Rapid Microwave-Assisted Henry Reaction in Solvent-Free Processes

Changsheng Gan; Xing Chen; Guoyin Lai; Zhiyong Wang

doi:10.1055/s-2006-932449

LETTER

Rapid Microwave-Assisted Henry Reaction in Solvent-Free Processes

Changsheng Gan, Xing Chen, Guoyin Lai, Zhiyong Wang*
Hefei national laboratory for Physical Science at Microscale and Department of Chemistry, University of Science & Technology of China, Hefei 230026, P. R. of China
Fax: +86(551)3603185; e-Mail: zwang3@ustc.edu.cn;

Abstract

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Abstract

The solvent-free Henry reactions of nitromethane with a series of carbonyl compounds were studied under microwave irradiation. By using different bases and Lewis acids, the solvent-free nitroaldol reaction of aldehydes were realized under microwave condition, affording the corresponding adducts with high yields. Particularly, aliphatic ketones, which were hardly carried out this reaction, could be the reaction substrates in the nitroaldol reactions by employment of 1,4-diazabicyclo[2.2.2]octane (DABCO) under a similar conditions, giving the corresponding adducts with moderate to good yields.

Key words

Henry reaction - microwave - Lewis acid - solvent-free - aliphatic ketones

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References

References and Notes

For recent reviews dealing with the Henry reaction and its use, see:

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The Henry reactions were carried out in Emrys Creator microwave reactor from Personal Chemistry, Sweden. The mixture after reaction was cooled down with compressed air produced by SPB-3 Automatic Air Source from the Analytic Technique Institute of Agilent in Beijing.
Typical Experimental Procedure for the Microwave-Assisted Henry Reaction of Benaldehydes with Nitromethane. To a 10 mL glass tube was added a mixture of benzaldehyde (0.212 g, 2 mmol), nitromethane (0.305 g, 5 mmol), Et₃N (0.202 g, 2 mmol), MgSO₄ (0.120 g, 1 mmol), and magnetic stir bar. The vessel was sealed with a pressure lock and placed into the cavity of microwave reactor. The reaction mixture was pre-stirred for 30 s. An initial microwave irradiation of 250 W was used, the temperature being ramped from r.t. to 80 °C. This step took about 50-60 s. At 80 °C the vessel was then held for a given time, as shown in Table [2] . After cooling the reaction mixture to r.t. with compressed air, which took about 5 min, the vessel was opened and 5 mL of Et₂O was added to the mixture. Then it was filtered through a silica gel plug. The filtrate was washed with H₂O, and dried over anhyd MgSO₄. After the removal of solvent, the crude product was purified by short column chromatography with PE-EtOAc (5:1, v/v) as the eluent. For those substrates listed in entries 5 and 6 in Table [1] and entries 4 and 5 in Table [2] , evaporation of Et₂O gave the pure products.

Spectral Data of Nitroalcohol Compounds.1-Phenyl-2-nitroethanol: IR (film): 3429, 1553 cm^-1. ¹H NMR (CDCl₃): δ = 3.24 (br, 1 H), 4.50 (m, 1 H), 4.59 (m, 1 H), 5.43 (dd, J = 3.2, 9.5 Hz, 1 H), 7.38-7.42 (m, 5 H) ppm. ¹³C NMR: 70.7, 80.9, 125.9, 128.6, 128.7, 138.2 ppm. HRMS: m/z calcd: 167.0582 [M]⁺; found: 167.0579.
1-(4-Chlorophenyl)-2-nitroethanol: IR (film): 3431, 1597, 1556 cm^-1. ¹H NMR (CDCl₃): δ = 3.19 (br, 1 H), 4.48 (dd, J = 3.4, 13.4 Hz, 1 H), 4.57 (dd, J = 9.2, 13.4 Hz, 1 H), 5.44 (dd, J = 3.4, 9.2 Hz, 1 H), 7.34 (d, J = 8.6 Hz, 2 H), 7.38 (d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR: 70.3, 81.0, 127.4, 129.2, 134.8, 136.6 ppm. HRMS: m/z calcd: 201.0193 [M]⁺; found: 201.0191.
1-(4-Nitrophenyl)-2-nitroethanol: IR (film): 3529, 1556, 1519 cm^-1. ¹H NMR (CDCl₃): δ = 3.20 (br, 1 H), 4.55-4.66 (m, 2 H), 5.62 (m, 1 H), 7.64 (d, J = 8.6 Hz, 2 H), 8.27 (d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR: 70.0, 80.7, 124.2, 127.0, 145.1, 148.1 ppm. HRMS: m/z calcd 212.0433 [M]⁺; found: 212.0441.
1-(2-Methoxyphenyl)-2-nitroethanol: IR (film): 3537, 2922, 1552, 1493, 1378 cm^-1. ¹H NMR (CDCl₃): δ = 3.13 (d, J = 5.7 Hz, 1 H), 3.89 (s, 3 H), 4.58 (dd, J = 8.9, 13.0 Hz, 1 H), 4.66 (dd, J = 3.3, 13.0 Hz, 1 H), 5.65 (m, 1 H), 6.92 (m, 1 H), 7.03 (m, 1 H), 7.34 (m, 1 H), 7.45 (m, 1 H) ppm. ¹³C NMR: 55.6, 67.9, 80.0, 111.5, 121.3, 122.2, 126.1, 129.9, 157.2 ppm. HRMS: m/z calcd: 197.0688 [M]⁺; found: 197.0693.
1-(4-Methoxyphenyl)-2-nitroethanol: IR (film): 3441, 1553 cm^-1. ¹H NMR (CDCl₃): δ = 2.93 (br, 1 H), 3.80 (s, 3 H), 4.46 (dd, J = 3.2, 13.1 Hz, 1 H), 4.59 (dd, J = 9.5, 13.1 Hz, 1 H), 5.38 (dd, J = 3.2, 9.5 Hz, 1 H), 6.91 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR: 56.1, 73.1, 84.9, 114.4, 129.3, 135.2, 158.1 ppm. HRMS: m/z calcd 197.0688 [M]⁺; found: 197.0694.
1-(1-Naphthyl)-2-nitroethanol: IR (film): 3448, 1553, 1378 cm^-1. ¹H NMR (CDCl₃): δ = 2.92 (br, 1 H), 4.61-4.71 (m, 2 H), 6.26 (m, 1 H), 7.51-7.60 (m, 3 H), 7.75-7.77 (m, 1 H), 7.84-7.90 (m, 2 H), 8.02 (m, 1 H) ppm. ¹³C NMR: 68.2, 80.8, 121.9, 123.8, 125.5, 126.0, 127.0, 129.2, 129.2, 129.6, 133.7, 133.8 ppm. HRMS: m/z calcd: 217.0739 [M]⁺; found: 217.0735.
1-Nitrooctan-2-ol: IR (film): 3410, 1555 cm^-1. ¹H NMR (CDCl₃): δ = 0.84 (t, J = 6.8 Hz, 3 H), 1.18-1.39 (m, 6 H), 1.40-1.54 (m, 4 H), 3.14 (br, 1 H), 4.22-4.30 (m, 1 H), 4.32-4.40 (m, 2 H) ppm. ¹³C NMR: 14.0, 22.5, 25.0, 29.0, 31.6, 33.8, 68.8, 80.8 ppm. HRMS: m/z calcd 175.1208 [M]⁺; found: 175.1215.
1-(Nitromethyl)cyclohexanol: IR (film): 3530, 3431, 2937, 2862, 1548, 1382 cm^-1. ¹H NMR (CDCl₃): δ = 1.34 (m, 1 H), 1.48-1.59 (m, 4 H), 1.62-1.72 (m, 5 H), 2.32 (br, 1 H), 4.44 (s, 2 H) ppm. ¹³C NMR: 21.5, 25.2, 34.9, 70.8, 84.8 ppm. HRMS: m/z calcd: 159.0895 [M]⁺; found: 159.0889.
1-(Nitromethyl)cyclopentanol: IR (film): 3423, 2925, 1549, 1383 cm^-1. ¹H NMR (CDCl₃): δ = 1.68-1.73 (m, 4 H), 1.81-1.91 (m, 4 H), 2.83 (br, 1 H), 4.54 (s, 2 H) ppm. ¹³C NMR: 23.8, 38.2, 80.2, 83.7 ppm. HRMS: m/z calcd: 145.0739 [M]⁺; found: 145.0745.
2-Methyl-1-nitropropan-2-ol: IR (film): 3385, 2924, 1548, 1461, 1260 cm^-1. ¹H NMR (CDCl₃): δ = 1.26 (s, 6 H), 2.55 (br, 1 H), 4.33 (s, 2 H) ppm. ¹³C NMR: 27.0, 69.8, 85.3 ppm. HRMS: m/z calcd 119.0582 [M]⁺; found: 119.0587.
1-Nitro-2-methylbutan-2-ol: IR (film): 3441, 2924, 1553, 1381 cm^-1. ¹H NMR (CDCl₃): δ = 0.99 (t, J = 7.5 Hz, 3 H), 1.30 (s, 3 H), 1.62 (q, J = 7.5 Hz, 2 H), 2.75 (br, 1 H), 4.44 (d, J = 11.8 Hz, 2 H) ppm. ¹³C NMR: 8.0, 24.1, 32.7, 72.0, 84.1 ppm. HRMS: m/z calcd 133.0739 [M]⁺; found: 133.0732.
2,4-Dimethyl-1-nitropentan-2-ol: IR (film): 3454, 2924, 1552, 1380 cm^-1. ¹H NMR (CDCl₃): δ = 0.97-1.01 (m, 6 H), 1.33 (s, 3 H), 1.46-1.54 (m, 2 H), 1.76-1.91 (m, 1 H), 2.82 (br, 1 H), 4.42 (d, J = 11.8 Hz, 2 H) ppm. ¹³C NMR: 22.5, 24.2, 29.9, 48.1, 72.3, 85.1 ppm. HRMS: m/z calcd 161.1052 [M]⁺; found: 161.1058.
2-Methyl-1-nitrobutane-2,3-diol (mixture of the two diastereoisomers): IR (film): 3401, 2986, 1551, 1382 cm^-1. ¹H NMR (CDCl₃): δ = 1.20-1.30 (m, 6 H), 2.88 (br, 2 H), 3.72-3.84 (m, 1 H), 4.43-4.71 (m, 2 H) ppm. ¹³C NMR: 17.0, 20.3, 21.0, 70.9, 72.8, 74.2, 74.4, 80.9, 82.4 ppm. HRMS: m/z calcd: 149.0688 [M]⁺; found: 149.0685.