Synthesis and reactivity of 5-and 6-hydroxy-benzo[b]furan-2-selenolates

Article abstract of DOI:10.1134/S1070428006100228

Treatment of 2,4-and 2,5-diacetoxyacetophenone semicarbazones with selenium dioxide gave 4-(2,4-and 2,5-diacetoxyphenyl)-1,2,3-selenadiazoles which were readily deacylated by the action of hydrochloric acid. 4-(2,4-and 2,5-Dihydroxyphenyl)-1,2,3-selenadia

Full text of DOI:10.1134/S1070428006100228

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 10, pp. 1521–1527. © Pleiades Publishing, Inc., 2006.
Original Russian Text © M.L. Petrov, D.A. Androsov, M.A. Abramov, I.P. Abramova, W. Dehaen, Yu.I. Lyakhovetskii, 2006, published in Zhurnal
Organicheskoi Khimii, 2006, Vol. 42, No. 10, pp. 1533–1539.
Synthesis and Reactivity of 5- and 6-Hydroxy-
benzo[b]furan-2-selenolates
M. L. Petrov, D. A. Androsov, M. A. Abramov, I. P. Abramova,
W. Dehaen, and Yu. I. Lyakhovetskii
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: mlpetrov@tu.spb.ru
Received May 13, 2005
Abstract—Treatment of 2,4- and 2,5-diacetoxyacetophenone semicarbazones with selenium dioxide gave
4-(2,4- and 2,5-diacetoxyphenyl)-1,2,3-selenadiazoles which were readily deacylated by the action of hydro-
chloric acid. 4-(2,4- and 2,5-Dihydroxyphenyl)-1,2,3-selenadiazoles thus obtained underwent decomposition in
the presence of potassium carbonate in acetonitrile with formation of 5- and 6-hydroxybenzo[b]furan-2-
selenolates which were subjected to alkylation.
DOI: 10.1134/S1070428006100228
We recently described a new method for the syn-
thesis of benzo[b]furan-2-thiolates and -selenolates via
intramolecular cyclization of thioketenes and seleno-
ketenes formed by decomposition of 4-(2-hydroxy-
phenyl)-1,2,3-thia- and -selenadiazoles in the presence
of bases [1–4] (Scheme 1). In continuation of our
studies on the developed procedure for the synthesis of
fused heterocycles, the present article reports on the
preparation of 4-(2,4- and 2,5-dihydroxyphenyl)-1,2,3-
selenadiazoles and their transformation into 5- and
6-hydroxybenzo[b]furan-2-selenolates. 2,5- and 2,6-Di-
substituted benzo[b]furans are promising as new
building blocks for supramolecular chemistry. 5- and
6-Hydroxybenzo[b]furan-2-selenolates can be used for
the synthesis of new dendrimers having peripheral
hydroxy groups which may be subjected to further
modifications [5, 6] or for the preparation of new
crownophanes. We previously synthesized such a thio
crown ether from 5-hydroxybenzo[b]furan-2-thiolate
[7]. It should also be noted that some derivatives of
benzo[b]furan-2-chalcogenolates exhibit biological ac-
tivity [8]; for example, 5-hydroxybenzo[b]furan deriv-
atives show antioxidant properties [9].
While attempting to obtain new derivatives of
5- and 6-hydroxybenzo[b]furan-2-selenolates having
an additional functional group in position 5 or 6, we
initially converted 2,4- and 2,5-dihydroxyacetophen-
ones Ia and Ib into the corresponding hitherto
unknown semicarbazones IIa and IIb. However, we
failed to obtain 1,2,3-selenadiazoles by a conventional
procedure [10], i.e., by the action of selenium dioxide
on semicarbazones IIa and IIb. Under these condi-
tions, selenium dioxide acted as common oxidant [11].
We previously synthesized 4-(2-hydroxy-5-methoxy-
phenyl)- and 4-(2-hydroxy-5-benzyloxyphenyl)-1,2,3-
selenadiazoles in an overall yield of ~50% by treat-
ment of 2-hydroxy-5-methoxy- and 2-hydroxy-5-ben-
zyloxyacetophenone semicarbazones with selenium
Scheme 1.
N
N
N
N
X
X
X
K2CO3
–N2
OH
O
OH
·
X
X
O
O
X = S, Se.
1521

PETROV et al.
1522
Scheme 2.
H
N
H
N
NH2
NH2
O
N
N
O
O
Me
Me
Me
H2NCONHNH2 ·HCl, AcONa
Ac2O, AcONa
HO
HO
AcO
OH
OH
OAc
Ia, Ib
IIa, IIb
IIIa, IIIb
N
N
N
N
Se
Se
SeO2, AcOH
AcO
HCl, MeOH
HO
OAc
OH
Va, Vb
IVa, IVb
I–V, 4-OH (a), 5-OH (b).
dioxide [12], but our attempts to remove methyl or
benzyl protecting group resulted in decomposition of
the selenadiazole ring. We also failed to obtain 2,4-
and 2,5-diacetoxyacetophenone semicarbazones from
2,4- and 2,5-diacetoxyacetophenones; as a result, 2,4-
and 2,5-dihydroxyacetophenone semicarbazones IIa
and IIb were formed. We succeeded in obtaining the
desired selenadiazoles according to Scheme 2. Treat-
ment of semicarbazones IIa and IIb with acetic anhy-
dride in the presence of sodium acetate gave the cor-
responding diacetoxy derivatives IIIa and IIIb, and
reactions of the latter with selenium dioxide in acetic
acid led to the formation of 4-(2,4- and 2,5-diacetoxy-
phenyl)-1,2,3-selenadiazoles IVa and IVb. Com-
pounds IVa and IVb were subjected to hydrolysis with
hydrochloric acid, and 4-(2,4- and 2,5-dihydroxy-
phenyl)-1,2,3-selenadiazoles Va and Vb were isolated
in an overall yield of ~45%.
ical shift of δC 140.75 (IVa), 145.06 (IVb), 139.34
1
(Va), or 147.71 ppm (IVb), J(C–77Se) = 135–145 Hz
1
{cf. δC 142.1 ppm, J(C–77Se) = 133 Hz for 4-(2-hy-
droxyphenyl)-1,2,3-selenadiazole [14]}.
Selenadiazoles IVa, IVb, Va, and Vb showed in the
mass spectra the molecular ion peaks with m/z values
corresponding to their molecular weights. Further frag-
mentation pattern was also consistent with the assumed
structure. The main fragmentation pathway of the
molecular ions derived from diacetoxy derivatives IVa
and IVb included elimination of nitrogen molecule,
followed by successive elimination of two neutral
ketene molecules (which is typical of phenyl acetates
[15]) and finally loss of selenium atom. The molecular
ions of selenadiazoles Va and Vb decomposed via
initial expulsion of nitrogen molecule, followed by
elimination of selenium; this fragmentation pathway is
the same as that observed in the light-induced or
thermal decomposition of selenadiazoles [16].
The structure of 4-(2,4- and 2,5-diacetoxyphenyl)-
1,2,3-selenadiazoles IVa and IVb and 4-(2,4- and 2,5-
dihydroxyphenyl)-1,2,3-selenadiazoles Va and Vb was
Like 4-(2-hydroxyaryl)-1,2,3-selenadiazoles [13]
and 4-(5-alkoxy-2-hydroxyphenyl)-1,2,3-selenadi-
azoles [12], 4-(2,4- and 2,5-dihydroxyphenyl)-1,2,3-
selenadiazoles Va and Vb readily undergo decomposi-
tion with liberation of nitrogen molecule even by the
action of such a weak base as potassium carbonate.
The reaction is likely to include several steps: depro-
tonation of the phenolic hydroxy group, intramolecular
charge transfer to the selenadiazole ring, decomposi-
tion of the heterocyclic anion with liberation of
nitrogen to give the corresponding alkyneselenolate,
intramolecular proton transfer with formation of
selenoketene, and intramolecular ring closure with
participation of the hydroxy group and selenoketene
fragment (Schemes 1, 3); 5- and 6-hydroxybenzo[b]-
1
confirmed by the H and 13C NMR and mass spectra.
1
The positions and multiplicities of signals in the H
and 13C NMR spectra of selenadiazoles IVa, IVb, Va,
and Vb were similar to the corresponding parameters
in the spectra of 4-(2-hydroxyphenyl)-1,2,3-selenadi-
azole [13] and 4-(5-alkoxy-2-hydroxyphenyl)-1,2,3-
selenadiazoles [12]. Signal from the 5-H proton in the
selenadiazole ring appeared as a singlet at δ 9.44
(IVa), 10.04 (IVb), 9.83 (Va), and 10.27 ppm (IVb)
with satellites due to coupling with selenium,
2J(H–77Se) = 39–43 Hz {cf. δ 10.09 ppm, 2J(H–77Se) =
42 Hz for 5-H in 4-(2-hydroxyphenyl)-1,2,3-selenadi-
azole [13]}. The C5 atom is characterized by a chem-
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SYNTHESIS AND REACTIVITY OF 5- AND 6-HYDROXY-...
1523
Scheme 3.
BuBr
HO
SeBu
O
VIIa, VIIb
O
K2CO3, MeCN
–N2
ClCH2CONHR
ClCH2C6H4R-4
HO
HO
HO
Se
Se
NHR
Va, Vb
O
O
VIa, VIb
VIIIa, VIIIb
R
Se
O
IXa, IXb
VII, 5-OH (a), 6-OH (b); VIII, 5-OH, R = H (a); 6-OH, R = 2,6-Me2C6H3 (b); IX, 5-OH, R = H (a), t-Bu (b).
furan-2-selenolate ions VIa and VIb thus formed are
intensely colored. Their formation was confirmed by
alkylation with butyl bromide, chloroacetamides, and
benzyl chlorides (Scheme 3). As a result, we obtained
30–89% of 5- and 6-hydroxy-2-butylselanylbenzo[b]-
furans VIIa and VIIb, 64–89% of 2-(5- and 6-hy-
droxybenzo[b]furan-2-ylselanyl)acetamides VIIIa and
VIIIb, and 59–69% of 2-benzylselanyl-5-hydroxy-
benzo[b]furans IXa and IXb.
and Bruker AMX-400 spectrometers (400 and
100 MHz, respectively), using residual proton and
carbon signals of the deuterated solvents as reference.
The mass spectra (electron impact, 70 eV) were ob-
tained on a Kratos MS 890 instrument with direct
sample admission into the ion source (ion source tem-
perature 200°C); the m/z values are given below for
ions containing 80Se isotope. The progress of reactions
was monitored by TLC on Silufol UV-254 plates; spots
were visualized under UV light or by treatment with
iodine vapor. The solvents used in this work were
purified and dehydrated by standard procedures.
The structure of alkylation products VII–IX was
confirmed by 1H and 13C NMR spectroscopy and mass
spectrometry. The positions and multiplicities of sig-
1
nals in their H and 13C NMR spectra were similar to
2,4-Dihydroxyacetophenone (Ia) was synthesized
by acylation of resorcinol [17], and 2,5-dihydroxy-
acetophenone (Ib) was obtained by the Fries reaction
of p-phenylene diacetate [18].
the corresponding parameters in the spectra of 2-alkyl-
selanylbenzo[b]furans [13, 14]. The 3-H proton in
the furan ring gave a singlet at δ 6.65–6.93 ppm (cf.
δ 6.80 ppm for 3-H in 2-methylselanylbenzo[b]furan
[14]). Likewise, the C3 signal in the 13C NMR spectra
of VII–IX was located at δC 112.64–114.71 ppm
against 110.8 ppm for 2-methylselanylbenzofuran [14].
The mass spectra of compounds VII–IX contained
peaks from the molecular ions whose isotope composi-
tion was consistent with the calculated one. The main
fragmentation pathway of the molecular ions of VII–
IX involved cleavage of the weakest Csp3–Se bond
with elimination of alkyl substituent and subsequent
loss of selenium atom, in keeping with the decomposi-
tion of known 2-alkylselanylbenzo[b]furans [13, 14].
2,4-Dihydroxyacetophenone semicarbazone
(IIa). A suspension of 7.7 g (50.7 mmol) of 2,4-di-
hydroxyacetophenone Ia, 6.8 g (61 mmol) of semi-
carbazide hydrochloride, and 10 g (122 mmol) of
sodium acetate in a mixture of 50 ml of propan-2-ol
and 50 ml of water was vigorously stirred for 2.5 h on
heating at the boiling point. The mixture was cooled to
15–18°C and left overnight, and the precipitate was
filtered off, washed with water (3×50 ml), and dried.
Yield 9.8 g (93%). Orange crystals, mp 249–250°C
(decomp.), Rf 0.47 (acetone–chloroform, 2:1). 1H NMR
spectrum (DMSO-d6), δ, ppm: 2.16 s (CH3C=N), 6.11 s
(NH2), 6.21 d (3-H), 6.27 d.d (5-H), 7.30 d (6-H),
9.46 s (NH), 9.64 s (4-OH), 12.98 s (2-OH). 13C NMR
spectrum (DMSO-d6), δC, ppm: 13.27 (CH3C=N),
103.43 (C3), 106.74 (C1), 112.65 (C5), 129.16 (C6),
149.98 (C=N), 155.73 (C=O), 159.56 (C2), 160.05
EXPERIMENTAL
The melting points were determined on a Boetius
1
13
melting point apparatus. The H and C NMR spectra
were recorded on Bruker Avance (300 and 75 MHz)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

PETROV et al.
1524
(C4). Mass spectrum, m/z (Irel, %): 210 (13) [M + H]+,
209 (2) [M]+, 193 (13) [M – NH2]+, 192 (4) [M – NH3]+,
167 [M – CON]+, 166 (9) [M – CONH]+, 152 (17)
[M – NCONH]+, 150 (16) [M – NHCONH2]+, 149 (11)
[M – CO(NH2)2]+, 136 (3) [M – NNHCONH2]+, 43
(100) [NHCO]+. Found, %: C 51.45, 51.71; H 5.02,
5.17. C9H11N3O3. Calculated, %: C 51.67; H 5.30.
(45) [M – 2CH2CO]+, 192 (100) [M – 2CH2CO – NH3]+,
165 (70) [M – 2CH2CO – CONH2]+, 149 (89) [M –
2CH2CO – NH2CONH2]+, 136 (65) [M – 2CH2CO –
NNH2CONH2]+, 43 (6) [CH3CO]+. Found, %: C 53.14,
53.37; H 5.18, 5.29. C13H15N3O3. Calculated, %:
C 53.24; H 5.16.
2,5-Diacetoxyacetophenone semicarbazone
(IIIb). A flask equipped with a magnetic stirrer and
a reflux condenser and protected from atmospheric
moisture was charged with 15.4 g (73.7 mmol) of
semicarbazone IIb, 11.2 g (137 mmol) of sodium
acetate, and 150 ml of acetic anhydride. The mixture
was heated to 100°C under vigorous stirring (the mix-
ture became homogeneous and turned brownish) and
was stirred for 0.5 h at 100°C. It was then cooled to
20–25°C and poured into 1 l of cold water. An oily
material separated and crystallized in 1 h; the solid
product was filtered off, washed with water (5×20 ml),
and dried. Yield 12.8 g (59%), colorless crystals,
2,5-Dihydroxyacetophenone semicarbazone
(IIb). A suspension of 13.3 g (87.5 mmol) of 2,5-hy-
droxyacetophenone (Ib), 11.7 g (104.9 mmol) of semi-
carbazide hydrochloride, and 17.3 g (86.6 mmol) of
sodium acetate in a mixture of 250 ml of ethanol and
20 ml of water was vigorously stirred for 2.5 h on
heating at the boiling point. The mixture was cooled to
15–18°C and left overnight, and the precipitate was
filtered off, washed with water (5×100 ml) and metha-
nol (100 ml), and dried. Yield 15.4 g (84%), yellow
crystals, mp 249–235°C (decomp.). 1H NMR spectrum
(DMSO-d6), δ, ppm: 2.16 s (CH3C=N), 6.19 s (NH2),
6.65 s (2H, 3-H, 4-H), 6.84 s (6-H), 8.81 s (5-OH),
9.60 s (NH), 11.88 s (2-OH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 13.53 (CH3C=N), 113.80 (C1),
117.46 (C6), 117.57 (C3), 121.05 (C4), 148.73 (C=N),
149.42 (C2), 150.70 (C5), 155.71 (C=O). Mass spec-
trum, m/z (Irel, %): 209 (32) [M]+, 192 (100) [M – NH3]+,
166 (39) [M – CONH]+, 149 (74) [M – CO(NH2)2]+,
136 (39) [M – NNHCONH2]+, 43 (37) [NHCO]+.
Found, %: C 51.38, 51.52; H 5.18, 5.41. C9H11N3O3.
Calculated, %: C 51.67; H 5.30.
1
mp 203–205°C, Rf 0.36 (chloroform). H NMR spec-
trum (DMSO-d6), δ, ppm: 2.09 s (CH3C=N), 2.24 s
and 2.27 s (CH3CO), 6.34 s (NH2), 7.16 m (2H, 3-H,
4-H), 7.36 s (6-H), 9.45 s (NH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 16.78 (CH3C=N), 21.15
(CH3CO), 122.82 and 123.00 (C4, C6), 124.66 (C1),
134.02 (C3), 142.41 (C2), 145.43 (C5), 148.17 (C=N),
155.32 (NC=O), 169.59 and 169.76 (C=O). Mass spec-
trum, m/z (Irel, %): 293 (13) [M]+, 251 (100) [M –
CH2CO]+, 234 (20) [M – CH2CO – NH3]+, 209 (51)
[M – 2CH2CO]+, 192 (77) [M – 2CH2CO – NH3]+, 165
(19) [M – 2 CH2CO – CONH2]+, 149 (51) [M –
2CH2CO – NH2CONH2]+, 136 (14) [M – 2CH2CO –
NNH2CONH2]+, 43 (90) [CH3CO]+. Found, %:
C 53.27, 53.39; H 5.09, 5.28. C13H15N3O3. Calculated,
%: C 53.24; H 5.16.
4-(2,4-Diacetoxyphenyl)-1,2,3-selenadiazole
(IVa). A flask equipped with a magnetic stirrer and
a reflux condenser connected to a gas-washing bottle
was charged with 5.6 g (19.1 mmol) of semicarbazone
IIIa, 35 ml of glacial acetic acid, and 15 ml of acetic
anhydride. The flask was protected from light, and
2.7 g (24.3 mmol) of powdered selenium dioxide was
added under stirring. The mixture was heated to 75–
80°C over a period of 1 h under vigorous stirring, and
it turned red–brown. The mixture was cooled to 20–
25°C and filtered from selenium, the filtrate was
diluted with 300 ml of cold water, and the precipitate
was filtered off, washed with cold water (5×20 ml),
and dried. Yield 5.4 g (87%), brick-red crystals,
mp 129–130°C. Recrystallization from ethyl acetate
gave light yellow prisms which gradually turned red on
exposure to light, mp 134–135°C (decomp.), Rf 0.78
2,4-Diacetoxyacetophenone semicarbazone
(IIIa). A flask equipped with a magnetic stirrer and
a reflux condenser and protected from atmospheric
moisture was charged with 9.8 g (46.9 mmol) of semi-
carbazone IIa, 7.1 g (86.6 mmol) of sodium acetate,
and 130 ml of acetic anhydride. The mixture was
heated to 100°C under vigorous stirring (the mixture
became homogeneous and turned yellowish) and was
stirred for 0.5 h at 100°C. It was then cooled to 20–
25°C and poured into 0.7 l of cold water. An oily
material separated and crystallized in 30 min; the solid
product was filtered off, washed with water (5×20 ml),
and dried. Yield 9.3 g (68%), colorless crystals,
mp 205–206°C, Rf 0.71 (acetone–chloroform, 2:1).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.11 s
(CH3C=N), 2.23 s and 2.27 s (CH3CO), 6.31 s (NH2),
7.02 d (3-H), 7.07 d.d (5-H), 7.59 d (6-H), 9.40 s
13
(NH). C NMR spectrum (DMSO-d6), δC, ppm: 16.91
(CH3C=N), 21.14 (CH3CO), 117.44 (C3), 119.85 (C1),
130.41 and 130.85 (C5, C6), 142.73 (C2), 148.38 (C=N),
150.80 (C4), 155.36 (NC=O), 169.30 and 169.43 (CO).
Mass spectrum, m/z (Irel, %): 293 (7) [M]+, 251 (65)
[M – CH2CO]+, 234 (23) [M – CH2CO – NH3]+, 209
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

SYNTHESIS AND REACTIVITY OF 5- AND 6-HYDROXY-...
1525
1
(chloroform–acetone, 3 : 1). H NMR spectrum
the mixture was filtered. The precipitate was washed
on a filter with methylene chloride (3×10 ml) and
dried. Yield 1.0 g (90%), pale yellow prisms, mp 115°C
(decomp.), Rf 0.46 (chloroform–acetone, 3:1). H NMR
spectrum (DMSO-d6), δ, ppm: 6.18 s (2OH), 6.39 d.d
(DMSO-d6), δ, ppm: 2.29 s and 2.34 s (CH3CO), 6.95 s
(3-H), 7.13 d (5-H), 8.07 d (6-H), 9.44 s (5'-H, 2JH–Se
=
41.4 Hz). 13C NMR spectrum (DMSO-d6), δC, ppm:
21.53 and 21.48 (CH3), 117.65 (C3), 120.23 (C5),
123.19 (C1), 132.06 (C6), 140.75 (C5'), 148.82 (C4),
151.68 (C2), 157.96 (C4'), 169.02 and 169.23 (CO).
Mass spectrum, m/z (Irel, %): 326 (1) [M]+, 298 (4)
[M – N2]+, 256 (3) [M – N2 – CH2CO]+, 214 (11) [M –
N2 – 2CH2CO] +, 134 (100) [M – N2 –2CH3CO – Se]+.
Found, %: C 44.27, 44.46; H 2.89, 3.17. C12H10N2O4Se.
Calculated, %: C 44.33; H 3.10.
1
(5-H), 6.56 d (3-H), 8.04 d (6-H), 9.83 s (5'-H, 2JH–Se
=
43 Hz). 13C NMR spectrum (DMSO-d6), δC, ppm:
103.42 (C1), 107.67 (C3), 110.89 (C5), 131.35 (C6),
139.34 (C5', 1JC–Se = 135 Hz), 156.35 (C2), 159.06 (C4),
159.48 (C4'). Mass spectrum, m/z (Irel, %): 242 (16)
[M]+, 214 (16) [M – N2]+, 134 (84) [M – N2 – Se]+, 42
(100) [CH2CO]+. Found, %: C 39.78, 40.01; H 2.23,
2.44. C8H6N2O2Se. Calculated, %: C 39.86; H 2.51.
4-(2,5-Diacetoxyphenyl)-1,2,3-selenadiazole
(IVb). The reaction was carried out as described above
for compound IVa. Powdered selenium dioxide, 5.8 g
(52.3 mmol), was added under stirring to a mixture of
12.8 g (43.7 mmol) of semicarbazone IIIb, 70 ml of
glacial acetic acid, and 30 ml of acetic anhydride. The
mixture was heated to 75–80°C over a period of 1 h
under vigorous stirring (it turned red–brown), cooled
to 20–25°C, and filtered from selenium. The filtrate
was diluted with 0.5 l of cold water and extracted with
methylene chloride (3×50 ml). The extracts were com-
bined, washed with cold water (5×200 ml) to remove
traces of acetic acid, dried, and evaporated on a rotary
evaporator. Yield 11.5 g (81%), pale brown substance;
the product was almost pure. Recrystallization from
ethyl acetate or benzene gave colorless crystals with
mp 133–134°C, Rf 0.27 (chloroform), 0.70 (chloro-
4-(2,5-Dihydroxyphenyl)-1,2,3-selenadiazole
(Vb) was synthesized in a similar way from 12.5 g
(7.7 mmol) of 1,2,3-selenadiazole IVb in 50 ml of
methanol containing 2 ml of concentrated hydrochloric
acid. Yield 1.7 g (92%), light yellow prisms, mp 170–
171°C (decomp.), Rf 0.4 (chloroform–acetone, 5:1).
1H NMR spectrum (DMSO-d6), δ, ppm: 6.68 d.d
(4-H), 6.85 d (3-H), 7.676 d (6-H), 9.20 s and 9.61 s
2
(OH), 10.27 s (5'-H, JH–Se = 40 Hz). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 115.72 (C6), 116.17 (C1),
1
118.6 (C4), 120.49 (C3), 147.71 (C5', JC–Se = 145 Hz),
150.35 (C5), 154.09 (C2), 159.08 (C4'). Mass spectrum,
m/z (Irel, %): 242 (10) [M]+, 214 (21) [M – N2]+, 134
(100) [M – N2 – Se]+, 105 (21) [M – N2 – Se – HCO]+.
Found, %: C 39.97, 40.12; H 2.45, 2.67. C8H6N2O2Se.
Calculated, %: C 39.86; H 2.51.
1
form–acetone, 10:1). H NMR spectrum (DMSO-d6),
2-Butylselanylbenzo[b]furan-5-ol (VIIa). A flask
equipped with a magnetic stirrer and a reflux con-
denser connected to a gas-washing bottle was protect-
ed from light, filled with argon, and charged with 0.5 g
(2.075 mmol) of selenadiazole Vb, 0.35 g (2.5 mmol)
of freshly calcined potassium carbonate, 0.284 g
(2.075 mmol) of butyl bromide, and 40 ml of freshly
distilled acetonitrile. The mixture was vigorously
stirred for 24 h at ~20°C, and it changed from light
yellow to brown. The solvent was removed on a rotary
evaporator, and the dark brown tarry residue was
treated with boiling hexane (3×15 ml). The extract
was cooled, and the precipitate was filtered off and
dried. Yield 0.20 g (36%), colorless needles, mp 59°C,
δ, ppm: 2.27 s (CH3CO), 7.35 d.d (4-H), 7.37 d (3-H),
2
13
7.88 d (6-H), 10.04 s (5'-H, JH–Se = 39 Hz). C NMR
spectrum (DMSO-d6), δC, ppm: 21.62 (CH3), 124.16
(C1), 125.12 (C6), 125.80 (C3), 126.81 (C4), 145.06
(C5'), 145.89 (C5), 149.06 (C2), 157.75 (C4'), 170.04
and 170.08 (CO). Mass spectrum, m/z (Irel, %): 326 (1)
[M]+, 298 (4) [M – N2]+, 256 (2) [M – N2 – CH2CO]+,
214 (9) [M – N2 – 2CH2CO]+, 134 (38) [M – N2 –
2 CH3CO – Se]+, 43 (100) [CH3CO]+. Found, %:
C 44.35, 44.52; H 3.18, 3.40. C12H10N2O4Se. Calculat-
ed, %: C 44.33; H 3.10.
4-(2,4-Dihydroxyphenyl)-1,2,3-selenadiazole
(Va). A flask equipped with a magnetic stirrer and
a reflux condenser and protected from light was
charged with 1.5 g (4.6 mmol) of 1,2,3-selenadiazole
IVa, 40 ml of methanol, and 2 ml of concentrated
hydrochloric acid. The mixture was heated for 6 h at
45–50°C under vigorous stirring (until it turned light
yellow and homogeneous), cooled to 15–18°C, left
overnight, and filtered from selenium. The solvent was
removed from the filtrate on a rotary evaporator, 50 ml
of methylene chloride was added to the residue, and
1
Rf 0.6 (chloroform–acetone, 1:1). H NMR spectrum
(DMSO-d6), δ, ppm: 0.9 t (CH3), 1.42 t.d (CH2CH2-
CH2), 1.7 q (CH3CH2), 2.95 t (SH2Se), 5.13 s (OH),
6.73 s (3-H), 6.75 d.d (6-H), 6.91 d (4-H), 7.29 d
(7-H). 13C NMR spectrum (DMSO-d6), δC, ppm: 13.48
(CH3), 22.67 (CH3CH2), 28.45 (CH2CH2CH2 ), 32.57
(CH2Se), 105.16 (C7), 111.25 (C4), 112.64 (C3), 113.69
(C6), 129.63 (C3a), 145.36 (C5), 151.38 (C2), 152.34
(C7a). Mass spectrum, m/z (Irel, %): 270 (51) [M]+, 214
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

PETROV et al.
1526
(21) [M – C4H8]+, 185 (21) [M – C4H8 – CHO]+, 134
(100) 214 (21) [M – C4H8 – Se]+, 105 (48) [M – C4H8 –
Se – CHO]+, 57 (50) [C4H8]+. Found, %: C 53.42,
53.71; H 5.41, 5.53. C12H14O2Se. Calculated, %:
C 53.55; H 5.24.
(C3, C6), 129.24 (C3a), 144.11 (C5), 150.91 (C2), 153.48
(C7a), 170.27 (CO). Mass spectrum, m/z (Irel, %): 271
(59) [M]+, 213 (100) [M – CH2CONH2]+, 185 (9) [M –
CH2CONH2 – CHO]+, 149 (51) [M – CH2CO – Se]+.
Found, %: C 44.35, 44.51; H 3.53, 3.62. C10H9NO3Se.
Calculated, %: C 44.47; H 3.36.
2-Butylselanylbenzo[b]furan-6-ol (VIIb). The re-
action was carried out as described above for com-
pound VIIa using 0.5 g (2.075 mmol) of selenadiazole
Va, 0.35 g (2.5 mmol) of freshly calcined potassium
carbonate, 0.284 g (2.075 mmol) of butyl bromide, and
40 ml of freshly distilled acetonitrile. The mixture was
vigorously stirred for 24 h at ~20°C (it changed from
light yellow to red and then to dark cherry). The sol-
vent was removed on a rotary evaporator, and the dark
brown tarry residue was subjected to column chroma-
tography (3×10 cm) on silica gel L 100/160 using
chloroform as eluent. Yield 0.17 g (30%), pale yellow
oily substance which gradually crystallized to colorless
N-(2,6-Dimethylphenyl)-2-(6-hydroxybenzo[b]-
furan-2-ylselanyl)acetamide (VIIIb). The reaction
was carried out as described above for VIIIa. A mix-
ture of 0.5 g (2.075 mmol) of selenadiazole Va, 0.37 g
(2.7 mmol) of freshly calcined potassium carbonate,
0.41 g (2.075 mmol) of 2-chloro-N-(2,6-dimethyl-
phenyl)acetamide, and 50 ml of freshly distilled ace-
tone was vigorously stirred for 48 h at ~20°C, 0.15 g
(2.7 mmol) of ammonium chloride was added, the
mixture was stirred for 2 h and filtered from inorganic
salts, and the solvent was removed from the filtrate on
a rotary evaporator. The residue, 0.7 g, was recrystal-
lized from 30 ml of aqueous methanol with addition of
a small amount of charcoal. Yield 0.50 g (64%), fine
colorless needles, mp 200–201°C, Rf 0.31 (chloro-
1
solid, mp 63–64°C, Rf 0.3 (chloroform). H NMR
spectrum (CDCl3), δ, ppm: 0.89 t (CH3), 1.43 t.d
(CH2CH2CH2), 1.7 q (CH3CH2), 2.91 t (CH2Se), 5.31 s
(OH), 6.8 d (5-H), 6.81 s (3-H), 6.97 s (7-H), 7.33 d
(4-H). 13C NMR spectrum (CDCl3), δC, ppm: 13.26
(CH3), 22.42 (CH3CH2), 28.56 (CH2CH2CH2), 32.34
(CH2Se), 97.89 (C7), 111.72 (C5), 114.05 (C3), 120.32
(C4), 122.27 (C3a), 142.4 (C7a), 153.29 (C6), 157.84
(C2). Mass spectrum, m/z (Irel, %): 270 (48) [M]+, 214
(51) [M – C4H8]+, 185 (23) [M – C4H8 – CHO]+, 134
(100) 214 (21) [M – C4H8 – Se]+, 105 (39) [M – C4H8 –
Se – CHO]+, 57 (30) [C4H8]+. Found, %: C 53.61,
53.83; H 5.12, 5.41. C12H14O2Se. Calculated, %:
C 53.55; H 5.24.
1
form–acetone, 10:1). H NMR spectrum (DMSO-d6),
δ, ppm: 2.15 s (CH3), 3.71 s (CH2CO), 6.74 d (5-H),
6.87 s (3-H), 6.94 d (7-H), 7.02 m (Harom), 7.29 d
(4-H), 9.36 br.s (OH, NH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 17.18 (CH3); 30.39 (CH2CO);
96.43 (C7); 112.32 (C5); 114.71 (C3); 120.33 (C3a, C4);
126.27, 127.47, 134.65, 135.11 (Carom); 140.33 (C7a);
155.93 (C6); 157.93 (C2); 166.81 (CO). Mass spec-
trum, m/z (Irel, %): 375 (52) [M]+, 213 (44) [M –
CH2CONHC6H3(CH3)2]+, 134 (25) [M – CHCONH-
C6H3(CH3)2 – Se]+, 121 (100) [NH2C6H3(CH3)2]+, 120
(100) [NHC6H3(CH3)2]+. Found, %: C 57.42, 57.49;
H 4.78, 4.87. C18H17NO3Se. Calculated, %: C 57.77;
H 4.58.
2-(5-Hydroxybenzo[b]furan-2-ylselanyl)acet-
amide (VIIIa). A flask equipped with a magnetic
stirrer and a reflux condenser connected to a gas-
washing bottle was protected from light and charged
with 0.40 g (1.66 mmol) of selenadiazole Vb, 0.62 g
(4.5 mmol) of freshly calcined potassium carbonate,
0.155 g (1.66 mmol) of chloroacetamide, and 30 ml of
freshly distilled tetrahydrofuran. The mixture was
heated for 3 h under reflux with vigorous stirring (the
mixture turned light brown), cooled to 15–18°C, and
filtered from inorganic salts, the filtrate was evaporat-
ed on a rotary evaporator, and the residue (0.44 g), was
recrystallized from 20 ml of water with addition of
a small amount of charcoal. Yield 0.40 g (89%), fine
colorless needles, mp 160–161°C, Rf 0.42 (ethyl ace-
2-Benzylselanylbenzo[b]furan-5-ol (IXa). Under
analogous conditions, a mixture of 0.40 g (1.66 mmol)
of selenadiazole Vb, 0.62 g (4.5 mmol) of freshly
calcined potassium carbonate, 0.21 g (1.66 mmol) of
benzyl chloride, and 30 ml of freshly distilled tetra-
hydrofuran was heated for 3 h under reflux with
vigorous stirring, cooled to 15–18°C, and evaporated
on a rotary evaporator. The dark brown tarry residue
was treated with boiling hexane (3 × 15 ml). The
extract was cooled, and the precipitate was filtered off
and dried. Yield 0.30 g (59%), colorless plates, mp 94–
95°C, Rf 0.40 (methylene chloride). 1H NMR spectrum
(CDCl3), δ, ppm: 4.18 s (CH2), 4.88 s (OH), 6.65 s
(3-H), 6.75 d (6-H), 6.89 s (4-H), 7.22 m (Harom),
7.33 d (7-H). 13C NMR spectrum (CDCl3), δC, ppm:
32.17 (CH2); 105.20 (C7); 111.19 (C4); 112.91 (C3);
1
tate). H NMR spectrum (DMSO-d6), δ, ppm: 3.61 s
(CH2), 6.69 d.d (6-H), 6.87 d (4-H), 6.93 s (3-H), 7.32 d
(7-H), 9.21 s (OH). 13C NMR spectrum (DMSO-d6),
δC, ppm: 30.51 (CH2), 104.82 (C7), 111.05 (C4), 113.14
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

SYNTHESIS AND REACTIVITY OF 5- AND 6-HYDROXY-...
1527
114.25 (C6); 127.01, 128.39, 128.65, 129.32, 137.95
(Carom); 129.33 (C3a); 144.77 (C5); 151.29 (C7a); 152.35
(C2). Mass spectrum, m/z (Irel, %): 304 (46) [M]+, 213
(18) [M – CH2Ph]+, 91 (100) [CH2Ph]+. Found, %:
C 59.72, 59.41; H 4.08, 4.19. C15H12O2Se. Calculated,
%: C 59.43; H 3.99.
2. D’hooge, B., Smeets, S., Toppet, S., and Dehaen, W.,
Chem. Commun., 1997, p. 1753.
3. Petrov, M.L., Abramov, M.A., and Dehaen, W., Russ. J.
Org. Chem., 2000, vol. 36, p. 605.
4. Abramov, M.A., Dehaen, W., D’hooge, B., Petrov, M.L.,
Smeets, S., Toppet, S., and Voets, M., Tetrahedron,
2000, vol. 56, p. 3933.
2-(4-tert-Butylbenzylselanyl)benzo[b]furan-5-ol
(IXb). Under analogous conditions, a mixture of 0.34 g
(1.41 mmol) of selenadiazole Vb, 0.49 g (3.55 mmol)
of freshly calcined potassium carbonate, 0.257 g
(1.66 mmol) of p-tert-butylbenzyl chloride, and 20 ml
of freshly distilled tetrahydrofuran was heated for 2 h
under reflux with vigorous stirring, cooled to 15–18°C,
and evaporated on a rotary evaporator. The brown
residue was treated with boiling hexane (3×15 ml).
The extract was cooled, and the precipitate was filtered
off and dried. Yield 0.35 g (69%), colorless crystals,
mp 121–122°C, Rf 0.32 (methylene chloride). 1H NMR
spectrum (CDCl3), δ, ppm: 1.29 s (CH3), 4.18 s (CH2),
4.87 s (OH), 6.67 s (3-H), 6.79 d.d (6-H), 6.91 d (4-H),
7.16 d (o-H), 7.32 d (m-H), 7.35 d (7-H). 13C NMR
spectrum (CDCl3), δC, ppm: 31.14 (CH3), 31.97 (CH2),
34.34 (CCH3), 105.16 (C7), 111.14 (C4), 112.79 (C3),
113.97 (C6), 125.37 (Cm), 128.38 (Co), 129.37 (C3a),
134.68 (Ci), 145.14 (C5), 150.06 (Cp), 151.26 (C7a),
152.30 (C2). Mass spectrum, m/z (Irel, %): 360 (23)
[M]+, 213 (37) [M – CH2C6H4C(CH3)3]+, 147 (100)
[CH2C6H4C(CH3)3]+, 132 (68) [CH2C6H4C(CH3)3 –
CH3]+, 117 (61) [CH2C6H4C(CH3)3 – 2CH3]+. Found,
%: C 63.77, 63.43; H 5.39, 5.62. C19H20O2Se. Cal-
culated, %: C 63.52; H 5.61.
5. Yamakawa, Y., Ueda, M., and Nagahata, R., J. Chem.
Soc., Perkin Trans. 1, 1998, p. 4135.
6. Loim, N.M. and Keldysheva, E.S., Izv. Ross. Akad.
Nauk, Ser. Khim., 2004, p. 1995.
7. Modern Cyclophane Chemistry, Gleiter, R. and
Hopf, H., Eds., Weinheim: Wiley, 2004, p. 566.
8. Petrov, M.L., Dehaen, W., Abramov, M.A., Abramo-
va, I., and Androsov, D.A., Russ. J. Org. Chem., 2002,
vol. 38, p. 1510.
9. Wierzbicki, M., Kirsch, G., Cagniat, D., Lieber-
mann, M., and Schafer, T.W., Eur. J. Med. Chem. Chim.
Therap., 1977, vol. 12, p. 557.
10. Malmstrom, J., Jonson, M., Cotgreave, I.A., Hammar-
trom, L., Sjodin, M., and Engman, L., J. Am. Chem.
Soc., 2001, vol. 123, p. 3434.
11. Lalezari, I., Shaffice, A., and Yalpani, M., Tetrahedron
Lett., 1969, vol. 58, p. 5105.
12. Fieser, L.F. and Fieser, M., Reagents for Organic
Synthesis, New York: Wiley, 1968. Translated under the
title Reagenty dlya organicheskogo sinteza, Moscow:
Mir, 1970, vol. 3, p. 246.
13. Petrov, M.L., Abramov, M.A., Abramova, I.P., and
Dehaen, W., Russ. J. Org. Chem., 2003, vol. 39, p. 261.
14. Petrov, M.L., Abramov, M.A., Abramova, I.P., De-
haen, W., and Lyakhovetskii, Yu.I., Russ. J. Org. Chem.,
2001, vol. 37, p. 1643.
15. Silverstein, R.M., Bassler, G.C., and Morrill, T.C., Spec-
trometric Identification of Organic Compounds, New
York: Wiley, 1974, 3rd ed. Translated under the title
Spektrometricheskaya identifikatsiya organicheskikh
soedinenii, Moscow: Mir, 1977, p. 72.
This study was performed under financial support
by the Ministry of Education of the Russian Federa-
tion, program “Development of Scientific Potential at
Higher School.”
16. Meier, H. and Zeller, K.P., Angew. Chem., 1977, p. 876.
17. Organic Syntheses, Horning, E.C., Ed., New York:
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