Green one-pot synthesis of 2h-pyrans under solvent-free conditions catalyzed by ethylenediammonium diacetate

Article abstract of DOI:10.1080/00397911.2011.594975

Ethylenediammonium diacetate readily catalyzes the Knoevenagel-type condensation between 1,3-dicarbonyl substrates and ,-unsaturated aldehydes at room temperature under solvent-free conditions. This rapid, efficient, and convenient one-pot approach to the

Full text of DOI:10.1080/00397911.2011.594975

Supplementary Information
Green one-pot synthesis of 2H-pyrans under solvent-free
conditions catalysed by ethylendiammonium diacetate
Martín J. Riveira* and Mirta P. Mischne*
Instituto de Química Rosario-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad
Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Santa Fe, Argentina. Fax: +54-341-4370477; Tel:
+54-341-4370477. E-mail: mischne@iquir-conicet.gov.ar; riveira@iquir-conicet.gov.ar
Table of Contents
1. General Information
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2. Experimental Section and Spectroscopic Data
3. 1H NMR, 13C NMR and DEPT Spectra
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GENERAL INFORMATION
Chemical reagents were purchased from commercial suppliers and used without
further purification, unless otherwise noted. Solvents were analytical grade or were purified
by standard procedures prior to use. Yields were calculated for material judged homogeneous
by thin layer chromatography and nuclear magnetic resonance (1H NMR). All reactions were
monitored by thin layer chromatography (TLC) performed on silica gel 60 F254 pre-coated
aluminum sheets, visualized by a 254 nm UV lamp, and stained with an ethanolic solution of
4-anisaldehyde. Column flash chromatography was performed using silica gel 60 (230 – 400
mesh). Melting points (m.p.) were taken on an electrothermal melting point apparatus and are
1
uncorrected. Nuclear magnetic resonance spectra were acquired at 300 MHz for H and 75
13
MHz for C using CDCl3 as solvent. Chemical shifts for proton nuclear magnetic resonance
(1H NMR) spectra are reported in parts per million relative to the signal of tetramethylsilane
at 0 ppm (internal standard) and coupling constants (J) are reported in hertz (Hz). Chemical
shifts for carbon nuclear magnetic resonance (13C NMR) spectra are reported in parts per
million relative to the center line of the CDCl3 triplet at 76.9 ppm. The following
abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, pent = pentet, br = broad. IR spectra were obtained using an FT-IR
spectrometer and only partial spectral data are listed. High resolution mass spectra were
performed on a mass spectrometer
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EXPERIMENTAL SECTION AND SPECTROSCOPIC DATA
Preparation of 1,2-ethylenediammonium diacetate (EDDA)
A 150 ml beaker containing 100 ml of dry ether and 13.37 ml (0.2 mol) of
ethylenediamine is placed in an ice-bath and a solution of glacial acetic acid (22.9 ml, 0.4
mol) in 20 ml ether is added with stirring at such a rate as to prevent boiling of the ether. The
solution is left to crystallize overnight, then filtered with suction, the crystals washed with
ether and recrystallised from approximately 50 ml methanol. Yield after drying in a vacuum
desiccator is around 27.5 g (75%) of colourless needles, mp 114 °C.
General procedure for the preparation of 2H-pyrans
A mixture of 1,3-dicarbonyl compound (1 mmol), α,β-unsaturated aldehyde (1 mmol),
and EDDA (0.1 mmol) was mixed in a mortar under solvent-free conditions. After completion
of the reaction indicated by thin layer chromatography (TLC), the residues were purified by
silica gel column chromatography (hexanes:ethyl acetate) to afford the desired products.
2,7,7-Trimethyl-2-(4-methylpent-3-en-1-yl)-2,6,7,8-tetrahydro-5H-chromen-5-one. (4a)
O
Pale yellow oil. IR (film): νmax/cm-1 2961, 2926, 1651, 1595,
1069. 1H NMR (CDCl3, 300 MHz, Me4Si): δ = 6.44 (d, J = 10.2
O
Hz, 1H), 5.17 (d, J = 10.0 Hz, 1H), 5.08 (tm, J = 7.0 Hz, 1H),
2.27 (bs, 2H), 2.24 (s, 2H), 2.08-1.98 (m, 2H), 1.76-1.66 (m, 1H), 1.67 (s, 3H), 1.62-1.52 (m,
13
1H), 1.58 (s, 3H), 1.36 (s, 3H), 1.07 (s, 3H), 1.06 (s, 3H). C NMR (CDCl3, 75 MHz): δ =
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194.1 (s), 170.2 (s), 131.7 (s), 123.5 (d), 121.2 (d), 116.1 (d), 108.9 (s), 82.2 (s), 50.2 (t), 42.2
(t), 41.5 (t), 32.0 (s), 28.4 (q), 28.0 (q), 27.3 (q), 25.5 (q), 22.3 (t), 17.4 (q).
2-Methyl-2-(4-methyl-pent-3-enyl)-2,6,7,8-tetrahydro-chromen-5-one. (4b)
Pale yellow oil. IR (film): νmax/cm-1 2966, 2926, 1651, 1589, 1452,
O
1
1348, 1070. H NMR (CDCl3, 300 MHz, Me4Si): δ = 6.46 (d, J =
O
10.1 Hz, 1H), 5.18 (d, J = 10.1 Hz, 1H), 5.08 (tm, J = 7.0 Hz, 1H),
2.40 (t, J = 6.3 Hz, 2H), 2.38 (t, J = 6.7 Hz, 2H), 2.08-2.01 (m, 2H), 1.97 (p, J = 6.6 Hz, 2H),
1.78-1.52 (m, 2H), 1.68 (bs, 3H), 1.59 (bs, 3H), 1.36 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ =
194.5 (s), 171.7 (s), 131.7 (s), 123.5 (d), 121.5 (d), 116.3 (d), 110.1 (s), 82.1 (s), 41.5 (t), 36.3
(t), 28.4 (t), 27.2 (q), 25.5 (q), 22.4 (t), 20.5 (t), 17.4 (q).
2-Methyl-2-(4-methylpent-3-en-1-yl)-2H,5H-pyrano[3,2-c]chromen-5-one. (4c)
Colourless oil. IR (film): νmax/cm-1 3073, 2970, 2924, 2853, 1716,
O
1
1607, 1362, 1036. H NMR (CDCl3, 300 MHz): δ = 7.80 (dd, J =
O
O
7.5, 1.2 Hz, 1H), 7.52 (ddd, J = 8.6, 7.3, 1.8 Hz, 1H), 7.32-7.25 (m,
2H), 6.59 (d, J = 10.2 Hz, 1H), 5.48 (d, J = 10.0 Hz, 1H), 5.09 (tm, J = 7.0 Hz, 1H), 2.18-2.10
(m, 2H), 1.94-1.68 (m, 2H), 1.61 (bs, 3H), 1.55 (bs, 3H), 1.52 (s, 3H). 13C NMR (CDCl3, 75
MHz): δ = 160.8 (s), 158.9 (s), 153.0 (s), 132.1 (s), 131.9 (d), 124.9 (d), 123.8 (d), 123.2 (d),
122.5 (d), 117.1 (d), 116.6 (d), 115.3 (s), 99.8 (s), 83.0 (s), 41.6 (t), 27.4 (q), 25.4 (q), 22.4 (t),
17.5 (q).
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2,6-Dimethyl-2-(4-methyl-pent-3-enyl)-2,6-dihydro-pyrano[3,2-c]quinolin-5-one.
(zanthosimuline, 2)
O
Colourless oil. IR (film): νmax/cm-1 3079, 3058, 2970, 2925, 1656,
1587, 1326, 1121. 1H NMR (CDCl3, 300 MHz, Me4Si): δ = 7.96 (dd,
N
O
J = 7.9, 1.4 Hz, 1H), 7.54 (ddd, J = 10.1, 7.3, 1.6 Hz, 1H), 7.31 (bd, J = 8.2 Hz, 1H), 7.22 (td,
J = 7.9, 0.8 Hz, 1H), 6.79 (d, J = 10.0 Hz, 1H), 5.48 (d, J = 10.0 Hz, 1H), 5.09 (tm, J = 7.0
Hz, 1H), 3.69 (s, 3H), 2.18-2.10 (m, 2H), 1.90-1.69 (m, 2H), 1.63 (bs, 3H), 1.55 (bs, 3H),
1.48 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ = 160.6 (s), 155.0 (s), 139.0 (s), 131.5 (s), 130.5
(d), 124.9 (d), 123.4 (d), 122.7 (d), 121.3 (d), 118.1 (d), 115.6 (s), 113.6 (d), 105.2 (s), 80.9
(s), 41.2 (t), 28.9 (q), 26.7 (q), 25.3 (q), 22.2 (t), 17.3 (q).
2-(4,8-Dimethyl-nona-3,7-dienyl)-2,7,7-trimethyl-2,6,7,8-tetrahydro-chromen-5-one. (4d)
Colourless to pale yellow oil. IR (film): νmax/cm-1
O
2963, 2926, 1643, 1593, 1420, 1065. 1H NMR
O
(CDCl3, 300 MHz, Me4Si): δ = 6.44 (d, J = 10.1 Hz,
1H), 5.18 (d, J = 10.1 Hz, 1H), 5.13-5.04 (m, 2H),
2.27 (bd, J = 1.4 Hz, 2H), 2.24 (s, 2H), 2.10-1.93 (m, 6H), 1.77-1.52 (m, 2H), 1.68 (bs, 3H),
1.60 (bs, 3H), 1.58 (bs, 3H), 1.37 (s, 3H), 1.07 (s, 3H), 1.06 (s, 3H). 13C NMR (CDCl3, 75
MHz): δ = 194.1 (s), 170.2 (s), 135.3 (s), 131.1 (s), 124.0 (d), 123.3 (d), 121.2 (d), 116.1 (d),
108.9 (s), 82.2 (s), 50.2 (t), 42.2 (t), 41.5 (t), 39.4 (t), 31.9 (s), 28.4 (q), 28.0 (q), 27.2 (q), 26.4
(t), 25.5 (q), 22.2 (t), 17.4 (q), 15.7 (q).
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2-(4,8-Dimethyl-nona-3,7-dienyl)-2-methyl-2H-pyrano[3,2-c]chromen-5-one. (ferprenin,
4e)
Pale yellow oil. IR (film): νmax/cm-1 2968, 2922, 1715, 1607, 1362,
O
1
1036. H NMR (CDCl3, 300 MHz, Me4Si): δ = 7.80 (dd, J = 7.8, 1.2
Hz, 1H), 7.52 (ddd, J = 8.7, 7.0, 1.6 Hz, 1H), 7.31-7.24 (m, 2H), 6.59
O
O
(d, J = 10.3 Hz, 1H), 5.49 (d, J = 10.3 Hz, 1H), 5.11 (tm, J = 7.0 Hz,
1H), 5.05 (tm, J = 7.0 Hz, 1H), 2.19-2.12 (m, 2H), 2.06-1.98 (m, 2H), 1.95-1.71 (m, 4H), 1.67
(bs, 3H), 1.58 (bs, 3H), 1.56 (bs, 3H), 1.52 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ =.160.6 (s),
158.8 (s), 152.9 (s), 135.7 (s), 131.8 (d), 131.1 (s), 124.9 (d), 123.9 (d), 123.7 (d), 122.9 (d),
122.4 (d), 117.0 (d), 116.5 (d), 115.2 (s), 99.7 (s), 82.9 (s), 41.5 (t), 39.3 (t), 27.2 (q), 26.3 (t),
25.4 (q), 22.2 (t), 17.4 (q), 15.7 (q).
2,2,7,7-Tetramethyl-2,6,7,8-tetrahydro-chromen-5-one. (4f)
O
Pale yellow crystals. Mp.: 39.0-40.0 ºC. IR (KBr): νmax/cm-1 3049, 2976,
1
2963, 1635, 1585, 1132, 1090. H NMR (CDCl3, 300 MHz, Me4Si): δ =
O
6.40 (d, J = 9.9 Hz, 1H), 5.23 (d, J = 9.9 Hz, 1H), 2.27 (bs, 2H), 2.25 (bs, 2H), 1.40 (s, 3H),
1.07 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ = 194.3 (s), 169.9 (s), 122.5 (d), 115.6 (d), 109.4
(s), 79.6 (s), 50.3 (t), 42.3 (t), 32.0 (s), 28.3 (q), 28.2 (q).
2,2-Dimethyl-2,6,7,8-tetrahydro-chromen-5-one. (4g)
O
1
Pale yellow oil. IR (film): νmax/cm-1 2982, 2943, 1637, 1589, 1410, 1094. H
O
NMR (CDCl3, 300 MHz, Me4Si): δ = 6.41 (d, J = 9.9 Hz, 1H), 5.24 (d, J =
9.9 Hz, 1H), 2.40 (t, J = 6.0 Hz, 2H), 2.38 (t, J = 6.0 Hz, 2H), 1.97 (p, J = 6.2 Hz, 2H), 1.402
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(s, 3H), 1.396 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ = 194.6 (s), 171.3 (s), 122.7 (d), 115.6
(d), 110.4 (s), 79.5 (s), 36.2 (t), 28.4 (t), 28.2 (2 × q), 20.4 (t).
2,2-Dimethyl-7-phenyl-2,6,7,8-tetrahydro-chromen-5-one. (4h)
O
Pale yellow oil. IR (film): νmax/cm-1 3086, 3061, 3028, 2976, 2934, 1643,
1591, 1412, 1138. 1H NMR (CDCl3, 300 MHz, Me4Si): δ = 7.37-7.30 (m,
Ph
O
2H), 7.28-7.21 (m, 3H), 6.44 (d, J = 10.1 Hz, 1H), 5.27 (d, J = 9.9 Hz, 1H), 3.40-3.27 (m,
1H), 2.72-2.55 (m, 4H), 1.45 (s, 3H), 1.38 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ = 193.5 (s),
170.4 (s), 142.5 (s), 128.5 (2 × d), 126.8 (d), 126.4 (2 × d), 122.9 (d), 115.5 (d), 110.1 (s),
79.9 (s), 43.4 (t), 38.6 (d), 35.9 (t), 28.5 (q), 28.0 (q).
2,2-Dimethyl-2H-pyrano[3,2-c]chromen-5-one. (4i)
Colourless oil. IR (film): νmax/cm-1 3077, 3054, 2970, 1709, 1674, 1600, 1361,
O
1031. 1H NMR (CDCl3, 300 MHz, Me4Si): δ = 7.79 (dd, J = 8.6, 1.8 Hz, 1H),
O
O
7.51 (ddd, J = 8.8, 7.9, 1.5 Hz, 1H), 7.29-7.23 (m, 2H), 6.53 (d, J = 9.9 Hz,
1H), 5.54 (d, J = 10.1 Hz, 1H), 1.55 (s, 6H). 13C NMR (CDCl3, 75 MHz): δ = 160.5 (s), 158.5
(s), 152.8 (s), 131.8 (d), 125.9 (d), 123.7 (d), 122.4 (d), 116.4 (d), 116.3 (d), 115.2 (s), 99.9
(s), 80.3 (s), 28.2 (2 × q).
2,2,6-Trimethyl-2,6-dihydro-pyrano[3,2-c]quinolin-5-one. (N-methylflindersine, 4j)
Pale yellow crystals. Mp.: 80.0-81.0 ºC. IR (KBr): νmax/cm-1 3057, 2972,
O
1641, 1625, 1325, 1122, 1092. 1H NMR (CDCl3, 300 MHz, Me4Si): δ = 7.92
(d, J = 7.8 Hz, 1H), 7.49 (ddd, J = 9.7, 7.3, 1.2 Hz, 1H), 7.25 (d, J = 8.5 Hz,
N
O
1H), 7.18 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 9.9 Hz, 1H), 5.52 (d, J = 9.9 Hz, 1H), 3.66 (s, 3H),
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1.50 (s, 6H). 13C NMR (CDCl3, 75 MHz): δ = 160.5 (s), 154.7 (s), 138.9 (s), 130.4 (d), 125.9
(d), 122.6 (d), 121.3 (d), 117.6 (d), 115.6 (s), 113.6 (d), 105.4 (s), 78.3 (s), 28.8 (s), 27.8 (2 ×
q).
3,7,7-Trimethyl-2-phenyl-2,6,7,8-tetrahydro-5H-chromen-5-one. (4k)
O
Colourless to pale yellow oil. IR (film): νmax/cm-1 3063, 3032, 2959, 1651,
1
1608, 1047. H NMR (CDCl3, 300 MHz, Me4Si): δ = 7.34 (bs, 5H), 6.46
Ph
O
(bs, 1H), 5.66 (s, 1H), 2.26-2.23 (m, 2H), 2.21-2.19 (m, 2H), 1.62 (bs, 3H), 1.04 (s, 3H), 1.02
(s, 3H). 13C NMR (CDCl3, 75 MHz): δ = 194.4 (s), 167.6 (s), 138.4 (s), 128.9 (d), 128.7 (2 ×
d), 127.6 (2 × d), 124.6 (s), 112.7 (d), 109.9 (s), 82.6 (d), 50.3 (t), 41.8 (t), 32.1 (s), 28.8 (q),
27.6 (q), 19.2 (q). HRMS: m/z calcd. for C18H21O2 (M + H+) 269.1536, found 269.1529.
2,3,7,7-Tetramethyl-2,6,7,8-tetrahydro-chromen-5-one. (4l)
O
Colourless solid. Mp.: 92.0-93.0 ºC. IR (KBr): νmax/cm-1 2972, 2957, 2918,
1
1651, 1603, 1398, 1140, 1055. H NMR (CDCl3, 300 MHz, Me4Si): δ =
O
6.18 (d, J = 0.7 Hz, 1H), 4.83 (q, J = 6.5 Hz, 1H), 2.32-2.18 (m, 4H), 1.73 (d, J = 0.8 Hz, 3H),
1.35 (d, J = 6.6 Hz, 3H), 1.08 (s, 3H), 1.04 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ = 194.2 (s),
167.5 (s), 126.8 (s), 111.5 (d), 110.1 (s), 76.9 (d), 50.2 (t), 41.7 (t), 32.0 (s), 28.7 (q), 27.6 (q),
19.0 (q), 18.5 (q).
O
2,3,7,7-Tetramethyl-2,6,7,8-tetrahydro-chromen-5-one. (4m,
inseparable mixture of diasteroisomers dr: 9:1)
O
H
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Colourless crystals. Mp.: 92.0-93.0 ºC. IR (film): νmax/cm-1 2995, 2920, 1659, 1597, 1398,
1157, 1027. 1H NMR (CDCl3, 300 MHz, Me4Si): δ = 6.09 (bs, 1H), 5.06-4.98 (m, 1H), 2.62-
2.32 (m, 7H), 2.12-1.92 (m, 4H), 1.40-1.25 (m, 1H), 1.28 (s, 3H), 0.85 (s, 3H). 13C NMR
(CDCl3, 75 MHz): δ = 195.3 (s), 171.8 (s), 132.7 (s), 114.2 (s), 110.6 (d), 71.7 (d), 48.2 (d),
41.6 (s), 40.0 (d), 36.4 (t), 31.6 (t), 27.6 (t), 25.28 (t), 25.27 (q), 21.6 (q), 20.6 (t).
1H NMR, 13C NMR and other Spectra
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