Reaction of selenium dioxide with aromatic ketones in the presence of boron triflouride etherate: A protocol for the synthesis of triarylethanones

Article abstract of DOI:10.1021/jo201985n

An efficient regioselective protocol for the C-C bond formation by the unexpected α,α-diarylation of aromatic ketones with unactivated arenes in the presence of selenium dioxide and boron trifluoride etherate has been developed. The generality and functio

Full text of DOI:10.1021/jo201985n

Note
pubs.acs.org/joc
Reaction of Selenium Dioxide with Aromatic Ketones in the Presence
of Boron Triflouride Etherate: A Protocol for the Synthesis of
Triarylethanones
Badaker M. Laloo, Hormi Mecadon, Md. Rumum Rohman, Iadeishisha Kharbangar, Icydora Kharkongor,
Mantu Rajbangshi, Rishanlang Nongkhlaw, and Bekington Myrboh*
Department of Chemistry, North-Eastern Hill University, Shillong 793022, Meghalaya, India
S
* Supporting Information
ABSTRACT: An efficient regioselective protocol for the C−C
bond formation by the unexpected α,α-diarylation of aromatic
ketones with unactivated arenes in the presence of selenium
dioxide and boron trifluoride etherate has been developed. The
generality and functional tolerance of this protocol is
demonstrated by the synthesis of a series of triarylethanones.
he direct insertion of an aryl moiety next to a carbonyl
group has been a long-standing problem in synthetic
Thus, treatment of p-chloroacetophenone (1a, 1 equiv) with
selenium dioxide (1 equiv) in the presence of boron trifluoride
etherate (49%, 2 equiv) and substrate 2a (16 mL) at room
temperature for 18 h afforded 1-(4-chlorophenyl)-2,2-dipheny-
lethanone (3a) in good yield (60%) (entry 1, Table 1). The
structure of 3a was assigned based on 1H, 13C NMR
spectroscopy, as well as by comparison with literature
data10,11 and confirmed by single-crystal X-ray diffraction
analysis (included in the Supporting Information). It may be
mentioned here that boron trifluoride etherate appears to be
specific for these reactions since the use of other Lewis acids
(AlCl3, SnCl4) either gave no reaction or resulted in the
formation of multiple products that are difficult to isolate.
Similarly, the reaction of 1b (R1 = 4-CH3), 1d (R1 = 3-NO2),
and 1g (R1 = 4-OCH3) with selenium dioxide and boron
trifluoride etherate in excess benzene (2a) at room temperature
for 18 h proceeded smoothly to give the trisubstituted
ethanones 3b, 3d, and 3g, respectively, in moderate to good
yields (entries 2, 4, and 7, Table 1).
Encouraged by these results, we turned our attention to
other substituted benzenes. Interestingly, the nature and
position of the substituents on the aromatic ketone does not
appear to affect the reaction. It may be also noted that
deactivated or weakly activated arenes, including the electron-
rich anisole, all reacted cleanly to give the corresponding 1,2,2-
triarylethanones (3c,e,f and 3h−q) (entries 3, 5−6, and 8−17,
Table 1) in consistently good yields (46−71%). It may be
noted that in the case of anisole and naphthalene 2 equiv of
each of the arenes is required. The reaction with naphthalene,
though it is a solid, proceeded without the need of any solvent
in the presence of boron trifluoride etherate, which also
provided the medium for the reaction. However, chlorobenzene
afforded the product 3q in 46% yield when the substrate is used
T
organic chemistry.1 The last two decades have seen a lot of
effort directed toward achieving a reliable method for the α-
arylation of ketones, as this reaction constitutes the key step in
the synthesis of a wide number of complex systems.2 Many new
methodologies involving the use of palladium-based catalysts
have been developed to achieve this goal. Prominent among
them are the works of Buchwald,3 Dominguez,4 Hartwig,5 and
Miura.6 While many of the methods described are quite
effective, their practicality is diminished by the time and cost
needed to prepare the reagents in stoichiometric amounts.
Furthermore, many of these procedures start from the already
monoarylated ketones and aryl or pseudohalides.7
On the basis of our earlier work on the BF3·Et2O-assisted
oxyplumbation studies, which led to the 1,2-carbonyl trans-
position of acetophenones,8 we were curious to know whether
selenium dioxide under similar reaction conditions would
provide the intermediate that could lead to similar rearrange-
ment. To our surprise, the reaction led to an unexpected α,α-
diarylation of the ketone to afford triarylethanones 3, the
structural analogues of the cancer therapy agent tamoxifen,9 in
good yields (Table 1). To the best of our knowledge, the use of
selenium dioxide and boron trifluoride etherate combination
for the direct α,α-diarylation of aromatic ketones has not been
reported. The new method we report herein is therefore highly
significant, quite general, and proceeds efficiently at ambient
temperature and ordinary reaction conditions. In contrast to
the general observation that electrophilic aromatic substitutions
give mixtures of regioisomers, we are able to isolate only one
regioisomer in all of the reactions carried out except in the case
of toluene, where trace amount of the ortho isomer is detected
1
(as is clear form the H and 13C NMR). The attractiveness of
the method is further augmented by the fact that the starting
materials used are quite common and inexpensive.
Received: September 26, 2011
Published: November 21, 2011
© 2011 American Chemical Society
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Note
a
Table 1. Reaction of Substituted Acetophenones with Arenes in the Presence of SeO2 and BF3·Et2O
c
entry
substrate 1 (R1)
substrate 2 (R2, R3, R4, R5)
product 3
yield (%)
1
2
1a; R1 = 4-ClC6H4
2a; R2 = R3 = R4 = R5 = H
3a
3b
3c
3d
3e
3f
60
58
61
65
68
55
57
63
70
69
59
65
71
57
63
69
46
41
39
58
1b; R1 = 4-CH3C6H4
2a
3
1c; R1 = 4-BrC6H4
2a
4
1d; R1 = 3-NO2C6H4
2a
5
1e; R1 = 4-NO2C6H4
2a
6
1f; R1 = 3-CH3OC6H4
2a
7
1g; R1 = 4-CH3OC6H4
2a
3g
3h
b
8
1c
2b; R2 = R3 = R5 = H, R4 = CH3
b
9
1d
2b
3i
3j
b
10
11
12
13
14
15
16
17
18
19
20
1e
2b
1b
2c; R2 = R5 = H, R3 = R4 = CH3
3k
3l
1c
2c
1e
2c
3m
3n
3o
3p
3q
1h; R1 = 2-CH3OC6H4
2d; R3 = R4 = H, R2 = R5 = CH3
1e
2d
1a
2e; R2 = R3 = R5 = H, R4 = OCH3
1e
2f; R2 = R3 = R5 = H, R4 = Cl
b
1i; 2-naphthyl
2b
2d
2g
3r
1i
3s
3t
1a
a
Reaction conditions: (i) substrate 1 (10 mmol), substrate 2a−d (16 mL), SeO2 (10 mmol), BF3·Et2O (49%, 6−7 mL), 0−23 °C, 14−18 h. (ii)
b
c
Same as (i) except for the arene 2e (20 mmol), 2f (80 mmol), and 2g (20 mmol) were used. Combined yields of ortho and para isomer. Isolated
yields.
a
Table 2. Reaction of Heteroaryl Ketones with Benzene and Substituted Benzenes in the Presence of SeO2 and BF3·Et2O
b
entry
substrate 4
substrate 2 (R2, R3, R4, R5)
product 5
yield (%)
1
2
3
4a
4a
4a
2a
2b
2c
5a
5b
5c
65
61
58
a
b
Reaction conditions are same as (i) in Table 1. Isolated yields.
in excess (entry 17, Table 1). This is presumably because
chlorobenzene exhibits decreased susceptibility to attack by the
electrophiles. The reaction with acetanilide and nitrobenzene,
however, gave only an intractible mixture. The scope of the
reaction was further investigated with extended aromatic
systems when it was found that, irrespective of whether the
extended aromatic ring is on the ketones or the arylating
substrate, diarylation takes place under the same reaction
conditions (products 3r−t, entries 18−20, Table 1).
To test the generality of the method, we extended our
investigation to other aromatic ketones. Thus when 2-
acetylthiophene (4a) was allowed to react with benzene (2a)
in the presence of selenium dioxide and boron trifluoride
etherate at room temperature for 18 h, a clean α,α-diarylation
took place to afford 2,2-diphenyl-1-(thiophen-2-yl)ethanone
(5a) (entry 1, Table 2) in 65% yield. In a similar fashion, 4a
reacted with substituted arenes 2b and 2c to give the
corresponding products 5b and 5c in good yields. However,
the reaction with heteroaryl ketones containing oxygen or
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Note
Scheme 1. Probable Mechanism for α,α-Diarylation
1-(4-Chlorophenyl)-2,2-diphenylethanone [3a, Table
1].10,11 Prepared from 1-(4-chlorophenyl)ethanone (1.30 mL, 10.0
mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 6 mL),
and dry benzene (16 mL) following the general procedure in 18 h.
Solvent system for column chromatography: 9.9:0.1−9.3:0.3; hexane/
ethylacetate. The product obtained after column chromatography was
further recrystallized from dichloromethane and hexane 9:1. The
product was isolated as light yellow crystals (1.85 g, 60% yield): mp
nitrogen failed to give the diarylated products (Table 2).
Similarly, reactions with acetophenones already substituted at
the α-carbon atom, such as propiophenone, do not give the
expected monoarylated ketones.
Notably, the same procedure was followed in all of the
reactions, and except for maintaining dry conditions, no other
precautions were taken. The commercial reagents were used
directly as received.
1
87−89 °C; H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.4 Hz, 2H),
7.36−7.24 (m, 12H), 5.96 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
197.0, 139.5, 138.7, 135.0, 130.4, 129.1, 128.9, 128.8, 127.3, 59.5; IR
(KBr) 3093, 3067, 2924, 2853, 1668 cm−1. Anal. Calcd for
C20H15ClO: C, 78.30; H, 4.93. Found: C, 78.17; H, 4.89.
A probable mechanism for this reaction may be depicted as
in Scheme 1. Enolization of the ketone (1) in the presence of
boron trifluoride etherate is the first step followed by reaction
with selenium dioxide to generate the intermediate 6. The
propensity of the selenium dioxide to get reduced to its zero
valency state is evidently the driving force behind the umpolung
arylation process12 resulting in a facile nucleophilic attack on
the α-carbon atom leading to the formation of the product 3
(Scheme 1). It may be noted that the proposed mechanism
bears a strong similarity to that proposed by Moriarty et al.,
where the intermediate 6 behaves like the electrophile C6H5I+-
OB−F3 in the α-methoxylation reactions by the hypervalent
iodine oxidation of silyl enol ethers.13 Further, the participation
of the intermediate 6 appears to be reasonable because, in all of
the reactions, at no instance was the formation of 2-aryl-2-oxo-
acetaldehyde observed.14 We thus feel that the proposed
mechanism is quite plausible.
In summary, we have reported a highly regioselective, first
direct double arylation of the α-carbon atom of aromatic
ketones without the use of expensive catalyst, thereby providing
a valuable addition to the existing triarylation methods.15 To
our knowledge, this is also the first report of a C−C bond
formation via the use of SeO2 as an intermediary. Ongoing
efforts are directed toward a detailed investigation on the
reaction of α-substituted aromatic ketones with selenium
dioxide in the presence of a Lewis acid which, as reported
above, did not give the expected product and also attempts at
selective monoarylation of aromatic ketones.16
2,2-Diphenyl-1-(p-tolyl)ethanone [3b, Table 1].11 Prepared
from 1-(p-tolyl)ethanone (1.34 g, 10.0 mmol), selenium dioxide (1.11
g, 10.0 mmol), BF3·Et2O (49%, 6 mL), and dry benzene (14 mL)
following the general procedure in 18 h. Solvent system for column
chromatography: 10.0:0.0−9.0:1.0; hexane/ethylacetate. The product
was isolated as light yellow solid (1.67 g, 58% yield): mp 105−107 °C;
1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 2H), 7.37−7.21
(m, 12H), 6.04 (s, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
197.8, 143.9, 139.2, 134.3, 129.3, 129.2, 129.1, 128.7, 127.1, 59.3, 21.6;
IR (KBr) 2924, 2855, 1675 cm−1. Anal. Calcd for C21H18O: C, 88.08;
H, 6.34. Found: C, 88.11; H, 6.29.
1-(4-Bromophenyl)-2,2-diphenylethanone [3c, Table 1].11
Prepared from 1-(4-bromophenyl)ethanone (1.99 g, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 6 mL), and dry
benzene (16 mL) following the general procedure in 18 h. Solvent
system for column chromatography: 9.9:0.1−9.3:0.3; hexane/ethyl-
acetate. The product was isolated as off white solid (2.15 g, 61%
1
yield): mp 104−106 °C; H NMR (400 MHz, CDCl3) δ 7.78 (d, J =
8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.30−7.16 (m, 10H), 5.88 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 197.2, 138.7, 135.4, 132.0,
130.5, 129.1, 128.8, 128.3, 127.3, 59.5; IR (KBr) 3062, 3024, 2923,
1678 cm−1. Anal. Calcd for C20H15BrO: C, 68.39; H, 4.30. Found: C,
68.47; H, 4.28.
1-(3-Nitrophenyl)-2,2-diphenylethanone [3d, Table 1]. Pre-
pared from 1-(3-nitrophenyl)ethanone (1.65 g, 10.0 mmol), selenium
dioxide (1.11 g, 10.0 mmol) BF3·Et2O (49%, 6 mL), and dry benzene
(16 mL) following the general procedure in 18 h. Solvent system for
column chromatography: 9.5:0.1−9.0:1.0; hexane/ethylacetate. The
product obtained after column chromatography was further recrystal-
lized from dichloromethane and hexane 9:2. The product was isolated
as light yellow crystals (2.07 g, 65% yield): mp 121−123 °C; 1H NMR
(400 MHz, CDCl3) δ 8.74 (m, 1H), 8.29−8.22 (m, 2H), 7.53 (t, J =
8.0 Hz, 1H), 7.29−7.18 (m, 10H), 5.94 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 196.0, 147.9, 138.0, 134.5, 130.1, 129.9, 129.1, 129.0, 127.6,
127.3, 123.8, 59.9; IR (KBr) 3079, 2920, 1693, 1529 cm−1. Anal. Calcd
for C20H15NO3: C, 75.70; H, 4.76; N, 4.41. Found: C, 75.68; H, 4.72;
N, 4.43.
1-(4-Nitrophenyl)-2,2-diphenylethanone [3e, Table 1]. Pre-
pared from 1-(4-nitrophenyl)ethanone (1.65 g, 10.0 mmol), selenium
dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and dry benzene
(16 mL) following the general procedure in 18 h. Solvent system for
column chromatography: 9.5:0.1−9.0:1.0; hexane/ethylacetate. The
product was isolated as light yellow crystals (2.16 g, 68% yield): mp
152−154 °C; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.8 Hz, 2H),
EXPERIMENTAL SECTION
■
General Procedure. A stirring mixture of the aryl or heteroaryl
methyl ketones (1 or 4) (10.0 mmol), selenium dioxide (10.0 mmol),
and arenes (2a−d) (16 mL) was cooled in an ice-salt mixture.
BF3·Et2O (49%, 7 mL) was then added dropwise over a period of 10
min, and the reaction mixture was allowed to stir at room temperature
for 14−18 h. The reaction mixture was quenched with water (20 mL)
and the red precipitate of selenium filtered off. The filtrate was
extracted with diethyl ether (2 × 20 mL), and the combined organic
extracts were washed with concentrated aqueous bicarbonate solution
(1 × 20 mL) followed by brine (1 × 10 mL). The organic extract was
dried over anhydrous Na2SO4 and concentrated. The triarylethanone
was purified by column chromatography on silica gel.
Arenes such as chlorobenzene (8 equiv), anisole (2 equiv), and
naphthalene (2 equiv) were used in the reaction.
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The Journal of Organic Chemistry
Note
8.10 (d, J = 8.8 Hz, 2H) 7.35−7.24 (m, 10H), 6.00 (s, 1H); 13C NMR
(400 MHz, CDCl3) δ 196.8, 150.1, 141.2, 138.1, 130.0, 129.1, 129.0,
127.6, 123.9, 60.2; IR (KBr) 3112, 3056, 3025, 2938, 2858, 1692, 1523
cm−1. Anal. Calcd for C20H15NO3: C, 75.70; H, 4.76; N, 4.41. Found:
C, 75.82; H, 4.73; N, 4.42.
system for column chromatography: 10.0:0.0−9.0:1.0; hexane/ethyl-
acetate. The product was isolated as white solid (2.03 g, 59% yield):
mp 108−110 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz,
2H), 7.12 (d, J = 8.0 Hz, 2H), 7.00−6.96 (m, 4H), 6.92−6.90 (m,
2H), 5.82 (s, 1H), 2.29 (s, 3H), 2.13 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 198.3, 143.6, 136.9, 136.8, 135.3, 134.5, 130.3, 130.0, 129.2,
129.1, 126.4, 58.7, 21.6, 19.9, 19.4; IR (KBr) 3014, 2970, 2920, 1670
cm−1. Anal. Calcd for C25H26O: C, 87.68; H, 7.65. Found: C, 87.71; H,
7.62.
1-(4-Bromophenyl)-2,2-bis(3,4-dimethylphenyl)ethanone
[3l, Table 1]. Prepared from 1-(4-bromophenyl)ethanone (1.99 g,
10.0 mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7
mL), and distilled o-xylene (16 mL) following the general procedure in
16 h. Solvent system for column chromatography: 9.9:0.1−9.6:0.4;
hexane/ethylacetate. The product was isolated as off white solid (2.65
g, 65% yield): mp 107−109 °C; 1H NMR (400 MHz, CDCl3) δ 7.78−
7.76 (m, 2H), 7.46−7.44 (m, 2H), 7.00 (d, J = 7.6 Hz, 2H), 6.93 (s,
2H), 6.88 (d, J = 7.6 Hz, 2H), 5.75 (s, 1H), 2.13 (s, 12H); 13C NMR
(400 MHz, CDCl3) δ 197.7, 137.0, 136.3, 135.6, 135.5, 131.8, 130.4,
130.2, 130.0, 128.0, 126.4, 58.9, 19.9, 19.4; IR (KBr) 3060, 2936, 2845,
1670 cm−1. Anal. Calcd for C24H23BrO: C, 70.77; H, 5.69. Found: C,
70.79; H, 5.66.
2,2-Bis(3,4-dimethylphenyl)-1-(4-nitrophenyl)ethanone
[3m, Table 1]. Prepared from 1-(4-nitrophenyl)ethanone (1.11 g,
10.0 mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7
mL), and distilled o-xylene (16 mL) following the general procedure in
14 h. Solvent system for column chromatography: 9.5:0.5−8.9:1.1;
hexane/ethylacetate. The product was isolated as yellow solid (2.66 g,
71% yield): mp 121−123 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (d,
J = 8.8 Hz, 2H), 8.13 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H),
7.04 (s, 2H), 6.99−6.97 (m, 2H), 5.87 (s, 1H), 2.24 (s, 12H); 13C
NMR (100 MHz, CDCl3) δ 197.2, 150.0, 141.5, 137.2, 135.9, 135.6,
130.2, 130.2, 130.0, 126.4, 123.8, 59.7, 19.9, 19.4; IR (KBr) 3101,
3069, 2921, 2856, 1694, 1524 cm−1. Anal. Calcd for C24H23NO3: C,
77.19; H, 6.21; N, 3.75. Found: C, 77.23; H, 6.16; N, 3.76.
1-(3-Methoxyphenyl)-2,2-diphenylethanone [3f, Table 1].11
Prepared from 1-(3-methoxyphenyl)ethanone (1.37 mL, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and dry
benzene (16 mL) following the general procedure in 18 h. Solvent
system for column chromatography: 9.8:0.2−9.6:0.4; hexane/ethyl-
acetate. The product was isolated as off white solid (1.67 g, 55%
1
yield): mp 106−108 °C; H NMR (400 MHz, CDCl3) δ 7.51 (d, J =
7.6 Hz, 1H), 7.46 (s, 1H,) 7.27−7.16 (m, 11H), 6.98 (dd, J = 2.0 Hz,
8.0 Hz, 1H), 5.95 (s, 1H), 3.73 (s, 3H); 13C NMR (400 MHz, CDCl3)
δ 198.1, 159.8, 139.1, 138.2, 129.6, 129.1, 128.7, 127.2, 121.6, 119.5,
113.3, 59.6, 55.4; IR (KBr) 3076, 3024, 2924, 2853, 1676 cm−1. Anal.
Calcd for C21H18O2: C, 83.42; H, 6.00. Found: C, 83.44; H, 5.94.
1-(4-Methoxyphenyl)-2,2-diphenylethanone [3g, Table 1].
Prepared from 1-(4-methoxyphenyl)ethanone (1.50 g, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 6 mL), and dry
benzene (16 mL) following the general procedure in 18 h. Solvent
system for column chromatography: 9.8:0.2−9.6:0.4; hexane/ethyl-
acetate. The product was isolated as white solid (1.73 g, 57% yield):
mp 105−107 °C; 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.8 Hz,
2H), 7.26−7.15 (m, 10H), 6.80 (d, J = 8.8 Hz, 2H), 5.92 (s, 1H), 3.75
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.7, 163.4, 139.4, 131.3,
130.6, 129.2, 128.7, 127.0, 59.1, 55.5; IR (KBr) 3059, 3028, 2923,
2847, 1673, 1260, 1023 cm−1. Anal. Calcd for C21H18O2: C, 83.42; H,
6.00. Found: C, 83.33; H, 5.95.
1-(4-Bromophenyl)-2,2-di-p-tolylethanone [3h, Table 1].
Prepared from 1-(4-bromophenyl)ethanone (1.99 g, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and dry
toluene (16 mL) following the general procedure in 16 h. Solvent
system for column chromatography: 9.8:0.2−9.6:0.4; hexane/ethyl-
acetate. The product was isolated as off white solid (2.39 g, 63%
1
yield): mp 127−130 °C; H NMR (400 MHz, CDCl3) δ 7.75 (d, J =
2,2-Bis(2,5-dimethylphenyl)-1-(2-methoxyphenyl)ethanone
[3n, Table 1]. Prepared from 1-(2-methoxyphenyl)ethanone (1.34
mL, 10.0 mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O
(49%, 7 mL), and distilled p-xylene (16 mL) following the general
procedure in 16 h. Solvent system for column chromatography:
9.8:0.2−9.7:0.3; hexane/ethylacetate. The product was isolated as off
white solid (2.05 g, 57% yield): mp 122−124 °C; 1H NMR (400 MHz,
CDCl3) δ 7.72 (dd, J = 1.6 Hz, 7.6 Hz, 1H), 7.30−7.26 (m, 1H),
6.98−6.66 (m, 8H), 6.36 (s, 1H), 3.63 (s, 3H), 2.12 (s, 6H), 2.11(s,
6H); 13C NMR (100 MHz, CDCl3) δ 200.5, 158.3, 137.2, 135.1,
133.5, 133.4, 131.6, 130.2, 130.0, 128.4, 127.5, 120.8, 111.9, 57.2, 55.5,
21.2, 19.5; IR (KBr) 2942, 2917, 2867, 1682, 1246, 1023 cm−1. Anal.
Calcd for C25H26O2: C, 83.76; H, 7.31. Found: C, 83.53; H, 7.39.
2,2-Bis(2,5-dimethylphenyl)-1-(4-nitrophenyl)ethanone [3o,
Table 1]. Prepared from 1-(4-nitrophenyl)ethanone (1.65 g, 10.0
mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL),
and distilled p-xylene (16 mL) following the general procedure in 14 h.
Solvent system for column chromatography: 9.5:0.5−8.9:1.1; hexane/
ethylacetate. The product was isolated as light yellow solid (2.36 g,
63% yield): mp 151−153 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (d,
J = 8.8 Hz, 2H), 8.01 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 7.6 Hz, 2H),
7.03 (d, J = 7.6 Hz, 2H), 6.67 (s, 2H), 6.11 (s, 1H), 2.22 (s, 12H); 13C
NMR (400 MHz, CDCl3) δ 197.9, 150.1, 141.4, 135.9, 135.5, 132.7,
130.8, 129.8, 129.6, 128.4, 124.0, 54.2, 21.2, 19.4; IR (KBr) 3108,
3080, 3026, 2971, 2943, 2918, 2863, 1686, 1520 cm−1. Anal. Calcd for
C24H23NO3: C, 77.19; H, 6.21; N, 3.75. Found: C, 77.21; H, 6.18; N,
3.76.
8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.03 (m, 8H), 5.79 (s, 1H), 2.21
(s, 6H); 13C NMR (100 MHz, CDCl3) δ 197.6, 136.9, 135.9, 135.6,
131.9, 130.6, 129.6, 129.5, 128.9, 58.9, 21.1; IR (KBr) 3088, 3057,
3024, 2917, 2860, 1685 cm−1. Anal. Calcd for C22H19BrO: C, 69.67; H,
5.05. Found: C, 69.86; H, 4.93.
1-(3-Nitrophenyl)-2,2-di-p-tolylethanone [3i, Table 1]. Pre-
pared from 1-(3-nitrophenyl)ethanone (1.65 g, 10.0 mmol), selenium
dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and dry toluene
(16 mL) following the general procedure in 14 h. Solvent system for
column chromatography: 9.5:0.5−8.8:1.2; hexane/ethylacetate. The
product was isolated off white crystalline solid (2.42 g, 70% yield): mp
125−127 °C; 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.27 (d, J =
8.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.08
(m, 8H), 5.87 (s, 1H), 2.24 (s, 6H); 13C NMR (400 MHz, CDCl3) δ
196.3, 148.4, 137.2, 135.2, 134.5, 129.9, 129.7, 129.5, 128.9, 127.2,
123.8, 59.2, 21.1; IR (KBr) 3085, 3026, 2919, 2868, 1694, 1526 cm−1.
Anal. Calcd for C22H19NO3: C, 76.50; H, 5.54; N, 4.06. Found: C,
76.52; H, 5.50; N, 4.10.
1-(4-Nitrophenyl)-2,2-di-p-tolylethanone [3j, Table 1]. Pre-
pared from 1-(4-nitrophenyl)ethanone (1.65 g, 10.0 mmol), selenium
dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and dry toluene
(16 mL) following the general procedure in 14 h. Solvent system for
column chromatography: 9.5:0.5−9.0:1.0; hexane/ethylacetate. The
product was isolated as yellow solid (2.39 g, 69% yield): mp 142−144
°C; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 8.8 Hz, 2H), 8.03 (d, J
= 8.8 Hz, 2H), 7.08−7.00 (m, 8H), 5.83 (s, 1H), 2.24 (s, 6H); 13C
NMR (100 MHz, CDCl3) δ 197.1, 150.0, 141.4, 137.3, 135.2, 130.0,
129.7, 128.9, 123.8, 59.6, 21.1; IR (KBr) 3102, 3073, 2921, 2856, 1692,
1529 cm−1. Anal. Calcd for C22H19NO3: C, 76.50; H, 5.54; N, 4.06.
Found: C, 76.43; H, 5.61; N, 4.15.
1-(4-Chlorophenyl)-2,2-bis(4-methoxyphenyl)ethanone [3p,
Table 1]. 1-(4-Chlorophenyl)ethanone (1.30 mL, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol) BF3·Et2O (49%, 7 mL), and
anisole (2.16 g, 20 mmol) following the general procedure in 14 h.
Solvent system for column chromatography: 9.8:0.2−8.0:2.0; hexane/
ethylacetate. The product was isolated as yellow viscous liquid (2.53 g,
69% yield): mp 120−122 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d,
J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.8 Hz, 4H),
2,2-Bis(3,4-dimethylphenyl)-1-(p-tolyl)ethanone [3k, Table
1]. Prepared from 1-(p-tolyl)ethanone (1.34 mL, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and
o-xylene (16 mL) following the general procedure in 18 h. Solvent
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The Journal of Organic Chemistry
Note
6.72 (d, J = 8.4 Hz, 4H), 5.75 (s, 1H), 3.59 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 197.6, 158.7, 139.3, 135.1, 131.2, 130.4, 130.1, 128.9,
114.3, 57.9, 55.2; IR (KBr) 3005, 2952, 2839, 1686, 1600, 1507, 1460,
1248, 1182 cm−1; MS (ES+) calcd for C22H19ClO3 366.10, found m/z
389.0 [M + Na]+. Anal. Calcd for C22H19ClO3: C, 72.03; H, 5.22;
Found: C, 72.16; H, 5.20.
1H), 7.50 (d, J = 4.4 Hz, 1H) 7.24−7.15 (m, 10H), 6.97 (t, J = 4.0 Hz,
1H), 5.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 191.1, 144.2,
138.8, 134.2, 132.9, 129.1, 128.8, 128.5, 127.3, 60.5; IR (KBr) 3112,
3090, 2925, 1651 cm−1. Anal. Calcd for C18H14OS: C, 77.66; H, 5.07;
S, 11.52; H. Found: C, 77.86; H, 5.15; S, 11.47.
1-(Thiophen-2-yl)-2,2-di-p-tolylethanone [5b, Table 2]. Pre-
pared from 1-(thiophen-2-yl)ethanone (1.08 mL, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and
dry toluene (16 mL) following the general procedure in 14 h. Solvent
system for column chromatography: 9.8:0.2−9.5:0.5; hexane/ethyl-
acetate. The product was isolated as off white solid (1.87 g, 61%
2,2-Bis(4-chlorophenyl)-1-(4-nitrophenyl)ethanone [3q,
Table 1]. Prepared from 1-(4-nitrophenyl)ethanone (1.65 g, 10.0
mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL),
and chlorobenzene (8.13 mL, 80 mmol) following the general
procedure in 16 h. Solvent system for column chromatography:
9.8:0.2−8.5:1.5; hexane/ethylacetate. The product was isolated as off
1
yield): mp 131−133 °C; H NMR (400 MHz, CDCl3) δ 7.65 (d, J =
1
white solid (1.78 g, 46% yield): H NMR (400 MHz, CDCl3) δ 8.19
3.6 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 7.12−7.03 (m, 8H), 6.96 (t, J =
4.0 Hz, 1H), 5.72 (s, 1H), 2.22 (s, 6H); 13C NMR (100 MHz, CDCl3)
δ 191.4, 144.3, 136.8, 136.1, 133.9, 132.7, 129.4, 128.9, 128.2, 59.8,
21.1; IR (KBr) 3085, 3018, 2919, 2858, 1647 cm−1. Anal. Calcd for
C20H18OS: C, 78.39; H, 5.92; S, 10.46. Found: C, 78.53; H, 5.87; S,
10.33.
(d, J = 8.8 Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.4 Hz, 4H),
7.09 (d, J = 8.4 Hz, 4H), 5.85 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
196.0, 150.3, 140.7, 136.1, 133.9, 130.3, 129.9, 129.3, 124.0, 58.7; IR
(KBr) 3103, 3073, 2925, 2855, 1695, 1530 cm−1. Anal. Calcd for
C20H13Cl2NO3: C, 62.19; H, 3.39; N, 3.63. Found: C, 62.08; H, 3.33;
N, 3.70.
1-(Naphthalen-2-yl)-2,2-di-p-tolylethanone [3r, Table 1].
Prepared from 1-(naphthalen-2-yl)ethanone (1.70 g, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol) BF3.Et2O (49%, 7 mL) and dry
toluene (16 mL) following the general procedure in 14 h. Solvent
system for column chromatography: 9.9:0.1−9.5:0.5; hexane/ethyl-
acetate. The product obtained after column chromatography was
further washed with n-pentane to give a light yellow solid (1.44 g, 41%
yield): mp 114−116 °C 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H),
8.06−7.45 (m, 6H), 7.20 (d, J = 8.0 Hz, 4H), 7.12 (d, J = 8.0 Hz, 4H)
6.13 (s, 1H), 2.29 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 198.5,
136.7, 136.4, 135.4, 134.2, 132.4, 130.6, 129.7, 129.4, 129.0, 128.4,
128.4, 127.7, 126.6, 124.7, 58.7, 21.0; IR (KBr) 3435, 3019, 2920,
2864, 1670, 1498, 1464 cm−1. Anal. Calcd for C26H22O: C, 89.11; H,
6.33. Found: C, 89.16; H, 6.40.
2,2-Bis(2,5-dimethylphenyl)-1-(naphthalen-2-yl)ethanone
[3s, Table 1]. Prepared from 1-(naphthalen-2-yl)ethanone (1.70 g,
10.0 mmol), selenium dioxide (1.11 g, 10.0 mmol) BF3·Et2O (49%, 7
mL), and p-xylene (16 mL) following the general procedure in 14 h.
Solvent system for column chromatography: 9.9:0.1−9.5:0.5; hexane/
ethylacetate. The product obtained after column chromatography was
further washed with n-pentane to give a light yellow (1.48 g, 39%
yield); mp 155−157 °C 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H),
7.98−7.77 (m, 4H), 7.55−7.46 (m, 2H), 7.12 (d, J = 7.6 Hz, 2H), 6.99
(d, J = 7.6 Hz, 2H), 6.79 (s, 2H), 6.34 (s, 1H), 2.26 (s, 6H) 2.20 (s,
6H); 13C NMR (100 MHz, CDCl3) δ 199.4, 136.7, 135.7, 135.5,
134.4, 132.8, 132.6, 130.6, 130.2, 130.0, 129.8, 128.6, 128.5, 128.0,
127.7, 126.7, 124.5, 53.7, 21.2, 19.6; IR (KBr) 3432, 3044, 3020, 2923,
2856, 1674, 1511, 1466, 1277 cm−1; MS (ES+) calcd for C28H26O
378.2, found m/z 401.4 [M + Na]+. Anal. Calcd for C28H26O: C,
88.85; H, 6.92. Found: C, 88.91; H, 6.81.
2,2-Bis(3,4-dimethylphenyl)-1-(thiophen-2-yl)ethanone [5c,
Table 2]. Prepared from 1-(thiophen-2-yl)ethanone (1.08 mL, 10.0
mmol), selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL),
and distilled o-xylene (16 mL) following the general procedure in 14 h.
Solvent system for column chromatography: 9.8:0.2−9.7:0.3; hexane/
ethylacetate. The product was isolated as white solid (1.94 g, 58%
yield): mp 73−75 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 3.6
Hz, 1H), 7.58 (d, J = 4.8 Hz, 1H), 7.08−7.00 (m, 7H), 5.75 (s, 1H),
2.21 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 191.6, 144.4, 136.9,
136.4, 135.5, 133.9, 132.7, 130.2, 129.9, 128.2, 126.4, 59.9, 19.9, 19.4;
IR (KBr) 2923, 2855, 1654 cm−1. Anal. Calcd for C22H22OS: C, 79.00;
H, 6.63; S, 9.59. Found: C, 79.21; H, 6.58; S, 9.50.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving 1H NMR and 13C NMR spectra compounds and
details of the X-ray diffraction analysis (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: bmyrboh@nehu.ac.in.
■
ACKNOWLEDGMENTS
■
Authors are thankful to the University Grants Commission
(UGC) for research fellowships, SAIF, North-Eastern Hill
University for NMR and mass data, and IIT, Guwahati for X-
ray analysis. Also, we gratefully acknowledged the UGC for
financial assistance vide project F. No. 40-83/2011(SR).
1-(4-Chlorophenyl)-2,2-di(naphthalen-1-yl)ethanone [3t,
Table 1]. Prepared from 1-(4-chlorophenyl)ethanone (1.30 mL,
10.0 mmol), selenium dioxide (1.11 g, 10.0 mmol) BF3 ·Et2O (49%, 7
mL), and naphthalene (2.56 g, 20 mmol) following the general
procedure in 14 h. Solvent system for column chromatography: 9.5:0.5
hexane/ethylacetate. The product obtained after column chromatog-
raphy was further washed with n-pentane to give a light yellow solid
(2.36 g, 58% yield): mp 220−223 °C 1H NMR (400 MHz, CDCl3) δ
7.97−7.00 (m, 8H), 7.51−7.11(m, 11H); 13C NMR (100 MHz,
CDCl3) δ 197.6, 139.7, 134.3, 134.2, 131.4, 131.4, 130.4, 130.3, 129.5,
129.3, 129.2, 128.4, 127.9, 125.9, 125.6, 122.9, 52.1; IR (KBr) 3445,
3053, 2922, 2853, 1689, 1587, 1570, 1397, 1310, 1290, 1203 cm−1;
LC-MS calcd for C22H19ClO3 406.1, found m/z 407.2 [M + H]+. Anal.
Calcd for C28H19ClO: C, 82.65; H, 4.71. Found: C, 82.79; H, 4.60.
2,2-Diphenyl-1-(thiophen-2-yl)ethanone [5a, Table 2]. Pre-
pared from 1-(thiophen-2-yl)ethanone (1.08 mL, 10.0 mmol),
selenium dioxide (1.11 g, 10.0 mmol), BF3·Et2O (49%, 7 mL), and
dry benzene (16 mL) following the general procedure in 18 h. Solvent
system for column chromatography: 9.8:0.2−9.5:0.5; hexane/ethyl-
acetate. The product was isolated as white solid (1.81 g, 65% yield):
mp 140−143 °C; 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 3.6 Hz,
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