Synthesis of 2-Substituted 1,3-Benzoselenazoles from Carboxylic Acids Promoted by Tributylphosphine

Article abstract of DOI:10.1002/ejoc.201402808

We report a general, practical, and simple metal-free method for the synthesis of 2-substituted 1,3-benzoselenazoles by the reaction of bis(2-aminophenyl)diselenide with a wide range of carboxylic acids, promoted by tributylphosphine. This efficient reaction furnishes 2-aryl-1,3-benzoselenazoles in good yields and tolerates a variety of substituents at the aryl moiety of carboxylic acids. For the first time, 2-alkyl-1,3-benzoselenazoles could be obtained from aliphatic carboxylic acids and thiazolidine-4-carboxylic acid in high chemical yields. The use of focused microwave irradiation considerably decreased the reaction time from 48 to 2 h. The experimental data provide insights into the mechanism of the reaction. A metal-free synthesis of 2-substituted 1,3-benzoselenazoles by the reaction of bis(2-aminophenyl)diselenide with carboxylic acids, promoted by tributylphosphine is reported. For the first time, 2-alkyl-1,3-benzoselenazoles could be obtained from aliphatic carboxylic acids and thiazolidine-4-carboxylic acid in high chemical yields. Microwave irradiation reduced the reaction time.

Full text of DOI:10.1002/ejoc.201402808

FULL PAPER
DOI: 10.1002/ejoc.201402808
Synthesis of 2-Substituted 1,3-Benzoselenazoles from Carboxylic Acids
Promoted by Tributylphosphine
Cátia Schwartz Radatz,[a] Daniel S. Rampon,[a] Renata A. Balaguez,[b] Diego Alves,*[b] and
Paulo Henrique Schneider*[a]
Keywords: Synthetic methods / Selenium heterocycles / Selenium / Carboxylic acids
We report a general, practical, and simple metal-free method
for the synthesis of 2-substituted 1,3-benzoselenazoles by the
reaction of bis(2-aminophenyl)diselenide with a wide range
of carboxylic acids, promoted by tributylphosphine. This ef-
ficient reaction furnishes 2-aryl-1,3-benzoselenazoles in
good yields and tolerates a variety of substituents at the aryl
moiety of carboxylic acids. For the first time, 2-alkyl-1,3-
benzoselenazoles could be obtained from aliphatic carb-
oxylic acids and thiazolidine-4-carboxylic acid in high chem-
ical yields. The use of focused microwave irradiation con-
siderably decreased the reaction time from 48 to 2 h. The ex-
perimental data provide insights into the mechanism of the
reaction.
2-halophenyl isocyanides with selenium and heteroatom nu-
cleophiles was disclosed by Kambe and co-workers for the
synthesis of 1,3-benzoselenazoles having heteroatom sub-
stituent (NRRЈ, OR and SR) groups at the 2-position,[9c]
Sashida and co-workers also focused on the construction of
the 1,3-benzoselenazole core;[9d] their approach involved the
preparation of benzoselanazoles by a copper-catalyzed one-
pot reaction of 2-iodoanilines and isoselenocyanates. More-
over, Kobayashi and co-workers[9e] conducted a study in
which 2-thio-organyl-1,3-benzoselenazole derivatives were
prepared in moderate yields from 2-halophenyl isothio-
cyanates in a reaction using nBuLi, elemental selenium, and
subsequent treatment with several electrophiles. Our group
recently reported the direct synthesis of 2-aryl-1,3-benzose-
lenazoles from the reaction of bis(2-aminophenyl) diselen-
ides with different aryl aldehydes, promoted by the reducing
agent sodium metabisulfite (Na2S2O5).[9f] This efficient
method furnishes the corresponding 2-aryl-substituted 1,3-
benzoselenazoles in high yields and tolerates a range of sub-
stituents at the aryl ring of the aldehydes. However, the
method could not be used to furnish products from alkyl
aldehydes. These reactions were conducted under conven-
tional heating as well as under microwave irradiation, be-
cause the use of focused microwave irradiation was found
to drastically decrease the reaction time.[9f]
Introduction
Research into the use of selenium-containing heterocyclic
compounds as potential pharmaceuticals,[1] new materi-
als,[2] and as reagents and catalysts[3] has expanded rapidly
in recent years. Recently, selenium-containing compounds
have attracted increased attention because of their ability
to act as glutathione peroxidase (GPX) mimics, catalytic
antioxidants, and cancer-chemopreventive compounds.[4]
Furthermore, substituted benzoheteroazole units, par-
ticularly benzoxazoles,[5] benzothiazoles,[6] and benzimid-
azoles,[7] are privileged heterocyclic systems because of their
excellent reactivities, notable chemical properties, and bio-
logical activities. Especially, the preparation of 2-substituted
1,3-benzothiazoles has attracted much attention because
this is an important class of bicyclic substructure with po-
tent utility as imaging agents for β-amyloid, antitumor
agents, calcium channel antagonists, antituberculotics, anti-
parasitics, chemiluminescent agents, and also as photosensi-
tizers.[8]
However, in the case of selenium analogues, there are few
reports on the synthesis of 2-substituted benzoselenazoles
and related compounds despite their potential impor-
tance.[9,10] In this respect, a copper(I)-catalyzed reaction of
[a] Instituto de Química, Universidade Federal do Rio Grande do
Sul, UFRGS,
In this context, microwave irradiation (MW) is an at-
tractive alternative to conventional heating to supply energy
to reactions. In most cases, microwave heating leads to a
drastic reduction in reaction times, improves workup pro-
cedures, and ultimately increases product yields.[11]
To our knowledge, there are no reports on the synthesis
of 2-substituted 1,3-benzoselenazoles from carboxylic acids.
Furthermore, until now, 2-alkyl-1,3-benzoselenazoles could
P. O. Box 15003, 9150-970 Porto Alegre - RS, Brazil
E-mail: paulos@iq.ufrgs.br
www.ufrgs.br
[b] LASOL – Universidade Federal de Pelotas – UFPel,
96010-900 Pelotas - RS, Brazil
E-mail: diego.alves@ufpel.edu.br
http://wp.ufpel.edu.br/lasol/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402808.
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. Alves, P. H. Schneider et al.
FULL PAPER
not be achieved by the available synthetic tools. In this con- the product 3a was obtained either in lower yields or were
text, our interest on the synthesis of organoselenium com- not detected, respectively (Table 1, entry 2 and 4). For the
pounds[9f,12] prompted us to explore a general procedure reactions using non-polar solvents, the best yield was ob-
with which to obtain 2-substituted 1,3-benzoselenazoles tained when toluene was employed (Table 1, entry 6).
from bis(2-aminophenyl) diselenide and carboxylic acids by
Having established THF and toluene to be the best sol-
using tributylphosphine under conventional heating or mi- vents in these first experiments, we next investigated some
crowave irradiation.
parameters regarding the stoichiometry of diaryl diselenide
1a and tributylphosphine. We observed that increasing the
amount of tributylphosphine from 1.0 to 1.5 equiv. gave a
small increase in yields in both solvents (Table 1, entries 7
and 8). When the reaction was performed using toluene as
the solvent and an excess of 3.0 equiv. of tributylphosphine,
product 3a was obtained in 75% yield (Table 1, entry 9).
By increasing the amount of diselenide 1a to 2.0 equiv. and
including 3.0 equiv. tributylphosphine, an excellent yield of
3a was observed in toluene as the solvent (Table 1, en-
try 10). Finally, we attempted to reduce the reaction time
to 24 h, but the yield decreased to 70% (Table 1, entry 12).
We observed the same tendency in THF, but with a slight
reduction in reaction yield (Table 1, entry 11).
Results and Discussion
To explore suitable reaction conditions for the synthesis
of 2-substituted 1,3-benzoselenazoles from carboxylic acids,
a set of experiments were performed by employing bis(2-
aminophenyl)diselenide (1a),[13] 4-bromobenzoic acid (2a),
and tributylphosphine as a model system. The reaction was
performed under conventional heating (Table 1).
In recent years, it has been shown that the use of focused
microwave irradiation (MW) in organic reactions can con-
siderably decrease the reaction time, often accompanied by
an increase in product yield.[11,14] Therefore, to reduce the
reaction time and the amount of substrate required for the
synthesis of benzoselenazole 3a, we performed experiments
using focused microwave irradiation (Table 2).
Table 1. Optimization of the reaction conditions.[a]
Entry Solvent
1a
Bu3P
[equiv.] [equiv.]
Temp.
[°C]
Time
[h]
Yield
[%][b]
Table 2. Optimization of the reaction conditions under microwave
irradiation.[a]
1
2
3
4
5
6
7
8
CH2Cl2
MeCN
THF
DMSO
o-xylene
toluene
THF
toluene
toluene
toluene
THF
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
1.5
3.0
3.0
3.0
3.0
r.t.
82
66
120
48
48
48
48
48
48
48
48
48
48
24
10
32
50
n.d.
54
63
60
68
75
97
83
70
120
140
110
66
110
110
110
66
9
Yield [%][b]
10
11
12
Entry
1a [equiv.]
Bu3P [equiv.]
Time [h]
1
2
3
4
5
6
1.0
1.0
1.0
1.0
0.5
1.0
1.0
1.0
1.0
3.0
3.0
3.0
3.0
3.0
2.0
3.0
3.0
3.0
0.5
1.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
43
54
89
92
67
70
15
n.d.
61
toluene
110
[a] Reactions were conducted with 2a (0.5 mmol, 1 equiv.) under an
N2 atmosphere. [b] Yield of isolated product.
7[c]
8[d]
9[e]
In the first experiment, 1a (0.5 mmol, 1 equiv.), 2a
(0.5 mmol, 1 equiv.), and tributylphosphine (0.5 mmol,
1 equiv.) were reacted in dichloromethane (5 mL) at room
temperature. Unfortunately, under these conditions, even
after 120 h, the desired benzoselenazole 3a was obtained in
only 10% yield (Table 1, entry 1). Thus, in an attempt to
increase the yield, a series of different solvents including
aprotic polar solvents [CH3CN, tetrahydrofuran (THF) and
dimethyl sulfoxide (DMSO)] and non-polar solvents (tolu-
ene and o-xylene) were evaluated (Table 1, entries 2–6).
[a] Reactions were conducted with 2a (0.25 mmol, 1 equiv.) under
an N2 atmosphere. [b] Yield of isolated product. [c] Reaction was
performed in an air atmosphere. [d] Reaction was performed using
DMSO as the solvent at 100 °C. [e] Reaction was performed using
THF as the solvent at 50 °C.
Thus, experiments were performed with 1a (0.25 mmol,
Among them, polar aprotic solvents of intermediate po- 1.0 equiv.), 2a (0.25 mmol, 1.0 equiv.), and tributylphos-
larity gave good results of benzoselenazole 3a; for example phine (0.75 mmol, 3.0 equiv.) in toluene as the solvent. In
the use of THF as solvent gave a yield of 50% (Table 1, these processes, 1a was dissolved in toluene (2 mL), and tri-
entry 3). When the reaction was performed in polar aprotic butylphosphine was then added and the mixture and stirred
solvents of higher polarity, such as acetonitrile and DMSO, at room temperature under an N2 atmosphere for 5 min.
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Synthesis of 2-Substituted 1,3-Benzoselenazoles
After this time, a slight decoloration of the solution was Table 3. Scope of the synthesis of 2-substituted 1,3-benzoselena-
zoles from carboxylic acids using MW irradiation.
observed. At this point, 2a was added and the reaction was
carried out under focused microwave irradiation at 100 °C.
First, the reaction was carried out for 0.5 h under MW
irradiation and the desired product 3a was obtained in 43%
yield (Table 2, entry 1). To our satisfaction, when the reac-
tions were performed for 1.0, 1.5 and 2 h, the yields of
product 3a progressively increased (entries 2–4) with an ex-
cellent yield of 92% 3a being obtained under MW irradia-
tion after 2 h (entry 4). This outstanding result gives only
5% difference in yield when compared with reactions under
conventional heating (Table 2, entry 4; vs. Table 1, en-
try 10), while employing a smaller amount of diselenide 1a
(1.0 equiv.) in just 2 h. When the reaction was performed
by using 0.5 equiv. 3a, the yield of product 3a decreased
to 67% (Table 2, entry 5). When the reaction was run with
2.0 equiv. tributylphosphine, the yield of 3a dropped to
70% (Table 2, entry 6).
In an additional experiment, all reagents were solubilized
in toluene under an air atmosphere. The reaction vial was
then tightly sealed and the mixture was irradiated in a mi-
crowave reactor for 2 h at 100 °C. By using this procedure,
the desired 1,3-benzoselenazole 3a was obtained in 15%
yield, confirming that an N2 atmosphere is essential for the
reaction.
To check the effect of solvent polarity in the reaction
under microwave irradiation, the system was carried out
with a polar aprotic solvent (DMSO); under these condi-
tions, 3a was not observed with conventional heating. In
this sense, DMSO was again not suitable for the reaction.
(Table 2, entry 8). Another study using THF was performed
(Table 2, entry 9), but due to the lower boiling point,[15] the
reaction was conducted at 50 °C. Even after 2 h reaction,
the desired product was obtained in only 61% yield
(Table 2, entry 8). These data suggest that the reaction re-
quires solvents of intermediate or low polarity, and also
that selenophosphonium salts formed in the reaction envi-
ronment might result in DMSO deoxygenation.[16]
To explore the scope and limitations of this method, the
reactions between 1a and a variety of carboxylic acids 2a–
m were performed, employing the optimal conditions under
microwave irradiation; the results are shown in Table 3.
Generally, all reactions proceeded smoothly, furnishing the
desired products in good yields.
Several aryl carboxylic acids reacted with 1a, furnishing
the corresponding 2-substituted 1,3-benzoselenazoles 3a–i
in moderate to excellent yields (Table 3, entries 1–9). As
shown in Table 3, electronic effects on the aryl moiety of
the carboxylic acid seemed to have an influence on the
product yield. For example, carboxylic acids with electron-
withdrawing groups at the aromatic ring gave better results
than those with electron-donating groups (entries 1–3 vs. 7–
9), suggesting that the addition of a nucleophile to the carb-
oxyl group has an important influence on the reaction path.
When benzoic acid was used, the desired product 2-phenyl-
1,3-benzoselenazole (3f) was reached in 75% yield (entry 6).
By the use of disubstituted carboxylic acids 2c and 2i, the
products 3c and 3i were obtained in good yields (entries 3
[a] Yield of pure isolated product.
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D. Alves, P. H. Schneider et al.
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and 9). Additionally, when the reactions were performed by nucleophile Bu3P attacks the selenium atom in 1a to pro-
using para and ortho hydroxybenzoic acid, good yields were duce phosphonium salt A. The carboxylic acid could then
obtained in both cases, demonstrating that the sterically de- form the pentacoordinate acyloxyphosphonium intermedi-
manding ortho substituent did not affect the reaction yield ate B as an activated ester, which, in turn, could generate
(entries 4 and 5). Indeed, substrates with an ortho hydroxy the 2-substituted 1,3-benzoselenazoles
3 through two
group gave a higher yield of the product (3e) because the routes: (R1) direct intramolecular nucleophilic attack of the
carboxyl group was more reactive due to the inductive ef- amine fragment on the carbonyl, producing amide C and
fect of oxygen and because of the slightly broken planarity Bu3P=O, followed by intramolecular condensation with a
with the aromatic ring, despite the electron-donating behav- selenolate anion, or (R2) intramolecular transfer of a selen-
ior.
ium atom to produce selenoester D and Bu3P=O, with sub-
sequent intramolecular attack of the nitrogen atom through
condensation to produce the product 3.
So far, the synthesis of 2-alkyl-substituted 1,3-benzo-
selenazoles has not been described.[9] Thus, to expand the
synthetic scope of this protocol, we carried out reactions
using aliphatic carboxylic acids 2j–m. Interestingly, despite
the electron-donating nature of the alkyl group, 2-alkyl-1,3-
benzoselenazoles were obtained in moderate to excellent
yields (Table 3, entries 10–13). These are important results
because the development of a broad, mild, and selective
chemical process for the construction of 2-substituted 1,3-
benzoselenazoles avoiding radical paths or metal-catalyzed
reactions has not been described before.[9,10]
When the reactions were carried out with butyric and
caprylic acid, the corresponding 1,3-benzoselenazoles 3j
and 3k were obtained in 90 and 95% yield, respectively
(Table 3, entries 10 and 11). The reaction was also per-
formed with the sterically hindered pivalic acid 2l and, to
our satisfaction, the product was obtained in good yield,
demonstrating that sterically demanding substituents have
only a small effect on the reaction yield (entry 12). Further-
more, 1,3-benzoselenazole (3m) was obtained in 63% yield
when the reaction was performed with formic acid 2m (en-
try 13).
Recently, our research group has described the biological
activities of (R)-Se-aryl-thiazolidine-4-carboselenoates.[17]
Motivated by these results, and to extend the scope of this
synthetic protocol, we reacted 1a with (S)-3-(tert-butoxy-
carbonyl)thiazolidine-4-carboxylic acid (2n) under the opti-
mized MW conditions. To our delight, the desired 1,3-
benzoselenazole 3n was reached in 76% yield (Table 3, en-
try 14).
Scheme 1. Analysis of the reaction mechanisms.
To shed light on this mechanism, an intermolecular com-
petition experiment was performed to determine which path
is operative. Under the standard conditions using MW irra-
Based on results of disulfide and diselenide bond cleav- diation, diphenyl diselenide 4a (1.0 equiv.) was added to the
age by phosphorus nucleophiles,[16b,18] we can propose two reaction flask along with tributylphosphine (3.0 equiv.) and
reaction pathways (Scheme 1, route R1 and R2). First, the toluene (Scheme 2). The mixture was stirred at room tem-
Scheme 2. Competition experiment.
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Synthesis of 2-Substituted 1,3-Benzoselenazoles
ated in a microwave reactor (CEM Explorer) for 2 h at 100 °C (tem-
perature was measured with an IR sensor on the outer surface of
the reaction vial), using an irradiation power of 100 W (the ramp
temperature rate was 3 min). When the reaction was complete, the
reaction mixture was diluted with a saturated solution of Na2CO3
(20 mL) and washed with dichloromethane (3ϫ 20 mL). The or-
ganic phase was separated, dried with MgSO4, and concentrated
under vacuum. The residue was purified by flash chromatography
on silica gel (hexane/ethyl acetate, 95:5) to give the product.
perature under an N2 atmosphere for 5 min, then 2a
(1.0 equiv.) and aniline 4b (1.0 equiv.) were added, and the
reaction was carried out under focused microwave irradia-
tion at 100 °C. By following the reaction by using GC–MS
analysis, we could not detect selenoester 5a production at
any reaction time point (0.5, 1.0, and 2.0 h), and only amide
5b was observed. However, under similar conditions for the
production of peptides, the first selenoester formation was
confirmed in low temperature experiments.[18c] In view of
this competition data, and since selenoester production was
observed from a intermolecular/intramolecular reaction
contest,[18c] we suppose that, in our case, when the reaction
occurs by two intramolecular nucleophiles, the attack of the
amine group occurs first, with the production of an amide
and then intramolecular condensation with a selenolate
anion (route R1).
2-(4-Bromophenyl)benzo[d][1,3]selenazole (3a): Yield 0.078 g (92%);
white solid; m.p. 124–126 °C. 1H NMR (300 MHz, CDCl3): δ =
8.01 (d, J = 8.1 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 7.78 (d, J =
8.2 Hz, 2 H), 7.52 (d, J = 8.3 Hz, 2 H), 7.41 (t, J = 7.2 Hz, 1 H),
7.24 (t, J = 7.3 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
171.6, 156.3, 139.0, 135.7, 132.9, 130.0, 127.2, 126.2, 126.1, 125.6,
125.5 ppm. IR (KBr): ν = 1510, 1475, 1432, 1392, 1303, 1216, 1064,
˜
937, 825, 752 cm–1. MS: m/z = 337 [M+]. C13H8BrNSe (336.90):
calcd. C 46.32, H 2.39, N 4.16; found C 46.68, H 2.30, N 5.65.
2-(4-Chlorophenyl)benzo[d][1,3]selenazole (3b): Yield 0.068 g (92%);
white solid; m.p. 98–100 °C. 1H NMR (300 MHz, CDCl3): δ = 8.09
(d, J = 8.1 Hz, 1 H), 7.96–7.91 (m, 3 H), 7.51–7.42 (m, 3 H), 7.31
(t, J = 7.5 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 170.9,
155.7, 138.4, 137.1, 134.7, 129.3, 129.1, 126.6, 125.5, 124.9,
Conclusion
We have described an efficient methodology for the syn-
thesis of 2-substituted 1,3-benzoselenazoles in high chemi-
cal yields. The reactions of bis(2-aminophenyl)diselenide
with a range of carboxylic acids were promoted by tributyl-
phosphine in toluene at 100 °C. Under these reaction condi-
tions, we were able to prepare 2-aryl- and 2-alkyl-1,3-benzo-
selenazoles from aryl and aliphatic carboxylic acids. An-
other benefit of the described procedure is that this protocol
minimizes energy demands, and the reaction time could be
reduced from 48 to only 2 h by using focused MW irradia-
tion.
124.8 ppm. IR (KBr): ν = 1512, 1479, 1398, 1091, 829, 752 cm–1.
˜
MS: m/z = 293 [M+]. HRMS: m/z calcd. for C13H8ClNSe [M +
H]+ 293.9589; found 293.9592.
2-(3,4-Difluorophenyl)benzo[d][1,3]selenazole (3c): Yield 0.069 g
1
(93%); yellow solid; m.p. 94–97 °C. H NMR (300 MHz, CDCl3):
δ = 8.14 (d, J = 8.0 Hz, 1 H), 7.91–7.98 (m, 2 H), 7.73–7.78 (m, 1
H), 7.54 (t, J = 7.8 Hz, 1 H), 7.30–7.40 (m, 2 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 171.7, 156.1, 154.5 (d, JC,F = 12.9 Hz),
153.0 (d, JC,F = 13.2 Hz), 151.1 (d, JC,F = 12.9 Hz), 149.7 (d, JC,F
= 12.9 Hz), 145.2, 139.1, 130.4 (d, JC,F = 77.4 Hz), 126.9 (d, JC,F
= 76.6 Hz), 125.6 (d, JC,F = 10.9 Hz), 118.6 (d, JC,F = 18.0 Hz),
117.3 (d, JC,F = 19.0 Hz) ppm. IR (KBr): ν = 1606, 1500, 1427,
˜
1309, 1268, 1106, 977, 757, 634 cm–1. MS: m/z = 295 [M+].
C13H7F2NSe (294.97): calcd. C 53.08, H 2.40, N 4.76; found C
55.07, H 2.48, N 4.13.
Experimental Section
4-(Benzo[d][1,3]selenazol-2-yl)phenol (3d): Yield 0.048 g (70%);
General Information: Tributylphosphine was purchased from Ald-
rich and used without further purifications. Toluene was obtained
from Sigma–Aldrich and dried by using standard methods.[19] The
reactions were monitored by thin-layer chromatography (TLC) and
column chromatography was performed using Merck Silica Gel
(230–400 mesh). NMR spectra were obtained with Varian Inova
300 and Bruker 400 spectrometers. Chemical shifts are given in
parts per million (δ) and are referenced from tetramethylsilane
1
dark-orange solid; m.p. 212–213 °C. H NMR [400 MHz, (CD3)2-
CO]: δ = 9.04 (s, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.86 (d, J =
8.0 Hz, 1 H), 7.81 (d, J = 8.6 Hz, 2 H), 7.35 (t, J = 7.3 Hz, 1 H),
7.17 (t, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR
[100 MHz, (CD3)2CO]: δ = 172.4, 161.1, 156.7, 138.4, 130.2, 128.6,
126.9, 125.7, 125.5, 124.7, 116.6 ppm. IR (KBr): ν = 3434, 1604,
˜
1484, 1432, 1292, 1218, 1172, 833, 756 cm–1. MS: m/z = 275 [M+].
C13H9NOSe (274.98): calcd. C 56.95, H 3.31, N 5.11; found C
56.60, H 2.80, N 5.05.
1
(TMS) in H NMR spectra and from CDCl3 or (CD3)2CO in 13C
NMR spectra. ATR/FTIR spectra were recorded with a Varian
FTIR-640 spectrometer. Low-resolution mass spectra were ob-
tained with a Shimadzu GC–MS-QP5050 mass spectrometer inter-
faced with a Shimadzu GC-17A gas chromatograph equipped with
2-(Benzo[d][1,3]selenazol-2-yl)phenol (3e): Yield 0.061 g (89%);
white solid; m.p. 128–130 °C. 1H NMR (300 MHz, CDCl3): δ =
12.57 (s, 1 H); 8.01 (d, J = 8.1 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H),
a DB-17 MS capillary column. Microwave heating was conducted 7.55 (d, J = 7.8 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.31–7.41 (m,
with a CEM Discover, mode operating systems working at
2.45 GHz, with a power programmable from 1 to 300 W.
2 H), 7.09 (t, J = 8.3 Hz, 1 H), 6.95 (t, J = 7.7 Hz, 1 H) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 174.7, 157.9, 154.2, 136.4, 133.5,
130.8, 127.4, 126.6, 125.3, 124.4, 120.4, 119.9, 118.4 ppm. IR
General Procedure for the Synthesis of 2-Substituted 1,3-Benzoselen-
azoles under Microwave Irradiation: In a 10 mL glass vial equipped
with a small magnetic stirring bar under an inert atmosphere, bis(2-
aminophenyl)diselenide 1a (0.25 mmol) was dissolved in anhydrous
toluene (1.5 mL) and n-tributylphosphine (0.75 mmol) was added.
The mixture was stirred at room temperature for ca. 5 min, then
carboxylic acid (0.25 mmol) was added and the mixture was irradi-
(KBr): ν = 3448, 1616, 1581, 1483, 1384, 1263, 1201, 798 cm–1. MS:
˜
m/z = 275 [M+]. C13H9NOSe (274.98): calcd. C 56.95, H 3.31, N
5.11; found C 54.40, H 3.26, N 5.36.
2-Phenylbenzo[d][1,3]selenazole (3f): Yield 0.049 g (75%); yellow so-
1
lid; m.p. 114–116 °C. H NMR (300 MHz, CDCl3): δ = 8.03 (d, J
= 8.1 Hz, 1 H), 7.91–7.94 (m, 2 H), 7.84 (d, J = 7.9 Hz, 1 H), 7.40–
Eur. J. Org. Chem. 2014, 6945–6952
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6949

D. Alves, P. H. Schneider et al.
FULL PAPER
7.42 (m, 4 H), 7.22 (t, J = 7.5 Hz, 1 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 173.2, 165.4, 156.4, 138.9, 136.8, 131.7, 129.7, 128.6,
H), 7.99 (d, J = 7.9 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 1 H), 7.36 (t, J
= 7.5 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 158.1,
127.0, 125.9, 125.5 ppm. IR (KBr): ν = 1587, 1552, 1510, 1479,
154.7, 137.1, 126.2, 125.6, 125.2, 125.1 ppm. IR (KBr): ν = 1693,
˜
˜
1430, 1299, 1216, 939, 763 cm–1. MS: m/z = 259 [M+]. C13H9NSe
(258.99): calcd. C 60.48, H 3.51, N 5.43; found C 60.09, H 3.07, N
5.35.
1583, 1475, 1427, 852, 752 cm–1. MS: m/z = 283 [M+]. HRMS: m/z
calcd. for C7H5NSe [M+·] 182.9587; found 183.0926.
(R)-tert-Butyl-4-(benzo[d][1,3]selenazol-2-yl)thiazolidine-3-carboxyl-
ate (3n): Yield 0.070 g (76%); yellow solid; m.p. 134–135 °C. [α]2D5
2-p-Tolylbenzo[d][1,3]selenazole (3g): Yield 0.047 g (69%); yellow
1
1
solid; m.p. 78–80 °C. H NMR (300 MHz, CDCl3): δ = 8.13 (d, J
= –15.9 (c = 0.0034 m, CH2Cl2). H NMR (300 MHz, CDCl3): δ =
= 8.1 Hz, 1 H), 7.93–7.97 (m, 3 H), 7.51 (t, J = 7.3 Hz, 1 H), 7.29– 8.00 (d, J = 8.1 Hz, 1 H), 7.89 (d, J = 7.9 Hz, 1 H), 7.46 (t, J =
7.35 (m, 3 H), 2.44 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ
= 173.2, 156.5, 142.2, 138.8, 134.2, 130.4, 126.9, 125.7, 125.4, 125.3,
7.8 Hz, 1 H), 7.30 (t, J = 7.7 Hz, 1 H), 5.53 (s, 1 H), 4.73 (d, J =
8.7 Hz, 1 H), 4.56 (s, 1 H), 3.56–3.46 (m, 2 H), 1.38 (s, 9 H) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 164.9, 154.4, 153.4, 138.0,
126.2, 125.3, 124.9, 124.5, 81.6, 64.2, 49.4, 37.7, 28.2 ppm. IR
(KBr): ν˜ = 1701, 1531, 1436, 1373, 1361, 856, 769 cm–1. MS: m/z
= 341. HRMS: m/z calcd. for (-BOC) C10H9N2SSe [M+·] 269.2288;
found (-BOC) 269.2274.
128.6, 22.2 ppm. IR (KBr): ν = 1604, 1490, 1432, 1305, 1220, 937,
˜
815, 754 cm–1. MS: m/z = 273 [M+]. C14H11NSe (273.01): calcd. C
61.77, H 4.07, N 5.15; found C 61.64, H 4.00, N 5.06.
2-(4-Methoxyphenyl)benzo[d][1,3]selenazole (3h): Yield 0.051 g
(71%); orange solid; m.p. 122–124 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.97 (d, J = 8.1 Hz, 1 H), 7.81–7.89 (m, 3 H), 7.38 (t,
J = 7.3 Hz, 1 H), 7.19 (t, J = 7.5 Hz, 1 H), 6.90 (d, J = 8.5 Hz, 2
H), 3.80 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 172.7,
162.6, 156.6, 138.7, 130.2, 129.7, 126.9, 125.4, 125.0, 115.0,
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and copies of the
1H and 13C NMR, IR and MS spectra of all compounds.
56.2 ppm. IR (KBr): ν = 1600, 1496, 1434, 1259, 1168, 1024, 831,
˜
Acknowledgments
765 cm–1. MS: m/z = 289 [M+]. C14H11NOSe (289.00): calcd. C
58.34, H 3.85, N 4.86; found C 58.12, H 3.48, N 4.67.
The authors are grateful to the Coordenação de Aperfeiçoamento
de Pessoal de Nível Superior (CAPES), the Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq), the Instituto
Nacional de Ciências e Tecnologia de Catálise em Sistemas Molec-
ulares e Nanoestruturados (INCT-CMN) and Fundação de Am-
paro à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
(PRONEM 11/2024-9) for financial support. C. S. R. thanks CNPq
for her Ph. D. fellowship.
2-(3,5-Dimethoxyphenyl)benzo[d][1,3]selenazole (3i): Yield 0.065 g
(81%); yellow solid; m.p. 100–101 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.10 (d, J = 8.2 Hz, 1 H), 7.92 (d, J = 8.4 Hz, 1 H),
7.48 (t, J = 7.8 Hz, 1 H), 7.31 (t, J = 7.8 Hz, 1 H), 7.17 (d, J =
2.3 Hz, 2 H), 6.59 (t, J = 2.3 Hz, 1 H), 3.88 (s, 6 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 172.3, 160.9, 155.5, 138.2, 137.8, 126.3,
125.3, 124.8, 124.7, 105.8, 103.2, 55.5 ppm. IR (KBr): ν = 1608,
˜
1593, 1473, 1435, 1321, 1271, 856, 763 cm–1. MS: m/z = 319 [M+].
HRMS: m/z calcd. for C15H13NO2Se [M + H]+ 320.0190; found
320.0198.
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2-Propylbenzo[d][1,3]selenazole (3j): Yield 0.051 g (90%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.89 (d, J = 8.1 Hz, 1 H), 7.75
(d, J = 8.4 Hz, 1 H), 7.31 (t, J = 7.8 Hz, 1 H), 7.19 (t, J = 7.8 Hz,
1 H), 2.97 (t, J = 7.5 Hz, 2 H), 1.38–1.26 (m, 2 H), 0.95 (t, J =
7.4 Hz, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 177.1, 154.6,
138.4, 125.9, 124.8, 124.7, 123.9, 39.6, 23.6, 13.7 ppm. IR (KBr): ν
˜
= 2958, 2929, 2870, 1701, 1591, 1577, 1450, 758, 721 cm–1. MS:
m/z = 225 [M+]. HRMS: m/z calcd. for C10H11NSe [M+·] 226.0135;
found 226.1659.
2-Heptylbenzo[d][1,3]selenazole (3k): Yield 0.067 g (95%); yellow
oil. 1H NMR (300 MHz, CDCl3): δ = 7.99 (d, J = 8.1 Hz, 1 H),
7.85 (d, J = 7.9 Hz, 1 H), 7.41 (t, J = 8.1 Hz, 1 H), 7.24 (t, J =
8.1 Hz, 1 H), 3.09 (t, J = 7.8 Hz, 2 H), 1.89–1.79 (m, 2 H), 1.69–
1.52 (m, 2 H), 1.39–1.22 (m, 4 H), 0.96–0.86 (m, 5 H) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 177.9, 155.1, 138.9, 126.4, 125.3,
125.2, 124.5, 38.2, 32.1, 30.7, 29.6, 29.5, 23.1, 14.6 ppm. IR (KBr):
ν = 2954, 2926, 2854, 1593, 1537, 1450, 1436, 758, 721 cm–1. MS:
˜
m/z = 281 [M+]. HRMS: m/z calcd. for C14H19NSe [M + H]+
282.0761; found 282.0768.
2-tert-Butylbenzo[d][1,3]selenazole (3l): Yield 0.046 g (78%); yellow
oil. 1H NMR (300 MHz, CDCl3): δ = 8.01 (d, J = 8.2 Hz, 1 H),
7.89 (d, J = 7.9 Hz, 1 H), 7.43 (t, J = 8.1 Hz, 1 H), 7.26 (t, J =
7.9 Hz, 1 H), 1.51 (s, 9 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
187.4, 153.3, 138.0, 126.0, 125.8, 124.1, 30.9, 28.2 ppm. IR (KBr): ν
˜
= 2960, 2927, 2900, 1527, 1436, 1363, 758, 721 cm–1. MS: m/z =
239 [M+]. HRMS: m/z calcd. for C11H13NSe [M + NH4]+·
257.0557; found 257.0611.
Benzo[d][1,3]selenazole (3m): Yield 0.029 g (63%); yellow oil. 1H
NMR (300 MHz, CDCl3): δ = 9.90 (s, 1 H), 8.18 (d, J = 8.2 Hz, 1
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6945–6952

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Received: June 23, 2014
Published Online: September 22, 2014
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