A selective and practical synthesis of nitroolefins

Article abstract of DOI:10.1002/adsc.200800509

A straightforward and general synthesis of nitroolefins from nitric oxide (NO) and olefins is presented. The direct nitration of aromatic olefins, allyl compounds, and acrylic acid derivatives proceeds smoothly at room temperature with high regioselectivity and good yields. The advantages of this novel procedure compared to established nitration procedures are demonstrated.

Full text of DOI:10.1002/adsc.200800509

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DOI: 10.1002/adsc.200800509
A Selective and Practical Synthesis of Nitroolefins
Irina Jovel,a Saisuree Prateeptongkum,a Ralf Jackstell,a Nadine Vogl,b
Christoph Weckbecker,b and Matthias Bellera,*
a
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax : (+49)-381-1281-51113; e-mail: matthias.beller@catalysis.de
Evonik Degussa GmbH, Health and Nutrition, Rodenbacher Chaussee 4, 63457 Hanau, Germany
b
Received: August 14, 2008; Published online: November 4, 2008
Abstract: A straightforward and general synthesis
of nitroolefins from nitric oxide (NO) and olefins is
presented. The direct nitration of aromatic olefins,
allyl compounds, and acrylic acid derivatives pro-
ceeds smoothly at room temperature with high re-
gioselectivity and good yields. The advantages of
this novel procedure compared to established nitra-
tion procedures are demonstrated.
agents such as NaNO2,[7] RONO2,[8]
CACTHNGUTERNNUG
(NO2)4,[9]
[13]
CeNH4A
CTHUNGTRENNUNG
been established for the nitration of olefins. However,
most of these protocols produce at least stoichiomet-
ric amounts of waste and show little functional group
tolerance. Surprisingly, direct nitrations with NO,
which is an economic and easily available nitrogen
source, have only been scarcely investigated.[14] Due
to its biological action NO was termed sometime ago
as “molecule of the year”.[15] Nevertheless, up to date
NO has attracted relatively little attention as nitration
reagent.
Keywords: nitration; nitric oxide (NO); nitroole-
fins; olefins
Formally, the nitration reaction constitutes a simple
substitution of hydrogen by NO2, however, in this oxi-
dation process several radical reactions are known to
Nitro-substituted compounds are of significant impor- be involved making the transformation more compli-
tance for the bulk and fine chemical industry as build- cated.[16] In Scheme 2 the assumed mechanism is
ing blocks for polymers, dyes, but also for the synthe- shown. The reaction is initiated by oxidation of NO
sis of pharmaceuticals and agrochemicals.[1] Most to NO2 with traces of oxygen present. NO2 reacts
often they serve as valuable intermediates for the cor- with the olefinic double bond to form a carbon-cen-
responding amines and carbonyl compounds, howev- tered radical. In this step the regioselectivity of the
er, even some naturally occurring bio-active nitro de- addition will be determined. Hence, the product with
rivatives are known.[2] For some time, we have been the most stable radical intermediate will be formed.
interested in the development of new and improved Next, the radical is trapped by NO, which is further
methods for the formation of carbon-nitrogen bonds. oxidized to the corresponding nitro derivative of a
In this respect catalytic hydroamination,[3,4] and hy- (nitrooxy)diazene. Subsequent elimination of nitrogen
droaminomethylation[5] of olefins and alkynes as well and HNO3 leads to the nitroalkene. Once the process
as environmentally friendly alkylation of alcohols and is initiated, NO2 results from the reaction of NO with
amines[6] have been of special interest to us.
HNO3.[17] The generation of N2 and the formation of
More recently, we became attracted by the possibil- nitrous acid (HNO2) and/or nitric acid (HNO3) have
ity to form carbon-nitrogen bonds via nitration of ole- been experimentally determined by chemical analysis
fins to form nitroolefins or nitroalkanes. The resulting of the products of the nitration reaction of olefins
products should be easily reduced to the correspond- with NO.[14] The proposed equation of this reaction is
ing amines (Scheme 1). Notably, such a reaction se- shown in Scheme 2.
quence offers a straightforward, atom-efficient access
At the start of our investigation we studied the re-
towards primary amines. Up to date a number of re- action of 4-methoxystyrene with NO as a model
system for the nitration of olefins. Selected results of
the preliminary screening of reaction conditions are
shown in Table 1. In general, the reaction proceeds
well already at a room temperature and low pressure
(2 bar) of NO. Notably, the reaction is highly solvent-
dependent, giving best results in 1,2-dichloroethane,
THF and CCl4 (Table 1, entries 3, 5 and 7). In these
Scheme 1. Envisoned synthesis of primary amines via nitra-
tion and hydrogenation.
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Scheme 2. Proposed mechanism and full equation of the nitration of olefins with NO.
Table 1. Nitration of 4-methoxystyrene under different reaction conditions.[a]
Entry
Solvent
Pressure bar
Temp. [8C]
Additive
Time [h]
Conv.[b] [%]
Yield[b] [%]
1
2
3
4
5
6
7
8
9
CH2Cl2
2
1
2
2
2
2
2
2
2
2
22
22
22
40
22
22
22
22
22
22
–
–
–
–
–
–
–
3
5
3
2
3
3
3
3
3
3
57
88
97
100
95
5
98
20
90
64
52
72
92 (90)
64
92 (90)
0
90
0
21
63
1,2-dichloroethane
1,2-dichloroethane
1,2-dichloroethane
THF
EtOH
CCl4
1,2-dichloroethane
1,2-dichloroethane
1,2-dichloroethane
HQ[c]
TEMPO[c]
N2O[d]
10
[a]
Reaction conditions: 2.0 mmol 4-methoxystyrene in 20 mL of solvent.
Conversion and yield determined by GC analysis with decane as internal standard; isolated yield is given in parenthesis.
Concentration: 10 mol%.
Partial pressure: 10 bar.
[b]
[c]
[d]
solvents, the reaction proceeds almost completely peridinyloxy), and N2O have been added to different
(conversion 95–98%) within 3 h at 2 bar NO and reactions (Table 1, entries 8–10). While HQ inhibited
room temperature. Here, an excellent yield (90–92%) the nitration completely, in the presence of TEMPO
of the target product 1-methoxy-4-(2-nitrovinyl)-ben- the yield of the nitration product was much lower
zene (1) is obtained, which is formed as a mixture of (21% instead 92%). Similarly, the addition of N2O de-
E/Z isomers in a ~1:1-ratio. Increasing the tempera- creased the conversion of the starting material and
ture or lowering the pressure decreased the product the product yield.
yield significantly. Notably, in protic solvents, for ex-
Next, we were interested in the scope and limita-
ample, EtOH, the reaction is strongly inhibited tions of our novel procedure with different olefins
(Table 1, entry 6). Due to the increased stability of (Table 2). For this purpose, we studied the reaction of
the benzyl radical, the nitration occurred fully regio- NO with various olefins at room temperature in
specific (>99%) giving the linear b-nitrostyrene. either 1,2-dichloroethane or THF. Besides 4-methoxy-
Under optimized conditions full conversion of the
ACHTUNGTRENsNGNU tyrene also styrene and other 2- and 4-substituted
olefin and high chemoselectivity are achieved. In styrene derivatives gave the corresponding nitroole-
some reactions the addition product of water to the fins (2–6) in 52–90% yield (Table 2, entries 1–5). In
activated double bond (1-hydroxy-1-phenyl-2-nitro- addition, substituents in both the a- and b-positions
ethane) could be obtained to a minor extent (<10% of the double bond are well tolerated giving the b-ni-
yield).
trostyrene derivatives 7 and 8 in good yield (Table 2,
In order to verify the radical character of the reac- entries 6 and 7). The reaction of 2-ethylhexyl acrylate
tion and also to improve of N-balance of the process, led to the novel b-nitroacrylate 9 (Table 2, entry 8).
hydroquinone (HQ), TEMPO (2,2,6,6-tetramethylpi- Even the sensitive methyl 2-acetamidoacrylate react-
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A Selective and Practical Synthesis of Nitroolefins
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Table 2. Reaction of various olefins with NO.[a]
Entry
1
Olefin
Product
Time [h]
3
Conv.[b] [%]
98
Yield[c] [%]
90
E/Z
94:6
2
3
4
5
3
100
92
90
57
83
52
>99:1
92:8
4
4
90
94:6
20
95
>99:1
6
7
3
4
100
96
69
88
90:10
>99:1
8
17
82
30
>99:1
9
4
100
100
53
92
1:0.66
1:1
10
20
11
12
13
14
3
100
100
86
81
66
68
39
1:0.68
75:25
90:10
80:20
3.5
3.5
24
100
15
22
97
81
–
[a]
Reaction conditions: 2.0 mmol olefin, in 20 mL 1,2-dichloroethane, at room temperature.
Conversion was determined by GC analysis with decane as internal standard.
Isolated yield is given.
[b]
[c]
ed to afford the 3-nitro-2-acetamidoacrylate 10 in ac- Again, the desired products are formed in high regio-
ceptable yield (53%). To the best of our knowledge selectivity in 66–81% yields (Table 2, entries 11–13).
the latter reaction is the first example of the nitration
Moreover, phenyl vinyl sulfide and 1,1-diphenyl-
of unsaturated a-amino acid derivatives. Methyl ethylene were reacted with NO (Table 2, entries 14
methacrylate led to the b-nitromethacylate 11 in high and 15). The resulting 1-nitro-2-thiophenylethylene is
yield (92%; Table 2, entry 10). In addition, we did an interesting new building block which might be
some reactions with allylic substrates, for example al- used for the otherwise difficult preparation of 1-thio-
lylbenzene, allyl phenyl ether, and allyl benzyl ether. 2-aminoalkanes.[18]
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Scheme 3. Comparison of nitration of three olefins with NO and NaNO2.
Finally, we compared the novel protocol with the
most common nitration reaction applying NaNO2 sim-
ilar to a literature protocol.[19] Methyl and ethyl meth-
acrylate as well as benzyl allyl ether were taken as
olefinic starting materials. As shown in Scheme 3 in
all cases the yield of nitro products was significantly
improved by using NO as nitration reagent. However,
in case of acrylates and methacrylates a mixture of
E/Z isomers is obtained. On the other hand using
benzyl allyl ether the selectivity is considerably im-
proved applying NO.
In conclusion, we have developed a convenient pro-
tocol for the synthesis of various nitroolefins. Starting
from easily available substrates a range of interesting
building blocks are obtained selectively under mild
conditions.
General Procedure for the Nitration with NaNO2
A stirred solution of olefin in benzene (50 mmol in 10 mL)
was treated with acetic acid:water (3:2, 20 mL) and the mix-
ture was cooled to 08C. Sodium nitrite (5 g, 70 mmol) was
gradually introduced over a period of 15 min. Then, the re-
action mixture was stirred at room temperature for 20 h.
The layers were separated, the organic layer was washed
with water and dried under MgSO4, and solvents were
evaporated. The products were isolated after purification by
column chromatography (silica gel 60, eluted by hexane/
ethyl acetate 2:1).
(E)-2-Ethylhexyl 3-nitroacrylate (9): 1H NMR (CDCl3):
d=0.75–0.90 (m, 6H, 2 CH3), 1.2–1.4 (m, 8H, 4 CH2), 1.58
(m, 1H, CH), 4.11 (m, 2H, OCH2), 7.02 (d, J=13.5 Hz, 1H,
=CHCO), 7.59 (d, J=13.5 Hz, 1H, =CHNO2); 13C NMR
(CDCl3): d=10.9, 14.0, 22.9, 23.7, 28.9, 30.3, 38.7, 68.8,
127.7, 148.9, 162.8; MS (70 eV, EI): m/z (%)=129 (2.74),
112 (7.90), 90 (3.22), 84 (8.06), 83 (17.74), 71 (56.45), 70
(43.55), 69 (22.58), 62 (9.68), 57 (100), 56 (16.13), 55 (37.10),
43 (53.22), 41 (38.71).
(E)-Methyl 2-acetamido-3-nitroacrylate (10): 1H NMR
(CDCl3): d=2.21 (s, 3H, CH3CO), 3.83 (s, 3H, CH3O), 6.71
(s, 1H, =CHNO2), 10.18 (s, 1H, NH); 13C NMR (CDCl3):
d=23.7, 53.9, 121.7, 137.8, 162.0, 168.1; MS (70 eV, EI): m/z
(%)=188 (M+, 1.34), 157 (8.41), 146 (75.06), 130 (11.62),
116 (10.04), 114 (19.08), 87 (14.58), 43 (100); HR-MS (EI):
m/z=188.04908, calcd. for C6H8N2O5: 188.04277; yellow
crystals, mp 818C.
Experimental Section
General Procedure for the Nitration with NO
In an autoclave under an argon atmosphere the correspond-
ing olefin (2 mmol) was dissolved in 1,2-dichloroethane
(20 mL). Autoclave was filled with NO gas under pressure
2 bar, and the mixture was stirred at room temperature for
the respective time (see Table 2). The solvent was removed
under vacuum, and the crude product was purified by
column chromatography (eluents: hexane/ethyl acetate in
different ratio).
1
(E)-(3-Nitroallyloxy)benzene (13): H NMR (CDCl3): d=
4.83 (dd, J=1.5, 2.9 Hz, 2H, CH2), 6.96–7.14 (m, 3H,
Arom.), 7.34–7.45 (m, 4H, arom+HC=CH); 13C NMR
(CDCl3): d=63.7, 114.6, 122.1, 129.8, 137.0, 140.2, 157.5; MS
(70 eV, EI): m/z (%)=179 (M+, 0.73), 134 (9.61), 105
(57.70), 103 (12.63), 91 (5.29), 79 (14.75), 77 (80.83), 65
(6.57), 51 (25.84), 39 (11.59); HRMS (EI): m/z=179.057506,
calcd. for C9H9NO3: 179.05769.
All the products (Table 1 and Table 2) have been identi-
1
fied by H, 13C NMR and mass spectrometry. The spectral
data obtained for known compounds 1–8, 11–12, 14–16 are
agreement with the data published in the literature.[20–32]
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A Selective and Practical Synthesis of Nitroolefins
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ack, D. Hollmann, D. Michalik, M. Beller, Tetrahedron
Lett. 2006, 47, 8881–8885; c) D. Hollmann, S. Bꢁhn, A.
Tillack, M. Beller, Chem. Commun. 2008, 3199–3201;
d) D. Hollmann, S. Bꢁhn, A. Tillack, M. Beller, Angew.
Chem. Int. Ed. 2007, 46, 8291–8294; Angew. Chem.
2007, 119, 8440–8444.
Acknowledgements
This work has been supported by the State of Mecklenburg-
Western Pomerania, the BMBF (Bundesministerium fꢀr Bil-
dung und Forschung), the Deutsche Forschungsgemeinschaft
(GRK and Leibniz-price) and Evonik-Degussa. We thank all
members of the analytical group of LIKAT for their support.
[7] J. R. Hwu, K.-L. Chen, S. Ananthan, H. V. Patel, Orga-
nometallics 1996, 15, 499–505.
[8] A. V. Stepanov, V. V. Veselovsky, Russ. Chem. Rev.
2003, 72, 327–341.
[9] C. P. Butts, J. L. Calvert, L. Eberson, M. P. Hartshorn,
W. T. Robinson, J. Chem. Soc., Perkin Trans. 2 1994, 7,
1485–1490.
[10] J.-L. Grenier, J.-P. Catteau, Ph. Cotelle, Synth.
Commun. 1999, 29, 1201–1208.
[11] O. Siri, L. Jaquinod, K. M. Smith, Tetrahedron Lett.
References
[1] a) S. A. Lawrence, in: Amines: Synthesis properties, and
applications, Cambridge University, Cambridge 2004;
b) J. F. Hartwig, in: Handbook of Organopalladium
Chemistry for Organic Synthesis, Vol. 1 (Ed.: E.-I. Ne-
gishi), Wiley-Interscience, New York, 2002, p 1051.
[2] a) R. Royer, Chimica Therapeutica 1969, 4, 389–406;
b) L. J. Ignarro, Angew. Chem. Int. Ed. 1999, 38, 1882–
1892; c) Z. Snellinx, A. Nepovim, S. Taghavi, J. Van-
gronsveld, T. Vanek, D. van der Lelie, Environmental
science and pollution research international 2002, 9, 48–
61.
[3] For some reviews see: a) J. J. Brunet, N. C. Chu, M. Ro-
driguez-Zubiri, Eur. J. Inorg. Chem. 2007, 4711–4722;
b) A. V. Lee, L. L. Schafer, Eur. J. Inorg. Chem. 2007,
2243–2255; c) R. Severin, S. Doye, Chem. Soc. Rev.
2007, 36, 1407–1420; d) K. C. Hultzsch, D. V. Gribkov,
F. Hampel, J. Organomet. Chem. 2005, 690, 4441–4452;
e) A. L. Odom, Dalton Trans. 2005, 225–233; f) J. F.
Hartwig, Pure Appl. Chem. 2004, 76, 507–516; g) S.
Doye, Synlett 2004, 1653–1672; h) J. Seayad, A. Tillack,
C. G. Hartung, M. Beller, Adv. Synth. Catal. 2002, 344,
795–813; i) M. Beller, C. Breindl, M. Eichberger, C. G.
Hartung, J. Seayad, O. Thiel, A. Tillack, H. Trauthwein,
Synlett 2002, 1579–1594.
[4] Some recent examples from our group: a) K. Alex, A.
Tillack, N. Schwarz, M. Beller, ChemSusChem. 2008, 1,
333–338; b) A. Tillack, V. Khedkar, J. Jiao, M. Beller,
Eur. J. Org. Chem. 2005, 5001–5012; c) V. Khedkar, A.
Tillack, C. Benisch, J.-P. Melder, M. Beller, J. Mol.
Catal. A: Chem. 2005, 241, 175–183; d) V. Khedkar, A.
Tillack, M. Michalik, M. Beller, Tetrahedron Lett. 2004,
45, 3123–3126; e) A. Tillack, H. Jiao, I. Garcia Castro,
C. G. Hartung, M. Beller, Chem. Eur. J. 2004, 10, 2409–
2420; f) M. Beller, J. Seayad, A. Tillack, H. Jiao,
Angew. Chem. Int. Ed. 2004, 43, 3368–3398; Angew.
Chem. 2004, 116, 3448–3479; g) V. Khedkar, A. Tillack,
M. Beller, Org. Lett. 2003, 5, 4767–4770.
[5] a) A. Moballigh, C. Buch, L. Routaboul, R. Jackstell,
H. Klein, A. Spannenberg, M. Beller, Chem. Eur. J.
2007, 13, 1594–1601;b) K.-S. Mueller, F. Koc, S.
Ricken, P. Eilbracht, Org. Biomol. Chem. 2006, 4, 826–
835; c) L. Routaboul, C. Buch, H. Klein, R. Jackstell,
M. Beller, Tetrahedron Lett. 2005, 46, 7401–7405; d) A.
Moballigh, A. Seayad, R. Jackstell, M. Beller, J. Am.
Chem. Soc. 2003, 125, 10311–10318; e) P. Eilbracht, L.
Bꢁrfacker, C. Buss, C. Hollmann, B. E. Kitsos-Rzychon,
C. L. Kranemann, T. Rische, R. Roggenbuck, A.
Schmidt, Chem. Rev. 1999, 99, 3329–3365.
2000, 41, 3583–3587.
[12] M. Tanaka, E. Muro, H. Ando, Q. Xu, M. Fujiwara, Y.
Souma, Y. Yamaguchi, J. Org. Chem. 2000, 65, 2972–
2978.
[13] G. Panke, T. Schwalbe, W. Stirner, Sh. Taghavi-Mogha-
dam, G. Wille, Synthesis 2003, 2827–2830.
[14] E. Hata, T. Yamada, T. Mukaiyama, Bull. Chem. Soc.
Jpn. 1995, 68, 3629–3636.
[15] E. Culotta, D. E. Koshland Jr, Science 1992, 258, 1862–
1865.
[16] R. Li, Zh. Liu, Y. Zhoh, L. Wu, Synlett 2006, 1367–
1368.
[17] D. R. Kelly, S. Jones, J. O. Adigun, K. S. V. Koh, D. E.
Hibbs, M. B. Hursthouse, S. K. Jackson, Tetrahedron
1997, 53, 17221–17234.
[18] H. Ishibashi, M. Uegaki, M. Sakai, Y. Takeda, Tetrahe-
dron 2001, 57, 2115–2120.
[19] S. Ranganathan, S. K. Kar, J. Org. Chem. 1970, 35,
3962–3964.
[20] S. M. Lindley, G. C. Flowers, J. E. Leffler, J. Org.
Chem. 1985, 50, 607–610.
[21] S. E. Denmark, B. S. Kesler, Y-Ch. Moon, J. Org.
Chem. 1992, 57, 4912–4924.
[22] C. Wang, S. Wang, Synth. Commun. 2002, 32, 3481–
3486.
[23] G. Kumaran, G. H. Kulkarni, Tetrahedron Lett. 1994,
35, 9099–9100.
[24] T. Ohe, S. Uemura, Bull. Chem. Soc. Jpn. 2003, 7,
1423–1431.
[25] J. G. Dingwall, J. Ehrenfreund, R. G. Hall, Tetrahedron
1989, 45, 3787–3808.
[26] H. Ohta, N. Kobayashi, K. Ozaki, J. Org. Chem. 1989,
54, 1802–1804.
[27] M. V. R. Reddy, B. Mehrotra, Y. D. Vankar, Tetrahe-
dron Lett. 1995, 36, 4861–4864.
[28] K. Jayakanthan, K. P. Madhusudanan, Y. D. Vankar,
Tetrahedron 2004, 60, 397–403.
[29] A. G. Myers, J. K. Barbay, B. Zhong, J. Am. Chem. Soc.
2001, 123, 7207–7219.
[30] D. Lucet, S. Sabelle, O. Kostelitz, T. Le Gall, Ch. Mios-
kowski, Eur. J. Org. Chem. 1999, 10, 2583–2591.
[31] N. Ono, A. Kamimura, A. Kaji, J. Org. Chem. 1986, 51,
2139–2142.
[6] a) D. Hollmann, A. Tillack, D. Michalik, R. Jackstell,
[32] H.-Y. Tu, Y.-H. Liu, Y. Wang, T.-Y. Luh, Tetrahedron
Lett. 2005, 46, 771–773.
M. Beller, Chem. Asian J. 2007, 2, 403–410; b) A. Till-
Adv. Synth. Catal. 2008, 350, 2493 – 2497
ꢂ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2497