An efficient copper-catalyzed synthesis of symmetrical bis(: N -arylbenzamide) selenides and their conversion to hypervalent spirodiazaselenuranes and hydroxy congeners

Article abstract of DOI:10.1039/c8dt04832k

A copper catalyzed efficient synthetic method has been developed to access bis(N-arylbenzamide) selenides from 2-halo-N-arylbenzamide substrates and disodium selenide in HMPA at 110 °C. The developed protocol tolerates substituents in both N-aryl and benz

Full text of DOI:10.1039/c8dt04832k

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PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
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An Efficient Copper-Catalyzed Synthesis of Symmetrical Bis(N-
Arylbenzamide) Selenides and Their Conversion to Hypervalent
Spirodiazaselenuranes and Hydroxy Congeners
Rahul Kadu,ǂ Monojit Batabyal,ǂ Heena Kadyan, Apurba Lal Koner, Sangit Kumar*
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal,
Bhopal By-pass Road, Bhauri, Bhopal-462066, India E-mail: sangitkumar@iiserb.ac.in
ǂ Both authors contributed equally
Abstract
A copper catalyzed efficient synthetic method has been developed to access bis(N-arylbenzamide)
selenides from 2-halo-N-arylbenzamides substrates and disodium selenide in HMPA at 110oC.
The developed protocol tolerates substituents in both N-aryl and benzamide rings of the 2-
halobenzamide substrates and provide an array of bis(N-arylbenzamide) selenides in practical
yields. The resulted selenides were transformed into hypervalent spirodiazaselenuranes by the
oxidation using aqueous hydrogen peroxide. (N-(1-Naphthyl)) spirodiazaselenurane is also
structurally characterized by single crystal X-ray study. Hydroxy-substituted spiroselenuranes
have been prepared by careful demethylation of methoxy-substituted selenides followed by
oxidation by hydrogen peroxide. Antioxidant properties for the decomposition of hydrogen
peroxide and for the deactivation of radicals of hydroxy-substituted spiroselenuranes have been
studied by thiol assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Both hydroxy-substituted
spiroselenuranes exhibit dual mimic functions of glutathione peroxidase (GPx) selenoenzyme and
α-tocopherol for decomposition of hydrogen peroxide and deactivation of radicals, respectively.
1

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Introduction
The Studies on hypervalent organochalcogens, particularly, chalcogenuranes have attracted great
deal of interest as they seem to open new frontiers in organic synthesis and medicinal chemistry.1
Several stable hypervalent organochalcogens, mainly sulfurane species have been reported in the
begining.2
CO2H
O
O
F3C
CF3
O
O
R
R
R
R
O
O
O
N
S
S
Se
Se
Se
O
O
O
O
N
F3C
CF3
O
O
O
2
1
3
4
5
, R = Me
6
7
, R = H
, R = Me
i
, R = Pr
CF3
O
F3C
O
O
O
O
O
O
Se
Se
Se
Se
Se
O
O
O
O
O
O
11
12
8
9
10
R
O
O
O
O
R
R
NR
Se
N
N
Se
N
Se
NR
N
O
O
R
13
14
15
16
17
, R = H
, R = Ph
, R = ortho-OMe
, R = meta-OH
, R = meta-OMe
18
19
20
21
, R = Me
, R = COOH
, R = Cl
, R = Br
Chart 1. Reported organospirosulfuranes and -selenuranes
2

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Interestingly, hypervalent spiro chalcogenuranes having trigonal bipyramidal TBP-geometry are
chiral molecules due to presence of C2-symmetry.3 The first spirodioxyselenurane 1 was
synthesized by Lesser and Weiss in 1914 (Chart 1).4 Subsequently, unsymmetrical carboxy
derivative 2 was synthesized and partially resolved by Lindgren,5 then germinal dimethyl
substituted compound 3 was found to possess high configurational stability even at elevated
temperature.6 Spirodiazasulfuranes having two nitrogen atoms at the apical position are rare, the
first nitrogen-substituted spirodiazasulfuranes 4 and 5 have been synthesized by Martin and co-
workers.7 The same group in 1979 reported a very facile synthesis of hypervalent spirosulfuranes
6 and 7.8 Spirotetraoxyselenurane 8 and various examples have also been reported and their acid
catalyzed equilibrium also been studied.9 The synthesis of oxaselenetane 9 and related analogues
have been reported by Okazaki et al. in 1993.10 Camphor-substituted unsymmetrical
spirodioxyselenurane 10 was also synthesized as pure diastereomers.11 In 2004, Back and co-
workers have reported the synthesis of spirodioxyselenurane 11 and its homologues and also
demonstrated their glutathione peroxide (GPx) mimetic activity.12 Although the aromatic
derivative 12 exhibited much reduced catalytic activity as compared to their aliphatic
counterparts,13 the substituted aromatic analogues have shown improved catalytic activity. Unlike
well explored spirodioxyselenuranes,14,15 spirodiazaselenuranes having apical nitrogen atoms are
unique. In 2007, for the first time Back et al. reported the relative instability of such
spirodiazaselenuranes 13.16
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O
O
O
ONa
HO
S
OH
NaNO2, HCl
Na2Se2 / H+
OH
NH2
OH
Se
O
Se
O
Se
HO
2-Iodobenzoic acid
Cu / DMF
OH
O
23
22
NH3
i. Zn, NaOH
NCS or H2O2
ii.Cu, 2-I-Ph-CO2H, K2CO3
Ph
O
K
HN
O
O
N
NH
O
1. SOCl2
OH
OH
O
excess KH
Se
Se
Se
Se
N
2. Ph-NH2
O
X
O
K
HN
Ph
NH2
X= Cl, OH
O
23
24
Route 1
Route 2
13a
13
K-Salt of
Ar
Li
HN
O
O
O
Ar
n-BuLi / THF, 0 0C
Ar
N
Se(dtc)2
N
H
Se
Li
O
HN
Ar
Route 3
Our approach
Ar
R
R
HN
O
O
O
R
Ar
N
Ar
Ar
i.Na2Se
N
Aq. H2O2
CH2Cl2
H
Se
Se
ii. CuI, HMPA
X
O
N
when, R = H, X= I
and R= OMe, X= Br
R
R
HN
O
Ar
Scheme 1. Synthetic routes of spirodiazaselenuranes and their precursors
The synthesis of organodiazaselenuranes involves multi-steps as depicted in Scheme 1.
Diazotization of anthranilic acid, subsequent quenching of diazotized intermediate by Na2Se2
resulted into 2-benzoic acid diselenide 22.17 Back et al. have reduced diselenide 23 using sodium
hydroxymethyl sulfate and followed by the coupling with 2-iodobenzoic acid mediated by copper
in DMF yielded desired monoselenide 23 (route 1). The reaction of 23 with N-chlorosuccinimide
4

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followed by quenching with ammonia and subsequently attempted oxidation of in-situ resulted 2-
benzamide selenide failed to provide spirodiazaselenuranes 13 and instead selenium cation 13a
was isolated which was stabilized Se…O intramolecular interaction. Interestingly, when reaction
mixture of in-situ formed siproselenurane was treated with KH, reaction provided potassium salt
of spiroselenurane. In an alternative approach to symmetrical selenide 24, reduction of diselenide
22 with Zn and NaOH followed by copper-mediated coupling with 2-iodobenzoic acid resulted
symmetric bis(2-benzoic acid) selenide 23. Subsequently, conversion of acid group of 23 into acyl
chloride by the reaction of thionyl chloride and followed by the coupling of primary aryl amines
resulted into the formation of desired key precursor N-arylphenyl selenide 24 (route 2).18 However,
oxidation of selenide 24 into spirodiselenurane Se(IV) has not been reported by Pietka-Ottlik and
Mlochowski.18
In 2010, the synthesis of N-phenylbezamide selenide 24 was achieved by ortho-lithiation method
in which dianion, resulted from ortho-lithiation of N-phenylbenzamide, was treated with selenium
dithiacarbamate Se(dtc)2.19 The resulted N-phenylbezamide selenide 24 was also structurally
characterized. Later same group reported the synthesis of N-aryl–substituted benzamide selenides
15-21 by treatment of 2-benzoic acid selenide 23 with thionyl chloride and subsequent quenching
with substituted-aryl amines. Interestingly, the selenide precursors 15-21 was successfully
transformed into stable spiroselenuranes.20,21 Also antioxidant activities of spiroselenuranes
against peroxynitrite and peroxides have been studied. In 2014 Kawashima and coworkers reported
synthesis and structure of tetra-coordinated selenazitidines.22
Owing to its high catalytic activity, ebselen having Se-N bond is one of the best candidate which
has undergone several clinical trials23 such as neuro and cardio protective agents, hearing loss
treatment. The presence of covalent Se-N and Se-O bonds at various stages of redox cycles have
been studied for GPx mimetics.24,25 Recently our group along with Engman et al. have reported
regenerable multifunctional ebselenol antioxidants 25-28 (Chart 2) for radical trapping and H2O2
decomposing activities.26 Mechanistic understanding of ebselenols suggests that the presence of
Se-N bond is crucial for peroxyl radical deactivating activity and also their regenerability by
ascorbic acid vitamin C.26 Radical chain breaking antioxidant activity of 2-(hydroxymethyl)-4-
hydroxyphenyl 3-hydroxypropyl selenide which is a precursor of its spiroselenurane has also been
evaluated.15a Our group is continuously working on the development of new and sustainable
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methodologies to construct organochalcogen compounds. We developed a copper-catalyzed Se-N
bond forming reaction for the synthesis isoselenazolones and ebselen molecules from 2-
halobenzamide substrates.27 Also benzamide substrates have been successfully exploited for
various carbon-carbon and carbon-heteroatom coupling reactions.28
O
O
O
O
HO
HO
N
N
N
OH
N
Se
Se
Se
Se
OH
25
26
27
28
O
HO
O
N
N
HO
Se
Se
OH
N
N
O
O
HO
29
30
Chart 2: Ebselenols 25-28 and synthesized spiroselenuranols 29-30
We envisage that the phenolic compounds 29 and 30 having tetravalent selenium and having Se-
N bond would serve as potent radical chain breaking antioxidant. Here in continuation of our work
on copper catalyzed Se-N bond forming reaction, we present a practical method to access
symmetrical bis(N-arylbenzamide) selenide precursors in gram quantity. Also, bis(N-
arylbenzamide) selenide precursors was transformed into spiroselenuranes following the reported
procedure by Mugesh and coworkers.19 Hydroxyselenuranes were achieved by de-methylation of
methoxysubstituted monoselenides by us using BBr3 followed by the spirocyclization. Hydrogen
peroxide decomposing and radical deactivating antioxidant activities of hydroxy-substituted
spiroselenuranes have also been evaluated by vitro assays.
Results and Discussion
Synthesis and Characterization: 2-Iodo/bromo-N-phenylbenzamide substrates 31-36 were
prepared by following literature procedure.29-30
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Table 1. Optimization of reaction conditions for the synthesis of selenide 24a
NHPh
O
O
Ph
Se-source,b copper salt
N
Se
H
solvent, 80oC
I
O
31
NHPh
24
Entry
Cu-Source
Base/Additive
Solvent
Yield of 24
1
CuI (10 mol%)c
CuOTf (10 mol%)c 1,10-Phen., Mg (one equiv) DMF
1,10-Phen., Mg (one equiv) DMF
traced
traced
traced
trace
50%
65%
75%
86%
25%
45%
30%
15%
2
3
CuI (100 mol%)
CuI (10 mol %)
CuI (10 mol %)
CuI (10 mol %)
CuI (10 mol %)
CuI (10 mol %)
─
1,10-Phen., Mg (one equiv) DMF
4
1,10-Phen.
1,10-Phen.
1,10-Phen.
1,10-Phen.
─
THF
5
DMF
6
DMSO
HMPA
HMPA
HMPA
HMPA
HMPA
PEG-400
7
8
9
─
10
11
12
CuI (10 mol%)
CuI (5 mol%)
─
Mg (one equiv)
Mg (one equiv)
NaBH4 (two equiv)e
a,b Selenium powder was used in entries 1-3 and disodium selenide Na2Se was used a source of
selenium in entries 4-11. Na2Se was in-situ generated by the reaction of selenium (4.15 g, 52.5
mmol) with sodium (2.53 g, 110 mmol) in the presence of catalytic amount of naphthalene (1.28
g, 10 mmol) in THF (30 mL). After formation of Na2Se, THF solvent was distilled, 2-iodo-N-
phenyl benzamide 24 (3.23 g, 100 mmol) and HMPA (5 mL) were added. The resulted reaction
mixture was heated at 80oC. c Selenium powder was used instead of Na2Se. d Observed by TLC.
e Na2Se was prepared by the reaction of NaBH4 (101 mg, 2.7 mmol) with selenium (128 mg, 1.6
mmol).
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Our initial trial for the synthesis of selenide 24 was unsuccessful by using selenium powder in the
presence of copper iodide and 1,10-phenanthroline catalyst and magnesium as a reductant31 in the
absence of a base (entry 1, Table 1). Further, the use of different copper source and even 100 mole
% CuI and 1,10-phenanthroline afforded only traces of selenide 24 (entries 2 and 3, Table 1). Next,
we envisage that the substitution of iodide by selenide dianion Se2─ in 2-iodobenzamide would
provide smooth access to symmetric selenide 24. For this purpose, selenium dianion was in-situ
generated by the reaction of selenium powder and sodium metal in the presence of naphthalene
catalyst in THF. The subsequent reaction of in-situ generated selenide anion with 2-iodophenyl
benzamide 31 in same solvent THF was unsuccessful (entry 4). The change in solvent from THF
to DMF led to 50% yield of the desired selenide 24 (entry 5). Further, DMSO afforded slightly
better yield 65% (entry 6). Nonetheless, selenide 24 was difficult to purify due to difficulty in
column chromatography of benzamide substrates. Next, we sought for a practical method which
devoid further purification to access selenide 24. The use of HMPA solvent together with copper
catalyst enabled substantial improvement in the yield of 24 by 10% (entry 7 vs entry 6, Table 1).
Interestingly, reaction noticed to be clean and better yield (86%) of selenide 24 was realized in the
absence of 1,10-phenanthroline ligand (entry 8).
The reaction in the absence of copper catalyst was ineffective and afforded only 25% yield of the
product 24 (entry 9, Table 1). Further, catalyst loading from 20 to 10 or 5 mole % was not
successful in the presence of magnesium additive and seems 20 mole % is essential for complete
conversion (entries 10-11, Table 1). We also attempted to substitute HMPA with benign and
greener solvent PEG-400. For this purpose, Na2Se was generated by the reaction of NaBH4 with
selenium in PEG-400. Subsequent reaction of 2-iodobenzamide 31 with Na2Se afforded only 15%
yield of 24 (entry 12, Table 1).
Next, substrate scope was explored under the optimized conditions (Scheme 2). Methoxy-
substituted-N-aryl-iodo-benzamides smoothly reacted to afford respective selenides 37-39 in 91-
94% yields. Similarly, N-naphthyl substituted substrate 35 underwent C-Se bond forming reaction
to give respective naphthyl selenide 40 quantitatively. Although, synthetic methods are available
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to prepare N-phenyl-benzamide selenides, synthesis of benzamide ring substituted selenides have
not been accomplished. Interestingly, methoxy-substituted benzamide ring containing bromo
substrate 36 also coupled smoothly to yield 41. Next, oxidation of divalent selenides 24 and 37-41
into tetravalent spirodizaselenuranes 14, 15, 17, 42-44 was studied. Oxidation occurred smoothly
by aqueous hydrogen peroxide and afforded spirodiazaselenuranes 14,19 15, and 17,20 and 42-44
quantitatively.
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Ar
O
R
R
HN
O
I
Ar
N
O
Se
Ar
i.Na2Se
Aq. H2O2
CH2Cl2
N
H
Se
ii. CuI, HMPA
O
N
Ar
R
31-35
HN
O
R
Ar
14 15 17 42 43
,
,
,
,
24 37 40
,
-
(98-99% yields)
O
(86-94% yields)
Ar
O
O
HN
O
Ar
N
O
O
Ph
i.Na2Se
Aq. H2O2
CH2Cl2
N
H
Se
Se
ii. CuI, HMPA
Br
O
N
Ar
O
36
HN
O
44
O
Ar
41
(98% yield)
(92% yield)
OMe
O
HN
HN
HN
HN
O
O
Se
O
O
Se
Se
Se
O
O
O
O
O
HN
HN
HN
HN
OMe
24
41
(86%)
40
(92%)
(89%)
37
38
39
2-OMe (94%)
3-OMe (91%)
4-OMe (94%)
O
N
O
N
O
O
N
O
N
OMe
Se
Se
Se
N
Se
N
N
O
N
OMe
O
O
O
O
14
(99%)
15
17
42
2-OMe (98%)
3-OMe (99%)
4-OMe (98%)
43
44
(98%)
(98%)
Scheme 2: Synthetic routes of monoselenenides and spirodiazaselenuranes
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Finally, demethylation reaction on methoxy-substituted spirodiazaselenuranes 15, 17, 42, and 44
were explored to access phenolic radical chain breaking antioxidants having tetravalent selenium
(Scheme 3).
R1
R2
O
R2
HN
O
R1
N
Aq. H2O2
CH2Cl2
BBr3
CH2Cl2, -78oC to rt
Se
Se
N
O
R1
O
R2
R2
HN
R2
O
R1
R1
N
15, R1 = ortho OMe, R2 = H
44, R1 = H, R2= OMe
37, 41
Se
N
R1
R1
R1
R2
O
R2
HN
R2
HN
29, R1 = ortho OH, R2 = H
30, R1 = H, R2 = OH
O
Aq. H2O2
CH2Cl2
O
BBr3
CH2Cl2, -78oC to rt
Se
Se
O
O
R2
HN
R2
HN
R1
R1
37, 41
45, R1 = ortho OH, R2 = H
46, R1 = H, R2= OH
Scheme 3: Synthesis of hydroxy-monoselenides and respective spirodiazaselenuranes
Demethylation of methoxy-substituted spirodiazaselenuranes 15, 17, 42, and 44 using BBr3
noticed to be sluggish procedure and the cleavage of Se-N bond of 15, 17, 42, and 44 was realized.
In the presence of an excess of BBr3, resulted in the demethylation of spirodiazaselenuranes 15,
17, 42, and 44 as the reaction was monitored by 1H NMR. However, cleavage of Se-N bond was
also realized which led to complex reaction mixture. Next demethylation was attempted using
sodium ethane thiolate, which also resulted in the cleavage of Se-N bond instead of demethylation.
In an alternative approach, methoxy-substituted selenides 37 and 41were treated with an excess of
BBr3 which provided hydroxy-substituted selenides 45-46. Careful variation in the stoichiometry
of BBr3 led to complete demethylation of methoxy substituent smoothly afforded 93 and 95%
yields respectively.
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Synthesized selenides 24, 37-41 and spirodiazaselenuranes 14, 15, 17, 42-44 were characterized
by multinuclear (1H, 13C and 77Se) NMR and mass spectrometry. Spirodiazaselenuranes exhibited
signals of 77Se NMR (571-596 ppm) which are significantly downfield shifted, due to tetravalency
of selenium, as compare to selenides which resonate in the range of 376-430 ppm. Structure of
naphthyl spirodiazaselenurane (rectangular, colorless white crystal) 43 is also studied by single
crystal X-ray diffractometer. (Bruker APEX2) Spirodiazaselenurane 43 crystallized in distorted
trigonal bipyramidal (TBP) with the electronegative nitrogen atoms occupying the apical positions
and two carbon atoms projecting lone pair at the equatorial position (Figure 1). Both enantiomers
are crystallized in single unit cell. Consequently, averages of both (bond distances and angles) are
presented. Se─C and Se─N distances are 1.93(1) and 2.0355(7)Å and N─Se─N is nearly linear
∠
174.15(3)° whereas C─Se─C is bent at 98.05(4)°.
∠
Figure 1. ORTEP view of 43 (both enantiomers) with 40% probability of thermal ellipsoids
Proposed mechanism: The tentative mechanism of the copper-catalyzed selenation reaction
is shown in the Scheme 4. Although, mechanism for copper-catalyzed carbon-selenium bond
formation has been proposed from carbon-halogen bond.27a,31,32 However, these reports utilized
bases namely sodium carbonate, potassium carbonate or potassium hydroxide. The presence of a
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base in the reaction of 2-iodoN-arylbenzamides resulted in the formation of Se-N heterocycles
instead of respective symmetric monoselenides.27a Also, addition of elemental selenium powder
instead of selenium dianion does not provide satisfactory result under the reaction conditions. This
suggests that the insertion of selenium powder into copper-carbon bond in the amidate intermediate
I is not a viable path under base free conditions.
Na2Se + CuI
O
Cu2Se
O
I
O
CuI
NHPh
CuIIII2
NHPh
NHPh
Cu)2Se
31
I
I
V
path a
path b
Na2Se
CuI
NHPh
O
O
O
O
31
NHPh
CuIIISe
NHPh
NHPh
I
SeCuI
)
SeCu
PhHN
2
Se
II
CuI
IV
III
24
O
Scheme 4: Mechanism for Cu-catalyzed selenide formation
It seems that under base-free conditions, copper undergo oxidative addition of C─I bond of
substrate 31 and form CuIII intermediate I (path a). Subsequent iodide ligands of copper might be
substituted by selenide ion to furnish copperIIIselenolate II. Migration of selenium into copper-
carbon bond might afford CuIselenolate intermediate III. Oxidative addition of another C-I bond
to Cu-complex III could provide copperIIIselenolate intermediate IV. Reductive elimination would
afford desired selenides 24 along with concomitant regeneration of CuI catalyst. In an alternative
path (b, see right side of the Scheme 2), CuI would undergo substitution with selenide dianion to
provide CuI2Se which might undergo oxidative addition with C-I bond of 31 to furnish intermediate
V. This intermediate having C─Cu─Se bonds could undergo reductive elimination reaction to
enable selenide 24 and release of CuI catalyst.
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Peroxide decomposing GPx-like antioxidant property: Peroxide decomposing antioxidant
activity as a mimic for glutathione peroxidase (GPx) selenoenzyme was evaluated by thiol assay33
using benzenethiol (PhSH) co-reductant and hydrogen peroxide as an oxidant in the presence of
synthesized spiroselenuranes 29 and 30. The oxidation of PhSH to diphenyl disulfide (PhSSPh)
by H2O2 was monitored by UV-visible spectrophotometry at 305 nm (eq. 1)
Catalyst
PhSH + H2O2
(1)
PhSSPh +
H2O
305 nm
The H2O2 decomposing antioxidant activity of 29 was found to be higher than the standard
diphenyl diselenide (Table 2). However, spiroselenurane 30 having hydroxyl group in anilinic ring
shows lower hydrogen peroxide decomposing antioxidant activity as compared to Ph2Se2.
Table 2. Thiol peroxidase assay of 29 and 30
entry
catalyst
Ph2Se2
29
reduction rate (ν0 = μM min-1)a
25.57 ± 5.233b
1
2
3
27.92 ± 4.5
30
13.06± 4.5
aAssay condition: The reactions were carried out in methanol at 25 oC. Catalyst: 0.1 mM; PhSH:
1.0 mM; hydrogen peroxide: 3.75 mM. The control experiments were performed under identical
conditions in the absence of selenium catalysts. The initial rates were corrected for the back
ground reaction between thiol and peroxide.
Radical chain breaking antioxidant property by DPPH assay: Radical chain breaking
antioxidant activity of the synthesized hydroxy-spiroselenuranes 29 and 30 has been evaluated by
their hydrogen transfer capacity to 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical (eq. 2) in 80%
methanol: water (v/v) at 25 oC.
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(2)
O
R
DPPHH +
HO
R
DPPH
+
CH3OH: H2O (8:2)
519 nm
Vitamin E
29 and 30
The formation of DPPHH by the reaction phenolic antioxidants 29 and 30 and DPPH• was
monitored by UV-visible spectrophotometer at 519 nm.35 The quenching of DPPH• (64 μM) by
Vitamin E (100 μM) is studied and compared with synthesized hydroxy-spiroselenuranes 29 and
30 (Figure 2).
Figure 2. Hydrogen transfer capacity of vitamin E, 29 and 30 to DPPH•
The H-atom abstraction rate constants were obtained from the plot of log of optical density of
DPPH• (64 μM) vs time (min)/ for vitamin E (6.25 μM), vitamin C (6.25 μM), 29 (6.25 μM), and
30 (6.25 μM) Figure 4.
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Figure 3. Rate constants for hydrogen transfer capacity of vitamin E, 29 and 30 to DPPH•
Although, DPPH-assay has some limitations to evaluate antioxidant activity due to reverse electron
transfer from DPPH─ to [Ph─OH]•+ 35c Nonetheless, some insights were gained about the
.
antioxidants 29 and 30 in comparison with benchmark antioxidant vitamin E. It is evident from
Figure 2 that vitamin E quenches maximum concentration of DPPH•, 29 medium and 30 is the
lowest at 0.64:1 concentration ratio of DPPH• and antioxidants [DPPH• (64 μM) and antioxidant
(100 μM)]. The lower rate constants for hydrogen transfer of spiroselenuranes 29 and 30 could be
due to the presence of tetravalent selenium which would increase the –O─H bond dissociation
energy. Further, hydroxyl group attached to electron withdrawing benzamide ring of 30 whereas
in 29, hydroxyl group is present in electron donating aniline ring. ortho-Hydroxy substituted
spiroselenurane 29 exhibit a rate constant of 0.583±0.138 min-1 which is comparable with vitamin
E (0.696±0.100 min-1). Similarly, para-substituted spiroselenurane 30 transfer hydrogen atom to
DPPH following the rate constant of 0.400±0.141 min-1. When spiroselenurane 29 was used along
with vitamin C co-reductant, the slightly higher rate constant (0.724 min-1) was realized.
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Conclusion: In summary, a copper-catalyzed practical method has been established for the
synthesis of symmetrical bis(N-arylbenzamide) selenides from iodo-N-phenylbenzamides and di-
sodium selenide without using any base. The developed protocol is practical and competitive to
earlier established ortho-lithiation and diazotization routes in which dianion (carbanion and
amidate ion) is an intermediate which shows sluggish reactivity towards selenation reactions. Also,
synthesis of hydroxy-spiroselenuranes containing tetravalent selenium has been achieved. Our
preliminary investigation of radical quenching activity on hydroxy-spiroselenuranes by DPPH
vitro assay suggests that hydroxy-spiroselenuranes could deactivates radicals. Further, hydroxy-
spiroselenuranes show some regeneration by co-reductant such as vitamin C, although, further
validation is required. Crystal structure study on naphthyl-spirodiazaselenurane shows racemic
mixture of both enantiomers. Currently, efforts are being made to develop an enantioselective
synthesis of hypervalent spirodiazaselenuranes molecules.
Experimental Section
General Experimental Details.
All reactions were carried out in oven-dried glassware with magnetic stirring. Elemental selenium
(60 mesh size), sodium, copper iodide, copper triflate, 1,10-pheananthroline, 2-iodobenzoic acid
and amines used in this study were purchased from commercial sources (Aldrich/Fluka) and used
without further purification. All the solvents were purified by a standard procedure and freshly
distilled prior to use. Anhydrous DMF and DMSO solvents with sure seal septa were purchased
from Sigma Aldrich and used without further drying. All NMR experiments were carried out on
Bruker 400/500 MHz spectrometer in CDCl3/DMSO-d6 solvents. NMR chemical shifts are
reported in ppm referenced to the solvent peaks of CDCl3 (7.26 ppm for 1H and 77 (± 0.07) ppm
1
for 13C) or DMSO-d6 (3.31 ppm for H2O, 2.47 ppm for H and 39.50 (±0.07) ppm for 13C),
respectively. The 77Se NMR spectra were obtained at 76.31 MHz in CDCl3 or DMSO-d6.
Chemical shifts are reported relative to dimethyl selenide (77Se) (0 ppm). The following
abbreviations were used to indicate multiplicity: s (singlet), brs (broad singlet), d (doublet), t
(triplet), q (quartet), dd (doublet of doublets), ddd (doublet of a doublet of a doublet) and m
(multiplet). High resolution mass (HRMS) analysis is performed on quadrupole-time of flight
Bruker MicroTOF-Q II mass spectrometer equipped with an ESI and APCI source, 80Se isotope is
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used in exact mass calculation; LR-GC mass analysis is performed on Agilent Technologies MS-
S975C inert XLEI/CIMSD with triple axis detector. X-ray single crystal structure data for
compound 43 (CCDC no. 1882307) were collected on a Bruker D8 VENTURE diffractometer
equipped with CMOS Photon 100 detector and MoKα (λ = 0.71073 Å) radiation was used. Room
temperature corresponds to 25oC (computing data collection: Bruker APEX2). Low temperature
reaction performed over EYELA PSL-1810. Column chromatography was performed on glass
columns loaded with silica gel (60-120 mesh size) purchased from RANKEM Pvt. Ltd. India. TLC
analysis of reaction mixtures was performed using Merck silica gel (60 F254) plates and spots
were visualized by UV irradiation. Melting points were recorded in capillary tubes and are
uncorrected. Substituted benzamides were prepared by reported procedure.28-29 1H and 13C NMR
of 2-halobenzamides (24, 37-39, 40-41) are presented in supporting information (SI).
Peroxide decomposing GPx-like antioxidant property (thiol assay): The thiol-peroxidase like
activity was performed spectrophotometrically (eq. 1). The test mixture contained benzenethiol
(1.0 mM), organoselenium catalyst (0.1 mM) and hydrogen peroxide (3.75 mM). Reaction of
model compound with PhSH and H2O2 were studied in dried HPLC grade MeOH by following the
appearance of diphenyl disulfide absorption at 305 nm at 25 oC using molar extinction coefficient
as 1.24 mM-1cm-1 for PhSSPh.26,33
Radical Chain Breaking Antioxidant Property by DPPH Assay:
Purification of DPPH (DPPH•): The crude solid was crystallized from benzene-petroleum ether
0
(1:1). The melting point was taken carefully after drying it well and it was found 132-133 C
(literature 135 0C).36
Kinetic study: Radical chain breaking antioxidant activity of the synthesized hydroxy-
spiroselenuranes 29 and 30 has been evaluated by their hydrogen transfer capacity to 2,2-diphenyl-
o
1-picrylhydrazyl (DPPH•) radical in 80% methanol: water (v/v) at 25 C at 519 nm.35 The
quenching of DPPH• by antioxidants were monitored by using UV-visible spectrophotometry.
Each experiments conducted thrice. Rate constant was calculated by plotting natural log of
absorbance (OD) of DPPH• vs time (min). The slope which is equal to rate constant was obtained
by liner fit.
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A typical synthetic procedure. 2,2'-selenobis(N-arylbenzamides): Under inert atmosphere, 4.15
g (52.5 mmol, 1.0 equiv) of grinded selenium powder and dry THF (30 mL) were taken in single
neck round bottom flask. To this suspension, 2.53 g (2.1 equiv, 110 mmol) of fresh Na-pieces was
added cautiously with stirring and followed by 1.28 g (2 equiv, 10 mmol) of naphthalene was
added. Further, reaction mixture was allowed to stir at room temperature for 12 h. During this
period, colour changes from reddish brown to off-white. THF solvent was evaporated under
vacuum. To this, 2 equivalents (100 mmols) of corresponding 2-iodo-N-arylbenzamides and 4-
metoxy-2-bromo-N-arylbenzamide (31-35, and 36) and 5 mL of HMPA was added to the reaction
mixture. 1.90 g (10 mmol, 0.2 equiv) of CuI was added and allowed to stir at 80 °C for 60 h.
Reaction mixture was added to 300-400 mL of brine and stirred vigorously for 3-4 h. Residue was
filtered out and washed with distilled water. Crude product was dried under vacuum. Selenides 24,
37-39, 40, 41 were purified by washing of crude product with diethyl ether (20 mL x 2) to remove
trace amount of unreacted starting material and dried under high vacuum.
1
2,2'-Selenobis(N-phenylbenzamide) (24):19,20 White solids, yield: 86%, 4.29 g. H NMR
(DMSO-d6, 500 MHz) δ 10.44 (s, 2H), 7.71 (t, J = 6.2 Hz, 6H), 7.36 – 7.32 (m, 10H), 7.10 (t, J =
7.3 Hz, 2H). 13C NMR (DMSO-d6, 126 MHz) δ 167.22, 139.56, 139.45, 134.54, 132.31, 131.33,
13
129.14, 128.57, 127.66, 124.21, 120.40. C NMR DEPT-135 (DMSO-d6, 126 MHz) δ 134.54,
131.33, 129.14, 128.57, 127.66, 124.21, 120.40 (all CH). 77Se NMR (DMSO-d6, 76 MHz) δ
419.33.
1
2,2'-Selenobis(N-(2-methoxyphenyl)benzamide) (37):20 White solid, yield: 94%, 4.81 g. H
NMR (CDCl3, 76.31 MHz) δ 8.52 (s, 2H), 8.36 (d, J = 7.7 Hz, 2H), 7.67 (dd, J = 7.2, 1.7 Hz, 2H),
7.48 (dd, J = 7.2, 1.7 Hz, 2H), 7.36-7.30 (m, 4H), 6.99 (td, J = 7.9, 1.5 Hz, 2H), 6.91 (t, J = 7.3
13
Hz, 2H), 6.75 (dd, J = 8.0, 0.9 Hz, 2H), 3.71 (s, 6H). C NMR (CDCl3, 101 MHz) δ 165.88,
148.18, 137.87, 134.80, 131.98, 131.41, 128.59, 127.71, 127.55, 123.88, 120.86, 119.67, 109.84,
55.63. 13C NMR DEPT-135 (CDCl3, 101 MHz) δ 134.80, 131.40, 128.60, 127.70, 123.85, 120.87,
119.67, 109.81 (all CH), 55.62 (CH3). 77Se NMR (CDCl3, 76 MHz) δ 427.11.
1
2,2'-Selenobis(N-(3-methoxyphenyl)benzamide) (38):20 White solid, yield: 91%, 4.65 g. H
NMR (CDCl3, 76.31 MHz) δ 8.03 (s, 2H), 7.60 (dd, J = 5.9, 3.2 Hz, 2H), 7.50 – 7.43 (m, 2H), 7.34
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– 7.26 (m, 4H), 7.15 – 7.09 (m, 3H), 6.84 (d, J = 7.9 Hz, 2H), 6.63 (dd, J = 8.2, 2.0 Hz, 2H), 3.71
(s, 6H). 13C NMR (CDCl3, 101 MHz) δ 166.39, 160.04, 138.85, 137.84, 134.81, 131.47, 130.79,
129.52, 128.98, 128.08, 112.19, 110.55, 105.50, 55.28. 13C NMR DEPT-135 (CDCl3, 101 MHz)
δ 134.81, 131.47, 129.52, 128.98, 128.08, 112.18, 110.55, 105.50 (all CH), 55.28 (CH3). 77Se NMR
(CDCl3, 76 MHz) δ 416.64.
2,2'-Selenobis(N-(4-methoxyphenyl)benzamide) (39): White solid, yield: 94%, m.p.: 165-167
0C, 4.81 g. 1H NMR (DMSO-d6, 76.31 MHz) δ 10.27 (s, 2H), 7.66 (d, J = 7.0 Hz, 2H), 7.58 (d, J
= 8.9 Hz, 4H), 7.39 – 7.27 (m, 6H), 6.86 (d, J = 8.9 Hz, 4H), 3.70 (s, 6H). 13C NMR (DMSO-d6,
101 MHz) δ 166.80, 156.03, 139.63, 134.50, 132.62, 132.42, 131.16, 128.50, 127.56, 121.94,
13
114.25, 55.66. C NMR DEPT-135 (DMSO-d6, 101 MHz) δ 134.50, 131.17, 128.49, 127.56,
121.94, 114.25 (all CH), 55.66(CH3). 77Se NMR (DMSO-d6, 76 MHz) δ 419.40.
0
2,2'-selenobis(N-(1-naphthyl)benzamide) (40): Yellow solid, yield: 89%, m.p.: 198-200 C,
1
5.08 g. H NMR (DMSO-d6, 76.31 MHz) δ 10.47 (s, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.90 (t, J =
11.2 Hz, 4H), 7.80 (d, J = 8.0 Hz, 2H), 7.61 – 7.33 (m, 14H). 13C NMR (DMSO-d6, 101 MHz) δ
168.18, 139.04, 134.65, 134.21, 133.92, 132.46, 131.42, 129.23, 128.96, 128.80, 128.47, 128.19,
13
127.78, 126.65, 126.52, 126.42, 126.38, 125.96, 123.79, 123.71(all CH). C NMR DEPT-135
(DMSO-d6, 101 MHz) δ 134.65, 131.42, 128.80, 128.47, 127.78, 126.65, 126.52, 126.38, 125.96,
123.79, 123.71. 77Se NMR (DMSO-d6, 76 MHz) δ 423.46; HRMS (ESI) m/z calculated for
C34H24N2O2Se [M+H]+ 573.1078, found 573.1079.
6,6'-Selenobis(3-methoxy-N-phenylbenzamide) (41): Yellowish white solid, yield: 92%, m.p.:
140-142 0C, 5.12 g. 1H NMR (500 MHz, DMSO-d6) δ 3.83 (s, 3H), 7.00 (dd, J = 8.7, 2.8 Hz, 1H),
7.05 – 7.13 (m, 1H), 7.21 – 7.27 (m, 2H), 7.33 (dd, J = 8.5, 7.4 Hz, 2H), 7.63 – 7.75 (m, 2H), 10.38
(s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 56.01, 113.79, 117.48, 120.40, 122.40, 124.16, 129.10,
136.03, 139.43, 140.86, 158.80, 166.96. 77Se NMR (95 MHz, DMSO-d6) δ 384.67. HRMS (ESI)
m/z calculated for C28H24N2O4Se [M-H]+ 531.0819, found 531.0801.
Spirodiazaselenuranes (14, 15,17, 42, 43, 44): Hydrogen peroxide (aqueous, 30%) was added to
a stirred CH2Cl2 solution containing of respective 2,2'-selenobis(N-arylbenzamide) 27, 35-39, 43,
and 44 (0.1 mmol, 1 equiv). The reaction mixture was allowed to stir for 20-24 h at 25 °C and then
solvent was evaporated to dryness. Resultant solids were pass through column of silica gel using
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petroleum ether/ethyl acetate as eluent to give the pure spirodiazaselenuranes 14, 15, 17, and 42-
44 in 96-99% yields.
(N-phenyl) spirodiazaselenuranes (14):19,20 White solid. Yield: 99%, 46.47 mg 1H NMR (CDCl3,
76.31 MHz) δ 8.27 (dd, J = 7.5, 1.2 Hz, 2H), 7.86 (d, J = 8.1 Hz, 2H), 7.72 – 7.67 (m, 6H), 7.62 –
13
7.57 (m, 2H), 7.40 (t, J = 7.9 Hz, 4H), 7.18 (t, J = 7.4 Hz, 2H). C NMR (CDCl3, 101 MHz) δ
164.60, 140.51, 135.62, 135.37, 133.91, 133.07, 129.87, 129.64, 126.44, 125.23, 123.35. 13C NMR
DEPT-135 (CDCl3, 101 MHz) δ 133.91, 133.07, 129.87, 129.64, 126.44, 125.24, 123.35 (all CH).
77Se NMR (CDCl3, 76 MHz) δ 571.79.
(N-(2-Methoxy)phenyl) spirodiazaselenuranes (15):20 White solid, yield: 98%, 52 mg. 1H NMR
(CDCl3, 76.31 MHz) δ 8.20 (dd, J = 7.5, 1.2 Hz, 2H), 8.11 (d, J = 8.0 Hz, 2H), 7.75 (dd, J = 7.8,
1.3 Hz, 2H), 7.64 – 7.60 (m, 3H), 7.55 – 7.51 (m, 2H), 7.25 – 7.19 (m, 2H), 7.06 – 6.98 (m, 4H),
13
6.85 (t, J = 8.5 Hz, 2H), 3.76 (s, 6H). C NMR (CDCl3, 101 MHz) δ 166.13, 153.40, 136.45,
134.78, 132.25, 131.58, 129.48, 128.18, 127.56, 126.96, 126.27, 121.44, 120.84, 112.23, 110.02,
55.80, 55.64. 13C NMR DEPT-135 (CDCl3, 101 MHz) δ 133.12, 132.25, 129.40, 128.18, 127.56,
126.96, 126.27, 121.44, 112.23, 110.02 (all CH), 55.80, 55.64 (CH3). 77Se NMR (CDCl3, 76 MHz)
δ 592.33.
(N-(3-Methoxy)phenyl) spirodiazaselenuranes (17):20 White solid, yield: 99%, 52 mg. 1H NMR
(CDCl3, 76.31 MHz) δ 8.26 (dd, J = 7.5, 1.2 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.69 (t, J = 7.3 Hz,
1H), 7.65 – 7.53 (m, 1H), 7.42 (t, J = 2.1 Hz, 1H), 7.32 – 7.22 (m, 1H), 7.15 (dd, J = 8.0, 1.1 Hz,
1H), 6.73 (dd, J = 8.2, 2.1 Hz, 1H), 3.81 (s, 3H). 13C NMR (CDCl3, 101 MHz) δ 164.61, 160.52,
141.74, 135.66, 135.37, 133.95, 133.07, 130.20, 129.80, 126.47, 115.41, 110.71, 109.26, 77.35,
13
77.03, 76.71, 55.40. C NMR DEPT-135 (CDCl3, 101 MHz) δ 133.95, 133.07, 130.20, 129.80,
126.47, 115.41, 110.71, 109.25 (all CH), 55.40 (CH3). 77Se NMR (CDCl3, 76 MHz) δ 574.75.
(N-(4-Methoxy)phenyl) spirodiazaselenuranes (42): White solid, yield: 98%, m.p.: 230-232 0C,
52 mg. 1H NMR (DMSO-d6, 76.31 MHz) δ 8.03 (d, J = 6.3 Hz, 2H), 7.78 – 7.64 (m, 10H), 6.93
13
(d, J = 8.9 Hz, 4H), 3.71 (s, 6H). C NMR (DMSO-d6, 101 MHz) δ 164.58, 156.63, 136.73,
136.07, 134.46, 134.02, 133.07, 129.05, 126.46, 125.94, 114.59, 55.70. 13C NMR DEPT-135
(DMSO-d6, 101 MHz) δ 134.02, 133.07, 129.05, 126.46, 125.94, 114.59, 55.69. 77Se NMR
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(DMSO-d6, 76 MHz) δ 584.24; HRMS (ESI) m/z calculated for C28H22N2O4Se [M+H]+ 531.0819,
found 531.0801.
(N-(1-Naphthyl)) spirodiazaselenuranes (43): Off white solid, yield: 98%, m.p.: 232-234 0C, 60
mg. 1H NMR (CDCl3, 500 MHz) δ 8.31 (dd, J = 7.5, 1.2 Hz, 2H), 8.28 (d, J = 7.6 Hz, 2H), 7.95
(d, J = 8.5 Hz, 4H), 7.85 (d, J = 8.2 Hz, 2H), 7.72 (t, J = 7.3 Hz, 2H), 7.60 – 7.52 (m, 10H). 13C
NMR (CDCl3, 126 MHz) δ 164.91, 136.24, 135.55, 135.16, 133.51, 133.02, 130.08, 129.88,
128.93, 127.56, 126.66, 126.48, 126.41, 125.78, 123.91. 13C NMR DEPT-135 (CDCl3, 126 MHz)
77
δ 133.51, 133.02, 130.08, 128.93, 127.56, 126.66, 126.48, 126.41, 125.78, 123.91. Se NMR
(CDCl3, 76 MHz) δ 578.27; HRMS (ESI) m/z calculated for C34H22N2O2Se [M+H]+ 570.0922,
found 571.0902. X-ray quality crystal were obtained from CH2Cl2 solvent.
5,5'-Dimethoxy-2,2'-diphenyl-1l4-1,1'-spirobi[benzo[d][1,2]selenazole]-3,3'(2H,2'H)-dione
1
(44): m.p.: 160-163 0C Yellowish white solid, yield: 98%, 52 mg. H NMR (500 MHz, DMSO-
d6) δ 3.85 (s, 3H), 7.16 (tt, J = 7.4, 1.2 Hz, 1H), 7.26 (dd, J = 9.0, 2.9 Hz, 1H), 7.35 – 7.43 (m,
2H), 7.55 (d, J = 2.9 Hz, 1H), 7.62 (d, J = 8.9 Hz, 1H), 7.79 – 7.94 (m, 2H). 13C NMR (126 MHz,
DMSO-d6) δ 56.46, 113.36, 120.27, 120.54, 124.13, 124.76, 126.97, 128.02, 129.43, 129.75,
137.95, 141.82, 163.25, 164.38. 77Se NMR (95 MHz, DMSO-d6) δ 580.02.
Hydroxy-substituted selenides (45, 46): In a long neck, 10 mL round bottom flask monoselenides
(37 and 41) (0.1 mmol) were dissolved in CH2Cl2 (10 mL) under nitrogen atmosphere and cooled
to -78 oC. After that, BBr3 (0.4 mL, 0.38 mmol, 1M solution in CH2Cl2) was added via a syringe
o
and the resulted solution was stirred at -78 C for 30 min. After this, reaction temperature was
raised to room temperature and the resulted reaction mixture was stirrer for 12 hours. CH2Cl2 was
evaporated under vacuum, the resulted residue was washed with distilled water and resulted sold
dried under vacuum. Crystallization from dichloromethane resulted in white crystalline solid.
2,2'-Selenobis(N-(2-hydroxyphenyl)benzamide) 45: White solid, yield: 92%, m.p.: 138-140 0C,
46 mg. 1H NMR (500 MHz, DMSO-d6) δ 6.82 (t, J = 7.7 Hz, 1H), 6.92 (dd, J = 8.1, 1.4 Hz, 1H),
7.03 (td, J = 7.7, 1.7 Hz, 1H), 7.43 (dd, J = 7.4, 1.9 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.79 (d, J =
7.4 Hz, 1H), 9.59 (s, 1H), 9.71 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 116.41, 119.44, 124.04,
77
126.07, 126.23, 127.63, 128.56, 131.42, 132.83, 134.58, 138.77, 149.40, 167.23. Se NMR (95
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MHz, DMSO-d6) δ 424.91. HRMS (ESI) m/z calculated for C26H20N2O4Se [M+H]+ 505.0661,
found 505.0681.
6,6'-selenobis(3-hydroxy-N-phenylbenzamide) 46: White solid, yield: 91%, m.p.: 98-100 0C, 45
1
mg. H NMR (500 MHz, DMSO-d6) δ 6.80 (dd, J = 8.5, 2.7 Hz, 1H), 7.02 (d, J = 2.7 Hz, 1H),
7.08 (tt, J = 7.3, 1.2 Hz, 1H), 7.14 (d, J = 8.6 Hz, 1H), 7.29 – 7.35 (m, 2H), 7.69 (d, J = 8.0 Hz,
2H), 9.88 (s, 1H), 10.32 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 115.15, 118.62, 120.21,
120.27, 124.05, 129.09, 136.17, 139.55, 141.09, 157.01, 167.24. 77Se NMR (95 MHz, DMSO-d6)
δ 376.39. HRMS (ESI) m/z calculated for C26H20N2O4Se [M-H]+ 503.0510, found 503.0428.
Hydroxy substituted spirodiazaselenuranes (29, 30): Hydrogen peroxide (aqueous, 30% w/w)
was added to a stirred CH2Cl2 solution containing of respective hydroxy substituted selenides (45,
46) (0.1 mmol, 1 equiv). The reaction mixture was allowed to stir for 20-24 h at 25 °C, progress
of the reaction was monitored by TLC, after complete conversion of selenides (45 and 46), solvent
was evaporated to dryness. The resulted white colored compounds were purified by crystallization
using CH2Cl2.
(N-(2-Hydroxy)phenyl) Spirodiazaselenuranes (29): White solid, yield: 98%, m.p.: 205-207 0C,
51 mg. 1H NMR (500 MHz, DMSO-d6) δ 6.90 (td, J = 7.6, 1.4 Hz, 1H), 6.98 (dd, J = 8.1, 1.4 Hz,
1H), 7.12 (td, J = 7.8, 1.7 Hz, 1H), 7.68 (td, J = 8.0, 1.6 Hz, 1H), 7.72 (dd, J = 7.8, 1.7 Hz, 1H),
7.76 (td, J = 7.4, 1.2 Hz, 1H), 8.07 (ddd, J = 17.8, 7.7, 1.4 Hz, 2H), 9.85 (s, 1H). 13C NMR (126
MHz, DMSO-d6) δ 14.56, 29.46, 31.17, 60.22, 116.39, 117.65, 119.42, 120.06, 126.52, 127.22,
77
128.07, 128.78, 129.05, 133.01, 133.95, 134.92, 137.62, 152.11, 165.29. Se NMR (95 MHz,
DMSO-d6) δ 596.04. HRMS (ESI) m/z calculated for C26H18N2O4Se [M+Na]+ 525.0326, found
525.0347
5,5'-Dihydroxy-2,2'-diphenyl-1l4-1,1'-spirobi[benzo[d][1,2]selenazole]-3,3'(2H,2'H)-dione
(30): Off white solid, yield: 98%, m.p.: 130-132 0C, 51 mg. 1H NMR (500 MHz, DMSO-d6) δ
6.81 (dd, J = 8.5, 2.7 Hz, 1H), 7.03 (d, J = 2.7 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1H), 7.15 (d, J = 8.6
Hz, 1H), 7.32 (t, J = 7.8 Hz, 3H), 7.70 (d, J = 8.1 Hz, 3H), 10.34 (s, 1H). 13C NMR (126 MHz,
CDCl3 with DMSO-d6) δ 165.53, 153.45, 138.64, 138.15, 128.54, 127.26, 123.80, 119.89,
119.09, 117.45, 117.40. 77Se NMR (95 MHz, DMSO-d6) δ 579.99. HRMS (ESI) m/z calculated
for C26H18N2O4Se [M+Na]+ 525.0326, found 525.0506
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Acknowledgements. SK thanks to DST-SERB New Delhi (EMR/2015/000061) and IISER
Bhopal for financial support. RK and MB for IISER Bhopal fellowships. We thankful to Mr.
Aditya Upadhyay, IISER Bhopal for solving crystal structure data of 43.
1
13
77
Supporting Information. H, C, Se NMR and mass spectra of synthesized compounds and
crystallographic details of spiroselenurane 43 (CCDC no. 1882307). These materials are available
from the website.
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