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Sanz-Cervera et al.
(TLC) was performed on Merck GF/UV 254 plates, and visualized with UV light at
254 nm. Melting points were measured using a Buchi M-560 melting-point and are
uncorrected. All of the NMR spectra were recorded on a Bruker Avance 300 DRX
1
(300 MHz for H NMR and 75 MHz for 13C NMR), with chemical shifts expressed as
values relative to tetramethylsilane as the internal standard and coupling constants (J
values) given in Hertz (Hz). High resolution mass spectra (HRMS) spectra were
recorded on a TRIPLETOFT5600 (ABSciex) with Electrospray Ionization in the posi-
tive ion mode.
5-Hydroxy-2-iodobenzaldehyde (4)
To a solution of 1.0 g (8.18 mmol) of 3-hydroxybenzaldehyde in 100 mL of dichlorome-
thane, was slowly added 1.078 g (12.28 mmol) of HBF4¢OEt2 at r.t., followed by the
addition of 3.045 g (8.18 mmol) of IPy2BF4 bis(pyridyl)iodonium(I) tetrafluoroborate.
The solution was stirred for 5 min at r.t., after which a solution of 15 mL of 1M HCl
were added in 15 mL of water. The aqueous layer was extracted with dichloromethane (3
£ 10 mL) and the combined organic layers were washed with 10 mL water and 25 mL
5% sodium thiosulfate aqueous solution and dried over Na2SO4. Removal of the volatiles
under reduced pressure afforded a brownish solid, which was recrystallized from chloro-
form to afford 443 mg (22%) of 5-hydroxy-2-iodobenzaldehyde 4 as a brownish solid,
mp. 130–132ꢀC, lit. mp. 125–126ꢀC.24 1H NMR (300 MHz, CD3COCD3): d 9.96 (s, 1H),
9.15 (s, 1H), 7.85 (d, J D 8.6 Hz, 1H), 7.34 (d, J D 3.1 Hz, 1H), 6.98 (dd, J1 D 8.5 Hz, J2
1
D 3.1 Hz, 1H); H RMN (300 MHz, CDCl3): d 9.99 (s, 1H), 7.79 (d, J D 8.4 Hz, 1H),
7.45 (d, J D 3.0 Hz, 1H), 6.91 (dd, J1 D 8.4 Hz, J2 D 3.0 Hz, 1H), 6.18 (br s, 1H); 13C
RMN (75 MHz, CD3COCD3): d 196.6 (CHO), 160.1 (C-5), 143.3 (C-3), 137.9 (C-1),
125.4 (C-4), 118.1 (C-6), 88.5 (C-2); 13C RMN (75 MHz, CDCl3) d ppm: 196.3 (CHO),
156.7 (C-5), 141.4 (C-3), 135.7 (C-1), 123.9 (C-4), 116.5 (C-6), 89.4 (C-2); HRMS (EI)
m/z: Calcd for C7H5IO2: 247.9334. Found: 247.9292.
3-Hydroxy-4-iodobenzaldehyde (5)
3-Hydroxybenzaldehyde (1.60 g, 13.18 mmol) was dissolved in 15 mL of 33% aque-
ous NH4OH in a 100 mL round-bottomed flask. Separately, iodine (3.72 g,
14.65 mmol) was added to 25 mL of 30% (w/v) solution of KI in water. The latter
solution was added dropwise to the 3-hydroxybenzaldehyde solution, after which the
reaction was stirred at rt for 2h. The reaction mixture was cooled then with an ice
bath and made acid with conc. HCl, which caused the appearance of a yellow gum.
The gum was taken up in Et2O, and the remaining aqueous solution was extracted
with more Et2O (3 £ 10 mL). The organic layers were pooled together, washed with
10 mL of an aqueous saturated solution of Na2S2O3, and dried over anh. Na2SO4.
After filtration and solvent removal under reduced pressure, an orange-colored solid
is obtained, which was crystallized from Et2O to afford 927 mg of 3-hydroxy-4-iodo-
benzꢀaldehyde 5 as a yellowish solid. Yield: 28%. M.p.: 128–130ꢀC, lit. mp. 128–
129 C.25 1H RMN (300 MHz, CD3COCD3): d 9.94 (s, 1H), 9.67 (s, 1H), 8.00 (d, J
D 8.0 Hz, 1H), 7.41 (d, J D 1.8 Hz, 1H), 7.20 (dd, J1 D 8.0 Hz, J2 D 1.8 Hz, 1H);
1H RMN (300 MHz, CDCl3) d ppm: 9.92 (s, 1H), 7.88 (d, J D 8.1 Hz, 1H), 7.44 (d,
J D 1.8 Hz, 1H), 7.18 (dd, J1 D 8.1 Hz, J2 D 1.8 Hz, 1H), 5.93 (br s, 1H); 13C
RMN (75 MHz, CD3COCD3): d 193.2 (CHO), 159.2 (C-3), 142.1 (C-5), 140.2 (C-1),
124.5 (C-6), 115.3 (C-2), 94.0 (C-4); 13C RMN (75 MHz, CDCl3): d 191.3 (CHO),
155.8 (C-3), 139.3 (C-5), 138.3 (C-1), 123.0 (C-6), 114.8 (C-2), 93.9 (C-4); HRMS
(EI) m/z: Calcd for C7H5IO2: 247.9334. Found: 247.9358.