A practical route for the preparation of aromatic trans-β-nitroolefins

Full text of DOI:10.1080/00304948.2010.495680

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A Practical Route for the Preparation of
Aromatic trans-β-Nitroolefins
G. Groszek a
a Faculty of Chemistry, Rzeszów University of Technology, Poland
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Nitroolefins, Organic Preparations and Procedures International: The New Journal for Organic
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Organic Preparations and Procedures International, 42:373–378, 2010
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print
DOI: 10.1080/00304948.2010.495680
OPPI BRIEFS
A Practical Route for the Preparation of Aromatic
trans-β-Nitroolefins
G. Groszek
Faculty of Chemistry, Rzeszo´w University of Technology, Poland
Nitroalkenes are valuable precursors for a wide variety of target compounds.1–4 They are
powerful dienophiles in the Diels-Alder reaction and readily undergo addition reactions
with many different nucleophiles.5,6 Furthermore, they can be transformed into a variety of
diverse functionalities.7
The standard method for the preparation of β-nitrostyrene is the reaction of ben-
zaldehyde with nitromethane using sodium hydroxide (1 eq.) in methanol followed by
acidification.8 However, procedures and operations in this method are very tedious. An-
other approach is to condense aromatic aldehydes in benzene or toluene in the presence of
amines to generate the nucleophile from the nitroalkane. The method involves heating the
mixture for several hours using a Dean-Stark water trap to drive the reaction to completion.
Another reagent system that has been used for the condensation of benzaldehyde with
nitroalkanes is methylamine hydrochloride, potassium acetate and trimethyl orthoformate
in methanol. This system serves as a water scavenger.9 The most versatile preparation of
nitroalkenes involves the Henry condensation of an aldehyde with a nitroalkane followed
by dehydration of the resulting 2-nitroalcohol (Scheme 1). The Henry condensation is rou-
tinely carried out under basic conditions. The most commonly used bases are alkali metal
alkoxides or hydroxides. Quaternary ammonium salts or metal complexes have also been
utilized. The dehydration step requires a separate reagent.4,9–11 For aryl aldehydes, it is
difficult to avoid polymerization of the nitrostyrene derivatives12,13 or/and of by-product
formation due to Nef reaction. Thus the yields are relatively low. An interesting solution
is to use organoamine-functionalized mesoporous catalysts, which helps control whether
Henry or Knoevenagel products are obtained from aryl aldehydes and nitromethane.14
An alternate method for this type of condensation is hereby proposed. The products are
easy to work-up and the procedure is quite general. The process involves K2CO3 and 18-
crown-6 ether as a catalyst and the reaction is carried out at 12◦C in 1,4-dioxane. Then, the
Received December 4, 2009.
Address correspondence to G. Groszek, Rzeszo´w University of Technology, Faculty of Chem-
istry, 6 Powstanco´w Warszawy Ave. 35-959, Rzeszo´w, Poland. E-mail: ggroszek@prz.edu.pl
373

374
Groszek
dehydration step is performed with acetic anhydride and sodium acetate without isolation
of intermediate nitroalcohol derivatives (Scheme 1).
R1
O
R1
OH
R5
R1
R2
R3
R2
R3
R2
R3
NO2
NO2
CH3NO2, K2CO3
Ac2O, NaOAc
H
,4-dioxane,
1
80°C, 2 h
R5
R5
crown ether
12°C, 24 h
R4
R4
R4
1a-g
2a-g
a) R1 = R2 = R3 = R4 = R5 = H; b) R1 = R3 = R4 = R5 = H, R2 = NO2
c) R1 = R2 = R4 = R5 = H, R3 = OMe; d ) R1 = OAc, R2 = OMe, R3 = R5 =
H, R4 = NO2; e) R1 = OAc, R2 = OMe, R3 = R4 = H, R5 = NO2
f) R1 = OBn, R2 = OMe, R3 = R4 = H, R5 = NO2; g) R1 = OBn, R2 = R3 =
H, R4 = OMe, R5 = NO2
Scheme 1
The scope of this method was extended to various substituted benzaldehydes 1a-g.
(Table) A relatively good yield of 65% was obtained with benzaldehyde. With p-
anisaldehyde (1c), the yield was somewhat disappointing (41%). Nonetheless, this result is
comparable to that reported by Cassel et al.15 however, Gairaud et al.16 was able to obtain
this product in 65% yield. Most likely, the reason was that extensive subsequent polymer-
ization of the nitrostyrene derivative was minimized, because weakly basic ammonium
acetate was used in glacial acetic acid. For trisubstituted benzaldehydes 1d-g, good yields
in the range from 70 to 87% were obtained. These results suggest that electron-withdrawing
groups in the aromatic ring favor the reaction. Although hydrolysis of the acetoxy groups
of 1d and 1e did occur during the condensation step, the phenolic groups were evidently
re-acetylated during the dehydration step. Indeed, when the condensation was performed
with 1d and 1e without using acetic anhydride and sodium acetate, the deprotected products
3d (R4 = NO2, R5 = H) and 3e (R4 = H, R5 = NO2) were obtained in yields of 24% and
45%, respectively (Scheme 2).
OH
OAc
O
NO2
MeO
MeO
CH3NO2, K2CO3
H
R5
dioxane,
crown ether
12°C, 24 h
R5
R4
R4
1d, 1e
3d, 3e
Scheme 2
When the condensation of 1d was carried out with pivaloyl chloride, the O-pivalated
nitrostyrene 4d was obtained in yield of 50% (Scheme 3).
These last two transformations were not optimized.

Preparation of Aromatic trans-β-Nitroolefins
375
OPv
OAc
O
CH3NO2, K2CO3
dioxane, crown ether
rt, 48 h
NO2
MeO
MeO
H
Me3CCOCl, rt, 10 min
NO2
NO2
1d
4d
Scheme 3
The mechanism of the reaction might be viewed by assuming that potassium carbonate
generates the nitronate ion, which exists as an ion pair with K+. This salt is poorly soluble
in the solvent, dioxane and 18-crown-6 ether are added to complex potassium ions, thus
−
making the CH2NO2 ion sufficiently free to attack the carbonyl group of the aldehyde.
However, the concentration of nitromethylene ion is still very low, and depends on the
equilibrium of the system involving nitromethane and potassium carbonate on one end,
and nitromethide potassium ion pair and potassium bicarbonate on the other. Elevated
temperatures help to improve the solubility of nitromethylene potassium salt, but reduce
the concentration of “naked” −CH2NO2 ions which are less effectively separated from
potassium ions by crown ether. Therefore, the reaction requires relatively low and constant
temperature. Hence, the optimal conditions for this version of Henry condensation require
a temperature of 12◦C, a ten-fold molar excess of nitromethane and at least 24 hours
for complete conversion. Additionally, potassium carbonate helps to keep the reaction
environment anhydrous. In order to obtain the nitrostyrene, the nucleophilic addition has
to be followed by dehydration with acetic anhydride and sodium acetate.
Table
Reaction of Aromatic Aldehydes with Nitromethane
Product
mp. (◦C)
Literature
mp. (◦C)
Yielda (%)
Yield (%)
Ref.
2a
65
50–51 (DCM/hexane)
83
60
57–58 (EtOH)
58–59 (MeOH)
56–57 (EtOH)
126 (EtOH)
8
16
17
17
18
15
16
2b
2c
64
122–125 (DCM/hexane)
83–85
–
47
35
65
–
70
91
82
– – –
41b
86–87 (EtOH)
86–87 (MeOH)
– – –
170–172
119–120 (MeOH)
158–161 (DCM/hexane)
2d
2e
2f
70
71
87
82
167–168 (EtOAc/hexane)
170–171 (EtOAc/hexane)
118–120 (DCM/hexane)
158–161 (DCM/hexane)
19
20
21
2g
a) Yield after crystallization.
b) Yield of crude product.

376
Groszek
In conclusion, an effective variation of the Henry condensation that is particularly suit-
able for trisubstituted benzaldehyde has been developed. The active methylene compound
was nitromethane in the presence of K2CO3 and 18-crown-6 ether in 1,4-dioxane.
Experimental Section
1
Melting points were determined on a Boe¨tius apparatus and are uncorrected. H and 13C
NMR spectra were recorded on Bruker (500 MHz) instrument in CDCl3. Chemical shifts
are expressed in δ with TMS as internal standard, coupling constants (J) are in Hz. IR
and UV spectra were recorded on Perkin Elmer and Hewlett Packard 8453 instruments,
respectively. Elemental analysis was performed on a AE 1108 Carlo Erba apparatus. Mass
spectra were obtained on a AMD-604 spectrometer. TLC plates were silica gel 60 F254
Merck. Substrates 1a-c and other materials were commercially available and compounds
1d and 1e were prepared according to literature procedures.19 Compounds 1f and 1g had
been previously prepared in our laboratory.21
General Procedure
Potassium carbonate (3.61 g, 0.026 mol) was suspended in 1,4-dioxane (100 mL) in a
round bottom flask, equipped with a magnetic stir bar. Then, nitromethane (7.0 mL, 7.91 g,
0.13 mol) was added and the mixture was stirred for 10 min at room temperature. The
reaction mixture was cooled to 12◦C and kept for 1 h, then the aromatic aldehyde (0.013 mol)
was added in the presence of 18-crown-6 ether (0.25 g, 0.9 mmol). The reaction progress
was monitored by TLC (toluene-MeOH, 6:0.5). After 24 h, the solid (inorganic salts) was
collected (and discarded), and then acetic anhydride (14 mL, 15.2 g, 0.15 mol) was added to
the filtrate followed by addition of sodium acetate (250 mg) and the mixture was heated at
80◦C for 2 h. The reaction mixture was poured into ice/H2O mixture (1.5 L). The precipitate
was collected and air-dried. The crude product was crystallized from appropriate solvents
system to give nitroolefins 2.
2-Acetoxy-3-methoxy-5-nitro-β-nitrostyrene (2d), mp. 167–168◦C (EtOAc/hexane);
Rf = 0.5 (toluene-MeOH, 5:1). IR (KBr): 3097, 1775 (C O), 1646 (C C), 1541, 1522,
1340 cm−1. 1H NMR (500 MHz, CDCl3): δ 8.08 (d, J = 2.4 Hz, 1 H, ArH), 8.02 (d, J =
13.8 Hz, 1 H, CH CHNO2), 7.91 (d, J = 2.4 Hz, 1 H, ArH), 7.65 (d, J = 13.8 Hz, 1 H,
CH CHNO2), 3.98 (s, 3 H, OCH3), 2.45 (s, 3 H, C(O)CH3). 13C NMR (125 MHz, CDCl3):
δ 20.5 (C(O)CH3), 56.9 (OCH3), 109.4, 114.9, 125.1, 130.8, 140.5, 144.4, 146.2, 152.6,
167.2 (C(O)CH3). MS (EI, 70 eV): m/z (%): 43 (100), 193 (15), 240 (6), 282 (1) [M]+.
HRMS-FAB, m/z [M]+ Calcd for C11H10N2O7: 282.0488. Found: 282.0493. UV (CHCl3),
λmax (ε): 282 nm (18900), (c = 0.10 mg/10 mL).
Anal. Calcd for C11H10N2O7: C, 46.82; H, 3.57; N, 9.93. Found: C, 46.95; H, 3.54; N,
10.02.
Condensation Procedure without Acetic Anhydride and Sodium Acetate
Condensation of 1d and 1e were performed as described above until complete conversion
was achieved (TLC, toluene-MeOH, 4:1). Then reaction mixture was poured into cold
water, the pH was adjusted to pH ∼6 with conc. hydrochloric acid. The precipitated solid

Preparation of Aromatic trans-β-Nitroolefins
377
was collected and air-dried and crystallized from ethyl acetate-hexane system solvents to
give previously unreported nitroolefins 3d and 3e in yields of 24 and 45%, respectively.
2-Hydroxy-3-methoxy-5-nitro-β-nitrostyrene (3d), mp. 190–191◦C (dec.) (EtOAc/
hexane); Rf = 0.3 (hexane-EtOAc, 2:1). IR (KBr): 3288 (OH), 1617 (C C), 1521, 1489,
1339, 1267 cm−1. 1H NMR (500 MHz, DMSO-d6): δ 11.76 (s, 1H, OH), 8.35 (d, J = 2.4,
1H, ArH), 8.28 (d, J = 13.6, 1H, CH CHNO2), 8.21 (d, J = 13.6, 1H, CH CHNO2),
7.82 (d, J = 2.4, 1H, ArH), 3.98 (s, 3H, OCH3). 13C NMR (125 MHz, DMSO-d6): δ 56.6
(OCH3), 108.4, 116.5, 119.1, 133.2, 139.4, 147.8 (2xC), 153.5. LRMS (EI, 70 eV) m/z
[%]: 51 (6), 76 (6), 77 (8), 89 (6), 133 (14), 135 (14), 147 (26), 148 (6), 193 (100), 240
(M+, 65). HRMS (EI), m/z [M]+ Calcd for C9H8N2O6: 240.0382. Found: 240.0375. UV
(EtOH), λmax (ε): 463 (25500), 409 (24700), 316 (15300), (c = 0.07 mg/10 mL) nm.
2-Hydroxy-3-methoxy-6-nitro-β-nitrostyrene (3e), mp. 181–183◦C (EtOAc/hexane);
Rf = 0.3 (hexane-EtOAc, 2:1). IR (KBr): 3448 (OH), 1632, 1579, 1512, 1479, 1342,
1
1274 cm−1. H NMR (500 MHz, DMSO-d6): δ 1.00 (s, 1H, OH), 8.23 (d, J = 13.5, 1H,
CH CHNO2), 8.03 (d, J = 13.5, 1H, CH CHNO2), 7.73 (d, J = 9.0, 1H, ArH), 7.25 (d,
J = 9.0, 1H, ArH), 3.98 (s, 3H, OCH3). 13C NMR (125 MHz, DMSO-d6): δ 56.7 (OCH3),
111.4, 111.8, 117.7, 131.1, 141.2, 142.6, 147.3, 152.1. HRMS (ESI), m/z [M+Na]+ Calcd
for C9H8N2O6Na: 263.0275. Found: 263.0273. UV (CH3CN), λmax (ε): 279 (14000), 356
(7800), (c = 0.20 mg/10 mL) nm.
Condensation with Pivaloyl Chloride in Dehydration Step
A mixture of aldehyde 1d (240 mg, 1.0 mmol), nitromethane (0.7 mL, 0.79 g, 1.3 mmol),
potassium carbonate (155 mg, 1.12 mmol) and 18-crown-6 ether (30 mg) in dioxane (15 mL)
was stirred at room temperature. The reaction progress was monitored by TLC (toluene-
MeOH, 4:1). After 48 h, the reaction was complete, and then pivaloyl chloride (0.5 mL,
4 mmol) was added to reaction mixture. After 10 min reaction mixture was poured into
water (100 mL), precipitate was collected and air-dried. The crude product was purified
by column chromatography (silica gel, eluted hexane/EtOAc; 95:5) and crystallized from
acetone to afford 4d (165 mg, yield 50%).
3-Methoxy-2-pivaloyloxy-5-nitro-β-nitrostyrene (4d), mp. 191–192◦C (acetone);
Rf = 0.6 (hexane-EtOAc, 3:2). IR (KBr): 3099, 2976, 1761 (C O), 1645, 1585, 1535,
1470, 1340, 1293 cm−1. 1H NMR (500 MHz, CDCl3): δ 8.08 (d, J = 2.4, 1H, ArH), 7.99
(d, J = 13.8, 1H, CH CHNO2), 7.89 (d, J = 2.4, 1H, ArH), 7.65 (d, J = 13.8, 1H,
CH CHNO2), 3.96 (s, 3H, OCH3), 1.45 (s, 9H, 3xCH3). 13C NMR (125 MHz, CDCl3): δ
27.1 (3xCH3), 39.6, 56.9 (OCH3), 109.3, 114.8, 125.2, 130.7, 140.4, 145.0, 146.0, 152.7,
175.1 (C O). LRMS (EI, 70 eV) m/z [%]: 324 (M+, 1), 240 (14), 194 (7), 193 (61), 147
(15), 135 (6), 85 (23), 76 (5), 57 (100), 41 (9). HRMS (EI), m/z [M]+ Calcd for C14H16N2O7:
324.0958. Found: 324.0966. UV (CH3CN), λmax (ε): 283 (21100), (c = 0.07 mg/10 mL)
nm.
Anal. Calcd for C14H16N2O7: C, 51.85; H, 4.97; N, 8.64. Found: C, 51.80; H, 4.98; N,
8.63.
Acknowledgment
This project was supported by Polish Ministry of Scientific Research and Information
Technologies, Grant no. 2 P05F 010 28.

378
Groszek
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