Nitroaldol-reaction of aldehydes in the presence of non-activated Mg:Al 2:1 hydrotalcite; A possible new mechanism for the formation of 2-aryl-1,3-dinitropropanes

Article abstract of DOI:10.1016/j.tet.2005.02.055

Commercially available, non-activated 2:1 Mg:Al hydrotalcite catalyzes the nitroaldol reaction between a variety of aromatic and aliphatic aldehydes and simple nitroalkanes such as nitromethane and nitroethane. A new mechanism is proposed for the formation of the 1,3-dinitropropanes. The threo/erythro diastereoselectivity of the nitroethane-adducts was determined by ¹H NMR spectroscopy and was found to range from 50:50 to 70:30. The substituents of the aromatic aldehydes influenced the isomer ratio.

Full text of DOI:10.1016/j.tet.2005.02.055

Tetrahedron 61 (2005) 4015–4021
Nitroaldol-reaction of aldehydes in the presence of non-activated
Mg:Al 2:1 hydrotalcite; a possible new mechanism for the
formation of 2-aryl-1,3-dinitropropanes
a
Agnieszka Cwik, Aliz Fuchs, Zoltan Hell and Jean-Marc Clacens
b
a,
c
*
´
aDepartment of Organic Chemical Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
bResearch Group for Organic Chemical Technology, Hungarian Academy of Sciences, H-1521 Budapest, Hungary
c
´
Institut de Recherches sur la Catalyse, 2, Avenue Albert Einstein, 69626 Villeurbanne Cedex, France
Received 27 August 2004; revised 2 February 2005; accepted 18 February 2005
Abstract—Commercially available, non-activated 2:1 Mg:Al hydrotalcite catalyzes the nitroaldol reaction between a variety of aromatic
and aliphatic aldehydes and simple nitroalkanes such as nitromethane and nitroethane. A new mechanism is proposed for the formation of the
1
1,3-dinitropropanes. The threo/erythro diastereoselectivity of the nitroethane-adducts was determined by H NMR spectroscopy and was
found to range from 50:50 to 70:30. The substituents of the aromatic aldehydes influenced the isomer ratio.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
reaction needs to avoid competitive reactions such as aldol
condensation, epimerization of stereogenic centers created
during the reaction, the Cannizzaro reaction, the Tishchenko
reaction, and the Nef-type reaction. Moreover, 2-nitro-
alcohols may be dehydrated to the nitroalkenes that readily
polymerize. Since the Henry reaction creates stereogenic
centers in the products, considerable effort has also been
directed toward the development of enantioselective
versions.9,10 A lot of various new catalysts have recently
been developed, like Amberlyst A-21,11 benzyltrimethyl-
ammonium hydroxide,12 rhodium complex,13 proaza-
The Henry reaction, which is also known as nitroaldol
addition, is a fundamental reaction in organic chemistry.1
The 2-nitroalkanols formed are an important class of
compounds often used as key intermediates in the synthesis
of numerous products. They are particularly versatile
intermediates for the synthesis of nitroalkenes, 2-amino-
alcohols and 2-nitro-ketones. They are also useful inter-
mediates in the synthesis of valuable pharmaceuticals and
pharmaceutical intermediates such as (S)-propanolol,2 or
(S)-(K)-pindolol,3 antibiotics (e.g., ezomycin,4 tuni-
camycin5), natural products such as the sex pheromone of
the Douglas Fir Tussock moth6 or cyclopeptide alkaloids.7
Moreover, 2-nitroalkanol derivatives are important as
fungicides.8 Due to their versatility, a considerable amount
of work about their synthesis has been reported.
phosphatranes,14
Mg–Al–O–tBu
heterobimetallic complexes with lanthanide BINOL
system,16 or guanidines.17
hydrotalcite,15
Nevertheless, the development of new catalyst and pro-
cedure of the Henry reaction has been constantly in focus,
because of the need to reduce the amount of toxic waste
materials and byproducts, to develop new asymmetric
catalyst, and to use less toxic, ‘green’ promoters.
Several organic and inorganic catalysts have been described
in the literature for the preparation of 2-nitroalcohols from
nitroalkane and carbonyl derivatives. These include alkali
metal hydroxides, alkaline earth oxides, carbonates,
bicarbonates, alkoxides, quaternary ammonium salts. Both
protic and aprotic solvents and solvent-free conditions have
been used. The development of new catalysts for the Henry
Nowadays, the use and design of environmental-friendly
solid acid and solid base catalysts has become an important
research target. These materials have a lot of useful
properties, for example, high versatility, easy treatment
and work-up, mild experimental conditions, high yield and
selectivity, they are inexpensive and often reusable.
Hydrotalcites (HT), the anionic layered double
hydroxides (LDHs) have potential application as
Keywords: Hydrotalcite; Henry reaction; 1,3-Dinitropropanes; Mechanism;
Diastereoselectivity.
Corresponding author. Tel.: C36 1 463 1414; fax: C36 1 463 3648;
e-mail: zhell@mail.bme.hu
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.02.055

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A. Cwik et al. / Tetrahedron 61 (2005) 4015–4021
adsorbents, anion-exchangers and basic catalysts. These
materials can be described by the formula [M(II)(1Kx)
mK
x/m
M(III)x (OH)2]xC(A )nH2O, where M(II) is a divalent ion
like Mg, Cu, Ni, Co, Mn, Zn; M(III) is a trivalent ion like Al,
Fe, Cr, Ga; A is the compensating anion like OHK, ClK,
NOK3 , CO32K, SO24K and x is in the range of 0.1–0.33,
closely resembles that of brucite, Mg(OH)2. In HT a number
of the divalent cations are replaced by trivalent cations,
resulting in positively charged layers. Charge-balancing
anions and water molecules are situated in the interlayers.18
Numerous studies on their structure,19 physical properties20
and their catalytic activity have been reported, for example,
in Michael addition,21 Knoevenagel condensation,22 or
Meerwein–Ponndorf–Verley reduction.23
Scheme 1.
Table 1. Effect of solvent on the reaction between 3-nitrobenzaldehyde 1f
and nitromethane using non-activated Mg:Al 2:1 HT
Entry Solvent
Temperature
(8C)
Time
(h)
Conversion
(%)a
1
2
3
4
5
Ethanol
20
20
20
20
20
1
1
1
3.5
5
46
40
65
75
95
Tetrahydrofuran
Nitromethane
Nitromethane
Nitromethane
In this paper, we present the development of an eco-
friendly, simple and convenient, catalytic diastereoselective
method for the synthesis of 2-nitroalkanols from nitro-
alkanes and aldehydes, catalyzed by commercially available
Mg:Al 2:1 hydrotalcite. Our research target was to
a Determined by 1H NMR, based on the starting aldehyde.
Table 2. Henry reaction between various aldehydes and nitromethane using Mg:Al 2:1 HT
2
R
Temperature (8C)
Time (h)
5
Conversiona (%)b
80 (74)b
2a27
20
2b
20
20
5
5
100 (91)b
100 (95)b
2c
2d
20
100
5
5
30
8
2e28
20
5
70 (62)b
2f29
20
5
100 (95)b (94)c
2g30
20
5
60 (54)b
2h15
2i31
2j29
20
20
5
5
86 (80)b
43
20
20
5
10
8
8
2k
20
5
47
2l27
20
20
20
5
5
5
100 (94)b
2m30
2n32
10
52
2o32
2p27
2q32
CH3
CH3–CH2
(CH3)3–C
20
20
20
5
5
5
(67)b
(90)b
40
a Determined by 1H NMR, based on the starting aldehyde.
b Isolated yield in parenthesis.
c Isolated yield after third cycle.

A. Cwik et al. / Tetrahedron 61 (2005) 4015–4021
4017
nitromethane (Scheme 1) in the presence of the catalyst
(6 mol%).
The reaction was carried out at room temperature in ethanol,
tetrahydrofuran, and nitromethane (Table 1). In the first two
cases (entries 1, 2), the conversions were rather similar. Not
surprisingly the use of nitromethane as solvent
Scheme 2.
Scheme 3.
investigate the catalytic activity of this type of hydrotalcite,
which does not need inert atmosphere, can be easily handled
and does not require high-temperature pretreatment or long
procedures like rehydration to be activated.
(20 mol equiv) gave the best results. Increasing the reaction
time led to significant increase in the conversion (see entries
4 and 5). Without HT no reaction was observed.
We investigated the reactivity of a variety of aldehydes
under the same reaction conditions as for 1f, and the
appropriate 2-nitroalcohols 2 were generally obtained in
good to excellent yield. The results are summarized in
Table 2. Compounds 2b,c,d,k have not been described in the
literature yet. Their structures were confirmed by their
spectroscopic data and elemental analysis (see Section 4).
The derivatives of benzaldehydes bearing electron-with-
drawing groups 1b,c,f and pyridine-2-carbaldehyde 1 l were
more reactive, giving 100% conversion, than those with
electron-donating groups 1d,g,i,j. Especially with salicyl-
aldehyde 1d and p-dimethylaminobenzaldehyde 1j the
conversions were very low, even after modification of the
reaction conditions like reaction temperature, or reaction
time, respectively.
2. Results and discussion
Based on the data provided by the manufacturer the
commercial Mg:Al 2:1 hydrotalcite (HAS-type) has the
molecular formula [Mg4Al2(OH)12]CO3, its specific surface
(BET) is 80 m2/g, and the pH of its 5% suspension
(filtered) is 8.6. The elemental analysis of the product
dried at 110 8C for 2 h gave Al2O3 20.5%, MgO 33.8%, CO2
11.0%, ClK!0.1%, SO24K!0.1%, NaC!0.5%.
To our best knowledge until now only patents had published
the use of these materials as catalysts for some polymeris-
ation reactions.24,25 Recently we described the synthesis of
4-hydroxyaryl piperidinols from bis-Mannich bases using
this catalyst.26
Reaction of salicylaldehyde 1d with nitromethane in the
presence of HT at 100 8C for 5 h gave a reaction mixture of
the nitroalcohol and an unknown product in a ratio of 3:1.
This was separated by column chromatography, using
First, we examined the reaction of 3-nitrobenzaldehyde and

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A. Cwik et al. / Tetrahedron 61 (2005) 4015–4021
dichloromethane as eluent, yielding a dark yellow solid. The
mass spectrometry showed that the new product was the 1,3-
nitroethane than nitromethane (8.456 and 10.211 at 25 8C,
respectively37).
1
dinitro-compound 3a. The H and 13C NMR spectra also
When nitroethane was used, the nitroaldol addition of
various aldehydes (Scheme 4) in THF as solvent at 60 8C in
the presence of catalytic amount of Mg:Al HT (2:1)
(6 mol%) gave the corresponding nitroalcohols in good
yields within 6.5 h (Table 3).
confirmed this structure. Repetition of this reaction in
boiling toluene with 1 equiv of nitromethane gave the same
product mixture.
Some related 1,3-dinitro-compounds have already been
described in the literature.33–36 The mechanism of their
formation was assumed to be a three-step base-catalysed
reaction as follows: (1) nitroaldol addition to form the
nitroalcohol; (2) dehydration of this to give the correspond-
ing nitrostyrene; (3) Michael-addition of nitromethane to
the nitrostyrene.33,35 However, during our synthesis we
could not isolate the nitrostyrene or even detect its
formation. This is in good agreement with the statements
in the literature that hydrotalcites are usually unable to
induce dehydration in aldol-type reactions, and with the
results reported by Choudary et al.15,39 for the Henry
reaction (Scheme 2).
Scheme 4.
The reaction can be applied both to aromatic and aliphatic
aldehydes. The highest diastereoselectivity was obtained
with ortho-substituted aldehydes 1b,c,d and with pyridine-
2-carbaldehyde 1h. The threo/erythro diastereoselectivity
was determined by 1H NMR spectroscopy. In their 1H NMR
spectra the extent of vicinal coupling constants of the
products between the a-N–C–H and the a-O–C–H verify the
formation of isomers. In the case of threo isomers JZ7–
9 Hz, and erythro isomers JZ3.2–4 Hz.38 In some cases we
obtained an excess of the erythro-isomer. It is interesting to
note the significant difference in the diastereoselectivity for
ortho-chlorobenzaldehyde with nitroethane compared with
the data reported by Bulbule et al.,38 where 100% threo
isomer was obtained.
When the pure Henry-product 2h was heated in boiling
toluene in the presence of HT, no formation of the
appropriate nitrostyrene was detected, the starting material
could be recovered.
In addition, reacting the pure 3,b-dinitro-styrene (prepared
by the traditional NaOH/methanol method) with nitro-
methane in the presence of HT in boiling nitromethane, the
conversion was quite slow, we observed the total consump-
tion of the styrene only after 3 h boiling.
If the formation of the 1,3-dinitro-compound had occurred
via the nitrostyrene and the formation of this latter had been
so slow, we should have detected the formation of the
nitrostyrene either by TLC of the reaction mixture or by
NMR. This means that in the case of HT, another
mechanism for the formation of the 1,3-dinitro-compounds
should be supposed. Since nitromethane has a tautomeric
aci form (Scheme 3) this could protonate the Henry-
product, this protonation would be followed by the loss of
water and the cation thus formed would be attacked by the
anion of nitromethane. Scheme 3 shows this supposed
reaction pathway. For the verification of this hypothesis we
In these reactions none of the appropriate 1,3-dinitro
compounds were observed. This can be explained with the
lower reaction temperature and the use of THF as solvent,
since in this case a small excess of nitroethane was used. In
the experiments with nitromethane the 1,3-dinitro com-
pounds were not observed if a solvent other than
nitromethane was used.
The catalyst was recovered from the reaction mixture by
simple filtration, washed with nitromethane and treated at
120 8C for 1 h. This could be successfully reused under the
above-reported conditions. These results show that Mg:Al
2:1 hydrotalcite was reusable for three cycles without loss of
activity (Table 2, 2f).
1
reacted 2h with nitroethane at 100 8C for 5 h. H NMR
investigation of the crude reaction product showed the
presence of the appropriate dinitro compound 6 (ca. 30%,
Scheme 3) and no nitrostyrene. The reaction was quite slow
but this can be explained with the lower pKa value of
Table 3. Reaction of nitromethane and aldehydes with Mg:Al 2:1 HT at 100 8C
3
R
Conversion (%)
30
Time (h)
5
Yield of 3 (%)a
3a
10
3b
3c
70
5
5
20
20
100
a Determined by 1H NMR.

A. Cwik et al. / Tetrahedron 61 (2005) 4015–4021
Table 4. Diastereoselective synthesis of 2-nitroalcohols catalysed by Mg:Al 2:1 HT
4019
4
R
Temperature (8C)
Conversiona (%)b
62
Erythro–threoc (%)
4a38
60
40:60
4b38
4c
60
60
60
60
86
85
32
57
66:34
70:30
70:30
30:70
4d
4e
4f38
60
(81)b
50:50
4g31
4h40
60
60
60
45:55
65:35
100 (95)b
4i41
4j42
CH3
CH3–CH2
20
60
(64)b
(92)b
47:53
48:52
1
a Determined by H NMR, based on the starting aldehyde.
b Isolated yield in parenthesis.
c Calculated by 1H NMR.
3. Conclusion
4.2. Characterization of hydrotalcite
The Mg:Al 2:1 hydrotalcite was the commercially product
In summary, we have shown that commercially available
non-activated Mg:Al 2:1 hydrotalcite is a highly efficient
basic catalyst for the Henry reaction. In the reaction with
nitromethane at room temperature we obtained only
2-nitroalcohols in good to excellent yields. By increasing
the temperature to 100 8C 1,3-dinitro compounds were
obtained. The advantages of our method developed are the
following: the reaction is eco-friendly since it minimises
harmful reagents; the experimental and work-up procedure
is very simple; the catalyst does not require any complicated
pre-treatment and is recyclable, and this method realises a
new application for the commercial HT product.
of Sud-Chemie AG, Munchen (HSA-type). The catalyst was
¨
dried at 120 8C for 1 h before use.
¨
The presence of the pure hydrotalcite structure was
confirmed by XRD pattern, and by thermogravimetry. The
XRD pattern of the HT sample exhibits the characteristic
reflections corresponding to a ordered-crystalline layered
structure (Fig. 1).16 From the (003) reflection (2QZ11.468)
we calculated the 7.72 A basal interlayer spacing. Corre-
spondingly, from the (110) reflection (2QZ60.418) the
˚
brucite-like layer thickness is 3.06 A.
˚
4. Experimental
4.1. General
Commercially available starting materials were used with-
1
out further purification. H NMR and 13C NMR spectra
were recorded on Bruker Avanche 300 (300 MHz) and
Bruker Avance DRX-500 (500 MHz) spectrometer using
TMS as internal standard. Melting points were determined
on Gallenkamp apparatus and were uncorrected. IR spectra
were recorded on a Perkin–Elmer Model 1600 instrument.
Figure 1.
X-ray diffraction (XRD) pattern was recorded on Philips
PW 1050/81 instrument with Cu Ka1 radiation (lZ
˚
1.54184 A) equipped with EVA Diffract-AT (Siemens
TLC was performed on Merck Kieselgel plates (60 F254
)
with an eluent: hexane–acetone 4:1. Column chromato-
graphy was carried out on Merck Kieselgel 60–240 mesh
using dichloromethane as eluent. The spectral and physical
data of the known compounds were identical with those
reported in the literature (for references see Tables 2 and 4).
The new compounds gave satisfactory elemental analysis.
Socabim) software. The samples were step-scanned in
steps of 0.028 (2Q) in the range from 3 to 708. Thermo-
gravimetric measurements (TG) were performed using
Setaram Labsys TG equipment (Setaram, France) with
10.9 mg test material at a heating rate of 10 K minK1 in the
temperature range 20–700 8C in nitrogen atmosphere. The

4020
A. Cwik et al. / Tetrahedron 61 (2005) 4015–4021
parameters obtained corresponded to those reported in the
literature.15
NMR (75 MHz, CDCl3) d (ppm): 71.2, 88.1, 127.8, 128.5,
130.1, 130.8, 132.9, 136.4. MS (EI): m/z (%) 279 (MC, 5),
261 (6), 232 (15), 214 (21), 172 (36). C8H8NO4Br. Anal.
Calcd C 36.64, H 5.34, N 3.05. Found C 36.87, H 5.29, N
3.16.
4.3. General procedure for the Henry reaction of
nitromethane and various aldehydes
A mixture of the aldehyde (5 mmol) and hydrotalcite
(0.13 g) in nitromethane (5.6 ml, 0.1 mol) was stirred at
room temperature for 5 h. The catalyst was filtered off and
washed with nitromethane (3 ml). The filtrate was evapor-
ated, and the residue, if necessary, was washed with
saturated aq NaHSO3 (2!10 ml). The organic phase was
dried over anhydrous MgSO4 and concentrated to give the
corresponding nitroalcohol derivative. The known products
were characterized by comparing the 1H NMR and melting
point data with those reported in the literature (for
references see Table 2).
4.5. General procedure for the reaction of nitroethane
and various aldehydes
A mixture of the aldehyde (5 mmol) and nitroethane
(6 mmol) with hydrotalcite (0.13 g) in THF (10 ml) was
stirred at 60 8C for 6.5 h. Then the catalyst was filtered off
and washed with THF (3 ml). The filtrate was evaporated,
and the residue, if necessary, was washed with saturated aq
NaHSO3 (2!10 ml). The organic phase was dried over
anhydrous MgSO4 and concentrated to give the correspond-
ing nitroalcohol derivative. The threo/erythro diastereo-
1
selectivity of the products was determined by H NMR
4.4. Spectral data of the new compounds
spectroscopy based on the vicinal coupling constants of the
products between the a-N–C–H and the a-O–C–H (see
Table 4). The known products were characterized by
comparing the 1H NMR and melting points data with
those reported in the literature (for references see Table 4).
4.4.1. 1-(2-Chlorophenyl)-2-nitro-ethanol (2b). 0.92 g
(91%), yellow oil, IR (neat): 1377, 1555, 3530 H NMR
1
(500 MHz, CDCl3) d (ppm): 3.35 (1H, br s, OH), 4.43 (1H,
dd, J1Z2 Hz, J2Z9 Hz, CH2), 4.64 (1H, dd, J1Z2 Hz, J2Z
11.5 Hz, CH2), 5.81 (1H, d, JZ9.5 Hz, CHOH), 7.26–7.39
(3H, m, Ph), 7.62–7.63 (1H, m, Ph). 13C NMR (75 MHz,
CDCl3) d (ppm): 71.2, 86.3, 127.9, 128.5, 130.7, 131.1,
132.7, 136.5. MS (EI): m/z (%) 201 (MC, 5), 185 (7), 183
(21), 156 (8), 154 (24), 143 (100), 141 (33), 110 (26).
C8H8NO3Cl. Anal. Calcd C 47.64, H 6.95, N 3.98. Found C
47.86, H 7.06, N 4.07.
4.6. Spectral data of the new compounds
4.6.1. 1-(2-Bromophenyl)-2-nitro-propan-1-ol (4c).
1.11 g (85%), yellow oil, IR (neat): 1372, 1548, 3520 H
1
NMR (300 MHz, CDCl3) d (ppm): 1.45 (3H, d, JZ6.6 Hz,
CH3), 1.47 (3H, d, JZ6.3 Hz, CH3), 3.23 (1H, br s, OH), 4.9
(1H, m, CHCH3), 5.6 (1H, d, JZ8.4 Hz, threo-CHOH), 5.81
(1H, d, JZ4.4 Hz, erythro-CHOH), 7.28–7.64 (3H, m, Ph),
7.9 (1H, m, Ph). 13C NMR (75 MHz, CDCl3) d (ppm): 16.1,
72.5, 73.9, 84.0, 88.3, 127.2, 128.2, 130.3, 132.1, 133.3,
137.5. MS (EI): m/z (%) 260 (MC, 2), 243 (21), 213 (15),
196 (100), 186 (29), 155 (44). C9H10NO3Br. Anal. Calcd C
41.54, H 3.80, N 5.38. Found C 41.82, H 3.95, N 5.56.
4.4.2. 1-(2-Bromophenyl)-2-nitro-ethanol (2c). 1.17 g
(95%), yellow oil, IR (neat): 1368, 1550, 3511 H NMR
1
(500 MHz, CDCl3) d (ppm): 3.12 (1H, br s, OH), 4.45 (1H,
dd, J1Z3.5 Hz, J2Z9.5 Hz, CH2), 4.67 (1H, dd, J1Z
2.5 Hz, J2Z11.5 Hz, CH2), 5.81 (1H, d, JZ9.5 Hz,
CHOH), 7.21–7.26 (1H, m, Ph), 7.38–7.41 (1H, m, Ph),
7.56–7.61 (1H, m, Ph), 7.65–7.68 (1H, m, Ph). 13C NMR
(75 MHz, CDCl3) d (ppm): 71.4, 87.2, 128.1, 128.8, 130.9,
131.4, 132.9, 137.1. MS (EI): m/z (%) 246 (MC, 2), 230 (8),
228 (7), 200 (6), 198 (6), 185 (14), 183 (14), 156 (100).
C8H8NO3Br. Anal. Calcd C 38.95, H 3.25, N 5.68. Found C
39.09, H 3.41, N 5.73.
4.6.2. 1-(2-Fluorophenyl)-2-nitro-propan-1-ol (4d).
0.32 g (32%), yellow oil, IR (neat): 1366, 1540, 3540 H
1
NMR (300 MHz, CDCl3) d (ppm): 1.38 (3H, d, JZ6.9 Hz,
CH3), 1.47 (3H, d, JZ6.9 Hz, CH3), 3.97 (1H, m, OH), 4.84
(1H, m, CHCH3), 5.42 (1H, d, JZ9.1 Hz, threo-CHOH),
5.74 (1H, d, JZ3.3 Hz, erythro-CHOH), 7.11–7.61 (3H, m,
Ph), 7.85 (1H, m, Ph). 13C NMR (75 MHz, CDCl3) d (ppm):
16.3, 73.1, 74.6, 87.8, 88.9, 128.2, 128.9, 131.4, 131.7,
133.1, 137.8. MS (EI): m/z (%) 199 (MC, 5), 181 (20), 152
(100), 134 (38), 125 (28), 95 (10). C9H10NO3F. Anal. Calcd
C 54.27, H 5.03, N 7.04. Found C 54.49, H 5.26, N 6.96.
4.4.3. 1-(2-Hydroxyphenyl)-2-nitro-ethanol (2d). 0.27 g
(30%), yellow oil, IR (neat): 1382, 1558, 3528 H NMR
1
(500 MHz, CDCl3) d (ppm): 4.31 (1H, s, OH), 4.61 (1H, dd,
J1Z3 Hz, J2Z10.5 Hz, CH2), 4.76 (1H, dd, J1Z3 Hz, J2Z
10 Hz, CH2), 5.61 (1H, d, JZ9.5 Hz, CHOH), 6.98–7.04
(2H, m, Ph), 7.5–7.57 (2H, m, Ph), 11.02 (1H, s, PhOH). 13C
NMR (75 MHz, CDCl3) d (ppm): 70.9, 84.5, 127.4, 128.4,
128.9, 130.6, 131.1, 135.4. MS (EI): m/z (%) 183 (MC, 2),
165 (7), 136 (15), 123 (100), 93 (10). C8H9NO4. Anal. Calcd
C 52.46, H 7.65, N 4.92. Found C 52.63, H 7.78, N 5.06.
4.6.3. 1-(3-Hydroxyphenyl)-2-nitro-propan-1-ol (4e).
0.56 g (57%), yellow oil, IR (neat): 1352, 1522, 3532 H
1
NMR (300 MHz, CDCl3) d (ppm): 1.31 (3H, d, JZ6.6 Hz,
CH3), 1.48 (3H, d, JZ6.6 Hz, CH3), 3.49 (1H, m, OH), 4.71
(1H, m, CHCH3), 4.95 (1H, d, JZ9 Hz, threo-CHOH), 5.34
(1H, d, JZ3.6 Hz, erythro-CHOH), 6.77–7.12 (4H, m, Ph).
13C NMR (75 MHz, CDCl3) d (ppm): 16.4, 73.3, 75.3, 87.6,
88.2, 122.1, 124.1, 130.4, 131.8, 133.4, 137.5. MS (EI): m/z
(%) 197 (MC, 2), 179 (5), 132 (15), 123 (68), 121 (100), 105
(15), 93 (10). C9H11NO4. Anal. Calcd C 54.82, H 5.58, N
7.11. Found C 54.99, H 5.72, N 7.38.
4.4.4. 1-(2-Hydroxy-5-bromophenyl)-2-nitro-ethanol
(2k). 0.66 g (47%), yellow oil, IR (neat): 1382, 1557,
3518 1H NMR (500 MHz, CDCl3) d (ppm): 3.61 (1H, br s,
OH), 4.59 (1H, dd, J1Z3 Hz, J2Z10.5 Hz, CH2), 4.71 (1H,
dd, J1Z3 Hz, J2Z10 Hz, CH2), 5.59 (1H, d, JZ10 Hz,
CHOH), 6.69 (1H, d, JZ9 Hz, Ph), 7.32–7.36 (1H, m, Ph),
7.65–7.69 (1H, d, JZ2 Hz, Ph), 10.93 (1H, s, PhOH). 13C

A. Cwik et al. / Tetrahedron 61 (2005) 4015–4021
4021
´
7. Heffner, R. J.; Jiang, J.; Jouillie, M. M. J. Am. Chem. Soc.
1992, 114, 10181.
4.7. General procedure for the synthesis of 1,3-dinitro
compounds
8. Mikite, G.; Jakucs, K.; Darvas, F.; Lopata, A. Pestic. Sci. 1982,
13, 557.
A mixture of the aldehyde (5 mmol) and hydrotalcite
(0.13 g) in nitromethane (5.6 ml, 0.1 mol) was stirred at
100 8C for 5 h. Then the catalyst was filtered off and washed
with nitromethane (3 ml). The solvent was evaporated, the
residue was purified by column chromatography (eluent:
dichloromethane) to give the new compounds.
9. Risgaard, T.; Gothelf, K. V.; Jorgersen, K. A. Org. Biomol.
Chem. 2003, 1, 153.
10. Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw,
J. T.; Downey, C. W. J. Am. Chem. Soc. 2003, 125, 12692.
11. Ballini, R.; Bosica, G.; Forconi, P. Tetrahedron 1996, 52,
1677.
12. Bulbule, V. J.; Jnaneshwara, G. K.; Deshmukh, R. R.; Borate,
H. B.; Deshpande, V. H. Synth. Commun. 2001, 31, 3623.
13. Kiyooka, S. I.; Tsutsui, T.; Maeda, H.; Kaneko, Y.; Isobe, K.
Tetrahedron Lett. 1995, 36, 6531.
4.7.1. 2-(2-Hydroxyphenyl)-1,3-dinitro-propane (3a).
0.34 g (30%), dark yellow oil, IR (neat): 1380, 1556, 3482
1H NMR (500 MHz, CDCl3) d (ppm): 4.37–4.45 (1H, m,
CH), 4.83–4.88 (4H, m, CH2), 5.91 (1H, br s, OH), 6.73 (1H,
d, JZ7.8 Hz, Ph), 6.85–6.90 (1H, m, Ph), 7.10–7.19 (2H, m,
Ph). 13C NMR (75 MHz, CDCl3) d (ppm): 40.3, 76.6, 111.9,
125.2, 128.1, 131.5, 132.0, 154.4. MS (EI): m/z (%) 226
(MC, 10), 210 (12), 192 (15), 162 (5), 150 (29), 149 (83),
117 (6), 77 (20), 60 (4). C9H10N2O5. Anal. Calcd C 47.79, H
4.42, N 12.39. Found C 47.25, H 4.11, N 12.09.
14. Kisanga, P. B.; Verkade, J. G. J. Org. Chem. 1999, 64, 4298.
15. Choudary, B. M.; Kantam, M. L.; Kavita, B. J. Mol. Catal. A
2001, 169, 193.
16. Sasai, H.; Suzuki, T.; Arai, S.; Shibasaki, M. J. Am. Chem. Soc.
1992, 114, 4418.
´ ´
17. Chinchilla, R.; Najera, C.; Sanchez-Agullo, P. Tetrahedron:
Asymmetry 1994, 5, 1393.
18. Cavani, F.; Trifiro, F.; Vaccari, A. Catal. Today 1991, 11, 173.
19. Reichle, W. T. Chemtech 1986, 1, 58.
4.7.2. 2-(4-Chlorophenyl)-1,3-dinitro-propane (3b).
0.86 g (70%), yellow oil, IR (neat): 1374, 1548 H NMR
1
20. Tichit, D.; Lhouty, M. H.; Guida, A.; Chiche, B. H.; Figueras,
F.; Auroux, A.; Bartalini, D.; Garrone, E. J. Catal. 1995, 151,
50.
(500 MHz, CDCl3) d (ppm): 4.30–4.35 (1H, m, CH), 4.74–
4.78 (4H, m, CH2), 7.18 (2H, d, JZ6.3 Hz, Ph), 7.35 (2H, d,
JZ8.4 Hz, Ph). 13C NMR (75 MHz, CDCl3) d (ppm): 41.2,
76.6, 128.8, 129.9, 130.3, 135.3. MS (EI): m/z (%) 244 (MC,
15), 197 (30), 151 (38), 137 (41), 125 (27), 115 (100), 112
(10), 89 (16), 77 (22). C9H9N2O4Cl. Anal. Calcd C 44.17, H
3.68, N 11.45. Found C 43.87, H 3.32, N 11.09.
21. Choudary, B. M.; Kantam, M. L.; Reddy, Ch. R. V.; Rao,
K. K.; Figueras, F. J. Mol. Catal. A 1999, 146, 279.
22. Choudary, B. M.; Kantam, M. L.; Kavita, B.; Reddy, Ch. K.;
Rao, K. K.; Figueras, F. Tetrahedron Lett. 1998, 39, 3555.
23. Kumbhar, P. S.; Sanchez-Valente, J.; Lopez, J.; Figueras, F.
Chem. Commun. 1998, 535.
4.7.3. 2-(3-Nitrophenyl)-1,3-dinitro-propane (3c). 1.28 g
(100%), dark yellow oil, IR (neat): 1365, 1584 H NMR
1
24. Staeuber, H.; Voerckel, V.; Wiegner, J.-P. PCT Int. Appl.
2003, Pat. Appl. No. WO 2002-US18991.
(300 MHz, CDCl3) d (ppm): 4.52–4.55 (1H, m, CH), 4.89–
4.93 (4H, m, CH2), 7.62–7.66 (1H, m, Ph), 7.76–7.79 (1H,
m, Ph), 8.17–8.20 (1H, m, Ph), 8.20–8.24 (1H, s, Ph). 13C
NMR (75 MHz, CDCl3) d (ppm): 40.8, 77.3, 124.4, 128.6,
130.4, 134.8, 137.5, 148.79. C9H9N3O6. Anal. Calcd C
42.35, H 3.53, N 16.47. Found C 42.02, H 3.23, N 16.11.
25. Takushima, T.; Takamoto, Y.; Tenra, T.; Miyaji, N. Jpn. Kokai
Tokkyo Koho 1999, Pat. Appl. No. Jp. 1997-300161.
26. Cwik, A.; Fuchs, A.; Hell, Z.; Clacens, J.-M. J. Mol. Catal. A
2004, 219, 377.
27. Meyers, A. I.; Sircar, J. C. J. Org. Chem. 1967, 32, 413.
28. Kamlet, 1938, US 2151517.
29. Boileau, J. Bull. Soc. Chim. Fr. 1953, 1007.
30. Youn, S. W.; Kim, Y. H. Synth. Lett. 2000, 6, 880.
31. Bailey, K. Tetrahedron 1972, 28, 3981.
Acknowledgements
32. Lucet, D.; Sabelle, S.; Kostelitz, O.; Le Gall, T.; Mioskowski,
Ch. Eur. J. Org. Chem. 1999, 10, 2583.
The financial support of the Hungarian Scientific Research
Fund (OTKA T-037757) is gratefully acknowledged. This
publication was prepared within the framework of the
Hungarian-French intergovernmental scientific and techno-
33. Lambert, A.; Lowe, A. J. Chem. Soc. 1947, 1517.
34. Alcantara, M. D.; Escribano, F. C.; Gomez-Sanchez, A.;
Dianez, M. J.; Estrada, M. B.; Castro, A. L.; Perez-Garrido, S.
Synthesis 1996, 1, 64.
´
logical cooperation, TeT project No. F-8/02.
35. Niazimbetova, Z. I.; Evans, D. H.; Liable-Sands, L. M.;
Rheingold, A. L. J. Electrochem. Soc. 2000, 147, 256.
36. Ferro, A.; Rezende, M. C.; Sepulveda-Boza, S.; Reyes-Parada,
M.; Cassels, B. K. J. Chem. Res. 2001, 7, 294.
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