Solvent- and Metal-Free Chalcogenation of Bicyclic Arenes Using I2/DMSO as Non-Metallic Catalytic System

Article abstract of DOI:10.1002/ejoc.201700744

We have developed a green and efficient protocol for the chalcogenation of bicyclic arenes by using I₂/DMSO as catalytic system under solvent- and metal-free conditions. This protocol allows access to several chalcogenated bicyclic arenes throu

Full text of DOI:10.1002/ejoc.201700744

A Journal of
Accepted Article
Title: Solvent- and metal-free chalcogenation of bicyclic arenes using
I2/DMSO as non-metallic catalytic system
Authors: Antonio Luiz Braga, Lais T. Silva, Juliano B. Azeredo, Sumbal
Saba, Jamal Rafique, and Adailton J. Bortoluzzi
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700744
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700744
Supported by

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
Solvent- and metal-free chalcogenation of bicyclic arenes using
I2/DMSO as non-metallic catalytic system
Lais T. Silva,[a] Juliano B. Azeredo,[b] Sumbal Saba,[a],[c] Jamal Rafique,*[a] Adailton J. Bortoluzzi,[a] and
Antonio L. Braga*[a]
Abstract: In this study, we developed a greener and efficient protocol
for the chalcogenylation of bicyclic arenes using the I2/DMSO catalytic
system under solvent- and metal-free conditions. This protocol
allowed access to several chalcogenated bicyclic arenes through
C(sp2)-H bond functionalization, in good to excellent yields, using MW
irradiation or conventional heating.
construction of 1-(arylthio)naphthols have been reported in the
literature.[9] Generally, one of the commen route is through C-H
bond functionalization of α-position of 2-naphthols 1a with
sulfenylating agents. This functionalization may occur through the
photo-induced reaction of 1-bromo-2-naphthol and 2-naphthols
with thiols, via a radical pathway,[10] or through an electrophilic
substitution reaction using sulfenylating agents. Among these
agents, thiols,[11] sodium sulfinates,[12] sulfonyl hydrazides,[13]
disulfides,[14]
organosulfonyl
chlorides[15]
and
N-
Introduction
organoylsuccinimides[16] are commonly used reagents (Scheme
1). Despite the merits of these methods, some of them have
limitations, such as the use of non-green solvents, transition metal
catalysis, additives, malodorous reagents, and pre-functionalized
coupling partners.
Organochalcogen compounds are recognized for their biological
[1]
activity.
In particular, certain enzymes containing selenium
show relevant antioxidant properties. Importantly, some
organochalcogen compounds present mimetic activity of these
enzymes, making them attractive synthetic targets.[2] Furthermore,
organoselenium compounds are widely applied in organic
synthesis, as reagents, in different transformations and in material
sciences.[3]
Similarly, the bicyclic arenes, especially naphthalene
derivatives are present in bioactive compounds, featuring a wide
range of activities such as antihypertensive,[4] anti-inflammatory,[5]
antimicrobial,[6]
anti-malarial[7]
and
anti-HIV.[8]
Several
commercially available drugs also have this moiety in their core
structure, e.g., propranolol, one of the most sold
antihypertensive drugs in the world, naproxen, a non-steroidal
anti-inflammatory & the anti-malarial drug primaquine (Figure 1).
Scheme 1. Reported work.
Recently,
Huang
and
co-workers
reported
the
functionalization of 2-naphthols and 2-naphthylamines using
sulfonyl hydrazides in the presence of an equivalent amount of
iodine and THF as solvent.[13a] However, to the best of our
knowledge, the selenylation of these nuclei has not yet been
explored.
On the other hand, the use of microwave (MW) irradiation in
C−Se and C−S bond formation,[17] can provide higher yields in
shorter reaction times. In addition, sustainable protocols and
solvent-free conditions are attractive alternative in organic
synthesis.[18]
Recently, our group successfully applied an I2/DMSO catalytic
oxidant system in the chalcogenation of various compounds.[19]
Thus, in relation to our continuing interest in the
organochalcogen chemistry, as well as the design of eco-friendly
processes,[19] herein we describe a novel protocol for the
chalcogeno-functionalization of 2-naphthols and derivatives
using a half equivalent of dichalcogenides in the presence of
iodine as a catalyst and an equivalent amount of DMSO as the
oxidant. This method avoids the use of solvents, additives and
transition-metals as well as can be performed under MW
irradiations or conventional heating.
Figure 1. Naphthalene based drug compounds.
Considering the biological relevance of organochalcogen
compounds and the wide spectrum of therapeutic properties of
naphthalene derivatives, few synthetic methods for the
[a] Departamento de Química, Universidade Federal de Santa Catarina
Florianópolis, 88040-900, SC-Brazil
braga.antonio@ufsc.br (ALB), jamal.chm@gmail.com (JR)
Homepage: http://labselen.ufsc.com/
[b] Departamento de Farmácia, Universidade Federal do Pampa,
Uruguaiana, 97500-970, RS-Brazil
[c] Department of chemistry, Shaheed Benazir Bhutto Women University,
Peshawar, 25000, KPK, Pakistan
Supporting information for this article is given via a link at the end of the
document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
Results and Discussion
Subsequently, the influence of the catalyst and the stoichiometric
oxidant on the reaction system was explored (Table 2). Carrying
out the reaction with 5 mol% of iodine afforded the product 3a in
45% yield (entry 1). A constant increase in the yield of 3a was
observed with the increase in catalyst loading (entry 2-4). There
was a slight increase in the yield using 25 mol% of I2 (entry 5),
which led us to select 20 mol%(entry 4) of catalyst for this
transformation. The reaction was ineffective in the absence
of iodine (entry 6).
Subsequently, we investigated the influence of the
oxidant on the reaction. Using 1.0 and 1.5 equivalents of
DMSO, the product 3a was obtained in 64 and 66% yields,
respectively (entries 7 and 8). When the amount of oxidant
was increased to 2 equivalents, the desired product was
obtained in 94% yield (entry 9). In the absence of oxidant,
the yield of 3a dropped to 6%, verifying that the presence of
DMSO is essential in this methodology.
To identify the optimum reaction conditions, 2-naphthol 1a (0.5
mmol) and diphenyl diselenide 2a (0.25 mmol) were selected as
standard substrates, in the presence of I2 (20 mol%) and 3
equivalents of DMSO (Table 1). The performance of the reaction
under different microwave irradiation times was evaluated, at 80
oC with 100 W of power. Carrying out the reaction for 1 min,
compound 3a was obtained in 42% yield (entry 1). An incremental
increase in the yield of 3a was observed with the increase of time
(entry 2-10). When the reaction was performed in 10 min, the
desired product was obtained in 83% yield (entry 5), but on
increasing the time to 15 min the reaction did not show any further
improvement(entry 6).
In the next step, the influence of the temperature and the
microwave power was studied. Decreasing the temperature from
o
80 C, the yield of the 3a decreased (entry 7-8). On performing
Using TBHP and H2O2 instead of DMSO, the yields of 3a
decreased to 7 and 45%, respectively (entries 11 and 12).
Lastly, the reaction was carried out applying conventional
heating in order to assess the influence of the heating
method (entry 13). Under this condition, 3a was obtained in
98% yield after 1 h of reaction. Thus, the methodology can
also be extended to conventional heating.
the reaction at a higher temperature, the yield of 3a did not
change (entry 9 vs 5). Next, the reaction was screened for
different levels of irradiation power (entry 10-11) and 100 W was
observed to be the ideal for this transformation (entry 8 vs 10-11).
In order to evaluate the influence of the heating source, the
reaction was also performed in a conventional oil bath heating
system (entry 12). Reaction under heating for, 1 h afforded 3a in
95% yield, indicating that this protocol can also be extended to
conventional heating.
Table 2. Optimization of Reaction Conditions[a]
Table 1. Optimization of Microwave Parameters[a]
entry
1
I2 (mol%)
Oxidant (equiv.)
DMSO (3)
DMSO (3)
DMSO (3)
DMSO (3)
DMSO (3)
DMSO (3)
DMSO (1)
DMSO (1.5)
DMSO (2)
-
Yield (%)[b]
45
5
entry
power (W)
T (°C)
t (min)
Yield (%)
[b]
2
10
15
20
25
-
59
70
83
85
-
1
2
100
100
100
100
100
100
100
100
100
50
80
80
80
80
80
80
40
60
100
80
80
80
1
2
42
50
51
64
83
83
22
40
83
73
84
95[c]
3
4
3
5
5
4
7
6
5
10
15
10
10
10
10
10
1 h
7
20
20
20
20
20
20
20
64
66
94
6
6
8
7
9
8
10
11
12
13
9
TBHP (3)
H2O2 (3)
7
10
11
12
45
98[c]
150
-
DMSO (2)
[a] Reaction conditions: 1a (0.5 mmol) and 2a (0.25 mmol). [b] Isolated
yields. [c] Conventional heating (oil bath).
[a] Reaction conditions: 1a (0.5 mmol) and 2a (0.25 mmol). [b] Isolated
yields. [c] Conventional heating (oil bath) – 1h.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
disulfide afforded the product 3l in 71% and 79% yields with
microwave and conventional heating, respectively.
After determining the best reaction conditions, the scope
of the protocol was evaluated (Table 3), under the two
heating conditions: microwave and conventional.
The structural variation of the oxygenated naphthalenic
substrates was also examined under our optimized reaction
conditions (Table 4). In general, good results were obtained
in these reactions under conventional heating. Using 2-
methoxynaphthalene as the substrate, the corresponding
product 4a was achieved in 22% yield in 15 min with
microwave, whereas the reaction under conventional heating
in 6 h increased the yield to 75%. Moreover, a decrease in
the yield of the product 4b under both conditions was
observed when 2-ethoxynaphthalene was used as the
substrate, possibly due to the steric hindrance of the ethoxy
group. In addition, a good result was achieved when methoxy
ether, substituted at the 7-position of the naphthalene ring by
a hydroxyl group, was employed in the reaction to furnish the
product 4c. Similarly, 7-bromo-2-naphthol provided the
product 4d in excellent yields using both methods.
The naphthalene nucleus containing an acetal group,
was also employed in order to enlarge the scope of this
transformation. However, the product 4e was obtained in low
yields. Similarly, the reaction of 2a with 5,6,7,8-
tetrahydronaphthalen-2-ol gave the product 4f in 13% yield,
under microwave irradiation and 60% yield under
conventional heating.
In general, good results were obtained for diorganyl
diselenides and disulfides. There were electronic effects of
the substituents on the yield of the desired products. Using
the methyl group in the ortho and para positions of the
diselenide, the corresponding products 3b and 3c were
obtained in good yields, under both conditions. A similar
effect was observed for the methoxy group in the ortho and
para positions of the diselenide. In this case, the results
obtained for the bis(2-methoxyphenyl)-diselenide showed
that the two methods gave similar results for the formation of
3d. However, the preparation of 3e under conventional
heating was more efficient than the microwave irradiations.
Using the bulky diselenide (R
=
1-naphthyl), the
corresponding product 3f was obtained in good yields under
both protocols. Similarly, good results were also achieved
with diaryl diselenides containing electro-withdrawing groups
in the para position e.g. the products containing chlorine and
fluorine 3g and 3h. With the trifluoromethyl group, CF3, in the
meta position, there was a decrease in the formation of 3i
,
under both conditions. Furthermore, the use of an aliphatic
diselenide provided the product 3j in good yields.
Table 3. Variation of dichalcogenides
Table 4. Structural variation of naphthalenic compounds
Further, the protocol was extended to synthesis 1-sulfenyl-
naphthols. Using diphenyl disulfide as substrate, the product 3k
was obtained in 54% yield under microwave heating and 77%
under conventional heating. Similarly, the use of di-para-methyl-
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
To further extend the substrate scope, naphthalen-2-amines
were treated with several dichalcogenides under the optimized
conditions, affording the corresponding products (4g – 4i).
Conventional heating was found to be the best approach
providing 4g in 80% yield from the reaction of naphthalen-2-amine
with diphenyl diselenide. Subsequently, the reaction of 2-
naphthylamine and diaryl disulfides resulted in the corresponding
thiolated products (4j – 4k). In this case, the use of microwave
irradiation was found to be the more efficient method for the
preparation of these compounds. Moreover, the selenylation of
methyl-2-naphthalen-sulfide was performed using diphenyl
diselenide under both conditions. In this case, the product 4l was
obtained in 20 % yield within 30 min of microwave irradiation and
74% yield within 24 h of conventional heating.
To investigate the synthetic utility of this methodology, a
scale-up reaction of 10 mmol was carried out under the optimized
conditions (Scheme 2). Through the reaction of 2-naphthol 1a with
diphenyl diselenide 2a, the product 3a was obtained in 55% yield
after 24 h of reaction under conventional heating. Interestingly,
the reaction under microwave afforded 3a in 80% yield.
Scheme 2. Reactions under scale-up conditions.
The structural assignment of compounds 3a and 4g was
carried out based on NMR analysis and confirmed by X-ray
diffraction,20 which showed the position at which the selenium
atom is connected (Table 3-4).
In order to gain some insight of the reaction mechanism for
this transformation, some controlled experiments were performed
(Scheme 3). The presence of a radical inhibitor (TEMPO, BHT or
hydroquinone) did not hinder the reaction and the product 3a was
obtained in 69, 81 and 66% yields, respectively [eqn (1)]. These
results indicate that the reaction does not proceed through radical
formation. In previous studies by our group,[19] a catalytic amount
of HI was used instead of iodine and the reaction afforded 3a in
69%. This suggests that HI is one of the intermediates of this
transformation [eqn (2)]. The importance of the presence of HI
was demonstrated by the fact that the reaction did not occur [eqn
(3)] when NaI was employed instead of HI.
The results from 2-naphthol and naphthalen-2-amine
motivated us to further extend this protocol to biologically active
bicyclic arenes e.g. quinolone and isoquinoline nuclei, which are
present in the structure of several drugs. The reaction of 3-
hydroxyquinoline, resulted in the corresponding product 5a in
58% under microwave irradiation (in 25 min) and 30% after 6 h
under conventional heating. In case of isoquinoline, the
selenylation was not successful while sulfenylation reaction gave
the corresponding product 5c in good yields with both methods.
Moderated yields were obtained for the selenylation and
sulfenylation of the 3-amino-quinolines to obtain the products 5d
and 5e, respectively.
Furthermore, the reaction of the anti-inflammatory naproxen
with diphenyl diselenide gave the coupled product 5f in moderate
yields with both microwave and conventional heating.
Table 5. Structural variation of biologically active compounds
Scheme 3. Control experiments.
Based on these results and on previous reports,[17,21]
a
mechanism for the chalcogenylation of 2-naphthol can be
proposed (Scheme 4). Initially, the electrophilic chalcogen
species A, RYI (Y=S, Se), is formed through the reaction between
diorganoyl dichalcogenide (RYYR) and the catalyst (I2). The
naphthol nucleophile would then react with the chalcogen atom of
the reactive RYI, at the 1-position, to form species B. This species
would undergo proton elimination in order to provide the expected
product C, with the concomitant formation of HI. Subsequently, HI
would react with DMSO to give the protonated sulfur species D.
This species would undergo water elimination and be instantly
transformed into iodine-dimethyl sulfide adduct E. Lastly, species
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
E
would be transformed into dimethyl sulfide, with the
benchtop FT-IR spectrometer. The melting points were
determined on digital equipment (Microquimica MQRPF-301) with
a heating plate. Column chromatography was conducted using
silica gel (230-400 mesh). Thin layer chromatography (TLC) was
performed using Merck Silica Gel GF254, with 0.25 mm thickness.
For the visualization, TLC plates were either placed under
ultraviolet light or stained with iodine vapor and acidic vanillin.
Most reactions were monitored by TLC for the disappearance of
the starting material.
regeneration of the catalyst (I2), to complete the cycle.
Chemical analysis: Unless otherwise noted, all reactions were
carried out open to the atmosphere. The reagents and solvents
were obtained from commercial suppliers and used without
further purification. All compounds were obtained with heating in
an oil bath or in a microwave reactor. The reactions were carried
out in 10 mL sealed glasses tubes (borosilicate) with a cap and
septum (silicon) in a commercially available CEM monomode
microwave reactor with IR monitoring and a noninvasive pressure
transducer. The yields are based on isolated compounds after
purification.
Scheme 4. Proposed mechanism for the reaction.
The appropriate naphthalene or quinoline (0.5 mmol) together
with diorganyl dichalcogenide (0.25 mmol), iodine (20 mol%, 240
mg) and DMSO (2 equiv., 0.073 mL) were mixed in a glass tube,
which was sealed and placed in a CEM Discover microwave
Conclusions
apparatus.
A maximum irradiation power of 100 W and
In summary, we have developed an effective, greener and
regioselective method for the direct chalcogenylation of
bicyclic arenes. This procedure afforded the desired
products in good to excellent yields under solvent and metal-
free conditions and can be applied using either conventional
heating or microwave irradiation.
The most notable features of this protocol are that it is
conducted under metal-free, solvent-free and mild conditions
open to the air, and short reaction times are achieved under
microwave irradiation. Additionally, with the use of this
optimized protocol we were able to access biologically
important Se/S-containing bicyclic arenes, such as
quinolines and isoquinolines.
temperature of 80 °C were applied, in most cases, for 10 min. The
reaction was also run in a flask under stirring with conventional
heating in an oil bath at 80 °C. The reaction time was monitored
by the disappearance of the starting material by TLC. The reaction
mixture was then dissolved in ethyl acetate or dichloromethane
(20 mL) and washed with 25 mL of an aqueous solution of 10%
Na2S2O4. The organic layer was separated, dried over MgSO4,
and concentrated under reduced pressure. The crude product
was purified by column chromatography over silica gel using a
mixture of hexane/ethyl acetate as the eluent.
1-(phenylselanyl)naphthalen-2-ol (3a): 140.2 mg, yield: 94%
(MW); 146.6 mg, yield: 98% (Conventional heating); yellow solid;
mp 77-78 °C (lit22 77-78 °C); purified with 97:3 hexane/ethyl
acetate. 1H NMR (200 MHz, CDCl3) δ = 8.12 (d, J = 8.9 Hz, 1H),
7.69 (d, J = 8.9 Hz, 1H), 7.61 (d, J = 8.0, 1H), 7.39-7.12 (m, 3H),
7.09-6.84 (m, 6H); 13C NMR (50 MHz, CDCl3) δ = 156.3, 135.8,
132.9, 130.6, 129.5, 129.1, 128.6, 127.9, 126.9, 126.9, 126.6,
123.8, 116.7, 109.1; IR (KBr): ѵ = 3393, 3053, 1566, 1514, 1476,
1462, 1438, 1382, 1195, 826 cm-1; HRMS (APPI+) m/z calculated
for C16H13OSe [M+H] 300.0048, found 300.0052.
Experimental Section
General Procedure: Proton nuclear magnetic resonance spectra
(1H NMR) and carbon-13 nuclear magnetic resonance spectra
(13C NMR) were obtained at 400 MHz or 100 MHz on a Varian
Mercury Plus and 200 MHz or 50 MHz on a Bruker AC-200 NMR
spectrometer. Spectra were recorded in CDCl3. Chemical shifts
(δ) are reported in ppm, referenced to the solvent (CDCl3) peak
with tetramethylsilane (TMS) as the external reference. The H1
NMR data reported are the chemical shift (δ), multiplicity, coupling
constant (J) in Hertz and integrated intensity. Abbreviations to
denote the multiplicity of a particular signal are: singlet (s), doublet
(d), triplet (t), quartet (q), quintet (quint), sextet (sext) and multiplet
(m). High-resolution mass spectra were recorded on a Bruker
micrOTOF-Q II mass spectrometer, using APPI and APCI as
ionization sources, equipped with an automatic syringe pump for
sample injection. Infrared spectra (FT-IR) reporting the frequency
of absorption (cm-1) were recorded on a Bruker Optics Alpha
1-(o-tolylselanyl)naphthalen-2-ol (3b): 129.5 mg, yield: 83%
(MW); 129.5, yield: 83% (Conventional heating); brown solid; mp
1
77-79 °C; purified with 98:2 hexane/ethyl acetate. H NMR (400
MHz, CDCl3) δ = 8.17 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.9 Hz, 1H),
7.74 (d, J = 8.0 Hz, 1H), 7.42 (ddd, J = 8.3, 6.9, 1.5 Hz, 1H), 7.35-
7.25 (m, 2H), 7.10 (d, J = 7.4 Hz, 1H), 6.98 (m, 2H), 6.75 (ddd, J
= 8.0, 7.73, 0.72 Hz, 1H), 6.53 (d, J = 7.9 Hz, 1H), 2.49 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3) δ = 156.7, 136.9, 136.1, 132.9,
131.2, 130.4, 129.6, 128.6, 128.0, 127.8, 127.1, 127.0, 126.4,
123.9, 116.7, 108.0, 21.56 (CH3); IR (KBr): ѵ = 3379, 3063, 1594,
1566, 1514, 1454, 1396, 1378, 1201, 823, 750 cm-1; HRMS
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
(APPI+) m/z calculated for C17H15OSe [M+H] 314.02050, found
314.02046.
1-(4-fluorophenylselanyl)naphthalen-2-ol (3g): 114.1 mg,
yield: 72% (MW); 131.5 mg, yield: 83% (Conventional heating);
brown solid; mp 87-89 °C; purified with 97:3 hexane/ethyl acetate.
1H NMR (200 MHz, CDCl3) δ = 8.23 (d, J = 8.5 Hz, 1H), 7.81 (d,
J = 8.9 Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.46 (ddd, J = 8.4, 6.9,
1.4 Hz, 1H), 7.37-7.23 (m, 2H), 7.19-6.98 (m, 3H), 6.87-6.65 (m,
2H); 13C NMR (50 MHz, CDCl3) δ = 162.0 (d, JC-F = 250 Hz), 156.2,
135.7, 132.9, 131.2 (d, JC-F = 7.8 Hz), 129.6, 128.3 (d, JC- = 28.6
Hz), 126.8, 125.0 (d, JC-F = 3.3 Hz), 123.9, 116.9, 116.7, 116.4,
109.5; IR (KBr): ѵ = 3402, 3350, 3061, 1596, 1484, 1461, 1387,
1220, 827, 754 cm-1; HRMS (APPI+) m/z calculated for
C16H11FOSe [M] 317.9954, found 317.9951.
1-(p-tolylselanyl)naphthalen-2-ol (3c): 109.5 mg, yield: 70%
(MW); 103.3 mg, yield: 66% (Conventional heating); brown solid;
1
mp 54-55 °C; purified with 97:3 hexane/ethyl acetate. H NMR
(400 MHz, CDCl3) δ = 8.27 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.9 Hz,
1H), 7.72 (d, J = 8.0 Hz, 1H), 7.44 (ddd, J = 8.10, 7.43, 0.78 Hz,
1H), 7.27- 7.33 (m, 2H), 7.15 (s, 1H), 7.04 (d, J = 8.0 Hz, 2H),
6.88 (d, J = 8.0 Hz, 2H), 2.16 (s, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ = 156.1, 136.7, 135.8, 132.7, 130.3, 129.5, 129.5, 128.5,
127.9, 126.9, 126.8, 123.7, 116.6, 109.6, 20.9 (CH3); IR (KBr): ѵ
= 3360, 3050, 1596, 1464, 1460, 1457, 1384, 1381, 1199, 809
cm-1; HRMS (APPI+) m/z calculated for C17H15OSe [M+H]
314.0205, found 314.0208.
1-(4-chlorophenylselanyl)naphthalen-2-ol (3h): 133.5 mg,
yield: 80% (MW); 135.2 mg, yield: 81% (Conventional heating);
brown solid, mp 98-99 °C; purified with 97:3 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = 8.20 (d, J = 8.5 Hz, 1H), 7.86 (d,
J = 8.9 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.5-7.43 (m, 1H), 7.37-
7.32 (m, 2H), 7.14-6.97 (m, 5H); 13C NMR (100 MHz, CDCl3) δ =
156.3, 135.6, 133.1, 132.8, 130.4, 129.6, 129.5, 128.8, 128.7,
128.2, 126.8, 123.9, 116.7, 108.8; IR (KBr): ѵ = 3364, 3058, 1593,
1568, 1475, 1436, 1384, 1196, 820, 754 cm-1; HRMS (APPI+) m/z
calculated for C16H11ClOSe [M] 333.9656, found 333.9654.
1-(4-methoxyphenylselanyl)naphthalen-2-ol (3d): 105.2 mg,
yield: 64% (MW); 113.5 mg, yield: 69% (Conventional heating);
yellow solid; mp 74-76 °C; purified with 94:6 hexane/ethyl acetate.
1H NMR (200 MHz, CDCl3) δ = 8.30 (d, J = 8.4 Hz, 1H), 7.79 (d,
J = 8.9 Hz, 1H), 7.72 (d, J = 8.2, 1H), 7.46 (ddd, J = 8.4, 6.9, 1.4
Hz, 1H), 7.37-7.24 (m, 2H), 7.23-7.05 (m, 3H), 6.71-6.55 (m, 2H),
3.62 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) δ = 159.0, 155.9,
135.8, 132.5, 131.6, 130.6, 129.5, 128.5, 127.9, 127.0, 123.7,
120.6, 116.6, 115.3, 110.5, 98.8, 55.3 (OCH3); IR (KBr): ѵ = 3347,
3061, 1617, 1592, 1491, 1457, 1349, 1248, 1179, 827 cm-1;
HRMS (APPI+) m/z calculated for C17H15O2Se [M+H] 330.01542,
found 330.01541.
1-(4-(trifluoromethyl)phenylselanyl)naphthalen-2-ol
(3i):
108.2 mg, yield: 59% (MW); 102.7 mg, yield: 56% (Conventional
heating); brown solid, mp 75-76 °C; purified with 98:2
hexane/ethyl acetate. 1H NMR (400 MHz, CDCl3) δ = 8.19 (d, J =
8.5 Hz, 1H), 7.88 (d, J = 8.9 Hz, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.55
– 7.45 (m, 2H), 7.39-7.32 (m, 3H), 7.17-7.08 (m, 2H), 7.01 (s, 1H);
13C NMR (50 MHz, CDCl3) δ = 156.5, 135.7, 133.4, 132.1, 130,4
(q, JC-F = 33.07), 129.9, 129.6, 128.7, 128.3, 126.6, 125.77 (q, JC-
F = 3.5 Hz), 124.1, 123.7 (q, JC-F = 271.5), 123.5 (q, JC-F = 3.5 Hz),
120.9, 116.8, 108.1; IR (KBr): ѵ = 3371, 3057, 1596, 1464, 1390,
1328, 1161, 1123, 827, 106 cm-1; HRMS (APPI+) m/z calculated
for C17H11F3OSe [M] 367.9922, found 367.9917.
1-(2-methoxyphenylselanyl)naphthalen-2-ol (3e): 62.5 mg,
yield: 38% (MW); 138.1 mg, yield: 84% (Conventional heating);
red solid; mp 58-60 °C; purified with 94:6 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = 8.26 (d, J = 8.5 Hz, 1H), 7.86 (d,
J = 8.9 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.46 (ddd, J = 8.4, 6.9,
1.3 Hz, 1H), 7.38-7.30 (m, 2H), 7.17 (s, 1H), 7.13-7.08 (m, 1H),
6.83 (dd, J = 8.2, 1.0 Hz, 1H), 6.64-6.55 (m, 2H), 3.94 (s, 3H,
OCH3); 13C NMR (100 MHz, CDCl3) δ = 157.3, 156.9, 136.4, 132.7,
129.6, 129.4, 128.6, 127.9, 127.8, 127.1, 123.8, 122.0, 119.4,
116.8, 110.7, 107.5, 56.1 (OCH3); IR (KBr): ѵ = 3357, 3050, 1596,
1575, 1474, 1388, 1276, 1127, 813, 747 cm-1; HRMS (APPI+) m/z
calculated for C17H15O2Se [M+H] 330.0154, found 330.0155.
1-(butylselanyl)naphthalen-2-ol (3j): 54.5 mg, yield: 39% (MW);
58.6 mg, yield: 42% (Conventional heating); brown oil; purified
with hexane. 1H NMR (400 MHz, CDCl3) δ = 8.33 (d, J = 8.5 Hz,
1H), 7.80- 7.74 (m, 2H), 7.53 (ddd, J = 8.21, 6.99, 1.17 Hz, 1H),
7.35 (ddd, J = 8.17, 7.08, 1.0 Hz, 1H), 7.27 (m, 2H), 2.69 (t, J =
7.3 Hz, 2H, CH2), 1,57 (quint, J = 7.43, 2H, CH2). 1.36 (sext, J =
4.48, 2H, CH2), 0.84 (t, J = 7.3 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ = 155.9, 135.9, 131.7, 129.4, 128.6, 127.5, 126.9, 123.6,
116.2, 109.9, 32.4(CH2), 28.8(CH2), 22.7(CH2), 13.4 (CH3); IR
(KBr): ѵ = 3357, 3058, 2960, 2946, 2870, 1617, 1596, 1516, 1464,
1388, 1349, 1203, 820, 754 cm-1; HRMS (APPI+) m/z calculated
for C14H16OSe [M] 280.0361, found 280.0359.
1-(naphthalen-1-ylselanyl)naphthalen-2-ol (3f): 144.5 mg,
yield: 83% (MW); 118.5 mg, yield: 68% (Conventional heating);
brown solid; mp 141-142 °C; purified with 97:3 hexane/ethyl
acetate. 1H NMR (400 MHz, CDCl3) δ = 8.27 (d, J = 8.4 Hz, 1H),
8.21 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.9 Hz, 1H), 7.78 (t, J = 8.0
Hz, 2H), 7.64-7.55 (m, 2H), 7.50 (t, J = 7.5 Hz, 1H), 7.44-7.28 (m,
3H), 7.07 (s, 1H), 7.01 (t, J = 7.8 Hz, 1H), 6.77 (d, J = 7.3 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ = 156.9, 136.2, 134.2, 133.1, 132.6,
129.7, 129.3, 128.9, 128.6, 128.1, 127.1, 126.9, 126.8, 126.4,
1-(phenylthio)naphthalen-2-ol (3k): 68.0 mg, yield: 54% (MW);
126.3, 126.2, 125.3, 123.9, 117.0, 108.0; IR (KBr): ѵ = 3364, 3051, 97.0 mg, yield: 77% (Conventional heating); white solid, mp 62-
1617, 1600, 1564, 1502, 1460, 1384, 1199, 772 cm-1; HRMS
(APPI+) m/z calculated for C20H15OSe [M+H] 350.0205, found
350.0207.
63 °C (lit23 61.5-62.5°); purified with 99:1 hexane/ethyl acetate. 1H
NMR (400 MHz, CDCl3) δ = 8.20 (d, J = 8.4 Hz, 1H), 7.85 (d, J =
8.9 Hz, 1H), 7.76 (d, J = 7.9 Hz, 1H), 7.5-7.42 (m, 1H), 7.40-7.26
(m, 2H), 7.19 (s, 1H), 7.09 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
= 157.08, 135.66, 135.44, 132.91, 129.55, 129.25, 128.66,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
128.04, 126.42, 125.95, 124.77, 123.95, 116.86, 108.06; IR (KBr):
ѵ = 3381, 3061, 1596, 1474, 1460, 1391, 1206, 1126, 824, 740
cm-1; HRMS (APPI+) m/z calculated for C16H13OS [M+H]
253.0682, found 253.0685.
7-bromo-1-(phenylselanyl)naphthalen-2-ol (4d): 154.9 mg,
yield: 82% (MW); 170.1 mg, yield: 90% (Conventional heating);
yellow solid; mp 79-80 °C; purified with 98:2 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = 8.43 (s, 1H), 7.76 (d, J = 8.9 Hz,
1H), 7.57 (d, J = 8.6 Hz, 1H), 7.38 (dd, J = 8.6, 1.9 Hz, 1H), 7.30
(d, J = 8.9 Hz, 1H), 7.13 (s, 1H), 7.10 (s, 5H); 13C NMR (100 MHz,
CDCl3) δ = 157.0, 137.3, 132.7, 130.2, 129.6, 129.5, 129.3, 129.2,
127.9, 127.3, 126.9, 122.8, 116.9, 108.5; IR (KBr): ѵ = 3654, 3063,
1580, 1507, 1475, 1271, 1149, 815, 746, 527 cm-1; HRMS
(APPI+) m/z calculated for C16H11BrOSe [M] 377.9150, found
377.9151.
1-(p-tolylthio)naphthalen-2-ol (3l): 94.4 mg, yield: 71% (MW);
105.1 mg, yield: 79% (Conventional heating); white solid, mp 73-
74 °C (lit23 61.5-63.5°); purified with 97:3 hexane/ethyl acetate. 1H
NMR (400 MHz, CDCl3) δ = 8.22 (d, J = 8.5 Hz, 1H), 7.84 (d, J =
8.9 Hz, 1H, 7.76 (d, J = 8.10 Hz, 1H), 7.45 (ddd, J = 8.3, 6.9, 1.5
Hz, 1H), 7.37-7.27 (m, 2H), 7.22 (s, 1H), 6.93 (s, 4H), 2.20 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3) δ = 157.02, 135.99, 135.61,
132.72, 131.91, 130.06, 129.63, 128.65, 127.97, 126.87, 124.88,
123.89, 116.97, 108.93, 20.96 (CH3); IR (KBr): ѵ = 3399, 3061,
3022, 1596, 1620, 1464, 1258, 1203, 823, 754 cm-1.
4-(phenylselanyl)naphtho[2,3-d][1,3]dioxole (4e): 24.5 mg,
yield: 15% (MW); 40.9 mg, yield: 25% (Conventional heating);
yellow solid; mp 63-64 °C; purified with 98:2 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = δ 8.28 (dd, J = 6.0, 3.5 Hz, 1H),
7.67 (dd, J = 6.1, 3.3 Hz, 1H), 7.38-7.34 (m, 2H), 7.26-7.21 (m,
2H), 7.18 (s, 1H), 7.17-7.10 (m, 3H), 6.07 (s, 2H, OCH2O); 13C
NMR (100 MHz, CDCl3) δ = 151.2, 146.5, 131.8, 131.2, 130.2,
129.9, 129.3, 127.7, 127.1, 126.4, 125.6, 125.1, 105.9, 102.9,
101.2 (OCH2O); IR (KBr): ѵ = 3072, 1600, 1572, 1474, 1318, 1241,
1049, 837, 730 cm-1; HRMS (APPI+) m/z calculated for
C17H12O2Se [M] 327.9998, found 327.9998.
(2-methoxynaphthalen-1-yl)(phenyl)selane (4a): 34.4 mg,
yield: 22% (MW); 117.3 mg, yield: 75% (Conventional heating);
yellow solid, mp 89-90 °C (lit24 pale yellow liquid); purified with
98:2 hexane/ethyl acetate. 1H NMR (400 MHz, CDCl3) δ = 8.36 (d,
J = 7.4 Hz, 1H), 7.75 (d, J = 9.0 Hz, 1H), 7.63 (d, J = 8.1 Hz, 1H),
7.34-7.28 (m, 1H), 7.23-7.17 (m, 1H), 7.14 (d, J = 9.0 Hz, 1H),
7.06-7.01 (m, 2H), 6.98-6.86 (m, 3H), 3.73 (s, 3H, OCH3); 13C
NMR (100 MHz, CDCl3) δ = 158.8, 136.5, 133.3, 131.9, 129.8,
129.4, 128.9, 128.3, 127.9, 127.7, 125.7, 124.1, 113.6,
29.8(OCH3); IR (KBr): ѵ = 3447, 3058, 1617, 1589, 1502, 1464,
1443, 1353, 1335, 1269, 1064, 1022, 810, 744 cm-1; HRMS
(APPI+) m/z calculated for C17H14OSe [M] 314.0205, found
314.0210.
(4a,5,6,7,8,8a-hexahydronaphthalen-1-yl)(phenyl)selane (4f):
19.7 mg, yield: 13% (MW); 90.9 mg, yield: 60% (Conventional
1
heating); red oil; purified with 9:1 hexane/ethyl acetate. H NMR
(400 MHz, CDCl3) δ = 7.25-7.06 (m, 5H), 6.91 (d, J = 8.3 Hz, 1H),
6.67 (s, 1H), 2.81 (t, J = 5.7 Hz, 2H, CH2), 2.71 (t, J = 5.7 Hz, 2H,
CH2), 1.76-1.65 (m, 4H, 2CH2); 13C NMR (100 MHz, CDCl3) δ =
155.2, 142.0, 132.9, 130.8, 130.3, 129.6, 129.0, 126.6, 116.0,
112.3, 30.9(CH2), 29.6(CH2), 23.6(CH2), 22.9 (CH2); IR (KBr): ѵ =
3392, 3061, 1586, 1474, 1468, 1440, 1304, 1206, 816, 737 cm-1;
HRMS (APPI+) m/z calculated for C16H17OSe [M+H] 304.0361,
found 304.0362.
(2-ethoxynaphthalen-1-yl)(phenyl)selane (4b): Reaction at
0.25 mmol of 2-ethoxynaphthalene and 0.13 mmol of diphenyl
diselenide. 14.5 mg, yield: 18% (MW); 48.2 mg, yield: 59%
(Conventional heating); yellow solid, mp 49-50 °C; purified with
1
98:2 hexane/ethyl acetate. H NMR (400 MHz, CDCl3) δ = 8.49
(d, J = 8.1 Hz, 1H), 7.90 (d, J = 9.0 Hz, 1H), 7.79 (d, J = 8.1 Hz,
1H), 7.48 (ddd, J = 8.4, 6.8, 1.3 Hz, 1H), 7.36 (ddd, J = 8.0, 6.8,
1.1 Hz, 1H), 7.30 (d, J = 9.0 Hz, 1H), 7.24-7.17 (m, 2H), 7.15- 7.05
(m, 3H), 4.15 (q, J = 7.0 Hz, 2H, OCH2), 1.29 (t, J = 7.0 Hz, 3H,
CH3); 13C NMR (100 MHz, CDCl3) δ = 158.2, 136.6, 133.6, 131.7,
129.9, 128.9, 128.3, 128.0, 127.6, 125.8, 124.2, 119.1, 115.1,
114.4, 65.9(OCH2), 14.9 (CH3); IR (KBr): ѵ = 3067, 1580, 1476,
1462, 1455, 1375, 1263, 1059, 805, 732 cm-1; HRMS (APPI+) m/z
calculated for C18H16OSe [M] 328.0362, found 328.0361.
1-(phenylselanyl)naphthalen-2-amine (4g): 74.5 mg, yield:
50% (MW); 119.3 mg, yield: 80% (Conventional heating); brown
red solid; mp 75-76 °C; purified with 97:3 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = 8.31 (d, J = 8.5 Hz, 1H), 7.72 (d,
J = 8.8, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.41 (ddd, J = 8.4, 6.9, 1.5
Hz, 1H), 7.26-7.20 (m, 1H), 7.15-7.06 (m, 5H), 7.03 (d, J = 8.7 Hz,
1H), 4.70 (s, 2H); 13C NMR (100 MHz, CDCl3) δ = 148.1, 137.0,
131.9, 131.8, 129.3, 128.7, 128.4, 128.4, 127.9, 126.7, 125.9,
122.6, 117.4, 105.5; IR (KBr): ѵ = 3381, 3065, 1613, 1558, 1474,
1064, 816, 733 cm-1; HRMS (APPI+) m/z calculated for
C16H14NSe [M+H] 300.0286, found 300.0287.
7-methoxy-1-(phenylselanyl)naphthalen-2-ol (4c): 59.3 mg,
yield: 36% (MW); 146.5 mg, yield: 89% (Conventional heating);
little purple; mp 82-83 °C; purified with 93:7 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = 7.76 (d, J = 8.8 Hz, 1H), 7.65 (d,
J = 8.8 Hz, 1H), 7.59 (d, J = 2.3 Hz, 1H), 7.22-7.06 (m, 7H), 6.98
(dd, J = 8.8, 2.4 Hz, 1H), 3.80 (s, 3H, OCH3); 13C NMR (100 MHz,
CDCl3) δ = 159.6, 156.9, 137.7, 132.5, 130.5, 130.2, 129.5, 129.4,
126.8, 124.8, 116.0, 114.0, 108.5, 106.3, 55.4 (OCH3); IR (KBr):
ѵ = 3358, 3053, 1614, 1475, 1458, 1423, 1375, 1278, 1218, 840,
732 cm-1; HRMS (APPI+) m/z calculated for C17H15O2Se [M+H]
331.0232, found 331.0230.
1-(4-chlorophenylselanyl)naphthalen-2-amine (4h): 97.9 mg,
yield: 59% (MW); 104.6 mg, yield: 63% (Conventional heating);
brown solid; mp 64-65 °C; purified with 97:3 hexane/ethyl acetate.
1H NMR (400 MHz, CDCl3) δ = 8.25 (d, J = 8.5 Hz, 1H), 7.70 (d,
J = 8.8 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.40 (ddd, J = 8.4, 6.9,
1.3 Hz, 1H), 7.23 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.06-7.00 (m,
4H), 6.99 (d, J = 8.8 Hz, 1H), 4.67 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ = 148.2, 136.8, 132.1, 131.9, 130.2, 130.1, 129.4, 128.5,
128.4, 127.9, 126.4, 122.7, 117.5, 105.2; IR (KBr): ѵ = 3392, 3058,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
1617, 1505, 1471, 1011, 813, 750 cm-1; HRMS (APPI+) m/z
calculated for C16H13ClNSe [M+H] 333.9894, found 333.9888.
1H), 7.60-7.49 (m, 2H), 7.26-7.08 (m, 6H), 13C NMR (50 MHz,
CDCl3) δ = 151.2, 143.9, 142.2, 130.3, 130.2, 129.9, 129.8, 129.2,
128.5, 127.4, 126.9, 126.9, 118.6; IR (KBr): ѵ = 3653, 3057, 1655,
1-(4-methoxyphenylselanyl)naphthalen-2-amine (4i): 83.2 mg, 1587, 1475, 1331, 1269, 761, 736 cm-1; HRMS (APPI+) m/z
yield: 52% (MW); 108.8 mg, yield: 68% (Conventional heating);
brown red solid; mp 89-90 °C; purified with 98:2 hexane/ethyl
acetate. 1H NMR (400 MHz, CDCl3) δ = 8.37 (d, J = 8.5 Hz, 1H),
7.73-7.67 (m, 2H), 7.43 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.27-7.22
(m, 1H), 7.16 – 7.11 (m, 2H), 7.04 (d, J = 8.7 Hz, 1H), 6.72 – 6.67
(m, 2H), 4.75 (s, 2H), 3.70 (s, 3H, OCH3); 13C NMR (100 MHz,
CDCl3) δ = 158.6, 158.4, 147.9, 137.0, 131.6, 130.9, 128.4, 127.8,
126.8, 122.6, 121.9, 117.5, 115.2, 107.0, 55.4 (OCH3); IR (KBr):
ѵ = 3437, 3051, 1614, 1492, 1464, 1248, 1026, 820, 758 cm-1;
HRMS (APPI+) m/z calculated for C17H16NOSe [M+H] 329.0314,
found 329.0313.1
calculated for C15H12NOSe [M+H] 302.0079, found 302.0077.
4-(phenylthio)isoquinolin-3-ol (5c): 82.2 mg, yield: 65% (MW);
82.2 mg, yield: 65% (Conventional heating); yellow solid, mp 121-
1
122 °C; purified with 80:20 hexane/ethyl acetate. H NMR (400
MHz, CDCl3) δ = 8.68 (s, 1H), 8.20-8.16 (m, 1H), 7.72-7.68 (m,
1H), 7.54 (ddd, J = 8.8, 6.7, 1.3 Hz, 1H), 7.26-7.11 (m, 5H), 7.10-
7.02 (m, 1H); 13C NMR (100 MHz, CDCl3) δ = 162.6, 147.4, 144.1,
137.1, 133.4, 129.1, 129.0, 126.8, 125.4, 124.3, 123.9, 122.2,
106.6; IR (KBr): ѵ = 3400, 3050, 2925, 1624, 1481, 1439, 1342,
1150, 754 cm-1; HRMS (APCI+) m/z calculated for C15H12NOS
[M+H] 254.0634, found 254.0635.
1-(phenylthio)naphthalen-2-amine (4j): 123.7 mg, yield: 99%
(MW); 73.8 mg, yield: 59% (Conventional heating); brown solid,
mp 64-65 °C (lit25 73.4-74.8 °C); purified with 97:3 hexane/ethyl
acetate. 1H NMR (400 MHz, CDCl3) δ = 8.26 (d, J = 8.5 Hz, 1H),
7.71-7.65 (m, 2H), 7.39 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.22 (ddd,
J = 8.0, 6.9, 1.1 Hz, 1H), 7.16-7.06 (m, 2H), 7.04-6.97 (m, 3H),
6.95 (d, J = 8.8 Hz, 1H), 4.63 (s, 2H); 13C NMR (100 MHz, CDCl3)
δ = 148.6, 136.9, 136.8, 131.9, 129.1, 128.5, 128.5, 127.9, 126.0,
125.1, 124.3, 122.7, 117.7, 104.7; IR (KBr): ѵ = 3399, 3305, 3169,
3050, 1617, 1474, 1349, 820, 740 cm-1; HRMS (APPI+) m/z
calculated for C16H14NS [M+H] 252.0841, found 252.0842.
4-(phenylselanyl)quinolin-3-amine (5d): 39.0 mg, yield: 26%
(MW); 58.5 mg, yield: 39% (Conventional heating); golden solid,
mp 153-154 °C; purified with 80:20 hexane/ethyl acetate. 1H NMR
(400 MHz, CDCl3) δ = 8.59 (s, 1H), 8.27-8.23 (m, 1H), 8.01-7.97
(m, 1H), 7.51-7.43 (m, 2H), 7.20-7.13 (m, 5H), 4.69 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ = 142.9, 142.8, 142.2, 131.2, 130.2,
129.9, 129.7, 129.6, 128.3, 126.8, 126.5, 125.6, 114.3; IR (KBr):
ѵ = 3442, 3309, 3055, 2922, 1610, 1474, 1150, 765, 734 cm-1;
HRMS (APCI+) m/z calculated for C15H13N2Se [M+H] 301.02389,
found 301.02390.
1-(p-tolylthio)naphthalen-2-amine (4k): 128.5 mg, yield: 97%
(MW); 108.6 mg, yield: 82% (Conventional heating); white solid,
mp 73-74 °C (lit23 72.5-73.5 °C); purified with 97:3 hexane/ethyl
acetate. 1H NMR (400 MHz, CDCl3) δ = 8.28 (d, J = 8.5 Hz, 1H),
7.74 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.43 (ddd, J =
8.4, 6.9, 1.3 Hz, 1H), 7.25 (ddd, J = 8.0, 5.7, 1.1 Hz, 1H), 7.04 (d,
J = 8.8 Hz, 1H), 6.99-6.90 (m, 4H), 4.70 (s, 2H), 2.23 (s, 3H, CH3);
13C NMR (100 MHz, CDCl3) δ = 148.5, 136.9, 135.0, 133.4, 131.8,
129.9, 128.6, 128.5, 127.9, 126.3, 124.5, 122.7, 117.8, 105.6,
20.9(CH3); IR (KBr): ѵ = 3475, 3370, 3054, 1620, 1471, 1429,
1356, 1081, 806, 750 cm-1; HRMS (APPI+) m/z calculated for
C17H16NS [M+H] 266.0998, found 266.1002.
4-(phenylthio)quinolin-3-amine (5e): 41.6 mg, yield: 33% (MW);
56.7 mg, yield: 45% (Conventional heating); golden solid, mp 157-
1
158 °C; purified with 80:20 hexane/ethyl acetate. H NMR (400
MHz, CDCl3) δ = 8.62 (s, 1H), 8.25-8.20 (m, 1H), 8.03-7.98 (m,
1H), 7.51-7.44 (m, 2H), 7.21-7.16 (m, 2H), 7.14-7.09 (m, 1H),
7.07-7.03 (m, 2H), 4.69 (s, 2H); 13C NMR (100 MHz, CDCl3) δ =
143.1, 142.9, 142.7, 134.8, 130.8, 129.8, 129.3, 128.3, 126.9,
126.0, 125.6, 124.2, 113.9; IR (KBr): ѵ = 3447, 3322, 3061, 1699,
1614, 1579, 1475, 768, 740 cm-1; HRMS (APCI+) m/z calculated
for C15H13N2S [M+H] 253.0794, found 253.0796.
(S)-2-(6-methoxy-5-(phenylselanyl)naphthalen-2-yl)
propanoic acid (5f): 19.2 mg, yield: 10% (MW); 38.4 mg, yield:
20% (Conventional heating); pale yellow solid, mp 125-126 °C;
purified with 80:20 hexane/ethyl acetate. 1H NMR (400 MHz,
CDCl3) δ = 8.44 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 9.1 Hz, 1H), 7.70
(s, 1H), 7.43 (dd, J = 8.9, 1.5 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H),
7.23-6.99 (m, 6H), 3.91 (s, 3H, OCH3), 3.91 (d, J = 7.1, 1H, CH),
1.57 (d, J = 7.1 Hz, 3H, CH3); 13C NMR (50 MHz, CDCl3) δ =
180.3, 158.9, 135.9, 135.5, 133.2, 131.9, 129.8, 129.6, 129.1,
128.6, 127.6, 126.7, 125.8, 113.9, 113.1, 57.2 (OCH3), 45.2 (CH),
18.2 (CH3); IR (KBr): ѵ = 3068, 2934, 1704, 1593, 1475, 1461,
1440, 1380, 1067, 802, 737 cm-1; HRMS (APPI+) m/z calculated
for C20H18O3Se [M] 386.0417, found 386.0419.
methyl(1-(phenylselanyl)naphthalen-2-yl)sulfane (4l): 32.9
mg, yield: 20% (MW); 121.7 mg, yield: 74% (Conventional
heating); yellow solid, mp 73-74 °C; purified with hexane. 1H NMR
(400 MHz, CDCl3) δ = 8.47 (d, J = 8.5 Hz, 1H), 7.84 (d, J = 8.8
Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.44 (ddd, J = 8.4, 6.9, 1.3 Hz,
1H), 7.39-7.31 (m, 2H), 7.18-7.02 (m, 5H), 2.44 (s, 3H, SCH3); 13
C
NMR (100 MHz, CDCl3) δ = 146.0, 136.1, 132.5, 131.4, 130.8,
129.4, 129.2, 128.5, 127.9, 127.9, 126.0, 125.3, 124.0, 122.2,
16.7(SCH3); IR (KBr): ѵ = 3058, 2915, 1579, 1474, 1435, 1384,
900, 855, 731, 689 cm-1; HRMS (APPI+) m/z calculated for
C17H14SSe [M] 329.9976, found 329.9978.
4-(phenylselanyl)quinolin-3-ol (5a): 87.1 mg, yield: 58% (MW);
45.0 mg, yield: 30% (Conventional heating); yellow solid, mp 110-
111 °C; purified with 80:20 hexane/ethyl acetate. H NMR (200
Acknowledgements
1
MHz, CDCl3) δ = 8.85 (s, 1H), 8.27-8.17 (m, 1H), 8.12-8.04 (m,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
[7]
a) Y. F. Hallock, K. P. Manfredi, J. W. Blunt, J. H. Cardellina II, M.
Schäffer, K.-P. Gulden, G. Bringmann, A. Y. Lee, J. Clardy, G. François,
M. R. Boyd, J. Org. Chem. 1994, 59, 6349-6355; b) M. J. Araújo, J. Bom,
R. Capela, C. Casimiro, P. Chambel, P. Gomes, J. Iley, F. Lopes, J.
Morais, R. Moreira, E. de Oliveira, V. do Rosário, N. Vale, J. Med. Chem.
2005, 48, 888-892; c) P. F. Salas, C. Herrmann, C. Orvig, Chem. Rev.
2013, 113, 3450-3492.
We gratefully acknowledge CAPES, CNPq, CERSusChem
GSK/FAPESP (grant 2014/50249-8), INCT-Catálise, FAPESC-
Pronex, HEC-SRGP-161, and FINEP for financial support. CNPq
is also acknowledged for the doctorate fellowship received by
L.T.S. Authors are also thankful to CEBIME for HRMS analysis.
[8]
[9]
M. R. Boyd, Y. F. Hallock, J. H. Cardellina II, K. P. Manfredi, J. W. Blunt,
J. B. McMahon, R. W. Buckheit, G. Bringmann, M. Schäffer, G. M. Cragg,
D. W. Thomas, J. G. Jato, J. Med. Chem. 1994, 37, 1740-1745.
a) M. Giampieri, A. Balbi, M. Mazzei, P. La Colla, C. Ibba, R. Loddo,
Antiviral Res. 2009, 83, 179-185; b) M. Kidwai, S. Saxena, M. K. R. Khan,
S. S. Thukral, Bioorg. Med. Chem. Lett. 2005, 15, 4295-4298; c) G. Liu,
J. R. Huth, E. T. Olejniczak, R. Mendoza, P. DeVries, S. Leitza, E. B.
Reilly, G. F. Okasinski, S. W. Fesik, T. W. von Geldern, J. Med. Chem.
2001, 44, 1202-1210; d) A. Y. Shen, C. T. Tsai, C. L. Chen, Eur. J. Med.
Chem. 1999, 34, 877-882.
Keywords: organochalcogen • selenite • green chemistry •
solvent free • microwave
[1]
a) Organoselenium Compounds: Their Chemistry and Biology, Vol. 1
(Eds.: D. L. Klayman, H. H. Günter), Wiley-Interscience, New York, 1973.
b) G. Dias, R. M. De Almeida, T. Moraes, H. J. Sudati, F. Dobrachinski,
S. Pavin, F. A. A. Soares, C. W. Nogueira, N. B. V. Barbosa, Physiol.
Behav. 2014, 124, 116-122; c) B. M. Gai, C. F. Bortolatto, C. A. Brꢀning,
V. A. Zborowski, A. L. Stein, G. Zeni, C. W. Nogueira, Neuropharm. 2014,
79, 580-589; d) M. A. Hort, M. R. Straliotto, P. M. Netto, J. B. T. da Rocha,
A. F. de Bem, R. M. Ribeiro-do-Valle, Cardiovasc. Pharmacol. 2011, 58,
91-101; e) C. W. Nogueira, G. Zeni, J. B. T. da Rocha, Chem. Rev, 2004,
104, 6255-6286; f) E. R. T. Tiekink, Dalton Trans. 2012, 41, 6390-6395;
g) J. Rafique, R. F. S. Canto, S. Saba, F. A. R. Barbosa, A. L. Braga,
Curr. Org. Chem. 2016, 20, 166-188. h) A. L. Braga and J. Rafique, in
The Chemistry of Organic Selenium and Tellurium Compounds, Vol. 4,
(Ed.: Z. Rappoport), Wiley & Sons, Ltd, Chichester, 2013, Ch. 13-15,
989-1174.
[10] a) D. Crich, M. Patel, Tetrahedron 2006, 62, 7824-7837; b) G. A. Blanco,
M. T. Baumgartner, New J. Chem. 2010, 34, 2306-2309; c) S. A.
Rodriguez, L. D. Mena, M. T. Baumgartner, Aust. J. Chem., 2016, 69,
919-924.
[11] a) Y. Maeda, M. Koyabu, T. Nishimura, S. Uemura, J. Org. Chem. 2004,
69, 7688-7693; b) S. K. R. Parumala, R. K. Peddinti, Green Chem. 2015,
17, 4068-4072; c) Saima, D. Equbal, A. G. Lavekar, A. K. Sinha, Org.
Biomol. Chem. 2016, 14, 6111-6118; d) F. Xiao, J. Tian, Q. Xing, H.
Huang, G.-J. Deng, Y. Liu, ChemistrySelect 2017, 2, 428-431; e) S. Song,
Y. Zhang, A. Yeerlan, B. Zhu, J. Liu, N. Jiao, Angew. Chem. Int. Ed. 2017,
56, 2487-2491.
[2]
a) V. Nascimento, E. E. Alberto, D. W. Tondo, D. Dambrowski, M. R.
Detty, F. Nome, A. L. Braga, J. Am. Chem. Soc. 2012, 134, 138-141; b)
B. K. Sarma, G. J. Mugesh, Am. Chem. Soc. 2005, 127, 11477-11485;
c) G. Roy, M. Nethaji, G. Mugesh, J. Am. Chem. Soc. 2004, 126, 2712-
2713; d) L. Flohꢁ, E. A. Gꢀnzler, H. H. Schock, FEBS Lett. 1979, 32, 132-
134; e) R. J. Shamberger, in Biochemistry of Selenium, Vol. 1 (Eds.: E.
Frieden), Springer Verlag, New York, 1983; f) G. Mugesh, W. W. Du Mont,
H. Sies, Chem. Rev. 2001, 101, 2125-2180; g) F. A. R. Barbosa, R. F. S.
Canto, S. Saba, J. Rafique, A. L. Braga, Bioorg. Med. Chem. 2016, 24,
5762-5770; h) J. Rafique, S. Saba, R. F. S. Canto, F. A. Frizon, W.
Hassan, E. P. Waczuk, M. Jan, D. F. Back, J. B. T. Rocha, A. L. Braga,
Molecules 2015, 20, 10095-10109.
[12] a) D. Wang, R. Zhang, S. Lin, Z. Yan, S. Guo, RSC Adv. 2015, 5, 108030-
108033; b) F. Xiao, S. Chen, J. Tian, H. Huang, Y. Liu, G.-J. Deng, Green
Chem. 2016, 18, 1538-1546.
[13] a) X. Kang, R. Yan, G. Yu, X. Pang, X. Liu, X. Li, L. Xiang, G. Huang, J.
Org. Chem. 2014, 79, 10605-10610; b) X. Li, Y. Xu, W. Wu, C. Jiang, C.
Qi, H. Jiang, Chem. Eur. J. 2014, 20, 7911-7915.
[14] a) G. A. Blanco, M. T. Baumgartner, Tetrahedron Lett. 2011, 52, 7061-
7063; b) P. Gogoi, S. R. Gogoi, M. Kalita, P. Barman, Synlett. 2013, 24,
873-877; c) C. D. Prasad, S. J. Balkrishna, A. Kumar, B. S. Bhakuni, K.
Shrimali, S. Biswas, S. Kumar, J. Org. Chem. 2013, 78, 1434-1443; d)
W. Ge, Y. Wei, Green Chem. 2012, 14, 2066-2070.
[15] D. Wang, S. Guo, R. Zhang, S. Lin, Z. Yan, RSC Adv. 2016, 6, 54377-
54381.
[3]
a) C. Paulmier in Selenium Reagents and Intermediates in Organic
Synthesis, Vol. 4 (Eds.: J. E. Baldwin), Pergamon Press - Oxford, United
Kingdom, 1986; b) D. M. Freudendahl, S. Santoro, S. A. Shahzad, C.
Santi, T. Wirth, Angew. Chem. Int. Ed. 2009, 48, 8409-8411; c) Selenium
and Tellurium Chemistry: From Small Molecules to Biomolecules and
Materials, Vol. 1 (Eds.: W. J. Derek, L. Risto), Springer-Verlag, Berlin,
2011; d) M. Godoi, M. W. Paixꢂo, A. L. Braga, Dalton Trans. 2011, 40,
11347-11355; e) H. J. J. Reich, Org. Chem. 1975, 40, 2570-2572; f) K.
B. Sharpless, R. F. Laurer, J. Am. Chem. Soc. 1972, 94, 7154-7155; g)
T. E. A. Frizon, J. Rafique, S. Saba, I. V. Bechtold, H. Gallardo, A. L.
Braga, Eur. J. Org. Chem. 2015, 16, 3470-3476; h) P. C.-W. Ho, J.
Rafique, J. Lee, M. L. Lee, H. A. Jenkins, J. F. Britten, A. L. Braga, I.
Vargas-Baca, Dalton Trans. 2017, 46, 6570-6579.
[16] T. Hostier, V. Ferey, G. Ricci, D. G. Pardo, J. Cossy, Org. Lett. 2015, 17,
3898-3901.
[17] a) Y. Ju, D. Kumar, R. S. Varma, J. Org. Chem. 2006, 71, 6697-6700; b)
Q. Wu, D. Zhao, X. Qin, J. Lan, J. You, Chem. Commun. 2011, 47, 9188-
9190; c) K. Görmer, H. Waldmann, G. Triola, J. Org. Chem. 2010, 75,
1811-1813; d) M. Godoi, G. V. Botteselle, J. Rafique, M. S. T. Rocha, J.
M. Pena, A. L. Braga, Asian J. Org. Chem. 2013, 2, 746-749; e) J. B.
Azeredo, M. Godoi, R. S. Schwab, G. V. Botteselle, A. L. Braga, Eur. J.
Org. Chem. 2013, 5188-5194.
[18] a) R. S. Varma, Green Chem. 1999, 1, 43-55; b) K. Tanaka, F. Toda,
Chem. Rev. 2000, 100, 1025-1074. c) J. Rafique, S. Saba, A. R.
Schneider, M. S. Franco, S. M. Silva, A. L. Braga, ACS Omega, 2017, 2,
2280-2290; d) J. Rafique, S. Saba, A. R. Rosário, G. Zeni, A. L. Braga,
RSC Adv. 2014, 4, 51648-51652.
[4]
[5]
a) P. Da Re, P. Da Re, G. P. Primofiore, A. Bertelli, J. Med.
Chem. 1972, 15, 868-869; b) H. U. Shetty, W. L. Nelson, J. Med.
Chem. 1986, 29, 2004-2008.
[19] a) J .Rafique, S. Saba, A. R. Rosário, A. L. Braga, Chem. Eur. J. 2016,
22, 11854-11862; b) S. Saba, J. Rafique, A. L. Braga, Catal. Sci. Tech.
2016, 6, 3087-3098; c) S. Saba, J. Rafique, A. L. Braga, Adv. Synth.
Catal. 2015, 357, 1446-1452; d) A. A. Vieira, J. B. Azeredo, M. Godoi, C.
Santi, E. N da Silva Júnior, A. L. Braga, J. Org. Chem. 2015, 80, 2120-
2127; e) J. B. Azeredo, M. Godoi, G. M. Martins, C. C. Silveira, A. L.
Braga, J. Org. Chem. 2014, 79, 4125-4130.
a) M. R. Hellberg, A. Namil, P. Delgado, K. C. David, T. L. Kessler, G.
Graff, K. S. Haggard, J. C. Nixon, J. Med. Chem. 1999, 42, 267-276; b)
J. Rautio, T. Nevalainen, H. Taipale, J. Vepsäläinen, J. Gynther, K. Laine,
T. Järvinen, J. Med. Chem. 2000, 43, 1489-1494; c) D. Sarigol, A.
Uzgoren-Baran, B. C. Tel, E. I. Somuncuoglu, I. Kazkayasi, K. Ozadali-
Sari, O. Unsal-Tan, G. Okay, M. Ertan, B. Tozkoparan, Bioorg. Med.
Chem. 2015, 23, 2518-2528.
[20] Selected crystal data are presented at the end of the Electronic
[6]
N. K. Shan, N. M. Shah, M. P. Patel, R. G. Patel, J. Chem. Sci. 2013,
125, 525-530.
Supplementary
Information
(ESI)
available:
See
DOI: 10.1039/x0xx00000x. Full crystallographic tables (including
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
structure factors) for compounds 3a and 4g have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 1541566 (3a) and CCDC 1541567 (4g).
These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[21] a) J. Luo, Z. Zhu, Y. Liu, X. Zhao, Org. Lett. 2015, 17, 3620-3623; b) S.
Guo, G. Wan, S. Sun, Y. Jiang, J.-T. Yua, J. Cheng, Chem. Commun.
2015, 51, 5085-5088; c) X. Wu, Q. Gao, S. Liu, A. Wu, Org. Lett. 2014,
16, 2888-2891; d) W. Ge, X. Zhu, Y. Wei, RSC Adv. 2013, 3, 10817-
10822; e) F. Xiao, H. Xie, S. Liu, G.-J. Geng, Adv. Synth. Catal. 2014,
356, 364-368.
[22] D. H. R. Barton, A. G. Brewster, S. V. Ley, C. M. Read, M. N. Rosenfeld,
J. Chem. Soc. 1981, 1, 1473-1476.
[23] Y. Maeda, M. Koyabu, T. Nishimura, S. Uemura, J. Org. Chem. 2004, 69,
7688-7693.
[24] T. Chatterjee, B. C. Ranu, J. Org. Chem. 2013, 78, 7145-7153.
[25] F. Xiao, S. Chen, C. Li, H. Huang, G. Deng, Adv. Synth. Catal. 2016, 358,
3881-3886.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700744
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
FULL PAPER
A greener and efficient protocol for the
chalcogenylation of bicyclic arenes
using the I2/DMSO catalytic system
Organoselenium chemistry,
Organosulfur chemistry, Green
chemistry
under
solvent-
and
metal-free
Lais T. Silva, Juliano B. Azeredo,
Sumbal Saba, Jamal Rafique,* Adailton
J. Bortoluzzi, and Antonio L. Braga*
conditions, was developed. This
protocol allowed access to several
chalcogenated bicyclic arenes through
C(sp2)-H bond functionalization.
Page No. – Page No.
Solvent- and metal-free
chalcogenation of bicyclic arenes
using I2/DMSO as non-metallic
catalytic system
This article is protected by copyright. All rights reserved.