Route to benzo- and pyrido-fused 1,2,4-triazinyl radicals via N ′-(Het)aryl- N ′-[2-nitro(het)aryl]hydrazides

Article abstract of DOI:10.1021/jo402481t

A two-step route to 1,3-disubstituted benzo- and pyrido-fused 1,2,4-triazinyl radicals is presented. The route involves the N′-(2-nitroarylation) of easily prepared N′-(het)arylhydrazides via nucleophilic aromatic substitution of 1-halo-2-nitroarenes, which in most cases gives N′-(het)aryl-N′-[2-nitro(het)aryl]hydrazides in good yields. Mild reduction of the nitro group followed by an acid-mediated cyclodehydration gives the fused triazines, which upon alkali treatment afford the desired radicals. Fifteen examples of radicals are presented bearing a range of substituents at N-1, C-3, and C-7, including the pyrid-2-yl and 8-aza analogues. This route to the N′-(het)aryl-N′-[2-nitro(het)aryl]hydrazides, which works well with benzo- and picolinohydrazides, required a modification for aceto- and trifluoroacetohydrazides that involved a multistep synthesis of asymmetrically 1,1-diaryl-substituted hydrazines.

Full text of DOI:10.1021/jo402481t

Article
pubs.acs.org/joc
Route to Benzo- and Pyrido-Fused 1,2,4-Triazinyl Radicals via
N′‑(Het)aryl‑N′‑[2-nitro(het)aryl]hydrazides
Andrey A. Berezin,† Georgia Zissimou,† Christos P. Constantinides,† Yassine Beldjoudi,‡
Jeremy M. Rawson,‡ and Panayiotis A. Koutentis*,†
†Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
‡Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, Ontario, Canada N9B 3P4
S
* Supporting Information
ABSTRACT: A two-step route to 1,3-disubstituted benzo-
and pyrido-fused 1,2,4-triazinyl radicals is presented. The route
involves the N′-(2-nitroarylation) of easily prepared N′-
(het)arylhydrazides via nucleophilic aromatic substitution of
1-halo-2-nitroarenes, which in most cases gives N′-(het)aryl-
N′-[2-nitro(het)aryl]hydrazides in good yields. Mild reduction
of the nitro group followed by an acid-mediated cyclo-
dehydration gives the fused triazines, which upon alkali
treatment afford the desired radicals. Fifteen examples of
radicals are presented bearing a range of substituents at N-1,
C-3, and C-7, including the pyrid-2-yl and 8-aza analogues. This route to the N′-(het)aryl-N′-[2-nitro(het)aryl]hydrazides, which
works well with benzo- and picolinohydrazides, required a modification for aceto- and trifluoroacetohydrazides that involved a
multistep synthesis of asymmetrically 1,1-diaryl-substituted hydrazines.
1. INTRODUCTION
Stable organic radicals are of interest as building blocks for
multifunctional molecular materials because of their unique
physical properties.1 These materials can combine optical,
transport, and magnetic properties that can be tuned by
introducing subtle structural changes at the molecular level.2a
Control over their solid-state packing and therefore their
macroscopic properties remains a challenge, and progress in
this area is expected to provide useful structure−property
relationships.2
We recently developed new synthetic routes3 to the air- and
moisture-stable benzo[1,2,4]triazinyls 1 (Blatter radicals) in an
Figure 1. General structures of the benzotriazinyl radicals 1,
effort to identify structure−magnetism correlations, and in the
benzotriazinone 2, and the imidazolo-, oxazolo-, and thiazolo-fused
process we elucidated a range of 1D magnetic behaviors.4
benzotriazinyl radicals 3−5.
During our studies we also discovered a high-yield route to the
useful benzotriazinone 2,3a,4a which is the oxidation product of
Scheme 1. Classical Route to Benzotriazinyl Radicals 1 via
Amidrazones 6
the Blatter radical 1 (R3 = H). New radical entities were
prepared from benzotriazinone 2, such as the π-extended fused
imidazolo-, oxazolo-, and thiazolobenzotriazinyls 3−5 (Figure
1).5 Blatter radicals 1 also mediate the controlled polymer-
ization of styrene.6
The classical route to 1,3-disubstituted 1,2,4-benzotriazinyls
1 involves oxidation of the amidrazones 6 in situ to give the
1,2,4-triazabutadienes 7, which then undergo an electrocyclic
ring closure to afford benzotriazines that further oxidize to the
desired 1,2,4-benzotriazinyls 1 (Scheme 1). The oxidative
cyclization sequence has been accelerated using a variety of
oxidants, including HgO,7a−c Ag2O,7d Pd−C/air/DBU,3a
Received: November 8, 2013
RuCl3,7e and potassium ferricyanide K3[Fe(CN)6].7f
© XXXX American Chemical Society
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These reactions afford the desired products in quite variable
yields, and our experience has demonstrated that this is highly
dependent on the purity of the starting amidrazone 6. When
the amidrazone has been purified by recrystallization, the yield
can be gratifyingly high (>90%).3a However, problems arise
because not all amidrazones are easily crystallized, and in
particular, electron-rich analogues rapidly oxidize upon storage.
Further difficulties arise during the synthesis of the desired
amidrazones. Two routes are commonly used (Scheme 2): The
Unlike Blatters’ method, which introduces the nitro group at
a latter stage of the synthesis via nitration of hydrazide 14, we
chose to construct intermediate 13 starting from 1-halo-2-
nitroarenes 18 and readily prepared N′-(het)arylhydrazides 19
(Scheme 4).
Scheme 4. Modified Synthesis of N′-(Het)aryl-N′-[2-
nitro(het)aryl]hydrazides 13
Scheme 2. Routes to Amidrazones 6 via Imidoyl Chlorides 8
and Hydrazonyl Chlorides 11
2. RESULTS AND DISCUSSION
2.1. Synthesis of N′-(Het)aryl-N′-[2-nitro(het)aryl]-
hydrazides 13. The first step in the preparation of the Blatter
radical 1a (R1 = R2 = Ph, R3 = H) involved condensation of 1-
fluoro-2-nitrobenzene (18a) with readily available N′-phenyl-
benzohydrazide (19a) to give N′-(2-nitrophenyl)-N′-phenyl-
benzohydrazide (13a) (Table 1). The reaction worked well in a
Table 1. Reaction of 1-Halo-2-nitroarenes 18 with
Hydrazides 19
first method involves the preparation of an N-arylimidoyl
chloride 8, which upon treatment with arylhydrazine gives a
mixture of three products (6, 9, and 10) since the hydrazine
can attack via both the α and β nitrogens. Thus, the amidrazone
6 needs to be isolated from this mixture by a careful extraction
sequence.8 The second method, which involves the formation
of the N-arylhydrazonyl chloride 119 and subsequent
condensation with a primary aniline, avoids the formation of
mixtures and is currently the preferred route.10
As part of our ongoing studies on 1,2,4-benzotriazines, we
required a reliable general route to benzotriazinyl radicals 1 that
supported variation of the substituents at N-1 and C-3 and on
the benzo-fused moiety. Herein we present a synthesis that
avoids the formation of any unstable (highly reactive)
intermediates such as the amidrazones 6 or the imidoyl/
hydrazonyl chlorides 8 and 11. Our strategy was inspired by an
early synthesis of benzotriazinyl radical developed by Blatter,11
which involved the preparation of the nitro-substituted
intermediate 13 from a 1,1-diarylated hydrazine 15, followed
by reduction of the nitro group to give amine 12 and
subsequent cyclodehydration (Scheme 3).
entry
Y
Hal
R1
R2
R3
13 (% yield)
13a (62)
1
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
F
F
F
F
F
F
F
F
F
F
F
F
F
F
Cl
Cl
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
a
F3C
H
13b (60)
3
4-FC6H4
thien-2-yl
pyrid-2-yl
Me
13c (63)
13d (61)
13e (85)
13f (23)
4
H
5
H
6
H
a
7
F3C
H
Me
13g (19)
8
F3C
13h (17)
a
9
F3C
H
F3C
13i (35)
10
11
12
13
14
15
16
4-NCC6H4
4-NCC6H4
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
Ph
Ph
13j (64)
13k (57)
13l (77)
13m (75)
H
thien-2-yl
Ph
H
H
pyrid-2-yl
pyrid-2-yl
Ph
a
F3C
H
13n (86)
a
13o (84)
a
Scheme 3. Blatter’s Route to Benzotriazinyl Radical 1 via
N
H
pyrid-2-yl
pyrid-2-yl
13p (81)
Hydrazide 14
a
Reaction run for 1 day only.
range of alcoholic solvents ROH (R = Me, Et, i-Pr, s-Bu), and
the optimum yield was obtained using K2CO3 (1.1 equiv) as
the base in EtOH upon heating to ca. 110 °C (sealed tube) for
2 days, which gave the desired product 13a in 62% yield (Table
1, entry 1). The use of the higher-boiling solvent s-BuOH (bp
98−100 °C) avoided the need for a sealed reaction vessel
without affecting the product yield (61%), but we proceeded to
prepare the other analogues using the EtOH/sealed tube
protocol because it was easier to remove EtOH from the
reaction mixture during the workup.
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The reaction tolerated hydrazides bearing benzonitrile
(Table 1, entries 10 and 11), pyrid-2-yl (Table 1, entries 5,
12−14, and 16), and thien-2-yl (Table 1, entries 4 and 11)
substituents and also worked when the 1-fluoro-2-nitrobenzene
(18a or 18b) was replaced with 2-chloro-3-nitropyridine (18c)
(Table 1, entries 15 and 16). Interestingly, the reaction with
either 2-fluoro-1-nitro-4-(trifluoromethyl)benzene (18b) or the
chloronitropyridine 18c required less time (1 vs 2 days) than
those with the fluoronitrobenzene 18a; longer reaction times (2
days) led to a drop in product yield, suggesting that the
products were not stable under the reaction conditions.
Disappointingly, the use of aceto- or trifluoroacetohydrazide
(19f or 19g, respectively) gave low to moderate yields (17−
35%) of the desired 1-phenyl-1-(2-nitroaryl)aceto- and
-trifluoroacetohydrazides 13f−i (Table 1, entries 6−9),
identifying a limitation for the protocol.
arylation of protected 1-arylhydrazines.14 However, these
methods are limited because they cannot readily be performed
on multigram scales. Furthermore, the classical methods require
harsh reaction conditions and complicated workups and have
limited functional group tolerance and low yields,14a while the
transition-metal-catalyzed couplings do not tolerate well the
presence of o-nitro-substituted haloarenes.14b,c
2.2. Reduction and Cyclodehydration of N′-(Het)aryl-
N′-[2-nitro(het)aryl]hydrazides 13 To Give Benzo- and
Pyrido-Fused Triazinyl Radicals 1. The second key step of
the synthesis of the Blatter radical 1a required the mild
reduction of the nitro group of N′-(2-nitrophenyl)-N′-phenyl-
benzohydrazide (13a). This was achieved using either Pd−C/
H2 in EtOH or In powder (4 equiv) in AcOH at ca. 20 °C,
which gave N′-(2-aminophenyl)-N′-phenylbenzohydrazide
(12a) in high yield (95−97%) (Scheme 6). Interestingly,
Nevertheless, this limitation was partly overcome via an
alternative multistep route that invoked the use of readily
available 1-benzylidene-2-phenylhydrazine (20) (Scheme 5).
a
Scheme 6. Synthesis of 1a from 13a
Scheme 5. Stepwise Route to N′-(2-Nitrophenyl)-N′-
phenylacetohydrazide (13f), N′-(2-Nitrophenyl)-N′-
phenyltrifluoroacetohydrazide (13h), and N′-(2-
Nitrophenyl)-N′-phenyl-1-adamantanecarbohydrazide (13q)
a
Reagents and conditions: (i) Pd−C (5 mol %), H2(g), EtOH, ca. 20
°C, 4 h (97%); (ii) In (4 equiv), AcOH, ca. 20 °C, 0.5 h (95%); (iii)
AcOH, ca. 118 °C, 10 min; (iv) 2 M NaOH, ca. 20 °C, 3 h.
benzohydrazide 12a was also recently prepared via the copper-
catalyzed coupling of 2-iodoaniline with N′-phenylbenzohy-
drazide (19a),14b providing an alternative route to this useful
intermediate.
Heating of 20 with 1-fluoro-2-nitrobenzene (18a) and K2CO3
(1.1 equiv) in DMSO at ca. 100 °C for 1 day gave 2-
benzylidene-1-(2-nitrophenyl)-1-phenylhydrazine (21) in 90%
yield, which upon treatment with excess NH2OH·HCl (10
equiv) in pyridine and heating to ca. 80 °C for 1 day released 1-
(2-nitrophenyl)-1-phenylhydrazine (22) in 80% yield together
with some recovered starting material 21 (17%). While we were
unable to drive this reaction to completion, it was suitable to
provide multigram quantities of the desired asymmetrically 1,1-
diaryl substituted hydrazine 22, which was then readily acylated
or trifluoracetylated to give the desired N′-(2-nitrophenyl)-N′-
phenylaceto- and -trifluoroacetohydrazides 13f and 13h in good
overall yields (69 and 59%, respectively). The procedure also
worked for the preparation of adamantane analogue 13q
(Scheme 5).
Additional optimization efforts for this multistep procedure
to broaden its scope are currently underway in our laboratory.
However, it is worthy of note that only a few methods for the
preparation of asymmetrically 1,1-diarylated hydrazines have
been reported, namely, the reduction of the corresponding
nitrosamines,12 the Hofmann rearrangement of the correspond-
ing ureas,13 and more recently the transition-metal-catalyzed N-
Heating of N′-(2-aminophenyl)benzohydrazide 12a in
AcOH at ca. 118 °C (reflux) for 10 min led to cyclodehydration
and formation of the benzotriazine 23a, which was oxidatively
unstable and rapidly gave a mixture containing the Blatter
radical 1a. In light of this, during the workup we treated the
reaction mixture with 2 M NaOH at ca. 20 °C for 3 h, which
converted benzotriazine 23a into the Blatter radical 1a in high
yield (87%). Fortunately, when In powder (4 equiv) was used
in AcOH, the reduction of the nitro group and the
cyclodehydration could be performed in one pot, and after
the alkali workup the radical was obtained directly in 91% yield
(Table 2, entry 1). Because of the high cost of In powder, we
examined the use of cheaper Sn and Fe (Table 2, entries 2 and
3). While the use of Fe powder required a large excess (10
equiv) to drive the reduction to completion and gave the
radical in only 68% yield (Table 2, entry 3), the use of Sn (4
equiv) gave the radical in an excellent 96% yield (Table 2, entry
2). Interestingly, the three-step procedure did not tolerate the
use of stronger reducing metals such as Zn or Cu, which cause
reductive ring contraction of benzotriazines to benzimida-
zoles.15 Furthermore, the use of less than 4 equiv of Sn powder
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Table 2. Reduction and In Situ Cyclodehydration To Give Benzotriazinyls 1
entry
Y
R1
R2
R3
metal (equiv)
time at Δ (min)
product (% yield)
1
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
In (4)
Sn (4)
Fe (10)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (3)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
Sn (4)
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
0
1a (91)
1a (96)
1a (68)
1b (81)
1c (88)
1d (87)
H
3
H
4
F3C
H
5
4-FC6H4
thien-2-yl
pyrid-2-yl
Me
6
H
a
7
H
1e (82)
1f (63)
1g (64)
1h (63)
1i (83)
1j (79)
1k (85)
1l (71)
1m (77)
12b (78)
12b (98)
8
H
9
Me
F3C
H
10
11
12
13
14
15
16
17
18
19
20
21
22
F3C
F3C
F3C
H
1-Ad
4-NCC6H4
4-NCC6H4
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
Ph
Ph
H
thien-2-yl
Ph
H
H
bc
,
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
pyrid-2-yl
Ph
H
bc
,
H
0
c
H
10
180
180
60
60
12b (22)/23b (66)
c
H
23b (82)
c
F3C
H
23c (88)
1n (77)
c
N
pyrid-2-yl
pyrid-2-yl
H
23d (91)
a
b
c
2 M NaOH, 3 days, 20 °C. Reaction time at ca. 20 °C was 2 h. No alkali workup.
led to slow or incomplete reactions, while increasing the
amount of Sn or replacing AcOH with formic acid led to lower
yields. Therefore, the use of Sn (4 equiv) in AcOH was chosen
for the reduction of analogues 13b−q (Table 2, entries 4−22).
Interestingly, the Sn/AcOH-mediated reduction of the N′-
(pyrid-2-yl)picolinohydrazides 13m, 13n, and 13p followed by
the alkali workup (2 M NaOH) gave only traces of the
expected benzo- and pyrido-fused triazinyl radicals (by TLC)
and mainly afforded the reduced leuco forms 23b−d,
respectively. Thus, for these examples we chose to maximize
the yields of the leuco forms 23b−d by avoiding the alkali
workup (Table 2, entries 18−20 and 22). Furthermore, the N′-
phenylpicolinohydrazide 13e was reduced and cyclodehydrated
to give the benzotriazine after only 10 min of heating (by TLC)
but required extended treatment (3 days) with 2 M NaOH for
full conversion into the desired radical 1e (82%; Table 2, entry
7), while the N′-(pyrid-2-yl)benzohydrazide 13l was converted
without any difficulty into the radical 1m (77%; Table 2, entry
15). This suggests that the 3-(pyrid-2-yl) substituent had a
more significant effect on the transformation than the 1-(pyrid-
2-yl) substituent. The N′-(pyrid-2-yl)picolinohydrazides 13m,
13n, and 13p notably all required longer heating times (1−3 h;
Table 2, entries 19, 20, and 22). For the N′-(pyrid-2-
yl)picolinohydrazide 13m, shorter heating times (Table 2,
entry 18) led to a mixture of the leuco form 23b (66%) and the
noncyclized amine 12b (22%), both of which were sufficiently
stable to be isolated and characterized. Interestingly, the
reduction of the N′-(pyrid-2-yl)picolinohydrazide 13m at ca. 20
°C required a minimum of 3 equiv of Sn powder to give amine
12b in 78% yield after only 2 h (Table 2, entry 16), whereas the
use of 2.2 equiv of Sn powder led to an incomplete reaction
after 12 h (data not shown) and the use of 4 equiv led to
quantitative (98%) conversion in only 0.5 h (Table 2, entry
17).
Since the alkali treatment of the 1,3-bis(pyrid-2-yl)-
substituted benzo- and pyrido-fused triazines 23b−d failed to
give reasonable yields of the desired radicals, we attempted to
prepare the radicals via oxidation. Treatment of triazines 23b−
d with HgO (10 equiv) in DCM at ca. 20 °C for 1 day led to no
reaction. The use of Pd−C (1.6 mol %) with DBU (0.1−1
equiv) in DCM at ca. 20 °C for 1 day gave for benzotriazines
23b and 23c mainly unreacted starting material and traces of
what might be radical (by TLC), while pyridotriazine 23d gave
a complex reaction mixture that was not investigated further.
Therefore, we treated the benzo- and pyrido-fused triazines
23b−d with the stronger oxidizing agent MnO2 (10 equiv) in
DCM, upon which benzotriazine 23b gave the purple-colored
benzotriazinone 24 in 53% yield while the 7-trifluorobenzo-
triazine 23c fortunately gave the desired radical 1o in a
moderate 49% yield (Scheme 7). Trifluoromethyl substitution
at C-7 has previously been shown to prevent the oxidation of
Blatter radicals to the benzotriazinones.4a Treating the pyrido-
fused triazine 23d with MnO2 gave neither radical nor quinone,
and the reaction remains under investigation.
The pyrid-2-yl-substituted benzotriazinyl radicals 1e, 1m, and
1o and the 3-(pyrid-2-yl)-substituted benzotriazinone 24
promise to be interesting compounds for metal coordination
studies, and this work is currently under investigation. Several
1,3-diphenylbenzotriazinones have also been shown to inhibit
both AChE and β-amyloid aggregation, and therefore, access to
D
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< 2.0060; Table 3), consistent with organic radicals with small
spin−orbit couplings. Some variation in line width was also
observed and presumably results from dipolar line broadening
in the solid state, which exhibits a 1/rn dependence. The g
factors for radicals 1c−o in solution (2.0035 < g < 2.0050;
Table 3) were similar to those observed in the solid state, but
the lower concentrations permitted the resolution of the 14N
hyperfine coupling to the three chemically distinct N atoms of
the triazinyl ring. The solution EPR spectra of these radicals
(Figures S1−S13 in the Supporting Information) are similar to
those observed for other benzotriazinyls.3−5,17,18 The seven-line
spectra are consistent with the coupling of the unpaired
electron with three similar but slightly nonequivalent 14N
nuclei. EPR spectra of radicals containing F (1c) and F3C (1g−
i and 1o) show additional coupling to 19F atoms (Figures S1,
S5−S7, and S13, respectively, in the Supporting Information).
In radicals 1g and 1h, the F3C group causes further splitting of
the EPR signals into quartets, implying rotational averaging of
the three fluorine nuclei. The hfcc from 19F is likely to result
mostly from spin polarization for radicals 1c (R2 = 4-FC6H4)
and 1h (R2 = F3C), where the F-containing groups are
connected to a nodal carbon (C-3), whereas the connection of
the F3C group via C-7 in radicals 1g, 1i, and 1o (R3 = F3C)
causes a slightly larger hfcc as a result of the mesomeric
influence of the F lone pairs. However, fluorine has a large
atomic hyperfine parameter,19 and therefore, coupling to F does
not represent a large spin density at F. The EPR spectrum of
pyridotriazinyl radical 1n (Figure 2) appears as a binomial
nonet arising from coupling of the unpaired electron with four
chemically distinct 14N atoms.
Scheme 7. MnO2 Oxidation of 1,3-Bis(pyrid-2-
yl)benzotriazines 23b and 23c
new pyridyl analogues can lead to inhibitors with improved
properties.16
2.3. EPR Spectroscopy. Previous EPR studies of 1,2,4-
benzotriazinyl radicals showed that the spin density is mainly
delocalized on the amidrazonyl fragment of the 1,2,4-triazinyl
cycle.7a,c,d,17,18 The largest hyperfine coupling constant (hfcc) is
observed on the N-1 atom (∼7.5 G), whereas the N-2 and N-4
coupling constants are smaller and approximately equal to each
other (∼5.1 G). These two coupling constants were separately
measured with further EPR and ENDOR studies by
Neugebauer on 15N-labeled derivatives and found to be 4.9 G
for N-2 and 5.2 G for N-4 (aN‑1 ≫ aN‑4 > aN‑2).18b
The EPR spectra were simulated to determine the g factors
and hfcc values. For radicals 1c, 1g−i, 1n, and 1o, additional
simulations of the second derivatives were necessary because of
the low resolution of the first-derivative spectra. Assignments of
the hfcc values are given according to Neugebauer’s
Room-temperature solid-state EPR studies of the new
radicals 1c−o (Figures S1−S13 in the Supporting Information)
all revealed essentially isotropic singlet EPR spectra (2.0040 < g
Table 3. Fitting Parameters of Simulated Spectra for Radicals 1a−o
g
a (G)
radical
solid state
2.0041
DCM
N-1
N-2
N-4
F-3
F-7
other
a
1a
2.0033
2.0036
2.0040
7.50
7.62
7.68
7.69
7.81
7.69
7.82
7.97
7.97
8.07
8.07
6.64
8.13
7.51
6.89
7.12
6.74
6.88
7.12
6.88
6.88
4.77
4.56
4.84
4.75
4.83
4.57
4.94
4.23
4.37
4.21
4.19
4.38
2.70
4.94
4.95
4.89
4.88
4.81
4.81
4.20
4.25
5.05
4.95
4.90
5.00
5.07
5.13
4.95
5.03
5.36
5.36
5.31
4.38
3.62
5.13
5.08
5.26
4.93
4.81
5.13
4.44
4.32
b
1b
3.46
d
1c
0.54
c
d
1c
0.73
1d
1e
1f
2.0040
2.0060
2.0042
2.0042
2.0040
2.0040
2.0041
2.0035
1g
3.14
3.02
c
1g
1h
2.0042
2.0047
2.0050
2.0042
1.89
1.26
4.39
4.02
c
1h
1i
4.44
4.75
c
1i
1j
2.0046
2.0040
2.0040
2.0046
2.0050
2.0040
2.0040
2.0040
2.0040
2.0040
1k
1l
1m
1n
e
2.00
c
e
1n
1.94
1o
2.0040
2.0040
4.38
4.32
c
1o
a
b
c
d
e
Reference 18b. Reference 4a. Simulated second-derivative EPR spectrum. aF for 4-FC6H4. aN‑8
.
E
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a
Table 4. Cyclic Voltammetry Data for Radicals 1a−o
b
−1/0
0/+1
1/2
+1/+2
radical
E
(V)
E
(V)
E
1/2
(V)
Ecell (V)
1/2
c
1a
−0.96
−0.84
−0.97
−0.93
−0.96
−1.06
−0.84
−0.89
−0.58
−1.06
−0.78
−0.67
−0.82
−0.83
−0.54
0.10
1.06
1.20
1.16
1.12
1.17
1.32
1.19
1.14
1.24
1.14
1.06
1.00
1.06
1.18
1.15
c
1b
0.36
0.19
0.19
0.21
0.26
0.35
0.25
0.66
0.08
0.28
0.33
0.24
0.35
0.61
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
Figure 2. Experimental (blue) and simulated (red) solution EPR
spectra of pyridotriazinyl radical 1n in DCM at ca. 20 °C. Fitting
parameters are shown in Table 3
1m
1n
1o
0.77
observations: the largest hfcc is on the N-1 atom (6.64−8.13
G), followed by that on N-4 (3.62−5.36 G), which is slightly
larger than that on N-2 (2.70−4.95 G). Electron-withdrawing
groups directly attached to the N-1 atom (1k, 1m, and 1o)
have the biggest impact on the electron distribution over the
amidrazonyl fragment, reducing the electron density on the
three triazinyl N atoms. The pyrido-fused ring in 1n has the
same effect, shifting electron density from the amidrazonyl unit
and resulting in smaller hfcc values (Table 3).
On the basis of the estimated hfcc values, we employed the
McConnell equation20,21 to calculate the spin density
distribution around the benzotriazinyl ring (Table T1 in the
Supporting Information). Atomic spin densities of the benzo-
fused rings in radicals 1c−n could not be experimentally
determined since line-broadening of the spectra resulted in
poor resolution of the hfcc. It is clear from Table T1 that most
of the spin density is mainly delocalized over the 1,2,4-triazinyl
ring, indicating the importance of this part of the molecule in
the solid-state packing and therefore in the transport and
magnetic properties of the radicals. However, the introduction
of electron-withdrawing or electron-donating groups directly on
N-1 can significantly alter this distribution.
2.4. Cyclic Voltammetry. The electrochemical behavior of
1 mM DCM solutions of the radicals 1c−o was probed by
cyclic voltammetry using n-Bu4NBF4 as a supporting electrolyte
and the ferrocene/ferrocenium (Fc/Fc+) couple as an internal
reference (Table 4 and Figures S14−S26 in the Supporting
Information). The redox behavior of radicals 1c−o is typical of
1,2,4-benzotriazinyls: two fully reversible waves that correspond
to −1/0 and 0/+1 processes. While substitution at C3 (the
nodal carbon) did not significantly alter the halfway oxidation
and reduction potentials (1c−f and 1h; Table 4), the 4-
cyanophenyl and pyrid-2-yl substituents at N-1, which are less
electron-releasing than phenyl, moderately facilitated the
reduction of the radicals (1k−m; Table 4).
Interestingly, the introduction of a strongly electron-
withdrawing F3C group at either C-3 (1h) or C-7 (1b) did
not cause a notable change in the redox potential; however,
when two such groups were combined, as in the 3,7-
bis(trifluoromethyl) radical 1i, they worked in a synergistic
manner and dramatically reduced the reduction potential to
−0.58 V and increased the oxidation potential to 0.66 V. A
similar effect was observed when pyrid-2-yl groups were placed
at N-1 and C-3 in the presence of a F3C group at C-7 (radical
a
The concentration of radicals used was 1 mM in DCM containing n-
Bu4NBF4 (0.1 M) as an electrolyte. Reference electrode = Ag/AgCl;
scan rate = 50 mV s−1; temperature = 20 °C. Fc/Fc+ (0.352 V) was
used as an internal reference.22 Ecell = E
− E . Reference 4a.
b
c
−1/0
0/+1
1/2
1/2
The above data indicate that the redox potentials of 1,2,4-
benzotriazinyls can be tailored by strategic substitution.
Customizing the redox potentials of 1,2,4-benzotriazinyls can
enable their broader application in the material sciences.
Nonetheless, the presence of more than one substituent was
needed to alter the electron density distribution and thus the
redox potential significantly.
3. CONCLUSIONS
A route to benzo- and pyrido-fused triazinyl radicals has been
developed that avoids the formation of unstable or highly
reactive intermediates, such as amidrazones or imidoyl
chlorides. The synthesis involves the preparation of 1-(2-
nitroaryl)-1-arylhydrazides from 1-halo-2-nitroarenes and 1-
arylhydrazides. Subsequent reduction of the nitro group using a
mild reducing agent (e.g., In or Sn powder) followed by in situ
acid-catalyzed cyclodehydration and finally an alkali workup
affords the desired radicals. For 3-alkyl-substituted benzotria-
zinyl radicals, an alternative multistep route that involves the
preparation of asymmetrically 1,1-diaryl-substituted hydrazines
provides overall higher yields. In this manner, 15 radicals with
varying substitution at the N-1, C-3, and C-7 positions were
prepared.
4. EXPERIMENTAL SECTION
4.1. General Methods. Anhydrous Na2SO4 was used to dry
organic extracts, and all volatiles were removed under reduced
pressure. All reaction mixtures and column eluents were monitored by
thin-layer chromatography (TLC) using commercial glass-backed
TLC plates (Kieselgel 60 F254 or, where stated, aluminum oxide 60
F254 neutral). 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 and employed
either silica gel 60 (<0.063 mm) or, where stated, aluminum oxide 60
G neutral (type E). Melting and decomposition points were
determined using either a Kofler hot-stage microscope apparatus or
a DSC with samples hermetically sealed in aluminum pans under an
argon atmosphere, using heating rates of 5 °C/min. The solvent used
for recrystallization is indicated after each melting point. UV spectra
were obtained using a UV/vis spectrophotometer, and inflections are
identified by the abbreviation “inf”. IR spectra were recorded on an
FTIR-NIR spectrometer with a Ge ATR accessory, and strong,
1o). For the latter, an additional oxidation peak was also
+1/+2
1/2
observed at E
= 0.77 V.
F
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medium, and weak peaks are represented by “s”, “m”, and “w”,
(d), 99.2 (s); MALDI-TOF m/z (%): 244 (MH+, 30), 242 (M+ − 1,
30), 231 (96), 225 (11), 199 (20), 158 (6), 133 (8), 115 (9), 109
(100).
1
respectively. H and 13C NMR spectra were recorded at 300 and 75
MHz, respectively, or at 500 and 125 MHz, 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 GC/MS with direct inlet probe.
MALDI-TOF MS was conducted on a time-of-flight (TOF) mass
spectrometer. Cyclic voltammetry (CV) measurements were per-
formed on a Princeton Applied Research 263A potentiostat/
galvanostat apparatus. The concentration of the benzotriazinyl radical
used was 1 mM in DCM containing tetra-n-butylammonium
tetrafluoroborate (n-Bu4NBF4) (0.1 M) as the electrolyte. The
4.3. 2-Nitrophenylation of Hydrazides 19 with 1-Halo-2-
nitro(het)arenes 18. 4.3.1. N′-(2-Nitrophenyl)-N′-phenylbenzohy-
drazide (13a) (Typical Procedure). To a stirred solution of N′-
phenylbenzohydrazide (19a) (1.167 g, 5.5 mmol) and 1-fluoro-2-
nitrobenzene (18a) (0.527 mL, 5.0 mmol) in EtOH (4 mL) at ca. 20
°C was added powdered K2CO3 (0.760 g, 5.5 mmol). The reaction
mixture was then sealed in a glass pressure tube and heated at ca. 110
°C for 2 days, allowed to cool to ca. 20 °C, diluted with DCM (10
mL), filtered through Celite, and rinsed with additional DCM, and the
volatiles were removed in vacuo. The residue was dissolved in DCM
(2 mL) and chromatographed (DCM) to give the title compound 13a
as yellow needles (1.667 g, 62%). Mp 170−172 °C (from EtOH)
(lit.33 171−172 °C); Rf 0.27 (DCM); νmax/cm−1 3283w (NH), 3082w,
3059w and 3040w (Ar CH), 1657s (CO), 1593m, 1530s, 1487s,
1477m, 1456w, 1447w, 1352s, 1306m, 1263m, 1248m, 1167w, 1155w,
1097w, 1076w, 1061w, 1026w, 980w, 932w, 893m, 853m, 804w,
773m; δH (300 MHz, CDCl3) 8.65 (1H, br s), 8.05 (1H, dd, J = 8.2,
1.4 Hz), 7.93 (1H, dd, J = 8.1, 1.1 Hz), 7.88−7.79 (2H, m), 7.68 (1H,
ddd, J = 7.9, 7.9, 1.5 Hz), 7.57 (1H, ddd, J = 7.3, 7.3, 1.3 Hz), 7.53−
7.37 (3H, m), 7.25−7.19 (3H, m), 6.95 (1H, dd, J = 7.4, 7.4 Hz),
6.90−6.82 (2H, m); δC (75 MHz, CDCl3) 166.5 (s), 145.7 (s), 145.0
(s), 138.8 (s), 134.7 (d), 132.5 (d), 131.8 (s), 131.1 (d), 129.2 (d),
128.8 (d), 127.3 (d), 127.1 (d), 126.2 (d), 121.7 (d), 114.9 (d);
identical to an authentic sample.
reference electrode was Ag/AgCl, and the scan rate was 50 mV/s.
ox
The Fc/Fc+ couple, for which E = 0.352 V in this system, was used
1/2
as an internal reference.22 EPR spectra were recorded on an X-band
EPR spectrometer at room temperature on solid-state samples of the
benzotriazinyls and on dilute solutions in DCM. For the dilute-
solution spectra, the microwave power was in the region 5−70 mW
with a modulation frequency of 50 or 100 kHz and a modulation
amplitude of 0.5−1.0 Gpp. Simulations of the solution spectra were
made using WinSim.23 The nearly isotropic nature of most of the
benzotriazinyl radical samples meant that the majority of the solid-
state samples could be initially modeled with an isotropic spectrum
using WinSim. N′-Phenylbenzohydrazide (19a),24 4-fluoro-N′-phenyl-
benzohydrazide (19b),25 N′-phenylthiophene-2-carbohydrazide
(19c),26 N′-phenylpicolinohydrazide (19d),27 N′-phenylacetohydra-
zide (19e),28 2,2,2-trifluoro-N′-phenylacetohydrazide (19f),29 N′-
(pyrid-2-yl)benzohydrazide (19i)30 N′-(pyrid-2-yl)picolinohydrazide
(19j),31 and 1-benzylidene-2-phenylhydrazine (20)32 were prepared
according to literature procedures.
4.3.2. N′-[2-Nitro-5-(trifluoromethyl)phenyl]-N′-phenylbenzohy-
drazide (13b). Similar treatment of N′-phenylbenzohydrazide (19a)
(1.167 g, 5.5 mmol) with 2-fluoro-1-nitro-4-(trifluoromethyl)benzene
(18b) (0.700 mL, 5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in
EtOH (4 mL) in a thick-walled glass tube that was sealed and heated
at ca. 110 °C for 1 day gave upon chromatography (DCM) the title
compound 13b as yellow needles (1.203 g, 60%). Mp (DSC) onset
165.3 °C, peak max 166.2 °C (from MeOH); Rf 0.59 (DCM); (anal.
found: C, 60.00; H, 3.41; N, 10.58. C20H14F3N3O3 requires C, 59.85;
H, 3.52; N, 10.47%); λmax(DCM)/nm (log ε) 234 (3.44), 263 (3.13),
410 (2.37); νmax/cm−1 3215m (NH), 3063w (Ar CH), 1670s (CO),
1618m, 1589m, 1524s, 1499m, 1487m, 1431m, 1371m, 1346s, 1323m,
1306s, 1294s, 1265m, 1234m, 1179s, 1163m, 1155m, 1123s, 1103m,
1076m, 1065m, 1028m, 962m, 895m, 872m, 849m, 833s, 800m, 779m,
756w, 735m; δH (500 MHz, DMSO-d6) 11.51 (1H, s), 8.07 (1H, d, J =
8.5 Hz), 7.87 (2H, dd, J = 8.5, 1.3 Hz), 7.71 (1H, s), 7.67−7.60 (2H,
m), 7.53 (2H, dd, J = 7.6, 7.6 Hz), 7.33 (2H, dd, J = 8.0, 8.0 Hz),
7.12−7.04 (3H, m); δC (125 MHz, DMSO-d6) 165.9 (s), 144.4 (s),
4.2. Synthesis of N′-(4-Cyanophenyl)hetarylhydrazides 19g
and 19h. 4.2.1. N′-(4-Cyanophenyl)benzohydrazide (19g) (Typical
Procedure). Hydrazin-4-ylbenzonitrile hydrochloride (0.509 g, 3
mmol) was suspended in DCM (5 mL), and Et3N (0.668 g, 6.6
mmol) was added. The mixture was immersed in an ice−salt bath (ca.
−5 °C), and benzoyl chloride (0.422 g, 3 mmol) was added dropwise
under vigorous stirring. The reaction mixture was allowed to slowly
(12 h) warm to ca. 20 °C, diluted with DCM (50 mL), and washed
with water (2 × 50 mL). The organic phase was separated and dried
(Na2SO4), and the volatiles were removed in vacuo. Trituration of the
residue with PhH (10 mL) precipitated the title compound 19g as
colorless needles (0.513 g, 72%). Mp 187−188 °C (from PhH); Rf
0.88 (t-BuOMe); (anal. found: C, 70.91; H, 4.61; N, 17.60.
C14H11N3O requires C, 70.87; H, 4.67; N, 17.71%); λmax(DCM)/
nm (log ε) 232 (3.60), 267 (4.00); νmax/cm−1 3316w and 3260m
(NH), 2216s (CN), 1628s, 1607s, 1578m, 1541m, 1512s, 1481m,
1447w, 1346w, 1296m, 1267m, 1176m, 1167m, 1157m, 1069w,
1024m, 1002w, 914w, 831s, 818m, 799m; δH (500 MHz, DMSO-d6)
10.53 (1H, s), 8.78 (1H, s), 7.91 (2H, d, J = 7.5 Hz), 7.60 (1H, dd, J =
7.5, 7.5 Hz), 7.56 (2H, d, J = 8.5 Hz), 7.51 (2H, dd, J = 7.5, 7.5 Hz),
6.83 (2H, d, J = 9.0 Hz); δC (125 MHz, DMSO-d6) 166.5 (s), 153.1
(s), 133.6 (d), 132.6 (s), 132.1 (d), 128.7 (d), 127.5 (d), 120.2 (s),
111.9 (d), 99.1 (s); MALDI-TOF m/z (%): 238 (M+, 41), 220 (15),
195 (8), 117 (10), 105 (100).
4.2.2. N′-(4-Cyanophenyl)thiophene-2-carbohydrazide (19h).
Similar treatment of 4-hydrazinylbenzonitrile hydrochloride (0.509 g,
3 mmol) with Et3N (0.668 g, 6.6 mmol) and dropwise addition of
thiophene-2-carbonyl chloride (0.440 g, 320.8 μL, 3 mmol) gave the
title compound 19h as colorless plates (0.511 g, 70%). Mp (DSC)
onset 236.3 °C, peak max 237.5 °C (from PhH); Rf 0.63 (t-BuOMe);
(anal. found: C, 59.47; H, 3.69; N, 17.42. C12H9N3OS requires C,
59.24; H, 3.73; N, 17.27%); λmax(DCM)/nm (log ε) 230 (3.52), 268
(4.03); νmax/cm −1 3207w and 3113w (NH), 2984w, 2224m (CN),
1663s (CO), 1632s, 1601w, 1530m, 1497s, 1414s, 1358s, 1337m,
1325w, 1302s, 1267m, 1221w, 1171w, 1101w, 1072w, 1040w, 1040w,
961w, 889s, 862s, 840w, 814w, 756s, 739s; δH (500 MHz, DMSO-d6)
10.55 (1H, s), 8.79 (1H, s), 7.88 (1H, d, J = 4.0 Hz), 7.85 (1H, d, J =
5.0 Hz), 7.56 (2H, d, J = 9.0 Hz), 7.21 (1H, dd, J = 4.5, 4.5 Hz), 6.80
(2H, d, J = 8.5 Hz); δC (125 MHz, DMSO-d6) 161.5 (s), 153.0 (s),
137.6 (s), 133.6 (d), 131.9 (s), 129.1 (d), 128.3 (d), 120.1 (s), 111.9
2
144.0 (s), 139.3 (s), 133.0 (q, JFC = 32.2 Hz), 132.4 (d), 131.5 (s),
129.3 (d), 128.6 (d), 127.6 (d), 126.8 (d), 123.7 (d), 122.9 (q, 1JFC
272.9 Hz), 120.4 (q, JFC = 2.7 Hz), 120.2 (q, JFC = 3.6 Hz), 118.3
(d); MALDI-TOF m/z (%): 402 (MH+, 25), 354 (16), 297 (21), 280
(53), 235 (28), 104 (100).
=
3
3
4.3.3. 4-Fluoro-N′-(2-nitrophenyl)-N′-phenylbenzohydrazide
(13c). Similar treatment of 4-fluoro-N′-phenylbenzohydrazide (19b)
(1.266 g, 5.5 mmol) with 1-fluoro-2-nitrobenzene (18a) (0.527 mL,
5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a
thick-walled glass tube that was sealed and heated at ca. 110 °C for 2
days gave upon chromatography (DCM) the title compound 13c as
yellow needles (1.106 g, 63%). Mp (DSC) onset 169.9 °C, peak max
170.8 °C (from EtOH); Rf 0.39 (DCM); (anal. found: C, 65.08; H,
3.95; N, 12.13. C19H14FN3O3 requires C, 64.95; H, 4.02; N, 11.96%);
λmax(DCM)/nm (log ε) 235 (3.44), 265 (3.18), 407 (2.27); νmax/cm−1
3269w (NH), 1659s (CO), 1605m, 1595m, 1530s, 1497s, 1477m,
1456w, 1408w, 1352s, 1329w, 1300w, 1263m, 1252m, 1238m, 1159m,
1155m, 1094w, 1059w, 1013w, 970w, 930w, 897m, 854m, 849m,
814w, 773s, 764m, 750s, 731m; δH (500 MHz, DMSO-d6) 11.36 (1H,
s), 7.95 (2H, dd, J = 8.8, 5.5 Hz), 7.87 (1H, dd, J = 8.2, 1.3 Hz), 7.68
(1H, ddd, J = 7.8, 7.8, 1.3 Hz), 7.57 (1H, d, J = 7.4 Hz), 7.40−7.31
(3H, m), 7.26 (2H, dd, J = 8.0, 8.0 Hz), 6.98 (1H, dd, J = 7.3, 7.3 Hz),
6.91 (2H, d, J = 8.0 Hz); δC (125 MHz, DMSO-d6) 164.8 (s), 164.3
1
(q, JFC = 249.8 Hz), 145.6 (s), 143.1 (s), 138.2 (s), 133.9 (d), 130.3
(d, 3JFC = 9.1 Hz), 129.0 (d), 128.4 (d, 4JFC = 2.7 Hz), 125.1 (d), 124.8
G
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(d), 122.1 (d), 116.8 (d), 115.6 (d, 2JFC = 21.8 Hz); MALDI-TOF m/
z (%): 352 (MH+, 53), 334 (14), 324 (14), 304 (49), 212 (100), 184
(10), 167 (32), 122 (27).
major and minor prototautomers: major 169.3 (s), 145.7 (s), 143.7
(s), 138.2 (s), 134.2 (d), 129.1 (d), 126.6 (d), 125.6 (d), 125.3 (d),
121.6 (d), 115.7 (d), 20.3 (q); minor 174.6 (s), 146.7 (s), 142.9 (s),
138.6 (s), 134.8 (d), 129.4 (d), 125.8 (d), 125.5 (d), 124.7 (d), 123.3
(d), 117.2 (d), 19.4 (q); MS (EI) m/z (%): 271 (M+, 55), 229 (100),
212 (58), 196 (4), 181 (62), 167 (92), 152 (18), 140 (9), 128 (9), 115
(5), 105 (6), 77 (74), 65 (7), 51 (29).
4.3.4. N′-(2-Nitrophenyl)-N′-phenyl-2-thiophenecarbohydrazide
(13d). Similar treatment of N′-phenylthiophene-2-carbohydrazide
(19c) (1.200 g, 5.5 mmol) with 1-fluoro-2-nitrobenzene (18a)
(0.527 mL, 5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4
mL) in a thick-walled glass tube that was sealed and heated at ca. 110
°C for 2 days gave upon chromatography (DCM) the title compound
13d as yellow needles (1.034 g, 61%). Mp (DSC) onset 170.8 °C,
peak max 171.7 °C (from 2-PrOH); Rf 0.20 (DCM); (anal. found: C,
60.11; H, 3.89; N, 12.31. C17H13N3O3S requires C, 60.17; H, 3.86; N,
12.38%); λmax(DCM)/nm (log ε) 239 (3.43), 264 inf (3.37), 410
(2.06); νmax/cm−1 3262w (NH), 3084w (Ar CH), 1645s (CO),
1609w, 1593m, 1526s, 1495m, 1477m, 1456w, 1449w, 1416m, 1352s,
1323m, 1304m, 1265m, 1244m, 1167w, 1146w, 1092w, 1061w,
1030w, 928w, 903w, 876m, 849s, 773m, 745s, 729m; δH (300 MHz,
DMSO-d6) 11.36 (1H, s), 7.94 (1H, d, J = 3.6 Hz), 7.91−7.85 (2H,
m), 7.70 (1H, ddd, J = 7.9, 7.9, 1.3 Hz), 7.58 (1H, d, J = 7.4 Hz), 7.35
(1H, ddd, J = 7.8, 7.8, 0.8 Hz), 7.31−7.18 (3H, m), 6.97 (1H, dd, J =
7.3, 7.3 Hz), 6.89 (2H, d, J = 7.9 Hz); δC (75 MHz, DMSO-d6) 160.8
(s), 145.7 (s), 143.1 (s), 138.2 (s), 136.3 (s), 134.0 (d), 132.3 (d),
129.6 (d), 129.0 (d), 128.2 (d), 125.3 (d), 125.2 (d), 125.0 (d), 122.1
(d), 116.6 (d); MALDI-TOF m/z (%): 340 (MH+, 28), 339 (M+,
100), 322 (12), 287 (21), 256 (55), 228 (17), 216 (31), 212 (18), 181
(8), 167 (5).
4.3.5. N′-(2-Nitrophenyl)-N′-phenylpicolinohydrazide (13e). Sim-
ilar treatment of N′-phenylpicolinohydrazide (19d) (1.173 g, 5.5
mmol) with 1-fluoro-2-nitrobenzene (18a) (0.527 mL, 5.0 mmol) and
K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled glass
tube that was sealed and heated at ca. 110 °C for 2 days gave upon
chromatography (DCM) the title compound 13e as yellow needles
(1.420 g, 85%). Mp (DSC) onset 178.3 °C, peak max 182.8 °C (from
EtOAc/n-pentane); Rf 0.70 (t-BuOMe); (anal. found: C, 64.80; H,
4.29; N, 16.89. C18H14N4O3 requires C, 64.66; H, 4.22; N, 16.76%);
λmax(DCM)/nm (log ε) 234 (3.32), 261 inf (2.99), 266 (3.03), 273 inf
(2.99); νmax/cm−1 3233m (NH), 3059w and 3009w (Ar CH), 1659s
(CO), 1603m, 1589m, 1570w, 1537m, 1495s, 1466m, 1431m,
1323w, 1308w, 1290w, 1256w, 1244m, 1177w, 1101w, 1090w, 1049w,
999m, 970w, 918m, 872m, 818m, 758s, 743s; δH (500 MHz, acetone-
d6) 10.46 (1H, s), 8.68 (1H, d, J = 4.5 Hz), 8.13 (1H, d, J = 8.0 Hz),
8.06−8.03 (2H, m), 7.89 (1H, d, J = 8.0 Hz), 7.81 (1H, dd, J = 8.0, 8.0
Hz), 7.68−7.66 (1H, m), 7.54 (1H, dd, J = 7.5, 7.5 Hz), 7.23 (2H, dd,
J = 8.5, 8.5 Hz), 6.92 (1H, d, J = 7.5, 7.5 Hz), 6.87 (2H, d, J = 8.0 Hz);
δC (75 MHz, acetone-d6) 163.8 (s), 150.0 (s), 149.6 (d), 147.3 (s),
146.3 (s), 139.2 (s), 138.7 (d), 135.4 (d), 130.6 (d), 129.9 (d), 128.2
(d), 128.0 (d), 126.7 (d), 123.3 (d), 122.2 (d), 115.8 (d); MALDI-
TOF m/z (%): 335 (MH+, 22), 334 (M+, 100), 317 (60), 288 (43).
4.3.6. N′-(2-Nitrophenyl)-N′-phenylacetohydrazide (13f). Similar
treatment of N′-phenylacetohydrazide (19e) (0.826 g, 5.5 mmol) with
1-fluoro-2-nitrobenzene (18a) (0.527 mL, 5.0 mmol) and K2CO3
(0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled glass tube that
was sealed and heated at ca. 110 °C for 2 days gave upon
chromatography (DCM/t-BuOMe, 1:1) the title compound 13f as
yellow needles (0.312 g, 23%). Mp (DSC) onset 140.9 °C, peak max
141.7 °C (from 2-PrOH); Rf 0.45 (t-BuOMe); (anal. found: C, 62.11;
H, 4.76; N, 15.56. C14H13N3O3 requires C, 61.99; H, 4.83; N,
15.49%); λmax(DCM)/nm (log ε) 236 (3.38), 264 (3.22), 404 (2.32);
νmax/cm−1 3256w (NH), 3084w and 3026w (Ar CH), 1697w, 1672s
(CO), 1595m, 1574w, 1526s, 1495s, 1479m, 1458w, 1354s, 1329m,
1317m, 1302m, 1258w, 1234m, 1182w, 1165w, 1132w, 1082w, 1040w,
1032w, 997w, 957w, 899w, 874w, 853w, 777s, 752m; δH (500 MHz,
DMSO-d6) mixture of major and minor prototautomers: major 10.54
(1H, s), 7.87 (1H, d, J = 8.0 Hz), 7.68 (1H, dd, J = 7.7, 7.7 Hz), 7.54
(1H, d, J = 7.9 Hz), 7.36 (1H, dd, J = 7.6, 7.6 Hz), 7.22 (2H, dd, J =
7.9, 7.9 Hz), 6.91 (1H, dd, J = 7.3, 7.3 Hz), 6.77 (2H, d, J = 8.0 Hz),
1.91 (3H, s); minor 10.12 (1H, s), 7.93 (1H, d, J = 8.0 Hz), 7.78 (1H,
dd, J = 7.7, 7.7 Hz), 7.59 (1H, d, J = 8.2 Hz), 7.41 (1H, dd, J = 7.6, 7.6
Hz), 7.29 (2H, dd, J = 7.9, 7.9 Hz), 7.03 (1H, dd, J = 7.3, 7.3 Hz), 6.83
(2H, d, J = 8.0 Hz), 1.96 (3H, s); δC (125 MHz, DMSO-d6) mixture of
4.3.7. N′-[2-Nitro-5-(trifluoromethyl)phenyl]-N′-phenylacetohy-
drazide (13g). Similar treatment of N′-phenylacetohydrazide (19e)
(0.826 g, 5.5 mmol) with 2-fluoro-1-nitro-4-(trifluoromethyl)benzene
(18b) (0.700 mL, 5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in
EtOH (4 mL) in a thick-walled glass tube that was sealed and heated
at ca. 110 °C for 1 day gave upon chromatography (DCM/t-BuOMe)
the title compound 13g as yellow needles (0.322 g, 19%). Mp (DSC)
onset 156.3 °C, peak max 157.2 °C (from c-hexane); Rf 0.16 (DCM);
(anal. found: C, 52.89; H, 3.39; N, 12.22. C15H12F3N3O3 requires C,
53.10; H, 3.57; N, 12.39%); λmax(DCM)/nm (log ε) 236 (3.13), 267
inf (2.94), 407 (2.24); νmax/cm−1 3167w (NH), 2994w, 1663m (C
O), 1614w, 1591m, 1537m, 1493m, 1458w, 1429m, 1371m, 1344s,
1312s, 1300s, 1256m, 1233w, 1177s, 1167s, 1128s, 1094m, 1070m,
1026w, 1003w, 976w, 872m, 854m, 837w, 829m, 820m, 772m, 752w;
δH (500 MHz, DMSO-d6) mixture of major and minor prototau-
tomers: major 10.78 (1H, s), 8.07 (1H, d, J = 8.4 Hz), 7.69 (1H, s),
7.65 (1H, d, J = 8.7 Hz), 7.29 (2H, dd, J = 7.9, 7.9 Hz), 7.03 (1H, dd, J
= 7.3, 7.3 Hz), 6.97 (2H, d, J = 8.2 Hz), 1.93 (3H, s); minor 10.23
(1H, s), 8.15 (1H, d, J = 8.4 Hz), 7.90 (1H, s), 7.76 (1H, d, J = 8.5
Hz), 7.33 (2H, d, J = 8.0 Hz), 7.11 (1H, dd, J = 7.4, 7.4 Hz), 2.01 (3H,
s); δC (125 MHz, DMSO-d6) mixture of major and minor
prototautomers: major 144.5 (s), 144.3 (s), 169.2 (s), 139.1 (s),
2
133.0 (q, JFC = 32.2 Hz), 129.2 (d), 126.8 (d), 123.2 (d), 122.9 (q,
3
3
1JFC = 273.4 Hz), 121.1 (q, JFC = 3.6 Hz), 120.8 (q, JFC = 3.6 Hz),
117.4 (d), 20.1 (q); minor (five C signals missing) 174.2 (s), 145.7
(s), 139.3 (s), 129.4 (d), 127.0 (d), 124.3 (d), 118.2 (d), 19.3 (q);
MALDI-TOF m/z (%): 340 (MH+, 44), 297 (100), 280 (29), 235
(23).
4.3.8. 2,2,2-Trifluoro-N′-(2-nitrophenyl)-N′-phenylacetohydrazide
(13h). Similar treatment of 2,2,2-trifluoro-N′-phenylacetohydrazide
(19f) (1.123 g, 5.5 mmol) with 1-fluoro-2-nitrobenzene (18a) (0.527
mL, 5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a
thick-walled glass tube that was sealed and heated at ca. 110 °C for 2
days gave upon chromatography (DCM) the title compound 13h as
yellow needles (0.276 g, 17%). Mp (DSC) onset 90.5 °C, peak max
91.5 °C (from n-hexane); Rf 0.61 (DCM); (anal. found: C, 51.69; H,
3.16; N, 12.82. C14H10F3N3O3 requires C, 51.70; H, 3.10; N, 12.92%);
λmax(DCM)/nm (log ε) 231 (3.34), 259 inf (3.13), 325 (2.51), 382
(2.07); νmax/cm−1 3319w (NH), 3103w and 3044w (Ar CH), 1740s
(CO), 1595w, 1578w, 1514m, 1497s, 1456w, 1350m, 1310m,
1298m, 1254w, 1207s, 1192m, 1175s, 1163s, 1113w, 1099w, 1067w,
934w, 901m, 878w, 853w, 793m, 775w, 766w, 741s; δH (300 MHz,
DMSO-d6) 12.46 (1H, s), 7.95 (1H, dd, J = 7.9, 1.1 Hz), 7.76 (1H,
ddd, J = 8.4, 7.2, 1.1 Hz), 7.55−7.41 (2H, m), 7.31 (2H, dd, J = 7.9,
7.9 Hz), 7.04 (1H, dd, J = 7.4, 7.4 Hz), 6.84 (2H, d, J = 7.9 Hz); δC
2
(75 MHz, DMSO-d6) 155.6 (q, JFC = 36.5 Hz), 144.9 (s), 144.2 (s),
136.9 (s), 134.4 (d), 129.2 (d), 126.5 (d), 126.7 (d), 125.3 (d), 122.8
1
(d), 116.8 (d), 115.5 (q, JFC = 289.0 Hz); MS (EI) m/z (%): 325
(M+, 23), 278 (41), 228 (18), 207 (6), 181 (46), 167 (29), 154 (40),
140 (10), 128 (8), 115 (4), 105 (7), 91 (7), 77 (100), 69 (22), 63
(13), 51 (83).
4.3.9. 2,2,2-Trifluoro-N′-[2-nitro-5-(trifluoromethyl)phenyl]-N′-
phenylacetohydrazide (13i). Similar treatment of 2,2,2-trifluoro-N′-
phenylacetohydrazide (19f) (1.123 g, 5.5 mmol) with 2-fluoro-1-nitro-
4-(trifluoromethyl)benzene (18b) (0.700 mL, 5.0 mmol) and K2CO3
(0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled glass tube that
was sealed and heated at ca. 110 °C for 1 day gave upon
chromatography the title compound 13i as yellow needles (0.688 g,
35%). Mp (DSC) onset 106.1 °C, peak max 107.5 °C (from n-
hexane); Rf 0.61 (DCM); (anal. found: C, 45.70; H, 2.29; N, 10.60.
C15H9F6N3O3 requires C, 45.81; H, 2.31; N, 10.69%); λmax(DCM)/
nm (log ε) 232 (3.06), 249 inf (2.94), 389 (2.05); νmax/cm−1 3204w
(NH), 3036w (Ar CH), 1713s (CO), 1614w, 1591m, 1541m,
H
dx.doi.org/10.1021/jo402481t | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1493m, 1458w, 1427m, 1352m, 1331m, 1314m, 1296m, 1271m,
1250m, 1217s, 1161s, 1142s, 1130s, 1109w, 1084s, 1072m, 1028w,
1005w, 951w, 905w, 878m, 851m, 827m, 810w, 770m, 754w, 745w;
δH (300 MHz, DMSO-d6) 12.59 (1H, s), 8.15 (1H, d, J = 8.5 Hz), 7.80
(1H, d, J = 8.9 Hz), 7.72 (1H, s), 7.36 (2H, dd, J = 7.9, 7.9 Hz), 7.13
(1H, dd, J = 7.4, 7.4 Hz), 6.98 (2H, d, J = 7.7 Hz); δC (75 MHz,
(500 MHz, CDCl3) 8.88 (1H, s), 8.08 (1H, dd, J = 5.0, 1.0 Hz), 8.06
(1H, dd, J = 8.0, 1.5 Hz), 8.01 (1H, dd, J = 8.0, 1.5 Hz), 7.88 (2H, dd,
J = 7.0, 1.5 Hz), 7.72 (1H, ddd, J = 7.8, 7.8, 1.5 Hz), 7.58−7.52 (2H,
m), 7.50−7.46 (3H, m), 6.84 (1H, d, J = 8.0 Hz), 6.79 (1H, dd, J = 7.0,
5.0 Hz); δC (500 MHz, CDCl3) 166.8 (s), 156.9 (s), 147.8 (d), 146.1
(s), 138.1 (d), 137.1 (s), 134.9 (d), 132.58 (d), 132.56 (d), 131.9 (s),
128.8 (d), 128.4 (d), 127.4 (d), 125.6 (d), 116.4 (d), 107.2 (d);
MALDI-TOF m/z (%): 336 (MH+ + 1, 10), 335 (MH+, 89), 317 (12),
288 (100), 200 (27), 174 (11).
2
DMSO-d6) 155.8 (q, JFC = 36.8 Hz), 145.2 (s), 143.9 (s), 137.8 (s),
2
133.4 (q, JFC = 32.9 Hz), 129.5 (d), 126.9 (d), 124.3 (d), 122.7 (q,
3
3
1JFC = 273.4 Hz), 122.5 (q, JFC = 3.6 Hz), 121.1 (q, JFC = 3.6 Hz),
118.2 (d), 115.4 (q, JFC = 288.2 Hz); MS (EI) m/z (%): 393 (M+,
1
4.3.13. N′-(2-Nitrophenyl)-N′-(pyrid-2-yl)picolinohydrazide
(13m). Similar treatment of N′-(pyrid-2-yl)picolinohydrazide (19k)
(1.180 g, 5.5 mmol) with 1-fluoro-2-nitrobenzene (18a) (0.527 mL,
5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a
thick-walled glass tube that was sealed and heated at ca. 110 °C for 2
days gave upon chromatography (t-BuOMe/n-hexane, 1:1) the title
compound 13m as yellow needles (1.260 g, 75%). Mp (DSC)
decomp. onset 256.6 °C, peak max 297.4 °C (from c-hexane); Rf 0.44
(t-BuOMe); (anal. found: C, 61.01; H, 3.84; N, 20.76. C17H13N5O3
requires C, 60.89; H, 3.91; N, 20.89%); λmax(DCM)/nm (log ε) 230
(3.41), 259 (3.24), 288 inf (2.99), 376 (2.14); νmax/cm−1 3341w
(NH), 1703m (CO), 1589s, 1572m, 1526s, 1485m, 1468s, 1433s,
1352m, 1300w, 1281w, 1236w, 1152w, 1107w, 1088w, 1069w, 1040w,
997w, 988w, 903w, 853w, 820w, 779m, 770m; δH (300 MHz, CDCl3)
10.34 (1H, s), 8.63 (1H, d, J = 4.7 Hz), 8.22 (1H, d, J = 7.9 Hz), 8.11−
8.04 (2H, m), 8.01 (1H, dd, J = 8.0, 1.2 Hz), 7.89 (1H, ddd, J = 7.7,
7.7, 1.6 Hz), 7.72 (1H, ddd, J = 7.7, 7.7, 1.3 Hz), 7.59−7.44 (3H, m),
6.88 (1H, d, J = 8.1 Hz), 6.78 (1H, dd, J = 7.2, 4.9 Hz); δC (75 MHz,
acetone-d6) 164.2 (s), 158.0 (s), 149.9 (s), 149.6 (d), 148.1 (d), 146.9
(s), 139.0 (d), 138.7 (d), 138.0 (s), 135.3 (d), 130.9 (d), 128.5 (d),
128.2 (d), 125.9 (d), 123.4 (d), 117.2 (d), 108.5 (d); MS (EI) m/z
(%): 335 (M+, 27), 318 (22), 289 (87), 271 (6), 257 (27), 210 (4),
197 (16), 185 (17), 168 (43), 154 (7), 106 (22), 78 (100), 51 (22).
4.3.14. N′-[2-Nitro-5-(trifluoromethyl)phenyl]-N′-(pyrid-2-yl)-
picolinohydrazide (13n). Similar treatment of N′-(pyrid-2-yl)-
picolinohydrazide (19k) (1.178 g, 5.5 mmol) with 2-fluoro-1-nitro-
4-(trifluoromethyl)benzene (18b) (0.700 mL, 5.0 mmol) and K2CO3
(0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled glass tube that
was sealed and heated at ca. 110 °C for 1 day gave upon
chromatography (DCM) the title compound 13n as yellow needles
(1.733 g, 86%). Mp (DSC) decomp. onset 197.7 °C, peak max 226.1
°C (from c-hexane); Rf 0.60 (t-BuOMe); (anal. found: C, 53.75; H,
2.94; N, 17.27. C18H12F3N5O3 requires C, 53.60; H, 3.00; N, 17.36%);
λmax(DCM)/nm (log ε) 230 (3.47), 261 (3.29), 273 inf (3.23), 291 inf
(3.04), 379 (2.28); νmax/cm−1 3343w (NH), 3061w (Ar CH), 1701m
(CO), 1591m, 1572w, 1535s, 1483m, 1468s, 1437s, 1337s, 1310s,
1263w, 1256w, 1236m, 1206w, 1177s, 1152s, 1132s, 1099m, 1065m,
1040w, 997w, 988w, 964w, 908w, 858m, 847w, 841w, 820w, 804w,
773m; δH (500 MHz, DMSO-d6) 11.94 (1H, s), 8.77 (1H, d, J = 4.7
Hz), 8.19 (1H, d, J = 8.4 Hz), 8.11−8.06 (2H, m), 8.01 (1H, dd, J =
4.9, 1.1 Hz), 7.96 (1H, d, J = 1.6 Hz), 7.77 (1H, dd, J = 8.6, 1.6 Hz),
7.75−7.69 (2H, m), 6.99 (1H, d, J = 8.5 Hz), 6.95 (1H, dd, J = 7.0, 5.1
Hz); δC (125 MHz, DMSO-d6) one C (d) signal missing, 163.8 (s),
155.6 (s), 148.9 (d), 148.6 (s), 146.6 (d), 145.6 (s), 138.8 (d), 138.0
(d), 137.1 (s), 133.3 (q, 2JFC = 32.7 Hz), 127.6 (d), 126.2 (d), 122.83
33), 346 (9), 296 (22), 279 (6), 249 (53), 235 (15), 154 (13), 145
(8), 77 (100), 69 (19), 63 (10), 51 (54).
4.3.10. N′-(4-Cyanophenyl)-N′-(2-nitrophenyl)benzohydrazide
(13j). Similar treatment of N′-(4-cyanophenyl)benzohydrazide (19j)
(1.305 g, 5.5 mmol) with 1-fluoro-2-nitrobenzene (18a) (0.527 mL,
5.0 mmol) and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a
thick-walled glass tube that was sealed and heated at ca. 110 °C for 2
days gave upon chromatography (DCM) the title compound 13j as
yellow needles (1.150 g, 64%). Mp (DSC) decomp. onset 260.7 °C,
peak max 262.7 °C (from c-hexane); Rf 0.30 (DCM); (anal. found: C,
67.12; H, 4.08; N, 15.53. C20H14N4O3 requires C, 67.03; H, 3.94; N,
15.63%); λmax(DCM)/nm (log ε) 232 (3.27), 270 (3.48), 374 (2.33);
νmax/cm−1 3289w (NH), 3067w (Ar CH), 2220m (CN), 1686m
(CO), 1667m, 1597s, 1526s, 1504s, 1483m, 1342s, 1300m, 1285m,
1260m, 1246m, 1179m, 1148w, 1078w, 1059w, 1026w, 928w, 893w,
851m, 827m, 800w, 783m; δH (500 MHz, DMSO-d6) 11.46 (1H, s),
8.05 (1H, d, J = 7.9 Hz), 7.88 (2H, d, J = 7.3 Hz), 7.83 (1H, ddd, J =
7.9, 7.9, 1.0 Hz), 7.79 (1H, d, J = 7.1 Hz), 7.67 (2H, d, J = 8.8 Hz),
7.64−7.56 (2H, m), 7.52 (2H, dd, J = 7.6, 7.6 Hz), 6.86 (2H, d, J = 8.8
Hz); δC (125 MHz, DMSO-d6) 165.9 (s), 150.1 (s), 145.7 (s), 136.1
(s), 134.8 (d), 133.4 (d), 132.4 (d), 131.5 (s), 128.8 (d), 128.5 (d),
128.3 (d), 127.7 (d), 125.3 (d), 119.3 (s), 114.4 (d), 101.7 (s);
MALDI-TOF m/z (%): 359 (MH+, 72), 343 (20), 331 (45), 239 (37),
208 (30), 105 (100).
4.3.11. N′-(4-Cyanophenyl)-N′-(2-nitrophenyl)thiophene-2-car-
bohydrazide (13k). Similar treatment of N′-(4-cyanophenyl)-
thiophene-2-carbohydrazide (19i) (1.340 g, 5.5 mmol) with 1-
fluoro-2-nitrobenzene (18a) (0.527 mL, 5.0 mmol) and K2CO3
(0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled glass tube
that was sealed and heated at ca. 110 °C for 2 days gave upon
chromatography (DCM) the title compound 13k as yellow needles
(1.04 g, 57%). Decomp. (DSC) onset 266.7 °C, peak max 267.5 °C
(from c-hexane); Rf 0.30 (DCM); (anal. found: C, 59.45; H, 3.17; N,
15.28. C18H12N4O3S requires C, 59.33; H, 3.32; N, 15.38%);
−1
λmax(DCM)/nm (log ε) 271 (3.58), 374 (2.21); νmax/cm
3281w
(NH), 3092w (Ar CH), 2220m (CN), 1672m and 1666m (CO),
1597s, 1526s, 1508s, 1480m, 1416m, 1352s, 1287m, 1260m, 1246m,
1202w, 1177m, 1144w, 1080m, 1065w, 1020w, 849s, 827m, 781m,
754w; δH (500 MHz, DMSO-d6) 11.49 (1H, s), 8.05 (1H, dd, J = 8.2,
1.3 Hz), 7.94 (1H, d, J = 3.3 Hz), 7.91 (1H, d, J = 4.9 Hz), 7.84 (1H,
ddd, J = 8.0, 8.0, 1.3 Hz), 7.77 (1H, dd, J = 8.1, 1.0 Hz), 7.67 (2H, d, J
= 9.0 Hz), 7.59 (1H, ddd, J = 8.0, 8.0, 1.3 Hz), 7.22 (1H, dd, J = 4.3,
4.3 Hz), 6.84 (2H, d, J = 9.0 Hz); δC (125 MHz, DMSO-d6) 160.8 (s),
150.0 (s), 145.6 (s), 136.0 (s), 135.8 (s), 134.9 (d), 133.4 (d), 132.7
(d), 130.0 (d), 128.9 (d), 128.4 (d), 128.3 (d), 125.4 (d), 119.3 (s),
114.3 (d), 101.8 (s); MALDI-TOF m/z (%): 364 (M+, 11), 325 (26),
271 (5).
4.3.12. N′-(2-Nitrophenyl)-N′-(pyrid-2-yl)benzohydrazide (13l).
Similar treatment of N′-(pyrid-2-yl)benzohydrazide (19j) (1.170 g,
5.5 mmol) with 1-fluoro-2-nitrobenzene (18a) (0.527 mL, 5.0 mmol)
and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled
glass tube that was sealed and heated at ca. 110 °C for 2 days gave
upon chromatography (t-BuOMe) the title compound 13l as yellow
needles (1.290 g, 77%). Mp (DSC) onset 178.6 °C, peak max 180.3
°C (from PhH); Rf 0.76 (t-BuOMe); (anal. found: C, 64.86; H, 4.33;
N, 16.87. C18H14N4O3 requires C, 64.66; H, 4.22; N, 16.76%);
λmax(DCM)/nm (log ε) 233 (4.72), 259 inf (4.47), 278 inf (4.39) 288
(4.33); νmax/cm−1 3269m (NH), 1660s (CO), 1589s, 1522s, 1487w,
1464s, 1433s, 1343s, 1300m, 1287m, 1262s, 1153w, 1078w, 1022w,
986w, 932w, 897w, 849w, 802w, 785m, 775m, 762s, 743w, 732w; δH
1
3
(d), 122.75 (q, JFC = 273.4 Hz), 122.0 (q, JFC = 3.6 Hz), 117.7 (d),
109.5 (d); MS (EI) m/z (%): 403 (M+, 9), 386 (7), 357 (36), 325
(10), 253 (8), 236 (14), 197 (6), 106 (21), 78 (100), 51 (23).
4.3.15. N′-(3-Nitropyrid-2-yl)-N′-phenylbenzohydrazide (13o).
Similar treatment of N′-phenylbenzohydrazide (19a) (1.167 g, 5.5
mmol) with 2-chloro-3-nitropyridine (18c) (0.793 g, 5.0 mmol) and
K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-walled glass
tube that was sealed and heated at ca. 110 °C for 1 day gave upon
chromatography (t-BuOMe) the title compound 13o as yellow needles
(1.400 g, 84%). Mp (DSC) onset 205.1 °C, peak max 206.3 °C (from
PhH); Rf 0.8 (t-BuOMe); (anal. found: C, 64.77; H, 4.28; N, 16.66.
C18H14N4O3 requires C, 64.66; H, 4.22; N, 16.76%); λmax(DCM)/nm
(log ε) 232 (4.32), 278 inf (4.17), 395 (3.36); νmax/cm−1 3250m
(NH), 1663s (CO), 1589s, 1564m, 1559m, 1518s, 1491s, 1449s,
1431s, 1356s, 1341m, 1321m, 1300w, 1275m, 1258s, 1146w, 1098w,
1028m, 930w, 907m, 856s, 851m, 804m, 773w, 752s; δH (500 MHz,
I
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CDCl3) 8.58 (1H, s), 8.45 (1H, dd, J = 3.5, 1.0 Hz), 8.13 (1H, dd, J =
8.0, 1.5 Hz), 7.81 (2H, d, J = 7.5 Hz), 7.57 (1H, dd, J = 7.5, 7.5 Hz),
7.47 (2H, dd, J = 7.5, 7.5 Hz), 7.38−7.32 (4H, m), 7.20 (1H, dd, J =
7.0, 7.0 Hz), 7.05 (1H, dd, J = 8.0, 5.0 Hz); δC (500 MHz, CDCl3)
166.5 (s), 151.9 (d), 150.3 (s), 143.6 (s), 135.1 (s), 135.0 (d), 132.6
(d), 131.5 (s), 129.3 (d), 128.9 (d), 127.4 (d), 126.0 (d), 122.1 (d),
117.5 (d); MALDI-TOF m/z (%): 336 (MH+ + 1, 6), 335 (MH+, 82),
317 (9), 288 (100), 200 (26), 174 (12).
Rf 0.40 (DCM/n-hexane, 1:1); identical to that described above.
Further elution gave the title compound 22 as red plates (0.920 g,
80%). Mp (DSC) onset 74.9 °C, peak max 76.5 °C (from MeOH); Rf
0.23 (DCM/n-hexane, 1:1); (anal. found: C, 62.93; H, 4.70; N, 18.28.
C12H11N3O2 requires C, 62.87; H, 4.84; N, 18.33%); λmax(DCM)/nm
(log ε) 242 (3.17), 274 (3.13), 288 inf (3.09), 419 (2.25); νmax/cm−1
3346w (NH), 3065w (Ar CH), 2918w, 2849w, 1589s, 1574w, 1518s,
1493s, 1456w, 1443w, 1358m, 1292m, 1265m, 1248m, 1163w, 1146w,
1113w, 1072w, 1040w, 941w, 864m, 843m, 775m, 758s, 746s, 729w;
δH (300 MHz, DMSO-d6) 7.81 (1H, d, J = 8.1 Hz), 7.58 (1H, ddd, J =
8.1, 8.1, 0.9 Hz), 7.50 (1H, d, J = 7.5 Hz), 7.28−7.17 (3H, m), 7.04
(2H, d, J = 7.9 Hz), 6.88 (1H, dd, J = 7.3, 7.3 Hz), 5.16 (2H, s); δC (75
MHz, CDCl3) 148.3 (s), 144.3 (s), 142.3 (s), 133.2 (d), 129.2 (d),
126.8 (d), 126.0 (d), 124.4 (d), 121.4 (d), 115.9 (d); MALDI-TOF
m/z (%): 230 (MH+, 14), 229 (M+, 100), 228 (80), 212 (61), 181 (7).
4.4.3. N′-(2-Nitrophenyl)-N′-phenylacetohydrazide (13f). To a
stirred solution of 1-(2-nitrophenyl)-1-phenylhydrazine (22) (0.500 g,
2.183 mmol) and Et3N (0.340 mL, 2.401 mmol) in DCM (10 mL) at
ca. −5 °C was added dropwise acetic anhydride (0.170 mL, 2.401
mmol). Over the next 4 h the reaction mixture was left to warm to ca.
20 °C, and then after a further 8 h the mixture was diluted with t-
BuOMe (30 mL) and washed with water (2 × 50 mL). The organic
phase was dried (Na2SO4) and concentrated in vacuo. The residue was
dissolved in DCM (1 mL) and chromatographed (DCM/t-BuOMe,
1:1) to give the title compound 13f as yellow needles (0.57 g, 96%).
Mp (DSC) onset 140.9 °C, peak max 141.7 °C (from 2-PrOH); Rf
0.45 (t-BuOMe); identical to that described above.
4.4.4. 2,2,2-Trifluoro-N′-(2-nitrophenyl)-N′-phenylacetohydrazide
(13h). Similar treatment of 1-(2-nitrophenyl)-1-phenylhydrazine (22)
(0.500 g, 2.183 mmol) with Et3N (0.340 mL, 2.401 mmol) and
trifluoroacetic anhydride (0.34 mL, 2.401 mmol) in DCM (10 mL)
gave upon chromatography (DCM) the title compound 13h as yellow
needles (0.582 g, 82%). Mp (DSC) onset 90.5 °C, peak max 91.5 °C
(from n-hexane); Rf 0.61 (DCM); identical to that described above.
4.4.5. N′-(2-Nitrophenyl)-N′-phenyl-1-adamantanecarbohydra-
zide (13q). Similar treatment of 1-(2-nitrophenyl)-1-phenylhydrazine
(22) (0.500 g, 2.183 mmol) with Et3N (0.340 mL, 2.401 mmol) and
1-adamantanecarbonyl chloride (0.34 mL, 2.401 mmol) in DCM (10
mL) gave upon chromatography (DCM) the title compound 13q as
yellow needles (0.50 g, 58%). Mp (DSC) onset 161.0 °C, peak max
162.8 °C (from c-hexane); Rf 0.24 (DCM); (anal. found: C, 70.62; H,
6.40; N, 10.66. C23H25N3O3 requires C, 70.57; H, 6.44; N, 10.73%);
λmax(DCM)/nm (log ε) 240 (2.98), 268 (2.89), 413 (2.07); νmax/cm−1
3314w and 3265w (NH), 2905m and 2851w (CH2), 1659s (CO),
1593s, 1574w, 1535s, 1526s, 1493s, 1477m, 1452m, 1350m, 1315w,
1300m, 1254w, 1227m, 1182w, 1165w, 1107w, 1086w, 1059w, 1049w,
916w, 853m, 831w, 781m, 741s, 731m; δH (500 MHz, DMSO-d6)
10.40 (1H, s), 7.81 (1H, d, J = 8.0 Hz), 7.63 (1H, dd, J = 7.8, 7.8 Hz),
7.43 (1H, d, J = 8.4 Hz), 7.30−7.18 (3H, m), 6.94 (1H, dd, J = 7.2, 7.2
Hz), 6.82 (2H, d, J = 8.0 Hz), 1.98 (3H, s), 1.84 (6H, s), 1.67 (6H, s);
δC (125 MHz, DMSO-d6) one C (s) signal missing, 175.7 (s), 145.6
(s), 142.4 (s), 138.6 (s), 133.7 (d), 128.8 (d), 125.1 (d), 124.5 (d),
124.0 (d), 121.9 (d), 116.7 (d), 39.6 (s), 38.0 (t), 35.9 (t), 27.4 (d);
MALDI-TOF m/z (%): 392 (MH+, 68), 391 (M+, 6), 374 (7), 358
(11), 353 (6), 346 (53), 330 (8), 212 (100), 196 (6), 181 (31), 167
(38).
4.3.16. N′-(3-Nitropyrid-2-yl)-N′-(pyrid-2-yl)picolinohydrazide
(13p). Similar treatment of N′-(pyrid-2-yl)picolinohydrazide (19j)
(1.180 g, 5.5 mmol) with 2-chloro-3-nitropyridine (18c) (0.793 g, 5.0
mmol) and K2CO3 (0.760 g, 5.5 mmol) in EtOH (4 mL) in a thick-
walled glass tube that was sealed and heated at ca. 110 °C for 1 day
gave upon chromatography (DCM/THF, 8:2) the title compound
13p as yellow flakes (1.360 g, 81%). Mp (DSC) decomp. onset 220.3
°C, peak max 254.2 °C (from PhH); Rf 0.74 (THF); (anal. found: C,
57.26; H, 3.64; N, 24.88. C16H12N6O3 requires C, 57.14; H, 3.60; N,
24.99%); λmax(DCM)/nm (log ε) 232 (4.49), 246 inf (4.39), 273
(4.32), 297 (4.32), 374 (3.52); νmax/cm−1 3334w (NH), 3076w (Ar
CH), 1701m (CO), 1589s, 1574m, 1526s, 1487m, 1472m, 1427s,
1356s, 1329m, 1279w, 1238m, 1148w, 1109w, 1090w, 1040w, 997w,
962w, 907w, 858m, 818w, 787w, 772w, 752m; δH (500 MHz, DMSO-
d6) 11.71 (1H, s), 8.74 (1H, d, J = 4.5 Hz), 8.56 (1H, dd, J = 4.5, 1.5
Hz), 8.37 (1H, dd, J = 8.0, 1.5 Hz), 8.07−8.03 (2H, m), 7.99 (1H, dd,
J = 4.5, 1.0 Hz), 7.75 (1H, ddd, J = 7.8, 7.8, 1.5 Hz), 7.69 (1H, ddd, J =
9.0, 5.0, 2.5 Hz), 7.34 (1H, dd, J = 8.5, 5.0 Hz), 7.14 (1H, d, J = 8.5
Hz), 6.99 (1H, dd, J = 6.5, 5.0 Hz); δC (125 MHz, DMSO-d6) 163.8
(s), 155.4 (s), 151.9 (d), 149.1 (s), 148.9 (d), 146.4 (d), 145.8 (s),
138.9 (d), 138.0 (d), 137.6 (s), 134.1 (d), 127.4 (d), 122.8 (d), 119.5
(d), 118.9 (d), 112.0 (d); MALDI-TOF m/z (%): 337 (MH+, 94), 328
(16), 312 (15), 290 (100), 271 (13).
4.4. Multistep Route to Hydrazides 13f, 13h, and 13q.
4.4.1. 2-Benzylidene-1-(2-nitrophenyl)-1-phenylhydrazine (21). A
stirred mixture of 2-benzylidene-1-phenylhydrazine (20) (5.00 g, 25.48
mmol), 1-fluoro-2-nitrobenzene (18a) (2.70 mL, 28.03 mmol), and
K2CO3 (3.87 g, 28.03 mmol) in DMSO (25 mL) was heated at ca. 100
°C for 15 h and then cooled to ca. 20 °C, diluted with t-BuOMe (200
mL), and washed with water (200 mL), 10% HCl (2 × 100 mL), 2 M
NaOH (2 × 100 mL), and brine. The organic phase was then
separated and dried (Na2SO4), and the volatiles were removed in
vacuo. The residue was dissolved in DCM (10 mL) and chromato-
graphed (DCM/n-hexane, 1:1) to give the title compound 21 as
yellow needles (7.27 g, 90%). Mp (DSC) onset 102.6 °C, peak max
104.8 °C (from EtOH); Rf 0.40 (DCM/n-hexane, 1:1); (anal. found:
C, 72.04; H, 4.84; N, 13.26. C19H15N3O2 requires C, 71.91; H, 4.76;
N, 13.24%); λmax(DCM)/nm (log ε) 239 (3.35), 296 inf (3.18), 326
(3.38), 438 inf (1.83); νmax/cm−1 3063w (Ar CH), 1603m, 1593m,
1566w, 1526s, 1493s, 1445m, 1381w, 1368m, 1329w, 1319w, 1296m,
1281m, 1229m, 1206m, 1163w, 1105w, 1086m, 1069m, 1038w,
1024w, 1003w, 955w, 934w, 905w, 864w, 847m, 781w, 758s, 739s; δH
(300 MHz, DMSO-d6) 8.16 (1H, dd, J = 8.1, 1.3 Hz), 7.87 (1H, ddd, J
= 7.7, 7.7, 1.3 Hz), 7.68 (1H, ddd, J = 7.8, 7.8, 1.2 Hz), 7.64−7.57
(2H, m), 7.43−7.30 (6H, m), 7.19 (1H, s), 7.14−7.06 (3H, m); δC (75
MHz, DMSO-d6) 146.3 (s), 143.9 (s), 136.8 (d), 135.0 (d), 134.9 (s),
133.8 (s), 129.54 (d), 129.47 (d), 128.68 (d), 128.58 (d), 128.55 (d),
126.3 (d), 125.8 (d), 123.1 (d), 118.3 (d); MALDI-TOF m/z (%):
318 (MH+, 22), 317 (M+, 100), 299 (2), 286 (11), 271 (29), 214 (2),
195 (4), 180 (68), 167 (2).
4.5. Reduction of Benzohydrazide 13a and Picolinohydra-
zides 13m, 13n, and 13p. 4.5.1. N′-(2-Aminophenyl)-N′-phenyl-
benzohydrazide (12a). 4.5.1.1. Method 1: Using Pd−C/H2 in EtOH.
To a solution of N′-(2-nitrophenyl)-N′-phenylbenzohydrazide (13a)
(0.333 g, 1.0 mmol) in EtOH (10 mL) at ca. 20 °C was added Pd/C
(10 mol %) (33 mg) in one portion. The reaction mixture was
evacuated and flushed with H2 (3×), filled with H2 (3 bar), and left to
stir for 4 h. During that time the yellow color of the reaction mixture
disappeared and consumption of H2 ceased. The mixture was filtered
through a short pad of Celite, and the volatiles were removed in vacuo.
Chromatography (Et2O/n-hexane, 1:1) of the residue gave the title
compound 12a as colorless needles (0.264 g, 97%). Mp (DSC) onset
176.6 °C, peak max 178.2 °C (from Et2O); Rf 0.71 (n-hexane/Et2O,
4.4.2. N′-(2-Nitrophenyl)-N′-phenylhydrazine (22). A stirred
mixture of 2-benzylidene-1-(2-nitrophenyl)-1-phenylhydrazine (21)
(1.59 g, 5.0 mmol) and H2NOH·HCl (3.47 g, 50.0 mmol) in pyridine
(20 mL) was heated at ca. 80 °C for 1 day. Upon cooling to ca. 20 °C,
the pyridine was removed in vacuo. The residue was suspended in
DCM, and excess H2NOH·HCl was separated by filtration. The filtrate
was diluted with DCM (100 mL) and washed with 2 M NaOH (2 ×
100 mL), 10% HCl (2 × 100 mL), and water (100 mL). The organic
phase was separated and dried (Na2SO4), and the volatiles were
removed in vacuo. The residue was dissolved in DCM (5 mL) and
chromatographed (DCM) to give recovered starting material 21 (0.27
g, 17%). Mp (DSC) onset 102.6 °C, peak max 104.8 °C (from EtOH);
−1
1:1); λmax(DCM)/nm (log ε) 239 (3.80), 294 (3.19); νmax/cm
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3387w and 3219w (NH), 3057w (Ar CH), 1651s (CO), 1612m,
1593m, 1582m, 1530m, 1460w, 1310m, 1256m, 1157w, 1136w,
1024w, 939w, 924w, 893w, 849w, 802w, 746s; δH (500 MHz, CDCl3)
8.15 (1H, s), 7.85 (2H, d, J = 7.5 Hz), 7.56 (1H, dd, J = 7.5, 7.5 Hz),
7.46 (2H, dd, J = 7.5, 7.5 Hz), 7.23 (2H, dd, J = 7.0, 7.0 Hz), 7.14 (2H,
dd, J = 7.5, 7.5 Hz), 6.88 (1H, dd, J = 7.0, 7.0 Hz), 6.81 (1H, dd, J =
8.5, 1.0 Hz), 6.78 (2H, d, J = 8.0 Hz), 6.73 (1H, ddd, J = 7.5, 7.5, 1.5
Hz), 4.72 (2H, br s); δC (125 MHz, CDCl3) 167.4 (s), 147.0 (s),
145.9 (s), 132.4 (d), 132.2 (s), 130.4 (s), 129.2 (d), 129.1 (d), 128.8
(d), 128.0 (d), 127.3 (d), 120.2 (d), 118.4 (d), 116.6 (d), 113.3 (d);
identical to an authentic sample.14b
4.5.1.2. Method 2: Using In in AcOH. To a vigorously stirred
suspension of N′-(2-nitrophenyl)-N′-phenylbenzohydrazide (13a)
(0.333 g, 1.0 mmol) in AcOH (5 mL) was added In powder (0.459
g, 4.0 mmol) in one portion, and the mixture was stirred at ca. 20 °C
for 0.5 h, filtered, and washed with Et2O. The organic phase was
washed with water (2 × 50 mL) and dried (Na2SO4), and the volatiles
were removed in vacuo. Chromatography (Et2O/n-hexane, 1:1) of the
residue gave the title compound 12a as colorless needles (0.264 g,
95%). Mp (DSC) onset 176.6 °C, peak max 178.2 °C (from Et2O); Rf
0.71 (n-hexane/Et2O, 1:1); δH (500 MHz, CDCl3) 8.15 (1H, s), 7.85
(2H, d, J = 7.5 Hz), 7.56 (1H, dd, J = 7.5, 7.5 Hz), 7.46 (2H, dd, J =
7.5, 7.5 Hz), 7.23 (2H, dd, J = 7.0, 7.0 Hz), 7.14 (2H, dd, J = 7.5, 7.5
Hz), 6.88 (1H, dd, J = 7.0, 7.0 Hz), 6.81 (1H, dd, J = 8.5, 1.0 Hz), 6.78
(2H, d, J = 8.0 Hz), 6.73 (1H, ddd, J = 7.5, 7.5, 1.5 Hz), 4.72 (2H, br s,
NH2); identical to that described above.
4.5.4. 1,3-Bis(pyrid-2-yl)-7-(trifluoromethyl)-1,4-dihydro-1,2,4-
benzotriazine (23c). Similar treatment of N′-[2-nitro-5-
(trifluoromethyl)phenyl]-N′-(pyrid-2-yl)picolinohydrazide (13n)
(403 mg, 1.0 mmol) with Sn powder (475 mg, 4.0 mmol) in AcOH
(5 mL) at ca. 20 °C for 0.5 h and then at ca. 118 °C for 3 h gave upon
chromatography (t-BuOMe) the title compound 23c as yellow needles
(313 mg, 88%). Mp (DSC) onset 132.6 °C, peak max 133.6 °C (from
n-hexane); Rf 0.20 (DCM); (anal. found: C, 60.81; H, 3.51; N, 19.68.
C18H12F3N5 requires C, 60.85; H, 3.40; N, 19.71%); λmax(DCM)/nm
(log ε) 233 (3.32), 266 (3.40), 326 (3.15), 429 (2.26); νmax/cm−1
3358w (NH), 3076w, 3059w and 3013w (Ar CH), 1661w, 1585m,
1568m, 1528w, 1518w, 1481w, 1470m, 1462m, 1433s, 1414s, 1368m,
1327s, 1315s, 1306m, 1300m, 1287m, 1267w, 1161s, 1152s, 1136w,
1111s, 1076m, 1055m, 1045w, 1038m, 999w, 986w, 966w, 930w,
910m, 872m, 856w, 820m, 814m, 791m, 777s, 750w, 743w, 735m,
727w; δH (500 MHz, DMSO-d6) 9.60 (1H, s), 8.71 (1H, d, J = 4.6
Hz), 8.26 (1H, dd, J = 4.7, 1.1 Hz), 8.22 (1H, d, J = 7.9 Hz), 8.09 (1H,
s), 7.99 (1H, ddd, J = 8.4, 8.4, 1.5 Hz), 7.80 (1H, ddd, J = 7.8, 7.8, 1.9
Hz), 7.65−7.58 (2H, m), 7.20 (1H, d, J = 8.4 Hz), 7.14 (1H, d, J = 8.2
Hz), 7.00 (1H, dd, J = 6.8, 5.2 Hz); δC (125 MHz, DMSO-d6) 155.2
(s), 148.3 (d), 147.8 (s), 147.2 (s), 146.5 (d), 138.2 (d), 137.7 (s),
1
137.3 (d), 129.3 (s), 125.7 (d), 124.3 (q, JFC = 271.6 Hz), 122.8 (q,
3
2JFC = 31.8 Hz), 121.5 (q, JFC = 3.6 Hz), 120.9 (d), 116.9 (d), 114.4
3
(d), 113.2 (q, JFC = 3.6 Hz), 110.3 (d); MALDI-TOF m/z (%): 356
(MH+, 18), 355 (M+, 10), 354 (51), 343 (17), 342 (100).
4.5.5. 1,3-Bis(pyrid-2-yl)-1,4-dihydro-1,2,4-pyridotriazine (23d).
Similar treatment of N′-(3-nitropyridin-2-yl)-N′-(pyridin-2-yl)-
picolinohydrazide (13p) (0.336 g, 1.0 mmol) with Sn powder
(0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 2 h and
then at ca. 118 °C for 3 h gave upon chromatography (EtOAc/THF,
9:1) the title compound 23d as orange needles (0.262 g, 91%). Mp
(DSC) onset 152.2 °C, peak max 154.9 °C (from PhH); Rf 0.20
(EtOAc); (anal. found: C, 66.57; H, 4.37; N, 29.02. C16H12N6 requires
C, 66.66; H, 4.20; N, 29.15%); λmax(DCM)/nm (log ε) 239 (4.14),
267 (4.09), 312 (3.95); νmax/cm−1 3343w (NH), 3053w and 3012w
(Ar CH), 1585m, 1566m, 1547w, 1487w, 1464s, 1418s, 1360w,
1304m, 1288m, 1225m, 1192w, 1150w, 1096w, 1069w, 1049w, 997m,
893w, 853w, 783s, 760m, 743m; δH (500 MHz, CDCl3) 8.53 (1H, d, J
= 5.0 Hz), 8.49 (1H, dd, J = 3.5, 1.5 Hz), 8.19 (1H, d, J = 8.0 Hz),
7.76−7.69 (3H, m), 7.65 (1H, dd, J = 5.0, 1.5 Hz), 7.62 (1H, d, J = 8.5
Hz), 7.34 (1H, dd, J = 5.0, 1.5 Hz), 7.03 (1H, dd, J = 5.0, 1.5 Hz),
6.68−6.63 (2H, m); δC (125 MHz, CDCl3) 154.1 (s), 147.8 (d), 147.8
(d), 147.2 (s), 145.2 (s), 145.2 (s), 141.4 (d), 137.4 (d), 136.6 (d),
128.3 (s), 124.9 (d), 121.0 (d), 119.3 (d), 119.2 (d), 118.8 (d), 116.3
(d); MALDI-TOF m/z (%): 290 (MH+, 13), 289 (M+, 100), 247 (6),
210 (22), 185 (100), 170 (30), 155 (4).
4.6. Preparation of Benzo- and Pyrido-Fused Triazinyl
Radicals 1a−n. 4.6.1. 1,3-Diphenyl-1,4-dihydro-1,2,4-benzotria-
zin-4-yl (1a) (Typical Procedure). To a vigorously stirred mixture of
N′-(2-nitrophenyl)-N′-phenylbenzohydrazide (13a) (0.333 g, 1.0
mmol) in AcOH (5 mL) at ca. 20 °C was added in one portion Sn
powder (0.475 g, 4.0 mmol), and after 0.5 h the mixture was heated at
ca. 118 °C for 10 min. The mixture was then allowed to cool to ca. 20
°C, diluted with DCM (50 mL), and washed with 2 M NaOH (2 × 50
mL), and the organic phase was separated. To the organic phase was
added 2 M NaOH (50 mL), and the biphasic mixture was stirred at ca.
20 °C for 12 h. The organic phase was separated, washed with water,
filtered (Celite), and rinsed with additional DCM, and the volatiles
were removed in vacuo. Chromatography of the residue (basic
alumina, DCM) gave the title compound 1a as black needles (0.274 g,
96%). Mp 109−111 °C (from EtOH) (lit.3a 109−110 °C); Rf 0.56
(Al2O3, DCM/n-hexane, 1:1); λmax(DCM)/nm (log ε) 271 (3.63),
322 (2.93), 372 (2.82), 429 (2.56), 494 (2.17); νmax/cm−1 3061w and
3003w (Ar CH), 1585w, 1481w, 1450m, 1395s, 1317w, 1252w,
1206w, 1175w, 1082w, 1065w, 1024w, 984w, 916w, 880w, 841w,
785m, 750s; identical to an authentic sample.
4.5.2. N′-(2-Aminophenyl)-N′-(pyrid-2-yl)picolinohydrazide
(12b). Similar treatment of N′-(2-nitrophenyl)-N′-(pyrid-2-yl)-
picolinohydrazide (13m) (0.335 g, 1.0 mmol) in AcOH (5 mL)
with Sn powder (0.475 g, 4.0 mmol) gave upon chromatography
(CHCl3/MeOH, 10:1) the title compound 12b (0.300 g, 98%) as
colorless flakes. Mp (DSC) onset 138.0 °C, peak max 144.2 °C (from
c-hexane); Rf 0.28 (CHCl3/MeOH, 10:1); (anal. found: C, 66.82; H,
5.06; N, 22.85. C17H15N5O requires C, 66.87; H, 4.95; N, 22.94%);
λmax(DCM)/nm (log ε) 233 (3.42), 260 inf (3.06), 294 (3.01); νmax
/
cm−1 3451w and 3341w (NH), 3059w and 3009w (Ar CH), 1695m,
1680m, 1620m, 1589s, 1566m, 1530m, 1503s, 1470s, 1429s, 1342m,
1337m, 1308m, 1285m, 1240m, 1152m, 1040m, 997m, 986m, 903m,
885m, 860m, 818m, 773m, 748s; δH (500 MHz, DMSO-d6) 11.25
(1H, s), 8.71 (1H, d, J = 4.6 Hz), 8.10−8.00 (3H, m), 7.67 (1H, ddd, J
= 5.9, 5.9, 1.9 Hz), 7.50 (1H, ddd, J = 8.0, 8.0, 1.7 Hz), 7.39 (1H, dd, J
= 7.9, 1.4 Hz), 7.05 (1H, ddd, J = 7.7, 7.7, 1.6 Hz), 6.78−6.70 (2H,
m), 6.56 (1H, ddd, J = 8.0, 8.0, 1.3 Hz), 6.36 (1H, d, J = 8.5 Hz), 5.49
(2H, s, NH2); δC (125 MHz, DMSO-d6) 164.2 (s), 157.1 (s), 149.2
(s), 148.6 (d), 147.4 (d), 146.6 (s), 137.9 (d), 137.3 (d), 130.1 (d),
128.7 (d), 127.8 (s), 127.1 (d), 122.5 (d), 116.0 (d), 115.4 (d), 114.4
(d), 107.1 (d); MALDI-TOF m/z (%): 305 (M+, 3), 303 (M+ − 2,
100), 198 (49), 183 (95), 105 (9).
4.5.3. 1,3-Bis(pyrid-2-yl)-1,4-dihydro-1,2,4-benzotriazine (23b).
Similar treatment of N′-(2-nitrophenyl)-N′-(pyrid-2-yl)-
picolinohydrazide (13m) (0.335 g, 1.0 mmol) with Sn powder
(0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h and then
at ca. 118 °C for 3 h gave upon chromatography (t-BuOMe) the title
compound 23b (0.234 g, 82%) as yellow needles. Mp (DSC) onset
118.5 °C, peak max 119.3 °C (from EtOH); Rf 0.24 (Et2O); (anal.
found: C, 71.15; H, 4.44; N, 24.31. C17H13N5 requires C, 71.06; H,
4.56; N, 24.37%); λmax(DCM)/nm (log ε) 232 (3.36), 273 (3.37), 342
(3.12), 426 (2.42); νmax/cm−1 3352w (NH), 3055w and 3009w (Ar
CH), 1585m, 1562w, 1503m, 1476m, 1460m, 1431s, 1416m, 1368m,
1310m, 1294m, 1269w, 1247w, 1192w, 1150m, 1105w, 1057w, 1042w,
995m, 980w, 930w, 891w, 853w, 800m, 762m, 745m; δH (300 MHz,
DMSO-d6) 9.17 (1H, s), 8.69 (1H, d, J = 4.7 Hz), 8.27−8.15 (2H, m),
7.97 (1H, ddd, J = 7.7, 7.7, 1.7 Hz), 7.80−7.66 (2H, m), 7.63−7.52
(2H, m), 7.03 (1H, dd, J = 7.4, 1.7 Hz), 6.96−6.75 (3H, m); δC (75
MHz, DMSO-d6) 155.5 (s), 148.5 (s), 148.3 (d), 147.7 (s), 146.6 (d),
138.0 (d), 137.3 (d), 133.9 (s), 128.6 (s), 125.5 (d), 124.2 (d), 122.6
(d), 120.9 (d), 117.3 (d), 116.0 (d), 114.6 (d), 109.9 (d); MS (EI) m/
z (%): 287 (M+, 83), 209 (100), 181 (9), 154 (5), 143 (4), 127 (4),
105 (14), 78 (34), 51 (13).
4.6.2. 1,3-Diphenyl-7-(trifluoromethyl)-1,4-dihydro-1,2,4-benzo-
triazin-4-yl (1b). Similar treatment of N′-[2-nitro-5-(trifluoromethyl)-
phenyl]-N′-phenylbenzohydrazide (13b) (0.401 g, 1.0 mmol) with Sn
powder (0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h
K
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and at ca. 118 °C for 10 min followed by stirring with 2 M NaOH (50
mL) for 12 h gave upon chromatography (basic alumina, DCM) the
title compound 1b as black needles (0.286 g, 81%). Mp 149−152 °C
(from c-hexane) (lit.3a 149−153 °C); Rf 0.56 (Al2O3, DCM/n-hexane,
1:1); λmax(DCM)/nm (log ε) 259 inf (4.04), 273 (4.21), 284 inf
(4.03), 323 (3.55), 373 (3.40), 431 (3.17), 495 (284); νmax/cm−1
1593w, 1506w, 1489m, 1452w, 1422m, 1395m, 1356m, 1337w,
1314m, 1281w, 1261m, 1248w, 1204w, 1150m, 1117s, 1063m, 1024w,
905m, 870m, 841m, 793w, 781m, 768m; identical to an authentic
sample.
4.6.3. 3-(4-Fluorophenyl)-1-phenyl-1,4-dihydro-1,2,4-benzotria-
zin-4-yl (1c). Similar treatment of 4-fluoro-N′-(2-nitrophenyl)-N′-
phenylbenzohydrazide (13c) (0.351 g, 1.0 mmol) with Sn powder
(0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h and at ca.
118 °C for 10 min followed by stirring with 2 M NaOH (50 mL) for
12 h gave upon chromatography (basic alumina, DCM) the title
compound 1c as black needles (0.266 g, 88%). Mp (DSC) onset 112.5
°C, peak max 113.1 °C (from c-hexane); Rf 0.69 (Al2O3, DCM); (anal.
found: C, 75.31; H, 4.28; N, 13.91. C19H13FN3 requires C, 75.48; H,
4.33; N, 13.90%); λmax(DCM)/nm (log ε) 271 (3.67), 282 inf (3.47),
323 (2.99), 372 (2.87), 426 (2.62), 494 (2.24); νmax/cm−1 3055w (Ar
CH), 1601w, 1582w, 1508w, 1481m, 1450w, 1416w, 1393s, 1325w,
1292w, 1246w, 1215m, 1155m, 1096w, 1082w, 1065w, 1042w, 1024w,
1016w, 1001w, 984w, 924w, 918w, 881w, 841m, 810w, 775m, 762s,
746m, 729s; MALDI-TOF m/z (%): 303 (MH+, 11), 302 (M+, 100),
290 (2).
1074w, 1026w, 999w, 935w, 912w, 853w, 746s; MALDI-TOF m/z
(%): 223 (MH+, 69), 222 (M+, 100), 210 (4), 181 (5).
4.6.7. 3-Methyl-1-phenyl-7-(trifluoromethyl)-1,4-dihydro-1,2,4-
benzotriazin-4-yl (1g). Similar treatment of N′-[2-nitro-5-
(trifluoromethyl)phenyl]-N′-phenylacetohydrazide (13g) (0.339 g,
1.0 mmol) with Sn powder (0.475 g, 4.0 mmol) in AcOH (5 mL)
at ca. 20 °C for 0.5 h and at ca. 118 °C for 10 min followed by stirring
with 2 M NaOH (50 mL) for 12 h gave upon chromatography (basic
alumina, DCM) the title compound 1g as dark-red needles (0.186 g,
64%). Mp (DSC) onset 120.9 °C, peak max 121.6 °C (from n-
hexane); Rf 0.57 (Al2O3, DCM); (anal. found: C, 62.18; H, 3.76; N,
14.59. C15H11F3N3 requires C, 62.07; H, 3.82; N, 14.48%);
λmax(DCM)/nm (log ε) 241 (3.40), 259 inf (3.04), 285 (2.71), 318
(2.81), 346 (2.76), 428 (2.33), 528 inf (1.86); νmax/cm−1 3103w (Ar
CH), 2982w and 2928w (CH3), 1678w, 1591m, 1504m, 1491m,
1418s, 1371m, 1356m, 1337m, 1315s, 1265s, 1256m, 1198m, 1163s,
1157s, 1128s, 1103s, 1072s, 1028w, 1001m, 926w, 918m, 870m, 816s,
779w, 762m, 733w; MALDI-TOF m/z (%): 291 (MH+, 40), 290 (M+,
100), 277 (4), 132 (9).
4.6.8. 1-Phenyl-3-(trifluoromethyl)-1,4-dihydro-1,2,4-benzotria-
zin-4-yl (1h). Similar treatment of 2,2,2-trifluoro-N′-(2-nitrophenyl)-
N′-phenylacetohydrazide (13h) (0.325 g, 1.0 mmol) with Sn powder
(0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h and then
at ca. 118 °C for 10 min followed by stirring with 2 M NaOH (50 mL)
for 12 h gave upon chromatography (basic alumina, DCM) the title
compound 1h (0.273 g, 99%) as dark-red needles. Mp (DSC) onset
109.7 °C, peak max 110.8 °C (from n-pentane); Rf 0.46 (t-BuOMe/n-
hexane, 1:1); (anal. found: C, 61.03; H, 3.35; N, 15.08. C14H9F3N3
requires C, 60.87; H, 3.28; N, 15.21%); λmax(DCM)/nm (log ε) 245
(3.50), 296 inf (2.65), 314 (2.98), 345 (2.92), 414 (2.38), 481 (2.19),
543 inf (1.84); νmax/cm−1 3075w (Ar CH), 1587w, 1570w, 1489w,
1462w, 1452w, 1422w, 1371w, 1333w, 1323w, 1300w, 1287w, 1260m,
1194s, 1175s, 1159m, 1132s, 1094s, 1070w, 1032w, 993m, 945w,
926w, 887w, 858w, 839w, 775s, 760s, 752s; MALDI-TOF m/z (%):
277 (MH+, 14), 276 (M+, 91), 264 (32), 222 (100), 181 (5).
4.6.9. 1-Phenyl-3,7-bis(trifluoromethyl)-1,4-dihydro-1,2,4-benzo-
triazin-4-yl (1i). Similar treatment of 2,2,2-trifluoro-N′-[2-nitro-5-
(trifluoromethyl)phenyl]-N′-phenylacetohydrazide (13i) (0.393 g, 1.0
mmol) with Sn powder (0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20
°C for 0.5 h and at ca. 118 °C for 10 min followed by stirring with 2 M
NaOH (50 mL) for 12 h gave upon chromatography (basic alumina,
DCM) the title compound 1i as dark-red needles (0.286 g, 83%). Mp
(DSC) onset 126.0 °C, peak max 127.5 °C (from n-hexane); Rf 0.61
(Al2O3, DCM/n-hexane, 1:1); (anal. found: C, 52.46; H, 2.32; N,
12.15. C15H8F6N3 requires C, 52.34; H, 2.34; N, 12.21%);
λmax(DCM)/nm (log ε) 244 (3.44), 261 inf (3.07), 318 (2.87), 340
(2.76), 414 (2.38), 478 (2.21); νmax/cm−1 3067w (Ar CH), 1591w,
1493w, 1456w, 1441w, 1416w, 1379w, 1341m, 1317m, 1275s, 1198s,
1175m, 1165m, 1150s, 1128s, 1096m, 1065s, 1026w, 999w, 910s,
870w, 862m, 835m, 802w, 768m, 737m; MALDI-TOF m/z (%): 345
(MH+, 10), 344 (M+, 86), 316 (4), 290 (100).
4.6.4. 1-Phenyl-3-(thien-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-yl
(1d). Similar treatment of N′-(2-nitrophenyl)-N′-phenyl-2-thiophene-
carbohydrazide (13d) (0.339 g, 1.0 mmol) with Sn powder (0.475 g,
4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h and at ca. 118 °C
for 10 min followed by stirring with 2 M NaOH (50 mL) for 12 h gave
upon chromatography (basic alumina, DCM) the title compound 1d
as dark-green needles (0.253 g, 87%). Mp (DSC) onset 133.7 °C, peak
max 134.6 °C (from EtOH); Rf 0.63 (Al2O3, DCM); (anal. found: C,
70.52; H, 4.24; N, 14.29. C17H12N3S requires C, 70.32; H, 4.17; N,
14.47%); λmax(DCM)/nm (log ε) 231 (3.35), 259 inf (3.38), 290
(3.74), 303 inf (3.57), 380 (2.85), 409 inf (2.77), 507 (2.34); νmax
/
cm−1 3103w, 3071w, 3063w, 3055w (Ar CH), 1533m, 1493m, 1479s,
1452s, 1435s, 1389s, 1360w, 1350w, 1327w, 1287m, 1252w, 1219m,
1206m, 1148w, 1121w, 1076m, 1055w, 1036w, 1024w, 1003w, 972w,
934w, 916w, 847m, 839m, 831m, 814w, 770m, 752s, 743s; MALDI-
TOF m/z (%): 291 (MH+, 18), 290 (M+, 100), 272 (6).
4.6.5. 1-Phenyl-3-(pyrid-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-yl
(1e). Similar treatment of N′-(2-nitrophenyl)-N′-phenyl-2-pyridine-
carbohydrazide (13e) (0.334 g, 1.0 mmol) with Sn powder (0.475 g,
4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h and at ca. 118 °C
for 10 min followed by stirring with 2 M NaOH (50 mL) for 3 days
gave upon chromatography (basic alumina, DCM/t-BuOMe) the title
compound 1e as black needles (0.235 g, 82%). Mp (DSC) onset 179.7
°C, peak max 181.7 °C (from PhH); Rf 0.40 (Al2O3, DCM); (anal.
found: C, 75.89; H, 4.44; N, 19.58. C18H13N4 requires C, 75.77; H,
4.59; N, 19.64%); λmax(DCM)/nm (log ε) 257 inf (3.31), 276 (3.39),
320 (2.79), 363 (2.74), 424 (2.43), 493 (2.08); νmax/cm−1 3065w,
3044w and 3036w (Ar CH), 1587m, 1580m, 1570m, 1562m, 1495m,
1481m, 1474m, 1454m, 1435m, 1385s, 1331m, 1308m, 1260m,
1211m, 1163m, 1099m, 1082m, 1072m, 1047m, 1026m, 995m, 937m,
891m, 881m, 845m, 837m, 797m, 789s, 758s, 739s; MALDI-TOF m/z
(%): 286 (MH+, 35), 285 (M+, 100), 267 (1), 185 (1).
4.6.6. 3-Methyl-1-phenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1f).
Similar treatment of N′-(2-nitrophenyl)-N′-phenylacetohydrazide
(13f) (0.271 g, 1.0 mmol) with Sn powder (0.475 g, 4.0 mmol) in
AcOH (5 mL) at ca. 20 °C for 0.5 h and at ca. 118 °C for 10 min
followed by stirring with 2 M NaOH (50 mL) for 12 h gave upon
chromatography (basic alumina, DCM) the title compound 1f as a
deep-red oil (0.140 g, 63%); Rf 0.56 (Al2O3, DCM); (anal. found: C,
75.56; H, 5.32; N, 18.92. C14H12N3 requires C, 75.65; H, 5.44; N,
18.91%); λmax(DCM)/nm (log ε) 241 (3.22), 259 inf (2.93), 286
(2.61), 318 (2.73), 348 (2.69), 424 (2.23), 548 inf (1.81); νmax/cm−1
3061w (Ar CH), 2924w (CH3), 1659w, 1585m, 1489s, 1452m,
1406m, 1327m, 1294m, 1271m, 1202w, 1171w, 1157w, 1124w,
4.6.10. 3-(Adamant-1-yl)-1-phenyl-1,4-dihydro-1,2,4-benzotria-
zin-4-yl (1j). Similar treatment of N′-(2-nitrophenyl)-N′-phenyl-1-
adamantanecarbohydrazide (13q) (0.391 g, 1.0 mmol) with Sn
powder (0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h
and at ca. 118 °C for 10 min followed by stirring with 2 M NaOH (50
mL) for 12 h gave upon chromatography (basic alumina, DCM/t-
BuOMe) the title compound 1j as dark-red needles (0.271 g, 79%).
Mp (DSC) onset 171.0 °C, peak max 172.1 °C (from MeOH); Rf 0.71
(Al2O3, DCM); (anal. found: C, 80.58; H, 7.17; N, 12.18. C23H24N3
requires C, 80.67; H, 7.06; N, 12.27%); λmax(DCM)/nm (log ε) 242
(3.40), 320 (2.87), 348 (2.84), 429 (2.48), 538 inf (1.74); νmax/cm−1
3092w, 3075w and 3038w (Ar CH), 1597w, 1591w, 1533s, 1487m,
1456w, 1368m, 1344w, 1333w, 1315w, 1298m, 1287m, 1256w, 1188w,
1175w, 1157w, 1113s, 1084w, 1076m, 1030w, 962w, 945w, 910w,
901w, 876w, 853m, 829w, 781m, 762w, 750m, 727w; MALDI-TOF
m/z (%): 343 (MH+, 20), 342 (M+, 100).
4.6.11. 1-(4-Cyanophenyl)-3-phenyl-1,4-dihydro-1,2,4-benzotria-
zin-4-yl (1k). Similar treatment of N′-(4-cyanophenyl)-N′-(2-
nitrophenyl)benzohydrazide (13j) (0.358 g, 1.0 mmol) with Sn
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powder (0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h
and at ca. 118 °C for 10 min followed by stirring with 2 M NaOH (50
mL) for 3 days gave upon chromatography (basic alumina, DCM) the
title compound 1k as dark-green needles (0.263 g, 85%). Mp (DSC)
onset 137.5 °C, peak max 140.0 °C (from n-hexane); Rf 0.64 (Al2O3,
DCM/n-hexane, 1:1); (anal. found: C, 77.52; H, 4.26; N, 17.95.
C20H13N4 requires C, 77.65; H, 4.24; N, 18.11%); λmax(DCM)/nm
(log ε) 233 (3.33), 270 (3.59), 345 (3.05), 370 (2.91), 461 (2.8), 503
inf (2.38); νmax/cm−1 3061w and 3028w (Ar CH), 2222m (CN),
1597m, 1501m, 1483s, 1450m, 1414w, 1398s, 1327w, 1315m, 1296w,
1288w, 1252w, 1206w, 1175m, 1152w, 1126w, 1065w, 1024w, 984w,
928w, 880w, 845m, 837m, 781w, 758s, 741m; MALDI-TOF m/z (%):
310 (MH+, 15), 309 (M+, 100), 297 (2).
4.6.12. 1-(4-Cyanophenyl)-3-(thien-2-yl)-1,4-dihydro-1,2,4-ben-
zotriazin-4-yl (1l). Similar treatment of N′-(4-cyanophenyl)-N′-(2-
nitrophenyl)-2-thiophenecarbohydrazide (13k) (0.364 g, 1.0 mmol)
with Sn powder (0.475 g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for
0.5 h and at ca. 118 °C for 10 min followed by stirring with 2 M
NaOH (50 mL) for 3 days gave upon chromatography (basic alumina,
DCM) the title compound 1l as dark-green needles (0.223 g, 71%).
Mp (DSC) onset 166.8 °C, peak max 168.8 °C (from EtOH); Rf 0.67
(Al2O3, DCM/n-hexane, 1:1); (anal. found: C, 68.42; H, 3.56; N,
17.68. C18H11N4S requires C, 68.55; H, 3.52; N, 17.77%);
λmax(DCM)/nm (log ε) 231 (3.28), 292 (3.52), 346 (3.00), 378 inf
MeOH, 5:1); (anal. found: C, 67.70; H, 3.71; N, 23.12. C17H11N5O
requires C, 67.77; H, 3.68; N, 23.24%); λmax(DCM)/nm (log ε) 243
(3.22), 298 (3.54), 308 inf (3.45), 342 (3.04), 355 inf (3.03), 489 inf
(2.56), 536 (2.72), 575 (2.66), 623 inf (2.33); νmax/cm−1 3071w (Ar
CH), 1626m, 1614m, 1601m, 1585s, 1570m, 1545s, 1470m, 1427m,
1396w, 1339w, 1292w, 1234m, 1198w, 1153w, 1117w, 1101w, 1090w,
1078w, 1049w, 997w, 974w, 908w, 851s, 822w, 793m, 764w, 741w; δH
(500 MHz, CDCl3) 8.83 (1H, d, J = 4.4 Hz), 8.65 (1H, d, J = 3.8 Hz),
8.30 (1H, d, J = 8.0 Hz), 8.03 (1H, ddd, J = 7.9, 7.9, 1.5 Hz), 7.86 (1H,
ddd, J = 7.9, 7.9, 1.3 Hz), 7.84−7.79 (2H, m), 7.49 (1H, dd, J = 7.3,
5.0 Hz), 7.41 (1H, dd, J = 7.1, 5.0 Hz), 7.29 (1H, d, J = 1.9 Hz), 6.68
(1H, d, J = 1.9 Hz); δC (125 MHz, CDCl3) 183.2 (s), 156.8 (s), 154.1
(s), 151.5 (s), 150.2 (d), 149.2 (s), 148.8 (d), 141.7 (d), 139.7 (d),
137.1 (d), 134.5 (s), 133.0 (d), 124.8 (d), 124.7 (d), 122.4 (d), 120.4
(d), 100.2 (d); MALDI-TOF m/z (%): 304 (MH+ + 2, 9), 303 (MH+
+ 1, 33), 302 (MH+, 100), 301 (M+, 40), 299 (31), 288 (6), 274 (47).
4.7.2. 1,3-Bis(pyrid-2-yl)-7-(trifluoromethyl)-1,4-dihydro-1,2,4-
benzotriazin-4-yl (1o). Similar treatment of 1,3-bis(pyrid-2-yl)-7-
(trifluoromethyl)-1,4-dihydro-1,2,4-benzotriazine (23c) (355 mg, 1.0
mmol) in DCM (10 mL) with MnO2 (869 mg, 10.0 mmol) at ca. 20
°C for 2 days gave upon chromatography (basic alumina, DCM/t-
BuOMe, 1:1) the title compound 1o (173 mg, 49%) as black needles.
Mp (DSC) onset 218.1 °C, peak max 222.9 °C (from MeCN); Rf 0.49
(Al2O3, DCM); (anal. found: C, 60.93; H, 3.07; N, 19.89. C18H11F3N5
requires C, 61.02; H, 3.13; N, 19.77%); λmax(DCM)/nm (log ε) 236
(3.16), 267 (3.29), 282 inf (3.26), 328 inf (2.96), 436 (2.41), 510
(1.95); νmax/cm−1 3061w and 3011w (Ar CH), 1585m, 1568w, 1514w,
1466m, 1429s, 1402m, 1375m, 1344s, 1325s, 1290m, 1271s, 1233w,
1190w, 1161s, 1115s, 1088m, 1061m, 1043w, 991w, 947w, 912m,
878m, 822m, 800m, 775m, 743m, 733w; MALDI-TOF m/z (%): 355
(MH+, 10), 354 (M+, 86), 342 (100), 339 (63), 182 (6), 78 (4).
(2.80), 396 inf (2.71), 469 (2.74), 499 inf (2.49), 602 (1.84); νmax
/
cm−1 3088w and 3063w (Ar CH), 2226m (CN), 1599m, 1585w,
1533m, 1501m, 1481s, 1456w, 1433s, 1391s, 1331m, 1288m, 1254w,
1217w, 1207w, 1180w, 1152m, 1115w, 1094w, 1055w, 1038w, 1018w,
970w, 932w, 851m, 841s, 829m, 750m, 743s, 729s; MALDI-TOF m/z
(%): 316 (MH+, 15), 315 (M+, 100), 303 (8), 123 (9).
4.6.13. 3-Phenyl-1-(pyrid-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-
yl (1m). Similar treatment of N′-(2-nitrophenyl)-N′-(pyrid-2-yl)-
benzohydrazide (13l) (0.334 g, 1.0 mmol) with Sn powder (0.475
g, 4.0 mmol) in AcOH (5 mL) at ca. 20 °C for 0.5 h and at ca. 118 °C
for 10 min followed by stirring with 2 M NaOH (50 mL) for 12 h gave
upon chromatography (basic alumina, DCM) the title compound 1m
as dark-green needles (0.220 g, 77%). Mp (DSC) onset 146.7 °C, peak
max 147.4 °C (from n-hexane/n-heptane, 1:1); Rf 0.71 (Al2O3, DCM/
n-hexane, 1:1); (anal. found: C, 75.62; H, 4.60; N, 19.48. C18H13N4
requires C, 75.77; H, 4.59; N, 19.64%); λmax(DCM)/nm (log ε) 232
inf (4.22), 273 (4.68), 315 (4.10), 380 (3.94), 429 (3.79); νmax/cm−1
3065w, 1584m, 1568w, 1485m, 1466m, 1449m, 1433s, 1398s, 1333w,
1314m, 1275w, 1256w, 1200w, 1175w, 1161w, 1150m, 1121w, 1028w,
989w, 922w, 863w, 849w, 785s, 772m, 760m, 752s, 745s, 737m, 731m;
MALDI-TOF m/z (%): 286 (MH+, 22), 285 (M+, 100).
4.6.14. 1,3-Diphenyl-1,4-dihydro-1,2,4-pyridotriazin-4-yl (1n).
Similar treatment of N′-(3-nitropyrid-2-yl)-N′-phenylbenzohydrazide
(13o) (0.334 g, 1.0 mmol) with Sn powder (0.475 g, 4.0 mmol) in
AcOH (5 mL) at ca. 20 °C for 0.5 h and at ca. 118 °C for 1 h followed
by stirring with 2 M NaOH (50 mL) for 3 h gave upon
chromatography (basic alumina, DCM) the title compound 1n as
dark-maroon needles (0.220 g, 77%). Mp (DSC) onset 147.8 °C, peak
max 141.4 °C (from n-hexane/n-heptane, 1:1); Rf 0.66 (Al2O3, DCM/
n-hexane, 1:1); (anal. found: C, 75.78; H, 4.63; N, 19.49. C18H13N4
requires C, 75.77; H, 4.59; N, 19.64%); λmax(DCM)/nm (log ε) 265
ASSOCIATED CONTENT
* Supporting Information
Experimental and simulated EPR data for all new radicals 1c−o,
cyclic voltammograms for radicals 1c−o, and 1H and 13C NMR
spectral data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: Koutenti@ucy.ac.cy.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the University of Cyprus (medium-size
grants) and the Cyprus Research Promotion Foundation
(Grants YΓEIA/BIOΣ/0308(BIE)/13, NEKYΠ/0308/02, and
ANABAΘMIΣH/0308/32) for support and the following
organizations in Cyprus for generous donations of chemicals
and glassware: the State General Laboratory, the Agricultural
Research Institute, and the Ministry of Agriculture and
Biotronics Ltd. Furthermore, we thank the A. G. Leventis
Foundation for helping to establish the NMR facility at the
University of Cyprus.
(4.49), 303 inf (4.17), 329 inf (4.01), 367 (3.87), 432 (3.83); νmax
/
cm−1 3061w (Ar CH), 1643m, 1624w, 1591w, 1541w, 1489m, 1468m,
1445m, 1423s, 1383m, 1319m, 1306m, 1283m, 1263m, 1242m,
1179w, 1109w, 1026w, 980w, 926w, 887w, 849w, 800m, 766m, 741m;
MALDI-TOF m/z (%): 286 (MH+, 20), 285 (M+, 100).
4.7. MnO2 Oxidation of 1,3-Bis(pyrid-2-yl)benzotriazines
23b and 23c. 4.7.1. 1,3-Bis(pyrid-2-yl)-1,2,4-benzotriazin-7(1H)-
one (24). To a stirred solution of 1,3-bis(pyrid-2-yl)-1,4-dihydro-1,2,4-
benzotriazine (23b) (287 mg, 1.0 mmol) in DCM (10 mL) at ca. 20
°C was added MnO2 (869 mg, 10.0 mmol). After 2 days the reaction
mixture was filtered through Celite and rinsed with additional DCM,
and the volatiles were removed in vacuo. The residue was
chromatographed on a short pad of silica (acetone) to give the title
compound 24 (159 mg, 53%) as blue flakes. Mp (DSC) decomp.
onset 175.9 °C, peak max 197.7 °C (from acetone); Rf 0.65 (CHCl3/
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