Diaryl diselenides and related compounds as oxygen-transfer agents

Article abstract of DOI:10.1080/10426500801900956

The progress in application of diaryl diselenides and related compounds as transfer agents is presented. The review is limited to the diaryl diselenides having electron-withdrawing substituents, such as nitro, trifluoromethyl, carbamoylphenyl, and polymeric diselenides PADS and PPDS. The methods of their synthesis are described. These compounds are used as effective catalyst for a simple and multi-electron hydroperoxide oxidation of different organic compounds. Transformation of functional groups, cycloalkanones ring contraction, cyclocondensation and degradation of electron-rich arenes is described. Mechanisms of the reactions involved Se(II) and Se(IV) intermediates are discussed.

Full text of DOI:10.1080/10426500801900956

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Phosphorus, Sulfur, and Silicon
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Diaryl Diselenides and Related
Compounds as Oxygen-Transfer
Agents
Mirosław Giurg a & Ludwik Syper a
a Faculty of Chemistry, Wroclaw University of
Technology, Wrocław, Poland
Published online: 29 Oct 2008.
To cite this article: Mirosaw Giurg & Ludwik Syper (2008) Diaryl Diselenides and
Related Compounds as Oxygen-Transfer Agents, Phosphorus, Sulfur, and Silicon and
the Related Elements, 183:4, 970-985, DOI: 10.1080/10426500801900956
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Phosphorus, Sulfur, and Silicon, 183:970–985, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801900956
Diaryl Diselenides and Related Compounds
as Oxygen-Transfer Agents
Miroslꢀaw Giurg and Ludwik Syper
Faculty of Chemistry, Wroclaw University of Technology, Wroclꢀaw,
Poland
The progress in application of diaryl diselenides and related compounds as transfer
agents is presented. The review is limited to the diaryl diselenides having electron-
withdrawing substituents, such as nitro, trifluoromethyl, carbamoylphenyl, and
polymeric diselenides PADS and PPDS. The methods of their synthesis are de-
scribed. These compounds are used as effective catalyst for a simple and multi-
electron hydroperoxide oxidation of different organic compounds. Transformation
of functional groups, cycloalkanones ring contraction, cyclocondensation and degra-
dation of electron–rich arenes is described. Mechanisms of the reactions involved
Se(II) and Se(IV) intermediates are discussed.
Keywords Antibiotic; arene; carboxylic acid; catalysis; diselenide; lactone; oxidation;
quinone
INTRODUCTION
Discovery of syn selenoxide elimination started a broad interest in
the application of organoselenium compounds in organic synthesis.1
Barton, Back, and Ley have popularized their role as stoichiometric
oxidants.2,3 During the last three decades, diaryl diselenides and re-
lated compounds have been extensively studied as oxidation catalysts
of practical importance.4,5 Several works have been recently done in our
laboratory and are presented briefly in this review. Our research inter-
est has been focused on diaryl diselenides 1 and related compounds, as
oxygen-transfer agents useful in organic synthesis. In these reactions,
the diselenides are oxidized by hydroperoxides to the corresponding
areneseleninic acids 2, which are the proper catalysts. They act via cor-
responding peroxyseleninic acids 35 and selenoxyradicals 4,6 as highly
electrophilic oxidants and electron acceptors, (Scheme 1).
Address correspondence to Miroslꢀaw Giurg, Department of Organic Chemistry, Fac-
ulty of Chemistry, Wroclꢀaw University of Technology, Wybrzez˙e Wyspian´skiego 27, 50-370
Wroclꢀaw, Poland. E-mail: miroslaw.giurg@pwr.wroc.pl
970

Diaryl Diselenides as Oxygen-Transfer Agents
971
O
O
O
.
Ar Se Se Ar
Ar Se OH
Ar Se OOH
Ar Se O
1
2
3
4
SCHEME 1 Active forms of diaryl diselenides oxygen–transfer catalysts.
The use of hydrogen peroxide and tert-butylhydroperoxide as the
stoichiometric oxidants is in accord with modern trends in organic
synthesis since both of those reagents are cheap and environmentally
friendly, and are used on both laboratory and industrial scales.7 Nev-
ertheless, both of them are low or only moderately active toward the
most of the organic substrates, and suitable activators must be used.5
It has been found that some organoselenium compounds are very effi-
cient activators of those convenient oxidants. The compounds having
selenium bonded to aromatic moieties are used almost exclusively as
the catalysts, because bond between selenium and sp3 carbon is rather
weak. Generally, functionalization of the aromatic ring with electron-
withdrawing nitro, carbamoylphenyl, and trifluoromethyl substituents
make the catalysts more efficient and selective.5 Recently we have
successfully employed poly(bis-9,10-anthracenyl)8 and poly(bis-1,2-
phenylene) diselenide,9 and silica-supported selenenamides.10 These
compounds are easy to prepare in laboratory from cheap, commercially
available arene halides or substituted anilines and elemental selenium.
The above described catalysts were used for functional group trans-
formations, ring rearrangement of cycloalkanones, oxidative degrada-
tion of naphthalene ring and electron-rich benzene ring, using 30%
aqueous hydrogen peroxide or 80% tert-butyl hydroperoxide (TBHP)
as stoichiometric oxidants.
PREPARATION OF DIARYL DISELENIDES AND RELATED
COMPOUNDS
2,2ꢀ-Dinitrodiphenyl diselenide 5 and its 4,4ꢀ-ditrifluoromethyl deriva-
tive 6 were obtained by treating of 2-nitrochlorobenzenes 7 or 8,
with dilithium diselenide at ambient temperature.11,12 2,2ꢀ- And 3,3ꢀ-
ditrifluoromethylphenyl diselenides 9 and 10 were prepared by Reich
and Renda procedure starting from trifluoromethylanilines 11 and 12
via trifluoromethyliodobenzenes 13 and 14 by insertion of elemental se-
lenium into Grignard reagents.12,13 Treatment of 1,2-diiodobenzene 15
or 9,10-dibromoantracene 16 with dilithium diselenide, at 110–
130◦C, gave polymeric 1,2-diphenylene diselenide 17 (PPDS) and poly-
meric 9,10-dianthracenyldiselenides 18 (PADS), respectively.8,9 The

972
M. Giurg and L. Syper
dihaloarenes were obtained from 2-iodoaniline or anthracene, respec-
tively, (Scheme 2).12,14
R1
NO2
NO2
_
NO2
Cl
F3C
Li2Se2, HMPA
20oC
Li2Se2, HMPA
20oC
_
)
Se
Se)2
2
5 (86%)
R1 = H (7); R1 = CF3 (8)
6 (60%)
R2
R2
R2
1) NaNO2, HCl
2) KI
1) Mg, Et2O
2) Se
_
3) air/base
Se
)
2
NH2
I
R2 = 2-CF3 (11);
R2 = 3-CF3 (12)
R2 = 2-CF3 (13, 84%)
R2 = 3-CF3 (14, 77%)
R2 = 2-CF3 (9, 75%)
R2 = 3-CF3 (10, 85%)
_
)
Se
2
I
NH2
I
Li2Se2, HMPA
100 - 130oC
1) NaNO2, HCl
2) NaI
_
)
Se
I
2
15 (85%)
17 (PPDS, 90%)
_
)
Se
2
Br
Br2, AcOH
Li2Se2, HMPA
100 - 130oC
_
)
Br
Se
2
16 (94%)
18 (PADS, 96%)
SCHEME 2 Preparation of diaryl diselenides.
2,2ꢀ-Dicarbamoylphenyldiphenyl diselenide 19 and related sele-
nenamide 20 and 21 were prepared from anthranilic acid via 2-
(chloroseleno)benzoyl chloride (22). The reaction of chloride 22 and ani-
line resulted in heterocyclic of 2-phenylbenzisoselenazol-3(2H)-one (20)
known as ebselen. When chloride 22 reacted with aminopropylsili-
cate 23, selenenylation of the primary amino group takes place exclu-
sively, and recoverable heterogenous silica-supported selenenamide 21
was produced. Ebselen treated with hydrazine hydrate underwent ring
opening to diselenide form 19, (Scheme 3).10,15
Because lithium diselenide is a very convenient and versatile reagent
for the introduction of selenium to organic substrates, and it can be
used to prepare inorganic selenium compounds, we describe our proven
procedure of its preparation in the Experimental section.

Diaryl Diselenides as Oxygen-Transfer Agents
973
O
COCl
COOH
NH2
PhNH2
1) NaNO2, HCl
N
2) Na2Se2
Se
SeCl
3) SOCl2
22 (47%)
20 (80%)
O
H2N-NH2 x H2O
H N-(CH ) Si
O
O
2
2 3
23
COCl
CONHPh
O
O
O
_
NH-(CH2)3-Si
Se
)
Se
2
21
19 (99%)
SCHEME 3 Preparation of selenenamides 20 and 21, and 2,2ꢀ-
dicarbamoyldiphenyl diselenide 19.
FUNCTIONAL GROUP TRANSFORMATIONS
2,2ꢀ-Dinitrodiphenyl diselenide (5) has been applied as a catalysts for
Baeyer–Villiger oxidation of aldehydes and aryl methyl ketones into
phenols formates 24 or acetates 25, which in one-pot procedures subse-
quently were hydrolyzed to phenols 26. That is a convenient method
for the synthesis of phenols with electron-donating substituents or
polycondensed ring systems.16 Oxidation of carbonyl compounds with
2-nitrobenzeneperoxyseleninic acid, used as a stoichiometric oxidant,
gave similar results.17 The above results present a new methodology
in hydroperoxide oxidation of organic substrates. The same reagent,
H2O2/cat. 5, has been used for oxidative transformation of azomethine
derivatives of carbonyl compounds. 1,1-Dimethyl hydrazones 27 were
converted into nitriles 28, whereas aldoximes 29 in the presence of
primary or secondary alcohols produced carboxy esters 30.18 Recently,
similar results we have observed, while ebselen (20) or silica-supported
selenenamide 21 have been applied, (Scheme 4).10,19,20
Catalytic activity of silica-supported selenenamide 21 was demon-
strated in tert-butylhydroperoxide oxidations of benzaldehydes to
benzoic acids, and benzylamines to benzonitriles. Moreover, this cata-
lyst was employed for hydrogen peroxide oxidation of tosylhydrazones
and oximes to parent carbonyl compounds and arenecarboxylic acids
depending on the substrate used and the reaction conditions.
The catalysts 21 was simply recovered by filtration and could be
reused.10Another polymeric catalyst, 1,2-diphenylene and 9,10-dian-
thracenyl diselenides 17 and 18 were used for preparative hydrogen
peroxide oxidation of aldazines, aldoximes and tosylhydrazones in THF

974
M. Giurg and L. Syper
O
C
O
A) H2O2/cat. 5 or
KOH, MeOH or
HCl, Me2C=O
Ar C R3
Ar O
R3
Ar OH
B) 2-NO2C5H4Se(O)OOH
R3 = H (24), R3 = Me (25)
26 (54-95%)
H2O2/cat. 5, ROH
H2O2/cat. 20, ROH
H2O2/cat. 5
O
H2O2/cat. 20
H2O2/cat. 21
R4 C N
R4 CH
X
R4 C OR
N
H2O2/cat. 21, ROH
30
X = NMe2 (27)
X = OH (29)
28
R = primary or secondary alkyl; R4 = alkyl, aryl, furyl, cinnamyl
SCHEME 4 Transformations of carbonyl compounds and its imine derivatives.
to arenecarboxylic acids,9 and 1,1-dimethylhydrazones in tert-butanol
to unsaturated and aromatic nitriles, in excellent preparative yields.21
RING REARANGEMENT OF CYCLOALKANONES
The 9,10-dianthracenyl diselenide (18) used in 0.6 mol % catalyzed
conversion of cyclohexanones and cycloheptanone 31 and 33 by hydro-
gen peroxide into medium ring cycloalkanecarboxylic acids 32 and 34
with good yields.8 Scarcely enolizable ketones, such cyclooctanone
and cyclododecanones 31 require higher concentration of the cata-
lyst (6 mol %) and prolonged reaction time, 1 to 4 days, respectively,
and the cycloheptane and cycloundecanecarboxylic acids 32 have been
obtained in good yields.22 Compounds with five- to seven-membered
rings are important substrates in the synthesis of natural products
and pharmaceuticals. They cannot be obtained via the Favorski re-
action in many instances. The presented route is more environmen-
tally friendly than the use of stoichiometric amounts of thallium(III)
salts.23 The oxidative rearrangement of ketones promoted either by
thallium(III) or by H2O2/cat. 18 occurs with similar diastereoselectiv-
ity, as ring contraction of bulky substituted cyclohexanone 33 to cis-3-
tert-butylcyclopentanecarboxylic acid (34), because both oxidants react
through an electrophilic addition to the enol form of the ketones.24,25
The ring contraction of 4-phenylcyclohexanone (35) promoted by hy-
pervalent iodine(III) compounds such iodobenzenediacetate has been

Diaryl Diselenides as Oxygen-Transfer Agents
975
used for the synthesis of 1-piperidinobenzobicyclo[2.2.1]heptane.26,27
In this example, the relative configuration of formed methyl
ester of 3-phenylcyclopentanecarboxylic acid was not assigned.
Oxidation of 35 with H2O2/cat. 18 system resulted in cis-3-
phenylcyclopentanecarboxylic acid (36) in moderate 43% yield, and
trans isomer is also formed.8 If cyclohexanone substituted with
methyl at 2-positions 37 and 39 have been used as substrates, only
Baeyer–Villiger rearrangement takes place, and lactone open chain 6-
hydroxyheptanecarboxylic acids 38 and 40 were the final products, (see
Experimental, and Scheme 5).22
COOH
O
[Ox.]
( )n
( )n
31
32
n = 1, 2, 3, 7 Method A/B
50-60%
COOH
COOH
O
[Ox.]
+
5
R
R5
R5
R5 = -Bu (33) Method A/C
R5 = -Bu (34, 50%/87%)
-
t
t
R5 = Ph (35) Method A
R5 = Ph (36, 43%)
4.3%
Me
R6
CH2 CH COOH
Me
HO CH
O
[Ox.]
CH2 CH2
R6
R6 = H (37) Method A
R6 = Me (39) Method A
R6 = H (38, 64%)
R6 = Me (40, 72%)
[Ox.]: Method A - H O /cat. 18 (0.6 mol %), -BuOH, reflux, 5-60 h;
t
2
2
Method B - H O /cat. 18 (6 mol %), -BuOH, reflux, 1-4 days;
t
2
2
Method C - TTN, CH2Cl2, 20oC
SCHEME 5 Cycloalkanones ring contraction.
It has been proposed that a Se(VI) species is responsible for oxida-
tive ring contraction.23 We propose that a Se(II) intermediate 41 is
responsible for the oxidative ring contraction, whereas a Se(IV) inter-
mediate catalyzes conventional Baeyer–Villiger ketone rearrangement,
(Scheme 5).22 In the contraction reaction, the key intermediate is the

976
M. Giurg and L. Syper
cyclopropanone formed as a result of electron-rich 9,10-dianthracenyl
diselenide elimination (Scheme 6).22
Ar-Se(O)OH + Ar-Se-Se-Ar + H2O
3 Ar-SeOH
41
OH
O
O
41
-H2O
SeAr
SeAr
SeAr
COOH
O
O
H2O
41
-H2O
-ArSeSeAr
SeAr
32
SCHEME 6 Mechanism of cyclohexanone ring contraction.
OXIDATIVE DEGRADATION OF NAPHTHALENE RING
Six-electron oxiadation of both hydroxynaphthalenes 42 and 43, ortho
substituted formyl 44 and 45 and its tosylhydrazone derivatives 46
and 47 with 30% hydrogen peroxide in THF in the presence of
poly(bis-1,2-diphenylene) diselenide (17, PPDS) is a convenient way
to obtain trans-2-carboxycinnamic acid 48. The results are similar for
both of the substrates, since the reaction proceeds via intermediate
1,2-naphthoquinone. None of hydroxylated 1-formylnaphthalene (49)
and its imine derivatives, such as oxime, azine, and tosylhydrazone 50
produce carboxycinnamic acid 48 with yield up to 50%, instead isomeric
(1-oxo-1,3-dihydroisobenzofuran-1-yl)acetic acid and 1-naphthoic acid
is formed (Scheme 7).9,28
30% Hydrogen peroxide in tert-butanol in the presence of bis-(2-
nitrophenyl)diselenides 5 and 6 at mild reaction conditions (55◦C, 6 h)
led to complete conversion of 2-naphthol to 2-carboxycinnamic acid 48.
The 6, having two electron-withdrawing substituents (nitro and triflu-
oromethyl groups), was a better one catalyst, because it gave the col-
orless product 48.12 The reagent, H2O2/cat. 6 was successfully applied
for oxidative degradation of 6- or 7- substituted 2-hydroxynaphthalenes
to cinnamic acids 51 with substituent on benzene remote ring carbon
atom, (Scheme 7).29 The ring substituted cinnamic acids could find syn-
thetic application, similarly to industrially produced trans-cinnamic
acid.32

Diaryl Diselenides as Oxygen-Transfer Agents
977
R8
O
O
[Ox.], 20oC
97%
[Ox.]
44-50%
R8 = CHO (49);
R8 = CH=NNHTs (50)
COOH
COOH
R8
OH
R7
OH
[Ox.]
63-98%
48
[Ox.]
54-98%
R8 = H,
R8 = CHO, (45);
R8 = CH=NNHTs (47)
(43);
R7 = H
R7 = CHO (44);
R7 = CH=NNHTs (46)
(42);
[Ox.]: 30% H2O2/cat. 17 (5 mol %), THF, reflux, 20 h.
R10
COOH
COOH
R10
OH
[Ox.]
9
R
9
R
R9 = R10 = H (43)
R9 and/or R10 = X
Method A
Method B
48 (100%)
51 (60-90%)
X = H, OH, OMe, COOH, COOMe
[Ox.]: Method A - 30% H O /cat. 5 or 6 (5 mol %), -BuOH, 55oC, 6 h;
t
2
2
Method B - 30% H2O2/cat. 6 (5 mol %), t-BuOH, reflux, 60 h
SCHEME 7 Oxidative domino transformation of 1- and/or 2-substituted
naphthalenes.
Interestingly, 2-formyl-1-methoxynaphthalene (52) and its deriva-
tive 53 is good benzofuranone 54 precursors.28 Its 4 and 7 methoxy
derivatives 55 and 56 were formed from corresponding methoxynaph-
thalenes 57 and 58, (Scheme 8).29 Phthalides are a core part of the
structure of several alkaloids, and isoochracinic acid, a toxic metabolite
from a parasite responsible for black spot disease of Japanese pears,
our compounds could be eligible intermediates for their synthesis.31
These results are in accordance with our previous experiments
on functional groups transformations. Naphthaldehyde imine deriva-
tives 59 underwent oxidative regeneration of the parent carbonyl com-
pounds 60.9 The electron-rich carbonyl compounds underwent Baeyer–
Villiger rearrangement to naphthol formate 61, which was directly
hydrolyzed to hydroxynaphthalene 62.16 If hydroxy or methoxy group
at ortho position is absent, ortho-hydroxylation takes place, similarly
as Barton proposed in benzeneseleninic(IV) acid and its anhydride

978
M. Giurg and L. Syper
OMe
CHO
OMe
O
CH=NNHTs
[Ox.]
48%
[Ox.]
O
81%
CH2COOH
52
54 (48%/81%)
53
[Ox.]: 30% H2O2/cat. 17 (5 mol %), THF, reflux, 20 h.
MeO
R11
O
O
OMe
O
[Ox.]
[Ox.]
O
CH2COOH
CH2COOH
MeO
56 (70%)
R
11 = 5-OH (58);
11 = 8-CH=NNHTs (57)
55 (45%)
R
[Ox.]: 30% H2O2/cat. 6 (5 mol %), t-BuOH, reflux, 60 h.
SCHEME 8 Oxidative domino naphthalene ring transformation.
oxidation of both naphthols to ortho-naphthoquinone (63).32 Baeyer–
Villiger oxidation of intermediate 63, consecutive ring opening of
cis-2-carboxycinnamic acid anhydride and isomerization, give finally
the stable trans-2-carboxycinnamic acid (48). The labile formyl and to-
sylhydrazone groups were source of acids which catalyze intramolecular
Michael addition of cinnamic acid 48 to phthalide form 54, (Scheme 9).
CH=NX
CHO
R12
OCHO
H2O2/cat. 17
H2O2/cat. 17
R12
R12
59
60
61
H+, H2O
- HCOOH
O
O
OH
R12
O
O
H2O2
H2O2/cat. 17
O
63
62
H+, H2O
O
COOH
COOH
COOH
COOH
O
CH2COOH
48
54
R12 = H, OH, OMe
SCHEME 9 Oxidation of naphthalene ring.

Diaryl Diselenides as Oxygen-Transfer Agents
979
OXIDATIVE DEGRADATION OF ELECTRON-RICH BENZENE
RING
Oxidative degradation of electron-rich benzene rings with formation of
quinone and ring cleaved products, such as carboxylic acids and lactones
expand the utility of benzenoid synthons in organic synthesis. Unfor-
tunately, aromatic hydrocarbons and its more oxidized derivatives as
catechols and ortho-quinones require strong oxidizing agents or acti-
vated hydroperoxides, and mixture of many different compounds are
produced in low yield, and this is a reason of a little synthetic value of
this methodology.33
We elaborated the practical hydroperoxide oxidation of phenol and
its derivatives. Unsubstituted phenol, its ortho hydroxy, methoxy and
formyl derivatives 64 with H2O2/cat. 6 system rearranged to 2,4-
hexadienedioic acids named muconic acid (65).34 Other 2- and 4-alkyl
substituted phenols 66 and 67 underwent ring rearrangement to 2-
and 3-substituted muconolactones 68 and 69. If both ortho positions
are substituted by alkyl group in phenols 70, 1,4-benzoquinones 71
were formed in good yield, (Scheme 10).35 A similar oxidation pattern
of catechol or hydroquinone ether by peracetic acid and TBHP/cat. 17
system was observed.6,36
HOOC
OH
R14
COOH
[Ox.]
64
65 (38-50%)
O
O
R15
R15
[Ox.]
O
[Ox.]
O
15
R
OH
CH2COOH
CH2COOH
68 (50-62%)
2-OH (66); 4-OH (67)
69 (30-81%)
R16
R16
O
OH
R16
[Ox.]
O
R16
70
R14 = H, OH, OMe, CHO; R15 = alkyl; R16 = Me, t-Bu
[Ox.]: H O /cat. 6 (5 mol %), -BuOH, reflux, 20 h
71 (74-83%)
t
2
2
SCHEME 10 Oxidative degradation of benzene ring.
Phenol having amino group in ortho position 72 is a good sub-
strate for enzymatic and biomimetic oxidative cyclocondensation to the

980
M. Giurg and L. Syper
2-amino-3H-phenoxazin-3-one known as questiomycin A (73).37,38
The naturally occurred questiomycin A prevents the proliferation of
some microorganisms, such mycobacteria.39,40 The cyclocondensation
of ortho-aminophenol, with the aid of dioxygen or hydroperoxides alone,
did not proceed, or questiomycin A was formed in low yield.41–43 More
satisfactory results were found in the presence of selenium catalysts,
particularly 2- and 3-di-trifluoromethyldiphenyl diselenides (9 and 10)
for TBHP oxidation, and 2,2ꢀ-dicarbamoylphenyldiphenyl diselenide
(19) and related ebselen (20) for H2O2 oxidation.43 Since the 2-amino-
3H-phenoxazin-3-one ring system is a basic part of the skeleton of acti-
nomycin D44, the anticancer antibiotic extensively used in recent years
in chemotherapy of cancer,45 we applied the above methodology for
the practical synthesis of the questiomycin A derivatives.46 2-Amino-
3-methylphenol (74) was oxidized to the dimethyl derivative of ques-
tiomycin A 75 smoothly because the methyl group in the vicinity of the
amino group strongly activates the substrate molecule. In contrast, an
electron-withdrawing carboxy substituent present at the same position
in 76 prevents the reaction and cinnabarinic acid (77) was not formed.
The electron donating methyl group in the vicinity to the hydroxyl group
of 2-amino-3-carboxy-6-methylphenol (78) made the substrate suscep-
tible to cyclocondensation, and actinocin (79) was formed as the sole
product (Scheme 11).45
R17
R17
R17
NH2
OH
N
O
NH2
O
[Ox.]
R18
R18
18
R
72
74
76
78
Method A-D
Method A/C
Method A/C
Method A
73 (80-92% )
75 (92%/64%)
77 ( - / - )
79 (81% )
R17 = R18 = H (72, 73 - questiomycin A);
R17 = Me, R18 = H (74, 75);
R
17 = COOH, R18 = H (76, 77 -
);
cinnabarinic acid
R17 = COOH, R18 = Me (78, 79 -
)
actinocin
[Ox.]: Method A - H2O2/cat. 20 (5 mol %), t-BuOH, 20oC, 20 h;
Method B - H2O2/cat. 19 (5 mol %), t-BuOH, 20oC, 20 h;
Method C - TBHP/cat. 10 (5 mol %), -BuOH, 55oC, 20 h;
t
Method D - TBHP/cat. 9 (5 mol %), -BuOH, 55oC, 20 h
t
SCHEME 11 Oxidative cyclocondensation of ortho-aminophenols.
In the first step of the oxidative cascade, the aminophenol 72 and
its derivatives having substituents in the ortho positions towards

Diaryl Diselenides as Oxygen-Transfer Agents
981
the amino and/or hydroxyl groups 74 and 78 (oAP) are oxidized
to the highly electrophilic quinone imine 80. The amino group of
other molecule of aminophenol (oAP), then adds to the quinone
imine 80, resulting in unstable intermediate, which tautomerizes to
more stable ortho-aminophenol aromatic 81. This oxidation-addition-
tautomerization sequence is repeated in the subsequent steps of the
reactions via intermediate 82 and 83. The final oxidation of 83 and
tautomerization of azaquinone 84 gives the aminophenoxazinone chro-
mophore 73, 75, and 79. Ortho-aminophenol with methyl group sub-
stituted at para position to the amino group in 85 was converted
to the 2-amino-4α,7-dimethyl-4,4α-dihydro-3H-phenoxazin-3-one (86),
and analogously substituted chloroaminophenol 87 gave 2-amino-7-
chloro-3H-phenoxazin-3-one (88) with one molecule of hydrochloride
elimination, (Schemes 11 and 12).43,46
R17
R17
R17
R17
H
N
R17
R17
H
N
NH2
O
NH2[Ox.]
OH
NH
O
NH2
OH
oAP
19
R
19
R
19
R
19
R
OH 19
OH 19
R18
R
R18
R18
R18
R18
R
R18
oAP
80
81
[Ox.]
(72, 74, 78, 85, 87)
17
R
R17
H
N
N
NH
OH
N
NH2
O
NH2
O
-HCl
19
R
19
R
O
O
19
Cl
O
19
R
R18
R
18
R
88 (42-44%)
R19 = Me (86, 42-55%)
82
17
R
R17
H
N
R17
R17
R17
R17
H
N
N
O
NH2
NH
O
NH2
OH
[Ox.]
O
O
O
R18
R18
R18
R18
R18
R18
73, 75, 79
84
83
R17 = R18 = H, R19 = Me, (85); R17 = R18 = H, R19 = Cl (87); R17 = H, Me, COOH; R18 = H, COOH
SCHEME 12 Mechanism of ortho-aminophenols cyclocondensation.
Catalyzed by organoselenium compounds hydroperoxide oxida-
tion of electron-rich benzene ring of hydroquinone ether and ortho-
aminophenol gave results similar to those, when one-electron oxidants
such as, cerium(IV), silver(II), or manganese(III) were the reagents.6,43
Moreover, formation of aminophenoxy radicals by oxidation of
ortho-aminophenol by above reagents are crucial steps in their con-
version to 2-aminophenoxazin-3-one, most probably by action of se-
lenoxyradical 4 intermediates, a strong electron acceptors.43 Our

982
M. Giurg and L. Syper
findings are also in accordance with well-known mechanisms of oxi-
dation of phenolic substrates by laccase and peroxidase.46
EXPERIMENTAL
Preparation of Dilithium Diselenide in 50 mmol Scale
A clean chunk of lithium (0.73–0.75 g) is weighted in kerosene. To an
oven dried 100 ml round bottom flask with a long neck, fitted with
a stopcock adapter, is placed 50 ml purified THF.47 From the above
chunk of lithium 0.10–0.20 g pieces are cut, dried with filter paper
and hammered to a thin foil on a greased with paraffin oil anvil. The
foil is folded and hammered again. This operation is repeated several
times. The wound foil of lithium is cut with scissors in such a way that
the small pieces of lithium fall directly into the flask containing THF.
4,4ꢀ-Di-tert-butylbiphenyl (0.10 g)48 is then added. The flask is fitted
with the stopcock adapter49 and connected to vacuum (water aspirator).
Some amount of THF is removed during its boiling. The connection with
vacuum is cut off by means of the stopcock and the flask is put into
an ultrasonic bath. During the sonication permanent green coloration
should appear after less than 15 min.50 The flask is removed from the
bath, the stopcock adapter dismounted and selenium (8.0 g) in the form
of powder is added. The adapter is put at its place and the mixture
is degassed as above. The closed flask is sonicated until all lithium is
consumed (about 4 h). During the sonication temperature of the bath
can raise to 40–50◦C. If lithium is not completely consumed during
the 4 h period of sonication a magnetic stirring bar is placed in the
flask, the reaction mixture is degassed, as above, and stirred overnight
at ambient temperature.52 The prepared dilithium diselenide can be
allowed to stand in the reaction flask, under vacuum for months, it is
quite stable but its solubility in THF is limited. As prepared dilithium
diselenide is soluble in hexamethyl phosphoramide (HMPA) (20 ml) or
DMF. The Li2Se2 complex with HMPA (deep green) is only moderately
susceptible towards the air.
Preparation of 6-Hydroxyheptanecarboxylic Acids 38 and 40 in
50 mmol Scale22
To
a stirred solution of 2-methylcyclohexanone (37) or 2,6-
dimethylcyclohexanone (39) (50 mmol) in tert-butanol (15 ml) heated
to 65◦C with a catalyst 18 (PADS, 100 mg, 0.30 mmol, 0.60 mol %), 30%
aqueous hydrogen peroxide (10 ml, 0.10 mol) was added dropwise for
45 min, and the mixture was refluxed for 3 or 21 h, respectively. The
solvent was distilled off and cold residue was extracted with chloroform

Diaryl Diselenides as Oxygen-Transfer Agents
983
(10 ml and 2 × 5 ml). The extract was treated with a pinch of Pt/C,
dried with anhydrous Na2SO4 and solvent was removed. Acids (38, 40)
were purified on silica gel (70–230 mesh, 100 g) using diethyl ether as
an eluent.
DATA
6-Hydroxyheptanecarboxylic Acid (38)
Colorless oil, (4.69 g, 64%). 1H NMR (300 MHz, DMSO-d6); 11.50 (s, 1H,
COOH), 4.30 (s, 1H, OH), 3.45–3.55 (m, 1H), 2.15 (t, J = 7.3 Hz, 2H),
1.40–1.50 (m, 2H), 1.20–1.30 (m, 4H), 0.98 (d, J = 6.1 Hz, 3H, Me). IR
(Film); 3370 cm−1 (OH), 2200–3600 cm−1 (COOH), 1711 cm−1 (C = O),
1150–1250 cm−1 (out of plane, C–O).
6-Hydroxy-2-methylheptanecarboxylic Acid (40)
Colorless oil, (5.74 g, 72%). 1H NMR (300 MHz, CDCl3); 6.23 (s, 2H, OH
and COOH), 3.75–3.85 (m, 1H), 2.40–2.53 (m, 1H), 1.60–1.75 (m, 1H),
1.35–1.55 (m, 5H), 1.19 (d, J = 6.0 Hz, 3H, Me), 1.18 (d, J = 6.8 Hz, 3H,
Me). 13C NMR (75 MHz, CDCl3); 181.5 (C=O), 39.2, 67.8 (CH), 38.7,
33.4, 23.2 (CH2), 23.0, 16.8 (CH3). IR (Film); 3380 cm−1 (OH), 2200–
3600 cm−1 (COOH), 1708 cm−1 (C=O), 1150–1250 cm−1 (out of plane,
C–O).
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Diaryl Diselenides as Oxygen-Transfer Agents
985
[47] To the preliminary purified THF 51 in round bottom flask with a long neck, several
pieces of clean sodium or potassium or both and benzophenone are added. The flask
is closed and put into an ultrasonic bath, and sonicated until deep blue, permanent
coloration appears. Next THF is distilled using a Vigroux column. The contact of
THF with ambient atmosphere should be avoided. Such a purified THF should be
used on the same day.
[48] Diphenyl acetylene can be used instead.11
[49] The stopcock adapter should be vacuum proof, silicone grease is used to tighten its
connections.
[50] If there is no deep permanent green coloration during 30 min, something is wrong
and the experiment should be discontinued.
[51] THF distilled from LiAlH4 is appropriate for the further purification.
[52] The period necessary for the completion of the reaction depends on purity of sele-
nium used. Selenium of lower purity grade reacts faster. The technical grade sele-
nium was found quite satisfactory.