A Simple Two-Step Synthesis of 1,2,3-Triiodoarenes
E
Anhydrous solvents were distilled over appropriate drying
agents before use. Analytical thin layer chromatography (TLC)
was performed on Merck silica gel 60 F254. Merck silica gel 60
(0.063–0.2 mm) was used for column chromatography. Visu-
alization of TLC was accomplished with UV light (254 nm).
NMR spectra were recorded on Bruker Avance 300 and
400 MHz spectrometers. The residual solvent protons (1H) or
J 8.0, 8.1). dC (d-CDCl3, 100 MHz) 138.5, 137.0, 130.0, 127.8,
112.3, 109.3. m/z 363.8008. HRMS (CI) Anal. Calc. for
C6H3ClI2 [Mþ] 363.8013.
Synthesis of 1-Bromo-2,3-Diiodobenzene (25)
The title compound was prepared using the general proce-
dure for ipso-iododecarboxylation of benzoic acid derivatives
and isolated in 80 % yield as a white solid, mp 92–938C. nmax
(KBr)/cmꢁ1 2987, 2962, 1601, 1542, 1118, 624. dH (d-CDCl3,
400 MHz) 7.81 (d, 1H, J 8.0), 7.58 (d, 1H, J 8.0), 6.89 (t, 1H,
J 8.0). dC (d-CDCl3, 100 MHz) 137.5, 131.3, 130.2, 129.1,
114.9, 108.8. m/z 407.7497. HRMS (CI) Anal. Calc. for
C6H3BrI2 [Mþ] 407.7507.
1
the solvent carbon (13C) were used as internal standards. H
NMR data are presented as follows: chemical shift in ppm (d)
downfield from trimethylsilane (TMS) (multiplicity, integra-
tion, coupling constant). The following abbreviations are used in
reporting the NMR data: s, singlet; bs, broad singlet; d, doublet;
t, triplet; q, quartet; dq, doublet of quartets; dd, doublet of
doublets; and m, multiplet. High-resolution mass spectra were
recorded using chemical ionization (CI) and electrospray ioni-
zation (ESI) techniques.
Synthesis of 1-Chloro-2,3,4-Triiodobenzene (27)
The title compound was prepared using the general proce-
dure for ipso-iododecarboxylation of benzoic acid derivatives
and isolated in 65 % yield as a white solid, mp: 85–868C. nmax
(KBr)/cmꢁ1 3088, 2941, 1605, 1544, 1142, 570. dH (d-CDCl3,
400 MHz) 7.83 (d, 1H, J 8.0), 7.13 (d, 1H, J 8). dC (d-CDCl3,
100 MHz) 138.9, 137.7, 128.9, 123.1, 112.6, 103.8. m/z
489.6970. HRMS (CI) Anal. Calc. for C6H2ClI3 [Mþ] 489.6979.
General Procedure for ortho-Diiodination of Benzoic Acid
Derivatives
In a flame-dried 100 mL round-bottom flask, benzoic acid
starting material (16.4 mmol, 1.0 equiv.), palladium acetate
(0.05 equiv.), iodobenzene diacetate (1.5 equiv.), and iodine
(1.5 equiv.) were dissolved in anhydrous DMF (40 mL) under
atmospheric air. The flask was then sealed with a septum and the
reaction mixture was stirred at 1008C for 24 h. The reaction
mixture was cooled to room temperature, diluted with ethyl
acetate, and then washed with 0.5 N HCl (4 ꢀ 20 mL). The
organic phase was washed with brine, dried over Na2SO4, and
concentrated in a rotary evaporator. The residue was purified by
column chromatography on silica gel (3 : 1 hexane/EtOAc) to
give the desired iodinated product.
Synthesis of Methyl 3,4,5-Triiodobenzoate (28)
The title compound was prepared using the general proce-
dure for ipso-iododecarboxylation of benzoic acid derivatives
and isolated in 75 % yield as a white solid, mp 145–1468C. nmax
(KBr)/cmꢁ1 3058, 2967, 1548, 1520, 1047, 654. dH (d-CDCl3,
400 MHz) 8.40 (s, 2H). dC (d-CDCl3, 100 MHz) 163.5, 139.0,
138.6, 129.3, 106.5, 52.3. m/z 513.7415. HRMS (CI) Anal. Calc.
for C8H5I3O2 [Mþ] 513.7424.
Synthesis of 3-Chloro-2,6-Diiodobenzoic Acid (15)
General Procedure for Metal–Iodine Exchange Reaction
of 1,2,3-Triiodoarenes
The title compound was prepared using the general proce-
dure for iodination of arene carboxylic acids and isolated in
81 % yield as a white solid, mp 148–1508C. nmax (KBr)/cmꢁ1
1790, 1652, 1548, 1152, 965. dH (d-CDCl3, 400 MHz) 7.74 (d,
1H, J 8.0), 7.20 (d, 1H, J 8.0). dC (d-CDCl3, 100 MHz) 172.2,
146.8, 142.6, 139.3, 130.3, 95.7, 86.9. m/z 406.7824. High-
resolution mass spectrometry (HRMS; ESI) Anal. Calc. for
C7H2ClI2O2 [M–H]ꢁ 406.7833.
Isopropyl magnesium chloride (2 M in THF, 0.23 mL,
0.70 mmol) was added to a solution of 1,2,3-triiodoarene
(0.66 mmol, 1 equiv.) in THF (15 mL) at ꢁ788C. The mixture
was stirred at that temperature for 2 h and then, the electrophile
was added. The solution was slowly warmed to room tempera-
ture and stirred overnight. Saturated NH4Cl was added and
the resulting mixture was stirred for 30 min at room tempera-
ture. The aqueous layer was extracted with Et2O (2 ꢀ 50 mL).
The organic phase was dried with Na2SO4, filtered, and then the
solvent was evaporated under reduced pressure. The crude
product was purified by flash chromatography (100 % hexane)
to yield the pure desired product.
General Procedure for ipso-Iododecarboxylation
of ortho-Diiodobenzoic Acid Derivatives
A mixture of ortho-diiodobenzoic acid derivative (2.67 mmol,
1.0 equiv.), NIS (2.0 equiv.), and 1,2-dichloroethane (DCE;
10 mL) were added to a flame-dried 100 mL round-bottom flask,
and the mixture was irradiated with 100 W (tungsten lamp)
under reflux conditions for 24 h. The reaction mixture was then
cooled to room temperature. The mixture was then washed with
saturated NaHSO3, saturated NaHCO3, and brine. The organic
layers were collected and then dried over anhydrous Na2SO4,
filtered, and concentrated in a rotary evaporator. The residue
was then purified by flash chromatography on silica gel (100 %
hexane) to give the desired iodinated product.
Synthesis of 2-Butyl-1,3-Diiodobenzene (33)
The title compound was prepared using the general proce-
dure for metal–iodine exchange reaction and isolated in 68 %
yield as a colourless oil. nmax (KBr)/cmꢁ1 3050, 2971, 1612,
1594, 1217, 1078, 684. dH (d-CDCl3, 300 MHz) 7.80 (d, 2H,
J 7.8), 6.47 (t, 1H, J 7.8), 3.04 (t, 2H, J 6.9), 1.52 (m, 4H), 1.01
(t, 3H, J 6.9). dC (d-CDCl3, 75 MHz) 146.5, 140.0, 129.1, 98.9,
46.6, 30.4, 22.8, 13.8. m/z 385.9016. HRMS (CI) Anal. Calc. for
C10H12I2 [Mþ] 385.9028.
Synthesis of 1-Chloro-2,3-Diiodobenzene (24)
The title compound was prepared using the general proce-
dure for ipso-iododecarboxylation of benzoic acid derivatives
and isolated in 83 % yield as a white solid, mp 83–848C. nmax
(KBr)/cmꢁ1 2978, 2948, 1642, 1581, 1100, 741. dH (d-CDCl3,
400 MHz) 7.75 (d, 1H, J 8.0), 7.39 (d, 1H, J 8.1), 6.98 (dd, 1H,
Synthesis of 1,3-Diiodo-2-methylbenzene (34)
The title compound was prepared using the general proce-
dure for metal–iodine exchange reaction and isolated in 64 %
yield as a colourless oil. nmax (KBr)/cmꢁ1 3102, 2942, 2810,