Efficient and highly selective method for the synthesis of 4-Iodo-3-substituted 1 H -Isoselenochromenes and -isothiochromenes

Article abstract of DOI:10.1055/s-0030-1258386

We present here our results on the preparation of 2-alkynylbenzyl selenide and sulfide derivatives via Sonogashira cross-coupling of benzyl chalcogenides with different alkynes. This cross-coupling reaction proceeded cleanly under mild conditions and was performed with propargyl alcohol as well as alkyl- and arylalkynes. Subsequent electrophilic-cyclization reaction of the 2-alkynylbenzyl selenide and sulfide derivatives using iodine as an electrophilic source gave 4-iodo-3-substituted 1H-isoselenochromenes and -isothiochromenes in moderate yields. The unique product obtained during the course of this cyclization contained a six-membered ring which was confirmed by X-ray diffraction analysis. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258386

PAPER
413
Efficient and Highly Selective Method for the Synthesis of 4-Iodo-3-substituted
1H-Isoselenochromenes and -isothiochromenes
Synthesis of Isos
a
r
e
nes and
o
Isothiochro
l
menes ine C. Schneider,a Cristiani Bortolatto,a Davi F. Back,b Paulo H. Menezes,c Gilson Zeni*a
a
Laboratório de Síntese, Reatividade, Avaliação Farmacológica e Toxicológica de Organocalcogênios, CCNE, UFSM,
Santa Maria, Rio Grande do Sul, CEP 97105-900, Brazil
Fax +55(55)32208978; E-mail: gzeni@pq.cnpq.br
Laboratório de Materiais Inorgânicos, CCNE, UFSM, Santa Maria, Rio Grande do Sul 97105-900, Brazil
Universidade Federal de Pernambuco, Departamento Química Fundamental, Recife, Pernambuco 50670-901, Brazil
b
c
Received 5 October 2010; revised 25 November 2010
corresponding 2-benzotelluropyrylium and 2-benzo-
selenopyrylium salts in good yields.9c As a result of com-
bining our knowledge of the synthesis of heterocycles
containing a chalcogen11 with the unexplored iodide-pro-
Abstract: We present here our results on the preparation of 2-alky-
nylbenzyl selenide and sulfide derivatives via Sonogashira cross-
coupling of benzyl chalcogenides with different alkynes. This
cross-coupling reaction proceeded cleanly under mild conditions
and was performed with propargyl alcohol as well as alkyl- and moted cyclization of 2-alkynylbenzyl chalcogenide deriv-
arylalkynes. Subsequent electrophilic-cyclization reaction of the 2-
atives, in this paper we reported a synthetic method for
alkynylbenzyl selenide and sulfide derivatives using iodine as an
isochalcogenochromenes starting from 2-alkynylbenzyl
electrophilic source gave 4-iodo-3-substituted 1H-isoseleno-
chalcogenides. Our idea is outlined in Scheme 1, which
chromenes and -isothiochromenes in moderate yields. The unique
consisted of (i) preparation of 2-bromobenzyl selenides
product obtained during the course of this cyclization contained a
and sulfides 1 from 2-bromobenzyl bromide, (ii) Sono-
gashira cross-coupling the 2-bromobenzyl selenides and
sulfides 1 with terminal alkynes to obtain 2-alkynylbenzyl
selenides and sulfides 2, and (iii) electrophilic cyclization
of 2-alkynylbenzyl selenides and sulfides 2 to form iso-
selenochromenes 3 (Y = Se) and isothiochromenes 3 (Y =
S), respectively (Scheme 1).
six-membered ring which was confirmed by X-ray diffraction anal-
ysis.
Key words: selenides, isochromenes, electrophilic cyclization, het-
erocycles
In recent years there has been increased interest in the syn-
thesis of heterocycles since they are of great importance in
organic and medicinal chemistry.1 The literature contains
a variety of synthetic approaches to heterocycle ring struc-
tures, much of which has been compiled into comprehen-
sive reviews.2,3 A great number of selenium heterocycles
have been synthesized and their chemistry has attracted a
good deal of interest and activity from a variety of stand-
points, such as structure, stereochemistry, reactivity, and
their application in organic synthesis.4 Selenophenes, as
important selenium heterocycles, are widely studied
agents with a diverse array of biological effects that in-
clude antioxidant,5 antinociceptive,6 and anti-inflammato-
ry properties,7 as well as efficacy as maturation-inducing
agents.8 Electrophilic cyclization is an alternative route
for the generation of highly functionalized chalcogen het-
erocycles employing electrophiles, like iodine or iodine
monochloride, and chalcogen derivatives.9 The synthetic
study of six-membered ring containing selenium has been
surprisingly limited.10 Among them, benzo[c]selenocou-
marins were prepared in good yields by Christiaens and
co-workers.10b More recently, Akiba and co-workers re-
ported the synthesis of isotellurochromenes and isosele-
nochromenes together with (Z)-1-methylene-2-tellura-
and -2-selenaindanes by an intramolecular cyclization
reaction. The isochromenes were transformed into the
Br
YR1
R1YYR1, NaBH4
EtOH
Br
Br
1
R2
H
"Pd", "Cu", Et3N
I2
YR1
Y
CH2Cl2
R2
R2
I
3
2
Y = Se, S; R1 = Me, n-Bu; R2 = alkyl, aryl
Scheme 1
To prepare 2-bromobenzyl selenides 1 (Y = Se), we chose
the alkylation of selenolates.12 In this way, the reaction of
2-bromobenzyl bromide with the alkylselenolate anion,
generated from dialkyl diselenide and sodium borohy-
dride in ethanol, at room temperature, gave the desired
product 1 (Y = Se) in good yield. For the introduction of
the terminal alkyne, we used the Sonogashira cross-
coupling.13 Thus the reaction of 2-bromobenzyl selenide 1
(Y = Se, 0.5 mmol) with terminal alkyne (2.5 equiv) using
PdCl2(PPh3)2 (2 mol%) as the palladium source, copper(I)
iodide (1 mol%) as co-catalyst and triethylamine (5 mL)
as solvent and base, at reflux for 12 hours, gave the de-
sired 2-alkynylbenzyl selenides 2 (Y = Se). Using this se-
quence, we were able to prepare a number of novel 2-
alkynylbenzyl selenides 2 (Y = Se) and the analogous sul-
SYNTHESIS 2011, No. 3, pp 0413–0418
x
x
.
x
x
.2
0
1
1
Advanced online publication: 23.12.2010
DOI: 10.1055/s-0030-1258386; Art ID: M06710SS
© Georg Thieme Verlag Stuttgart · New York

414
C. C. Schneider et al.
PAPER
fides 2 (Y = S) to illustrate the generality and scope of the electron-withdrawing (Cl) group delivered the products
reaction (Table 1).
2h and 2j in comparable yields (entries 8 and 10). Finally,
we then explored the possibility of expanding our method-
ology to 2-alkynylbenzyl sulfides. It was found that the re-
action worked well, affording the 2-alkynylbenzyl
sulfides 2l–s in moderate to excellent yields, under the
same reaction conditions.
We gained a good understanding of this process by study-
ing the scope and limitations of this reaction. First, to de-
termine the real influence of the terminal alkyne, we kept
the butyl benzyl selenide 1 (YR1 = SeBu) invariant
(Table 1). Interestingly, all entries provided the corre-
sponding 2-alkynylbenzyl selenides 2 (Y = Se) in accept- After the success in the synthesis of 2-alkynylbenzyl chal-
able yields. Both alkyl- and bulky alkyl-substituted cogenides 2, we next focused our attention on the devel-
alkynes gave the products in similar yields, e.g. 2a and 2b opment of an optimum set of conditions for the
(entries 1 and 2). Our experiments showed that the reac- electrophilic cyclization. For this purpose, the reaction of
tion with propargyl or homopropargyl alcohols gave the 2f with iodine was chosen as a model system.
corresponding products 2c–e in good yields, although the
Table 2 Influence of Reaction Conditions on the Iodo Cyclization
yield was lower for the propargyl alcohol itself (entries 3–
5). In addition to alkylalkynes and propargyl alcohols, the
reaction took place with arylalkynes and we observed that
the reaction was not sensitive to electronic effects in the
aromatic ring of the arylalkynes. For example, aryl-
alkynes having either an electron-donating (Me) or an
of Butyl 2-Phenylbenzyl Selenide (2f)a
E+, solvent
SeBu
Se
temperature
I
3d
2f
Entry
E+ (equiv)
I2 (2.0)
Solvent
Temp
Yield (%)
69
Table 1 Synthesis of 2-Alkynylbenzyl Selenides 2 (Y = Se) and Sul-
fides 2 (Y = S)a
1
2
CH2Cl2
Et2O
r.t.
YR1
YR1
R2
H
I2 (2.0)
r.t.
32
PdCl2(PPh3)2 (2 mol%)
CuI (1 mol%), Et3N
Br
R2
1
Entry
1
2
3
I2 (2.0)
MeCN
THF
r.t.
35
YR1
R2
Product
Yielda (%)
51
4
I2 (2.0)
r.t.
41
5
I2 (2.0)
EtOH
r.t.
47
SeBu
SeBu
SeBu
SeBu
SeBu
SeBu
SeBu
SeBu
SeBu
SeBu
SeBu
SMe
SMe
SMe
SMe
SMe
SMe
SMe
SMe
(CH2)4Me
t-Bu
2a
2b
2c
2d
2e
2f
6
I2 (1.1)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
r.t.
47
2
60
7
I2 (3.0)
r.t.
45
3
C(OH)Me2
CH2OH
(CH2)2OH
Ph
83
8
ICl (1.1)
ICl (2.0)
ICl (3.0)
ICl (2.0)
r.t.
35
4
61
9
r.t.
55
5
85
10
11
r.t.
n.r.
n.r.
6
69
–20 C
7
2-MeOC6H4
4-MeC6H4
3-MeC6H4
4-ClC6H4
1-naphthyl
(CH2)4Me
t-Bu
2g
2h
2i
67
a Reactions performed using 2f (0.25 mmol), 2 h.
8
50
9
54
Thus, the reaction of substrate 2f (0.25 mmol) with iodine
(2.0 equiv) was performed at room temperature using dif-
ferent solvents (Table 2). A comparison of the effective-
ness of the solvents showed that all of them yielded
cyclized product 3d (entries 1–5), but dichloromethane
was the most efficient since the product was obtained in
69% yield after two hours (entry 1). It is important to note
that when the amount of the electrophile was changed
from 2.0 to 1.1 or 3.0 equivalents the yield of 3d de-
creased (entry 1 vs entries 6 and 7). Examining the elec-
trophile source showed that 1.1 to 3.0 equivalents of
iodine monochloride gave the target product 3d in unac-
ceptable yield (entries 8–11). Thus, the optimum condi-
tions for this electrophilic cyclization were identified as 2-
alkynylbenzyl chalcogenide 2 (1.0 equiv), iodine (2.0
equiv) as the electrophilic source, dichloromethane as the
solvent, at room temperature for two hours.
10
11
12
13
14
15
16
17
18
19
2j
55
2k
2l
80
75
2m
2n
2o
2p
2q
2r
2s
61
C(OH)Me2
CH2OH
Ph
92
59
75
4-MeC6H4
4-ClC6H4
1-naphthyl
85
76
85
a Isolated yields.
Synthesis 2011, No. 3, 413–418 © Thieme Stuttgart · New York

PAPER
Synthesis of Isoselenochromenes and Isothiochromenes
415
Since the success of this reaction probably is dependent
on the nature of the group directly linked to the selenium
atom,13 we decided to explore this influence by using dif-
ferent alkyl, aryl, and benzyl groups; the results are shown
in Table 3. Inspection of these results revealed that butyl
and propyl selenides 2t,u resulted in the formation of 3d
in high yields (entries 1 and 2). Benzyl 2-phenylbenzyl se-
lenide (2v) also gave the product 3d, but in moderate yield
(entry 3). Performing the reaction with phenyl 2-phenyl-
benzyl selenide (2x) did not give the desired product even
after a long reaction time (entry 4). These results demon-
strated that the efficiency of the cyclization reaction sig-
nificantly depends on steric effects and that it only occurs
with 2-alkynylbenzyl selenide that contain a Se–Csp3
bond.
Table 4 Synthesis of Isoselenochromenes 3 (Y = Se) and Isothio-
chromenes 3 (Y = S) via Electrophilic Cyclization of 2-Alkynylben-
zyl Chalcogenides 2a
YR1
Y
I2 (2.0 equiv)
CH2Cl2, 2 h
R2
R2
I
2
3
Entry Substrate
Product Yield (%)
2
Y
R1
R2
1
2
2a
2b
2e
2f
Se
Se
Se
Se
Se
Se
Se
Se
S
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Me
Me
Me
Me
Me
Me
(CH2)4Me
t-Bu
3a
3b
3c
3d
3e
3f
–
52
32
69
3
(CH2)2OH
Ph
4
Table 3 Influence of the Group Bonded to the Selenium Atoma
b
5
2g
2h
2i
2-MeOC6H4
4-MeC6H4
3-MeC6H4
1-naphthyl
t-Bu
–
SeR1
Se
I2 (2.0 equiv)
CH2Cl2, 2 h
6
62
70
65
30
–
I
7
3g
3h
3i
3d
8
2k
2m
2n
2o
2p
2q
2s
Entry
Substrate
Yield (%)
9
2
R1
Pr
10
11
12
13
14
S
C(OH)Me2
CH2OH
3j
1
2
3
4
2t
70
69
56
n.r.
S
3k
3l
–
2u
2v
2x
Bu
Bn
Ph
S
Ph
48
55
60
S
4-MeC6H4
1-naphthyl
3m
3n
S
a Reactions performed with 2t–x (0.25 mmol), I2 (2.0 equiv), CH2Cl2,
a Reactions performed using 2 (0.25 mmol), I2 (2.0 equiv), CH2Cl2, 2
2 h.
h.
b A complex inseparable mixture of products was observed.
In order to demonstrate the efficiency of this reaction, we
explored the generality of our method by extending these
conditions to various 2-alkynylbenzyl chalcogenides 2;
the results are summarized in Table 4. In most cases,
the corresponding 4-iodo-3-substituted-1H-isoseleno-
chromenes 3 (Y = Se) and -isothiochromenes (Y = S) were
obtained in moderate yields. Table 4 shows the limitations
in this methodology; 2-alkynylbenzyl selenides 2a and 2g
containing a pentyl or anisyl group (entries 1 and 5) and
2-alkynylbenzyl sulfides 2n and 2o containing a propar-
gyl or homopropargyl alcohol (entries 10 and 11) did not
give the desired products.
genochromene product and the other possible product
contains a five-membered ring, e.g. a dihydrobenzo[c]se-
lenophene. In order to determine the nature of the co- and/
or byproducts formed in addition to the isolated iodo-
isochalcogenochromenes 3, we analyzed the crude reac-
tion mixture, which showed that only one product was
formed. This encouraged us to confirm the structure of our
cyclized product using X-ray crystallography, which in-
deed proved to be the isochalcogenochromene 3
(Figure 1).
We believe that the mechanism of this cyclization reaction
involves; (i) coordination of the C≡C bond to iodine to
generate the iodonium intermediate A, which activates the
triple bond towards nucleophilic attack, (ii) anti-nucleo-
philic attack of the selenium atom on the activated iodoni-
um intermediate to produce the salt B, and (iii) facile
removal of the alkyl group via SN2 displacement by the io-
dide anion present in the reaction mixture to generate the
4-iodoisochalcogenochromene product 3 and one mole-
cule of R1I (Scheme 2). This cyclization could give a
mixture of two isomers, one being the expected isochalco-
I2
YR1
Y
R2
R2
2
I
3
IR1
I2
I–
R1
YR1
Y
R2
I
R2
I
A
B
Scheme 2
Synthesis 2011, No. 3, 413–418 © Thieme Stuttgart · New York

416
C. C. Schneider et al.
PAPER
Alkyl 2-Bromobenzyl Chalcogenides 1; General Procedure
To a soln of alkyl dichalcogenide (5 mmol) in EtOH (50 mL), under
argon was added NaBH4 (30 mmol) at r.t. with vigorous stirring. To
this soln was added 2-bromobenzyl bromide (10 mmol) and the
mixture was stirred at r.t. for 5 h. The mixture was diluted with
EtOAc (20 mL) and washed with brine (2 × 30 mL). The organic
phase was separated, dried (MgSO4), and concentrated under vacu-
um. The residue was purified by flash chromatography (hexane).
Alkyl 2-(Substituted-ethynyl)benzyl Chalcogenides 2; General
Procedure
To a Schlenck tube, under argon, containing Pd(PPh3)2Cl2 (2 mol%)
and Et3N (5 mL) was added the 2-bromobenzyl chalcogenide 1 (0.5
mmol) and the resulting soln was stirred at r.t. for 5 min. After this
time, the terminal alkyne (2.5 equiv) dissolved in Et3N (0.5 mL) was
then added dropwise, and the mixture was stirred for an additional
5 min. CuI (1 mol%) was added and the soln was stirred at reflux
for 12 h. The mixture was diluted with CH2Cl2 (10 mL), and washed
with brine (3 × 10 mL). The organic phase was separated, dried
(MgSO4), and concentrated under vacuum. The residue was puri-
fied by flash chromatography (silica gel, EtOAc–hexane).
Figure 1 ORTEP view of the compound 3d
We described herein efficient methodology for the syn-
thesis of 2-alkynylbenzyl chalcogenide derivatives via
Sonogashira cross-coupling of 2-bromobenzyl chalco-
genides with different alkynes. This cross-coupling reac-
tion proceeded cleanly under mild conditions and was
performed with propargyl alcohols, as well as alkyl- and
arylalkynes. The product obtained subsequent underwent
an efficient electrophilic cyclization reaction using iodine
as electrophilic source, giving the corresponding 4-iodo-
1H-isochalcogenochromenes in moderate yields. Regard-
ing the five- versus six-membered ring, it is important to
point out that the unique product obtained during the
course of this cyclization contained a six-membered ring,
which was determined by X-ray diffraction analysis.
Butyl 2-(Phenylethynyl)benzyl Selenide (2f)
Yield: 0.225 g (69%).
1H NMR (400 MHz, CDCl3): d = 7.55–7.48 (m, 3 H), 7.36–7.30 (m,
4 H), 7.24 (t, J = 7.3 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1 H), 4.01 (s, 2
H), 2.57 (t, J = 7.3 Hz, 2 H), 1.62 (quint, J = 7.6 Hz, 2 H), 1.33 (sex-
tet, J = 7.3 Hz, 2 H), 0.83 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 142.05, 132.24, 131.41, 129.01,
128.36, 128.28, 128.24, 126.44, 123.24, 122.41, 94.30, 87.70,
32.58, 25.34, 23.99, 23.03, 13.47.
Proton nuclear magnetic resonance spectra (1H NMR) were ob-
tained at 200 MHz on a DPX-200 NMR spectrometer or at 400 MHz
on DPX-400 NMR spectrometer. Spectra were recorded in CDCl3
solutions. Chemical shifts are reported in ppm, referenced to the
solvent peak of CDCl3 or tetramethylsilane (TMS) as the external
reference. Data are reported as follows: chemical shift (d), multi-
plicity, coupling constant (J) in Hz and integrated intensity. Carbon-
13 nuclear magnetic resonance spectra (13C NMR) were obtained
either at 50 MHz on a DPX-200 NMR spectrometer or at 100 MHz
on a DPX-400 NMR spectrometer. Spectra were recorded in CDCl3
solutions. Chemical shifts are reported in ppm, referenced to the
solvent peak of CDCl3. Abbreviations to denote the multiplicity of
a particular signal are s (singlet), d (doublet), t (triplet), q (quartet),
quint (quintet), sex (sextet) and m (multiplet). High-resolution mass
spectra were recorded on a MS50TC double focusing magnetic sec-
tor mass spectrometer using EI at 70 eV. Column chromatography
was performed using silica gel (230–400 mesh) following the meth-
ods described by Still. Thin-layer chromatography (TLC) was per-
formed using silica gel GF254, 0.25 mm thickness. For
visualization, TLC plates were either placed under ultraviolet light,
or stained with iodine vapour or acidic vanillin. Most reactions were
monitored by TLC for disappearance of starting material. Air- and
moisture-sensitive reactions were conducted in flame-dried or
oven-dried glassware equipped with tightly fitted rubber septa and
under a positive atmosphere of dry argon. Reagents and solvents
were handled using standard syringe techniques. Temperatures
above room temperature were maintained by use of a mineral oil
bath with an electrically heated coil connected to a Variac control-
ler.
MS: m/z (%) = 328 (7), 272 (20), 191 (100), 165 (25).
Butyl 2-[(2-Methoxyphenyl)ethynyl]benzyl Selenide (2g)
Yield: 0.239 g (67%).
1H NMR (400 MHz, CDCl3): d = 7.54 (td, J = 7.6, 1.4 Hz, 2 H),
7.32–7.26 (m, 2 H), 7.23 (td, J = 7.6, 1.4 Hz, 1 H), 7.17 (td, J = 7.3,
1.4 Hz, 1 H), 6.92 (td, J = 7.3, 1.2 Hz, 1 H), 6.88 (d, J = 8.3 Hz, 1
H), 4.08 (s, 2 H), 3.90 (s, 3 H), 2.57 (t, J = 7.6 Hz, 2 H), 1.61 (quint,
J = 7.6 Hz, 2 H), 1.32 (sextet, J = 7.6 Hz, 2 H), 0.81 (t, J = 7.3 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 159.99, 142.23, 133.05, 132.03,
129.67, 128.97, 128.14, 126.32, 122.80, 120.35, 112.59, 110.56,
91.85, 90.82, 55.68, 32.52, 25.22, 23.67, 23.05, 13.47.
MS: m/z (%) = 358 (11), 301 (25), 221 (22), 206 (100), 178 (70),
115 (31).
Butyl 2-(4-Tolylethynyl)benzyl Selenide (2h)
Yield: 0.170 g (50%).
1H NMR (400 MHz, CDCl3): d = 7.43 (d, J = 8.0 Hz, 2 H), 7.31–
7.13 (m, 6 H), 4.00 (s, 2 H), 2.57 (t, J = 7.6 Hz, 2 H), 2.35 (s, 3 H),
1.62 (quint, J = 7.3 Hz, 2 H), 1.33 (sextet, J = 7.6 Hz, 2 H), 0.83 (t,
J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 141.94, 138.37, 132.16, 131.31,
129.05, 128.98, 128.17, 126.41, 122.62, 120.18, 94.52, 87.05,
32.59, 25.37, 23.98, 23.02, 21.43, 13.48.
MS: m/z (%) = 342 (5), 286 (16), 205 (100), 190 (36).
Anal. Calcd for C20H22Se: C, 70.37; H, 6.50. Found: C, 70.51; H,
6.60.
Selected spectral and analytical data are given. The characterization
of additional new products is provided in the Supporting Informa-
tion.
Butyl 2-(3-Tolylethynyl)benzyl Selenide (2i)
Yield: 0.184 g (54%).
Synthesis 2011, No. 3, 413–418 © Thieme Stuttgart · New York

PAPER
Synthesis of Isoselenochromenes and Isothiochromenes
417
1H NMR (400 MHz, CDCl3): d = 7.49 (dd, J = 7.6,1.2 Hz, 1 H),
7.36–7.30 (m, 3 H), 7.26–7.13 (m, 4 H), 4.01 (s, 2 H), 2.58 (t,
J = 7.6 Hz, 2 H), 2.35 (s, 3 H), 1.63 (quint, J = 7.3 Hz, 2 H), 1.34
(sextet, J = 7.6 Hz, 2 H), 0.84 (t, J = 7.6 Hz, 3 H).
MS: m/z (%) = 411 (100), 285 (32), 270 (57), 205 (93), 189 (49).
4-Iodo-3-(naphthalen-1-yl)-1H-isoselenochromene (3h)
Yield: 0.290 g (65%).
13C NMR (100 MHz, CDCl3): d = 142.06, 138.00, 132,28, 132.01,
129.20, 129.05, 128.57, 128.33, 128.23, 126.48, 123.08, 122.55,
94.53, 87.36, 32.64, 25.39, 24.04, 23.09, 21.21, 13.52.
1H NMR (400 MHz, CDCl3): d = 7.95–7.93 (m, 1 H), 7.88–7.81 (m,
3 H), 7.52–7.46 (m, 3 H), 7.37–7.35 (m, 1 H), 7.30–7.26 (m, 2 H),
7.15–7.13 (m, 1 H), 4.12 (d, J = 12.5 Hz, 1 H), 3.98 (d, J = 12.5 Hz,
1 H).
13C NMR (100 MHz, CDCl3): d = 142.12, 137.14, 135.95, 133.73,
133.43, 131.27, 129.75, 129.13, 128.73, 128.43, 127.65, 126.50,
126.43, 126.19, 125.50, 125.42, 95.47, 27.00.
MS: m/z (%) = 342 (4), 284 (9), 205 (100), 190 (46).
Anal. Calcd for C20H22Se: C, 70.37; H, 6.50. Found: C, 70.61; H,
6.69.
Butyl 2-[(4-Chlorophenyl)ethynyl]benzyl Selenide (2j)
MS: m/z (%) = 447 (20), 321 (20), 240 (100), 119 (44).
Yield: 0.199 g (55%).
Anal. Calcd for C16H13ISe: C, 46.74; H, 3.19. Found: C, 46.90; H,
3.27.
1H NMR (400 MHz, CDCl3): d = 7.49–7.44 (m, 3 H), 7.32–7.16 (m,
5 H), 3.98 (s, 2 H), 2.57 (t, J = 7.6 Hz, 2 H), 1.62 (quint, J = 7.3 Hz,
2 H), 1.34 (sextet, J = 7.3 Hz, 2 H), 0.84 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 142.10, 134.27, 132,61, 132.29,
129.05, 128.65, 128.58, 126.52, 122.09, 121.74, 93.18, 88.66,
32.57, 25.34, 24.03, 23.02, 13.50.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
MS: m/z (%) = 362 (4), 306 (20), 225 (94), 189 (100).
Anal. Calcd for C19H19ClSe: C, 63.08; H, 5.29. Found: C, 63.25; H,
5.35.
We are grateful to CNPq, CAPES and FAPERGS (PRONEX
10/0005-1), for financial support. CNPq is also acknowledged for a
fellowship (to G.Z. and C.C.S.).
4-Iodo-3-substituted Isoselenochromenes 3 (Y = Se) and
Isothiochromenes 3 (Y = S); General Procedure
References
To a soln of the alkyne 2 (0.25 mmol) and CH2Cl2 (2 mL) was grad-
ually added I2 (2.0 equiv) dissolved in CH2Cl2 (6 mL). The mixture
was allowed to stir at r.t. for 2 h. The excess I2 was removed by
washing with sat. aq Na2S2O3. The mixture was then extracted with
EtOAc (3 × 10 mL). The combined organic extracts were dried
(MgSO4 and concentrated under vacuum.
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4-Iodo-3-phenyl-1H-isoselenochromene (3d)
Yield: 0.273g (69%).
1H NMR (400 MHz, CDCl3): d = 7.80–7.78 (m, 1 H), 7.42–7.32 (m,
5 H), 7.29–7.22 (m, 2 H), 7.11–7.09 (m, 1 H), 3.93 (s, 2 H).
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130.04, 128.82, 128.57, 128.06, 127.48, 125.92, 91.41, 26.81.
MS: m/z (%) = 397 (44), 269 (17), 191 (100).
Anal. Calcd for C15H11ISe: C, 45.37; H, 2.79. Found: C, 45.52; H,
2.87.
4-Iodo-3-(4-tolyl)-1H-isoselenochromene (3f)
Yield: 0.254 g (62%).
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7.33 (d, J = 7.8 Hz, 2 H), 7.30–7.25 (m, 2 H), 7.20 (d, J = 7.8 Hz, 2
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130.12, 129.53, 128.77, 128.73, 127.88, 127.44, 125.90, 90.88,
26.83, 21.39.
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Anal. Calcd for C16H13ISe: C, 46.74; H, 3.19. Found: C, 46.85; H,
3.28.
3-Iodo-3-(3-tolyl)-1H-isoselenochromene (3g)
Yield: 0.287 g (70%).
1H NMR (400 MHz, CDCl3): d = 7.79 (d, J = 7.3 Hz, 1 H), 7.29–
7.16 (m, 6 H), 7.11 (d, J = 7.3 Hz, 1 H), 3.93 (s, 2 H), 2.38 (s, 3 H).
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133.60, 131.51, 130.64, 129.35, 128.77, 127.96, 127.46, 127.05,
125.91, 91.18, 26.81, 21.37.
Synthesis 2011, No. 3, 413–418 © Thieme Stuttgart · New York

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Synthesis 2011, No. 3, 413–418 © Thieme Stuttgart · New York