D
D. Sang et al.
Paper
Synthesis
In summary, by employing carbodiimides as hydrogen
iodide scavengers, a facile procedure has been developed
for the cleavage of aryl alkyl ethers using aluminum triio-
dide as the ether cleaving reagent. The method is compati-
ble with a variety of acid-labile functional groups, and the
substrate is not limited to alkyl o-hydroxyphenyl ethers.
Further evaluation of this ether cleaving method as well as
the screening of alternative acid scavengers is in progress
and will be disclosed in due course.
1H NMR (400 MHz, CDCl3): δ = 6.90–6.85 (m, 2 H), 6.84–6.79 (m, 2 H),
5.23 (br s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 143.48, 121.31, 115.53.
3,4-Dihydroxybenzaldehyde (Protocatechualdehyde, 4d)
[CAS Reg. No. 139-85-8]
Off-white solid; yield: 0.654 g (94%); Rf = 0.38 (PE/EtOAc, 1:1); mp
155–156 °C.
1H NMR (400 MHz, DMSO-d6): δ = 9.83 (br s, 2 H), 9.69 (s, 1 H), 7.27
(d, J = 8.0 Hz, 1 H), 7.24 (s, 1 H), 6.91 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 191.59, 152.59, 146.33, 129.31,
125.03, 115.97, 114.78.
All reagents and solvents were purchased and used as received with-
out further purification. 1H and 13C spectra were recorded using a
Bruker Avance-400 FTNMR spectrometer at r.t. with TMS as the inter-
nal standard. Column chromatography was carried out using 230–
300 mesh silica gel. TLC was carried out using GF254 precoated silica
gel plates. Melting points are uncorrected. PE = petroleum ether.
2,3-Dihydroxybenzaldehyde (4e)
[CAS Reg. No. 24677-78-9]
Yellow solid; yield: 0.442 g (64%); Rf = 0.48 (PE/EtOAc, 3:1); mp 106 °C
(Lit.17 105–107 °C).
1H NMR (400 MHz, DMSO-d6): δ = 10.20 (s, 1 H), 10.11 (s, 1 H), 9.82 (s,
1 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.07 (d, J = 8.0 Hz, 1 H), 6.79 (t, J = 8.0 Hz,
1 H).
13C NMR (100 MHz, DMSO-d6): δ = 193.28, 150.17, 146.59, 123.15,
121.69, 120.07, 119.78.
Hydroxychavicol (4-Allylbenzene-1,2-diol, 2);10 General Procedure
To a suspension of AlI3 (5.5 mmol, 1.1 equiv) in hot CH3CN (40 mL)
were added sequentially DIC (0.379 g, 3 mmol, 0.6 equiv) and eugenol
(1, 0.821 g, 5.0 mmol). The mixture was stirred for 18 h at 80 °C, and
then it was cooled to r.t., acidified with HCl (2 mol/L, 10 mL), and ex-
tracted with EtOAc (3 × 50 mL). The organic phases were combined,
washed with sat. aq Na2S2O3 (10 mL) and brine (10 mL), and was dried
(MgSO4). The solvent was removed on a rotary evaporator and the
residue was purified by flash column chromatography (PE/EtOAc, 4:1)
to afford 2 (0.750 g, 99%) as a white solid; mp 45–46 °C.
1H NMR (400 MHz, CDCl3): δ = 6.79 (d, J = 8 Hz, 1 H), 6.71 (d, J = 2 Hz,
1 H), 6.63 (dd, J1 = 8 Hz, J2 = 2 Hz, 1 H), 5.92 (ddt, J1 = 17.2 Hz, J2 = 10.4
Hz, J2 = 6.8 Hz, 1 H), 5.05 (dq, J1 = 16.8 Hz, J2 = 1.6 Hz, 1 H), 5.03 (dq,
J1 = 10.0 Hz, J2 = 1.6 Hz, 1 H), 5.00 (br s, 2 H), 3.26 (d, J = 6.4 Hz, 2 H).
5-Allyl-2,3-dihydroxybenzaldehyde (4f)22
Yellow solid; yield: 0.144 g (40%); Rf = 0.54 (PE/EtOAc, 3:1); mp 56 °C.
1H NMR (400 MHz, CDCl3): δ = 10.95 (s, 1 H), 9.86 (s, 1 H), 7.05 (s, 1
H), 6.96 (s, 1 H), 6.08–5.79 (m, 1 H), 5.63 (s, 1 H), 5.23–4.97 (m, 2 H),
3.35 (d, J = 6.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 196.72, 146.73, 144.71, 136.66,
132.29, 123.70, 122.13, 120.28, 116.52, 39.20.
13C NMR (100 MHz, CDCl3): δ = 143.43, 141.65, 137.60, 133.25,
121.00, 115.69, 115.57, 115.33, 39.49.
2-Bromo-4,5-dihydroxybenzaldehyde (4g)
[CAS Reg. No. 4815-99-0]
Yellow solid; yield: 0.666 g (61%); Rf = 0.53 (PE/EtOAc, 1:1).
1H NMR (400 MHz, DMSO-d6): δ = 10.21 (br s, 2 H), 9.95 (s, 1 H), 7.25
(s, 1 H), 7.05 (s, 1 H).
4-Prop-1-enylbenzene-1,2-diol (Isohydroxychavicol, 4a)20
White wax solid; yield: 0.708 g (94%); Rf = 0.72 (PE/EtOAc, 1:1); mp
102–103 °C.
13C NMR (100 MHz, DMSO-d6): δ = 190.44, 153.55, 146.14, 125.27,
120.02, 117.45, 115.57.
1H NMR (400 MHz, CDCl3): δ = 6.86 (s, 1 H), 6.79–6.74 (m, 2 H), 6.25
(d, J = 15.6 Hz, 1 H), 6.08–5.99 (m, 1 H), 5.40 (br s, 2 H), 1.83 (d, J = 6.4
Hz, 3 H).
3,4-Dihydroxy-5-nitrobenzaldehyde (4h)
13C NMR (100 MHz, CDCl3): δ = 143.45, 142.44, 131.84, 130.23,
[CAS Reg. No. 116313-85-0]
124.05, 119.13, 115.46, 112.56, 18.34.
Yellow solid; yield: 0.395 g (43%); Rf = 0.31 (PE/EtOAc, 3:1, + 1 drop
HCO2H); mp 133–134 °C.
5,5′-Diallylbiphenyl-2,3,2′,3′-tetraol (4b)21
1H NMR (400 MHz, DMSO-d6): δ = 10.96 (br s, 2 H), 9.81 (s, 1 H), 7.98
White solid; yield: 0.585 g (79%); Rf = 0.33 (PE/EtOAc, 1:1); mp 155 °C.
1H NMR (400 MHz, CD3Cl): δ = 6.79 (s, 2 H), 6.71 (s, 2 H), 6.12 (br s, 2
H), 5.97 (ddt, J1 = 16.8 Hz, J2 = 10.0 Hz, J3 = 6.4 Hz, 2 H), 5.58 (br s, 2 H),
5.10 (d, J = 16.8 Hz, 2 H), 5.07 (d, J = 9.2 Hz, 2 H), 3.33 (d, J = 6.8 Hz, 4
H).
(s, 1 H), 7.47 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 191.03, 148.77, 147.74, 137.70,
127.35, 120.15, 116.10.
13C NMR (101 MHz, CD3Cl): δ = 144.68, 138.42, 137.31, 133.97,
4-Nitrobenzene-1,2-diol (4-Nitrocatechol, 4i)
124.86, 122.29, 115.93, 114.96, 39.66.
[CAS Reg. No. 3316-09-4]
Yellow solid; yield: 0.165 g (21%); Rf = 0.80 (PE/EtOAc, 1:1); mp 178
°C.
1H NMR (400 MHz, DMSO-d6): δ = 10.50 (br s, 1 H), 10.13 (br s, 1 H),
7.63 (d, J = 8.8 Hz, 1 H), 7.60 (s 1 H), 6.89 (d, J = 8.8 Hz, 1 H).
Catechol (4c)
[CAS Reg. No. 120-80-9]
White solid; yield: 0.497 g (90%); Rf = 0.63 (PE/EtOAc, 1:1); mp 105–
108 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F