Oxidation of α-sulfonyl selenides: Formation of selenolesters

Article abstract of DOI:10.1039/a806192k

Treatment of 7-phenylseleno-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benzimidazole 6,6-dioxide 7a in CH₂Cl₂ with m-chloroperbenzoic acid (MCPBA) and 28% H₂O₂ at room temperature gave Se-phenyl 2-[(benzimidazol-l-yl)methyl]selenobenzoate 8a. Similarly, the oxidation of sulfone 7a in THF with aqueous Oxone7 at room temperature gave the same selenolester 8a. The formation of selenolesters 8 can be explained by assuming either the involvement of oxaseleniranium cation 13, having a sulfinate group at C-2 of the benzimidazole moiety, as an intermediate which is believed to be formed by an intramolecular nucleophilic attack of the polarized oxygen of the Se=O bond of selenoxide 6 to the α-carbon next to the sulfonyl group, or Pummerer-type reactions.

Full text of DOI:10.1039/a806192k

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Oxidation of á-sulfonyl selenides: Formation of selenolesters
Jae Sang Yi and Kyongtae Kim*
Department of Chemistry, Seoul National University, Seoul 151-742, Korea
Received (in Cambridge) 5th August 1998, Accepted 2nd November 1998
Treatment of 7-phenylseleno-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benzimidazole 6,6-dioxide 7a in
CH2Cl2 with m-chloroperbenzoic acid (MCPBA) and 28% H2O2 at room temperature gave Se-phenyl 2-
[(benzimidazol-1-yl)methyl]selenobenzoate 8a. Similarly, the oxidation of sulfone 7a in THF with aqueous Oxone
at room temperature gave the same selenolester 8a. The formation of selenolesters 8 can be explained by assuming
either the involvement of oxaseleniranium cation 13, having a sulfinate group at C-2 of the benzimidazole moiety,
as an intermediate which is believed to be formed by an intramolecular nucleophilic attack of the polarized oxygen
of the Se᎐O bond of selenoxide 6 to the α-carbon next to the sulfonyl group, or Pummerer-type reactions.
᎐
selenoxide into benzaldehyde,5 or displacement of the sulfonyl
Introduction
group by nucleophilic attack of the polarized oxygen of a Se᎐O
᎐
We have previously shown that 7,12-dihydrobenzo[5,6]-
[1,3]thiazepino[3,2-a]benzimidazole 6,6-dioxide 11 can be
utilized for the synthesis of various benzimidazole derivatives
such as 1-(2-vinylbenzyl)benzimidazolin-2-ones 2,1 2-alkoxy-
1-(2-formylbenzyl)benzimidazoles 3a, 2-alkylthio-1-(2-formyl-
benzyl)benzimidazoles 3b, 1-(2-formylbenzyl)benzimidazole 4,
and 1-(2-formylbenzyl)benzimidazol-2-one 5.2
bond of the dipolar selenoxide functionality, although only
rarely have sulfones been usefully employed as leaving groups
in reactions forming new carbon–carbon bonds.6 With this in
mind, we have undertaken the selenation of sulfone 1, followed
by oxidation reactions.
Results and discussion
Treatment of compound 1 in THF with n-BuLi (1–1.5 equiv.)
at Ϫ78 ЊC, followed by addition of benzeneselenenyl bromide,
gave α-sulfonyl selenide 7a (18%) (Scheme 1). Substitution of
Scheme 1
In continuing to explore new functionalized benzimidazole
derivatives, which are of biological interest,3 we became in-
terested in an α-sulfonyl selenoxide 6, characterized by bonding
of sulfonyl and areneseleninyl moieties to the same carbon
atom with a hydrogen atom and a phenyl group, because the
chemistry of such a system has never been studied despite
extensive research on the oxidation of α-sulfonyl selenides
having an alkyl group at the α-position.4 One might envisage
the formation of α-sulfonyl selenenate as an intermediate, as
proposed in the thermal decomposition of benzyl phenyl
n-BuLi for LDA (2 equiv.) as a base afforded 7a (19%). The
yield of 7a increased to 65% when NaH followed by n-BuLi was
used. Treatment of compound 1 with NaH, followed by the
addition of benzenselenenyl bromide, gave a reaction mixture
which showed two spots corresponding to compound 7a
(Rf = 0.6, EtOAc–n-hexane 1:2) and bis(phenylseleno) sulfone
10a (Rf = 0.7, EtOAc–n-hexane 1:2) on TLC in spite of the use
of equimolar amounts of NaH and substrate 1. The top spot
corresponding to bisselenide 10a disappeared after the addition
of n-BuLi, and intensified fluorescence was observed from the
J. Chem. Soc., Perkin Trans. 1, 1999, 71–76
71

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bottom spot corresponding to compound 7a by visualization
with a mineral UV lamp.
opening, followed by loss of a sulfur dioxide, which is in reverse
order of the preceding path (13 → 14 → 15) would give a
carbanion 17 (13 → 16 → 17). Protonation of 17 would
give selenolesters 8. On the other hand, one may consider the
possible involvement of a Pummerer-type of reaction on com-
pound 6, which would lead to seleninium ion 18.10 Nucleophilic
attack of water to give the alcohol 19, followed by a C–S
bond cleavage would give sulfinate 16. Surprisingly, there is no
precedent for this type of bond cleavage yielding selenolesters
in the reported Pummerer reactions.
The possibility of an intramolecular proton transfer from
an oxaseleniranium moiety to the carbanion at C-2 of the
benzimidazole moiety of an intermediate 14 was ruled out
owing to the failure of the isolation of a deuterium in-
corporated compound 8 from its deuterated precursor 7a-D,
which was prepared as shown in Scheme 3.
Since compound 10a, formed in minute amounts, was able to
be removed by carefully performed column chromatography
without using n-BuLi, analogous monoselenide products 7b–g
were isolated by chromatographic separation of the reaction
mixture without using n-BuLi.
Oxidation of selenide 7a with MCPBA in CH2Cl2 at rt gave
selenolester 8a (36%), diphenyl diselenide 9a (25%), and
unchanged reagent 7a (34% recovery). Selected oxidants such as
28% H2O2, Oxone, and sodium periodate were employed to see
if the yield of selenolester 8a could be increased. The reaction
of compound 7a with 28% H2O2 in CH2Cl2 (1.2 equiv.) for 5 h
at rt gave selenolester 8a (25%) together with diselenide 9a
(21%). However, treatment of compound 7a in MeOH with
aq. Oxone (1.1 equiv.) for 20 h at rt gave methyl 2-[(benz-
imidazol-1-yl)methyl]benzoate 11 (38%). In contrast, treatment
of compound 7a in THF with the same oxidant (1.1 equiv.)
in water for 24 h at rt gave compound 8a (21%) along with
diselenide 9a (39%). Interestingly, compound 7a in MeOH
reacted with aq. NaIO4 (1.1 equiv.) at reflux to give ester 11
(31%) and methyl 2-[(2-methoxybenzimidazol-1-yl)methyl]-
benzoate 12 (14%).
Treatment of compound 1 with NaH in THF under nitrogen
at rt, followed by addition of D2O, gave deuterated compound
1-D (27%) and undeuterated 1 (63%). The deuterium content
of product 1-D increased to 60% by performing one more
deuteration under the same conditions as in the first one.
Compound 1-D (60% D content) was converted into selenide
7a-D (55%). Deuterium content of 7a-D (30%) was determined
by comparing the intensities of the proton signal of an NCH2
and a methine proton signal of the SO2CHSePh moiety. Treat-
ment of compound 7a-D with MCPBA afforded compound
8 of which the 1H NMR spectrum did not indicate the
incorporation of D at C-2 (δ-value of H at C-2: 7.91) of
the benzimidazole moiety. Therefore, it may be reasonable
to assume that either m-chlorobenzoic acid or water acts
as a proton donor depending on the oxidants employed. In
view of this, pathway 13 → 14 → 15 may be more
plausible than the alternative pathway 13 → 16 → 17 if
oxaseleniranium ions are involved because, for the former,
protonation of the carbanion of 14 precedes deprotonation of
the oxaseleniranium cation of intermediate 14, whereas for the
latter, deuteration of a carbanion 17 may be possible owing to
the precedent deprotonation of an oxaseleniranium cation 13.
In order to test the generality of the reaction, phenyl α-
phenylsulfonylbenzyl selenide 21 was prepared from benzyl
phenyl sulfone 20, benzeneselenenyl bromide, and LDA. Treat-
ment of sulfone 21 with Oxone in a mixture of THF and water
(5:2) for 10 min gave selenolester 22 (44%) (Scheme 4).
Although MCPBA was a better oxidant than the other
oxidants employed, it was more laborious to separate the
desired product from the MCPBA-mediated oxidation mixture
than from the other oxidant-mediated reaction mixtures.
Therefore, Oxone in THF was used for the other oxidation
reactions.
However, the same oxidation of α-sulfonyl-α-methyl
selenide 23 with Oxone gave an elimination product 24 (65%)
(Scheme 5).
The structures of selenolesters 8 were determined on the
basis of their spectroscopic data and elemental analyses. There
have been a variety of methods for the synthesis of selenol-
esters.7 Nevertheless, the formation of aryl selenolesters 8 from
the oxidation of α-sulfonyl areneselenides 7 is of interest from a
mechanistic point of view. The formation of selenolesters 8 may
be explained by assuming the involvement of oxaseleniranium
cation 13 having a sulfinate group at C-2 of the benzimidazole
moiety as an intermediate, which is believed to be formed
by an intramolecular nucleophilic attack of the polarized
In summary, treatment of α-sulfonyl selenides having one
α-hydrogen but without β-hydrogens, i.e., 7-phenylseleno-
7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benzimidazole 7a
and phenyl α-phenylsulfonylbenzyl selenide 21, with oxidants
such as MCPBA, 28% H2O2, and Oxone in THF gives the
corresponding selenolesters 8 and 22, respectively. The form-
ation of selenolesters can be explained by the involvement of
either an oxaseleniranium cation or Pummerer type of reaction,
in which the former, to the best of our knowledge, has never
been proposed in the literature and there is no precedent for the
formation of selenolester in Pummerer reactions.
oxygen of a Se᎐O bond of selenoxide 6 to the α-carbon next to
᎐
the sulfonyl group (Scheme 2). To the best of our knowledge,
neither oxaselenirane nor oxaseleniranium cation has appeared
in the literature, although there are a number of literature
reports in which oxathiiranes, analogous to oxaselenirane,
have been proposed as intermediates.8 Loss of sulfur dioxide
from the intermediate 13 to give a carbanion 14, followed by
protonation, which is analogous to the formation of the parent
benzimidazole via benzimidazol-2-ylsulfinate as an inter-
mediate in alkaline autoxidation of benzimidazole-2-thione
with oxygen and tert-butoxide in tert-butanol,9 would give a
new oxaseleniranium cation 15, which undergoes deproton-
ation concomitant with a bond cleavage between oxygen and
selenium atoms to give selenolesters 8. Alternatively, first ring
Experimental
The 1H NMR spectra were recorded at 80, 200, or 300 MHz in
CDCl3 solution containing tetramethylsilane as an internal
standard; J-values are given in Hz. IR spectra were recorded in
KBr or for thin-film samples on KBr plates. Mass spectra were
obtained by electron impact at 70 eV. Elemental analyses
were determined by the Korea Basic Science Center. Column
chromatography was performed using silica gel (Merck, 70–
230 mesh, ASTM). Mps were determined on a Fisher-Johns
melting point apparatus and are uncorrected. Solvents were
pre-dried over sodium.
72
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Scheme 2
Scheme 4
Scheme 3
sequently n-BuLi (0.3 ml of 2.5 M solution in n-hexane,
0.120 mmol) was added during 5 min. The mixture was
additionally stirred for 30 min at rt, followed by quenching
with water. The reaction mixture was extracted with EtOAc
(40 ml × 3). The extracts were dried over MgSO4. After removal
of the solvent in vacuo, the residue was chromatographed
on a silica gel column (2 × 10 cm). Elution with a mixture
of n-hexane and EtOAc (2:1) gave diphenyl diselenide 9a (78
mg, 33%), 7,7-bis(phenylseleno)-7,12-dihydrobenzo[5,6][1,3]-
Reaction of 7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benz-
imidazole 6,6-dioxide 1 with NaH
To a solution of compound 1 (284 mg, 1.00 mmol) in dried
THF (25 ml) at rt under nitrogen was added NaH (36 mg,
1.50 mmol). The mixture was stirred for 10 min, followed by
dropwise addition of a solution of benzeneselenenyl bromide
(354 mg, 1.50 mmol) in THF (30 ml) for 30 min and sub-
J. Chem. Soc., Perkin Trans. 1, 1999, 71–76
73

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(200 mg, 0.703 mmol), NaH (17 mg, 0.708 mmol), and di-
o-tolyl diselenide (175 mg, 0.700 mmol) gave title compound 7c
(97 mg, 31%), mp 196–198 ЊC (from CH2Cl2–n-hexane) (Found:
C, 58.5; H, 3.9; N, 6.25; S, 7.1%); νmax(KBr)/cmϪ1 3056, 2928,
1452, 1318, 1142 and 1120; δH(80 MHz) 2.44 (3H, s, CH3), 5.50
(2H, s, NCH2), 5.76 (1H, s, SO2CH), 6.67–7.74 (11H, m, ArH)
and 7.74–8.01 (1H, m, ArH), and 7,7-bis(2-tolylseleno)-7,12-
dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benzimidazole 6,6-di-
oxide 10c (13 mg, 3%), mp 221–223 ЊC (from CH2Cl2) (Found:
C, 56.1; H, 3.9; N, 4.4; S, 5.1. C29H24N2O2SSe2 requires C, 55.95;
H, 3.89; N, 4.50; S, 5.15%); νmax(KBr)/cmϪ1 3056, 2912, 1320,
1142, 1082, 819, 624 and 430; δH(80 MHz) 2.48 (6H, s, 2CH3),
5.73 (2H, s, NCH2), 6.56–7.66 (14H, m, ArH), 7.78–8.14 (1H,
m, ArH) and 8.14–8.48 (1H, m, ArH).
7-(4-Chlorophenylseleno)-7,12-dihydrobenzo[5,6][1,3]thiaze-
pino[3,2-a]benzimidazole 6,6-dioxide 7d. The reaction of com-
pound 1 (284 mg, 1.00 mmol), NaH (26 mg, 1.08 mmol), and
4-chlorobenzeneselenenyl bromide, which was prepared in situ
from di-4-chlorophenyl diselenide (209 mg, 0.548 mmol) and
bromine (88 mg, 0.551 mmol), gave title compound 7d (205 mg,
43%), mp 116–118 ЊC (from CH2Cl2–n-hexane) (Found: C, 53.5;
H, 3.3; N, 5.7; S, 6.9. C21H15ClN2O2SSe requires C, 53.23;
H, 3.19; N, 5.91; S, 6.76%); νmax(KBr)/cmϪ1 3056, 2484, 1459,
1318, 1142, 1120, 1081, 1011 and 909; δH(80 MHz) 5.44 (2H,
s, NCH2), 5.86 (1H, s, SO2CH), 6.70–7.64 (11H, m, ArH) and
7.76–8.06 (1H, m, ArH), and 7,7-bis(4-chlorophenylseleno)-
7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benzimidazole
6,6-dioxide 10d (11 mg, 2%), mp 202–204 ЊC (from CH2Cl2–n-
hexane) (Found: C, 49.0; H, 2.7; N, 4.2; S, 5.0.
C27H18Cl2N2O2SSe2 requires C, 48.98; H, 2.74; N, 4.22; S,
4.83%); νmax(KBr)/cmϪ1 3056, 1462, 1328, 1142, 1123 and 742;
δH(80 MHz) 5.52 (2H, s, NCH2), 6.58–6.99 (4H, m, ArH), 6.99–
7.77 (10H, m, ArH), 7.77–8.08 (1H, m, ArH) and 8.43–8.73
(1H, m, ArH).
Scheme 5
thiazepino[3,2-a]benzimidazole 6,6-dioxide 10a (14 mg, 2%),
mp 180–181 ЊC (from CH2Cl2–n-hexane) (Found: C, 53.9; H,
3.2; N, 4.9; S, 5.4. C27H20N2O2SSe2 requires C, 54.10; H, 3.36;
N, 4.67; S, 5.35%); νmax(KBr)/cmϪ1 3056, 1690, 1321, 1148, 822
and 736; δH(80 MHz) 5.53 (2H, s, NCH2), 6.48–7.57 (16H, m,
ArH), 7.57–8.13 (1H, m, ArH) and 8.47–8.74 (1H, m, ArH),
and 5-phenylseleno-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-
a]benzimidazole 6,6-dioxide 7a (284 mg, 65%), mp 108–111 ЊC
(from EtOH) (Found: C, 57.3; H, 3.8; N, 6.5; S, 7.3.
C21H16N2O2SSe requires C, 57.40; H, 3.67; N, 6.38; S, 7.30%);
νmax(KBr)/cmϪ1 3056, 2912, 1456, 1427, 1318, 1142 and 822;
δH(80 MHz) 5.43 (2H, s, NCH2), 5.88 (1H, s, SO2CH), 7.06–
7.15 (2H, m, ArH), 7.21–7.53 (10H, m, ArH) and 7.91–7.98
(1H, m, ArH). Elution with the same solvent mixture (1:2) gave
unchanged substrate 1 (41 mg, 14% recovery).
7-(2-Thienylseleno)-7,12-dihydrobenzo[5,6][1,3]thiazepino-
[3,2-a]benzimidazole 6,6-dioxide 7e. The reaction of compound
1 (284 mg, 1.00 mmol), NaH (24 mg, 1.00 mmol), and
thiophene-2-selenenyl bromide, which was prepared in situ from
di-2-thienyl diselenide (194 mg, 0.598 mmol) and bromine
(96 mg, 0.601 mmol), gave title compound 7e (172 mg, 39%),
mp 160–161 ЊC (from EtOAc–n-hexane) (Found: C, 51.0; H,
3.2; N, 6.35; S, 7.1. C19H14N2O2S2Se requires C, 51.24; H, 3.17;
N, 6.29; S, 7.20%); νmax(KBr)/cmϪ1 3056, 2912, 1430, 1321,
1123, 1094, 819 and 793; δH(80 MHz) 5.49 (2H, s, NCH2), 5.86
(1H, s, SO2CH), 6.50–6.75 (2H, m, ArH), 7.18–7.63 (8H, m,
ArH) and 7.83–8.06 (1H, m, ArH).
General procedure for the synthesis of 7-(arylseleno)-7,12-
dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benzimidazole 6,6-
dioxides 7b–g
To a solution of compound 1 in THF (100 ml) under nitrogen
was added NaH. The mixture was stirred for 1 h at rt followed
by dropwise addition of di-p-tolyl diselenide and di-o-tolyl
diselenide for products 7b and 7c, respectively, during 5 min.
For products 7d–g, the corresponding areneselenenyl bromide,
which was prepared in situ by treatment of the corresponding
diarene diselenide 9 with bromine in THF (10–15 ml) for 5 min
at rt under nitrogen, was added dropwise. The mixture was
additionally stirred for 1 h. After removal of the solvent in
vacuo, the residue was extracted with CH2Cl2 (150 ml × 2), and
dried over MgSO4. Chromatography (230–400 mesh, 2 × 10
cm) of the residue using a mixture of EtOAc and n-hexane
(1:2) gave the corresponding diselenide 9d–g and selenides 7b–g
and 10c,d.
7-(Biphenyl-4-ylseleno)-7,12-dihydrobenzo[5,6][1,3]thiaze-
pino[3,2-a]benzimidazole 6,6-dioxide 7f. The reaction of com-
pound 1 (193 mg, 0.678 mmol), NaH (17 mg, 0.708 mmol),
and biphenyl-4-ylselenenyl bromide, which was prepared in situ
from bis(biphenyl-4-yl) diselenide (157 mg, 0.328 mmol) and
bromine (54 mg, 0.338 mmol), gave title compound 7f (115 mg,
33%), mp 206–208 ЊC (from MeOH–CH2Cl2) (Found: C, 63.15;
H, 4.0; N, 5.6; S, 6.2. C27H20N2O2SSe requires C, 62.91; H, 3.91;
N, 5.43; S, 6.22%); νmax(KBr)/cmϪ1 3056, 2960, 1321, 1235,
1142, 1004, 826 and 611; δH(80 MHz) 5.39 (2H, s, NCH2), 5.89
(1H, s, SO2CH), 6.87–7.63 (16H, m, ArH) and 7.69–8.02 (1H,
m, ArH).
7-(4-Tolylseleno)-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-
a]benzimidazole 6,6-dioxide 7b. The reaction of compound 1
(284 mg, 1.00 mmol), NaH (29 mg, 1.21 mmol), and di-p-tolyl
diselenide (275 mg, 1.10 mmol) gave title compound 7b (153 mg,
33%), mp 170–171 ЊC (from CH2Cl2–n-hexane) (Found: C, 58.0;
H, 4.1; N, 6.2; S, 7.0. C22H18N2O2SSe requires C, 58.28; H, 4.00;
N, 6.18; S, 7.07%); νmax(KBr)/cmϪ1 3040, 2912, 1321, 1142 and
819; δH(80 MHz) 2.20 (3H, s, CH3), 5.40 (2H, s, NCH2), 5.80
(1H, s, SO2CH), 6.61–6.96 (2H, m, ArH), 6.96–7.57 (9H, m,
ArH) and 7.64–8.01 (1H, m, ArH).
5-(1-Naphthylseleno)-7,12-dihydrobenzo[5,6][1,3]thiazepino-
[3,2-a]benzimidazole 6,6-dioxide 7g. The reaction of compound
1 (300 mg, 1.06 mmol), NaH (28 mg, 1.17 mmol), and
naphthalene-1-selenenyl bromide, which was prepared in situ
from di-1-naphthyl diselenide (263 mg, 0.637 mmol) and
bromine (102 mg, 0.638 mmol), gave title compound 7g (193
mg, 37%), mp 204–206 ЊC (from CH3CN) (Found: C, 61.4;
H, 3.6; N, 5.9; S, 6.6. C25H18N2O2SSe requires C, 61.13; H, 3.71;
7-(2-Tolylseleno)-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-
a]benzimidazole 6,6-dioxide 7c. The reaction of compound 1
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N, 5.72; S, 6.55%); νmax(KBr)/cmϪ1 3056, 2912, 1325, 1241,
1146, 1126 and 720; δH(80 MHz) 5.42 (2H, s, NCH2), 5.79 (1H,
s, SO2CH) and 6.39–8.49 (15H, m, ArH).
General procedure for the synthesis of Se-aryl 2-[(benzimid-
azol-1-yl)methyl]selenobenzoates 8
A solution of a sulfone 7 (0.165–0.225 mmol) in THF (30 ml)
was treated with aq. Oxone (0.182–0.281 mmol in 20 ml) for
10 min, and the mixture was stirred for 20–36 h at rt. The
mixture was worked up as described in method (iv) above.
Oxidation of compound 7a
(i) Using MCPBA. To a solution of compound 7a (500 mg,
1.14 mmol) in dried CH2Cl2 (60 ml) was added dropwise a
solution of MCPBA (302 mg, 1.25 mmol) in CH2Cl2 (40 ml)
during 10 min. The mixture was stirred for 1 h at rt. After
removal of the solvent, the residue was chromatographed on
a silica gel column (2 × 15 cm). Elution with a mixture of EtOAc
and n-hexane (1:2) gave diselenide 9a (45 mg, 25%) and
unchanged reagent 7a (168 mg, 34% recovery). Elution with
EtOAc–n-hexane (1:1) gave Se-phenyl 2-[(benzimidazol-
1-yl)methyl]selenobenzoate 8a (162 mg, 36%), mp 54–55 ЊC
(CH2Cl2–n-hexane) (Found: C, 64.7; H, 4.2; N, 7.2. C21H16-
N2OSe requires C, 64.45; H, 4.12; N, 7.16%); νmax(neat)/cmϪ1
3040, 2912, 1683, 1437, 1350, 1270 and 1187; δH(300 MHz) 5.56
(2H, s, NCH2), 6.87–6.90 (1H, m, ArH), 7.17–7.35 (3H, m,
ArH), 7.37–7.45 (5H, m, ArH), 7.55–7.58 (2H, m, ArH),
Se-4-Tolyl 2-[(benzimidazol-1-yl)methyl]selenobenzoate 8b.
The reaction of compound 7b (75 mg, 0.165 mmol) and Oxone
(112 mg, 0.182 mmol) gave unchanged substrate 7b (24 mg, 32%
recovery), diselenide 9b (7 mg, 24%), and title compound 8b
(24 mg, 35%), as a liquid (Found: C, 65.0; H, 4.3; N, 7.0.
C22H18N2OSe requires C, 65.19; H, 4.48; N, 6.91%); νmax(neat)/
cmϪ1 3056, 2928, 1683, 1485, 1363, 803 and 762; δH(80 MHz)
2.39 (3H, s, CH3), 5.59 (2H, s, NCH2), 6.68–7.62 (11H, m, ArH)
and 7.62–8.19 (2H, m, ArH, N᎐CH).
᎐
Se-2-Tolyl 2-[(benzimidazol-1-yl)methyl]selenobenzoate 8c.
The reaction of compound 7c (95 mg, 0.210 mmol) and Oxone
(141 mg, 0.229 mmol) gave diselenide 9c (45 mg, 63%) and title
compound 8c (28 mg, 33%), as a liquid (Found: C, 65.0; H, 4.6;
N, 6.9. C22H18N2OSe requires C, 65.19; H, 4.48; N, 6.91%);
νmax(neat)/cmϪ1 3056, 2928, 1690 and 883; δH(80 MHz) 2.40
(3H, s, CH3), 5.56 (2H, s, NCH2), 6.72–7.01 (1H, m, ArH),
7.83–7.87 (1H, m, ArH), 7.91 (1H, s, N᎐CH) and 8.04–8.07
᎐
(1H, m, ArH).
(ii) Using 28% H2O2. To solution of compound 7a (385 mg,
0.876 mmol) in CH2Cl2 (50 ml) was added 28% H2O2 (128 mg,
1.05 mmol). The mixture was stirred for 5 h at rt, followed by
quenching with aq. sodium hydrogen carbonate (10%), and the
mixture was extracted with CH2Cl2 (100 ml × 2). The extracts
were worked up as usual. Chromatography (2 × 10 cm) of the
reaction mixture with a mixture of EtOAc and n-hexane (1:1)
gave diselenide 9a (29 mg, 21%), starting material 7a (18 mg, 5%
recovery), and selenobenzoate 8a (88 mg, 25%).
7.01–7.68 (9H, m, ArH), 7.11–7.99 (2H, m, ArH, N᎐CH) and
7.99–8.29 (1H, m, ArH).
᎐
Se-4-Chlorophenyl 2-[(benzimidazol-1-yl)methyl]selenobenz-
oate 8d. The reaction of compound 7d (100 mg, 0.211 mmol)
and Oxone (143 mg, 0.233 mmol) gave unchanged starting
material 7d (53 mg, 53% recovery) and title compound 8d (35
mg, 38%) as a liquid (Found: C, 59.0; H, 3.8; N, 6.2. C21H15-
ClN2OSe requires C, 59.24; H, 3.55; N, 6.58%); νmax(neat)/
cmϪ1 3056, 2928, 1686, 1277 and 813; δH(80 MHz) 5.57 (2H,
s, NCH2), 6.74 (11H, m, ArH) and 7.64–8.19 (2H, m, ArH,
(iii) Using Oxone (potassium peroxymonosulfate) in MeOH.
To a solution of compound 7a (610 mg, 1.39 mmol) in MeOH
(50 ml) was added dropwise aq. Oxone (940 mg, 1.53 mmol
in 50 ml) during 30 min. The mixture was stirred for 20 h at rt
and worked up as usual. Chromatography (2 × 15 cm) of the
reaction mixture using EtOAc–n-hexane (1:1) gave compound
9a (21 mg, 10%), unchanged substrate 7a (192 mg, 31%
recovery), and methyl 2-[(benzimidazol-1-yl)methyl]benzoate
11 (142 mg, 38%), mp 130–131 ЊC (from EtOAc–n-hexane)
(Found: C, 71.9; H, 5.4; N, 10.6. C16H14N2O2 requires C, 72.17;
H, 5.30; N, 10.51%); νmax(neat)/cmϪ1 3056, 2944, 1702, 1594,
1484, 1446, 1418, 1347, 1280, 1088 and 883; δH(200 MHz) 3.90
(3H, s, OCH3), 5.83 (2H, s, NCH2), 6.65–6.82 (1H, m, ArH),
7.20–7.42 (5H, m, ArH), 7.85–7.97 (1H, m, ArH), 7.90 (1H, s,
N᎐CH) and 8.02–8.15 (1H, m, ArH); δ (50 MHz) 47.1, 52.3,
N᎐CH).
᎐
Se-2-Thienyl
2-[(benzimidazol-1-yl)methyl]selenobenzoate
8e. The reaction of compound 7e (100 mg, 0.225 mmol) and
Oxone (173 mg, 0.281 mmol) gave unchanged starting material
7e (41 mg, 41% recovery) and title compound 8e (27 mg, 31%) as
a liquid (Found: C, 57.2; H, 3.6; N, 7.1; S, 7.85. C19H14N2OSSe
requires C, 57.43; H, 3.55; N, 7.05; S, 8.07%); νmax(neat)/cmϪ1
1680, 1475, 748, 730 and 681; δH(300 MHz) 5.61 (2H, s, NCH2),
6.65–6.82 (2H, m, ArH), 6.85–7.18 (5H, m, ArH), 7.23 (1H, s,
N᎐CH), 7.32–7.53 (3H, m, ArH) and 7.81–7.96 (1H, m, ArH).
᎐
Se-Biphenyl-4-yl 2-[(benzimidazol-1-yl)methyl]selenobenzoate
8f (attempted preparation). A solution of compound 7f (90 mg,
0.175 mmol) in THF (25 ml) was treated with aq. Oxone (118
mg, 0.192 mmol in 20 ml) for 10 min, and the mixture was
stirred for 24 h at rt. Work-up as usual gave bis(biphenyl-4-yl)
diselenide 9f (12 mg, 30%) and unchanged substrate 7f (17 mg,
19% recovery). No title compound 8f was formed.
᎐
C
110.0, 120.4, 122.2, 123.1, 127.6, 127.9, 131.3, 133.0, 134.0,
137.9, 143.8 and 167.1.
(iv) Using Oxone in aq. THF. To a solution of compound
7a (210 mg, 0.478 mmol) in THF (40 ml) was added dropwise
aq. Oxone (323 mg, 0.525 mmol in 30 ml) during 10 min. The
mixture was stirred at rt for 24 h and worked up as usual.
Chromatography (1 × 15 cm) of the reaction mixture using
EtOAc–n-hexane (1:1) gave diselenide 9a (29 mg, 39%),
unchanged starting material 7a (47 mg, 22% recovery) and
selenobenzoate 8a (39 mg, 21%).
Se-1-Naphthyl 2-[(benzimidazol-1-yl)methyl]selenobenzoate
8g. The reaction of compound 7g (100 mg, 0.204 mmol) and
Oxone (135 mg, 0.220 mmol) gave starting material 7g (36 mg,
36% recovery) and title compound 8g (38 mg, 42%) as a liquid
(Found: C, 68.25; H, 4.0; N, 6.4. C25H18N2OSe requires C,
68.29; H, 4.11; N, 6.35%); νmax(neat)/cmϪ1 3136, 2720, 1686,
1190 and 860; δH(300 MHz) 5.65 (2H, s, NCH2), 6.75–6.85
(v) Using NaIO4. To a solution of compound 7a (239 mg,
0.544 mmol) in MeOH (25 ml) was added dropwise aq. NaIO4
(128 mg, 0.598 mmol in 15 ml) during 15 min. The reaction
mixture was stirred for 3 h at reflux and worked up as usual.
Chromatography (2 × 15 cm) of the reaction mixture using
EtOAc–n-hexane (1:1) gave methyl 2-[(2-methoxybenzimid-
azol-1-yl)methyl]benzoate 12 (23 mg, 14%) and analogue 11
(46 mg, 31%).
(1H, m, ArH), 6.97–7.24 (6H, m, ArH), 7.30 (1H, s, N᎐CH),
᎐
7.40–7.62 (5H, m, ArH) and 7.82–8.08 (3H, m, ArH).
7-Deuterio-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benz-
imidazole 6,6-dioxide 1-D
To a solution of compound 1 (700 mg, 2.46 mmol) in THF
(100 ml) under nitrogen was added NaH (65 mg, 2.71 mmol).
J. Chem. Soc., Perkin Trans. 1, 1999, 71–76
75

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The mixture was stirred for 10 min at rt, followed by the
addition of D2O (98 mg, 4.90 mmol), and the mixture was
additionally stirred for 20 min. After removal of the solvent, the
residue was extracted with EtOAc (400 ml × 3). The extracts
were dried over MgSO4. Removal of the solvent, followed by
recrystallization of the residue, gave compound 1 (600 mg,
85%) in which yield of labelled isomer 1-D was calculated to be
27%. Compound 1-D (560 mg, 1.96 mmol; D content 27%) was
treated with NaH (52 mg, 2.17 mmol) and D2O (78 mg, 3.90
mmol) for 20 min under the same conditions as in the first
reaction. Work-up gave back compound 1-D (500 mg, 89%)
having 60% D content.
mixture gave phenyl selenobenzoate 22 (175 mg, 44%), mp 38–
39 ЊC (from CH2Cl2–n-hexane) (lit.,12 38–40 ЊC).
7-Methyl-7-phenylseleno-7,12-dihydrobenzo[5,6][1,3]thiazepino-
[3,2-a]benzimidazole 6,6-dioxide 23
To a solution of compound 7 (120 mg, 0.265 mmol) in THF
(25 ml) at rt under nitrogen was added NaH (6.6 mg, 0.28
mmol), the mixture was stirred for 10 min and then methyl
iodide (383 mg, 2.70 mmol) was added. The mixture was stirred
for 30 min and worked up as usual. Elution with a mixture
of EtOAc and n-hexane (1:2) gave diselenide 9a (4 mg, 9%).
Elution with EtOAc–n-hexane (1:1) gave title compound 23
(88 mg, 72%), mp 84–86 ЊC (from EtOAc–n-hexane) (Found:
C, 58.0; H, 3.9; N, 6.3; S, 7.1. C22H18N2O2SSe requires C, 58.28;
H, 4.00; N, 6.18; S, 7.07%); νmax(KBr)/cmϪ1 1456, 1427, 1318
and 1145; δH(80 MHz) 2.09 (3H, s, CH3), 5.29–6.05 (2H, q,
J 7.5, NCH2) and 6.65–8.12 (13H, m, ArH).
7-Deuterio-7-phenylseleno-7,12-dihydrobenzo[5,6][1,3]thiaze-
pino[3,2-a]benzimidazole 6,6-dioxide 7a-D
Compound 1-D (400 mg, 1.41 mmol; 60% D content) was
treated with NaH (41 mg, 1.71 mmol) and benzeneselenenyl
bromide (354 mg, 1.50 mmol) under the same conditions as for
the preparation of compound 7a. From the reaction mixture
were isolated title compound 7a-D (342 mg, 55%; 30% D con-
tent) and diselenide 9a (75 mg, 32%).
7-Methylene-7,12-dihydrobenzo[5,6][1,3]thiazepino[3,2-a]benz-
imidazole 6,6-dioxide 24
To a solution of selenide 23 (71 mg, 0.157 mmol) in THF
(20 ml) at rt was added aq. Oxone (96 mg, 0.156 mmol in
10 ml). The mixture was stirred for 1 h and worked up as usual.
Elution with a mixture of EtOAc and n-hexane (1:2) gave
title compound 24 (31 mg, 65%), mp 218–220 ЊC (from CH2Cl2–
n-hexane) (Found: C, 64.9; H, 4.1; N, 9.4; S, 10.8. C16H12N2O2S
requires C, 64.85; H, 4.08; N, 9.45; S, 10.82%); νmax(KBr)/cmϪ1
1452, 1305 and 1139; δH(300 MHz) 5.55 (2H, s, NCH2), 6.32
(1H, s, ᎐CH), 6.87 (1H, s, ᎐CH) and 7.57–7.91 (8H, m, ArH);
Oxidation of sulfone 7a-D with MCPBA
A solution of compound 7a-D (297 mg, 0.653 mmol; 30% D
content) in CH2Cl2 (100 ml) was treated with MCPBA (180 mg,
0.745 mmol) for 3 h at rt. The mixture was worked up according
to the same procedure as described for the reaction of the
parent sulfone 7a with MCPBA. From the reaction mixture
were isolated selenobenzoate 8a (140 mg, 52%), diselenide 9a
(37 mg, 35%), and unchanged starting material 7a-D (27 mg,
9% recovery; 30% D content).
᎐
᎐
m/z (EI) 296 (Mϩ, 54%), 231 (100) and 232 (97).
Acknowledgements
We are grateful to the Center for Biofunctional Molecules
Preparation of benzyl phenyl sulfone 20
To a solution of benzyl phenyl sulfide (3.00 g, 15.0 mmol)
in diethyl ether (100 ml) at rt was added MCPBA (11.0 g,
45.0 mmol) during 30 min. The mixture was stirred for
10 h. After removal of the solvent in vacuo, the residue was
neutralized with aq. sodium hydrogen carbonate (10%). The
mixture was extracted with EtOAc (200 ml × 2) and the extracts
were dried (MgSO4). Removal of the solvent in vacuo, followed
by chromatography (2 × 10 cm) using a mixture of n-hexane
and EtOAc (2:1) as eluant, gave title sulfone 20 (3.35 g, 96%),
mp 142–144 ЊC (lit.,11 144–145 ЊC).
(CBM) for financial support.
References
1 S. C. Yoon and K. Kim, Heterocycles, 1995, 41, 103.
2 S. C. Yoon and K. Kim, J. Org. Chem., 1996, 61, 793.
3 (a) F. Janssens, J. Torremans, M. Janssen, R. A. Stokbroekx,
M. Luyckx and P. A. J. Janssen, J. Med. Chem., 1985, 28, 1934;
(b) L. Bonsignore, G. Loy and D. Secci, J. Heterocycl. Chem., 1992,
29, 1033.
4 N. S. Simpkins, Tetrahedron Lett., 1988, 29, 6787.
5 I. D. Entwistle, R. A. W. Johnstone and J. H. Varley, J. Chem. Soc.,
Chem Commun., 1976, 61.
Phenyl á-phenylselenobenzyl sulfone 21
6 (a) J. L. Fabre, M. Julia and J. N. Verpeaux, Bull. Soc. Chim. Fr.,
1985, 762; (b) G. Pattenden and D. A. Whiting, J. Chem. Soc., Perkin
Trans. 1, 1975, 897; (c) B. M. Trost and M. R. Ghadiri, J. Am. Chem.
Soc., 1986, 108, 1098.
7 (a) K. A. Jensen, L. Boje and L. Henriksen, Acta Chem. Scand.,
1972, 26, 1465; (b) H. Ishibara, S. Sato and Y. Hirabayashi, Bull.
Chem. Soc. Jpn., 1977, 50, 3007; (c) K. C. Nicolaou and N. A.
Petasis, Selenium in Natural Products Synthesis, CIS, Inc.,
Philadelphia, 1984, ch. 8, p. 248.
8 (a) L. Carlsen, N. Harrit and A. Holm, J. Chem. Soc., Perkin Trans.
1, 1976, 1404; (b) R. H. Schlessinger and A. G. Schultz, Tetrahedron
Lett., 1969, 4513; (c) J. Silhanek and M. Zbirovsky, Chem.
Commun., 1969, 878; (d) L. Carlsen, H. Egsgaard, E. Schaumann
and J. Ehlers, J. Chem. Ind. (London), 1979, 851; (e) L. Carlsen,
H. Egsgaard and E. Schaumann, J. Chem. Soc., Perkin Trans. 2,
1980, 1206; ( f ) R. A. Aitken, M. J. Drysdale and B. M. Ryan,
J. Chem. Soc., Chem. Commun., 1993, 1699; (g) M. G. Matturro,
R. P. Reynolds, R. V. Kastrup and C. F. Pictroski, J. Am. Chem.
Soc., 1986, 108, 2775.
To a solution of sulfone 20 (930 mg, 4.01 mmol) in THF (60 ml)
at rt was added dropwise LDA (514 mg, 4.80 mmol). The
mixture was stirred for 1 h, followed by the addition of a
solution of benzeneselenenyl bromide (944 mg, 4.00 mmol) in
THF (30 ml), and the mixture was stirred for 30 min before
being extracted with EtOAc (100 ml × 2), and the extracts
were dried over MgSO4. After removal of the solvent in vacuo,
the residue was chromatographed on a silica gel column (2 × 10
cm). Elution with a mixture of EtOAc and n-hexane (1:2) gave
diselenide 9a (263 mg, 42%), and a mixture of starting sulfone
20 (465 mg, 50% recovery) and seleno sulfone 21 (585 mg, 38%)
1
of which the ratio was determined on the basis of H NMR
spectroscopic data, δH(80 MHz) 4.26 (2H, s, CH2SO2), 5.13
(1H, s, CHSO2) and 6.81–7.93 (25H, s, ArH).
Oxidation of a mixture of sulfones 20 and 21 with oxone
9 Y. H. Kim, H. J. Kim and G. H. Yon, J. Chem. Soc., Chem.
Commun., 1984, 1064.
10 O. De. Lucchi, U. Miotti and G. Modena, Org. React., 1991, 40, 157.
11 B. J. Auret, D. R. Boyd, H. B. Henbest and S. Ross, Chem.
Commun., 1968, 2371.
12 P. M. Gregory, P. L. Narender, D. Bruce and D. O. Jerome,
J. Org. Chem., 1985, 50, 811.
To a solution of the mixture of sulfones 20 (465 mg, 2.00 mmol)
and 21 (585 mg, 1.51 mmol) in THF (50 ml) was added aq.
Oxone (928 mg, 1.51 mmol in 20 ml) during 5 min. The mixture
was stirred for 10 min and then was extracted with EtOAc
(100 ml × 2), and the extract was worked up as usual. Elution
with a mixture of n-hexane and EtOAc (2:1) gave diselenide
9a (43 mg, 18%). Continued elution with the same solvent
Paper 8/06192K
76
J. Chem. Soc., Perkin Trans. 1, 1999, 71–76