Synthesis of unsymmetrical benzils using N-heterocyclic carbene catalysis

Article abstract of DOI:10.1016/j.tet.2011.04.020

In this paper, we propose a novel and efficient method for the preparation of various unsymmetrical benzils. We first demonstrate the nucleophilic aroylation of N-phenylbenzimidoyl chlorides with aromatic aldehydes using N-heterocyclic carbene as the catalyst to afford 1-aryl-2-phenyl-2-(phenylimino) ethanones. These iminoethanones were then converted to 1,2-diaryl-1,2-diketones by acid-promoted hydrolysis.

Full text of DOI:10.1016/j.tet.2011.04.020

Tetrahedron 67 (2011) 4710e4715
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of unsymmetrical benzils using N-heterocyclic carbene catalysis
*
Yumiko Suzuki , Abu Bakar Md., Takashi Tanoi, Naoko Nomura, Masayuki Sato
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
In this paper, we propose a novel and efficient method for the preparation of various unsymmetrical
benzils. We first demonstrate the nucleophilic aroylation of N-phenylbenzimidoyl chlorides with aro-
matic aldehydes using N-heterocyclic carbene as the catalyst to afford 1-aryl-2-phenyl-2-(phenylimino)
ethanones. These iminoethanones were then converted to 1,2-diaryl-1,2-diketones by acid-promoted
hydrolysis.
Received 10 February 2011
Received in revised form 5 April 2011
Accepted 7 April 2011
Available online 20 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
N-Heterocyclic carbene
Organocatalysis
Unsymmetrical benzil
Nucleophilic aroylation
1. Introduction
biologically active diarylheterocycles.7e11 Two common methods
are primarily employed for the preparation of unsymmetrical
In the last decade, N-heterocyclic carbenes (NHCs) have attracted
considerable attention as organocatalysts due to their unique cata-
lytic properties, facile reactions, and selectivities.1e5 Many reports
have indicated the great potential of NHCs as organocatalysts
for a variety of organic reactions. In 1992, our former co-workers,
Miyashita and his colaborators reported that the NHC generated from
1,3-dimethylimidazolium iodide (30 mol %) catalyzes nucleophilic
substitutions at the imino carbon atom of N-phenylbenzimidoyl
chlorides.6 In this reaction, the chlorine substituent is replaced by
the aroyl groups originating from aromatic aldehydes to afford 1,2-
diphenyl-2-(phenylimino)ethanones,andmoreover, thehydrolysisof
the iminoethanones afforded corresponding benzils (1,2-diaryl-1,2-
diketones).
benzils. One route involves an addition reaction of the anion de-
rived from cyanohydrins to aromatic aldehydes and the oxidation
of the obtained benzoins.8,12 However, in this method, the use of
toxic cyanation reagents is problematic. The other route involves
the FriedeleCrafts reaction between benzenes and 2-phenylacetyl
chlorides and the oxidation of the products.9e11,13 In this case, it is
difficult to control the regioselectivities in FriedeleCrafts acylation,
and moreover, this route is not always applicable to the synthesis
due to the directing and activating effects of the substituents.
In this study, we present an alternative synthetic route for
unsymmetrical benzils (Scheme 1). Our route consists of NHC-
catalyzed aroylation of N-phenylbenzimidoyl chlorides with aro-
matic aldehydes and the hydrolysis of the aroylated products, i.e.,
iminoethanones. The substrates of the catalytic reaction, N-phe-
nylbenzimidoyl chlorides, are easily obtained by the chlorination of
Unsymmetrical benzils are important building blocks in organic
synthesis because they are intermediates for the synthesis of
Scheme 1.
* Correspondingauthor. E-mail address: suzuyumi@u-shizuoka-ken.ac.jp (Y. Suzuki).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.020

Y. Suzuki et al. / Tetrahedron 67 (2011) 4710e4715
4711
benzanilides. Further, in order to increase the efficiency of the
synthesis, we investigated the optimization of the reaction condi-
tions for the NHC catalysis.
that the benzoin condensation process is significantly affected by
the nature of the substituents in the aldehydes.20,21 The aroylation
of 5 and 11 with various aldehydes also afforded iminoethanones
10 and 13 in good to moderate yields. In the case of 12, the reaction
yield increased from 69% to 80% when imidazolium salt 15 was
used instead of 3.
2. Results and discussions
In order to prepare the unsymmetrical benzils, iminoethanones
4, 10, 13, and 14 were hydrolyzed under acidic conditions; the
results are shown in Table 4. Treatment of 4, 10, 13, and 14 with
10% HCl in THF at room temperature for 3 h afforded benzils
16e19 in good to excellent yields (entries 1, 2, and 4e14), except
for the product with the furyl substituent 16f (entry 3). The acidic
condition damaged the furan nucleus of 4f and/or 16f. A milder
hydrolysis condition is required for 4f to prevent the
decomposition.
In our experiments, we first carried out the reaction according to
the procedure previously reported by Miyashita and his co-workers.6
A mixture of N-phenylbenzimidoyl chloride 1, 4-chlorobenzaldehyde
2a (1.1 equiv), NaH (1.3 equiv), and 30 mol % of 1,3-dimethylimida-
zolium iodide 3 in THF was refluxed to afford 1-(4-chlorophenyl)-2-
phenyl-2-(phenyl)iminoethanone 4a in 63% yield (Table 1; entry 1).
The reaction was then conducted with the reduced catalyst loadings
(entries 2e5). The reduced reaction rate was compensated by using
1.5 equiv of 2a in the case of the reactions with 10 mol % of 3 (entries 2
and 3). When 3 mol % and 1 mol % of 3 were used, longer reaction
times(8hfor3 mol%and 18 hfor1mol%)wereneeded toobtain4ain
91% and 75% yields, respectively (entries 4 and 5); further, when DMF
and acetonitrile were used instead of THF as the solvent, the yields of
4a decreased (entries 6 and 7).
3. Conclusion
We have developed an efficient method for the synthesis of un-
symmetrical benzils 16e19 using the NHC-catalyzed aroylation of
Table 1
Aroylation of N-phenylbenzimidoyl chloride 1 with 4-chlorobenzaldehyde 2a
Entry
2a (equiv)
3 (mol %)
Solvent
Temp (ꢀC)
Time (h)
Yield (%)
1a
2
3
4
5
6
7
1.1
1.1
1.5
1.5
1.5
1.1
1.5
30
10
10
3
1
30
3
THF
THF
THF
THF
THF
DMF
CH3CN
Reflux
Reflux
Reflux
Reflux
Reflux
60
3
3
3
8
18
2
63
51
78
91
75
29
41
60
7
a
The condition reported by Miyashita and his co-workers.6
The use of other NHCs and a base was also examined in the re-
action of 5 with 2b (Table 2). When the reactionwas carried out using
10 mol % of 3 as a catalyst precursor and NaH as a base, the product
10b was obtained in 79% yield (entry 1). In contrast, when DBU was
used instead of NaH, the reaction did not proceed (entry 2). The NHC
originating from 6 is a well-used ligand. However, the bulky N-sub-
stituents of the NHC seemed to prevent the reaction course (entry 3).
On the other hand, the NHC generated from benzimidazolim salt 7
catalyzed the reaction to afford 10a in 12% yield (entry 4). The at-
tempt to use the NHCs generated from triazolium salt 8 and thiazo-
lium salt 9 as catalysts resulted in the recovery of 2b (entries 6e9).
The results of the aroylation reaction of 1 and other N-phe-
nylimidoyl chlorides 5, 11, and 12 with various aromatic alde-
hydes 2aej are shown in Table 3. Imidoyl chlorides 1, 5, 11, and
12 were prepared by the chlorination of the corresponding
N-phenylarenecarboxamides.14e18 All the reactions were per-
formed in the presence of 3 mol % of catalysts using 1.5 equiv of
aldehydes to N-phenylimidoyl chlorides in refluxing THF. The re-
action of 1 with aldehydes 2b, c, and eeg afforded iminoethanones
4b, c, and eeg in good yields (entries 1e7). On the other hand, the
yields of 4d and h were moderate, presumably due to the steric
hindrances caused by the o-methyl substituent of 4d and bulky
naphthalene of 4h. The aroylation reaction is considered to proceed
through a common intermediate with NHC-catalyzed benzoin
condensation, i.e., the ‘acyl anion equivalent.’6,19 It is well known
N-phenylimidoyl chlorides 1, 5, 11, and 12 with aromatic aldehydes
2aej followed by acidic hydrolysis. The aroylationwas catalyzed with
only 3 mol % of 3 and 15. The substrates of the first reaction, N-phe-
nylimidoyl chlorides 1, 5,11, and 12 were prepared by the chlorination
of the corresponding N-phenylarenecarboxamides. Note that various
aromatic aldehydes are applicable to the aroylation. Moreover, a large
variety of aldehydes and N-phenylarenecarboxamides are easily
accessible. BycombiningN-phenylarenecarboxamidesand aldehydes
appropriately, it is possible to prepare various unsymmetrical benzils
by employing our method.
4. Experimental section
4.1. General procedure for the synthesis of iminoethanones
To a mixture of the N-phenylbenzimidoyl chlorides 1, 5, 11, and
12 (1 mmol), aromatic aldehyde 2aej (1.5 mmol), and 1,3-dime-
thylimidazolium iodide 3 (6.7 mg, 0.03 mol) in THF (20 ml), NaH
(60% in oil, 52 mg, 1.3 mmol) was added with stirring under argon
atmosphere. The reaction mixture was then refluxed for the in-
dicated time (shown in Table 3) and poured into ice water. Sub-
sequently, the products were extracted with ethyl acetate and
washed with brine; the solvent was then evaporated. The residue
was purified by silica gel column chromatography (n-hexane/ethyl
acetate) to obtain iminoethanones 4, 10, 13, and 14.

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Y. Suzuki et al. / Tetrahedron 67 (2011) 4710e4715
Table 2
Aroylation of N-phenylbenzimidoyl chloride 5 with 4-methoxybenzaldehyde 2b
Entry
Azolium salt
Base
Yield (%)
1
3
3
6
7
7
8
8
9
9
NaH
DBU
NaH
NaH
DBU
NaH
DBU
NaH
DBU
79
d
d
12b
d
d
d
d
d
2a
3
4
5a
6
7a
8
9a
a
The reaction was carried out using 5 (1 mmol), 2b (1.5 mmol), and DBU (10 mmol) in THF (20 ml).
The hydrolyzed product, 1-(4-chlorolphenyl)-2-(4-methoxyphenyl)ethane-1,2-dione was also obtained in 7% yield.
b
Table 3
Aroylation of imidoyl chlorides 1, 5, 11, and 12 with aldehydes 2aej
Entry
Imidoyl chloride
Aldehyde
Time (h)
Iminoethanone
Yield (%)
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
5
5
5
5
5
11
11
11
11
11
11
12
12
2b
2c
2d
2e
2f
2g
2h
2b
2c
2f
7
6
7
7
7
7
7
6
6
6
6
6
9
10
9
10
10
9
4b
4c
4d
4e
4f
4g
4h
10b
10c
10f
10i
10j
13a
13b
13e
13f
13g
13i
14b
14b
80
74
60
76
90
86
51
75
82
80
90
91
49
42
36
74
81
85
69
80
9
10
11
12
13
14
15
16
17
18
19
20a
2i
2j
2a
2b
2e
2f
2g
2i
2b
2b
6
6
a
Imidazolium salt 15 was used instead of 3.

Y. Suzuki et al. / Tetrahedron 67 (2011) 4710e4715
4713
mp 79e81 ꢀC; IR (ATR) cmꢁ1: 1647 (C]O); 1H NMR (CDCl3)
d
: 3.65
Table 4
Hydrolysis of iminoethanones 4, 10, 13, and 14 to unsymmetrical benzils 16e19
(3H, s), 6.85e6.91 (2H, m), 7.09 (2H, td, J¼7.5,1.1 Hz), 7.39e7.46 (4H,
m), 7.61 (2H, dd, J¼7.5, 1.1 Hz), 7.85 (2H, dt, J¼6.9, 1.7 Hz); 13C NMR
(CDCl3) d: 55.5, 111.8, 120.1, 121.0, 124.1, 125.8, 128.1, 128.6, 130.5,
130.9, 135.3, 135.7, 149.9, 159.5, 167.9, 195.6; HRMS (FAB) calcd for
C21H18NO2 (Mþ1): 316.1338. Found: 316.1328.
4.1.6. 1-(Furan-2-yl)-2-phenyl-2-(phenylimino)ethanone (4f). Brown
needles (recrystallized from n-hexane/acetone); 90%, mp
Entry
Iminoethanone
1,2-Diaryl-1,2-diketone
Yield (%)
1
2
3
4
5
6
7
8
4a
4b
4f
4g
16a
16b
16f
16g
16h
17b
17f
16a (17i)
17j
18a
18f
100
100
47
100
100
88
100
63
86
100
82
100
100
90
134e136 ꢀC; IR (ATR) cmꢁ1: 1655 (C]O); 1H NMR (CDCl3)
d: 6.41
(1H, dd, J¼3.4, 1.1 Hz), 6.92 (2H, dt, J¼7.5, 1.2 Hz), 6.98e7.01 (2H,
m), 7.19 (2H, td, J¼7.5, 1.7 Hz), 7.43e7.46 (2H, m), 7.50e7.52 (2H,
m), 7.89 (2H, dt, J¼7.5, 1.7 Hz); 13C NMR (CDCl3)
d: 112.8, 120.4,
4h
10b
10f
10i
10j
13a
13f
13g
13i
14b
121.4, 124.9, 128.2, 128.8, 128.9, 129.0, 130.2, 131.8, 134.8, 148.3,
149.2, 151.3, 164.7, 184.4; HRMS (FAB) calcd for C18H14NO2 (Mþ1):
276.1025. Found: 276.1023.
9
10
11
12
13
14
4.1.7. 2-Phenyl-2-(phenylimino)-1-(thiophen-2-yl)ethanone
18g
18i
19b
(4g)6. Yellow prisms (recrystallized from n-hexane/acetone); 86%,
mp 116e118 ꢀC; IR (ATR) cmꢁ1: 1640 (C]O); 1H NMR (CDCl3)
d:
6.94 (2H, d, J¼8.0 Hz), 6.97e7.00 (2H, m), 7.18 (2H, t, J¼8.0 Hz),
7.43e7.46 (3H, m), 7.49 (1H, td, J¼7.5, 2.3 Hz), 7.62 (1H, dd, J¼5.1,
1.1 Hz), 7.90 (2H, dd, J¼8.6, 1.1 Hz); 13C NMR (CDCl3)
d: 120.6, 125.0,
128.3, 128.6, 128.8, 128.9, 131.8, 135.0, 136.0, 136.2, 142.3, 149.3,
165.3, 189.3.
4.1.8. 1-(Naphthalen-1-yl)-2-phenyl-2-(phenylimino)ethanone
(4h). Yellow powder (recrystallized from n-hexane/acetone); 47%,
mp 143e145 ꢀC; IR (ATR) cmꢁ1: 1655 (C]O); 1H NMR (CDCl3)
d:
4.1.1. 1-(4-Chlorophenyl)-2-phenyl-2-(phenylimino)ethanone
6.76 (1H, t, J¼7.5 Hz), 6.88 (2H, d, J¼7.5 Hz), 7.01 (2H, t, J¼7.5 Hz),
7.35 (1H, t, J¼7.5 Hz), 7.45 (2H, td, J¼7.5, 1.7 Hz), 7.52 (2H, td, J¼7.5,
1.1 Hz), 7.60 (1H, td, J¼6.9, 1.1 Hz), 7.79 (1H, d, J¼8.0 Hz), 7.87 (1H,
dd, J¼7.5, 1.1 Hz), 7.98 (1H, d, J¼8.0 Hz), 7.95 (2H, dd, J¼6.9, 1.7 Hz),
(4a)6. Yellow oil, 91%; IR (ATR) cmꢁ1: 1670 (C]O); 1H NMR (CDCl3)
d
: 6.86 (2H, d, J¼7.5 Hz), 6.96 (1H, t, J¼7.5 Hz), 7.14 (2H, t, J¼7.5 Hz),
7.29e7.32 (2H, m), 7.44 (2H, t, J¼7.5 Hz), 7.49e7.52 (1H, m),
7.67e7.70 (2H, m), 7.85 (2H, dd, J¼7.5, 1.7 Hz); 13C NMR (CDCl3)
d:
9.04 (1H, d, J¼8.6 Hz); 13C NMR (CDCl3)
d: 120.4, 124.4, 124.5, 125.8,
120.5, 125.0, 128.2, 128.8, 129.0, 129.4, 130.7, 132.0, 133.0, 134.9,
141.0, 149.1, 165.9, 196.6.
126.9, 128.4, 128.6, 128.6, 128.9, 129.1, 130.3, 131.2, 131.7, 133.8,
135.4, 135.7, 149.4, 167.1, 199.5; HRMS (FAB) calcd for C24H18NO
(Mþ1): 336.1388. Found: 336.1353.
4.1.2. 1-(4-Methoxyphenyl)-2-phenyl-2-(phenylimino)ethanone
(4b)6. Yellow granules (recrystallized from n-hexane/acetone);
4.1.9. 2-(4-Chlorophenyl)-1-(4-methoxyphenyl)-2-(phenylimino)
80%, mp 73e74 ꢀC; IR (ATR) cmꢁ1: 1657 (C]O); 1H NMR (CDCl3)
d:
ethanone (10b)6. Yellow oil; 75%; IR (ATR) cmꢁ1: 1660 (C]O); 1H
3.79 (3H, s), 6.80 (2H, dt, J¼8.0, 1.7 Hz), 6.90e6.96 (3H, m), 7.15 (2H,
t, J¼7.5 Hz), 7.42 (2H, td, J¼8.0, 1.7 Hz), 7.48 (1H, td, J¼7.5, 1.1 Hz),
7.73 (2H, dt, J¼9.2, 2.3 Hz), 7.87 (2H, dd, J¼7.5, 1.1 Hz); 13C NMR
NMR (CDCl3)
d
: 3.81 (3H, s), 6.81 (2H, d, J¼8.5 Hz), 6.90 (2H, dd,
J¼8.5,1.0 Hz), 6.96 (1H, t, J¼7.5 Hz), 7.15 (2H, t, J¼7.5 Hz), 7.41 (2H, d,
J¼8.5 Hz), 7.74 (2H, d, J¼9.0 Hz), 7.85 (2H, d, J¼8.5 Hz).
(CDCl3) d: 55.6, 114.2, 120.5, 124.7, 127.9, 128.2, 128.7, 128.8, 131.7,
131.9, 135.3, 149.5, 164.5, 166.6, 195.9.
4.1.10. 2-(4-Chlorophenyl)-2-(phenylimino)-1-p-tolylethanone
(10c). Yellow needles (recrystallized from ether/hexane); 82%; mp
4.1.3. 1-(4-Methylphenyl)-2-phenyl-2-(phenylimino)ethanone
100e102 ꢀC; 1H NMR (CDCl3)
d
: 2.33 (3H, s), 6.89 (2H, d, J¼7.5 Hz),
(4c). Yellow oil, 74%; IR (ATR) cmꢁ1: 1665 (C]O); 1H NMR (CDCl3)
6.95 (1H, t, J¼7.5 Hz), 7.14 (2H, d, J¼8.0 Hz), 7.14 (2H, t, J¼7.5 Hz),
7.41 (2H, d, J¼8.5 Hz), 7.64 (2H, d, J¼8.5 Hz), 7.82 (2H, d, J¼8.5 Hz);
d
: 2.32 (3H, s), 6.89 (2H, d, J¼7.5 Hz), 6.94 (1H, t, J¼7.5 Hz), 7.12e7.15
(4H, m), 7.43 (2H, t, J¼7.5 Hz), 7.48 (1H, td, J¼7.5, 1.1 Hz), 7.66 (2H, d,
13C NMR (CDCl3)
d: 21.9,120.5, 124.9, 128.7, 129.1, 129.5, 129.5, 129.7,
J¼8.6 Hz), 7.86 (2H, dt, J¼7.5, 1.1 Hz); 13C NMR (CDCl3)
d: 21.9, 120.6,
132.1, 133.7, 138.0, 145.9, 149.1, 165.2, 196.8; HRMS (FAB) calcd for
C21H17ClNO (Mþ1): 334.0999. Found: 334.1005.
124.7, 128.2, 128.7, 128.9, 129.6, 129.7, 131.7, 132.3, 135.3, 145.6,
149.4, 166.5, 197.2; HRMS (FAB) calcd for C21H18NO (Mþ1):
300.1388. Found: 300.1389.
4.1.11. 2-(4-Chlorophenyl)-1-(furan-2-yl)-2-(phenylimino)-ethanone
(10f). Yellow needles (recrystallized from ethyl acetate/n-hexane);
4.1.4. 1-(2-Methylphenyl)-2-phenyl-2-(phenylimino)ethanone
80%, mp 106e107 ꢀC; 1H NMR (CDCl3)
d
: 6.41 (1H, dd, J¼4.0, 2.0 Hz),
(4d). Yellow oil, 60%; IR (ATR) cmꢁ1: 1667 (C]O); 1H NMR (CDCl3)
6.91 (2H, dd, J¼8.5, 1.0 Hz), 6.99e7.02 (2H, m), 7.20 (2H, t, J¼7.5 Hz),
7.42 (2H, d, J¼8.5 Hz), 7.52 (1H, d, J¼1.0 Hz), 7.83 (2H, d, J¼8.5 Hz);
d
: 2.41 (3H, s), 6.78 (2H, d, J¼7.5 Hz), 6.91 (1H, t, J¼7.5 Hz),
7.08e7.13 (4H, m), 7.28 (1H, td, J¼7.5, 1.1 Hz), 7.46 (2H, t, J¼7.5 Hz),
13C NMR (CDCl3)
d: 112.9, 120.4, 121.4, 125.1, 128.9, 129.1, 129.5,
7.49e7.55 (2H, m), 7.92 (2H, dd, J¼7.5, 1.1 Hz); 13C NMR (CDCl3)
d
:
133.2, 138.1, 148.5, 148.9, 151.1, 163.4, 183.9; HRMS (FAB) calcd for
C18H13NO2 (Mþ1): 310.0635. Found: 310.0661.
21.9, 120.6, 124.7, 128.2, 128.7, 128.9, 129.6, 129.7, 131.7, 132.3,
135.3, 145.6, 149.4, 166.5, 197.2; HRMS (FAB) calcd for C21H18NO
(Mþ1): 300.1388. Found: 300.1394.
4.1.12. 2-(4-Chlorophenyl)-1-phenyl-2-(phenylimino)ethanone
(10i)6. Yellow prisms (recrystallized from methanol); 90%, mp
4.1.5. 1-(2-Methoxyphenyl)-2-phenyl-2-(phenylimino)ethanone
106e107 ꢀC; IR (ATR) cmꢁ1: 1670 (C]O); 1H NMR (CDCl3)
d: 6.88
(4e). Yellow granules (recrystallized from n-hexane/acetone); 76%,
(2H, dd, J¼8.5, 1.0 Hz), 6.94 (1H, t, J¼7.5 Hz), 7.14 (2H, t, J¼8.5 Hz),

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Y. Suzuki et al. / Tetrahedron 67 (2011) 4710e4715
7.35 (2H, t, J¼8.5 Hz), 7.42 (2H, d, J¼8.5 Hz), 7.50 (1H, t, J¼7.5 Hz),
7.73 (2H, d, J¼8.5 Hz), 7.83 (2H, d, J¼8.5 Hz).
(NO2); 1H NMR (CDCl3)
d
: 6.91 (2H, dd, J¼8.6, 1.2 Hz), 6.97e7.00
(1H, m), 7.16 (2H, t, J¼7.5 Hz), 7.36 (2H, t, J¼7.5 Hz), 7.50e7.53 (1H,
m), 7.72 (2H, dd, J¼8.0, 1.2 Hz), 8.05e8.08 (2H, m), 8.27e8.30 (2H,
4.1.13. 2-(4-Chlorophenyl)-1-(naphthalen-2-yl)-2-(phenylimino)-
m); 13C NMR (CDCl3)
d: 120.5, 124.1, 125.8, 129.0, 129.2, 129.4, 134.1,
ethanone (10j). Yellow needles (recrystallized from ether/hexane);
135.0, 140.5, 148.5, 149.6, 164.0, 196.9.
91%, mp 124e126 ꢀC; 1H NMR (CDCl3)
d
: 6.89 (1H, t, J¼7.5 Hz), 6.93
(2H, dd, J¼8.5, 1.0 Hz), 7.10 (2H, t, J¼7.5 Hz), 7.42 (2H, d, J¼8.5 Hz),
7.52 (1H, td, J¼7.5, 1.0 Hz), 7.59 (1H, td, J¼7.5, 1.0 Hz), 7.80 (2H, t,
J¼8.5 Hz), 7.85 (2H, td, J¼8.5, 1.0 Hz), 7.87 (2H, d, J¼8.5 Hz), 8.21
4.1.20. 1-(4-Methoxyphenyl)-2-(naphthalen-2-yl)-2-(phenylimino)
ethanone (14b). Yellow oil; 80%; 1H NMR (CDCl3)
d: 3.84 (3H), 6.81
(2H, d, J¼8.5 Hz), 6.95 (2H, d, J¼8.5 Hz), 7.17 (1H, t, J¼8.5 Hz), 7.49
(1H, td, J¼8.0, 1.0 Hz), 7.55 (1H, td, J¼8.0, 1.0 Hz), 7.79 (2H, d,
J¼8.5 Hz), 7.82 (2H, d, J¼8.5 Hz), 7.87 (1H, d, J¼8.5 Hz), 7.93 (1H, d,
(1H, s); 13C NMR (CDCl3)
d: 120.5, 123.5, 125.0, 127.2, 128.0, 128.8,
129.1, 129.2, 129.5, 129.6, 129.9, 131.8, 132.4, 132.7, 133.8, 136.2,
138.1, 149.1, 165.1, 197.4; HRMS (FAB) calcd for C24H17ClNO (Mþ1):
370.0999. Found: 370.1002.
J¼8.5 Hz), 8.11 (1H, s), 8.23 (1H, dd, J¼8.0,1.0 Hz); 13C NMR (CDCl3)
d:
55.8, 114.1, 120.4, 123.7, 124.6, 126.6, 127.7, 127.8, 127.8, 128.6, 128.7,
130.0, 131.9, 132.6, 134.8, 136.2, 149.4, 164.4, 166.5, 195.8; HRMS (FAB)
calcd for C25H20NO2 (Mþ1): 366.1494. Found: 366.1513.
4.1.14. 1-(4-Chlorophenyl)-2-(4-nitrophenyl)-2-(phenylimino)-etha-
none (13a)6. Yellow needles (recrystallized from n-hexane/ace-
tone); 49%, mp 164e166 ꢀC; IR (ATR) cmꢁ1: 1665 (C]O), 1514, 1341
(NO2); 1H NMR (CDCl3)
d
: 6.91 (2H, dd, J¼7.5, 1.1 Hz), 7.00e7.03 (1H,
m), 7.17e7.20 (2H, m), 7.31e7.34 (2H, m), 7.64e7.67 (2H, m),
8.04e8.06 (2H, m), 8.28e8.31 (2H, m); 13C NMR (CDCl3)
: 120.5,
4.2. Hydrolysis of iminoethanones
d
To a stirring solution of iminoethanones 4, 10, 13, and 14
(0.2 mmol) in THF (3 ml), 10% HCl (1 ml) was added. The reaction
mixture was then stirred at room temperature for 3 h and poured
into water. The products were extracted with ethyl acetate,
washed with brine, and dried over MgSO4. The solvent was
evaporated and the residue was purified by silica gel column
chromatography (n-hexane/ethyl acetate¼4:1) to obtain benzils
16e19.
124.1, 126.0, 129.1, 129.1, 129.6, 130.6, 132.3, 140.2, 141.6, 148.3,
149.6, 163.4, 195.8.
4.1.15. 1-(4-Methoxyphenyl)-2-(4-nitrophenyl)-2-(phenylimino)-
ethanone (13b)6. Yellow granules (recrystallized from n-hexane/
acetone); 42%, mp 99e101 ꢀC; IR (ATR) cmꢁ1: 1655 (C]O), 1520,
1343 (NO2); 1H NMR (CDCl3)
d
: 3.80 (3H, s), 6.81 (2H, d, J¼9.2 Hz),
6.95 (2H, dd, J¼7.5, 1.2 Hz), 7.00 (1H, t, J¼7.5 Hz), 7.18 (2H, t,
J¼7.5 Hz) 7.70e7.72 (2H, m), 8.05e8.07 (2H, m), 8.26e8.28 (2H, m);
4.2.1. 1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (16a)6. Yellow
13C NMR (CDCl3)
d
: 55.7,114.5,120.5, 124.0,125.7,127.2,129.0, 129.2,
needles (recrystallized from methanol/water); quant., mp
132.0, 140.8, 148.7, 149.5, 164.2, 165.0, 195.0.
67e70 ꢀC; IR (ATR) cmꢁ1: 1663 (C]O); 1H NMR (CDCl3)
d: 7.50
(2H, dt, J¼8.6, 1.9 Hz), 7.53 (2H, d, J¼8.6 Hz), 7.68 (1H, m), 7.93
4.1.16. 1-(2-Methoxyphenyl)-2-(4-nitrophenyl)-2-(phenylimino)-
ethanone (13e). Yellow granules (recrystallized from n-hexane/ac-
etone); 36%, mp 122e124 ꢀC; IR (ATR) cmꢁ1: 1655 (C]O), 1520,
(2H, dt, J¼8.6, 1.9 Hz), 7.97 (2H, dd, J¼8.6, 1.2 Hz); 13C NMR
(CDCl3)
d: 129.2, 129.5, 130.0, 131.3, 131.4, 132.9, 135.2, 141.7,
193.2, 194.0.
1344 (NO2); 1H NMR (CDCl3)
d: 3.65 (3H, s), 6.75e6.80 (3H, m), 6.88
(1H, t, J¼7.5 Hz), 6.93 (1H, t, J¼7.5 Hz), 7.12 (2H, t, J¼7.5 Hz), 7.45
4.2.2. 1-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (16e)6. Yellow
(1H, dt, J¼8.6, 1.7 Hz), 7.60 (1H, dd, J¼7.5, 1.7 Hz), 8.04 (2H, dt, J¼8.6,
oil, quant.; IR (ATR) cmꢁ1: 1670, 1659 (C]O); 1H NMR (CDCl3)
d: 3.88
1.7 Hz), 8.27 (2H, dt, J¼8.6, 1.7 Hz); 13C NMR (CDCl3)
d
: 55.5, 111.7,
(3H, s), 6.97 (2H, dt, J¼9.5, 1.7 Hz), 7.50 (2H, t, J¼7.5 Hz), 7.64 (1H, t,
119.8,123.8,124.9,125.3,128.7,129.0,130.5,136.3,141.0,149.1,149.1,
159.4, 165.6, 194.8; HRMS (FAB) calcd for C21H17N2O4 (Mþ1):
361.1188. Found: 361.1175.
J¼7.5 Hz), 7.93e7.97 (4H, m); 13C NMR (CDCl3)
d: 55.8, 114.5, 126.2,
129.1, 130.0, 132.5, 133.3, 134.9, 165.1, 193.3, 195.0.
4.2.3. 1-(Furan-2-yl)-2-phenylethane-1,2-dione (16f)7. Yellow oil,
47%; IR (ATR) cmꢁ1: 1655 (C]O); 1H NMR (CDCl3)
d: 6.62e6.63 (1H,
4.1.17. 1-(Furan-2-yl)-2-(4-nitrophenyl)-2-(phenylimino)-ethanone
m), 7.37 (1H, d, J¼3.5 Hz), 7.51 (2H, t, J¼8.0 Hz), 7.66 (1H, m), 7.75
(13f). Yellow needles (recrystallized from n-hexane/acetone); 74%,
(1H, m), 8.01e8.03 (2H, m); 13C NMR (CDCl3)
d: 113.1, 123.5, 129.0,
mp 137e139 ꢀC; IR (ATR) cmꢁ1: 1647 (C]O), 1516, 1346 (NO2); 1
H
130.3, 132.6, 135.0, 149.4, 150.0, 180.5, 191.7.
NMR (CDCl3)
d
: 6.43e6.44 (1H, m), 6.95 (2H, dd, J¼8.6, 1.1 Hz),
7.03e7.06 (2H, m), 7.22 (2H, t, J¼7.5 Hz), 7.53 (1H, s), 8.08 (2H, dt,
J¼6.9, 1.7 Hz), 8.28 (1H, dt, J¼6.9, 1.7 Hz); 13C NMR (CDCl3)
d: 113.2,
4.2.4. 1-Phenyl-2-(thiophen-2-yl)ethane-1,2-dione (16g). Yellow oil,
quant.; IR (ATR) cmꢁ1: 1674, 1643 (C]O); 1H NMR (CDCl3)
: 7.18
d
120.4, 121.6, 124.0, 125.9, 129.0, 129.2, 140.1, 148.5, 148.8, 149.5,
150.9, 162.4, 183.3; HRMS (FAB) calcd for C18H13N2O4 (Mþ1):
321.0875. Found: 321.0870.
(1H, dt, J¼8.6, 1.1 Hz), 7.51 (2H, t, J¼7.5 Hz), 7.66 (1H, m), 7.80 (1H,
dd, J¼6.9, 1.1 Hz), 7.83 (1H, dd, J¼6.9, 1.1 Hz), 8.03 (2H, dd, J¼8.6,
1.1 Hz); 13C NMR (CDCl3)
137.1, 140.0, 185.7, 192.2.
d: 129.0, 129.1, 130.4, 132.7, 135.0, 137.9,
4.1.18. 2-(4-Nitrophenyl)-2-(phenylimino)-1-(thiophen-2-yl)-etha-
none (13g)6. Yellow columns (recrystallized from n-hexane/ace-
tone), 81%, mp 119e121 ꢀC; IR (ATR) cmꢁ1: 1638 (C]O), 1518, 1346
4.2.5. 1-(Naphthalen-1-yl)-2-phenylethane-1,2-dione (16h). Yellow
needles, quant.; mp 98e99 ꢀC; IR (ATR) cmꢁ1: 1670,1651 (C]O); 1H
(NO2); 1H NMR (CDCl3)
d
: 6.98e7.00 (3H, m), 7.04 (1H, t, J¼7.5 Hz),
7.22 (2H, t, J¼7.5 Hz), 7.40 (1H, dd, J¼4.0, 1.1 Hz), 7.68 (1H, dd, J¼4.0,
1.1 Hz), 8.09e8.12 (2H, m), 8.28e8.31 (2H, m); 13C NMR (CDCl3)
NMR (CDCl3)
d
: 7.48 (1H, d, J¼7.5 Hz), 7.52 (2H, t, J¼8.1 Hz),
7.61e7.67 (2H, m), 7.75 (1H, t, J¼7.5 Hz), 7.91 (1H, dd, J¼7.5, 1.2 Hz),
7.94 (1H, d, J¼8.6 Hz), 8.03 (2H, d, J¼7.5 Hz), 8.12 (1H, d, J¼8.0 Hz),
d:
120.6, 124.0, 128.0,128.8, 129.1,129.2,136.1, 137.1, 140.3, 141.5,148.5,
149.6, 162.9, 188.3.
9.31 (1H, d, J¼8.6 Hz); 13C NMR (CDCl3)
d: 124.6, 126.0, 127.3, 128.7,
128.9, 129.2, 129.6, 130.1, 131.0, 133.4, 134.2, 134.9, 135.3, 136.1,
194.7, 197.3.
4.1.19. 1-(Naphthalen-1-yl)-2-(4-nitrophenyl)-2-(phenylimino)etha-
none (13i)6. Orange prisms (recrystallized from n-hexane/ace-
tone); 85%, mp 134e136 ꢀC; IR (ATR) cmꢁ1: 1668 (C]O), 1516, 1343
4.2.6. 1-(4-Chlorophenyl)-2-(4-methoxyphenyl)ethane-1,2-dione
(17b)6. Yellow needles (recrystallized from ether/hexane), 88%; mp

Y. Suzuki et al. / Tetrahedron 67 (2011) 4710e4715
4715
102e103 ꢀC; 1H NMR (CDCl3)
7.48 (2H, d, J¼8.5 Hz), 7.93 (4H, t, J¼8.5 Hz).
d
: 3.90 (3H, s), 6.99 (2H, d, J¼8.5 Hz),
(2H, d, J¼8.6 Hz); 13C NMR (CDCl3)
d: 124.3, 129.4, 130.2, 131.1,132.4,
135.6, 137.4, 151.2, 192.2, 193.0.
4.2.7. 1-(4-Chlorophenyl)-2-(furan-2-yl)ethane-1,2-dione
4.2.13. 1-(4-Methoxyphenyl)-2-(naphthalen-2-yl)ethane-1,2-dione
(19b). Yellow oil, 90%; 1H NMR (CDCl3)
: 3.88 (3H, s), 6.98 (2H, d,
(17f). Yellow needles (recrystallized from ether/hexane), 100%; mp
d
115e116 ꢀC; 1H NMR (CDCl3)
d, J¼4.0 Hz), 7.50 (2H, d, J¼8.5 Hz), 7.78 (1H, d, J¼1.5 Hz), 8.00 (2H,
d, J¼8.5 Hz); HRMS (FAB) calcd for C12H8ClO3 (Mþ1): 235.0162.
Found: 235.0176.
d
: 6.65 (1H, dd, J¼4.0, 2.0 Hz), 7.42 (1H,
J¼8.5 Hz), 7.54 (1H, t, J¼7.5 Hz), 7.63 (1H, t, J¼8.0 Hz), 7.89 (1H, t,
J¼8.5 Hz), 7.95 (1H, d, J¼8.5 Hz), 8.00 (2H, d, J¼8.5 Hz), 8.09 (2H, dd,
J¼8.5, 1.5 Hz), 8.15 (1H, d, J¼8.5 Hz), 8.41 (1H, d, J¼8.5 Hz); 13C NMR
(CDCl3) d: 55.6, 114.3, 123.7, 125.3, 126.1, 127.1, 127.9, 129.1, 129.9,
130.4, 132.4, 133.4, 136.3, 165.0, 193.2, 194.9; HRMS (FAB) calcd for
4.2.8. 1-(4-Chlorophenyl)-2-(naphthalen-2-yl)ethane-1,2-dione
C19H15O3 (Mþ1): 291.1021. Found: 291.1022.
(17j). Yellow needles (recrystallized from ether/hexane), 100%;
mp 130e132 ꢀC; 1H NMR (CDCl3)
d
: 7.51 (2H, d, J¼8.5 Hz), 7.58
Acknowledgements
(1H, td, J¼7.5, 1.5 Hz), 7.67 (1H, td, J¼7.5, 1.0 Hz), 7.92 (2H, t,
J¼8.5 Hz), 7.98 (2H, d, J¼8.5 Hz), 8.09 (2H, dd, J¼8.5, 1.5 Hz), 8.40
This research was supported in part by a Grant-in-Aid for Sci-
entific Research (C) (KAKENHI No. 20295546) from the Japan
Society for the Promotion of Science.
(1H, s); 13C NMR (CDCl3)
d: 123.7, 127.4, 128.1, 129.4, 129.6, 129.8,
130.1, 130.2, 131.4, 131.5, 132.0, 132.4, 133.8, 136.5, 141.7, 193.3,
194.1; HRMS (FAB) calcd for C18H12ClO2 (Mþ1): 295.0526. Found:
295.0537.
References and notes
1. N-Heterocyclic Carbenes in Synthesis; Nolan, S. P., Ed.; WILEY-VCH GmbH &
KGaA: Weinheim, 2006.
4.2.9. 1-(4-Chlorophenyl)-2-(4-nitrophenyl)ethane-1,2-dione
(18a)6. Yellow needles, quant.; mp 201e203 ꢀC; IR (ATR) cmꢁ1
:
2. Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606e5655.
1672, 1653 (C]O), 1522, 1348 (NO2); 1H NMR (CDCl3)
d: 7.53 (2H, d,
ꢀ
3. Marion, N.; Díe-Gonzale, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46,
2988e3000.
J¼8.6 Hz), 7.94 (2H, d, J¼8.6 Hz), 8.16 (2H, d, J¼9.2 Hz), 8.36 (2H, d,
J¼9.2 Hz); 13C NMR (CDCl3)
d: 124.3, 129.8, 130.8, 131.2, 131.5, 137.2,
4. Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534e541.
5. Nair, V.; Bindu, S.; Sreekumar, V. Angew. Chem., Int. Ed. 2004, 43, 5130e5135.
6. Miyashita, A.; Matsuda, H.; Higashino, T. Chem. Pharm. Bull. 1992, 40,
2627e2631.
142.4, 151.3, 191.4, 191.5.
7. Katritzky, A. R.; Zhang, D.; Kirichenko, K. J. Org. Chem. 2005, 70, 3271e3274.
8. Barta, T. E.; Stealey, M. A.; Collins, P. W.; Weier, R. M. Bioorg. Med. Chem. Lett.
1998, 8, 3443e3448.
9. Singh, S. K.; Saibaba, V.; Ravikumar, V.; Rudrawar, S. V.; Daga, P.; Rao, C. S.;
Akhila, V.; Hegde, P.; Rao, Y. K. Bioorg. Med. Chem. Lett. 2004, 12, 1881e1893.
10. Bostrom, J.; Berggren, K.; Elebring, T.; Greasley, P. J.; Wilstermann, M. Bioorg.
Med. Chem. 2007, 15, 4077e4084.
4.2.10. 1-(Furan-2-yl)-2-(4-nitrophenyl)ethane-1,2-dione
(18f). Yellow needles, 82%; mp 126e128 ꢀC; IR (ATR) cmꢁ1: 1678,
1651 (C]O); 1H NMR (CDCl3)
d
: 6.67e6.68 (1H, m), 7.50 (1H, d,
J¼7.5 Hz), 7.82 (1H, s), 8.23 (2H, dt, J¼8.6,1.7 Hz), 8.35 (2H, dt, J¼8.6,
1.7 Hz); 13C NMR (CDCl3)
: 113.5, 124.1, 124.6, 131.5, 137.2, 149.6,
d
150.1, 151.2, 178.2, 189.2; HRMS (FAB) calcd for C12H8NO5 (Mþ1):
11. Wilsterman, J. M.; Berggren, A. I. K. PCT Int. Appl., 2003, 27 pp.
12. Deuchert, K.; Hertenstein, U.; Huenig, S.; Wehner, G. Chem. Ber. 1979, 112,
2045e2061.
246.0402. Found: 246.0432.
13. Fuson, R. C.; Hoch, P. E. J. Am. Chem. Soc. 1949, 71, 1585e1586.
14. Ugi, I.; Beck, F.; Fetzer, U. Chem. Ber. 1962, 95, 126e135.
15. Eloy, F.; Deryckere, A.; Maffrand, J. P. Eur. J. Med. Chem. 1974, 9, 602e606.
16. Houghton, P. G.; Pipe, D. F.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1 1985,
1471e1479.
17. Van den Nieuwendijk, A. M. C. H.; Pietra, D.; Heitman, L.; Goeblyoes, A.; IJzer-
man, A. P. J. Med. Chem. 2004, 47, 663e672.
18. Haeger, I.; Froehlich, R.; Wuerthwein, E.-U. Eur. J. Inorg. Chem. 2009, 2415e2428.
19. Miyashita, A.; Kurachi, A.; Matsuoka, Y.; Tanabe, N.; Suzuki, Y.; Iwamoto, K.;
Higashino, T. Heterocycles 1997, 44, 417e426.
20. Ide, W. S.; Buck, J. S. In Organic Reactions; Bachmann, W. E., Fieser, L. F., Blatt, A.
H., Johnson, J. R., Eds.; John Wiley: New York, NY, USA, 1948; Vol. 4,
pp 278e434.
21. Miyashita, A.; Suzuki, Y.; Iwamoto, K.; Higashino, T. Chem. Pharm. Bull. 1994, 42,
2633e2635.
4.2.11. 1-(4-Nitrophenyl)-2-(thiophen-2-yl)ethane-1,2-dioꢁn1e
1676, 1635 (C]O); 1H NMR (CDCl3)
d: 7.23 (1H, m), 7.90 (2H, td,
(18g). Yellow needles, quant.; mp 142e144 ꢀC; IR (ATR) cm
:
J¼6.9, 1.1 Hz), 8.23 (2H, dt, J¼6.9, 1.1 Hz), 8.34 (2H, dt, J¼9.1, 1.7 Hz);
13C NMR (CDCl3)
183.5, 189.7.
d: 124.1, 129.2, 131.5, 137.2, 137.5, 138.1, 139.1, 151.2,
4.2.12. 1-(4-Nitrophenyl)-2-phenylethane-1,2-dione (18i)6. Yellow
needles, quant.; mp 137e139 ꢀC; IR (ATR) cmꢁ1: 1674, 1661 (C]O),
1526, 1346 (NO2); 1H NMR (CDCl3)
t, J¼7.5 Hz), 7.99 (2H, d, J¼7.5 Hz), 8.17 (2H, dt, J¼8.6, 1.7 Hz), 8.36
d
: 7.55 (2H, t, J¼7.5 Hz), 7.71 (1H,