Solvent-free synthesis of γ-nitroketones and γ-nitroesters promoted by the ionic liquid/K2CO3 catalytic system

Article abstract of DOI:10.1055/s-2006-950306

A convenient solvent-free synthesis of γ-nitroketones and γ-nitroesters based on the reaction of nitroalkanes with α,β-unsaturated carbonyl compounds in the ultrasonically activated heterogeneous catalytic system 1-butyl-3-methylimidazolium tetrafluorobor

Full text of DOI:10.1055/s-2006-950306

PAPER
3849
Solvent-Free Synthesis of g-Nitroketones and g-Nitroesters Promoted by the
Ionic Liquid/K2CO3 Catalytic System
Solvent-Free
S
e
ynthesis of
r
g
-Nitrok
g
etones and
g
-Nitroester
y
s
G. Zlotin,* Andrey V. Bogolyubov, Galina V. Kryshtal, Galina M. Zhdankina, Marina I. Struchkova,
Vladimir A. Tartakovsky
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russia
Fax +7(495)1355328; E-mail: zlotin@ioc.ac.ru
Received 22 June 2006; revised 31 July 2006
Herein we report the first example of a convenient, envi-
Abstract: A convenient solvent-free synthesis of g-nitroketones
ronment-friendly synthesis of g-nitroketones and g-nitro-
and g-nitroesters based on the reaction of nitroalkanes with a,b-un-
esters 3 based on the reaction of nitroalkanes 1a–c with
saturated carbonyl compounds in the ultrasonically activated hete-
rogeneous catalytic system 1-butyl-3-methylimidazolium tetra-
a,b-unsaturated carbonyl compounds 2a–i promoted by a
fluoroborate ([bmim][BF4])/K2CO3 has been developed. The sys- recoverable heterogeneous catalytic system, 1-butyl-3-
tem retained its catalytic activity over three reaction cycles.
methylimidazolium tetrafluoroborate ([bmim][BF4])/
K2CO3. Lower nitroalkanes, such as nitroethane (1a), 2-
nitropropane (1b), and nitrocyclohexane (1c), were used
as donors and a,b- unsaturated ketones 2a–f and esters
2g–i as acceptors (Scheme 1, Tables 1 and 2).
Key words: Michael additions, ionic liquids, catalysis, esters, ke-
tones
Conjugate addition of nitroalkanes to electron-deficient
alkenes (the Michael reaction) is a convenient method for
the formation of new C–C bonds.1 The reaction products
generally contain also other functional groups (carbonyl,
ester, etc.) along with the nitro group and can be used for
the synthesis of pharmacologically useful polyfunctional
compounds, in particular g-amino butyric acid (GABA)
derivatives.2 There are several protocols detailing the re-
action under homogeneous3 or heterogeneous,4a–c in par-
ticular, phase-transfer catalysis (PTC) conditions.4a The
addition products were synthesized in moderate to high
yields, yet the recovery of a solvent and/or PTC remains a
challenge because of their good solubility in hydrocar-
bons and Et2O used for product isolation.5
To optimize the reaction conditions, we first studied reac-
tions of 2-nitropropane (1b) with (E)-4-phenylbut-3-en-2-
one (2b) and with (E)-methyl but-2-enoate (2h) at 20–
30 °C in various [bmim][BF4]/2 and base (K2CO3)/2 ra-
tios (Table 3). In all experiments a slight excess (140
mol%) of 1b with respect to 2b,h was used to reach com-
R3
R4
R2
R1
O
O
R2
R4
NO2
or (for 2i)
3a–t
i
+
R1
NO2
1a–c
R3
O
O
2a–i
MeO
OMe
NO2
4
Recently ionic liquids (ILs)6a,b with fluorinated anions
have attracted attention as recoverable solvents in reac-
tions of CH-acidic compounds (carbonyl compounds, ma-
lonic, acetoacetic, cyanoacetic esters) with electron-
deficient alkenes.7a–f ILs were also used as phase-transfer
catalysts (PTC) in Michael7a and some other reactions em-
ploying CH-acidic compounds.8a,b Promising results were
obtained in reactions promoted by heterogeneous IL/solid
base systems.8a Due to poor solubility in organic solvents,
components of these systems can be separated from the
reaction products and recycled. Recently, the first exam-
ples of nitroalkane reactions with activated alkenes in
Scheme 1 Reagents and conditions: (i) K2CO3 (30 mol%),
[bmim][BF4] (90 mol%), 20–30 °C, ultrasonic irradiation.
Table 1 R1–R4 in Compounds 1, 2
Compound Nitroalkane 1
Alkene 2
R1
R2
H
R3
R4
a
b
c
d
e
f
Me
Ph
Ph
Ph
Me
Ph
Me
Me
Me
-(CH2)5-
c-Pr
Me
9
ionic liquids [bmim]OH7e and [bmim]PF6 under homo-
–
–
–
–
–
–
–
–
–
–
–
–
geneous conditions have been published. Yet, to the best
of our knowledge, so far IL/solid base heterogeneous sys-
tems have not been used in reactions of nitroalkanes with
activated alkenes.
a
–
Me
b
–
Me
g
h
i
Ph
Me
H
OEt
OMe
OMe
SYNTHESIS 2006, No. 22, pp 3849–3854
x
x
.x
x
.
2
0
0
6
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950306; Art ID: Z12906SS
© Georg Thieme Verlag Stuttgart · New York
a MeC(Me)=CH(CH2)2CH(Me)CH2.
b MeC(Me)=CH(CH2)2C(Me)=CH.

3850
S. G. Zlotin et al.
PAPER
Table 2 R1–R4 in Compounds 3
Table 3 Optimization of the Reaction Conditionsa
Entry 2 Time Temp IL
3
a
b
c
d
e
f
R1
R2
H
R3
R4
Base ))) Product Yield
(h)
15
15
10
15
10
15
15
6
(°C)
20
30
30
30
30
30
30
30
30
(mol%) (mol%)
(%)b
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Ph
1
2
3
4
5
6
7
8
9
2b
440
440
440
440
90
140
140
140
30
–
–
+
+
+
+
–
+
+
3d
3d
3d
3d
3d
3d
3t
41
Me
Me
H
Ph
2b
2b
2b
2b
2b
2h
2h
2h
50
Me
Me
Me
Me
c-Pr
c-Pr
c-Pr
Me
Me
Me
Me
Me
Me
Me
Me
OEt
OEt
OMe
OMe
68
Me
Me
28c
80
-(CH2)5-
Me
30
H
0
30
<10c
65
g
h
i
Me
Me
440
440
90
140
140
30
-(CH2)5-
Me
3t
87
H
6
3t
92
j
Me
Me
a Compound 1b (140 mol%), and 2b, h (100 mol%) were used.
b Isolated yields.
k
l
-(CH2)5-
Me
c Compound 2b was not completely consumed (TLC).
a
H
–
a
which afforded the highest product yields in model reac-
tions (Table 4). The proposed protocol appeared to be ap-
plicable to the synthesis of g-nitroketones 3a–p, and g-
nitroesters 3q–t bearing different substituents. Nitroeth-
ane (1a) and alkenes 2d,h, having relatively small methyl
groups at the reaction site, possess higher activity in the
Michael reaction. Nitrocyclohexane (1c) and a,b-unsatur-
ated ketones 2c,e,f containing voluminous cyclic or
branched isoprenoid moieties, were less reactive. Yet, re-
actions performed up to complete alkene conversion, af-
forded products 3 in comparable or higher yields than
those reported. In some cases we managed to shorten the
reaction time (Table 4, entries 2–5) and reduce the nitroal-
kane amount (Table 4, entries 3–5, 9, 17, 19). The reac-
tion between methyl acrylate (2i) that does not contain
substituents at the b-position of the C=C bond, and nitro-
ethane (1a) under the studied conditions gave a mixture of
mono- and bis-addition products. We managed to obtain
pure bis-adduct 4 using a 2.2-fold excess of the alkene 2i.
Thus, the heterogeneous system [bmim][BF4]/K2CO3 has
higher catalytic activity than ionic liquid [bmim][OH],
where compounds 1a and 2i form only a mono-adduct.7e
m
n
o
p
q
r
s
Me
Me
H
–
b
Me
–
b
Me
Me
–
b
-(CH2)5-
Me
–
H
Ph
Me
Me
H
Ph
Me
Me
Me
t
Me
Me
a MeC(Me)=CH(CH2)2CH(Me)CH2.
b MeC(Me)=CH(CH2)2C(Me)=CH.
plete alkene conversion. The excess of 1b was separated
from the reaction products 3d,t by distillation under re-
duced pressure. Yields of adducts 3d,t were found to be
moderate when the reactions were performed with K2CO3
(140 mol%) in a relatively diluted IL solution (440 mol%
with respect to 2) (Table 3, entries 1, 2, 7). Ultrasonic ir-
radiation shortened the reaction time and enhanced prod-
uct yields (Table 3, entries 3, 8). In this case, stirring was
not required, simplifying the small-scale experiments.
The influence of the amount of base on reaction efficacy
was rather sophisticated. Its fivefold reduction with re-
spect to IL reduced the reaction time and product yield,
due to incomplete alkene consumption (Table 3, entry 4).
Yet, simultaneous diminishing of the base and IL amounts
to 30 mol% and 90 mol%, respectively, allowed the for-
mation of compounds 3d,t in an excellent yield and with
high selectivity (Table 3, entries 5, 9). In the absence of
IL, the reaction actually did not occur (Table 3, entry 6).
Substitution of K2CO3 with less basic KHCO3 resulted in
complete recovery of the starting compounds.
The proposed method was applied to the synthesis of new
g-nitrocyclopropyl ketones 3f –h and g-nitroketones 3l–p
with carbonyl groups incorporated into the isoprenoid
backbone. The latter may be used as intermediates for the
synthesis of natural isoprenoid analogs with pharmaco-
logical activity.14 Nitroalkanes 1a–c reacted with
pseudoionone 2f regioselectively at the C3=C4 double
bond, whereas the C5=C6 bond remained unchanged
(Scheme 2).15 The structure of compounds 3n–p was es-
tablished by 13C NMR DEPT experiments, in which two
tertiary sp2-hybridized carbon signals in the regions d =
131.6–131.7 (C10) and d = 140.6–141.5 (C6) were record-
ed. The E/Z-isomer ratios (C5=C6) determined by H5 inte-
gral intensities in respective isomer mixtures, were in
agreement with the isomeric composition of the starting
alkene 2f (3:2).
Next, we examined the scope of the reaction using the cat-
alytic system [bmim][BF4] (90 mol%)/K2CO3 (30 mol%),
Synthesis 2006, No. 22, 3849–3854 © Thieme Stuttgart · New York

PAPER
Solvent-Free Synthesis of g-Nitroketones and g-Nitroesters
1H NMR (CDCl3) d, J (Hz)c,d
3851
Table 4 Compounds 3a–t and 4 Prepareda
Entry 1 + 2
Time
(h)
Prod- Yield 3 (%)b
Mp (°C)
or nD
20
uct
(cycle)
1
1a + 2a 10 (1e)
3a
96 (1), 95 (2), 98–100,
96 (3) (Lit.10 91) 115–116f
dr ~1: 1,
3a (isomer 1):f 1.58 (d, J = 7.5, 3 H, CH3), 3.48 (dd, J = 18.5, 7.0, 1 H,
CHH), 3.60 (dd, J = 18.5, 7.0, 1 H, CHH), 4.05 (q, J = 7.0, 1 H,
CHCHNO2), 5.01 (p, J = 6.8, 1 H, CHNO2), 7.20–7.38 (m, 5 H,
C6H5CH), 7.45 (t, J = 8.0, 2 H, C6H5C=O), 7.56 (t, J = 8.0, 1 H,
C6H5C=O), 7.94 (d, J = 8.0, 2 H, C6H5C=O)
(Lit.10 100)
2
3
1b + 2a 10 (24g)
3b
3c
95 (Lit.
147–148
(Lit.11a
146.5–147)
1.55 (s, 3 H, CH3), 1.63 (s, 3 H, CH3), 3.28 (dd, J = 17.8, 3.0, 1 H, CHH),
3.68 (dd, J = 17.8, 9.8, 1 H, CHH), 4.16 (dd, J = 9.8, 3.0, 1 H, CHPh),
7.20–7.35 (m, 5 H, C6H5CH), 7.43 (t, J = 7.8, 2 H, C6H5C=O), 7.55 (t,
J = 7.8, 1 H, C6H5C=O), 7.87 (d, J = 7.8, 2 H, C6H5C=O)
95,11a 9811b
)
1a + 2b 8 (100,h
82 (Lit. 83,12a nD20 1.5200
48,12b 7512c) dr
~1: 1
1.28 (d, J = 7.5, 1.65 H, CHCH3), 1.47 (d, J = 7.5, 1.35 H, CHCH3), 1.97
(s, 1.65 H, COCH3), 2.08 (s, 1.35 H, COCH3), 2.67–3.06 (m, 2 H, CH2),
3.64–3.77 (m, H, CHPh), 4.68–4.92 (m, H, CHNO2), 7.10–7.35 (m, 5 H,
C6H5)
240i)
4
5
1b + 2b 10 (240h,i) 3d
1c + 2b 26 (300h) 3e
80 (Lit.
62–63
1.48 [s, 3 H, (CH3)2CNO2], 1.57 [s, 3 H, (CH3)2CNO2], 2.03 (s, 3 H,
CH3C=O), 2.72 (dd, J = 17.7, 3.2, 1 H, CHH), 3.08 (dd, J = 17.7, 9.9,
1 H, CHH), 3.93 (dd, J = 9.9, 3.2, 1 H, CHPh), 7.15–7.35 (m, 5 H, C6H5)
95,12a 76,12c
(Lit.12d
6412d
)
63.0–63.5)
87 (Lit.12a 82) 73–75
1.02–1.72 [m, 8 H, CHH(CH2)3CHH], 2.02 (s, 3 H, CH3), 2.32 [br dd,
J = 53.0, 14.4, 2 H, CHH(CH2)3CHH], 2.92 (dd, J = 17.3, 5.0, 1 H,
CHHC=O), 3.02 (dd, J = 17.3, 9.4, 1 H, CHHC=O), 3.65 (dd, J = 9.4,
5.0, 1 H, CHPh), 7.10–7.35 (m, 5 H, C6H5)
6
7
8
1a + 2c 20
1b + 2c 20
1c + 2c 20
3f
93
dr ~1: 1
nD20 1.5307
0.67–0.98 (m, 4 H, CH2CH2), 1.31 (d, J = 8.3, 1.5 H, CH3), 1.50 (d,
J = 8.3, 1.5 H, CH3), 1.73–1.95 (m, 1 H, CHC=O), 2.82–3.19 (m, 2 H,
CH2C=O), 3.70–3.82 (m, 1 H, CHPh), 4.74–4.93 (m, 1 H, CHNO2),
7.13–7,37 (m, 5 H, C6H5)
3g
3h
83
80
54–56
85–86
0.67–0.93 (m, 4 H, CH2CH2), 1.50 (s, 3 H, CH3), 1.58 (s, 3 H, CH3),
1.80–1.91 (m, 1 H, CHC=O), 2.88 (dd, J = 17.0, 3.0, 1 H, CHHC=O),
3.19 (dd, J = 17.0, 10.4, 1 H, CHHC=O), 3.98 (dd, J = 10.4, 3.0, 1 H,
CHPh), 7.14–7.37 (m, 5 H, C6H5)
0.66–0.94 [m, 4 H, (CH2)2], 1.03–1.73 [m, 8 H, CHH(CH2)3CHH], 1.78–
1.90 (m, 1 H, CHC=O), 2.43 [br dd, J = 52.0, 13.5, 2 H,
CHH(CH2)4CHH], 3.07 (dd, J = 15.6, 7.3, 1 H, CHHC=O), 3.17 (dd,
J = 15.6, 9.4, 1 H, CHHC=O), 3.68 (dd, J = 9.4, 7.3, 1 H, CHPh), 7.09–
7.35 (m, 5 H, C6H5)
9
1a + 2d 2 (2j)
3i
88 (1), 90 (2) nD20 1.4450
0.80 (d, J = 7.5, 2.25 H, CH3CHCH2), 0.89 (d, J = 7.5, 0.75 H,
CH3CHCH2), 1.42 (d, J = 7.5, 0.75 H, CH3CHNO2), 1.46 (d, J = 7.5, 2.25
H, CH3CHNO2), 2.09 (s, 0.75 H, CH3C=O), 2.12 (s, 2.25 H, CH3C=O),
2.35 (dd, 1 H, J = 16.9, 7.2, 1 H, CHHC=O), 2.62 (dd, 1 H, J = 16.9, 4.8,
1 H, CHHC=O), 2.42–2.55 (m, 1 H, CH3CHCH2), 4.45–4.63 (m, 1 H,
CHNO2)
(Lit.13d 73)
(Lit.13d
dr ~3: 1
1.4443)
10
11
12
1b + 2d 3 (48k)
3j
3k
3l
78 (Lit.
nD20 1.4519
(Lit.12d
1.4518)
0.92 (d, J = 7.5, 3 H, CH3CHCH2), 1.50 [s, 3 H, (CH3)2CNO2], 1.54 [s,
3 H, (CH3)2CNO2], 2.13 (s, 3 H, CH3C=O), 2.25 (dd, J = 17.0, 10.0, 1 H,
CHH), 2.44 (dd, J = 15.5, 1.6, 1 H, CHH), 2.68–2.84 (m, 1 H,
CH3CHCH2)
88,12d 6013b
)
1c + 2d
4
54
nD20 1.4750
nD20 1.4710
0.97 (d, J = 7.0, 3 H, CH3CHCH2), 1.18–1.79 [m, 8 H,
CHH(CH2)3CHH], 2.22 (dd, J = 17.3, 9.3, 1 H, CHH), 2.50 (dd, J = 17.3,
2.3, 1 H, CHH), 2.58 [br dd, J = 37.0, 16.6, 2 H, CHH(CH2)4CHH],
2.45–2.58 (m, 1 H, CH3CHCH2)
1a + 2e 30
72
dr ~3: 1
0.83–0.97 (m, 3 H, C6-CH3), 1.00–1.20 (m, 2 H, H7), 1.24–1.40 (m, 3 H,
H5 and H6), 1.42–1.47 (m, 3 H, CH3CHNO2), 1.59 (s, 3 H, H11), 1.67 (s,
3 H, H12), 1.85–2.08 (m, 2 H, H8), 2.15 (s, 2.25 H, H1), 2.17 (s, 0.75 H,
H1), 2.31–2.48 (m, 1 H, H3), 2.55–2.72 (m, 2 H, H3 and H4), 4.62–4.79
(m, 1 H, CHNO2), 5.05 (t, J = 7.0, 1 H, H9)
Synthesis 2006, No. 22, 3849–3854 © Thieme Stuttgart · New York

3852
S. G. Zlotin et al.
PAPER
Table 4 Compounds 3a–t and 4 Prepareda (continued)
Entry 1 + 2
Time
(h)
Prod- Yield 3 (%)b
Mp (°C)
or nD
1H NMR (CDCl3) d, J (Hz)c,d
20
uct
(cycle)
13
1b + 2e 30
3m
48
nD20 1.4731
0.85 (d, J = 5.6, 3 H, C6-CH3), 0.90–1.10 (m, 2 H, H7), 1.10–1.25 (m,
3 H, H5 and H6), 1.48 [s, 6 H, (CH3)2CNO2], 1.57 (s, 3 H, H11), 1.65 (s, 3
H, H12), 1.80–2.05 (m, 2 H, H8), 2.14 (s, 3 H, H1), 2.26 (dt, J = 17.5, 6.0,
1 H, H3), 2.57 (dd, J = 17.5, 6.0, 1 H, H3), 2.78–2.90 (m, 1 H, H4), 5.05
(dd, J = 14.5, 7.3, 1 H, H9)
14
15
16
17
1a + 2f 22
3n
3o
3p
3q
90
dr ~1: 1
nD20 1.4810
nD20 1.4850
nD20 1.4991
1.41 (d, J = 7.0, 3 H, CH3CHNO2), 1.57–1.71 (m, 9 H, C6-CH3, H11 and
H12), 2.00–2.19 (m, 7 H, H1, H7 and H8), 2.24–2.70 (m, 2 H, H3), 3.27–
3.44 (m, 1 H, H4), 4.50–4.70 (m, 1 H, CHNO2), 4.81–4.95 (m, 1 H, H9),
5.01 (q, J = 6.5, 0.6 H, H5), 5.10 (J = 6.5, 0.4 H, H5) (E/Z = ~3:2)
1b + 2f 22
85
79
1.47 (s, 3 H, CH3CNO2), 1.49 (s, 3 H, CH3CNO2), 1.53–1.70 (m, 9 H, C6-
CH3, H11 and H12), 1.95–2.16 (m, 7 H, H1, H7 and H8), 2.21–2.46 (m, 2 H,
H3), 3.45–3.61 (m, 1 H, H4), 4.76 (t, J = 8.4, 1 H, H9), 4.96 (t, J = 7.2,
0.6 H, H5), 5.09 (J = 7.2, 0.4 H, H5) (E/Z = ~3:2)
1c + 2f 22
1.15–1.70 [m, 8 H, CHH(CH2)3CHH], 1.55–1.75 (m, 9 H, C6-CH3, H11
and H12), 1.80–1.95 [m, 2 H, CHH(CH2)4CHH], 1.95–2.60 (m, 9 H, H1,
H3, H7, H8), 3.30 (qd, J = 10.0, 2.3, 1 H, H4), 4.77 (t, J = 8.2, 1 H, H9),
5.03 (t, J = 7.4, 0.6 H, H5), 5.11 (J = 7.4, 0.4 H, H5) (E/Z = ~3:2)
1a + 2g 15 (0.5l)
88 (Lit.13c 95) 3q (isomer 1): 3q (isomer 1):f 1.13 (t, J = 7.5, 3 H, OCH2CH3), 1.57 (d, J = 7.2, 3 H,
dr ~1: 1 CH3CHNO2), 2.75 [dd, J = 16.0, 8.7, 1 H, CHHC(O)], 2.87 [dd, J = 16.0,
nD20 1.5026f
3q (isomer 2): 6.4, 1 H, CHHC(O)], 3.74 (q, J = 7.5, 1 H, CHPh), 4.05 (q, J = 7.5, 2 H,
nD20 1.5035f
OCH2), 4.91 (p, J = 7.0, 1 H, CHNO2), 7.40 (d, J = 6.5, 2 H, C6H5), 7.62
(t, J = 6.5, 3 H, C6H5).
3q (isomer 2):f 1.07 (t, J = 7.5, 3 H, OCH2CH3), 1.34 (d, J = 7.2, 3 H,
CH3CHNO2), 2.67 [dd, J = 15.8, 5.0, 1 H, CHHC(O)], 2.78 [dd, J = 15.8,
10.0, 1 H, CHHC(O)], 3.67 (dt, J = 5.0, 9.1, 1 H, CHPh), 3.97 (q, J = 7.5,
2 H, OCH2), 4.80 (m, 1 H, CHNO2), 7.20 (d, J = 6.5, 2 H, C6H5), 7.25–
7.40 (m, 3 H, C6H5)
18
1b + 2g 23 (48k)
3r
90 (Lit.13b 27) nD20 1.5060
1.05 (t, J = 7.5, 3 H, OCH2CH3), 1.52 [s, 3 H, (CH3)2CNO2], 1.61 [s, 3 H,
(CH3)2CNO2], 2.68 (dd, J = 17.2, 4.4, 1 H, CHH), 2.89 (dd, J = 17.2,
10.6, 1 H, CHH), 3.86–4.04 (m, 3 H, OCH2 and CHPh), 7.17–7.37 (m,
5 H, C6H5)
19
20
21
1a + 2h 4 (2m)
1b + 2h 7 (24g)
1a + 2i 16 (24n)
3s
3t
4
91 (1), 91 (2), nD20 1.4413
98 (3) (Lit.5 90)
dr ~1:1
0.98 (d, J = 7.1 Hz, 3 H, CH3CHCH2), 1.46 (d, J = 7.6 Hz, 1.35 H,
CH3CHNO2), 1.50 (d, J = 7.6 Hz, 1.65 H, CH3CHNO2), 2.13–2.68 (m,
3 H, CH3CHCH2), 3.66 (s, 3 H, OCH3), 4.50–4.66 (m, 1 H, CHNO2)
92 (Lit.11a 61) nD20 1.4475
0.97 (d, J = 7.5 Hz, 3 H, CH3CH), 1.52 [s, 6 H, (CH3)2CNO2], 2.08 (dd,
J = 15.6, 9.4, 1 H, CHH), 2.36 (dd, J = 15.6, 2.4, 1 H, CHH), 2.65–2.80
(m, 1 H, CH), 3.66 (s, 3 H, OCH3)
84o (Lit.13e 40) nD20 1.4601
1.55 (s, 3 H, CH3C), 2.10–2.46 (m, 8 H, 4 CH2), 3.69 (s, 6 H, 2 CH3O)
(Lit.13f
1.4600)
a Reaction conditions: 1a–c (140 mol%), 2a–i (100 mol%), K2CO3 (30 mol%), [bmim][BF4] (90 mol%), 30 °C, ultrasonic irradiation.
b Isolated yield of 3 (column chromatography).
c All compounds 3 showed characteristic peaks for the nitro and carbonyl groups. IR (film or KBr pellets): 1344–1360 (NO2, s), 1536–1548
(NO2, as), 1720–1740 cm–1 (C=O).
d Satisfactory microanalyses were obtained for newly synthesized compounds 3f–h,l–p and 4: C 0.28, H 0.18, N 0.24. 13C NMR data of
the compounds are given in the experimental part.
e Reaction conditions: MeONa/MeOH, 50 °C.10
f Data for a single diastereoisomer.
g Reaction conditions: DBU/MeCN, 20 °C.11a
h Reaction conditions: 4-benzyl-2-carboxy-1-methylimidazolidine/nitroalkane (3 equiv), 20 °C.12a
i Reaction conditions: Et2NH/nitroalkane (9 equiv), 20 °C.12c
j Reaction conditions: KF/18-crown-6/MeCN/nitroalkane (20 equiv), 80 °C.13a
k Reaction conditions: MeONa/MeOH, 65 °C.13b
l Reaction conditions: tetramethylguanidine (cat.), MeOH, 65 °C, 0.5 h.13c
m Reaction conditions: K2CO3/aliquat/nitroalkane (3 equiv)/ultrasound, 20 °C.5
n Reaction conditions: KF/EtOH, 5 h, 100 °C.13e
o Yield based on 2i.
Synthesis 2006, No. 22, 3849–3854 © Thieme Stuttgart · New York

PAPER
Solvent-Free Synthesis of g-Nitroketones and g-Nitroesters
3853
were recorded on Bruker AM-300 (300.13 MHz {1H}) and DRX-
500 spectrometers (500.13 MHz {1H}, 125.76 MHz {13C}) in
CDCl3 at r.t. Chemical shifts of 1H were measured relative to Me4Si
as internal standard, 13C, relative to CDCl3. IR spectra were record-
ed as thin films or KBr pellets on a Specord M-82. Elemental anal-
yses were performed at the Analytical Laboratory of Zelinsky
Institute of Organic Chemistry on a PerkinElmer 2400 analyzer.
R1
R2
O2N
1
11
10
12
9
8
O
1a–c
O
2
4
5
6
3
i
7
2f (E/Z = 3:2)
3n–p (E/Z = 3:2)
Scheme 2 Reagents and conditions: (i) K2CO3 (30 mol%),
[bmim][BF4] (90 mol%), 30 °C, ultrasonic irradiation.
Reaction of Nitroalkanes 1 with Activated Alkenes 2; Typical
Procedure
A mixture of nitroalkane 1 (3.5 mmol), activated alkene 2
(2.5 mmol) (7.7 mmol in the case of 2i), [bmim][BF4] (0.50 g,
2.25 mmol), and K2CO3 (0.10 g, 0.75 mmol) was kept in an ultra-
sonic bath at 30 °C until the reaction was complete (TLC monitor-
ing, Table 4). The mixture was cooled to r.t. and extracted with
benzene or Et2O (3 × 5 mL). The combined organic extracts were
washed with H2O (3 × 10 mL), dried (MgSO4) and passed through
a silica gel layer (diameter = 10 mm, height = 20 mm). The solvent
and excess of nitroalkane 1 were distilled off on a rotary evaporator
and the residue was purified by column chromatography (eluent:
hexanes–Et2O, 14:1). Yields, melting points, nD20 and 1H NMR data
for compounds 3a–t and 4 are given in Table 4. 13C NMR data for
the newly synthesized compounds 3f–h, 3l–p are given below.
As a rule, reactions of nitroethane (1a) with b-substituted
electron-deficient alkenes 2 under the studied conditions
afford diastereomeric mixtures of compounds 3. The dr
1
ratio determined by H NMR spectroscopy depended on
the alkene structure. In crude adducts 3a,c,f,n,q,s, it was
close to 1:1, and in g-nitroketones 3i,l to 3:1. Pure diaste-
reomers 3a (isomer 1), 3q (isomer 1) and 3q (isomer 2)
were obtained by crystallization (CCl4) or column chro-
matography (silica gel, Et2O–n-hexane, 1:15) of respec-
tive isomer mixtures.
The studied reaction proceeded in heterogeneous systems
composed of solid (K2CO3) and one or two (in the case of
compounds 3l,m) liquid phases (IL and eutectic solution
of compounds 1–3). The emergence of the three-phase
system is explained by the poor solubility of compounds
1–3 in IL. Possibly, IL acts both as a PTC and as a solvent
liquefying the reaction mixture under the studied condi-
tions.16 Apparently, ultrasonic activation enhanced the re-
action rate by increasing the interfacial surface and
intensifying the mass-transfer.
1-Cyclopropyl-4-nitro-3-phenylpentan-1-one (3f)
13C NMR: d = 10.7, 11.0, 16.8, 17.6, 20.8, 21.0, 44.6, 44.7, 45.4,
46.0, 86.3, 87.0, 127.7, 128.1, 128.2, 128.4, 128.6, 128.8, 138.2,
207.1, 207.8.
1-Cyclopropyl-4-methyl-4-nitro-3-phenylpentan-1-one (3g)
13C NMR: d = 10.7, 10.9, 20.8, 22.5, 25.8, 44.0, 49.0, 91.2, 127.8,
128.4, 129.3, 137.8, 207.3.
1-Cyclopropyl-3-(1-nitrocyclohexyl)-3-phenylpropan-1-one
(3h)
13C NMR: d = 10.7, 11.0, 21.0, 22.1, 22.3, 24.4, 31.5, 33.7, 49.8,
94.3, 127.7, 128.3, 129.2, 138.0, 207.8.
We took advantage of the poor solubility of IL and the sol-
id base in the organic phase and repeatedly used the cata-
lytic system in the Michael reaction. Recoverability of the
system K2CO3/[bmim][BF4] as well as yields and charac-
terization data for adducts 3 and 4 are given in Table 4.
After each reaction cycle, adducts 3a,i,s and the excessive
amount of 1a were extracted with benzene or Et2O and
fresh portions of the starting compounds were added to
the residue. The catalytic system retained its activity over
at least three reaction cycles.
6,10-Dimethyl-4-(1-nitroethyl)undec-9-en-2-one (3l)
13C NMR: d = 14.8 (CH3), 15.7 (CH3), 15.9 (CH3), 16.3 (CH3), 17.7
(CH3), 19.2 (CH3), 19,3 (CH3), 19.7 (CH3), 19.9 (CH3), 25.2 (CH2),
25.3 (CH2), 25.7 (CH3), 29.5 (CH), 29.6 (CH), 29.7 (CH), 30.4 (C1),
30.5 (C1), 35.3 (C4), 35.4 (C4), 36.3 (CH2), 36.7 (CH2), 37.1 (CH2),
37.2 (CH2), 37.4 (CH2), 37.9 (CH2), 38.4 (CH2), 43.3 (C3), 43.6
(C3), 43.7 (C3), 43.8 (C3), 84.2 (CNO2), 84.4 (CNO2), 84.8 (CNO2),
85.2 (CNO2), 124.4 (C9), 124.5 (C9), 131.6 (C10), 206.7 (C2).
6,10-Dimethyl-4-(2-nitropropan-2-yl)undec-9-en-2-one (3m)
13C NMR: d = 17.8 (CH3), 18.9 (CH3), 20.7 (CH3), 23.8 (CH3), 23.9
(CH3), 24.0 (CH3), 24.1 (CH3), 25.2 (CH2), 25.5 (CH2), 25.8 (CH3),
30.0 (CH), 30.1 (CH3), 30.2 (CH3), 35.3 (CH2), 38.1 (CH2), 38.6
(CH2), 38.9 (C4), 39.2 (CH2), 45.2 (C3), 45.5 (C3), 91.6 (CNO2),
124.5 (C9), 131.5 (C10), 206.1 (C2), 206.3 (C2).
To conclude, we have developed an efficient, green-
chemistry synthesis of functionally substituted aliphatic
nitro compounds based on the reaction of nitroalkanes
with electron deficient alkenes in the ultrasonically acti-
vated heterogeneous recoverable catalytic system: ionic
liquid [bmim][BF4]/K2CO3.
6,10-Dimethyl-4-(1-nitroethyl)undeca-5,9-dien-2-one (3n)
13C NMR: d = 16.3 (CH3), 16.6 (CH3), 16.8 (CH3), 17.6 (CH3), 23.3
(CH3), 25.6 (CH3), 26.2 (CH2), 30.5 (CH3), 32.2 (CH2), 37.2 (C4),
37.6 (C4), 38.2 (C4), 38.6 (C4), 39.7 (CH2), 45.0 (CH2), 45.1 (CH2),
45.4 (CH2), 84.9 (CNO2), 85.2 (CNO2), 85.8 (CNO2), 86.0 (CNO2),
120.6 (C5), 121.0 (C5), 121.5 (C5), 123.7 (C9), 131.6 (C10), 132.0
(C10), 140.6 (C6), 140.8 (C6), 141.0 (C6), 205.7 (C2), 206.4 (C2).
Starting compounds 1a–c, 2a,b,g–i and K2CO3 were purchased
from Acros and used without further purification. a,b-Unsaturated
ketones 2c,8a 2d,17a 2e,17b 2f,17c and [bmim][BF4]18 were synthesized
by reported methods using commercially available (Acros) citronel-
lal and citral (95%, E/Z (3:2) mixture, GC). Solvents were purified
by standard procedures. Reactions were monitored by TLC on Silu-
fol precoated aluminum plates (eluent: benzene–EtOAc, 95:5),
which were visualized under UV radiation. Silica gel 0.060–
0.200 mm (Acros) was used for column chromatography. Reactions
were performed in a RELTEC 1/100TN ultrasonic bath, volume
1.6 L, operation frequency 47 kHz. Mps were measured on a Boet-
6,10-Dimethyl-4-(2-nitropropan-2-yl)undeca-5,9-dien-2-one
(3o)
13C NMR: d = 16.7 (CH3), 17.6 (CH3), 21.9 (CH3), 22.2 (CH3), 23.4
(CH3), 24.9 (CH3), 25.1 (CH3), 25.6 (CH3), 26.2 (CH2), 30.4 (CH3),
32.4 (CH2), 39.9 (CH2), 41.5 (C4), 42.0 (C4), 44.5 (CH2), 44.7
1
ius apparatus and are not uncorrected. H and 13C NMR spectra
Synthesis 2006, No. 22, 3849–3854 © Thieme Stuttgart · New York

3854
S. G. Zlotin et al.
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(CH2), 91.0 (CNO2), 121.3 (C5), 121.5 (C5), 123.8 (C9), 124.0 (C9),
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Acknowledgment
We thank the Russian Foundation of Basic Researches (grants 05-
03-08175, 06-03-32603) and the Russian Academy of Sciences
(Basic Research Program of the Presidium of RAS) for the financial
support.
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Synthesis 2006, No. 22, 3849–3854 © Thieme Stuttgart · New York