Metal-Free Three-Component Coupling Reaction of Ketones with Electron-rich Arenes and Selenium Dioxide for the Synthesis of α-Arylselanyl Ketones

Article abstract of DOI:10.1021/acs.joc.0c02028

A metal-free three-component coupling reaction of aryl alkyl/alkyl ketones, SeO2, and phenols/anisoles is described. This multicomponent reaction provides a straightforward and facile pathway for the synthesis of α-((4-hydroxy/methoxyphenyl)selanyl)-aryl alkyl/alkyl ketones in the presence of p-toluenesulfonic acid for the C-Se bond formation process. The method offers an attractive and simple procedure using commonly available shelf reagents to deliver organoselenides that, to our knowledge, are being reported here for the first time.

Full text of DOI:10.1021/acs.joc.0c02028

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Note
Metal-Free Three-Component Coupling Reaction of Ketones with
Electron-rich Arenes and Selenium Dioxide for the Synthesis of
α‑Arylselanyl Ketones
Kmendashisha Wanniang, O. Risuklang Shangpliang, Ibakyntiew D. Marpna, Tyrchain Mitre Lipon,
Badaker M. Laloo, and Bekington Myrboh*
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ABSTRACT: A metal-free three-component coupling reaction of aryl
alkyl/alkyl ketones, SeO2, and phenols/anisoles is described. This
multicomponent reaction provides a straightforward and facile pathway
for the synthesis of α-((4-hydroxy/methoxyphenyl)selanyl)-aryl alkyl/
alkyl ketones in the presence of p-toluenesulfonic acid for the C−Se
bond formation process. The method offers an attractive and simple
procedure using commonly available shelf reagents to deliver organo-
selenides that, to our knowledge, are being reported here for the first
time.
Scheme 1. Synthesis of α-Phenylseleno Ketones
he last three decades have witnessed the emergence of
organoselenium compounds as important reagents and
T
intermediates in organic synthesis. Many of these compounds
have been studied and reported because of their interesting
reactivities,1 potential biological activities, and pharmaceutical
properties.2 Among these compounds, α-phenylseleno ketones
have been recognized as the versatile intermediates in organic
synthesis, particularly for the introduction of unsaturated
function via syn-elimination.3 In addition, α-phenylseleno
ketones can also be transformed into other useful synthetic
intermediates, which are common structural elements found in
naturally occurring substances4a and in a number of
pharmaceutically relevant molecules4b,c such as α-hydroxy
esters,4d allylic alcohols,4e allylic amines,4f α-amino acids,4g and
terminal aziridines.4h Very recently, Pandey et al. have
extended the synthetic utility of α-phenylseleno ketones as a
precursor in the synthesis of intermolecular α-arylation of
ketones by cross-coupling with electron-rich arenes.5 Fur-
thermore, Cotgreave6a and Engman6b have described the
biological importance of α-phenylseleno ketones and reported
that it mimics the properties of glutathione peroxidase, like
ebselen. Various synthetic methods employing different
selenium sources have been developed for the synthesis of α-
phenyl selenylation of ketones.3−11 In 1997, Houllemare and
co-workers have reported a method for the preparation of α-
phenylseleno ketones and aldehydes using phenylselenium
trichloride as an electrophilic selenium reagent (Scheme 1a).7e
Nishiyama et al. have shown that the synthesis of α-
phenylseleno ketones can be achieved by the palladium
metal complex-catalyzed method in the reaction of α-
haloketones with phenyl tributylstannyl selenide as the
phenylselenylating agents (Scheme 1b).8c In 2015, Movassagh
Received: August 22, 2020
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© XXXX American Chemical Society
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a
and Takallou reported a method using a versatile reagent
N,N,N-triphenylselenylisocyanuric acid (TPSCA) in the L-
prolinamide-promoted process for the α-phenylselenenylation
of ketones (Scheme 1c).10c Recently, Cao and his group have
shown the direct selenylation of ketones using sodium
selenites-based reagents (Scheme 1d).11 Although the
literature review revealed that the reported methods are
adequate; however, some of the selenylating reagents suffer
various drawbacks as they require well-defined reaction
conditions due to their instability toward air and moisture,
are synthesized in multiple step reactions, form various reactive
byproducts, are expensive, and release malodorous and highly
toxic vapors. Thus, an alternative method for the synthesis of
α-phenylseleno ketones using stable selenium reagents under
mild reaction conditions would indeed be useful to organic
chemists.
Table 1. Optimization of Reaction Conditions
temperature
time
(h)
yield
(%)
entry
acid (equiv)
solvent
(°C)
1
2
3
4
5
6
7
8
PTSA (0.25)
PTSA (0.25)
PTSA (0.25)
PTSA (0.5)
PTSA (0.7)
toluene
toluene
toluene
toluene
toluene
rt
rt
18
36
6
3
3
3
3
3
20
50
50
85
40
50
55
30
20
0
60
60
60
60
60
60
60
60
60
BF3·Et2O (0.5) toluene
TFA (0.5)
PTSA (0.5)
PTSA (0.5)
PTSA (0.5)
toluene
DCM
CH3CN
DMSO
toluene
Recently, we have demonstrated the successful use of SeO2
as an efficient inorganic reagent, which, in the presence of a
Lewis acid, facilitated the reaction between aromatic ketones
and aromatic hydrocarbons to affect C−C coupling at the α-
carbon atom,12a while the same reaction catalyzed by an
organic acid p-toluenesulfonic acid monohydrate (PTSA)
yielded unsymmetrical benzils.12b Again, aryl methyl ketones
reacted efficiently with secondary amines in DMSO in the
presence of SeO2 to affect α-selenoamidation of aryl methyl
ketones,12c while in the presence of PTSA, alkyl/aryl ketones
reacted with aliphatic alcohols mediated by SeO2 to generate a
library of α-ketoacetals.12d It is evident from these reactions
involving SeO2 that the nature of the acid and/or the solvent
used to play a major role in determining the path of the
reaction. We were keen to know, therefore, the direction the
reaction would take when alkyl/aryl ketones are allowed to
react with phenols in the presence of PTSA. Thus, inspired by
our earlier success in the use of SeO2-mediated reactions in
organic syntheses and in continuation of our work in this area
of research, we wish to report here a new method for the
synthesis of α-((hydroxy/methoxyphenyl)selanyl)-aryl/alkyl
ketones by reacting aryl/alkyl ketones with phenols/anisoles
in the presence of SeO2 catalyzed by PTSA. To the best of our
knowledge, this is the first instance where selenium dioxide is
directly used as the selenium source in a one-pot reaction
between ketones and phenols/anisoles, resulting in the
incorporation of selenium at the α-carbon of the ketones.
We began our investigation by employing propiophenone
(1a) and phenol (3a) as the model substrates to determine the
optimal reaction conditions (Table 1). In an initial attempt, a
mixture of propiophenone (1a, 1 equiv), phenol (3a, 1.2
equiv), and selenium dioxide (2, 1 equiv) was stirred with
PTSA (0.25 equiv) in toluene (1 mL) at room temperature for
18 h, where we obtained only 20% yield of the desired product
4a (Table 1, entry 1). When the same reaction was carried out
for a longer reaction time (36 h), the yield of the product
increases to 50% (Table 1, entry 2). When the reaction
temperature was raised to 60 °C, the yield of 4a remained at
50%, but the reaction time was greatly reduced (Table 1, entry
3). With further optimization by varying amounts of the acid
(Table 1, entries 4 and 5), it was found that 0.5 equiv of PTSA
gave the optimum yield of the product 4a (85%, Table 1, entry
4). When the amount of PTSA was increased (Table 1, entry
5), multiple spot formation was observed, and only 40% yield
of product 4a was obtained. Among the acids (Table 1, entries
4, 6 and 7) and solvents (Table 1, entries 4, 8−10) studied,
PTSA is the most efficient catalyst, and toluene is the best
9
10
11
18
18
24
NR
a
Reaction conditions: ketone (1a) (1 mmol, 1.0 equiv), SeO2 (2) (1
mmol, 1.0 equiv), phenol (3a) (1.2 mmol, 1.2 equiv), solvent (1 mL),
60 °C.
medium that provides the best result in terms of yields (Table
1, entry 4). Finally, no desired product was formed in the
absence of PTSA (Table 1, entry 11), demonstrating its
indispensable role in the reaction scheme.
With the optimal reaction conditions in hand, the scope of
the reaction was investigated. Differently substituted aryl ethyl
ketones, such as propiophenone (1a), 4-methylpropiophenone
(1b), 4-chloropropiophenone (1c), 4-bromopropiophenone
(1d) and 2-chloropropiophenone (1e), were first selected to
react with phenol (3a) (Scheme 2). Aryl ethyl ketones bearing
electron-donating or electron-withdrawing groups in the ring
were successfully converted to give the corresponding products
in excellent yields (4a, 85%; 4b, 80%; 4c, 86%; 4d, 79%; 4e,
88%). The scope of the reaction was further applied to
aromatic ketones with an extended aliphatic counterpart with
equal success. Thus, butyrophenone (1f) and valerophenone
(1g) gave 2-((4-hydroxyphenyl)selanyl)-1-phenylbutan-1-one
(4f) and 2-((4-hydroxyphenyl)selanyl)-1-phenylpentan-1-one
(4g), respectively, in good yields.
Next, we investigated the substrate scope of electron-
donating phenols derivatives reacting with different substituted
aryl ethyl ketones including 2-methylphenol (3b) with 2-
chloropropiophenone (1e) and 2-methoxyphenol (3c) with
propiophenone (1a), where the desired products 4h and 4i
were obtained in 87% and 82% yields. Under similar
conditions, phenols with an electron-withdrawing group such
as 2-chlorophenol (3d) when reacted with 4-methylpropio-
phenone (1b) also afforded the desired product 4j in good
yield (78%). Disubstituted phenols such as 2,5-dimethyl
phenol (3e) and 2,6-dimethyl phenol (3f), which contribute
to the steric hindrance effect, gave the corresponding products
4k and 4l in satisfactory yields (75% and 86%). Unfortunately,
when 2-napthol was treated with 1a, the expected product was
not obtained. Also, reactions of substituted phenols at the
para-position such as 4-nitrophenol and 4-aminophenol were
carried out; however, the desired products were not obtained
as the para-position, which is the reactive site, was blocked.
This protocol was also extended toward anisole and aniline
derivatives. To our delight, anisole (5a) and 2-methyl anisole
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a
a
Scheme 2. Substrate Scope of Aryl Alkyl Ketones
Scheme 3. Substrate Scope of Alkyl Methyl Ketones
a
Reaction conditions: ketones (1) (1 mmol, 1.0 equiv), SeO2 (2) (1
mmol, 1.0 equiv), phenols (3)/anisoles (5) (1.2 mmol, 1.2 equiv),
PTSA (0.5 mmol, 0.5 equiv), solvent (1 mL), rt.
structure of the products was defined by the XRD data of
compound 8c (included in the Supporting Information).
To demonstrate the potential applicability of the method in
organic synthesis, a gram scale reaction of 1a with 2 and 3a was
carried out under standard conditions, yielding the product 4a
in 81% yield (Scheme 4).
Scheme 4. Gram-Scale Reaction
a
Reaction conditions: ketones (1) (1 mmol, 1.0 equiv), SeO2 (2) (1
mmol, 1.0 equiv), phenols (3)/anisoles (5) (1.2 mmol, 1.2 equiv),
PTSA (0.5 mmol, 0.5 equiv), solvent (1 mL), 60 °C.
(5b) also coupled with propiophenone (1a) and 4-
bromopropiophenone (1d) to give the α-selenylated product
6a, 6b, and 6c in moderate yields (55−60%). However, the
formation of the desired product was not observed when aryl
ethyl ketone was treated with aniline. Other aromatic systems
like chlorobenzene and benzaldehyde do not react at all with
aryl ethyl ketones, while the reaction with acetophenone
displayed multiple spot formation. This explains that the
method is reactive toward those substrates that have phenol-
like reactivity.
The plausible mechanism involved in the reaction of ketone
1 with phenol 3 in the presence of SeO2 and PTSA is depicted
in Scheme 5. The initial reaction of the enolate anion 9 with
SeO2 resulted in the formation of α,α-diketoselenide 10
(isolated and characterized). Evidently, nucleophilic attack by
phenol 3 on the selenium intermediate yielded product 4 with
Scheme 5. Plausible Mechanism
The generality of this protocol was further expanded to
aliphatic ketones. The synthesis of α-((4-hydroxyphenyl)-
selanyl)alkyl ketones, however, proceeded at room temper-
ature (Scheme 3). Reactions of phenol with aliphatic ketones
such as ethyl methyl ketone (7a) and methyl propyl ketone
(7b) afforded the corresponding products 8a and 8b in 79%
and 81% yields, respectively. Likewise, reactions of branched
aliphatic ketones such as isobutyl methyl ketone (7c) and
isopentyl methyl ketone (7d) furnished the desired products
8c in 80% and 8d in 86% yields. When 3-methyl-2-butanone
(7e) and benzyl acetone (7f) were allowed to react with
phenol, the desired products 8e and 8f were obtained in 78%
and 85% yields, respectively. It was observed that reactions of
isobutyl methyl ketone (7c) with electron-donating substituted
phenols such as 2-methyl phenol (3b) and 2,6-dimethyl phenol
(3e) resulted in high yields of the corresponding products 8g
(87%) and 8h (89%). Further, the confirmation of the
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monitored by thin-layer chromatography (TLC). The mixture was
diluted with ethyl acetate (2 × 10 mL). The combined filtrate was
transferred to a separating funnel, neutralized with aqueous NaHCO3
(2 × 10 mL), and washed with aqueous NaCl (2 × 10 mL). The
organic layer was separated, dried over anhydrous Na2SO4, and
reduced under a vacuum. The crude products were purified by silica
column chromatography using ethyl acetate−hexane as an eluent to
obtain the corresponding products 8a−h.
2-((4-Hydroxyphenyl)selanyl)-1-phenylpropan-1-one (4a). This
compound was prepared following procedure A, using a mixture of
propiophenone (134 mg, 1 mmol), phenol (113 mg, 1.2 mmol), and
SeO2 (111 mg, 1 mmol). The product was obtained as a pale yellow
solid (260 mg, 85%), which was purified by column chromatography
SiO2 (5:95 ethyl acetate/hexane): IR (KBr film) 3491, 1674, 1487,
1427, 1223, 708 cm−1; mp 88−90 °C; 1H NMR (400 MHz, DMSO-
d6) δ 9.82 (s, 1H), 7.93 (d, J = 7.6 Hz, 2H), 7.59 (t, J = 7.2 Hz, 1H),
7.48 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.67 (d, J = 8.4 Hz,
2H), 4.93 (q, J = 6.8 Hz, 1H), 1.40 (d, J = 6.8 Hz, 3H) ppm; 13C{1H}
NMR (100 MHz, CDCl3) δ 196.9, 157.8, 139.2, 135.6, 133.1, 128.7,
128.5, 116.5, 115.1, 38.9, 16.5 ppm; 77Se NMR (57.25 MHz, CDCl3)
δ 359.35 ppm; HRMS (ESI) m/z calcd for C15H14O2Se [M + H]+
307.0237, found 307.0208.
2-((4-Hydroxyphenyl)selanyl)-1-(p-tolyl)propan-1-one (4b). This
compound was prepared following procedure A, using a mixture of 4-
methylpropiophenone (148 mg, 1 mmol), phenol (113 mg, 1.2
mmol), and SeO2 (111 mg, 1 mmol). The product was obtained as a
pale yellow solid (257 mg, 80%), which was purified by column
chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr film)
3329, 1648, 1601, 1578, 1218, 831 cm−1; mp 120−122 °C; 1H NMR
(400 MHz, CDCl3) δ 7.87 (d, J = 8.0 Hz, 2H), 7.28−7.23 (m, 4H),
6.85 (s, 1H), 6.68 (d, J = 8.8 Hz, 2H), 4.60 (q, J = 6.8 Hz, 1H), 2.43
(s, 3H), 1.59 (d, J = 6.8 Hz, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 196.9, 158.0, 144.2, 139.3, 133.2, 129.5, 128.8, 116.6, 115.4,
39.0, 21.8, 16.8 ppm; HRMS (ESI) m/z calcd for C16H16O2Se [M +
H]+: 321.0394, found 321.0379.
the elimination of one mole of the ketone, which presumably
takes part again in the diselenide formation. The formation of
the proposed intermediate 10 was further strengthened by the
reaction of 1a with SeO2 and PTSA in toluene where the
intermediate 2,2′-selenobis(1-phenylpropan-1-one) (10) was
isolated in 80% yield.
In conclusion, we have developed a new method for the
selenylation of ketones by the direct coupling of alkyl/aryl
ketones with phenols derivatives via a selenium bridge using
cheap and easily available SeO2 in a one-step procedure, in the
presence of PTSA. All reactions carried out provide easy access
to hitherto unreported α-phenylseleno ketones in moderate to
excellent yields.
EXPERIMENTAL SECTION
■
General Information. All reagents and solvents were purchased
from commercial suppliers and used without further purification.
Thin-layer chromatography (TLC) was performed on aluminum
sheets precoated with silica gel 60F254 (0.2 mm thicknesses), in which
the spots were visualized with UV light (λ = 254 nm). For
purification, column chromatography was carried out on silica gel
100−200 mesh. Melting points were recorded by the open capillary
tube method and are uncorrected. IR spectra were recorded on a
PerkinElmer Spectrum 400 FTIR instrument, and the frequencies are
expressed in cm−1. 1H NMR and 13C NMR spectra were recorded on
a Bruker Avance II-400 spectrometer in CDCl3 and DMSO-d6 using
tetramethylsilane (TMS) as an internal standard; chemical shifts (δ)
values are expressed in parts per million (ppm) and coupling
constants (J) in hertz (Hz). HRMS was recorded on an Agilent 6520
Q-TO spectrometer, and ESI-MS was recorded on a Waters UPLC-
TQD mass spectrometer. 77Se NMR spectra were recorded on a
Mercury Plus 300 Hz NMR spectrometer in ppm using Me2Se as an
internal standard.
1-(4-Chlorophenyl)-2-((4-hydroxyphenyl)selanyl)propan-1-one
(4c). This compound was prepared following procedure A, using a
mixture of 4-chloropropiophenone (168 mg, 1 mmol), phenol (113
mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol). The product was
obtained as a brown crystalline solid (293 mg, 86%), which was
purified by column chromatography SiO2 (5:95 ethyl acetate/
hexane): IR (KBr film) 3386, 1653, 1585, 1425, 1276, 1214, 827
Gram-Scale Synthesis of 4a. In a round-bottom flask, a mixture
of aryl alkyl ketones (1) (10 mmol, 1.341 g, 1.0 equiv), SeO2 (2) (10
mmol, 1.109 g, 1.0 equiv), phenols (3) (12 mmol, 0.941 g, 1.2 equiv),
PTSA (5 mmol, 0.951 g, 0.5 equiv), and toluene (10 mL) was added.
ο
The reaction mixture was allowed to stir for 3 h at 60 C in an oil
bath. After the completion of the reaction, which was monitored by
thin-layer chromatography (TLC), the mixture was cooled to room
temperature and diluted with ethyl acetate (200 mL). The combined
filtrate was transferred to a separating funnel, neutralized with
aqueous NaHCO3 (2 × 100 mL), and washed with aqueous NaCl (2
× 100 mL). The organic layer was separated, dried over anhydrous
Na2SO4, and reduced under a vacuum. The crude product was
purified by silica column chromatography (5:95 ethyl acetate/hexane)
to obtain the corresponding product 4a in 81% yield.
1
cm−1; mp 145−147 °C; H NMR (400 MHz, CDCl3, with 1% v/v
TMS) δ 7.82 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.8 Hz, 2H), 7.16 (d, J
= 8.8 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H), 4.49 (q, J = 6.8 Hz, 1H), 1.52
(d, J = 6.4 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 195.7,
157.8, 139.6, 139.2, 133.9, 129.9, 129.0, 116.5, 114.9, 38.9, 16.4 ppm;
77Se NMR (57.25 MHz, CDCl3) δ 456.60 ppm; HRMS (ESI) m/z
calcd for C15H13ClO2Se [M + H]+ 340.9848, found 340.9842.
1-(4-Bromophenyl)-2-((4-hydroxyphenyl)selanyl)propan-1-one
(4d). This compound was prepared following procedure A, using a
mixture of 4-bromopropiophenone (213 mg, 1 mmol), phenol (113
mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol). The product was
obtained as a pale yellow solid (303 mg, 79%), which was purified by
column chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr
film) 3290, 1653, 1580, 1488, 1425, 1276, 1216, 834 cm−1; mp 110−
112 °C; 1H NMR (400 MHz, CDCl3, with 1% v/v TMS) δ 7.74 (d, J
= 8.8 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 6.62
(d, J = 8.4 Hz, 2H), 4.48 (q, J = 6.8 Hz, 1H), 1.52 (d, J = 6.4 Hz, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 195.8, 157.8, 139.2, 134.4,
131.9, 130.0, 128.2, 116.5, 115.0, 38.9, 16.4 ppm; HRMS (ESI) m/z
calcd for C15H13BrO2Se [M + H]+ 384.9342, found 384.9324.
1-(3-Chlorophenyl)-2-((4-hydroxyphenyl)selanyl)propan-1-one
(4e). This compound was prepared following procedure A, using a
mixture of 3-chloropropiophenone (168 mg, 1 mmol), phenol (113
mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol). The product was
obtained as a pale yellow solid (300 mg, 88%), which was purified by
column chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr
film) 3334, 1652, 1580, 1428, 1230, 826, 701 cm−1; mp 114−116 °C;
1H NMR (400 MHz, CDCl3, with 1% v/v TMS) δ 7.76 (s, 1H), 7.67
General Procedure A for the Synthesis of 2-((4-Hydroxy/
methoxy-phenyl)selanyl)-aryl Alkyl Ketones (4a−l/6a−c). A
mixture of aryl alkyl ketones (1) (1.0 mmol), SeO2 (2) (1.0 mmol,
111 mg), phenols (3)/anisoles (5) (1.2 mmol), PTSA (0.5 mmol, 95
mg), and toluene (1 mL) was added in a round-bottom flask. The
ο
reaction mixture was allowed to stir in an oil bath at 60 C for 3 h.
After the completion of the reaction, which was monitored by thin-
layer chromatography (TLC), the mixture was cooled to room
temperature and diluted with ethyl acetate (2 × 10 mL). The
combined filtrate was transferred to a separating funnel, neutralized
with aqueous NaHCO3 (2 × 10 mL), and washed with aqueous NaCl
(2 × 10 mL). The organic layer was separated, dried over anhydrous
Na2SO4, and reduced under a vacuum. The crude products were
purified by silica column chromatography using ethyl acetate−hexane
as an eluent to obtain the corresponding products (4a−l/6a−c).
General Procedure B for the Synthesis of 3-((4-
Hydroxyphenyl)selanyl)-alkyl ketones 8a−h. A mixture of alkyl
ketones (7) (1.0 mmol), SeO2 (2) (1.0 mmol, 111 mg), phenols (3)
(1.2 mmol), PTSA (0.5 mmol, 95 mg), and toluene (1 mL) was
added in a round-bottom flask. The reaction mixture was stirred at
room temperature for 1.5 h. The completion of the reaction was
D
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(d, J = 8.0 Hz, 1H), 7.43 (d, J = 8 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H),
7.15 (d, J = 6.8 Hz, 2H), 6.68 (d, J = 6.8 Hz, 2H), 4.44 (q, J = 6.8 Hz,
1H), 1.50 (d, J = 5.6 Hz, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 194.7, 158.7, 138.8, 137.6, 134.6, 132.5, 129.7, 128.4, 126.4,
116.5, 114.9, 39.7, 16.6 ppm; HRMS (ESI) m/z calcd for
C15H13ClO2Se [M + H]+ 340.9848, found 340.9840.
acetate/hexane): IR (KBr film) 3324, 1644, 1569, 1397, 1293, 712
cm−1; mp 96−98 °C; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.0
Hz, 2H), 7.30 (s, 1H), 7.19−7.16 (m, 3H), 6.83 (d, J = 8.4 Hz, 1H),
5.75 (s, 1H), 4.56 (q, J = 6.8 Hz, 1H), 2.35 (s, 3H), 1.53 (d, J = 6.4
Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 196.1, 152.7,
143.9, 137.7, 137.6, 133.1, 129.3, 128.5, 120.1, 117.1, 116.9, 39.6,
21.7, 16.9 ppm; 77Se NMR (57.25 MHz, CDCl3) δ 458.67 ppm;
HRMS (ESI) m/z calcd for C16H15ClO2Se [M + H]+ 355.0004, found
355.0009.
2-((4-Hydroxyphenyl)selanyl)-1-phenylbutan-1-one (4f). This
compound was prepared following procedure A, using a mixture of
butyrophenone (148 mg, 1 mmol), phenol (113 mg, 1.2 mmol), and
SeO2 (111 mg, 1 mmol). The product was obtained as a pale yellow
solid (270 mg, 84%), which was purified by column chromatography
SiO2 (5:95 ethyl acetate/hexane): IR (KBr film) 3272, 1649, 1578,
1489, 1429, 1269, 1220, 1095, 701 cm−1; mp 107−109 °C; 1H NMR
(400 MHz, CDCl3, with 1% v/v TMS) δ 7.82 (d, J = 7.2 Hz, 2H),
7.44 (t, J = 7.2 Hz, 1H), 7.33 (t, J = 8.0 Hz, 2H), 7.12 (s, 1H), 7.09
(d, J = 8.4 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 4.21 (t, J = 7.2 Hz, 1H),
1.86−1.79 (m, 1H), 1.74−1.68 (m, 1H), 0.93 (t, J = 7.2 Hz, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 196.4, 158.0, 139.1, 136.0,
133.2, 128.7, 128.4, 116.5, 114.8, 47.1, 23.3, 12.7 ppm; HRMS (ESI)
m/z calcd for C17H18O2Se [M + H] 321.0394, found 321.0383.
2-((4-Hydroxyphenyl)selanyl)-1-phenylpentan-1-one (4g). This
compound was prepared following procedure A, using a mixture of
valerophenone (162 mg, 1 mmol), phenol (113 mg, 1.2 mmol), and
SeO2 (111 mg, 1 mmol). The product was obtained as a pale yellow
solid (271 mg, 81%), which was purified by column chromatography
SiO2 (5:95 ethyl acetate/hexane): IR (KBr film) 3422, 1651, 1581,
1428, 1230, 702 cm−1; mp 108−110 °C; 1H NMR (400 MHz,
CDCl3) δ 7.88 (d, J = 8.0 Hz, 2H), 7.51 (t, J = 7.2 Hz, 1H), 7.40 (t, J
= 7.6 Hz, 2H), 7.17 (d, J = 7.6 Hz, 2H), 6.62 (d, J = 8.0 Hz, 2H), 6.56
(s, 1H), 4.38 (t, J = 7.2 Hz, 1H), 1.91−1.82 (m, 1H), 1.79−1.70 (m,
1H), 1.52−1.44 (m, 1H), 1.42−1.31 (m, 1H),0.88 (t, J = 7.6 Hz, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 196.5, 157.9, 139.1, 136.1,
133.1, 128.7, 128. 4, 116.5, 44.9, 32.2, 21.2, 13.9 ppm; HRMS (ESI)
m/z calcd for C17H18O2Se [M + H]+ 335.0550, found 335.0511.
1-(3-Chlorophenyl)-2-((4-hydroxy-3-methylphenyl)selanyl)-
propan-1-one (4h). This compound was prepared following
procedure A, using a mixture of propiophenone (168 mg, 1 mmol),
2-methylphenol (130 mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol).
The product was obtained as a yellow crystalline solid (309 mg, 87%),
which was purified by column chromatography SiO2 (5:95 ethyl
acetate/hexane): IR (KBr film) 3403, 1667, 1568, 1483, 1334, 1223,
703 cm−1; mp 88−90 °C; 1H NMR (400 MHz, CDCl3, with 1% v/v
TMS) δ 7.74 (s, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.44 (d, J = 8.0 Hz,
1H), 7.31 (t, J = 7.6 Hz, 1H), 7.08 (s, 1H), 7.04 (d, J = 8.4 Hz, 1H),
6.56 (d, J = 8.0 Hz, 1H), 5.26 (s,1H), 4.45 (q, J = 6.8 Hz, 1H), 2.11
(s, 3H), 1.54 (d, J = 6.8 Hz, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 194.2, 154.7, 139.1, 136.6, 135.4, 133.7, 131.7, 128.8, 127.6,
125.5, 124.2, 114.8, 114.6, 38.4, 15.5, 14.6 ppm; HRMS (ESI) m/z
calcd for C16H15ClO2Se [M + H]+ 355.0004, found 354.9993.
2-((4-Hydroxy-3-methoxyphenyl)selanyl)-1-phenylpropan-1-one
(4i). This compound was prepared following procedure A, using a
mixture of propiophenone (134 mg, 1 mmol), 2-methoxyphenol (149
mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol). The product was
obtained as a pale yellow crystalline solid (275 mg, 82%), which was
purified by column chromatography SiO2 (5:95 ethyl acetate/
hexane): IR (KBr film) 3359, 1665, 1581, 1499, 1442, 1309, 1211,
709 cm−1; mp 75−77 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J =
7.6 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.36 (t, J = 8.0 Hz, 2H), 6.94
(d, J = 7.2 Hz, 1H), 6.76−6.74 (m, 2H), 5.65 (s, 1H), 4.57 (q, J = 7.2
Hz, 1H), 3.73 (s, 3H), 1.54 (d, J = 6.8 Hz, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 195.4, 145.9, 145.3, 135.0, 131.8, 130.0, 127.5,
127.4, 118.6, 115.0, 114.0, 54.9, 38.7, 15.9 ppm; 77Se NMR (57.25
MHz, CDCl3) δ 464.76 ppm; HRMS (ESI) m/z calcd for
C16H16O3Se [M + H]+ 337.0343, found 337.0331.
2-((4-Hydroxy-3,5-dimethylphenyl)selanyl)-1-(p-tolyl)propan-1-
one (4k). This compound was prepared following procedure A, using
a mixture of 4-methylpropiophenone (148 mg, 1 mmol), 2, 6-
dimethylphenol (146 mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol).
The product was obtained as a pale yellow solid (263 mg, 75%),
which was purified by column chromatography SiO2 (5:95 ethyl
acetate/hexane): IR (KBr film) 3419, 1750, 1476, 1336, 1201, 746
1
cm−1; mp 134−136 °C; H NMR (400 MHz, CDCl3) δ 7.73 (d, J =
8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.96 (s, 2H), 4.92 (s, 1H), 4.51
(q, J = 6.8 Hz, 1H), 2.35 (s, 3H), 2.09 (s, 6H), 1.53 (d, J = 6.8 Hz,
3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 195.3, 152.8, 142.6,
136.7, 132.4, 128.2, 127.6, 123.0, 114.8, 38.5, 20.7, 15.9, 14.7 ppm;
HRMS (ESI) m/z calcd for C18H20O2Se [M + H]+ 349.0707, found
349.0702.
1-(4-Chlorophenyl)-2-((4-hydroxy-2,5-dimethylphenyl)selanyl)-
propan-1-one (4l). This compound was prepared following
procedure A, using a mixture of 4-chloropropiophenone (168 mg, 1
mmol), 2,5-dimethylphenol (146 mg, 1.2 mmol), and SeO2 (111 mg,
1 mmol). The product was obtained as a yellow crystalline solid (318
mg, 86%), which was purified by column chromatography SiO2 (5:95
ethyl acetate/hexane): IR (KBr film) 3416, 1656, 1588, 1372, 1232,
748 cm−1; mp 108−110 °C; 1H NMR (400 MHz, CDCl3, with 1% v/
v TMS) δ 7.68 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.03 (s,
1H), 6.55 (s, 1H), 5.13 (s, 1H), 4.44 (q, J = 6.8 Hz, 1H), 2.16 (s,
3H), 2.05 (s, 3H), 1.54 (d, J = 6.4 Hz, 3H) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 194.7, 154.5, 141.3, 140.4, 138.2, 133.2, 128.8, 127.6,
121.2, 116.6, 115.6, 38.4, 21.9, 15.5, 14.0 ppm; HRMS (ESI) m/z
calcd for C17H17ClO2Se [M + H]+ 369.0161, found 369.0182.
2-((4-Methoxyphenyl)selanyl)-1-phenylpropan-1-one (6a). This
compound was prepared following procedure A, using a mixture of
propiophenone (134 mg, 1 mmol), anisole (130 mg, 1.2 mmol), and
SeO2 (111 mg, 1 mmol). The product was obtained as a yellow
crystalline solid (177 mg, 55%), which was purified by column
chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr film)
1
1663, 1585, 1487, 1268,1241, 709 cm−1; mp 77−79 °C; H NMR
(400 MHz, CDCl3) δ 7.84 (d, J = 7.6 Hz, 2H), 7.48 (t, J = 7.2 Hz,
1H), 7.37 (t, J = 7.2 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 6.73 (d, J = 8.8
Hz, 2H), 4.54 (q, J = 6.8 Hz, 1H), 3.73 (s, 3H), 1.51 (d, J = 7.2 Hz,
3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 196.1, 160.6, 138.8,
135.9, 132.7, 128.5, 128.4, 116.8, 114.7, 55.2, 39.5, 16.9 ppm; HRMS
(ESI) m/z calcd for C16H16O2Se [M + H]+ 321.0394, found
321.0380.
2-((4-Methoxy-3-methylphenyl)selanyl)-1-phenylpropan-1-one
(6b). This compound was prepared following procedure A, using a
mixture of propiophenone (134 mg, 1 mmol), 2-methylanisole (146
mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol). The product was
obtained as a pale yellow solid (195 mg, 58%), which was purified by
column chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr
1
film) 1662, 1587, 1489, 1247, 1133, 705 cm−1; mp 80−82 °C; H
NMR (400 MHz, CDCl3, with 1% v/v TMS) δ 7.90 (d, J = 7.6 Hz,
2H), 7.54 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 8.0 Hz, 2H), 7.23−7.18 (m,
2H), 6.70 (d, J = 8.4 Hz, 1H), 4.60 (q, J = 6.8 Hz, 1H), 3.82 (s, 3H),
2.15 (s, 3H), 1.60 (d, J = 6.8 Hz, 3H) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 196.3, 158.8, 139.4, 136.2, 136.0, 132.7, 128.4, 127.5,
116.3, 110.4, 55.3, 39.6, 39.3, 16.9, 16.1 ppm; HRMS (ESI) m/z calcd
for C17H18O2Se [M + H] 335.0550, found 335.0533.
2-((3-Chloro-4-hydroxyphenyl)selanyl)-1-(p-tolyl)propan-1-one
(4j). This compound was prepared following procedure A, using a
mixture of 4-methylpropiophenone (148 mg, 1 mmol), 2-
chlorophenol (155 mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol).
The product was obtained as a pale yellow solid (277 mg, 78%),
which was purified by column chromatography SiO2 (5:95 ethyl
1-(4-Bromophenyl)-2-((4-methoxy-3-methylphenyl)selanyl)-
propan-1-one (6c). This compound was prepared following
procedure A, using a mixture of 4-bromopropiophenone (213 mg, 1
mmol), 2-methylanisole (146 mg, 1.2 mmol), and SeO2 (111 mg, 1
mmol). The product was obtained as a yellow solid (248 mg, 60%),
E
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Note
which was purified by column chromatography SiO2 (5:95 ethyl
acetate/hexane): IR (KBr film) 1662, 1588, 1447, 1334, 1230, 709
(s, 3H), 0.89 (t, J = 7.6 Hz, 3H), ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 206.09, 158.0, 139.1, 116.5, 116.4, 58.8, 29.4, 24.9, 20.1, 9.9
ppm; HRMS (ESI) m/z calcd for C12H16O2Se [M + H]+ 273.0394,
found 273.0388.
1
cm−1; mp 100−102 °C; H NMR (400 MHz, CDCl3, with 1% v/v
TMS) δ 7.65 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H), 7.12−7.08
(m, 2H), 6.62 (d, J = 8.4 Hz, 1H), 4.45 (q, J = 6.4 Hz, 1H), 3.76 (s,
3H), 2.08 (s, 3H), 1.52 (d, J = 6.4 Hz, 3H) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 195.2, 158.9, 139.4, 136.1, 134.9, 131.6, 129.9, 127.7,
127.6, 116.2, 110.4, 55.3, 39.6, 16.7, 16.0 ppm; HRMS (ESI) m/z
calcd for C17H17BrO2Se [M + H]+ 412.9655, found 412.9631.
3-((4-Hydroxyphenyl)selanyl)butan-2-one (8a). This compound
was prepared following procedure B, using a mixture of butanone (72
mg, 1 mmol), phenol (113 mg, 1.2 mmol), and SeO2 (111 mg, 1
mmol). The product was obtained as a pale yellow solid (193 mg,
79%), which was purified by column chromatography SiO2 (5:95
ethyl acetate/hexane): IR (KBr film) 3283, 1680, 1579, 1489, 1431,
1272, 1224, 835 cm−1; mp 88−90 °C; 1H NMR (400 MHz, CDCl3) δ
7.24 (d, J = 7.6 Hz, 2H), 6.91 (s, 1H), 6.59 (d, J = 8.0 Hz, 2H), 3.67
(q, J = 6.8 Hz, 1H), 2.35 (s, 3H), 1.36 (d, J = 6.4 Hz, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 206.7, 157.9, 138.7, 116.6,
114.7, 45.8, 27.1, 15.7 ppm; 77Se NMR (57.25 MHz, CDCl3) δ
425.92 ppm; HRMS (ESI) m/z calcd for C10H12O2Se [M + H]+
245.0081, found 245.0073.
3-((4-Hydroxyphenyl)selanyl)pentan-2-one (8b). This compound
was prepared following procedure B, using a mixture of pentanone
(86 mg, 1 mmol), phenol (113 mg, 1.2 mmol), and SeO2 (111 mg, 1
mmol). The product was obtained as a yellow crystalline solid (209
mg, 81%), which was purified by column chromatography SiO2 (5:95
ethyl acetate/hexane): IR (KBr film) 3201, 1672, 1580, 1490, 1360,
1294, 1230, 835 cm−1; mp 87−89 °C; 1H NMR (400 MHz, CDCl3) δ
7.23 (d, J = 7.2 Hz, 2H), 6.71 (s, 1H), 6.59 (d, J = 6.8 Hz, 2H), 3.42
(t, J = 7.6 Hz, 1H), 2.32 (s, 3H), 1.76−1.68 (m, 1H), 1.64−1.56 (m,
1H), 0.94 (t, J = 7.2 Hz, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 206.2, 157.8, 138.5, 116.6, 114.8, 54.2, 27.4, 22.8, 12.6
ppm; HRMS (ESI) m/z calcd for C11H14O2Se [M + H]+ 259.0237,
found 259.0230.
3-((4-Hydroxyphenyl)selanyl)-4-phenylbutan-2-one (8f). This
compound was prepared following procedure B, using a mixture of
4-phenyl-2-butanone (148 mg, 1 mmol), phenol (113 mg, 1.2 mmol),
and SeO2 (111 mg, 1 mmol). The product was obtained as a yellow
solid (288 mg, 85%), which was purified by column chromatography
SiO2 (5:95 ethyl acetate/hexane): IR (KBr film) 3135, 1670, 1596,
1489, 1435, 1270, 833 cm−1; mp 102−104 °C; 1H NMR (400 MHz,
CDCl3) δ 7.26 (d, J = 8.4 Hz, 2H), 7.21−7.10 (m, 5H), 6.74 (s, 1H),
6.64 (d, J = 8.0 Hz, 2H), 3.82 (t, J = 7.2 Hz, 1H), 3.10−3.05 (m, 1H),
2.97−2.91 (m, 1H), 2.27 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 204.5, 157.1, 137.9, 137.8, 127.9, 127.6, 125.7, 115.7, 113.8,
51.3, 35.0, 27.1 ppm; 77Se NMR (57.25 MHz, CDCl3) δ 410.77 ppm;
HRMS (ESI) m/z calcd for C16H16O2Se [M + H]+ 321.0394, found
321.0374.
3-((4-Hydroxy-3-methylphenyl)selanyl)-4-methylpentan-2-one
(8g). This compound was prepared following procedure B, using a
mixture of 4-methyl-2-pentanone (100 mg, 1 mmol), 2-methylphenol
(130 mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol). The product was
obtained as a pale yellow solid (250 mg, 87%), which was purified by
column chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr
1
film) 3422, 1672, 1587, 1272, 1079, 816 cm−1; mp 87−89 °C; H
NMR (400 MHz, CDCl3) δ 7.18 (s, 1H), 7.07 (d, J = 8.4 Hz, 1H),
6.49 (d, J = 8.0 Hz, 1H), 6.02 (s, 1H), 3.23 (d, J = 10.8 Hz, 1H), 2.26
(s, 3H), 2.10 (s, 3H), 1.97−1.89 (m, 1H), 1.17 (d, J = 6.8 Hz, 3H),
0.90 (d, J = 4 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ
203.7, 156.8, 138.5, 135.1, 125.6, 115.9, 115.5, 61.6, 28.5, 28.2, 21.7,
21.0, 16.2 ppm; HRMS (ESI) m/z calcd for C13H18O2Se [M + H]+
287.0550, found 287.0561.
3-((4-Hydroxy-3,5-dimethylphenyl)selanyl)-4-methylpentan-2-
one (8h). This compound was prepared following procedure B, using
a mixture of 4-methyl-2-pentanone (100 mg, 1 mmol), 2,6-
dimethylphenol (146 mg, 1.2 mmol), and SeO2 (111 mg, 1 mmol).
The product was obtained as a pale yellow solid (269 mg, 89%),
which was purified by column chromatography SiO2 (5:95 ethyl
acetate/hexane): IR (KBr film) 3398, 1684, 1580, 1474, 1360, 1196,
731 cm−1; mp 116−118 °C; 1H NMR (400 MHz, CDCl3) δ 7.06 (s,
2H), 4.87 (s, 1H), 3.22 (d, J = 10.4 Hz, 1H), 2.20 (s, 3H), 2.11 (s,
6H), 1.97−1.90 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H), 0.90 (d, J = 6.4
Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 204.5, 153.5,
136.4, 124.2, 116.7, 62.5, 28.3, 27.7, 21.6, 21.1, 15.8 ppm; 77Se NMR
(57.25 MHz, CDCl3) δ 357.10 ppm; HRMS (ESI) m/z calcd for
C14H20O2Se [M + H]+ 301.0707, found 301.0694.
Synthesis of 2,2′-Selenobis(1-phenylpropan-1-one) (10). This
compound was obtained by treating propiophenone (1a, 134 mg, 1.0
mmol, 1 equiv) with SeO2 (2, 111 mg, 1.0 mmol, 1 equiv) in the
presence of PTSA (95 mg, 0.5 mmol, 0.5 equiv) in toluene (1 mL) by
heating in an oil bath at 60 °C for 2 h. After the completion of the
reaction, which was monitored by thin-layer chromatography (TLC),
the mixture was cooled to room temperature and diluted with ethyl
acetate (2 × 10 mL). The combined filtrate was transferred to a
separating funnel, neutralized with aqueous NaHCO3 (2 × 10 mL),
and washed with aqueous NaCl (2 × 10 mL). The organic layer was
separated, dried over anhydrous Na2SO4, and reduced under a
vacuum. The product was obtained as a yellow solid (277 mg, 80%),
which was purified by column chromatography SiO2 (2:98 ethyl
acetate/hexane): IR (KBr film) 3422, 1676, 1446, 1427, 1332, 1233,
797 cm−1; mp 80−82 °C; H NMR (400 MHz, Chloroform-d) δ 8.00
(dd, J = 0.8 Hz, 1.6 Hz, 4H), 7.59 (tt, J = 1.2 Hz, 2.0 Hz, 1.2 Hz, 2H),
7.50 (dt, J = 1.2 Hz, 1.2 Hz, 1.6 Hz, 4H), 4.74 (q, J = 6.8 Hz, 2H),
1.60 (d, J = 6.8 Hz, 6 H); 13C NMR (101 MHz, CDCl3) δ 197.3,
135.6, 133.5, 128.9, 128.8, 128.7, 39.2, 18.2; MS (ES+) calcd for
C18H18O2Se 345.31, found 368.85 [M + Na]+.
3-((4-Hydroxyphenyl)selanyl)-4-methylpentan-2-one (8c). This
compound was prepared following procedure B, using a mixture of 4-
methyl-2-pentanone (100 mg, 1 mmol), phenol (113 mg, 1.2 mmol),
and SeO2 (111 mg, 1 mmol). The product was obtained as a pale
yellow crystalline solid (218 mg, 80%), which was purified by column
chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr film)
1
3451, 1645, 1491, 1438, 1228, 1193, 831 cm−1; mp 74−76 °C; H
NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 6.97 (s, 1H),
6.57 (d, J = 8.4 Hz, 2H), 3.24 (d, J = 10.0 Hz, 1H), 2.29 (s, 3H),
1.96−1.86 (m, 1H), 1.17 (d, J = 6.8 Hz, 3H), 0.89 (d, J = 6.4 Hz,
3H), ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 205.7, 157.7, 138.1,
116.6, 115.4, 62.1, 27.7, 27.4, 21.5, 20.9 ppm; MS (ES+) calcd for
C12H16O2Se 272.0, found m/z 273.0 [M + H]+.
3-((4-Hydroxyphenyl)selanyl)-5-methylhexan-2-one (8d). This
compound was prepared following procedure B, using a mixture of
5-methyl-2-hexanone (mg, 1 mmol), phenol (113 mg, 1.2 mmol), and
SeO2 (111 mg, 1 mmol). The product was obtained as a yellow
crystalline solid (246 mg, 86%), which was purified by column
chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr film)
1
3165, 1672, 1576, 1488, 1362, 1270, 827 cm−1; mp 80−82 °C; H
NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.4 Hz, 2H), 7.18 (s, 1H),
6.57 (d, J = 8.8 Hz, 2H), 3.61 (t, J = 7.6 Hz, 1H), 2.33 (s, 3H), 1.70−
1.64 (m, 1H), 1.58−1.48 (m, 2H), 0.87−0.82 (m, 6H) ppm; 13C{1H}
NMR (100 MHz, CDCl3) δ 206.4, 157.8, 138.5, 116.6, 115.3, 50.8,
38.2, 27.1, 26.7, 22.4, 22.4 ppm; HRMS (ESI) m/z calcd for
C H O Se [M + H]+ 287.0550, found 286.0559.
̀
13 19
2
3-((4-Hydroxyphenyl)selanyl)-3-methylpentan-2-one (8e). This
compound was prepared following procedure B, using a mixture of 3-
methyl-2-pentanone (100 mg, 1 mmol), phenol (113 mg, 1.2 mmol),
and SeO2 (111 mg, 1 mmol). The product was obtained as a pale
yellow crystalline solid (213 mg, 78%), which was purified by column
chromatography SiO2 (5:95 ethyl acetate/hexane): IR (KBr film)
1
3433, 1661, 1277, 1248, 839 cm−1; mp 78−70 °C; H NMR (400
MHz, CDCl3) δ 7.20 (s, 1H), 7.17(d, J = 7.2 Hz, 2H), 6.60 (d, J = 8.0
Hz, 2H), 2.39 (s, 3H), 1.91−1.82 (m, 1H), 1.77−1.68 (m, 1H), 1.37
F
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Organoselenium Compounds in Biology and Medicine: Synthesis,
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02028.
■
sı
Copies of 1H and 13C NMR spectra for all new
compounds and crystallographic descriptions for com-
pound 8c (PDF)
FAIR data, including the primary NMR FID files, for
compounds, 4a−4l, 6a−6c, and 8a−8h (ZIP)
Accession Codes
CCDC 1973308 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
Bekington Myrboh − Centre for Advanced Studies in
Chemistry, Department of Chemistry, North-Eastern Hill
University, Shillong 793022, India; orcid.org/0000-0001-
9349-2216; Email: bmyrboh@nehu.ac.in
■
Biological and Therapeutic Treatments. RSC 2017. (h) Lenardao, E.
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J.; Sancineto, L.; Santi, C. New Frontiers in Organoselenium
Compounds; Springer, 2018.
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and Nucleophilic Organoselenium Reagents. New Routes to α, β-
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Authors
Kmendashisha Wanniang − Centre for Advanced Studies in
Chemistry, Department of Chemistry, North-Eastern Hill
University, Shillong 793022, India
O. Risuklang Shangpliang − Centre for Advanced Studies in
Chemistry, Department of Chemistry, North-Eastern Hill
University, Shillong 793022, India
Ibakyntiew D. Marpna − Centre for Advanced Studies in
Chemistry, Department of Chemistry, North-Eastern Hill
University, Shillong 793022, India
Tyrchain Mitre Lipon − Centre for Advanced Studies in
Chemistry, Department of Chemistry, North-Eastern Hill
University, Shillong 793022, India
Badaker M. Laloo − Centre for Advanced Studies in
Chemistry, Department of Chemistry, North-Eastern Hill
University, Shillong 793022, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02028
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
K.W. thanks SAIF-NEHU and SAIF-CDRI Lucknow for NMR
and HRMS analysis, DST PURSE Program for X-ray analysis,
and the University Grants Commission (UGC) for financial
assistance under the National Fellowship for Higher Education
(NFHE) scheme. B.M. acknowledges financial assistance from
SERB, DST (SB/EMEQ-006/3013).
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