Synthesis of 4-Selanyl- And 4-Tellanyl-1 H-isochromen-1-ones Promoted by Diorganyl Dichalcogenides and Oxone

Article abstract of DOI:10.1021/acs.joc.1c00271

A new method was developed for the synthesis of 4-chalcogenyl-1H-isochromen-1-ones through the 6-endo-dig electrophilic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides under ultrasound irradiation. The reactions were performed under mild

Full text of DOI:10.1021/acs.joc.1c00271

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Synthesis of 4‑Selanyl- and 4‑Tellanyl‑1H‑isochromen-1-ones
Promoted by Diorganyl Dichalcogenides and Oxone
Helen A. Goulart, José S. S. Neto, Angelita M. Barcellos, Krigor B. Silva, Maiara C. de Moraes,
̃
Raquel G. Jacob, Eder J. Lenardao, Thiago Barcellos, and Gelson Perin*
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ABSTRACT: A new method was developed for the synthesis of 4-
chalcogenyl-1H-isochromen-1-ones through the 6-endo-dig electro-
philic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides
under ultrasound irradiation. The reactions were performed under
mild conditions, using Oxone as a green oxidant to promote the
cleavage of the chalcogen−chalcogen bond in diorganyl diselenides
and ditellurides to generate electrophilic species in situ. A total of 25
compounds were selectively obtained after 30−70 min, in good to
excellent yields (74−95%). This procedure was extended to prepare
5H-selenopheno[3,2-c]isochromen-5-ones. Additionally, for the first
time, the 4-chalcogenyl-1H-isochromen-1-ones were used as sub-
strates in the thionation reaction, using Lawesson’s reagent and microwave irradiation under solvent-free conditions, obtaining the
thio derivatives in yields of up to 99% in only 15 min.
growing field of research.3 Several reports describe that the
insertion of an organoselenium or organosulfur moiety in a
heterocycle can potentialize its biological activities. As has
INTRODUCTION
1H-2-Benzopyran-1-ones or 1H-isochromen-1-ones are ben-
zannulated analogues of the six-membered oxygen heterocycle
■
already been recognized, molecules containing chalcogen show
antioxidant, antinociceptive, antidepressant, anticancer, anti-
bacterial, and antifungal properties.4 In this sense, some new
protocols were developed to prepare chalcogen-substituted
1H-isochromen-1-ones.5 In 2003, Yao and Larock6 reported
the synthesis of a variety of substituted isochromen-1-ones in
excellent yields by the reaction of 2-(1-alkynyl)benzoates with
ICl, I2, PhSeCl, 4-NO2C6H4SCl, and HI (Scheme 1a). Later,
the regioselective synthesis of 1H-isochromen-1-ones by the
iron(III)/diorganyl dichalcogenide-mediated cyclization of 2-
alkynylaryl esters was described (Scheme 1b).7 More recently,
a metal-free protocol to the formation in situ of RSCl/ArSeCl
and their application in the intramolecular cyclization of 2-(1-
alkynyl)benzoates was described (Scheme 1c).8
α-pyrone (2H-pyran-2-one) (Figure 1). The 1H-isochromen-
Searching for an environmentally benign oxidizing agent,
potassium peroxymonosulfate, marketed as Oxone, has
emerged as an excellent alternative due to its low cost,
stability, water solubility, simplicity in handling, and low
toxicity. Oxone is a triple salt (2KHSO5·KHSO4·K2SO4)
Figure 1. Examples of biologically active compounds with the
isochromen-1-one scaffold.
1-one core occurs in nature as a secondary metabolite of plants
and lower microorganisms or as a component of some insect
pheromones and venoms.1 As a structural subunit in natural
products, this class of compounds exhibits remarkable
bioactivities and structural diversity (Figure 1); for example,
they show therapeutic applications such as anticancer,
antibacterial, antidiabetic, fungicidal, and anti-inflammatory.1,2
Nowadays, connecting the pharmacological potential of
several heterocyclic compounds with organochalcogens is a
Special Issue: Enabling Techniques for Organic Syn-
thesis
Received: February 3, 2021
https://doi.org/10.1021/acs.joc.1c00271
J. Org. Chem. XXXX, XXX, XXX−XXX
© XXXX American Chemical Society
A

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Scheme 1. Methods for the Synthesis of Chalcogen-1H-
isochromen-1-ones
RESULTS AND DISCUSSION
■
We started our investigation by searching for the best reaction
conditions for the preparation of 3-phenyl-4-(phenylselanyl)-
1H-isochromen-1-one 3a, with methyl 2-(phenylethynyl)-
benzoate 1a (0.250 mmol) and diphenyl diselenide 2a as
model substrates in the presence of Oxone. Thus, in a first
experiment, a mixture of 1a (0.250 mmol), 2a (0.125 mmol),
and Oxone (0.250 mmol) in ethanol (2.0 mL) was stirred at
room temperature for 24 h in a conventional system (magnetic
stirrer), affording the desired product 3a in 30% yield (Table 1,
entry 1).
Table 1. Optimization Studies to Prepare 3-Phenyl-4-
a
(phenylselanyl)-1H-isochromen-1-one 3a
b
2a
Oxone
time
(h)
amplitude
(%)
yield
(%)
no. (mmol)
(mmol)
solvent
EtOH
1
2
3
4
5
6
7
8
0.125
0.125
0.125
0.150
0.170
0.200
0.250
0.150
0.250
0.250
0.250
0.250
0.250
0.250
0.250
0.250
24
c
d
30
3.0
1.0
0.5
0.5
0.5
0.5
1.5
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
77
71
95
93
93
96
72
60
60
60
60
60
60
EtOH/
H2O
9
0.150
0.150
0.150
0.150
0.150
0.150
0.150
0.150
0.150
0.150
0.150
0.150
0.250
0.250
0.250
0.250
0.250
0.250
0.250
0.250
0.375
0.187
0.250
0.250
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
0.5
1.0
0.5
1.25
60
60
60
60
60
60
60
60
60
60
80
40
PEG-400
glycerol
H2O
DCM
CH3CN
DMF
AcOEt
THF
EtOH
EtOH
EtOH
EtOH
69
60
NR
NR
50
traces
16
10
92
93
91
93
containing about 50% of active oxidant/mole, which is the
10
11
12
13
14
15
16
17
18
19
20
9
−
anion peroxymonosulfate (HSO5 ). In view of the good
performance of Oxone, it has been used in a great number of
green organic transformations, especially cyclization ones.10
A
successful example is the cyclization of 2-alkynylbenzoic acid in
water for the synthesis of isocoumarin.11 Over the past few
years, our group has strived toward developing safer, cleaner,
and less expensive procedures applying Oxone to prepare
organochalcogen compounds.12 For instance, the diselenide/
Oxone system was used to prepare 4-organoselanyl-1H-
pyrazoles,13 5-methylselanyl-4,5-dihydroisoxazoles,14 and 4-
(chalcogenyl)isoquinoline N-oxides.15 This strategy was
successfully used by us in the synthesis of 5H-selenopheno-
[3,2-c]isochromen-5-ones through a double intramolecular
cyclization of methyl 2-(organyl-1,3-diynyl)benzoate (Scheme
1d).16
a
Reactions were performed using a mixture of 1a (0.250 mmol), 2a,
and Oxone in 2.0 mL of solvent under US. Yields obtained after
column chromatography. Reaction performed under magnetic
stirring at room temperature. Reaction performed under conven-
tional heating (oil bath at 78 °C) and magnetic stirring. NR = no
reaction.
b
c
d
Another way to make organic synthesis greener is by using
ultrasonic irradiation (US) as an alternative energy source. The
ultrasound is a well-established tool used to promote reactions
through a specific activation based on acoustic cavitation. This
physical phenomenon can modify the course of reactions,
improving yields and increasing the selectivity in a shorter
reaction time than the conventional procedures.17 In this
sense, and in continuation to our interest in green procedures
correlated with organochalcogen chemistry, herein we describe
an alternative method for the preparation of 4-chalcogenyl-1H-
isochromen-1-ones. Our new proposal involves the US-
promoted 6-endo-dig electrophilic cyclization of 2-alkynylaryl
esters and diorganyl dichalcogenides using Oxone as a green
oxidant (Scheme 1e).
Aiming to improve the reaction yield and to reduce the
reaction time, the reaction was performed at 78 °C (refluxing
ethanol). After 3 h, the expected product 3a was obtained in
77% yield (Table 1, entry 2). To achieve the product 3a in an
acceptable yield and in shorter reaction time, we decided to
change our initial strategy by performing the reaction under
ultrasonic irradiation (US) at an amplitude of 60% and a
frequency of 20 kHz (Cole-Parmer model CPX 130 ultrasonic
processor). To our delight, when the reaction was sonicated
for 1 h (monitored by thin layer chromatography (TLC)), a
similar yield of 3a was obtained (71%), proving that the
efficient energy transfer by the US can significantly reduce the
reaction time (Table 1, entry 3). Inspired by this outcome, the
B
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following additional experiments were conducted using US at
60% of amplitude. First, we studied the effect of the amount of
diphenyl diselenide 2a in the reaction (Table 1, entries 4−7).
Fortunately, using a 20% excess of 2a (0.150 mmol), the
product 3a was obtained in 95% yield after only 0.5 h of
sonication (Table 1, entry 4). However, larger amounts of 2a
(0.170, 0.200, and 0.250 mmol) were not effective in
increasing the reaction yield, giving the product 3a in 93%,
93%, and 96% yield, respectively (Table 1, entries 5−7).
Next, a study about the influence of the solvent in the
reaction was performed, and the reaction was tested in polar
protic and aprotic solvents (Table 1, entries 8−16). In the
reactions using a mixture of ethanol/water (1:1), polyethylene
glycol-400 (PEG-400), glycerol, acetonitrile, ethyl acetate and
tetrahydrofuran, the product 3a was obtained in lower yields
compared to the reaction in ethanol (Table 1, entry 4 vs 8−10,
13, 15, and 16). No reaction was observed when water or
dichloromethane was used as solvent, while only trace amounts
of isochromen-1-one 3a were observed using dimethylforma-
mide; in all cases, the starting materials were recovered (Table
1, entries 11−12 and 14). The use of larger (0.375 mmol) or
smaller amounts (0.187 mmol) of Oxone, did not alter the
reaction performance, giving the product 3a in 92% and 93%
yield after 0.5 and 1.0 h of sonication, respectively (Table 1,
entries 17 and 18). Finally, a study was carried out to evaluate
the effect of the amplitude of the US in the reaction (Table 1,
entries 19 and 20). We observed that by increasing the
amplitude to 80% there was no significant change in both the
reaction time (0.5 h) and the yield of product 3a (Table 1,
entry 19). However, by reducing the amplitude to 40%, a
longer reaction time (1.25 h) was required for the
consumption of the starting materials, while the yield of 3a
did not change significantly (Table 1, entry 20). Based on the
results depicted on Table 1, the best reaction conditions to
prepare 3a were defined as the sonication (60% of amplitude)
of a mixture of 0.250 mmol of 2-alkynylaryl ester 1a, 0.150
mmol of diphenyl diselenide 2a ,and 0.250 mmol of Oxone in
2.0 mL of ethanol as the solvent (Table 1, entry 4).
Scheme 2. Scope of the Reaction to Synthesize 4-
(Organylselanyl)-1H-isochromen-1-ones 3a−q
a,b
Under the optimized conditions, a series of isochromen-1-
ones 3 were prepared by this newly established approach. We
examined the generality and limitations of this method with a
variety of diorganyl dichalcogenides 2 and 2-alkynylaryl esters
1 (Schemes 2−4).
a
Reactions were performed using a mixture of 1 (0.250 mmol), 2
(0.150 mmol), and Oxone (0.250 mmol) in 2.0 mL of EtOH under
ultrasonic irradiation. Yields are of pure products, after column
chromatography. The leaving group in 1 is R = CH3 (1a).
b
c
Initially, we have checked the possibility of performing these
n
reactions with other alkoxy groups in the ester 1 (R = C8H17
and C6H5CH2) and with carboxylic acid. When octyl 2-
(phenylethynyl)benzoate 1b was used, product 3a was
obtained in 92% yield, requiring more time for the
consumption of the starting materials (45 min) compared to
the reaction using methyl 2-(phenylethynyl)benzoate 1a.
Benzyl 2-alkynylbenzoate 1c and 2-(phenylethynyl)benzoic
acid 1d were good substrates for the reaction, affording 3a in
91% and 90% yield, after 30 and 45 min of sonication,
respectively (Scheme 2). The electrophilic cyclization of 2-
(phenylethynyl)benzoic acid 1d was already described, and a
mixture of five- and six-membered ring products was
obtained.10a,18 To our satisfaction, our novel protocol proved
to be highly regioselective also for this substrate, providing
only the six-membered product.
donating groups 2b (R2 = 4-CH3C6H4) and 2c (R2 = 4-
CH3OC6H4) were suitable substrates for the reaction, and the
respective products 3b and 3c were obtained in 90% and 93%
yield after 30 min (Scheme 2). The presence of electron-
withdrawing substituents decreased the reactivity of the diaryl
diselenide 2, and longer reaction times were necessary for the
consumption of the starting materials compared to the
electron-donating ones. Thus, diaryl diselenides 2d (R2 = 4-
ClC6H4), 2e (R2 = 4-FC6H4), and 2f (R2 = 3-CF3C6H4)
afforded 3d, 3e, and 3f in 90%, 92%, and 92% yield,
respectively, after reaction times of 50−70 min (Scheme 2).
When the bulky dimesityl diselenide 2g was used, the
corresponding product 3g was obtained in 91% yield after 50
min of reaction (Scheme 2). The reactions were conducted
satisfactorily with alkyl diselenides such as bis(2-naphthyl-
methyl) diselenide 2h, diethyl diselenide 2i, and dibutyl
diselenide 2j, affording the respective products 3h, 3i, and 3j in
Next, we turned our attention to investigate the scope of
diorganyl diselenides 2 in the reaction with methyl 2-
(phenylethynyl)benzoate 1a and Oxone in ethanol. Diaryl
diselenides substituted at the para-position with electron-
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82%, 90%, and 94% yield, respectively, after 35−40 min of
reaction (Scheme 2).
substrate in the reaction with 2a, the expected isochromen-1-
one 3s (R = H) was isolated in 74% yield. In this case, a
second, unexpected product was detected in trace amounts,
which was characterized as 3s′ (R = C2H5), as indicated by
GC/MS analysis (Scheme 3b).
The effect of the substituent R1 in the pendant 2-alkynyl
group of the arylester 1 was investigated in the reaction with
diphenyl diselenide 2a (Schemes 2 and 3). When methyl 2-
Interested in this result, we look for a strategy to selectively
obtain the product with the alkoxy group in the structure. For
that, methyl 2-(3-hydroxy-3-methylbut-1-yn-1-yl)benzoate 1n
was used as substrate in the reaction with 2a under the optimal
conditions, using ethanol as solvent. To our satisfaction, the
ether 3t (R = C2H5) was selectively obtained in 92% yield
(Scheme 3c). This can be explained by the formation of the
alkynyl carbocation intermediate, from the elimination of a
water molecule, followed by the nucleophilic attack by the
alcohol solvent.19 The elimination of water from the propargyl
alcohol is favored in the acidic medium of the reaction, due to
the presence of Oxone (pH = 1). This hypothesis was proved
by changing the reaction solvent for methanol, giving, after 30
min, the product containing the methyl ether derivative 3u in
89% yield (Scheme 3c).
Scheme 3. Synthesis of 4-(Organylselanyl)-1H-isochromen-
1-ones 3r−u
In the sequence, we turned our attention on the reaction
between 2-alkynylaryl ester 1a and diphenyl ditelluride (2k)
under the optimal conditions defined for the analogue
diselenides. Unfortunately, no reaction occurred after 60 min
of sonication, and the starting materials were recovered at the
end of the reaction. Recently, some of us20 have observed that
the use of glycerol as a solvent favors the achievement of high
temperatures under ultrasonic irradiation. Thus, we wonder if
this solvent could make possible the formation of products
using the recalcitrant ditelluride as chalcogen source.
Fortunately, when the reaction was repeated using glycerol
(2.0 mL) as solvent instead ethanol, the expected tellurium-
substituted product 3v was obtained in 84% yield after 60 min
(Scheme 4). Generally, electrophilic species of tellurium are
ethynylbenzoate 1e (R1 = H) reacted with 2a under the
optimal conditions, the isochromen-1-one 3k was obtained in
89% yield after 30 min. There is no remarkable electronic
effect caused by the presence of electron-donating substituents
at the ortho- or para-position of the aromatic ring in the methyl
2-(arylethynyl)benzoate 1. Thus, compounds 3l (R1 = 2-
CH3OC6H4) and 3m (R1 = 4-CH3OC6H4) were obtained in
88% and 90% yield, respectively, by the reaction of 1f and 1g
with 2a (Scheme 2). The use of substrate 1f, substituted with
an o-methoxy group, could favor the O-cyclization reaction,
leading to the benzofuran derivative. However, our method
was selective to the formation exclusively of the isochromen-1-
one 3l. When methyl 2-[4-(t butyl)phenylethynyl]benzoate 1h
(R1 = 4-tC4H9C6H4) reacted with 2a under the optimal
conditions, the expected isochromen-1-one 3n was obtained in
84% yield after 30 min of sonication. The presence of an
electron-withdrawing substituent, however, reduced the
reactivity of the substrate 1, and the 2-alkynylaryl ester 1i
(R1 = 4-ClC6H4) required 60 min to be cyclized to the
expected isochromen-1-one 3o, in 92% yield. Furthermore,
alkynes 1j (R1 = nC4H9) and 1k (R1 = Si(CH3)3) were suitable
substrates for the reaction, and the respective products 3p and
3q were obtained in 85% and 92% yield, respectively, after 45
min (Scheme 2). The usefulness of this US-promoted protocol
in preparative synthesis was demonstrated in a reaction using
3.0 mmol (0.711 g) of methyl 2-(phenylethynyl)benzoate (1a)
and 1.8 mmol (0.565 g) of diphenyl diselenide (2a), affording
1.021 g of pure 3a (yield 90%) after 30 min of sonication.
Next, we evaluated the influence of the presence of a
hydroxyl substituent in the 2-alkynyl group in the esters 1l−n,
in the reaction with diphenyl diselenide 2a (Scheme 3).
Methyl 2-(3-hydroxyprop-1-yn-1-yl)benzoate 1l reacted with
diselenide 2a under the optimized conditions to produce the
corresponding product 3r in 83% yield (Scheme 3a). When
methyl 2-(3-hydroxybut-1-yn-1-yl)benzoate 1m was used as
Scheme 4. Synthesis of 4-(Organyltellanyl)-1H-isochromen-
1-ones 3v−x and 3-Phenyl-1H-isochromen-1-one 3y
unstable in open air and decompose more easily in the reaction
medium, thus requiring inert atmosphere. The high yield
obtained of 3v indicates that our protocol is suitable also to
electrophilic cyclization involving electrophilic tellurium
species, without the need for special apparatus and inert
atmosphere. The same reaction conditions were then extended
to other substituted diaryl ditellurides (2l−n) and to dibutyl
ditelluride (2o) (Scheme 4). Diaryl ditellurides substituted
with electron-donating groups 2l (R1 = 4-CH3C6H4) and 2m
(R1 = 4-CH3OC6H4) were good substrates for the reaction,
and the respective products 3w and 3x were obtained in 82%
and 78% yield, respectively. On the other hand, the electron-
deficient diaryl ditelluride 2n (R1 = 4-ClC6H4) and dibutyl
D
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ditelluride 2o (R1 = C4H9) were not reactive under the optimal
conditions, and the expected tellurium-containing products
could not be prepared. In both reactions, the obtained product
was 3-phenyl-1H-isochromen-1-one 3y, formed from the loss
of the respective organotellurium groups after the cyclization
(Scheme 4).
5a was not detected, and the starting substrate 3a was
recovered (Scheme 6).
Scheme 6. Synthesis of 1H-Isochromene-1-thiones 5
After, we try to expand the scope of products to sulfur-
containing compounds in their structure. We examined the
reaction between 2-alkynylaryl ester 1a, diphenyl disulfide 2p
and Oxone using ethanol or glycerol as a solvent for the
reactions. Unfortunately, in both cases the desired product 3z
was not obtained, even after 2 h of sonication, and the starting
material 1a was recovered. This lack of reactivity of disulfide
could be attributed, at least in part, to the stronger S−S bond
compared to the Se−Se and Te−Te ones, making the
formation of the electrophilic species of sulfur more difficult.
Additionally, considering the great importance presented by
selenophenes in chemistry, material field, and their promising
biological activities,21 we decided to extend our protocol to the
synthesis of isochromenones fused to selenophenes 4 (Scheme
5). For that, methyl 2-(phenylbuta-1,3-diyn-1-yl)benzoate 1o
Seeking to obtain the desired products in acceptable yields,
through clean reaction conditions and short reaction times, we
have adapted a procedure previously described by Saeed and
Ashraf that uses microwave irradiation to perform the
thionation of 3-aryl-1H-isochromene-1-ones.23 Thus, a mixture
of 3a (0.250 mmol) and Lawesson’s reagent (0.130 mmol) was
irradiated in a microwave reactor at 140 °C, using an
irradiation power of 200 W (100 psi) under solvent-free
conditions. After 15 min (monitored by TLC), the desired
product 5a was obtained in 98% yield (Scheme 6). For the first
time, we have demonstrated the synthesis of this highly
functionalized 3-organyl-4-(organylselanyl)-1H-isochromene-
1-thione 5. Motivated by this result, we evaluated the reactivity
of a variety of 4-(organylselanyl)-1H-isochromen-1-ones 3. In
general, our method proved to be efficient, affording the
corresponding selenylated isochromenethiones 5a−d in
excellent yields (90−99%) in only 15 min. However, when
4-(phenyltellanyl)-1H-isochromen-1-one 3v was employed, the
expected product 5e was not detected, and the starting
material was recovered (Scheme 6).
Scheme 5. Synthesis of 5H-Selenopheno[3,2- c]isochromen-
a,b
5-ones 4a−c
a
Reactions were performed using a mixture of 1 (0.250 mmol), 2
(0.30 mmol), and Oxone (0.50 mmol) in 2.0 mL of EtOH under
b
ultrasonic irradiation. Yields are of pure products, after column
To achieve substantial support to elucidate the mechanism
of the synthesis of 4-chalcogenyl-1H-isochromen-1-ones 3,
some control experiments were conducted (Scheme 7). The
reaction between 2-alkynylaryl ester 1a and diphenyl diselenide
2a was performed using the standard conditions but in the
presence of 3 equiv of the radical inhibitors hydroquinone and
2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) (Scheme 7a).
After 30 min of reaction, the isochromen-1-one 3a was isolated
in 90% and 60% yield using hydroquinone and TEMPO,
respectively. The lower yield of product 3a in the reaction
using TEMPO is attributed to the parallel formation of the
product 6 (identified by 2D NMR spectroscopy; for more
details, see the Supporting Information), formed by the
transesterification reaction and the addition of the solvent to
the triple bond in 1a. These findings suggest that the present
transformation is not going through a radical pathway.
Moreover, when the reaction was performed in the absence
of diphenyl diselenide 2a, the cyclization product 3y was not
detected, even after 60 min of reaction (Scheme 7b). This
result demonstrates that the C−Se bond formation does not
occur after the ring closure step and that 3y is not an
intermediate in this reaction. Finally, the reaction was carried
out in the absence of Oxone, and after 60 min, no product was
formed (as indicated by GC/MS analysis), indicating the need
of using this oxidant in the reaction medium (Scheme 7c).
chromatography.
and methyl 2-(octa-1,3-diyn-1-yl)benzoate 1p were used as
substrates in the reaction with 2i and 2j. To our satisfaction,
the double intramolecular cyclization reactions were successful,
and the expected products 4a−c were obtained in 80%, 88%,
and 79% yield, respectively, after reaction times of 60−75 min
(Scheme 5).
Finally, we studied the synthetic potential of isochromen-1-
ones 3 using them as substrates in thionation reactions. The
conventional procedures reported in the literature for the
thionation involve refluxing a mixture of the substrate and a
large excess of 2,4-bis(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-
dithiadiphosphetane (the Lawesson’s reagent) in dry toluene
or benzene for several hours under inert atmosphere.22 As
mentioned before, our research group has invested in the
development of green methods for obtaining organochalcogen
compounds. Along this line, we decided to investigate the use
of ultrasound irradiation as an energy source in the thionation
reaction. For this, we initially tested the reaction between
compound 3a (0.250 mmol) and the Lawesson’s reagent
(0.130 mmol), using ethanol (2.0 mL) as solvent and US at an
amplitude of 60% and a frequency of 20 kHz. Unfortunately,
after 1 h of sonication, the expected 1H-isochromene-1-thione
E
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Scheme 7. Control Experiments
Scheme 8. Possible Reaction Mechanism
Next, we seek to identify the possible reactive intermediates
generated by the reaction of diphenyl diselenide 2a with
Oxone through high-resolution mass spectrometry (HRMS)
analysis. For this, a mixture of diselenide 2a (0.150 mmol) and
Oxone (0.250 mmol) was solubilized in EtOH and maintained
at room temperature under constant stirring. After 1 h, an
aliquot of the reaction mixture (0.05 mL) was diluted in
MeOH (2 mL) and filtered. The filtrate was immediately
injected in an APCI ionization source and analyzed in positive
and negative modes. The HRMS spectrum recorded under
negative mode revealed the ion at m/z 252.9073, of low
intensity. Through the analysis of the exact mass, isotopic
pattern, and product ions from the fragmentation (MS2), the
elemental formula C6H5O4SSe I can be inferred (Scheme 8a),
which refers to the proposed intermediate arising from the
oxidation of diselenide 2a by Oxone (Figures S108 and S109).
Also, the ion at m/z 268.9022 was observed. The exact mass
analysis, as well as the isotopic pattern and fragmentation,
allow us to infer that it refers to the elemental formula
C6H5O5SSe, which corresponds to the oxidized adduct of
intermediate I, which it is believed to be generated in the
ionization source. However, its presence contributes to the
intermediate I assignment (Figures S108 and S109). Under
positive mode, the ions at m/z 173.9584, 190.9600, and
204.9759 were recorded with higher intensity (Figures S110
and S111). The ion at m/z 173.9584 is attributed to the
formula C6H6OSe [M]+, corresponding to the proposed
intermediate benzeneseleninic acid (II). The ion at m/z
190.9600 is attributed to the benzeneseleninic acid (IV)
(C6H6O2Se [M + H]+). Finally, the ion at m/z 204.9759 was
indicated as the methyl ester of seleninic acid (V). This
intermediate was previously described by us,13 which was
detected in the 77Se NMR experiments (δ 1218 ppm). During
our HRMS mechanistic studies, no peaks related to the
intermediates VII and VIII were observed. Thus, based on our
results and in the literature,13,16 a reasonable mechanism is
proposed, as outlined in Scheme 8.
At first, the diselenide 2a reacts with Oxone to afford two
electrophilic selenium species, C6H5SeOSO3 (I) and
−
C6H5SeOH (II) (Scheme 8). The electrophiles I and II, in
the presence of solvent and Oxone, can be transformed into
benzeneseleninic acid IV and methylbenzeneseleninate V
(when R = CH3). The species II can react with H+ from the
+
reaction medium, leading to C6H5SeOH2 VI. The inter-
mediates I and VI are most probably the active electrophiles in
the reaction with substrate 1a. Following, the 2-alkynylaryl
ester 1a interacts with the electrophilic species I or VI,
affording the seleniranium intermediate VII and releasing the
−
sulfate anion (KSO4 ) and water (H2O) to the medium. Then
an intramolecular attack by the double bond of the carbonyl
group occurs, forming the cation isochromen-1-one inter-
mediate VIII, by a 6-endo-dig electrophilic cyclization. In the
last step, a displacement of the methyl group from VIII by a
nucleophile present in the reaction medium affords the
expected isochromen-1-one 3a.
CONCLUSIONS
■
In conclusion, a simple and general metal-free approach to
prepare 4-chalcogenyl-1H-isochromen-1-ones 3 through of the
6-endo-dig electrophilic cyclization between 2-alkynylaryl esters
1 and diorganyl dichalcogenides 2 promoted by Oxone was
developed. The protocol using ultrasound irradiation is
versatile and was efficiently applied to several 2-alkynylaryl
esters 1 and diorganyl dichalcogenides 2, obtaining the
products 3 with high regioselectivity and yields that varied
from good to excellent (74−95%). In addition, the synthetic
potential of this class of compounds was demonstrated, and
their respective isochromenethione analogues 5 were obtained
through the thionation reaction using Lawesson’s reagent and
microwave irradiation under solvent-free conditions.
F
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yield 1.309 g (60%); yellow oil. 1H NMR (CDCl3, 400 MHz) δ
(ppm) = 7.91 (dd, J = 7.8 and 1.2 Hz, 1H); 7.51 (dd, J = 7.8 and 1.2
Hz, 1H); 7.44 (td, J = 7.8 and 1.2 Hz, 1H); 7.34 (td, J = 7.8 and 1.2
Hz, 1H); 3.91 (s, 3H); 2.85 (br s, 1H); 1.64 (s, 6H). 13C{1H} NMR
(CDCl3, 100 MHz) δ (ppm) = 166.7, 133.9, 131.9, 131.6, 130.3,
127.8, 123.2, 99.0, 80.8, 65.6, 52.1, 31.2. MS (rel int, %) m/z: 218
(0.5), 203 (30.4), 171 (100.0), 129 (35.2). HRMS (APCI-QTOF)
m/z: [M + Na]+ calcd for C13H14O3Na 241.0841; found: 241.0832.
Procedure for the Synthesis of 3-Organyl-4-(organylchal-
cogenyl)-1H-isochromen-1-ones 3a−y. To a 10.0 mL glass tube
were added the appropriate methyl 2-(organylethynyl)benzoate 1
(0.25 mmol), diorganyl dichalcogenide 2 (0.15 mmol, 1.2 equiv),
Oxone (0.25 mmol, 0.077 g, 1 equiv), and solvent (2.0 mL). The
amplitude of the ultrasound waves was fixed at 60%. Then the
reaction mixture was sonicated for the time required to consume the
starting material 1. The progress of the reaction was monitored by
TLC. After that, the resulting solution was received in water (10.0
mL), and the product was extracted with ethyl acetate (3 × 10.0 mL).
The organic layer was separated, dried with MgSO4, and concentrated
under vacuum. The residue was purified by column chromatography
using silica gel and hexane/ethyl acetate as eluent to afford 3a−y.
Preparation of 3a in Gram Scale. To a 20.0 mL glass tube were
added the methyl 2-(phenylethynyl)benzoate 1a (3.0 mmol, 0.711 g),
diphenyl diselenide 2a (1.8 mmol, 0.565 g, 1.2 equiv), Oxone (3.0
mmol, 0.921 g, 1 equiv), and ethanol (8.0 mL). The amplitude of the
ultrasound waves was fixed at 60%. Then the reaction mixture was
sonicated for 30 min. After that, the resulting solution was received in
water (30.0 mL), and the product was extracted with ethyl acetate (3
× 30.0 mL). The organic layer was separated, dried with MgSO4, and
concentrated under vacuum. The residue was purified by column
chromatography using silica gel and hexane/ethyl acetate (95:5) as
eluent to afford 1.021 g of pure 3a (yield 90%).
EXPERIMENTAL SECTION
■
General Information. The reactions were monitored by TLC
carried out on Merck silica gel (60 F254) using UV light as
visualization agent and the mixture between 5% of vanillin in 10%
of H2SO4 under heating conditions as developing agents. Column
chromatography was performed using Merck silica gel (pore size 60 Å,
230−400 mesh). Low-resolution mass spectra (MS) were measured
on a Shimadzu GC-MS-QP2010 mass spectrometer. High-resolution
mass spectra (HRMS) were recorded in positive-ion mode (APCI/
ESI) using a Q-TOF spectrometer. Hydrogen nuclear magnetic
resonance (1H NMR) and carbon-13 nuclear magnetic resonance
(13C NMR) spectra were obtained on Bruker Avance III HD
spectrometer at 400 at 100 MHz, respectively. Spectra were recorded
in CDCl3 solutions. Chemical shifts (δ) 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. The 77Se NMR chemical shifts are
reported in ppm relative to the internal standard C6H5SeSeC6H5 (δ
463 ppm). The 125Te NMR chemical shifts are reported in ppm
relative to the internal standard C6H5TeTeC6H5 (δ 422 ppm).
Abbreviations to denote the multiplicity of a particular signal are s
(singlet), d (doublet), t (triplet), q (quartet), quint (quintet), sext
(sextet), dd (double doublet), td (triple doublet), and m (multiplet).
Ultrasonic waves were generated by a Cole Parmer CPX 130
operating with an amplitude of 60% and a maximum power of 130 W
at 20 kHz. The temperature of the reactions under US was monitored
with an Incoterm digital infrared thermometer. Microwave reactions
were conducted using a CEM Discover focused microwave oven,
operating at 2.45 GHz with a power of 200 W, in a glass vessel (10
mL) sealed with Teflon cap, under magnetic stirring. Melting point
(mp) values were measured in a Marte PFD III instrument with a 0.1
°C precision. Oxone was purchased from Sigma-Aldrich.
3-Phenyl-4-(phenylselanyl)-1H-isochromen-1-one (3a).7 Purified
by column chromatography (hexane/ethyl acetate = 95:5); yield
Procedure for the Synthesis of Methyl 2-(Organylethynyl)-
benzoate Derivatives 1. Compounds 1a−x were prepared
according to a published procedure.24 Unpublished compounds 1h,
1l, 1m, and 1n were obtained using the same procedure.
1
0.090 g (95%); white solid, mp 134−136 °C. H NMR (CDCl3, 400
MHz) δ (ppm) = 8.27 (dd, J = 7.9 and 1.0 Hz, 1H); 7.98−7.95 (m,
1H); 7.63−7.56 (m, 3H); 7.46−7.42 (m, 1H); 7.36−7.28 (m, 3H);
7.12−7.06 (m, 5H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) =
161.7, 159.5, 138.4, 135.3, 134.0, 131.8, 130.1, 129.7, 129.6, 129.5,
128.8, 128.7, 128.2, 127.8, 126.4, 120.8, 104.7. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 295.5. MS (rel int, %) m/z: 378 (24.8),
193 (14.7), 105 (100.0), 77 (19.2).
Methyl 2-(4-tert-Butylphenylethynyl)benzoate (1h). Purified by
column chromatography (hexane/ethyl acetate = 97:3); yield 2.629 g
(90%); brown oil. 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.96 (dd,
J = 7.9 and 1.1 Hz, 1H); 7.63 (dd, J = 7.9 and 1.1 Hz, 1H); 7.52−7.46
(m, 3H); 7.39−7.36 (m, 3H); 3.96 (s, 3H); 1.33 (s, 9H). 13C{1H}
NMR (CDCl3, 100 MHz) δ (ppm) = 166.8, 151.8, 133.9, 131.8,
131.6, 131.4, 130.4, 127.7, 125.3, 123.9, 120.3, 94.5, 87.6, 52.1, 34.8,
31.1. MS (rel int, %) m/z: 292 (59.9), 277 (100.0), 202 (15.5), 109
(11.2). HRMS (APCI-QTOF) m/z: [M + H]+ calcd for C20H21O2
293.1542; found: 293.1543.
3-Phenyl-4-(4-tolylselanyl)-1H-isochromen-1-one (3b7). Purified
by column chromatography (hexane/ethyl acetate = 95:5); yield
1
0.088 g (90%); white solid, mp 170−173 °C. H NMR (CDCl3, 400
MHz) δ (ppm) = 8.26 (dd, J = 7.9 and 1.0 Hz, 1H); 8.00−7.96 (m,
1H); 7.63−7.57 (m, 3H); 7.45−7.41 (m, 1H); 7.37−7.29 (m, 3H);
7.02−6.99 (m, 2H); 6.92−6.89 (m, 2H); 2.17 (s, 3H). 13C{1H} NMR
(CDCl3, 100 MHz) δ (ppm) = 161.7, 159.3, 138.5, 136.4, 135.3,
134.0, 130.2, 130.0, 129.7, 129.6, 129.0, 128.6, 128.3, 127.9, 127.7,
120.8, 105.0, 20.9. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) =
288.6. MS (rel int, %) m/z: 392 (18.2), 287 (10.8), 105 (100.0), 77
(18.8).
Methyl 2-(3-Hydroxyprop-1-yn-1-yl)benzoate (1l). Purified by
column chromatography (hexane/ethyl acetate = 80:20); yield 1.521
1
g (80%); brown oil. H NMR (CDCl3, 400 MHz) δ (ppm) = 7.90
(dd, J = 7.7 and 1.2 Hz, 1H); 7.52 (dd, J = 7.7 and 1.2 Hz, 1H); 7.43
(td, J = 7.7 and 1.2 Hz, 1H); 7.34 (td, J = 7.7 and 1.2 Hz, 1H); 4.55
(s, 2H); 3.90 (s, 3H); 3.47 (br s, 1H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 166.5, 134.1, 131.7, 131.4, 130.1, 127.8, 123.3, 92.9,
83.7, 52.1, 51.3. MS (rel int, %) m/z: 190 (38.1), 147 (100.0), 101
(37.7), 77 (55.5). HRMS (APCI-QTOF) m/z: [M + Na]+ calcd for
C11H10O3Na 213.0528; found: 213.0524.
4-(4-Methoxyphenylselanyl)-3-phenyl-1H-isochromen-1-one
(3c). Purified by column chromatography (hexane/ethyl acetate =
1
95:5); yield 0.095 g (93%); white solid, mp 94−97 °C. H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.24 (dd, J = 7.9 and 1.1 Hz, 1H);
8.04−8.01 (m, 1H); 7.64−7.60 (m, 1H); 7.58−7.56 (m, 2H); 7.43−
7.39 (m, 1H); 7.36−7.30 (m, 3H); 7.05−7.01 (m, 2H); 6.64−6.60
(m, 2H); 3.62 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) =
161.7, 158.9, 158.8, 138.4, 135.2, 134.0, 131.4, 130.0, 129.8, 129.6,
128.5, 128.2, 127.7, 121.3, 120.8, 115.1, 105.9, 55.2. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 279.8. MS (rel int, %) m/z: 408 (27.4),
223 (37.9), 105 (100.0), 77 (28.1). HRMS (APCI-QTOF) m/z: [M
+ H]+ calcd for C22H17O3Se 409.0343; found: 409.0338.
Methyl 2-(3-Hydroxybut-1-yn-1-yl)benzoate (1m). Purified by
column chromatography (hexane/ethyl acetate = 80:20); yield 1.673
1
g (82%); yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm) = 7.89
(dd, J = 7.8 and 1.0 Hz, 1H); 7.50 (dd, J = 7.8 and 1.0 Hz, 1H); 7.41
(td, J = 7.8 and 1.0 Hz, 1H); 7.32 (td, J = 7.8 and 1.0 Hz, 1H); 4.83
(q, J = 6.6 Hz, 1H); 3.98 (br s, 1H); 3.89 (s, 3H); 1.58 (d, J = 6.6 Hz,
3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 166.5, 133.8,
131.5, 131.3, 130.0, 127.6, 123.1, 96.4, 82.0, 58.3, 51.9, 23.9. MS (rel
int, %) m/z: 204 (38.1), 187 (33.2), 147 (100.0), 101 (33.2), 77
(15.5). HRMS (APCI-QTOF) m/z: [M + Na]+ calcd for
C12H12O3Na 227.0684; found: 227.0674.
4-(4-Chlorophenylselanyl)-3-phenyl-1H-isochromen-1-one
(3d7). Purified by column chromatography (hexane/ethyl acetate =
1
95:5); yield 0.093 g (90%); white solid, mp 139−142 °C. H NMR
Methyl 2-(3-Hydroxy-3-methylbut-1-yn-1-yl)benzoate (1n). Pu-
rified by column chromatography (hexane/ethyl acetate = 75:25);
(CDCl3, 400 MHz) δ (ppm) = 8.28 (dd, J = 7.9 and 1.0 Hz, 1H);
7.93−7.90 (m, 1H); 7.65−7.61 (m, 1H); 7.56−7.53 (m, 2H); 7.48−
G
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7.44 (m, 1H); 7.37−7.30 (m, 3H); 7.07−7.01 (m, 4H). 13C{1H}
NMR (CDCl3, 100 MHz) δ (ppm) = 161.5, 159.7, 138.1, 135.4,
133.8, 132.6, 130.2, 130.1, 129.9, 129.8, 129.6, 128.8, 128.0, 127.8,
120.8, 104.6. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 295.9. MS
(rel int, %) m/z: 412 (9.9), 304 (4.2), 105 (100.0), 77 (23.8).
4-(4-Fluorophenylselanyl)-3-phenyl-1H-isochromen-1-one (3e7).
Purified by column chromatography (hexane/ethyl acetate = 95:5);
yield 0.091 g (92%); white solid, mp 137−140 °C. 1H NMR (CDCl3,
400 MHz) δ (ppm) = 8.35 (dd, J = 7.8 and 1.0 Hz, 1H); 8.07−8.04
(m, 1H); 7.75−7.70 (m, 1H); 7.65−7.62 (m, 2H); 7.56−7.53 (m,
1H); 7.45−7.39 (m, 3H); 7.18−7.13 (m, 2H); 6.91−6.85 (m, 2H).
13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 161.9 (d, 1JC−F = 245.0
Hz), 161.6, 159.4, 138.2, 135.3, 133.9, 131.2 (d, 3JC−F 7.8 Hz), 130.1,
129.8, 129.7, 128.7, 128.0, 127.8, 125.9 (d, 4JC−F 3.3 Hz), 120.8, 116.6
3H); 2.47 (t, J = 7.3 Hz, 2H); 1.32 (quint, J = 7.3 Hz, 2H); 1.09 (sext,
J = 7.3 Hz, 2H); 0.66 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 161.9, 157.9, 139.0, 135.1, 134.3, 130.1, 129.7,
128.4, 128.1, 127.7, 120.7, 105.1, 31.5, 28.7, 22.5, 13.4. 77Se{1H}
NMR (CDCl3, 76 MHz) δ (ppm) = 156.8. MS (rel int, %) m/z: 358
(48.1), 193 (100.0), 105 (69.1), 77 (47.5).
4-(Phenylselanyl)-1H-isochromen-1-one (3k). Purified by column
chromatography (hexane/ethyl acetate = 95:5); yield 0.067 g (89%);
white solid, mp 111−113 °C. 1H NMR (CDCl3, 400 MHz) δ (ppm)
= 8.30 (dd, J = 7.9 and 1.0 Hz, 1H); 7.82−7.79 (m, 1H); 7.76 (s,
1H); 7.72−7.67 (m, 1H); 7.54−7.50 (m, 1H); 7.36−7.32 (m, 2H);
7.23−7.18 (m, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) =
161.5, 149.8, 136.9, 135.2, 130.2, 130.0, 129.9, 129.4, 129.1, 127.1,
127.0, 121.8, 107.7. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) =
286.1. MS (rel int, %) m/z: 302 (61.4), 165 (72.5), 105 (100.0), 77
(36.5). HRMS (APCI-QTOF) m/z: [M + H]+ calcd for C15H11O2Se
302.9924; found: 302.9921.
2
(d, JC−F = 21.8 Hz), 105.3. 77Se{1H} NMR (CDCl3, 76 MHz) δ
(ppm) = 289.7. MS (rel int, %) m/z: 396 (20.1), 288 (10.6), 105
(100.0), 77 (21.7).
3-(2-Methoxyphenyl)-4-(phenylselanyl)-1H-isochromen-1-one
3-Phenyl-4-[3-(trifluoromethyl)phenylselanyl]-1H-isochromen-1-
(3l).5c Purified by column chromatography (hexane/ethyl acetate =
one (3f). Purified by column chromatography (hexane/ethyl acetate =
1
1
95:5); yield 0.090 g (88%); white solid, mp 109−111 °C. H NMR
95:5); yield 0.103 g (92%); white solid, mp 81−83 °C. H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.37 (dd, J = 7.9 and 0.7 Hz, 1H);
8.02−7.98 (m, 1H); 7.75−7.70 (m, 1H); 7.64−7.59 (m, 2H); 7.58−
7.52 (m, 1H); 7.47−7.37 (m, 5H); 7.31−7.24 (m, 2H). 13C{1H}
NMR (CDCl3, 100 MHz) δ (ppm) = 161.4, 160.0, 137.9, 135.5,
(CDCl3, 400 MHz) δ (ppm) = 8.35 (dd, J = 7.9 and 1.0 Hz, 1H);
7.97−7.95 (m, 1H); 7.69−7.64 (m, 1H); 7.53−7.49 (m, 1H); 7.43−
7.38 (m, 1H); 7.37−7.35 (m, 1H); 7.21−7.18 (m, 2H); 7.15−7.10
(m, 3H); 7.0−6.96 (m, 1H); 6.93−6.90 (m, 1H); 3.71 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 162.2, 157.2, 157.1,
138.1, 135.1, 131.6, 131.4, 130.8, 129.7, 129.4, 129.1, 128.5, 127.8,
126.3, 123.7, 121.1, 120.0, 110.8, 107.5, 55.3. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 296.7. MS (rel int, %) m/z: 408 (34.9),
300 (67.8), 135 (100.0), 77 (46.6).
2
133.7, 132.9, 132.0, 131.6 (q, JC−F = 32.3 Hz), 130.3, 129.9, 129.8,
129.5, 128.9, 127.9, 127.8, 125.6 (q, 3JC−F = 3.8 Hz), 123.5 (q, 1JC−F
=
4
271.3 Hz), 123.3 (q, JC−F = 3.6 Hz), 120.8, 104.3. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 305.1. MS (rel int, %) m/z: 446 (36.2),
338 (25.1), 105 (100.0), 77 (33.1). HRMS (APCI-QTOF) m/z: [M
+ H]+ calcd for C22H14F3O2Se 447.0111; found: 447.0104.
3-(4-Methoxyphenyl)-4-(phenylselanyl)-1H-isochromen-1-one
(3m).7 Purified by column chromatography (hexane/ethyl acetate =
4-(Mesitylselanyl)-3-phenyl-1H-isochromen-1-one (3g). Purified
1
by column chromatography (hexane/ethyl acetate = 95:5); yield
95:5); yield 0.092 g (90%); white solid, mp 155−158 °C. H NMR
1
0.096 g (91%); white solid, mp 110−113 °C. H NMR (CDCl3, 400
(CDCl3, 400 MHz) δ (ppm) = 8.34 (dd, J = 8.3 and 1.2 Hz, 1H);
8.04−8.0 (m, 1H); 7.70−7.63 (m, 3H); 7.52−7.48 (m, 1H); 7.21−
7.13 (m, 5H); 6.92−6.88 (m, 2H); 3.83 (s, 3H). 13C{1H} NMR
(CDCl3, 100 MHz) δ (ppm) = 161.8, 161.0, 159.5, 138.7, 135.3,
132.0, 131.3, 129.6, 129.5, 128.6, 128.4, 128.1, 126.34, 126.27, 120.6,
113.1, 103.7, 55.3. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) =
297.0. MS (rel int, %) m/z: 408 (31.1), 300 (91.9), 135 (100.0), 77
(21.0).
MHz) δ (ppm) = 8.23 (dd, J = 7.8 and 0.9 Hz, 1H); 7.76−7.73 (m,
1H); 7.57−7.53 (m, 1H); 7.42−7.36 (m, 3H); 7.35−7.28 (m, 3H);
6.62 (s, 2H); 2.09 (s, 6H); 2.07 (s, 3H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 161.9, 156.1, 141.0, 138.5, 137.7, 134.8, 134.1,
129.8, 129.7, 129.6, 129.0, 128.3, 128.0, 127.7, 127.2, 120.6, 107.3,
23.6, 20.7. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 210.3. MS
(rel int, %) m/z: 420 (28.7), 105 (100.0), 77 (19.8). HRMS (APCI-
QTOF) m/z: [M + H]+ calcd for C24H21O2Se 421.0707; found:
421.0700.
3-(4-tert-Butylphenyl)-4-(phenylselanyl)-1H-isochromen-1-one
(3n). Purified by column chromatography (hexane/ethyl acetate =
1
95:5); yield 0.091 g (84%); brown solid, mp 51−53 °C. H NMR
4-(Naphthalen-2-ylmethylselanyl)-3-phenyl-1H-isochromen-1-
one (3h). Purified by column chromatography (hexane/ethyl acetate
(CDCl3, 400 MHz) δ (ppm) = 8.37−8.33 (m, 1H); 8.04−8.01 (m,
1H); 7.70−7.66 (m, 1H); 7.65−7.61 (m, 2H); 7.53−7.48 (m, 1H);
7.43−7.39 (m, 2H); 7.22−7.14 (m, 5H); 1.33 (s, 9H). 13C{1H} NMR
(CDCl3, 100 MHz) δ (ppm) = 161.8, 159.6, 153.5, 138.5, 135.3,
132.0, 131.0, 129.6, 129.5, 128.7, 128.5, 128.2, 126.4, 124.7, 120.8,
104.1, 34.8, 31.2. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 294.1.
MS (rel int, %) m/z: 434 (32.8), 326 (30.7), 161 (100.0), 77 (9.2).
HRMS (APCI-QTOF) m/z: [M + H]+ calcd for C25H23O2Se
435.0863; found: 435.0858.
1
= 95:5); yield 0.091 g (82%); white solid, mp 98−101 °C. H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.25 (dd, J = 7.7 and 0.8 Hz, 1H);
8.17−8.14 (m, 1H); 7.72−7.64 (m, 2H); 7.48−7.43 (m, 3H); 7.36−
7.32 (m, 2H); 7.28−7.22 (m, 1H); 7.13−7.11 (m, 4H); 7.06−7.04
(m, 1H); 6.88−6.85 (m, 1H); 3.80 (s, 2H). 13C{1H} NMR (CDCl3,
100 MHz) δ (ppm) = 161.7, 159.3, 138.8, 135.2, 134.8, 133.8, 133.0,
132.3, 129.9, 129.8, 129.5, 128.4, 128.1, 128.0, 127.5, 127.4, 127.3,
127.2, 126.8, 126.2, 125.9, 120.5, 104.8, 32.4. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 251.5. MS (rel int, %) m/z: 442 (3.3),
141 (100.0), 105 (2.9). HRMS (APCI-QTOF) m/z: [M + H]+ calcd
for C26H19O2Se 443.0550; found: 443.0547.
3-(4-Chlorophenyl)-4-(phenylselanyl)-1H-isochromen-1-one
(3o).7 Purified by column chromatography (hexane/ethyl acetate =
1
95:5); yield 0.095 g (92%); white solid, mp 105−108 °C. H NMR
4-(Ethylselanyl)-3-phenyl-1H-isochromen-1-one (3i).7 Purified by
column chromatography (hexane/ethyl acetate = 95:5); yield 0.074 g
(90%); yellow solid, mp 120−123 °C. 1H NMR (CDCl3, 400 MHz) δ
(ppm) = 8.36 (dd, J = 7.8 and 0.7 Hz, 1H); 8.26−8.23 (m, 1H);
7.85−7.80 (m, 1H); 7.71−7.67 (m, 2H); 7.58−7.54 (m, 1H); 7.46−
7.43 (m, 3H); 2.56 (q, J = 7.4 Hz, 2H); 1.17 (t, J = 7.4 Hz, 3H).
13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 161.9, 158.0, 139.0,
135.1, 134.3, 130.1, 129.7, 128.4, 128.1, 127.7, 120.7, 104.8, 22.3,
15.0. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 189.6. MS (rel
int, %) m/z: 330 (40.9), 193 (100.0), 105 (17.3), 77 (37.0).
4-(n-Butylselanyl)-3-phenyl-1H-isochromen-1-one (3j).7 Purified
by column chromatography (hexane/ethyl acetate = 95:5); yield
(CDCl3, 400 MHz) δ (ppm) = 8.27−8.23 (m, 1H); 8.0−7.94 (m,
1H); 7.63−7.58 (m, 1H); 7.52−7.50 (m, 2H); 7.45−7.41 (m, 1H);
7.27−7.24 (m, 2H); 7.10−7.05 (m, 5H). 13C{1H} NMR (CDCl3, 100
MH) δ (ppm) = 161.4, 158.2, 138.2, 136.2, 135.4, 132.3, 131.5, 131.0,
129.7, 129.5, 128.9, 128.7, 128.2, 128.0, 126.6, 120.7, 105.1. 77Se{1H}
NMR (CDCl3, 76 MHz) δ (ppm) = 295.0. MS (rel int, %) m/z: 412
(25.5), 304 (16.1), 139 (100.0), 111 (14.7).
3-n-Butyl-4-(phenylselanyl)-1H-isochromen-1-one (3p).7 Purified
by column chromatography (hexane/ethyl acetate = 95:5); yield
1
0.076 g (85%); yellow solid, mp 51−54 °C. H NMR (CDCl3, 400
MHz) δ (ppm) = 8.31−8.27 (m, 1H); 7.96−7.93 (m, 1H); 7.68−7.63
(m, 1H); 7.49−7.44 (m, 1H); 7.26−7.15 (m, 5H); 3.04 (t, J = 7.4 Hz,
2H); 1.69 (quint, J = 7.4 Hz, 2H); 1.38 (sext, J = 7.4 Hz, 2H); 0.90 (t,
J = 7.4 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 163.8,
162.1, 138.4, 135.2, 131.3, 129.6, 129.4, 128.8, 128.0, 127.3, 126.4,
1
0.084 g (94%); yellow solid, mp 62−64 °C. H NMR (CDCl3, 400
MHz) δ (ppm) = 8.30−8.26 (m, 1H); 8.20−8.17 (m, 1H); 7.77−7.73
(m, 1H); 7.65−7.60 (m, 2H); 7.51−7.46 (m, 1H); 7.40−7.36 (m,
H
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120.4, 104.2, 34.4, 30.1, 22.3, 13.7. 77Se{1H} NMR (CDCl3, 76 MHz)
δ (ppm) = 264.0. MS (rel int, %) m/z: 358 (98.3), 274 (84.9), 159
(86.6), 57 (100.0).
125Te{1H} NMR (CDCl3, 127 MHz) δ (ppm) = 508.5. MS (rel int,
%) m/z: 429 (M+ + 1, 0.1), 312 (7.6), 91 (100.0).
3-Phenyl-4-(4-tolyltellanyl)-1H-isochromen-1-one (3w). Purified
by column chromatography (hexane/ethyl acetate = 95:5); yield
0.091 g (82%); yellow solid, mp 114−117 °C. 1H NMR (CDCl3, 400
MHz) δ (ppm) = 8.31 (dd, J = 7.9 and 1.0 Hz, 1H); 8.13−8.10 (m,
1H); 7.70−7.66 (m, 1H); 7.56−7.53 (m, 2H); 7.51−7.47 (m, 1H);
7.43−7.37 (m, 3H); 7.29−7.25 (m, 2H); 6.95−6.91 (m, 2H); 2.26 (s,
3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 162.1, 161.1,
139.8, 137.6, 136.3, 135.5, 135.3, 132.8, 130.5, 129.94, 129.9, 129.6,
128.6, 127.7, 120.4, 111.1, 93.8, 21.0. 125Te{1H} NMR (CDCl3, 127
MHz) δ (ppm) = 497.9. MS (rel int, %) m/z: 442 (40.8), 312 (62.0),
105 (100.0), 77 (45.1). HRMS (APCI-QTOF) m/z: [M + H]+ calcd
for C22H17O2Te 443.0291; found: 443.0286.
4-(Phenylselanyl)-3-(trimethylsilyl)-1H-isochromen-1-one (3q).
Purified by column chromatography (hexane/ethyl acetate = 95:5);
yield 0.086 g (92%); yellow solid, mp 108−110 °C. 1H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.31−8.28 (m, 1H); 7.80−7.77 (m,
1H); 7.63−7.59 (m, 1H); 7.50−7.46 (m, 1H); 7.19−7.12 (m, 5H);
0.42 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 170.2,
162.6, 136.8, 134.9, 131.7, 129.3, 129.0, 128.0, 126.9, 126.2, 121.9,
116.3, −0.5. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 271.1. MS
(rel int, %) m/z: 374 (13.3), 359 (11.5), 217 (22.2), 73 (100.0).
HRMS (APCI-QTOF) m/z: [M + H]+ calcd for C18H19O2SeSi
375.0320; found: 375.0312.
3-(Hydroxymethyl)-4-(phenylselanyl)-1H-isochromen-1-one (3r).
Purified by column chromatography (hexane/ethyl acetate = 80:20);
yield 0.069 g (83%); brown oil. We noticed that this product is quite
unstable. After purification, the solvent was quickly removed under
vacuum and the NMR spectra were collected. 1H NMR (CDCl3, 400
MHz) δ (ppm) = 8.32−8.29 (m, 1H); 8.03−8.0 (m, 1H); 7.73−7.69
(m, 1H); 7.55−7.50 (m, 1H); 7.31−7.28 (m, 2H); 7.23−7.18 (m,
3H); 4.95 (s, 2H); 2.69 (br s, 1H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 161.4, 159.3, 137.6, 135.5, 129.8, 129.7, 129.6,
129.5, 129.0, 127.7, 127.0, 121.0, 105.7, 62.6. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 252.7. MS (rel int, %) m/z: 332 (87.4),
273 (48.7), 165 (100.0), 77 (36.2). HRMS (APCI-QTOF) m/z: [M
+ H]+ calcd for C16H13O3Se 333.0030; found: 333.0030.
3-(1-Hydroxyethyl)-4-(phenylselanyl)-1H-isochromen-1-one (3s).
Purified by column chromatography (hexane/ethyl acetate = 80:20);
yield 0.064 g (74%); yellow oil. 1H NMR (CDCl3, 400 MHz) δ
(ppm) = 8.31 (dd, J = 7.9 and 1.0 Hz, 1H); 8.03−8.0 (m, 1H); 7.73−
7.69 (m, 1H); 7.54−7.50 (m, 1H); 7.29−7.26 (m, 2H); 7.23−7.18
(m, 3H); 5.67−5.61 (m, 1H); 2.48 (br s, 1H); 1.51 (d, J = 6.6 Hz,
3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 161.7, 161.4,
137.8, 135.4, 130.6, 129.8, 129.6, 129.2, 128.8, 127.8, 126.8, 121.0,
103.8, 67.8, 21.8. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 249.9.
MS (rel int, %) m/z: 346 (51.8), 273 (29.2), 193 (67.6), 147 (100.0),
77 (37.8). HRMS (APCI-QTOF) m/z: [M + H]+ calcd for
C17H15O3Se 347.0186; found: 347.0181.
4-(4-Methoxyphenyltellanyl)-3-phenyl-1H-isochromen-1-one
(3x). Purified by column chromatography (hexane/ethyl acetate =
1
95:5); yield 0.089 g (78%); yellow solid, mp 130−132 °C. H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.31 (dd, J = 7.8 and 0.8 Hz, 1H);
8.17−8.14 (m, 1H); 7.73−7.69 (m, 1H); 7.55−7.52 (m, 2H); 7.51−
7.48 (m, 1H); 7.45−7.39 (m, 3H); 7.36−7.32 (m, 2H); 6.68−6.65
(m, 2H); 3.72 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) =
162.2, 160.7, 159.7, 139.9, 138.1, 136.3, 135.3, 132.7, 130.0, 129.9,
129.6, 128.6, 127.7, 120.5, 115.5, 104.0, 94.3, 55.1. 125Te{1H} NMR
(CDCl3, 127 MHz) δ (ppm) = 491.9. MS (rel int, %) m/z: 458
(36.5), 328 (100.0), 105 (92.2), 77 (67.1). HRMS (APCI-QTOF)
m/z: [M + H]+ calcd for C22H17O3Te; 459.0240, found: 459.0239.
3-Phenyl-1H-isochromen-1-one (3y).7 Purified by column chro-
matography (hexane/ethyl acetate = 95:5); yield from (4-
ClC6H4Te)2: 0.047 g (84%) and yield from (C4H9Te)2: 0.050 g
7
1
(90%); white solid, mp 87−90 °C. H NMR (CDCl3, 400 MHz) δ
(ppm) = 8.31−8.28 (m, 1H); 7.89−7.85 (m, 2H); 7.73−7.69 (m,
1H); 7.51−7.40 (m, 5H); 6.94 (s, 1H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 162.3, 153.6, 137.5, 134.8, 131.9, 129.9, 129.6,
128.8, 128.1, 125.9, 125.2, 120.5, 101.8. MS (rel int, %) m/z: 222
(100.0), 194 (79.1), 105 (27.0), 77 (46.0).
Procedure for the Synthesis of 4a−c. To a 10.0 mL glass tube
were added the appropriate 1,3-diyne 1o−p (0.25 mmol), dialkyl
diselenide 2 (0.300 mmol, 2.4 equiv), Oxone (0.500 mmol, 0.154 g,
2.0 equiv), and solvent (2.0 mL). The amplitude of the ultrasound
waves was fixed at 60%. Then the reaction mixture was sonicated for
the time required to consume the starting material 1. The progress of
the reaction was monitored by gas chromatography. After that, the
resulting solution was received in water (10.0 mL), and the product
was extracted with ethyl acetate (3 × 10.0 mL). The organic layer was
separated, dried with MgSO4, and concentrated under vacuum. The
residue was purified by column chromatography using silica gel and
hexane/ethyl acetate as eluent to afford 4a−c.
3-(Ethylselanyl)-2-phenyl-5H-selenopheno[3,2-c]isochromen-5-
one (4a).16 Purified by column chromatography (hexane/ethyl
acetate = 96:4); yield 0.087 g (80%); yellow solid, mp 155−158 °C
(lit.16 155−157 °C). 1H NMR (CDCl3, 400 MHz) δ (ppm) = 8.39−
8.35 (m, 1H); 7.74 (td, J = 7.7 and 1.1 Hz, 1H); 7.62−7.58 (m, 2H);
7.52−7.42 (m, 5H); 2.93 (q, J = 7.5 Hz, 2H); 1.29 (t, J = 7.5 Hz, 3H).
13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 161.8, 152.5, 148.7,
3-(2-Ethoxypropan-2-yl)-4-(phenylselanyl)-1H-isochromen-1-
one (3t). Purified by column chromatography (hexane/ethyl acetate =
90:10); yield 0.089 g (92%); yellow oil. 1H NMR (CDCl3, 400 MHz)
δ (ppm) = 7.69−7.66 (m, 1H); 7.44−7.40 (m, 1H); 7.36−7.32 (m,
1H); 7.24−7.15 (m, 6H); 4.20 (q, J = 7.1 Hz, 2H); 2.25 (s, 3H); 2.18
(s, 3H); 1.20 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz)
δ (ppm) = 195.3, 167.8, 154.3, 140.2, 131.7, 131.4, 130.7, 130.6,
130.4, 129.01, 128.99, 128.5, 126.5, 124.6, 61.4, 26.5, 23.5, 13.9.
77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 357.3. MS (rel int, %)
m/z: 388 (2.6), 231 (100.0), 149 (74.2), 77 (18.2). HRMS (APCI-
QTOF) m/z: [M + H]+ calcd for C20H21O3Se 389.0656; found:
389.0652.
3-(2-Methoxypropan-2-yl)-4-(phenylselanyl)-1H-isochromen-1-
one (3u). Purified by column chromatography (hexane/ethyl acetate
1
= 90:10); yield 0.083 g (89%); yellow oil. H NMR (CDCl3, 400
MHz) δ (ppm) = 7.68−7.65 (m, 1H); 7.43−7.39 (m, 1H); 7.36−7.32
(m, 1H); 7.23−7.19 (m, 3H); 7.17−7.13 (m, 3H); 3.62 (s, 3H); 2.25
(s, 3H); 2.17 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) =
195.1, 168.2, 154.0, 140.1, 131.2, 131.1, 130.7, 130.6, 130.4, 129.0,
128.9, 128.3, 126.5, 124.6, 52.2, 26.3, 23.3. 77Se{1H} NMR (CDCl3,
76 MHz) δ (ppm) = 357.8. MS (rel int, %) m/z: 374 (3.0), 217
(100.0), 163 (59.1), 77 (19.7). HRMS (APCI-QTOF) m/z: [M +
H]+ calcd for C19H19O3Se 375.0499; found: 375.0494.
135.6, 135.33, 135.26, 130.9, 129.6, 128.9, 128.5, 128.0, 123.6, 119.2,
117.9, 113.9, 21.9, 15.4. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) =
536.8, 227.1. MS (rel int, %) m/z: 434 (100.0), 406 (29.7), 326
(61.7), 297 (54.4), 207 (27.9).
3-(Butylselanyl)-2-phenyl-5H-selenopheno[3,2-c]isochromen-5-
one (4b).16 Purified by column chromatography (hexane/ethyl
acetate = 96:4); yield 0.102 g (88%); yellow solid, mp 80−82 °C
(lit.16 80−82 °C). 1H NMR (CDCl3, 400 MHz) δ (ppm) = 8.37−834
(m, 1H); 7.74 (td, J = 7.7 and 1.3 Hz, 1H); 7.62−7.58 (m, 2H);
7.52−7.41 (m, 5H); 2.89 (t, J = 7.4 Hz, 2H); 1.52 (quint, J = 7.4 Hz,
2H); 1.28 (sext, J = 7.4 Hz, 2H); 0.79 (t, J = 7.4 Hz, 3H). 13C{1H}
NMR (CDCl3, 100 MHz) δ (ppm) = 161.8, 152.5, 148.6, 135.6,
135.3, 135.2, 130.9, 129.6, 128.9, 128.4, 128.0, 123.6, 119.2, 117.9,
114.2, 32.1, 28.1, 22.6, 13.4. 77Se{1H} NMR (CDCl3, 76 MHz) δ
(ppm) = 536.2, 194.9. MS (rel int, %) m/z: 462 (79.0), 406 (89.6),
326 (100.0), 189 (72.6), 89 (25.5).
3-Phenyl-4-(phenyltellanyl)-1H-isochromen-1-one (3v).7 Purified
by column chromatography (hexane/ethyl acetate = 95:5); yield
1
0.090 g (84%); white solid, mp 135−137 °C. H NMR (CDCl3, 400
MHz) δ (ppm) = 8.31 (dd, J = 7.9 and 1.1 Hz, 1H); 8.10−8.05 (m,
1H); 7.67−7.63 (m, 1H); 7.56−7.52 (m, 2H); 7.49−7.45 (m, 1H);
7.43−7.33 (m, 5H); 7.16−7.06 (m, 3H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 162.1, 161.3, 139.7, 136.3, 135.4, 135.0, 132.7,
130.0, 129.9, 129.64, 129.6, 128.7, 127.7, 127.5, 120.5, 115.5, 93.7.
I
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2-Butyl-3-(butylselanyl)-5H-selenopheno[3,2-c]isochromen-5-
one (4c).16 Purified by column chromatography (hexane/ethyl acetate
= 96:4); yield 0.087 g (79%); yellow solid, mp 60−63 °C (lit.16 60−
62 °C). 1H NMR (CDCl3, 400 MHz) δ (ppm) = 8.32−8.28 (m, 1H);
7.68 (td, J = 7.9 and 1.3 Hz, 1H); 7.45−7.41 (m, 1H); 7.38−7.35 (m,
1H); 3.11 (t, J = 7.6 Hz, 2H); 2.91 (t, J = 7.4 Hz, 2H); 1.69 (quint, J
= 7.3 Hz, 2H); 1.60 (quint, J = 7.3 Hz, 2H); 1.50−1.36 (m, 4H); 0.98
(t, J = 7.3 Hz, 3H); 0.88 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (CDCl3,
100 MHz) δ (ppm) = 162.0, 154.5, 152.0, 135.5, 135.1, 130.7, 127.4,
123.1, 118.1, 115.4, 114.4, 34.4, 32.8, 32.4, 28.0, 22.6, 22.2, 13.8, 13.5.
77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 521.8, 168.7. MS (rel
130.1, 130.0, 129.3, 128.4, 127.8, 125.4, 31.6, 29.0, 22.5, 13.4.
77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 164.1. MS (rel int, %)
m/z: 374 (25.1), 165 (33.1), 105 (100.0), 77 (72.7). HRMS (APCI-
QTOF) m/z: [M]+ calcd for C19H18OSSe 374.0244; found:
374.0260.
Ethyl 2-(1,2-Diethoxy-2-phenylvinyl)benzoate (6). Purified by
column chromatography (hexane/ethyl acetate = 95:5); yield 0.021 g
1
(25%); white solid, mp 70−73 °C. H NMR (CDCl3, 400 MHz) δ
(ppm) = 8.05−8.02 (m, 2H); 7.75−7.72 (m, 1H); 7.41−7.37 (m,
3H); 7.35−7.32 (m, 1H); 7.31−7.26 (m, 2H); 4.30 (q, J = 7.2 Hz,
2H); 3.47−3.41 (m, 4H); 1.34 (t, J = 7.2 Hz, 3H); 1.19 (t, J = 7.2 Hz,
6H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm) = 193.9, 169.7,
135.7, 135.4, 132.7, 132.3, 129.8, 129.7, 128.6, 128.4, 128.2, 127.9,
102.0, 61.2, 58.4, 14.9, 14.0. MS (rel int, %) m/z: 311 (M+-C2H5,
5.3), 251 (68.1), 149 (100.0), 105 (19.4), 77 (20.6). HRMS (APCI-
QTOF) m/z: [M-C2H5]+ calcd for C21H24O4 311.1283; found:
311.1282.
int, %) m/z: 442 (70.6), 385 (43.4), 343 (62.3), 305 (37.4), 263
(100.0).
Procedure for the Synthesis of 1H-isochromene-1-thione
5a−d. Compounds 5 were prepared according to a published
procedure, with minor changes.23 In a 10 mL glass vial equipped with
small magnetic stirring bar was added the mixture of Lawesson’s
reagent (0.13 mmol, 0.053 g, 1.04 equiv) and the respective 3 (0.25
mmol). Then the reaction mixture was irradiated in a focused
microwave reactor (CEM) at 140 °C (temperature was measured
with an IR sensor on the outer surface of the reaction vial) for 15 min,
using an irradiation power of 200 W and pressure of 100 psi (the
ramp temperature rate was 40 s). The progress of the reaction was
monitored by TLC. The reaction mixture 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 with MgSO4, and concentrated
under vacuum. The residue was purified by column chromatography
using silica gel and hexane/ethyl acetate as eluent to afford 5a−d.
3-Phenyl-4-(phenylselanyl)-1H-isochromene-1-thione (5a). Puri-
fied by column chromatography (hexane/ethyl acetate = 95:5); yield
0.097 g (98%); yellow solid, mp 140−142 °C. 1H NMR (CDCl3, 400
MHz) δ (ppm) = 8.79−8.74 (m, 1H); 8.08−8.04 (m, 1H); 7.71−7.66
(m, 3H); 7.51−7.39 (m, 4H); 7.19−7.14 (m, 5H). 13C{1H} NMR
(CDCl3, 100 MHz) δ (ppm) = 199.9, 161.9, 135.6, 133.6, 133.1,
133.0, 131.5, 130.34, 130.3, 129.9, 129.5, 129.1, 128.4, 127.9, 126.7,
108.1. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 295.3. MS (rel
int, %) m/z: 394 (63.4), 237 (100.0), 105 (60.4), 77 (57.8). HRMS
(APCI-QTOF) m/z: [M]+ calcd for C21H14OSSe 393.9931; found:
393.9932.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00271.
■
sı
Copies of 1H, 13C{1H}, 77Se{1H}, and 125Te{1H} spectra
of all the synthesized compounds (PDF)
FAIR data, including the primary NMR FID files, for
compounds 3a−y, 4a−c, 5a−d, and 6 (ZIP)
AUTHOR INFORMATION
Corresponding Author
■
̂
Gelson Perin − Laboratório de Síntese Organica Limpa −
LASOL, CCQFA, Universidade Federal de Pelotas − UFPel,
96010-900 Pelotas, RS, Brazil; orcid.org/0000-0003-
0359-0811; Email: gelson_perin@ufpel.edu.br
Authors
̂
Helen A. Goulart − Laboratório de Síntese Organica Limpa −
4-(4-Methoxyphenylselanyl)-3-phenyl-1H-isochromene-1-thione
LASOL, CCQFA, Universidade Federal de Pelotas − UFPel,
(5b). Purified by column chromatography (hexane/ethyl acetate =
1
96010-900 Pelotas, RS, Brazil
95:5); yield 0.105 g (99%); yellow solid, mp 111−113 °C. H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.76−8.71 (m, 1H); 8.16−8.12 (m,
1H); 7.73−7.68 (m, 3H); 7.49−7.40 (m, 4H); 7.11 (d, J = 8.6 Hz,
2H); 6.70 (d, J = 8.6 Hz, 2H); 3.70 (s, 3H). 13C{1H} NMR (CDCl3,
100 MHz) δ (ppm) = 199.9, 161.3, 159.0, 135.4, 133.6, 133.04, 133.0,
131.8, 130.25, 130.2, 130.0, 129.3, 128.4, 127.8, 121.0, 115.1, 109.4,
55.2. 77Se{1H} NMR (CDCl3, 76 MHz) δ (ppm) = 282.5. MS (rel
int, %) m/z: 424 (18.3), 165 (30.5), 105 (100.0), 77 (42.6). HRMS
(APCI-QTOF) m/z: [M]+ calcd for C22H16O2SSe 424.0036; found:
424.0032.
̂
José S. S. Neto − Laboratório de Síntese Organica Limpa −
LASOL, CCQFA, Universidade Federal de Pelotas − UFPel,
96010-900 Pelotas, RS, Brazil
̂
Angelita M. Barcellos − Laboratório de Síntese Organica
Limpa − LASOL, CCQFA, Universidade Federal de Pelotas
− UFPel, 96010-900 Pelotas, RS, Brazil
̂
Krigor B. Silva − Laboratório de Síntese Organica Limpa −
LASOL, CCQFA, Universidade Federal de Pelotas − UFPel,
96010-900 Pelotas, RS, Brazil
4-(4-Chlorophenylselanyl)-3-phenyl-1H-isochromene-1-thione
(5c). Purified by column chromatography (hexane/ethyl acetate =
Maiara C. de Moraes − Laboratory of Biotechnology of
Natural and Synthetic Products, Universidade de Caxias do
Sul, 95070-560 Caxias do Sul, RS, Brazil
1
95:5); yield 0.098 g (92%); yellow solid, mp 123−125 °C. H NMR
(CDCl3, 400 MHz) δ (ppm) = 8.78−8.75 (m, 1H); 8.03−8.0 (m,
1H); 7.74−7.70 (m, 1H); 7.68−7.65 (m, 2H); 7.54−7.50 (m, 1H);
7.47−7.40 (m, 3H); 7.16−7.08 (m, 4H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 199.7, 162.0, 135.7, 133.4, 133.2, 132.8, 132.6,
130.5, 130.3, 129.8, 129.7, 129.6, 128.2, 128.0, 107.9. 77Se{1H} NMR
(CDCl3, 76 MHz) δ (ppm) = 295.3. MS (rel int, %) m/z: 428 (32.2),
237 (100), 165 (56.8), 105 (97.5). HRMS (APCI-QTOF) m/z: [M]+
calcd for C21H13ClOSSe 427.9541; found: 427.9556.
̂
Raquel G. Jacob − Laboratório de Síntese Organica Limpa −
LASOL, CCQFA, Universidade Federal de Pelotas − UFPel,
96010-900 Pelotas, RS, Brazil
̂
Eder J. Lenardao − Laboratório de Síntese Organica Limpa −
̃
LASOL, CCQFA, Universidade Federal de Pelotas − UFPel,
96010-900 Pelotas, RS, Brazil; orcid.org/0000-0001-
7920-3289
4-(n-Butylselanyl)-3-phenyl-1H-isochromene-1-thione (5d). Pu-
rified by column chromatography (hexane/ethyl acetate = 95:5); yield
Thiago Barcellos − Laboratory of Biotechnology of Natural
and Synthetic Products, Universidade de Caxias do Sul,
95070-560 Caxias do Sul, RS, Brazil; orcid.org/0000-
0001-9872-4602
1
0.084 g (90%); yellow solid, mp 66−68 °C. H NMR (CDCl3, 400
MHz) δ (ppm) = 8.80−8.77 (m, 1H); 8.29−8.26 (m, 1H); 7.85−7.81
(m, 1H); 7.75−7.73 (m, 2H); 7.57−7.52 (m, 1H); 7.48−7.45 (m,
3H); 2.56 (t, J = 7.2 Hz, 2H); 1.40 (quint, J = 7.2 Hz, 2H); 1.17 (sext,
J = 7.2 Hz, 2H); 0.74 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (CDCl3, 100
MHz) δ (ppm) = 200.1, 160.6, 135.4, 133.9, 133.6, 133.2, 130.3,
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00271
J
https://doi.org/10.1021/acs.joc.1c00271
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(9) Hussain, H.; Green, I. R.; Ahmed, I. Journey Describing
Applications of Oxone in Synthetic Chemistry. Chem. Rev. 2013, 113,
3329−3371.
Notes
The authors declare no competing financial interest.
(10) (a) Zheng, Y.; Liu, M.; Qiu, G.; Xie, W.; Wu, J. Synthesis of 3-
(Bromomethylene)isobenzofuran-1(3H)-ones through Regioselective
5-Exo-Dig Bromocyclization of 2-Alkynylbenzoic Acids. Tetrahedron
2019, 75, 1663−1668. (b) Uyanik, M.; Kato, T.; Sahara, N.; Katade,
O.; Ishihara, K. High-Performance Ammonium Hypoiodite/Oxone
Catalysis for Enantioselective Oxidative Dearomatization of Arenols.
ACS Catal. 2019, 9, 11619−11626. (c) Uyanik, M.; Sahara, N.;
Katade, O.; Ishihara, K. Chemoselective Oxidative Spiroetherification
and Spiroamination of Arenols Using I+/Oxone Catalysis. Org. Lett.
2020, 22, 560−564. (d) Wang, Y.-C.; Liu, J.-B.; Zhou, H.; Xie, W.;
Rojsitthisak, P.; Qiu, G. Ortho-Hydroxylative Ipso-Cyclization of N-
Arylpropiolamide. J. Org. Chem. 2020, 85, 1906−1914.
ACKNOWLEDGMENTS
This study was financed in part by the Coordenaca
■
̧
o
̃
de
Aperfeic
̧oamento 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 R.G.J.,
E.J.L., and G.P.
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