reaction mixture was heated at reflux for 1 h, cooled to ca. 20 °C,
poured over a silica flash column and chromatographed (DCM) to afford the title compound 10b
(20.7 mg, 26%) as green plates; mp (hotꢀstage) sublimation 279.1‒285.3 °C; mp (DSC) onset:
288.2 °C, peak max: 288.5 °C (PhMe), Rf 0.88 (DCM/tꢀBuOMe; 90:10); Anal. Calcd for
C17H6F3N7S: C, 51.39; H, 1.52; N, 24.68. Found: C, 51.28; H, 1.48; N, 24.57%; λmax(DCM)/nm 271
inf (log ɛ 3.69), 298 (3.84), 369 (3.35), 390 (3.32), 446 (3.68), 473 (3.80), 524 inf (1.98), 573
(3.11), 623 (3.17), 679 (3.09), 762 inf (2.72); νmax/cmꢀ1 3044w (aryl CꢀH), 2214s (C≡N), 1545s,
1508m, 1491m, 1420s, 1371s, 1277s, 1263m, 1221m, 1198s, 1179m, 1157m, 1148s, 1117s, 1065s,
949m, 858s, 845m, 829m, 799m, 772m, 739s; δH(500 MHz, CDCl3) 7.73‒7.65 (3H, m), 7.58ꢀ7.56
(2H, m), 6.70 (1H, s, Hꢀ8); δC(125 MHz, CDCl3) 154.3 (s), 152.7 (s), 149.8 (s), 144.9 (s), 144.7 (q,
2JCF 39.6), 139.6 (s), 136.4 (s), 131.8 (d), 131.0 (d), 124.7 (d), 118.7 (q, 1JCF 272.9), 114.5 (s, C≡N),
114.2 (s, C≡N), 96.4 (d), 70.9 [s, C(CN)2]; m/z (MALDIꢀTOF) 399 (MH++1, 20%), 398 (MH+, 57),
397 (M+, 100), 153 (57).
ASSOCIATED CONTENT
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Supporting Information Available.
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Crystallographic, computational, UVꢀvis, CV, NMR, DSC and TGA data and discussion (PDF).
Crystallographic file for compounds 2b, 2d, 4c and 10b (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: Koutenti@ucy.ac.cy
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors thank the University of Cyprus and the Cyprus Research Promotion Foundation.
REFERENCES
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Payne, G. F. Connecting Biology to Electronics: Molecular Communication via Redox Modality.
Adv. Healthcare Mater. 2017, 6, 1700789.
(2) (a) Wikström, M.; Sharma, V.; Kaila, V. R. I.; Hosler, J. P.; Hummer, G. New Perspectives on
Proton Pumping in Cellular Respiration. Chem. Rev. 2015, 115, 2196ꢀ2221. (b) Blumberger, J.
Recent Advances in the Theory and Molecular Simulation of Biological Electron Transfer
Reactions. Chem. Rev. 2015, 115, 11191ꢀ11238. (c) Jones, D. P.; Sies, H. The Redox Code.
Antioxid. Redox Signal. 2015, 23, 734ꢀ746. (d) Circu, M. L.; Aw, Y. T. Reactive Oxygen Species,
Cellular Redox Systems, and Apoptosis. Free Radical Biol. Med. 2010, 48, 749–762. (e) Kang, J.;
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