Copper-catalyzed oxidation of deoxybenzoins to benzils under aerobic conditions

Article abstract of DOI:10.1055/s-0033-1338451

A novel copper-catalyzed approach to benzils from readily available deoxybenzoins under neutral conditions using air as the oxidant has been developed. The reaction tolerates a variety of useful substituents including chloro, bromo, iodo, keto, ester, and cyano groups. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1338451

PAPER
▌1701
paper
Copper-Catalyzed Oxidation of Deoxybenzoins to Benzils under Aerobic
Conditions
Oxidation of Deoxybenzoins to Benzils
Sandro Cacchi, Giancarlo Fabrizi, Antonella Goggiamani,* Antonia Iazzetti, Rosanna Verdiglione
Dipartimento di Chimica e Tecnologie del Farmaco, La Sapienza, Università di Roma, P.le A. Moro 5, 00185 Rome, Italy
Fax +39(06)49912780; E-mail: antonella.goggiamani@uniroma1.it
Received: 17.01.2013; Accepted after revision: 08.04.2013
could be isolated only in 15% yield at 80 °C, the main
product being benzoic acid (50% yield) (Table 1, entry 1).
The starting material was recovered in 35% yield. Pleas-
ingly, increasing the reaction temperature to 100 °C led to
the isolation of 2a in 95% yield (entry 2). However, when
these conditions were applied to 1b (R1 = H; R2 = 4-MeO)
the reaction afforded 2b in 24% yield and p-anisic acid
was isolated in 70% yield (entry 3). Thus, the reaction
conditions were optimized for this substrate by exploring
the influence of temperature, copper salts, ligands, and
solvents on the reaction outcome. Increasing the reaction
temperature to 130 °C led to the isolation of the desired
oxidation product in 48% yield along with significant
amounts of p-anisic acid (entry 4). The use of other copper
salts and ligands gave similar results (entries 5–9). Similar
results were also obtained in m-xylene (entry 10) whereas
the starting material was recovered in almost quantitative
yield using 1,4-dioxane, acetonitrile, and toluene (entries
11–13). An increase in the yield (57%) was observed in
1,2,4-trimethylbenzene and by substituting air for oxygen
(entry 14). When the reaction was carried out under the
latter conditions by decreasing the reaction temperature to
100 °C, 2b could be isolated in a satisfactory 62% yield
(entry 15). When the behavior of 1a under these condi-
tions was evaluated, it was found that 2a was formed in
high yield although lower than that observed in o-xylene
under oxygen. Thus, it was decided to use both the oxida-
tion protocols [Cu(OAc)2, Ph3P, o-xylene, O2, 100 °C and
Cu(OAc)2, Ph3P, 1,3,5-trimethylbenzene, air, 100 °C]
when other substrates were investigated to explore the
scope and generality of the reaction. Most probably, the
Abstract: A novel copper-catalyzed approach to benzils from read-
ily available deoxybenzoins under neutral conditions using air as
the oxidant has been developed. The reaction tolerates a variety of
useful substituents including chloro, bromo, iodo, keto, ester, and
cyano groups.
Key words: copper, catalysis, oxidation, deoxybenzoins, benzils
As part of our continuing interest in the synthesis of het-
erocycles,1 we lately focused on the development of new
approaches to heterocyclic derivatives starting from 1,2-
diketones, a class of versatile synthetic intermediates.2
Among the wide variety of methods described in literature
for their preparation,3 the recently reported conversion of
readily available deoxybenzoins to benzils in the presence
of DABCO and air4 appeared to us particularly attractive
and convenient as well as environmentally benign. Unfor-
tunately, when the conversion of 1a into 2a was attempted
under the described conditions, a reaction described to af-
ford 2a in 95% yield,4 the desired product was isolated
only in 19% yield and the starting material was recovered
in 74% yield (Scheme 1). Similar disappointing results
were also obtained with 1b–d (Scheme 1).
We then turned our attention to the other methods that al-
low for the synthesis of benzils via oxidation of deoxy-
benzoins. However, they are all based on the use of
stoichiometric amounts or an excess of oxidants such as
selenium dioxide,3a thallium nitrate,3b pyridinium chloro-
chromate,3g,h potassium permanganate,3i and copper bro-
mide adsorbed onto alumina.3k Furthermore, methods
based on thallium and chromium salts suffer from the
drawback of using toxic reagents. Therefore, it appeared
to us of interest to explore an alternative, more environ-
mentally friendly approach. Particularly, given the known
ability of copper to catalyze oxidation reactions,5,6 we set-
tled to investigate the feasibility of a copper-catalyzed ox-
idation process.
R2
R1
DABCO, air
DMF, 90 °C
O
1a: R1 = R2 = H
1b: R1 = MeO; R2 = H
1c: R1 = Cl; R2 = I
1d: R1 = H; R2 = CN
The starting deoxybenzoins were prepared by Friedel–
Crafts acylation reactions or palladium-catalyzed cross-
coupling of aryl halides with acetophenones.7
R2
O
R1
Our study was started by examining the oxidation of 1a
(R1 = R2 = H) with Cu(OAc)2 and Ph3P in o-xylene under
a balloon of oxygen. An initial screening showed that 2a
O
2a (19% yield; 1a recovered in 74% yield)
2b (20% yield; 1b recovered in 80% yield)
2c (traces; 1c recovered in 60% yield)
2d (traces; 1d recovered in 90% yield)
SYNTHESIS 2013, 45, 1701–1707
Advanced online publication: 15.05.2013
DOI: 10.1055/s-0033-1338451; Art ID: SS-2013-Z0055-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Scheme 1 Reaction of deoxybenzoins with DABCO under aerobic
conditions

1702
S. Cacchi et al.
PAPER
Table 1 Optimization Studiesa
O
HO
Ar
Ar
Ar
+
Ph
Ph
O
3
O
O
1
2
Entry Ar
[Cu]
Ligand
Atmosphere Solvent
Temp Time 2 Yield
3 Yield
(°C)
(h)
(%)b
(%)b
1
2
Ph
1a
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OTf)2 (20%)
CuI (15%)
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
−
O2
O2
O2
O2
O2
O2
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
m-xylene
80
100
100
130
130
130
130
130
130
130
24
4
15
95
24
2a 50c
2a
3a
3a
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3a
Ph
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1a
−
3
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
Ph
4
2b 70
2b 19
2b 31
4
0.75 48
5
3
44
46
6
Ph3P (30%)
24
2b
6
7
CuI (20%)
proline (40%) O2
O2
CHDAe (30%) O2
0.75 24
5.5 50
2b 30d
8
CuCl2 (20%)
−
2b
2b
8
9
Cu(OAc)2 (15%)
Cu(OAc)2 (10%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
Cu(OAc)2 (15%)
2.25 48
0.75 48
−
10
11
12
13
14
15
16
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
Ph3P (30%)
O2
O2
O2
O2
air
air
air
2b 19
f
1,4-dioxane 130
24
4
−
−
−
2b
2b
2b
2b
2b
2a
−
−
−
−
−
−
f
f
MeCN
toluene
130
130
0.75
1,2,4-TMBg 130
1,2,4-TMBg 100
1,2,4-TMBg 100
0.75 57
0.75 62
0.75 83
a Reactions were carried out on a 0.4 mmol scale in 1.6 mL of solvent.
b Yields are given for isolated products.
c Starting material 1a was recovered in 34% yield.
d Starting material 1a was recovered in 9% yield.
e CHDA: cyclohexane-1,2-diamine.
f Starting material 1a was recovered in 99% yield.
g 1,2,4-TMB: 1,2,4-trimethylbenzene.
best method is to evaluate the effectiveness of these pro-
tocols each time.
Cu(II)
Ar
O
Ar
As shown by the results summarized in Table 2, the reac-
tion affords benzils from deoxybenzoins in moderate to
excellent yields and tolerates a variety of useful substitu-
ents including chloro, bromo, iodo, keto, ester, and cyano
groups. Substituents in the ortho position of the benzylic
fragment are also tolerated (Table 2, entry 19).
1
O2
•
O
O
O2
•
Ar
Ar
Ar
Ar
O
A
O
Cu(I)
Although the detailed mechanism of this copper-cata-
lyzed oxidation is unclear at the moment, it is likely that
the reaction proceeds according to the following elemen-
tary steps (Scheme 2): initial formation of the benzylic
radical A from the starting deoxybenzoin 1 combined with
the reduction of the copper(II) catalyst to copper(I); sub-
sequent reaction of 1 with oxygen to afford the peroxora-
dical B; conversion of the latter into the hydroperoxide C
via capture of a hydrogen from the reaction medium; and
elimination of water8 to give the benzil derivative 2. Copper(I)
is reoxidized to the active copper(II) catalyst by oxygen.
B
[H•]
OH
O
O
Ar
Ar
Ar
Ar
– H2O
O
O
C
2
Scheme 2 Proposed reaction mechanism for the copper-catalyzed
oxidation of deoxybenzoins to benzyls
Synthesis 2013, 45, 1701–1707
© Georg Thieme Verlag Stuttgart · New York

PAPER
Oxidation of Deoxybenzoins to Benzils
1703
Table 2 Copper-Catalyzed Oxidation of Deoxybenzoins 1 to Benzyls 2a
O
Ar2
Ar2
Cu(OAc)2, Ph3P
100 °C
Ar1
Ar1
O
O
1
2
Entry
Deoxybenzoin 1
Time (h)b
Benzil 2, yield (%)c,d
O
1
2
3
4
0.75
0.75
95e
1a
1b
1c
1d
1e
2a
83
85f
O
O
O
4
5
6
7
0.75
2.5
1
2b
55
70
66
62
O
O
MeO
MeO
I
I
O
2c
O
O
Cl
Cl
CN
CN
O
2d
O
O
OMe
OMe
O
0.75
2b
O
O
O
O
O
8
9
1f
7
2e
70
45
O
O
1g
0.5
2f
O
CO2Me
COMe
CO2Me
O
10
11
1h
1i
1
5
2g
72
53
O
O
O
COMe
O
2h
O
O
12
13
1.5
4.5
53
1j
2i
43e
O
O
Cl
Cl
I
I
O
14
1k
7
2j
60
O
O
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1701–1707

1704
S. Cacchi et al.
PAPER
Table 2 Copper-Catalyzed Oxidation of Deoxybenzoins 1 to Benzyls 2a (continued)
O
Ar2
Ar2
Cu(OAc)2, Ph3P
100 °C
Ar1
Ar1
O
O
1
2
Entry
Deoxybenzoin 1
Time (h)b
2.5
Benzil 2, yield (%)c,d
Br
Br
O
15
1l
2k
75
O
O
O
Br
Br
16
17
1m
1n
9
2l
60
56
O
O
Cl
Cl
OMe
OMe
O
0.5
2m
O
O
Cl
Cl
OMe
OMe
O
18
19
1o
1p
0.75
2n
2o
51
62
O
O
MeO
MeO
O
7
O
O
Br
Br
a Unless otherwise stated, reactions were carried out on a 0.4 mmol scale in 1.6 mL of 1,2,4-trimethylbenzene at 100 °C under air using 15 mol%
of Cu(OAc)2 and 30 mol% of Ph3P.
b Reaction times are for a 100% conversion.
c Yields are given for isolated products.
d Variable amounts of carboxylic acids were formed as well as other by-products that have not been investigated.
e Reactions carried out in o-xylene under a balloon of O2.
f On a 10 mmol scale.
Deoxybenzoins via Friedel–Crafts Acylation; 2-(4-Chlorophe-
nyl)-1-phenylethanone (1j); Typical Procedure
A flask equipped with a magnetic stirring bar was charged with 2-
(4-chlorophenyl)acetyl chloride (283.5 mg, 219 μL, 1.5 mmol),
CH2Cl2 (2 mL), and benzene (234 mg, 267 μL, 3.0 mmol). The so-
In summary, a simple and convenient copper-catalyzed
oxidation of deoxybenzoins to benzils under neutral con-
ditions using air as the oxidant has been developed. The
reaction allows for the preparation of benzils in moderate
to excellent yields and tolerates a variety of useful substit- lution was stirred under N2 at 0 °C before adding AlCl3 (219 mg,
1.65 mmol). The reaction mixture was stirred at r.t. for 0.5 h. After
this time, it was poured onto ice, extracted with CH2Cl2 (150 mL),
and washed with brine (50 mL). The combined organic layers were
dried (Na2SO4), filtered, and concentrated under reduced pressure.
uents including chloro, bromo, iodo, keto, ester, and cya-
no groups.
The residue was purified by gradient elution flash chromatography
on silica gel (n-hexane–EtOAc mixtures) to give 1j as a white solid;
yield: 256 mg (88%); mp 132–134 °C (Lit.9 mp 132–134 °C).
Melting points were determined with a Büchi B-545 apparatus and
are uncorrected. Deoxybenzoins were prepared through Friedel–
Crafts acylation reactions or palladium-catalyzed cross-coupling of
aryl halides with acetophenones.6 All the other reagents and sol-
vents are commercially available and were used as purchased, with-
Deoxybenzoins via Palladium-Catalyzed Cross-Coupling of
Aryl Halides with Acetophenones; 1-(4-Cyanophenyl)-2-
phenylethan-1-one (1d); Typical Procedure
1
out further purification. H NMR (400.13 MHz) and 13C NMR
(100.6 MHz) spectra were recorded with a Bruker Avance 400 spec-
trometer. IR spectra were recorded on a JASCO FT/IR-430 spectro-
photometer. Mass spectra were determined with a QP2010 gas
chromatograph mass spectrometer (EI ion source).
A Carousel reaction tube (Radley Discovery) was charged with
Pd(OAc)2 (7 mg, 0.03 mmol), XPhos (29 mg, 0.06 mmol), and tol-
uene (2 mL). The solution was stirred under N2 at r.t. for 10 min be-
fore adding t-BuONa (720 mg, 7.5 mmol), 4-acetylbenzonitrile
(522 mg, 3.6 mmol), and bromobenzene (471 mg, 3 mmol) dis-
solved in toluene (2 mL). The reaction mixture was warmed at
90 °C and stirred for 5 h. After cooling, the mixture was diluted with
Synthesis 2013, 45, 1701–1707
© Georg Thieme Verlag Stuttgart · New York

PAPER
Oxidation of Deoxybenzoins to Benzils
1705
Et2O (150 mL) and washed with H2O (50 mL) and brine (150 mL).
The organic layer was dried (Na2SO4), filtered, and concentrated
under reduced pressure. The residue was purified by gradient elu-
tion flash chromatography (n-hexane–EtOAc mixtures) to afford 1d
as a white solid; yield: 471 mg (71%); mp 110–112 °C.
IR (KBr): 3112, 3073, 3046, 2225, 1683, 1660, 1594, 1172, 881
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.12 (d, J = 8.8 Hz, 2 H), 8.00 (dd,
J = 8.4, 0.8 Hz, 2 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.73 (t, J = 7.6 Hz,
1 H), 7.57 (t, J = 8.0 Hz, 2 H).
1,2-Diarylethanediones; Benzil (2a); Typical Procedure
A Carousel reaction tube (Radley Discovery) was charged with
Cu(OAc)2 (12 mg, 0.06 mmol), Ph3P (31 mg, 0.12 mmol), and
1,2,4-trimethylbenzene (1 mL). The solution was stirred under air at
r.t. for 10 min before adding 1,2-diphenylethanone (78.5 mg, 0.4
mmol) dissolved in 1,2,4-trimethylbenzene (0.6 mL). The reaction
mixture was warmed at 100 °C and stirred for 1 h. After cooling, the
mixture was diluted with Et2O (150 mL) and washed with a sat. aq
NH4Cl (50 mL) and brine (50 mL). The organic layer was dried
(Na2SO4), filtered, and concentrated under reduced pressure. The
residue was purified by gradient elution flash chromatography on
silica gel (n-hexane–EtOAc mixtures) to give 2a as a pale yellow
solid; yield: 71.4 mg (83%); mp 91–93 °C; Rf = 0.18 (n-hexane–
EtOAc, 95:5).
13C NMR (100.6 MHz, CDCl3): δ = 193.0, 192.4, 135.9, 135.4,
132.8, 132.5, 130.2, 130.0, 129.2, 117.9, 117.6.
MS: m/z (%) = 163 (6.3), 235 (M+, 7.2), 102 (26.6), 51 (42.9), 77
(62.2), 105 (100).
Anal. Calcd for C15H9NO2: C, 76.59; H, 3.86; N, 5.95. Found: C,
76.65; H, 3.87; N, 5.96.
1-Phenyl-2-p-tolylethane-1,2-dione (2e)
Yield: 62.8 mg (70%); yellow oil; Rf = 0.20 (n-hexane–EtOAc,
97:3).
IR (neat): 2923, 2854, 1674, 1604, 1450, 1384, 1214, 1174, 875
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 7.2 Hz, 2 H), 7.90 (d,
J = 8.4 Hz, 2 H), 7.68 (t, J = 7.2 Hz, 1 H), 7.53 (t, J = 8.0 Hz, 2 H),
7.33 (d, J = 8.0 Hz, 2 H), 2.46 (s, 3 H).
IR (KBr): 2921, 2856, 1658, 1594, 1450, 1384, 1211, 1101, 875
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 7.2 Hz, 4 H), 7.67 (t,
J = 7.6 Hz, 2 H), 7.53 (t, J = 7.6 Hz, 4 H).
13C NMR (100.6 MHz, CDCl3): δ = 194.8, 194.3, 146.2, 134.8,
133.1, 130.6, 130.0, 129.9, 129.7, 129.0, 21.9.
13C NMR (100.6 MHz, CDCl3): δ = 194.6, 134.9, 133.0, 129.9,
129.1.
MS: m/z (%) = 224 (M+, 1.5), 51 (22.7), 65 (24.3), 105 (25.1), 77
(34.8), 91 (37.0), 119 (100).
MS: m/z (%) = 210 (M+, 0.2), 64 (10.1), 105 (11.6), 51 (14.8), 92
(15.6), 77 (43.1), 135 (100).
Anal. Calcd for C15H12O2: C, 80.34; H, 5.39. Found: C, 80.42; H,
5.40.
Anal. Calcd for C14H10O2: C, 79.98; H, 4.79. Found: C, 79.88; H,
4.78.
1-(2-Methoxyphenyl)-2-phenylethane-1,2-dione (2f)
Yield: 40.4 mg (45%); pale yellow solid; mp 53–55 °C; Rf = 0.20
(n-hexane–EtOAc, 97:3).
1-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (2b)
Yield: 52.8 mg (55%); yellow oil; Rf = 0.19 (n-hexane–EtOAc,
90:10).
IR (KBr): 3064, 2969, 2929, 1994, 1820, 1679, 1596, 1452, 1205,
1166, 881 cm–1.
IR (neat): 2933, 2842, 1779, 1675, 1596, 1265, 1216, 1166, 1024,
875 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 7.6 Hz, 2 H), 7.69–
7.51 (m, 3 H), 7.38–7.29 (m, 4 H), 2.73 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.00–7.96 (m, 4 H), 7.66 (t, J = 7.6
Hz, 1 H), 7.52 (t, J = 7.6 Hz, 2 H), 7.00 (d, J = 8.8 Hz, 2 H), 3.90 (s,
3 H).
13C NMR (100.6 MHz, CDCl3): δ = 196.8, 194.8, 141.3, 134.7,
133.7, 133.2, 133.0, 132.6, 129.9, 129.0, 128.5, 126.0, 21.9.
MS: m/z (%) = 224 (M+, 1.4), 51 (21.5), 65 (23.3), 105 (25.2), 77
(35.2), 91 (37.3), 119 (100).
13C NMR (100.6 MHz, CDCl3): δ = 194.9, 193.2, 165.0, 134.7,
133.2, 132.4, 129.9, 129.0, 126.1, 114.4, 55.6.
MS: m/z (%) = 240 (M+, 0.7), 64 (10.2), 105 (12.0), 92 (15.0), 51
Anal. Calcd for C15H12O2: C, 80.34; H, 5.39. Found: C, 80.39; H,
5.38.
(15.7), 77 (44.4), 135 (100).
Methyl 4-(2-Oxo-2-phenylacetyl)benzoate (2g)
Yield: 77.2 mg (72%); pale yellow solid; mp 65–67 °C; Rf = 0.19
(n-hexane–EtOAc, 85:15).
Anal. Calcd for C15H12O3: C, 74.99; H, 5.03. Found: C, 74.90; H,
5.04.
IR (KBr): 2954, 2927, 2848, 1720, 1671, 1436, 1286, 1209, 1105,
885 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.18 (d, J = 8.4 Hz, 2 H), 8.06 (d,
J = 8.0 Hz, 2 H), 8.00 (d, J = 7.6 Hz, 2 H), 7.70 (t, J = 7.6 Hz, 1 H),
7.54 (t, J = 7.6 Hz, 2 H), 3.97 (s, 3 H).
1-(4-Chlorophenyl)-2-(4-iodophenyl)ethane-1,2-dione (2c)
Yield: 103.8 mg (70%); yellow solid; mp 208–210 °C; Rf = 0.18 (n-
hexane–EtOAc, 97:3).
IR (KBr): 3087, 2954, 2913, 1662, 1579, 1394, 1209, 1172, 1091,
881 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.94–7.91 (m, 4 H), 7.19 (d, J =
8.4 Hz, 2 H), 7.52 (d, J = 8.4 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 193.7, 193.6, 165.8, 136.1,
135.3, 135.1, 132.8, 130.1, 130.0, 129.8, 126.3, 52.6.
13C NMR (100.6 MHz, CDCl3): δ = 193.0, 192.3, 141.8, 138.5,
MS: m/z (%) = 135 (9.1), 51 (22.1), 163 (24.7), 77 (51.3), 105 (100).
132.1, 131.3, 131.1, 131.0, 129.5, 103.9.
MS: m/z (%) = 370 (M+, 6.0), 203 (18.3), 51 (18.7), 141 (35.3), 111
Anal. Calcd for C16H12O4: C, 71.64; H, 4.51. Found: C, 71.59; H,
4.50.
(58.1), 50 (71.5), 231 (85.1), 76 (85.6), 139 (100).
1-(4-Acetylphenyl)-2-phenylethane-1,2-dione (2h)
Yield: 53.4 mg (53%); pale yellow solid; mp 78–80 °C; Rf = 0.20
(n-hexane–EtOAc, 85:15).
Anal. Calcd for C14H8ClIO2: C, 45.38; H, 2.18. Found: C, 45.42; H,
2.17.
IR (KBr): 2923, 2852, 1677, 1436, 1213, 885 cm–1.
4-(2-Oxo-2-phenylacetyl)benzonitrile (2d)
Yield: 62.1 mg (66%); pale yellow solid; mp 110–112 °C; Rf = 0.20
(n-hexane–EtOAc, 85:15).
1H NMR (400 MHz, CDCl3): δ = 8.09–8.01 (m, 4 H), 7.99 (d, J =
1.2 Hz, 2 H), 7.69 (t, J = 7.6 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 2 H), 2.65
(s, 3 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1701–1707

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S. Cacchi et al.
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13C NMR (100.6 MHz, CDCl3): δ = 197.1, 193.7, 193.6, 141.3,
136.0, 135.1, 132.7, 130.1, 129.9, 129.1, 128.7, 26.9.
MS: m/z (%) = 252 (M+, 2.51), 91 (10.7), 147 (24.5), 77 (44.8), 105
1-(4-Chlorophenyl)-2-(4-methoxyphenyl)ethane-1,2-dione (2m)
Yield: 61.5 mg (56%); pale yellow solid; mp 127–128 °C; Rf = 0.19
(n-hexane–EtOAc, 90:10).
IR (KBr): 3093, 3002, 2937, 2838, 1670, 1654, 1598, 1267, 1214,
1168, 1027, 881 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96–7.92 (m, 4 H), 7.49 (d, J =
8.4 Hz, 2 H), 6.99 (d, J = 8.8 Hz, 2 H), 3.90 (s, 3 H).
(100).
Anal. Calcd for C16H12O3: C, 76.18; H, 4.79. Found: C, 76.22; H,
4.78.
1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (2i)
Yield: 51.9 mg (53%); pale yellow solid; mp 71–73 °C; Rf = 0.20
(n-hexane–EtOAc, 96:4).
13C NMR (100.6 MHz, CDCl3): δ = 193.3, 192.4, 165.1, 141.4,
132.4, 131.6, 131.2, 129.4, 125.9, 114.4, 55.7.
MS: m/z (%) = 274 (M+, 1.5), 139 (18.2), 77 (20.2), 141 (52.2), 135
(100).
IR (KBr): 2931, 1666, 1585, 1450, 1402, 1209, 1174, 1095, 875
cm–1.
Anal. Calcd for C15H11ClO3: C, 65.58; H, 4.04. Found: C, 65.66; H,
4.03.
1H NMR (400 MHz, CDCl3): δ = 8.00–7.93 (m, 4 H), 7.69 (t, J = 7.6
Hz, 1 H), 7.56–7.49 (m, 4 H).
13C NMR (100.6 MHz, CDCl3): δ = 193.9, 193.0, 141.6, 135.1,
132.8, 131.4, 131.2, 129.9, 129.4, 129.1.
MS: m/z (%) = 245 (M+, 0.6), 141 (10.5), 139 (29.8), 51 (35.8), 77
1,2-Bis(4-methoxyphenyl)ethane-1,2-dione (2n)
Yield: 55.1 mg (51%); yellow solid; mp 131–132 °C; Rf = 0.17 (n-
hexane–EtOAc, 85:15).
IR (KBr): 3025, 2925, 2850, 1654, 1598, 1571, 1263, 1160, 1016,
879 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.8 Hz, 4 H), 7.00 (d,
J = 8.8 Hz, 4 H), 3.91 (s, 6 H).
(56.8), 105 (100).
Anal. Calcd for C14H9ClO2: C, 68.72; H, 3.71. Found: C, 68.69; H,
3.72.
1-(4-Iodophenyl)-2-phenylethane-1,2-dione (2j)
Yield: 80.7 mg (60%); yellow solid; mp 89–90 °C; Rf = 0.20 (n-hex-
ane–EtOAc, 97:3).
13C NMR (100.6 MHz, CDCl3): δ = 193.5, 164.9, 132.4, 126.3,
114.3, 55.6.
MS: m/z (%) = 270 (M+, 2.2), 77 (17.9), 207 (49.4), 44 (85.1), 135
(100).
IR (KBr): 3060, 2927, 2861, 1670, 1579, 1394, 1211, 1174, 879
cm–1.
Anal. Calcd for C16H14O4: C, 71.10; H, 5.22. Found: C, 71.18; H,
5.23.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 7.6 Hz, 2 H), 7.91 (d,
J = 8.4 Hz, 2 H), 7.71–7.68 (m, 3 H), 7.54 (t, J = 7.6 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 193.9, 193.7, 138.4, 135.1,
132.8, 132.3, 131.0, 130.0, 129.1, 103.7.
MS: m/z (%) = 336 (M+, 0.5), 203 (6.5), 231 (19.1), 51 (32.7), 50
(33.7), 77 (56.7), 105 (100).
1-(2-Bromophenyl)-2-phenylethane-1,2-dione (2o)
Yield: 71.7 mg (62%); yellow oil; Rf = 0.18 (n-hexane–EtOAc,
96:4).
IR (neat): 2923, 1677, 1585, 1450, 1253, 1027 860 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.09 (d, J = 0.8 Hz, 2 H), 7.85–
7.83 (m, 1 H), 7.71–7.62 (m, 2 H), 7.58–7.44 (m, 4 H).
Anal. Calcd for C14H9IO2: C, 50.03; H, 2.70. Found: C, 50.10; H,
2.71.
13C NMR (100.6 MHz, CDCl3): δ = 194.2, 191.5, 136.0, 134.5,
134.4, 133.8, 132.7, 132.6, 130.4, 128.9, 127.8, 121.8.
MS: m/z (%) = 289 (M+, 2.0), 183 (11.2), 155 (12.9), 51 (32.9), 77
1-(4-Bromophenyl)-2-phenylethane-1,2-dione (2k)
Yield: 86.7 mg (75%); yellow solid; mp 81–83 °C; Rf = 0.18 (n-hex-
ane–EtOAc, 97:3).
(54.5), 105 (100).
IR (KBr): 3087, 2967, 2927, 1668, 1579, 1450, 1398, 1209, 1174,
1070, 873 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 7.2 Hz, 2 H), 7.86 (d,
J = 8.4 Hz, 2 H), 7.71–7.67 (m, 3 H), 7.54 (t, J = 7.6 Hz, 2 H).
Anal. Calcd for C14H9BrO2: C, 58.16; H, 3.14. Found: C, 58.21; H,
3.13.
13C NMR (100.6 MHz, CDCl3): δ = 193.9, 193.3, 135.1, 132.8,
132.5, 131.7, 131.3, 130.5, 130.0, 129.1.
Acknowledgment
We gratefully acknowledge MURST and the University ‘La
Sapienza’, Rome, for financial support.
MS: m/z (%) = 289 (M+, 2.0), 183 (9.0), 155 (11.9), 51 (32.8), 77
(55.5), 105 (100).
Anal. Calcd for C14H9BrO2: C, 58.16; H, 3.14. Found: C, 58.20; H,
3.13.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
1-(4-Bromophenyl)-2-(4-chlorophenyl)ethane-1,2-dione (2l)
Yield: 77.7 mg (60%); yellow solid; mp 203–205 °C; Rf = 0.21 (n-
hexane–EtOAc, 97:3).
IR (KBr): 2923, 1664, 1587, 1209, 1172, 835 cm–1.
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Synthesis 2013, 45, 1701–1707