Base-free conjugate addition of aliphatic nitro compounds to enones in BmimNTf2: A recyclable synthesis of γ-nitro ketones

Article abstract of DOI:10.1016/j.tet.2012.05.024

A base-free, recyclable approach for the conjugate addition of aliphatic nitro compounds to enones to give γ-nitro ketones is presented. Reactions are carried out in an ionic liquid with a basic anionic moiety, such as BmimNTf₂, as the solvent,

Full text of DOI:10.1016/j.tet.2012.05.024

Tetrahedron 68 (2012) 5852e5856
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Base-free conjugate addition of aliphatic nitro compounds to enones
in BmimNTf2: a recyclable synthesis of
g
-nitro ketones
,
b
b
c,
*
Raffaella Mancuso a , Alessandro Palmieri , Roberto Ballini , Bartolo Gabriele
*
a
ꢀ
Dipartimento di Chimica, Universita della Calabria, Ponte Pietro Bucci 12/C, Arcavacata di Rende (CS), Italy
“Green Chemistry Group”, School of Science and Technology, Chemistry Division, Universita di Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy
Dipartimento di Scienze Farmaceutiche, Universita della Calabria, 87036 Arcavacata di Rende (CS), Italy
b
ꢀ
c
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
A base-free, recyclable approach for the conjugate addition of aliphatic nitro compounds to enones to
Received 7 February 2012
Received in revised form 11 April 2012
Accepted 1 May 2012
give g-nitro ketones is presented. Reactions are carried out in an ionic liquid with a basic anionic moiety,
such as BmimNTf2, as the solvent, under mild conditions (25 ꢀC for 24 h). The IL medium could be re-
cycled several times without any appreciable loss of activity, after a simple extraction procedure for the
separation of the reaction product.
Available online 12 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Conjugate addition
Enones
Ionic liquids
Nitro compounds
g-Nitro ketones
R3
O
R2
O
R1CHNO2 + R3CH CHCR4
R2
1. Introduction
base
R1
R4
The base-promoted conjugate addition of aliphatic nitro
NO2
3
2
1
compounds 1 to enones 2 is a powerful method for the synthe-
sis of
g
-nitro ketones 3,1 which are very useful synthetic
R3
O
R2
R1
BH+
B
intermediates for the preparation of a variety of fine chemicals.2
B
BH+
2
R1CNO2
R2
R4
1
3
The classical reaction conditions involve the use of a base,
NO2
necessary for the
responding carbanion, followed by the nucleophilic attack of the
latter to the -carbon of the enone 2 with formation of the enolate
a-deprotonation of 1 with formation of the cor-
Scheme 1. Mechanism of base-promoted conjugate addition of aliphatic nitro com-
pounds 1 to enones 2 to give
-nitro ketones 3 (B¼base).
b
g
of a
g-nitro ketone, protonation of which then affords the final
product 3 (Scheme 1, B¼base).1
2. Results and discussion
In this work, we report the first example of conjugate addition of
aliphatic nitro compounds 1 to enones 2 in an ionic liquid (IL)
solvent, such as BmimNTf2. Owing to the intrinsic basicity of the
1-Nitrooctane 1a and methyl vinyl ketone 2a were used as
model substrates for assessing the reactivity of aliphatic nitro
compounds with enones in an IL as the solvent. The results
obtained by reacting 1a with 2a in the presence of Et3N as the base
and in several classical ILs, such as BmimBF4, BmimOTf, BmimPF6,
and BmimCl, are shown in Table 1, entries 1e4. As can be seen, the
expected 5-nitrododecan-2-one 3aa was formed in all cases, even
though the use of BmimCl required a higher temperature and led to
a lower product yield (entry 4).
solvent, our method allows the formation of g-nitro ketones 3 in
good yields in the absence of external bases; moreover, the reaction
medium can be recycled several times without appreciable loss of
activity.
In any case, these results confirmed the possibility to use an IL as
the reaction medium for this kind of reaction. The use of ILs in
organic synthesis has recently attracted great attention, due to the
* Corresponding authors. Tel.: þ39 0984 492816; fax: þ39 0984 492044 (R.M.);
tel.: þ39 0984 492813; fax: þ39 0984 492044 (B.G.); e-mail addresses: raffaella.-
mancuso@unical.it (R. Mancuso), b.gabriele@unical.it (B. Gabriele).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.024

R. Mancuso et al. / Tetrahedron 68 (2012) 5852e5856
5853
Table 1
300 MHz and 75 MHz, respectively, with Me4Si as internal stan-
dard. Chemical shifts ( ) and coupling constants (J) are given in
Reactions of 1-nitrooctane 1a with methyl vinyl ketone 2a in different ionic liquids
d
(ILs)a
parts per million and in hertz, respectively. IR spectra were taken
with a Jasco FT-IR 4200 spectrometer. Mass spectra were obtained
using a Shimadzu QP-2010 GCeMS apparatus at 70 eV ionization
voltage. Microanalyses were carried out with a Carlo Erba Ele-
mental Analyzer Mod. 1106. All reactions were analyzed by TLC on
silica gel 60 F254 and by GLC using a Shimadzu GC-2010 gas chro-
matograph and capillary columns with polymethylsiliconeþ5%
phenylsilicone as the stationary phase (HP-5). Column chroma-
tography was performed on silica gel 60 (Merck, 70e230 mesh).
O
O
base
IL
C7H15CHCH2CH2CCH3
CHCCH3
C7H15CH2NO2 H2C
+
1a
2a
NO2
3aa
Entry
Solvent
T (ꢀC)
Base
Runb
Yield of 3aac (%)
1
2
3
4
5
BmimBF4
BmimOTf
BmimPF6
BmimCl
25
25
25
80
25
Et3Nd
Et3Nd
Et3Nd
Et3Nd
None
1
1
1
1
1
2
3
4
5
6
60
46
57
42
60
59
60
58
58
57
BmimNTf2
4.2. Preparation of substrates and ionic liquids
Enones were commercially available (Aldrich, Fluka) and were
used as received. Nitro compounds 1b, 1f, 1g, 1j were commercially
available. Compounds 1a, 1c, 1e, 1i were synthesized by halide
displacement as reported in the literature.4a Compound 1d was
synthesized by nitration and protection of the methyl vinyl keto-
a
All reactions were carried out for 24 h in the given ionic liquid as the solvent
(0.2 mmol of 1a per mL of solvent) with a 2a/1a molar ratio of 1.2.
b
Run 1 corresponds to the first experiment, the next runs to recycles. See text for
ne.4b 2-Phenylnitroethane 1h was obtained by reduction of
b-
details.
nitrostyrene.4c Ionic liquids BmimNTf2,5 BmimOTf6 were prepared
according to literature procedures. All the other ionic liquids were
prepared as we previously described.7
c
Isolated yield based on starting 1a.
d
20 mol % with respect to 1a.
very important characteristics of these non-conventional solvents:
they are stable, non-flammable, non-volatile, recyclable, and in
some cases may even promote organic reactions.3 In order to fur-
ther improve our initial results, we then turned out our attention to
the use of an IL with a basic anionic moiety, such as BmimNTf2. The
use of this IL, in fact, could permit the formation of 3aa from 1a and
2a in the absence of an external base, making the whole process
more simple and convenient. When we allowed 1a to react with 2a
in BmimNTf2 at 25 ꢀC for 24 h in the absence of any external base,
3aa was indeed formed in 60% isolated yield, thus confirming the
validity of our hypothesis (Table 1, entry 5, Run 1). We also tested
the possibility to recycle the solvent several times, after extracting
the reaction product with Et2O. As can be seen from the results
reported in Table 1, entry 5, Runs 2e6, the IL could be recycled up to
five times without appreciable loss of activity.
4.3. General procedure for the synthesis of
in BmimNTf2 (Tables 1 and 2)
g-nitro ketones 3
To a stirred solution of 1 (0.42 mmol) in BmimNTf2 (2 mL) was
added the enone 2 (0.51 mmol) under nitrogen, and the resulting
mixture was allowed to stir at 25 ꢀC (Table 1, entry 5 and Table 2,
entries 1e9, 11) or 40 ꢀC (Table 2, entry 10) for 24 h. The product
was extracted with Et2O (6ꢁ2.5 mL), and the residue, after elimi-
nation of Et2O under vacuum, was used as such for the next recycle
(see below). The collected ethereal phases were concentrated and
the product purified by column chromatography (SiO2, hexane/
AcOEt from 95:5 to 70:30) to give g-nitro ketones 3. The isolated
yields obtained in each experiment are reported in Tables 1 and 2.
The next experiments were aimed at generalizing the process to
the use of different nitro compounds and enones. The results
obtained using other simple and functionalized nitro compounds,
shown in Table 2, demonstrate that the process is quite general, the
4.4. Recycling procedure (Tables 1 and 2)
To the residue obtained as described above were added 1
(0.42 mmol) and 2 (0.51 mmol), dissolved in Et2O. Et2O was re-
moved under vacuum, and then the same procedure described
above was followed.
corresponding g-nitro ketones being consistently formed in fair to
good yields (51e73%). We have also tested the medium recyclability
in other two cases (Table 2, entries 1 and 6), and the possibility to
recycle the IL several times, without significant decrease of activity,
was confirmed.
4.5. Characterization of products
4.5.1. 5-Nitrododecan-2-one (3aa). Yield: 58 mg, 60% (Table 1, en-
3. Conclusion
try 1). Yellow oil. IR (film):
n
¼2932 (s), 1719 (s), 1443 (s), 1359 (s),
1163 (m) cmꢂ1 1H NMR (300 MHz, CDCl3):
;
d
¼4.52e4.43 (m, 1H,
In conclusion, in this work we have reported the first example of
the use of ILs as reaction media for the conjugate addition of ali-
phatic nitro compounds 1 to enones 2 for the synthesis of g-nitro
ketones 3. We have found that an IL with a basic anionic moiety,
such as BmimNTf2, may allow the reaction to occur in the absence
of any external base. Moreover, the IL medium could be recycled
several times without any appreciable loss of activity, after a simple
extraction procedure for the separation of the reaction product.
CHNO2), 2.50e2.43 (m, 2H, CH2CO), 2.14 (s, 3H, Me), 2.12e2.03 (m,
2H, CH2CH2CO), 2.01e1.89 [m, 1H, CH3(CH2)5CHHCHNO2],
1.75e1.63 [m, 1H, CH3(CH2)5CHHCHNO2], 1.38e1.17 [m, 10H,
CH3(CH2)5], 0.86 (t, 3H, J¼6.8 Hz, CH3CH2); 13C NMR (75 MHz,
CDCl3):
d¼206.7, 88.2, 39.2, 34.2, 31.8, 30.32, 29.2, 29.1, 27.6, 25.9,
22.8, 14.3; GCeMS: m/z¼229 (Mþ, absent), 109 (9), 83 (30), 69 (27),
55 (32), 43 (100); Anal. Calcd for C12H23NO3 (229.32): C, 62.85; H,
10.11; N, 6.11; found C, 62.90; H, 10.19; N, 6.07.
4. Experimental section
4.1. General
4.5.2. 5-Nitrodecan-2-one (3ba). Yield: 51 mg, 60% (Table 2, entry
1). Yellow oil. IR (film):
n
¼2930 (s), 1720 (s), 1441 (s), 1361 (s), 1167
(m) cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼4.58e4.42 (m, 1H, CHNO2),
2.48 (t, 2H, J¼6.9 Hz, CH2CO), 2.21e1.86 [m, 4H, CH2CH(NO2)CH2],
2.15 (s, 3H, Me), 1.47e1.16 [m, 6H, CH3(CH2)3], 0.87 (t, 3H, J¼6.2 Hz,
Melting points were determined with a Reichert Thermovar
apparatus. 1H NMR and 13C NMR spectra were recorded at 25 ꢀC on
a Bruker DPX Avance 300 spectrometer in CDCl3 solutions at
CH3CH2); 13C NMR (75 MHz, CDCl3):
d¼206.7, 88.2, 39.2, 34.1, 31.2,
30.2, 27.6, 25.6, 22.5,14.1; GCeMS: m/z¼201 (Mþ, absent),137 (7), 95

5854
R. Mancuso et al. / Tetrahedron 68 (2012) 5852e5856
Table 2
Base-free synthesis of
a
g-nitro ketones 3 by conjugate addition of aliphatic nitro compounds 1 to enones 2 in BmimNTf2
R3
O
R2
O
BmimNTf2
+ R3CH
R1
R4
CHCR4
R1CHNO2
25-40 °C
24 h
NO2
R2
2
1
3
Entry
1
2
3
Runb
1
Yield of 3c (%)
O
O
C5H11CHCH2CH2CCH3
1
C5H11CH2NO2 1b
60
CHCCH3
2a
H2C
NO2
3ba
2
3
4
5
6
61
61
59
60
60
O
Ph(CH2)2CHCH2CH2CCH3
2
3
4
5
Ph(CH2)2CH2NO2 1c
PhCH2CH2NO2 1d
H2C]CH(CH2)3CH2NO2 1e
1c
2a
1
1
1
1
53
51
65
55
NO2
3ca
O
2a
2a
PhCH2CHCH2CH2CCH3
NO2
3da
O
H2C CH(CH2)3CHCH2CH2CCH3
NO2
3ea
O
O
Ph(CH2)2CHCH2CH2CCH2CH3
CHCCH2CH3
2b
H2C
NO2
3cb
O
O
6
EtO2CCH2NO2 1f
1
60
EtO2C
NO2
2c
3fc
2
3
4
5
6
61
61
59
60
60
O
EtO2CCHNO2
7
2c
2c
2c
2c
1
1
1
72
65d
70
EtO2C
H3C
CH3
1g
NO2
O
3gc
O
O
8
NO2
1h
O
O
NO2
3hc
O
9
NC(CH2)4CH2NO2 1i
NC
3ic
NO2
O
O
O
10e
1
1
68
73
NO2
Ph
Ph
1j
NO2
3jc
O
O
EtO2C
Ph
11
1f
Ph
NO2
3fd
2d
a
Unless otherwise noted, all reactions were carried out at 25 ꢀC for 24 h in BmimNTf2 as the solvent (0.2 mmol of 1 per mL of solvent) with a 2/1 molar ratio of 1.2.
Run 1 corresponds to the first experiment, the next runs to recycles. See text for details.
Isolated yield based on starting 1. The formation of unidentified heavy products (chromatographically immobile materials) accounted for the difference between the
b
c
substrate conversion and the product yield.
d
The two diastereomers A and B could be separated and isolated in 38% and 27% yield, respectively.
The reaction was carried out at 40 ꢀC.
e

R. Mancuso et al. / Tetrahedron 68 (2012) 5852e5856
5855
(19), 81 (15), 69 (30), 55 (46), 43 (100), 29 (19); Anal. Calcd for
C10H19NO3 (201.26): C, 59.68; H, 9.52; N, 6.96; found C, 59.71; H,
9.55; N, 6.93.
CO2CH2CH3)], 2.90e2.70 [A (m, 1H, CHCHNO2)þB (m, 1H,
CHCHNO2)], 2.52e1.90 [A (m, 6H, cyclohexanone ring)þB (m, 6H,
cyclohexanone ring)], 1.84e1.47 [A (m, 2H, cyclohexanone ring)þB
(m, 2H, cyclohexanone ring)], 1.36e1.28 [A (m, 3H, Me)þB (m, 3H,
4.5.3. 5-Nitro-7-phenylheptan-2-one (3ca). Yield: 53 mg, 53%
Me)]; 13C NMR (75 MHz, CDCl3):
d¼207.85 (A or B), 207.82 (B or A),
(Table 2, entry 2). Yellow oil. IR (film):
(w), 1549 (s), 1452 (m), 1362 (s), 1256 (w), 1167 (m), 916 (w), 874
(w), 751 (m), 703 (m) cmꢂ1 1H NMR (300 MHz, CDCl3):
n
¼2929 (m), 1721 (s), 1606
163.09 (A or B), 162.97 (B or A), 91.23 (A or B), 91.13 (B or A), 63.3
(AþB), 43.19 (A or B), 43.12 (B or A), 40.8 (AþB), 39.03 (A or B), 38.99
(B or A), 27.29 (A or B), 27.13 (B or A), 24.2 (A or B), 24.06 (B or A),
13.9 (AþB); GCeMS (AþB): m/z¼229 [Mþ, 1], 183 (14), 182 (14), 153
(20), 137 (65), 136 (30), 126 (19), 125 (30), 109 (74), 97 (61), 95 (22),
85 (35), 81 (100), 79 (30), 69 (35), 68 (55), 67 (41), 55 (78); Anal.
Calcd for C10H15NO5 (229.23): C, 52.40; H, 6.60; N, 6.11; found C,
52.35; H, 6.61; N, 6.12.
;
d
¼7.33e7.27 (m, 2H, aromatic), 7.22 (t, 1H, J¼7.7 Hz, aromatic), 7.16
(d, 2H, J¼7.7 Hz, aromatic), 4.54e4.46 (m, 1H, CHNO2), 2.71e2.55
(m, 2H, PhCH2), 2.52e2.43 (m, 2H, CH2CO), 2.38e2.26 (m, 1H,
BnCHHCHNO2), 2.17e1.94 [m, 3H, BnCHHCHNO2þBnCH2CH(NO2)
CH2], 2.14 (s, 3H, Me); 13C NMR (75 MHz, CDCl3):
d
¼206.6, 139.9,
128.9, 128.6, 126.7, 87.4, 39.2, 35.8, 32.1, 30.3, 27.7; GCeMS:
m/z¼235 (Mþ, absent), 169 (10), 129 (36), 107 (28), 91 (87), 79 (10),
65 (20), 43 (100); Anal. Calcd for C13H17NO3 (235.28): C, 66.36; H,
7.28; N, 5.95; found C, 66.40; H, 7.31; N, 5.92.
4.5.8. Ethyl 2-nitro-2-(3-oxocyclohexyl)propionate (3gc). (Mixture
of diastereomers AþB, A:B ratio ca. 1:1, determined by GLC). Yield:
74 mg, 72% (Table 2, entry 7). Yellow oil. IR (film):
n
¼3417 (m, br),
2938 (m), 1714 (s), 1555 (s), 1447 (m), 1384 (m), 1130 (m), 1081 (m),
4.5.4. 5-Nitro-6-phenylhexan-2-one (3da). Yield: 48 mg, 51% (Table
952 (w), 864 (w) cmꢂ1 1H NMR (300 MHz, CDCl3):
;
d
¼4.34e4.23
2, entry 3). Yellow oil. IR (film):
(s), 1455 (m), 1366 (s),1252 (w),1166 (m), 917 (w), 875 (w), 748 (m),
701 (m) cmꢂ1 1H NMR (300 MHz, CDCl3):
n
¼2932 (m), 1715 (s), 1605 (w), 1548
[A (m, 2H, CO2CH2CH3)þB (m, 2H, CO2CH2CH3)], 2.89e2.72 [A (m,
1H, CHCHNO2)þB (m, 1H, CHCHNO2)], 2.53e1.84 [A (m, 8H,
cyclohexanone ring)þB (m, 8H, cyclohexanone ring)], 1.79 [A (s,
3H, CH3CNO2)], 1.78 [B (s, 3H, CH3CNO2)], 1.34e1.24 [A (m, 3H,
CO2CH2CH3)þB (m, 3H, CO2CH2CH3)]; 13C NMR (75 MHz, CDCl3):
;
d
¼7.33e7.22 (m, 3H,
aromatic), 7.18e7.13 (m, 2H, aromatic), 4.80e4.70 (m, 1H, CHNO2),
3.26 (dd, 1H, J¼8.5, 14.1 Hz, PhCHH), 3.05 (dd, 1H, J¼5.6, 14.1 Hz,
PhCHH), 2.53e2.46 (m, 2H, CH2CO), 2.20e2.10 [m, 2H, BnCH(NO2)
d
¼208.4 (AþB), 166.3 (A), 166.2 (B), 95.0 (B), 94.9 (A), 63.0 (AþB),
CH2], 2.13 (s, 3H, Me); 13C NMR (75 MHz, CDCl3):
d
¼206.6, 135.4,
43.5 (A), 43.3 (B), 42.7 (B), 42.4 (A), 40.8 (AþB), 26.3 (A), 26.0 (B),
24.3 (A), 24.2 (B), 19.0 (A), 18.6 (B), 13.8 (AþB); GCeMS:
diastereomer A: m/z¼243 [Mþ, absent], 197 (13), 196 (11), 167 (21),
151 (30), 150 (27), 123 (100), 111 (12), 97 (35), 95 (85), 81 (32), 67
(26), 55 (46); diastereomer B: m/z¼243 [Mþ, absent], 196 (30), 167
(11), 151 (24), 150 (33), 123 (100), 111 (10), 97 (25), 95 (83), 81 (29),
67 (25), 55 (44); Anal. Calcd for C11H17NO5 (243.26): C, 54.31; H,
7.04; N, 5.76; found C, 54.40; H, 7.03; N, 5.77.
129.1, 127.7, 89.1, 40.3, 39.2, 30.3, 27.4; GCeMS: m/z¼221 (Mþ, ab-
sent), 174 (51), 117 (100), 91 (55), 43 (59); Anal. Calcd for C12H15NO3
(221.25): C, 65.14; H, 6.83; N, 6.33; found C, 65.17; H, 6.87; N, 6.30.
4.5.5. 5-Nitronon-8-en-2-one (3ea). Yield: 55 mg, 65% (Table 2,
entry 4). Yellow oil. IR (film):
1716 (s), 1642 (w), 1557 (m), 1436 (m), 1361 (s), 1168 (m), 995 (m),
917 (m) cmꢂ1 1H NMR (300 MHz, CDCl3):
n
¼3079 (w), 2929 (s), 2864 (m),
;
d
¼5.83e5.66 (m, 1H,
H2C]CH), 5.09e4.93 (m, 2H, H2C]CH), 4.58e4.44 (m, 1H,
CHNO2), 2.55e2.45 (m, 2H, CH2CO), 2.20e1.90 [m, 4H,
CH2CH(NO2)CH2], 2.16 (s, 3H, Me), 1.82e1.63 (m, 2H, ]CHCH2),
1.51e1.36 (m, 2H, ]CHCH2CH2); 13C NMR (75 MHz, CDCl3):
4.5.9. 3-[2-(2-Methyl-[1,3]dioxolan-2-yl)]-1-nitroethylcyclohexanone
(3hc, diastereomerA). Yield: 41 mg, 38% (Table 2, entry 8). Yellow oil.
IR (film):
(m),1165 (m),1085 (m),1038 (w), 950 (w) cmꢂ1; 1H NMR (300 MHz,
CDCl3):
n¼3415 (m, br), 2942 (m), 1719 (s), 1550 (s), 1449 (w), 1374
d
¼206.4, 137.4, 115.6, 87.8, 39.0, 33.2, 32.9, 30.1, 27.4, 24.9;
d
¼4.57 (ddd, J¼10.3, 6.6, 1.5 Hz, 1H, CHNO2), 4.02e3.84 (m,
GCeMS: m/z¼199 (Mþ, absent), 153 (11), 135 (28), 109 (12), 95
(100), 94 (29), 93 (98), 91 (19), 81 (24), 79 (44), 71 (35), 67 (80);
Anal. Calcd for C10H17NO3 (199.25): C, 60.28; H, 8.60; N, 7.03;
found C, 60.35; H, 8.59; N, 7.02.
4H, OCH2CH2O), 2.69 (dd, J¼15.4, 10.3 Hz, 1H, CHHCHNO2),
2.56e2.36 (m, 2H, cyclohexanone ring), 2.34e1.98 (m, 6H, cyclo-
hexanone ringþCHHCHNO2), 1.44e1.22 (m, 2H, cyclohexanone
ring), 1.32 (s, 3H, Me); 13C NMR (75 MHz, CDCl3):
d¼208.7, 107.9,
87.2, 64.9, 64.8, 44.3, 42.1, 40.9, 39.3, 27.0, 24.3, 24.1; GCeMS:
m/z¼257 [Mþ, absent], 242 (4), 195 (32), 149 (5), 107 (6), 87 (100);
Anal. Calcd for C12H19NO5 (257.28): C, 56.02; H, 7.44; N, 5.44; found
C, 56.15; H, 7.43; N, 5.43.
4.5.6. 6-Nitro-8-phenyloctan-3-one (3cb). Yield: 58 mg, 55% (Table
2, entry 5). Yellow oil. IR (film):
(s), 1457 (m), 1363 (s), 1247 (w), 1161 (m), 916 (w), 875 (w), 743 (m),
699 (m) cmꢂ1 1H NMR (300 MHz, CDCl3):
n
¼2939 (m), 1718 (s), 1609 (w), 1551
;
d¼7.33e7.27 (m, 2H,
aromatic), 7.21 (t, 1H, J¼7.7 Hz, aromatic), 7.16 (d, 2H, J¼7.7 Hz,
aromatic), 4.55e4.46 (m, 1H, CHNO2), 2.71e2.55 (m, 2H, PhCH2),
2.48e2.36 (m, 4H, CH2COCH2CH3), 2.35e2.26 (m, 1H,
BnCHHCHNO2), 2.12 [q, 2H, J¼6.8 Hz, BnCH2CH(NO2)CH2],
2.06e1.95 (m, 1H, BnCHHCHNO2), 1.04 (t, 3H, J¼7.3 Hz, COCH2CH3);
4.5.10. 3-[2-(2-Methyl-[1,3]dioxolan-2-yl)]-1-nitroethylcyclohexanone
(3hc, diastereomer B). Yield: 30 mg, 27% (Table 2, entry 8). Yellow oil.
IR (film):
(m), 1169 (m), 1087 (m), 1040 (w), 956 (w) cmꢂ1; 1H NMR (300 MHz,
CDCl3):
n¼3417 (m, br), 2940 (m), 1722 (s), 1554 (s), 1446 (w), 1381
d
¼4.65 (dd, br, J¼10.3, 5.1 Hz,1H, CHNO2), 4.02e3.82 (m, 4H,
13C NMR (75 MHz, CDCl3):
d
¼209.3, 139.9, 128.8, 128.5, 126.6, 87.4,
OCH2CH2O), 2.71 (dd, J¼15.4,10.3 Hz,1H, CHHCHNO2), 2.50e1.94 (m,
8H, cyclohexanone ringþCHHCHNO2), 1.45e1.21 (m, 2H, cyclohexa-
37.8, 36.2, 35.8, 32.1, 27.7, 7.9; GCeMS: m/z¼249 (Mþ, absent), 183
(11), 130 (33), 115 (26), 107 (27), 91 (96), 57 (100), 29 (21); Anal.
Calcd for C14H19NO3 (249.31): C, 67.45; H, 7.68; N, 5.62; found C,
67.49; H, 7.71; N, 5.59.
none ring), 1.33 (s, 3H, Me); 13C NMR (75 MHz, CDCl3):
d¼208.9,
107.9, 87.0, 64.9, 64.8, 43.0, 42.0, 40.8, 39.4, 28.0, 24.4, 24.1; GCeMS:
m/z¼257 [Mþ, absent], 242 (3), 195 (32), 149 (7), 107 (6), 87 (100);
Anal. Calcd for C12H19NO5 (257.28): C, 56.02; H, 7.44; N, 5.44; found
C, 56.14; H, 7.45; N, 5.43.
4.5.7. Ethyl nitro-(3-oxocyclohexyl)acetate (3fc). Yield: 58 mg, 60%
(Table 2, entry 6). (Mixture of diastereomers AþB, A:B ratio ca. 1:1,
determined by 1H NMR). Yellow oil. IR (film):
n
¼3481 (m, br), 3415
4.5.11. 6-Nitro-6-(oxocyclohexyl)hexanenitrile (3ic). (Mixture of di-
astereomers AþB, A:B ratio ca. 1:1, determined by GLC). Yield:
(m, br), 2941 (m), 2868 (w), 1748 (s), 1714 (s), 1558 (s), 1449 (w),
1373 (m), 1181 (m), 1097 (m), 1019 (m), 858 (w) cmꢂ1 1H NMR
(300 MHz, CDCl3):
¼5.10 [A (d, J¼6.6 Hz, 1H, CHNO2)], 5.06 [B (d,
J¼8.1 Hz, 1H, CHNO2)], 4.37e4.26 [A (m, 2H, CO2CH2CH3)þB (m, 2H,
;
70 mg, 70% (Table 2, entry 9). Yellow oil. IR (film):
2941 (m), 2871 (m), 2246 (w), 1713 (s), 1548 (s), 1451 (w), 1425
(w), 1383 (m), 1232 (w), 1007 (w), 1064 (w) cmꢂ1 1H NMR
n
¼3413 (m, br),
d
;

5856
R. Mancuso et al. / Tetrahedron 68 (2012) 5852e5856
(300 MHz, CDCl3):
d
¼4.46e4.27 [A (m, 1H, CHNO2)þB (m, 1H,
Acknowledgements
CHNO2)], 2.56e1.95 [A (m, 9H, 4CH2þCHCHNO2)þB (m, 9H,
4CH2þCHCHNO2)], 1.93e1.32 [A (m, 6H, 3CH2)þB (m, 6H, 3CH2)],
1.31e1.20 [A (m, 2H, CH2)þB (m, 2H, CH2)]; 13C NMR (75 MHz,
Financial support from the University of Calabria (Rende, Italy),
the University of Camerino (Italy), and the Ministero dell’Istruzione
ꢀ
CDCl3):
d
¼208.8 (A), 208.7 (B), 119.1 (AþB), 92.2 (AþB), 43.8 (AþB),
dell’Universita e della Ricerca (MIUR, Rome, Italy, FIRB National
41.7 (AþB), 40.9 (AþB), 29.9 (AþB), 27.4 (AþB), 25.1 (AþB), 24.8
(AþB), 24.1 (AþB), 15.3 (AþB); GCeMS: diastereomer A: m/z¼238
[Mþ, absent], 193 (12), 192 (84), 191 (19), 174 (10), 162 (13), 134 (13),
123 (25), 110 (13), 97 (35), 96 (21), 95 (17), 82 (18), 81 (35), 79 (25),
69 (39), 67 (37), 55 (100); diastereomer B: m/z¼238 [Mþ, absent],
192 (72), 191 (34), 162 (11), 134 (12), 123 (34), 110 (14), 97 (35), 96
(21), 95 (18), 83 (14), 82 (17), 81 (35), 79 (23), 69 (39), 67 (38), 55
(100); Anal. Calcd for C12H18N2O3 (238.28): C, 60.49; H, 7.61; N,
11.76; found C, 60.55; H, 7.60; N, 11.74.
Project ‘Metodologie di nuova generazione nella formazione di
legami carbonio-carbonio e carbonio-eteroatomo in condizioni
eco-sostenibili’) is gratefully acknowledged.
References and notes
1. See, for example: Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M. Chem.
Rev. 2005, 105, 933e972; Rosini, G.; Ballini, R.; Petrini, M.; Marotta, E. Angew.
Chem., Int. Ed. Engl. 1986, 25, 941e942; Ballini, R.; Fiorini, D.; Gil, M. V.; Palmieri,
A. Tetrahedron 2004, 60, 2799e2804; Ballini, R.; Bosica, G.; Livi, D.; Palmieri, A.;
Maggi, R.; Sartori, G. Tetrahedron Lett. 2003, 44, 2271e2273; Manzano, R.;
4.5.12. 3-(1-Nitro-2-oxo-2-phenyethyl)cyclohexanone (3jc). (Mix-
ture of diastereomers AþB, A:B ratio ca. 1:0.65, determined by 1H
NMR). Yield: 75 mg, 68% (Table 2, entry 10). Yellow oil. IR (film):
ꢁ
ꢁ
ꢁ
Andres, J. M.; Alvarez, R.; Muruzabal, R. D.; de Lera, A. R.; Pedrosa, R. Chem.dEur.
J. 2011, 17, 5931e5938.
2. See, for example: Ballini, R.; Petrini, M. Arkivoc 2009, ix, 195e223; Ballini, R.;
Petrini, M.; Rosini, G. Molecules 2008, 13, 319e330; Ballini, R.; Barboni, L.; Bo-
sica, G.; Fiorini, D.; Palmieri, A. Pure Appl. Chem. 2006, 78, 1857e1866; Ballini,
R.; Barboni, L.; Fiorini, D.; Palmieri, A.; Petrini, M. Arkivok 2006, vi, 127e152;
Ballini, R.; Atta-ur-Rahman, Ed. Studies in Natural Products Chemistry; Elsevier:
Amsterdam, 1997; Vol. 19, p 117.
n
¼2950 (m), 1713 (s), 1553 (s), 1449 (w), 1364 (m), 1271 (m), 1228
(m), 1187 (w), 687 (m) cmꢂ1 1H NMR (300 MHz, CDCl3):
¼8.07e7.94 [A (m, 2H, aromatic)þB (m, 2H, aromatic)], 7.76e7.63
;
d
[A (m, 1H, aromatic)þB (m, 1H, aromatic)], 7.61e7.46 [A (m, 2H,
aromatic)þB (m, 2H, aromatic)], 6.03 [A (d, J¼8.1 Hz, 1H, CHNO2)],
6.00 [B (d, J¼8.1 Hz, 1H, CHNO2)], 3.18e2.90 [A (m, 1H, CHCHNO2)],
2.76e2.57 [B (m, 1H, CHCHNO2)], 2.57e1.86 [A (m, 6H, cyclohexa-
none ring)þB (m, 6H, cyclohexanone ring)], 1.85e1.44 [A (m, 2H,
cyclohexanone ring)þB (m, 2H, cyclohexanone ring)]; 13C NMR
3. For some recent books and reviews, see: Ionic Liquids: Theory, Properties, New
Approaches; Kokorin, A., Ed.; InTech: Rijeka, 2011; Ionic Liquids: Applications and
Perspectives; Kokorin, A., Ed.; InTech: Rijeka, 2011; Dupont, J. Acc. Chem. Res.
2011, 44, 1223e1231; Chiappe, C.; Rajamani, S. Eur. J. Org. Chem. 2011, 28,
5517e5539; Wilpiszewska, K.; Spychaj, T. Carbohydr. Polym. 2011, 86, 424e428;
Ferraz, R.; Branco, L. C.; Prudencio, C.; Noronha, J. P.; Petrovski, Z. ChemMedChem
2011, 6, 975e985; Hallett, J. P.; Welton, T. Chem. Rev. 2011, 111, 3508e3576; Jutz,
F.; Andanson, J.-M.; Baiker, A. Chem. Rev. 2011, 111, 322e353; Zhang, Q.; Zhang,
S.; Deng, Y. Green Chem. 2011, 13, 2619e2637; Freudenmann, D.; Wolf, S.; Wolff,
M.; Feldmann, C. Angew. Chem., Int. Ed. 2011, 50, 11050e11060; Isambert, N.;
Duque, M. D. M. S.; Plaquevent, J.-C.; Genisson, Y.; Rodriguez, J.; Constantieux, T.
Chem. Soc. Rev. 2011, 40, 1347e1357; Petkovic, M.; Seddon, K. R.; Rebelo, L. P. N.;
Pereira, C. S. Chem. Soc. Rev. 2011, 40, 1383e1403; Hubbard, C. D.; Illner, P.; van
Edik, R. Chem. Soc. Rev. 2011, 40, 272e290; Lee, J. W.; Shin, J. Y.; Chun, Y. S.; Bin, J.
H.; Song, C. E.; Lee, S.-G. Acc. Chem. Res. 2010, 43, 785e994; Torimoto, T.; Tsuda,
T.; Okazaki, K.-i.; Kuwabata, S. Adv. Mater. 2010, 22, 1196e1221; Sun, P.; Arm-
strong, D. W. Anal. Chim. Acta 2010, 661, 1e16; Moniruzzaman, M.; Nakashima,
K.; Kamiya, N.; Goto, M. Biochem. Eng. J. 2010, 48, 295e314; Olivier-Bourbigou,
H.; Magna, L.; Morvan, D. Appl. Catal., A 2010, 373, 1e56; Ma, Z.; Yu, J.; Dai, S. Adv.
Mater. 2010, 22, 261e285; Esperanca, J. M. S. S.; Canongia Lopes, J. N.; Tariq, M.;
Santos, L. M. N. B. F.; Magee, J. W.; Rebelo, L. P. N. J. Chem. Eng. Data 2010, 55,
3e12; Geirnoth, R. Angew. Chem., Int. Ed. 2010, 49, 2834e2839; Thi, P. T. P.; Cho,
C.-W.; Yun, Y.-S. Water Res. 2010, 44, 352e372; Coleman, D.; Gathergood, N.
Chem. Soc. Rev. 2010, 39, 600e637; Hayes, R.; Warr, G. G.; Atkin, R. Phys. Chem.
Chem. Phys. 2010, 12, 1709e1723.
(75 MHz, CDCl3):
d
¼208.2 (B), 207.7 (A), 187.3 (A), 187.0 (B), 135.1 (A
or B), 134.6 (A or B), 133.6 (A or B), 130.2 (A or B), 129.4 (A or B),
128.8 (A or B), 128.5 (A or B), 128.3 (A or B), 91.9 (A), 91.6 (B), 44.5
(AþB), 43.5 (B), 43.3 (A), 40.9 (AþB), 27.5 (A or B), 27.2 (B or A), 24.3
(B), 24.2 (A); GCeMS: diastereomer A: m/z¼261 [Mþ, absent], 215
(27), 105 (100), 97 (8), 77 (33); diastereomer B: m/z¼261 [Mþ, ab-
sent], 215 (13), 187 (2), 145 (3), 120 (4), 115 (4), 105 (100), 97 (9), 91
(5), 77 (38); Anal. Calcd for C14H15NO4 (261.27): C, 64.36; H, 5.79; N,
5.36; found C, 64.45; H, 5.77; N, 5.35.
4.5.13. Ethyl 2-nitro-5-oxo-5-phenylpentanoate (3fd). Yield: 81 mg,
73% (Table 2, entry 11). Yellow oil. IR (film):
1684 (s),1557 (m),1448 (w),1370 (m),1266 (m),1214 (m), 1024 (m),
751 (m), 690 (m) cmꢂ1; 1H NMR (300 MHz, CDCl3):
n
¼2984 (m), 1748 (s),
d¼7.97e7.90 (m,
4. (a) Ballini, R.; Barboni, L.; Palmieri, A. Green Chem. 2008, 10, 1004e1006; (b)
Gabrielli, S.; Palmieri, A.; Perosa, A.; Selva, M.; Ballini, R. Green Chem. 2011, 13,
2026e2028; (c) Rosini, G.; Ballini, R.; Sorrenti, P. Tetrahedron 1983, 39,
4127e4132; (d) Kodukulla, R. P. K.; Trivedi, G. K.; Vora, J. D.; Mathur, H. H. Synth.
Commun. 1994, 24, 819e832.
5. Huddleston, J. G.; Visser, A. E.; Reichert, W. M.; Willauer, H. D.; Broker, G. A.;
Rogers, R. D. Green Chem. 2001, 156e164.
6. Crosthwaite, J. M.; Aki, S. N. V. K.; Maginn, E. J.; Brennecke, J. F. J. Phys. Chem. B
2004, 108, 5113e5119.
7. Gabriele, B.; Mancuso, R.; Lupinacci, E.; Spina, R.; Salerno, G.; Veltri, L.;
2H on phenyl ring), 7.62e7.54 (m, 1H on phenyl ring), 7.51e7.42 (m,
2H on phenyl ring), 5.38 (dd, J¼7.8, 6.6 Hz, 1H, CHNO2), 4.29 (q,
J¼7.1 Hz, 2H, CO2CH2CH3), 3.22e3.06 (m, 2H, CH2CO), 2.77e2.61 (m,
2H, CH2CHNO2), 1.03 (t, J¼7.1 Hz, 3H, Me); 13C NMR (75 MHz,
CDCl3):
d
¼197.5, 164.4, 133.6, 128.8, 128.04, 127.99, 87.0, 63.1, 33.7,
24.6, 13.9; GCeMS: m/z¼265 (Mþ, absent), 235 (2), 218 (2), 105
(100), 77 (23); Anal. Calcd for C13H15NO5 (265.26): C, 58.86; H, 5.70;
N, 5.28; found C, 58.95; H, 5.69; N, 5.27.
Dibenedetto, A. Tetrahedron 2009, 65, 8507e8512.