Catalytic oxidation of N -phenylamidrazones to 1,3-Diphenyl-1,4-dihydro-1, 2,4-benzotriazin-4-yls: An improved synthesis of blatters radical

Article abstract of DOI:10.1055/s-0029-1218782

Blatters radical, 1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1a, R =H), and several of its C-7 substituted analogues (R =CF₃, Cl, Br, I, Me, OMe) were prepared in good-to-excellent yields through catalytic oxidation of the corresponding

Full text of DOI:10.1055/s-0029-1218782

PAPER
2075
Catalytic Oxidation of N-Phenylamidrazones to 1,3-Diphenyl-1,4-dihydro-
1,2,4-benzotriazin-4-yls: An Improved Synthesis of Blatter’s Radical
1
, 3-Diphenyl-
a
n
-1,2,4-benzo
a
triazin-4-yl
y
s
iotis A. Koutentis,* Daniele Lo Re
Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
E-mail: koutenti@ucy.ac.cy; fax +357(22)892809
Received 18 January 2010; revised 16 March 2010
Until now, Blatter’s radical (1a) was available in only
moderate yields by treatment of the N-phenylamidrazone
4a with either a large excess of toxic mercury(II) oxide16
or an expensive oxidant such as silver(II) oxide.17 As part
Abstract: Blatter’s radical, 1,3-diphenyl-1,4-dihydro-1,2,4-benzo-
triazin-4-yl (1a, R = H), and several of its C-7 substituted analogues
(R = CF3, Cl, Br, I, Me, OMe) were prepared in good-to-excellent
yields through catalytic oxidation of the corresponding amidrazones
by using palladium-on-carbon (1.6 mol%) and 1,8-diazabicyc- of our studies on benzotriazin-4-yl radicals, we required a
lo[5.4.0]undec-7-ene (0.1–1.0 equiv) in air. The reaction conditions
better method for converting valuable and relatively inac-
were suitable for the preparation of Blatter’s radical on a one-gram
scale in up to 87% yield.
cessible amidrazones into stable radicals. We have there-
fore developed a mild and high-yielding method using
both palladium-on-carbon and 1,8-diazabicyclo[5.4.0]un-
dec-7-ene (DBU) in an atmosphere of air.
Key words: catalysis, oxidations, ring closure, heterocycles, or-
ganic radicals, benzotriazines, DBU
Initially, several oxidants were screened as replacements
for mercury(II) oxide; 2,3-dichloro-5,6-dicyanobenzo-
Organic radicals have attracted the interest of many
1,4-quinone, N-chlorosuccinimide, potassium peroxy-
scientists1 owing to their potential uses as organic
monosulfate (Oxone), cerium(IV) ammonium nitrate, and
magnets2 and conductors.3 Recently, several applications
selenium dioxide were all tested without success. Sodium
of organic radicals have been developed, such as organic
periodate (10 equiv) gave the desired product in 75%
batteries,4 magnetic inks,5 electrochromic devices,6 pho-
yield, but the reaction was slow (7 days), whereas more
tosensitive devices,7 and spin probes.8
powerful oxidants, such manganese dioxide (20 equiv, 8
Blatter’s radical (1a; R = H), which has been described as
indefinitely stable9 or as super-stable,10 forms semicon-
ducting, pressure-sensitive, charge-transfer complexes
with tetracyanoquinodimethane (TCNQ),11 and was the
inspiration behind the charge-separated zwitterionic bis-
cyanine tetraphenylhexaazaanthracene 3 (TPHA).12 In ad-
dition, extensive studies of its magnetic behavior have
been reported.13 Moreover, some 1,2,4-benzotriazines
have shown herbicidal behavior (e.g., benzotriazine 2)14
or antitumor properties.15
days) or potassium permanganate (10 equiv, 3 days) gave
the over-oxidized benzotriazinone 5 in 68% and 82%
yields, respectively. Fortunately, the reaction with a cata-
lytic amount of palladium-on-carbon (1.6 mol%, 1 day) in
an oxygen atmosphere gave the radical 1a rapidly in 65%
yield.
Palladium-on-carbon is known to catalyze the aerobic ox-
idation of alcohols,18 and studies have suggested that
these oxidations are influenced by the pH.18b,19 We there-
fore examined the use of palladium-on-carbon in the pres-
ence of various organic bases. Under an oxygen
atmosphere, treatment of N-phenylamidrazone 4a with
palladium-on-carbon and pyridine, 4-(dimethylamino)py-
ridine (DMAP), triethylamine, or ethyl(diisopropyl)-
amine (Hünig’s base) (1 equiv) for one day gave the de-
sired product in good yields (67–94%). Surprisingly, with
DBU as the base, the reaction reached completion rapidly
(~ 4 h) and gave the benzotriazin-4-yl 1a in 93% yield.
With the aim of simplifying the reaction further, the same
reactions were performed under atmosphere of air. After
one day, pyridine, DMAP, triethylamine, and Hünig’s
base each gave an incomplete reaction, and the product
mixture contained some benzotriazinone 5, whereas DBU
gave the radical 1a in 95% yield after only three hours.
When the reaction was performed under an oxygen-free
atmosphere (argon), only a trace of the radical 1a was de-
tected by thin-layer chromatography (TLC) after one day,
suggesting that some oxygen was needed for the conver-
sion to occur. Furthermore, under an air atmosphere in the
Ph
N
Ph
N
Ph
N
Me
N
N
N
N
N
N
Ph
Ph
Ph
N
N
Ph
N
H
•
1a
2
3
Ph
HN
Ph
O
N
N
N
N
H
Ph
N
Ph
5
4a
Figure 1
SYNTHESIS 2010, No. 12, pp 2075–2079
x
x.
x
x
.
2
0
1
0
Advanced online publication: 10.05.2010
DOI: 10.1055/s-0029-1218782; Art ID: T01510SS
© Georg Thieme Verlag Stuttgart · New York

2076
P. A. Koutentis, D. Lo Re
PAPER
presence of palladium-on-carbon (1.6 mol%), the number Furthermore, the formation of TPHA 3 from the corre-
of equivalents of DBU required could be reduced to only sponding bisamidrazone was achieved by using an excess
0.1 without significantly increasing the reaction time (6 h) of DBU (2.8 equiv, 14 d; 40%).12
or affecting the yield (98%). With these improved condi-
Several electron-rich and electron-deficient amidrazones
tions, Blatter’s radical (1a) could be prepared on a one-
4b–g (0.5 mmol) were treated with DBU with and without
gram scale in 87% yield, although with an increased reac-
palladium-on-carbon to compare the improved palladium-
tion time (18.5 h). At the same scale (1 g), the reaction
catalyzed oxidative cyclization with the transition-metal-
time could be reduced (6 h) by bubbling dry air into the re-
free oxidative route to the corresponding 7-substituted
1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yls 1b–g
(Table 2).
action mixture, confirming the need for aerobic conditions
(Table 1).
Table 1 Preparation of 1,3-Diphenyl-1,4-dihydro-1,2,4-benzotriaz-
Table 2 Synthesis of Various 1,3-Diphenyl-1,4-dihydro-1,2,4-ben-
in-4-yl (1a) from N-Phenylamidrazone 4a
zotriazin-4-yls 1a–g from N-Phenylamidrazones 4a–ga
Ph
N
Ph
HN
Ph
N
Ph
HN
R
R
N
N
N
N
N
Ph
N
H
4a
Ph
N
Ph
N
Ph
•
•
H
1a
4a–g
1a–g
Pd/C
(mol%)
DBU
(equiv)
Atmosphere Time
(h)
Yield of 1a
(%)
R
DBU
(equiv)
Pd/C
(mol%)
Time
(h)
Product
Yield
(%)
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
0
0
O2
24
24
6
65
H
0.1
1
1.6
0
7
26
6.5
23
8
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
85
0
air
O2
trace
87
H
77
0.1
0.1
0.1
0.1
1
CF3
CF3
Cl
0.1
1
1.6
0
80b
74b
82
air
air
air
O2
6
98
18.5
6
87b
82b,c
93
1
1.6
0
Cl
1
23
9
62b
94
4
Br
0.1
1
1.6
0
1
air
argon
O2
3
95
Br
22
6
70b
81
1
24
26
22
24
24
trace
79
I
1
1.6
0
1
I
1
23
7
62b
70
0
1
air
O2
91
Me
Me
OMe
OMe
1
1.6
0
d
0
0.1
0.1
–
1
24
4
1f
56
d
0
air
–
1
1.6
0
1g
1g
72
a Reaction conditions: 4a (0.174 mmol), CH2Cl2 (1 mL), r.t.
b Reaction conditions: 4a (1 g, 3.48 mmol) in CH2Cl2 (20 mL), r.t.
c Dry air was bubbled into the mixture.
1
24
58b
a Reaction conditions: 4a–g (0.5 mmol), CH2Cl2 (3 mL), DBU, Pd/C
(1.6 mol% or 0 mol%), r.t., air.
d Incomplete reaction.
b With 4 Å molecular sieves.
In the absence of palladium-on-carbon, treatment of the
amidrazone 4a with DBU (1 equiv) for one day gave the
desired radical 1a in 91% yield. Under analogous condi-
tions with replacement of DBU by pyridine, DMAP, tri-
ethylamine, or Hünig’s base gave only traces of the
radical (by TLC). An attempt to use DBU in a catalytic
amount (10 mol%) under an atmosphere of either air or
oxygen led to an incomplete reaction after one day; longer
reaction times led to increasingly complex reaction mix-
tures (by TLC). The presence of DBU was therefore
shown to be critical, but its role is not clear. Rapid reac-
tions required both DBU and palladium-on-carbon. DBU
is a strong base,20 but it can also act as a soft nucleophile.21
In all cases, the palladium-catalyzed oxidative cycliza-
tions came to completion faster (4–9 h) than did the tran-
sition-metal-free cyclizations (22–26 h). Nevertheless, in
several of the palladium-catalyzed examples (R = Cl, I,
Me, OMe), it was noteworthy that with catalytic amounts
of DBU, the reaction failed to reach completion; when
prolonged reaction times were used, complex mixtures
containing the over-oxidized benzotriazinone 5 (as ob-
served by TLC) were obtained. In these cases (R = Cl, I,
Me, OMe), the problem was solved by the use of one
equivalent of DBU. In the case of amidrazone 4b, some N-
[4-(trifluoromethyl)phenyl]benzamide was observed by
Synthesis 2010, No. 12, 2075–2079 © Thieme Stuttgart · New York

PAPER
1,3-Diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yls
2077
1,3-Diphenyl-1,2,4-benzotriazin-7(1H)-one (5)
TLC; amidrazones can hydrolyze under basic conditions
to afford benzanilides;22 in this case, the introduction of
molecular sieves (4 Å) to the reaction mixture permitted
the use of a catalytic amount of DBU.
KMnO4 (275 mg, 1.74 mmol) was added to a stirred soln of amidra-
zone 4a (50 mg, 0.174 mmol) in benzene (2 mL), and the mixture
was refluxed for 3 d until the starting material was consumed and a
polar purple compound was detected [TLC; t-BuOMe–hexane
(1:4)]. The solvent was evaporated under reduced pressure and the
residue was purified by dry flash chromatography (EtOAc) to give
purple crystals; yield: 42.9 mg (82%); mp 215–218 °C (benzene)
(Lit.7 216–217.5 °C).
The precise mechanism of the DBU/palladium/oxygen re-
action is beyond the scope of the present study and, in
mechanistic terms, it is not clear why this reaction pro-
ceeds so rapidly. DBU can deprotonate the N-phenyl-
amidrazones to afford anions that, owing to their
energetically raised HOMOs, are more susceptible to ox-
idation. Dioxygen present in the air can act as the oxidant,
and it is noteworthy that under a dioxygen-depleted atmo-
sphere of argon, only traces of radicals were observed.
Furthermore, palladium is well known to abstract hydro-
gen atoms and it can coordinate with nitrogen lone pairs,
thereby assisting the reaction through resonance stabiliza-
tion of an intermediate species.23 Finally, amine ligands
can stabilize active palladium species, thereby preventing
aggregation and deactivation of the catalyst.24 Neverthe-
less, predicting the order and number of mechanistic
events on the basis of the current study would be highly
speculative, and a deeper mechanistic understanding will
require additional studies.
IR (ATR): 3063w (Ar CH), 2923s, 2849m, 1612m (C=O), 1590s,
1538s, 1456m, 1386m, 1309m, 1234m, 1190m, 1101m, 1067w,
973m, 908w, 853m, 816m, 774m, 749m, 692m, 668m, 608m cm–1.
1H NMR (300 MHz, CDCl3): d = 8.32–8.24 (m, 2 H), 7.73 (d, 1 H,
J = 9.7 Hz, H-5), 7.67–7.56 (m, 5 H), 7.55–7.45 (m, 3 H), 7.33 (dd,
1 H, J = 9.7, 2.1 Hz, H-6), 6.12 (d, 1 H, J = 2.1 Hz, H-8).
13C NMR (75 MHz, CDCl3): d = 182.4 (Ar C=O, C-7), 155.3 (Ar
C), 151.3 (Ar C), 142.8 (Ar C), 141.4 (Ar C), 136.9 (Ar C), 134.2
(Ar C), 132.6 (Ar CH), 131.0 (Ar CH), 130.6 (Ar CH), 130.5 (Ar
CH), 129.2 (Ar CH), 127.1 (Ar CH), 126.0 (Ar CH), 98.2 (Ar CH,
C-8).
MS (EI, 70 eV): m/z (%) = 300 (27) [M+ + 1], 299 (100) [M+], 282
(6), 271 (60), 168 (38), 139 (10), 104 (4), 103 (5), 89 (6), 77 (67),
63 (27), 51 (21).
UV/Vis (CH2Cl2): lmax (log e) = 231 (4.32), 299 (4.61), 544 (3.82).
N¢-Phenyl-N-[4-(trifluoromethyl)phenyl]benzenecarbohydra-
zonamide (4b); Typical Procedure
In summary, we have developed an improved preparation
of Blatter’s radical (1a) and related analogues from the
corresponding amidrazones by using DBU and, optional-
ly, palladium-on-carbon. The solid-state properties of the
new benzotriazin-4-yl radicals will be reported in the near
future.
F3CC6H4NH2 (0.52 mL, 4.22 mmol) was added to a stirred soln of
PhNHN=CCIPh (0.972 g, 4.22 mmol) in dry benzene (2.5 mL), and
the mixture was refluxed for 8 h until TLC (t-BuOMe–hexane 1:4)
showed the presence of a new more polar compound and the ab-
sence of the starting material. The mixture was then concentrated
under reduced pressure, and the residue was purified by dry flash
chromatography [t-BuOMe–hexane (1:9)] to give colorless crys-
tals; yield: 520 mg (35%); mp 127–130 °C (t-BuOMe–hexane 1:9).
Solvents CH2Cl2 and benzene were freshly distilled from CaH2 un-
der argon. Reactions were protected by means of CaCl2 drying
tubes. Anhyd MgSO4 was used for drying organic extracts, and all
volatiles were removed under reduced pressure. All reaction mix-
tures and column eluents were monitored by TLC using commercial
aluminum-backed TLC plates (Merck Kieselgel 60 F254). The plates
were visualized under UV radiation at 254 and 365 nm. The tech-
nique of dry flash chromatography (Merck silica gel 60; <0.063
mm) was used throughout for all non-TLC-scale chromatographic
separations. Melting points were determined by using a PolyTherm-
A, Wagner & Munz, Koefler-Hotstage microscope apparatus. Sol-
vents used for recrystallization are indicated after the melting
points. UV spectra were recorded by using a Perkin-Elmer Lambda-
25 UV/vis spectrophotometer, and inflection points are identified
by the abbreviation ‘inf’. IR spectra were recorded on a Shimadzu
FTIR-NIR Prestige-21 spectrometer with Pike Miracle Ge ATR ac-
cessory and strong, medium, and weak peaks are shown as s, m, and
w, respectively. 1H and 13C NMR spectra were recorded on a Bruker
Avance 300 machine at 300 and 75 MHz, respectively. CH and CH2
assignments were supported by 13C NMR DEPT 90 and DEPT 135
experiments. Deuterated solvents were used to achieve a homonu-
clear lock, and the signals are referenced to the deuterated solvent
peaks. Low-resolution (EI) mass spectra were recorded on a Shi-
madzu Q2010 GCMS with a direct inlet probe. EPR measurements
were carried out on a Bruker EMX spectrometer by using an X-
Band (9.8 GHz) microwave bridge at 290 K. N¢-Phenylbenzohydra-
zonoyl chloride,25 N,N¢-diphenylbenzenecarbohydrazonamide (4a),
N-(4-methylphenyl)-N¢-phenylbenzenecarbohydrazonamide (4f),26
N-(4-chlorophenyl)-N¢-phenylbenzenecarbohydrazonamide (4c),27
N-(4-bromophenyl)-N¢-phenylbenzenecarbohydrazonamide (4d),28
IR (ATR): 3333w (Ar NH), 1653w, 1643m, 1616m, 1601s, 1582w,
1559w, 1527m, 1505m, 1491m, 1445w, 1433w, 1404w, 1331s,
1318s, 1296w, 1246s, 1185m, 1167m, 1155m, 1110s, 1069s,
1024w, 827s, 771m, 753s, 718w cm–1.
1H NMR (300 MHz, CDCl3): d = 7.75 (br s, 1 H, NH), 7.71–7.67
(m, 2 H) 7.46 (d, J = 8.4 Hz, 2 H), 7.38–7.36 (m, 3 H), 7.31–7.26
(m, 2 H), 7.14 (d, J = 7.8 Hz, 2 H), 6.91 (t, J = 7.2 Hz, 1 H), 6.74 (d,
J = 8.4 Hz, 2 H).
MS (EI, 70 eV): m/z (%) = 356 (10) [M+ + 1], 355 (42) [M+], 249
(4), 248 (22), 195 (6), 194 (42), 167 (4), 145 (10), 104 (12), 91
+
(100), 77 (C6H5 , 23), 65 (26), 51 (9).
Anal. Calcd for C20H16F3N3: C, 67.60; H, 4.54; N, 11.82. Found: C,
67.58; H, 4.57; N, 11.83.
N-(4-Iodophenyl)-N¢-phenylbenzenecarbohydrazonamide (4e)
Colorless crystals; yield: 840 mg (47%); mp 161–165 °C (cyclohex-
ane).
IR (ATR): 3331w and 3316w (ArNH), 1643m, 1597m, 1583m,
1506m, 1487s, 1444w, 1434w, 1391w, 1346m, 1306m, 1301m,
1287w, 1253m, 1242m, 1180w, 1140m, 1061m, 1026w, 999w,
921w, 885w, 810s, 768m, 755s, 703s cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70–7.67 (m, 3 H), 7.49 (d,
J = 8.6 Hz, 2 H), 7.37–7.35 (m, 3 H), 7.30–7.25 (m, 2 H), 7.12 (d,
J = 7.8 Hz, 2 H), 6.89 (t, J = 7.2 Hz, 1 H), 6.47 (d, J = 8.7 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 144.7 (Ar C), 141.1 (Ar C), 138.1
(Ar CH), 134.2 (Ar C), 129.2 (Ar CH), 129.0 (Ar CH), 128.6 (Ar
CH), 126.4 (Ar CH), 120.4 (Ar CH), 118.2 (Ar CH), 113.3 (Ar CH),
82.8 (C-I).
and
N-(methoxyphenyl)-N¢-phenylbenzenecarbohydrazonamide
(4g),16 were prepared according to literature procedures.
Synthesis 2010, No. 12, 2075–2079 © Thieme Stuttgart · New York

2078
P. A. Koutentis, D. Lo Re
PAPER
MS (EI, 70 eV): m/z (%) = 414 (13) [M+ + 1], 413 (71) [M+], 307
IR (ATR): 3069w, 2926w, 1591w, 1566w, 1476s, 1449m, 1393s,
1317w, 1265w, 1242w, 1196w, 1130w, 1070w, 1061w, 1022w,
926w, 889m, 827m, 777s, 758w, 740w cm–1.
(4), 306 (28), 195 (12), 194 (72), 193 (7), 179 (9), 104 (9), 91 (100),
+
77 (20) [C6H5 ], 76 (17), 65 (25), 64 (12), 51 (9).
Anal. Calcd for C19H16IN3: C, 55.22; H, 3.90; N, 10.17. Found: C,
55.27; H, 3.89; N, 10.19.
MS (EI, 70 eV): m/z (%) = 365 (40) [M+ + 2], 364 (100) [M+ + 1],
363 (36) [M+], 362 (97) [M+ – 1], 283 (11) [M+ – Br], 259 (9), 180
(20), 179 (17), 178 (18), 152 (12), 151 (17), 103 (14), 77 (68), 51
(30), 50 (8).
1,3-Diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1a): Typical
Procedure
UV/Vis (CH2Cl2): lmax (log e) = 277 (3.62), 322 (2.87), 376 (2.84),
434 (2.59), 498 (2.08).
DBU (7.5 mL, 0.05 mmol) and 5% Pd/C (17 mg, 1.6 mol%) were
added to a stirred soln of amidrazone 4a (143.5 mg, 0.5 mmol) in
dry CH2Cl2 (1 mL). The mixture was stirred at r.t. for 7 h until TLC
[t-BuOMe–hexane (1:4)] showed the absence of the starting mate-
rial and the presence of a new fast-running brown compound. The
solvent was evaporated under reduced pressure, and the residue was
purified dry flash chromatography [t-BuOMe–hexane (1:9)] to give
needle-shaped black crystals; yield: 121 mg (85%); mp 109–110 °C
(EtOH), (Lit.9 113–115 °C); g = 2.0033.
Anal. Calcd for C19H13BrN3: C, 62.83; H, 3.61; N, 11.57. Found: C,
62.85; H, 3.60; N, 11.52.
7-Iodo-1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1e)
Brown crystals; yield: 166 mg (81%), mp 149–152 °C (cyclohex-
ane); g = 2.0026.
IR (ATR): 1684w, 1653w, 1591w, 1559m, 1539w, 1505w, 1489m,
1477s, 1456m, 1449m, 1392s, 1318m, 1267w, 1246w, 1193w,
1176w, 1069w, 1057w, 1024m, 883s, 828s, 780m, 774s, 739m
cm–1.
IR (ATR): 3061w, 3003w, 1585w, 1481s, 1450m, 1395s, 1317w,
1252w, 1206w, 1175w, 1082w, 1065w, 1024w, 984w, 916w, 880w,
841w, 785m, 750s cm–1.
MS (EI, 70 eV): m/z (%) = 411 (93) [M+ + 1], 410 (100) [M+], 334
(6), 307 (5), 284 (19), 283 (46) [M+ – I], 282 (23), 205 (7), 180 (14),
179 (15), 178 (12), 152 (10), 127 (5), 104 (11), 103 (13), 77 (44)
MS (EI, 70 eV): m/z (%) = 285 (44) [M+ + 1], 284 (100) [M+], 181
(16), 180 (15), 179 (21), 178 (14), 152 (12), 77 (58), 76 (22), 51
(30), 50 (15).
+
[C6H5 ], 51 (27).
UV/Vis (CH2Cl2): lmax (log e) = 271 (3.63), 322 (2.93), 372 (2.82),
429 (2.56), 494 (2.17).
UV/Vis (CH2Cl2): lmax (log e) = 280 (3.37), 323 (2.77), 377 (2.71),
438 (2.37), 481 inf (1.72).
1,3-Diphenyl-7-(trifluoromethyl)-1,4-dihydro-1,2,4-benzotriaz-
in-4-yl (1b)
Brown needles; yield: 141 mg (80%); mp 149–153 °C (cyclohex-
Anal. Calcd for C19H13IN3: C, 55.63; H, 3.19; N, 10.24. Found: C,
55.59; H, 3.07; N, 10.17.
ane); g = 2.0036.
7-Methyl-1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1f)
Brown crystals, yield: 104 mg (70%); mp 160–163 °C (cyclohex-
ane); g = 2.0053.
IR (ATR): 1593w, 1506w, 1489m, 1452w, 1422m, 1395m, 1356m,
1337w, 1314m, 1281w, 1261m, 1248w, 1204w, 1150m, 1117s,
1063m, 1024w, 905m, 870m, 841m, 793w, 781m, 768m cm–1.
MS (EI, 70 eV): m/z (%) = 353 (M+ + 1, 33%), 352 (M+, 100), 249
IR (ATR): 3063w, 2920w, 1696w, 1684w, 1653w, 1592m, 1559w,
1539w, 1503m, 1490m, 1459w, 1452m, 1420w, 1394s, 1327m,
1279w, 1257w, 1170m, 1087w, 1067w, 1024m, 1002w, 929w,
917w, 862w, 849w, 844w, 803s, 780s, 759s, 712m cm–1.
+
(6), 247 (6), 226 (4), 180 (6), 103 (5), 77 (C6H5 , 26), 51 (10).
UV/Vis (CH2Cl2): lmax (log e) = 259 inf (4.04), 273 (4.21), 284 inf
(4.03), 323 (3.55), 373 (3.40), 431 (3.17), 495 (2.84).
MS (EI, 70 eV): m/z (%) = 299 (68%) [M+ + 1], 298 (100) [M+], 283
(7), 222 (10), 195 (16), 180 (10), 167 (5), 165 (7), 149 (40), 114 (5),
Anal. Calcd for C20H13F3N3: C, 68.18; H, 3.72; N, 11.93. Found: C,
68.27; H, 3.63; N, 11.89.
+
104 (4), 89 (10), 77 (23) [C6H5 ], 72 (7), 65 (4), 57 (5), 51 (12).
UV/Vis (CH2Cl2): lmax (log e) = 275 (4.21), 283 inf (4.10), 322
(3.55), 373 (3.35), 433 (2.95), 481 inf (1.58).
7-Chloro-1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1c)
Brown crystals; yield: 130 mg (82%); mp 149–152 °C (cyclohex-
ane); g = 2.0030.
Anal. Calcd for C20H16N3: C, 80.51; H, 5.41; N, 14.08. Found: C,
80.50; H, 5.31; N, 13.92.
IR (ATR): 3069w, 2924w, 1614w, 1591w, 1474s, 1449w, 1394m,
1356w, 1317w, 1294w, 1265w, 1242w, 1192w, 1150w, 1092w,
1082w, 1024w, 897m, 846w, 829m, 779m cm–1.
MS (EI, 70 eV): m/z (%) = 321 (11) [M+ + 3], 320 (35) [M+ + 2],
319 (34) [M+ + 1], 318 (100) [M+], 283 (6) [M+ – Cl], 282 (6), 215
(10), 214 (5), 213 (9), 180 (12), 179 (11), 178 (15), 77 (49), 76 (11),
75 (15), 51 (23), 50 (6).
7-Methoxy-1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl
(1g)
Brown crystals, yield: 113 mg (72%); mp 140–143 °C (Lit.29 144–
145 °C) (cyclohexane); g = 2.0032.
IR (ATR): 3061w, 3011w, 1603w, 1589w, 1578w, 1542w, 1501s,
1487s, 1466w, 1439w, 1418w, 1395m, 1348w, 1315w, 1263w,
1213m, 1163w, 1152w, 1125w, 1099w, 1065w, 1032m, 1003w,
989w, 917w, 851w, 831w, 795w, 773s, 733w, 716m cm–1.
MS (EI, 70 eV): m/z (%) = 315 (40) [M+ + 1], 314 (100) [M+], 271
(19), 168 (15), 106 (10), 77 (32), 63 (15).
UV/Vis (CH2Cl2): lmax (log e) = 275 (3.55), 322 (2.81), 374 (2.72),
436 (2.48), 480 inf (2.05).
Anal. Calcd for C19H13ClN3: C, 71.59; H, 4.11; N, 13.18. Found: C,
71.47; H, 4.03; N, 13.12.
UV/Vis (CH2Cl2): lmax (log e) = (3.15), 277 (3.42), 312 (2.37), 375
(2.45), 417 (2.16), 436 (2.26).
7-Bromo-1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (1d)
Brown crystals; yield: 171 mg (94%), mp 160–162 °C (Lit.4 176–
178 °C) (cyclohexane); g = 2.0030.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Synthesis 2010, No. 12, 2075–2079 © Thieme Stuttgart · New York

PAPER
1,3-Diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yls
2079
(12) Hutchison, K.; Srdanov, G.; Hicks, R.; Yu, H.; Wudl, F.
J. Am. Chem. Soc. 1998, 120, 2989.
(13) Mukai, K.; Inoue, K.; Achiwa, N.; Jamali, J. B.; Krieger, C.;
Neugebauer, F. A. Chem. Phys. Lett. 1994, 224, 569; and
references cited therein.
(14) Waldrep, T. W.; Rieder, B. J.; Thibault, T. D.; Canada, E. G.
J. Agric. Food Chem. 1991, 39, 392.
(15) (a) Fuchs, T.; Chowdhury, G.; Barnes, C. L.; Gates, K. S.
J. Org. Chem. 2001, 66, 107. (b) Anderson, R. F.; Shinde, S.
S.; Hay, M. P.; Gamace, S. A.; Denny, W. A. Org. Biomol.
Chem. 2005, 3, 2167. (c) Anderson, R. F.; Shinde, S. S.;
Hay, M. P.; Denny, W. A. J. Am. Chem. Soc. 2006, 128, 245.
(16) Neugebauer, F. A.; Umminger, I. Chem. Ber. 1980, 113,
1205.
Acknowledgment
The authors wish to thank Mr Harry Krassos and Dr Georgia Loizou
for early experiments, and Mr Christos P. Constantindes for measu-
ring the ESR spectra. We also wish to thank the Cyprus Research
Promotion Foundation [Grant No. YΓΕΙΑ/BIOS/0308-(BIE)/13],
and we are grateful to the following organizations in Cyprus for ge-
nerous donations of chemicals and glassware: the State General La-
boratory, the Agricultural Research Institute, and the Ministry of
Agriculture. Finally, we thank the A. G. Leventis Foundation for
helping to establish the NMR facility at the University of Cyprus.
References
(17) Kadirov, M. K.; Buzkyn, B. I.; Gazetdinova, N. G. Russ.
Chem. Bull. 2002, 51, 1796.
(1) For reviews see: (a) Forrester, A. R.; Hay, M. J.; Thomson,
R. H. Organic Chemistry of Stable Free Radicals; Academic
Press: London, 1968. (b) Hicks, R. G. Org. Biomol. Chem.
2007, 5, 1321.
(2) (a) Miller, J. S.; Epstein, A. J. MRS Bull. 2000, 21.
(b) Veciana, J.; Iwamura, H. MRS Bull. 2000, 41.
(c) Crayston, J. A.; Devine, J. N.; Walton, J. C. Tetrahedron
2000, 56, 7829. (d) Miller, J. S. Adv. Mater. (Weinheim,
Ger.) 2002, 14, 1105.
(3) Haddon, R. C. Nature (London, U. K.) 1975, 256, 394.
(4) Kentaro, N.; Satoh, M.; Shigeyaki, I.; Hiroshi, Y.; Yutaka,
B.; Yukiko, M.; Etsuo, H. US 6866964, 2005.
(5) Shinichiro, N. JP 7138507 (A), 1995.
(6) Kazuo, M.; Hiroyoshi, H.; Hiroshi, A.; Furukana, K.;
Masamitsu, O. JP 58023878 (A), 1983.
(18) (a) Sheldon, R. A.; Dakka, J. Catal. Today 1994, 19, 215;
and references cited therein. (b) Mallat, T.; Baiker, A.
Catal. Today 1994, 19, 247; and references cited therein.
(c) Besson, M.; Gallezot, P. Catal. Today 2000, 57, 127; and
references cited therein. (d) Hou, W. B.; Dehm, N. A.; Scott,
R. W. J. J. Catal. 2008, 253, 22.
(19) Brink, G.-J. T.; Arends, I. W. C. E.; Sheldon, R. A. Science
(Washington, DC) 2000, 287, 1636.
(20) Cowley, A. H. Acc. Chem. Res. 1984, 17, 386.
(21) Michaelidou, S. S.; Koutentis, P. A. Synthesis 2009, 4167;
and references cited therein.
(22) Neilson, D. G.; Roger, R.; Heatlie, W. M.; Newlands, L. R.
Chem. Rev. 1970, 70, 151.
(23) Guy, K. A.; Shapley, J. R. Organometallics 2009, 28, 4020.
(24) Tokunaga, M.; Harada, S.; Iwasawa, T.; Obora, Y.; Tsuji, Y.
Tetrahedron Lett. 2007, 48, 6860.
(25) Ghiglieri-Bertez, C.; Coquelet, C.; Alazet, A.; Bonne, C.
Eur. J. Med. Chem. 1987, 22, 147.
(26) Pechmann, H. V. Ber. Dtsch. Chem. Ges. 1895, 28, 869.
(27) Nuhn, P.; Buege, A.; Harenberg, P.; Lettau, H.; Moschner,
K.; Rauchmaul, M.; Schneider, R. Pharmazie 1993, 48, 340.
(28) Blatter, H. M. US 3423409, 1969.
(7) Lawton, W. R. US 3600168, 1966.
(8) Sutcliffe, L. H. Phys. Med. Biol. 1998, 43, 1987.
(9) Blatter, H. M.; Lukaszewski, H. Tetrahedron Lett. 1968, 9,
2701.
(10) Gubaidullin, A. T.; Buzykin, B. I.; Litvinov, I. A.;
Gazetdinova, N. G. Russ. J. Gen. Chem. 2004, 74, 939.
(11) (a) Hutchison, K.; Srdanov, G.; Menon, R.; Gabriel, J.;
Knight, B.; Wudl, F. J. Am. Chem. Soc. 1996, 118, 13081.
(b) Hutchison, K.; Srdanov, G.; Menon, R.; Gabriel, J.;
Knight, B.; Wudl, F. Synth. Met. 1997, 86, 2147.
(29) Huisgen, R.; Wulff, J. Chem. Ber. 1969, 102, 1848.
Synthesis 2010, No. 12, 2075–2079 © Thieme Stuttgart · New York