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Henry Reaction
Henry Reaction
2 (2005) 1195
A series of 1-aryl-2-nitroalkan-1-ols (5a ± m; Table 2) was prepared in yields of 64 ± 94% by Henry reaction
between aromatic aldehydes and nitroalkanes in the presence of a dual catalytic system of KOH and
polystyrene-supported tributylammonium chloride (PsTBAC; 2). The reactions were performed either in H2O
containing 10% of THF or, in the case of liquid reagents (aldehydes and nitroalkanes), in neat H2O at room
temperature. The immobilized phase-transfer catalyst, designed to be used for large-scale industrial processes,
could be easily separated from the products, and effectively re-used several times, basically without loss in
activity.
solubility [12] of most organic reagents in H2O is not an obstacle to their reactivity,
which often is even higher in the absence of organic co-solvents.
Herein, we report an environmentally benign process for the simple, polymer-
supported phase-transfer catalysis of nitro alcohols in aqueous medium.
Table 1. Model Nitroaldol Reaction with Different Catalysts. Conditions: H2O/THF 100 : 10, r.t. The reactions
work similarly well in neat H2O for liquid reagents.
We found that THF as a co-solvent is not really necessary for the reactions to
proceed. The results hardly changed in neat H2O, when the reactants were liquids at
ambient temperature. When we used an excess of nitroalkane (1.5 equiv.), the reaction
CHEMISTRY & BIODIVERSITY ± Vol. 2 (2005) 1197
was faster, but the yield only slightly increased. Since benzaldehyde is prone to air
oxidation, traces of benzoic acid should be neutralized in situ with base by adjusting a
pH of 8 ± 9, before the Henry reaction is started. Also, the reaction time should be kept
minimal to avoid side reactions.
As shown in Table 1, Et3N (Entries 1 and 5) is an efficient catalyst for nitroaldol
reactions. However, stoichiometric amounts and recycling problems limit its use in
industrial processes. When KOH, the base in the classical Henry reaction, was solely
used (Entry 2), the yield decreased due to side reactions. When PsTEAC or PsTBAC
(0.1 equiv.) were used in combination with a small amount of KOH, good results were
obtained. Thereby, PsTBAC (2) gave slightly higher yields of 5 compared to PsTEAC
(1).
Encouraged by these results, other aldehydes were examined as substrates under
similar conditions of the dual catalytic system PsTBAC/KOH. Thereby, 10% of THF
(0.5 ml) was added as a co-solvent, since the solid aromatic aldehydes had to be brought
into the aqueous solution. The results of these experiments are collected in Table 2.
Table 2. Synthesis of Nitro Alcohols 5 by Henry Reaction with PsTBAC (2). Condition, PsTBAC (2; 0.1 mol-
equiv.), KOH, H2O/THF 100 : 10, r.t.
Experimental Part
General. All commercially available solvents and regents were used without further purification. Thin-layer
chromatography (TLC) was performed on silica-gel F 254 plates; visualization under UV light. Flash-column
chromatography (FC) was performed on silica gel (100 ± 200 mesh). 1H- and 13C-NMR Spectra were recorded at
400 and 100 MHz, resp., and were referenced to internal solvent signals; d in ppm, J in Hz. All compounds were
fully characterized, including GC/MS (Agilent 6890N, 5793N, HP-5).
Syntheses of the Catalysts PsTEAC (1) and PsTBAC (2). To a flask, Chloromethyl resin (5.0 g, 200 ±
400 mesh, 3.5 mmol Cl/g) was added in DMF (15 ml), and the resin was stirred for 2 h. Then, Et3N or Bu3N
(20 ml) was added, and the mixture was heated at 808 for 24 h, filtered, and dried in vacuum. The residue was
marinated in anh. EtOH, and stirred for 12 h at 808. Then, the solid-supported catalyst was dried in vacuum. The
concentration of onium cations, which is the same as that of the Cl anions, was determined indirectly by
titration of Cl with AgNO3 soln.
Typical Procedure for Nitroaldol Reactions Catalyzed by PsTBAC. To a soln. of, e.g., benzaldehyde (3a;
0.351 g, 3.31 mmol) in H2O (5 ml) and THF (0.5 ml) 1), nitroethane (4b; 0.272 g, 3.63 mmol), one drop of aq.
40% KOH soln., and PsTBAC (2; 0.20 g, ca. 10 mol-% of onium ions) were added. The mixture was stirred at r.t.
for 8 h. Then, excess H2O was added, the suspension was filtered (B¸chner funnel), and washed with AcOEt.
The aq. layer was extracted with AcOEt (3 15 ml), the org. phase was dried (Na2SO4 ) and concentrated, and
the crude product was purified by FC (SiO2 ; AcOEt/petroleum ether 1 : 10) to afford 89% of 2-nitro-1-
phenylpropan-1-ol (5b).
Data of 2-Nitro-1-phenylethanol (5a). 1H-NMR (CDCl3 ): 3.30 ± 3.70 (1 H); 4.36 ± 4.51 (2 H); 5.31 (1 H),
7.22 ± 7.80 (5 H). 13C-NMR (CDCl3 ): 70.74 (C(1)); 80.87 (C(2)); 125.46 ± 138.09 (Ph).
Data of 2-Nitro-1-phenylpropan-1-ol (5b). 1H-NMR (CDCl3 ; anti-isomer): 1.45 (3 H); 2.90 ± 3.30 (1 H);
4.72 (1 H); 5.32 (1 H); 7.31 ± 7.85 (5 H). 1H-NMR (CDCl3 ; syn-isomer): 1.26 (3 H); 2.90 ± 3.30 (1 H); 4.74 (1 H);
4.97 (1 H); 7.31 ± 7.85 (5 H).
Data of 1-(4-Bromophenyl)-2-nitroethan-1-ol (5c). 1H-NMR (CDCl3 ): 3.60 ± 4.00 (1 H); 4.47 ± 4.59 (2 H);
5.41 (1 H); 7.25 ± 7.72 (4 H).
Data of 1-(4-Chlorophenyl)-2-nitroethan-1-ol (5d). 1H-NMR (CDCl3 ): 3.30 ± 3.70 (1 H); 4.42 ± 4.55 (2 H);
5.38 (1 H); 7.27 ± 7.76 (4 H).
Data of 1-(2-Chlorophenyl)-2-nitroethan-1-ol (5e). 1H-NMR (CDCl3 ): 3.40 ± 3.80 (1 H); 4.40 (1 H); 4.60
(1 H); 5.78 (1 H); 7.22 ± 7.33 (3 H); 7.41 ± 7.61 (1 H).
Data of 2-Nitro-1-(4-nitrophenyl)ethan-1-ol (5f). 1H-NMR (CDCl3 ): 3.80 ± 4.20 (1 H); 4.64 (2 H); 5.64
(1 H); 7.62 ± 8.37 (4 H).
Data of 1-(2-Methoxyphenyl)-2-nitroethan-1-ol (5g). 1H-NMR (CDCl3 ): 3.30 ± 3.70 (1 H); 4.59 (2 H); 5.60
(1 H); 6.87 ± 7.79 (4 H).
Data of 1-(4-Methylphenyl)-2-nitroethan-1-ol (5h). 1H-NMR (CDCl3 ): 2.37 (3 H); 3.60 ± 4.00 (1 H); 4.42 ±
4.59 (2 H); 5.38 (1 H); 7.15 ± 7.74 (4 H).
Data of 1-(4-Chlorophenyl)-2-nitropropan-1-ol (5i). 1H-NMR (CDCl3 ; anti-isomer): 1.46 (3 H); 3.30 ± 3.70
(1 H); 4.63 (1 H); 5.35 (J 4.0, 1 H); 7.28 ± 7.81 (4 H). 1H-NMR (CDCl3 ; syn-isomer): 1.28 (3 H); 3.30 ± 3.70
(1 H); 4.75 (1 H); 5.00 (J 8.0, 1 H); 7.28 ± 7.81 (4 H).
Data of 1-(2-Chlorophenyl)-2-nitropropan-1-ol (5j). 1H-NMR (CDCl3 ; anti-isomer): 1.41 (3 H); 3.40 ± 3.80
(1 H); 4.08 (1 H); 5.84 (J 2.8, 1 H); 7.27 ± 7.64 (4 H). 1H-NMR (CDCl3 ; syn-isomer): 1.41 (3 H); 3.40 ± 3.80
(1 H); 4.87 (1 H); 5.60 (J 4.8, 1 H), 7.27 ± 7.64 (4 H).
Data of 2-Nitro-1-(4-nitrophenyl)propan-1-ol (5k). 1H-NMR (CDCl3 ; anti-isomer): 1.48 (3 H); 3.80 ± 4.20
(1 H); 4.10 (1 H); 5.59 (J 3.6, 1 H), 7.62 ± 8.40 (4 H). 1H-NMR (CDCl3 ; syn-isomer): 1.37 (3 H); 3.80 ± 4.20
(1 H); 4.80 (1 H); 5.22 (J 4.4, 1 H), 7.62 ± 8.40 (4 H).
Data of 1-(2-Methoxyphenyl)-2-nitropropan-1-ol (5l). 1H-NMR (CDCl3 ; anti-isomer): 1.42 (3 H); 3.30 ±
3.70 (1 H); 3.85 (3 H); 4.88 (1 H); 5.55 (J 3.6, 1 H); 6.86 ± 7.80 (4 H). 1H-NMR (CDCl3 ; syn-isomer): 1.30
(3 H); 3.30 ± 3.70 (1 H); 3.85 (3 H); 4.98 (1 H); 5.16 (J 8.8, 1 H); 6.86 ± 7.80 (4 H).
Data of 1-(4-Methylphenyl)-2-nitropropan-1-ol (5m). 1H-NMR (CDCl3 ; anti-isomer): 1.45 (3 H); 2.32
(3 H); 4.64 (1 H); 5.26 (J 4.4, 1 H); 7.13 ± 7.73 (4 H). 1H-NMR (CDCl3 ; syn-isomer): 1.24 (3 H); 2.32 (3 H);
4.73 (1 H); 4.93 (J 9.2, 1 H); 7.13 ± 7.73 (4 H).
This study was financially supported in part by the Natural Science Foundation of China (No. 29933050 and
20373082).
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