Phenylation reaction of α-acylnitromethanes to give 1,2-diketone monooximes: Involvement of carbon electrophile at the position a to the nitro group

Article abstract of DOI:10.1055/s-0029-1217036

The generality and the effects of substituents on phenylation reactions of α-acylnitromethanes catalyzed by trifluoromethanesulfonic acid have been studied. α-Aroylnitromethanes afforded benzil monooximes in good yield. In the case of aliphatic α-acylnitromethane, a similar phenylation reaction proceeded, but the yield of the phenylated 1,2-dione monooxime was low. These phenylation reactions represent examples of the generation of carbocation electrophiles at the α-position of a nitro group. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1217036

PAPER
4129
Phenylation Reaction of a-Acylnitromethanes To Give 1,2-Diketone
Monooximes: Involvement of Carbon Electrophile at the Position a to the
Nitro Group
Phenylation
Reaction
o
i
f
a
-Ac
k
ylnitrometha
i
nes hiro Takamoto, Hiroaki Kurouchi, Yuko Otani, Tomohiko Ohwada*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax +81(3)58414735; E-mail: ohwada@mol.f.u-tokyo.ac.jp
Received 17 July 2009; revised 31 July 2009
oxygen nucleophile, such as water or sulfonate anion in
sulfuric acid.2 Friedel–Crafts type reaction of aci-nitro
species 1 of nitroalkanes (R = alkyl group) with benzene,
catalyzed by trifluoromethanesulfonic acid (TFSA), af-
Abstract: The generality and the effects of substituents on phe-
nylation reactions of a-acylnitromethanes catalyzed by trifluo-
romethanesulfonic acid have been studied. a-Aroylnitromethanes
afforded benzil monooximes in good yield. In the case of aliphatic
a-acylnitromethane, a similar phenylation reaction proceeded, but fords phenylated oximes in moderate to good yields.3
the yield of the phenylated 1,2-dione monooxime was low. These
While the substitution of an electron-withdrawing group
phenylation reactions represent examples of the generation of car-
bocation electrophiles at the a-position of a nitro group.
(the R group), such as esters and ketones, facilitates the
phenylation reaction, this reaction has been little ex-
plored.3,4 In this paper we examine the generality and sub-
Key words: a-ketonitromethane, 1,2-dione monooxime, electro-
philic aromatic substitutions, umpolung, protonation
stituent effects of acid-catalyzed phenylation reactions of
a-acylnitromethanes (2; Table 1), affording phenylated
1,2-diketone monooxime derivatives of type 3.
The generation of a cationic center at the a-position of a
A general synthetic method for generating a-acylni-
nitro group is a kind of umpolung (reverse polarity), be-
tromethanes was recently reported by Katritzky et al., in-
cause the protons at the a-position of the nitro group are
volving the addition of a nitroate dianion, generated from
acidic enough to be deprotonated, thereby generating a
nitromethane by the action of two equivalents of potassi-
carbanion species that is able to act as a nucleophile
um tert-butoxide, to N-acylbenzotriazoles (Scheme 2).5,6
(Scheme 1). The chemistry of carbanions derived from ni-
tro compounds has been studied for a long time, and the
synthetic usefulness of Henry-type reactions (nitroaldol
H
N
O
O
N
reaction) and enhanced C-nucleophiles of a,a-doubly
deprotonated primary nitroalkanes (nitroate dianions) is
well established.1 On the other hand, the chemistry of car-
bocations derived from nitro groups has not been exten-
sively studied. The Nef and Meyer reactions in acidic
media, which yield aldehydes/ketones and carboxylic
acids, respectively, were among the earliest examples of
the carbocation chemistry of nitro compounds.2
SOCl2
X
N
X
R
R
R
CH2Cl2
or
DMF
CH2Cl2
or
DMF–Et3N
X = OH
O
X = Cl
O
MeNO2
NO2
t-BuOK (2.2 equiv)
N
N
R
DMSO, r.t.
N
2a–l
These named reactions involve a cationic carbon species
at the a-position of the nitro group, i.e., an O-protonated
aci-nitro species (1; Scheme 1), which is attacked by an
Scheme 2 Preparation of a-acylnitromethanes
In the presence of TFSA, a-aroylnitromethanes reacted
with benzene to give substituted benzil monooxime deriv-
atives 3. We optimized the reaction conditions (acid, co-
solvent, reaction time, etc.) by using a-benzoylni-
tromethane 2a as a representative example (Table 1). The
reaction did not proceed even at reflux using trifluoroace-
tic acid (TFA; entries 1 and 2), whereas a large excess of
TFSA (50 equiv with respect to the starting material 2a)
gave a low yield of the phenylated product (entry 7). The
optimal reaction conditions involved the use of ten equiv-
alents of TFSA and dichloromethane as a co-solvent; un-
der these conditions, the reaction time was reduced to 20
minutes (entry 9).
H
H
H
OH
R
NO2
R
R
N
H
H
H
H
base
acid
H+
OH
OH
R
N
R
NO2
H
O
OH
O
N
R
N
O
OH
1
nucleophile
electrophile
Scheme 1 Umpolung (reverse polarity) of a nitro group
SYNTHESIS 2009, No. 24, pp 4129–4136
xx.
x
x
.
2
0
0
9
Advanced online publication: 12.10.2009
DOI: 10.1055/s-0029-1217036; Art ID: F13909SS
© Georg Thieme Verlag Stuttgart · New York
The reaction showed apparent acidity dependence
(Table 2). As the acidity of the acid medium increased, the

4130
M. Takamoto et al.
PAPER
phenylation reaction started, and the yield of the product dia (entries 6–8); this is probably due to formation of by-
3a increased. Practically, however, the yield was maxi- products arising from C–C bond cleavage: in neat TFSA,
mized when the ratio of TFSA to TFA reached 45:55 benzaldoxime (6%) and benzoic acid (5%) were formed.3
(w/w) (entry 5), and slightly decreased in more acidic me-
We studied the substituent effects in this reaction
Table 1 Optimization of Reaction Conditionsa
(Table 3). Aromatic electrophilic substituents (halogens
and electron-withdrawing groups, 2b–h) seemed to facil-
itate the reaction, whereas aromatic electron-donating
substituents (2i or 2j) reduced the reaction rate. In the case
of TFSA, the yield was higher than those found in TFSA–
TFA mixtures [45:55 (w/w)]. Probably, the remote elec-
tron-donating substituent decreases the electron-
withdrawing ability of the whole aroyl group, thereby at-
tenuating the electron-deficiency of the carbon electro-
philic center of 4 (Scheme 3). On the other hand, an ali-
phatic keto-substituent (2k or 2l) significantly reduced the
yield of the phenylated product. Formation of by-products
arising from C–C bond cleavage was enhanced [see
Table 3, footnotes (c) and (d)]. We checked the stability of
the phenylated oxime products in the acidic reaction me-
dium (Table 4), in order to examine whether the reduction
of the yields in TFSA may be due to the instability of the
product oxime in the strongly acidic medium. However,
as shown in Table 4, when the isolated oxime products
were exposed to the reaction conditions, and then worked
up in the usual manner, they were recovered in high
yields, thus excluding involvement of degradation reac-
O
O
NO2
acid
N
co-solvent
OH
2a
3a
Entry Acid
(equiv)
Benzene Co-
(equiv) solvent
Temp Time Yield of
(°C) (min) 3a (%)b
1
TFA (100)
10
none
reflux 96 h
(72 °C)
0
2
3
4
5
6
7
8
9
TFA (100)
TFSA (10)
TFSA (10)
TFSA (10)
TFSA (10)
TFSA (50)
TFSA (10)
TFSA (10)
10
10
50
10
50
10
50
50
CH2Cl2
none
0
0
0
0
0
0
0
0
24 h
60
0
52
none
60
59
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
120
63
60
60
60
20
72
33
complex
73c
+
OH
OH
a Reaction conditions: 2a (1.5 mmol), co-solvent (1.5 mL), benzene,
acid, 0 °C.
N
Ar
Ar
OH
b Isolated yield after column chromatography.
c Ohwada et al. reported that a 71% yield of 3a was obtained under
similar reaction conditions [TFSA (10 equiv), benzene (30 equiv) and
CH2Cl2 as a co-solvent].3
R
R
O
O
N
OH OH
N
2 H+
O–
+
OH
Ar
O
Ar
OH
H
2
N
Table 2 Acidity Dependence of the Reactiona
OH
(R = H)
4
(50 equiv)
O
O
A: O,O-diprotonated aci-nitro species
NO2
acid (10 equiv)
OH
OH
OH
20 min
CH2Cl2, 0 °C
N
– H2O
N
N
OH
4
4
Ar
OH
Ar
OH
2a
3a
H+
(R = H)
H
Ph
Ph
Entry Ratio of TFSA/TFA (w/w) Acidity (–H0) Yield of 3a (%)b
B: O-protonated nitrile oxide
OH
1
2
3
4
5
6
7
8
0:100
1:99
2.7
7.8
0
0
OH
– H2O
Ar
N
Ar
OH
H+
(R = H)
N
OH
Ph
10:90
30:70
45:55
70:30
90:10
100:0
9.6
8
C: α-nitroso cation
11.1
11.6
12.4
13.0
14.1
71
83
70
72
73
OH
O
N
N
Ar
OH
OH
H
– H2O
R
N
N
4
Ar
OH
Ar
O
H+
O
Ph
Ph
OH
(R = H)
Ar
a Reaction conditions: a-nitroketone (1.5 mmol), acid (10 equiv), ben-
zene (50 equiv), CH2Cl2 (1.5 mL).
R
Scheme 3 Proposed reaction mechanisms
b Isolated yield.
Synthesis 2009, No. 24, 4129–4136 © Thieme Stuttgart · New York

PAPER
Phenylation Reaction of a-Acylnitromethanes
4131
tions such as Beckmann rearrangement of the product each other with respect to the order in which events such
oxime.
as elimination of water and removal of the a-proton take
place. Furthermore, the formation of by-products (benz-
aldoxime and substituted benzoic acid) through C–C bond
cleavage can be accounted for in terms of the involvement
of the phenylated nitroso (or equivalent) intermediate
(found in intermediates A and C, Scheme 4 and see be-
low). However, mechanism C seems to be ruled out (see
below), and so mechanism A is considered the most likely
candidate.
Several reaction mechanisms have been proposed for this
reaction and, in view of the requirement for strongly acid-
ic media, all of them involve dicationic species, i.e., O,O-
diprotonated aci-nitro species (A),3 O-protonated nitrile
oxide (B),7 and a-nitroso cation (C) (Scheme 3). Mecha-
nism C, i.e., transformation of the nitro group into a ni-
troso group, is relevant to the mechanism of the Nef
reaction under reducing conditions (e.g., catalyzed by
TiCl3).8 These reaction mechanisms (A–C) differ from
Table 3 Substituent Effect in the Phenylation Reaction
Entry Substrate 2
Temp (°C)
Time (min)
Product 3a
Yield (%)
TFSA
TSFA–TFA (45:55)
83
O
O
NO2
a
0
20
73
N
OH
N
O
O
NO2
NO2
b
0
0
20
20
67
80
83
Cl
OH
OH
Cl
Br
O
O
c
66b
N
Br
O
O
NO2
d
0
0
0
20
20
20
70
67
65
74
81
76
N
O2N
OH
O2N
Cl
O
O
Cl
NO2
e
N
OH
O
O
NO2
f
N
OH
F3C
F3C
F3C
O
O
F3C
NO2
NO2
NO2
g
0
0
0
20
20
86
75
68
90
78
41
N
OH
O
O
h
N
OH
Br
Br
O
O
i
110
N
MeO
OH
MeO
Synthesis 2009, No. 24, 4129–4136 © Thieme Stuttgart · New York

4132
M. Takamoto et al.
PAPER
Table 3 Substituent Effect in the Phenylation Reaction (continued)
Entry Substrate 2
Temp (°C)
Time (min)
Product 3a
Yield (%)
TFSA
TSFA–TFA (45:55)
62
O
O
NO2
j
0
80
70
N
OH
O
O
k
0
0
20
20
21c
28d
18c
25d
NO2
N
OH
O
O
l
NO2
N
OH
a A mixture of anti- and syn-oximes was obtained in some cases, e.g. in the case of 3b, a mixture of oxime isomers (72:28) was obtained in the
reaction using TFSA–TFA (45:55).
b Benzaldoxime (11%) and 4-bromobenzoic acid (13%) were obtained as by-products.
c Benzaldoxime was isolated in 21% yield in neat TFSA, or 10% yield in TFSA–TFA (45:55).
d Benzaldoxime was isolated in 55% yield in neat TFSA, or 19% yield in TFSA–TFA (45:55).
Finally, we carried out a similar phenylation reaction with
a-aroylnitroethane (a secondary nitroalkane), such as 5b,
however, a complex mixture was formed. Interestingly, in
the presence of TFSA, 5b yielded the enol tautomer 6b as
a stable compound in 74% yield upon aqueous work-up
(Scheme 5).9
O
OH
NO2
NO2
TFSA (10 equiv)
CH2Cl2, 0 °C, 60 min
74% yield
Cl
Cl
5b
6b
Scheme 5
This result is consistent with facile deprotonation of the a-
proton of the nitro group in TFSA to generate 4 (R = CH3,
Scheme 3), which is a stabilized cation in this case. This
observation may exclude mechanism C (Scheme 3) from
further consideration in the present phenylation reaction.
Melting points were determined with a Yanaco micro melting-point
apparatus and are uncorrected. 1H- (400 MHz) and 13C NMR (100
MHz) spectra were recorded on a Bruker Avance 400 instrument.
Chemical shifts were calibrated with 1% TMS as an internal stan-
dard or with the solvent peak, and are shown in ppm; coupling con-
stants are shown in hertz (Hz). The following abbreviations are
used: s = singlet, d = doublet, t = triplet, q = quartet, dd = double
doublet, dt = double triplet, m = multiplet, br s = broad singlet and
br d = broad doublet. Low-resolution mass spectra (LRMS) and
high-resolution mass spectra (HRMS) were recorded on a Bruker
microTOF (ESI) instrument.
In summary, we have established the generality and stud-
ied the substituent effects of phenylation reactions of a-
acylnitromethane.10 Aromatic a-aroylnitromethanes af-
forded benzil monooximes in good yield. Generally, in the
case of aromatic electron-withdrawing substituents, re-
gioselective synthesis of these monooximes from benzil
(1,2-diketone) derivatives will be difficult, because the
electrophilicity of the carbonyl group adjacent to the elec-
tron-deficient aromatic ring is enhanced.
Synthesis of N-Benzoylbenzotriazole from Acid Chloride; Typ-
ical Procedure
To a solution of benzotriazole (2.62 g, 22 mmol) in anhydrous DMF
(80 mL), Et3N (3.08 mL, 22 mmol) and benzoyl chloride (20 mmol)
were added at 0 °C (ice-water bath) under an Ar atmosphere, and
the reaction was stirred for 2 h at 0 °C. The mixture was poured into
aq HCl (2 N, 160 mL) and extracted with EtOAc (3 × 200 mL). The
organic layer was washed with brine (2 × 50 mL) and dried over
In the case of aliphatic a-acylnitromethanes, a similar
phenylation reaction occurs, although the yield of phenyl-
ated 1,2-dione monooxime is low. The present phenyla-
tion reactions represent examples of cationic electrophiles
generated at the a-position of a nitro group.
OH
OH
N
H+
(A)
(C)
Ar
OH
OH
N
H
– H2O
Ph
O
H2O
+
Ar CO2H
OH
Ar
Ph
H
H+
N
Ar
O
H
Ph
Scheme 4
Synthesis 2009, No. 24, 4129–4136 © Thieme Stuttgart · New York

PAPER
Phenylation Reaction of a-Acylnitromethanes
4133
Benzoylnitromethane (2a)
Recrystallized from CH2Cl2–n-hexane.
Table 4 Recovery of Phenylated Oxime after Exposure to Acidic
Reaction Conditionsa
Colorless prisms; mp 103–105 °C.
1H NMR (400 MHz, CDCl3): d = 7.88 (d, J = 8.0 Hz, 2 H), 7.69 (t,
J = 7.6 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 2 H), 5.89 (s, 2 H).
13C NMR (100 MHz, DMSO-d6): d = 188.9, 135.3, 133.9, 129.6,
128.9, 83.3.
Product
Recovery (%)b
O
87
N
Anal. Calcd for C8H7NO3·1/12H2O: C, 57.66; H, 4.33; N, 8.40.
Found: C, 57.74; H, 4.35; N, 8.38.
OH
3a
O
4-Chlorobenzoylnitromethane (2b)
Recrystallized from CH2Cl2–MeOH–n-hexane.
90
94
90
Colorless needles; mp 144–145 °C.
1H NMR (400 MHz, DMSO-d6): d = 7.94 (d, J = 8.4 Hz, 2 H), 7.68
(d, J = 8.8 Hz, 2 H), 6.53 (s, 2 H).
13C NMR (100 MHz, DMSO-d6): d = 188.0, 140.3, 132.6, 130.8,
129.7, 83.2.
N
Br
OH
3c
O
Anal. Calcd for C8H6ClNO3·1/4H2O: C, 47.08; H, 3.21; N, 6.86.
Found: C, 47.07; H, 3.28; N, 6.82.
N
O2N
OH
3d
4-Bromobenzoylnitromethane (2c)
Recrystallized from EtOAc–n-hexane.
O
Colorless prisms; mp 142–143 °C.
N
1H NMR (400 MHz, DMSO-d6): d = 7.87–7.81 (m, 4 H), 6.53 (s,
2 H).
OH
3j
13C NMR (100 MHz, DMSO-d6): d = 188.3, 132.9, 132.7, 130.8,
a Reaction conditions: oxime (0.2 mmol), TFSA (10 equiv), CH2Cl2
(2 mL) at 0 °C, 90 min.
129.6, 83.2.
b Isolation yield.
Anal. Calcd for C8H6BrNO3·1/4H2O: C, 38.66; H, 2.64; N, 5.64.
Found: C, 38.76; H, 2.69; N, 5.73.
Na2SO4. The solvent was evaporated and the crude residue was pu-
rified by column chromatography (typically EtOAc–n-hexane, 1:5),
to give N-benzoylbenzotriazole as a white solid (73% yield).
4-Nitrobenzoylnitromethane (2d)
Recrystallized from EtOH–n-hexane.
Yellow prisms; mp 148–149 °C.
1H NMR (400 MHz, DMSO-d6): d = 8.39 (d, J = 8.4 Hz, 2 H), 8.12
(d, J = 8.4 Hz, 2 H), 6.61 (s, 2 H).
Synthesis of N-(4-Trifluoromethyl)benzoylbenzotriazole from
the Acid; Typical Procedure
To a solution of benzotriazole (32 mmol, 4 equiv, 3.81 g) in anhy-
drous CH2Cl2 (30 mL), a solution of thionyl chloride (0.96 g, 8
mmol) in anhydrous CH2Cl2 (10 mL) was added dropwise at r.t.
over 3 min. After 30 min stirring at r.t., 4-trifluoromethylbenzoic
acid (8 mmol, 1.52 g) was added in one portion to the pale-yellow
solution (white precipitates appeared immediately). After 4 h stir-
ring at r.t., the solid was filtered off and washed with CH2Cl2. The
combined organic layer (150 mL) was washed with aq NaOH (0.4
M, 2 × 50 mL) and H2O (100 mL), and dried over MgSO4. The or-
ganic solvent was evaporated to give a pale-yellow solid, which was
purified by column chromatography (silica gel; EtOAc–n-hexane,
1:8) to give N-(4-trifluoromethyl)benzoylbenzotriazole as a while
solid (1.85 g, 80% yield).
13C NMR (100 MHz, DMSO-d6): d = 188.3, 151.2, 138.5, 130.4,
124.5, 83.4.
Anal. Calcd for C8H6N2O5: C, 45.72; H, 2.88; N, 13.33. Found: C,
45.65; H, 3.09; N, 13.35.
3-Chlorobenzoylnitromethane (2e)
Recrystallized from EtOH–n-hexane.
Colorless needles; mp 91–93 °C.
1H NMR (400 MHz, CDCl3): d = 7.97 (d, J = 2.0 Hz, 1 H), 7.89 (d,
J = 7.6 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 1 H), 7.62 (dt, J = 3.2, 8.0 Hz,
1 H), 6.56 (s, 2 H).
13C NMR (100 MHz, DMSO-d6): d = 188.0, 135.7, 134.9, 134.4,
Synthesis of a-Acylnitromethanes 2a–l; Typical Procedure
The synthesis of the a-acylnitromethanes was carried out as de-
scribed in the literature.5,6
131.5, 128.7, 127.5, 83.3.
Anal. Calcd for C8H6ClNO3: C, 48.14; H, 3.03; N, 7.02. Found: C,
48.11; H, 3.22; N, 7.06.
A mixture of MeNO2 (11 mmol, 1.1 equiv) and t-BuOK (22 mmol,
2.2 equiv) in DMSO (50 mL) was stirred for 10 min under Ar at
16 °C (water bath). A solution of N-benzoylbenzotriazole (10
mmol, 1.0 equiv) in DMSO (50 mL) was added dropwise to the
above solution at 16 °C (water bath), and the mixture was stirred at
r.t. for 17 h. The mixture was poured into aq HCl (2 N, 100 mL),
and then extracted with EtOAc (3 × 100 mL). The organic layer was
washed with H2O (2 × 50 mL), dried over Na2SO4 and the solvent
was evaporated to give a residue, which was purified by recrystalli-
zation (40% yield) to give 2a.
4-Trifluoromethylbenzoylnitromethane (2f)
The crude product was subjected to column chromatography
(EtOAc–n-hexane, 2:3) then recrystallized from EtOAc–n-hexane.
Yield: 75%; colorless plates; mp 94–95 °C.
1H NMR (400 MHz, DMSO-d6): d = 8.13 (d, J = 8.0 Hz, 2 H), 7.99
(d, J = 8.0 Hz, 2 H), 6.60 (s, 2 H).
Synthesis 2009, No. 24, 4129–4136 © Thieme Stuttgart · New York

4134
M. Takamoto et al.
PAPER
13C NMR (100 MHz, DMSO-d6): d = 188.5, 137.1, 134.2, 128.8,
126.5, 125.4, 83.4.
13C NMR (100 MHz, CDCl3): d = 196.8, 83.0, 33.9, 7.0.
MS (ESI): m/z = 118.0 [M + H]+.
Anal. Calcd for C9H6F3NO3: C, 46.36; H, 2.59; N, 6.01. Found: C,
46.37; H, 2.88; N, 5.99.
Anal. Calcd for C4H7NO3: C, 41.03; H, 6.83; N, 11.96. Found: C,
40.87; H, 5.91; N, 12.04.
3-Trifluoromethylbenzoylnitromethane (2g)
Recrystallized from CH2Cl2–n-hexane.
Reaction of a-Acylnitromethanes with Benzene in Acid; Gener-
al Procedure
Pale-yellow cubes; mp 79–80 °C.
To a solution of 2a–l (1.5 mmol) and benzene (6.5 mL, 75 mmol, 50
equiv) in anhydrous CH2Cl2 (1.5 mL), TFSA (1.3 mL, 15 mmol, 10
equiv) was added at 0 °C (ice-water bath) under Ar, and the mixture
was stirred for 20 min. The mixture was poured into ice-water (100
mL) and the mixture was extracted with CHCl3 (3 × 100 mL). The
organic layer was washed with brine (2 × 50 mL), and dried over
Na2SO4. The solvent was evaporated and the resulting crude prod-
uct was purified by flash column chromatography (typically with
EtOAc–n-hexane, 1:10→2:3) to give 3a–l. The reaction yields are
shown in Table 3.
1H NMR (400 MHz, CDCl3): d = 8.14 (br s, 1 H), 8.08 (d, J = 8.4
Hz, 1 H), 7.96 (d, J = 8.4 Hz, 1 H), 7.72 (t, J = 8.4 Hz, 1 H), 5.91 (s,
2 H).
13C NMR (100 MHz, CDCl3): d = 184.7, 134.1, 132.2, 131.5, 131.4,
131.4, 130.2, 125.1, 81.0.
Anal. Calcd for C9H6F3NO3: C, 46.36; H, 2.59; N, 6.01. Found: C,
46.33; H, 2.81; N, 6.11.
4-Bromo-o-methylbenzoylnitromethane (2h)
Recrystallized from EtOH–n-hexane.
Benzilmonooxime (3a)
Colorless prisms; mp 137–138 °C.
1H NMR (400 MHz, CDCl3): d = 8.05 (d, J = 8.0 Hz, 1 H), 8.00 (d,
J = 8.0 Hz, 2 H), 7.63–7.57 (m, 3 H), 7.49–7.43 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 191.4, 155.6, 136.4, 133.5, 130.4,
130.0, 129.4, 129.1, 128.4, 128.2.
Colorless plates; mp 108 °C.
1H NMR (400 MHz, DMSO-d6): d = 7.75 (d, J = 8.4 Hz, 1 H), 7.66
(s, 1 H), 7.62 (d, J = 84 Hz, 1 H), 6.41 (s, 2 H), 2.46 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 190.4, 142.3, 135.3, 132.5,
132.1, 129.6, 127.7, 84.4.
Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N, 6.22. Found: C,
74.49; H, 5.17; N, 6.29.
Anal. Calcd for C9H8BrNO3: C, 41.17; H, 3.26; N, 5.33. Found: C,
41.26; H, 3.24; N, 5.12.
4-Chlorobenziloxime (3b)
Colorless prisms; mp 125–126 °C.
1H NMR (400 MHz, CDCl3): d = 7.97 (d, J = 8.8 Hz, 2 H), 7.83 (br
s, 1 H, OH), 7.58–7.56 (m, 2 H), 7.44–7.41 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 190.2, 155.6, 140.0, 134.8, 131.8,
130.1, 129.3, 128.9, 128.7, 128.3.
4-Methoxybenzoylnitromethane (2i)
Recrystallized from EtOH–n-hexane.
Colorless fine needles; mp 154–155 °C.
1H NMR (400 MHz, CDCl3): d = 7.89 (d, J = 7.2 Hz, 2 H), 7.00 (d,
J = 8.8 Hz, 2 H), 5.83 (s, 2 H), 3.90 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 183.9, 165.0, 130.7, 126.4, 114.5,
81.0, 55.7.
Anal. Calcd for C14H10ClNO2: C, 64.75; H, 3.88; N, 5.39. Found: C,
64.60; H, 4.09; N, 5.39.
Anal. Calcd for C9H9NO4: C, 55.39; H, 4.65; N, 7.18. Found: C,
55.38; H, 4.71; N, 7.40.
4-Bromobenziloxime (3c)
Colorless prisms; mp 134 °C.
4-Methylbenzoylnitromethane (2j)
Recrystallized from EtOH–n-hexane.
1H NMR (400 MHz, CDCl3): d = 8.31 (br s, 1 H), 7.89 (d, J = 6.8
Hz, 2 H), 7.61 (d, J = 6.8 Hz, 2 H), 7.59–7.56 (m, 2 H), 7.46–7.44
(m, 3 H).
Colorless needles; mp 139–140 °C.
1H NMR (400 MHz, DMSO-d6): d = 7.83 (d, J = 8.0 Hz, 2 H), 7.40
(d, J = 8.4 Hz, 2 H), 6.50 (s, 2 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 190.4, 155.6, 135.2, 131.9, 131.7,
130.1, 129.3, 128.8, 128.8, 128.3.
13C NMR (100 MHz, DMSO-d6): d = 188.3, 146.1, 131.4, 130.1,
129.0, 83.2, 21.8.
Anal. Calcd for C14H10BrNO2: C, 55.29; H, 3.31; N, 4.61. Found: C,
55.39; H, 3.45; N, 4.67.
Anal. Calcd for C9H9NO3: C, 60.33; H, 5.06; N, 7.82. Found: C,
60.36; H, 5.10; N, 7.83.
4-Nitrobenziloxime (3d)
Colorless prisms; mp 183–184 °C.
1H NMR (400 MHz, CD3OD): d = 8.35 (d, J = 8.0 Hz, 2 H), 8.16 (d,
J = 8.8 Hz, 2 H), 7.54–7.45 (m, 5 H).
1-Nitro-4-methylpenta-2-one (2k)
Colorless oil.
1H NMR (400 MHz, DMSO-d6): d = 5.80 (s, 2 H), 2.44 (d, J = 6.8
Hz, 2 H), 2.04 (hept, J = 6.8 Hz, 1 H), 0.87 (d, J = 6.4 Hz, 6 H).
13C NMR (100 MHz, DMSO-d6): d = 191.6, 155.2, 149.7, 143.8,
131.5, 130.0, 129.9, 129.7, 128.3, 123.6.
13C NMR (100 MHz, CDCl3): d = 195.8, 83.6, 49.1, 24.5, 22.3.
Anal. Calcd for C14H10N2O4: C, 62.22; H, 3.73; N, 10.37. Found: C,
61.96; H, 3.91; N, 10.34.
HRMS (ESI): m/z [M – H]– calcd. for C6H10NO3 : 144.0661; found:
–
144.0664.
3-Chlorobenziloxime (3e)
Colorless prisms; mp 137 °C.
1H NMR (400 MHz, CDCl3): d = 8.00 (br s, 1 H), 7.97 (br s, 1 H),
7.90 (d, J = 8.0 Hz, 1 H), 7.58–7.56 (m, 3 H), 7.47–7.42 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 190.1, 155.6, 138.1, 134.6, 133.2,
130.3, 130.1, 129.7, 129.4, 128.8, 128.5, 128.3.
1-Nitrobutan-2-one (2l)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 5.30 (s, 2 H), 2.57 (q, J = 7.2 Hz,
2 H), 1.13 (t, J = 7.2 Hz, 3 H).
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Phenylation Reaction of a-Acylnitromethanes
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Anal. Calcd for C14H10ClNO2: C, 64.75; H, 3.88; N, 5.39. Found: C,
64.73; H, 4.06; N, 5.36.
1H NMR (400 MHz, CDCl3): d = 7.80 (br s, 1 H), 7.46–7.41 (m,
3 H), 7.33–7.31 (m, 2 H), 2.81 (d, J = 6.8 Hz, 2 H), 2.26 (hept,
J = 6.8 Hz, 1 H), 0.98 (d, J = 6.4 Hz, 6 H).
4-Trifluoromethylbenziloxime (3f)
Colorless prisms; mp 137–138 °C.
1H NMR (400 MHz, CDCl3): d = 8.10 (d, J = 8.4 Hz, 2 H), 8.05 (br
s, 1 H), 7.74 (d, J = 8.4 Hz, 2 H), 7.58–7.55 (m, 2 H), 7.48–7.46 (m,
3 H).
13C NMR (100 MHz, CDCl3): d = 198.8, 156.7, 150.4, 129.1, 128.8,
127.9, 47.0, 25.2.
Anal. Calcd for C12H15NO2·1/8H2O: C, 69.46; H, 7.41; N, 6.75.
Found: C, 69.43; H, 7.10; N, 6.88.
13C NMR (100 MHz, CDCl3): d = 190.5, 155.8, 139.6, 134.4, 130.6,
130.2, 129.3, 128.5, 128.3, 125.3, 125.2.
1-Phenyl-1,2-butanedione-1-oxime (3l)
Colorless powder; mp 114–115 °C.
Anal. Calcd for C15H10F3NO2: C, 61.44; H, 3.44; N, 4.78. Found: C,
61.29; H, 3.49; N, 4.73.
1H NMR (400 MHz, CDCl3): d = 8.23 (s, 1 H), 7.43–7.40 (m, 3 H),
7.34–7.31 (m, 2 H), 2.95 (q, J = 7.2 Hz, 2 H), 1.16 (t, J = 7.2 Hz,
3 H).
3-Trifluoromethylbenziloxime (3g)
Recrystallized from n-hexane.
13C NMR (100 MHz, CDCl3): d = 199.2, 156.5, 129.5, 129.1, 128.2,
127.9, 31.6, 8.0.
Colorless needles; mp 100–101 °C.
Anal. Calcd for C10H11NO2·1/8H2O: C, 66.93; H, 6.32; N, 7.81.
Found: C, 67.20; H, 6.30; N, 7.72.
1H NMR (400 MHz, CDCl3): d = 8.28 (br s, 1 H), 8.24 (br s, 1 H,
OH), 8.19 (br d, J = 7.6 Hz, 1 H), 7.84 (br d, J = 7.6 Hz, 1 H), 7.61
(t, J = 7.6 Hz, 1 H), 7.58–7.55 (m, 2 H), 7.48–7.45 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 190.1, 155.7, 137.3, 133.6, 133.6,
131.0, 130.2, 129.6, 129.4, 129.0, 128.3, 127.3.
Acid-Catalyzed Tautomerization of a-Aroylnitroethane
To a solution of 5b (1.0 mmol, 213.6 mg) in anhydrous CH2Cl2 (1.0
mL), TFSA (0.87 mL, 10 mmol, 10 equiv) was added at 0 °C (ice-
water bath) under Ar, and the mixture was stirred for 60 min. The
mixture was poured into ice-water and the mixture was extracted
with CHCl3 (3 × 100 mL). The organic layer was washed with brine
(2 × 50 mL), and dried over Na2SO4. The solvent was evaporated
and the resulting crude product was purified by flash column chro-
matography (EtOAc–n-hexane, 1:1) to give 6b (159 mg, 74%
yield).
Anal. Calcd for C15H10F3NO2: C, 61.44; H, 3.44; N, 4.78. Found: C,
61.22; H, 3.52; N, 4.71.
4-Bromo-o-methylbenziloxime (3h)
Recrystallized from CHCl3–n-hexane.
Colorless needles; mp 139 °C.
1H NMR (400 MHz, CDCl3): d = 8.01 (br s, 1 H), 7.55–7.42 (m,
a-(4-Chlorobenzoyl)nitroethane (5b)
8 H), 2.44 (s, 3 H).
Colorless fine needles; mp 77–77.5 °C.
13C NMR (100 MHz, CDCl3): d = 193.8, 156.8, 139.9, 136.5, 134.1,
131.1, 130.2, 129.5, 128.6, 128.3, 128.2, 125.8, 20.3.
1H NMR (400 MHz, CDCl3): d = 7.90 (d, J = 8.8 Hz, 2 H), 7.51 (d,
J = 8.8 Hz, 2 H), 6.09 (q, J = 7.2 Hz, 1 H), 1.84 (d, J = 7.2 Hz, 3 H).
Anal. Calcd for C15H12Br3NO2·1/4H2O: C, 55.83; H, 3.90; N, 4.34.
Found: C, 55.59; H, 3.86; N, 4.32.
13C NMR (100 MHz, CDCl3): d = 188.5, 141.5, 131.9, 130.2, 129.6,
84.7, 16.0.
Anal. Calcd for C9H8ClNO3: C, 50.60; H, 3.77; N, 6.56. Found: C,
50.32; H, 3.88; N, 6.43.
4-Methoxybenziloxime (3i)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 9.24 (br s, 1 H), 8.01 (d, J = 8.8
Hz, 2 H), 7.61 (m, 2 H), 7.39 (m, 3 H), 6.91 (d, J = 8.4 Hz, 2 H),
3.83 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 190.0, 164.1, 155.3, 132.9, 129.9,
129.5, 129.4, 129.1, 128.2, 113.8, 55.5.
1-(4-Chlorophenyl)-1-hydroxy-2-nitroprop-1-ene (6b)
Recrystallized from n-hexane–CH2Cl2.
Colorless plates; mp 144–145 °C.
1H NMR (400 MHz, CDCl3): d = 9.46 (br s, 1 H), 8.00 (d, J = 8.8
Hz, 2 H), 7.44 (d, J = 8.4 Hz, 2 H), 2.12 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 164.0, 140.9, 131.3, 129.1, 128.7,
124.9, 19.7.
Anal. Calcd for C15H13NO3·1/4H2O: C, 69.35; H, 5.24; N, 5.39.
Found: C, 69.08; H, 5.25; N, 5.38.
4-Methylbenziloxime (3j)
Recrystallized from CH2Cl2–n-hexane.
Anal. Calcd for C9H8ClNO3·1/8H2O: C, 50.07; H, 3.85; N, 6.49.
Found: C, 50.18; H, 3.83; N, 6.29.
Colorless prisms; mp 108–109 °C.
1H NMR (400 MHz, DMSO-d6): d = 12.37 (s, 1 H), 7.83 (d, J = 8.0
Hz, 2 H), 7.50–7.45 (m, 2 H), 7.44–7.43 (m, 3 H), 7.34 (d, J = 8.0
Hz, 2 H), 2.32 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 191.0, 155.6, 144.6, 133.8, 130.5,
129.9, 129.4, 129.3, 129.2, 128.2, 21.7.
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
on Priority Areas ‘Advanced Molecular Transformations of Carbon
Resources’ from the Ministry of Education, Culture, Sports, Sci-
ence and Technology, Japan.
Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C,
75.06; H, 5.74; N, 5.87.
References
4-Methyl-1-phenyl-1,2-pentanedione-1-oxime (3k)
(1) Rosini, G. In Comprehensive Organic Synthesis, Vol. 2;
Heathcock, C. H., Ed.; Pergamon Press: Oxford, 1991,
Chap. 1.10, 321.
Recrystallized from n-hexane–CH2Cl2.
Colorless cubes; mp 126–126.5 °C.
(2) (a) Hawthorne, M. F. J. Am. Chem. Soc. 1957, 79, 2510.
(b) Kornblum, N.; Brown, R. A. J. Am. Chem. Soc. 1965, 87,
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1742. (c) Kornblum, N.; Brown, R. A. J. Am. Chem. Soc.
1964, 86, 2681. (d) Edward, J. T.; Tremaine, P. H. Can. J.
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(7) (a) Coustard, J.-M.; Jacquesy, J.-C.; Violeau, B.
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Chem. Soc. Jpn. 1985, 58, 2519.
(3) Ohwada, T.; Yamagata, N.; Shudo, K. J. Am. Chem. Soc.
1991, 113, 1364.
(4) Kearney, T.; Harris, P. A.; Jackson, A.; Joule, J. A. Synthesis
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(5) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003,
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(8) McMurry, J.; Melton, J. J. Org. Chem. 1973, 38, 4367.
(9) Detection of 1H-NOE between the CH3 group and the
aromatic ortho-protons supported the assignment of the E-
geometry of the olefin of 6b.
(6) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Gromova, A. V.;
Witek, R.; Steel, P. J. J. Org. Chem. 2005, 70, 9211.
(10) The reaction of 2a also proceeded with substituted benzenes,
p-xylene and anisole, to give the corresponding oximes in
comparable yields (see ref 3).
Synthesis 2009, No. 24, 4129–4136 © Thieme Stuttgart · New York