Intramolecular homolytic substitution with amidyl radicals: A free-radical synthesis of ebselen and related analogues

Article abstract of DOI:10.1021/jo970019t

Irradiation of a water-cooled benzene solution of pyridine-2-thioneoxycarbonyl (PTOC) imidate esters 9 derived from N-butyl-2-(benzylseleno)benzamide (6, R = Bu), 2-(benzylseleno)-N-hexylbenzamide (6, R = Hex), N-benzyl-2-(benzylseleno)benzamide (6, R = Bn), and 2-(benzylseleno)-N-cyclohexylbenzamide (6, R = c-Hex) with a 250-W low-pressure mercury lamp affords the corresponding 1,2-benzisoselenazol-3(2H)-ones (1) in yields of 81-91% (R = primary alkyl) and 45% (R = c-Hex). Presumably, these transformations involve formation of amidyl radicals 2 which undergo subsequent intramolecular homolytic substitution at the selenium atom with expulsion of a benzyl radical. PTOC imidate esters derived from 2-(benzylseleno)benzanilide (6, R = Ph) and 2-(benzylseleno)-N-tert-butylbenzamide (6, R = t-Bu) were unable to be prepared in this manner. 1,2-Benzisoselenazol-3(2H)-ones (1, R = Ph, Hex, i-Pr, t-Bu) could also be prepared in 76-85% yield by reaction of the corresponding 2,2'-diselenobis(benzamide) (15) with benzoyl or tert-butyl peroxide. The mechanisms of these transformations are discussed.

Full text of DOI:10.1021/jo970019t

J . Org. Chem. 1997, 62, 3103-3108
3103
In tr a m olecu la r Hom olytic Su bstitu tion w ith Am id yl Ra d ica ls: A
F r ee-Ra d ica l Syn th esis of Ebselen a n d Rela ted An a logu es
Mei C. Fong and Carl H. Schiesser*
School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia 3052
Received J anuary 2, 1997X
Irradiation of a water-cooled benzene solution of pyridine-2-thioneoxycarbonyl (PTOC) imidate esters
9 derived from N-butyl-2-(benzylseleno)benzamide (6, R ) Bu), 2-(benzylseleno)-N-hexylbenzamide
(6, R ) Hex), N-benzyl-2-(benzylseleno)benzamide (6, R ) Bn), and 2-(benzylseleno)-N-cyclohexyl-
benzamide (6, R ) c-Hex) with a 250-W low-pressure mercury lamp affords the corresponding 1,2-
benzisoselenazol-3(2H)-ones (1) in yields of 81-91% (R ) primary alkyl) and 45% (R ) c-Hex).
Presumably, these transformations involve formation of amidyl radicals 2 which undergo subsequent
intramolecular homolytic substitution at the selenium atom with expulsion of a benzyl radical.
PTOC imidate esters derived from 2-(benzylseleno)benzanilide (6, R ) Ph) and 2-(benzylseleno)-
N-tert-butylbenzamide (6, R ) t-Bu) were unable to be prepared in this manner. 1,2-Benzisoselen-
azol-3(2H)-ones (1, R ) Ph, Hex, i-Pr, t-Bu) could also be prepared in 76-85% yield by reaction of
the corresponding 2,2′-diselenobis(benzamide) (15) with benzoyl or tert-butyl peroxide. The
mechanisms of these transformations are discussed.
In tr od u ction
then several syntheses have been reported.8-12 The
highest-yielding of these involves the treatment of 2-
(methylseleno)benzanilide (3), itself prepared in several
steps from anthranilic acid,9 with phosphorus pentachlo-
ride followed by hydrolysis.10 This procedure affords
ebselen in 80-90% yield and appears to be commercially
viable.11 The most expedient method was reported by
Engman in 1989 and utlizes a one-pot procedure in which
benzanilide is ortho-lithiated and treated with selenium
powder followed by cupric bromide oxidative ring clo-
sure;12 ebselen is obtained in 63% yield.
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) (1,
R ) Ph)) is a nontoxic low molecular weight selenium-
containing heterocycle exhibiting antiinflammatory, an-
tiatherosclerotic, and cytoprotective properties.1 During
the last decade several groups have worked toward a
better understanding of the pharmacology of 1 (R ) Ph)
since it was first discovered that ebselen mimics the
hydroperoxide reducing ability of glutathione peroxidase
(GPx),2 in particular phospholipid hydroperoxide glu-
tathione peroxidase.3 The reader is referred to a recent
review by Schewe in which the unique antiinflammatory
antioxidant molecular actions of ebselen are discussed.1
Ebselen is remarkable in its catalytic ability and in its
ability to inhibit a number of enzymes involved in
inflammation; ebselen appears to inhibit lipoxyganases,
nitric oxide synthases, NADPH, oxidase, and protein
kinase C as well 1,4,5-trisphosphate-induced calcium
release.1,4 Unlike other antioxidants such as R-tocopherol
and probucol which act as lipid free-radical scavengers
and prevent lipid peroxidation, ebselen appears to be a
poor radical scavenger acting instead to reduce hydro-
peroxy-lipids after their formation. The extraordinarily
low toxicity of ebselen has been discussed in terms of the
failure of 1 (R ) Ph) to release selenium metal during
biotransformation.5 It is not surprising therefore that
ebselen is currently undergoing Phase III clinical trials
in J apan as an antioxidant.6
Work in our laboratories has recently focused on the
design and application of free-radical homolytic substitu-
tion chemistry. Given that homolytic substitution is an
effective method for the formation of bonds to higher
heteroatoms,13 and given our recent successes in the
application of alkyl, aryl, and iminyl radical substitution
at the selenium atom in alkyl selenides during the
preparation of a wide variety of selenium-containing
heterocycles,14 it struck us that analogues (1) of ebselen
and indeed ebselen itself should be amenable to prepara-
tion through intramolecular homolytic substitution by
amidyl radicals 2 in appropriately substituted benza-
mides. We now report that photochemical decomposition
of pyridine-2-thioneoxycarbonyl (PTOC) imidate esters
9, or reaction of 2,2′-diselenobis(N-alkylbenzamides) 15
with benzoyl or tert-butyl peroxides affords ebselen and
analogues (1) in 56-91% yield.
Ebselen (1, R ) Ph) was first prepared in 1924;7 since
X Abstract published in Advance ACS Abstracts, April 1, 1997.
(1) Schewe, T. Gen. Pharmacol. 1995, 26, 1153.
(2) Mu¨ller, A.; Cadenas, E.; Graf, P.; Sies, H. Biochem. Pharmacol.
1984, 33, 3235. Wendel, A.; Fausel, M.; Safayhi, H.; Tiegs, G.; Otter,
R. Biochem. Pharmacol. 1984, 33, 3241.
(3) Maiorino, M.; Roveri, A.; Coassin, M.; Ursini, F. Biochem.
Pharmacol. 1988, 37, 2267.
(4) Dimmeler, S.; Bru¨ne, B.; Ullrich, V. Biochem. Pharmacol. 1991,
42, 1151.
(5) Catineau, R.; Tihange, G.; Plenevaux, A.; Christiaens, L.; Guil-
laume, M.; Welter, A.; Dereu, N. J . Labelled Compd. Radiopharm.
1985, 23, 59.
(6) Drugs Future 1995, 20, 1057.
(7) Lesser, R.; Weiss, R. Ber. Dtsch. Chem. Ges. 1924, 57, 1077.
(8) Lambert, C.; Hilbert, M.; Christiaens, L.; Dereu, N. Synth.
Commun. 1991, 21, 85.
(9) Ruwet, A.; Renson, M. Bull. Soc. Chim. Belg. 1969, 78, 571.
(10) Weber, R.; Renson, M. Bull. Soc. Chim. Fr. 1976, 1124.
(11) European Patent EP 44453.
(12) Engman, L.; Hallberg, A. J . Org. Chem. 1989, 54, 2964.
(13) Schiesser, C. H.; Wild, L. M. Tetrahedron 1996, 52, 13265 and
references cited therein.
(14) Schiesser, C. H.; Sutej, K. J . Chem. Soc., Chem. Commun. 1992,
57. Schiesser, C. H.; Sutej. K. Tetrahedron Lett. 1992, 33, 5137. Lyons,
J . E.; Schiesser, C. H.; Sutej, K. J . Org. Chem. 1993, 58, 5632.
Benjamin, L. J .; Schiesser, C. H.; Sutej, K. Tetrahedron 1993, 49, 2557.
Schiesser, C. H.; Fong, M. C.; Schiesser, C. H. Tetrahedron Lett. 1993,
34, 4347. Lucas, M. A.; Schiesser, C. H. J . Org. Chem. 1996, 61, 5754.
S0022-3263(97)00019-4 CCC: $14.00 © 1997 American Chemical Society

3104 J . Org. Chem., Vol. 62, No. 10, 1997
Fong and Schiesser
Sch em e 1
Resu lts a n d Discu ssion
P h otolysis of P TOC im id a te ester s (9). Given the
sensitivity of alkyl selenides toward oxidation,15 haloge-
nation,15 and chain-carrying radicals such as tributyl-
stannyl,13 some considerable thought was given to the
amidyl radical precursor to be used in this study; N-
haloamides16 and precursors requiring tributyltin hy-
dride17 would be clearly unsuitable. Eventually we
decided to explore the use of the PTOC imidate esters 4
and N-acyl PTOC carbamates 5 recently developed by
Newcomb and Esker.18,19 Unfortunately, attempts to
prepare the N-acyl PTOC carbamate derivatives of
amides 6 by reacting the corresponding trimethylsilyl
amides with phosgene as described by Newcomb and
Esker19 were met with little success. We recently re-
ported that amides 6 react with trimethylsilyl triflate
followed by phosgene to afford benzoselenazine-2,4-diones
7.20
The 2-(benzylseleno)benzamides 6 required in this
study were prepared from 2-benzylselenobenzoic acid
following our previously published procedure.20 Amides
6 bearing primary and secondary alkyl substituents were
readily converted into the corresponding iminyl chloride
8 by reaction with 20% phosgene in toluene (Scheme 1).
These reactions are normally carried out in benzene but
can be carried out in deuteriochloroform and are conve-
niently followed by 1H NMR spectroscopy. Amides 6
exhibit characteristic singlets corresponding to the ben-
zylic methylenes in the range δ (CDCl3) 4.07-4.12. After
the addition of phosgene the formation of primary alkyl-
substituted iminyl chlorides (8: R ) Bu, Hex, Bn) is
usually complete within 24 h at room temperature with
N-cyclohexyl 2-(benzylseleno)benzamide (6: R ) c-Hex)
requiring 4 days. The benzylic methylene is observed to
shift upfield by 0.02-0.04 ppm in each case. Unfortu-
nately, 2-(benzylseleno)benzanilide (6: R ) Ph) and
N-tert-butyl 2-(benzylseleno)benzamide (6: R ) tert-
butyl) failed to react under standard conditions. At
elevated temperatures (50 °C) the reaction of the phenyl
amide (6: R ) Ph) was only 20% complete after 3 days,
while the tert-butyl analogue (6: R ) t-Bu) had not
reacted. After 5 days at 80 °C substantial decomposition
was observed in each case. We attribute the lack of
reactivity of the former substrate to the low nucleophi-
licity of the conjugated amide (6: R ) Ph), while steric
factors may be responsible for the lack of reactivity of
the latter.
The iminyl chlorides 8 were not isolated but reacted
immediately with the sodium salt of N-hydroxypyridine-
2-thione to presumably afford PTOC imidate esters 9 in
situ. To our delight, subsequent irradiation with a 250
W low-pressure mecrury lamp (white light) gave the
corresponding benzisoselenazolones (1: R * Ph, t-Bu)
after chromatography (Scheme 1). These reactions are
readily followed by 77Se NMR spectroscopy; starting
amides 6 exhibit signals in the range δ 367-371, while
the ebselen analogues 1 display signals at δ 814-942.
Apart from starting amide 6, byproducts included 2-(ben-
zylthio)pyridine (10) (major), 2,2′-dithiobis(pyridine) (11)
(minor) and bibenzyl (minor) which were conveniently
removed by chromatography or, in the case of 11,
treatment of the crude reaction mixture with saturated
copper(II) sulfate. Presumably, photochemical decom-
position of the PTOC imidate ester 9 affords the amidyl
radical 2 which undergoes intramolecular homolytic
substitution at the selenium atom in 2 with expulsion of
the benzyl radical to afford the ebselen analogues 1.
Initial photolyses were carried out in benzene at
concentrations of approximately 0.1 M and afforded 1 in
27-80% yields. Attempts to optimize the reaction condi-
tions soon revealed a marked concentration dependence.
For example, the butyl-substituted precursor 9 (R ) Bu)
afforded 1 (R ) Bu) in yields ranging from 56% (0.2 M)
to 90% (0.01 M) with the remaining mass balance
comprised predominantly of starting amide (6: R ) Bu)
and sulfides (10, 11); similar results were obtained for
the other primary alkyl-substituted precursors in this
study. In addition, elevated temperatures (80 °C) re-
sulted in marginal decreases in the yield of 1. Reactions
(15) The Chemistry of Organic Selenium and Tellurium Compounds;
Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1986.
(16) Barton, D. H. R.; Beckwith, A. L. J .; Goosen, A. J . Chem. Soc.
1965, 181. Glover, S. A.; Goosen, A. J . Chem. Soc. Perkin Trans. 1
1974, 2353. Kuehne, M. E.; Horne, D. A. J . Org. Chem. 1975, 40, 1287.
Mackiewicz, P.; Furstoss, R.; Waegell, B.; Cote, R.; Lessard, J . J . Org.
Chem. 1978, 43, 3746. Glover, S. A.; Goosen, A. J . Chem. Soc., Perkin
Trans. 1 1978, 653. Chow, Y. L.; Perry, R. A. Can. J . Chem. 1985, 63,
2203.
(17) Esker, J . L.; Newcomb, M. Tetrahedron Lett. 1993, 34, 6877.
(18) Esker, J . L.; Newcomb, M. J . Org. Chem. 1993, 58, 4933.
(19) Esker, J . L.; Newcomb, M. J . Org. Chem. 1994, 59, 2779.
(20) Fong, M. C.; Laws, M. J .; Schiesser, C. H. Aust. J . Chem. 1995,
48, 1221.

Intramolecular Homolytic Substitution with Amidyl Radicals
J . Org. Chem., Vol. 62, No. 10, 1997 3105
Sch em e 2
Sch em e 3
PhSe•) or electron transfer chemistry21 in which triphen-
ylstannyl cation is involved (Scheme 3). Subsequent
rapid self-combination of radicals 16 presumably leads
to the diselenide 15. Homolytic attack by oxygen-
centered radicals at tin is not unprecedented. Scaiano
reported that tert-butoxyl radicals undergo homolytic
substitution at the tin atom in hexabutylditin.22
It is well establised that diselenides rapidly trap
radicals.13 With this in mind, the diselenides (15: R )
Hex, i-Pr, t-Bu, R * Ph) were reacted further with
benzoyl peroxide (1.0 equiv) in benzene under reflux. To
our delight, the 2-alkyl-1,2-benzisoselenazol-3(2H)-ones
(1: R ) Hex, i-Pr, t-Bu) were isolated in 76-85% yield
after chromatography.23 Once again 77Se NMR spectros-
copy serves as a convenient tool for monitoring the
reaction outcomes, with starting diselenides 15 exhibiting
signals at δ 365-371, significantly further upfield than
those observed for 1 (δ 814-942).
Only low yields of ebselen (1: R ) Ph) were obtained
when 2,2′-diselenobis(benzanilide) (15: R ) Ph) was
subjected to this procedure, presumably due to the low
solubility of the amide (15: R ) Ph) in benzene. In order
to overcome these difficulties 2,2′-diselenobis(benzanilide)
(15: R ) Ph) was reacted with benzoyl peroxide (1 equiv)
in chlorobenzene at 120 °C to afford ebselen in 44% yield
(Scheme 2). When benzoyl peroxide was replaced with
tert-butyl peroxide (1 equiv) and this reaction repeated,
ebselen was isolated in 34% yield, the major product
being 2-(methylseleno)benzanilide (3) which was isolated
in 54% yield. Presubably 3 arises by intermolecular
homolytic substitution of methyl radicals, generated by
fragmentation of tert-butoxyl radicals,24 at the selenium
atom in 2,2′-diselenobis(benzanilide) (15: R ) Ph).
Increasing the amount of tert-butyl peroxide and ensur-
ing that the reaction was terminated soon after consump-
tion of starting material (15: R ) Ph)25,26 resulted in a
dramatic increase in the yield of ebselen. Thus, when
the reaction of 15 (R ) Ph) was carried out at 120 °C in
a 1:1 mixture of tert-butyl peroxide and chlorobenzene
as solvent, ebselen (1: R ) Ph) was isolated in 76% yield
carried out in a water-cooled vessel at concentrations of
between 0.01 and 0.024 M proved optimum for our
requirements. Under these conditions 2-butyl-1,2-benz-
isoselenazol-3(2H)-one (1, R ) Bu), 2-hexyl-1,2-benziso-
selenazol-3(2H)-one (1, R ) Hex), 2-benzyl-1,2-benziso-
selenazol-3(2H)-one (1, R ) Bn), and 2-cyclohexyl-1,2-
benzisoselenazol-3(2H)-one (1, R ) c-Hex) were obtained
in 90, 91, 81, and 45% yield, respectively.
The concentration dependence described above is con-
sistent with ring-closure competing with bimolecular
addition of 2 to the precursor 9 to afford the thiopyridyl
amide 12. This competition would be expected to favor
cyclization at lower concentrations; 12 then decomposes
to give the starting amide 6 on workup (Scheme 1).
Rea ction s of 2-(Tr ip h en ylsta n n yl)selen oben za -
m id es (12) w ith P er oxid es. Having demonstrated that
ebselen analogues (1: R * Ph, t-Bu) are readily prepared
through the use of intramolecular homolytic attack of
amidyl radicals at selenium, we next turned our attention
to solving the problems associated with the preparation
of ebselen itself. We rationalized that if appropriately
substituted amides 13 devoid of abstractable alkyl hy-
drogens could be prepared, then reaction with benzoyl-
oxyl or tert-butoxyl radicals should result in abstraction
of the amide hydrogen in 13 with formation of the
corresponding amidyl radical 14. The triphenylstannyl
group appeared to meet the required criteria of good
leaving radical while being devoid of abstractable hydro-
gens. To that end, N-hexyl-2-(triphenylstannyl)sele-
nobenzamide (13: R ) Hex), N-phenyl-2-(triphenylstan-
nyl)selenobenzamide (13: R ) Ph), N-isopropyl-2-(tri-
phenylstannyl)selenobenzamide (13: R ) i-Pr), and
N-tert-butyl-2-(triphenylstannyl)selenobenzamide (13: R
) t-Bu) were prepared in 62-78% yield by the reaction
of the corresponding benzylseleno amide 6 with triphen-
yltin hydride under standard radical conditions. The
stannyl selenides 13 exhibit signals at around δ -30 in
their 77Se NMR spectra.
To our surprise, treatment of 13 with benzoyl peroxide
(0.5 equiv) under reflux did not produce the expected
heterocycle 1. Instead, the 2,2′-diselenobis(benzamide)
(15: R ) Hex, Ph, i-Pr, t-Bu) was isolated in 54-87%
yield (Scheme 2). These transformations appear to be
general; indeed (triphenylstannyl)phenyl selenide25 (17)
reacts with benzoyl peroxide under the described condi-
tions to afford diphenyl diselenide in quantitative yield.
The transformation of stannyl selenides into diselenides
by the action of benzoyl peroxide represents a new, albeit
unorthodox, method for the preparation of diselenides.
We speculate that this transformation involves either
homolytic substitution by benzoyloxyl radical at the tin
atom in 13 or 17 with expulsion of selenyl radical (16 or
(21) Rossi, R. A.; de Rossi, R. H. Aromatic Substitution by the SRN
Mechanism; American Chemical Society: Washington, DC, 1983.
(22) Scaiano, J . C. J . Am. Chem. Soc. 1980, 102, 5399.
1
(23) The transformation of 13 into 1 can be achieved by the reaction
of 13 with 1.5 equiv of benzoyl peroxide in benzene under reflux. In
our hands, superior yields were always obtained by the stepwise
transformation 13 f 15 f 1, especially in the preparation of ebselen
(1: R ) Ph) where solubility problems are encountered.
(24) Walling, C.; Wagner, P. J . J . Am. Chem. Soc. 1964, 86, 3368.
(25) A reviewer suggested that tert-butyl peroxide may be undergo-
ing induced decomposition at 120 °C, thus acting as a more effective
scavenger of methyl radicals at higher concentrations.
(26) TLC analysis indicated that the starting material was consumed
after 16 h. Prolonged exposure to tert-butyl peroxide at 120 °C resulted
in a significantly darker reaction mixture and diminished yields of
ebselen (1, R ) Ph).

3106 J . Org. Chem., Vol. 62, No. 10, 1997
Fong and Schiesser
Phosgene was purchased from Fluka as a 20% solution in
toluene (1.93 M). All melting points and boiling points are
uncorrected. NMR spectra were recorded in benzene-d6 unless
otherwise stated. Elemental analyses were carried out by
Chemical and Micro Analytical Services Pty. Ltd. Reactions
involving tert-butyl peroxide at 120 °C were carried out behind
a protective (safety) shield.
Sch em e 4
2-(Ben zylselen o)-N-ter t-bu tylben za m id e (6: R ) t-Bu )
was prepared according to our previously published proce-
dure20 using 2-(benzylseleno)benzoic acid,20 and t-butylamine
and isolated as a white crystalline solid (61%): mp ) 153 °C
(sharp); 1H NMR (CDCl3) δ 1.43 (9H, s), 4.11 (2H, s), 5.85 (1H,
s(br)), 7.23-7.26 (7H, m), 7.45-7.48 (2H, m); 13C NMR (CDCl3)
δ 28.8, 31.9, 51.9, 126.6, 126.9, 127.2, 128.4, 128.9, 130.2, 130.4,
132.7, 137.9, 139.2, 168.0; 77Se NMR (C6H6) δ 367; IR (KBr) ν
1626, 3287 cm-1; MS m/ z (relative intensity) 347 (M+, 4.9),
256 (68), 200 (100), 91 (82). Anal. Calcd for C18H21NOSe: C,
62.4; H, 6.1; N, 4.0. Found: C, 62.3; H, 6.0; N, 3.9.
2-(Ben zylselen o)-N-cycloh exylben za m id e (6: R ) c-
Hex) was prepared according to our previously published
procedure20 using 2-(benzylseleno)benzoic acid20 and cyclo-
hexylamine and isolated as a white crystalline solid (91%): mp
1
) 171-172 °C; H NMR (CDCl3) δ 1.12-1.25 (3H, m), 1.32-
1.47 (2H, m), 1.60-1.76 (3H, m), 1.98-2.04 (2H, m), 3.88-
3.98 (1H, m), 4.10 (2H, s), 5.90 (1H, s(br)), 7.16-7.32 (7H, m),
7.48-7.52 (2H, s); 13C NMR (CDCl3) δ 24.9, 25.6, 31.9, 33.0,
48.8, 126.6, 126.9, 127.8, 128.4, 128.9, 130.4, 130.8, 132.8,
137.9, 138.1, 167.6; 77Se NMR (C6H6) δ 369; IR (KBr) ν 1617,
3237 cm-1; MS m/ z (relative intensity) 372 (M - H+, 4.9), 281
(48), 228 (19), 200 (38), 91 (100), 83 (41). Anal. Calcd for
C20H23NOSe: C, 64.5; H, 6.2; N, 3.8. Found: C, 64.5; H, 6.2;
N, 3.7.
after recrystallization. As this procedure affords ebselen
from 2,2′-diselenobis(benzanilide) in yields superior to
those reported previously,8-12 and since 2,2′-diselenobis-
(benzanilide) is readily available by ortho-lithiation of
benzanilide,8,12 this method represents an efficient and
convenient procedure for the small-scale preparation of
ebselen.
St a n d a r d P r ot ocol A for t h e P r ep a r a t ion of 1,2-
Ben zisoselen a zol-3(2H)-on es (1) by th e P TOC Im id a te
Ester Meth od . N-Bu tyl-1,2-ben zisoselen a zol-3(2H)-on e
(1: R ) Bu ). 20% Phosgene in toluene (1.93 M, 2.40 mL, 4.64
mmol) was added via syringe to a cooled (0-5 °C) solution of
2-(benzylseleno)-N-butylbenzamide (6: R ) Bu) (400 mg, 1.16
mmol) and DMF (9.0 µL, 120 µmol) in benzene (20 mL). The
solution was stirred at rt overnight. The solvent was removed
in vacuo and replaced with dry ether (20 mL), the sodium salt
of N-hydroxypyridine-2-thione (210 mg, 2.31 mmol) added, and
the mixture stirred overnight while shielded from background
light. The precipitate was filtered off and washed with cold
CH2Cl2 (5 mL), the combined organic phases were dried
(MgSO4), and the solvent was removed in vacuo. The yellow-
green residue was dissolved in benzene (50 mL) and the
solution transferred to a water-cooled reaction vessel and
irradiated with a 250 W low-pressure mercury lamp (white
light) at a distance of 20 cm for 3 h. The solvent was removed
in vacuo, the residue separated by flash chromatography
(CH2Cl2), and the title compound isolated as a white solid (240
mg, 90%): mp ) 92 °C (sharp) (lit.10 92 °C); 1H NMR (CDCl3)
δ 0.93 (3H, t, J ) 7.3 Hz), 1.33-1.46 (2H, m), 1.59-1.73 (2H,
m), 3.84 (2H, t, J ) 7.2 Hz), 7.38 (1H, t, J ) 7.4 Hz), 7.51-
7.60 (2H, m), 8.01 (1H, d, J ) 8.1 Hz); 13C NMR (CDCl3) δ
13.7, 19.8, 32.6, 44.5, 123.9, 126.1, 127.6, 128.8, 131.8, 137.6,
Mech a n istic con sid er a tion s. While we are confi-
dent that the photochemical transformations of PTOC
imidate esters 9 into benzisoselenazol-3(2H)-ones (1)
involve intramolecular homolytic substitution by amidyl
radicals 2 at the selenium atom with expulsion of benzyl
radical, we are less confident about the mechanism of
the reactions of diselenides (15) with benzoyl peroxide.
Reich and J asperese reported that diselenides 18 react
with tert-butyl hydroperoxide to afford selenazolone 19,
a reaction which presumably involves oxidative ring-
closure.27 In addition, Pryor and Bickley reported that
benzoyl peroxide undergoes accelerated decomposition in
the presence of alkyl sulfides and disulfides, a process
consistent with nucleophilic attack of sulfide at the
peroxidic oxygen in benzoyl peroxide.28 In an analogous
fashion, 15 may well react with benzoyl peroxide to afford
1 and selenobenzoate 20 which, in turn, undergoes
further cyclization to give another 1 equiv of 1 (Scheme
4). The extra steric demand imposed by tert-butyl
peroxide reduces the likelihood of this peroxide reacting
in an analogous fashion to its benzoyl analogue. At this
time we feel that tert-butyl peroxide is more likely to form
tert-butoxyl radicals upon thermolysis. Abstraction of the
amide hydrogen in 1 then generates the amidyl radical
21; subsequent cyclization provides ebselen.
167.1; 77Se (C6H6) NMR δ 872; IR (KBr) ν 1554, 1588 cm-1
;
MS m/ z (relative intensity) 255 (M+, 39.8), 220 (55), 199 (71),
184 (100), 156 (43), 78 (56). HRMS Calcd for C11H13NO80Se:
255.0162, found: 255.0166.
We are currently investigating further the mechanistic
details of the ring-closures reported in this paper.
N-Hexyl-1,2-ben zisoselen a zol-3(2H)-on e (1: R ) Hex)
was prepared according to standard protocol A using 2-(ben-
zylseleno)-N-hexylbenzamide (6: R ) Hex). Flash chroma-
tography (CH2Cl2) afforded 1 (R ) Hex) as a white crystalline
Exp er im en ta l Section
1
solid (91%): mp ) 84-85 °C; H NMR (CDCl3) δ 0.89 (3H, t,
J ) 7.2 Hz), 1.30-1.42 (6H, m), 1.68-1.75 (2H, m), 3.86 (2H,
t, J ) 7.2 Hz), 7.42 (1H, t, J ) 7.5 Hz), 7.58-7.64 (2H, m),
8.05 (1H, d, J ) 7.8 Hz); 13C NMR (CDCl3) δ 13.9, 22.4, 26.2,
30.5, 31.4, 44.8, 124.0, 126.0, 127.6, 128.6, 131.7, 137.7, 167.0;
77Se (C6H6) NMR δ 872; IR (KBr) ν 1554, 1585 cm-1; MS m/ z
(relative intensity) 283 (M+, 26.9), 220 (48), 199 (66), 184 (100),
156 (27), 78 (30). Anal. Calcd for C13H17NOSe: C, 55.3; H,
6.0; N, 5.0. Found: C, 55.2; H, 6.1; N, 4.7.
(Phenylseleno)triphenyltin (17) was prepared according to
the procedure of Macmullin and Peach.29 Triphenyltin hy-
dride, benzoyl peroxide, and tert-butyl peroxide were pur-
chased from Aldrich. The sodium salt of N-hydroxypyridine-
2-thione (sodium pyrion) was a gift from Harcross Chemicals.
(27) Reich, H. J .; J asperese, C. P. J . Am. Chem. Soc. 1987, 109, 5549.
(28) Pryor, W. A.; Bickley, H. T. J . Org. Chem. 1972, 37, 2885.
(29) Macmullin, E. C. ; Peach, M. E. J . Organomet. Chem. 1973,
52, 355.
N-Ben zyl-1,2-ben zisoselen a zol-3(2H)-on e (1: R ) Bn )
was prepared according to standard protocol A using N-benzyl-

Intramolecular Homolytic Substitution with Amidyl Radicals
J . Org. Chem., Vol. 62, No. 10, 1997 3107
2-(benzylseleno)benzamide (6: R ) Bn). Flash chromatogra-
phy (CH2Cl2) afforded 1 (R ) Bn) as a white crystalline solid
(81%): mp ) 139-140 °C (lit.30 141-144 °C); 1H NMR (CDCl3)
(74), 91 (54), 77 (34). HRMS Calcd for C28H27NO120Sn:
513.1115, found: 513.1098.
N-ter t-Bu t yl-2-[(t r ip h en ylst a n n yl)selen o]b en za m id e
(13: R ) t-Bu ) was prepared according to standard protocol
B using 2-(benzylseleno)-N-tert-butylbenzamide (6: R ) t-Bu).
Flash chromatography afforded 13 (R ) t-Bu) as a pale oil
(62%): 1H NMR (acetone-d6) δ 1.41 (9H, s), 6.53 (1H, s(br)),
6.90 (1H, dt, J ) 1.5, 7.8 Hz), 7.13 (1H, t, J ) 7.2 Hz), 7.27
(1H, dt, J ) 1.5, 7.5 Hz), 7.23-7.41 (9H, m), 7.48 (1H, d, J )
7.8 Hz), 7.58-7.63 (6H, m); 13C NMR (acetone-d6) δ 28.9, 51.8,
123.0, 127.4, 128.3, 129.4, 129.6, 130.2, 137.3, 138.9, 139.0,
144.3, 169.1; MS m/ z (relative intensity) 527 (M+ - Se, 100),
471 (34), 351 (32), 197 (75), 105 (42), 77 (45). HRMS Calcd
for C29H29NO120Sn: 527.1271, found: 527.1255.
δ 5.02 (2H, s), 7.35-7.58 (8H, m), 8.08 (1H, d, J ) 8.1 Hz); 13
C
NMR (CDCl3) δ 48.6, 123.9, 126.2, 127.4, 128.0, 128.3, 128.5,
128.8, 128.9, 132.0, 137.2, 167.1; 77Se NMR (C6H6) δ 878; IR
(KBr) ν 1556, 1590 cm-1; MS m/ z (relative intensity) 289 (M+,
18.0), 220 (82), 184 (41), 156 (57), 91 (100), 78 (69). HRMS
Calcd for C14H11NO80Se: 289.0005, found: 289.0011.
N-Cycloh exyl-1,2-ben zisoselen a zol-3(2H)-on e (1: R )
c-Hex) was prepared according to standard protocol A using
2-(benzylseleno)-N-cyclohexylbenzamide (6: R ) c-Hex). Flash
chromatography (CH2Cl2) afforded 1 (R ) c-Hex) as a white
1
crystalline solid (45%): mp ) 159-160 °C; H NMR (CDCl3)
Sta n d a r d P r otocol C for th e P r ep a r a tion of 2,2′-
Diselen obis(ben za m id es) (15) fr om 2-[(tr ip h en ylsta n -
n yl)selen o]ben za m id es (13). N,N′-Dip h en yl-2,2′-d isele-
n obis(ben za m id e) (15: R ) P h ). Benzoyl peroxide (100 mg,
0.4 mmol) was added to a stirred solution of N-phenyl-2-
[(triphenylstannyl)seleno]benzamide (13) (R ) Ph) (610 mg,
0.98 mmol) in dry benzene (40 mL). The solution was heated
at reflux under nitrogen overnight. N,N′-Diphenyl-2,2′-dise-
lenobis(benzamide) (15: R ) Ph) was collected by filtration
as a white crystalline solid (213 mg, 79%): mp ) 260-263 °C
(lit.31 263-265 °C); 1H NMR (DMSO-d6) δ 7.15 (2H, t, J ) 7.2
Hz), 7.39-7.48 (8H, m), 7.75-7.80 (6H, m), 7.95 (2H, d, J )
7.2 Hz), 10.56 (s, 2H); 13C NMR (DMSO-d6) δ 120.6, 124.2,
126.5, 128.7, 128.8, 130.2, 132.0, 132.1, 133.8, 138.7, 166.4;
77Se (DMSO) NMR δ 451; IR (KBr) ν 1634, 3288 cm-1; MS m/ z
(relative intensity) 471 (M+ - SeH, 5.5), 261 (31), 195 (93),
167 (57), 156 (68), 91 (63), 77 (100).
N,N′-Dih exyl-2,2′-diselen obis(ben zam ide) (15: R ) Hex)
was prepared according to standard protocol C using N-hexyl-
2-[(triphenylstannyl)seleno]benzamide (13: R ) Hex) and
isolated as a white crystalline solid after recrystallization
(ethanol) (87%): mp ) 164-165 °C; 1H NMR (DMSO-d6) δ 0.88
(6H, t, J ) 6.8 Hz), 1.26-1.37 (12H, M), 1.51-1.59 (4H, m),
3.29 (4H, q(apparent), J ) 6.9 Hz) 7.30-7.40 (4H, m), 7.69
(2H, d, J ) 7.5 Hz), 7.78 (2H, dd, J ) 1.5, 7.5 Hz), 8.74 (2H,
t, J ) 5.7 Hz); 13C NMR (DMSO-d6) δ 14.0, 22.1, 26.2, 29.0,
31.1, 39.4, 126.2, 127.8, 129.9, 131.5, 131.9, 133.3, 167.3; 77Se
(DMSO) NMR δ 442; IR (KBr) ν 1610, 3329 cm-1; MS m/ z
(relative intensity) 487 (M+ - SeH, 0.6), 282 (24), 212 (34),
199 (46), 184 (100), 156 (21). Anal. Calcd for C26H36N2O2Se2:
C, 55.1; H, 6.4; N, 5.0. Found: C, 55.2; H, 6.7; N, 4.8.
N,N′-Diisop r op yl-2,2′-d iselen obis(ben za m id e) (15: R )
i-P r ) was prepared according to standard protocol C using
N-isopropyl-2-[(triphenylstannyl)seleno]benzamide (13: R )
i-Pr) and isolated as a white crystalline solid after recrystal-
lization (ethanol) (56%): mp ) 259-260 °C; 1H NMR (DMSO-
d6) δ 1.21 (12H, d, J ) 6.6 Hz), 4.11 (2H, sept, J ) 6.6 Hz),
7.29-7.41 (4H, m), 7.69 (2H, d, J ) 7.8 Hz), 7.80 (2H, d, J )
7.5 Hz), 8.54 (2H, d, J ) 7.8 Hz); 13C NMR (DMSO-d6) δ 22.3,
41.4, 126.1, 128.0, 130.0, 131.5, 131.9, 133.5, 166.5; 77Se
(DMSO) NMR δ 451; IR (KBr) ν 1609, 3292 cm-1; MS m/ z
(relative intensity) 483 (M+ - H, 2.6), 404 (3), 242 (92), 199
(92), 184 (100), 156 (56), 77 (30). HRMS Calcd for C20H23N2-
O280Se2: 483.0089, found: 483.0109.
δ 1.15-1.54 (5H, m), 1.69-1.74 (1H, m), 1.83-1.87 (2H, m),
2.04-2.11 (2H, m), 4.44-4.52 (1H, m), 7.40 (1H, t, J ) 7.6
Hz), 7.55 (1H, t, J ) 7.6 Hz), 7.58-7.64 (1H, m), 8.04 (1H, d,
J ) 7.8 Hz); 13C NMR (CDCl3) δ 25.2, 25.5, 34.1, 53.6, 123.8,
125.9, 128.5, 131.4, 137.3, 137.8, 166.4; 77Se (C6H6) NMR δ
825; IR (KBr) ν 1554, 1584 cm-1; MS m/ z (relative intensity)
281 (M+, 15.3), 220 (43), 199 (100), 184 (21), 156 (32), 78 (41).
Anal. Calcd for C13H15NOSe: C, 55.7; H, 5.3; N, 5.0. Found:
C, 55.6; H, 5.3; N, 5.0.
Sta n d a r d P r otocol B for th e P r ep a r a tion of 2-[(Tr i-
ph en ylstan n yl)selen o]ben zam ides (13). N-P h en yl-2-[(tr i-
p h en ylsta n n yl)selen o]ben za m id e (13: R ) P h ). Triphen-
yltin hydride (530 mg, 1.51 mmol) was added to a solution of
2-(benzylseleno)-N-phenylbenzamide (6: R ) Ph) (500 mg, 1.37
mmol) and azobis(isobutryonitrile) (AIBN) (10 mg, 60 µmol)
in dry benzene (20 mL) and the solution heated overnight at
reflux under nitrogen. The white precipitate was removed by
filtration and the solvent removed in vacuo. The residue was
separated by flash chromatography (23% ethyl acetate/
petroleum ether) to afford the title stannyl selenide (13: R )
Ph) as a white crystalline solid after recrystallization (ethanol)
(585 mg, 68%): mp ) 144-145 °C; 1H NMR (acetone-d6) δ 6.93
(1H, dt, J ) 1.7, 7.2 Hz), 7.07 (1H, t, J ) 6.9 Hz), 7.15 (1H, t,
J ) 7.2 Hz), 7.23-7.26 (11H, m), 7.39-7.51 (10H, m), 7.80
(1H, s(br); 13C NMR (acetone-d6) δ 120.0, 121.7, 124.1, 127.3,
128.66, 128.70, 128.8, 129.7, 129.9, 136.5, 136.9, 137.7, 139.3,
141.9, 166.4; 77Se (acetone) NMR δ -32; IR (KBr) ν 1647, 3275
cm-1; MS m/ z (relative intensity) 547 (M+ - Se, 20), 469 (2),
350 (11), 274 (45), 195 (100), 156 (21), 77 (29). The structure
of 13 (R ) Ph) was confirmed by X-ray analysis.31
N-Hexyl-2-[(tr ip h en ylsta n n yl)selen o]ben za m id e (13:
R ) Hex) was prepared according to standard protocol B using
2-(benzylseleno)-N-hexylbenzamide (6: R ) Hex). Flash chro-
matography afforded 13 (R ) Hex) as a white crystalline solid
after recrystallization (ethanol) (78%): mp ) 143-144 °C; 1H
NMR (acetone-d6) δ 0.87 (3H, t, J ) 6.6 Hz), 1.26-1.41 (6H,
m), 1.48-1.58 (2H, m), 3.24 (2H, q(apparent), J ) 6.6 Hz), 6.96
(1H, dt, J ) 1.5, 7.8 Hz), 7.03 (1H, s(br)), 7.14 (1H, t, J ) 7.5
Hz), 7.25 (1H, d, J ) 7.8 Hz), 7.34-7.41 (9H, m), 7.49 (1H, d,
J ) 7.8 Hz), 7.57-7.62 (6H, m) ; 13C NMR (acetone-d6) δ 14.3,
23.3, 27.4, 30.2, 32.3, 40.2, 124.2, 127.5, 128.5, 129.4, 130.0,
130.2, 137.5, 138.9, 139.8, 143.5, 169.7; IR (KBr) ν 1641, 3296
cm-1; MS m/ z (relative intensity) 555 (M+ - Se, 100), 350 (27),
284 (29), 197 (63), 105 (42), 77 (44). Anal. Calcd for C31H33
-
N,N′-Di-ter t-bu tyl-2,2′-d iselen obis(ben za m id e) (15: R
) t-Bu ) was prepared according to standard protocol C using
N-tert-butyl-2-[(triphenylstannyl)seleno]benzamide (13: R )
t-Bu) and isolated as a white crystalline solid after recrystal-
lization (ethanol) (54%): mp ) 215-216 °C; 1H NMR (acetone-
d6) δ 1.50 (18H, s), 7.22 (2H, t, J ) 7.2 Hz), 7.29 (2H, t, J )
7.5 Hz), 7.38 (2H, s(br)), 7.67 (2H, d, J ) 7.5 Hz), 7.79 (2H, d,
J ) 7.8 Hz); 13C NMR (acetone-d6) δ 29.0, 52.4, 126.7, 128.3,
131.2, 131.8, 133.1, 136.0, 168.6; 77Se (acetone) NMR δ 445;
IR (KBr) ν 1622, 3441 cm-1; MS m/ z (relative intensity) 431
(M+ - SeH, 3.3), 255 (65), 200 (100), 184 (50), 156 (19), 77
(21). Anal. Calcd for C22H28N2O2Se2: C, 51.8; H, 5.5; N, 5.5.
Found: C, 51.9; H, 5.7; N, 5.3.
NOSeSn: C, 58.8; H, 5.2; N, 2.2. Found: C, 58.6; H, 5.3; N,
2.1.
N-Isop r op yl-2-[(t r ip h en ylst a n n yl)selen o]b en za m id e
(13: R ) i-P r ) was prepared according to standard protocol
B using 2-(benzylseleno)-N-isopropylbenzamide (6: R ) i-Pr).
Flash chromatography afforded 13 (R ) i-Pr) as a white
semisolid (78%): 1H NMR (acetone-d6) δ 1.15 (6H, d, J ) 6.6
Hz), 4.08 (1H, sept, J ) 6.6 Hz), 6.93 (1H, dt, J ) 1.5, 7.5 Hz),
7.13 (1H, t, J ) 7.8 Hz), 7.25 (1H, dd, J ) 1.5, 7.5 Hz), 7.37-
7.39 (9H, m), 7.47 (2H, d, J ) 7.8 Hz), 7.58-7.60 (6H, m); 13
C
NMR (acetone-d6) δ 22.6, 42.0, 123.8, 127.5, 128.4, 129.4, 129.9,
130.2, 137.3, 138.8, 139.5, 143.5, 168.9; MS m/ z (relative
intensity) 513 (M+ - Se, 100), 350 (33), 257 (33), 242 (78), 197
Sta n d a r d P r otocol D for th e P r ep a r a tion of 1,2-
Ben zisoselen a zol-3(2H)-on es (1) by th e Ben zoyl P er ox-
id e Met h od . N-H exyl-1,2-b en zisoselen a zol-3(2H )-on e
(1: R ) Hex). Benzoyl peroxide (70 mg, 0.29 mmol) was
added to a stirred suspension of N,N′-dihexyl-2,2′-diseleno-
(30) Fischer, H.; Dereu, N. Bull. Soc. Chim. Belg. 1987, 96, 757.
(31) Fong, M. C.; Gable, R. W.; Schiesser, C. H. Acta. Crystallogr.
1996, C52, 1886.

3108 J . Org. Chem., Vol. 62, No. 10, 1997
Fong and Schiesser
bis(benzamide) (15: R ) Hex) (150 mg, 0.26 mmol) in benzene
(12 mL). The mixture was heated to reflux at which point a
clear solution was obtained which was heated at reflux under
nitrogen overnight. The solvent was removed in vacuo, the
residue dissolved in CH2Cl2 and washed with saturated sodium
bicarbonate (2 × 15 mL) and dried (MgSO4). Removal of the
solvent afforded 1 (R ) Hex) as a crystalline solid after
recrystallization (125 mg, 83%) exhibiting physical data identi-
cal to those reported above (protocol A).
N-Isop r op yl-1,2-b en zisoselen a zol-3(2H )-on e (1: R )
i-P r ) was prepared according to standard protocol D using
N,N′-diisopropyl-2,2′-diselenobis(benzamide) (15: R ) i-Pr) in
chlorobenzene as solvent and isolated as a white crystalline
solid after recrystallization (ethanol) (85%): mp ) 105-106
°C; 1H NMR (CDCl3) δ 1.36 (6H, d, J ) 6.6 Hz), 4.87 (1H, sept,
J ) 6.6 Hz), 7.41 (1H, t, J ) 6.9 Hz), 7.56 (1H, t, J ) 8.1 Hz),
7.65 (1H, d, J ) 8.1 Hz), 8.03 (1H, d, J ) 7.8 Hz); 13C NMR δ
23.3, 46.5, 123.9, 126.0, 128.5, 129.5, 131.6, 137.5, 166.5; 77Se
(C6H6) NMR δ 814; IR (KBr) ν 1596, 1562 cm-1; MS m/ z
(relative intensity) 241 (M+, 36.6), 226 (33), 199 (100), 184 (44),
156 (58), 77 (37). Anal. Calcd for C10H11NOSe: C, 50.0; H,
4.6; N, 5.8. Found: C, 50.0; H, 4.6; N, 5.9.
(2 × 10 mL) and dried (MgSO4) and the solvent removed in
vacuo. The residue was recrystallized (ethanol) to afford 1 (R
) Ph) as a white solid (38 mg, 76%): mp ) 182-183 °C (lit.7
1
182-183 °C); H NMR (DMSO-d6) δ 7.28 (1H, t, J ) 7.0 Hz),
7.44-7.52 (3H, m), 7.64-7.73 (3H, m), 7.93 (1H, d, J ) 7.8
Hz), 8.10 (1H, d, J ) 7.8 Hz); 13C NMR (DMSO-d6) δ 124.7,
125.8, 126.3, 128.0, 128.5, 129.2, 132.3, 138.9, 139.7, 165.0;
77Se (DMSO) NMR δ 942; IR (KBr) ν 1593, 1560 cm-1; MS m/ z
(relative intensity) 275 (M+, 100), 195 (73), 184 (9), 167 (22),
156 (14), 91 (6). HRMS Calcd for C13H9NO80Se: 274.9849,
found: 274.9850.
2-(Meth ylselen o)ben za n ilid e (3). tert-Butyl peroxide (39
µL, 0.21 mmol) was added to a stirred solution of 2,2′-
diselenobis(benzanilide) (15: R ) Ph) (115 mg, 0.21 mmol) in
chlorobenzene (30 mL) and the solution stirred at 120 °C under
nitrogen for 36 h. After washing with water (2 × 10 mL) and
drying (MgSO4), the solvent was removed in vacuo and the
residue separated by preparative TLC (1:9 petroleum ether:
CH2Cl2). The fraction of lower Rf proved to be 3 which was
isolated as a white solid (65 mg, 54%): mp ) 173-174 °C (lit.10
1
176 °C); H NMR (CDCl3) δ 2.31 (3H, s), 7.16 (1H, t, J ) 7.2
Hz), 7.29-7.51 (5H, m), 7.65 (3H, m), 7.93 (1H, s(br)); 13C NMR
(CDCl3) δ 7.5, 120.1, 124.6, 125.8, 128.0, 129.1, 130.2, 131.2,
133.2, 135.9, 137.8, 166.4; MS m/ z (relative intensity) 291 (M+,
24), 276 (21), 199 (100), 184 (13), 156 (19), 91 (94). The
structure of 3 was confirmed by X-ray analysis.30
N-ter t-Bu t yl-1,2-b en zisoselen a zol-3(2H )-on e (1: R )
t-Bu ) was prepared according to standard protocol D using
N,N′-di-tert-butyl-2,2′-diselenobis(benzamide) (15: R ) t-Bu)
and isolated as a white crystalline solid after recrystallization
1
(ethanol) (76%): mp ) 230-231 °C; H NMR (CDCl3) δ 1.68
The fraction of higher Rf proved to be N-phenyl-1,2-benz-
isoselenazol-3(2H)-one (1: R ) Ph) (39 mg, 34%).
(9H, s), 7.36-7.41 (1H, m), 7.52-7.59 (2H, m), 7.96 (1H, d, J
) 7.8 Hz); 13C NMR (CDCl3) δ 29.0, 58.7, 123.2, 125.9, 128.3,
130.0, 131.5, 136.8, 166.9; 77Se (acetone) NMR δ 847; IR (KBr)
ν 1588, 1558 cm-1; MS m/ z (relative intensity) 255 (M+, 12.5),
199 (100), 156 (21), 105 (18). Anal. Calcd for C11H13NOSe:
C, 52.0; H, 5.1; N, 5.5. Found: C, 52.0; H, 5.3; N, 5.2.
N-P h en yl-1,2-ben zisoselen a zol-3(2H)-on e (1: R ) P h )
(Ebselen , 1: R ) P h ). tert-Butyl peroxide (500 µL) was added
to a stirred solution of 2,2′-diselenobis(benzanilide) (15: R )
Ph) (50 mg, 90 µmol) in chlorobenzene (700 µL) and the
solution stirred under nitrogen at 120 °C for 16 h.26,32 The
white solid was filtered off and the filtrate washed with water
Ack n ow led gm en t. We thank Ms. Melissa Laws for
providing spectral data on 3 and the Australian Re-
search Council for financial support.
J O970019T
(32) Heating concentrated tert-butyl peroxide at 120 °C is potentially
hazardous and should never be attempted on a large scale. This
experiment was carried our behind a protective (safety) shield.