Benzo[1,2-c:3,4-c′]bis[1,2,5]selenadiazole, [1,2,5]selenadiazolo-[3, 4-e]-2,1,3-benzothiadiazole, furazanobenzo-2,1,3-thiadiazole, furazanobenzo-2,1,3-selenadiazole and related heterocyclic systems

Article abstract of DOI:10.1002/jhet.5570410616

The first synthesis of benzo[1,2-c:3,4- c′]bis[1,2,5]selenadiazole has been developed starting from commercially available 4-nitrobenzo-2,1,3- selenadiazole. Improved syntheses of the related heterocycles [1,2,5]selenadiazolo[3,4-e]-2,1,3-benzothiadiazole, furazanobenzo-2,1,3- thiadiazole and furazanobenzo-2,1,3-selenadiazole are also reported.

Full text of DOI:10.1002/jhet.5570410616

Nov-Dec 2004
955
Benzo[1,2-c:3,4-c']bis[1,2,5]selenadiazole, [1,2,5]Selenadiazolo-
[3,4-e]-2,1,3-benzothiadiazole, Furazanobenzo-2,1,3-thiadiazole,
Furazanobenzo-2,1,3-selenadiazole and Related Heterocyclic Systems
Catherine M. Cillo and Timothy D. Lash*
Department of Chemistry, Illinois State University,
Normal, Illinois 61790-4160, U.S.A.
E-mail: tdlash@ilstu.edu
Received June 21, 2004
The first synthesis of benzo[1,2-c:3,4- c']bis[1,2,5]selenadiazole has been developed starting from com-
mercially available 4-nitrobenzo-2,1,3-selenadiazole. Improved syntheses of the related heterocycles
[1,2,5]selenadiazolo[3,4-e]-2,1,3-benzothiadiazole, furazanobenzo-2,1,3-thiadiazole and furazanobenzo-
2,1,3-selenadiazole are also reported.
J. Heterocyclic Chem., 41, 955 (2004).
There is presently a great deal of interest in the synthesis
matched set of tricycles is presented [14].
of porphyrins that show strong absorption bands above
650 nm [1]. These types of derivatives have been mooted
for applications that range from the design of novel materi-
als [2] to photosensitizers for medicinal applications [3].
Fusion of aromatic rings to porphyrin systems often
induces relatively small effects on the porphyrin chro-
mophore [1,4], although porphyrins with fused acenaph-
thylene rings have been shown to have highly modified
UV-vis spectra [5-7]. Porphyrins with fused heterocyclic
rings have been little explored up to this time, although
these have the potential to have many valuable properties.
Recently, we have shown that porphyrins with fused ben-
zothiadiazole, benzoxadiazole and benzoselenadiazole
units 1a-c have very unusual UV-vis spectra, and the
related zinc complexes exhibit strong absorption bands
between 600 and 650 nm [7-9]. These results encouraged
us to consider the synthesis of porphyrins fused to the
related tricyclic systems 2-7. In principle, the c-annelated
pyrroles required for porphyrin synthesis can be prepared
by reaction of the related nitro-derivatives with isocyano-
acetate esters in the presence of a non-nucleophilic base
such as DBU [5-13]. Although five of these heterocycles
are known compounds, the diselena-tricycle 4 has not been
described previously. In this paper, we report the first syn-
thesis of benzo[1,2-c:3,4- c']bis[1,2,5]selenadiazole (4) by
a three step route starting from commercially available
4-nitrobenzo-2,1,3-selenadiazole (8b). In addition,
improved routes to heterocycles 5-7 are described and a
comparison of the spectroscopic properties for this
Although 4,5-furazanobenzofurazan (2) [15,16] and
benzo[1,2-c:3,4-c']bis[1,2,5]thiadiazole (3) [17] are rea-
sonably well studied systems, little or no work has been
carried out on the remaining heterocycles 4-7. Tricycle
3 can be prepared in good yields from 4-nitrobenzo-
2,1,3-thiadiazole (8a) (Scheme 1). Amination under
basic conditions with hydroxylamine gave the
nitroamine 9a in 92% yield, and this is readily reduced
to the corresponding diamine 10a with sodium hydrosul-
fite (Na S O ) in boiling water [17]. This brilliant red
2 2
4
colored diamine can then be cyclized with thionyl chlo-
ride in refluxing pyridine to give 3 in quantitative yield.
The related tricycle [1,2,5]selenadiazolo[3,4-e]-2,1,3-
benzothiadiazole (7) has previously been prepared in
62% yield under optimized conditions by reacting
diamine 10a with selenium dioxide [18]. We find that
quantitative yields of 7 are obtained by cyclizing 10a
with selenium oxychloride in refluxing chloroform-pyri-
dine (Scheme 1), conditions that represent a signifi-
cantly improved procedure for preparing this little stud-
ied heterocycle.

956
C. M. Cillo and T. D. Lash
Vol. 41
Given the success of these syntheses, this approach was
adapted for the preparation of the new heterocyclic system
benzo[1,2-c:3,4- c']bis[1,2,5]selenadiazole (4). Amination
of 4-nitrobenzo-2,1,3-selenadiazole (8b) with hydroxy-
lamine and potassium hydroxide gave the nitroamine 9b in
79% yield (Scheme 1). Unfortunately, unlike the previous
work on 9a, reduction of the nitro group for 9b with
sodium hydrosulfite gave poor results. However, the
required diamine 10b could be obtained in 62% yield by
adapting the conditions reported by Pesin and coworkers
using ferrous sulfate in aqueous ammonia as the reducing
agent [19]. Cyclization of 10b with selenium oxychloride
in refluxing chloroform-pyridine gave 4 in quantitative
yield.
Furazanobenzofurazan (2) was prepared by adapting lit-
erature procedures [15,16]. Commercially available 5-
chlorobenzofuroxan (11) was nitrated with nitric acid and
sulfuric acid to give the bright orange colored compound 5-
chloro-4-nitrobenzofuroxan 12 in 90% yield (Scheme 2).
This was cyclized with sodium azide in a methanol-ace-
tone-water mixture to give furoxanobenzofuroxan 13 in
85% yield. Deoxygenation of the bis-N-oxide was
achieved by treatment with triethyl phosphite. In the origi-
nal work, the excess triethyl phosphite was removed by
distillation and, following chromatography, 2 was isolated
in 51% yield [16]. In our hands, the best results were
obtained when the excess triethyl phosphite was hydrol-
ysed with 2 N hydrochloric acid and the product was puri-
fied by flash chromatography on silica eluting with petro-
leum ether. These conditions gave 2 in 67% yield.

Nov-Dec 2004
Benzo[1,2-c:3,4-c']bis[1,2,5]selenadiazole
957
Figure 1. 400 MHz proton NMR spectra of heterocyclic N-oxides, showing the presence of isomers due to a ring opening-ring closing equilibrium
process.
A. Proton NMR spectrum of 4,5-furoxanofuroxan 13 in perdeuteriated dimethylsulfoxide showing the presence of three isomers 13a, 13b and 13c.
B. Proton NMR spectrum of furoxanobenzothiadiazole 16 in deuteriochloroform showing the presence of two isomers 16a and 16b.
C. Proton NMR spectrum of furoxanobenzoselenadiazole 19 in perdeuteriated dimethylsulfoxide showing the presence of two isomers 19a and 19b.

958
C. M. Cillo and T. D. Lash
Vol. 41
Furazanobenzothiadiazole 5 was previously prepared
the two isomers were present in a ratio of 3:1. The 400
MHz proton NMR spectrum of selenium N-oxide 19 in
perdeuteriated dimethylsulfoxide shows the presence of
two similar isomers 19a and 19b in a ratio of 6:4. The
major isomer produces a singlet at 7.9 ppm, presumably
due to the two protons having identical chemical shift val-
ues, while the other species gives rise to an AB quartet
near 7.6 ppm (Figure 1C). Again, this equilibrium was
solvent dependent and in a mixture of perdeuteriated
dimethylsulfoxide and deuteriochloroform the proton
NMR spectrum showed the two isomers in the ratio of 3:1.
The interconversion must involve a ring opening-ring clos-
ing mechanism most likely involving a dinitroso-interme-
diate 20 (Scheme 4). The presence of these equilibrium
mixtures could also be observed in the carbon-13 NMR
spectra for 13, 16 and 19.
As 2-7 are a matched set of heterocycles with all possi-
ble combinations of oxygen, sulfur and selenium, the spec-
troscopic properties were compared and contrasted. Full
NMR data is provided in the experimental section,
although the proton NMR spectra are limited due to the
presence of only two hydrogen atoms in these structures.
For the symmetrical heterocycles 2, 3 and 4 in perdeuteri-
ated dimethylsulfoxide, the proton NMR spectrum con-
sisted of a singlet at 7.84, 8.17 and 7.81 ppm, respectively.
These data suggest a higher diatropic character in the sul-
fur heterocycles. The asymmetrical heterocycles 5-7 gave
AB quartets in the same chemical shift region.
The UV-vis spectra for the heterocycles in methanol
showed considerable variation. The symmetrical systems,
as expected, gave the simplest spectra and showed a major
band that underwent strong bathochromic shifts going
from O to S to Se. The oxygen system 2 showed fine
structure with a strong band near 230 nm. The sulfur ver-
sion 3 gave this band at 281 nm, while the new selenium
heterocycle gave the main band at 312 nm (Figure 2). A
second band was present for all three systems at 203-205
nm. The mixed SSe heterocycle 7 gave a spectrum that
showed features intermediary between 5 and 6, as might be
expected, and two main bands were observed at 204 and
294 nm. However, 5 gave three bands at 202, 251 and 308
nm, while 6 afforded three bands at 203, 261 and 331 nm,
with additional fine structure evident for the longer wave-
length absorption.
(Scheme 3) from 5-nitrobenzothiadiazole 14 in modest
overall yield [20]. In this study, reaction of 14 with
hydroxylamine afforded the 4-amino-derivative 15 in 92%
yield. Ghosh and Everitt cyclized nitroamine 15 with
sodium hypochlorite to give furoxanobenzothiadiazole 16
in 20% yield [20]. This can then be deoxygenated with tri-
ethyl phosphite to give 5. We obtained superior results by
synthesizing 5 from 5-amino-4-nitrobenzothiadiazole 9a
(Scheme 4). Cyclization of 9a with sodium hypochlorite
gave 16 in 62% yield, and subsequent deoxygenation with
triethyl phosphite afforded tricycle 5 as a light brown pow-
der in 67% yield. This represents a 37% overall yield in
three steps from commercially available 4-nitrobenzothia-
diazole 8a, whereas Ghosh and Everitt only obtained 5 in
an overall 11.4% yield in their 3 step synthesis from
5-nitrobenzothiadiazole 14 [20].
Furazanobenzo-2,1,3-selenadiazole 6 was previously
prepared by Cada et al. from the spirocycle 17 (Scheme 5)
[21]. Reduction of 17 with sodium hydrosulfite gave the
diamine 18, and this was cyclized with selenium dioxide to
give 6 in 22% yield [21]. Apart from the low yield in the
final step, the synthesis of the key precursor 17 requires
multiple steps and this cannot be considered to be a practi-
cal route to this heterocyclic system. We adapted the
chemistry we had used to prepare heterocycle 5 in the syn-
thesis of the selenium analogue 6 (Scheme 4). Treatment
of nitroamine 9b with sodium hypochlorite and potassium
hydroxide in ethanol gave the N-oxide 19 in 66% yield.
This could then be deoxygenated with triethyl phosphite to
give 6 in 86% yield. The overall yield in this case from
commercially available 4-nitrobenzoselenadiazole 8b was
44%, again representing a considerable improvement over
the previous methodology for 6.
N-Oxide derivatives were generated as intermediates in
the synthesis of heterocycles 2, 5 and 6. Previous investi-
gations of furoxanobenzofuroxan 13 by Boulton et al. had
demonstrated that the N-oxides existed in equilibrium
between three isomeric forms 13a, 13b and 13c [15].
Isomer 13c is less favored due to steric interactions and is
present as a minor form. The original study was per-
formed using a 60 MHz NMR spectrometer [15]. Figure
1A displays the 400 MHz proton NMR spectrum for 13,
and this confirms the presence of all three forms. This
type of equilibration is also observed for furoxanobenzo-
thiadiazole 16 and furoxanobenzoselenadiazole 19,
although only two forms are possible for these N-oxides.
The 400 MHz proton NMR spectrum of 16 in deuteri-
ochloroform (Figure 1B) shows the presence of two sets of
doublets for 16a and 16b, where the former represents
approximately 55% of the equilibrium mixture. However,
it is worth noting that these equilibria are solvent and con-
centration dependent. In perdeuteriated dimethylsulfox-
ide, 16 gave a poorer quality proton NMR spectrum where
The EI MS fragmentation patterns were also of interest.
All of these systems were robust to this technique and gave
the molecular ion as the base peak. Furazanobenzofurazan
2 gave a fragment ion at m/z 132 corresponding to loss of
.
NO , while benzo[1,2-c:3,4-c']bis[1,2,5]thiadiazole (3)
gave a peak at m/z 167 corresponding to loss of HCN
(Figure 3). These fragmentations are consistent with pre-
vious observations for benzoxadiazoles and benzothiadia-
zoles [22]. Although the bis-selenium system 4 gave a
very small cluster near m/z 262 corresponding to loss of

Nov-Dec 2004
Benzo[1,2-c:3,4-c']bis[1,2,5]selenadiazole
959
Figure 2. UV spectra of symmetrical heterocycles 2 (A), 3 (B) and 4 (C)
in methanol.
HCN, the main fragment ion was a cluster centered on m/z
+
160 that corresponds to Se . The mixed systems gave
2
similar data to 2 and 3. The OS and OSe systems 5 and 6,
respectively, both gave fragment ions corresponding to
.
loss of NO , while the SSe system 7 showed loss of HCN.
.
Hence, the data demonstrates that loss of NO occurs
Figure 3. 70 eV electron impact mass spectra of 2 (A), 3 (B) and 4 (C).
where this is possible and loss of HCN is only observed
when oxygen is not present. However, loss of HCN does
not seem to be very favored for the SeSe system 4. It is
also worth noting that the selenium containing heterocy-
cles all show characteristic clusters for the molecular ions
and fragment ions due to the presence of five naturally
occurring isotopes for this element.
In conclusion, benzo[1,2-c:3,4- c']bis[1,2,5]selenadia-
zole 4 has been synthesized for the first time and superior
routes to the related heterocycles 5-7 have been developed.
These systems are potentially useful in the synthesis of
novel highly conjugated porphyrin systems. In addition,

960
C. M. Cillo and T. D. Lash
Vol. 41
4,5-Diamino-2,1,3-benzothiadiazole (10a).
interesting N-oxides were prepared as intermediates in the
synthesis of heterocycles 2, 5 and 6.
5-Amino-4-nitro-2,1,3-benzothiadiazole (9a) (4.0 g) was sus-
pended in an 800 mL beaker with 188 mL of hot water. The solution
was vigorously stirred and heated on a hot plate until boiling, and
sodium hydrosulfite (16.88 g) was added over a 30 second period
causing the solution to turn a deep red color and foam. Heating was
continued for an additional 2 minutes, after which the solution was
filtered through a preheated funnel and filtration flask. The filtrate
was cooled to room temperature and the red precipitate collected by
suction filtration and recrystallized from water. Following vacuum
drying, the diamine (2.3 g, 68%) was obtained as a bright red pow-
EXPERIMENTAL
Nuclear magnetic resonance spectra were obtained on a Varian
NMR spectrometer operating at 400 MHz (proton) and 100 MHz
(C-13), respectively, in deuteriochloroform or hexadeuteriodi-
methylsulfoxide solvents. Chemical shifts are reported to the
1
residual chloroform H NMR signal at 7.26 ppm and the C-13
signal at 77.23 ppm, or the analogous dimethylsulfoxide signals
at 2.49 and 39.7 ppm, respectively. UV spectra were recorded on
a Varian Cary 1 Bio UV-visible spectrophotometer. Electron
impact mass spectral determinations were made at the Mass
Spectral Laboratory, School of Chemical Sciences, University of
Illinois at Urbana-Champaign, supported in part by a grant from
the National Institute of General Medical Sciences (GM 27029).
Elemental analyses were obtained from the School of Chemical
Sciences Microanalysis Laboratory at the University of Illinois.
Melting points were taken on a Mel-Temp apparatus and are
uncorrected. 4-Nitro-2,1,3-benzothiadiazole, 4-nitro-2,1,3-ben-
zoselenadiazole, 5-chloro-4-nitrobenzofuroxan, triethyl phos-
phite and selenium oxychloride were purchased from Aldrich or
Acros. Sodium hypochlorite solution, available chlorine content
10-13%, was purchased from Aldrich. Concentrated aqueous
ammonia (29.05% w/v) was obtained from Fisher; 12% w/v
aqueous ammonia was prepared by diluting 41.3 mL of the con-
centrated ammonia solution to a volume of 100 mL with deion-
ized water. Solvents were all of reagent grade and were obtained
from Fisher.
1
der, mp 167-168 °C (lit. mp [17] 168-169 °C); H nmr (dimethylsul-
foxide-d ): δ 4.94 (2H, br s), 5.10 (2H, br s), 7.16 (1H, d, J = 8.8
6
13
Hz), 7.24 (1H, d, J = 9.2 Hz); C nmr (dimethylsulfoxide-d ): δ
6
109.2, 120.9, 127.1, 131.2, 149.1, 150.9.
4,5-Diamino-2,1,3-benzoselenadiazole (10b).
Ferrous sulfate heptahydrate (12.3 g) was added in three por-
tions to a suspension of 5-amino-4-nitro-2,1,3-benzoselenadia-
zole (9b) (1.54 g) in 12% aqueous ammonia (68 mL), while stir-
ring with moderate heating (45-50 °C). The mixture was then
brought to a boil and stirred for 30 minutes, after which the solu-
tion was filtered through a preheated funnel and filtration flask.
The black residue on the filter paper was set aside. The fitrate
was cooled in an ice bath for 45 minutes, and the resulting pre-
cipitate collected by suction filtration and saved as product A.
The set aside black residue was redissolved in the remaining fil-
trate and the mixture vigorously stirred while heating to boiling
temperatures for an additional 15 minutes. The mixture was
again filtered hot through an oven heated filtration funnel, and
the black residue on the filter paper discarded. The filtrate was
allowed to cool to room temperature and refrigerated overnight.
The resulting precipitate was collected by filtration and saved as
product B. The remaining filtrate was extracted with 3 x 200 mL
of ethyl acetate, dried over sodium sulfate and evaporated on a
rotary evaporator to give product C. The product fractions A, B
and C were combined to give the diamine (0.84 g, 62%) as black
5-Amino-4-nitro-2,1,3-benzothiadiazole (9a).
4-Nitro-2,1,3-benzothiadiazole (4.00 g) was dissolved in hot
methanol (175 mL) in a 500 mL three-necked flask equipped
with an addition funnel, a drying tube, a stir bar and a thermome-
ter. Hydroxylamine hydrochloride was added to the hot solution,
after which the flask was immediately cooled to -15 °C in a dry
ice/acetone bath while maintaining vigorous stirring of the mix-
ture. A solution of potassium hydroxide (15.0 g) in methanol
(100 mL) was then added dropwise, maintaining the temperature
at ≤ -10 °C . Once the addition was complete, the dark solution
was allowed to warm to room temperature. The solution was
then stirred into 1.25 L of water, and the resulting green precipi-
tate collected by suction filtration and dried in vacuo to give the
title compound (4.03 g, 92%) as a green powder, mp 278-279 °C
1
crystals, mp 51-52 °C (lit. mp [19] 51 °C); H nmr (dimethylsul-
foxide-d ): δ 4.72 (2H, br s), 5.04 (2H, br s), 6.97 (1H, d, J = 9
6
13
Hz), 7.17 (1H, d, J = 9 Hz); C nmr (dimethylsulfoxide-d ): δ
6
111.6, 120.8, 128.4, 129.9, 140.3, 149.6.
Benzo[1,2-c:3,4-c']bis[2,1,3]thiadiazole (3).
A solution of thionyl chloride (3 mL) in chloroform (1.8 mL)
was added dropwise over a 10 minute period to a stirred suspen-
sion of 4,5-diamino-2,1,3-benzothiadiazole (10a; 0.600 g) in
chloroform (10.2 mL) and pyridine (3 mL). The resulting solu-
tion was stirred under reflux for 15 minutes. The solvents were
removed under reduced pressure to give a brown solid. This was
scraped into ice water and allowed to stir for 1 hour. The result-
ing suspension was collected by suction filtration and dried in
vacuo overnight to afford 3 (0.593 g, 100%) as a reddish-brown
1
(lit. mp [17] 278-279 °C); H nmr (dimethylsulfoxide-d ): δ
6
7.42 (1H, d, J = 9.6 Hz), 7.99 (1H, d, J = 9.2 Hz), 9.02 (2H, br s);
13
C nmr (dimethylsulfoxide-d ): δ 119.3, 127.8, 128.7, 150.2,
6
150.6, 151.4.
5-Amino-4-nitro-2,1,3-benzoselenadiazole (9b).
The nitro-amine 9b was prepared from 4-nitro-2,1,3-benzosele-
nadiazole (5.00 g) and hydroxylamine hydrochloride (7.36 g)
under the foregoing conditions. The reaction solution was poured
into 1.25 L of water and gave an olive green precipitate. This was
collected by suction filtration and dried in vacuo to give 9b (4.20
solid, mp 179-180 °C (lit. mp [17] 179.5-180.5 °C); uv
1
(methanol): λ
(log ε) 203 (4.07), 281 nm (4.55); H nmr
max
10
13
(dimethylsulfoxide-d ): δ 8.17 (1H, s); C nmr (dimethylsul-
6
foxide-d ): δ 124.6, 148.6, 156.8; ms: (electron impact) m/z
6
+
(relative intensity) 196 (10), 195 (11), 194 (100) (M ), 167 (7.5).
g, 79%) as a pale green powder, mp 294-295 °C (lit. mp [23] 295
Benzo[1,2-c:3,4-c']bis[2,1,3]selenadiazole (4).
1
°C); H nmr (dimethylsulfoxide-d ): δ 7.37 (1H, d, J = 9.6 Hz),
6
13
7.80 (1H, d, J = 9.6 Hz), 9.08 (2H, br s); C nmr (dimethylsul-
A solution of selenium oxychloride (4 mL) in chloroform (2.6
mL) was added dropwise over a 15 minute period to a stirred sus-
foxide-d ): δ 121.1, 127.9, 130.7, 151.9, 154.1, 156.3.
6

Nov-Dec 2004
Benzo[1,2-c:3,4-c']bis[1,2,5]selenadiazole
961
pension of 4,5-diamino-2,1,3-benzoselenadiazole (10b; 0.800 g)
in chloroform (13.4 mL) and pyridine (4 mL). The resulting
solution was stirred under reflux for 15 minutes. The solvents
were removed under reduced pressure to give a brown tar. This
was scraped into ice-water and allowed to stir for 1 hour. The
resulting suspension was suction filtered to collect the solid
which was dried in vacuo overnight to afford 4 (1.08 g, 100%) as
ethanol gave furoxanobenzofuroxan (3.06 g, 85%) as an orange
powder, mp 93-94 °C (lit mp [15] 94-95 °C); uv (methanol): λ
max
(log ε) 202 (4.02), 236 (3.84), 284 (4.02), 309 (4.12), 322
10
1
(4.16), 340 nm (3.97); H nmr (dimethylsulfoxide-d ): δ 7.39
6
(2H, s, isomer 13b), 7.57 (1H, d, J = 9.6 Hz, isomer 13a), 7.67
13
(1H, d, J = 10 Hz, isomer 13a), 7.80 (2H, s, isomer 13c); C nmr
(dimethylsulfoxide-d ): δ 104.4, 112.0, 113.6, 116.5, 120.1,
6
a reddish-brown solid, mp 318 °C, dec.; uv (methanol): λ
120.9, 142.2, 144.9, 153.2.
max
1
(log ε) 205 (4.00), 312 (4.13), 393 nm (sh, 3.15); H nmr
10
4,5-Furazanobenzofurazan (2).
13
(dimethylsulfoxide-d ): δ 7.81 (2H, s); C nmr (dimethylsul-
6
A solution of 4,5-furoxanobenzofuroxan (0.50 g) in triethyl
phosphite (10 mL) was refluxed under nitrogen for 1 hour. The
mixture was poured into 2 N hydrochloric acid and stirred as it
boiled in an exothermic reaction for 5 minutes. The resulting
solution was extracted with dichloromethane (3 x 200 mL), dried
over sodium sulfate, and the solvent removed under reduced
pressure. The residue was dissolved in a small volume of
dichloromethane and place on a silica gel flash chromatography
column. This was eluted initially with petroleum ether (60-90°)
and then the polarity was gradually increased to 50/50
dichloromethane-petroleum ether. Evaporation of the solvent on
a rotary evaporator gave a yellow oil, but this solidified on cool-
ing in an ice bath to give 2 (0.28 g, 67%) as bright yellow crys-
foxide-d ): δ 126.9, 155.5, 161.2; ms: (electron impact) m/z
6
(relative intensity) 293.9 (2.7), 292.9 (2.3), 291.9 (29), 290.9
+
(7.6), 289.9 (100) (M ), 288.9 (11), 287.9 (89), 286.9 (28), 285.9
(52), 284.9 (14), 283.9 (20), 282.9 (5.2), 282.9 (4.6), 281.9 (4.6),
+
161.8 (15), 159.8 (50) (Se ), 157.9 (45), 156.9 (13), 155.9 (26),
2
78
154.9 (7), 153.9 (10). HRMS (EI): Calcd for C H N Se
6
2
4
2
(285.8625); Found 285.8631, ∆ = -0.5 mDa, error -1.9 ppm.
Anal. Calcd. for C H N Se : C, 25.02; H, 0.70. Found: C,
6
2
4
2
25.23; H, 0.78.
[1,2,5]Selenadiazolo[3,4-e]-2,1,3-benzothiadiazole (7).
A solution of selenium oxychloride (4 mL) in chloroform (2.6
mL) was added dropwise over a 15 minute period to a stirred sus-
pension of 4,5-diamino-2,1,3-benzothiadiazole (10a; 0.800 g) in
chloroform (13.4 mL) and pyridine (4 mL). The resulting solu-
tion was stirred under reflux for 15 minutes. The solvents were
removed under reduced pressure to give a brown tar. This was
scraped into ice water and allowed to stir for 1 hour. The result-
ing suspension was suction filtered to collect the solid which was
dried in vacuo overnight to afford 4 (0.97 g, 100%) as a reddish-
brown solid, mp 235-236 °C (lit mp [18] 234-235 °C); uv
tals, mp 59-60 °C (lit. mp [16] 60-61 °C); uv (methanol): λ
max
1
(log ε) 203 (4.05), 229 (4.42), 234 (4.42), 259 nm (4.05); H
10
13
nmr (dimethylsulfoxide-d ): δ 7.84 (2H, s); C nmr (dimethyl-
6
sulfoxide-d ): δ 122.5, 141.4, 151.2; ms: (electron impact) m/z
6
+
(relative intensity) 163 (10), 162 (100) (M ), 132 (8.7).
Furoxanobenzothiadiazole (16).
5-Amino-4-nitro-2,1,3-benzothiadiazole (0.50 g) was dis-
solved in a 10% w/v solution of potassium hydroxide in ethanol
(375 mL) with vigorous stirring and moderate heating. The sus-
pension was then cooled to ≤ -10 °C and treated with aqueous
sodium hypochlorite solution (available chlorine 10-13%, 67
mL). The coolant bath was removed and the solution allowed to
warm to room temperature and stir for 1 hour. Reduction of the
volume under reduced pressure to about 100 mL, followed by
dilution with 100 mL of water, gave a precipitate and this was
collected by suction filtration and dried in vacuo overnight. The
title N-oxide (0.31 g, 62%) was obtained as a buff solid, mp 144-
(methanol): λ
(log ε) 204 (4.17), 294 (4.41), 326 nm (sh,
max
10
1
3.19); H nmr (dimethylsulfoxide-d ): δ 7.93-8.02 (2H, AB
quartet, J = 10 Hz); C nmr (dimethylsulfoxide-d ): δ 123.8,
6
13
6
127.5, 151.0, 153.2, 157.0, 161.1; ms: (electron impact) m/z (rel-
+
ative intensity) 245 (2.1), 244 (24), 243 (10), 242 (100) (M ),
241 (6.1), 240 (51), 239 (19), 238 (21), 217 (4.9), 216 (2.3), 215
(21), 213 (11).
5-Chloro-4-nitrobenzofurazan (12).
5-Chlorobenzofuroxan (10.0 g) was dissolved in sulfuric acid
(60 mL) and cooled to 0 °C in an ice-salt bath. Nitric acid (4.03
g) in concentrated sulfuric acid (10 mL) was added over 15 min-
utes, while maintaining the temperature of the mixture at ≤ 5 °C.
The solution was poured with stirring into ice-water, and the
resulting orange precipitate collected by filtration and dried in
vacuo overnight. The nitro compound (11.3 g, 90%) was
obtained as bright orange crystals, mp 79-80 °C (lit. mp [15] 78-
145 °C (lit. mp [20] 144-145 °C); uv (methanol): λ
208 (4.02), 268 (4.18), 326 nm (3.88); H nmr (deuteriochloro-
(log ε)
max
10
1
form): δ 7.43 (1H, d, J = 9.6 Hz, isomer 16a), 7.65-7.69 (2H, 2
overlapping doublets, isomers 16a/b), 7.79 (1H, d, J = 9.6 Hz,
13
isomer 16b); C nmr (dimethylsulfoxide-d ): δ 116.4, 121.2,
6
125.1, 128.3, 153.3, 156.4, 158.0.
Furoxanobenzoselenadiazole (19).
1
81 °C); H nmr (deuteriochloroform): δ 7.27 (1H, d, J = 10 Hz),
13
7.60 (1H, d, J = 9.6 Hz); C nmr (dimethylsulfoxide-d ): δ
5-Amino-4-nitro-2,1,3-benzoselenadiazole (0.60 g) was dis-
solved in a 10% w/v solution of potassium hydroxide in ethanol
(375 mL) with vigorous stirring and moderate heating. The sus-
pension was then cooled to ≤ -10 °C and treated with aqueous
sodium hypochlorite solution (available chlorine 10-13%, 67
mL). The coolant bath was removed and the solution allowed to
warm to room temperature and stir for 1 hour. Reduction of the
volume under reduced pressure to about 100 mL, followed by
dilution with 100 mL of water, gave a precipitate and this was
collected by suction filtration and dried in vacuo overnight.
Recrystallization from chloroform-hexanes gave the N-oxide
(0.39 g, 66%) was obtained as a peach colored powder, mp [20]
6
95.8, 110.3, 116.5, 141.1, 149.1, 166.9.
4,5-Furoxanobenzofuroxan (13).
A solution of sodium azide (1.24 g) in an acetone-methanol-
water mixture (10 mL, 1:2:2) was added to a stirred solution of 5-
chloro-4-nitrobenzofurazan (4.00 g) in an acetone-methanol mix-
ture (8 mL, 1:1). Once spontaneous effervescence had ceased
(approximately 1 hour), the product was precipitated by the drop-
wise addition of water. In some cases an oil formed. However,
upon overnight refrigeration, a deep orange solid formed and this
was collected by suction filtration. Recrystallization from

962
C. M. Cillo and T. D. Lash
Vol. 41
Pandey and G. Zheng in The Porphyrin Handbook, Vol. 6, eds. K. M.
Kadish, K. M. Smith and R. Guilard, Academic Press, San Diego,
2000, pp 157-230.
[4] T. D. Lash, J. Porphyrins Phthalocyanines, 5, 267 (2001).
[5a] T. D. Lash and P. Chandrasekar, J. Am. Chem. Soc., 118,
8767 (1996); [b] J. D. Spence and T. D. Lash, J. Org. Chem. 65,
1530 (2000).
245-246 °C; uv (methanol): λ
339 (3.87), 363 nm (3.74); H nmr (dimethylsulfoxide-d ): δ
7.44 (1H, d, J = 10 Hz, isomer 19b), 7.64 (1H, d, J = 10 Hz, iso-
mer 19b), 7.74 (2H, s, isomer 19a); C nmr (dimethylsulfoxide-
(log ε) 214 (3.81), 287 (4.05),
10
max
1
6
13
d ): δ 115.2, 120.0, 128.2, 131.2, 153.3, 160.1, 161.7.
6
Anal. Calcd. for C H N O Se: C, 29.89; H, 0.84. Found: C,
6
2 4 2
29.98; H, 0.83.
[6] P. Chandrasekar and T. D. Lash, Tetrahedron Lett., 37,
4873 (1996).
Furazanobenzo-2,1,3-thiadiazole (5).
[7] T. D. Lash, P. Chandrasekar, A. T. Osuma, S. T. Chaney
and J. D. Spence, J. Org. Chem., 63, 8455 (1998).
[8] T. D. Lash, C. Wijesinghe, A. T. Osuma and J. R. Patel,
Tetrahedron Lett., 38, 2031 (1997).
[9] C. M. Cillo and T. D. Lash, Book of Abstracts for the
227th National Meeting of the American Chemical Society,
Anaheim, CA, March 28-April 1, 2004, Abstract No. ORGN 206.
[10a] D. H. R. Barton and S. Z. Zard, J. Chem. Soc., Chem.
Commun., 1098 (1985); [b] D. H. R. Barton, J. Kervagoret and S. Z.
Zard, Tetrahedron, 46, 7587 (1990).
[11a] D. A. May, Jr. and T. D. Lash, J. Org. Chem., 57, 4820
(1992); [b] T. D. Lash, J. R. Bellettini, J. A. Bastian and K. B.
Couch, Synthesis, 170 (1994); [c] M. A. Drinan and T. D. Lash, J.
Heterocyclic Chem., 31, 255 (1994); [d] D. H. Burns, C. S. Jabara
and M. W. Burden, Synth. Comm., 25, 379 (1995).
[12a] T. D. Lash, B. H. Novak and Y. Lin, Tetrahedron Lett., 35,
2493 (1994); [b] T. D. Lash and B. H. Novak, Tetrahedron Lett., 36,
4381 (1995); [c] Y. Lin and T. D. Lash, Tetrahedron Lett., 36, 9441
(1995); [d] T. D. Lash and B. H. Novak, Angew. Chem., Int. Ed.
Engl., 34, 683 (1995); [e] B. H. Novak and T. D. Lash, J. Org.
Chem., 63, 3998 (1998); [f] T. D. Lash and V. Gandhi, J. Org.
Chem., 65, 65, 8020 (2000); [g] T. D. Lash, M. L. Thompson, T. M.
Werner and J. D. Spence, Synlett, 213 (2000); [h] T. D. Lash, T. M.
Werner, M. L. Thompson and J. M. Manley, J. Org. Chem., 66, 3152
(2001).
Furoxanobenzothiadiazole (0.80 g) was dissolved in triethyl
phosphite (15 mL) and heated under reflux for 1 hour under nitro-
gen. The resulting reddish solution was poured into 2 N
hydrochloric acid (15 mL) and stirred as it boiled in an exothermic
reaction for 5 minutes. The flask was allowed to cool in the freezer
for 15 minutes. The resulting precipitate was collected by suction
filtration and dried in vacuo to afford the tricycle (0.48 g, 67%) as
a pale brown powder, mp 131 °C (lit. mp [20] 130-131 °C); uv
(methanol): λ
(log ε) 202 (3.67), 251 (3.86), 308 nm (3.67);
max
10
1
H nmr (dimethylsulfoxide-d ): δ 8.08-8.15 (2H, AB quartet, J =
6
13
10 Hz); C nmr (dimethylsulfoxide-d ): δ 118.9, 128.5, 144.2,
6
144.8, 150.9, 157.4; ms: (electron impact) m/z (relative intensity)
+
180 (5.6), 179 (10), 178 (100) (M ), 149 (2.4), 148 (22).
Furazanobenzo-2,1,3-selenadiazole (6).
Furoxanobenzoselenadiazole (0.45 g) was dissolved in triethyl
phosphite (10 mL) and heated under reflux for 1 hour under nitro-
gen. The resulting reddish solution was poured into 2 N
hydrochloric acid (10 mL) and stirred as it boiled in an exother-
mic reaction for 5 minutes. The flask was allowed to cool in the
freezer for 15 minutes. The resulting precipitate was collected by
suction filtration and dried in vacuo to afford the tricycle (0.36 g,
86%) as a brown powder, mp 196-197 °C (lit. mp [21] 196 °C);
[13a] N. Ono, H. Hironaga, K. Ono, S. Kaneko, T. Murashima,
T. Ueda, C. Tsukamura and T. Ogawa, J. Chem. Soc., Perkin Trans. 1,
417 (1996); [b] T. Murashima, K. Fujita, K. Ono, T. Ogawa, H. Uno,
N. Ono, J. Chem. Soc., Perkin Trans. 1, 1403 (1996).
[14] Results taken, in part, from C. M. Cillo, M.S. Thesis,
Illinois State University, 2004.
[15] A. J. Boulton, A. C. Gripper Gray and A. R. Katritzky, J.
Chem. Soc., 5958 (1965).
[16] J. W. Barton, M. C. Goodland, K. J. Gould, J. F. W.
McOmie, W. R. Mound and S. A. Saleh, Tetrahedron, 35, 241 (1979).
[17] A. P. Komin and M. Carmack, J. Heterocyclic Chem., 12,
829 (1975).
[18] A. Gieren, H. Betz, T. Hübner, V. Lamm, R. Neidlein and
D. Droste, Z. Naturforsch., 39b, 485 (1984).
[19] V. G. Pesin, M. N. Papirnik and N. V. Ostashkova-
Kul'kova, Zh. Org. Khim., 25, 1804 (1989).
[20] P. B. Ghosh and B. J. Everitt, J. Med. Chem., 17, 203
(1974).
uv (methanol): λ
(3.93); H nmr (dimethylsulfoxide-d ): δ 7.90 (1H, d, J = 9.6
Hz), 7.98 (1H, d, J = 10 Hz); C nmr (dimethylsulfoxide-d ): δ
117.7, 131.6, 147.0, 148.2, 151.3, 160.9; ms: (electron impact)
m/z (relative intensity) 228 (19), 227 (8.9), 226 (100) (M ), 225
(4.8), 224 (51), 223 (18), 222 (20), 198 (2.8), 196 (13), 194 (7).
(log ε) 203 (4.06), 261 (4.08), 331 nm
max
10
1
6
13
6
+
Acknowledgements.
This material is based upon work supported by the National
Science Foundation under Grant Nos. CHE-9732054 and CHE-
0134472, and the Petroleum Research Fund, administered by the
American Chemical Society. C.M.C. also acknowledges a sum-
mer fellowship from Abbott laboratories.
REFERENCES AND NOTES
[21] A. Cada, W. Kramer, R. Neidlein and H. Suschitzky, Helv.
Chim. Acta, 73, 902 (1990).
[22] A. R. Katritzky, Handbook of Heterocyclic Chemistry;
Pergamon Press: Oxford, UK, 1985, pp 113-116.
[23] C. Brizzi, D. Dal Monte and E. Sandri, Ann. Di Chim., 54,
476 (1964).
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Kadish, K. M. Smith and R. Guilard, Academic Press, San Diego,
2000, pp 125-199.
[2] J. Fabian, H. Nakazumi and M. Matsuoka, Chem. Rev., 92,
1197 (1992).
[3a] R. Bonnett, Chem. Soc. Rev. 24, 19 (1995); [b] R. K.