Conjugated addition reactions of nitroalkanes with electrophilic alkenes in aqueous media

Article abstract of DOI:10.1002/(SICI)1099-0690(199802)1998:2<355::AID-EJOC355>3.0.CO;2-2

The Michael reaction of various nitroalkanes 1 with electrophilic alkenes 2 can be performed in NaOH (0.025-0.1 M), without any organic solvent. In many cases the presence of cetyltrimethylammonium chloride (CTACI), as cationic surfactant, produces better

Full text of DOI:10.1002/(SICI)1099-0690(199802)1998:2<355::AID-EJOC355>3.0.CO;2-2

FULL PAPER
Conjugated Addition Reactions of Nitroalkanes with Electrophilic Alkenes in
Aqueous Media
Roberto Ballini* and Giovanna Bosica
`
Dipartimento di Scienze Chimiche dell’Universita,
Via S. Agostino 1, I-62032 Camerino, Italy
Received August 11, 1997
Keywords: Water / Michael addition / Nitroalkanes / Surfactants
The Michael reaction of various nitroalkanes 1 with electro- factant, produces better results. Good yields of the products
philic alkenes 2 can be performed in NaOH (0.025Ϫ0.1
M
),
3 are obtained even with hindered, and functionalized star-
without any organic solvent. In many cases the presence of
cetyltrimethylammonium chloride (CTACl), as cationic sur-
ting materials.
Nucleophilic addition of carbanions to electrophilic al- a large excess of nitroalkane,[4d] or the help of ultrasound[4e]
kenes activated by an electron-withdrawing group (the are required.
Michael reaction) is one of the most important pro-
The need to accomplish this important synthetic trans-
cedures[1] in organic synthesis for the formation of a new
formations under milder conditions and with less toxic and
carbonϪcarbon bond.
environmentally compatible materials has led us to develop
In this context the use of primary and secondary nitroal-
this procedure of Michael reaction in aqueous media
kanes as carbanions is a valuable tool considering that the
(Scheme 1, Table 1).
nitro group can be further transformed into various func-
tionalities.[2] As routine procedures, this reaction is per-
formed in the presence of different organic bases in homo-
geneous solutions[3] or, alternatively, under heterogeneous
catalysis.[4]
Increasingly demanding environmental legislation, public
1؊3
R1
R2
EWG
and corporate pressure and resulting drive towards clean
technology in the chemical industry, with the emphasis on
reduction of waste at source, will require increasing atten-
tion on the use of less toxic and environmentally compatible
materials in the design of new synthetic methods.[5]
Established chemical processes that are often based on
technology developed in the first half of the 20th century,
may no longer be acceptable in these environmentally con-
scious days.[6]
For this purpose, in recent years, there has been increas-
ing interest in the use of water as an attractive medium for
many organic reactions.[7][8] Moreover, the aqueous me-
dium allows the right control of pH, while the solubility of
most reagents in water is not an obstacle to the reactivity
which, on the contrary, is often improved.[9]
a
b
c
d
e
f
H
H
H
CH3
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CN
C2H5
CH3(CH2)3
CH3 CH3
H
H
H
H
C6H5
CH3CHOH(CH2)2
g
h
i
CH3
C2H5
CN
CH3 CH3
H
CN
j
CH3(CH2)4
CN
k
l
Ϫ(CH2)5Ϫ
CH3
CN
H
H
H
SO2Ph
SO2Ph
SO2Ph
SO2Ph
SO2Ph
SO2Ph
SO2Ph
m
n
o
p
q
r
C2H5
CH3(CH2)4
CH3 CH3
H
H
H
C6H5
CH3CO(CH2)2
CH3O2C(CH2)2
We have reported in a recent communication[10] that
nitroalkanes can be efficiently reacted with α,β-unsaturated
ketones in an aqueous media using a solution of sodium
hydroxide. Under these conditions nitroalkanes easily react
with a variety of conjugated enones in very short reaction
times.
Our procedure is performed using a solution of sodium
hydroxide 0.025Ϫ0.1  (see Table 1) in the presence of cata-
lytic amount of cetyltrimethylammonium chloride (CTACl)
as cationic surfactant. We tested different concentrations of
base but 0.025  NaOH gave the best results. For the com-
pounds 3a, b, d 0.1  NaOH produced higher yields, as
Electron-deficient alkenes,[1] such as α,β-unsaturated es- soon as the absence of CTACl sometime gave higher yields
ters, nitriles, sulphones are less active than the correspond- (entry 3a؊c, l, m, p).
ing ketones in the Michael reaction with nitroalkanes. In
Under these conditions both primary and secondary
fact strong basic conditions,[3k] long reaction times,[3a][3l][3m] nitroalkanes easily react with a variety of electrophilic al-
Eur. J. Org. Chem. 1998, 355Ϫ357
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0202Ϫ0355 $ 17.50ϩ.50/0
355

R. Ballini, G. Bosica
FULL PAPER
Table 1. Preparation of nitroderivatives 3
kenes, we consider this procedure an attractive general op-
tion of the conventional methods due to its evident econ-
omical and ecological advantages.
Product Yield bp [°C/Torr]
NaOH CTACl Reaction
time [h]
3
[%]
or mp [°C]
Financial support by the C.N.R. Italy and the University of Ca-
merino are gratefully acknowledged.
a
b
c
d
e
f
80
80
58
54
59
55
50
57
74
61
78
70
58
61
56
90
50
51
86/1 (89Ϫ90/2)[12] 0.1
92/1 (97Ϫ98/2)[12] 0.1
No
No
1
1
2
8
2
3
1
1
2
1
4
2
2
1
1
2
2
1
Oil
0.025 No
Experimental Section
Oil
0.1
Yes
Oil
0.025 Yes
0.025 Yes
0.025 Yes
0.025 Yes
0.025 Yes
0.025 Yes
0.025 Yes
0.025 No
0.025 No
0.025 Yes
0.025 Yes
0.025 No
0.025 Yes
0.025 Yes
All the reactions were monitored by TLC and gas-chromato-
graphic analyses, performed with a Carlo Erba Fractovap 4160
using a capillary column of duran glass (0.32 mm ϫ 25 mt),
stationary phase OV1 (film thickness 0.4Ϫ0.45 nm). Ϫ All 1H-
NMR spectra were recorded in CDCl3, at 200 MHz with a Varian
Gemini 200. Chemical shifts are expressed in ppm downfield from
tetramethylsilane. Ϫ IR spectra were recorded with a Perkin-Elmer
257 spectrometer. Ϫ All the products were purified, when neces-
sary, by flash chromatography on Merck silica gel with EtOAc/
cyclohexane as eluent, or by distillation. Ϫ Elementary analyses
were performed using a C,H,N,S Analyzer Model 185 from Hew-
lett-Packard. Ϫ The compound 4 has been prepared as previously
reported.[11]
Oil
g
h
i
Oil
Oil
Oil
j
Oil
k
l
39Ϫ42
54Ϫ55
58Ϫ60
35Ϫ37
Oil
m
n
o
p
q
r
89Ϫ91
71Ϫ72
Oil
Table 2. Selected spectroscopic data of nitro derivatives 3
kenes (α,β-unsaturated ketones, esters, sulphones, and ni-
triles), and the need of diluted solution of base prevents
polymerisations or polyadditions often observed during
this reaction.
Product IR (film)
1H NMR (CDCl3/TMS)
δ, J [Hz]
3
ν˜ [cmϪ1
]
Satisfactory to good yields were obtained in short reac-
tion times (1Ϫ8 h), additionally, the very mild reaction con-
ditions allow the preservation of functionalities like ketones,
hydroxyl, and ester.
a
b
c
1720, 1535 1.55 (d, 3 H, J ϭ 6.6), 2.0Ϫ2.45 (m, 4
H), 3.7 (s, 3 H), 4.55Ϫ4.75 (m, 1 H).
1730, 1535 0.97 (t, 3 H, J ϭ 7.4), 1.75Ϫ2.43 (n, 6
H), 3.7 (s, 3 H), 4.4Ϫ4.55 (m, 1 H)
1730, 1535 0.89 (t, 3 H, J ϭ 7.2), 1.2Ϫ1.4 (m, 4 H),
1.6Ϫ2.3 (m, 4 H), 2.31Ϫ2.4 (m, 2 H),
3.68 (s, 3 H), 4.55 (m, 1 H, J ϭ 4.7)
An important extension of this procedure is the efficient
tandem conjugated additionϪelimination (HBr) observed
when nitroalkanes 1a؊d react with 4 (Scheme 2). The ob-
tained α,β-unsaturated esters 5a؊d (55Ϫ72% yield) are of
special interest because they can be simultaneously em-
ployed as electrophiles (Michael addition) and/or as nucleo-
philes at carbon bearing the nitro group (entry 5a؊c),
moreover, the presence of the latter functionality facilitates
several other conversions, due to the high versatility of this
group (Scheme 2).[2]
d
e
f
1730, 1530 1.6 (s, 6 H), 2.2Ϫ2.4 (m, 4 H), 3.68 (s, 3
H)
1730, 1535 2.3Ϫ2.9 (m, 4 H), 3.7 (s, 3 H), 5.5Ϫ5.6
(m, 1 H), 7.4Ϫ7.5 (m, 5 H)
3380, 1720, 1.2 (d, 3 H, J ϭ 6.1), 1.4Ϫ1.58 (m, 4 H),
1535
1.8Ϫ2.4 (m, 6 H), 3.68 (s, 3 H),
3.73Ϫ3.85 (m, 1 H)
g
h
2220, 1535 1.65 (d, 3 H, J ϭ 6.7), 1.95Ϫ2.57 (m, 4
H), 4.6Ϫ4.8 (m, 1 H)
2220, 1535 1.0 (t, 3 H, J ϭ 7.4), 1.75Ϫ2.55 (m, 6 H),
4.45Ϫ4.6 (m, 1 H)
i
j
2220, 1535 1.7 (s, 6 H), 2.28Ϫ2.7 (m, 4 H)
2220, 1535 0.8Ϫ1.0 (m, 3 H), 1.2Ϫ1.65 (m, 6 H),
1.0Ϫ2.6 (m, 6 H), 4.5Ϫ4.65 (m, 1 H)
2220, 1535 1.25Ϫ1.8 (m, 10 H), 2.18Ϫ2.55 (m, 4 H)
1530, 1360, 1.59 (d, 3 H, J ϭ 6.8), 2.15Ϫ2.5 (m, 2
k
l
1135
H), 3.15 (t, 2 H, J ϭ 7.7), 4.65Ϫ4.8 (m, 1
H), 7.5Ϫ7.8 (m, 3 H)
m
n
1530, 1360, 0.9Ϫ1.0 (m, 3 H), 1.7Ϫ2.5 (m, 4 H), 3.1
1137
(t, 2 H, J ϭ 7.7), 4.5Ϫ4.75 (m, 1 H),
7.5Ϫ7.75 (m, 3 H), 7.85Ϫ7.96 (m, 2 H)
1530, 1360, 0.8Ϫ0.93 (m, 3 H), 1.2Ϫ1.4 (m, 6 H),
1135
1.6Ϫ2.1 (m, 2 H), 2.2Ϫ2.45 (m, 2 H), 3.1
(t, 2 H, J ϭ 7.7), 4.52Ϫ4.76 (m, 1 H),
7.5Ϫ7.75 (m, 3 H), 7.85Ϫ7.96 (m, 2 H)
o
p
q
1530, 1360, 1.6 (s, 6 H), 2.25Ϫ2.4 (m, 2 H),
1135
3.05Ϫ3.15 (m, 2 H), 7.5Ϫ7.75 (m, 3 H),
7.85Ϫ7.96 (m, 2 H)
1530, 1360, 2.5Ϫ2.95 (m, 2 H), 3.05Ϫ3.15 (m, 2 H),
1135
R1
R2
5.65 (t, 1 H, J ϭ 7.6), 7.3Ϫ7.5 (m, 5 H),
7.55Ϫ7.75 (m, 2 H)
1؊5
1700, 1530, 2.0Ϫ2.18 (m ϩ s, 5 H), 2.2Ϫ2.42 (m, 2
1360, 1135 H), 2.44Ϫ2.54 (m, 2 H), 3.0Ϫ3.2 (m, 2
H), 4.6Ϫ4.7 (m, 1 H), 7.58Ϫ7.73 (m, 3
a
b
c
H
CH3
H
C2H5
H
CH3
CH3(CH2)3
CH3
H), 7.88Ϫ7.9 (m, 2 H)
d
r
1720, 1530, 2.0Ϫ2.5 (m, 6 H), 3.13 (t, 2 H, J ϭ 7.7),
1360, 1135 3.68 (s, 3 H), 4.6Ϫ4.8 (m, 1 H), 7.53Ϫ7.7
(m, 3 H), 7.85Ϫ7.95 (m, 2 H)
In conclusion, since our method can be applied to a vari-
ety of combinations of nitroalkanes and electrophilic al-
356
Eur. J. Org. Chem. 1998, 355Ϫ357

Conjugated Addition Reactions of Nitroalkanes with Electrophilic Alkenes in Aqueous Media
FULL PAPER
Michael Addition of Nitroalkanes (1) to Electrophilic Alkenes (2).
Ϫ General Procedure: Nitroalkane (45 mmol) and the alkene 2 (30 H, J ϭ 7.1 Hz), 4.6Ϫ4.78 (m, 1 H), 5.65 (m, 1 H), 6.23 (m, 1 H).
mmol) were added to a solution of 0.025  NaOH (0.1  for entry Ϫ C9H15NO4 (201.1): calcd. C 53.72, H 7.51, N, 6.96; found C
7.1 Hz), 1.72Ϫ2.12 (m, 2 H), 2.81 ( d, 2 H, J ϭ 5.2 Hz), 4.22 (q, 2
3a, b, d; 70 ml). Then, cetyltrimethylammonium chloride (CTACl, 53.88, H 6.88, N 7.05.
3 mmol; without CTACl for entry 3a؊c, l, m, p) was added at room
5c: Oil (61% yield). Ϫ IR (film): ν˜ ϭ 1705 cmϪ1, 1625, 1545. Ϫ
temperature and the resulting mixture was stirred, at the same tem-
perature, for the appropriate time (TLC, GC, see Table 1), then
saturated with NaCl and extracted with Et2O (4 ϫ 25 ml). The
organic phase was dried (MgSO4), concentrated, and the crude
product, when necessary, was purified by flash chromatography
(EtOAc/cyclohexane, 2:8) or by distillation giving the pure product
3 (Tables 2 and 3).
1H NMR (CDCl3): δ ϭ 0.8Ϫ2.2 (m, 12 H), 2.72Ϫ2.98 (m, 2 H),
4.15Ϫ4.32 (m, 2 H), 4.7Ϫ4.9 (m, 1 H), 5.8 (s, 1 H), 6.4 (s, 1 H). Ϫ
C11H19NO4 (229.1): calcd. C 57.62, H 8.35, N 6.11; found C 57.89,
H 8.48, N 6.00.
5d: Oil (55% yield). Ϫ IR (film): ν˜ ϭ 1710 cmϪ1, 1625, 1535. Ϫ
1H NMR (CDCl3): δ ϭ 1.3 (t, 3 H, J ϭ 7.1 Hz), 1.58 (s, 6 H), 3.0
(s, 2 H), 4.2 (q, 2 H, J ϭ 7.1 Hz), 5.58 (s, 1 H), 6.3 (s, 1 H). Ϫ
C9H15NO4 (201.1): calcd. C 53.72, H 7.51, N 6.96; found C 53.61,
H 7.64, N 6.87.
Table 3. Microanalyses of nitroderivatives 3
3 Empirical Molec.
Calcd.
Found
Formula
mass
C
H
N
S
C
H
N
S
[1]
P. Perlmutter, Conjugated Addition Reactions in Organic Syn-
thesis, Tetrahedron Organic Chemistry Series, vol. 9, Pergamon
Press, Oxford, 1992.
a
b
c
d
e
f
g
h
i
C6H11NO4
C7H13NO4
C9H17NO4
C7H13NO4
C11H13NO4 223.1 59.18 5.87 6.27
C10H19NO5 233.1 51.49 8.21 6.00
161.2 44.72 6.88 8.69
175.2 47.99 7.47 7.99
203.1 53.19 8.43 6.89
175.2 47.99 7.47 7.99
Ϫ
44.87 6.75 8.77
48.19 7.55 7.86
53.30 8.36 6.99
48.10 7.57 7.90
59.07 5.96 6.13
51.55 8.13 5.89
46.94 6.18 21.97
50.77 6.98 19.58
50.53 7.18 10.77
58.78 8.66 17.48
59.24 7.88 17.44
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
[2] [2a]
D. Seebach, E. W. Colvin, F. Lehr, T. Weller, Chimia 1979,
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[3] [3a]
G. P. Pollini, A. Barco, G. DeGiuli, Synthesis 1972, 44Ϫ45.
[3b]
Ϫ
P. Bakuzis, M. L. F. Bakuzis, T. F. Weingartner, Tetra-
[3c]
hedron Lett. 1978, 2371Ϫ2374. Ϫ
A. Hamada, Tetrahedron Lett. 1983, 24, 555Ϫ556. Ϫ
Stevens, A. W. M. Lee, J. Chem. Soc., Chem. Commun. 1982,
D. Miller, K. B. Moorthy,
C5H8N2O2
128.1 46.87 6.29 21.86
[3d]
R. V.
C6H10N2O2 142.1 50.69 7.09 19.70
C6H10N2O2 142.1 50.69 7.09 19.70
C9H16N2O2 184.1 58.67 8.75 17.37
C9H14N2O2 182.1 59.32 7.74 17.56
[3e]
102Ϫ103. Ϫ
J. H. Clark, D. G. Cork, Chem. Lett. 1983,
j
k
l
1145Ϫ1148. Ϫ [3f] J. H. Clark, D. J. Cork, J. Chem. Soc., Chem.
[3g]
Commun. 1982, 635Ϫ636. Ϫ
Y. Nakashita, M. Hesse, Helv.
C10H13NO4S 243.1 49.47 5.38 5.75 13.18 49.44 5.27 5.78 13.09
Chim. Acta 1983, 66, 845Ϫ860. Ϫ [3h] J. E. McMurry, J. Melton,
m C11H15NO4S 257.1 51.35 5.87 5.44 12.46 51.20 5.99 5.37 12.33
[3i]
J. Org. Chem. 1973, 38, 4367Ϫ4373. Ϫ
T. Miyakoshi, T.; S.
n
o
p
q
r
C14H21NO4S 299.1 56.17 7.07 4.68 10.71 56.01 7.15 4.77 10.59
C11H15NO4S 257.1 51.35 5.86 5.44 12.46 51.39 5.77 5.51 12.37
C15H15NO4S 305.4 59.00 4.95 4.58 10.50 58.88 5.04 4.66 10.57
C13H17NO5S 299.3 52.16 5.72 4.68 10.71 52.09 5.79 4.60 10.59
C13H17NO6S 315.3 55.10 6.05 4.94 11.31 55.01 5.99 5.02 11.38
Saito, Yukagaku 1982, 31, 31Ϫ34; Chem. Abstr. 1982, 97, 38526.
[3j]
Ϫ
N. Ono, H. Miyake, A. Kaji, J. Chem. Soc., Chem. Com-
[3k]
mun. 1983, 875Ϫ876. Ϫ
N. Ono, A. Kamimura, A. Kaji,
[3l]
Synthesis 1984, 226Ϫ227. Ϫ
D. W. Chasar, Synthesis 1982,
841Ϫ842. Ϫ [3m] R. Andruszkiewicz, R. B. Silverman, Synthesis
1989, 953Ϫ955.
[4a] J. H. Clark, D. G. Cork, H. W. Gibbs, J. Chem. Soc., Perkin
[4]
General Procedure for the Michael Addition of Nitroalkanes
Trans 1 1983, 2253Ϫ2258. Ϫ [4b] G. Rosini, E. Marotta, R. Bal-
[4c]
(1a؊d) to Electrophilic Alkenes (4): Nitroalkane 1a؊d (12 mmol)
and the alkene 4 (10 mmol) were added to a solution of NaOH
(0.1 , 20 ml). Then, cetyltrimethylammonium chloride (CTACl, 1
mmol) was added at room temperature and the resulting mixture
was stirred, at the same temperature, for 2 h, then saturated with
NaCl and extracted with Et2O (4 ϫ 15 ml). The organic phase was
dried (MgSO4), concentrated, and the crude product was purified
by flash chromatography (EtOAc/cyclohexane, 2:8) giving the pure
product 5a؊d.
5a: Oil (72% yield). Ϫ IR (film): ν˜ ϭ 1710 cmϪ1, 1630, 1545. Ϫ
1H NMR (CDCl3): δ ϭ 1.3 (t, 3 H, J ϭ 7.2 Hz), 1.58 (d, 3 H, J ϭ
7.1 Hz), 2.7Ϫ2.95 (m, 2 H), 4.22 (q, 2 H, J ϭ 7.2 Hz), 4.75Ϫ5.00
(m, 1 H), 5.68 (s, 1 H), 6.28 (s, 1 H). Ϫ C8H13NO4 (187.1): calcd.
C 51.33, H 6.99, N 7.48; found C 51.22, H 7.07, N 7.35.
lini, M. Petrini, Synthesis 1986, 237Ϫ 238. Ϫ
R. Ballini,
[4d]
M. Petrini, G. Rosini, Synthesis 1987, 711Ϫ713. Ϫ
D. E.
Bergbreiter, J. J. Lalonde, J. Org. Chem. 1987, 52, 1601Ϫ1603.
[4e]
Ϫ
B. Jouglet, L. Blanco, G. Rousseau, Synlett 1991,
[4f]
907Ϫ908. Ϫ
B. C. Ranu, S. Bhar, Tetrahedron 1992, 48,
[4g]
1327Ϫ1332. Ϫ
R. Ballini, P. Marziali, A. Mozzicafreddo, J.
Org. Chem. 1996, 61, 3209Ϫ3211.
[5a] J. Amato, Science 1993, 259, 1538Ϫ1541. Ϫ [5b] D. L. llman,
Chem. Eng. News 1993, 71, 5Ϫ6. Ϫ [5c] D. L. llman, Chem. Eng.
News 1994, 72, 22Ϫ27.
[5]
[6]
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303Ϫ310.
[7]
[8]
[9]
C. J. Li, Chem. Rev. 1993, 93, 2023Ϫ2035.
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[10]
[11]
[12]
5b: Oil (71% yield). Ϫ IR (film): ν˜ ϭ 1710 cmϪ1, 1630, 1530. Ϫ
1H NMR (CDCl3): δ ϭ 0.98 (t, 3 H, J ϭ 7.3 Hz), 1.31 (t, 3 H, J ϭ
[97242]
Eur. J. Org. Chem. 1998, 355Ϫ357
357