PAPER
Selective Reduction by Hantzsch Ester
773
1H NMR (300 MHz, DMSO-d6): d = 2.26 (s, 3 H), 3.13 (dd, J = 6.6,
16.5 Hz, 1 H), 3.27 (dd, J = 8.4, 16.5 Hz, 1 H), 4.19 (dd, J = 6.6, 8.4
Hz, 1 H), 7.00 (m, 2 H), 7.24 (m, 2 H).
13C NMR (75.43 MHz, DMSO-d6): d = 25.2, 29.0, 52.0, 90.6,
116.1, 120.5, 121.9, 124.5, 127.9, 128.5, 151.0, 166.1, 177.6, 203.0.
suitable target for catalytic hydrogenation due to the lia-
bility of the cyano group under such conditions, but it
could be reduced by HEH in high yield with the cyano
group intact. In addition, as HEH does not reduce elec-
tron-rich carbon–carbon double bonds,1e the selective re-
duction of the 3,4-double bond of 3-substituted coumarins
could be achieved in the presence of isolated carbon–car-
bon double bonds. Catalytic hydrogenation, however,
lacks such selectivity.
EI-MS: m/z (%) = 190 (M+, 47), 147 (100).
3-Benzoyl-3,4-dihydrocoumarin (2d)
Colorless crystals; mp 99–100 °C.
1H NMR (300 MHz, CDCl3): d = 3.17 (dd, J = 6.6, 17.8 Hz, 1 H),
3.52 (dd, J = 10.0, 17.8 Hz, 1 H), 4.71 (dd, J = 6.6, 10.0 Hz, 1 H),
7.10 (m, 2 H), 7.19 (m, 1 H), 7.29 (m, 1 H), 7.49 (m, 2 H), 7.61 (m,
1 H), 7.95 (m, 2 H).
In summary, the selective reduction of the endocyclic
double bond of the 3-(electron-withdrawing group)-sub-
stituted coumarins can be effectively achieved by using
Hantzsch 1,4-dihydropyridine as the reducing agent.
13C NMR (75.43 MHz, CDCl3): d = 27.0, 47.1, 116.7, 121.1, 124.8,
128.2, 128.5, 128.8, 133.9, 135.4, 151.3, 165.9, 193.8.
EI-MS: m/z (%) = 252 (M+, 9), 147 (100), 105 (85), 77 (63).
Melting points were measured with a Yanagimoto melting point ap-
paratus and are uncorrected. 1H and 13C NMR spectra were recorded
on a Varian Mercury Plus 300 NMR spectrometer at 300 MHz (1H
NMR) and 75 MHz (13C NMR). Chemical shifts are given in ppm
with reference to internal TMS. EI-MS spectra were recorded on an
HP 5988A spectrometer. High-resolution mass spectra (HRMS)
were recorded on a Bruker Daltonics APEX II 47e spectrometer by
ESI.
3-Ethoxycarbonyl-5,6-benzo-3,4-dihydrocoumarin (2e)
Colorless crystals; mp 112–114 °C.
1H NMR (300 MHz, CDCl3): d = 1.21 (t, J = 6.4 Hz, 3 H), 3.53 (dd,
J = 6.0, 16.0 Hz, 1 H), 3.77 (dd, J = 9.0, 16.0 Hz, 1 H), 3.87 (dd,
J = 6.0, 9.0 Hz, 1 H), 4.20 (q, J = 6.4 Hz, 2 H), 7.23 (d, J = 9.0 Hz,
1 H), 7.48 (m, 1 H), 7.58 (m, 1 H), 7.78 (d, J = 9.0 Hz, 1 H), 7.87
(m, 2 H).
13C NMR (75.43 MHz, CDCl3): d = 13.8, 23.2, 45.6, 62.0, 113.8,
116.7, 122.6, 125.2, 127.2, 128.5, 129.1, 130.7, 130.8, 148.8, 164.5,
167.5.
The substrates 1a–1g were prepared from the salicylic aldehyde (or
2-hydroxylnaphthaldehyde) and respective b-dicarbonyl com-
pounds according to the general procedure of Knoevenagel reac-
tion.13a Compounds 1h,13b 1i,13c 1j,13d 1k,13e were prepared
according to the corresponding literature. Hantzsch 1,4-dihydropy-
ridine (HEH) was prepared following Hantzsch’s procedure.14
EI-MS: m/z (%) = 270 (M+, 18), 197 (100).
3-Acetyl-5,6-benzo-3,4-dihydrocoumarin (2f)
Colorless needles; mp 154–156 °C.
1H NMR (300M Hz, CDCl3): d = 2.23 (s, 3 H), 3.93 (s, 2 H), 7.19
(d, J = 9.0 Hz, 1 H), 7.48 (m, 1 H), 7.58 (m, 1 H), 7.73 (d, J = 9.0
Hz, 1 H), 7.82 (m, 2 H), 13.56 (s, 1 H).
13C NMR (75.43 MHz, CDCl3): d = 19.4, 23.7, 90.2, 112.2, 117.3,
122.3, 125.1, 127.1, 128.6, 128.8, 130.7, 131.1, 147.4, 168.6, 178.2.
EI-MS: m/z (%) = 240 (M+, 33), 197 (100).
Reduction of 3-Substituted Coumarins by HEH; General Pro-
cedure
A solution (3 mL) of the substituted coumarin (1 mmol) and HEH
(1 mmol) was refluxed under an argon atmosphere. After the reac-
tion was complete as indicated by TLC analysis, the solvent was
evaporated under reduced pressure, and the product was isolated
from the residue by flash chromatography on silica gel; further pu-
rification by recrystallization (EtOH) gave dihydrocoumarins as
colorless crystals (92–98%).
3-Benzoyl-5,6-benzo-3,4-dihydrocoumarin (2g)
Colorless needles; mp 160–162 °C.
3-Ethoxycarbonyl-3,4-dihydrocoumarin (2a)
Colorless crystals; mp 50–51 °C.
1H NMR (300 MHz, CDCl3): d = 3.51 (dd, J = 6.9, 16.5 Hz, 1 H),
3.70 (dd, J = 10.5, 16.5 Hz, 1 H), 4.76 (dd, J = 6.9, 10.5 Hz, 1 H),
7.20 (m, 1 H), 7.46 (m, 5 H), 7.76 (m, 3 H), 7.94 (m, 2 H).
13C NMR (75.43 MHz, CDCl3): d = 23.0, 46.2, 114.4, 116.8, 122.7,
125.2, 127.2, 128.7 (2×), 129.1, 130.8, 130.9, 133.9, 135.4, 148.8,
165.7, 193.9.
1H NMR (300 MHz, CDCl3): d = 1.36 (t, J = 7.2 Hz, 3 H), 3.17 (dd,
J = 6.2, 16.5 Hz, 1 H), 3.39 (dd, J = 8.7, 16.5 Hz, 1 H), 3.75 (dd,
J = 6.2, 8.7 Hz, 1 H), 4.19 (q, J = 7.2 Hz, 2 H), 7.02 (m, 1 H), 7.07
(m, 1 H), 7.21 (m, 2 H).
13C NMR (75.43 MHz, CDCl3): d = 13.6, 26.9, 46.0, 61.8, 116.4,
120.56, 124.5, 128.0, 128.4, 151.1, 164.6, 167.3.
EI-MS: m/z (%) = 302 (M+, 12), 276 (13), 197 (100), 105 (73).
EI-MS: m/z (%) = 220 (M+, 8), 173 (14), 147 (100).
3-Cyano-3,4-dihydrocoumarin (2h)
Colorless needles; mp 130–131 °C.
3-Methoxycarbonyl-3,4-dihydrocoumarin (2b)
Colorless crystals; mp 90–91 °C.
1H NMR (300 MHz, CDCl3): d = 3.40 (m, 2 H), 3.91 (dd, J = 12.0,
6.6 Hz, 1 H), 7.12 (m, 1 H), 7.20 (m, 1 H), 7.26 (m, 1 H), 7.36 (m,
1 H).
1H NMR (300 MHz, CDCl3): d = 3.12 (dd, J = 6.0, 16.2 Hz, 1 H),
3.36 (dd, J = 9.0, 16.2 Hz, 1 H), 3.70 (s, 3 H), 3.72 (dd, J = 6.0, 9.0
Hz, 1 H), 7.00 (m, 1 H), 7.07 (m, 1 H), 7.21 (m, 2 H).
13C NMR (75.43 MHz, CDCl3): d = 28.5, 33.1, 114.4, 117.3, 119.0,
13C NMR (75.43 MHz, CDCl3): d = 27.0, 46.0, 52.9, 116.7, 120.6,
125.5, 128.2, 129.7, 151.0, 160.7.
124.8, 128.2, 128.6, 151.2, 164.6, 167.9.
EI-MS: m/z (%) = 173 (M+, 92), 118 (42), 107 (61), 106 (62), 78
(100).
EI-MS: m/z (%) = 206 (M+, 15), 173 (20), 147 (100).
HRMS (ESI): m/z calcd for C10H7NO2Na+: 196.0369; found:
196.0367.
3-Acetyl-3,4-dihydrocoumarin (2c)
Colorless crystals; mp 75–76 °C.
Synthesis 2006, No. 5, 771–774 © Thieme Stuttgart · New York