Synthesis of benzo[b]chalcogenophenes fused to selenophenesviaintramolecular electrophilic cyclization of 1,3-diynes

Article abstract of DOI:10.1039/d0ob02362k

We describe herein an alternative and transition-metal-free procedure for the access of benzo[b]chalcogenophenes fused to selenophenesviaintramolecular cyclization of 1,3-diynes. This efficient protocol involves a double cyclization of 1,3-diynyl chalcogen derivatives promoted by the electrophilic species of organoselenium generatedin situby the oxidative cleavage of the Se-Se bond of dibutyl diselenide using Oxone in acetonitrile as solvent in an open-flask at 80 °C. In this study, 15 selenophenes with broad substrate scope were prepared in moderate to excellent yields (55-98%) with short reaction times (0.5-3.0 h).

Full text of DOI:10.1039/d0ob02362k

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2020, DOI: 10.1039/D0OB02362K.
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DOI: 10.1039/D0OB02362K
ARTICLE
Synthesis of benzo[b]chalcogenophenes fused to selenophenes via
intramolecular electrophilic cyclization of 1,3-diynes
Paola S. Hellwig,a Jonatan S. Guedes,a Angelita M. Barcellos,a Raquel G. Jacob,a Claudio C. Silveira,b
Eder J. Lenardãoa and Gelson Perin*a
Received 00th March 2020,
Accepted 00th March 2020
We describe herein an alternative and transition-metal-free procedure for the access of benzo[b]chalcogenophenes fused
to selenophenes via intramolecular cyclization of 1,3-diynes. This efficient protocol involves a double cyclization of 1,3-diynyl
chalcogen derivatives promoted by electrophilic species of organoselenium generated in situ by the oxidative cleavage of
the Se-Se bond of dibutyl diselenide using Oxone® in acetonitrile as solvent in an open-flask at 80 °C. In this study, 15
selenophenes with broad substrate scope were prepared in moderate to excelent yields (55-98%) and short reaction times
(0.5-3.0 h).
DOI: 10.1039/x0xx00000x
www.rsc.org/
the synthesis of benzo[b]furan-fused selenophenes (Scheme 1a).18
Subsequently, the same group reported the synthesis of
chalcogenisochromene-fused chalcogenophenes by the cascade
Introduction
Organoselenium compounds have received increased
attention in recent years, due to their promising applications as
catalysts,1 as versatile synthetic intermediates2 allowing
selective transformations,3 and to their biological activities.4 In
parallel, a number of selenophenes are known to display a wide
range of biological activities, such as antibacterial,5
antioxidant,6 antidepressant,7 antitumoral,8 anticonvulsant,9
hepatoprotective10 and antinociceptive (Figure 1).11 Apart from
their biological activities, selenophenes have also been used in
the preparation of materials that show potential as optical
properties,12 semiconductors,13 solar cells14 and film
transistors.15
cyclization of ortho-diynyl benzyl chalcogenides promoted by iron(III)
chloride in the presence of dialkyl dichalcogenides (Scheme 1b).19
Moreover, Sonawane and co-workers20 reported the synthesis of
selenophene-fused quinoline-based heteroacenes by the
intramolecular cascade cyclization of 1,3-diyne promoted by iron and
dialkyl diselenides (Scheme 1c). Recently, our group synthesized 5H-
selenopheno[3,2-c]isochromen-5-ones by the double intramolecular
cyclization of methyl 2-(organyl-1,3-diynyl)benzoate promoted by
electrophilic species of selenium, which were generated in situ by the
reaction of dialkyl diselenides with Oxone® (Scheme 1d).21
Potassium peroxymonosulfate is commercially available as
a stable triple salt (2KHSO5.KHSO4.K2SO4), sold under the trade
name Oxone®. This reactant has been widely explored in
organic synthesis due to its low cost, stability, water solubility
and low toxicity.22 Oxone® is also known as an oxidizing agent
containing 50% active oxidant/mol in its formulation, the anion
OH
F
OH
Se
N
Se
Se
hepatoprotective effects
antinociceptive
HO
OH
Se
antitumoral
anticonvulsant
Se
- 22
peroxymonosulfate HSO5 , responsible for several classical
antidepressant
synthetic transformations, such as functional group oxidation,23
halogenation reactions,24 cross coupling,25 synthesis of
heterocycles,26 among others.27 Regarding the combination of
Oxone® with organoselenium chemistry,28 our group and others
have reported several useful reactions, including the oxidation
of selenides to the corresponding selenones28a,b and the
synthesis of several Se-containing heterocycles through
electrophilic cyclization, like 4-organoselanyl-1H-pyrazoles
Figure 1 Some biologically active selenophenes.
Due to the growing importance and utility of these selenium
heterocyclic in organic synthesis, different methodologies have been
reported for their preparation. Traditional methods for the synthesis
of selenophenes involve the addition of either nucleophilic or
electrophilic selenium species to appropriate acyclic precursors
containing the π-system, followed by an intramolecular cyclization16
or by the cyclization of appropriate organoselenium substrates.17 In
this context, the iron-promoted tandem cyclization of 1,3-diynyl-
chalcogen derivatives with dialkyl diselenides has been described for
from
α,β-alkynyl
hydrazones,28c
2,3-bis-
from 2-
organochalcogenylbenzo[b]chalcogenophenes
functionalized chalcogenoalkynes,28d 1-aryl-4-(organylselanyl)-
1H-pyrazoles by direct cyclocondensation and C−H bond
selenylation reactions starting from hydrazines, 1,3-diketones
and diorganyl diselenides28e and in the ultrasound-promoted
radical synthesis of 5-methylselanyl-4,5-dihydroisoxazoles.28f
a. LASOL-CCQFA, Universidade Federal de Pelotas – UFPel; P.O. Box 354, 96010-900,
Pelotas, RS, Brazil. http://wp.ufpel.edu.br/lasol; gelson_perin@ufpel.edu.br (G.
Perin).
b. Departamento de Química, Universidade Federal de Santa Maria - UFSM,
CEP: 97105-900, Santa Maria - RS, Brazil.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: Figures of the NMR spectra of
all the prepared compounds. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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ARTICLE
Journal Name
3a was
a)
R
R
methoxyphenyl)selenopheno[3,2-b]benzofuran
View Article Online
DOI: 10.1039/D0OB02362K
Se
obtained in 85% yield (Table 1, entry 1).
3Se
)2, FeCl3.6H2O
R2
(R
R2
Z =
O
R1
CH2Cl2, reflux, 4-24 h
Z
3
O S Se
, ,
Se
Z =
R
O S Se
,
,
; R = F, CH3; R1 = R3 = alkyl
R2 = alkyl, aryl, heteroaryl
1
Z
1b h j o
- , - (50-95%)
R
35-89%
R = CH3, C3H7, C4H9
ZR
ZR
b)
R1
4
R1
i
iii
Z
R
Y
Z
C4H9
R2
I
RZ
Y
(C4H9 )2, FeCl3
Br
R1
R2
iv
ii
DCE, 0 ºC to 85 ºC
0.5-24 h
Y
Br
ZR
ZR
O Se
, ; Y =
Se Te
,
Z =
40-83%
ZR 1a i p
, , (54-75%)
5
6
R = alkyl; R1 = H, heteroalkyl, aryl; R2 = aryl, heteroaryl
Scheme 2 Reaction conditions: i) CBr4 (1.2 equiv), PPh3 (2.5 equiv), CH2Cl2, 0
°C, 3.0 h, 80-95% yields; ii) BuLi (2.0 equiv), I2 (1.0 equiv), THF, 0 °C, 1.5 h, 65-
89% yields; iii) CuI (20 mol%), pyrrolidine, 0 °C, 0.2 h, 50-95% yields; iv) CuI
(20 mol%), DBU (2 equiv), DMSO, 25 °C, 8-12 h, 54-75% yields.
R2
R2
c)
R1
Se
R1
3Se
)2, FeCl3.6H2O
(R
CH2Cl2, reflux, 5-8 h
3
Se
R
Z
Z
N
R
N
The use of inert atmosphere was also examined, and a
similar yield of compound 3a was observed under this
condition, indicating that it is not necessary in this reaction
(Table 1, entry 2). Following, the effect of using different
amounts of diselenide 2a was evaluated (Table 1, entries 3 and
4). A decrease in the yield of 3a was observed when the amount
of 2a was reduced to 0.25 mmol, and it was obtained in 50%
yield after 2 h (Table 1, entry 3). By using 0.50 mmol of 2a, the
product 3a was obtained in 89% yield after 1.5 h (Table 1, entry
4).
; R = CH3; R1 = R2 = H, CH3; R3 = alkyl
70-88%
S Se
Z =
,
O
O
d)
Oxone®
OCH3
O
1Se
(R
)
2
+
EtOH, reflux
1-2.5 h
1
Se
R
Se
40-86%
R = alkyl, aryl; R1 = alkyl
R
R
e) This Work
R1
Se
Oxone®
R1
Se
(C4H9
)
2
CH3CN, 80 ºC
open flask
Se
C4H9
2a
1
Z
Z
R
3
R = alkyl; R1 = alkyl, aryl;
=
Z
O S Se
, ,
Scheme 1 Previously reported methods and our general reaction scheme.
Table 1 Optimization of the reaction conditions for the synthesis of 3a.a
O
CH3
Considering our interest in developing green protocols for
the synthesis of organoselenium compounds and the
importance of the selenophene nucleus, we report here an
alternative and transition-metal-free procedure for the access
of fused selenophenes. This protocol involves the electrophilic
cyclization of 1,3-diynyl chalcogen derivatives 1 promoted by
dibutyl diselenide 2a and Oxone® for the synthesis of
benzo[b]chalcogenophene-fused selenophenes 3 (Scheme 1e).
O
CH3
Se
Se
(C4H9
)
2a
2
Oxone®, solvent
conditions
Se
C4H9
O
O
CH3
1a
3a
#
2a
Oxone®
(mmol)
Solvent
T
Time
(h)
Yield
3a (%)b
(mmol)
(°C)
1
2c
3
0.38
0.38
0.25
0.50
0.38
0.38
0.38
0.38
0.38
0.38
0.50
0.50
0.50
0.50
0.75
0.25
0.50
0.50
0.50
0.50
EtOH
EtOH
70
70
1.5
1.5
2.0
1.5
1.5
1.5
1.5
24.0
2.5
2.5
85
82
50
89
80
74
95
30
58
84
EtOH
70
Results and discussion
4
EtOH
70
Our investigations in this direction begun with the synthesis
of the starting material 1,3-diynes 1 (Scheme 2). For this,
previously synthesized29,30 or commercially available 2-
chalcogenbenzaldehydes 4 were subjected to the Corey-Fucks
reaction, producing the respective dibromoalkenes 5.31 The
dibromoalkenes, after reacting with butyllithium followed by
the addition of iodine, provided the alkynyl iodides 6,32 which
when reacting with terminal alkynes via Cadiot-Chodkiewicz
coupling provided the unsymmetrical 1,3-diynes 1b-h, j-o.33 In
addition, the symmetrical diynes 1a, 1i and 1p were synthesized
by copper-catalyzed homocoupling reaction of dibromoalkenes
5 using a DBU/DMSO system.34
Thus, interested in obtaining the fused selenophenes 3, the
1,4-bis(2-methoxyphenyl)buta-1,3-diyne 1a and dibutyl
diselenide 2a were chosen as model substrates to perform the
optimization studies in the reaction with Oxone® under air
condition. Firstly, we added 1,3-diyne 1a (0.25 mmol), dibutyl
diselenide 2a (0.38 mmol) and Oxone® (0.5 mmol) in ethanol at
70 °C for 1.5 h, and the desired 3-(butylselanyl)-2-(2-
5
EtOH
70
6
EtOH
70
7
CH3CN
glycerol
PEG-400
DMF
80
8
100
100
140
9
10
a Reaction conditions: A mixture of 1,3-diyne 1a (0.25 mmol), Oxone®
and dibutyl diselenide 2a in the solvent (3.0 mL) was stirred at the
temperature and time indicated. b Isolated yields after purification by
c
column chromatography. Performed under inert atmosphere of
nitrogen.
Based on these results, the amount of dibutyl diselenide 2a was
fixed in 0.38 mmol and the effect of using different amounts of
Oxone® was evaluated. However, using 0.75 mmol or 0.25
mmol of Oxone®, the yield of 3a decreases to 80% and 74% after
1.5 h, respectively (Table 1, entries 5 and 6). In order to improve
the performance of the reaction, other solvents were also
evaluated including acetonitrile, glycerol, PEG-400 and DMF
(Table 1, entries 7-10). Fortunately, using acetonitrile as
solvent, the yield of product 3a increased to 95% after 1.5 h
(Table 1, entry 7). Thus, from the results presented on Table 1,
2 | J. Name., 2012, 00, 1-3
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the best reaction conditions to prepare fused selenophene 3a the optimal conditions to afford the fused selenophene 3k in
View Article Online
DOI: 10.1039/D0OB02362K
involve stirring a mixture of 1,3-diyne 1a (0.25 mmol), dibutyl 85% yield after 1.0 h (Table 2, entry 12). In contrast, the presence
diselenide 2a (0.38 mmol) and Oxone® (0.50 mmol) using of substituents in the phenyl ring of the 1,3-diynes 1 negatively
acetonitrile (3.0 mL) as the solvent at 80 °C for 1.5 h (Table 1, affects the reaction. The 1,3-diyne 1k, containing electron-
entry 7).
donating group (R1 = 4-CH3C6H4,) was more reactive than the
Once the best conditions were determined for the synthesis electron-withdrawing analogue 1l (R1 = 4-ClC6H4), affording the
of benzo[b]furan fused selenophene 3a, the scope and respective products 3l and 3m in 80% and 70% yields after 2.0
limitations of the methodology were explored by reacting h and 3.0 h, respectively (Table 2, entries 13 and 14). In addition,
different 1,3-diynyl chalcogen derivatives 1 with a variety of when the 2-naphthyl- and alkyl-substituted 1,3-diynes 1m and 1n
dialkyl dichalcogenides 2, and the results are shown in Table 2. were employed as substrates under the optimal conditions, the
No product was observed when dibutyl telluride or dimethyl products 3n and 3o were obtained in moderate to good yields (65%
disulfide were used as substrates in the reaction with 1a, even and 83%) after 1.5 and 2.5 h, respectively (Table 2, entries 15 and
after 5 h of reaction, and the starting materials were recovered 16)
(Table 2, entries 2 and 3). decomposition during the purification process by column
After that, the performance of the reaction using chromatography
unsymmetrical 1-(buta-1,3-diyn-1-yl)-2-methoxybenzenes 1b-h After, we evaluated the use of the unsymmetrical 1,3-diyne 1o
. The low yield of the compound 3n could be attributed to its
.
was evaluated. When the 1,3-diyne containing an electron- bearing two potential nucleophiles, i.e., a competitive cyclization
neutral substituent in the phenyl ring (R1 = C6H5, 1b) was used, reaction between nucleophilic oxygen and sulfur at the ortho-
the expected product 3d was obtained in 93% yield after 1.0 h position of opposite aryl groups. Under this competitive condition,
(Table 2, entry 4). The presence of an electron-donating occurred the formation of the benzothiophene-fused selenophene
substituent (R1 = 4-CH3OC6H4, 1c) positively affected the 3p in 79% yield after 0.5 h, due to the higher nucleophilicity of the
reaction, affording the respective fused selenophene 3e in 98% sulfur atom compared to the oxygen one (Table 2, entry 17).18 Lastly,
yield after 0.8 h (Table 2, entry 5). Additional analysis to prove the symmetric selenodiyne 1p was used in the reaction with
the structure of the compound 3e can be found in the SI (Figures diselenide 2a, affording the expected dibenzo[b]selenophene 3q in
37-42). The presence of an electron-withdrawing substituent, 86% yield after 3.0 h (Table 2, entry 18).
however, decreased the reactivity of 1,3-diynes 1d (R1 = 4-
In order to acquire substantial support to a possible reaction
ClC6H4)and 1e (R = 2-ClC6H4), and the respective products 3f and mechanism, some control experiments were designed. Firstly,
3g were obtained in 83% and 85% yields after 1.5 h and 2.5 h the reaction was conducted in the presence of 3 equiv. of the
(Table 2, entries 6 and 7).
radical inhibitors benzene-1,4-diol (hydroquinone) and 2,2,6,6-
Additionally, when 1,3-diyne substituted with 2-naphthyl tetramethylpiperidin-1-oxyl (TEMPO). In these experiments, the
group 1f was used in the reaction with Bu2Se2, the product 3a was formed in 92% yield using hydroquinone and in
corresponding product 3h was obtained in 89% yield after 0.5 h 78% yield using TEMPO (Scheme 3). These findings suggest that
of reaction (Table 2, entry 8). The alkyl-substituted 1,3-diyne 1g a radical pathway is not involved in the reaction.
O
CH3
O
CH3
was also a suitable substrate for the reaction, affording the
respective product 3i in 55% yield after 1.0 h (Table 2, entry 9).
The low yield could be attributed to its decomposition during
the purification process by column chromatography. In order to
extend the scope of this protocol, we tested the reactivity of the
1,3-diyne 1h. However, after 1.5 h of reaction, an inseparable
mixture of the first cyclization product, the second cyclization
product and other byproducts was observed by GC/MS (Table
2, entry 10; see Fig. S67 in the ESI for experimental details and
figures of chromatogram and mass spectra).
The effect of the presence of a nucleophilic heteroatom
different of oxygen in the 1,3-diyne was evaluated. When the
symmetric 1,3-diyne thio-substituted at the 2-position of the
alkylated aryl ring 1i was used in the reaction with 2a, 3,3'-
bis(butylselanyl)-2,2'-dibenzo[b]thiophene 3j was surprisingly
obtained in 77% yield after 3.0 h (Table 2, entry 11). Although
the selenium atom is more nucleophilic than the sulfur one, we
believe that the steric hindrance of the SeC4H9 group, inhibits
the formation of the Se-cyclization product compared to the S-
cyclization one.35 The unsymmetrical [2-(phenylbuta-1,3-diyn-
1-yl)phenyl](propyl)sulfide 1j reacted with diselenide 2a under
SeSe
2a
C4H9
C4H9
radical scavenger
Se
standard conditions
hydroquinone = 92%
TEMPO = 78%
O
CH3
Se
C4H9
1a
O
3a
Scheme 3 Reactions in the presence of radical scavengers hydroquinone
and TEMPO.
Based on the control experiments and in the literature,18,28c-e
a
plausible mechanism for the formation of the
benzo[b]chalcogenophenes fused selenophene 3a-i, k-p from
the reaction of 1,3-diyne 1a with dibutyl diselenide 2a
promoted by Oxone® is presented in Scheme 4. Firstly, dibutyl
diselenide 2a reacts with Oxone® to affords two electrophilic
selenium species, A and B. In the cyclization step, the 1,3-diyne
1a reacts with the electrophilic species A or B to form the
-
seleniranium intermediate C, releasing the sulfate anion (KSO4 )
and water (H2O) to the medium. After an intramolecular attack
by the electron pair of the oxygen, the cation benzofuran
intermediate D is formed. Then, the displacement of the methyl
D occurs after an attack by
nucleophilic species present in the reaction medium, affording
group from intermediate
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DOI: 10.1039/D0OB02362K
Table 2 Scope of the reaction to prepare the benzo[b]chalcogenophene-fused chalcogenophenes 3a-q.a,b
R1
Y
Oxone®
R1
2Y
(R
)
2
CH3CN, 80 ºC
open flask
2
Y
R
Z
Z
R
1a j
-
2a c
-
3a q
-
Product 3 (Yield %) -
Product 3 (Yield %) -
#
1
1,3-diyne 1
(R2Y)2
#
1,3-diyne 1
(R2Y)2
reaction time
reaction time
O
CH3
O
CH3
OH
Se
(C4H9Se)2
(C4H9Se)2
10
_d
O
CH3
2a
2a
Se
C4H9
1h
O
O
CH3
3a
1a
95% (1.5 h)
Se
C4H9
S
O
CH3
Te
S
C3H7
S
C4H9
(C4H9Te)2
(C4H9Se)2
2
1a
1a
11
Se
2b
2a
Te
C4H9
O
3j
3b
77% (3.0 h)
NRc (5.0 h)
S
C3H7
1i
1j
O
CH3
S
Se
(CH3S)2
2c
(C4H9Se)2
3
4
12
13
S
C3H7
S
CH3
2a
Se
C4H9
O
S
3c
3k
NRc (5.0 h)
85% (1.0 h)
Se
Se
(C4H9Se)2
(C4H9Se)2
O
CH3
Se
C4H9
2a
2a
Se
C4H9
1b
O
S
C3H7
S
3d
3l
1k
93% (1.0 h)
80% (2.0 h)
OCH3
Cl
OCH3
Cl
Se
Se
(C4H9Se)2
(C4H9Se)2
5
6
14
15
OCH3
S
C3H7
2a
2a
1c
SeC4H9
1l
SeC4H9
O
S
3e
3m
70% (3.0 h)
98% (0.8 h)
Cl
Cl
Se
(C4H9Se)2
(C4H9Se)2
Se
O
CH3
S
C3H7
2a
2a
Se
C4H9
1d
1m
O
Se
C4H9
3f
S
3n
83% (1.5 h)
65% (1.5 h)
Cl
Cl
Se
(C4H9Se)2
(C4H9Se)2
7
8
16
17
Se
Se
C4H9
2a
2a
O
CH3
O
3g
S
C3H7
1e
1n
85% (2.5 h)
Se
C4H9
S
3o
83% (2.5 h)
O
CH3
O
CH3
Se
Se
(C4H9Se)2
(C4H9Se)2
Se
C4H9
2a
2a
O
CH3
S
C3H7
S
1f
Se
C4H9
3h
89% (0.5 h)
3p
1o
O
79% (0.5 h)
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Se
C4H
Se
DOI: 10.1039/D0OB09 2362K
Se
C9H4
Se
(C4H9Se)2
(C4H9Se)2
9
18
Se
C4H9
3q
86% (3.0 h)
Se
2a
2a
Se
C4H9
O
CH3
1p
1g
Se
C4H9
O
3i
55% (1.0 h)
a Reactions performed using 1,3-diynes 1 (0.25 mmol), dialkyl dichalcogenide 2 (0.38 mmol), acetonitrile (3.0 mL) and Oxone® (0.50 mmol) at 80 °C.
b Isolated yields. c The product was not formed and the starting materials were recovered. d An inseparable mixture of the first cyclization product
and second cyclization product, besides other byproducts, was obtained.
the intermediate E. Following, E reacts in the same way with A
In summary, we have developed an alternative and
or B to give the seleniranium intermediate F, and after an transition-metal-free procedure for the access of fused
intramolecular attack (Path a) by the selenium electron pair, the selenophenes and dibenzo[b]chalcogenophenes. This protocol
fused selenophene cation intermediate G is formed. The involves a double cyclization of 1,3-diynyl chalcogen-derivatives
displacement of the butyl group from the selenonium cation promoted by electrophilic species of selenium generated in situ
affords the expected product 3a. In contrast, the formation of by the reaction of dibutyl diselenide with Oxone®. The synthetic
the dibenzo[b]thiophene 3j or -selenophene 3q can be feasibility and versatility were demonstrated by the good yields
attributed to the intermolecular attack (Path b) by the electron (55-98%) and short reaction times (0.5-3.0 h) for the
pair of the chalcogen atom (Z = S or Se) in the seleniranium preparation of 15 compounds, with broad substrate scope.
intermediate F, generated from the symmetric 1,3-diyne sulfur-
or selenium-substituted at the 2-position of the alkylated aryl
ring 1i and 1p (Scheme 4).
Experimental
General remarks
Formation of the electrophiles:
Oxone®
The reactions were monitored by thin TLC sheets ALUGRAM® Xtra SIL
SeSe
2a
Se
Se
C4H9
C4H9
C4H9 OSO3K
C4H9 OH2
+
A
B
G/UV254. For visualization, TLC plates were either placed under UV
light, stained with iodine vapor and 5% vanillin in 10% H2SO4 and
heat. Column chromatography was performed using Merck Silica Gel
(pore size 60 Å, 230-400 mesh). Carbon-13 nuclear magnetic
resonance (13C NMR) and hydrogen nuclear magnetic resonance
spectra (1H NMR) were obtained on Bruker Avance III HD
spectrometers at 100 MHz at 400 MHz, respectively. Spectra were
recorded in CDCl3 solutions. Chemical shifts are reported in ppm,
referenced to tetramethylsilane (TMS) as the internal reference for
1H NMR and the solvent peak of CDCl3 for 13C NMR. Coupling
constants (J) are reported in Hertz and chemical shift (δ) in ppm.
Abbreviations to denote the multiplicity of a particular signal are s
(singlet), d (doublet), dd (doublet of doublet), t (triplet), td (triplet of
dublet), quint (quintet), sext (sextet) and m (multiplet). Low-
resolution mass spectra (MS) were measured on a Shimadzu GC-MS-
QP2010 mass spectrometer. The HRMS analyses were performed in
a Bruker micrOTOF-QII spectrometer equipped with an APCI source
operating in positive mode. The samples were solubilized in
acetonitrile and analyzed by direct infusion. Melting point (m.p.)
values were measured in a Marte PFD III instrument with a 0.1 °C
precision. Oxone® was purchased from Sigma-Aldrich. The 1,3-diynes
1 were previously prepared as described in the Support Information.
Cyclization steps:
Se
A
C4H9 OSO3K
Se
C4H9
- KSO4
- H2O
or
Z
Z
R
R
C
1
Z
R
Z
R
Se
C4H9
OH2
C4H9
Se
B
KO3SO
Se
Z
Z
C4H9
R
A
Se
C4H9
Z
R
- (R)nNu
Z
or
C4H9
- KSO4 - H2O
R
D
E
Nu
Se
OH2
B
Nu
C4H9
Se
a
b
Se
Z
Z
R
C4H9
Path a
O
CH3
Z
O
R = CH3
Se
Se
C4H9
O
G
F
C4H9
Path b
Se
Z
S
Se
C4H9
R = C3H7 or
- (C4H9)nNu
C4H9
Z
Se
Z
O
CH3
Se
C4H9
Se
C4H9
General procedure for the synthesis of 3-(butylselanyl)-2-
organylselenofeno[3,2-b]benzochalcogenophenes 3
O
3j
3q
S
)
(Z =
(Z =
3a
Se
)
Scheme
benzo[b]calcogenophene-fused
dibenzo[b]chalcogenophenes 3j and 3q.
4
Proposed mechanism for the synthesis of
selenophenes 3a-i,k-p and
To a 25.0 mL two-necked round-bottomed flask equipped with
magnetic stirring and a reflux system containing the appropriate 1,3-
diynes 1a-p (0.25 mmol), a solution of dibutyl diselenide 2a (0.38
mmol, 0.104 g) in acetonitrile (3.0 mL) and Oxone®
Conclusions
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
(KHSO5.1/2KHSO4.1/2K2SO4, FW = 307 g.mol-1, 0.50 mmol, 0.15 g) were 412 (66.6), 374 (45.5), 332 (85.2), 302 (18.8), 267 (11.V0ie),w2A5rt2icle(2O1n.l7in)e,
DOI: 10.1039/D0OB02362K
added under air atmosphere. The resulting mixture was stirred at 80 223 (27.8), 187 (49.9), 57 (15.6), 41 (40.6).
°C for the time indicated in Table 2. The reactions were monitored by
TLC until total disappearance of the 1,3-diyne 1. After this time, the 3-(Butylselanyl)-2-(2-chlorophenyl)selenopheno[3,2-b]benzofuran
1
3g:18 Yield: 0.100 g (85%); yellow oil. H NMR (CDCl3, 400 MHz) 
(ppm) = 7.67-7.63 (m, 2H); 7.50 (dd, J = 7.7, 1.5 Hz, 1H); 7.45-7.42 (m,
1H); 7.38-7.29 (m, 4H); 2.93 (t, J = 7.3 Hz, 2H); 1.55 (quint, J = 7.3 Hz,
2H); 1.29 (sext, J = 7.3 Hz, 2H); 0.81 (t, J = 7.3 Hz, 3H). 13C NMR (CDCl3,
100 MHz)  (ppm) = 160.0, 157.1, 145.6, 135.3, 134.4, 132.7, 130.0,
129.7, 126.4, 126.3, 124.7, 123.2, 119.6, 118.0, 112.5, 110.2, 32.3,
27.4, 22.6, 13.4. MS (rel. int., %) m/z: 468 (M+, 50.9), 412 (10.3), 374
(78.1), 332 (31.7), 302 (11.2), 267 (15.0), 252 (20.9), 223 (23.3), 187
(63.5), 57 (23.7), 44 (100.0).
resulting solution was received in water (10.0 mL) and the product
was extracted with ethyl acetate (3x 10.0 mL). The organic layer was
separated, dried over anhydrous MgSO4 and concentrated under
vacuum. The residue was purified by column chromatography using
silica gel and hexane/ethyl acetate (95:05) as the eluent. Yield: 55-
98%.
3-(Butylselanyl)-2-(2-methoxyphenyl)selenopheno[3,2-
1
b]benzofuran 3a:18 Yield: 0.110 g (95%); yellow oil. H NMR (CDCl3,
400 MHz)  (ppm) = 7.62-7.60 (m, 2H); 7.42 (dd, J = 7.5, 1.4 Hz, 1H);
7.38-7.25 (m, 3H); 7.01 (t, J = 7.4 Hz, 1H); 6.95 (d, J = 8.3 Hz, 1H); 3.81
(s, 3H); 2.94 (t, J = 7.4 Hz, 2H); 1.53 (quint, J = 7.4 Hz, 2H); 1.27 (sext,
J = 7.4 Hz, 2H); 0.78 (t, J = 7.4 Hz, 3H). 13C NMR (CDCl3, 100 MHz) 
(ppm) = 160.4, 157.0, 156.6, 144.8, 131.9, 130.0, 126.6, 125.3, 124.2,
123.0, 120.2, 119.5, 117.2, 112.3, 111.0, 109.2, 55.4, 32.2, 26.9, 22.6,
13.4. MS (rel. int., %) m/z: 464 (M+, 68.9), 407 (10.9), 376 (12.9), 327
(98.9), 312 (68.8), 285 (13.7), 256 (17.7), 247 (100.0), 218 (32.2), 189
(56.2), 176 (42.4), 77 (11.3), 57 (20.5), 41 (77.6).
3-(Butylselanyl)-2-(naphthalen-2-yl)selenopheno[3,2-
b]benzofuran 3h:18 Yield: 0.108 g (89%); yellow solid; m.p. = 69-71
1
°C. H NMR (CDCl3, 400 MHz)  (ppm) = 8.05 (s, 1H); 7.89-7.83 (m,
3H); 7.77 (dd, J = 8.5, 1.8 Hz, 1H); 7.66-7.63 (m, 2H); 7.51-7.48 (m,
2H); 7.35-7.28 (m, 2H); 2.97 (t, J = 7.4 Hz, 2H); 1.54 (quint, J = 7.4 Hz,
2H); 1.27 (sext, J = 7.4 Hz, 2H); 0.75 (t, J = 7.4 Hz, 3H). 13C NMR (CDCl3,
100 MHz)  (ppm) = 161.0, 157.0, 149.3, 134.1, 133.1, 132.9, 128.6,
128.2, 127.9, 127.7, 127.2, 126.5, 126.4, 124.5, 123.2, 119.6, 118.2,
116.7, 112.4, 107.1, 32.2, 27.8, 22.6, 13.4. MS (rel. int., %) m/z: 484
(M+, 97.2), 478 (20.3), 427 (100.0), 398 (25.1), 347 (26.6), 319 (34.7),
268 (25.1), 239 (74.2), 237 (50.3), 212 (7.9), 207 (52.0), 163 (5.6), 119
(9.0), 73 (21.1), 57 (9.3), 41 (29.9).
3-(Butylselanyl)-2-phenylselenopheno[3,2-b]benzofuran
3d:18
Yield: 0.101 g (93%); yellow oil. 1H NMR (CDCl3, 400 MHz)  (ppm) =
7.67-7.62 (m, 4H); 7.46-7.29 (m, 5H); 2.97 (t, J = 7.4 Hz, 2H); 1.58-
1.51 (m, 2H); 1.28 (sext, J = 7.4 Hz, 2H); 0.79 (t, J = 7.4 Hz, 3H). 13
C
NMR (CDCl3, 100 MHz)  (ppm) = 161.0, 157.1, 149.5, 136.6, 129.5,
128.4, 128.3, 126.4, 124.5, 123.2, 119.6, 116.5, 112.4, 106.8, 32.2,
27.8, 22.6, 13.4. MS (rel. int., %) m/z: 434 (M+, 71.2), 427 (15.0), 377
(54.5), 375 (28.5), 298 (100.0), 268 (36.7), 189 (36.7), 163 (11.5), 57
(10.2), 41 (25.9).
3-(Butylselanyl)-2-hexylselenopheno[3,2-b]benzofuran 3i: Yield:
0.061 g (55%); yellow oil. 1H NMR (CDCl3, 400 MHz)  (ppm) = 7.61-
7.58 (m, 2H); 7.29-7.26 (m, 2H); 3.12 (t, J = 7.4 Hz, 2H); 2.94 (t, J = 7.4
Hz, 2H); 1.72 (quint, J = 7.4 Hz, 2H); 1.62 (quint, J = 7.4 Hz, 2H); 1.45-
1.38 (m, 4H); 1.35-1.32 (m, 4H); 0.92-0.85 (m, 6H). 13C NMR (CDCl3,
100 MHz)  (ppm) = 160.4, 157.0, 155.7, 126.6, 123.8, 123.0, 119.1,
114.0, 112.3, 106.9, 33.4, 32.6, 32.5, 31.6, 28.8, 27.9, 22.7, 22.6, 14.1,
13.5. MS (rel. int., %) m/z: 442 (M+, 51.0), 385 (21.9), 371 (40.0), 367
(20.5), 340 (14.0), 315 (51.3), 313 (46.2), 305 (74.2), 281 (40.0), 235
(100.0), 207 (26.4), 115 (11.5), 57 (11.1), 41 (40.1). HRMS (APCI-
QTOF) calculated mass for C20H27OSe2 [M+H]+: 443.0392, found:
443.0388.
3-(Butylselanyl)-2-(4-methoxyphenyl)selenopheno[3,2-
b]benzofuran 3e: Yield: 0.114 g (98%); yellow oil. 1H NMR (CDCl3, 400
MHz)  (ppm) = 7.62-7.60 (m, 2H); 7.54 (d, J = 8.8 Hz, 2H); 7.32-7.25
(m, 2H); 6.94 (d, J = 8.8 Hz, 2H); 3.82 (s, 3H); 2.94 (t, J = 7.4 Hz, 2H);
1.53 (quint, J = 7.4 Hz, 2H); 1.28 (sext, J = 7.4 Hz, 2H); 0.78 (t, J = 7.4
Hz, 3H). 13C NMR (CDCl3, 100 MHz)  (ppm) = 160.9, 159.7, 156.9,
149.6, 130.7, 129.1, 126.4, 124.2, 123.1, 119.4, 115.7, 113.8, 112.2,
106.0, 55.2, 32.2, 27.7, 22.5, 13.4. 77Se NMR (CDCl3, 76 MHz)  (ppm)
= 502.1, 183.0. MS (rel. int., %) m/z: 464 (M+, 100.0), 407 (30.2), 376
(18.8), 328 (43.8), 313 (13.6), 256 (15.1), 176 (34.1), 57 (7.9), 41
(25.4). HRMS (APCI-QTOF) calculated mass for C21H21O2Se2 [M+H]+:
464.9872, found: 464.9858.
3,3’-Bis(butylselanyl)-2,2’-dibenzo[b]thiophene 3j: Yield: 0.104 g
1
(77%); yellow solid, m.p. = 108-109 °C. H NMR (CDCl3, 400 MHz) 
(ppm) = 8.07 (d, J = 7.9 Hz, 2H); 7.85 (d, J = 7.9 Hz, 2H); 7.49-7.44 (m,
2H); 7.43-7.39 (m, 2H); 2.70 (t, J = 7.4 Hz, 4H); 1.46 (quint, J = 7.4 Hz,
4H); 1.22 (sext, J = 7.4 Hz, 4H); 0.74 (t, J = 7.4 Hz, 6H). 13C NMR (CDCl3,
100 MHz)  (ppm) = 141.6, 140.3, 138.5, 125.4, 125.2, 124.9, 122.8,
122.1, 32.5, 28.9, 22.7, 13.4. MS (rel. int., %) m/z: 538 (M+, 4.1), 481
(5.8), 424 (6.1), 401 (10.7), 346 (28.7), 344 (100.0), 342 (53.7), 320
(15.5), 264 (19.7), 207 (10.7), 73 (14.2), 41 (87.0). HRMS (APCI-QTOF)
calculated mass for C24H27S2Se2 [M+H]+: 538.9885, found: 538.9880.
3-(Butylselanyl)-2-(4-chlorophenyl)selenopheno[3,2-b]benzofuran
1
3f:18 Yield: 0.097 g (83%); white solid; m.p. = 104-105 °C. H NMR
(CDCl3, 400 MHz)  (ppm) = 7.65 (t, J = 8.3 Hz, 2H); 7.55 (d, J = 8.5 Hz,
2H); 7.41 (d, J = 8.5 Hz, 2H); 7.37-7.30 (m, 2H); 2.97 (t, J = 7.3 Hz, 2H);
1.54 (quint, J = 7.3 Hz, 2H); 1.29 (sext, J = 7.3 Hz, 2H); 0.80 (t, J = 7.3
Hz, 3H). 13C NMR (CDCl3, 100 MHz)  (ppm) = 160.9, 157.1, 147.8,
135.1, 134.4, 130.7, 128.6, 126.2, 124.7, 123.3, 119.7, 116.8, 112.4,
107.4, 32.3, 27.9, 22.6, 13.4. MS (rel. int., %) m/z: 468 (M+, 100.0),
3-(Butylselanyl)-2-phenylbenzo[b]selenopheno[2,3-d]thiophene
1
3k:18 Yield: 0.096 g (85%); yellow oil. H NMR (CDCl3, 400 MHz) 
(ppm) = 7.86 (d, J = 7.7 Hz, 1H); 7.73 (d, J = 7.7 Hz, 1H); 7.64 (d, J = 6.9
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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ARTICLE
Hz, 2H); 7.43-7.30 (m, 5H); 2.76 (t, J = 7.4 Hz, 2H); 1.46 (quint, J = 7.4 3-(Butylselanyl)-2-(2-methoxyphenyl)benzo[b]selenoVpiehweAnrotic[l2e,O3n-line
Hz, 2H); 1.21 (sext, J = 7.4 Hz, 2H); 0.73 (t, J = 7.4 Hz, 3H). 13C NMR d]tiophene 3p:18 Yield: 0.095 g (79%); yellow oil. H NMR (CDCl3, 400
1
DOI: 10.1039/D0OB02362K
(CDCl3, 100 MHz)  (ppm) = 151.9, 147.4, 140.3, 136.4, 136.0, 131.9, MHz)  (ppm) = 7.87 (d, J = 7.7 Hz, 1H); 7.75 (d, J = 7.7 Hz, 1H); 7.45
129.7, 128.3, 124.7, 124.3, 123.6, 121.8, 114.0, 32.2, 28.5, 22.5, 13.4. (d, J = 7.4 Hz, 1H); 7.40-7.31 (m, 3H); 7.05-6.96 (m, 2H); 3.82 (s, 3H);
MS (rel. int., %) m/z: 450 (M+, 56.6), 396 (16.9), 392 (61.9), 314 2.77 (t, J = 7.3 Hz, 2H); 1.47 (quint, J = 7.3 Hz, 2H); 1.23 (sext, J = 7.3
Hz, 2H); 0.76 (t, J = 7.3 Hz, 3H). 13C NMR (CDCl3, 100 MHz)  (ppm) =
156.7, 147.4, 145.9, 140.5, 136.2, 133.0, 132.2, 130.1, 125.3, 124.6,
124.2, 123.6, 121.7, 120.2, 116.4, 111.0, 55.4, 32.2, 27.7, 22.6, 13.5.
MS (rel. int., %) m/z: 480 (M+, 100.0), 424 (39.4), 392 (20.4), 344
(90.5), 328 (60.0), 312 (15.7), 207 (34.3), 41 (41.7).
(100.0), 309 (36.4), 234 (46.8), 207 (22.3), 187 (12.3), 73 (13.5), 57
(8.9), 41 (23.5).
3-(Butylselanyl)-2-(4-tolylphenyl)benzo[b]selenopheno[2,3-
d]thiophene 3l:18 Yield: 0.093 g (80%); yellowish oil. 1H NMR (CDCl3,
400 MHz)  (ppm) = 7.88 (d, J = 8.1 Hz, 1H); 7.75 (d, J = 7.6 Hz, 1H);
7.55 (d, J = 8.1 Hz, 2H); 7.39 (td, J = 7.6, 1.2 Hz, 1H); 7.34 (td, J = 7.6, 3,3’-Bis(butylselanyl)-2,2’-dibenzo[b]selenophene 3q: Yield: 0.136 g
(86%); yellow solid, m.p. = 53-55 °C. 1H NMR (CDCl3, 400 MHz) 
1.2 Hz, 1H); 7.24 (d, J = 7.9 Hz, 2H); 2.79 (t, J = 7.3 Hz, 2H); 2.40 (s,
3H); 1.48 (quint, J = 7.3 Hz, 2H); 1.25 (sext, J = 7.3 Hz, 2H); 0.76 (t, J =
(ppm) = 8.13 (d, J = 7.7 Hz, 2H); 7.87 (d, J = 7.7 Hz, 2H); 7.46 (t, J = 7.7
7.3 Hz, 3H). 13C NMR (CDCl3, 100 MHz)  (ppm) = 152.2, 147.4, 140.3, Hz, 2H); 7.34 (t, J = 7.7 Hz, 2H); 2.71 (t, J = 7.4 Hz, 4H); 1.48 (quint, J
138.3, 136.1, 133.6, 131.6, 129.6, 129.0, 124.7, 124.3, 123.6, 121.7, = 7.4 Hz, 4H); 1.28-1.19 (m, 4H); 0.75 (t, J = 7.4 Hz, 6H). 13C NMR
113.6, 32.2, 28.5, 22.6, 21.3, 13.4. MS (rel. int., %) m/z: 464 (M+,
49.3), 392 (20.3), 328 (66.0), 312 (17.6), 248 (25.0), 202 (13.7), 44
(100.0).
(CDCl3, 100 MHz)  (ppm) = 143.5, 143.1, 142.2, 127.6, 125.6, 125.13,
125.1, 125.0, 32.5, 29.0, 22.8, 13.5. MS (rel. int., %) m/z: 634 (M+,
2.5), 631 (13.2), 497 (21.0), 438 (100.0), 360 (20.8), 317 (5.0), 200
(34.5), 180 (4.3), 137 (8.7), 91 (13.9), 83 (44.4). HRMS (APCI-QTOF)
calculated mass for C24H27Se4 [M+H]+: 634.8774, found: 634.8763.
3-(Butylselanyl)-2-(4-chlorophenyl)benzo[b]selenopheno[2,3-
d]thiophene 3m:18 Yield: 0.085 g (70%); white solid; m.p. = 63-65 °C.
1H NMR (CDCl3, 400 MHz)  (ppm) = 7.88-7.86 (m, 1H); 7.74-7.72 (m,
1H); 7.57 (d, J = 8.5 Hz, 2H); 7.40-7.36 (m, 3H); 7.33 (dd, J = 7.3, 1.3
Hz, 1H); 2.77 (t, J = 7.3 Hz, 2H); 1.46 (quint, J = 7.3 Hz, 2H); 1.23 (sext,
J = 7.3 Hz, 2H); 0.75 (t, J = 7.3 Hz, 3H). 13C NMR (CDCl3, 100 MHz) 
(ppm) = 150.2, 147.4, 140.4, 135.9, 134.8, 134.3, 132.1, 130.9, 128.5,
124.8, 124.5, 123.7, 121.8, 114.6, 32.2, 28.6, 22.5, 13.4. MS (rel. int.,
%) m/z: 484 (M+, 18.6), 482 (15.5), 479 (8.2), 427 (15.6), 389 (12.6),
347 (26.0), 206 (12.3), 44 (100.0).
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This study was financed in part by the Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) -
Finance Code 001. FAPERGS (PqG 19/2551-0001867-3), CNPq
and FINEP are acknowledged for financial support. CNPq is also
acknowledged for fellowships to RGJ, CCS, EJL and GP. Prof.
Thiago Barcellos from University of Caxias do Sul is
acknowledged for providing the HRMS analysis.
3-(Butylselanyl)-2-(naphthalen-2-yl)benzo[b]selenopheno[2,3-
d]thiophene 3n: Yield: 0.081 g (65%); orange oil. 1H NMR (CDCl3, 400
MHz)  (ppm) = 8.12 (s, 1H); 7.92-7.87 (m, 4H); 7.84 (dd, J = 8.5, 1.7
Hz, 1H); 7.80 (d, J = 8.0 Hz, 1H); 7.54-7.52 (m, 2H); 7.43 (td, J = 7.6,
1.3 Hz, 1H); 7.38 (td, J = 7.6, 1.3 Hz, 1H); 2.80 (t, J = 7.3 Hz, 2H); 1.49
(quint, J = 7.3 Hz, 2H); 1.27-1.27 (m, 2H); 0.72 (t, J = 7.3 Hz, 3H). 13
C
References
NMR (CDCl3, 100 MHz)  (ppm) = 151.8, 147.6, 140.4, 136.1, 133.9,
133.1, 132.9, 132.2, 128.9, 128.3, 127.9, 127.7, 127.5, 126.6, 126.5,
124.8, 124.4, 123.7, 121.8, 114.3, 32.2, 28.6, 22.5, 13.4. MS (rel. int.,
%) m/z: 500 (M+, 55.4), 443 (54.3), 363 (57.4), 362 (100.0), 282 (57.5),
237 (23.6). HRMS (APCI-QTOF) calculated mass for C24H21SSe2 [M+H]-
+: 500.9692, found: 500.9692.
1
a) F. V. Singh and T. Wirth, Catal. Sci. Technol., 2019, 9, 1073;
b) D. M. Freudendahl, S. A. Shahzad and T. Wirth, Eur. J. Org.
Chem., 2009, 1649; c) M. Godoi, M. W. Paixão and A. L. Braga,
Dalton Trans., 2011, 40, 11347; d) L. Shao, Y. Li, J. Lu and X.
Jiang, Org. Chem. Front., 2019, 6, 2999; e) S. Chu, H. Cao, T.
Chen, Y. Shi and L. Yu, Catal. Comm., 2019, 129, 105730; f) E.
J. Lenardão, C. Santi and L. Sancineto, in Organoselenium
Compounds as Reagents and Catalysts to Develop New Green
Protocols. Springer: Cham, 2018, pp. 1-98.
3-(Butylselanyl)-2-hexylbenzo[b]selenopheno[2,3-d]thiophene 3o:
Yield: 0.095 g (83%); yellow oil. 1H NMR (CDCl3, 400 MHz)  (ppm) =
7.87-7.84 (m, 1H); 7.71-7.69 (m, 1H); 7.37 (td, J = 7.6, 1.2 Hz, 1H);
7.31 (td, J = 7.6, 1.2 Hz, 1H); 3.15 (t, J = 7.4 Hz, 2H); 2.84 (t, J = 7.4 Hz,
2H); 1.73 (quint, J = 7.4 Hz, 2H); 1.61 (sext, J = 7.4 Hz, 2H); 1.44-1.32
(m, 8H); 0.92-0.85 (m, 6H). 13C NMR (CDCl3, 100 MHz)  (ppm) =
157.5, 146.0, 140.3, 136.2, 129.9, 124.6, 123.9, 123.7, 121.4, 114.3,
33.7, 32.9, 32.7, 31.6, 28.9, 28.3, 22.8, 22.6, 14.1, 13.5. MS (rel. int.,
%) m/z: 458 (M+, 44.4), 400 (20.2), 386 (18.5), 331 (39.6), 321 (46.2),
251 (100.0), 171 (31.7), 41 (42.0). HRMS (APCI-QTOF) calculated
mass for C20H27SSe2 [M+H]+: 459.0161, found: 459.0159.
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